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Predictors of Stillbirth in Sub-Saharan Africa

From the ¹Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; ²School of Medicine, University of Alabama, Birmingham, Alabama; ³Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Seattle, Washington; ⁴National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; ⁵Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; ⁶Department of Biostatistics, University of Washington, Seattle, Washington; ⁷Family Health International, Durham, North Carolina; ⁸UNC Project, Lilongwe, Malawi; and ⁹College of Medicine, Drexel University, Philadelphia, Pennsylvania.

OBJECTIVE: To describe the incidence and predictors of stillbirth in a predominantly human immunodeficiency virus (HIV)-infected African cohort.

METHODS: Human Immunodeficiency Virus (HIV) Prevention Trials Network (HPTN) 024 was a randomized controlled trial of empiric antibiotics to reduce chorioamnionitis-related perinatal HIV transmission. A proportion of HIV-uninfected individuals were enrolled to reduce community-based stigma surrounding the trial. For this analysis, only women who gave birth to singleton infants were included.

RESULTS: Of 2,659 women enrolled, 2,434 (92%) mother– child pairs met inclusion criteria. Of these, 2,099 (86%) infants were born to HIV-infected women, and 335 (14%) were born to HIV-uninfected women. The overall stillbirth rate was 32.9 per 1,000 deliveries (95% confidence interval [CI] 26.1–40.7). In univariable analyses, predictors for stillbirth included previous stillbirth (odds ratio [OR] 2.3, 95% CI 1.2–4.3), antenatal hemorrhage (OR 14.4, 95% CI 4.3–47.9), clinical chorioamnionitis (OR 20.9, 95% CI 5.1–86.2), and marked polymorphonuclear infiltration on placental histology (OR 2.9, 95% CI 1.7–5.2). When compared with pregnancies longer than 37 weeks, those at 34–37 weeks (OR 1.7, 95% CI 0.8–3.4) and those at less than 34 weeks (OR 22.8, 95% CI 13.6–38.2) appeared more likely to result in stillborn delivery. Human immunodeficiency virus infection was not associated with a greater risk for stillbirth in either univariable (OR 1.5, 95% CI 0.7–3.0) or multivariable (adjusted OR 1.11, 95% CI 0.38–3.26) analysis. Among HIV-infected women, however, decreasing CD4 cell count was inversely related to stillbirth risk (P=.009).

CONCLUSION: In this large cohort, HIV infection was not associated with increased stillbirth risk. Further work is needed to elucidate the relationship between chorioamnionitis and stillbirth in African populations.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00021671

LEVEL OF EVIDENCE: II

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