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

Howell, A; Thilaganathan, B; Margelyte, R; Burden, C; Cheng, V; Sandall, J; Viner, M; Brigante, L; Anumba, D; Winter, C; et al. Howell, A; Thilaganathan, B; Margelyte, R; Burden, C; Cheng, V; Sandall, J; Viner, M; Brigante, L; Anumba, D; Winter, C; Harlev-Lam, B; Draycott, T; Judge, A; Lenguerrand, E (2026) Why current risk factor-based approaches fall short in predicting stillbirth: a national cohort study of nulliparous women in England. BMC Medicine, 24 (1). p. 94. ISSN 1741-7015 https://doi.org/10.1186/s12916-025-04598-7
SGUL Authors: Thilaganathan, Baskaran

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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 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. RESULTS: 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). 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.

Item Type: Article
Additional Information: © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Keywords: Maternal risk factors, Nulliparous women, Stillbirth, Humans, Female, England, Pregnancy, Stillbirth, Risk Factors, Adult, Retrospective Studies, Parity, Risk Assessment, Young Adult, Cohort Studies, Prenatal Care, Body Mass Index
SGUL Research Institute / Research Centre: Academic Structure > Cardiovascular & Genomics Research Institute
Academic Structure > Cardiovascular & Genomics Research Institute > Vascular Biology
Journal or Publication Title: BMC Medicine
ISSN: 1741-7015
Language: en
Related URLs:
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Projects:
Project IDFunderFunder ID
UNSPECIFIEDTommy's CharityUNSPECIFIED
Dates:
Date Event
2026-02-12 Published
2026-01-22 Published Online
2025-12-18 Accepted
URI: https://openaccess.sgul.ac.uk/id/eprint/118414
Publisher's version: https://doi.org/10.1186/s12916-025-04598-7

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