Induction of labor at 39 weeks in low-risk nulliparous women did not result in a significantly lower frequency of a composite adverse perinatal outcome, but it did result in a significantly lower frequency of cesarean delivery. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ARRIVE ClinicalTrials.gov number, NCT01990612 .).

Background Infants born at 34 to 36 weeks’ gestation (late preterm) have greater risks of adverse respiratory and other outcomes, than those born at 37 weeks gestation or later. It is not known whether betamethasone administered to women at risk for late preterm delivery decreases risks of neonatal morbidities. Methods We conducted a multicenter randomized trial of women with a singleton gestation at high risk for late preterm delivery. Participants were randomized to two injections of 12 mg betamethasone or matching placebo 24 hours apart. The primary outcome was a neonatal composite of treatment in the first 72 hours (continuous positive airway pressure or high flow nasal cannula for at least two hours, supplemental oxygen with a fraction of inspired oxygen of at least 30 percent for at least four hours, extra corporeal membrane oxygenation or mechanical ventilation) or stillbirth or neonatal death before 72 hours. Results 2,831 patients were randomized. The primary outcome occurred in 11.6% of the betamethasone group versus 14.4%, in the placebo group (Relative Risk 0.80, 95% confidence interval 0.66-0.97, P=0.02). Severe respiratory morbidity, transient tachypnea of the newborn, surfactant use, and bronchopulmonary dysplasia were also significantly less common in the betamethasone group. There were no significant differences between groups in the incidence of chorioamnionitis or neonatal sepsis. Neonatal hypoglycemia was more common in the betamethasone group. (24.0% versus 14.9%, RR 1.61, 95% CI 1.38-1.88, P<0.001) Conclusions Administration of betamethasone to women at risk for late preterm delivery significantly reduced the rate of neonatal respiratory morbidity.

In this large, routine prenatal-screening population, cfDNA testing for trisomy 21 had higher sensitivity, a lower false positive rate, and higher positive predictive value than did standard screening with the measurement of nuchal translucency and biochemical analytes. (Funded by Ariosa Diagnostics and Perinatal Quality Foundation; NEXT ClinicalTrials.gov number, NCT01511458.).

Importance Maternal immunization with tetanus toxoid and reduced diphtheria toxoid acellular pertussis (Tdap) vaccine could prevent infant pertussis. The effect of vaccine-induced maternal antibodies on infant responses to diphtheria and tetanus toxoids acellular pertussis (DTaP) immunization is unknown. Objective To evaluate the safety and immunogenicity of Tdap immunization during pregnancy and its effect on infant responses to DTaP. Design, Setting and Participants Phase I, randomized, double-masked, placebo-controlled clinical trial conducted in private (Houston) and academic (Durham, Seattle) obstetric practices from 2008 to 2012. Forty eight healthy 18–45 year-old pregnant women received Tdap (n=33) or placebo (n=15) at 30–32 weeks’ gestation with cross-over Tdap immunization postpartum. Interventions Tdap vaccination at 30–32 weeks’ gestation or post-partum. Outcome Measures Primary: Maternal and infant adverse events, pertussis illness and infant growth and development (Bayley-III screening test) until 13 months of age. Secondary: Antibody concentrations in pregnant women before and 4 weeks after Tdap immunization or placebo, at delivery and 2 months postpartum, and in infants at birth, 2 months, and after the third (7 months) and fourth (13 months) doses of DTaP. Results All participants delivered healthy newborns. No Tdap-associated serious adverse events occurred in women or infants. Injection site reactions after Tdap immunization were reported in 78.8% (95% CI: 61.1%, 91.0%) and 80% (CI: 51.9%, 95.7%) pregnant and postpartum women, respectively. Injection site pain was the predominant symptom. Systemic symptoms were reported in 36.4% (CI: 20.4%, 54.9%) and 73.3% (CI: 44.9%, 92.2%) pregnant and postpartum women, respectively. Malaise and myalgia were most common. Growth and development were similar in both infant groups. No cases of pertussis occurred. Significantly higher concentrations of pertussis antibodies were measured at delivery in women who received Tdap during pregnancy and in their infants at birth and at age 2 months when compared to infants of women immunized postpartum. Antibody responses in infants of Tdap recipients during pregnancy were modestly lower after 3 DTaP doses, but not different following the fourth dose. Conclusions and Relevance This preliminary safety assessment did not find an increased risk of adverse events among women who received Tdap vaccine at 30–32 weeks’ gestation or their infants. Maternal immunization with Tdap resulted in high concentrations of pertussis antibodies in infants during the first 2 months of life and did not substantially alter infant responses to DTaP. Further research is needed to provide definitive evidence of the safety and efficacy of Tdap vaccination during pregnancy. Trial Registration ClinicalTrials.gov, study identifier: NCT00707148. URL: http://www.clinicaltrials.gov

While cell-free DNA (cfDNA) testing for fetal aneuploidy has been shown to have a high detection rate for trisomy, most large studies have included only high-risk populations. This blinded, prospective study tested the performance of screening with cfDNA for common trisomies in the general population.Maternal blood samples were collected from women at 35 centers in the United States, Canada, and Europe with a singleton pregnancy between 10.0 and 14.3 weeks' gestation. Samples were sent to a single clinical laboratory for cfDNA testing. The patients were also screened for aneuploidy using measurement of nuchal translucency and biochemical analytes. Participants and providers were blinded to the cfDNA testing results but were informed of the standard screening results. Medical records of physical examination at birth and genetic testing were used to inform newborn outcomes. The area under the receiver operating characteristic curve (AUC) for cfDNA testing for trisomy 21 compared with standard testing was the primary outcome. The AUC of the 2 types of testing for trisomies 13 and 18 were the secondary outcomes.A total of 18,955 women were enrolled between March 2012 and April 2013, and after all exclusions, 15,841 patients were included in the cohort. Mean gestational age was 12.5 weeks, and mean maternal age was 31 years. In the cohort, 1 in 236 pregnancies (n = 68) had chromosomal abnormalities. For trisomy 21, the AUC for cfDNA testing was 0.999, and for standard screening, the AUC was 0.958 (P = 0.001). Cell-free DNA identified all 38 cases of trisomy 21 with 100% sensitivity (95% confidence interval [CI], 90.7%-100%), and standard screening had a sensitivity of 78.0%, identifying 30 of the 38 cases (95% CI, 62.7%-90.4%; P = 0.008). However, if one considered the 3 trisomy 21 cases among those patients with "no results," the sensitivity was really 38 of 41, or 92%, which is not that different from traditional combined screening. In women without trisomy 21, cfDNA had a false-positive rate of 0.06% (95% CI, 0.03%-0.11%), and standard screening had a falsepositive rate of 5.4% (95% CI, 5.1%-5.8%; P < 0.001). In the 11,994 low-risk pregnancies (maternal age <35 years), cfDNA had 6 false-positive results for trisomy 21 but identified all 19 cases. For trisomy 18, cfDNA had a positive predictive value of 90.0% (95% CI, 55.5%-99.7%) and a false-positive rate of 0.01% (95% CI, 0%-0.04%) compared with a 14.0% positive predictive value for standard screening (95% CI, 6.3%-25.8%) and a false-positive rate of 0.31% (95% CI, 0.23%-0.41%). For trisomy 13, cfDNA identified both confirmed cases, and standard screening identified 1 of the 2.In the detection of trisomy 21, cfDNA was found to have a higher sensitivity and specificity with a far lower false-positive rate than standard screening. Further studies on the cost-effectiveness of cfDNA are recommended.