Maternal pre-pregnancy diabetes and risk of all-cause and cause-specific infant mortality

BACKGROUND: Maternal pre-pregnancy diabetes is associated with a higher risk of adverse pregnancy outcomes. Few large, cohort studies have assessed associations with a wide large range of causes of infant death. METHODS: This retrospective cohort study included all singleton live births to women aged 18-49 years in the US National Vital Statistics System from 2011 to 2020. Multivariable Poisson regression models were used to estimate adjusted relative risks (RRs) with 95% confidence intervals (CIs) for all-cause and cause-specific infant mortality. RESULTS: Of 34 918 803 pregnant women with singleton live births, 302 823 had pre-pregnancy diabetes with 3585 corresponding infant deaths [estimated mortality rate per 10 000 infants with 95% CI was 78.60 (75.96-81.25)] compared with 34 615 980 without pre-pregnancy diabetes and 171 989 corresponding infant deaths [42.63 (42.41-42.86)]. The adjusted RR (95% CI) of pre-pregnancy diabetes compared with no pre-pregnancy diabetes was 1.84 (1.78-1.91) for infant death, 1.89 (1.81-1.97) for neonatal death, 1.85 (1.77-1.94) for early neonatal death, 2.04 (1.87-2.23) for late neonatal death, and 1.75 (1.65-1.86) for postneonatal deaths. The association was stronger (RR: 2.03, 95% CI: 1.88-2.20) with lower maternal age (<25 years) than with higher maternal age (≥40 years) (RR: 1.44, 95% CI: 1.28-1.63). Associations varied across maternal race, smoking, and body mass index. Significantly increased risk was observed for 48 out of 73 specific causes of death. CONCLUSION: Our findings confirm that maternal pre-pregnancy diabetes is an important risk factor for infant death, encompassing a wide range of causes of death, and suggest that these effects may be systemic given the large number of specific causes of death affected.