Yasser El-Sayed, MD

All Publications

• Association between small-for-gestational age and neurocognitive impairment at two years of corrected age among infants born at preterm gestational ages: a cohort study. Journal of perinatology Girsen, A. I., Do, S. C., El-Sayed, Y. Y., Hintz, S. R., Blumenfeld, Y. J. 2017

  Abstract

  To investigate the association between small-for-gestational age (SGA) and neurocognitive impairment at 2 years of corrected age among infants born at preterm gestational ages.A secondary analysis of a prospectively conducted NICHD/Maternal-Fetal Medicine Units BEAM trial. Non-anomalous pregnancies delivered before 37 weeks of gestation were included in the analysis. Neurocognitive outcomes at 2 years of corrected age were compared between infants who were SGA (<10% for gestational age) and those appropriately grown (AGA). The primary outcome was a severe or moderate neurocognitive impairment at 2 years of corrected age among survivors, defined as either mental (MDI) or psychomotor (PDI) developmental index score <70 for severe and <85 for moderate impairment.Of 2299 preterm neonates 67 (3%) were SGA. SGA infants were more often twin pregnancies (31% vs 17%, P=0.003) and delivered more often by cesarean section (63% vs 40%, P<0.001) at similar gestational ages (30.0±2.6 vs 29.5±2.8 weeks, P=0.11). At 2 years of corrected age, SGA and AGA survivors had similar rates of neurocognitive impairment (MDI <70: 18% vs 18%, P=1.0; MDI <85: 44% vs 46%, P=0.96; PDI <70: 20% vs 15%, P=0.51; PDI <85: 40% vs 34%, P=0.48).In this cohort, SGA at preterm gestational ages was associated with similar rates of neurocognitive impairment at two years of corrected age among surviving infants.Journal of Perinatology advance online publication, 27 April 2017; doi:10.1038/jp.2017.58.

  View details for DOI 10.1038/jp.2017.58

  View details for PubMedID 28448062

• Risk Factors for Severe Postpartum Hemorrhage After Cesarean Delivery: Case-Control Studies. Anesthesia and analgesia Butwick, A. J., Ramachandran, B., Hegde, P., Riley, E. T., El-Sayed, Y. Y., Nelson, L. M. 2017

  Abstract

  Women who undergo intrapartum caesarean delivery (CD) are at increased risk of postpartum hemorrhage (PPH) compared with those undergoing prelabor CD. To determine whether the presence and strength of the associations between individual risk factors and severe PPH vary among women undergoing prelabor CD or intrapartum CD, stratified analyses are needed according to CD subtype.To identify risk factors for severe PPH within 2 distinct CD populations, prelabor CD and intrapartum CD, we performed 2 case-control studies. Women in each study cohort delivered at a tertiary obstetric center in the United States between 2002 and 2012. For each study, cases were women who had a blood loss ≥1500 mL or who received an intraoperative or postoperative transfusion up to 48 hours after delivery. Risk factors for severe PPH among women undergoing prelabor CD or intrapartum CD were examined in separate logistic regression models.For prelabor CD, we identified 269 cases and 550 controls. Clinical factors with the highest adjusted odds for severe PPH during prelabor CD were general anesthesia (adjusted odds ratio [aOR] = 22.3; 95% confidence interval [CI] = 4.9-99.9; reference group = spinal anesthesia), multiple pregnancies (aOR = 8.0; 95% CI = 4.2-15.0; reference group = singleton pregnancy), and placenta previa (aOR = 6.3; 95% CI = 3.4-11.8). For intrapartum CD, we identified 278 cases and 572 controls. Clinical factors with the highest adjusted odds for severe PPH during intrapartum CD were general anesthesia (aOR = 5.4; 95% CI = 1.7-17.1), multiple pregnancies (aOR = 3.2; 95% CI = 1.7-6.3), and a predelivery hemoglobin ≤ 9.9 g/dL (aOR = 3.0; 95% CI = 1.3-6.9; reference group = predelivery hemoglobin ≥ 11 g/dL).Women who undergo prelabor CD and intrapartum CD have several shared risk factors for severe PPH (general anesthesia and multiple pregnancies). However, the risk factor profiles for severe PPH differed between these CD cohorts. Recognizing these differences may be important when planning resources and interventions for high-risk patients undergoing either prelabor or intrapartum CD.

  View details for DOI 10.1213/ANE.0000000000001962

  View details for PubMedID 28277324

• Effect of a High-Rate Versus a Low-Rate Oxytocin Infusion for Maintaining Uterine Contractility During Elective Cesarean Delivery: A Prospective Randomized Clinical Trial. Anesthesia and analgesia Duffield, A., McKenzie, C., Carvalho, B., Ramachandran, B., Yin, V., El-Sayed, Y. Y., Riley, E. T., Butwick, A. J. 2017; 124 (3): 857-862

  Abstract

  Oxytocin is routinely used as prophylaxis against uterine atony. During elective cesarean delivery (CD), an oxytocin bolus is used to initiate adequate uterine tone, followed by an oxytocin infusion to maintain uterine contractility. However, it is unclear whether oxytocin maintenance infusion rate influences total estimated blood loss (EBL).We performed a prospective, randomized, double-blind trial in 51 women undergoing elective CD. Women were randomly assigned to receive an oxytocin maintenance infusion of 2.5 or 15 U/h. All women received an oxytocin 1 U bolus to initiate adequate uterine tone. The primary outcome was EBL. EBL values between groups were compared using a Mann-Whitney U test; P < .05 as statistically significant. The median EBL difference with 95% confidence intervals was also calculated. Secondary outcomes included adequacy of uterine tone, use of additional uterotonics, and oxytocin-related side effects, including hypotension.Of 51 women, 24 received a low-rate infusion and 27 received a high-rate infusion. Median (interquartile range) EBL values in the low-rate and high-rate groups were 634 (340-886) mL versus 512 (405-740) mL, respectively (P = .7). The median difference in EBL between groups was 22 mL; 95% confidence interval = -158 to 236 mL. The rate of postpartum hemorrhage did not differ between groups (low-rate group: 4/24 [16.7%] versus high-rate group: 4/26 [15.4%]). There were no between-group differences over time (first 20 minutes after commencing infusion) in the incidence of adequate uterine tone (P = .72) or hypotension (P = .32).Among women undergoing elective CD receiving an oxytocin maintenance infusion, EBL and uterine tone did not differ between women receiving 2.5 U/h oxytocin and those receiving 15 U/h oxytocin. Our findings suggest that efficacy can be obtained with a low oxytocin maintenance infusion rate; however, dose-finding studies are needed to determine the infusion rate that optimizes drug efficacy while minimizing side effects.

  View details for DOI 10.1213/ANE.0000000000001658

  View details for PubMedID 28212181

  View details for PubMedCentralID PMC5319709

• Utility of third trimester sonographic measurements for predicting SGA in cases of fetal gastroschisis. Journal of perinatology Blumenfeld, Y. J., Do, S., Girsen, A. I., DAVIS, A. S., Hintz, S. R., Desai, A. K., Mansour, T., Merritt, T. A., Oshiro, B. T., El-Sayed, Y. Y., Shamshirsaz, A. A., Lee, H. C. 2017

  Abstract

  To assess the accuracy of different sonographic estimated fetal weight (EFW) cutoffs, and combinations of EFW and biometric measurements for predicting small for gestational age (SGA) in fetal gastroschisis.Gastroschisis cases from two centers were included. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated for different EFW cutoffs, as well as EFW and biometric measurement combinations.Seventy gastroschisis cases were analyzed. An EFW<10% had 94% sensitivity, 43% specificity, 33% PPV and 96% NPV for SGA at delivery. Using an EFW cutoff of <5% improved the specificity to 63% and PPV to 41%, but decreased the sensitivity to 88%. Combining an abdominal circumference (AC) or femur length (FL) z-score less than -2 with the total EFW improved the specificity and PPV but decreased the sensitivity.A combination of a small AC or FL along with EFW increases the specificity and PPV, but decreases the sensitivity of predicting SGA.Journal of Perinatology advance online publication, 26 January 2017; doi:10.1038/jp.2016.275.

  View details for DOI 10.1038/jp.2016.275

  View details for PubMedID 28125100

• Prediction of neonatal respiratory distress in pregnancies complicated by fetal lung masses. Prenatal diagnosis Girsen, A. I., Hintz, S. R., Sammour, R., Naqvi, A., El-Sayed, Y. Y., Sherwin, K., Davis, A. S., Chock, V. Y., Barth, R. A., Rubesova, E., Sylvester, K. G., Chitkara, R., Blumenfeld, Y. J. 2017

  Abstract

  The objective of this article is to evaluate the utility of fetal lung mass imaging for predicting neonatal respiratory distress.Pregnancies with fetal lung masses between 2009 and 2014 at a single center were analyzed. Neonatal respiratory distress was defined as intubation and mechanical ventilation at birth, surgery before discharge, or extracorporeal membrane oxygenation (ECMO). The predictive utility of the initial as well as maximal lung mass volume and congenital pulmonary airway malformation volume ratio by ultrasound (US) and magnetic resonance imaging (MRI) was analyzed.Forty-seven fetal lung mass cases were included; of those, eight (17%) had respiratory distress. The initial US was performed at similar gestational ages in pregnancies with and without respiratory distress (26.4 ± 5.6 vs 22.3 ± 3 weeks, p = 0.09); however, those with respiratory distress had higher congenital volume ratio at that time (1.0 vs 0.3, p = 0.01). The strongest predictors of respiratory distress were maximal volume >24.0 cm(3) by MRI (100% sensitivity, 91% specificity, 60% positive predictive value, and 100% negative predictive value) and maximal volume >34.0 cm(3) by US (100% sensitivity, 85% specificity, 54% positive predictive value, and 100% negative predictive value).Ultrasound and MRI parameters can predict neonatal respiratory distress, even when obtained before 24 weeks. Third trimester parameters demonstrated the best positive predictive value. © 2017 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/pd.5002

  View details for PubMedID 28061000

• Nifedipine maintenance tocolysis and perinatal outcome: an individual participant data meta-analysis BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY van Vliet, E. O., Dijkema, G. H., Schuit, E., Heida, K. Y., Roos, C., van der Post, J. A., Parry, E. C., McCowan, L., Lyell, D. J., El-Sayed, Y. Y., Carr, D. B., Clark, A. L., Mahdy, Z. A., Uma, M., Sayin, N. C., Varol, G. F., Mol, B. W., Oudijk, M. A. 2016; 123 (11): 1753-1760

  Abstract

  Preterm birth is the leading cause of neonatal mortality and morbidity in developed countries. Whether continued tocolysis after 48 hours of rescue tocolysis improves neonatal outcome is unproven.To evaluate the effectiveness of maintenance tocolytic therapy with oral nifedipine on the reduction of adverse neonatal outcomes and the prolongation of pregnancy by performing an individual patient data meta-analysis (IPDMA).We searched PubMed, Embase, and Cochrane databases for randomised controlled trials of maintenance tocolysis therapy with nifedipine in preterm labour.We selected trials including pregnant women between 24 and 36(6/7)  weeks of gestation (gestational age, GA) with imminent preterm labour who had not delivered after 48 hours of initial tocolysis, and compared maintenance nifedipine tocolysis with placebo/no treatment.The primary outcome was perinatal mortality. Secondary outcome measures were intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), infant respiratory distress syndrome (IRDS), prolongation of pregnancy, GA at delivery, birthweight, neonatal intensive care unit admission, and number of days on ventilation support. Pre-specified subgroup analyses were performed.Six randomised controlled trials were included in this IPDMA, encompassing data from 787 patients (n = 390 for nifedipine; n = 397 for placebo/no treatment). There was no difference between the groups for the incidence of perinatal death (risk ratio, RR 1.36; 95% confidence interval, 95% CI 0.35-5.33), intraventricular haemorrhage (IVH) ≥ grade II (RR 0.65; 95% CI 0.16-2.67), necrotising enterocolitis (NEC) (RR 1.15; 95% CI 0.50-2.65), infant respiratory distress syndrome (IRDS) (RR 0.98; 95% CI 0.51-1.85), and prolongation of pregnancy (hazard ratio, HR 0.74; 95% CI 0.55-1.01).Maintenance tocolysis is not associated with improved perinatal outcome and is therefore not recommended for routine practice.Nifedipine maintenance tocolysis is not associated with improved perinatal outcome or pregnancy prolongation.

  View details for DOI 10.1111/1471-0528.14249

  View details for Web of Science ID 000384679100004

  View details for PubMedID 27550838

• Randomized, Double-Blinded Trial of Magnesium Sulfate Tocolysis versus Intravenous Normal Saline for Preterm Nonsevere Placental Abruption AMERICAN JOURNAL OF PERINATOLOGY Colon, I., Berletti, M., Garabedian, M. J., Wilcox, N., Williams, K., El-Sayed, Y. Y., Chueh, J. 2016; 33 (7): 696-702

  Abstract

  Objective To evaluate the efficacy and safety of magnesium sulfate in the resolution of vaginal bleeding and contractions in nonsevere placental abruption. Study Design Thirty women between 24 and 34 weeks of gestation diagnosed with nonsevere placental abruption were randomized to receive magnesium sulfate tocolysis or normal saline infusion. The primary outcome was the proportion of women undelivered at 48 hours with resolution of vaginal bleeding and uterine contractions. Maternal and neonatal outcomes were also compared. Results Fifteen (50%) women received magnesium sulfate tocolysis and 15 (50%) received intravenous saline. There was no difference in the number of women who were undelivered at 48 hours with resolution of vaginal bleeding and contractions in the magnesium sulfate (80.0%) and saline (66.7%; p-value = 0.68) groups. There were no differences between groups in the gestational age at randomization, time to uterine quiescence, time on study drug, length of hospitalization, days from randomization to delivery, incidence of side effects, or admissions to the neonatal intensive care unit. Conclusions Magnesium sulfate tocolysis did not provide a significant difference in pregnancy prolongation in the management of preterm nonsevere placental abruption. Recruitment goals were not met due to the introduction of the use of magnesium sulfate for neuroprotection.

  View details for DOI 10.1055/s-0036-1571324

  View details for Web of Science ID 000376521500010

  View details for PubMedID 26871905

• Does Time of Delivery Influence the Risk of Neonatal Morbidity? American journal of perinatology Brookfield, K. F., O'Malley, K., El-Sayed, Y. Y., Blumenfeld, Y. J., Butwick, A. J. 2016; 33 (5): 502-509

  Abstract

  Objective To examine whether time of delivery influences the risk of neonatal morbidity among women with singleton pregnancies. Study Design Secondary analysis of data from the Maternal Fetal Medicine Units Network Factor V Leiden Mutation study. We categorized time of delivery as day (07:00-16:59), evening (17:00-23:59), and overnight (midnight-06:59). Severe neonatal morbidity was defined by at least one of the following: respiratory distress syndrome, transient tachypnea of the newborn, sepsis, seizures, neonatal intensive care admission, or a 5-minute APGAR ≤3. We calculated frequencies of severe neonatal morbidity by time of delivery. Multivariate analysis was performed to determine whether time of delivery was independently associated with severe neonatal morbidity. Results Among 4,087 women, 1,917 (46.9%) delivered during the day, 1,140 (27.9%) delivered in the evening, and 1,030 (25.2%) delivered overnight. We observed no significant differences in the rates of neonatal morbidity between delivery time periods (day: 12.3%; evening: 12.8%; overnight: 12.6%; p = 0.9). No significant association was observed between time of delivery and neonatal morbidity after adjustment for maternal, obstetric, and peripartum factors. Conclusion Our findings suggest that time of delivery is not associated with severe neonatal morbidity.

  View details for DOI 10.1055/s-0035-1567891

  View details for PubMedID 26595143

• Labor outcome at extremely advanced maternal age. American journal of obstetrics and gynecology Osmundson, S. S., Gould, J. B., Butwick, A. J., Yeaton-Massey, A., El-Sayed, Y. Y. 2016; 214 (3): 362 e1-7

  Abstract

  Women of advanced maternal age (AMA) are at increased risk for cesarean delivery compared to non-AMA women. However, it is unclear whether how this association is altered by parity and the presence or absence of a trial of labor.We sought to examine modes of delivery and maternal outcomes among AMA women stratified by parity and the presence or absence of a trial of labor.This is a retrospective cohort study of all women delivering singletons births at ≥20 weeks' gestation in the state of California from 2007 through 2011. Data were extracted from maternal discharge data linked to infant birth certificate records. We compared non-AMA women (age 20-34 years, reference group) to AMA women who were classified as follows: age 35-39, 40-44, 45-49, and ≥50 years). The primary outcome was route of delivery (cesarean vs vaginal) stratified by parity and whether a trial of labor occurred (prelabor vs intrapartum cesarean delivery). The association between a trial of labor and perinatal morbidity was also studied.There were 1,346,889 women who met inclusion criteria, which included 181 (0.01%) women who were age ≥50 years at the time of delivery. Overall, 34.7% underwent a cesarean delivery and this risk differed significantly by age group (30.5%, 20-34 years; 40.5%, 35-39 years; 47.3%, 40-44 years; 55.6%, 45-49 years; 62.4%, >50 years). Nulliparous women age ≥50 years were significantly less likely to undergo a trial of labor compared to the reference group (relative risk [RR], 0.44; 95% confidence interval [CI], 0.32-0.62). Furthermore, nulliparous women age ≥50 years were significantly more likely to experience an intrapartum cesarean delivery (RR, 2.61; 95% CI, 1.31-5.20), however the majority (74%) who underwent a trial of labor experienced a vaginal delivery. Compared to the reference group, women age ≥50 years were 5 times more likely to experience severe maternal morbidity (1.7% vs 0.3%; RR, 5.08; 95% CI, 1.65-15.61) and their infants 3 times more likely to require neonatal intensive care unit admission (14.9% vs 5.2%; RR, 3.1; 95% CI, 2.2-4.4), however these outcomes were not associated significantly with having undergone a trial of labor, a cesarean delivery following labor, or a prelabor cesarean delivery. Similar trends were observed among multiparous women.Compared to non-AMA women, women age ≥50 years with a singleton pregnancy experience significantly higher rates of cesarean delivery. However the majority of those who undergo a trial of labor will have a vaginal delivery. Neither a trial of labor nor a prelabor cesarean delivery is significantly associated with maternal or neonatal morbidity. These data support either approach in women of extremely AMA.

  View details for DOI 10.1016/j.ajog.2015.09.103

  View details for PubMedID 26454124

• Early Screening and Treatment of Women with Prediabetes: A Randomized Controlled Trial. American journal of perinatology Osmundson, S. S., Norton, M. E., El-Sayed, Y. Y., Carter, S., Faig, J. C., Kitzmiller, J. L. 2016; 33 (2): 172-179

  Abstract

  To examine whether women with prediabetes benefit from early treatment for gestational diabetes mellitus (GDM).Women with a glycosylated hemoglobin A1C (A1C) of 5.7 to 6.4% at <14 weeks were recruited. Participants were randomized to usual care or treatment for GDM with diet, blood glucose monitoring, and insulin as needed. The primary outcome was a 75-g oral glucose tolerance test at 26 to 28 weeks. Secondary outcomes included cesarean delivery, birthweight, weight gain, and A1C change.Between May 2012 and June 2014, 95 women were enrolled and 83 had data for analysis; 42 were randomized to treatment and 41 to usual care. The groups were similar in baseline characteristics with 40% obese. There was no difference in the primary outcome (treatment 45.2% vs. control 56.1%; relative risk [RR] 0.80; 95% confidence interval [CI] 0.53-1.24) except that women in the treatment group had a significantly lower A1C over time than women in the control group (p = 0.04). Nonobese women (n = 50) treated for GDM experienced a 50% reduction in GDM compared with controls (29.6 vs. 60.9%; RR 0.49; 95% CI 0.25-0.95).Early treatment for women with a first-trimester A1C of 5.7 to 6.4% did not significantly reduce the risk of GDM except in nonobese women.

  View details for DOI 10.1055/s-0035-1563715

  View details for PubMedID 26344009

• Maternal characteristics and mid-pregnancy serum biomarkers as risk factors for subtypes of preterm birth. BJOG : an international journal of obstetrics and gynaecology Jelliffe-Pawlowski, L. L., Baer, R. J., Blumenfeld, Y. J., Ryckman, K. K., O'Brodovich, H. M., Gould, J. B., Druzin, M. L., El-Sayed, Y. Y., Lyell, D. J., Stevenson, D. K., Shaw, G. M., Currier, R. J. 2015; 122 (11): 1484-1493

  Abstract

  To examine the relationship between maternal characteristics, serum biomarkers and preterm birth (PTB) by spontaneous and medically indicated subtypes.Population-based cohort.California, United States of America.From a total population of 1 004 039 live singleton births in 2009 and 2010, 841 665 pregnancies with linked birth certificate and hospital discharge records were included.Characteristics were compared for term and preterm deliveries by PTB subtype using logistic regression and odds ratios adjusted for maternal characteristics and obstetric factors present in final stepwise models and 95% confidence intervals. First-trimester and second-trimester serum marker levels were analysed in a subset of 125 202 pregnancies with available first-trimester and second-trimester serum biomarker results.PTB by subtype.In fully adjusted models, ten characteristics and three serum biomarkers were associated with increased risk in each PTB subtype (Black race/ethnicity, pre-existing hypertension with and without pre-eclampsia, gestational hypertension with pre-eclampsia, pre-existing diabetes, anaemia, previous PTB, one or two or more previous caesarean section(s), interpregnancy interval ≥ 60 months, low first-trimester pregnancy-associated plasma protein A, high second-trimester α-fetoprotein, and high second-trimester dimeric inhibin A). These risks occurred in 51.6-86.2% of all pregnancies ending in PTB depending on subtype. The highest risk observed was for medically indicated PTB <32 weeks in women with pre-existing hypertension and pre-eclampsia (adjusted odds ratio 89.7, 95% CI 27.3-111.2).Our findings suggest a shared aetiology across PTB subtypes. These commonalities point to targets for further study and exploration of risk reduction strategies.Findings suggest a shared aetiology across preterm birth subtypes. Patterns may inform risk reduction efforts.

  View details for DOI 10.1111/1471-0528.13495

  View details for PubMedID 26111589

• Fetofetal Transfusion Syndrome in Monochorionic-Triamniotic Triplets Treated with Fetoscopic Laser Ablation: Report of Two Cases and A Systematic Review. AJP reports Blumenfeld, Y. J., Shamshirsaz, A. A., Belfort, M. A., Hintz, S. R., Moaddab, A., Ness, A., Chueh, J., El-Sayed, Y. Y., Ruano, R. 2015; 5 (2): e153-60

  Abstract

  Objective This study aims to determine the clinical outcomes of monochorionic-triamniotic (MT) pregnancies complicated by severe fetofetal transfusion undergoing laser photocoagulation. Study Design We report two cases of MT triplets complicated by fetofetal transfusion syndrome (FFTS) and a systematic review classifying cases into different subtypes: MT with two donors and one recipient, MT with one donor and two recipients, MT with one donor, one recipient, and one unaffected triplet. The number of neonatal survivors was analyzed based on this classification as well as Quintero staging. Results A total of 26 cases of MT triples complicated by FFTS were analyzed. In 56% of the cases, the FFTS involved all three triplets, 50% of whom had an additional donor and 50% an additional recipient. Among the 24 cases that survived beyond 1 week after the procedure, the average gestational age of delivery was 29.6 weeks, and the average interval from procedure to delivery was 10.1 weeks. The overall neonatal survival rate was 71.7%, with demises occurring equally between donor and recipient triplets. Overall neonatal survival including survival of at least two fetuses occurred with equal frequency between the different groups. Conclusion Significant neonatal survival can be achieved in most cases of MT triplets with FFTS.

  View details for DOI 10.1055/s-0035-1552931

  View details for PubMedID 26495175

  View details for PubMedCentralID PMC4603872

• Serological Targeted Analysis of an ITIH4 Peptide Isoform: A Preterm Birth Biomarker and Its Associated SNP Implications JOURNAL OF GENETICS AND GENOMICS Tan, Z., Hu, Z., Cai, E. Y., Alev, C., Yang, T., Li, Z., Sung, J., El-Sayed, Y. Y., Shaw, G. M., Stevenson, D. K., Butte, A. J., Sheng, G., Sylvester, K. G., Cohen, H. J., Ling, X. B. 2015; 42 (9): 507-510

  View details for DOI 10.1016/j.jgg.2015.06.001

  View details for Web of Science ID 000361919400006

  View details for PubMedID 26408095

• Implementing Mass Cytometry at the Bedside to Study the Immunological Basis of Human Diseases: Distinctive Immune Features in Patients with a History of Term or Preterm Birth CYTOMETRY PART A Gaudilliere, B., Ganio, E. A., Tingle, M., Lancero, H. L., Fragiadakis, G. K., Baca, Q. J., Aghaeepour, N., Wong, R. J., Quaintance, C., El-Sayed, Y. Y., Shaw, G. M., Lewis, D. B., Stevenson, D. K., Nolan, G. P., Angst, M. S. 2015; 87A (9): 817-829

  Abstract

  Single-cell technologies have immense potential to shed light on molecular and biological processes that drive human diseases. Mass cytometry (or Cytometry by Time Of Flight mass spectrometry, CyTOF) has already been employed in clinical studies to comprehensively survey patients' circulating immune system. As interest in the "bedside" application of mass cytometry is growing, the delineation of relevant methodological issues is called for. This report uses a newly generated dataset to discuss important methodological considerations when mass cytometry is implemented in a clinical study. Specifically, the use of whole blood samples versus peripheral blood mononuclear cells (PBMCs), design of mass-tagged antibody panels, technical and analytical implications of sample barcoding, and application of traditional and unsupervised approaches to analyze high-dimensional mass cytometry datasets are discussed. A mass cytometry assay was implemented in a cross-sectional study of 19 women with a history of term or preterm birth to determine whether immune traits in peripheral blood differentiate the two groups in the absence of pregnancy. Twenty-seven phenotypic and 11 intracellular markers were simultaneously analyzed in whole blood samples stimulated with lipopolysaccharide (LPS at 0, 0.1, 1, 10, and 100 ng mL(-1) ) to examine dose-dependent signaling responses within the toll-like receptor 4 (TLR4) pathway. Complementary analyses, grounded in traditional or unsupervised gating strategies of immune cell subsets, indicated that the prpS6 and pMAPKAPK2 responses in classical monocytes are accentuated in women with a history of preterm birth (FDR<1%). The results suggest that women predisposed to preterm birth may be prone to mount an exacerbated TLR4 response during the course of pregnancy. This important hypothesis-generating finding points to the power of single-cell mass cytometry to detect biologically important differences in a relatively small patient cohort. © 2015 International Society for Advancement of Cytometry.

  View details for DOI 10.1002/cyto.a.22720

  View details for Web of Science ID 000360590500009

• Implementing Mass Cytometry at the Bedside to Study the Immunological Basis of Human Diseases: Distinctive Immune Features in Patients with a History of Term or Preterm Birth. Cytometry. Part A : the journal of the International Society for Analytical Cytology Gaudillière, B., Ganio, E. A., Tingle, M., Lancero, H. L., Fragiadakis, G. K., Baca, Q. J., Aghaeepour, N., Wong, R. J., Quaintance, C., El-Sayed, Y. Y., Shaw, G. M., Lewis, D. B., Stevenson, D. K., Nolan, G. P., Angst, M. S. 2015; 87 (9): 817-829

  Abstract

  Single-cell technologies have immense potential to shed light on molecular and biological processes that drive human diseases. Mass cytometry (or Cytometry by Time Of Flight mass spectrometry, CyTOF) has already been employed in clinical studies to comprehensively survey patients' circulating immune system. As interest in the "bedside" application of mass cytometry is growing, the delineation of relevant methodological issues is called for. This report uses a newly generated dataset to discuss important methodological considerations when mass cytometry is implemented in a clinical study. Specifically, the use of whole blood samples versus peripheral blood mononuclear cells (PBMCs), design of mass-tagged antibody panels, technical and analytical implications of sample barcoding, and application of traditional and unsupervised approaches to analyze high-dimensional mass cytometry datasets are discussed. A mass cytometry assay was implemented in a cross-sectional study of 19 women with a history of term or preterm birth to determine whether immune traits in peripheral blood differentiate the two groups in the absence of pregnancy. Twenty-seven phenotypic and 11 intracellular markers were simultaneously analyzed in whole blood samples stimulated with lipopolysaccharide (LPS at 0, 0.1, 1, 10, and 100 ng mL(-1) ) to examine dose-dependent signaling responses within the toll-like receptor 4 (TLR4) pathway. Complementary analyses, grounded in traditional or unsupervised gating strategies of immune cell subsets, indicated that the prpS6 and pMAPKAPK2 responses in classical monocytes are accentuated in women with a history of preterm birth (FDR<1%). The results suggest that women predisposed to preterm birth may be prone to mount an exacerbated TLR4 response during the course of pregnancy. This important hypothesis-generating finding points to the power of single-cell mass cytometry to detect biologically important differences in a relatively small patient cohort. © 2015 International Society for Advancement of Cytometry.

  View details for DOI 10.1002/cyto.a.22720

  View details for PubMedID 26190063

• A Randomized Trial of Intrapartum Fetal ECG ST-Segment Analysis NEW ENGLAND JOURNAL OF MEDICINE Belfort, M. A., Saade, G. R., Thom, E., Blackwell, S. C., Reddy, U. M., Thorp, J. M., Tita, A. T., Miller, R. S., Peaceman, A. M., McKenna, D. S., Chien, E. K., Rouse, D. J., Gibbs, R. S., El-Sayed, Y. Y., Sorokin, Y., Caritis, S. N., VanDorsten, J. P. 2015; 373 (7): 632-641

  Abstract

  It is unclear whether using fetal electrocardiographic (ECG) ST-segment analysis as an adjunct to conventional intrapartum electronic fetal heart-rate monitoring modifies intrapartum and neonatal outcomes.We performed a multicenter trial in which women with a singleton fetus who were attempting vaginal delivery at more than 36 weeks of gestation and who had cervical dilation of 2 to 7 cm were randomly assigned to "open" or "masked" monitoring with fetal ST-segment analysis. The masked system functioned as a normal fetal heart-rate monitor. The open system displayed additional information for use when uncertain fetal heart-rate patterns were detected. The primary outcome was a composite of intrapartum fetal death, neonatal death, an Apgar score of 3 or less at 5 minutes, neonatal seizure, an umbilical-artery blood pH of 7.05 or less with a base deficit of 12 mmol per liter or more, intubation for ventilation at delivery, or neonatal encephalopathy.A total of 11,108 patients underwent randomization; 5532 were assigned to the open group, and 5576 to the masked group. The primary outcome occurred in 52 fetuses or neonates of women in the open group (0.9%) and 40 fetuses or neonates of women in the masked group (0.7%) (relative risk, 1.31; 95% confidence interval, 0.87 to 1.98; P=0.20). Among the individual components of the primary outcome, only the frequency of a 5-minute Apgar score of 3 or less differed significantly between neonates of women in the open group and those in the masked group (0.3% vs. 0.1%, P=0.02). There were no significant between-group differences in the rate of cesarean delivery (16.9% and 16.2%, respectively; P=0.30) or any operative delivery (22.8% and 22.0%, respectively; P=0.31). Adverse events were rare and occurred with similar frequency in the two groups.Fetal ECG ST-segment analysis used as an adjunct to conventional intrapartum electronic fetal heart-rate monitoring did not improve perinatal outcomes or decrease operative-delivery rates. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and Neoventa Medical; ClinicalTrials.gov number, NCT01131260.).

  View details for DOI 10.1056/NEJMoa1500600

  View details for Web of Science ID 000359707700008

  View details for PubMedID 26267623

• Mode of anaesthesia for preterm Caesarean delivery: secondary analysis from the Maternal-Fetal Medicine Units Network Caesarean Registry†‡. British journal of anaesthesia Butwick, A. J., El-Sayed, Y. Y., Blumenfeld, Y. J., Osmundson, S. S., Weiniger, C. F. 2015; 115 (2): 267-274

  Abstract

  Preterm delivery is often performed by Caesarean section. We investigated modes of anaesthesia and risk factors for general anaesthesia among women undergoing preterm Caesarean delivery.Women undergoing Caesarean delivery between 24(+0) and 36(+6) weeks' gestation were identified from a multicentre US registry. The mode of anaesthesia was classified as neuraxial anaesthesia (spinal, epidural, or combined spinal and epidural) or general anaesthesia. Logistic regression was used to identify patient characteristic, obstetric, and peripartum risk factors associated with general anaesthesia.Within the study cohort, 11 539 women had preterm Caesarean delivery; 9510 (82.4%) underwent neuraxial anaesthesia and 2029 (17.6%) general anaesthesia. In our multivariate model, African-American race [adjusted odds ratio (aOR)=1.9; 95% confidence interval (CI)=1.7-2.2], Hispanic ethnicity (aOR=1.5; 95% CI=1.2-1.8), other race (aOR=1.4; 95% CI=1.1-1.9), and haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome or eclampsia (aOR=2.8; 95% CI=2.2-3.5) were independently associated with receiving general anaesthesia for preterm Caesarean delivery. Women with an emergency Caesarean delivery indication had the highest odds for general anaesthesia (aOR=3.5; 95% CI=3.1-3.9). For every 1 week decrease in gestational age at delivery, the adjusted odds of general anaesthesia increased by 13%.In our study cohort, nearly one in five women received general anaesthesia for preterm Caesarean delivery. Although potential confounding by unmeasured factors cannot be excluded, our findings suggest that early gestational age at delivery, emergent Caesarean delivery indications, hypertensive disease, and non-Caucasian race or ethnicity are associated with general anaesthesia for preterm Caesarean delivery.

  View details for DOI 10.1093/bja/aev108

  View details for PubMedID 25956901

• Maternal serum markers, characteristics and morbidly adherent placenta in women with previa JOURNAL OF PERINATOLOGY Lyell, D. J., Faucett, A. M., Baer, R. J., Blumenfeld, Y. J., Druzin, M. L., El-Sayed, Y. Y., Shaw, G. M., Currier, R. J., Jelliffe-Pawlowski, L. L. 2015; 35 (8): 570-574

  Abstract

  To examine associations with morbidly adherent placenta (MAP) among women with placenta previa.Women with MAP (cases) and previa alone (controls) were identified from a cohort of 236 714 singleton pregnancies with both first and second trimester prenatal screening, and live birth and hospital discharge records; pregnancies with aneuploidies and neural tube or abdominal wall defects were excluded. Logistic binomial regression was used to compare cases with controls.In all, 37 cases with MAP and 699 controls with previa alone were included. Risk for MAP was increased among multiparous women with pregnancy-associated plasma protein-A (PAPP-A) ⩾95th percentile (⩾2.63 multiple of the median (MoM); adjusted OR (aOR) 8.7, 95% confidence interval (CI) 2.8 to 27.4), maternal-serum alpha fetoprotein (MS-AFP) ⩾95th percentile (⩾1.79 MoM; aOR 2.8, 95% CI 1.0 to 8.0), and 1 and ⩾2 prior cesarean deliveries (CDs; aORs 4.4, 95% CI 1.5 to 13.6 and 18.4, 95% CI 5.9 to 57.5, respectively).Elevated PAPP-A, elevated MS-AFP and prior CDs are associated with MAP among women with previa.

  View details for DOI 10.1038/jp.2015.40

  View details for Web of Science ID 000358684100008

• Risk Factors for Prolonged Postpartum Length of Stay Following Cesarean Delivery AMERICAN JOURNAL OF PERINATOLOGY Blumenfeld, Y. J., El-Sayed, Y. Y., Lyell, D. J., Nelson, L. M., Butwick, A. J. 2015; 32 (9): 825-832

  Abstract

  Objective This study aims to identify risk factors for prolonged postpartum length of stays (LOS) after cesarean delivery (CD). Study Design Patients undergoing CD were sourced from a multicenter registry of 19 academic centers between 1999 and 2002 (n = 57,067). Prolonged postpartum LOS was defined as a hospitalization duration ≥ 90th centile. Maternal, antepartum, perioperative, and neonatal variables were compared between women with and without prolonged postpartum LOS. Results The 90th centile for postpartum LOS was 4 days, with 14,954 women experiencing prolonged postpartum LOS. Women with perioperative complications had the highest independent risk for a prolonged postpartum LOS: ileus (adjusted odds ratio [aOR] = 12.28; 95% confidence interval CI = 8.98-16.8); endometritis (aOR = 10.45; 95% CI = 9.51-11.5), and wound complications (aOR = 5.49; 95% CI = 4.54-6.63). Several antepartum, perioperative, and neonatal variables were associated with a prolonged postpartum LOS. Conclusion Perioperative complications had the highest risk for prolonged LOS after CD. Strategies to reduce perioperative complications are needed to decrease the health care burden of prolonged post-CD LOS.

  View details for DOI 10.1055/s-0034-1543953

  View details for Web of Science ID 000358571000004

• Early-onset severe preeclampsia by first trimester pregnancy-associated plasma protein A and total human chorionic gonadotropin. American journal of perinatology Jelliffe-Pawlowski, L. L., Baer, R. J., Currier, R. J., Lyell, D. J., Blumenfeld, Y. J., El-Sayed, Y. Y., Shaw, G. M., Druzin, M. L. 2015; 32 (7): 703-712

  Abstract

  This study aims to evaluate the relationship between early-onset severe preeclampsia and first trimester serum levels of pregnancy-associated plasma protein A (PAPP-A) and total human chorionic gonadotropin (hCG).The association between early-onset severe preeclampsia and abnormal levels of first trimester PAPP-A and total hCG in maternal serum were measured in a sample of singleton pregnancies without chromosomal defects that had integrated prenatal serum screening in 2009 and 2010 (n = 129,488). Logistic binomial regression was used to estimate the relative risk (RR) of early-onset severe preeclampsia in pregnancies with abnormal levels of first trimester PAPP-A or total hCG as compared with controls.Regardless of parity, women with low first trimester PAPP-A or high total hCG were at increased risk for early-onset severe preeclampsia. Women with low PAPP-A (multiple of the median [MoM] ≤ the 10th percentile in nulliparous or ≤ the 5th percentile in multiparous) or high total hCG (MoM ≥ the 90th percentile in nulliparous or ≥ the 95th percentile in multiparous) were at more than a threefold increased risk for early-onset severe preeclampsia (RR, 4.2; 95% confidence interval [CI], 3.0-5.9 and RR, 3.3; 95% CI, 2.1-5.2, respectively).Routinely collected first trimester measurements of PAPP-A and total hCG provide unique risk information for early-onset severe preeclampsia.

  View details for DOI 10.1055/s-0034-1396697

  View details for PubMedID 25519199

• Early-Onset Severe Preeclampsia by First Trimester Pregnancy-Associated Plasma Protein A and Total Human Chorionic Gonadotropin AMERICAN JOURNAL OF PERINATOLOGY Jelliffe-Pawlowski, L. L., Baer, R. J., Currier, R. J., Lyell, D. J., Blumenfeld, Y. J., El-Sayed, Y. Y., Shaw, G. M., Druzin, M. L. 2015; 32 (7): 703-711

  View details for DOI 10.1055/s-0034-1396697

  View details for Web of Science ID 000355418600014

  View details for PubMedID 25519199

• Peripartum and neonatal outcomes of small- for- gestational- age infants with gastroschisis PRENATAL DIAGNOSIS Girsen, A. I., Do, S., Davis, A. S., Hintz, S. R., Desai, A. K., Mansour, T., Merritt, T. A., Oshiro, B. T., El-Sayed, Y. Y., Blumenfeld, Y. J. 2015; 35 (5): 477-482

  Abstract

  Neonates with gastroschisis are often small-for-gestational-age (SGA) based on population nomograms. Our objective was to evaluate the effect of SGA on perinatal and neonatal outcomes in cases of gastroschisis.Retrospective study of neonates with prenatally diagnosed gastroschisis from two academic centers between 2008-13. Perinatal and neonatal outcomes of neonates with SGA at birth were compared with appropriate for gestational age (AGA) neonates. The primary composite outcome was defined as any of: neonatal sepsis, short bowel syndrome at discharge, prolonged mechanical ventilation (upper quartile for the cohort), bowel atresia, or death.We identified 112 cases of gastroschisis, 25 of whom (22%) were SGA at birth. There were no differences in adverse peripartum outcomes between SGA and AGA infants. No difference was found in the primary composite neonatal outcome (52% vs. 36%, p=0.21), but SGA infants were more likely to have prolonged mechanical ventilation (44% vs. 22%, p=0.04) and prolonged LOS (52% vs. 22%, p=0.007). After adjusting for GA at delivery, SGA remained associated with prolonged LOS (OR=4.3, CI:1.6 - 11.8).Among infants with gastroschisis, SGA at birth is associated with a 4-fold increase in odds for prolonged LOS, independent of GA. © 2015 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/pd.4562

  View details for Web of Science ID 000353987100011

  View details for PubMedID 25613462

• Antenatal Corticosteroids for Preterm Premature Rupture of Membranes: Single or Repeat Course? AMERICAN JOURNAL OF PERINATOLOGY Brookfield, K. F., El-Sayed, Y. Y., Chao, L., Berger, V., Naqvi, M., Butwick, A. J. 2015; 32 (6): 537-543

  View details for DOI 10.1055/s-0034-1396690

  View details for Web of Science ID 000354342400005

  View details for PubMedID 25545441

• Second-line uterotonics and the risk of hemorrhage-related morbidity AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Butwick, A. J., Carvalho, B., Blumenfeld, Y. J., El-Sayed, Y. Y., Nelson, L. M., Bateman, B. T. 2015; 212 (5)

  View details for DOI 10.1016/j.ajog.2015.01.008

  View details for Web of Science ID 000353598500025

  View details for PubMedID 25582104

• Antenatal corticosteroids for preterm premature rupture of membranes: single or repeat course? American journal of perinatology Brookfield, K. F., El-Sayed, Y. Y., Chao, L., Berger, V., Naqvi, M., Butwick, A. J. 2015; 32 (6): 537-544

  Abstract

  Objective The aim of this article is to determine the risk of maternal chorioamnionitis and neonatal morbidity in women with preterm premature rupture of membranes (PPROM) exposed to one corticosteroid course versus a single repeat corticosteroid steroid course. Study Design Secondary analysis of a cohort of women with singleton pregnancies and PPROM. The primary outcome was a clinical diagnosis of maternal chorioamnionitis. Using multivariate logistic regression, we controlled for maternal age, race, body mass index, diabetes, gestational age at membrane rupture, preterm labor, and antibiotic administration. Neonatal morbidities were compared between groups controlling for gestational age at delivery. Results Of 1,652 women with PPROM, 1,507 women received one corticosteroid course and 145 women received a repeat corticosteroid course. The incidence of chorioamnionitis was similar between groups (single course = 12.3% vs. repeat course = 11.0%; p = 0.8). Women receiving a repeat corticosteroid course were not at increased risk of chorioamnionitis (adjusted odds ratio, 1.28; 95% confidence interval, 0.69-2.14). A repeat course of steroids was not associated with an increased risk of any neonatal morbidity. Conclusion Compared with a single steroid course, our findings suggest that the risk of maternal chorioamnionitis or neonatal morbidity may not be increased for women with PPROM receiving a repeat corticosteroid course.

  View details for DOI 10.1055/s-0034-1396690

  View details for PubMedID 25545441

• Second-line uterotonics and the risk of hemorrhage-related morbidity. American journal of obstetrics and gynecology Butwick, A. J., Carvalho, B., Blumenfeld, Y. J., El-Sayed, Y. Y., Nelson, L. M., Bateman, B. T. 2015; 212 (5): 642 e1-7

  Abstract

  Uterine atony is a leading cause of postpartum hemorrhage (PPH). Although most cases of PPH respond to first line therapy with uterine massage and oxytocin administration, second line uterotonics including methylergonovine and carboprost are integral for the management of refractory uterine atony. Despite their ubiquitous use, it is uncertain whether the risk of hemorrhage-related morbidity differs in women exposed to methylergonovine or carboprost at Cesarean delivery (CD).We performed a secondary analysis using the Maternal-Fetal Medicine Units Network Cesarean Registry. We identified women who underwent CD and received either methylergonovine or carboprost for refractory uterine atony. The primary outcome was hemorrhage-related morbidity defined as intraoperative or postoperative red blood cells (RBC) transfusion or the need for additional surgical interventions including uterine artery ligation, hypogastric artery ligation, or peripartum hysterectomy for atony. We compared the risk of hemorrhage-related morbidity in those exposed to methylergonovine vs. carboprost. Propensity-score matching was used to account for potential confounders.The study cohort comprised 1,335 women; 870 (65.2%) women received methylergonovine and 465 (34.8%) women received carboprost. After accounting for potential confounders, the risk of hemorrhage-related morbidity was higher in the carboprost group than the methylergonovine group (RR = 1.7; 95% CI = 1.2 - 2.6).In this propensity-score matched analysis, methylergonovine was associated with reduced risk of hemorrhage-related morbidity during CD compared to carboprost. Based on these results, methylergonovine may be a more effective second line uterotonic.

  View details for DOI 10.1016/j.ajog.2015.01.008

  View details for PubMedID 25582104

• Correlation of continuous glucose monitoring profiles with pregnancy outcomes in nondiabetic women. American journal of perinatology Sung, J. F., Kogut, E. A., Lee, H. C., Mannan, J. L., Navabi, K., Taslimi, M. M., El-Sayed, Y. Y. 2015; 32 (5): 461-468

  Abstract

  Objective To determine whether hyperglycemic excursions detected by continuous glucose monitoring (CGM) correlate with birth weight percentile and other pregnancy outcomes, and whether CGM correlates better with these outcomes than a single glucose value from a 1-hour glucose challenge test (GCT). Study Design This was a prospective observational study of 55 pregnant patients without preexisting diabetes, who wore a CGM device for up to 7 days, between 24 and 28 weeks' gestation. The area under the curve (AUC) of hyperglycemic excursions above various thresholds (110, 120, 130, 140, and 180 mg/dL) was calculated. These AUC values, and results from a standard 50-g GCT, were correlated with our primary outcome of birth weight percentile, and secondary outcomes of unplanned operative delivery, pregnancy complications, delivery complications, fetal complications, and neonatal complications. Results A consistent correlation was seen between all AUC thresholds and birth weight percentile (r = 0.29, p < 0.05 for AUC-110, -120, -130, and -140; r = 0.25, p = 0.07 for AUC-180). This correlation was stronger than that of 1-hour oral GCT (r =  - 0.02, p = 0.88). There was no association between AUC values and other outcomes. Conclusions Among nondiabetic pregnant patients, hyperglycemic excursions detected by CGM show a stronger correlation to birth weight percentile than blood glucose values obtained 1-hour after a 50-g oral GCT.

  View details for DOI 10.1055/s-0034-1390344

  View details for PubMedID 25262455

• Correlation of Continuous Glucose Monitoring Profiles with Pregnancy Outcomes in Nondiabetic Women AMERICAN JOURNAL OF PERINATOLOGY Sung, J. F., Kogut, E. A., Lee, H. C., Mannan, J. L., Navabi, K., Taslimi, M. M., El-Sayed, Y. Y. 2015; 32 (5): 461-467

  Abstract

  Objective To determine whether hyperglycemic excursions detected by continuous glucose monitoring (CGM) correlate with birth weight percentile and other pregnancy outcomes, and whether CGM correlates better with these outcomes than a single glucose value from a 1-hour glucose challenge test (GCT). Study Design This was a prospective observational study of 55 pregnant patients without preexisting diabetes, who wore a CGM device for up to 7 days, between 24 and 28 weeks' gestation. The area under the curve (AUC) of hyperglycemic excursions above various thresholds (110, 120, 130, 140, and 180 mg/dL) was calculated. These AUC values, and results from a standard 50-g GCT, were correlated with our primary outcome of birth weight percentile, and secondary outcomes of unplanned operative delivery, pregnancy complications, delivery complications, fetal complications, and neonatal complications. Results A consistent correlation was seen between all AUC thresholds and birth weight percentile (r = 0.29, p < 0.05 for AUC-110, -120, -130, and -140; r = 0.25, p = 0.07 for AUC-180). This correlation was stronger than that of 1-hour oral GCT (r =  - 0.02, p = 0.88). There was no association between AUC values and other outcomes. Conclusions Among nondiabetic pregnant patients, hyperglycemic excursions detected by CGM show a stronger correlation to birth weight percentile than blood glucose values obtained 1-hour after a 50-g oral GCT.

  View details for DOI 10.1055/s-0034-1390344

  View details for Web of Science ID 000352807900006

  View details for PubMedID 25262455

• Magnesium sulfate exposure and neonatal intensive care unit admission at term. Journal of perinatology Girsen, A. I., Greenberg, M. B., El-Sayed, Y. Y., LEE, H., Carvalho, B., Lyell, D. J. 2015; 35 (3): 181-185

  Abstract

  Objective:The aim of this study was to investigate the effect of maternal magnesium sulfate (MgSO4) exposure for eclampsia prophylaxis on neonatal intensive care unit (NICU) admission rates for term newborns.Study Design:A secondary analysis of the Maternal-Fetal Medicine Unit Network Cesarean Registry, including primary and repeat cesarean deliveries, and failed and successful trials of labor after cesarean was conducted. Singleton pregnancies among women with preeclampsia and >37 weeks of gestation were included. Pregnancies with uterine rupture, chorioamnionitis and congenital malformations were excluded. Logistic regression analysis was used to determine associations between MgSO4 exposure and NICU admission. P<0.05 was considered statistically significant.Result:Two thousand one hundred and sixty-six term pregnancies of women with preeclampsia were included, of whom 1747 (81%) received MgSO4 for eclampsia prophylaxis and 419 (19%) did not. NICU admission rates were higher among newborns exposed to MgSO4 vs unexposed (22% vs 12%, P<0.001). After controlling for neonatal birth weight, gestational age and maternal demographic and obstetric factors, NICU admission remained significantly associated with antenatal MgSO4 exposure (adjusted odds ratio 1.9, 95% confidence interval 1.3 to 2.6, P<0.001). Newborns exposed to MgSO4 were more likely to have Apgar scores <7 at 1 and 5 min (15% vs 11% unexposed, P=0.01 and 3% vs 0.7% unexposed, P=0.008). There were no significant differences in NICU length of stay (median 5 (range 2 to 91) vs 6 (3 to 15), P=0.5).Conclusion:Antenatal maternal MgSO4 treatment was associated with increased NICU admission rates among exposed term newborns of mothers with preeclampsia. This study highlights the need for studies of maternal MgSO4 administration protocols that optimize maternal and fetal benefits and minimize risks.Journal of Perinatology advance online publication, 16 October 2014; doi:10.1038/jp.2014.184.

  View details for DOI 10.1038/jp.2014.184

  View details for PubMedID 25321647

• Maternal glucose response to betamethasone administration. American journal of perinatology Langen, E. S., Kuperstock, J. L., Sung, J. F., Taslimi, M., Byrne, J., El-Sayed, Y. Y. 2015; 30 (2): 143-148

  Abstract

  Objective This study aims to describe the pattern of maternal glucose response to betamethasone administration using a continuous glucose monitoring system. Study Design A prospective observational trial was conducted among women receiving clinically indicated betamethasone between 24 and 34 weeks gestation. At the time of initial betamethasone administration, a continuous glucose monitoring device was inserted which measured interstitial fluid glucose levels every 5 minutes. Glucose levels were monitored for 7 days, until delivery, or until hospital discharge, whichever came first. We recorded the percentage of time women spent above three glucose thresholds: 110, 144, and 180 mg/dL, respectively. Results A total of 17 women were enrolled at the time of betamethasone administration and data were available for 15 patients. There were 11 nondiabetic and 4 diabetic women. Both diabetic and nondiabetic women had the highest recorded blood glucose readings between 24 and 48 hours after the first injection of betamethasone. In that period, nondiabetic women spent 73, 40, and 17% of the time with blood glucose levels above the 110, 144, and 180 mg/dL thresholds, respectively. Conclusion Nondiabetic women receiving betamethasone manifest significant hyperglycemia after betamethasone administration. If delivery is imminent, maternal glucose response to betamethasone may need to be monitored to prevent possible neonatal hypoglycemia.

  View details for DOI 10.1055/s-0034-1376387

  View details for PubMedID 24915559

• Maternal Glucose Response to Betamethasone Administration AMERICAN JOURNAL OF PERINATOLOGY Langen, E. S., Kuperstock, J. L., Sung, J. F., Taslimi, M., Byrne, J., El-Sayed, Y. Y. 2015; 32 (2): 143-147

  View details for DOI 10.1055/5-0034-1376387

  View details for Web of Science ID 000348628800005

• Risk factors for obstetric morbidity in patients with uterine atony undergoing Caesarean delivery BRITISH JOURNAL OF ANAESTHESIA Butwick, A. J., Carvalho, B., El-Sayed, Y. Y. 2014; 113 (4): 661-668

  View details for DOI 10.1093/bja/aeu150

  View details for Web of Science ID 000343087400019

• Association between maternal characteristics, abnormal serum aneuploidy analytes, and placental abruption. American journal of obstetrics and gynecology Blumenfeld, Y. J., Baer, R. J., Druzin, M. L., El-Sayed, Y. Y., Lyell, D. J., Faucett, A. M., Shaw, G. M., Currier, R. J., Jelliffe-Pawlowski, L. L. 2014; 211 (2): 144 e1-9

  Abstract

  The objective of the study was to examine the association between placental abruption, maternal characteristics, and routine first- and second-trimester aneuploidy screening analytes.The study consisted of an analysis of 1017 women with and 136,898 women without placental abruption who had first- and second-trimester prenatal screening results, linked birth certificate, and hospital discharge records for a live-born singleton. Maternal characteristics and first- and second-trimester aneuploidy screening analytes were analyzed using logistic binomial regression.Placental abruption was more frequent among women of Asian race, age older than 34 years, women with chronic and pregnancy-associated hypertension, preeclampsia, preexisting diabetes, previous preterm birth, and interpregnancy interval less than 6 months. First-trimester pregnancy-associated plasma protein-A of the fifth percentile or less, second-trimester alpha fetoprotein of the 95th percentile or greater, unconjugated estriol of the fifth percentile or less, and dimeric inhibin-A of the 95th percentile or greater were associated with placental abruption as well. When logistic models were stratified by the presence or absence of hypertensive disease, only maternal age older than 34 years (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.0-2.0), pregnancy-associated plasma protein-A of the 95th percentile or less (OR, 1.9; 95% CI, 1.2-3.1), and alpha fetoprotein of the 95th percentile or greater (OR, 2.3; 95% CI, 1.4-3.8) remained statistically significantly associated for abruption.In this large, population-based cohort study, abnormal maternal aneuploidy serum analyte levels were associated with placental abruption, regardless of the presence of hypertensive disease.

  View details for DOI 10.1016/j.ajog.2014.03.027

  View details for PubMedID 24631707

• Association between maternal characteristics, abnormal serum aneuploidy analytes, and placental abruption. American journal of obstetrics and gynecology Blumenfeld, Y. J., Baer, R. J., Druzin, M. L., El-Sayed, Y. Y., Lyell, D. J., Faucett, A. M., Shaw, G. M., Currier, R. J., Jelliffe-Pawlowski, L. L. 2014; 211 (2): 144 e1-9

  View details for DOI 10.1016/j.ajog.2014.03.027

  View details for PubMedID 24631707

• Anticoagulant prescribing practices and anesthetic interventions among anticoagulated pregnant patients: a retrospective study. International journal of obstetric anesthesia Butwick, A., Hass, C., Wong, J., Lyell, D., El-Sayed, Y. 2014; 23 (3): 238-245

  Abstract

  The peripartum management of anticoagulated patients poses important challenges for obstetric anesthesiologists, especially when deciding to perform neuraxial block. However, there is limited evidence evaluating anticoagulant prescribing practices and neuraxial block utilization in this setting. Our objective was to examine peripartum anticoagulant prescribing and anesthetic practices in a cohort of anticoagulated patients receiving subcutaneous enoxaparin, and subcutaneous or intravenous unfractionated heparin.We performed a retrospective study of anticoagulant prescribing patterns and anesthetic interventions among patients receiving enoxaparin and/or unfractionated heparin who delivered at a USA obstetric center over a seven-year period.We identified 101 patients who received enoxaparin and/or unfractionated heparin before delivery. Thirty-nine (38.6%) patients received enoxaparin only, 41 (40.6%) patients received enoxaparin bridged to subcutaneous unfractionated heparin, 11 (10.9%) patients received enoxaparin and were converted to intravenous unfractionated heparin and 10 (9.9%) patients received only subcutaneous unfractionated heparin. The overall rate of neuraxial block utilization was 80.2%. The median [IQR] time-period between the last dose of enoxaparin and neuraxial block was significantly shorter for patients who received only enoxaparin vs. enoxaparin with subcutaneous unfractionated heparin (54h [12-192h] (n=26) vs. 216h [39-504h] (n=23), P=0.04). Among patients who received only subcutaneous unfractionated heparin, the time period between unfractionated heparin and neuraxial block was 24h [19-51h].In this study, the neuraxial block rate was high among patients receiving enoxaparin and/or subcutaneous unfractionated heparin with patients undergoing relatively long periods off anticoagulation. Careful multidisciplinary planning is recommended for the peripartum management of anticoagulated pregnant patients.

  View details for DOI 10.1016/j.ijoa.2014.03.007

  View details for PubMedID 24910353

• Noninvasive prenatal diagnosis in a fetus at risk for methylmalonic acidemia GENETICS IN MEDICINE Gu, W., Koh, W., Blumenfeld, Y. J., El-Sayed, Y. Y., Hudgins, L., Hintz, S. R., Quake, S. R. 2014; 16 (7): 564-567

  View details for DOI 10.1038/gim.2013.194

  View details for Web of Science ID 000338601400012

• Noninvasive prenatal diagnosis in a fetus at risk for methylmalonic acidemia. Genetics in medicine Gu, W., Koh, W., Blumenfeld, Y. J., El-Sayed, Y. Y., Hudgins, L., Hintz, S. R., Quake, S. R. 2014; 16 (7): 564-567

  Abstract

  Purpose:Prenatal diagnosis of fetal Mendelian disorders can benefit from noninvasive approaches using fetal cell-free DNA in maternal plasma. Detecting metabolic disorders before birth can result in immediate treatment postpartum in order to optimize outcome.Methods:We developed a mathematical model and an experimental methodology to analyze the case of a fetus with a 25% risk of inheriting two known mutations in MUT that cause methylmalonic acidemia. To accomplish this, we measured allelic counts at the mutation sites and the fetal fraction from high minor-allele-frequency single-nucleotide polymorphism positions.Results:By counting linked alleles, the test was able to distinguish 11 positive markers from the negative controls and thereby determine whether or not the mutations carried by the parents were inherited by the fetus. For a homozygous fetus, the Z-score of the mutation site was 5.97, whereas the median Z-score of all the linked alleles was 4.56 when all negative (heterozygous) controls had a Z-score <2.5.Conclusion:The application of this methodology for diagnosing methylmalonic acidemia shows that this is a cost-effective and noninvasive approach to diagnosing known mutations related to Mendelian disorders in the fetus.Genet Med advance online publication 9 January 2014Genetics in Medicine (2014); doi:10.1038/gim.2013.194.

  View details for DOI 10.1038/gim.2013.194

  View details for PubMedID 24406457

• Investigation of maternal environmental exposures in association with self-reported preterm birth. Reproductive toxicology Patel, C. J., Yang, T., Hu, Z., Wen, Q., Sung, J., El-Sayed, Y. Y., Cohen, H., Gould, J., Stevenson, D. K., Shaw, G. M., Ling, X. B., Butte, A. J. 2014; 45: 1-7

  Abstract

  Identification of maternal environmental factors influencing preterm birth risks is important to understand the reasons for the increase in prematurity since 1990. Here, we utilized a health survey, the US National Health and Nutrition Examination Survey (NHANES) to search for personal environmental factors associated with preterm birth. 201 urine and blood markers of environmental factors, such as allergens, pollutants, and nutrients were assayed in mothers (range of N: 49-724) who answered questions about any children born preterm (delivery <37 weeks). We screened each of the 201 factors for association with any child born preterm adjusting by age, race/ethnicity, education, and household income. We attempted to verify the top finding, urinary bisphenol A, in an independent study of pregnant women attending Lucile Packard Children's Hospital. We conclude that the association between maternal urinary levels of bisphenol A and preterm birth should be evaluated in a larger epidemiological investigation.

  View details for DOI 10.1016/j.reprotox.2013.12.005

  View details for PubMedID 24373932

• Noninvasive in vivo monitoring of tissue-specific global gene expression in humans. Proceedings of the National Academy of Sciences of the United States of America Koh, W., Pan, W., Gawad, C., Fan, H. C., Kerchner, G. A., Wyss-Coray, T., Blumenfeld, Y. J., El-Sayed, Y. Y., Quake, S. R. 2014; 111 (20): 7361-7366

  Abstract

  Circulating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs. We used high-throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape circulating RNA in a cohort of human subjects. By focusing on genes whose expression is highly specific to certain tissues, we were able to identify the relative contributions of these tissues to circulating RNA and to monitor changes in tissue development and health. As one application of this approach, we performed a longitudinal study on pregnant women and analyzed their combined cell-free RNA transcriptomes across all three trimesters of pregnancy and after delivery. In addition to the analysis of mRNA, we observed and characterized noncoding species such as long noncoding RNA and circular RNA transcripts whose presence had not been previously observed in human plasma. We demonstrate that it is possible to track specific longitudinal phenotypic changes in both the mother and the fetus and that it is possible to directly measure transcripts from a variety of fetal tissues in the maternal blood sample. We also studied the role of neuron-specific transcripts in the blood of healthy adults and those suffering from the neurodegenerative disorder Alzheimer's disease and showed that disease specific neural transcripts are present at increased levels in the blood of affected individuals. Characterization of the cell-free transcriptome in its entirety may thus provide broad insights into human health and development without the need for invasive tissue sampling.

  View details for DOI 10.1073/pnas.1405528111

  View details for PubMedID 24799715

• On-time scheduled cesarean delivery start time process-improvement initiative. Obstetrics and gynecology Blumenfeld, Y. J., Riley, E., Hilton, G., Lee, H. C., El-Sayed, Y. Y., Druzin, M. L. 2014; 123: 138S-9S

  Abstract

  Cesarean deliveries comprise approximately 30% of all births, many of which are scheduled. Given the labile nature of labor and delivery units, scheduled cesarean deliveries are often delayed. Our aim was to improve on-time scheduled cesarean delivery start times.A multidisciplinary team (obstetrician-gynecologist, nursing, anesthesia, and hospital administration) met to review scheduled cesarean delivery data, identify logistic barriers to on-time starts, and develop a plan to improve cesarean delivery start times. After identifying possible barriers to on-time starts, the following process was instituted: planned preoperative visit 1-2 days before scheduled cesarean delivery, mandatory submission of History & Physical and consent forms by the time of the preoperative visit, and initial preparation of the first scheduled patient for cesaren delivery by nighttime nursing before morning change of shift. The process launched on March 1, 2013. Data from scheduled cesarean deliveries 6 months before and 3 months after the initiative were reviewed and analyzed.Of 1,298 total cesarean deliveries, 423 were scheduled, defined as cesarean delivery scheduled at least 24 hours in advance (300 before and 123 after the initiative). Sixty-four of 300 scheduled cesarean deliveries (21.3%) were on time before compared with 67 of 123 (54.5%) after the initiative began (P<.001). Among delayed cases, there was no difference in the average delay time between those before and after the initiative (55.7 compared with 54.4 minutes P=.93); however, 50.7% of cases were either on time or delayed by 15 minutes or less before the initiative compared with 69.9% of cases after (P<.001).A multidisciplinary initiative significantly increased scheduled cesarean delivery on-time start times.

  View details for DOI 10.1097/01.AOG.0000447113.07157.f3

  View details for PubMedID 24770007

• In response. Anesthesia and analgesia Macario, A., Carvalho, B., Tan, J. M., Sultan, P., El-Sayed, Y. Y. 2014; 118 (4): 884-885

  View details for DOI 10.1213/ANE.0000000000000114

  View details for PubMedID 24651247

• Oral misoprostol versus vaginal dinoprostone for labor induction in nulliparous women at term. Journal of perinatology Faucett, A. M., Daniels, K., Lee, H. C., El-Sayed, Y. Y., Blumenfeld, Y. J. 2014; 34 (2): 95-99

  Abstract

  Objective:To compare the efficacy of oral misoprostol to vaginal dinoprostone for labor induction in nulliparous women.Study design:Admissions for labor induction from January 2008 to December 2010 were reviewed. Patients receiving oral misoprostol were compared with those receiving vaginal dinoprostone. The primary outcome was time from induction agent administration to vaginal delivery. Secondary outcomes included vaginal delivery within 24 h, mode of delivery and maternal and fetal outcomes.Result:A total of 680 women were included: 483 (71%) received vaginal dinoprostone and 197 (29%) received oral misoprostol. Women who received oral misoprostol had a shorter interval to vaginal delivery (27.2 vs 21.9 h, P<0.0001) and were more likely to deliver vaginally in <24 h (47% vs 64%, P=0.001). There was no increase in the rate of cesarean delivery or adverse maternal or neonatal outcomes.Conclusion:Labor induction with oral misoprostol resulted in shorter time to vaginal delivery without increased adverse outcomes in nulliparous women.

  View details for DOI 10.1038/jp.2013.133

  View details for PubMedID 24157494

• High rate of preterm birth in pregnancies complicated by rheumatoid arthritis. American journal of perinatology Langen, E. S., Chakravarty, E. F., Liaquat, M., El-Sayed, Y. Y., Druzin, M. L. 2014; 31 (1): 9-14

  Abstract

  Objective To describe the outcomes of pregnancies complicated by rheumatoid arthritis (RA) and to estimate potential associations between disease characteristics and pregnancy outcomes.Study Design We reviewed all pregnancies complicated by RA delivered at our institution from June 2001 through June 2009. Fisher exact tests were used to calculate odds ratios. Univariable regression was performed using STATA 10.1 (StataCorp, College Station, TX). A p value of ≤ 0.05 was considered statistically significant.Results Forty-six pregnancies in 40 women were reviewed. Sixty percent of pregnancies had evidence of disease flare and 28% delivered prior to 37 weeks. We did not identify associations between preterm birth and active disease at conception or during pregnancy. In univariate analysis, discontinuation of medication because of pregnancy was associated with a significantly earlier gestational age at delivery (362/7 versus 383/7 weeks, p = 0.022).Conclusion Women with RA may be at higher risk for preterm delivery.

  View details for DOI 10.1055/s-0033-1333666

  View details for PubMedID 23359233

• High Rate of Preterm Birth in Pregnancies Complicated by Rheumatoid Arthritis AMERICAN JOURNAL OF PERINATOLOGY Langen, E. S., Chakravarty, E. F., Liaquat, M., El-Sayed, Y. Y., Druzin, M. L. 2014; 31 (1): 9-13

  View details for DOI 10.1055/s-0033-1333666

  View details for Web of Science ID 000329362900002

  View details for PubMedID 23359233

• Isolated umbilical vein varix with a poor outcome despite close fetal surveillance. Journal of ultrasound in medicine Brookfield, K. F., Osmundson, S. S., Chetty, S., Chueh, J., Blumenfeld, Y. J., Barth, R. A., El-Sayed, Y. Y. 2013; 32 (9): 1680-1682

  View details for DOI 10.7863/ultra.32.9.1680

  View details for PubMedID 23980233

• Brief report: a cost analysis of neuraxial anesthesia to facilitate external cephalic version for breech fetal presentation. Anesthesia and analgesia Carvalho, B., Tan, J. M., Macario, A., El-Sayed, Y. Y., Sultan, P. 2013; 117 (1): 155-159

  Abstract

  BACKGROUND:In this study, we sought to determine whether neuraxial anesthesia to facilitate external cephalic version (ECV) increased delivery costs for breech fetal presentation.METHODS:Using a computer cost model, which considers possible outcomes and probability uncertainties at the same time, we estimated total expected delivery costs for breech presentation managed by a trial of ECV with and without neuraxial anesthesia.RESULTS:From published studies, the average probability of successful ECV with neuraxial anesthesia was 60% (with individual studies ranging from 44% to 87%) compared with 38% (with individual studies ranging from 31% to 58%) without neuraxial anesthesia. The mean expected total delivery costs, including the cost of attempting/performing ECV with anesthesia, equaled $8931 (2.5th-97.5th percentile prediction interval $8541-$9252). The cost was $9207 (2.5th-97.5th percentile prediction interval $8896-$9419) if ECV was attempted/performed without anesthesia. The expected mean incremental difference between the total cost of delivery that includes ECV with anesthesia and ECV without anesthesia was $-276 (2.5th-97.5th percentile prediction interval $-720 to $112).CONCLUSION:The total cost of delivery in women with breech presentation may be decreased (up to $720) or increased (up to $112) if ECV is attempted/performed with neuraxial anesthesia compared with ECV without neuraxial anesthesia. Increased ECV success with neuraxial anesthesia and the subsequent reduction in breech cesarean delivery rate offset the costs of providing anesthesia to facilitate ECV.

  View details for DOI 10.1213/ANE.0b013e31828e5bc7

  View details for PubMedID 23592608

• A Cost Analysis of Neuraxial Anesthesia to Facilitate External Cephalic Version for Breech Fetal Presentation ANESTHESIA AND ANALGESIA Carvalho, B., Tan, J. M., Macario, A., El-Sayed, Y. Y., Sultan, P. 2013; 117 (1): 155-159

  View details for DOI 10.1213/ANE.0b013e31828e5bc7

  View details for Web of Science ID 000326512300025

• Effect of magnesium sulfate exposure on term neonates JOURNAL OF PERINATOLOGY Greenberg, M. B., Penn, A. A., Whitaker, K. R., KOGUT, E. A., El-Sayed, Y. Y., Caughey, A. B., Lyell, D. J. 2013; 33 (3): 188-193

  Abstract

  To compare neonatal intensive care unit and special care unit (NICU) admission rates between term neonates exposed to antenatal magnesium sulfate (MS) and those unexposed.We performed a retrospective cohort study of all singleton neonates ≥37 weeks born to women with pre-eclampsia from August 2006 to July 2008. Cases were defined by antenatal exposure to MS and controls by absence of MS exposure. The primary outcome was NICU admission. Data were analyzed via univariable and multivariable regression analyses.In all, 28 (14.7%) out of 190 MS-exposed neonates ≥37 weeks were admitted to the NICU, compared with 4 (5.4%) of 74 non-exposed neonates (P=0.04). This association persisted after controlling for potential confounding variables including severe pre-eclampsia and cesarean delivery (AOR 3.69, 1.13 to 11.99). NICU admission was associated in a dose-dependent relationship with total hours and mean dose of MS exposure. Number needed to harm with MS was 11 per NICU admission. Among neonates admitted to the NICU, MS-exposed were more likely to require fluid and nutritional support than unexposed neonates (60.7 vs 0%, P=0.04), and trended toward more frequent requirement for respiratory support and greater length of stay.In term neonates, MS exposure may be associated independently with NICU admission in a dose-dependent relationship. Requirements for fluid and nutritional support are common in this group, likely due to feeding difficulties in exposed neonates. Assessment of acute care needs among all neonates exposed to MS for maternal eclampsia prophylaxis should be considered.

  View details for DOI 10.1038/jp.2012.95

  View details for Web of Science ID 000315664700005

  View details for PubMedID 22836873

• Peripartum outcomes and anaesthetic management of parturients with moderate to complex congenital heart disease or pulmonary hypertension ANAESTHESIA Maxwell, B. G., El-Sayed, Y. Y., Riley, E. T., Carvalho, B. 2013; 68 (1): 52-59

  Abstract

  We performed a retrospective cohort analysis of pregnancies among women with moderate to complex congenital heart disease or pulmonary hypertension over a 12-year period, resulting in a cohort of 107 cases in 65 women. Neuraxial analgesia or anaesthesia was provided in 84%, 89% and 95% of spontaneous vaginal, operative vaginal and caesarean deliveries, respectively. The caesarean delivery rate was 43% compared to our institution average of 27% over the same period (p = 0.02), and 38% had operative vaginal deliveries compared to a 10.5% institution rate (p < 0.01). Invasive monitoring was used in 28% of all deliveries. There were one maternal and two neonatal deaths. This study provides detailed anaesthetic and peripartum management of women with congenital heart disease, a patient population in whom evidence-based practice and data are largely lacking. We observed a predominance of neuraxial anaesthetic techniques, increased caesarean and operative delivery rates, and favourable maternal and neonatal outcomes. Multicentre studies and registries to compare anaesthetic and obstetric management strategies further and delineate risk factors for adverse outcomes are required.

  View details for DOI 10.1111/anae.12058

  View details for Web of Science ID 000312304000012

  View details for PubMedID 23121251

• Utilization of available prenatal screening and diagnosis: effects of the California screen program JOURNAL OF PERINATOLOGY Blumenfeld, Y. J., Taylor, J., Lee, H. C., Hudgins, L., Sung, J. F., El-Sayed, Y. Y. 2012; 32 (12): 907-912

  Abstract

  In 2009, the California Genetic Disease Branch introduced an aneuploidy screening program allowing Medi-Cal (state insured) patients access to state-sponsored first-trimester screening. The objective of this study was to assess the effect of greater access to prenatal screening on available resources at a single center.Data of prenatal screening and diagnostic procedures performed 4 months before the introduction of the program were compared with those of 12 months following the introduction.Between December 2008 and March 2010, 7689 women underwent first trimester screening, 1286 underwent amniocentesis and 398 underwent chorionic villus sampling. When a comparison was made between the 4 months before and the 12 months after the program's introduction, a greater number of nuchal translucency (NT) examinations was seen to have been performed (384 per month vs 513 per month, P=0.001). Prenatal diagnostic procedures did not increase, but a greater proportion was performed for positive screen results.Introduction of the California screening program was associated with increased NT procedures and fewer invasive procedures for advanced maternal age.

  View details for DOI 10.1038/jp.2012.8

  View details for Web of Science ID 000311831700002

  View details for PubMedID 22402484

• Detecting Prenatal Microdeletions Non-Invasively: Case of a 22q11.2 Deletion Annual Meeting of the Association-for-Molecular-Pathology Gu, W., Fan, H., Blumenfeld, Y., El-Sayed, Y., Quake, S. ELSEVIER SCIENCE INC. 2012: 638–38

  View details for Web of Science ID 000310178600021

• Diagnosis and Management of Arrest Disorders: Duration to Wait SEMINARS IN PERINATOLOGY El-Sayed, Y. Y. 2012; 36 (5): 374-378

  Abstract

  To assess the thresholds of normal and protracted labor in contemporary US parturients. Select studies addressing first- and second-stage labor duration among contemporary cohorts of women in the United States were reviewed. Particular emphasis was placed on the work of the Consortium on Safe Labor. Duration of labor appears longer today than in the past. For both nulliparous and multiparous women, labor may take >6 hours to progress from 4 to 5 cm and >3 hours to progress from 5 to 6 cm of dilation. A cervical dilation of 6 cm appears to be a better landmark for the start of the active phase. The 95th percentile for duration of the second stage in a nulliparous woman with conduction anesthesia is closer to 4 hours. Current data on first and second stages of labor allow for an opportunity to reconsider traditionally accepted thresholds of normal and protracted labor, and thus affect consequent labor management paradigms.

  View details for DOI 10.1053/j.semperi.2012.04.022

  View details for Web of Science ID 000309628900012

  View details for PubMedID 23009971

• Non-invasive prenatal measurement of the fetal genome NATURE Fan, H. C., Gu, W., Wang, J., Blumenfeld, Y. J., El-Sayed, Y. Y., Quake, S. R. 2012; 487 (7407): 320-?

  Abstract

  The vast majority of prenatal genetic testing requires invasive sampling. However, this poses a risk to the fetus, so one must make a decision that weighs the desire for genetic information against the risk of an adverse outcome due to hazards of the testing process. These issues are not required to be coupled, and it would be desirable to discover genetic information about the fetus without incurring a health risk. Here we demonstrate that it is possible to non-invasively sequence the entire prenatal genome. Our results show that molecular counting of parental haplotypes in maternal plasma by shotgun sequencing of maternal plasma DNA allows the inherited fetal genome to be deciphered non-invasively. We also applied the counting principle directly to each allele in the fetal exome by performing exome capture on maternal plasma DNA before shotgun sequencing. This approach enables non-invasive exome screening of clinically relevant and deleterious alleles that were paternally inherited or had arisen as de novo germline mutations, and complements the haplotype counting approach to provide a comprehensive view of the fetal genome. Non-invasive determination of the fetal genome may ultimately facilitate the diagnosis of all inherited and de novo genetic disease.

  View details for DOI 10.1038/nature11251

  View details for Web of Science ID 000306506500033

  View details for PubMedID 22763444

• Rectus muscle and visceral peritoneum closure at cesarean delivery and intraabdominal adhesions 78th Annual Meeting of the Pacific-Coast-Obstetrical-and-Gynecological-Society Lyell, D. J., Caughey, A. B., Hu, E., Blumenfeld, Y., El-Sayed, Y. Y., Daniels, K. MOSBY-ELSEVIER. 2012

  Abstract

  The purpose of this study was to evaluate the effect of the rectus muscle and visceral peritoneum closure at cesarean delivery on adhesions.We performed a secondary analysis of a prospective cohort study of women who underwent first repeat cesarean delivery. Surgeons scored the severity and location of adhesions. Records were abstracted to assess previous surgical techniques.The original cohort included 173 patients. Rectus muscle closure was associated with fewer combined filmy and dense adhesions overall (27.5% vs 46%; P = .04) and fewer dense adhesions overall (17.5% vs 46%; P = .001; adjusted odds ratio, [aOR], 0.24; 95% confidence interval [CI], 0.09-0.65), particularly from fascia to omentum (aOR, 0.08; 95% CI, 0.007-0.82). Visceral peritoneum closure was associated with increased dense fascia-to-omentum adhesions (aOR, 15.78; 95% CI, 1.81-137.24).Closure of the rectus muscles at cesarean delivery may reduce adhesions, and visceral peritoneum closure may increase them. Surgical techniques at cesarean delivery should be assessed independently, because they may have opposite effects on adhesion formation.

  View details for DOI 10.1016/j.ajog.2012.02.033

  View details for Web of Science ID 000304442900029

  View details for PubMedID 22463952

• Trends in Cesarean Delivery for Twin Births in the United States: 1995-2008 Reply OBSTETRICS AND GYNECOLOGY Lee, H. C., Gould, J. B., Boscardin, W. J., El-Sayed, Y. Y., Blumenfeld, Y. J. 2012; 119 (3): 658-659

  View details for DOI 10.1097/AOG.0b013e318248f682

  View details for Web of Science ID 000300637400029

• Continuous Glucose Monitoring During Pregnancy in Women With Polycystic Ovary Syndrome OBSTETRICS AND GYNECOLOGY Sung, J. F., Taslimi, M. M., El-Sayed, Y. Y. 2012; 119 (2): 383-384

  View details for Web of Science ID 000299604300035

  View details for PubMedID 22270301

• Maternal glucose response to betamethasone administration 32nd Annual Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) Langen, E., Lewis, J., Sung, J., Taslimi, M., Byrne, J., El-Sayed, Y. MOSBY-ELSEVIER. 2012: S98–S98

  View details for Web of Science ID 000298889900194

• Profiling maternal plasma cell-free RNA by RNA-sequencing: a comprehensive approach 32nd Annual Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) Koh, W., Fan, C., Blumenfeld, Y., Wong, R., El-Sayed, Y., Kogut, E., Quake, S. MOSBY-ELSEVIER. 2012: S324–S324

  View details for Web of Science ID 000298889900725

• Plasma proteomic profiles in preterm labor (PTL) and preterm premature rupture of membranes (PPROM) 32nd Annual Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) Sung, J., Whitin, J., Yang, Q., Madan, A., El-Sayed, Y. MOSBY-ELSEVIER. 2012: S224–S224

  View details for Web of Science ID 000298889900491

• Trends in Cesarean Delivery for Twin Births in the United States 1995-2008 OBSTETRICS AND GYNECOLOGY Lee, H. C., Gould, J. B., Boscardin, W. J., El-Sayed, Y. Y., Blumenfeld, Y. J. 2011; 118 (5): 1095-1101

  Abstract

  To estimate trends and risk factors for cesarean delivery for twins in the United States.This was a cross-sectional study in which we calculated cesarean delivery rates for twins from 1995 to 2008 using National Center for Health Statistics data. We compared cesarean delivery rates by year and for vertex compared with breech presentation. The order of presentation for a given twin pair could not be determined from the available records and therefore analysis was based on individual discrete twin data. Multivariable logistic regression was used to estimate independent risk factors, including year of birth and maternal factors, for cesarean delivery.Cesarean delivery rates for twin births increased steadily from 53.4% to 75.0% in 2008. Rates rose for the breech twin category (81.5%-92.1%) and the vertex twin category (45.1%-68.2%). The relative increase in the cesarean delivery rate for preterm and term neonates was similar. After risk adjustment, there was an average increase noted in cesarean delivery of 5% each year during the study period (risk ratio 1.05, 95% confidence interval 1.04-1.05).Cesarean delivery rates for twin births increased dramatically from 1995 to 2008. This increase is significantly higher than that which could be explained by an increase in cesarean delivery for breech presentation of either the presenting or second twin.

  View details for DOI 10.1097/AOG.0b013e3182318651

  View details for Web of Science ID 000296292600018

  View details for PubMedID 22015878

  View details for PubMedCentralID PMC3202294

• Decreased Circulating Soluble Tie2 Levels in Preeclampsia May Result from Inhibition of Vascular Endothelial Growth Factor (VEGF) Signaling JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Sung, J. F., Fan, X., Dhal, S., Dwyer, B. K., Jafari, A., El-Sayed, Y. Y., Druzin, M. L., Nayak, N. R. 2011; 96 (7): E1148-E1152

  Abstract

  Recent studies have found dysregulation in circulating levels of a number of angiogenic factors and their soluble receptors in preeclampsia. In this study, we examined the mechanism of production of soluble Tie2 (sTie2) and its potential connection to the failure of vascular remodeling in preeclamptic pregnancies.Serum samples were collected prospectively from 41 pregnant subjects at five different time points throughout pregnancy. Five of these subjects developed preeclampsia. For a second study, serum and placental samples were collected at delivery from preeclamptic and gestational age-matched controls. We examined serum sTie2 levels, and angiopoietin 1, angiopoietin 2, and Tie2 mRNA expression and localization in placental samples from the central basal plate area. We also examined the effects of vascular endothelial growth factor (VEGF) and a matrix metalloproteinase (MMP) inhibitor on proteolytic shedding of Tie2 in uterine microvascular endothelial cells.Serum sTie2 levels were significantly lower in preeclamptic subjects starting at 24-28 wk of gestation and continued to be lower through the time of delivery. In culture experiments, VEGF treatment significantly increased sTie2 levels in conditioned media, whereas the MMP inhibitor completely blocked this increase, suggesting that VEGF-induced Tie2 release is MMP dependent.Our data suggest, for the first time, an interaction between VEGF and Tie2 in uterine endothelial cells and a potential mechanism for the decrease in circulating sTie2 levels in preeclampsia, likely through inhibition of VEGF signaling. Further studies on VEGF-Tie2 interactions during pregnancy should provide new insights into the mechanisms underlying the failure of vascular remodeling in preeclampsia and other pregnancy complications.

  View details for DOI 10.1210/jc.2011-0063

  View details for Web of Science ID 000292454500015

  View details for PubMedID 21525162

• Neonatal medical admission in a term and late-preterm cohort exposed to magnesium sulfate 31st Annual Western Conference on Perinatal Research Greenberg, M. B., Penn, A. A., Thomas, L. J., El-Sayed, Y. Y., Caughey, A. B., Lyell, D. J. MOSBY-ELSEVIER. 2011

  Abstract

  The purpose of this study was to estimate neonatal intensive care unit and special care unit (NICU) admission rates and care needs among term and late-preterm neonates who are exposed to antenatal magnesium sulfate.We conducted a retrospective cohort study of all singleton neonates of ≥35 weeks' gestation who were exposed immediately antenatally to magnesium sulfate for maternal eclampsia prophylaxis (August 2006 through July 2008).Fifty-one of 242 neonates (21.1%) who, at ≥35 weeks' gestation, had been exposed to antenatal magnesium sulfate were admitted to the NICU. NICU admission was associated in a dose-dependent fashion with total hours and mean dose of magnesium: >12 hours exposure, odds ratio, 2.81 (95% confidence interval, 1.31-6.03); >30 g exposure, odds ratio, 2.59 (95% confidence interval, 1.22-5.51). Infants in NICU who were diagnosed with hypermagnesemia required fluid or nutritional support more frequently (91.3% vs 39.3%; P < .001) than those without hypermagnesemia.Antenatal magnesium sulfate exposure is associated with NICU admission among term and late-preterm neonates in a dose-dependent fashion. Fluid and nutritional assistance commonly are needed in this cohort.

  View details for DOI 10.1016/j.ajog.2011.01.046

  View details for Web of Science ID 000291477300029

  View details for PubMedID 21376302

• MR imaging in cases of antenatal suspected appendicitis - a meta-analysis JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Blumenfeld, Y. J., Wong, A. E., Jafari, A., Barth, R. A., El-Sayed, Y. Y. 2011; 24 (3): 485-488

  Abstract

  Appendicitis is the most common surgical emergency in pregnancy. Acute appendicitis is often difficult to diagnose clinically, and concerns regarding antenatal CT imaging limit its use resulting in high false negative rates at laparotomy. MRI has recently been reported as a reasonable alternative to CT imaging in cases of suspected appendicitis. Our objective was to perform a meta-analysis of recently published data regarding the utility of MR imaging in cases of antenatal suspected acute appendicitis.We searched the PubMed database using keywords 'MRI', 'appendicitis', and 'pregnancy'. Five case series describing the role of MRI in cases of antenatal appendicitis were included. The sensitivity, specificity, positive, and negative predictive values were calculated.Two hundred twenty-nine patients were included in the study. In the first analysis in which non-diagnostic scans were excluded, the sensitivity, specificity, positive and negative predictive values of MRI for diagnosing appendicitis were 95.0%, 99.9%, 90.4%, and 99.5%, respectively. In the second analysis, which included non-diagnostic scans, the sensitivity, specificity, positive and negative predictive values were 90.5%, 98.6%, 86.3%, and 99.0%, respectivelyMR imaging may be useful in cases of suspected antenatal appendicitis. Data are still limited and larger prospective studies are necessary to confirm this finding.

  View details for DOI 10.3109/14767058.2010.506227

  View details for Web of Science ID 000286993000020

  View details for PubMedID 20695758

• Decreased Circulating sTie2 Levels in Preeclampsia May Involve Inhibition of VEGF Signaling Sung, J. F., Fan, X., Dwyer, B. K., Dhal, S., El-Sayed, Y. Y., Druzin, M. L., Nayak, N. R. SAGE PUBLICATIONS INC. 2011: 79A–79A

  View details for Web of Science ID 000291721700029

• Diagnositic utility of ultrasound and MRI in women with placenta previa and placental invasion 31st Annual Scientific Meeting of the Society-of-Maternal-Fetal-Medicine (SMFM) Langen, E., El-Sayed, Y., Druzin, M., Park, M., Lee, H. MOSBY-ELSEVIER. 2011: S137–S137

  View details for Web of Science ID 000285927500334

• Maternal morbidity in pregnancies complicated by abnormal placentation 31st Annual Scientific Meeting of the Society-of-Maternal-Fetal-Medicine (SMFM) Langen, E., El-Sayed, Y., Druzin, M., Park, M., Lee, H. MOSBY-ELSEVIER. 2011: S57–S57

  View details for Web of Science ID 000285927500107

• The Effect of Preterm Premature Rupture of Membranes on Neonatal Mortality Rates 30th Annual Clinical Meeting of the Society-for-Maternal-Fetal-Medicine Blumenfeld, Y. J., Lee, H. C., Gould, J. B., Langen, E. S., Jafari, A., El-Sayed, Y. Y. LIPPINCOTT WILLIAMS & WILKINS. 2010: 1381–86

  Abstract

  To estimate the effect of preterm premature rupture of membranes (PROM) on neonatal mortality.A cross-sectional study using a state perinatal database (California Perinatal Quality Care Collaborative) was performed. Prenatal data, including ruptured membranes, corticosteroid administration, maternal age, maternal race, maternal hypertension, mode of delivery, and prenatal care, were recorded. Mortality rates were compared for neonates born between 24 and 34 weeks of gestation without preterm PROM to those with recent (less than 18 hours before delivery) and prolonged (more than 18 hours before delivery) preterm PROM. Neonatal sepsis rates were also examined.Neonates born between 24 0/7 and 34 0/7 weeks of gestation from 127 California neonatal intensive care units between 2005 and 2007 were included (N=17,501). When analyzed by 2-week gestational age groups, there were no differences in mortality rates between those born with and without membrane rupture before delivery. The presence of prolonged preterm PROM was associated with decreased mortality at 24 to 26 weeks of gestation (18% compared with 31% for recent preterm PROM; odds ratio [OR] 1.79; confidence interval [CI] 1.25-2.56) but increased mortality at 28 to 30 weeks of gestation (4% compared with 3% for recent preterm PROM; OR 0.44; CI 0.22, 0.88) when adjusted for possible confounding factors. Sepsis rates did not differ between those with recent or prolonged preterm PROM at any gestational age.The presence of membrane rupture before delivery was not associated with increased neonatal mortality in any gestational age group. The effects of a prolonged latency period were not consistent across gestational ages.

  View details for DOI 10.1097/AOG.0b013e3181fe3d28

  View details for Web of Science ID 000284491000021

  View details for PubMedID 21099606

• Regional anesthesia for external cephalic version: its time has come JOURNAL OF PERINATOLOGY Caughey, A. B., El-Sayed, Y. Y. 2010; 30 (9): 569-570

  View details for DOI 10.1038/jp.2010.89

  View details for Web of Science ID 000281388500001

  View details for PubMedID 20802508

• Maternal-fetal and neonatal pharmacogenomics: a review of current literature JOURNAL OF PERINATOLOGY Blumenfeld, Y. J., Reynolds-May, M. F., Altman, R. B., El-Sayed, Y. Y. 2010; 30 (9): 571-579

  Abstract

  Pharmacogenomics, the study of specific genetic variations and their effect on drug response, will likely give rise to many applications in maternal-fetal and neonatal medicine; yet, an understanding of these applications in the field of obstetrics and gynecology and neonatal pediatrics is not widespread. This review describes the underpinnings of the field of pharmacogenomics and summarizes the current pharmacogenomic inquiries in relation to maternal-fetal medicine-including studies on various fetal and neonatal genetic cytochrome P450 (CYP) enzyme variants and their role in drug toxicities (for example, codeine metabolism, sepsis and selective serotonin reuptake inhibitor (SSRI) toxicity). Potential future directions, including alternative drug classification, improvements in drug efficacy and non-invasive pharmacogenomic testing, will also be explored.

  View details for DOI 10.1038/jp.2009.183

  View details for Web of Science ID 000281388500002

  View details for PubMedID 19924131

  View details for PubMedCentralID PMC3098749

• Oral Misoprostol and Vaginal Isosorbide Mononitrate for Labor Induction A Randomized Controlled Trial 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Collingham, J. P., Fuh, K. C., Caughey, A. B., Pullen, K. M., Lyell, D. J., El-Sayed, Y. Y. LIPPINCOTT WILLIAMS & WILKINS. 2010: 121–26

  Abstract

  To estimate whether vaginal isosorbide mononitrate, added to oral misoprostol for cervical ripening and labor induction, shortens time to vaginal delivery.A prospective, randomized trial was conducted. Women scheduled for labor induction between 32 and 42 weeks and with unfavorable cervices (modified Bishop score 6 or lower) were randomized to receive oral misoprostol every 4 hours, up to four doses, with or without isosorbide mononitrate every 6 hours, up to two doses. A strict protocol was used, including timing of oxytocin use and amniotomy. Side effects were assessed 6 hours after study initiation. One hundred forty-two patients were required to detect a change in time to vaginal delivery of 4 hours (alpha=.05 and beta=.20). Data were analyzed by intent to treat. Student's t, chi square, Fisher's exact, and Mann-Whitney tests were used where appropriate with P< or =.05 deemed significant.One hundred fifty-six women were randomized; three were excluded after randomization. Seventy-eight women received misoprostol, and 78 received misoprostol with isosorbide mononitrate. Demographic characteristics were similar between groups. The time to vaginal delivery was not reduced when isosorbide mononitrate was added to misoprostol. Cesarean delivery rates and contraction and fetal heart rate abnormalities were similar between groups. Side effects were also similar between groups, except that women given isosorbide mononitrate experienced headaches more often. Neonatal outcomes were similar between groups.The addition of vaginal isosorbide mononitrate to oral misoprostol for cervical ripening and labor induction did not reduce time to vaginal delivery and was associated with a greater incidence of headache.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00374621.I.

  View details for Web of Science ID 000278998600019

  View details for PubMedID 20567177

• Single- versus double-layer hysterotomy closure at primary caesarean delivery and bladder adhesions BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY Blumenfeld, Y. J., Caughey, A. B., El-Sayed, Y. Y., Daniels, K., Lyell, D. J. 2010; 117 (6): 690-694

  Abstract

  To determine the association between single-layer (one running suture) and double-layer (second layer or imbricating suture) hysterotomy closure at primary caesarean delivery and subsequent adhesion formation.A secondary analysis from a prospective cohort study of women undergoing first repeat caesarean section.Department of Obstetrics and Gynecology, Stanford University, Stanford, CA, USA.One hundred and twenty-seven pregnant women undergoing first repeat caesarean section.Patient records were reviewed to identify whether primary caesarean hysterotomies were closed with a single or double layer. Data were analysed by Fisher's exact tests and multivariable logistic regression.Prevalence rate of pelvic and abdominal adhesions.Of the 127 women, primary hysterotomy closure was single layer in 56 and double layer in 71. Single-layer hysterotomy closure was associated with bladder adhesions at the time of repeat caesarean (24% versus 7%, P = 0.01). Single-layer closure was associated in this study with a seven-fold increase in the odds of developing bladder adhesions (odds ratio, 6.96; 95% confidence interval, 1.72-28.1), regardless of other surgical techniques, previous labour, infection and age over 35 years. There was no association between single-layer closure and other pelvic or abdominal adhesions.Primary single-layer hysterotomy closure may be associated with more frequent bladder adhesions during repeat caesarean deliveries. The severity and clinical implications of these adhesions should be assessed in large prospective trials.

  View details for DOI 10.1111/j.1471-0528.2010.02529.x

  View details for Web of Science ID 000276509100007

  View details for PubMedID 20236104

• Daily Compared With 8-Hour Gentamicin for the Treatment of Intrapartum Chorioamnionitis A Randomized Controlled Trial 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Lyell, D. J., Pullen, K., Fuh, K., Zamah, M., Caughey, A. B., Benitz, W., El-Sayed, Y. Y. LIPPINCOTT WILLIAMS & WILKINS. 2010: 344–49

  Abstract

  To assess whether daily gentamicin is as effective as 8-hour gentamicin for the treatment of intrapartum chorioamnionitis.Women with a clinical diagnosis of chorioamnionitis between 32 and 42 weeks of gestation were randomly assigned in labor to receive either daily gentamicin (5 mg/kg intravenously (IV), then 2 placebo doses IV after 8 and 16 hours) or 8-hour gentamicin (2 mg/kg IV, then 1.5 mg/kg IV after 8 and 16 hours). Both groups received ampicillin (2 grams IV every 6 hours for a total of four doses). Patients who underwent cesarean delivery also received clindamycin (900 mg IV every 8 hours, for a total of three doses). The primary outcome was treatment success, defined by resolution of chorioamnionitis after 16 hours of treatment without development of endometritis. One hundred twenty-six patients were required to have 95% confidence that daily gentamicin is at worst 15% inferior to 8-hour dosing with an alpha of .05 and a beta of 0.2.One hundred twenty-six women were enrolled, of whom 63 received daily gentamicin and 63 received 8-hour gentamicin. One patient was excluded from data analysis. Baseline maternal and obstetric characteristics were similar between groups except for longer mean duration of ruptured membranes in the 8-hour group (679+/-514 compared with 469+/-319 minutes; P =.03). Treatment success was equal between groups (94% daily gentamicin compared with 89% 8-hour gentamicin, P =.53). There were no differences in maternal or neonatal morbidities, including neonatal sepsis and newborn hearing screen.Daily and 8-hour gentamicin appear equally effective for the treatment of intrapartum chorioamnionitis.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00185991.I.

  View details for Web of Science ID 000273872500020

  View details for PubMedID 20093909

• Cost-effectiveness of external cephalic version for term breech presentation BMC PREGNANCY AND CHILDBIRTH Tan, J. M., Macario, A., Carvalho, B., Druzin, M. L., El-Sayed, Y. Y. 2010; 10

  Abstract

  External cephalic version (ECV) is recommended by the American College of Obstetricians and Gynecologists to convert a breech fetus to vertex position and reduce the need for cesarean delivery. The goal of this study was to determine the incremental cost-effectiveness ratio, from society's perspective, of ECV compared to scheduled cesarean for term breech presentation.A computer-based decision model (TreeAge Pro 2008, Tree Age Software, Inc.) was developed for a hypothetical base case parturient presenting with a term singleton breech fetus with no contraindications for vaginal delivery. The model incorporated actual hospital costs (e.g., $8,023 for cesarean and $5,581 for vaginal delivery), utilities to quantify health-related quality of life, and probabilities based on analysis of published literature of successful ECV trial, spontaneous reversion, mode of delivery, and need for unanticipated emergency cesarean delivery. The primary endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted year of life gained. A threshold of $50,000 per quality-adjusted life-years (QALY) was used to determine cost-effectiveness.The incremental cost-effectiveness of ECV, assuming a baseline 58% success rate, equaled $7,900/QALY. If the estimated probability of successful ECV is less than 32%, then ECV costs more to society and has poorer QALYs for the patient. However, as the probability of successful ECV was between 32% and 63%, ECV cost more than cesarean delivery but with greater associated QALY such that the cost-effectiveness ratio was less than $50,000/QALY. If the probability of successful ECV was greater than 63%, the computer modeling indicated that a trial of ECV is less costly and with better QALYs than a scheduled cesarean. The cost-effectiveness of a trial of ECV is most sensitive to its probability of success, and not to the probabilities of a cesarean after ECV, spontaneous reversion to breech, successful second ECV trial, or adverse outcome from emergency cesarean.From society's perspective, ECV trial is cost-effective when compared to a scheduled cesarean for breech presentation provided the probability of successful ECV is > 32%. Improved algorithms are needed to more precisely estimate the likelihood that a patient will have a successful ECV.

  View details for DOI 10.1186/1471-2393-10-3

  View details for Web of Science ID 000296428000001

  View details for PubMedID 20092630

• Second-Trimester Serum Cytokines in Women Who Develop Spontaneous Preterm Labor at Less than 28 Weeks' Gestation versus Term Labor AMERICAN JOURNAL OF PERINATOLOGY Yang, Q., El Sayed, Y., Shaw, G. M., Fu, J., Schilling, J., Madan, A. 2010; 27 (1): 31-36

  Abstract

  We sought to determine if there is a relationship between serum concentrations of cytokines and the development of preterm labor. A panel of 28 cytokines was measured using the multiplex assay in serum samples collected between 15 and 18 weeks' gestation from women who developed spontaneous preterm labor and delivered between 24 and 28 weeks' gestation (N = 25) and from women who delivered at term (>or=37 weeks; N = 25). Sixteen of the 28 cytokines measured were detected. Except for vascular endothelial growth factor, which showed a trend toward a significant increase in patients who developed preterm labor, there was no difference in cytokine levels between groups in preterm labor and in term labor. Serum cytokine changes in women who develop spontaneous preterm labor possibly occur in the period between 18 weeks' gestation and the onset of labor.

  View details for DOI 10.1055/s-0029-1234037

  View details for Web of Science ID 000273825200006

  View details for PubMedID 19644787

• The effect of ruptured membranes on early neonatal sepsis 30th Annual Clinical Meeting of the Society-for-Maternal-Fetal-Medicine Blumenfeld, Y., Lee, H., Gould, J., Greenberg, M., Sung, J., El-Sayed, Y. MOSBY-ELSEVIER. 2009: S168–S168

  View details for Web of Science ID 000279559500437

• Comprehensive maternal-fetal pharmacogenomics - a novel pharmacogenomic thumbprint 30th Annual Clinical Meeting of the Society-for-Maternal-Fetal-Medicine Blumenfeld, Y., Fan, C., Sangkuhl, K., Altman, R., El-Sayed, Y., Quake, S. MOSBY-ELSEVIER. 2009: S254–S254

  View details for Web of Science ID 000279559500695

• Hepatocyte growth factor (HGF) is upregulated at the fetomaternal junction in preeclamptic placentas 30th Annual Clinical Meeting of the Society-for-Maternal-Fetal-Medicine Sung, J., Fan, X., Nguyen, T., Dhal, S., El-Sayed, Y., Druzin, M., Nayak, N. MOSBY-ELSEVIER. 2009: S269–S269

  View details for Web of Science ID 000279559500740

• Do ruptured membranes remote from term affect neonatal mortality? 30th Annual Clinical Meeting of the Society-for-Maternal-Fetal-Medicine Blumenfeld, Y., Lee, H., Gould, J., Langen, E., Jafari, A., El-Sayed, Y. MOSBY-ELSEVIER. 2009: S167–S168

  View details for Web of Science ID 000279559500436

• Multiple Cytokine Profile in Plasma and Amniotic Fluid in a Mouse Model of Pre-Term Labor AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY Yang, Q., El-Sayed, Y., Rosenberg-Hasson, Y., Hirschberg, D. L., Nayak, N. R., Schilling, J., Madan, A. 2009; 62 (5): 339-347

  Abstract

  The rate of pre-term birth in the United States continues to rise despite several interventions. Induction of pro-inflammatory cytokines and chemokines has been implicated in the activation of the cascade of events resulting in pre-term labor. To date, no comprehensive panel of the cytokine profile in PTL has been published.To address cytokine profiles in pre-term labor, levels of 19 plasma and amniotic fluid cytokines were measured using a multiplex immunoassay in an inflammation-induced murine model of pre-term labor.Pro-inflammatory mediators, RANTES, KC, IL-6, and IL-12p40 were increased by 3 hr and remained high at 15 hr. Concentrations of KC, IL-6, IL-1beta, and MIP-1alpha were increased in the amniotic fluid at 15 hr. Plasma levels of anti-inflammatory mediators IL-10 and IL-13 at 15 hr were unchanged and decreased respectively.These results suggest that stimulation of several pro-inflammatory cytokines occurs very early in the cascade of events and remains increased, whereas anti-inflammatory cytokines are either unchanged or decreased until the onset of delivery in an inflammation-induced mouse model of pre-term labor.

  View details for DOI 10.1111/j.1600-0897.2009.00743.x

  View details for Web of Science ID 000270610900009

  View details for PubMedID 19811468

• Microfluidic digital PCR enables rapid prenatal diagnosis of fetal aneuploidy 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Fan, H. C., Blumenfeld, Y. J., El-Sayed, Y. Y., Chueh, J., Quake, S. R. MOSBY-ELSEVIER. 2009

  Abstract

  The purpose of this study was to demonstrate that digital polymerase chain reaction (PCR) enables rapid, allele independent molecular detection of fetal aneuploidy.Twenty-four amniocentesis and 16 chorionic villus samples were used for microfluidic digital PCR analysis. Three thousand and sixty PCR reactions were performed for each of the target chromosomes (X, Y, 13, 18, and 21), and the number of single molecule amplifications was compared to a reference. The difference between target and reference chromosome counts was used to determine the ploidy of each of the target chromosomes.Digital PCR accurately identified all cases of fetal trisomy (3 cases of trisomy 21, 3 cases of trisomy 18, and 2 cases of triosmy 13) in the 40 specimens analyzed. The remaining specimens were determined to have normal ploidy for the chromosomes tested.Microfluidic digital PCR allows detection of fetal chromosomal aneuploidy utilizing uncultured amniocytes and chorionic villus tissue in less than 6 hours.

  View details for DOI 10.1016/j.ajog.2009.03.002

  View details for Web of Science ID 000265253800029

  View details for PubMedID 19375573

• Successful pregnancy and cesarean delivery via noninvasive ventilation in mitochondrial myopathy JOURNAL OF PERINATOLOGY Yuan, N., El-Sayed, Y. Y., Ruoss, S. J., Riley, E., Enns, G. M., Robinson, T. E. 2009; 29 (2): 166-167

  Abstract

  We report a case study of a 22-year-old woman with mitochondrial thymidine kinase 2 deficiency and chronic respiratory failure due to severe neuromuscular weakness requiring noninvasive positive pressure ventilation (NIPPV) since 12 years of age. During pregnancy and cesarean delivery, she was successfully supported with NIPPV. A multidisciplinary team approach should be used in pregnant patients with these disorders with specific attention to management of pulmonary complications, selection of route of delivery, anesthesia, and analgesia.

  View details for DOI 10.1038/jp.2008.178

  View details for Web of Science ID 000263492700016

  View details for PubMedID 19177045

• Maintenance Nifedipine Tocolysis Compared With Placebo A Randomized Controlled Trial 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Lyell, D. J., Pullen, K. M., Mannan, J., Chitkara, U., Druzin, M. L., Caughey, A. B., El-Sayed, Y. Y. LIPPINCOTT WILLIAMS & WILKINS. 2008: 1221–26

  Abstract

  To estimate whether maintenance nifedipine tocolysis after arrested preterm labor prolongs pregnancy and improves neonatal outcomes.A prospective, randomized double-blind, multicenter study was conducted. After successful tocolysis, patients were randomly assigned to receive 20 mg nifedipine or an identical-appearing placebo every 4-6 hours until 37 weeks of gestation. The primary outcome was attainment of 37 weeks of gestation. Patients were enrolled between 24 weeks and 34 weeks if they had six or fewer contractions per hour, intact membranes, and less than 4 cm cervical dilation. Exclusion criteria were placental abruption or previa, fetal anomaly incompatible with life, or maternal medical contraindication to tocolysis. Sixty-six patients were required for 80% power to detect a 50% reduction in birth before 37 weeks, with a two-tailed alpha of 0.05. Data were analyzed by intent to treat.Seventy-one patients were randomly assigned. Two patients were excluded after randomization and one was lost to follow-up. Thirty-five patients received placebo, and 33 received nifedipine. There were no maternal demographic differences between groups; the placebo group was significantly more dilated and effaced at study entry. There was no difference in attainment of 37 weeks (39% nifedipine compared with 37% placebo, P>.91), mean delay of delivery (33.5+/-19.9 days nifedipine compared with 32.6+/-21.4 days placebo, P=.81) or delay of delivery for greater than 48 hours or 1, 2, 3, or 4 weeks. Neonatal outcomes were similar between groups.When compared with placebo, maintenance nifedipine tocolysis did not confer a large reduction in preterm birth or improvement in neonatal outcomes.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00185952I.

  View details for Web of Science ID 000261316200006

  View details for PubMedID 19037029

• DIGITAL PCR ENABLES RAPID PRENATAL DIAGNOSIS OF FETAL ANEUPLOIDY 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Fan, C., Blumenfeld, Y., Chueh, J., El-Sayed, Y., Quake, S. MOSBY-ELSEVIER. 2008: S30–S30

  View details for DOI 10.1016/j.ajog.2008.09.089

  View details for Web of Science ID 000262205700066

• RANDOMIZED CLINICAL TRIAL OF CERVICAL RIPENING AND LABOR INDUCTION USING ORAL MISOPROSTOL WITH OR WITHOUT INTRAVAGINAL ISOSORBIDE MONONITRATE 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Collingham, J., Fuh, K., Caughey, A., Pullen, K., Lyell, D., Druzin, M., Kogut, E., El-Sayed, Y. MOSBY-ELSEVIER. 2008: S53–S53

  View details for DOI 10.1016/j.ajog.2008.09.172

  View details for Web of Science ID 000262205700146

• Perinatal outcomes among Asian-white interracial couples 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Nystrom, M. J., Caughey, A. B., Lyell, D. J., Druzin, M. L., El-Sayed, Y. Y. MOSBY-ELSEVIER. 2008

  Abstract

  To investigate whether perinatal outcomes among interracial Asian-white couples are different than among Asian-Asian and white-white couples.This was a retrospective study of Asian, white, and Asian-white couples delivered at the Lucile Packard Children's Hospital from 2000-2005. Asian-white couples were subdivided into white-mother/Asian-father or Asian-mother/white-father. Perinatal outcomes included gestational diabetes, hypertensive disorders of pregnancy, preterm delivery, birth weight >4000 g and <2500 g, and cesarean delivery.In the study population of 868 Asian-white, 3226 Asian, and 5575 white couples there were significant outcome differences. Compared with white couples, Asian-white couples had an increased incidence of gestational diabetes (aOR 2.4 for white-mother/Asian-father and aOR 2.6 for Asian-mother/white-father), though not as high as Asian couples (aOR 4.7). Asian-white couples had larger babies (median 3360 g for Asian-mother/white-father and 3320 g for white-mother/Asian-father vs 3210 g for Asian, P < .001), but only Asian-mother/white-father couples had an increased rate of cesarean delivery (aOR 1.3-2.0).Significant differences in perinatal outcomes exist between Asian, white, and interracial Asian-white couples.

  View details for DOI 10.1016/j.ajog.2008.06.065

  View details for Web of Science ID 000260045700021

  View details for PubMedID 18928981

• Two cases of cholestasis in the first trimester of pregnancy after ovarian hyperstimulation FERTILITY AND STERILITY Zamah, A. M., El-Sayed, Y. Y., Milki, A. A. 2008; 90 (4)

  Abstract

  To report two cases of early onset cholestasis of pregnancy associated with IVF and ovarian hyperstimulation syndrome.Case report.University-based IVF program.Two patients with first-trimester cholestasis of pregnancy after IVF that was associated with ovarian hyperstimulation syndrome.In vitro fertilization-embryo transfer, management of hyperstimulation syndrome, and cholestasis of pregnancy.Clinical pregnancy course and pregnancy outcomes.The first patient was treated with ursodeoxycholic acid and had resolution of symptoms within the first trimester. The second patient initially had a miscarriage but did redevelop cholestasis of pregnancy in the latter stages of a pregnancy resulting from frozen embryo transfer.We report two cases of intrahepatic cholestasis of pregnancy in the first trimester of pregnancies by IVF in association with ovarian hyperstimulation syndrome and markedly elevated maternal serum estrogen levels. Early recognition of this unusual clinical presentation allows for optimal pregnancy management by both the reproductive endocrinologist and the obstetrician.

  View details for DOI 10.1016/j.fertnstert.2007.08.072

  View details for Web of Science ID 000207699700028

  View details for PubMedID 18929050

• Population trends in cesarean delivery for breech presentation in the United States, 1997-2003 Annual Meeting of the Pediatric-Academic-Societies/Society-of-Pediatric-Research Lee, H. C., El-Sayed, Y. Y., Gould, J. B. MOSBY-ELSEVIER. 2008

  Abstract

  The objective of the study was to determine whether cesarean delivery for breech has increased in the United States.We calculated cesarean rates for term singletons in breech/malpresentation from 1997 to 2003 using National Center for Health Statistics data. We compared rates by sociodemographic groups and state. Multivariable logistic regression models were constructed to see whether factors associated with cesarean delivery differed over time.Breech cesarean rates increased overall from 83.8% to 85.1%. There was a significant increase in rates for most sociodemographic groups. There was little to no increase for mothers younger than 30 years old. There was wide variability in rates by state, 61.6-94.2% in 1997. Higher breech incidence correlated with lower cesarean rates, suggesting potential state bias in reporting breech.In the United States, breech infants are predominantly born by cesarean. There was a small increase in this trend from 1998 to 2002. There is wide variability by state, which is not explained by sociodemographic patterns and may be due to reporting differences.

  View details for DOI 10.1016/j.ajog.2007.11.059

  View details for Web of Science ID 000257205200021

  View details for PubMedID 18295181

  View details for PubMedCentralID PMC2533265

• Antibiotic prophylaxis for prevention of postpartum perineal wound complications - A randomized controlled trial 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine Duggal, N., Mercado, C., Daniels, K., Bujor, A., Caughey, A. B., El-Sayed, Y. Y. LIPPINCOTT WILLIAMS & WILKINS. 2008: 1268–73

  Abstract

  To estimate whether prophylactic antibiotics at the time of repair of third- or fourth-degree perineal tears after vaginal delivery prevent wound infection and breakdown.This was a prospective, randomized, placebo-controlled study. Patients who sustained third- or fourth-degree perineal tears after a vaginal delivery were recruited for the study. Each patient was given a single intravenous dose of a second-generation cephalosporin (cefotetan or cefoxitin) or placebo before repair of third- or fourth-degree perineal tears. Obstetricians and patients were blinded to study drug. The perineum was inspected for evidence of infection or breakdown at discharge from the hospital and at 2 weeks postpartum. Primary end points were gross disruption or purulent discharge at site of perineal repair by 2 weeks postpartum.One hundred forty-seven patients were recruited for the study. Of these, 83 patients received placebo and 64 patients received antibiotics. Forty patients (27.2%) did not return for their 2-week appointment. Of the patients seen at 2 weeks postpartum, 4 of 49 (8.2%) patients who received antibiotics and 14 of 58 (24.1%) patients who received placebo developed a perineal wound complication (P=.037). There were no differences between groups in parity, incidence of diabetes, operative delivery, or third-degree compared with fourth-degree lacerations.By 2 weeks postpartum, patients who received prophylactic antibiotics at the time of third- or fourth-degree laceration repair had a lower rate of perineal wound complications than patients who received placebo.ClinicalTrials.gov, www.clincaltrials.gov, NCT00186082.I.

  View details for Web of Science ID 000256191400003

  View details for PubMedID 18515507

• Concealed maternal blood glucose excursions correlate with birth weight centile. Journal of diabetes science and technology Taslimi, M. M., Navabi, K., Acosta, R., Helmer, A., El-Sayed, Y. Y. 2008; 2 (3): 456-460

  Abstract

  The objective of this study was to test the hypothesis that maternal blood glucose excursions correlate with deviation from optimized birth weight.Patients were recruited for 3-day continuous glucose monitoring (CGM) plus self-blood glucose monitoring followed by routine diabetes screening at 26-28 weeks gestation. Patients and caregivers were blinded to CGM results. The magnitude and duration of blood glucose (BG) excursions were measured as a "glycemia index." A customized birth weight centile was calculated.Twenty-three patients consented, 21 completed the study: 5 diabetic and 16 nondiabetic individuals. The duration of CGM was 72 (+/-7.2) hours, and each patient performed self-BG monitoring >/=3 times per day. All diabetic and 10 nondiabetic patients had several measured BG excursions above 130 mg/dl. A positive correlation was observed between birth weight centile and glycemia index above 130 (p < 0.03); the trend persisted for nondiabetic patients alone (p < 0.05). No significant correlation was noted between birth weight centile and average 3-day CGM values, 3-day fasting BG, average 3-day self-BG monitoring values, or diabetes screening BG value.The glycemia index has a better correlation with birth weight centile than BG measured by conventional methods in a mixed diabetic and nondiabetic population. Fetal exposure to maternal blood glucose excursions correlates positively with fetal growth, even in nondiabetic patients with apparently normal glucose tolerance.

  View details for PubMedID 19885210

• Alpha-thalassemia and limb defects in humans: A possible hypoxic mechanism? Adam, M. P., Chueh, J., El-Sayed, Y. Y., Stenzel, A., Vogel, H., Weaver, D. D., Hoyme, H. E. WILEY-BLACKWELL. 2008: 315–15

  View details for Web of Science ID 000256655000057

• Pre-eclampsia and nasal CPAP: Part 1. Early intervention with nasal CPAP in pregnant women with risk-factors for pre-eclampsia: Preliminary findings SLEEP MEDICINE Guillerninault, C., Palombini, L., Poyares, D., Takaoka, S., Huynh, N. T., El-Sayed, Y. 2007; 9 (1): 9-14

  Abstract

  Pre-eclampsia is a leading cause of maternal-fetal morbidity and mortality. Significant overlap exists between the risk factors for pre-eclampsia and sleep-disordered breathing. Nasal continuous positive airway pressure (CPAP) has been proposed as therapy for pre-eclampsia. This prospective, longitudinal study was designed to characterize sleep-related breathing patterns in pregnant women with pre-eclampsia risk factors, and to describe the effects of early nasal CPAP therapy in these patients.Twelve pregnant women with pre-eclampsia risk factors underwent polysomnography to characterize sleep-related breathing abnormalities and baseline blood pressure determination. Patients with airflow-limitation underwent nasal CPAP titration and were treated with optimal pressures. Periodic assessments of CPAP compliance and tolerance, sleep quality, and blood pressure control were performed until delivery or pre-eclampsia onset. CPAP retitration was performed between weeks 20 and 22 of pregnancy.Mean respiratory disturbance index was 8.5+/-2.6 events/h of sleep, and initial nasal CPAP pressures were 5-6 cm H(2)O with an increase to 6-9 cm H2O after recalibration. All subjects with chronic hypertension maintained blood pressures below 140/90 with a mean diurnal blood pressure of 122+/-2.5 mmHg over 83+/-1.5 mmHg. Patient characteristics of obesity and prior pre-eclampsia were associated with pregnancies complicated by spontaneous abortion, premature delivery, or pre-eclampsia.Early application of nasal CPAP in pregnant women alleviated sleep-related breathing disturbances but was not sufficient to prevent negative pregnancy outcomes. Obesity and prior pre-eclampsia appeared to be important factors and were associated with the worst complications. However, nasal positive pressure may still be beneficial to decrease severity of outcomes, particularly if individualized to patient risk factors, more particularly hypertension at pregnancy onset.

  View details for DOI 10.1016/j.sleep.2007.04.020

  View details for Web of Science ID 000252696300003

  View details for PubMedID 17644420

• Once daily vs. 8-hour gentamicin dosing for chorioamnionitis 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Pullen, K., Zamah, M., Fuh, K., Caughey, A., Benitz, W., Lyell, D., El-Sayed, Y. MOSBY-ELSEVIER. 2007: S68–S68

  View details for Web of Science ID 000251708500204

• Bacterial flora-typing with targeted, chip-based Pyrosequencing BMC MICROBIOLOGY Sundquist, A., Bigdeli, S., Jalili, R., Druzin, M. L., Waller, S., Pullen, K. M., El-Sayed, Y. Y., Taslimi, M. M., Batzoglou, S., Ronaghi, M. 2007; 7

  Abstract

  The metagenomic analysis of microbial communities holds the potential to improve our understanding of the role of microbes in clinical conditions. Recent, dramatic improvements in DNA sequencing throughput and cost will enable such analyses on individuals. However, such advances in throughput generally come at the cost of shorter read-lengths, limiting the discriminatory power of each read. In particular, classifying the microbial content of samples by sequencing the < 1,600 bp 16S rRNA gene will be affected by such limitations.We describe a method for identifying the phylogenetic content of bacterial samples using high-throughput Pyrosequencing targeted at the 16S rRNA gene. Our analysis is adapted to the shorter read-lengths of such technology and uses a database of 16S rDNA to determine the most specific phylogenetic classification for reads, resulting in a weighted phylogenetic tree characterizing the content of the sample. We present results for six samples obtained from the human vagina during pregnancy that corroborates previous studies using conventional techniques.Next, we analyze the power of our method to classify reads at each level of the phylogeny using simulation experiments. We assess the impacts of read-length and database completeness on our method, and predict how we do as technology improves and more bacteria are sequenced. Finally, we study the utility of targeting specific 16S variable regions and show that such an approach considerably improves results for certain types of microbial samples. Using simulation, our method can be used to determine the most informative variable region.This study provides positive validation of the effectiveness of targeting 16S metagenomes using short-read sequencing technology. Our methodology allows us to infer the most specific assignment of the sequence reads within the phylogeny, and to identify the most discriminative variable region to target. The analysis of high-throughput Pyrosequencing on human flora samples will accelerate the study of the relationship between the microbial world and ourselves.

  View details for DOI 10.1186/1471-2180-7-108

  View details for Web of Science ID 000253968300001

  View details for PubMedID 18047683

• Magnesium sulfate compared with nifedipine for acute tocolysis of preterm labor: A Randomized controlled trial - In reply OBSTETRICS AND GYNECOLOGY Lyell, D. J., El-Sayed, Y. Y. 2007; 110 (5): 1171-1171

  View details for Web of Science ID 000250360800036

• Randomized comparison of intravenous terbutaline vs nitroglycerin for acute intrapartum fetal resuscitation 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine Pullen, K. M., Riley, E. T., Waller, S. A., Taylor, L., Caughey, A. B., Druzin, M. L., El-Sayed, Y. Y. MOSBY-ELSEVIER. 2007

  Abstract

  The purpose of this study was to compare terbutaline and nitroglycerin for acute intrapartum fetal resuscitation.Women between 32-, 42 weeks' gestation were assigned randomly to 250 microg of terbutaline or 400 microg nitroglycerin intravenously for nonreassuring fetal heart rate tracings in labor. The rate of successful acute intrapartum fetal resuscitation and the maternal hemodynamic changes were compared. Assuming a 50% failure rate in the terbutaline arm, we calculated that a total of 110 patients would be required to detect a 50% reduction in failure in the nitroglycerin group (50% to 25%), with an alpha value of .05, a beta value of .20, and a power of 80%.One hundred ten women had nonreassuring fetal heart rate tracings in labor; 57 women received terbutaline, and 53 women received nitroglycerin. Successful acute resuscitation rates were similar (terbutaline 71.9% and nitroglycerin 64.2%; P = .38). Terbutaline resulted in lower median contraction frequency per 10 minutes (2.9 [25-75 percentile, 1.7- 3.3] vs 4 [25-75 percentile, 2.5- 5]; P < .002) and reduced tachysystole (1.8% vs 18.9%; P = .003). Maternal mean arterial pressures decreased with nitroglycerin (81-76 mm Hg; P = .02), but not terbutaline (82-81 mm Hg; P = .73).Although terbutaline provided more effective tocolysis with less impact on maternal blood pressure, no difference was noted between nitroglycerin and terbutaline in successful acute intrapartum fetal resuscitation.

  View details for DOI 10.1016/j.ajog.2007.06.063

  View details for Web of Science ID 000250097300031

  View details for PubMedID 17904983

• Cesarean delivery outcomes after a prolonged second stage of labor 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine Sung, J. F., Daniels, K. I., Brodzinsky, L., El-Sayed, Y. Y., Caughey, A. B., Lyell, D. J. MOSBY-ELSEVIER. 2007

  Abstract

  We hypothesized that prolonged second stage of labor increases the incidence of unintentional hysterotomy extensions at cesarean delivery.A retrospective cohort of term pregnant women who underwent primary cesarean delivery after failed second stage of labor at Stanford University was assessed for hysterotomy extensions and other maternal and neonatal morbidities. Groups included second stage length of 1-3 hours and >4 hours. Data were analyzed with the use of chi-square and Fisher's exact tests.Of the 239 women who were studied, the second stage of labor lasted 1-3 hours in 82 patients and >4 hours in 157 patients. Prolonged second stage of labor was associated with unintentional hysterotomy extensions (40% vs 26%; P = .03), particularly to the cervix (29% vs 5%; P = .005), and with surgery that lasted >90 minutes (9% vs 1%; P = .01). The incidence of hysterotomy extensions was associated positively with the length of the second stage. Other maternal and neonatal morbidities were similar between groups.Prolonged second stage of labor is associated with an increase in unintentional hysterotomy extensions at cesarean delivery and prolonged operative time. The future risk of hysterotomy extensions merits further investigation.

  View details for DOI 10.1016/j.ajog.2007.07.005

  View details for Web of Science ID 000249531300033

  View details for PubMedID 17826431

• Magnesium sulfate compared with nifedipine for acute tocolysis of preterm labor - A randomized controlled trial 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Lyell, D. J., Pullen, K., Campbell, L., Ching, S., Druzin, M. L., Chitkara, U., Burrs, D., Caughey, A. B., El-Sayed, Y. Y. LIPPINCOTT WILLIAMS & WILKINS. 2007: 61–67

  Abstract

  To compare the efficacy and side effects of intravenous magnesium to oral nifedipine for acute tocolysis of preterm labor.A multicenter randomized trial was performed. Patients in active preterm labor who were at 24 to 33 weeks and 6 days of gestation were randomly assigned to receive magnesium sulfate or nifedipine. The primary outcome was arrest of preterm labor, defined as prevention of delivery for 48 hours with uterine quiescence.One hundred ninety-two patients were enrolled. More patients assigned to magnesium sulfate achieved the primary outcome (87% compared with 72%, P=.01). There were no differences in delivery within 48 hours (7.6% magnesium sulfate compared with 8.0% nifedipine, P=.92), gestational age at delivery (35.8 compared with 36.0 weeks, P=.61), birth before 37 and 32 weeks (57% compared with 57%, P=.97, and 11% compared with 8%, P=.39), and episodes of recurrent preterm labor. Mild and severe maternal adverse effects were significantly more frequent with magnesium sulfate. Birth weight, birth weight less than 2,500 g, and neonatal morbidities were similar between groups, but newborns in the magnesium sulfate group spent longer in the neonatal intensive care unit (8.8+/-17.7 compared with 4.2+/-8.2 days, P=.007).Patients who received magnesium sulfate achieved the primary outcome more frequently. However, delay of delivery, gestational age at delivery, and neonatal outcomes were similar between groups. Nifedipine was associated with fewer maternal adverse effects.

  View details for Web of Science ID 000247572700011

  View details for PubMedID 17601897

• Perinatal outcomes after successful and failed trials of labor after cesarean delivery. American journal of obstetrics and gynecology El-Sayed, Y. Y., Watkins, M. M., Fix, M., Druzin, M. L., Pullen, K. M., Caughey, A. B. 2007; 196 (6): 583 e1-5

  Abstract

  To compare maternal and neonatal outcomes after successful and failed trials of labor after cesarean in women at term, excluding uterine ruptures, and to examine predictors of successful and failed trials of labor.Matched maternal and neonatal data from 1993-1999 in women with singleton term pregnancies with prior cesarean undergoing trial of labor were reviewed. Women with uterine rupture were excluded. Maternal and neonatal outcomes were analyzed for successful and failed trials. Predictors of success and failure were examined.1284 women and their neonates were available for analysis. 1094 (85.2%) had a vaginal birth and 190 (14.8%) underwent repeat cesarean. Failed trials of labor were associated with higher incidence of choriamnionitis (25.8% vs. 5.5%, P<.001), postpartum hemorrhage (35.8% vs. 15.8%, P<.001), hysterectomy (1% vs. 0%, P=.022), neonatal jaundice (17.4% vs.10.2%, P=.004) and composite major neonatal morbidities (6.3% vs. 2.8%, P=.014).Failed trial of labor in women at term with prior cesarean is associated with increased maternal and neonatal morbidities.

  View details for PubMedID 17547905

• Perinatal outcomes after successful and failed trials of labor after cesarean delivery 73rd Annual Meeting of the Pacific-Coast-Obstetrical-and-Gynecological-Society El-Sayed, Y. Y., Watkins, M. M., Fix, M., Druzin, M. L., Pullen, K. M., Caughey, A. B. MOSBY-ELSEVIER. 2007: 583–85

  View details for DOI 10.1016/j.ajog.2007.03.013

  View details for Web of Science ID 000247137600035

• Use of a community mobile health van to increase early access to prenatal care MATERNAL AND CHILD HEALTH JOURNAL Edgerley, L. P., El-Sayed, Y. Y., Druzin, M. L., Kiernan, M., Daniels, K. I. 2007; 11 (3): 235-239

  Abstract

  To examine whether the use of a community mobile health van (the Lucile Packard Childrens Hospital Women's Health Van) in an underserved population allows for earlier access to prenatal care and increased rate of adequate prenatal care, as compared to prenatal care initiated in community clinics.We studied 108 patients who initiated prenatal care on the van and delivered their babies at our University Hospital from September 1999 to July 2004. One hundred and twenty-seven patients who initiated prenatal care in sites other than the Women's Health Van, had the same city of residence and source of payment as the study group, and also delivered their babies at our hospital during the same time period, were selected as the comparison group. Gestational age at which prenatal care was initiated and the adequacy of prenatal care - as defined by Revised Graduated Index of Prenatal Care Utilization (RGINDEX) - were compared between cases and comparisons.Underserved women utilizing the van services for prenatal care initiated care three weeks earlier than women using other services (10.2 +/- 6.9 weeks vs. 13.2 +/- 6.9 weeks, P = 0.001). In addition, the data showed that van patients and non-van patients were equally likely to receive adequate prenatal care as defined by R-GINDEX (P = 0.125).Women who initiated prenatal care on the Women's Health Van achieved earlier access to prenatal care when compared to women initiating care at other community health clinics.

  View details for DOI 10.1007/s10995-006-0174-z

  View details for Web of Science ID 000246578900005

  View details for PubMedID 17243022

• Is external cephalic version cost-effective? 39th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Tan, J. M., Macario, A., Carvalho, B., El-Sayed, Y. LIPPINCOTT WILLIAMS & WILKINS. 2007: B16–B16

  View details for Web of Science ID 000246032500055

• A cost-analysis of neuraxial analgesia to facilitate external cephalic version 39th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Tan, J. M., Macario, A., El-Sayed, Y., Carvalho, B. LIPPINCOTT WILLIAMS & WILKINS. 2007: B53–B53

  View details for Web of Science ID 000246032500129

• Delivery mode by race for breech presentation in the US JOURNAL OF PERINATOLOGY Lee, H. C., El-Sayed, Y. Y., Gould, J. B. 2007; 27 (3): 147-153

  Abstract

  To determine if there are differential cesarean delivery rates by race and other socio-demographic factors for women with breech infants.We calculated cesarean delivery rates for 186 727 White, African American, Hispanic and Asian women delivering breech singletons with gestational age 26 to 41 weeks born in 1999 and 2000 using data from the National Center for Health Statistics. Multivariable logistic regression was used to determine differences in mode of delivery by race, adjusting for socio-demographic and medical factors.Cesarean rates for breech were >80% in most gestational age groups. In 14 of 18 groups, Whites had higher cesarean delivery rates than African Americans. However, this finding did not persist after risk adjustment. Hispanics were more likely to deliver by cesarean delivery than African Americans and Whites.Breech singleton infants are predominantly born by cesarean delivery. Although African-American women with breech presentation have lower cesarean delivery rates than Whites, this difference is not present after adjusting for socio-demographic and medical factors. Hispanics were more likely to be delivered by cesarean delivery and this difference was amplified after risk adjustment. Asians had slightly lower cesarean rates after risk adjustment, but this varied widely according to Asian subgroup.

  View details for DOI 10.1038/sj.jp.7211668

  View details for Web of Science ID 000244420900003

  View details for PubMedID 17314983

• Cesarean delivery on maternal request: Wise use of finite resources? A view from the trenches SEMINARS IN PERINATOLOGY Druzin, M. L., El-Sayed, Y. Y. 2006; 30 (5): 305-308

  Abstract

  Cesarean section rates are rising in the United States and were at an all time high of 29 percent in 2004. Within this context, the issue of cesarean section on maternal request has been described as being part of a "perfect storm" of medical, legal and personal choice issues, and the lack of an opposing view. An increasing cesarean section rate adds an economic burden on already highly stressed medical systems. There is an incremental cost of cesarean section compared to vaginal delivery. The issue of cost must also be considered more broadly. Rising cesarean section rates are associated with a longer length of stay and a higher occupancy rate. This high occupancy rate leads to the diversion of critical care obstetric transports and has dramatically reduced patient satisfaction. These diversions, and the resultant inability to provide needed care to pregnant women, represent a profound societal cost. These critical care diversions and reduced patient satisfaction also negatively impact a health care institution's financial bottom line and competitiveness. The impact of a rising cesarean section rate on both short and long-term maternal and neonatal complications, and their associated costs, must also be taken into account. The incidence of placenta accreta is increasing in conjunction with the rising cesarean section rate. The added costs associated with this complication (MRI, Interventional Radiology, transfusion, hysterectomy, and intensive care admission) can be prohibitive. It has also been demonstrated that infants born by scheduled cesarean delivery are more likely to require advanced nursery support (with all its associated expense) than infants born to mothers attempting vaginal delivery. The practice of maternal request cesarean section, with limited good data and obvious inherent risk and expense, is increasing in the USA. Patient autonomy and a woman's right to choose her mode of delivery should be respected. However, in our opinion, based on the current evidence regarding cesarean delivery on maternal request, promotion of primary cesarean section on request as a standard of care or as a mandated part of patient counseling for delivery will result in a highly questionable use of finite resources. As of 2004, 46 million Americans did not even have basic health insurance. It is critical that we not allow ourselves to be dragged into the eye of a "perfect storm." This conference is an important step in the rational and objective analysis of this issue.

  View details for DOI 10.1053/j.semperi.2006.07.012

  View details for Web of Science ID 000241449600013

  View details for PubMedID 17011403

• Perinatal outcomes among Asian American and Pacific Islander women 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Rao, A. K., Daniels, K., El-Sayed, Y. Y., Moshesh, M. K., Caughey, A. B. MOSBY-ELSEVIER. 2006: 834–38

  Abstract

  The purpose of this study was to examine perinatal outcomes between Asian American and Pacific Islander subgroups.This is a retrospective study of all Asian American/Pacific Islander women who were delivered at Stanford University Medical Center from 1998 to 2003. Asian American women were subdivided into the following groups: Indian/Pakistani, Chinese, Filipino, Japanese, Korean, Pacific Islanders (individuals from Tonga, Samoa, Guam, or Polynesia), and Vietnamese. Perinatal outcomes included gestational hypertension/preeclampsia, gestational diabetes mellitus, preterm delivery, cesarean delivery, birthweight <2500 g, and birthweight >4000 g.In the study population of 3779 Asian American women, there were statistically significant differences (P < .01) between most of the outcomes that were examined. Filipina women had the highest risk of gestational hypertension/preeclampsia (adjusted odds ratio, 2.21); Indian/Pakistani women had the highest risk of preterm delivery (adjusted odds ratio, 1.67), gestational diabetes mellitus (adjusted odds ratio, 1.39), and low birthweight at term (adjusted odds ratio, 2.30); and Pacific Islander women had the highest risk of macrosomia (adjusted odds ratio, 3.67).Significant differences in perinatal outcomes exist between subgroups of the Asian American and Pacific Islander community. Future research on race/ethnicity and perinatal outcomes should examine heterogeneity among these groups before collapsing these individual subgroups into the larger group "Asian." Individuals should be counseled regarding perinatal risk according to their specific Asian subgroup.

  View details for DOI 10.1016/j.ajog.2006.06.079

  View details for Web of Science ID 000240473500031

  View details for PubMedID 16949421

• Vascular-type disruptive defects in fetuses with homozygous alpha-thalassemia: report of two cases and review of the literature PRENATAL DIAGNOSIS Adam, M. P., Chueh, J., El-Sayed, Y. Y., Stenzel, A., Voge, H., Weaver, D. D., Hoyme, H. E. 2005; 25 (12): 1088-1096

  Abstract

  The thalassemias are an inherited group of heterogeneous anemias in which one or more of the globin chains in the hemoglobin tetramer are absent. Fetuses with homozygous alpha-thalassemia, which is particularly prevalent in people of Southeast Asian extraction, experience deficient alpha-globin chain synthesis and cannot produce hemoglobin F (the primary fetal hemoglobin after 8 weeks' gestation). Instead, they produce an anomalous hemoglobin, hemoglobin Bart's, with an unusually high affinity for oxygen, leading to profound anemia and tissue hypoxia.Here we report on two fetuses with homozygous alpha-thalassemia who displayed structural defects of a vascular disruptive type. Both fetuses demonstrated limb anomalies, including terminal transverse limb deficiencies, and one fetus was found to have a brain malformation consisting of a neuronal migrational defect. The limb anomalies and suspected brain malformation were detected on prenatal ultrasound prior to confirmation of the diagnosis of alpha-thalassemia in one case; in the other case prenatal records were not available. While microcephaly, hydrocephalus, and retarded brain growth have been rarely reported in association with homozygous alpha-thalassemia, this is the first report of a true brain malformation in an affected fetus. Limb anomalies, on the other hand, appear to be more frequent. Recently, aggressive in utero and postnatal therapies for homozygous alpha-thalassemia have been attempted with some success.Our cases and those from the medical literature suggest that couples need to be counseled about the risks of congenital anomalies of a vascular disruptive type in affected fetuses. Furthermore, data from the literature suggests that in utero therapy may not significantly decrease these risks as such anomalies may be present prior to the institution of therapy. In addition, in hydropic infants with vascular disruptive defects, especially in those of Southeast Asian origin, homozygous alpha-thalassemia should be suspected as a likely etiology.

  View details for DOI 10.1002/pd.1276

  View details for Web of Science ID 000234280900003

  View details for PubMedID 16231329

• Perinatal outcomes among Asian Americans/Pacific islanders 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Rao, A. K., Daniels, K., El-Sayed, Y. Y., Moshesh, M. K., Caughey, A. B. MOSBY-ELSEVIER. 2005: S182–S182

  View details for Web of Science ID 000233947800639

• Factors that predict prematurity and preeclampsia in pregnancies that are complicated by systemic lupus erythematosus 71st Annual Meeting of the Central-Association-of-Obstetricians-and-Gynecologists Chakravarty, E. F., Colon, I., Langen, E. S., Nix, D. A., El-Sayed, Y. Y., Genovese, M. C., Druzin, M. L. MOSBY-ELSEVIER. 2005: 1897–1904

  Abstract

  The purpose of this study was to describe the outcomes of a 10-year cohort of pregnancies in patients with systemic lupus erythematosus and to evaluate clinical and laboratory markers for adverse outcomes.We reviewed all pregnancies in patients with systemic lupus erythematosus who were seen at Stanford University from 1991 to 2001. Univariate analyses were performed to identify potential risk factors for adverse outcomes.Sixty-three pregnancies in 48 women were identified. Approximately 35% of the pregnancies occurred in women with previous renal disease and 10% in women with previous central nervous system disease. Flares occurred in 68% of the pregnancies, the majority of which were mild to moderate. Preeclampsia complicated 12 pregnancies. Factors that were associated with premature delivery included prednisone use at conception (relative risk, 1.8), the use of antihypertensive medications (relative risk, 1.8), and a severe flare during pregnancy (relative risk, 2.0). Thrombocytopenia was associated with an increased risk of preeclampsia (relative risk, 3.2).Flares, most of which were mild to moderate, occurred most of the pregnancies in our cohort of patients with systemic lupus erythematosus. Thrombocytopenia, hypertension, and prednisone use may be predictive factors for particular adverse outcomes.

  View details for DOI 10.1016/j.ajog.2005.02.063

  View details for Web of Science ID 000230037600034

  View details for PubMedID 15970846

• Randomized comparison of intravenous nitroglycerin and subcutaneous terbutaline for external cephalic version under tocolysis AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY El-Sayed, Y. Y., Pullen, K., Riley, E. T., Lyell, D., Druzin, M. L., Cohen, S. E., Chitkara, U. 2004; 191 (6): 2051-2055

  Abstract

  The purpose of this study was to compare the efficacy and safety of intravenous nitroglycerin with that of subcutaneous terbutaline as a tocolytic agent for external cephalic version at term.We performed a prospective randomized trial. Patients between 37 and 42 weeks of gestation were assigned randomly to receive either 200 microg of intravenous nitroglycerin therapy or 0.25 mg of subcutaneous terbutaline therapy for tocolysis during external cephalic version. The rate of successful external cephalic version and side effects were compared between groups.Of 59 randomly assigned patients, 30 patients received intravenous nitroglycerin, and 29 patients received subcutaneous terbutaline. The overall success rate of external cephalic version in the study was 39%. The rate of successful external cephalic version was significantly higher in the terbutaline group (55% vs 23%; P = .01). The incidence of palpitations was significantly higher in patients who received terbutaline therapy (17.2% vs 0%; P = .02), as was the mean maternal heart rate at multiple time periods.Compared with intravenous nitroglycerin, subcutaneous terbutaline was associated with a significantly higher rate of successful external cephalic version at term.

  View details for DOI 10.1016/j.ajog.2004.04.040

  View details for Web of Science ID 000225925800030

  View details for PubMedID 15592291

• Medical versus surgical management of biliary tract disease in pregnancy 56th Annual Meeting of the Southwestern-Surgical-Congress Lu, E. J., Curet, M. J., El-Sayed, Y. Y., Kirkwood, K. S. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2004: 755–59

  Abstract

  The management of symptomatic cholelithiasis during pregnancy remains controversial. We compared outcomes after medical versus surgical management of biliary tract disease in pregnant patients.We reviewed the clinical course of patients with symptomatic cholelithiasis during pregnancy from 1992 to 2002 at two university hospitals.Seventy-six women with 78 pregnancies were admitted with biliary tract disease. Of the 63 women who presented with symptomatic cholelithiasis, 10 underwent surgery while pregnant. There were no deaths, preterm deliveries, or intensive care unit admissions. Fifty-three patients were treated medically. Their clinical courses were complicated by symptomatic relapse in 20 patients (38%), by labor induction to control biliary colic (8 patients), and by premature delivery in 2 patients. Each relapse in the medically managed group accounted for an additional five days in hospital.Surgical management of symptomatic cholelithiasis in pregnancy is safe, decreases days in hospital, and reduces the rate of labor induction and preterm deliveries.

  View details for DOI 10.1016/j.amsjurg.2004.09.002

  View details for Web of Science ID 000226183600040

  View details for PubMedID 15619495

• Vaginal versus ultrasound examination of fetal occiput position during the second stage of labor AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Chou, M. R., Kreiser, D., Taslimi, M. M., Druzin, M. L., El-Sayed, Y. Y. 2004; 191 (2): 521-524

  Abstract

  The purpose of this study was to determine whether ultrasonography is more accurate than vaginal examination in the determination of fetal occiput position in the second stage of labor.Eighty-eight patients in the second stage of labor were evaluated by vaginal examination and by combined transabdominal and transperineal ultrasound examination to determine occiput position. These predictions of position were compared with the actual delivery position at vaginal delivery after spontaneous restitution or at cesarean delivery. Different examiners performed the vaginal examinations and the ultrasound examinations. Each examiner was blinded to the determination of the other examiner.Vaginal examination determined fetal occiput position correctly 71.6% of the time; ultrasound examination determined fetal occiput position correctly 92.0% of the time (P=.018).Ultrasound examination is more accurate than vaginal examination in the diagnosis of fetal occiput position in the second stage of labor.

  View details for DOI 10.1016/j.ajog.2004.01.029

  View details for Web of Science ID 000203976500020

  View details for PubMedID 15343230

• Cost-effectiveness of a trial of labor after previous cesarean delivery depends on the a priori chance of success CLINICAL OBSTETRICS AND GYNECOLOGY Macario, A., El-Sayed, Y. Y., Druzin, M. L. 2004; 47 (2): 378-385

  View details for Web of Science ID 000231530600009

  View details for PubMedID 15166861

• Neu-Laxova syndrome: Detailed prenatal diagnostic and post-mortem findings and literature review AMERICAN JOURNAL OF MEDICAL GENETICS PART A Manning, M. A., Cunniff, C. M., Colby, C. E., El-Sayed, Y. Y., Hoyme, H. E. 2004; 125A (3): 240-249

  Abstract

  Neu-Laxova syndrome (NLS) is a lethal, autosomal recessive multiple malformation syndrome with many features resulting from severe skin restriction and decreased fetal movement. It is characterized by ichthyosis, marked intrauterine growth restriction (IUGR), microcephaly, short neck, central nervous system (CNS) anomalies, limb deformities, hypoplastic lungs, edema, and abnormal facial features including severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, and malformed ears. We present two new patients with NLS with striking prenatal diagnostic findings and detailed post-mortem examinations and review the previously described cases in the literature. Data from these patients suggest that the NLS represents a heterogeneous phenotype. Prenatal ultrasound findings of marked ocular proptosis in a growth restricted, edematous fetus should prompt consideration of a diagnosis of the NLS.

  View details for DOI 10.1002/ajmg.a.20467

  View details for Web of Science ID 000189316800004

  View details for PubMedID 14994231

• Central nervous system lupus and pregnancy: 11-year experience at a single center. journal of maternal-fetal & neonatal medicine El-Sayed, Y. Y., Lu, E. J., Genovese, M. C., Lambert, R. E., Chitkara, U., Druzin, M. L. 2002; 12 (2): 99-103

  Abstract

  To describe the pregnancy outcomes in women with central nervous system (CNS) manifestations of lupus.Between 1991 and 2002, the outcome of five pregnancies in four patients with CNS lupus were retrospectively reviewed. All patients had an established history of systemic lupus erythematosus (SLE), and either a history of CNS lupus or active CNS lupus. Pregnancy outcomes assessed included term and preterm birth, intrauterine growth restriction, abnormal antepartum testing, perinatal mortality, pre-eclampsia and other maternal morbidities.Evidence of active CNS lupus symptoms developed in three of the five pregnancies. Two pregnancies were complicated by early onset pre-eclampsia, abnormal antepartum testing and extreme prematurity, with one subsequent neonatal death. The remaining three pregnancies had good neonatal outcomes, but were complicated by severe maternal post-pregnancy exacerbations, and the eventual death of one patient.CNS lupus in pregnancy represents an especially severe manifestation of SLE, and may involve great maternal and fetal risks.

  View details for PubMedID 12420839

• A longitudinal analysis of maternal serum insulin-like growth factor I (IGF-I) and total and nonphosphorylated IGF-binding protein-1 in human pregnancies complicated by intrauterine growth restriction IGFBP 2000 Meeting Bhatia, S., Faessen, G. H., Carland, G., Balise, R. L., Gargosky, S. E., Druzin, M., El-Sayed, Y., Wilson, D. M., Giudice, L. C. ENDOCRINE SOC. 2002: 1864–70

  Abstract

  In cord blood and late gestation maternal serum, IGF-I is positively correlated with birth weight, whereas IGF-binding protein-1 (IGFBP-1) is inversely correlated with birth weight. Our goal was to determine whether maternal serum or amniotic fluid concentrations of IGF-I, IGFBP-1, or nonphosphorylated IGFBP-1 (npIGFBP-1) in early gestation predict later fetal growth abnormalities. Maternal serum was collected prospectively across gestation (5-40 wk) from 749 pregnant subjects. Amniotic fluid was collected after amniocentesis during wk 15-26 from 207 subjects. We compared median serum concentrations of IGF-I, IGFBP-1, and npIGFBP-1 in 38 subjects who delivered growth-restricted infants with the control group of 236 subjects with normal weight infants for each gestational age grouping, wk 5-12, 13-23, and 24-34. In the control group median IGF-I concentrations were 14.8, 11, and 15.6 nmol/liter for wk 5-12, 13-23, and 24-34, respectively, compared with 13.7, 14.3, and 10.6 nmol/liter in the intrauterine growth restriction (IUGR) group. Median IGFBP-1 concentrations were 8.5, 30.4, and 24.4 nmol/liter, respectively, in controls, compared with 11.4, 28.6, and 25.5 nmol/liter in the IUGR group. Median npIGFBP-1 concentrations were 6.9, 22, and 17.4 nmol/liter, respectively, in controls, compared with 5.0, 32.1, and 24.2 nmol/liter in the IUGR group. In the control group the median amniotic fluid IGFBP-1 level was 13,160 nmol/liter, and the median npIGFBP-1 level was 15,970 nmol/liter; in the IUGR group these levels were 13,440 and 18,440 nmol/liter, respectively. No clinically useful differences were found between the IUGR and control groups. Our results do not support the use of maternal serum IGF-I or IGFBP-1 or amniotic fluid IGFBP-1 or npIGFBP-1 early in gestation to predict later fetal growth restriction.

  View details for Web of Science ID 000174963100066

  View details for PubMedID 11932331

• Fetal ear length measurement: a useful predictor of aneuploidy? ULTRASOUND IN OBSTETRICS & GYNECOLOGY Chitkara, U., Lee, L., Oehlert, J. W., Bloch, D. A., Holbrook, R. H., El-Sayed, Y. Y., Druzin, M. L. 2002; 19 (2): 131-135

  Abstract

  To determine the usefulness of short ear length (EL) measurement in the prenatal detection of fetuses with chromosomal abnormalities.Fetal EL measurements, routine biometry and complete anatomic survey for fetal abnormalities were prospectively performed by antenatal sonography.One thousand eight hundred and forty-eight patients with singleton pregnancies undergoing genetic amniocentesis in the second or third trimester.Complete data for EL, biometry and anatomic survey for major structural abnormalities and minor sonographic markers of chromosomal abnormality were available in 1311 fetuses. Of these, 48 (3.7%) had an abnormal karyotype and 1263 (96.3%) had a normal karyotype. Using an EL measurement of < or = 10th percentile for corresponding gestational age in normal fetuses as abnormal cut-off values, detection rates for chromosomal abnormalities by short EL were determined.Among the 48 abnormal karyotypes, 34 were considered significant, and 11 of these 34 (32.4%) fetuses had short EL. In 14 cases, the karyotypic abnormality was considered non-significant and fetal EL was normal in all cases. Of the 34 fetuses with significant chromosomal abnormalities, six (17.6%) on antenatal sonography had no detectable abnormal findings, other than short EL. An increased biparietal diameter (BPD)/EL ratio of > or = 4.0 was also noted in fetuses with an abnormal karyotype, but the sensitivity and predictive value of increased BPD/EL ratio alone or increased BPD/EL ratio in combination with short EL was no better than the sensitivity and predictive value of short EL alone. A combination of short EL and abnormal ultrasound, however, gave a much higher positive predictive value (46%) for significant chromosomal abnormalities.Our findings suggest that in women at high risk for fetal chromosomal abnormality, a short fetal EL measurement on prenatal ultrasound, either alone or in combination with other sonographically detectable structural abnormalities, may be a useful parameter in predicting fetal aneuploidy.

  View details for Web of Science ID 000174123500004

  View details for PubMedID 11876803

• Mask induction with sevoflurane in a parturient with severe tracheal stenosis ANESTHESIOLOGY Ratner, E. F., Cohen, S. E., El Sayed, Y., Druzin, M. 2001; 95 (2): 553-555

  View details for Web of Science ID 000170237800040

  View details for PubMedID 11506134

• Decreased amniotic fluid index in low-risk pregnancy JOURNAL OF REPRODUCTIVE MEDICINE Kreiser, D., El-Sayed, Y. Y., Sorem, K. A., Chitkara, U., Holbrook, R. H., Druzin, M. L. 2001; 46 (8): 743-746

  Abstract

  To evaluate the perinatal outcomes of pregnancies complicated by isolated decreased amniotic fluid volume (AFI) after 30 weeks' gestation (AFI < or = 5 or > 5 cm but < 2.5th percentile).We retrospectively studied 150 low-risk singleton pregnancies > 30 weeks' gestation with decreased AFI. We also compared the outcomes of 57 pregnancies with AFI < or = 5 cm to those of 93 pregnancies with AFI > 5 cm but < 2.5th percentile (borderline AFI). Pregnancy outcome was assessed with respect to antepartum, intrapartum and neonatal measures. Statistical significance (P < .05) between groups was determined by means of the Student t test and chi 2 analysis.There were no statistically significant differences between pregnancies with AFI < or = 5 cm and those with AFI > 5 cm but < 2.5th percentile with respect to labor induction for an abnormal nonstress test (7.0% vs. 7.5%, overall 7.3%), cesarean sections for fetal heart rate abnormalities (7.0% vs. 7.5%, overall 7.3%), presence of meconium (16.1% vs. 15.7%, overall 16%) and Apgar score < 7 at five minutes (0 vs. 1.1%, overall 0.66%). There were no perinatal deaths in either group. Antepartum variable decelerations were more common in pregnancies with AFI < or = 5 cm as compared to those with AFI > 5 cm but < 2.5th percentile (63.1% vs. 45.1%, P = .007; overall 53.3%).With antepartum monitoring, perinatal outcome in low-risk pregnancies with an isolated decreased AFI after 30 weeks' gestation (< or = 5 or > 5 cm but < 2.5th percentile) appears to be good.

  View details for Web of Science ID 000170694100009

  View details for PubMedID 11547649

• Cost-effectiveness of a trial of labor after previous cesarean OBSTETRICS AND GYNECOLOGY Chung, A., Macario, A., El-Sayed, Y. Y., Riley, E. T., Duncan, B., Druzin, M. L. 2001; 97 (6): 932-941

  Abstract

  To determine the cost-effective method of delivery, from society's perspective, in patients who have had a previous cesarean.We completed an incremental cost-effectiveness analysis of a trial of labor relative to cesarean using a computerized model for a hypothetical 30-year old parturient. The model incorporated data from peer-reviewed studies, actual hospital costs, and utilities to quantify health-related quality of life. A threshold of $50,000 per quality-adjusted life-years was used to define cost-effective.The model was most sensitive to the probability of successful vaginal delivery. If the probability of successful vaginal birth after cesarean (VBAC) was less than 0.65, elective repeat cesarean was both less costly and more effective than a trial of labor. Between 0.65 and 0.74, elective repeat cesarean was cost-effective (the cost-effectiveness ratio was less than $50,000 per quality-adjusted life-years), because, although it cost more than VBAC, it was offset by improved outcomes. Between 0.74 and 0.76, trial of labor was cost-effective. If the probability of successful vaginal delivery exceeded 0.76, trial of labor became less costly and more effective. Costs associated with a moderately morbid neonatal outcome, as well as the probabilities of infant morbidity occurring, heavily impacted our results.The cost-effectiveness of VBAC depends on the likelihood of successful trial of labor. Our modeling suggests that a trial of labor is cost-effective if the probability of successful vaginal delivery is greater than 0.74. Improved algorithms are needed to more precisely estimate the likelihood that a patient with a previous cesarean will have a successful vaginal delivery.

  View details for Web of Science ID 000169206300013

  View details for PubMedID 11384699

• New therapies for the pregnant patient with diabetes. Diabetes technology & therapeutics El-Sayed, Y. Y., Lyell, D. J. 2001; 3 (4): 635-640

  Abstract

  Gestational diabetes complicates 3-5% of pregnancies. Of diabetes seen during pregnancy, 10% is pregestational and the remaining 90% represents gestational diabetes. (1,2) Pregnancy in women with pregestational diabetes is especially high risk. Spontaneous abortion, preterm labor, congenital malformations, preeclampsia, macrosomia, birth injury, and cesarean section are all increased in these pregnancies. Deterioration of maternal health during pregnancy, especially in the setting of diabetes-induced end-organ disease, is a real concern. Vigilant surveillance and management of associated disorders such as retinopathy, nephropathy, and chronic hypertension are required. During the preinsulin era, maternal and perinatal mortality in pregnancies complicated by pregestational diabetes was approximately 50%. (1,2) Although modern obstetrical management and the appropriate use of insulin have dramatically improved maternal-fetal outcomes, pregnant patient with diabetes remains at increased risk for complications. There is no doubt that optimizing maternal glucose control is a key element in avoiding established perinatal risks. The most effective means to accomplish this control are topics of active research. Further, hormonal changes during pregnancy can make glycemic control difficult even for the most compliant and educated patient. This paper discusses several new approaches, either currently in practice or under consideration, to pregnancies complicated by diabetes, including oral hypoglycemic agents, lispro, the insulin pump, and transplantation.

  View details for PubMedID 11911177

• Is a trial of labor in a patient who has had a previous cesarean delivery cost-effective? Chung, A. J., Macario, A., El-Sayed, Y. Y., Riley, E. T., Druzin, M. L. LIPPINCOTT WILLIAMS & WILKINS. 2000: U212–U212

  View details for Web of Science ID 000089136800986

• Ultrasonographic ear length measurement in normal second-and third-trimester fetuses AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Chitkara, U., Lee, L., El-Sayed, Y. Y., Holbrook, R. H., Bloch, D. K., Oehlert, J. W., Druzin, M. L. 2000; 183 (1): 230-234

  Abstract

  We sought to develop a nomogram for fetal ear length measurements from a large population of healthy second- and third-trimester fetuses and to investigate the correlation of fetal ear length with other standard fetal biometry measurements, as follows: biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length.Ear length measurement was obtained prospectively in 4240 singleton fetuses between 15 and 40 weeks' gestational age. Either complete data for normal karyotype on amniocentesis or normal infant examination at birth or both were available in 2583 cases. These constituted the final study population.A nomogram was developed by linearly regressing ear length on gestational age (Ear length [in millimeters] = 1.076 x Gestational age [in weeks] - 7. 308). There was a high correlation between ear length and gestational age (r = 0.96; P =.0001).The results of this study provide normative data on growth of fetal ear length from 15 to 40 weeks' gestation. Good correlation was also observed between ear length and other fetal biometric measurements (biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length).

  View details for Web of Science ID 000088565500039

  View details for PubMedID 10920337

• Is a trial of labor in a patient who has had a previous cesarean delivery cost-effective? Chung, A., Macario, A., El-Sayed, Y., Riley, E. T., Duncan, B., Sheinberg, D. LIPPINCOTT WILLIAMS & WILKINS. 2000: U11–U11

  View details for Web of Science ID 000086274300035

• Surgical training in selective pelvic arterial ligation or use of embolization only - Reply AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Chitkara, U., Hansch, E., El-Sayed, Y. 2000; 182 (1): 252-252

  View details for Web of Science ID 000084987100044

• A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Branch, D. W., Peaceman, A. M., Druzin, M., Silver, R. K., El-Sayed, Y., SILVER, R. M., Esplin, M. S., Spinnato, J., Harger, J. 2000; 182 (1): 122-127

  Abstract

  Treatment with heparin and low-dose aspirin improves fetal survival among women with antiphospholipid syndrome. Despite treatment, however, these pregnancies are frequently complicated by preeclampsia, fetal growth restriction, and placental insufficiency, often with the result of preterm birth. Small case series suggest that intravenous immune globulin may reduce the rates of these obstetric complications, but the efficacy of this treatment remains unproven. This pilot study was undertaken to determine the feasibility of a multicenter trial of intravenous immune globulin and to assess the impact on obstetric and neonatal outcomes among women with antiphospholipid syndrome of the addition of intravenous immune globulin to a heparin and low-dose aspirin regimen.This multicenter, randomized, double-blind pilot study compared treatment with heparin and low-dose aspirin plus intravenous immune globulin with heparin and low-dose aspirin plus placebo in a group of women who met strict criteria for antiphospholipid syndrome. All patients had lupus anticoagulant, medium to high levels of immunoglobulin G anticardiolipin antibodies, or both. Patients with a single live intrauterine fetus at

  View details for Web of Science ID 000084987100019

  View details for PubMedID 10649166

• Congenital diaphragmatic hernia: the perinatalogist's perspective. Pediatrics in review Halamek, L. P., El-Sayed, Y. Y. 1999; 20 (10): e67-70

  View details for PubMedID 10512894

• Pelvic arterial embolization for control of obstetric hemorrhage: A five-year experience 66th Annual Meeting of the Central-Association-of-Obstetricians-and-Gynecologists Hansch, E., Chitkara, U., McAlpine, J., El-Sayed, Y., Dake, M. D., Razavi, M. K. MOSBY-ELSEVIER. 1999: 1454–60

  Abstract

  Obstetric hemorrhage is a significant cause of maternal morbidity and death. Postpartum hemorrhage that cannot be controlled by local measures has traditionally been managed by bilateral uterine artery or hypogastric artery ligation. These techniques have a high failure rate, often resulting in hysterectomy. In contrast, endovascular embolization techniques have a success rate of >90%. An additional benefit of the latter procedure is that fertility is maintained. We report our experience at Stanford University Medical Center in which this technique was used in 6 cases within the past 5 years.Six women between the ages of 18 and 41 years underwent placement of arterial catheters for emergency (n = 3) or prophylactic (n = 3) control of postpartum bleeding. Specific diagnoses included cervical pregnancy (n = 1), uterine atony (n = 3), and placenta previa and accreta (n = 2).Control of severe or anticipated postpartum hemorrhage was obtained with transcatheter embolization in 4 patients. A fifth patient had balloon occlusion of the uterine artery performed prophylactically, but embolization was not necessary. In a sixth case, bleeding could not be controlled in time, and hysterectomy was performed. The only complication observed with this technique was postpartum fever in 1 patient, which was treated with antibiotics and resolved within 7 days.Uterine artery embolization is a superior first-line alternative to surgery for control of obstetric hemorrhage. Use of transcatheter occlusion balloons before embolization allows timely control of bleeding and permits complete embolization of the uterine arteries and hemostasis. Given the improved ultrasonography techniques, diagnosis of some potential high-risk conditions for postpartum hemorrhage, such as placenta previa or accreta, can be made prenatally. The patient can then be prepared with prophylactic placement of arterial catheters, and rapid occlusion of these vessels can be achieved if necessary.

  View details for Web of Science ID 000081088200038

  View details for PubMedID 10368488

• Randomized comparison of intravenous nitroglycerin and magnesium sulfate for treatment of preterm labor OBSTETRICS AND GYNECOLOGY El-Sayed, Y. Y., Riley, E. T., Holbrook, R. H., Cohen, S. E., Chitkara, U., Druzin, M. L. 1999; 93 (1): 79-83

  Abstract

  To compare the safety and efficacy of high-dose intravenous (IV) nitroglycerin with those of IV magnesium sulfate for acute tocolysis of preterm labor.Thirty-one women with preterm labor before 35 weeks' gestation were assigned randomly to IV magnesium sulfate or IV nitroglycerin for tocolysis. Preterm labor was defined as the occurrence of at least two contractions in 10 minutes, with cervical change or ruptured membranes. Acute tocolysis was defined as tocolysis for up to 48 hours. Magnesium sulfate was administered as a 4-g bolus, then at a rate of 2-4 g/h. Nitroglycerin was administered as a 100-microg bolus, then at a rate of 1- to 10-microg/kg/min. The primary outcome measure was achievement of at least 12 hours of successful tocolysis.Thirty patients were available for analysis. There were no significant differences in gestational age, cervical dilation, or incidence of ruptured membranes between groups at the initiation of tocolysis. Successful tocolysis was achieved in six of 16 patients receiving nitroglycerin, compared with 11 of 14 receiving magnesium sulfate (37.5 versus 78.6%, P = .033). Tocolytic failures (nitroglycerin versus magnesium sulfate) were due to persistent contractions with cervical change or rupture of previously intact membranes (five of 16 versus two of 14), persistent hypotension (four of 16 versus none of 14), and other severe side effects (one of 16 versus one of 14). Maternal hemodynamic alterations were more pronounced in patients who received nitroglycerin, and 25% of patients assigned to nitroglycerin treatment had hypotension requiring discontinuation of therapy.Tocolytic failures were more common with nitroglycerin than with magnesium sulfate. The hemodynamic alterations noted in patients receiving nitroglycerin, including a 25% incidence of persistent hypotension, might limit the usefulness of IV nitroglycerin for the acute tocolysis of preterm labor.

  View details for Web of Science ID 000077885200017

  View details for PubMedID 9916961

• Diltiazem for maintenance tocolysis of preterm labor: comparison to nifedipine in a randomized trial. The Journal of maternal-fetal medicine El-Sayed, Y. Y., Holbrook, R. H., Gibson, R., Chitkara, U., Druzin, M. L., Baba, D. 1998; 7 (5): 217-221

  Abstract

  The objective of this study was to compare the safety and efficacy of maintenance tocolysis with oral diltiazem to oral nifedipine in achieving 37 weeks gestation. After successful intravenous tocolysis with magnesium sulfate, 69 women with preterm labor at <35 weeks gestation were randomly assigned to nifedipine (20 mg orally every 4-6 hr), or diltiazem (30-60 mg orally every 4-6 hr). The primary outcome was the percentage of patients achieving 37 weeks gestation. Maternal cardiovascular alterations and neonatal outcomes were also assessed. Sixty-nine patients were available for final analysis. Less patients on diltiazem as compared to nifedipine achieved 37 weeks (15.1% vs. 41.7%, P = 0.019). Gestational age at delivery was also less for patients receiving diltiazem (35.5 +/- 3.5 weeks vs. 33.4 +/- 3.9 weeks, P = 0.022). There were fewer days gained in utero from randomization to delivery with diltiazem as compared to nifedipine; however, this difference was not statistically significant (22.4 +/- 16.3 days vs. 31.2 +/- 24.4 days, P = 0.084). Maternal blood pressure and pulse during tocolysis did not differ significantly between groups. Despite the theoretical advantages of diltiazem tocolysis, maintenance tocolysis with diltiazem offered no benefit over nifedipine in achieving 37 weeks gestation. The cardiovascular alterations with either drug in normotensive, pregnant patients appear minimal.

  View details for PubMedID 9775988

• Obstetric and gynecologic care of women with epilepsy EPILEPSIA El-Sayed, Y. Y. 1998; 39: S17-S25

  Abstract

  Optimal gynecologic and obstetric care for women with epilepsy requires a multidisciplinary approach throughout the various life stages. Epilepsy has important effects on puberty, contraceptive efficacy, pregnancy and fetal development, and menopause. This article discusses these effects and makes recommendations for gynecologic and obstetric care of patients with epilepsy, with particular focus on pregnancy. Despite very real risks to both the developing fetus and the mother, the majority of women with epilepsy--with appropriate pregnancy planning and management--have good pregnancy outcomes.

  View details for Web of Science ID 000078030000004

  View details for PubMedID 9915616

• INTRATHECAL SUFENTANIL FOR LABOR ANALGESIA - SENSORY CHANGES, SIDE-EFFECTS, AND FETAL HEART-RATE CHANGES ANESTHESIA AND ANALGESIA Cohen, S. E., CHERRY, C. M., Holbrook, R. H., ELSAYED, Y. Y., Gibson, R. N., Jaffe, R. A. 1993; 77 (6): 1155-1160

  Abstract

  This study was designed to evaluate intrathecal (IT) sufentanil for labor analgesia with respect to sensory changes, side effects, and fetal heart rate (FHR) changes. In Phase I of the study, data regarding duration of analgesia and hemodynamic changes were obtained retrospectively from the labor and anesthetic records of 90 patients who had received IT sufentanil, 10 micrograms in 1 mL of saline, during active labor. In Phase II, an additional 18 parturients who received similar treatment were studied prospectively to document sensory, motor, and hemodynamic changes, as well as the incidence of side effects. In Phase I, analgesia occurred rapidly and lasted 124 +/- 68 min (SD); 19% of patients required no further analgesia before delivery. In Phase II, median time to onset of analgesia was 3 min (range 1-6 min) and mean duration of analgesia was 96 +/- 36 min. Decreased sensation to pinprick and cold occurred within 6 min extending from T4 to L4 (upper and lower median levels) in the majority of patients. All subjects requested additional analgesia within approximately 30 min of recession of sensory changes. Motor strength remained normal throughout. Hypotension (systolic blood pressure [BP] < or = 90 mm Hg or > 20% decrease in systolic BP) occurred in 14% and 11% of patients in Phase I and II, respectively. Perineal itching preceded analgesia in 95% of patients and all subjects experienced mild sedation. FHR changes occurred in 15% of cases but were not associated with adverse neonatal outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1993MK04800013

  View details for PubMedID 8250307