First-trimester aspirin allocation strategies and preterm preeclampsia in women with pregestational diabetes: A national multicenter observational cohort study.

Abstract

Introduction: Women with pregestational diabetes mellitus (PGDM) are at increased risk of preeclampsia (PE) and are commonly prescribed aspirin prophylaxis based on clinical risk factors alone. First-trimester screening algorithms may allow a more individualized allocation of aspirin. We aimed to compare the association between three first-trimester aspirin allocation strategies and the incidence of preterm PE in women with PGDM in routine clinical practice.

Material and methods: This retrospective multicenter observational cohort study included 519 singleton pregnancies with PGDM managed at six tertiary hospitals in Spain between January 2017 and December 2022. Women were classified according to the strategy used to allocate aspirin prophylaxis: clinical risk factor-based prophylaxis, first-trimester algorithm-based screening without placental growth factor (PlGF), or algorithm-based screening including PlGF. The primary outcome was preterm PE (<37 weeks). Secondary outcomes included overall and severe PE, gestational age at delivery, spontaneous preterm birth, birthweight, small-for-gestational-age infants, and neonatal intensive care unit admission. Multivariable regression models were adjusted for prespecified maternal characteristics.

Results: Among 519 pregnancies, 255 were managed using clinical risk factor-based prophylaxis, 119 using the algorithm without PlGF, and 145 using the algorithm with PlGF. Aspirin was prescribed to 100%, 16.8%, and 28.3% of women, respectively. Preterm PE rates were 4.7%, 5.9%, and 4.2%, respectively. After multivariable adjustment, no statistically significant differences in preterm PE were observed for the algorithm without PlGF (adjusted odds ratio [aOR] 1.89, 95% confidence interval [CI] 0.62-5.45) or with PlGF (aOR 1.33, 95% CI 0.41-3.91) compared with clinical risk factor-based prophylaxis. Secondary maternal and perinatal outcomes were also comparable across groups.

Conclusions: In women with PGDM, algorithm-based aspirin allocation strategies were associated with substantially lower aspirin exposure without evidence of increased preterm PE or adverse perinatal outcomes compared with clinical risk factor-based prophylaxis. However, given the observational design, baseline differences, and limited number of events, the study was not powered to demonstrate equivalence or exclude smaller clinically relevant differences. These findings should therefore be considered exploratory and require confirmation in adequately powered prospective studies.