Fergal D. Malone

Neonatal outcomes in twin pregnancies delivered moderately preterm, late preterm, and term

We compared neonatal outcomes in twin pregnancies following moderately preterm birth (MPTB), late preterm birth (LPTB), and term birth. A secondary analysis of a multicenter, randomized controlled trial of multiple gestations was conducted. MPTB was defined as delivery between 32 (0)/(7) and 33 (6)/(7) weeks and LPTB between 34 (0)/(7) and 36 (6)/(7) weeks. Primary outcome was a neonatal outcome composite consisting of one or more of the following: neonatal death, respiratory distress syndrome, early onset culture-proven sepsis, stage 2 or 3 necrotizing enterocolitis, bronchopulmonary dysplasia, grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, pneumonia, or severe retinopathy of prematurity. Among 552 twin pregnancies, the MPTB rate was 14.5%, LPTB 49.8%, and term birth rate 35.7%. The rate of the primary outcome was different between groups: 30.0% for MPTB, 12.8% for LPTB, 0.5% for term birth ( P < 0.001). Compared with term neonates, the primary neonatal outcome composite was increased following MPTB (relative risk [RR] 58.5; 95% confidence interval [CI] 11.3 to 1693.0) and LPTB (RR 24.9; 95% CI 4.8 to 732.2). Twin pregnancies born moderately and late preterm encounter higher rates of neonatal morbidities compared with twins born at term.

Failed Labor Induction Toward an Objective Diagnosis

OBJECTIVE: To evaluate maternal and perinatal outcomes in women undergoing labor induction with an unfavorable cervix according to duration of oxytocin administration in the latent phase of labor after ruptured membranes. METHODS: This was a secondary analysis of a randomized multicenter trial in which all cervical examinations from admission were recorded. Inclusion criteria: nulliparas at or beyond 36 weeks of gestation undergoing induction with a cervix of 2 cm or less dilated and less than completely effaced. The latent phase of labor was defined as ending at a cervical dilation of 4 cm and effacement of at least 90%, or at a cervical dilation of 5 cm regardless of effacement. RESULTS: A total of 1,347 women were analyzed. The overall vaginal delivery rate was 63.2%. Most women had exited the latent phase after 6 hours of oxytocin and membrane rupture (n=939; 69.7%); only 5% remained in the latent phase after 12 hours. The longer the latent phase, the lower the vaginal delivery rate. Even so, 39.4% of the 71 women who remained in the latent phase after 12 hours of oxytocin and membrane rupture were delivered vaginally. Chorioamnionitis, endometritis, or both, and uterine atony were the only maternal adverse outcomes related to latent-phase duration: adjusted odds ratios (95% confidence intervals) of 1.12 (1.07, 1.17) and 1.13 (1.06, 1.19), respectively, for each additional hour. Neonatal outcomes were not related to latent-phase duration. CONCLUSION: Almost 40% of the women who remained in the latent phase after 12 hours of oxytocin and membrane rupture were delivered vaginally. Therefore, it is reasonable to avoid deeming labor induction a failure in the latent phase until oxytocin has been administered for at least 12 hours after membrane rupture. LEVEL OF EVIDENCE: III

Maternal 25-Hydroxyvitamin D and Preterm Birth in Twin Gestations

OBJECTIVE: To assess whether there was an independent association between maternal 25-hydroxyvitamin D concentrations at 24–28 weeks of gestation and preterm birth in a multicenter U.S. cohort of twin pregnancies. METHODS: Serum samples from women who participated in a clinical trial of 17 &agr;-hydroxyprogesterone caproate for the prevention of preterm birth in twin gestations (2004–2006) were assayed for 25-hydroxyvitamin D concentrations using liquid chromatography tandem mass spectrometry (n=211). Gestational age was determined early in pregnancy using a rigorous algorithm. Preterm birth was defined as delivery of the first twin or death of either twin at less than 35 weeks of gestation. RESULTS: The mean serum 25-hydroxyvitamin D concentration was 82.7 nmol/L (standard deviation 31.5); 40.3% of women had concentrations less than 75 nmol/L. Preterm birth at less than 35 weeks of gestation occurred in 49.4% of women with 25-hydroxyvitamin D concentrations less than 75 nmol/L compared with 26.2% among those with concentrations of 75 nmol/L or more (P<.001). After adjustment for maternal race and ethnicity, study site, parity, prepregnancy body mass index, season, marital status, education, gestational age at blood sampling, smoking status, and 17 &agr;-hydroxyprogesterone caproate treatment, maternal 25-hydroxyvitamin D concentration of 75 nmol/L or more was associated with a 60% reduction in the odds of preterm birth compared with concentrations less than 75 nmol/L (adjusted odds ratio [OR] 0.4, 95% confidence interval [CI] 0.2–0.8). A similar protective association was observed when studying preterm birth at less than 32 weeks of gestation (OR 0.2, 95% CI 0.1–0.6) and after confounder adjustment. CONCLUSIONS: Late second-trimester maternal 25-hydroxyvitamin D concentrations less than 75 nmol/L are associated with an increase in the risk of preterm birth in this cohort of twin pregnancies. LEVEL OF EVIDENCE: II

Association of polymorphisms in neuroprotection and oxidative stress genes and neurodevelopmental outcomes after preterm birth

OBJECTIVE: To estimate the associations between polymorphisms in neuronal homeostasis, neuroprotection, and oxidative stress candidate genes and neurodevelopmental disability. METHODS: This was a nested case-control analysis of a randomized trial of magnesium sulfate administered to women at imminent risk for early (before 32 weeks) preterm birth for the prevention of death or cerebral palsy in their offspring. We evaluated 21 single-nucleotide polymorphisms (SNPs) in 17 genes associated with neuronal homeostasis, neuroprotection, or oxidative stress in umbilical cord blood. Cases included infant deaths (n=43) and children with cerebral palsy (n=24), mental delay (Bayley Mental Developmental Index less than 70; n=109), or psychomotor delay (Bayley Psychomotor Developmental Index less than 70; n=91) diagnosed. Controls were race-matched and sex-matched children with normal neurodevelopment. Associations between each SNP and each outcome were assessed in logistic regression models assuming an additive genetic pattern, conditional on maternal race and infant sex, and adjusting for study drug assignment, gestational age at birth, and maternal education. RESULTS: The odds of cerebral palsy were increased more than 2.5 times for each copy of the minor allele of vasoactive intestinal polypeptipe (VIP, rs17083008) (adjusted odds ratio 2.67, 95% confidence interval 1.09–6.55, P=.03) and 4.5 times for each copy of the minor allele of N-methyl-D-aspartate receptor subunit 3A (GRIN3A, rs3739722) (adjusted odds ratio 4.67, 95% CI 1.36–16.01, P=.01). The association between the advanced glycosylation end product-specific receptor (AGER, rs3134945) SNP and mental delay was modulated by study drug allocation (P=.02). CONCLUSION: Vasoactive intestinal polypeptipe and GRIN3A SNPs may be associated with cerebral palsy at age 2 in children born preterm. LEVEL OF EVIDENCE: II

Association of Cervical Effacement With the Rate of Cervical Change in Labor Among Nulliparous Women.

OBJECTIVE: To assess the association of cervical effacement with the rate of intrapartum cervical change among nulliparous women. METHODS: We conducted a secondary analysis of a prospective trial of intrapartum fetal pulse oximetry. For women who had vaginal deliveries, interval-censored regression was used to estimate the time to dilate at 1-cm intervals. For each given centimeter of progressive cervical dilation, women were divided into those who had achieved 100% cervical effacement and those who had not. The analysis was performed separately for women in spontaneous labor and those who were given oxytocin. RESULTS: A total of 3,902 women were included in this analysis, 1,466 (38%) who underwent labor induction, 1,948 (50%) who underwent labor augmentation (combined for the analysis), and 488 (13%) who labored spontaneously. For women in spontaneous labor, the time to dilate 1 cm was shorter for those who were 100% effaced starting at 4 cm of cervical dilation (P=.01 to <.001). For women who received oxytocin, the time to dilate 1 cm was shorter for those who were 100% effaced throughout labor (P<.001). CONCLUSION: The rate of cervical dilation among nulliparous women is associated with not only the degree of cervical dilation, but also with cervical effacement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00098709.