Prenatal Low-Dose Aspirin for Prevention of Preeclampsia and Preterm Birth: An Updated Review

By Marie Farver

Updated October 2025

Introduction

Preeclampsia remains a significant threat to maternal and fetal health worldwide, affecting 1-8% of pregnancies and causing approximately 76,000 maternal and 500,000 infant deaths annually (U.S. Preventive Services Task Force, 2021). In California, preeclampsia and eclampsia together constitute the second leading cause of pregnancy-related deaths. Since delivery remains the only curative treatment for preeclampsia, identifying effective preventative strategies has become a critical focus of maternal-fetal medicine research.

Low-dose aspirin has emerged as a proven intervention for reducing preeclampsia risk, particularly when initiated early in pregnancy. Recent evidence has sparked important discussions about optimal dosing strategies, with emerging research suggesting that higher doses may offer greater protection for certain high-risk populations.

Mechanism of Action

Aspirin's protective effects stem from its selective inhibition of cyclooxygenase-1 (COX-1), which reduces thromboxane A2 synthesis while preserving prostacyclin production. This mechanism restores the vascular balance essential for healthy placental development and function (Jones Pullins et al., 2025). The anti-inflammatory properties and reduced platelet aggregation affect placental development, reduce inflammation, and increase blood flow to the placenta—addressing the fundamental pathophysiology of preeclampsia, which arises from defective placental formation and function.

Evidence Base for Aspirin in Preeclampsia Prevention

Multiple large-scale studies have demonstrated aspirin's efficacy in preventing preeclampsia. The landmark ASPRE trial (Aspirin for Evidence-Based Preeclampsia Prevention) found that 150 mg of aspirin started at 11-13 weeks of gestation reduced the rate of preterm preeclampsia to 1.6% compared to 4.3% in the placebo group, with no adverse reactions observed in mothers or babies (Rolnik et al., 2017).

A comprehensive 2017 meta-analysis of 45 randomized controlled trials involving over 21,000 women demonstrated that aspirin started at or before 16 weeks of gestation significantly reduced both preeclampsia and intrauterine growth restriction (IUGR), with optimal dosing identified at 100-150 mg daily (Roberge et al., 2017). The U.S. Preventive Services Task Force (USPSTF) reviewed evidence from 16 randomized controlled trials involving 15,767 participants and found that low-dose aspirin prophylaxis resulted in significant reductions in preeclampsia (pooled RR 0.85, 95% CI 0.75-0.95), preterm birth (pooled RR 0.80, 95% CI 0.67-0.95), small for gestational age (RR 0.82, 95% CI 0.68-0.99), and perinatal mortality (pooled RR 0.79, 95% CI 0.66-0.96) in individuals at increased risk (Davidson et al., 2021).

Benefits Beyond Preeclampsia Prevention

Preterm Birth Reduction

In addition to preventing preeclampsia, low-dose aspirin has demonstrated significant benefits in reducing preterm birth. A 2020 randomized, double-blind, placebo-controlled trial funded by the National Institutes of Health specifically investigated low-dose aspirin for the prevention of preterm delivery in nulliparous women with singleton pregnancies. The ASPIRIN Study found that low-dose aspirin reduces the risk of preterm birth before 37 weeks by 11% and early preterm birth before 34 weeks by 25% in first-time mothers (Hoffman et al., 2020). This substantial reduction in early preterm birth is particularly significant, as deliveries before 34 weeks are associated with increased neonatal morbidity and mortality. These findings highlight that aspirin's benefits extend beyond preeclampsia prevention to include meaningful reductions in preterm delivery, further supporting its use in high-risk populations.

The Emerging Evidence for Higher-Dose Aspirin

Dose-Response Relationship

Recent research has established a clear dose-response relationship for aspirin in preeclampsia prevention. A systematic review and meta-analysis by Ghesquiere et al. (2023) specifically compared aspirin dosages of 75-81 mg versus 150-162 mg when initiated in the first trimester. The pooled analysis of four randomized controlled trials involving 552 participants demonstrated that aspirin dosages of 150-162 mg were associated with a significant reduction in preterm preeclampsia compared to 75-81 mg (3 studies; 472 participants; RR 0.34, 95% CI 0.15-0.79; p=0.01). Additionally, the higher dose showed a significant reduction in severe preeclampsia (3 studies; 472 participants; RR 0.23, 95% CI 0.09-0.62; p=0.003).

Studies Supporting 162 mg Dosing

Multiple recent studies have specifically evaluated 162 mg aspirin with promising results:

The ASPREO Trial (2025): This randomized controlled trial investigated 162 mg versus 81 mg aspirin in high-risk obese pregnant individuals. Among 220 participants, the primary outcome of preeclampsia with severe features occurred in 35% of the 162 mg group compared to 40% in the 81 mg group (posterior RR 0.88, 95% CI 0.64-1.22). Bayesian analysis indicated a 78% probability of benefit with the higher dose, with an estimated 12% reduction in severe preeclampsia. The authors concluded that these findings support conducting a larger multicenter trial (Amro et al., 2025).

Henry Ford Health System Studies: A retrospective cohort study of 3,597 patients at Henry Ford Health found that the rate of preeclampsia was significantly lower in patients receiving 162 mg aspirin (10.1%) compared to those receiving 81 mg (14.2%), with an odds ratio of 0.68 (95% CI 0.46-0.99; p=0.043). Importantly, this represented a 29% reduction in preeclampsia rates without any increase in bleeding complications, including postpartum hemorrhage, postpartum hematoma, or intraventricular hemorrhage in newborns (Ayyash et al., 2024).

Considerations for Specific Populations

Emerging evidence suggests that certain patient factors may reduce aspirin's effectiveness at lower doses. Altered pharmacokinetics during pregnancy and obesity have been identified as factors that may necessitate higher dosing. In studies of obese pregnant individuals, aspirin resistance was successfully overcome with 162 mg dosing (Jones Pullins et al., 2025).

Alternative Findings

It is important to note that not all studies have shown superiority of higher doses. A large cohort study by Kupka et al. (2025) of 13,828 women in Sweden found no difference in preeclampsia incidence between those using 150-160 mg aspirin (9.5% developed preeclampsia) versus 75 mg aspirin (8.9% developed preeclampsia), with an adjusted relative risk of 1.07 (95% CI 0.93-1.24). The authors concluded that either dose may be reasonable, though they acknowledged that large randomized trials are still needed.

Current Clinical Guidelines

Who Should Receive Aspirin

The USPSTF, American College of Obstetricians and Gynecologists (ACOG), and the Society for Maternal-Fetal Medicine (SMFM) recommend low-dose aspirin for pregnant individuals with at least one high-risk factor or at least two moderate-risk factors for preeclampsia (American College of Obstetricians and Gynecologists, 2018).

High-risk factors include:

• History of preeclampsia, especially with adverse outcomes

• Multiple gestation

• Chronic hypertension

• Type 1 or Type 2 diabetes mellitus

• Chronic kidney disease

• Autoimmune disease (systemic lupus erythematosus, antiphospholipid syndrome)

Moderate-risk factors include:

• First pregnancy (nulliparity)

• Maternal age ≥35 years (with age ≥40 years showing statistically significant increased risk)

• Body mass index >30 kg/m²

• Family history of preeclampsia

• Black race (as a proxy for underlying structural racism, not biological factors)

• Lower socioeconomic status

• Personal history of low birth weight or small for gestational age

• Previous adverse pregnancy outcome

• Pregnancy interval >10 years

• Conception via in vitro fertilization

ACOG specifically recommends daily low-dose aspirin for pregnant individuals aged 35 years or older when combined with at least one other moderate risk factor, assigning this a Grade 1B recommendation (American College of Obstetricians and Gynecologists, 2022). A Grade 1B recommendation is a strong recommendation that applies to most patients, meaning clinicians should follow it unless a clear and compelling rationale for an alternative approach is present. The "Grade 1" designation indicates that following the recommendation will do more good than harm for most, if not all, patients. The "B" designation means that the best estimates of benefits and risks come from randomized controlled trials with important limitations or very strong evidence of some other form, and further research is likely to have an impact on confidence in the estimates of benefit and risk (UpToDate, 2025). The risk of preeclampsia increases linearly with advancing maternal age and becomes statistically significant at age 40 and older (American College of Obstetricians and Gynecologists, 2022).

Timing and Duration

The optimal timing for aspirin initiation is between 12 and 16 weeks of gestation, ideally before 16 weeks. Early initiation is critical because the pathophysiology of preeclampsia develops in early pregnancy. Meta-analyses have demonstrated that aspirin started after 16 weeks shows no significant reduction in severe preeclampsia or IUGR (Roberge et al., 2017).

Aspirin should be continued daily until delivery, with some evidence suggesting that evening dosing may be more effective than morning administration. Low-dose aspirin has little to no benefit when started after 23 weeks of gestation or for women already diagnosed with preeclampsia.

Current Dosing Recommendations

While the standard recommended dose in the United States remains 81 mg daily, recent evidence increasingly supports considering 162 mg for certain populations, particularly:

• High-risk obese individuals (BMI ≥30 kg/m²)

• Patients with multiple risk factors

• Populations where aspirin resistance may be a concern

Current evidence suggests that aspirin's pharmacological effects remain highly specific to COX-1 at the 162 mg dose, minimizing concerns about broader prostaglandin inhibition. As Jones Pullins et al. (2025) conclude, "current evidence increasingly supports 162 mg as the optimal dose for preeclampsia prevention, offering greater effectiveness than the commonly used 81 mg dose, without significant evidence of increased risk."

Safety Profile

Maternal Safety

Extensive evidence from randomized controlled trials demonstrates the safety of low-dose aspirin in pregnancy. Trials involving over 30,000 women did not demonstrate evidence of harm from daily low-dose aspirin use during pregnancy, with bleeding complications remaining uncommon. Pooled analyses showed no statistically significant increases in placental abruption (pooled RR 1.15, 95% CI 0.76-1.72), postpartum hemorrhage (pooled RR 1.03, 95% CI 0.94-1.12), or other bleeding complications (American College of Obstetricians and Gynecologists, 2018).

Fetal and Neonatal Safety

Studies have consistently found no increased risk of adverse fetal outcomes with low-dose aspirin:

Congenital Anomalies: Large studies have found no increased risk of birth defects with low-dose aspirin exposure, even when taken during the first trimester. Earlier concerns about conditions like gastroschisis have not been substantiated by larger clinical trials (Sun et al., 2022).

Neonatal Bleeding: The most recent Cochrane meta-analysis found no increased risk of neonatal intracranial hemorrhage (10 trials, 26,184 infants) or other neonatal hemorrhagic complications (8 trials, 27,032 infants) associated with maternal ingestion of low-dose aspirin during the third trimester (American College of Obstetricians and Gynecologists, 2018).

Ductus Arteriosus: Unlike high-dose NSAIDs, low-dose aspirin use in the third trimester has not been linked to premature closure of the fetal ductus arteriosus. Daily administration of low-dose aspirin during the second and third trimesters does not alter uteroplacental or fetoplacental hemodynamics and does not cause moderate or severe constriction of the ductus arteriosus (Grab et al., 2000).

Fetal Growth: Rather than causing harm, low-dose aspirin has been shown to reduce the risk of fetal growth restriction and preterm birth in high-risk pregnancies.

Neurodevelopmental Outcomes

Recent evidence provides strong reassurance regarding long-term neurodevelopmental safety:

A 2024 randomized controlled trial found that antenatal low-dose aspirin exposure was not associated with altered neurodevelopmental outcomes at age 3 years (Hoffman et al., 2024). Earlier studies, including the CLASP study, found reassuring results regarding congenital malformations, major motor deficits, and severe neuromotor or developmental delays identifiable in early childhood (Klebanoff et al., 1996).

Limited information on low-dose aspirin exposure during pregnancy does not suggest an increased chance for problems with physical or mental development in infants at 18 months of age, and studies of children up to 5 years of age found no effects on learning or behavior (MotherToBaby, 2024).

Important Distinction: Dose Matters

It is critical to note that chronic exposure to analgesic doses of aspirin greater than 300 mg per day from 30 weeks of pregnancy may be associated with neonatal bleeding complications and premature closure of the ductus arteriosus. However, these effects have not been reported with low-dose aspirin use (81-162 mg daily).

Additional Preventive Strategies

While aspirin remains the cornerstone of preeclampsia prevention, other interventions may provide complementary benefits:

Calcium Supplementation: In populations with low dietary calcium intake, calcium supplementation (1.5-2.0 grams of elemental calcium daily) has been shown to reduce preeclampsia risk by 47%, with more pronounced effects in high-risk pregnancies (Kumsa et al., 2025).

Lifestyle Modifications: Maintaining a healthy weight, engaging in regular physical activity, and adhering to a balanced diet rich in fruits, vegetables, whole grains, and lean proteins can reduce preeclampsia risk. Obesity (BMI >30 kg/m²) is a significant risk factor, and dietary patterns high in ultra-processed foods and added sugars are associated with increased risk (Kinshella et al., 2022).

Conclusion

Low-dose aspirin represents one of the most effective and well-studied interventions for preeclampsia prevention, with an extensive body of evidence demonstrating both efficacy and safety. The key to maximizing benefit lies in early initiation (ideally before 16 weeks of gestation) in appropriately selected high-risk populations.

Recent evidence suggests that higher doses (150-162 mg) may offer superior protection compared to the standard 81 mg dose, particularly for obese individuals and those with multiple risk factors, though more research is needed to definitively establish optimal dosing strategies. Current data support that 162 mg aspirin provides enhanced benefit without increased bleeding complications, with several studies demonstrating a 20-29% reduction in preeclampsia rates compared to 81 mg dosing.

Healthcare providers should engage in shared decision-making with patients, considering individual risk factors, emerging evidence on dosing, and patient preferences. As research continues to evolve, aspirin therapy remains a cornerstone of preeclampsia prevention, offering a simple, low-cost intervention that can significantly improve maternal and fetal outcomes.

The USPSTF assigns a Grade B recommendation to low-dose aspirin for preeclampsia prevention, indicating moderate certainty that the net benefit is moderate to substantial. With reassuring safety data spanning decades of use and growing evidence for dose optimization, aspirin prophylaxis should be offered to all eligible pregnant individuals as part of comprehensive prenatal care.

References

American College of Obstetricians and Gynecologists. (2018). ACOG Committee Opinion No. 743: Low-dose aspirin use during pregnancy. Obstetrics & Gynecology, 132(1), e44–e52. https://doi.org/10.1097/AOG.0000000000002708

American College of Obstetricians and Gynecologists. (2022). Obstetric Care Consensus No. 11: Pregnancy at age 35 years or older. Obstetrics & Gynecology, 140(2), 348–366. https://doi.org/10.1097/AOG.0000000000004873

Amro, F. H., Blackwell, S. C., Pedroza, C., Fishel Bartal, M., Chauhan, S. P., & Sibai, B. M. (2025). Aspirin 162 mg vs 81 mg for preeclampsia prophylaxis in high-risk obese individuals: A comparative effectiveness open-label randomized trial (ASPREO). American Journal of Obstetrics & Gynecology MFM, 232(3), 315.e1–315.e8. https://doi.org/10.1016/j.ajogmf.2024.101620

Ayyash, M., Goyert, G., Garcia, R., Khangura, R., Pitts, D., Jacobsen, G., & Shaman, M. (2024). Efficacy and safety of aspirin 162 mg for preeclampsia prophylaxis in high-risk patients. American Journal of Perinatology, 41(S 01), e2410–e2417. https://doi.org/10.1055/s-0043-1771260

Davidson, K. W., Barry, M. J., Mangione, C. M., Cabana, M., Caughey, A. B., Davis, E. M., Donahue, K. E., Doubeni, C. A., Krist, A. H., Kubik, M., Li, L., Ogedegbe, G., Owens, D. K., Pbert, L., Silverstein, M., Stevermer, J., Tseng, C. W., & Wong, J. B. (2021). Aspirin use to prevent preeclampsia and related morbidity and mortality: US Preventive Services Task Force recommendation statement. JAMA, 326(12), 1186–1191. https://doi.org/10.1001/jama.2021.14781

Ghesquiere, L., Guerby, P., Marchant, I., Foisy, M. A., Roberge, S., & Bujold, E. (2023). Comparing aspirin 75 to 81 mg vs 150 to 162 mg for prevention of preterm preeclampsia: Systematic review and meta-analysis. American Journal of Obstetrics & Gynecology MFM, 5(7), 101000. https://doi.org/10.1016/j.ajogmf.2023.101000

Grab, D., Paulus, W. E., Erdmann, M., Terinde, R., Oberhoffer, R., Lang, D., Muche, R., & Kreienberg, R. (2000). Effects of low-dose aspirin on uterine and fetal blood flow during pregnancy: Results of a randomized, placebo-controlled, double-blind trial. Ultrasound in Obstetrics & Gynecology, 15(1), 19–27. https://doi.org/10.1046/j.1469-0705.2000.00009.x

Hoffman, M. K., Goudar, S., Dhaded, S. M., Figueroa, L., Mazariegos, M., Krebs, N. F., & Hibberd, P. L. (2024). Neurodevelopment of children whose mothers were randomized to low-dose aspirin during pregnancy. Obstetrics & Gynecology, 143(4), 554–561. https://doi.org/10.1097/01.AOG.0000941300.81651.4c

Hoffman, M. K., Goudar, S. S., Kodkany, B. S., Metgud, M., Somannavar, M., Okitawutshu, J., Lokangaka, A., Tshefu, A., Bose, C. L., Mwapule, A., Mwenechanya, M., Chomba, E., Carlo, W. A., Chicuy, J., Figueroa, L., Garces, A., Krebs, N. F., Jessani, S., Zehra, F., Saleem, S., & ASPIRIN Study Group. (2020). Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): A randomised, double-blind, placebo-controlled trial. Lancet, 395(10220), 285–293. https://doi.org/10.1016/S0140-6736(19)32973-3

Jones Pullins, M. E., Battarbee, A. N., & Tita, A. T. (2025). Aspirin dosage for preeclampsia prophylaxis: An argument for 162-mg dosing. American Journal of Obstetrics & Gynecology MFM, 7(1), 101620. https://doi.org/10.1016/j.ajogmf.2024.11.029

Kinshella, M. W., Omar, S., Scherbinsky, K., Moussa, H., Crocker, E., Okunoye, G. O.,

Klebanoff, M. A., Berendes, H. W., & Rip, M. R. (1996). Low dose aspirin in pregnancy and early childhood development: Follow up of the collaborative low dose aspirin study in pregnancy. BJOG: An International Journal of Obstetrics & Gynaecology, 103(7), 684–689. https://doi.org/10.1111/j.1471-0528.1996.tb09844.x

Kumsa, M., Mislu, A., Arage, G., Abate, M., Beriye, T., Mehari Reda, A., & Yimer, M. (2025). Effects of calcium supplementation on the prevention of preeclampsia: An umbrella review of systematic reviews and meta-analyses. BMC Pregnancy and Childbirth, 25(1), 82. https://pubmed.ncbi.nlm.nih.gov/40109721/

Kupka, E., Hesselman, S., Gunnarsdóttir, J., Wikman, A., & Skalkidou, A. (2025). Prophylactic aspirin dose and preeclampsia. JAMA Network Open, 8(2), e2457828. https://doi.org/10.1001/jamanetworkopen.2024.57828

Moore, S. E., & Adegnika, A. A. (2022). Calcium for pre-eclampsia prevention: A systematic review and network meta-analysis to guide personalised antenatal care. BJOG: An International Journal of Obstetrics & Gynaecology, 129(11), 1833–1843. https://doi.org/10.1111/1471-0528.17222

MotherToBaby. (2024). Low dose aspirin. In Fact Sheets. Organization of Teratology Information Specialists. https://www.ncbi.nlm.nih.gov/books/NBK582805/

Roberge, S., Bujold, E., & Nicolaides, K. H. (2018). Aspirin for the prevention of preterm and term preeclampsia: Systematic review and metaanalysis. American Journal of Obstetrics and Gynecology, 218(3), 287–293.e1. https://doi.org/10.1016/j.ajog.2017.11.561

Roberge, S., Nicolaides, K., Demers, S., Hyett, J., Chaillet, N., & Bujold, E. (2017). The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: Systematic review and meta-analysis. American Journal of Obstetrics and Gynecology, 216(2), 110–120.e6. https://doi.org/10.1016/j.ajog.2016.09.076

Rolnik, D. L., Wright, D., Poon, L. C. Y., O'Gorman, N., Syngelaki, A., de Paco Matallana, C., Akolekar, R., Cicero, S., Janga, D., Singh, M., Molina, F. S., Persico, N., Jani, J. C., Plasencia, W., Papaioannou, G., Tenenbaum-Gavish, K., Meiri, H., Gizurarson, S., Maclagan, K., & Nicolaides, K. H. (2017). Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. New England Journal of Medicine, 377(7), 613–622. https://doi.org/10.1056/NEJMoa1704559

Sun, S., Qian, H., Li, C., Xie, F., Sun, L., Dang, L., Wang, R., Li, H., Ma, L., Wang, X., & Lu, J. (2022). Effect of low dose aspirin application during pregnancy on fetal congenital anomalies. BMC Pregnancy and Childbirth, 22, 802. https://doi.org/10.1186/s12884-022-05142-8

U.S. Preventive Services Task Force. (2021). Aspirin use to prevent preeclampsia and related morbidity and mortality: Preventive medication. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/low-dose-aspirin-use-for-the-prevention-of-morbidity-and-mortality-from-preeclampsia-preventive-medication

UpToDate. (2025). GRADE: Grading recommendations. Wolters Kluwer. https://www.uptodate.com/contents/grade/2

Marie Farver is a nurse and lactation consultant specializing in maternal-fetal health. For more information about prenatal care and pregnancy wellness, visit Birth and Babies by Design.