Protocol for a drugs exposure pregnancy registry for implementation in resource-limited settings

Abstract

BackgroundThe absence of robust evidence of safety of medicines in pregnancy, particularly those for major diseases provided by public health programmes in developing countries, has resulted in cautious recommendations on their use. We describe a protocol for a Pregnancy Registry adapted to resource-limited settings aimed at providing evidence on the safety of medicines in pregnancy.Methods/DesignSentinel health facilities are chosen where women come for prenatal care and are likely to come for delivery. Staff capacity is improved to provide better care during the pregnancy, to identify visible birth defects at delivery and refer infants with major anomalies for surgical or clinical evaluation and treatment. Consenting women are enrolled at their first antenatal visit and careful medical, obstetric and drug-exposure histories taken; medical record linkage is encouraged. Enrolled women are followed up prospectively and their histories are updated at each subsequent visit. The enrolled woman is encouraged to deliver at the facility, where she and her baby can be assessed.DiscussionIn addition to data pooling into a common WHO database, the WHO Pregnancy Registry has three important features: First is the inclusion of pregnant women coming for antenatal care, enabling comparison of birth outcomes of women who have been exposed to a medicine with those who have not. Second is its applicability to resource-poor settings regardless of drug or disease. Third is improvement of reproductive health care during pregnancies and at delivery. Facility delivery enables better health outcomes, timely evaluation and management of the newborn, and the collection of reliable clinical data. The Registry aims to improves maternal and neonatal care and also provide much needed information on the safety of medicines in pregnancy.

Polydactyly, postaxial, type B

“…Since 95% of the affected infants have no other malformations, isolated postaxial polydactyly has been considered a “mild” abnormality. Because of its isolated nature, the lack of medical significance and the fact that it has never been shown to be produced by any human teratogens (Holmes, ), it can be excluded as an outcome in studies of putative teratogens in populations in Africa (Mehta, Clerk, & Allen, ). If included as a significant malformation, it would be the most common outcome identified and, yet, not likely to be a teratogenic effect.…”

Surveillance monitoring for safety of in utero antiretroviral therapy exposures: current strategies and challenges

“…Additionally, the World Health Organization is creating a centralized database for drug exposures in pregnancy [74]. The aim is to be able to pool data from LMICs in order to have power to study rare outcomes and rare exposures across different settings.…”

“…Differences in measurement or definitions of outcomes can lead both to under- and over-diagnosis and have to be considered during primary study design as it not possible to control for differences in meta-analysis or data pooling. It is encouraging that steps have been taken by the research community and by the WHO towards building future sustainable collaborations between key cohorts across the globe [74,78]. …”

Inclusion of pregnant women in antiretroviral drug research: what is needed to move forwards?

“…The WHO Pregnancy Registry was piloted in 2010/2011 in Brazil, Ghana, Kenya, Uganda and Tanzania, as a pregnancy surveillance system for low-and middle-income countries (LMICs). It has, however, not been widely implemented and challenges are anticipated with data completeness and validity [54][55][56]. Together these surveillance studies and registries may identify signals of potential teratogenicity which can be evaluated across all available resources [50,51].…”