Aspirin Halves Recurrent Preterm Birth in Placental MVM

Preventing recurrent preterm birth remains a major clinical dilemma in obstetrics worldwide. Consequently, obstetricians continue to seek tailored interventions to improve pregnancy outcomes for at-risk women. A secondary analysis of the Dutch APRIL trial offers compelling evidence for a precision medicine approach. Specifically, the study evaluated whether low-dose aspirin prevents preterm delivery in women with placental vascular lesions.

Key Findings from the APRIL Trial Secondary Analysis

The original APRIL trial studied women with a history of spontaneous preterm labor across 34 centres. In this secondary analysis, researchers examined placental histology reports from previous spontaneous deliveries using Amsterdam criteria. Histology reports were available for 160 women, representing 41.3% of the study cohort. Among these women, 27.5% exhibited signs of maternal vascular malperfusion (MVM).

The clinical outcomes showed a dramatic divergence based on placental pathology. Among women with MVM, recurrent preterm birth occurred in 4.2% receiving aspirin compared to 45.0% receiving placebo. Therefore, aspirin produced a 91% relative risk reduction in this high-risk vascular subgroup. In contrast, participants without MVM did not experience significant benefit from aspirin therapy. In that group, delivery before 37 weeks occurred in 29.3% with aspirin versus 17.2% with placebo.

Placental Pathology and Recurrent Preterm Birth Prevention

Maternal vascular malperfusion reflects abnormal spiral artery remodeling and impaired uteroplacental perfusion. Clinicians frequently encounter these vascular lesions in preeclampsia and fetal growth restriction. However, placental malperfusion also plays a hidden role in a notable subset of spontaneous preterm deliveries. As a result, non-targeted interventions often show mixed efficacy across unselected populations.

By identifying vascular lesions, clinicians can pinpoint women who will truly benefit from antiplatelet therapy. Low-dose aspirin improves trophoblast invasion, enhances blood flow, and suppresses thromboxane production. Furthermore, early initiation before 16 weeks of gestation maximizes these vascular benefits. Consequently, examining placental histology after any preterm delivery provides critical guidance for managing subsequent pregnancies.

Clinical Implications for Obstetric Practice in India

Preterm delivery imposes a massive health and economic burden in India and other emerging nations. Nevertheless, routine histopathological evaluation of the placenta remains underutilized in many Indian maternity units. These latest findings highlight the clinical necessity of submitting placentas for expert examination following spontaneous preterm labor. Indeed, histology reports can guide personalized prophylactic care in subsequent pregnancies.

Currently, guidelines widely recommend daily low-dose aspirin for women at high risk of preeclampsia. Thus, extending this strategy to women with proven placental vascular lesions represents a logical, low-cost intervention. Indian practitioners should actively review prior placental histology during preconception counselling and early antenatal visits. In addition, obstetricians should initiate low-dose aspirin early in gestation when they identify maternal vascular lesions.

Frequently Asked Questions

Q1: What is maternal vascular malperfusion (MVM) of the placenta?

Maternal vascular malperfusion refers to a constellation of placental lesions resulting from deficient maternal spiral artery remodeling and altered uteroplacental blood flow.

Q2: Why did low-dose aspirin work only in the subgroup with MVM?

Aspirin targets vascular dysfunction and platelet activation. Therefore, it directly treats the vascular pathology of MVM rather than inflammatory or cervical causes.

Q3: When should clinicians initiate low-dose aspirin in subsequent pregnancies?

Clinicians typically start low-dose aspirin before 16 weeks of gestation to support optimal trophoblast invasion and placental vascular remodeling.

References

1. Meliëzer JAL et al. Low-Dose Aspirin in the Prevention of Recurrent Spontaneous Preterm Birth Stratified by Placental Maternal Vascular Malperfusion: Secondary Analysis of a Randomized Trial. BJOG. 2026 Oct 23. doi: 10.1111/1471-0528.70350. PMID: 42919680.
2. Landman GW et al. Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study): A multicentre, randomised, double-blinded, placebo-controlled trial. PLoS Med. 2022;19(2):e1003891.
3. Kupka E et al. Low-dose aspirin use in pregnancy and the risk of preterm birth: a Swedish register-based cohort study. Am J Obstet Gynecol. 2023;228(3):333.e1-333.e10.