The antepartum stillbirth syndrome: risk factors and pregnancy conditions identified from the INTERGROWTH-21st Project

BJOG. 2018 Aug;125(9):1145-1153. doi: 10.1111/1471-0528.14463. Epub 2016 Dec 28.


Objectives: To identify risk factors for antepartum stillbirth, including fetal growth restriction, among women with well-dated pregnancies and access to antenatal care.

Design: Population-based, prospective, observational study.

Setting: Eight international urban populations.

Population: Pregnant women and their babies enrolled in the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project.

Methods: Cox proportional hazard models were used to compare risks among antepartum stillborn and liveborn babies.

Main outcome measures: Antepartum stillbirth was defined as any fetal death after 16 weeks' gestation before the onset of labour.

Results: Of 60 121 babies, 553 were stillborn (9.2 per 1000 births), of which 445 were antepartum deaths (7.4 per 1000 births). After adjustment for site, risk factors were low socio-economic status, hazard ratio (HR): 1.6 (95% CI, 1.2-2.1); single marital status, HR 2.0 (95% CI, 1.4-2.8); age ≥40 years, HR 2.2 (95% CI, 1.4-3.7); essential hypertension, HR 4.0 (95% CI, 2.7-5.9); HIV/AIDS, HR 4.3 (95% CI, 2.0-9.1); pre-eclampsia, HR 1.6 (95% CI, 1.1-3.8); multiple pregnancy, HR 3.3 (95% CI, 2.0-5.6); and antepartum haemorrhage, HR 3.3 (95% CI, 2.5-4.5). Birth weight <3rd centile was associated with antepartum stillbirth [HR, 4.6 (95% CI, 3.4-6.2)]. The greatest risk was seen in babies not suspected to have been growth restricted antenatally, with an HR of 5.0 (95% CI, 3.6-7.0). The population-attributable risk of antepartum death associated with small-for-gestational-age neonates diagnosed at birth was 11%.

Conclusions: Antepartum stillbirth is a complex syndrome associated with several risk factors. Although small babies are at higher risk, current growth restriction detection strategies only modestly reduced the rate of stillbirth.

Tweetable abstract: International stillbirth study finds individual risks poor predictors of death but combinations promising.

Keywords: Antepartum stillbirth; INTERGROWTH-21st; birth weight; fetal growth restriction.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Cross-Sectional Studies
  • Female
  • Fetal Growth Retardation / epidemiology
  • Fetal Growth Retardation / etiology
  • Fetal Weight
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Pregnancy
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Stillbirth / epidemiology*
  • Syndrome