title: Assessment of the safety of antimalarial drug use during early pregnancy (ASAP): protocol for a multicenter prospective cohort study in Burkina Faso, Kenya and Mozambique.
abstract: BACKGROUND
  A major unresolved safety concern for malaria case management is the use of artemisinin combination therapies (ACTs) in the first trimester of pregnancy. There is a need for human data to inform policy makers and treatment guidelines on the safety of artemisinin combination therapies (ACT) when used during early pregnancy.
  
  
  METHODS
  The overall goal of this paper is to describe the methods and implementation of a study aimed at developing surveillance systems for identifying exposures to antimalarials during early pregnancy and for monitoring pregnancy outcomes using health and demographic surveillance platforms. This was a multi-center prospective observational cohort study involving women at health and demographic surveillance sites in three countries in Africa: Burkina Faso, Kenya and Mozambique [(ClinicalTrials.gov Identifier: NCT01232530)]. The study was designed to identify pregnant women with artemisinin exposure in the first trimester and compare them to: 1) pregnant women without malaria, 2) pregnant women treated for malaria, but exposed to other antimalarials, and 3) pregnant women with malaria and treated with artemisinins in the 2nd or 3rd trimesters from the same settings. Pregnant women were recruited through community-based surveys and attendance at health facilities, including antenatal care clinics and followed until delivery. Data from the three sites will be pooled for analysis at the end of the study. Results are forthcoming.
  
  
  CONCLUSIONS
  Despite few limitations, the methods described here are relevant to the development of sustainable pharmacovigilance systems for drugs used by pregnant women in the tropics using health and demographic surveillance sites to prospectively ascertain drug safety in early pregnancy.
  
  
  BACKGROUND
  NCT01232530.
authors.affiliation: Clinical Research Unit of Nanoro, Institut de Recherche en Sciences de la Santé (IRSS), Bobo-Dioulasso, Burkina Faso. tintohalidou@yahoo.fr.
authors.forename: Halidou
authors.initials: H
authors.lastname: Tinto
authors.affiliation: Eduardo Mondlane University, Maputo, Mozambique. esevene68@gmail.com.|Centro de Investigação em Saúde da Manhiça, Maputo, Mozambique. esevene68@gmail.com.
authors.forename: Esperança
authors.initials: E
authors.lastname: Sevene
authors.affiliation: Liverpool School of Tropical Medicine (LSTM), Liverpool, UK. stephanie.dellicour@lstmed.ac.uk.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dellicour
authors.affiliation: Departments of Pharmacy and Global Health, School of Public Health, University of Washington (UW), Seattle, USA. gcalip@uic.edu.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Calip
authors.affiliation: Medical Research Council, Fajara, The Gambia. udalessandro@mrc.gm.
authors.forename: Umberto
authors.initials: U
authors.lastname: d'Alessandro
authors.affiliation: Centro de Investigação em Saúde da Manhiça, Maputo, Mozambique. eusebio.macete@manhica.net.
authors.forename: Eusébio
authors.initials: E
authors.lastname: Macete
authors.affiliation: Clinical Research Unit of Nanoro, Institut de Recherche en Sciences de la Santé (IRSS), Bobo-Dioulasso, Burkina Faso. naksaid2006@yahoo.fr.
authors.forename: Seydou
authors.initials: S
authors.lastname: Nakanabo-Diallo
authors.affiliation: Clinical Research Unit of Nanoro, Institut de Recherche en Sciences de la Santé (IRSS), Bobo-Dioulasso, Burkina Faso. kazienga_adama@yahoo.fr.
authors.forename: Adama
authors.initials: A
authors.lastname: Kazienga
authors.affiliation: Clinical Research Unit of Nanoro, Institut de Recherche en Sciences de la Santé (IRSS), Bobo-Dioulasso, Burkina Faso. innocentvalea@yahoo.fr.
authors.forename: Innocent
authors.initials: I
authors.lastname: Valea
authors.affiliation: Clinical Research Unit of Nanoro, Institut de Recherche en Sciences de la Santé (IRSS), Bobo-Dioulasso, Burkina Faso. hsorgho@hotmail.com.
authors.forename: Hermann
authors.initials: H
authors.lastname: Sorgho
authors.affiliation: Centro de Investigação em Saúde da Manhiça, Maputo, Mozambique. anifa.vala@manhica.net.
authors.forename: Anifa
authors.initials: A
authors.lastname: Valá
authors.affiliation: Eduardo Mondlane University, Maputo, Mozambique. orvalho.joaquim@manhica.net.|Centro de Investigação em Saúde da Manhiça, Maputo, Mozambique. orvalho.joaquim@manhica.net.
authors.forename: Orvalho
authors.initials: O
authors.lastname: Augusto
authors.affiliation: Centro de Investigação em Saúde da Manhiça, Maputo, Mozambique. maria.ruperez@isglobal.org.|Instituto de Salud Global de Barcelona, Barcelona, Spain. maria.ruperez@isglobal.org.
authors.forename: Maria
authors.initials: M
authors.lastname: Ruperez
authors.affiliation: Centro de Investigação em Saúde da Manhiça, Maputo, Mozambique. clara.menendez@isglobal.org.|Instituto de Salud Global de Barcelona, Barcelona, Spain. clara.menendez@isglobal.org.
authors.forename: Clara
authors.initials: C
authors.lastname: Menendez
authors.affiliation: Kenya Medical Research Institute Centre for Global Health Research, Kisumu, Kenya. pouma@ke.cdc.gov.
authors.forename: Peter
authors.initials: P
authors.lastname: Ouma
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA. mud8@cdc.gov.|Centers for Disease Control and Prevention, Nairobi, Kenya. mud8@cdc.gov.
authors.forename: Meghna
authors.initials: M
authors.lastname: Desai
authors.affiliation: Liverpool School of Tropical Medicine (LSTM), Liverpool, UK. Feiko.TerKuile@lstmed.ac.uk.
authors.forename: Feiko
authors.initials: F
authors.lastname: Ter Kuile
authors.affiliation: Medical Research Council, Fajara, The Gambia. stergach@uw.edu.
authors.forename: Andy
authors.initials: A
authors.lastname: Stergachis
mesh_terms: D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use; D002985:Clinical Protocols; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008288:Malaria / Q000188:drug therapy*; D008431:Maternal-Fetal Exchange; D018579:Patient Selection; D060735:Pharmacovigilance; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000188:drug therapy*; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies; D012107:Research Design; D018401:Sample Size
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin