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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