Association of prenatal antibiotics with measures of infant adiposity and the gut microbiome

BackgroundPrenatal antibiotic exposure has been associated with analtered infant gutmicrobiome compositionand higher risk ofchildhood obesity, but no studies have examined if prenatal antibiotics simultaneouslyalter the gutmicrobiome and adiposity in infants.MethodIn this prospective study (Nurture: recruitment 2013-2015 in North Carolina, United States), we examined in 454 infants the association of prenatal antibiotic exposure (by any prenatal antibiotic exposure; by trimester of pregnancy; by number of courses; by type of antibiotics) with infant age- and sex-specific weight-for-length z score (WFL-z) and skinfold thicknesses (subscapular, triceps, abdominal) at 12months of age. In a subsample, we also examined whether prenatal antibiotic exposure was associated with alterations in the infant gutmicrobiome at ages 3 and 12months.ResultsCompared to infants not exposedto prenatal antibiotics, infants who were exposed to any prenatal antibiotics had 0.21 (95% confidence interval [CI] 0.02, 0.41) higher WFL-z at 12months, and 0.28 (95% CI 0.02, 0.55) higher WFL-z if they were exposed to antibiotics in the second trimester, after adjustment for potential confounders, birth weight, and gestational age. We also observed a dose-dependent association (P-value for trend=0.006) with infants exposed to 3 courses having 0.41 (95% CI 0.13, 0.68) higher WFL-z at 12months. After further adjustment for delivery method, only second-trimester antibiotic exposure remained associated with higher infant WFL-z (0.27, 95% CI 0.003, 0.54) and subscapular skinfold thickness (0.49mm, 95% CI 0.11, 0.88) at 12months. Infants exposed to second-trimester antibiotics versusnot had differential abundance of 13 bacterial amplicon sequence variants (ASVs) at age 3months and 17 ASVs at 12months (false discovery rate adjusted P-value <0.05).ConclusionsPrenatal antibiotic exposure in the second trimester was associated with analtered infant gutmicrobiome compositionat 3 and 12months and with higher infant WFL-z and subscapular skinfold thickness at 12months.