Association between pregestational diabetes and mortality among appropriate-for-gestational age birthweight infants

Existing studies have shown that pregestational diabetes is a significant risk factor for adverse birth outcomes. However, it is unclear, whether pregestational diabetes and neonatal birthweight that is appropriate for the gestational age (AGA), a proxy for overall adequate glycemic control, is associated with higher infant mortality. To address this controversy, this study investigated the relationship between pregestational diabetes and infant mortality in appropriate-for-gestational age infants in the United States.

Data from the National Vital Statistics System-Linked Birth-Infant Death dataset, including 6,962,028 live births between 2011 and 2013 were analyzed. The study was conducted in the US and data were analyzed in Milwaukee, Wisconsin. The outcome was mortality among AGA newborns, defined as annual deaths per 1000 live births with birthweights between the 10th and 90th percentiles for gestational age delivering at ≥37 weeks. The exposure was pregestational diabetes. Covariates were maternal demographics, behavioral/clinical, and infant factors. Logistic regression was used with p values <.05 considered statistically significant.

A total of 6,962,028 live births met inclusion criteria. Of these, a total of 11,711 (1.0%) term AGA birthweight infants died before their first birthday. About 35,689 (0.5%) mothers were diagnosed with pregestational diabetes prior to pregnancy with 0.3% of infants whose mothers had diabetes dying in their first year of life. In the unadjusted model, pregestational diabetes had a significant association with increased odds of mortality in term AGA infants (OR: 1.9, 95% CI: 1.6 - 2.3). AGA mortality remained significantly higher for women with pregestational diabetes compared to controls, after adjusting for maternal demographics (OR: 1.9, 95% CI: 1.6-2.3), behavioral/clinical characteristics (OR: 1.6, 95% CI: 1.3-2.0), and infant factors (OR: 1.3, 95% CI: 1.1-1.6).

In term pregnancies, pregestational diabetes was significantly associated with 30% higher mortality among AGA birthweight infants. Our study is innovative in its focus on AGA infants that overall is associated with good maternal glycemic control during pregnancy and in theory should confer a risk for infant mortality that is similar to pregnancies not complicated by pregestational diabetes. Despite this, we still found that even term AGA infants have higher risk of mortality in the setting of maternal pregestational diabetes. Implications of our findings underscore the importance of close antepartum surveillance and optimization of glycemic control preconception, identification of treatment targets, and health policies to reduce infant mortality. The results from this study may assist other researchers and clinicians understand how best to target future interventions to reduce term infant mortality and the burden of pregestational diabetes in the United States.