Why current risk factor-based approaches fall short in predicting stillbirth: a national cohort study of nulliparous...

Stillbirth is a profound and devastating outcome of pregnancy that has a long-lasting emotional and physiological impact on parents and families. Current risk assessment approaches largely rely on maternal characteristics and clinical history, yet their predictive accuracy remains poor, particularly among nulliparous women (women with no previous birth beyond 24 weeks of gestation). We evaluated the extent to which routinely collected pregnancy risk factors can predict stillbirth and assessed their contribution among singleton births in nulliparous women.

We conducted a population-based retrospective cohort study of 876,279 nulliparous women receiving maternity care across 130 National Health Service (NHS) Trusts in England between 2015 and 2019. Thirty-one maternal and pregnancy factors routinely collected during antenatal care were analysed. We used modified Poisson regressions with generalised estimating equations to account for clustering of women within Trusts to compute risk ratios (RR) and 95% confidence intervals (CI). We calculated adjusted population attributable risks (PARs) for significant factors.

Among 876,279 nulliparous women receiving maternity care, 2568 stillbirths occurred. Modifiable maternal characteristics associated with increased risk included elevated body mass index (BMI) (RR 1.22, 95% CI 1.03-1.45 for BMI 35- < 40 kg/m²; RR 1.70, 95% CI 1.39-2.07 for BMI ≥ 40 kg/m², both compared to BMI 18.5- < 25 kg/m²), smoking at booking (RR 1.34, 95% CI 1.19-1.51), current substance misuse (RR 1.52, 95% CI 1.16-1.98), lack of folic acid consumption before conception (RR 1.28, 95% CI 1.16-1.40) or during pregnancy (RR 1.38, 95% CI 1.18-1.61), and late antenatal booking after 12 weeks of gestation (RR 1.18, 95% CI 1.07-1.30). Fetal growth restriction accounted for the largest population attributable risk for stillbirth (RR 2.96, 95% CI 2.73-3.21).

Maternal and clinical risk factors explain only a fraction of stillbirths in nulliparous women and cannot underpin a clinically useful prediction model. These findings demonstrate the limitations of risk-based screening strategies and highlight the need for integrated approaches that combine maternal characteristics with biochemical, biophysical, and system-level factors to achieve meaningful advances in stillbirth prevention.