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

Amy E Howell, Basky Thilaganathan, Ruta Margelyte, Christy Burden, Hung-Yuan Cheng, Jane Sandall, Maria Viner, Lia Brigante, Dilly O.C. Anumba, Cathy Winter, Birte Harlev-Lam, Timothy J Draycott, Andrew Judge, Erik Lenguerrand*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Background:
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.

Methods:
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 generalized 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.

Results:
Among 876,279 nulliparous women receiving maternity care, 2,568 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 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).

Conclusions:
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.
Original languageEnglish
JournalBMC Medicine
Publication statusAccepted/In press - 18 Dec 2025

Keywords

  • Stillbirth
  • Nulliparous women
  • Maternal risk factors

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