There are insufficient data on the safety in early pregnancy of the artemisinins, a new class of antimalarials. Assessment of drug teratogenicity requires large sample sizes for an adequate risk-benefit assessment. There is currently limited pharmacovigilance infrastructure in malaria-endemic countries. Monitoring drug safety in early pregnancy is especially challenging, as it requires early pregnancy detection to assess any potential increased risk of miscarriage, prospective follow-up to reduce recall and survival biases, and accurate data on gestational age assessment. Record linkage approaches for pregnancy pharmacovigilance using routinely generated health records could be a pragmatic and cost-effective approach for pharmacovigilance in early pregnancy, but has not been evaluated in resource-poor settings.
Our objective was to assess the feasibility of record linkage using routinely collected healthcare data as a pragmatic means of monitoring the safety in early pregnancy of artemisinin-based combination therapies (ACTs) in Senegal.
Data (2004–2008) from paper-based registers from outpatient clinics, antenatal care services (ANC) and the delivery unit from the St Joseph dispensary in Mlomp, south-western Senegal, were entered into databases. Record linkage based on a probabilistic matching approach was used to identify pregnancies exposed to ACTs in the first trimester of pregnancy. Two record linkage software packages (Link-Plus and FRIL) were compared and output data were reviewed independently by two investigators.
Information on 685 pregnancies was extracted, 536 of which were from the geographic catchment area and eligible for record linkage; 94.6 % of them resulted in live births, 2.6 % in stillbirths and 2.8 % in miscarriages. Major congenital malformations were identified in 1.6 % of births. Seventy-three and 75 true matches between pregnancy outcome and the outpatient treatment registers were identified by two different record linkage software packages, respectively. Record linkage identified seven exposures to ACTs in the first trimester, all of which resulted in normal live-births.
Probabilistic record linkage is a potentially cost-effective method to assess the safety of antimalarials in early pregnancy in resource-constrained settings to assess increased risk of overall birth defects, and stillbirths in settings with good existing health records and well defined target populations.
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This work was made possible by the dedication of the healthcare personnel of St Joseph Dispensary in Mlomp and the help of Sister Marie Joelle.
SD is partly funded by the Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine. SD is also grateful to the US Centers for Disease Control and Prevention for salary support through a cooperative agreement between the Division of Parasitic Diseases and Malaria (Centers for Disease Control and Prevention, USA) and the Malaria Epidemiology Unit of the Child and Reproductive Health group, Liverpool School of Tropical Medicine held by FtK. Travel expenses for SD and PT were covered by a pharmacovigilance planning grant from the Bill & Melinda Gates Foundation to the University of Washington held by AS.
Conflict of interest
The authors declare no conflict of interest. PO is a staff member of the WHO; the authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions, policy or views of the WHO.
Author’s contributions SD, FtK, OG and PO contributed to the concept of the project. SD and FtK developed the protocol with contributions from PO, PB and AS. SD and PT conducted the data collection and record linkage analyses. PB supervised the data collection. SD and FtK wrote the first draft of the manuscript; all authors reviewed and revised the final version.
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Dellicour, S., Brasseur, P., Thorn, P. et al. Probabilistic Record Linkage for Monitoring the Safety of Artemisinin-Based Combination Therapy in the First Trimester of Pregnancy in Senegal. Drug Saf 36, 505–513 (2013). https://doi.org/10.1007/s40264-013-0059-1
- Record Linkage
- True Match
- Last Menstrual Period
- Health Facility Delivery