Clinical Focus

  • Neonatal-Perinatal Medicine
  • Neonatology

Academic Appointments

Professional Education

  • Fellowship:Stanford University Neonatology Fellowship (1985) CA
  • Residency:Stanford Medicine Pediatric Residency (1982) CA
  • Internship:Stanford Medicine Pediatric Residency (1979) CA
  • Board Certification: Pediatrics, American Board of Pediatrics (1983)
  • Medical Education:Stanford University School of Medicine (1978) CA
  • Board Certification: Neonatal-Perinatal Medicine, American Board of Pediatrics (1985)

Research & Scholarship

Current Research and Scholarly Interests

Neonatology, patent ductus arteriosus, pulmonary hypertension of the newborn, infant ventilation, neonatal clinical protocols/clinical pathways.

Clinical Trials

  • Ampicillin / Sulbactam vs. Ampicillin / Gentamicin for Treatment of Chorioamnionitis Not Recruiting

    Chorioamnionitis is an infection of the placenta and amniotic membranes (bag of waters) surrounding the baby inside of a pregnant woman prior to delivery. This infection is somewhat common and is routinely treated with antibiotics given to the mother both before and after the baby is born. Currently it is not known what is the best choice of antibiotics to treat this type of infection, but commonly used treatments include Unasyn (ampicillin/sulbactam) or ampicillin/gentamicin. We plan to compare these two different antibiotic regimens to see if one is better than the other at treating and preventing bad outcomes from chorioamnionitis in women and babies.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mara Greenberg, (415) 867 - 2051.

    View full details


2017-18 Courses


All Publications

  • Changing Management of the Patent Ductus Arteriosus: Effect on Neonatal Outcomes and Resource Utilization. American journal of perinatology Chock, V. Y., Goel, V. V., Palma, J. P., Luh, T. M., Wang, N. A., Gaskari, S., Punn, R., Silverman, N. H., Benitz, W. E. 2017


    Objective This historical cohort study investigated how a shift toward a more conservative approach of awaiting spontaneous closure of the patent ductus arteriosus (PDA) in preterm infants has affected neonatal outcomes and resource utilization. Methods We retrospectively studied very low birth weight infants diagnosed with a PDA by echocardiogram (ECHO) in 2006-2008 (era 1), when medical or surgical PDA management was emphasized, to those born in 2010-2012 (era 2) when conservative PDA management was encouraged. Multiple regression analyses adjusted for gestational age were performed to assess differences in clinical outcomes and resource utilization between eras. Results More infants in era 2 (35/89, 39%) compared with era 1 (22/120, 18%) had conservative PDA management (p < 0.01). Despite no difference in surgical ligation rate, infants in era 2 had ligation later (median 24 vs. 8 days, p < 0.0001). There was no difference in clinical outcomes between eras, while number of ECHOs per patient was the only resource measure that increased in era 2 (median 3 vs. 2 ECHOs, p = 0.003). Conclusion In an era of more conservative PDA management, no increase in adverse clinical outcomes or significant change in resource utilization was found. Conservative PDA management may be a safe alternative for preterm infants.

    View details for DOI 10.1055/s-0037-1601442

    View details for PubMedID 28376547

  • An Electronic Health Record Investigation of Lenticulostriate Vasculopathy Features. American journal of perinatology Frankovich, J., Egan, M., Mahony, T., Benitz, W., Shaw, G. 2017; 34 (3): 253-258


    Objective Lenticulostriate vasculopathy (LSV) is characterized by linear hyperechogenicities in the basal ganglia found on the head ultrasounds of infants. We reviewed electronic health records of infants with and without LSV to investigate whether physician dictations indicated symptoms which could reflect subtle basal ganglia injury. Study Design In a case-control study, we analyzed data from 46 infants with LSV and 127 controls. Infants were stratified between term and preterm birth. Odds ratios (ORs) and 95% confidence intervals were calculated for tone abnormalities, apnea, feeding difficulties, seizures, and movement abnormalities in the presence of LSV. Results Both term and preterm infants with LSV showed elevated risks for tone abnormalities (OR: 3.6 and 2.9, respectively). Term infants with LSV showed elevated risks for hypotonia (OR: 4.3), apnea (OR: 2.9), and feeding difficulties (OR: 4.1). Preterm infants with LSV showed elevated risks for truncal hypotonia (OR: 3.9) and hyperreflexia (OR: 3.9). Conclusion Our findings provide some evidence that LSV is associated with an increased risk of early signs of abnormal development, possibly relating to signs of subtle basal ganglia injury. Historically LSV has been considered incidental. The associations identified here suggest that LSV findings are worthy of further study.

    View details for DOI 10.1055/s-0036-1585417

    View details for PubMedID 27471823

  • Chorioamnionitis and Culture-Confirmed, Early-Onset Neonatal Infections. Pediatrics Wortham, J. M., Hansen, N. I., Schrag, S. J., Hale, E., Van Meurs, K., Sánchez, P. J., Cantey, J. B., Faix, R., Poindexter, B., Goldberg, R., Bizzarro, M., Frantz, I., Das, A., Benitz, W. E., Shane, A. L., Higgins, R., Stoll, B. J. 2016; 137 (1): 1-11


    Current guidelines for prevention of neonatal group B streptococcal disease recommend diagnostic evaluations and empirical antibiotic therapy for well-appearing, chorioamnionitis-exposed newborns. Some clinicians question these recommendations, citing the decline in early-onset group B streptococcal disease rates since widespread intrapartum antibiotic prophylaxis implementation and potential antibiotic risks. We aimed to determine whether chorioamnionitis-exposed newborns with culture-confirmed, early-onset infections can be asymptomatic at birth.Multicenter, prospective surveillance for early-onset neonatal infections was conducted during 2006-2009. Early-onset infection was defined as isolation of a pathogen from blood or cerebrospinal fluid collected ≤ 72 hours after birth. Maternal chorioamnionitis was defined by clinical diagnosis in the medical record or by histologic diagnosis by placental pathology. Hospital records of newborns with early-onset infections born to mothers with chorioamnionitis were reviewed retrospectively to determine symptom onset.Early-onset infections were diagnosed in 389 of 396,586 live births, including 232 (60%) chorioamnionitis-exposed newborns. Records for 229 were reviewed; 29 (13%) had no documented symptoms within 6 hours of birth, including 21 (9%) who remained asymptomatic at 72 hours. Intrapartum antibiotic prophylaxis exposure did not differ significantly between asymptomatic and symptomatic infants (76% vs 69%; P = .52). Assuming complete guideline implementation, we estimated that 60 to 1400 newborns would receive diagnostic evaluations and antibiotics for each infected asymptomatic newborn, depending on chorioamnionitis prevalence.Some infants born to mothers with chorioamnionitis may have no signs of sepsis at birth despite having culture-confirmed infections. Implementation of current clinical guidelines may result in early diagnosis, but large numbers of uninfected asymptomatic infants would be treated.

    View details for DOI 10.1542/peds.2015-2323

    View details for PubMedID 26719293

    View details for PubMedCentralID PMC4702021

  • Red Blood Cell Transfusion Is Not Associated with Necrotizing Enterocolitis: A Review of Consecutive Transfusions in a Tertiary Neonatal Intensive Care Unit JOURNAL OF PEDIATRICS Wallenstein, M. B., Arain, Y. H., Birnie, K. L., Andrews, J., Palma, J. P., Benitz, W. E., Chock, V. Y. 2014; 165 (4): 678-682


    To explore the association between red blood cell transfusion and necrotizing enterocolitis (NEC) in a neonatal intensive care unit with liberal transfusion practices.A retrospective cohort study was conducted for all infants weighing <1500 g who received at least 1 packed red blood cell transfusion between January 2008 and June 2013 in a tertiary neonatal intensive care unit. The primary outcome was NEC, defined as Bell stage II or greater. The temporal association of NEC and transfusion was assessed using multivariate Poisson regression.The study sample included 414 very low birth weight infants who received 2889 consecutive red blood cell transfusions. Twenty-four infants (5.8%) developed NEC. Four cases of NEC occurred within 48 hours of a previous transfusion event. Using multivariate Poisson regression, we did not find evidence of a temporal association between NEC and transfusion (P = .32).There was no association between NEC and red blood cell transfusion. Our results differ from previous studies and suggest that the association between NEC and transfusion may be contextual.

    View details for DOI 10.1016/j.jpeds.2014.06.012

    View details for Web of Science ID 000342694200009

  • Prevention of traumatic stress in mothers of preterms: 6-month outcomes. Pediatrics Shaw, R. J., St John, N., Lilo, E., Jo, B., Benitz, W., Stevenson, D. K., Horwitz, S. M. 2014; 134 (2): e481-8


    Symptoms of posttraumatic stress disorder are a well-recognized phenomenon in mothers of preterm infants, with implications for maternal health and infant outcomes. This randomized controlled trial evaluated 6-month outcomes from a skills-based intervention developed to reduce symptoms of posttraumatic stress disorder, anxiety, and depression.One hundred five mothers of preterm infants were randomly assigned to (1) a 6- or 9-session intervention based on principles of trauma-focused cognitive behavior therapy with infant redefinition or (2) a 1-session active comparison intervention based on education about the NICU and parenting of the premature infant. Outcome measures included the Davidson Trauma Scale, the Beck Depression Inventory II, and the Beck Anxiety Inventory. Participants were assessed at baseline, 4 to 5 weeks after birth, and 6 months after the birth of the infant.At the 6-month assessment, the differences between the intervention and comparison condition were all significant and sizable and became more pronounced when compared with the 4- to 5-week outcomes: Davidson Trauma Scale (Cohen's d = -0.74, P < .001), Beck Anxiety Inventory (Cohen's d = -0.627, P = .001), Beck Depression Inventory II (Cohen's d = -0.638, P = .002). However, there were no differences in the effect sizes between the 6- and 9-session interventions.A brief 6-session intervention based on principles of trauma-focused cognitive behavior therapy was effective at reducing symptoms of trauma, anxiety, and depression in mothers of preterm infants. Mothers showed increased benefits at the 6-month follow-up, suggesting that they continue to make use of techniques acquired during the intervention phase.

    View details for DOI 10.1542/peds.2014-0529

    View details for PubMedID 25049338

  • Prevention of traumatic stress in mothers of preterms: 6-month outcomes. Pediatrics Shaw, R. J., St John, N., Lilo, E., Jo, B., Benitz, W., Stevenson, D. K., Horwitz, S. M. 2014; 134 (2): e481-8

    View details for DOI 10.1542/peds.2014-0529

    View details for PubMedID 25049338

  • Evaluation of serial urine viral cultures for the diagnosis of cytomegalovirus infection in neonates and infants. Pediatric and developmental pathology Chisholm, K. M., Aziz, N., McDowell, M., Guo, F. P., Srinivas, N., Benitz, W. E., Norton, M. E., Gutierrez, K., Folkins, A. K., Pinsky, B. A. 2014; 17 (3): 176-180


    Cytomegalovirus (CMV) is the most common cause of congenital infection worldwide. Urine viral culture is the standard for CMV diagnosis in neonates and infants. The objectives of this study were to compare the performance of serial paired rapid shell vial cultures (SVC) and routine viral cultures (RVC), and to determine the optimal number of cultures needed to detect positive cases. From 2001 to 2011, all paired CMV SVC and RVC performed on neonates and infants less than 100 days of age were recorded. Testing episodes were defined as sets of cultures performed within 7 days of one another. A total of 1264 neonates and infants underwent 1478 testing episodes; 68 (5.4%) had at least one episode with a positive CMV culture. In episodes where CMV was detected before day 21 of life, the first specimen was positive in 100% (16/16) of cases. When testing occurred after 21 days of life, the first specimen was positive in 82.7% (43/52) of cases, requiring three cultures to reach 100% detection. The SVC was more prone to assay failure than RVC. Overall, when RVC was compared to SVC, there was 86.0% positive agreement and 99.9% negative agreement. In conclusion, three serial urine samples are necessary for detection of CMV in specimens collected between day of life 22 and 99, while one sample may be sufficient on or before day of life 21. Though SVC was more sensitive than RVC, the risk of SVC failure supports the use of multimodality testing to optimize detection.

    View details for DOI 10.2350/14-01-1432-OA.1

    View details for PubMedID 24617645

  • Predictors of bronchopulmonary dysplasia or death in premature infants with a patent ductus arteriosus. Pediatric research Chock, V. Y., Punn, R., Oza, A., Benitz, W. E., Van Meurs, K. P., Whittemore, A. S., Behzadian, F., Silverman, N. H. 2014; 75 (4): 570-575


    Background:Preterm infants with a PDA are at risk for death or development of BPD. However, PDA treatment remains controversial. We investigated if PDA treatment and other clinical or echocardiographic (ECHO) factors were associated with the development of death or BPD.Methods:We retrospectively studied clinical and ECHO characteristics of preterm infants with birth weight <1500 g and ECHO diagnosis of a PDA. Logistic regression and classification and regression tree (CART) analyses were performed to assess variables associated with the combined outcome of death or BPD.Results:Of 187 preterm infants with a PDA, 75% were treated with indomethacin or surgery and 25% were managed conservatively. Death or BPD occurred in 80 (43%). Logistic regression found lower gestational age (OR 0.5), earlier year of birth during the study period (OR 0.9), and larger ductal diameter (OR 4.3) were associated with the decision to treat the PDA, while gestational age was the only variable associated with death or BPD (OR 0.6, 95% CI 0.5-0.8).Conclusion:Only lower gestational age and not PDA treatment or ECHO score was associated with the adverse outcome of death or BPD. Further investigation of PDA management strategies and effects on adverse outcomes of prematurity is needed.Pediatric Research (2013); doi:10.1038/pr.2013.253.

    View details for DOI 10.1038/pr.2013.253

    View details for PubMedID 24378897

  • Anti-Ge3 causes late-onset hemolytic disease of the newborn: the fourth case in three Hispanic families. Transfusion Pate, L. L., Myers, J. C., Palma, J. P., Viele, M., Galel, S. A., Ferrer, Z., Gonzalez, C. L., Benitz, W. E., Garratty, G., Fontaine, M. J. 2013; 53 (10): 2152-2157


    BACKGROUND: The Gerbich (Ge) blood group system consists of 11 antigens carried on red blood cell (RBC) membrane glycophorins C and D; of these, Ge:3 antigen is of high prevalence, and the anti-Ge3 is found to be clinically significant. CASE REPORT: A 34-week neonate born to a Hispanic mother with anti-Ge3 developed late-onset hemolysis with hyperbilirubinemia and was successfully treated with transfusions from her mother. Relevant clinical findings and laboratory results for this case are summarized and compared to three other previously reported cases; all babies were born from a mother of Hispanic ethnicity. CONCLUSION: Hemolytic disease of the fetus and new born associated with anti-Ge3 is rare but should be considered when working up a broadly reactive RBC antibody screen in women of Hispanic ethnicity. Early identification of pregnant women with anti-Ge3 is recommended for prenatal transfusion planning and close monitoring of the newborn infant for evidence of late-onset anemia.

    View details for DOI 10.1111/trf.12027

    View details for PubMedID 23241141

  • Prevention of traumatic stress in mothers with preterm infants: a randomized controlled trial. Pediatrics Shaw, R. J., St John, N., Lilo, E. A., Jo, B., Benitz, W., Stevenson, D. K., Horwitz, S. M. 2013; 132 (4): e886-94


    The current study evaluates a treatment intervention developed with the goal of reducing symptoms of posttraumatic stress, depression, and anxiety in parents of premature infants.A total of 105 mothers of preterm infants (25-34 weeks' gestational age; >600 g) were randomized to receive a 6-session intervention developed to target parental trauma as well as facilitate infant redefinition (n = 62) or to an active comparison group (n = 43). Mothers in the intervention group received a combination of trauma-focused treatments, including psychoeducation, cognitive restructuring, progressive muscle relaxation, and development of their trauma narrative. The intervention also incorporated material targeting infant redefinition, defined as the process of changing the mother's negative perceptions of her infant and the parenting experience.Mothers in the intervention group reported a greater reduction in both trauma symptoms (Cohen's d = 0.41, P = .023) and depression (Cohen's d = 0.59, P < .001) compared with the comparison group. Patients under both conditions improved significantly in terms of anxiety, with no differences between groups. Results of the moderator analysis showed that mothers with higher ratings of baseline NICU stress benefited more from the intervention compared with mothers who had lower ratings (P = .036).This short, highly manualized intervention for mothers of preterm infants statistically significantly reduced symptoms of trauma and depression. The intervention is feasible, can be delivered with fidelity, and has high ratings of maternal satisfaction. Given that improvements in mothers' distress may lead to improved infant outcomes, this intervention has the potential for a high public health impact.

    View details for DOI 10.1542/peds.2013-1331

    View details for PubMedID 23999956

  • Prevention of Postpartum Traumatic Stress in Mothers with Preterm Infants: Manual Development and Evaluation. Issues in mental health nursing Shaw, R. J., Sweester, C. J., St John, N., Lilo, E., Corcoran, J. B., Jo, B., Howell, S. H., Benitz, W. E., Feinstein, N., Melnyk, B., Horwitz, S. M. 2013; 34 (8): 578-586


    Premature birth has been associated with multiple adverse maternal psychological outcomes that include depression, anxiety, and trauma as well as adverse effects on maternal coping ability and parenting style. Infants who are premature are more likely to have poorer cognitive and developmental functioning and, thus, may be harder to parent, both as infants and as they get older. In response to these findings, a number of educational and behavioral interventions have been developed that target maternal psychological functioning, parenting, and aspects of the parent-infant relationship. The current study aimed to both develop and evaluate a treatment that integrates, for the first time, effective interventions for reducing symptoms of posttraumatic stress disorder (PTSD) and enhancing maternal-infant interactions. Conclusions from the study indicate that the intervention is feasible, able to be implemented with a high level of fidelity, and is rated as highly satisfactory by participants. Though encouraging, these findings are preliminary, and future studies should strive to reproduce these findings with a larger sample size and a comparison group.

    View details for DOI 10.3109/01612840.2013.789943

    View details for PubMedID 23909669

  • Prevention of Postpartum Traumatic Stress in Mothers with Preterm Infants: Manual Development and Evaluation ISSUES IN MENTAL HEALTH NURSING Shaw, R. J., Sweester, C. J., John, N. S., Lilo, E., Corcoran, J. B., Jo, B., Howell, S. H., Benitz, W. E., Feinstein, N., Melnyk, B., Horwitz, S. M. 2013; 34 (8): 578-586


    Premature birth has been associated with multiple adverse maternal psychological outcomes that include depression, anxiety, and trauma as well as adverse effects on maternal coping ability and parenting style. Infants who are premature are more likely to have poorer cognitive and developmental functioning and, thus, may be harder to parent, both as infants and as they get older. In response to these findings, a number of educational and behavioral interventions have been developed that target maternal psychological functioning, parenting, and aspects of the parent-infant relationship. The current study aimed to both develop and evaluate a treatment that integrates, for the first time, effective interventions for reducing symptoms of posttraumatic stress disorder (PTSD) and enhancing maternal-infant interactions. Conclusions from the study indicate that the intervention is feasible, able to be implemented with a high level of fidelity, and is rated as highly satisfactory by participants. Though encouraging, these findings are preliminary, and future studies should strive to reproduce these findings with a larger sample size and a comparison group.

    View details for DOI 10.3109/01612840.2013.789943

    View details for Web of Science ID 000209366600003

  • Neonatal Informatics: Transforming Neonatal Care Through Translational Bioinformatics. NeoReviews Palma, J. P., Benitz, W. E., Tarczy-Hornoch, P., Butte, A. J., Longhurst, C. A. 2012; 13 (5): e281-e284


    The future of neonatal informatics will be driven by the availability of increasingly vast amounts of clinical and genetic data. The field of translational bioinformatics is concerned with linking and learning from these data and applying new findings to clinical care to transform the data into proactive, predictive, preventive, and participatory health. As a result of advances in translational informatics, the care of neonates will become more data driven, evidence based, and personalized.

    View details for PubMedID 22924023

    View details for PubMedCentralID PMC3424284

  • Patent ductus arteriosus: to treat or not to treat? ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION Benitz, W. E. 2012; 97 (2): F80-F82


    Persistent patency of the ductus arteriosus in the preterm infant is associated with numerous morbidities, including higher rates of bronchopulmonary dysplasia and increased mortality. These strong associations have led to widespread use of cyclooxygenase inhibitors and surgical ligation to achieve ductal closure in the expectation that closing the ductus will reduce these complications. Each of these interventions has its own associated adverse effects. Neither individual randomised controlled trials nor meta-analyses of those trials have been able to demonstrate long-term benefits of these treatments despite their efficacy in inducing ductal closure and reducing the need for ductal ligation. Despite the potential shortcomings of those trials, they provide substantial cumulative evidence that early, routine treatment to close a persistently patent ductus arteriosus in preterm infants does not improve outcomes and should therefore be abandoned. Future trials of these interventions for patent ductus management should address different questions. Persistence of ductal patency should be considered a sign of rather than a direct cause of the several morbidities with which it is clearly associated. Practitioners should tolerate ductal patency and learn to manage its causes and consequences rather than focusing on achievement of ductal closure.

    View details for DOI 10.1136/archdischild-2011-300381

    View details for Web of Science ID 000301633800001

    View details for PubMedID 22174019

  • Learning to live with patency of the ductus arteriosus in preterm infants JOURNAL OF PERINATOLOGY Benitz, W. E. 2011; 31: S42-S48


    Treatment of persistent patency of the ductus arteriosus in preterm infants remains heterogeneous and controversial. Routine early treatment to induce ductal closure is not beneficial, but the potential criteria for, timing of, methods for and benefits of later ductal closure have not been determined. Management strategies for infants awaiting spontaneous closure or meeting criteria for treatment may be based on pathophysiological considerations but require evaluation in clinical trials. Better diagnostic tools allowing the identification of infants who might benefit from ductal closure, supplemented by data from clinical trials confirming realization of that potential, are urgently needed.

    View details for DOI 10.1038/jp.2010.175

    View details for Web of Science ID 000289236900007

    View details for PubMedID 21448203

  • Adjunct Laboratory Tests in the Diagnosis of Early-Onset Neonatal Sepsis CLINICS IN PERINATOLOGY Benitz, W. E. 2010; 37 (2): 421-?


    Early-onset sepsis remains a major diagnostic problem in neonatal medicine. Definitive diagnosis depends on cultures of blood or other normally sterile body fluids. Abnormal hematological counts, acute-phase reactants, and inflammatory cytokines are neither sensitive nor specific, especially at the onset of illness. Combinations of measurements improve diagnostic test performance, but the optimal selection of analytes has not been determined. The best-established use of these laboratory tests is for retrospective determination that an infant was not infected, based on failure to mount an acute-phase response over the following 24 to 48 hours.

    View details for DOI 10.1016/j.clp.2009.12.001

    View details for Web of Science ID 000279583900008

    View details for PubMedID 20569816

  • Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis? JOURNAL OF PERINATOLOGY Benitz, W. E. 2010; 30 (4): 241-252


    Medical and surgical interventions are widely used to close a persistently patent ductus arteriosus in preterm infants. Objective evidence to support these practices is lacking, causing some to question their usage. Emerging evidence suggests that treatments that close the patent ductus may be detrimental. This review examines the history of and evidence underlying these treatments. Neither individual trials, pooled data from groups of randomized-controlled trials, nor critical examination of the immediate consequences of treatment provide evidence that medical or surgical closure of the ductus is beneficial in preterm infants. These conclusions are supported by sufficient evidence. Neither continued routine use of these treatments nor additional clinical trials using similar designs seems to be justified. A definitive trial, comparing current standard management with novel strategies not primarily intended to achieve ductal closure, may be necessary to resolve doubts regarding the quality or conduct of prior studies.

    View details for DOI 10.1038/jp.2010.3

    View details for Web of Science ID 000276569300001

    View details for PubMedID 20182439

  • 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


    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,, NCT00185991.I.

    View details for Web of Science ID 000273872500020

    View details for PubMedID 20093909

  • Combining hand techniques with electric pumping increases milk production in mothers of preterm infants JOURNAL OF PERINATOLOGY Morton, J., Hall, J. Y., Wong, R. J., Thairu, L., Benitz, W. E., Rhine, W. D. 2009; 29 (11): 757-764


    Pump-dependent mothers of preterm infants commonly experience insufficient production. We observed additional milk could be expressed following pumping using hand techniques. We explored the effect on production of hand expression of colostrum and hands-on pumping (HOP) of mature milk.A total of 67 mothers of infants <31 weeks gestation were enrolled and instructed on pumping, hand expression of colostrum and HOP. Expression records for 8 weeks and medical records were used to assess production variables.Seventy-eight percent of the mothers completed the study. Mean daily volumes (MDV) rose to 820 ml per day by week 8 and 955 ml per day in mothers who hand expressed >5 per day in the first 3 days. Week 2 and/or week 8 MDV related to hand expression (P<0.005), maternal age, gestational age, pumping frequency, duration, longest interval between pumpings and HOP (P<0.003). Mothers taught HOP increased MDV (48%) despite pumping less.Mothers of preterm infants may avoid insufficient production by combining hand techniques with pumping.

    View details for DOI 10.1038/jp.2009.87

    View details for Web of Science ID 000271187300009

    View details for PubMedID 19571815

  • Use of caffeine for apnea of prematurity also has long-term neurodevelopmental benefits JOURNAL OF PEDIATRICS Benitz, W. E. 2008; 152 (5): 740-741

    View details for Web of Science ID 000255375700035

    View details for PubMedID 18410790

  • 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
  • Postnatal cytomegalovirus infection from frozen breast milk in preterm, low birth weight infants PEDIATRIC INFECTIOUS DISEASE JOURNAL Lee, H. C., Enright, A., Benitz, W. E., Madan, A. 2007; 26 (3): 276-276

    View details for Web of Science ID 000245089900022

    View details for PubMedID 17484235

  • The use of inhaled nitric oxide in the premature infant with respiratory distress syndrome. Minerva pediatrica Van Meurs, K., Hintz, S., Rhine, W., Benitz, W. 2006; 58 (5): 403-422


    The identification of the biologic properties of nitric oxide (NO) is one of the key scientific discoveries of the century, but its potential for treating human disease is yet to be fully realized. NO has a basic role in regulating vascular tone of the pulmonary circulation, and recent animal models have suggested a more wide reaching influence on perinatal lung development. In animal models, NO has effects on lung growth, angiogenesis, airway smooth muscle proliferation, vascular remodeling, surfactant function, inflammation, and pulmonary mechanics. However, despite extensive basic science investigation and completion of several large clinical trials, the role of NO in the treatment of the premature infant with respiratory distress syndrome remains unclear. One must conclude that the interaction of lung immaturity, ventilator and oxygen-induced lung injury, and NO biology in the premature newborn is incompletely understood. Clinical trial results of inhaled NO therapy in the premature infant are accumulating, but the results do not suggest a clear-cut advantage for the population at greatest risk for death and disability. Whether trial design, dose, duration of therapy, or other factors are responsible has not been determined. Further research is needed to answer these questions and more clearly define the population of premature infants who may derive benefit from this new therapy.

    View details for PubMedID 17008853

  • Criteria supporting the study of drugs in the newborn Newborn Drug Development Initiative Workshop Ward, R. M., Benitz, W. E., Benjamin, D. K., Blackmon, L., Giacoia, G. P., Hudak, M., Lasky, T., Rodriguez, W., Selen, A. ELSEVIER. 2006: 1385–98


    Profound changes in the development and the maturation of neonates' organs and organ systems over variable periods of time potentially place neonates at increased risk and/or at different risks compared with adults or older children on exposure to pharmaceutical agents. Most studies of drugs in neonates focus on pharmacokinetic and pharmacodynamic end points and include insufficient numbers of patients to permit evaluation of safety. Only one fourth to one third of approved drugs have received adequate pediatric study to permit labeling for treatment of all appropriate pediatric populations.The initial goal of the Newborn Drug Prioritization Group was to develop a reproducible, objective process for evaluating drugs most in need of study in the neonatal population based on a universally acceptable priority ranking. The criteria would be applicable across therapeutic classes and would identify those drugs for which immediate study was most needed.Because the therapeutic requirements of the neonate are unique in comparison to older infants and children, the National Institute of Child Health and Human Development and the US Food and Drug Administration (FDA) developed the Newborn Drug Development Initiative to address the limited study of off-patent drugs in newborns. In March 2003, they convened a meeting of pediatric pharmacologists and pediatric specialists from the FDA, the American Academy of Pediatrics, the National Institutes of Health, and academic institutions to discuss how to increase the study of drugs for the newborn. One of the working groups was charged to develop generic criteria for overall prioritization of drugs for study in newborns. Because resources are limited, and not all drugs identified by the 4 clinically focused working groups can receive study at the same time, a process for priority ranking is necessary.The panel identified 4 general categories containing different numbers of criteria as important for ranking drugs for priority investigation: (1) the disease and indication, including elements such as the potential for adverse outcomes, frequency in newborns, and level of evidence for treatment of newborns; (2) drug characteristics, including elements such as duration of dosing, lack of age-appropriate formulation, clinically relevant drug-drug and drug-disease interactions, and drug disposition in newborns; (3) feasibility and methodology for newborn studies, including both analytical considerations and clinical end points; and (4) the ethical basis for study, including elements to address benefit or harm due to exposure to the study drug, study methodology, and benefit of the new treatment relative to established standard therapy. Based on these categories, a list of criteria to warrant study of a drug in newborns was developed.A process for judicious use of limited resources to rectify these deficiencies remains an urgent public health need.

    View details for DOI 10.1016/j.clinthera.2006.09.007

    View details for Web of Science ID 000241685600013

    View details for PubMedID 17062311

  • Comparison of rapid intrapartum screening methods for group B streptococcal vaginal colonization JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Aziz, N., Baron, E. J., D'Souza, H., Nourbakhsh, M., Druzin, M. L., Benitz, W. E. 2005; 18 (4): 225-229


    To compare optical immunoassay (OIA) and rapid polymerase-chain reaction (PCR) with enrichment broth culture for intrapartum detection of vaginal group B streptococcal (GBS) colonization.Paired vaginal swabs from 315 consecutive term pregnant women at the time of presentation for delivery to a university medical center were tested for GBS by OIA, PCR, and culture. Sensitivity, specificity, and positive and negative predictive values were calculated.Vaginal colonization was identified by culture in 56 subjects (17.8%). The sensitivity of OIA (7.1%, 95% confidence interval 5.1-9.5%) was significantly less than that of unenhanced rapid PCR (62.5%, 95% CI 48.5-74.8%).Neither PCR nor OIA is sufficiently sensitive for intrapartum detection of vaginal GBS colonization. Rapid PCR is more sensitive, but further improvements in technique to increase sensitivity will be necessary if PCR is to have a useful role in the management of women at time of presentation for delivery.

    View details for DOI 10.1080/14767050500278048

    View details for Web of Science ID 000234009900003

    View details for PubMedID 16318971

  • Food, toys, and love: pediatric palliative care. Current problems in pediatric and adolescent health care Sourkes, B., Frankel, L., Brown, M., Contro, N., Benitz, W., Case, C., Good, J., Jones, L., Komejan, J., Modderman-Marshall, J., Reichard, W., Sentivany-Collins, S., Sunde, C. 2005; 35 (9): 350-386

    View details for PubMedID 16301200

  • Utilization and outcomes of neonatal cardiac extracorporeal life support: 1996-2000. Pediatric critical care medicine Hintz, S. R., Benitz, W. E., Colby, C. E., Sheehan, A. M., Rycus, P., Van Meurs, K. P. 2005; 6 (1): 33-38


    Extracorporeal life support for neonatal respiratory failure has decreased, but utilization and outcome of cardiac extracorporeal life support are not well characterized. Among neonates born 1996-2000, our objects were to evaluate changes in utilization and outcome of cardiac extracorporeal life support and characterize correlates of survival.Retrospective analysis of Extracorporeal Life Support Organization Registry data.Intensive care units participating in the ELSO registry.Patients placed on extracorporeal life support for center-specified "cardiac support" at 15 days was associated with improved survival among hypoplastic left heart syndrome patients (p = .03), and survivors had fewer mean extracorporeal life support hours (89.3 +/- 52.3 vs. 147.5 +/- 129.7, p = .015). Logistic regression showed that only greater number of hours on extracorporeal life support was independently associated with nonsurvival.Neonatal cardiac extracorporeal life support use increased substantially from 1996 to 2000, with survival to discharge or transfer in more than one third of patients. Hypoplastic left heart syndrome was not associated with nonsurvival. Fewer hours on extracorporeal life support, diagnoses of persistent pulmonary hypertension of the neonate and transposition of the great arteries, and extracorporeal life support at <3 days were associated with survival.

    View details for PubMedID 15636656

  • Reduction in red blood cell transfusions using a bedside analyzer in extremely low birth weight infants. Journal of perinatology Madan, A., Kumar, R., Adams, M. M., Benitz, W. E., Geaghan, S. M., Widness, J. A. 2005; 25 (1): 21-25


    Preterm infants typically experience heavy phlebotomy losses from frequent laboratory testing in the first few weeks of life. This results in anemia, requiring red blood cell (RBC) transfusions. We recently introduced a bedside point-of-care (POC) blood gas analyzer (iSTAT, Princeton, NJ) that requires a smaller volume of blood to replace conventional Radiometer blood gas and electrolyte analysis used by our neonatal intensive care unit (NICU). The smaller volume of blood required for sampling (100 vs 300-500 microl), provided an opportunity to assess if a decrease in phlebotomy loss occurred and, if so, to determine if this resulted in decreased transfusions administered to extremely low birth weight (ELBW) infants.We hypothesized that the use of the POC iSTAT analyzer that measures pH, PCO(2), PO(2), hemoglobin, hematocrit, serum sodium, serum potassium and ionized calcium would result in a significant decrease in the number and volume of RBC transfusions in the first 2 weeks of life.A retrospective chart review was conducted of all inborn premature infants with birth weights less than 1000 g admitted to the NICU that survived for 2 weeks of age during two separate 1-year periods. Blood gas analysis was performed by conventional laboratory methods during the first period (designated Pre-POC testing) and by the iSTAT POC device during the second period (designated post-POC testing). Data collected for individual infants included the number of RBC transfusions, volume of RBCs transfused, and the number and kind of blood testing done. There was no effort to change either the RBC transfusion criteria applied or blood testing practices.The mean (+/-SD) number of RBC transfusions administered in the first 2 weeks after birth was 5.7+/-3.74 (n=46) in the pre-POC testing period to 3.1+/-2.07 (n=34) in the post-POC testing period (p<0.001), a 46% reduction. The mean volume of RBC transfusions decreased by 43% with use of the POC analyzer, that is, from 78.4+/-51.6 ml/kg in the pre-POC testing group to 44.4+/-32.9 ml/kg in the Post-POC testing group (p<0.002). There was no difference between the two periods in the total number of laboratory blood tests done.Use of a bedside blood gas analyzer is associated with clinically important reductions in RBC transfusions in the ELBW infant during the first two weeks of life.

    View details for PubMedID 15496875

  • Reduction in red blood cell transfusions using a bedside analyzer in extremely low birth weight infants Annual Meeting of the Pediatric-Academic-Societies Kumar, R., Madan, A., Benitz, W. E., Widness, J. A. NATURE PUBLISHING GROUP. 2004: 548A–548A
  • Low yield of ancillary diagnostic studies in neonates infected with Candida. Journal of perinatology Colby, C. E., Drohan, L., Benitz, W., Hintz, S. R. 2004; 24 (4): 241-246


    Fungal infection can be a significant complication for the critically ill neonate. However, the usefulness of extensive radiologic and ophthalmologic investigations in this population has not been thoroughly elucidated.To report the incidence of organ fungal involvement diagnosed by ancillary testing (echocardiogram, ophthalmologic examination, brain imaging, and renal ultrasound (RUS)) among neonatal intensive care unit (NICU) patients with Candida infection.This was a single center review of all NICU patients with Candida-positive cultures of blood, urine, peritoneal fluid, endotracheal tube aspirate, or cerebrospinal fluid from January 1, 1997 to June 1 2002. Data regarding the number of positive cultures, species isolated, and presence of specific risk factors and clinical symptoms were recorded for each case, as well as occurrence, timing and results of ancillary testing.In all, 66 patients had at least one positive culture for Candida. The majority (71%) were <1500 g at birth, and mean gestational age was 29.5+/-5.6 weeks. Echocardiograms were obtained in 54/66 (82%), and ophthalmology examinations were obtained in 36/66 (55%); none of these was consistent with fungal involvement. Brain imaging was performed in 50/66 (76%), only one of which was positive, in a patient with 16 positive blood cultures for Candida albicans. RUS were performed in 58/66 (88%) of patients, with concerning findings for fungal involvement in seven of the studies. RUS findings alone did not appear to consistently influence the length of therapy.Ancillary evaluations to investigate for fungal dissemination were undertaken frequently, but were of overall low yield. Although ancillary testing may be of limited additional value in centers with a low threshold for suspecting fungal infections and an aggressive approach to therapy, potentially important findings, which could impact management, may occur.

    View details for PubMedID 15014535

  • Retinopathy of prematurity and pulse oximetry: a national survey of recent practices. Journal of perinatology Anderson, C. G., Benitz, W. E., Madan, A. 2004; 24 (3): 164-168


    To determine if practices related to the use of pulse oximetry in the first 2 weeks following birth and after 2 weeks of age have a relationship to the rate of retinopathy of prematurity (ROP) and retinal ablation surgery in infants < or =1500 g.A questionnaire was mailed in July 2001 to 318 neonatal intensive care units (NICUs) in the United States and information was collected regarding SpO2 guidelines and the rate of both severe ROP and retinal ablation surgery.A total of 142 surveys were returned (45%). In all, 87% of the NICUs had SpO2 guidelines, and 60% of these centers maintained a different range of SpO2 for infants < or = or >2 weeks of age. The range of SpO2 was 82 to 100% with an average minimum (min) and maximum (max) of 89 and 95%, respectively. In the NICUs with an SpO2 max of >98% in the first 2 weeks following birth, the rate of retinal ablation surgery was 5.5 vs 3% in those units with a max SpO2 >98% (p<0.05). After 2 weeks of age, the rate of retinal ablation surgery was 3.3% when max SpO2 was >92 vs 1.3% when the max SpO2 was < or =92% (p<0.00001). The rate of > or =stage 3 ROP after 2 weeks of age was 5.5% when max SpO2 was >92 vs 2.4% when max SpO2 was < or =92% (p<0.0005).NICUs in the US today have a wide range of SpO2 guidelines. The results of this survey show a "gradient of risk" towards less retinal ablation surgery when the max SpO2 is <98% in the first 2 weeks following birth (p<0.05). There was a statistically significant lower rate of > or =stage 3 ROP and retinal ablation surgery when the max SpO2 was < or =92% after the first 2 weeks of age. A randomized, controlled trial is needed to establish a safe upper limit of SpO2 in the premature infant at risk for developing ROP.

    View details for PubMedID 14999216

  • Readmission for newborn jaundice: The value of the Coombs' test in predicting the need for phototherapy CLINICAL PEDIATRICS Madan, A., Huntsinger, K., Burgos, A., Benitz, W. E. 2004; 43 (1): 63-68


    Current practice at our hospital is to perform a direct antiglobulin test (DAT) on cord blood samples of all infants born to blood type O or Rh-negative mothers. Measurement of serum total bilirubin (STB) level and follow-up after discharge are at the discretion of the individual physician. The purposes of the present study were, first, to determine the clinical utility of performing a routine DAT and, second, to define the clinical characteristics of infants readmitted to the hospital for phototherapy. The study was done over a 1-year period extending from January 1 to December 31, 2000. A retrospective review of the DAT results of all infants born to type O or Rh-negative mothers was conducted. The 2 groups of infants included those who had a positive cord blood DAT and were treated with phototherapy and those who needed readmission to the hospital for phototherapy. We found that routine DAT testing of cord blood from term nonjaundiced infants born to O positive mothers is not necessary. Infants with 2 or more risk factors for jaundice irrespective of the results of the DAT are at an increased risk for needing readmission for phototherapy.

    View details for Web of Science ID 000188183500008

    View details for PubMedID 14968894

  • Prevention of medication errors in the pediatric inpatient setting PEDIATRICS Gorman, R. L., Bates, B. A., Benitz, W. E., Burchfield, D. J., Maxwell, L., Ring, J. C., Walls, R. P., Walson, R. D., Koteras, R. J., Neff, J. M., Eichner, J. M., Hardy, D. R., Percelay, J., Sigrest, T., Stucky, E. R. 2003; 112 (2): 431-436


    Although medication errors in hospitals are common, medication errors that result in death or serious injury occur rarely. Even before the Institute of Medicine reported on medical errors in 1999, the American Academy of Pediatrics and its members had been committed to improving the health care system to provide the best and safest health care for infants, children, adolescents, and young adults. This commitment includes designing health care systems to prevent errors and emphasizing the pediatrician's role in this system. Human and device errors can lead to preventable morbidity and mortality. National and state legislative actions have heightened public awareness of these events. All involved persons, beginning with the physician and including every member of the health care team, must be better educated about and engaged in the several steps recommended to decrease these errors. The safe administration of medications to hospitalized infants and children requires additional specific safeguards that are above and beyond those for adult patients. Pediatricians should help hospitals develop effective programs for safely providing medications, reporting medication errors, and creating an environment of medication safety for all hospitalized pediatric patients.

    View details for Web of Science ID 000184538500046

    View details for PubMedID 12897304

  • Maintaining adequate anticoagulation on extracorporeal membrane oxygenation therapy: Hemochron Junior Low Range versus Hemochron 400. The Journal of extra-corporeal technology Colby, C. E., Sheehan, A., Benitz, W., Van Meurs, K., Halamek, L. P., Moss, R. L. 2003; 35 (1): 35-38


    Extracorporeal membrane oxygenation (ECMO) therapy requires that patients be anticoagulated to prevent clotting and thrombotic complications. There are several bedside whole blood microcoagulation systems available to determine activated clotting time (ACT) levels. Many ECMO centers use Hemochron (International Technidyne, Edison, NJ) products to determine ACT levels. During the study period, we used the Hemochron 400 and then changed to the Hemochron Junior Low Range. There were two specific aims of this study. First, to determine if there was a difference in ACT levels measured by these two distinct Hemochron products both marketed for the use in ECMO therapy. Second, to determine if the differing ACT levels produced by these two devices affected clinical outcomes. We compared ACT levels between two devices on 70 paired blood specimens obtained from four neonatal ECMO patients receiving heparin. A retrospective review of 77 ECMO patients was performed to analyze frequency of circuit emergencies and length of ECMO circuit life while using the two products. In lower ACT ranges, the Hemochron Jr. LR consistently yielded higher ACT values than the Hemochron 400. In higher ACT ranges, the Hemochron Jr. LR consistently yielded lower ACT values than the Hemochron 400. Without calibration, after changing devices, this discrepancy led to shorter circuit life and more circuit clotting complications. After calibration and adjustment in target ACT values, there was a trend toward longer circuit life, and there were fewer clotting complications. There is a difference in the ACT values produced by Hemochron 400 and Hemochron Jr. LR. Failure to calibrate target ACT levels after changing machines may lead to shorter circuit life and more clotting complications.

    View details for PubMedID 12680494

  • Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures: Addendum PEDIATRICS Gorman, R., Bates, B. A., Benitz, W. E., Burchfield, D. J., Ring, J. C., Walls, R. P., WALSON, P. D., Alexander, J., Bennett, D. R., Hagino, O. R., Matsui, D., Riley, L. E., Giacoia, G. P., Cote, C. J., Koteras, R. J. 2002; 110 (4): 836-838


    The purpose of this addendum to the 1992 policy statement is to clarify some of the terms used in that document and to more thoroughly delineate the responsibilities of the practitioner when sedating children.

    View details for Web of Science ID 000178330200040

    View details for PubMedID 12359805

  • Perinatal screening for group B streptococci: Cost-benefit analysis of rapid polymerase chain reaction PEDIATRICS Haberland, C. A., Benitz, W. E., Sanders, G. D., Pietzsch, J. B., Yamada, S., Nguyen, L., Garber, A. M. 2002; 110 (3): 471-480


    To evaluate the costs and benefits of a group B streptococci screening strategy using a new, rapid polymerase chain reaction test in a hypothetical cohort of expectant mothers in the United States.Cost-benefit analysis using the human capital method. We developed a decision model to analyze the costs and benefits of a hypothetical group B streptococci screening strategy using a new, rapid polymerase chain reaction test as compared with the currently recommended group B streptococci screening guidelines-prenatal culture performed at 35 to 37 weeks or risk-factor-based strategy with subsequent intrapartum treatment of the expectant mothers with antibiotics to prevent early-onset group B streptococcal infections in their infants.A hypothetical cohort of pregnant women and their newborns.Screening strategies for group B streptococci using the new polymerase chain reaction technique, the 35- to 37-week culture, or maternal risk factors.Infant infections averted, infant deaths, infant disabilities, costs, and societal benefits of healthy infants.A screening strategy using the new polymerase chain reaction test generates a net benefit of $7 per birth when compared with the maternal risk-factor strategy. For every 1 million births, 80 700 more women would receive antibiotics, 884 fewer infants would become infected with early-onset group B streptococci, and 23 infants would be saved from death or disability. The polymerase chain reaction-based strategy generates a net benefit of $6 per birth when compared with the 35- to 37-week prenatal culture strategy and results in fewer maternal courses of antibiotics (64 080 per million births), fewer perinatal infections with early-onset group B streptococci (218/million), and a reduction in 6 infant deaths and severe infant disability per million births. The benefits hold over a wide range of assumptions regarding key factors in the analysis.Although additional clinical trials are needed to establish the accuracy of this new polymerase chain reaction test, initial studies suggest that strategies using this test will be superior to the other 2 strategies. Using the rapid polymerase chain reaction test becomes less attractive as the cost of the test increases. The test's greatest strengths lie in its ability to identify women and infants at risk at the time of labor, thereby decreasing the number of false-positives and false-negatives seen with the other 2 strategies and allowing for more accurate and effective intrapartum prophylaxis.

    View details for Web of Science ID 000177762900013

    View details for PubMedID 12205247

  • Perinatal treatment to prevent early onset group B streptococcal sepsis. Seminars in neonatology : SN Benitz, W. E. 2002; 7 (4): 301-314


    Implementation of the 1996 consensus recommendations for perinatal antibiotic prophylaxis has produced a remarkable reduction in the rate of early-onset group B streptococcal sepsis.

    View details for PubMedID 12401300

  • Uses of drugs not described in the package insert (off-label uses) PEDIATRICS Ward, R. M., Bates, B. A., Benitz, W. E., Burchfield, D. J., Ring, J. C., Walls, R. P., WALSON, P. D. 2002; 110 (1): 181-183


    New regulatory initiatives have been designed to ensure that new drugs and biologicals include adequate pediatric labeling for the claimed indications at the time of, or soon after, approval. However, because such labeling may not immediately be available, off-label use (or use that is not included in the approved label) of therapeutic agents is likely to remain common in the practice of pediatrics. This policy statement was written to address questions practitioners have regarding off-label use. The purpose of off-label use is to benefit the individual patient. Practitioners may use their professional judgment to determine these uses. Practitioners should understand that the Food and Drug Administration does not regulate off-label use.

    View details for Web of Science ID 000176560200043

    View details for PubMedID 12093968

  • Racial differences in birth weight of term infants in a northern California population. Journal of perinatology Madan, A., Holland, S., Humbert, J. E., Benitz, W. E. 2002; 22 (3): 230-235


    Census data show that an increasing proportion of the population of the United States is of Asian or Hispanic origin. Reference curves used to characterize fetal growth relative to gestational age are predominantly based on data for White infants. The goal of this study was to compare the birth weight distributions for term Asian or Hispanic infants with that for White infants, and to determine whether the prevalence of small (SGA) or large size(LGA) for gestational age differs between Asian or Hispanic and White infants.A community hospital in Northern California.Data was collected prospectively from May 1 to September 13, 2000 on all singleton term infants born at this hospital. Gestational age was assessed by the best obstetrical estimate and ethnicity was determined by parental report. Infants were categorized as White, Hispanic, Chinese, Asian Indian, Other Asian, and Other. Birth weights, length, and head circumferences were compared using ANOVA and the Student-Newman-Keuls test. Differences in rates of diagnosis of SGA or LGA were assessed by chi square.1539 infants were included in the study sample; 30% were White, 21% Asian Indian, 15% Chinese, 9% Hispanic, 7% other Asian, and 18% Other. Asian (Chinese, Asian Indian, or Other Asian), Hispanic, and Other babies had lower mean birth weights, shorter mean lengths, and smaller mean head circumferences than White babies. Asian, Hispanic, and Other male babies were lighter, shorter, and had smaller heads than white male babies. Asian females, but not Hispanic or Other ones, were lighter and had smaller head circumferences than White females; Asian Indian, Other Asian, and Other females had shorter lengths than White female infants. Indian and Other Asian, but not Chinese, babies were more likely than White babies to be SGA; babies in all three Asian groups were less likely than White babies to be LGA.Failure to account for ethnic differences in intrauterine growth may lead to inaccurate diagnosis of fetal growth abnormalities in infants of Asian ancestry.

    View details for PubMedID 11948387

  • Effect of an evidence-based hand washing policy on hand washing rates and false-positive coagulase negative staphylococcus blood and cerebrospinal fluid culture rates in a level III NICU. Journal of perinatology Sharek, P. J., Benitz, W. E., Abel, N. J., Freeburn, M. J., Mayer, M. L., Bergman, D. A. 2002; 22 (2): 137-143


    To determine the effect of implementing an evidence-based hand washing policy on between-patient hand washing compliance and on blood and cerebrospinal fluid (CSF) culture rates in a level III neonatal intensive care unit (NICU).An evidence-based hand washing policy, supported by an intensive education program, was introduced in a regional NICU. A total of 2009 preintervention neonates (16,168 patient days) over 17 months were compared to 676 postintervention neonates (5779 patient days) over 6 months. Hand washing compliance and rates of blood and CSF cultures yielding coagulase negative staphylococci (CONS) were compared before and after intervention.Compliance with appropriate between-patient hand washing improved (from 47.4% to 85.4%, p=0.001) after the hand washing policy was introduced. The rate of cultures positive for CONS declined from 6.1+/-2.3 to 3.2+/-1.6 per 1000 patient days (p=0.005). Most of this reduction was attributable to a reduction in false-positive cultures, from 4.2+/-2.4 to 1.9+/-1.8 per 1000 patient days (p=0.042), but there was a trend toward decreased true-positive cultures (from 2.1+/-1.2 to 1.2+/-1.0 per 1000 patient days, p=0.074) as well. Potential confounders and demographics factors were similar between the control and intervention subjects.Implementation of an evidence-based hand washing policy resulted in a significant increase in hand washing compliance and a significant decrease in false-positive coagulase negative staphylococcal blood and CSF culture rates. Exploratory data analysis revealed a possible effect on true-positive coagulase negative staphylococcal blood and CSF culture rates, but these results need to be confirmed in future studies.

    View details for PubMedID 11896519

  • Acetaminophen toxicity in children PEDIATRICS Ward, R. M., Bates, B. A., Benitz, W. E., Burchfield, D. J., Ring, J. C., Walls, R. P., WALSON, P. D., Alexander, J., Bennett, D. R., Cvetkovich, T., Hagino, O. R., Macleod, S. M., Mithani, S., Mulinare, J., Riley, L. E., Yaffe, S. J., Cote, C. J., Meltzer, E. O., Kearns, G. L., McCarver, D. G., Notterman, D. A., Spielberg, S. J., Koteras, R. J. 2001; 108 (4): 1020-1024


    Acetaminophen is widely used in children, because its safety and efficacy are well established. Although the risk of developing toxic reactions to acetaminophen appears to be lower in children than in adults, such reactions occur in pediatric patients from intentional overdoses. Less frequently, acetaminophen toxicity is attributable to unintended inappropriate dosing or the failure to recognize children at increased risk in whom standard acetaminophen doses have been administered. Because the symptoms of acetaminophen intoxication are nonspecific, the diagnosis and treatment of acetaminophen intoxication are more likely to be delayed in unintentional cases of toxicity. This statement describes situations and conditions that may contribute to acetaminophen toxicity not associated with suicidal intentions.

    View details for Web of Science ID 000171319600051

    View details for PubMedID 11581462

  • The transfer of drugs and other chemicals into human milk PEDIATRICS Ward, R. M., Bates, B. A., Benitz, W. E., Burchfield, D. J., Ring, J. C., Walls, R. P., WALSON, P. D. 2001; 108 (3): 776-789
  • Medication errors in children JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Poole, R. L., Benitz, W. E. 2001; 286 (8): 915-915

    View details for Web of Science ID 000170577300013

    View details for PubMedID 11509042

  • Venoarterial versus venovenous extracorporeal membrane oxygenation in congenital diaphragmatic hernia: The Extracorporeal Life Support Organization Registry, 1990-1999 31st Annual Meeting of the Section-on-Surgery of the American-Academy-of-Pediatrics Dimmitt, R. A., Moss, R. L., Rhine, W. D., Benitz, W. E., Henry, M. C., VanMeurs, K. P. W B SAUNDERS CO-ELSEVIER INC. 2001: 1199–1204


    Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) traditionally has been the mode of support used in congenital diaphragmatic hernia (CDH). A few studies report success using venovenous (VV) ECMO. The purpose of this study is to compare outcomes in CDH patients treated with VA and VV.The authors queried the Extracorporeal Life Support Organization Registry for newborns with CDH treated with ECMO from January 1, 1990 through December 31, 1999. They analyzed the pre-ECMO data, ECMO course, and complications.VA was utilized in 2,257 (86%) and VV in 371 (14%) patients. The pre-ECMO status was similar, with greater use of nitric oxide, surfactant, and pressors in VV. Survival rate was similar (58.4% for VV and 52.2% for VA, P =.057). VA was associated with more seizures (12.3% v 6.7%, P =.0024) and cerebral infarction (10.5% v 6.7%, P =.03). Sixty-four treatments were converted from VV to VA (VV-->VA). Survival rate in VV-->VA was not significantly different than VA (43.8% v 52.2%, respectively; P =.23). VV-->VA and VA patients had similar neurologic complications.CDH patients treated with VV and VA have similar survival rates. VA had more neurologic complications. The authors identified no disadvantage to the use of VV as an initial mode of ECMO for CDH, although some infants may need conversion to VA.

    View details for DOI 10.1053/jpsu.2001.25762

    View details for Web of Science ID 000170120300021

    View details for PubMedID 11479856

  • Secondary infection presenting as recurrent pulmonary hypertension. Journal of perinatology Hintz, S. R., Benitz, W. E., Halamek, L. P., Van Meurs, K. P., Rhine, W. D. 2000; 20 (4): 262-264


    Primary infection in the neonate, especially group B streptococcal infection, has long been recognized as a cause of persistent pulmonary hypertension of the newborn (PPHN), sometimes requiring treatment with inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO). However, secondary nosocomial infections in the neonatal period have not been widely reported as a cause of severe recurrent pulmonary hypertension (PHTN). We now present two cases of secondary infection in the neonate leading to significant PHTN. In both cases, the infants presented with PPHN soon after birth, requiring transfer to a level 3 neonatal intensive care unit and treatment with high-frequency oscillatory ventilation and iNO. After successful resolution of the initial PPHN, including extubation to nasal cannula, both infants developed signs of severe recurrent PHTN, leading to reintubation, high-frequency oscillatory ventilation and iNO therapy, and consideration of ECMO. In both cases, blood cultures taken at the time of recurrence of PHTN returned positive, one for Staphylococcus epidermidis, the other for methicillin-resistant Staphylococcus aureus. These unusual cases present the possibility of severe recurrent PHTN requiring iNO or ECMO in the setting of secondary infection. We speculate that these infants, although extubated after their first episodes of PHTN, were at risk for recurrence of PHTN due to continued pulmonary vascular reactivity.

    View details for PubMedID 10879342

  • Mortality and time to death in very low birth weight infants: California, 1987 and 1993 PEDIATRICS Gould, J. B., Benitz, W. E., Liu, H. 2000; 105 (3)


    Recent advances in perinatal technology have dramatically increased the survival of very low birth weight (VLBW) infants (<1500 g). The possibility that these advances may also prolong the time to death and increase pain and suffering has been of concern, but there have been no population-based evaluations of this issue.Infant, neonatal, and postneonatal mortality rates and time to death for infants 500 to 749 g, 750 to 999 g, 1000 to 1499 g, and all VLBW infants born during 1987 were compared with those outcomes for infants born in 1993 using statewide California linked birth/death cohort files. To assess the effects of improved survival and changes in time until death, we calculated the total days of life preceding an infant death per 1000 live born infants (TDD).VLBW infants comprised.96% of California's live births in 1987 and.92% of those in 1993. Between 1987 and 1993, VLBW infant mortality rate decreased 28.4% (from 290.7 to 208.3 per 1000 live born VLBW infants), VLBW neonatal mortality rate decreased 30. 3% (from 244.5 to 170.4), and VLBW postneonatal mortality rate decreased 25.3% (from 61.2 to 45.7 per 1000 VLBW alive at 28 days; P <.05 for each rate). Infant mortality rates decreased by 18.8% (718. 1 to 583.0 per 1000) for infants 500 to 749 g, 43.3% (375.1 to 202. 6) for infants 750 to 999 g, and 40.1% (127.9 to 76.7) for infants 1000 to 1449 g (P <.05 for each group). Neonatal mortality and postneonatal mortality rates also decreased in all 3 VLBW subgroups. These reductions in mortality rates were not accompanied by a significant difference in the distribution of times to death or a significant increase in the average time to death for all VLBW infants (22.0 vs 23.6 days) or for those with birth weights of 500 to 749 g (12.7 vs 71.5 days). Reduced mortality in larger infants was accompanied by an increase in the average time to death, from 24. 3 to 32.5 days in infants 750 to 999 g and from 32.3 to 47.0 days in infants 1000 to 1449 g. TDD decreased from 6410 to 4908 days for all VLBW infants. TDD was also reduced 26.4% (2401 days), 24.3% (2115 days), and 22.5% (1043 days) for the 3 VLBW birth weight groups.Both mortality rate and timing of death are important when assessing the impact of advances in perinatal technology. Although the average time to death was significantly increased in VLBW infants weighing >750 g, between 1987 and 1993, advances in perinatal technology dramatically decreased VLBW mortality. In the State of California in 1993, this resulted in 452 fewer VLBW deaths and 8233 fewer days preceding a VLBW death than expected.

    View details for Web of Science ID 000085681100008

    View details for PubMedID 10699139

  • Alveolar capillary dysplasia: diagnostic potential for cardiac catheterization. Journal of perinatology Hintz, S. R., Vincent, J. A., Pitlick, P. T., Fineman, J. R., Steinhorn, R. H., Kim, G. E., Benitz, W. E. 1999; 19 (6): 441-446


    Alveolar capillary dysplasia is a rare cause of persistent pulmonary hypertension of the newborn. Infants with this condition die despite maximal medical intervention including inhaled nitric oxide therapy and extracorporeal membrane oxygenation. To date, diagnosis of this lethal condition was made by open lung biopsy or during postmortem examination. We examined the possibility that distinct cardiac catheterization findings could be used in the diagnosis of this lethal disorder.We present three infants with fatal persistent pulmonary hypertension of the newborn refractory to extracorporeal membrane oxygenation and inhaled nitric oxide therapy, two with postmortem autopsy confirmation of alveolar capillary dysplasia. Each infant underwent cardiac catheterization to complete the diagnostic evaluations.Significant right ventricular hypertension and normal pulmonary venous return were demonstrated, but a markedly diminished or absent capillary blush phase was noted in each infant. This finding is distinct from the normal capillary blush seen in infants with persistent pulmonary hypertension of the newborn of other etiologies.Cardiac catheterization may provide a useful alternative to tissue examination in the diagnosis of alveolar capillary dysplasia.

    View details for PubMedID 10685275

  • Risk factors for early-onset group B streptococcal sepsis: Estimation of odds ratios by critical literature review PEDIATRICS Benitz, W. E., Gould, J. B., Druzin, M. L. 1999; 103 (6)


    To identify and to establish the prevalence of ORs factors associated with increased risk for early-onset group B streptococcal (EOGBS) infection in neonates. streptococcal (EOGBS) infection in neonates.Literature review and reanalysis of published data.Risk factors for EOGBS infection include group B streptococcal (GBS)-positive vaginal culture at delivery (OR: 204), GBS-positive rectovaginal culture at 28 (OR: 9.64) or 36 weeks gestation (OR: 26. 7), vaginal Strep B OIA test positive at delivery (OR: 15.4), birth weight 18 hours (OR: 7.28), intrapartum fever >37.5 degrees C (OR: 4.05), intrapartum fever, PROM, or prematurity (OR: 9.74), intrapartum fever or PROM at term (OR: 11.5), chorioamnionitis (OR: 6.43). Chorioamnionitis is reported in most (88%) cases in which neonatal infection occurred despite intrapartum maternal antibiotic therapy. ORs could not be estimated for maternal GBS bacteriuria during pregnancy, with preterm premature rupture of membranes, or with a sibling or twin with invasive GBS disease, but these findings seem to be associated with a very high risk. Multiple gestation is not an independent risk factor for GBS infection.h Mothers with GBS bacteriuria during pregnancy, with another child with GBS disease, or with chorioamnionitis should receive empirical intrapartum antibiotic treatment. Their infants should have complete diagnostic evaluations and receive empirical treatment until infection is excluded by observation and negative cultures because of their particularly high risk for EOGBS infection. Either screening with cultures at 28 weeks gestation or identification of clinical risk factors, ie, PROM, intrapartum fever, or prematurity, may identify parturients whose infants include 65% of those with EOGBS infection. Intrapartum screening using the Strep B OIA rapid test identifies more at-risk infants (75%) than any other method. These risk identifiers may permit judicious selection of patients for prophylactic interventions.

    View details for Web of Science ID 000080613400006

    View details for PubMedID 10353974

  • Preventing early-onset group B streptococcal sepsis: Strategy development using decision analysis PEDIATRICS Benitz, W. E., Gould, J. B., Druzin, M. L. 1999; 103 (6)


    To evaluate recommended strategies for prevention of early-onset group B streptococcal infections (EOGBS) with reference to strategies optimized using decision analysis.The EOGBS attack rate, prevalence and odds ratios for risk factors, and expected effects of prophylaxis were estimated from published data. Population subgroups were defined by gestational age, presence or absence of intrapartum fever or prolonged rupture of membranes, and presence or absence of maternal group B streptococcus (GBS) colonization. The EOGBS prevalence in each subgroup was estimated using decision analysis. The number of EOGBS cases prevented by an intervention was estimated as the product of the expected reduction in attack rate and the number of expected cases in each group selected for treatment. For each strategy, the number of residual EOGBS cases, cost, and numbers of treated patients were calculated based on the composition of the prophylaxis group. Integrated obstetrical-neonatal strategies for EOGBS prevention were developed by targeting the subgroups expected to benefit most from intervention.Reductions in EOGBS rates predicted by this decision analysis were smaller than those previously estimated for the strategies proposed by the American Academy of Pediatrics in 1992 (32.9% vs 90.7%), the American College of Obstetricians and Gynecologists in 1992 (53.8% vs 88.8%), and the Centers for Disease Control and Prevention in 1996 (75.1% vs 86.0%). Strategies based on screening for GBS colonization with rectovaginal cultures at 36 weeks or on use of a rapid test to screen for GBS colonization on presentation for delivery, combining intrapartum prophylaxis for selected mothers and postpartum prophylaxis for some of their infants, would require treatment of fewer patients and prevent more cases (78.4% or 80.1%, respectively) at lower cost.No strategy can prevent all EOGBS cases, but the attack rate can be reduced at a cost <$12 000 per prevented case. Supplementing intrapartum prophylaxis with postpartum ampicillin in a few infants is more effective and less costly than providing intrapartum prophylaxis for more mothers. Better intrapartum screening tests offer the greatest promise for increasing efficacy. Integrated obstetrical and neonatal regimens appropriate to the population served should be adopted by each obstetrical service. Surveillance of costs, complications, and benefits will be essential to guide continued iterative improvement of these strategies.

    View details for Web of Science ID 000080613400005

    View details for PubMedID 10353973

  • Antimicrobial prevention of early-onset group B streptococcal sepsis: Estimates of risk reduction based on a critical literature review PEDIATRICS Benitz, W. E., Gould, J. B., Druzin, M. L. 1999; 103 (6)


    To identify interventions that reduce the attack rate for early-onset group B streptococcal (GBS) sepsis in neonates.Literature review and reanalysis of published data.The rate of early-onset GBS sepsis in high-risk neonates can be reduced by administration of antibiotics. Treatment during pregnancy (antepartum prophylaxis) fails to reduce maternal GBS colonization at delivery. With the administration of intravenous ampicillin, the risk of early-onset infection in infants born to women with preterm premature rupture of membranes is reduced by 56% and the risk of GBS infection is reduced by 36%; addition of gentamicin may increase the efficacy of ampicillin. Treatment of women with chorioamnionitis with ampicillin and gentamicin during labor reduces the likelihood of neonatal sepsis by 82% and reduces the likelihood of GBS infection by 86%. Universal administration of penicillin to neonates shortly after birth (postpartum prophylaxis) reduces the early-onset GBS attack rate by 68% but is associated with a 40% increase in overall mortality and therefore is contraindicated. Intrapartum prophylaxis, alone or combined with postnatal prophylaxis for the infants, reduces the early-onset GBS attack rate by 80% or 95%, respectively.Women with chorioamnionitis or premature rupture of membranes and their infants should be treated with intravenous ampicillin and gentamicin. Intrapartum antimicrobial prophylaxis may be appropriate for other women whose infants are at increased but less extreme risk, and supplemental postpartum prophylaxis may be indicated for some of their infants. Selection of appropriate candidates and prophylaxis strategies requires careful consideration of costs and benefits for each patient. group B streptococcus, neonatal sepsis, early-onset sepsis, prevention, prophylaxis.

    View details for Web of Science ID 000080613400007

    View details for PubMedID 10353975

  • Serial serum C-reactive protein levels in the diagnosis of neonatal infection PEDIATRICS Benitz, W. E., Han, M. Y., Madan, A., Ramachandra, P. 1998; 102 (4)


    To evaluate serial serum C-reactive protein (CRP) levels for diagnosis of neonatal infection.A regional intensive care nursery and two community intensive care nurseries.All neonates treated for suspected bacterial infection were prospectively evaluated using a standardized clinical pathway. Infants were categorized as having proven sepsis (bacteria isolated from blood, cerebrospinal fluid, or urine culture), probable sepsis (clinical and laboratory findings consistent with bacterial infection without a positive culture), or no sepsis (findings not consistent with sepsis), without consideration of CRP levels. Infants whose blood cultures yielded skin flora but who demonstrated no other signs of bacterial infection were not considered to have sepsis. CRP levels were determined at the initial evaluation and on each of the next two mornings. Sensitivity, specificity, predictive values, and likelihood ratios were calculated for the first (CRP #1), second (CRP #2), higher of the second and third (CRP #2 and #3), or highest of all three CRP levels (CRP x 3).Sepsis was suspected within the first 3 days after birth in 1002 infants (early-onset) and on 184 occasions in 134 older infants (late-onset). There were 20 early-onset and 53 late-onset episodes of proven sepsis, and 74 early-onset and 12 late-onset episodes of probable sepsis. CRP #1 had sensitivities of 39.4% and 64.6% for proven or probable sepsis and 35.0% and 61.5% for proven sepsis in early-onset and late-onset episodes, respectively. CRP levels on the morning after the initial evaluation (CRP #2) had higher sensitivities (92. 9% and 85.0% for proven or probable sepsis and 78.9% and 84.4% for proven sepsis in early-onset and late-onset episodes, respectively), and normal results were associated with lower likelihoods of infection (likelihood ratios for normal results of 0.10 and 0.19 for proven or probable sepsis and 0.27 and 0.21 for proven sepsis, in early-onset and late-onset episodes, respectively). Three serial serum CRP levels had sensitivities of 97.8% and 98.1% for proven or probable sepsis and 88.9% and 97.5% for proven sepsis in early-onset and late-onset episodes, respectively. The negative predictive values for CRP x 3 were 99.7% and 98.7% for both proven or probable sepsis and for proven sepsis in early-onset and late-onset episodes, respectively. A CRP level obtained at the time of the initial evaluation can be omitted without significant loss of sensitivity or negative predictive value: the sensitivities of CRP #2 and #3 were 97.6% and 94.4% for proven or probable sepsis and 88.9% and 96.4% for proven sepsis in early-onset and late-onset episodes, respectively; negative predictive values were 99.7% both for proven and for proven or probable early-onset sepsis, 97.6% for proven or probable late-onset infection, and 98.8% for proven late-onset infection. Serial normal CRP levels were associated with a markedly reduced likelihood of infection as compared with that in the entire population before testing, with likelihood ratios ranging from 0.03 to 0.16 for the various subgroups. Maximum CRP levels >3 mg/dL had positive predictive values >20% for proven or probable early-onset infections and for proven or probable and proven late-onset infections, but only those >6 mg/dL had such a high positive predictive value for proven early-onset sepsis.Serial CRP levels are useful in the diagnostic evaluation of neonates with suspected infection. Two CRP levels <1 mg/dL obtained 24 hours apart, 8 to 48 hours after presentation, indicate that bacterial infection is unlikely. The sensitivity of a normal CRP at the initial evaluation is not sufficient to justify withholding antibiotic therapy. The positive predictive value of elevated CRP levels is low, especially for culture-proven early-onset infections.

    View details for Web of Science ID 000076277600016

    View details for PubMedID 9755278

  • Neutrophil CD11b expression as a diagnostic marker for early-onset neonatal infection JOURNAL OF PEDIATRICS Weirich, E., Rabin, R. L., Maldonado, Y., Benitz, W., Modler, S., Herzenberg, L. A., Herzenberg, L. A. 1998; 132 (3): 445-451


    To determine whether neutrophil surface expression of CD11b predicts early-onset infection or suspected infection in at-risk infants.CD11b expression on peripheral blood neutrophils was determined by flow cytometry of whole blood samples. Blood (0.1 ml) was obtained from a convenience sample of at-risk infants admitted to the neonatal intensive care unit, stained with antibodies detecting CD11b and CD15, chilled, and analyzed within 8 hours. Blood for culture, blood counts, and C-reactive protein (CRP) determination was obtained simultaneously. Subjects were grouped on the basis of culture results and clinical signs, and investigators were blinded to CD11b level.Of 106 subjects, seven had positive bacterial or viral cultures ("confirmed infection"), 17 had clinical signs of infection but negative cultures ("suspected infection"), and 82 had negative cultures and no clinical signs ("no infection"). Neutrophil CD11b was elevated in all infants with confirmed infection, 94% with suspected infection, and none with no infection. The negative and positive predictive values, sensitivity, and specificity were 100%, 99%, 96%, and 100%, respectively, for diagnosis of neonatal infection at initial evaluation. CD11b levels correlated with peak CRP (r2 = 0.76, p < 0.0001); however, CD11b was elevated at the time of admission in all five infants with proven bacterial infection, whereas CRP was normal until the second day in the neonatal intensive care unit in three of these five. Both infants with positive viral cultures had elevated CD11b, but the CRP levels remained within normal limits. The negative predictive value of neutrophil CD11b for identifying suspected or confirmed infection was 99%.This assay for neutrophil CD11b is a promising test for exclusion of early-onset neonatal infection. If validated prospectively, this assay may reduce hospital and antibiotic use in the population of neonates at risk for early-onset infection.

    View details for Web of Science ID 000072877800018

    View details for PubMedID 9544899

  • Serial measurements of serum C-reactive protein in the diagnosis of neonatal infection Han, M. Y., Madan, A., Ramachandran, P., Benitz, W. E. AMER ACAD PEDIATRICS. 1997: 493–94
  • Hemopericardium from coronary artery laceration complicating extracorporeal membrane oxygenation. Journal of perinatology Rhine, W. D., Hartman, G. E., Shochat, S. J., Benitz, W. E., Van Meurs, K. P. 1997; 17 (3): 189-192


    We report the clinical course and successful surgical treatment of hemopericardium resulting from coronary artery (CA) laceration in two patients with congenital diaphragmatic hernia (CDH) undergoing extracorporeal membrane oxygenation (ECMO) bypass.Retrospective case review.Two neonates with CDH had needle aspiration for either pneumothorax or pericardial effusion before initiation of ECMO. While on bypass, progressive hemopericardium led to narrow pulse pressure and decreased venous return that limited bypass flow. Widened cardiac silhouette on chest radiographs suggested hemopericardium; echocardiography was confirmatory in one case. The underlying diagnosis of CA laceration was made during pericardiotomy and treated with surgical patching.Pre-ECMO history of cardiothoracic needle aspiration is important because complications such as hemothorax or hemopericardium may arise once ECMO bypass is initiated. Inadvertent CA laceration may lead to acute hemopericardium, compromising venous drainage. However, CA laceration can be successfully repaired while the patient is on bypass.

    View details for PubMedID 9210072

  • Neonatal severity of illness scoring systems: A comparison CLINICAL PEDIATRICS Fleisher, B. E., Murthy, L., Lee, S., Constantinou, J. C., Benitz, W. E., Stevenson, D. K. 1997; 36 (4): 223-227


    Several different scoring systems have been developed to predict neonatal morbidity and mortality. In this investigation we compared the utility of four severity of illness scoring systems (SISS) as predictors of days on ventilatory (DOV), length of hospital stay (LOS), and mortality in very-low-birth weight (VLBW) premature infants who required mechanical ventilation. The SISS assessed were the Score for Neonatal Acute Physiology (SNAP); the Score for Neonatal Acute Physiology-Perinatal Extension (SNAP + PE); Clinical Risk Index for Babies (CRIB), and the Sinkin Score at 12 hours (SS12). Results revealed significant correlations among the SS12, SNAP, SNAP + PE, CRIB, birth weight (BW), DOV, and LOS. However, none of the systems we assessed offered striking advantage over BW in a VLBW ventilated group.

    View details for Web of Science ID A1997WU89500007

    View details for PubMedID 9114994

  • Sedation administered to very low birth weight premature infants. Journal of perinatology Heller, C., Constantinou, J. C., Vandenberg, K., Benitz, W., Fleisher, B. E. 1997; 17 (2): 107-112


    The aim of this study was to evaluate the impact of individualized developmental care for very low birth weight infants on the amount of sedation used in their treatment.A randomized control trial was conducted. Each infant in the experimental group underwent evaluation weekly, and individualized behaviorally oriented care plans, aimed at reducing stress and promoting self-regulatory behaviors, were prepared and implemented. Control infants received the usual standard of nursery care. Total doses of opioids and chloral hydrate were calculated. Severity of illness during the initial hospital stay was stratified with use of the Neonatal Medical Index.Severely ill infants in the treatment group required less chloral hydrate than those in the control group. Infants who were not severely ill received little or no sedation, and among this subgroup treatment and control infants did not differ.We speculate that developmentally based care reduces stress levels in severely ill very low birth weight infants and thus decreases sedation requirements.

    View details for PubMedID 9134507

  • Plasma concentrations after rectal administration of acetaminophen in preterm neonates Annual Meeting of the American-Society-of-Anesthesiologists Lin, Y. C., Sussman, H. H., Benitz, W. E. BLACKWELL PUBLISHING. 1997: 457–59


    Acetaminophen is frequently administered to infants and children for its antipyretic and analgesic properties. Oral administration is the route of choice in daily practice. In some circumstances this is impractical. Rectal administration of acetaminophen is an alternative route. This study measures plasma concentrations following rectal administration of acetaminophen 20 (10% Infants' Tylenol Drops, McNeil Consumer Product Co., diluted with an equal volume of sterile water) in five preterm neonates. Serial arterial blood samples were obtained at 0, 15, 30, 60, 120, and 240 min. Pharmacokinetic parameters were (mean +/- SD): Cmax (maximum plasma concentration) of 8.38 +/- 3.92 and Tmax (time to reach maximum plasma concentration) of 78.0 +/- 40.2 min. Our results show that 20 of acetaminophen rectally results in low plasma levels in preterm neonates.

    View details for Web of Science ID A1997YE09300005

    View details for PubMedID 9365971

  • Nitrovasodilator therapy for severe respiratory distress syndrome. Journal of perinatology Benitz, W. E., Rhine, W. D., Van Meurs, K. P., Stevenson, D. K. 1996; 16 (6): 443-448


    Improved gas exchange in infants with severe respiratory distress syndrome has been reported in association with infusion of nitroprusside and during inhalation of nitric oxide. To evaluate the association between nitrovasodilator therapy and clinical improvement in premature neonates with severe respiratory distress syndrome, we reviewed the courses of 22 infants with severe respiratory distress syndrome who were treated with sodium nitroprusside for at least 24 hours. These infants had birth weights of 2049 +/- 828 gm (range 720 to 3430 gm), gestational ages of 32.5 +/- 3.5 weeks (range 25 to 38 weeks), high ventilator settings before treatment (FIO2 of 100%, peak inspiratory pressures of 37.8 +/- 6.1 cm H2O [range 30 to 50 cm H2O], and mean airway pressures of 18.0 +/- 3.3 cm H2O [range 12.3 to 26 cm H2O]), and low pretreatment PaO2 of 49.3 +/- 9.4 mm Hg (range 27 to 69 mm Hg). Baseline oxygenation indexes were 39.4 +/- 12.1 (range 18.6 to 66.7). Nitroprusside infusion was temporally associated with increased PaO2, decreased PaCO2, and reduced oxygenation index. Potentially beneficial changes were inconsistent in infants with pulmonary interstitial emphysema and were greatest in infants treated with end-expiratory pressures of at least 4 cm H2O. These observations provide a basis for the hypothesis that nitrovasodilator therapy produces improvement in gas exchange in premature infants with severe respiratory distress syndrome.

    View details for PubMedID 8979182

  • INDIVIDUALIZED DEVELOPMENTAL CARE FOR VERY-LOW-BIRTH-WEIGHT PREMATURE-INFANTS CLINICAL PEDIATRICS Fleisher, B. E., Vandenberg, K., Constantinou, J., Heller, C., Benitz, W. E., Johnson, A., Rosenthal, A., Stevenson, D. K. 1995; 34 (10): 523-529


    Forty very-low-birth-weight neonatal intensive care unit (NICU) infants with birth weights < or = 1,250 g were randomly assigned to treatment or control groups. Behavior of the treatment infants was systematically evaluated, and individualized developmentally oriented care plans were implemented to enhance stability. Treatment babies required fewer days of intermittent mandatory ventilation and continuous positive airway pressure and achieved full enteral feedings sooner. Length of hospital stay and hospital charges were less for treatment than control infants. There were favorable effects on treatment infants' behavioral performance at 42 weeks' postconceptional age. These results support the hypothesis that behaviorally sensitive, developmentally oriented care improves medical and neurodevelopmental outcome in the NICU.

    View details for Web of Science ID A1995RZ28800003

    View details for PubMedID 8591679

  • LOBAR LUNG TRANSPLANTATION AS A TREATMENT FOR CONGENITAL DIAPHRAGMATIC-HERNIA JOURNAL OF PEDIATRIC SURGERY VanMeurs, K. P., Rhine, W. D., Benitz, W. E., Shochat, S. J., Hartman, G. E., Sheehan, A. M., Starnes, V. A. 1994; 29 (12): 1557-1560


    The mortality rate for infants severely affected with congenital diaphragmatic hernia (CDH) remains high despite significant advances in surgical and neonatal intensive care including delayed repair and extracorporeal membrane oxygenation (ECMO). Because of the increasingly successful experience with single-lung transplantation in adults; this approach has been suggested as a potential treatment for CDH infants with unsalvageable pulmonary hypoplasia. The authors report on a newborn female infant who was the product of a pregnancy complicated by polyhydramnios. At birth, she was found to have a right-sided CDH and initially was treated with preoperative ECMO, followed by delayed surgical repair. Despite the CDH repair and apparent resolution of pulmonary hypertension, the infant's condition deteriorated gradually after decannulation, and escalating ventilator settings were required as well as neuromuscular paralysis and pressor support because of progressive hypoxemia and hypercarbia. A lung transplant was performed 8 days after decannulation, using the right lung obtained from a 6-week-old donor. The right middle lobe was excised because of the size discrepancy between the donor and recipient. After transplantation, the patient was found to have duodenal stenosis and gastroesophageal reflux, which required duodenoduodenostomy and fundoplication. The patient was discharged from the hospital 90 days posttransplantation, at 3 1/2 months of age. Currently she is 24 months old and doing well except for poor growth. This case shows the feasibility of single-lung transplantation for infants with CDH, and the potential use of ECMO as a temporary bridge to transplantation. Lobar lung transplantation allowed for less stringent size constraints for the donor lung.

    View details for Web of Science ID A1994PW61200018

    View details for PubMedID 7877027



    Computed tomography scans of the head and early neurodevelopmental assessment (Bayley Scales of Infant development) were recorded for 24 surviving infants who received venovenous extracorporeal membrane oxygenation and were compared with those of infants treated with venoarterial bypass matched by diagnosis and oxygenation index before extracorporeal membrane oxygenation. A comparable neuroradiographic and early neurodevelopmental outcome was documented for survivors of venoarterial and venovenous extracorporeal membrane oxygenation.

    View details for Web of Science ID A1994PA95200025

    View details for PubMedID 8040782

  • BILIRUBIN MEASUREMENTS AND LONG-TERM NEUROLOGIC OUTCOME PEDIATRICS Rhine, W. D., Benitz, W. E., Dennery, P. A., Stevenson, D. K., Seidman, D. S. 1994; 94 (2): 246-246

    View details for Web of Science ID A1994NY95600030

    View details for PubMedID 8036087



    The effective fractional inspired oxygen concentration (FiO2) of supplemental oxygen provided to infants via nasal cannula may be adjusted by changing cannula flow rate or oxygen concentration, factors within our control. However, FiO2 also varies with changes in the patient's breathing, factors beyond our control. While a stable oxygen delivery is desirable, combinations of flow and concentration that maximize stability over time need to be studied.To assess the impact of different weaning strategies on the stability of inspired oxygen concentrations delivered to infants via nasal cannulas and to identify optimum strategies maximizing that stability.Theoretical analysis and comparison with previously published measurements.We derived equations predicting the FiO2 delivered to infants via nasal cannula, incorporating traditional adjustments of cannula flow rate and oxygen concentration, as well as considering the impact of the infant's inspiratory time, tidal volume, and fraction of nasal breathing. We compared predicted results with previously published measures and evaluated strategies to maximize oxygen delivery stability over time.Predicted values correlated well with published hypopharyngeal measurements (r = .97) and were unbiased, accurate predictors of FiO2. Effective FiO2 was least likely to be affected by changes in patient-controlled controlled factors when the nasal cannula flow rate was as low as possible.To minimize variability in oxygen delivery via nasal cannula to infants, cannula flow should be reduced to the lowest possible flow by using undiluted (100%) oxygen. Supplemental oxygen may then be weaned by making small reductions in cannula flow. Cannula oxygen concentration should be reduced below 100% only after the minimum calibrated flow rate is reached. Such a strategy may maximize the stability of delivered oxygen over time as well as minimize the size of changes in delivered oxygen at each step of the weaning process.

    View details for Web of Science ID A1994ND43200014

    View details for PubMedID 8130865

  • A paradigm for making difficult choices in the intensive care nursery. Cambridge quarterly of healthcare ethics Benitz, W. E. 1993; 2 (3): 281-294

    View details for PubMedID 8293217

  • NONINVASIVE METHODS FOR ESTIMATING INVIVO OXYGENATION CLINICAL PEDIATRICS Benaron, D. A., Benitz, W. E., Ariagno, R. L., Stevenson, D. K. 1992; 31 (5): 258-273


    Clinical signs of hypoxia and hyperoxia are nonspecific and unreliable, yet both are potentially injurious. Noninvasive methods of oxygen assessment fill the gap between clinical observation and invasive tests, helping physicians deliver sufficient oxygen with minimum toxicity. Potential sites for oxygen measurement vary between the blood and the mitochondria; each method measures at a different site and detects different types of hypoxia and hyperoxia. Thus, values obtained by two different methods are not equivalent, giving each method unique strengths and weaknesses. We review two clinical methods (pulse oximetry and transcutaneous oximetry), as well as four experimental methods (near-infrared spectrophotometry, magnetic resonance spectroscopy, magnetic resonance saturation imaging, and time-of-flight absorbance spectrophotometry). The principles of each method and the clinical situations in which each succeeds or fails are discussed. A fundamental understanding of each method can help in deciding which methods, if any, are appropriate for a given patient and how best to correct observed oxygenation problems once they are discovered.

    View details for Web of Science ID A1992HU95600001

    View details for PubMedID 1582091


    View details for Web of Science ID A1990DJ67300002

    View details for PubMedID 2187490


    View details for Web of Science ID A1990CT73000009

    View details for PubMedID 2179837



    Proliferation of smooth muscle cells is an important component of pulmonary arterial morphogenesis, both during normal development and pathologic remodeling. However, little is known of the factors that regulate smooth muscle proliferation in these vessels. To investigate the hypothesis that factors produced by endothelial cells may regulate smooth muscle cell growth, we studied the effects of culture medium conditioned by fetal bovine pulmonary arterial endothelium on proliferation of smooth muscle cells in culture. This conditioned medium contains an inhibitor of smooth muscle proliferation that is degraded by nitrous acid, heparinase, and heparitinase, but resists degradation by protease, boiling, and chondroitin ABC lyase, indicating that the inhibitor is structurally similar to heparin. Inhibitor release occurs in both growing and confluent endothelial cell cultures and in the presence and absence of serum. A growth-inhibiting proteoglycan purified to homogeneity from endothelial cell-conditioned medium has physicochemical characteristics similar to those of the prototypic basement membrane heparan sulfate proteoglycan of the Englebreth-Holm-Swarm tumor: an overall size of approximately 10(6) D, heparan sulfate chains of 60,000 D, and a buoyant density of 1.33 g/ml. Antibody raised against the tumor basement proteoglycan recognizes this endothelial heparan sulfate proteoglycan, and Western blotting after SDS-PAGE demonstrates that the core proteins of both proteoglycans migrate as a doublet at apparent molecular weights of 450,000 and 360,000 D. Heparan sulfate glycosaminoglycan prepared from purified medium proteoglycan is a potent inhibitor of smooth muscle cell growth, exhibiting activity approximately 1,000 times greater than that of heparin. These results indicate that endothelial cells cultured from fetal bovine pulmonary arteries produce a basement membrane heparan sulfate proteoglycan that is a potent inhibitor of smooth muscle proliferation. This proteoglycan may mediate endothelial regulation of smooth muscle growth during development or pathologic pulmonary arterial remodeling.

    View details for Web of Science ID A1990DB94000003

    View details for PubMedID 2137707



    Previous investigations have demonstrated specific receptors and associated mitogenic actions for insulin and insulinlike growth factors I and II (IGF-I and II) in postnatal bovine aortic smooth muscle. Using fetal tissue we have observed different patterns of binding and action for these peptides. Smooth muscle cells isolated from near-term fetal bovine aortae were studied in early passage. Specific receptors for both IGF-I and IGF-II were identified. Specific binding averaged 5.7%/2.5 X 10(5) cells for IGF-I, and 16.2% for IGF-II, and 0.3% for insulin. High affinity Kd for both IGF receptors were nanomolar. IGF-II was fivefold less potent than IGF-I in displacing IGF-I binding. IGF-I showed no affinity for the IGF-II receptor. Insulin, at physiologic concentrations, was incapable of displacing either IGF-I or IGF-II binding. Cellular incorporation of [methyl-3H]thymidine was stimulated at the lowest dose of IGF-I tested, 0.5 ng/ml. IGF-II showed no effect up to 100 ng/ml, after which a sharp increase in incorporation was noted. Insulin had a similar effect only at concentrations greater than 0.5 micrograms/ml, with a maximal response noted at 5 to 10 micrograms/ml. Our results indicate that fetal bovine aortic smooth muscle cells have an abundance of IGF receptors but lack specific insulin receptors. In addition, IGF-II binding levels are three times higher than for IGF-I. These results are consistent with observations in other species, in which a predominance of IGF over insulin receptors has been demonstrated in fetal tissue, and provide further evidence for a role for the IGFs in embryonic cellular metabolism.

    View details for Web of Science ID A1988Q249100011

    View details for PubMedID 2971643

  • ENDOTOXIN AND PULMONARY CELL INJURY SURGERY GYNECOLOGY & OBSTETRICS Bloom, R. J., Simon, L. M., Benitz, W. E. 1988; 167 (2): 92-98


    The physiopathologic similarity between adult respiratory distress syndrome (ARDS) secondary to sepsis and endotoxin-induced pulmonary abnormalities has provided extensive descriptive information confirming bacterial endotoxin as a factor initiating the heterogeneous pulmonary changes in ARDS. The present studies have used an established in vitro model for pulmonary cell injury to examine bacterial endotoxin 1, as a direct cytotoxic agent on the two major alveolar cell types, pulmonary endothelium and epithelium; 2, as a stimulant of neutrophil-mediated pulmonary cell injury, and 3, to examine effector mechanisms of cell-mediated damage by studying the potential effectiveness of antioxidants and antiproteolytic agents in the inhibition of this process. Endotoxin direct toxicity and stimulation of neutrophil-mediated pulmonary cell injury was observed in both pulmonary cell populations in systems free of activated serum complement. Endothelial cells were observed to be more susceptible to both the direct effect of endotoxin and to neutrophil-mediated injury when compared with epithelial cell derived monolayers. The addition of an antiprotease (soybean trypsin inhibitor [STI]) was superior to antioxidants (catalase, superoxide dismutase) in reducing the neutrophil-mediated endothelial toxicity (stimulated 51CR per cent release) observed. A 92 per cent degree of protection was observed with the highest dose of STI (5 milligrams per milliliter) used. Proteases released by activated neutrophils on endotoxin stimulation appear to be the predominant toxic species responsible for endothelial injury in this system.

    View details for Web of Science ID A1988P562700002

    View details for PubMedID 3041636

  • Outcome of neonates with birth weights of less than 801 grams. Journal of perinatology Stevenson, D. K., Petersen, K. R., Yates, B. L., Benitz, W. E., Gale, R. 1988; 8 (2): 82-87


    The follow-up results of intensive care for 68 infants with birth weights less than 801 g treated at Stanford University Hospital were reviewed. The overall survival rate for these infants was 35%, but was 50% for those infants who had been successfully resuscitated in the delivery room and were admitted to the Intensive Care Nursery. Infants under 601 g in weight or less than 25 weeks gestation were more likely to die in the delivery room, but survival among those admitted to the Intensive Care Nursery did not depend on birth weight or gestational age. One-minute and 5-minute Apgar scores less than 5 and interstitial emphysema were associated with increased risk of neonatal death. Only two of 22 survivors (9%) were severely handicapped and another eight (36%) had remediable disabilities at 2 years of age. No infant developed hydrocephalus and only one infant had spasticity. We suggest that the low incidence of major handicaps among survivors encourages the vigorous resuscitation of infants weighing less than 801 g at birth, yet strategies must be developed that will minimize both prolonged dying and the cost of intensive care for nonviable infants.

    View details for PubMedID 2461442



    Hypoxemia refractory to oxygen administration and assisted ventilation is found in many clinical conditions and results from a variety of pathophysiologic disorders. Recent clinical and laboratory experience has demonstrated that the choice of therapy for an infant with refractory hypoxemia depends upon identification of the underlying etiologic and pathophysiologic conditions. The ideal therapies for many of these conditions have not yet been defined. We have provided, based on our experience, guidelines for selection of the most appropriate of the currently available therapies for many of these patients.

    View details for Web of Science ID A1988M299000005

    View details for PubMedID 2831603



    Echoencephalograms were obtained for 118 of 121 successive infants who were admitted to the Stanford intensive care nursery, weighed 1,000 g or less at birth, and survived long enough for at least one study to be performed. Eighty-eight of these infants survived and were followed up for 1 to 3 years; psychometric testing (Bayley Scales of Infant Development, Stanford-Binet Intelligence Scale, or both) was performed on 81% of these infants. Subependymal-intraventricular hemorrhages or intraparenchymal hemorrhages were associated with impaired development, but ventriculomegaly was not. The absence of echoencephalographic abnormalities did not exclude the possibility of impaired development in many infants. Periventricular leukomalacia was not observed. These data support independent scoring of subependymal-intraventricular hemorrhages, intraparenchymal hemorrhages, and ventriculomegaly, rather than use of combined scales for prognostic purposes.

    View details for Web of Science ID A1987K089700005

    View details for PubMedID 3612216



    The diagnostic and therapeutic strategies described above have been presented sequentially for the sake of clarity, but in practice should be performed as quickly as possible in any infant who remains cyanotic despite receiving 100% oxygen. The practitioner must proceed with emergent stabilization of the infant with specific therapies for identified problems and nonspecific therapies for suspected problems, recognizing that the coexistence of two or more pathophysiologic entities is not uncommon. By the time of transport, the practitioner may have laid the groundwork for further diagnostic procedures and therapies by having already classified the infant into one of four primary pathophysiologic categories, as outlined in Table 4. Although congenital heart disease may be highly suspected, confirmation may not be possible without echocardiography. The practitioner, however, should not be discouraged by failure to achieve a specific etiologic diagnosis, despite careful analysis of all the information obtained from diagnostic evaluations prior to transport. Hypoxemia refractory to oxygen administration and assisted ventilation is found in many clinical conditions and results from a variety of pathophysiological disorders. The pediatrician caring for such an infant has primary responsibility for stabilization and preparation for transport of the infant to a Level III facility, and for communicating information about diagnostic procedures and therapeutic maneuvers that might facilitate extended resuscitative efforts by the neonatologist accepting responsibility for the transport and subsequent care of the infant.

    View details for Web of Science ID A1987J242000001

    View details for PubMedID 3595037

  • Immediate management of the asphyxiated infant: facilitating the cardiorespiratory transition from fetus to newborn. Journal of perinatology Stevenson, D. K., Frankel, L. R., Benitz, W. E. 1987; 7 (3): 221-225


    The authors discuss the possible ways of managing the asphyxiated infant by considering the respiratory circumstances of the fetus and newborn. However, they conclude that further multicenter clinical trials are required to evaluate the efficacy of the various methods of management of delayed transition in cardiorespiratory function after birth.

    View details for PubMedID 3504458



    The purpose of this study was to record prospectively the frequency of and potential harm caused by errant medication orders at two large pediatric hospitals. The objective of the study was to assess the impact of pharmacist intervention in preventing potential harm. The study was conducted during a 6-month period. A total of 281 and 198 errors were detected at the institutions. The overall error rates for the two hospitals were 1.35 and 1.77 per 100-patient days, and 4.9 and 4.5 per 1,000 medication orders, respectively. Pediatric patients aged 2 years and less and pediatric intensive care unit patients received the greatest proportion of errant orders. Neonatal patients received the lowest rate of errant orders. The most common type of error was incorrect dosage, and the most prevalent type of error was overdosage. Antibiotics was the class of drugs for which errant orders were most common. Orders for theophylline, analgesics, and fluid and electrolytes, including hyperalimentation, were also frequently in error. In general, the error rate was greatest among physicians with the least training, but no physician group was error free. Involving pharmacists in reviewing drug orders significantly reduced the potential harm resulting from errant medication orders.

    View details for Web of Science ID A1987H150200010

    View details for PubMedID 3575028

  • ENDOTOXIN EFFECTS ON CELL-PERMEABILITY Taylor, J. R., Bloom, R. J., Simon, L. M., Benitz, W. SLACK INC. 1987: A386–A386


    Normal pulmonary arterial development in the relatively hypoxic intrauterine environment and pulmonary arterial remodeling in hypoxic infants include extension of the smooth muscle layer into normally nonmuscular arteries and thickening of the arterial media in the muscular arteries. These changes require proliferation of immature smooth muscle cells or differentiation of smooth muscle cell precursors. Because the mechanisms that regulate these processes have not been clearly defined, we asked whether decreased oxygen tensions could promote either hyperplasia or hypertrophy of smooth muscle cell precursors in vitro. We have studied cells that proliferate and migrate out of explants from the media of the pulmonary arteries of near-term bovine fetuses, because these cells are representative of those that are involved in normal arterial development and possibly also in arterial remodeling. Decreases in oxygen tension within and below the physiologic range do not cause hyperplasia or hypertrophy of these cells. Instead, cell proliferation decreased at oxygen tensions below 60 mm Hg. The effects of hypoxia on proliferation of aortic and pulmonary arterial smooth muscle cells were identical, but effects on proliferation of dermal fibroblasts and endothelial cells were smaller in magnitude and evident only at lower oxygen tensions. These findings suggest that hypoxia does not act directly on smooth muscle cells to produce increased quantities of these cells in the pulmonary arteries during normal prenatal development or during remodeling of the pulmonary arteries of the hypoxic neonate, implying that other factors mediate these phenomena.

    View details for Web of Science ID A1986E253200012

    View details for PubMedID 3774412



    An optimal outcome for a distressed newborn infant can be achieved only if immediate resuscitation is followed by appropriate cardiopulmonary intensive care. In the preceding article in this series, we provided recommendations for drug therapy during the initial resuscitation. When an infant is stable enough for transfer to an intensive care nursery, extended cardiopulmonary intensive care should be initiated. If the infant remains distressed, this may require drug therapy to improve cardiac output, either by enhancing cardiac performance (dopamine, dobutamine or epinephrine) or by reducing afterload (nitroprusside). Drugs that alter the distribution of the circulation may be required for infants with persistent hypoxemia due to pulmonary hypertension or congenital heart disease (tolazoline, nitroprusside, prostaglandin E(1)), or with pulmonary congestion due to persistent patency of the ductus arteriosus (indomethacin). Infants with pulmonary disease may benefit from administration of agents that alter pulmonary function (furosemide, nitroprusside or neuromuscular blockers). Finally, treatment of the underlying disorder, with antibiotics or naloxone, for example, must not be neglected.

    View details for Web of Science ID A1986D218900003

    View details for PubMedID 3529631



    Resuscitation of a neonate requires both immediate cardiopulmonary resuscitation and extended intensive care. Initial resuscitation of the neonate, as for adults, must include support of the airway, breathing and circulation. Because of the unique physiology of a newborn infant, some aspects of drug therapy differ significantly from their counterparts in the resuscitation of adults, and hypoglycemia and hypothermia pose special threats to a distressed neonate. Epinephrine and atropine can be administered via an endotracheal tube, but vascular access, which is most easily obtained by cannulating an umbilical vessel, is required for administering other drugs. Initial drug therapy, including glucose, oxygen and bicarbonate, is intended to restore metabolic homeostasis. Bicarbonate administration must be preceded by adequate alveolar ventilation. Drugs used to increase cardiac output early in resuscitation include those that increase heart rate, increase preload or improve myocardial function. Other drugs used in extended intensive care may also improve cardiac output, alter the distribution of the circulation or alter pulmonary function or gas exchange. These agents will be reviewed in a subsequent article.

    View details for Web of Science ID A1986C700700004

    View details for PubMedID 3727530



    Proliferation of smooth muscle cells from the pulmonary arteries and aortas of fetal calves is inhibited by heparin in vitro. This effect is reversible and dose dependent. Comparisons with effects of other polysaccharides indicate that only extensively sulfated polysaccharides inhibit proliferation of smooth muscle cells but that specific structural features of heparin are required to achieve maximum effect. Heparin-Sepharose chromatography of medium containing fetal calf serum reduces the ability of that medium to promote growth of smooth muscle cells from fetal pulmonary arteries, suggesting that heparin may remove soluble growth factors in serum. However, inhibition of fetal pulmonary artery smooth muscle cell proliferation by heparin is identical in media supplemented either with serum prepared from fetal calf plasma, in which platelet-derived growth factor (PDGF) is not detectable, or with fetal calf serum, which contains relatively abundant PDGF (114 pg/ml). Thus, inhibition of fetal pulmonary artery smooth muscle cell proliferation by heparin is not mediated solely by decreased availability or activity of exogenous PDGF. These studies suggest that morphogenesis of the smooth muscle investment of the pulmonary arteries could be regulated by local production of heparin-like inhibitors of smooth muscle cell growth.

    View details for Web of Science ID A1986A837200001

    View details for PubMedID 2420809

  • USE OF SODIUM-NITROPRUSSIDE IN NEONATES - EFFICACY AND SAFETY JOURNAL OF PEDIATRICS Benitz, W. E., MALACHOWSKI, N., Cohen, R. S., Stevenson, D. K., Ariagno, R. L., Sunshine, P. 1985; 106 (1): 102-110


    Sodium nitroprusside was administered to 58 neonates, including 11 with severe respiratory distress syndrome, 15 with persistent pulmonary hypertension of the newborn, 28 with clinical shock, three with systemic hypertension, and two with pulmonary hypoplasia, all refractory to conventional intensive therapy. Nitroprusside was infused at 0.2 to 6.0 micrograms/kg/min for periods of 10 minutes to 126 hours. Infants with severe respiratory distress syndrome had increased PaO2 and decreased PaCO2 or peak inspiratory pressure, and nearly all (82%) survived. Infants with persistent pulmonary hypertension of the newborn had variable responses; improvement did not correlate with survival, but survival (47%) was identical to that in an earlier series of infants given tolazoline. Infants in shock had improved perfusion, urine output, and serum bicarbonate levels, and these responses were significantly related to survival. Hypertension was controlled in all three hypertensive infants. Adverse effects were very uncommon. Toxic effects were not observed. Sodium nitroprusside is effective and can be used safely in circulatory disorders in the neonate.

    View details for Web of Science ID A1985AAH1500023

    View details for PubMedID 3917495

  • GROWTH FAILURE SECONDARY TO DEXAMETHASONE IN PRETERM NEONATES Sweeney, T., Benitz, W. E., Baldwin, R. E., Ariagno, R. L. SLACK INC. 1985: A149–A149


    Bilirubin binding affinities and capacities and apparent unbound ("free") bilirubin levels were determined in serum samples from 47 high-risk newborns, in 22 samples of cord serum, and in serum samples from 15 Greek children with marked hyperbilirubinemia, by both fluorescence quenching and peroxidase methods. The free fatty acid:albumin molar ratio was also determined for serum samples from high-risk newborns. In vitro and in vivo measurements suggest that free fatty acids are rarely present at levels that produce significant displacement of bilirubin, which is in agreement with previous studies. The two bilirubin binding assays showed only fair correlation with sizable discrepancies for many specimens. Technical difficulties inherent in the fluorescence quenching method and possible sources of error are discussed. Our observations suggest that routine application of these two assays as the primary criterion for therapeutic intervention (e.g., exchange transfusion) is premature.

    View details for Web of Science ID A1984SJ47800009

    View details for PubMedID 6718091



    Laryngeal coccidioidomycosis with severe upper airway obstruction occurred in a 5-year-old boy. Diagnosis was confirmed by positive serum precipitin and complement fixation titers, pathologic demonstration of typical Coccidioides spherules in biopsy specimens from subglottic tissue and paratracheal lymph nodes, and culture of C. immitis from the subglottic tissue specimen. The child was treated successfully with tracheostomy and intravenously administered amphotericin B (total dose of 60 mg/kg).

    View details for Web of Science ID A1983RK85100007

    View details for PubMedID 6638327

  • PROTEIN-COMPOSITION OF GLIAL AND NERVE-FIBERS FEBS LETTERS Benitz, W. E., DAHL, D., Williams, K. W., Bignami, A. 1976; 66 (2): 285-289

    View details for Web of Science ID A1976CA47300031

    View details for PubMedID 955093