Scheduled Early-Term Birth: A Proven Strategy to Prevent Pre-eclampsia in High-Risk Pregnancies

Highlights

• Screening at 36 weeks’ gestation effectively identifies women at high risk for developing term pre-eclampsia.
• Scheduled birth at 37–38 weeks for women with a risk ≥1 in 50 reduces the incidence of pre-eclampsia by 30%.
• The intervention does not increase the rates of emergency cesarean sections or neonatal intensive care unit (NICU) admissions.
• This risk-stratified approach provides a viable solution for preventing term pre-eclampsia, where aspirin has historically shown limited efficacy.

The Challenge of Term Pre-eclampsia

Pre-eclampsia remains a leading cause of maternal and perinatal morbidity and mortality worldwide. While significant strides have been made in preventing early-onset pre-eclampsia (before 34 weeks) through early screening and low-dose aspirin initiation in the first trimester, term pre-eclampsia (occurring at or after 37 weeks) has remained a persistent clinical challenge. Term pre-eclampsia accounts for approximately 75% of all pre-eclampsia cases and is associated with serious complications, including placental abruption, maternal stroke, and stillbirth.

Current preventive strategies, primarily focused on the first trimester, have a diminishing effect as pregnancy progresses toward term. By the time a woman reaches the third trimester, the window for pharmaceutical intervention with aspirin has closed. Consequently, clinicians have lacked a robust, evidence-based intervention to mitigate the risk of pre-eclampsia in the final weeks of pregnancy. The PREVENT-PE trial sought to address this unmet medical need by investigating whether identifying high-risk women at 36 weeks and offering scheduled early-term birth could safely reduce the disease burden.

The PREVENT-PE Trial: Study Design and Methodology

PREVENT-PE was an open-label, adaptive, randomized controlled trial conducted across two major maternity hospitals in the United Kingdom. The study population included women aged 16 years or older with singleton pregnancies and live fetuses. Exclusion criteria were kept minimal to ensure generalizability, excluding only those with pre-existing pre-eclampsia at the time of screening or those participating in conflicting trials.

Screening and Risk Stratification

Between 35+0 and 36+6 weeks’ gestation, consenting participants underwent a standardized risk assessment. This assessment utilized a competing risks model that incorporated maternal characteristics, medical history, and biophysical markers (such as mean arterial pressure). Based on this screening, women were stratified by their risk of developing pre-eclampsia. The threshold for ‘high risk’ was set at ≥1 in 50.

Intervention vs. Usual Care

Participants were randomly assigned in a 1:1 ratio to either the intervention group or the control group. In the intervention group, women identified as high-risk (≥1 in 50) were offered scheduled birth (either by induction of labor or elective cesarean section) between 37+0 and 38+6 weeks. Women in the intervention group with a risk below the threshold received usual care. In the control group, all women received usual care at term, regardless of their calculated risk, which typically involves expectant management until at least 40 weeks unless clinical indications for earlier delivery arise.

Key Findings: Efficacy in Reducing Pre-eclampsia

The trial analyzed data from 8,094 women, with 4,037 in the intervention group and 4,057 in the control group. The cohort was diverse, with 25.9% of participants self-reporting non-White ethnicity, enhancing the external validity of the findings.

Primary Outcome

The primary endpoint was birth with pre-eclampsia, defined by the International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria. The results demonstrated a significant reduction in the incidence of pre-eclampsia in the intervention group compared to the control group:

• Intervention Group: 3.9% (158 of 4,037)
• Control Group: 5.6% (226 of 4,057)
• Adjusted Risk Ratio (aRR): 0.70 [95% CI 0.58–0.86]

This 30% relative risk reduction is clinically substantial, suggesting that for every 60 women managed with this risk-stratified approach, one case of pre-eclampsia is prevented.

Secondary Outcomes and Safety

A critical concern with early-term birth (37–38 weeks) is the potential for increased neonatal morbidity and higher rates of operative delivery. However, the PREVENT-PE data provided reassurance on both fronts. There were no statistically significant differences between the intervention and control groups regarding:

• Emergency Cesarean Section Rates: The intervention did not lead to a surge in emergency surgeries, suggesting that scheduled inductions at this stage are generally successful.
• Neonatal Care Unit Admission: Rates of NICU admission remained comparable, alleviating fears that birth at 37 or 38 weeks would cause widespread respiratory distress or other neonatal complications.
• Serious Adverse Events: Serious adverse events occurred in 0.1% of the intervention group vs. 0.2% of the control group (p=0.30).

Expert Commentary and Clinical Implications

The PREVENT-PE trial represents a paradigm shift in late-pregnancy care. For decades, the obstetric community has debated the optimal timing of delivery for women at risk of complications. The HYPITAT trial previously established that induction of labor at 37 weeks is beneficial once gestational hypertension or mild pre-eclampsia is already present. PREVENT-PE takes this a step further by demonstrating that we can intervene before the disease clinically manifests.

The 36-Week Screening Window

The choice of the 36-week mark for screening is strategic. It allows clinicians to use the most current physiological data to predict term events while providing sufficient time to plan for a scheduled birth. The use of a 1:50 risk threshold appears to balance the benefits of prevention against the logistical requirements of increased early-term inductions.

Biological Plausibility

The biological rationale for this intervention lies in the ‘two-stage’ model of pre-eclampsia. By the third trimester, the primary driver of pre-eclampsia is often a mismatch between the metabolic demands of the fetus/placenta and the maternal cardiovascular capacity. By scheduling birth in the early-term period, clinicians effectively remove the placenta before the maternal system reaches a tipping point of systemic inflammation and endothelial dysfunction.

Limitations and Generalizability

While the results are compelling, some limitations exist. The open-label nature of the trial is inherent to studies involving delivery timing, but it could introduce bias in how clinicians manage blood pressure. Furthermore, while NICU admissions did not increase, long-term neurodevelopmental outcomes for children born at 37 vs. 40 weeks were not the focus of this study and warrant continued observation. Finally, the implementation of this model requires robust 36-week screening infrastructure, including ultrasound and specialized software for risk calculation.

Conclusion

The PREVENT-PE trial provides high-level evidence that a policy of risk-stratified, planned early-term birth can significantly reduce the incidence of pre-eclampsia. By identifying high-risk women at 36 weeks, healthcare systems can transition from reactive management to proactive prevention. Importantly, this reduction in maternal disease does not come at the cost of increased neonatal morbidity or surgical intervention, making it a highly attractive strategy for modern obstetric practice. Future guidelines should consider incorporating third-trimester risk assessment to optimize the timing of birth for those at greatest risk.

Funding and Trial Registration

The PREVENT-PE trial was funded by the Fetal Medicine Foundation. The trial is registered with ISRCTN, number ISRCTN41632964.

References

1. Goadsby J, Syngelaki A, Magee LA, von Dadelszen P, Akolekar R, Webster S, Wright A, Wright D, Nicolaides KH. Scheduled birth at term for the prevention of pre-eclampsia (PREVENT-PE): an open-label randomised controlled trial. Lancet. 2026 Jan 3;407(10523):67-77.
2. Poon LC, Shennan A, Hyett JA, et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention. Int J Gynaecol Obstet. 2019;145 Suppl 1:1-33.
3. Koopmans CM, Bijlenga D, Groen H, et al. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks’ gestation (HYPITAT): a multicentre, open-label randomised controlled trial. Lancet. 2009;374(9694):979-988.