Impact of Maternal Diabetes in Pregnancy on Newborn IgG Antibody Repertoire and Infection Risk in the First 6 Months of Life

OBJECTIVE: To investigate whether maternal diabetes in pregnancy was associated with altered neonatal global IgG repertoire and early-life infections in offspring. RESEARCH DESIGN AND METHODS: This study included 2,702 mother-infant pairs enrolled at birth and followed longitudinally at the Boston Medical Center. Maternal diabetes and infant infections were extracted from electronic medical records. Cord blood IgG antibodies against a wide range of microbes were quantified using Phage ImmunoPrecipitation Sequencing. RESULTS: Overall, 327 infants (12.1%) were born to mothers with gestational diabetes mellitus (GDM) and 138 (5.1%) to mothers with pregestational diabetes mellitus (PDM). Of these, 416 infants (15.4%) and 1,425 infants (52.7%) had at least one infection in the neonatal period and the first 6 months of life, respectively. Compared with no diabetes, both maternal GDM (risk ratio [RR] 1.20, 95% CI 1.09-1.32) and PDM (RR 1.28, 95% CI 1.12-1.47) were significantly associated with an elevated risk of infections in infants during the first 6 months. These associations were particularly pronounced among infants born preterm, delivered via cesarean section, or with lower IgG repertoire diversity. Additionally, PDM was associated with a lower newborn's global IgG repertoire diversity, compared with no diabetes, with the effect more marked among infants whose mothers had prepregnancy overweight or obesity. CONCLUSIONS: This study provides strong evidence of an increased infection risk in the infants of mothers with diabetes and a reduced IgG repertoire diversity in those of PDM mothers. Lower IgG diversity exacerbated the diabetes-infection link. These findings suggest that maternal metabolic conditions may impact an infant's passive immunity and susceptibility to infections.