Background rates of adverse pregnancy outcomes for assessing the safety of maternal vaccine trials in sub-Saharan Africa.
BACKGROUND
Maternal immunization has gained traction as a strategy to diminish maternal and young infant mortality attributable to infectious diseases. Background rates of adverse pregnancy outcomes are crucial to interpret results of clinical trials in Sub-Saharan Africa.


METHODS
We developed a mathematical model that calculates a clinical trial's expected number of neonatal and maternal deaths at an interim safety assessment based on the person-time observed during different risk windows. This model was compared to crude multiplication of the maternal mortality ratio and neonatal mortality rate by the number of live births. Systematic reviews of severe acute maternal morbidity (SAMM), low birth weight (LBW), prematurity, and major congenital malformations (MCM) in Sub-Saharan African countries were also performed.


RESULTS
Accounting for the person-time observed during different risk periods yields lower, more conservative estimates of expected maternal and neonatal deaths, particularly at an interim safety evaluation soon after a large number of deliveries. Median incidence of SAMM in 16 reports was 40.7 (IQR: 10.6-73.3) per 1,000 total births, and the most common causes were hemorrhage (34%), dystocia (22%), and severe hypertensive disorders of pregnancy (22%). Proportions of liveborn infants who were LBW (median 13.3%, IQR: 9.9-16.4) or premature (median 15.4%, IQR: 10.6-19.1) were similar across geographic region, study design, and institutional setting. The median incidence of MCM per 1,000 live births was 14.4 (IQR: 5.5-17.6), with the musculoskeletal system comprising 30%.


CONCLUSIONS
Some clinical trials assessing whether maternal immunization can improve pregnancy and young infant outcomes in the developing world have made ethics-based decisions not to use a pure placebo control. Consequently, reliable background rates of adverse pregnancy outcomes are necessary to distinguish between vaccine benefits and safety concerns. Local studies that quantify population-based background rates of adverse pregnancy outcomes will improve safety assessment of interventions during pregnancy.
Emory University School of Medicine, Atlanta, Georgia, United States of America.
Lauren A V
LA
Orenstein
Evan W
EW
Orenstein
Ibrahima
I
Teguete
Mamoudou
M
Kodio
Milagritos
M
Tapia
Samba O
SO
Sow
Myron M
MM
Levine
D017954:Africa South of the Sahara / Q000453:epidemiology; D002986:Clinical Trials as Topic; D000013:Congenital Abnormalities / Q000453:epidemiology; D005260:Female; D006801:Humans; D007226:Infant Mortality; D007230:Infant, Low Birth Weight / Q000502:physiology; D007231:Infant, Newborn; D008962:Models, Theoretical; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology*; D014612:Vaccines / Q000009:adverse effects*
D014612:Vaccines