We present a comprehensive review of pregnancy outcomes in Sub-Saharan Africa intended to inform safety assessments of current and future clinical trials conducted in pregnant women or neonates. The observation-time model of maternal and neonatal mortality accounts for the logistical realities of variation in gestational age at recruitment, time to delivery, and follow-up time. This model yields lower mortality estimates than multiplying mortality rates by cumulative live births, especially if a safety evaluation is conducted immediately after a cluster of deliveries. Overall, our review noted that the incidences of maternal and neonatal mortality, severe acute maternal morbidity, stillbirths, and major congenital malformations are highest in West Africa, the least developed sub-region of the continent. However, relatively few detailed published studies of severe acute maternal morbidity and congenital malformations in Sub-Saharan Africa exist, especially in the community setting.
Of all adverse pregnancy outcomes, the incidences of SAMM and MCM were the most variable across sub-regions. Studies with more stringent organ failure/management-based definitions found lower incidences of SAMM. Many studies of major congenital malformations were not included because malformations among live- and stillborn infants could not be separated. The limited time frame and diagnostic tools to detect congenital malformations in many studies may have led to systematic underreporting of specific types of malformations not readily apparent by physical examination at birth, such as many cardiovascular anomalies.
This compilation of pregnancy outcomes relevant to a maternal immunization clinical trial is consistent with the few other published summaries of pregnancy outcomes in Sub-Saharan Africa. Kaye et al 
present a novel and pioneering review of causes of SAMM and case-fatality ratios. Although our review provides corroborating results, it also advances the field by providing several notable enhancements as we update the literature search, focus more explicitly on the background incidence of SAMM, and apply more stringent requirements for the catchment population. Careful interpretation is necessary to compare background rates of SAMM with those observed in a trial, as superior antenatal surveillance may decrease SAMM but better management of emergencies could prevent deaths, thereby elevating the rate of near-miss cases.
Our systematic review of LBW and prematurity does not yield nationally representative populations as are sought out in Demographic and Health Surveys and Multiple Indicator Cluster Surveys 
. Nevertheless, it allows designers of clinical trials to tailor expected background rates to recruitment sites by geographic and institutional setting. Despite this different approach, importantly, our overall estimates of the incidence of LBW are comparable to UNICEF values for sub-Saharan Africa overall (14%), Eastern and Southern Africa (14%), and West and Central Africa (13%) 
We recognize that our study has several limitations. First, we do not address differences in neonatal and maternal mortality rates among sub-populations within an individual country or across time that arise from geographic, socioeconomic, educational, and health access diversity. Thus, a DSMB should use its expertise and the best available data to select the most locally appropriate background rates for anticipated adverse event calculations. Second, pregnant women under the active surveillance of a clinical trial tend to have better access to medical care and therefore superior pregnancy outcomes relative to the general population. As in all mathematical models and systematic reviews, we are limited by the quality of the data informing our calculations. Many countries in Sub-Saharan Africa contribute incomplete vital registration data to systematic analyses of maternal mortality, stillbirths, and neonatal mortality 
on which our calculations are based. Additionally, while our search included English, French, and Portuguese language publications, it ignores publications from sub-Saharan African countries in journals not included in MEDLINE.
The global public health community awaits with great anticipation the results of several ongoing clinical trials in developing countries that explore whether maternal immunization improves pregnancy outcomes and enhances young infant survival. In some of these trials, investigators have chosen to avoid the use of pure placebo in the control group, instead providing a licensed vaccine with an independent potential benefit that does not influence the primary outcome. For example, in an ongoing clinical trial in Mali assessing the effectiveness of maternal influenza immunization against influenza in mothers and their infants, the pregnant women randomized to the control group receive quadrivalent meningococcal conjugate vaccine (NCT01430689). In such situations where for ethical reasons the study design does not include a true placebo group, reliable background rates of adverse pregnancy outcomes are invaluable to help distinguish between vaccine benefits and safety concerns. Further studies that clarify locally relevant, population-based background rates of adverse pregnancy outcomes will improve safety assessment of maternal interventions.