Highlights
- Low-dose aspirin initiated before 16 weeks gestation reduces early preterm birth by approximately 42% in pregnancies at high risk for preterm pre-eclampsia.
- Aspirin use is associated with delaying delivery timing, with more pronounced effects in earlier gestational ages and iatrogenic early preterm births related to pre-eclampsia.
- The intervention corresponds with a shift from early to late preterm birth rates and shows benefits in pregnancies complicated by small-for-gestational-age (SGA) neonates.
- Findings provide mechanistic insight supporting aspirin’s role in modulating pathways leading to preterm delivery, with clinical implications for targeted prevention strategies in Asia and similar populations.
Background
Preterm birth remains a leading cause of neonatal morbidity and mortality worldwide, with pre-eclampsia (PE)—particularly preterm PE—being a major contributor to iatrogenic preterm deliveries. PE is characterized by new-onset hypertension and multisystem involvement after 20 weeks of gestation, with adverse maternal and fetal outcomes. Preventive strategies include administering low-dose aspirin in women identified as high risk early in pregnancy.
Despite advances, the relationship between aspirin administration and its impact on timing and type of preterm birth, especially within high-risk Asian populations, has been less delineated. This review synthesizes evidence from a rigorous multicenter randomized clinical trial evaluating the effect of aspirin on delaying preterm birth in women screened for preterm PE risk via Bayes’ theorem-based algorithms.
Key Content
Study Design and Methods
The referenced study is a secondary analysis from a multicenter stepped-wedge cluster randomized trial across 18 maternity/diagnostic units in 10 Asian regions between August 2019 and February 2022. Women undergoing first-trimester screening using a Bayesian triple test assessed for preterm PE risk (adjusted risk ≥1 in 100) were included.
Eligible high-risk women received low-dose aspirin (< 16 weeks until 36 weeks gestation). The primary outcomes measured were incidences of early preterm birth (24+0 to 31+6 weeks) and late preterm birth (32+0 to 36+6 weeks), differentiated by delivery type (spontaneous vs. iatrogenic) and pregnancy complications such as PE and SGA neonates.
Statistical analysis included computing adjusted relative risks (aRRs) with 95% confidence intervals (CIs) and applying a shift model to evaluate aspirin’s effect on delivery timing, hypothesizing aspirin delays preterm birth to later gestational ages.
Major Findings
- Among 42,897 women screened, 4,688 were high risk; 2,909 (62.05%) received aspirin.
- Aspirin reduced early preterm birth risk by 42% (aRR 0.577; 95% CI: 0.380-0.852), with a compensatory rise in late preterm birth (trend P<0.01), indicative of delivery timing delay rather than outright prevention of all preterm birth.
- Similar risk reductions were observed in iatrogenic preterm births and cases with SGA neonates.
- In pregnancies complicated by PE, aspirin lowered iatrogenic early preterm birth risk by 60% (aRR 0.398; 95% CI: 0.192-0.788), but had no significant impact on iatrogenic late preterm birth.
- The shift model demonstrated aspirin delays early preterm birth significantly: delaying delivery by 3.63 weeks at 24 weeks gestation, tapering to 0.25 weeks at 37 weeks, suggesting reduced severity or postponement of preterm complications.
Contextual Evidence from Literature
Low-dose aspirin (commonly 75–150 mg daily) modulates prostaglandin synthesis and placental vascular function by inhibiting platelet aggregation and improving endothelial function. Multiple meta-analyses and guideline recommendations (e.g., ACOG, FIGO) endorse aspirin for PE prevention in high-risk women, generally initiated before 16 weeks.
Prior large trials such as ASPRE (Rolnik et al., 2017) have demonstrated risk reduction for preterm PE and associated neonatal morbidity with aspirin. However, detailed analyses on aspirin’s impact on timing and type of preterm birth are limited.
Asian populations may have differing baseline risks and aspirin responses due to genetic, environmental, and healthcare differences, making this multicenter Asian trial especially pertinent.
Expert Commentary
This comprehensive analysis substantiates aspirin’s beneficial role beyond PE prevention by specifically demonstrating its capacity to delay early preterm deliveries, especially those driven by iatrogenic decisions tied to PE severity.
Delaying preterm birth can meaningfully enhance neonatal outcomes by allowing greater in utero maturation. The observed upward shift toward late preterm births may reflect clinical stabilizations delaying delivery without compromising maternal or fetal safety.
However, aspirin’s lack of effect on late iatrogenic preterm births in PE pregnancies suggests that once advanced complications manifest, aspirin’s protective impact diminishes, highlighting the multifactorial nature of preterm birth.
Clinicians should consider integrating early first-trimester risk assessments and initiation of low-dose aspirin as standard care for high-risk pregnancies, with diligent monitoring of gestational progression.
Limitations include adherence variability, potential confounders inherent to stepped-wedge designs, and generalizability restricted to Asian populations and screening protocols used.
Mechanistically, aspirin’s anti-inflammatory and vascular effects likely underlie the delayed delivery, although precise pathways remain to be clarified.
Conclusion
The evidence consolidates low-dose aspirin as a vital intervention to reduce early preterm birth incidence and delay timing of delivery in women at high risk for preterm pre-eclampsia. These findings illuminate a nuanced understanding of aspirin’s role in pregnancy management and underpin guideline development tailored to Asian populations.
Further research is warranted to explore aspirin’s mechanistic pathways, optimal dosing, and integration with other preventive strategies across diverse populations.
References
- Leung HHY, Papastefanou I, Chen Y, et al. Aspirin delays preterm birth in pregnancies at high risk for preterm pre-eclampsia: evidence from randomized clinical trial in Asia. Ultrasound Obstet Gynecol. 2025 Jul;66(1):24-32. doi: 10.1002/uog.29255. PMID: 40454801.
- Rolnik DL, Wright D, Poon LC, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med. 2017 Jun 8;377(7):613-622. doi: 10.1056/NEJMoa1704559. PMID: 28657857.
- Aspres Study Group. Screening for preterm preeclampsia by maternal factors and biomarkers at 11–13 weeks gestation. Ultrasound Obstet Gynecol. 2021;57(3):426-435.
- American College of Obstetricians and Gynecologists. Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Obstet Gynecol. 2020;135(5):e237–e260.
- FIGO Working Group on Good Clinical Practice and Ethics. The use of low-dose aspirin in the prevention of preterm pre-eclampsia: update on safety and efficacy. Int J Gynecol Obstet. 2021;152(2):192-200.
