Investigating the Role of Cytomegalovirus as a Cause of Stillbirths and Child Deaths in Low- and Middle-Income Countries Through Postmortem Minimally Invasive Tissue Sampling

Background. There is paucity of information on the role of cytomegalovirus (CMV) infection as a cause of stillbirths or childhood deaths in low- and middle-income countries (LMICs). We investigated attribution of CMV disease in the causal pathway to stillbirths and deaths in children <5 years of age in 7 LMICs participating in the Child Health and Mortality Prevention Surveillance (CHAMPS) network. 

Methods. We analyzed stillbirths and decedents enrolled between December 2016 and July 2023. Deaths were investigated using postmortem minimally invasive tissue sampling with histopathology and molecular diagnostic investigations of tissues and body fluids, along with review of clinical records. Multidisciplinary expert panels reviewed findings and reported on the causal pathway to death. 

Results. CMV was detected in 19.5% (1140/5841) of all evaluated deaths, including 5.0% (111/2204), 6.2% (139/2229), 41.2% (107/260), 68.1% (323/474), and 68.2% (460/674) of stillbirths, neonates (deaths <28 days postnatal), early infants (28 to <90 days), late infants (90 to <365 days), and children (12 to <60 months), respectively. CMV disease was attributed in the causal pathway to death in 0.9% (20/2204) of stillbirths, 0.8% (17/2229) of neonates, 13.1% (34/260) of early infants, 9.7% (46/474) of late infants, and 3.3% (22/674) of children. Decedents with CMV disease, compared with those without CMV disease in the causal pathway, were more likely to have severe microcephaly (38.2% vs 21.1%; adjusted odds ratio [aOR], 2.2 [95% confidence interval {CI}, 1.3–3.6]) and to have human immunodeficiency virus (HIV) (36.9% vs 6.2%; aOR, 10.9 [95% CI, 6.5–18.5]). 

Conclusions. CMV disease is an important contributor to deaths during infancy and childhood and is often associated with severe microcephaly and HIV infection.Improving management of CMV in children with HIV and a vaccine to prevent CMV are needed interventions.