Neurodevelopmental pediatric follow-up after the azithromycin prevention in labor use study

Abstract

OBJECTIVE: To evaluate the association between 2 g of intrapartum azithromycin given to laboring mothers and neurodevelopmental outcomes after birth asphyxia.

METHODS: This was a neurodevelopmental follow-up study of children born at 34 weeks of gestation or later who had concern for asphyxia and whose mothers were enrolled in A-PLUS (the Azithromycin Prevention in Labor Use Study). Mothers in A-PLUS were randomized to receive a single oral dose of azithromycin (2 g) or placebo during labor. This follow-up to A-PLUS spanned six sites across five countries (India [two sites], Pakistan, Zambia, Democratic Republic of Congo, and Guatemala). Asphyxia was defined as 5-minute Apgar score less than 7 or the need for bag-and-mask ventilation at birth. The primary outcome was the CCS (Cognitive Composite Score) of the BSID-III (Bayley Scales of Infant and Toddler Development, 3rd Edition) at a corrected age of 24±1 months. Secondary outcomes included the LCS (Language Composite Score) and MCS (Motor Composite Score) of the BSID-III at a corrected age of 24±1 months. Masked examiners administered the BSID-III and the ASQ-3 (Ages & Stages Questionnaires, 3rd Edition). Outcomes were analyzed using a generalized linear model and were adjusted for site, gestational age at delivery, and maternal and child baseline characteristics that differed between treatment groups.

RESULTS: Of 529 eligible mother-child dyads screened, 403 (197 in the azithromycin arm and 206 in the placebo arm) were enrolled and completed the neurodevelopmental follow-up at a corrected age of 24±1 months. The primary outcome, the CCS of the BSID-III, did not differ significantly between groups (azithromycin: 90.9±11.2 vs placebo: 90.9±11.7; mean difference: 0.29; 95% CI, -1.77 to 2.34). No significant differences were observed between treatment arms in the BSID-III's LCS and MCS or in the total scores of the ASQ-3's five domains. Subgroup analysis by region (sub-Saharan Africa vs South Asia) also showed no differences in BSID-III or ASQ-3 scores between the azithromycin and placebo groups.

CONCLUSION: In this follow-up study, a single oral dose of azithromycin given to laboring mothers who delivered neonates with birth asphyxia did not improve neurodevelopmental outcomes at 2 years of age.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03871491.