Table 1.

Studies which evaluated the safety of mefloquine for treatment of malaria in pregnant women

Reference	Study year and location	Study design	Study women	MQ safety on pregnancy outcomes	MQ tolerability	Comments
Harinasuta et al. 1990 [45]	Thailand	Clinical trial which compared MQ to QN for the treatment of multi-resistant falciparum malaria	N = 85 women (all trimesters) treated with MQ vs N = 72 treated with QN	No differences in stillbirth rates between groups	All mild and transient adverse events.	Small sample size
						Limited information on procedures and results available
Okeyeh et al. 1996 [47]	Nigeria	Non comparative MQ treatment study in pregnant women (12.5 mg/kg)	N = 33 women in 2nd and 3rd trimester	No stillbirths and congenital malformations reported	Minimal side effects	Small sample size
						Low dose of MQ used
Sowunmi et al. 1998 [49]	Nigeria	Open label trial which compared artemether to artemether + MQ in the treatment of uncomplicated malaria	N = 45 women in 2nd and 3rd trimesters	No abortion, stillbirth or congenital anomalies were observed	Minimal adverse events reported in the artemether – MQ group (dizziness and abdominal pain) in 2/45 patients	Small sample size
			n = 23 artemether			Open label trial
			n = 22 artemether + MQ
McGready et al. 1998 [43]	1991-96	Non- randomized comparative MQ treatment study, cohort series	N = 372	Similar rates of congenital anomalies and stillbirths among groups	The most common adverse effects following MQ were dizziness (36%) and anorexia (23%)	Open label cohort series Groups not well matched
	Thailand		n = 194 treated with MQ (in 2nd and 3rd trimesters)
			n = 93 treated with QN
			n = 85 MQ + QN
Nosten et al. 1999 [44]	1991-94	Retrospective analysis of the pregnancy outcomes of women exposed to MQ compared to those not exposed (based on ANC registries and self-reported information from interviews)	N = 208 pregnancies exposed to MQ (mainly 2nd and 3rd trimesters) vs	Increased risk of reported stillbirths in women exposed to MQ:	No data available	Analysis with several limitations
	Thailand		N = 656 exposed to QN vs	(9/208) 4.5% (MQ group) vs		1) Four women out of the nine with a stillbirth had been exposed to other anti-malarials;
			N = 909 exposed to other anti-malarials vs	(10/656) 1.6% (QN group) vs
			N = 2,470 not exposed to anti-malarials	(12/909) 1.4% (other anti-malarials) vs
				(40/2470) 1.8% (not exposed)		2) Recall bias possible (results based on self-reported data)
McGready et al. 2000 [40]	1995-97	Open randomized comparison of different malaria treatments in pregnant women in the 2nd and 3rd trimesters	N = 108	No differences in the rates of congenital anomalies, stillbirths or birth weight between the treatment groups	No serious adverse effects were reported	Small sample size
	Thailand		n = 42 QN 7 days		Dizziness was more frequent in the QN group than in the MQ (87 vs 45%)	MQ combined with AS
			vs			Open label
			n = 66 MQ (25 mg/kg) + AS 3 days
Bounyasong 2001 [48]	Thailand	Open randomized comparison of different malaria treatments in pregnant women in the 2nd and 3rd trimesters	N = 60	No data available	QN group reported more adverse effects than the MQ group (nausea, vomiting, vertigo, tinnitus and hypoglycaemia)	Small sample size
			n = 29 QN 7 days vs			MQ combined with AS
			n = 28 AS + MQ			Open label
			3 Lost to follow-up
Adam et al. 2004 [46]	1998-2001	Prospective study which evaluated the efficacy and safety of MQ in women who presented with malaria after a full course of CQ therapy	N = 40	No abortion, stillbirth and congenital anomalies were observed	35% reported nausea and 17.5% itching	Small sample size
	Sudan		Pregnant women in the 2nd or 3rd trimester of gestation			Non comparative study