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

OBJECTIVES To investigate whether maternal diabetes mellitus in pregnancy was associated with altered neonatal global IgG repertoire and early-life infections in offspring. RESEARCH DESIGN AND METHODS This study included 2702 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 (12.1%) infants were born to mothers with gestational diabetes mellitus (GDM) and 138 (5.1%) to mothers with pregestational diabetes mellitus (PDM). 416 (15.4%) and 1425 (52.7%) infants had at least 1 infection in the neonatal period and the first 6 months of life, respectively. Compared to 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 six 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 to no diabetes, with the effect more marked among infants whose mothers had pre-pregnancy 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.