The epidemiology of stillbirth: The INTERGROWTH-21st Newborn Cross-Sectional Study

Background. INTERGROWTH-21st is a prospective, multi-ethnic, population-based project exploring growth from early pregnancy to two years of age. The Newborn Cross- Sectional Study (NCSS) component of INTERGROWTH-21st was designed to evaluate the population characteristics and pregnancy outcomes for the 8 study sites included in the project. The INTERGROWTH-21st geographic areas were in: Pelotas, Brazil; Beijing, China; Nagpur, India; Torino, Italy; Nairobi, Kenya; Muscat, Oman; Oxford, United Kingdom; Seattle, United States. Methods. Using the data gathered from the NCSS until the time that I completed my course work in Oxford, I attempted to identify potential risk factors for stillbirth in the INTERGROWTH-21st population. Stillbirth is defined as all foetal deaths occurring after at least 18 weeks gestation in order to capture stillbirths using the most inclusive definition. I also created the Foetal Death Supplementary Form to collect information on the causes of stillbirth that were not included in the original instrument according to Goldenberg et al. Results/ Conclusions. I had available data from 6 study sites at the time of preparing this thesis. The population includes 43,078 pregnancies resulting in 43,781 total births. Of these, 295 were stillbirths representing an overall foetal death rate of 6.7 per 1000 births. Maternal education of primary school or lower [Odds ratio (OR): 2.10, 95% Confidence interval (CI): 1.45-3.04], maternal age &gt;40 (OR: 2.52, 95% CI: 1.55-4.08), single marital status at parturition (OR: 1.70, 95% CI: 1.06-2.71) and maternal use of alcohol (OR: 4.60, 95% CI: 1.88-11.29), tobacco (OR: 1.83, CI: 1.18-2.83), or recreational drugs (OR: 4.27, CI: 1.57-11.63) during pregnancy independently increased the risk of stillbirth. Maternal medical conditions during pregnancy such as malaria (OR: 9.17, 95% CI: 3.69-22.76), HIV/AIDS (OR: 5.84, 95% CI: 2.72-12.54), and syphilis (OR: 7.11, 95% CI: 1.71-29.53) led to significantly higher stillbirth rates. Foetuses in breech presentation were at the greatest risk for stillbirth (OR: 5.00, 95% CI: 3.59-6.98). Caesarean delivery significantly reduced stillbirth risk (OR: 0.35, 95% CI: 0.27-0.47). The cause of death was unknown for 47% of stillbirths. Placental/cord complications, foetal genetic, structural, and karyotypic abnormalities, and maternal medical conditions accounted for 19%, 11%, and 9% of all stillbirths, respectively. Conclusions. These analyses suggest a need for a more detailed stillbirth evaluation to understand the causes associated with half of all stillbirths. Expanding access to obstetric and antenatal care could reduce stillbirth, but this is a complex syndrome that requires multiple interventions for its prevention.</p

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

Objectives: We aimed to identify risk factors for antepartum stillbirth including fetal growth restriction, amongst 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 amongst antepartum stillborn and liveborn babies. Main outcome measures: Antepartum stillbirth was defined as any fetal death after 16 weeks of 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, 2·0 (1·4-2·8); age 40 years, 2·2 (1·4-3·7); essential hypertension 4·0 (2·7-5·9); HIV/AIDS 4·3 (2·0-9·1); preeclampsia 1·6 (1·1-3·8), multiple pregnancy 3·3 (2.0-5·6) and antepartum haemorrhage 3.3 (2.5-4.5). Birth weight < 3rd centile was associated with antepartum stillbirth, 4.6 (3.4-6.2). The greatest risk was in babies not suspected to have been growth restricted antenatally, 5.0 (3.6-7.0). The population attributable risk of antepartum death associated with SGA 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