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The Safety of Artemisinin Derivatives for the Treatment of Malaria in the 2nd or 3rd Trimester of Pregnancy: A Systematic Review and Meta-Analysis

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Kovacs, Stephanie D., vanEijk, Anna ORCID: https://orcid.org/0000-0003-1635-1289, Sevene, Esperanca, Dellicour, Stephanie, Weiss, Noel S., Emerson, Scott, Steketee, Richard, terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617 and Stergachis, Andy (2016) 'The Safety of Artemisinin Derivatives for the Treatment of Malaria in the 2nd or 3rd Trimester of Pregnancy: A Systematic Review and Meta-Analysis'. PLoS ONE, Vol 11, Issue 11, e0164963.

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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, I2 = 0%, 3 studies); 0.58 (95% CI 0.31–1.16, I2 = 0%, 6 studies); and 1.00 (95% CI 0.27–3.75, I2 = 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, I2 = 86.7%, 3 studies); 1.10 (95% CI 0.79–1.54, I2 = 0%, 4 studies); and 0.79 (95% CI 0.37–1.67, I2 = 0%, 3 studies) for miscarriage, stillbirth and congenital anomalies respectively. Treatment with artemisinin in 2nd and 3rd 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.

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials
WA Public Health > Health Problems of Special Population Groups > WA 310 Maternal welfare
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WQ Obstetrics > Childbirth. Prenatal Care > WQ 175 Prenatal care
WQ Obstetrics > Pregnancy Complications > WQ 240 Pregnancy complications (General)
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.pone.0164963
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 22 Nov 2016 11:09
Last Modified: 16 Aug 2019 13:40
URI: https://archive.lstmed.ac.uk/id/eprint/6350

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