title: Probabilistic record linkage for monitoring the safety of artemisinin-based combination therapy in the first trimester of pregnancy in Senegal.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Child and Reproductive Health Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, Merseyside L3 5QA, UK. sdell@liv.ac.uk
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dellicour
authors.forename: Philippe
authors.initials: P
authors.lastname: Brasseur
authors.forename: Per
authors.initials: P
authors.lastname: Thorn
authors.forename: Oumar
authors.initials: O
authors.lastname: Gaye
authors.forename: Piero
authors.initials: P
authors.lastname: Olliaro
authors.forename: Malik
authors.initials: M
authors.lastname: Badiane
authors.forename: Andy
authors.initials: A
authors.lastname: Stergachis
authors.forename: Feiko O
authors.initials: FO
authors.lastname: ter Kuile
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology / Q000209:etiology; D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D037621:Artemisinins / Q000009:adverse effects* / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000453:epidemiology; D008498:Medical Record Linkage; D008875:Middle Aged; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000188:drug therapy* / Q000453:epidemiology; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D012675:Senegal / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D037621:Artemisinins; C031327:artemisinin