13: Method of delivery and neonatal outcomes in preterm, small for gestational age infants

in preterm, small for gestational age infants Erika F. Werner, David Savitz, Teresa Janevic, Stephen F. Thung, Edmund F. Funai, Heather Lipkind Johns Hopkins University, Gynecology and Obstetrics, Baltimore, MD, Brown University, Departments of Epidemiology and Obstetrics and Gynecology, Providence, RI, Yale University, Global Health Initiative, New Haven, CT, Yale University, Ob/Gyn & Reprod Science, New Haven, CT OBJECTIVE: Cesarean delivery (CD) has been proposed as an obstetric strategy to improve neonatal outcomes for premature fetuses with intrauterine growth restriction (IUGR). The relative rarity of this clinical situation has made prospective randomized studies challenging and has even limited retrospective cohort studies. This study was undertaken to compare neonatal outcomes by method of delivery in preterm ( 34 week), small for gestational age (SGA) infants in a large diverse cohort. STUDY DESIGN: Birth data for 1995 to 2003 from New York City were linked to hospital discharge data. Data were limited to singleton, live born, vertex neonates delivered between 25 and 34 weeks. Births complicated by known congenital anomalies, birth weight 500 grams and those requiring forceps or vacuum assistance were excluded. Deliveries were also excluded if there was a maternal history of prior CD. SGA was used as a surrogate for IUGR. Any diagnosis of intraventricular hemorrhage (IVH), seizure, sepsis, subdural hemorrhage, respiratory distress syndrome (RDS), or five minute Apgar 7 was considered a significant neonatal morbidity. Associations between method of delivery and neonatal morbidities were estimated using logistic regression. RESULTS: 2560 SGA neonates meeting the study criteria were identified; 46% were delivered vaginally and 54% were delivered by CD. There was no significant difference in IVH, subdural hemorrhage, seizure or sepsis between the CD and vaginal delivery (VD) groups. CD compared to VD was associated with increased odds of RDS. The increased odds persisted after controlling for maternal age, ethnicity, education, primary payor, pre-pregnancy weight, gestational age at delivery, diabetes and hypertension. CD compared to VD was associated with increased odds of five minute Apgar 7 using unadjusted odds (odds ratio: 1.4; 95% CI 1.1-1.9), but this difference dissipated after adjusting for confounding factors. CONCLUSION: CD was not associated with decreased odds of any neonatal complications and was associated with significantly higher odds of RDS in SGA preterm neonates. 14 Effect of prescription medications on 17-alphahydroxyprogesterone caproate (17-OHPC) metabolism Yang Zhao, Courtney Cuppett, Steve Caritis, Raman Venkataramanan University of Pittsburgh, School of Pharmacy, Pittsburgh, PA, Magee-Womens Hospital, University of Pittsburgh, Maternal Fetal Medicine, Pittsburgh, PA OBJECTIVE: 17-OHPC and certain prescription medications are metabolized by the CYP3A4 enzyme. We hypothesize that these medications may compete with 17-OHPC for metabolism. Any alteration in 17-OHPC metabolism may affect the concentration of 17-OHPC and impact its efficacy. STUDY DESIGN: Pooled (n 5) human CYP3A4 microsomes were incubated for 60 min at 37C with 17-OHPC (2.5ug/mL) alone or in combination with 21 different medications known to be CYP3A4 substrates or inhibitors. Incubations were carried out in a solution of phosphate buffer and magnesium chloride. An NADPH-generating system was used to initiate metabolism. HPLC was performed to measure unmetabolized 17-OHPC concentration. RESULTS: Thirteen of the 21 drugs tested exhibited inhibitory effects on 17-OHPC metabolism. 17-OHPC metabolism was inhibited by 80% when incubated with montelukast, esomeprazole, nelfinavir, or ritonavir. Metabolism of 17-OHPC was inhibited by 50-80% in the presence of fluconazole, itraconazole, voriconazole, sertraline, haloperidol, trazodone, tacrolimus, or bergamottin. Only 20-50% inhibition was observed in the presence of fluticasone. CONCLUSION: 17-OHPC metabolism is inhibited by several prescription medications. Concomitant use of these medications during pregnancy may lead to significant alterations in 17-OHPC metabolism and ultimately impact the overall efficacy of 17-OHPC in the prevention of preterm birth. This work was supported by NICHD Obstetric-Fetal Pharmacology Research Units Network grant HD047905.