Maternal infection at delivery and risk of stillbirth and early neonatal death: nested case–control studies in East African pregnancy cohorts

Background: Stillbirths and early neonatal deaths remain common in low- and middle-income countries. Maternal infections are likely contributors, but data are extremely limited. We aimed to describe maternal infections at delivery and their association with perinatal death. Methods: We investigated maternal infections at delivery in two hospitals in East Africa: in Kilifi County Hospital (2011–2017), Kenya, and Hiwot Fana Comprehensive Specialised Hospital (2019–2020), Ethiopia. We compared 642 mothers delivering stillbirths/newborns dying in the first 24 h after birth (cases) and 855 mothers with newborns surviving ≥ 24 h (controls) from pregnancy cohorts. We tested maternal blood with molecular diagnostic panels (TaqMan Array Cards). In Ethiopia, vagino-rectal swabs and oropharyngeal swabs were also tested, along with conventional microbiological testing (blood cultures for bacteraemia). We tested associations between maternal infection and perinatal death for each site. We did a sensitivity analysis restricted to controls with good pregnancy outcomes in Kenya. Where appropriate, we calculated the population attributable fraction. Results: Maternal bacteraemia was associated with increased odds of perinatal death in Ethiopia (adjusted odds ratio aOR3.7 [1.5–9.2]) in hospital deliveries. Maternal bacterial infection (detected molecularly) was associated with perinatal death in Kenya (aOR2.7 [1.2-6.0]), but only in analyses with controls restricted to those with good pregnancy outcomes. From these analyses, for perinatal deaths among hospital deliveries, the PAF for maternal bacterial infection was 6.1% (4.0%-8.2%) in HFCSH and 4.9% (2.6%-7.2%) in KCH. The study was under-powered to identify specific infections. Conclusions: Maternal bacterial infection is associated with perinatal death in high-burden settings, and accounted for around 5% of perinatal deaths in hospital deliveries. Improved prevention, and/or detection and treatment of maternal bacterial infection may contribute to reductions in perinatal mortality in hospital deliveries.