title: Safety of artemether-lumefantrine exposure in first trimester of pregnancy: an observational cohort.
abstract: BACKGROUND
  There is limited data available regarding safety profile of artemisinins in early pregnancy. They are, therefore, not recommended by WHO as a first-line treatment for malaria in first trimester due to associated embryo-foetal toxicity in animal studies. The study assessed birth outcome among pregnant women inadvertently exposed to artemether-lumefantrine (AL) during first trimester in comparison to those of women exposed to other anti-malarial drugs or no drug at all during the same period of pregnancy.
  
  
  METHODS
  Pregnant women with gestational age <20 weeks were recruited from Maternal Health clinics or from monthly house visits (demographic surveillance), and followed prospectively until delivery.
  
  
  RESULTS
  2167 pregnant women were recruited and 1783 (82.3%) completed the study until delivery. 319 (17.9%) used anti-malarials in first trimester, of whom 172 (53.9%) used (AL), 78 (24.4%) quinine, 66 (20.7%) sulphadoxine-pyrimethamine (SP) and 11 (3.4%) amodiaquine. Quinine exposure in first trimester was associated with an increased risk of miscarriage/stillbirth (OR 2.5; 1.3-5.1) and premature birth (OR 2.6; 1.3-5.3) as opposed to AL with (OR 1.4; 0.8-2.5) for miscarriage/stillbirth and (OR 0.9; 0.5-1.8) for preterm birth. Congenital anomalies were identified in 4 exposure groups namely AL only (1/164[0.6%]), quinine only (1/70[1.4%]), SP (2/66[3.0%]), and non-anti-malarial exposure group (19/1464[1.3%]).
  
  
  CONCLUSIONS
  Exposure to AL in first trimester was more common than to any other anti-malarial drugs. Quinine exposure was associated with adverse pregnancy outcomes which was not the case following other anti-malarial intake. Since AL and quinine were used according to their availability rather than to disease severity, it is likely that the effect observed was related to the drug and not to the disease itself. Even with this caveat, a change of policy from quinine to AL for the treatment of uncomplicated malaria during the whole pregnancy period could be already envisaged.
authors.affiliation: Ifakara Health Institute, Rufiji HDSS, P,O Box 40, Rufiji, Tanzania. dfmosha@hotmail.com.
authors.forename: Dominic
authors.initials: D
authors.lastname: Mosha
authors.forename: Festo
authors.initials: F
authors.lastname: Mazuguni
authors.forename: Sigilbert
authors.initials: S
authors.lastname: Mrema
authors.forename: Esperanca
authors.initials: E
authors.lastname: Sevene
authors.forename: Salim
authors.initials: S
authors.lastname: Abdulla
authors.forename: Blaise
authors.initials: B
authors.lastname: Genton
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007231:Infant, Newborn; D008288:Malaria / Q000188:drug therapy*; D008875:Middle Aged; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D011446:Prospective Studies; D011803:Quinine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D011803:Quinine