Skip to main content

Table 2 Safety outcomes: maternal adverse events and pregnancy outcomes in women exposed to artemisinin compounds. Randomized trials

From: The safety of artemisinins during pregnancy: a pressing question

Study site, year
Ref
Antimalarial treatment N (% follow up) Outcomes of interests
    Maternal Safety ¥ Pregnancy outcomes
Nigeria, 1994–1997 [14] 1) Artemether IM + mefloquine n = 22
2) Artemether IM n = 23
45 (100%) Minimal, only A+M: abdominal discomfort (9%) and dizziness (9%) Neonatal jaundice (n = 2 A & n = 1 A+M)
6 (13%) followed up to 1 year
Thailand, 1995–1998 [10] 1) Quinine n = 29
2) Artesunate+ mefloquine n = 28
60 (95%) Neurological exam: all normal.
Nausea (16%), vomiting (12%), vertigo (12%), tinnitus (18%), and hypoglycaemia (3%) more frequent in Q (p < 0.05). Other no difference: Palpitation (6%), blurring vision (11%).
Neonatal jaundice (n = 5 Q & n = 1 A+M)
46 (81%) followed up to 1 year
TBB, 1995–1997 [12] 1) Quinine n = 42
2) Artesunate+ mefloquine n = 66
108 (85%) Neurological exam
1 maternal death*
Tinnitus (15%) and dizziness (42%) more frequent in Q (p < 0.05).
Headache (21%), nausea (45%), abdominal pain (28%), vertigo (12%), muscle/joint pain (32%), and anorexia (35%) no difference with Q (p > 0.05).
Abortions (n = 2 A+M)
46 (49%) followed up to 1 year
Neonatal deaths (n = 2 A+M & n = 1 Q)
TBB, 1997–2000 [13] 1) Quinine)+ clindamycin n = 65
2) Artesunate n = 64
129 (91%) Tinnitus (9%) more frequent in Q+C (p < 0.05). Headache (30%), dizziness (41%) nausea (25%), vomiting (8%), abdominal pain (18%), rash (9%), contractions (35%), muscle/joint pain (12%), and anorexia (42%) no difference with Q+C (p > 0.05). Stillbirths (n = 1 A & n = 1 Q+C)
Congenital abnormality: midline epidermoid cyst (n = 1 Q+C)
Neonatal deaths (n = 1 A & n = 2 Q+C)
72 (62%) followed up to 1 year
TBB, 2001–2003 [11] 1)Quinine n = 42
2) Artesunate atovaquone-proguanil (AAP) n = 39
81 (91%) 1 maternal death**
Tinnitus (24%) more frequent in Q (p < 0.05).
Stillbirth (n = 1 not specified maternal death)
Congenital abnormalities: polythelia (n = 1 AAP); cleft lip & palate (n = 1 AAP); aural atresia (n = 1 Q)
Neonatal deaths (n = 1 A & n = 2 Q+C)
59 (78%) followed up to 1 year
Developmentally delayed (n = 1 AAP)
TOTAL No 1 st trimester, P. falciparum or mixed malaria 17% to 100% symptomatic 242 artemisinins exposures 423 (94%) 2 maternal deaths
Neurological exam in 2 studies
Stillbirths (n = 1 A; n = 1 Q+C & n = 1 unknown)
Congenital abnormality: (n = 2 A & n = 2 Q)
Neonatal deaths (n = 4 A+M & n = 5 Q)
229 (59%) infant followed up to 1 year
  1. ¥ Prevalence of possible ADRs are only reported for the artemisinin treatment groups
  2. * cause unrelated to malaria (treatment group NR)
  3. ** caused by a ruptured liver abscess (treatment group NR)
  4. Abbreviation: ADR: adverse drug reaction; AE: adverse event; IM: intramuscular injection; NR: not reported; Q: quinine; A: artemisinin derivative; A+M: artesunate+mefloquine; TBB: Thai-Burmese border