Abstract

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. © The Author(s) 2025; all rights reserved.