title: Exposure to artemether-lumefantrine (Coartem) in first trimester pregnancy in an observational study in Zambia.
abstract: BACKGROUND
  In general, safety data following exposure to drugs in the first trimester of pregnancy are scarce. More specifically, data on the safety of artemisinin-based combination therapy (ACT) in pregnancy still remain limited. Therefore, pregnant women from Choma, Zambia, who were exposed to artemether-lumefantrine (AL) for the treatment of uncomplicated malaria were followed up and evaluated in a prospective cohort study. This report assessed the longitudinal safety outcomes of the pregnant women inadvertently exposed during the first trimester.
  
  
  METHODS
  Participants were classified based on the drug used to treat their most recent malaria episode: artemether-lumefantrine (AL) versus sulphadoxine-pyrimethamine (SP) and/or quinine. All enrolled women were followed up until six weeks post-delivery and the live births for 12 months.
  
  
  RESULTS
  There were 294 first trimester exposures in the observational cohort (pregnant women: AL = 150, AL and SP = 9 and SP and/or quinine = 135). Similar rates of perinatal mortality (stillbirths and neonatal deaths) were observed for each treatment arm (AL 4.4%, SP and/or quinine 3.9%). At delivery (newborns: AL = 135, AL and SP = 7 and SP and/or quinine = 129), the gestational age (measured using the Dubowitz total scores), length and head circumference of the newborns were similar between the two arms. Low birth weights were reported in 10.2% (95% CI 6.0, 16.6) and 6.7% (95% CI 3.4, 12.6) of newborns in the AL and SP and/or quinine arms, respectively. Overall development (including neurodevelopmental parameters) was similar between the two arms, both at 14 weeks and 12 months of age.
  
  
  CONCLUSIONS
  Exposure to AL and SP in the first trimester was not associated with particular safety risks such as perinatal mortality, preterm deliveries or low birth weights. Such outcomes as well as infant neurodevelopmental parameters up to 12 months were similar between the two arms. These findings add to the body of data suggesting that randomized clinical trials could now be the way forward to assess safety and efficacy of ACT in the first trimester of pregnancy.
authors: Christine
authors: C
authors: Manyando
authors: Eric M
authors: EM
authors: Njunju
authors: Mailis
authors: M
authors: Virtanen
authors: Kamal
authors: K
authors: Hamed
authors: Melba
authors: M
authors: Gomes
authors: Jean-Pierre
authors: JP
authors: Van Geertruyden
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000009:adverse effects* / Q000627:therapeutic use; D036861:Delivery, Obstetric / Q000706:statistics & numerical data; D004338:Drug Combinations; D004983:Ethanolamines / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008288:Malaria / Q000188:drug therapy / Q000453:epidemiology; D018811:Maternal Exposure / Q000706:statistics & numerical data*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000453:epidemiology; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D055815:Young Adult; D015024:Zambia / Q000453:epidemiology
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes