Neonatal outcomes in term and preterm infants following adjunctive azithromycin antibiotic prophylaxis for non-elective cesarean delivery.

OBJECTIVE: It is currently unknown whether adjunctive azithromycin prophylaxis at the time of non-elective cesarean has differential effects on neonatal outcomes in the context of prematurity. The objective of this study was to compare whether neonatal outcomes differ in term and preterm infants exposed to adjunctive azithromycin prophylaxis before non-elective cesarean delivery. STUDY DESIGN: A planned secondary analysis of a multi-center randomized controlled trial that enrolled women with singleton pregnancies ≥24 weeks gestation undergoing non-elective cesarean delivery (during labor or ≥4 h after membrane rupture). Women received standard antibiotic prophylaxis and were randomized to either adjunctive azithromycin (500 mg) or placebo. The primary composite outcome was neonatal death, suspected or confirmed neonatal sepsis, and serious neonatal morbidities (NEC, PVL, IVH, BPD). Secondary outcomes included NICU admission, neonatal readmission, culture positive infections and prevalence of resistant organisms. Odds ratios (OR) for the effect of azithromycin versus placebo were compared between gestational age strata (preterm [less than 37 weeks] versus term [37 weeks or greater]). Tests of interaction examined homogeneity of treatment effect with gestational age. RESULTS: The analysis includes 2,013 infants, 226 preterm (11.2%) and 1,787 term. Mean gestational ages were 34 and 39.5 weeks, respectively. Within term and preterm strata, maternal and delivery characteristics were similar between the azithromycin and placebo groups. There was no difference in the odds of composite neonatal outcome between those exposed to azithromycin versus placebo in preterm neonates (OR 0.82, 95% CI 0.48-1.41) and in term neonates (OR 1.06, 95% CI 0.77-1.46), with no difference between gestational age strata (p = 0.42). Analysis of secondary outcomes also revealed no differences in treatment effects within or between gestational age strata. CONCLUSION: Exposure to adjunctive azithromycin antibiotic prophylaxis for non-elective cesarean delivery does not increase neonatal morbidity or mortality in term or preterm infants. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov, NCT01235546.

Is low-dose aspirin therapy to prevent preeclampsia more efficacious in non-obese women or when initiated early in pregnancy?

OBJECTIVE: Late timing of intervention and maternal obesity are potential explanations for the modest effect of aspirin for preeclampsia prevention. We explored whether low-dose aspirin (LDA) is more effective in women at increased risk when initiated before 16 weeks' gestation or given to non-obese women. METHODS: Secondary analysis of a trial to evaluate LDA (60 mg/d) for preeclampsia prevention in high-risk women. Participants were randomized to LDA or placebo between 13 and 26 weeks. We stratified the effect of LDA on preeclampsia by (a) timing of randomization (< 16 or ≥ 16 weeks gestation) and (b) body mass index (BMI) class (non-obese and obese). The Breslow-Day test for homogeneity was used to assess for variations in effect of LDA across gestational age and BMI groups. RESULTS: Of 2503 women, 461 (18.4%) initiated LDA < 16 weeks. LDA effect was not better when initiated < 16 weeks (RR: 0.93, 95% CI: 0.67-1.31) versus ≥ 16 weeks (RR: 0.90, 95% CI: 0.75-1.08), (p value for interaction = 0.87). Similarly, LDA effect was not better in non-obese (RR: 0.91, 95% CI: 0.7-1.13) versus obese women (RR: 0.89, 95% CI: 0.7-1.13), (p value for interaction = 0.85). CONCLUSION: LDA for preeclampsia prevention was not more effective when initiated < 16 weeks or used in non-obese women at risk for preeclampsia. No particular subgroup of women was more or less likely to benefit from LDA therapy.