Adverse pregnancy outcomes between the anti-malarial drugs: Is there a difference between the drugs recommended by World Health Organization? Results of a mixed treatment comparison analysis of randomized clinical trials and cohort studies
Affiliations: [a] Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain
| [b] Department of Oral Health, College of Medicine, Nursing and Health Sciences, Fiji National University, Suva, Fiji
| [c] School of Population and Public Health, University of British Columbia, Vancouver, Canada
Correspondence:
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Address for correspondence: Dr. Kannan Sridharan, Associate Professor, Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain. Tel.: +973 33453123; E-mail: skannandr@gmail.com.
Abstract: BACKGROUND:Data regarding the relative safety profile of anti-malarial drugs in pregnancy is sparse mainly limited by the absence of head-to-head clinical trials. The present study is a network meta-analysis of safety of anti-malarial drugs used to treat malaria in pregnant women. METHODS:A thorough literature search using the search strategy “Malaria [tiab] AND (Pregnant [tiab] OR Pregnancy [tiab])” was carried out for either randomized controlled trials or prospective cohort studies in pregnant malarial women prescribed any of the recommended anti-malarial drugs by World Health Organization (WHO) and that have reported adverse pregnancy outcomes such as miscarriage, still birth, and neonatal deaths. Odds ratio with 95% confidence interval was used as the effect estimate. Random-effects model and Markov Chain Monte Carlo simulation method was used to generate pooled estimates. Sensitivity analysis was performed excluding data from first trimester and GRADE approach was used to categorize the quality of evidence. RESULTS:A total of 1242 papers were obtained with the search strategy, of which seven evaluating 10 treatment arms in a total of 5510 participants were included in the present meta-analysis. The pooled estimates revealed significantly lower risks of abortion with quinine and artemisinin-lumefantrine compared to dihydroartemisinin-piperaquine, artesunate with mefloquine and artesunate with amodiaquine. But when a cohort study that was conducted in the first trimester of pregnancy was excluded, no significant differences were observed in the risk of abortion between the anti-malarial drugs. No significant differences in the risk of either stillbirths or neonatal deaths were observed with any of the drugs. The quality of evidence was found to be very low due to serious limitations in both the precision and indirectness. CONCLUSION:WHO recommended anti-malarials in pregnancy have similar risk profiles with regard to abortion, stillbirth and neonatal deaths.
