Maternal Diabetes Types and the Risk of Pregnancy Loss and Specific Malformations in the Infant

To compare the risk of pregnancy loss and the prevalence of specific major congenital malformations (MCMs) in newborns between mothers with pregestational diabetes mellitus (DM) type 1 (T1DM) and type 2 (T2DM).

We used the Merative MarketScan Commercial Claims and Encounters Database (2011-2021) to identify pregnancies among women enrolled from 180 days before to 280 days after the last menstrual period. Diabetes types, pregnancy losses, and MCMs diagnosed within 90 days after birth were identified using validated algorithms. Antidiabetic treatments were used as a proxy for T2DM progression. Analyses of MCMs were restricted to live birth pregnancies linked to infants.

Of 2,090,452 eligible pregnancies, 4584 had T1DM and 14,156 had T2DM diagnoses recorded. The spontaneous abortion risk was 17.5% for mothers with T1DM, 21.7% for mothers with T2DM, and 15.9% for mothers without DM. The stillbirth risk was 0.8%, 0.9%, and 0.4%, respectively. The largest adjusted odds ratios relative to no DM were for cardiac malformations for both T1DM (2.79, 95% CI 2.13-3.64) and T2DM (2.02, 95% CI 1.74-2.35). The prevalence of central nervous system, urinary, gastrointestinal, and musculoskeletal malformations was also elevated for both DM types; although they were slightly more frequent in the offspring of mothers with T1DM (which is mostly insulin dependent) compared to T2DM. Among mothers with T2DM, MCM risk was highest in those on insulin therapy.

Relative to mothers without pregestational DM, mothers with T2DM had higher risks of spontaneous abortion, and mothers with T1DM or T2DM had a higher risk of stillbirths and a higher prevalence of many different MCMs in their offspring. Within patients with T2DM, the risk of MCM depended on disease progression.