학술논문

The Safety of Artemisinin Derivatives for the Treatment of Malaria in the 2nd or 3rd Trimester of Pregnancy: A Systematic Review and Meta-Analysis
Document Type
Medical condition overview
Source
PLoS ONE. November 8, 2016, Vol. 11 Issue 11, e0164963
Subject
Genetic disorders -- Drug therapy -- Safety and security measures -- Analysis
Birth defects -- Drug therapy -- Safety and security measures -- Analysis
Antimalarials -- Safety and security measures -- Analysis
Drugs -- Safety and security measures -- Analysis
Malaria -- Drug therapy -- Safety and security measures -- Analysis
Pregnant women -- Drug therapy -- Safety and security measures -- Analysis
Health
Science and technology
Drug therapy
Diseases
Analysis
Safety and security measures
Language
English
ISSN
1932-6203
Abstract
Given the high morbidity for mother and fetus associated with malaria in pregnancy, safe and efficacious drugs are needed for treatment. Artemisinin derivatives are the most effective antimalarials, but are associated with teratogenic and embryotoxic effects in animal models when used in early pregnancy. However, several organ systems are still under development later in pregnancy. We conducted a systematic review and meta-analysis of the occurrence of adverse pregnancy outcomes among women treated with artemisinins monotherapy or as artemisinin-based combination therapy during the 2nd or 3rd trimesters relative to pregnant women who received non-artemisinin antimalarials or none at all. Pooled odds ratio (POR) were calculated using Mantel-Haenszel fixed effects model with a 0.5 continuity correction for zero events. Eligible studies were identified through Medline, Embase, and the Malaria in Pregnancy Consortium Library. Twenty studies (11 cohort studies and 9 randomized controlled trials) contributed to the analysis, with 3,707 women receiving an artemisinin, 1,951 a non-artemisinin antimalarial, and 13,714 no antimalarial. The PORs (95% confidence interval (CI)) for stillbirth, fetal loss, and congenital anomalies when comparing artemisinin versus quinine were 0.49 (95% CI 0.24-0.97, I.sup.2 = 0%, 3 studies); 0.58 (95% CI 0.31-1.16, I.sup.2 = 0%, 6 studies); and 1.00 (95% CI 0.27-3.75, I.sup.2 = 0%, 3 studies), respectively. The PORs comparing artemisinin users to pregnant women who received no antimalarial were 1.13 (95% CI 0.77-1.66, I.sup.2 = 86.7%, 3 studies); 1.10 (95% CI 0.79-1.54, I.sup.2 = 0%, 4 studies); and 0.79 (95% CI 0.37-1.67, I.sup.2 = 0%, 3 studies) for miscarriage, stillbirth and congenital anomalies respectively. Treatment with artemisinin in 2.sup.nd and 3.sup.rd trimester was not associated with increased risks of congenital malformations or miscarriage and may be was associated with a reduced risk of stillbirths compared to quinine. This study updates the reviews conducted by the WHO in 2002 and 2006 and supports the current WHO malaria treatment guidelines malaria in pregnancy.
Author(s): Stephanie D. Kovacs 1,*, Anna Maria van Eijk 2, Esperanca Sevene 3, Stephanie Dellicour 2, Noel S. Weiss 1, Scott Emerson 4, Richard Steketee 5, Feiko O. ter Kuile [...]