Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/114457
Title: First-trimester artemisinin derivatives and quinine treatments and the risk of adverse pregnancy outcomes in Africa and Asia: A meta-analysis of observational studies
Author: Dellicour, Stephanie
Sevene, Esperança Júlia Pires
McGready, Rose
Tinto, Halidou
Mosha, Domnic
Manyando, Christine
Rulisa, Stephen.
Desai, Meghna
Ouma, Peter
Oneko, Martina
Vala, Anifa
Rupérez, María
Macete, Eusébio
Menéndez, Clara
Nakanabo-Diallo, Seydou
Kazienga, Adama
Valéa, Innocent
Calip, Gregory S.
Augusto, Orvalho
Genton, Blaise
Njunju, Eric M.
Moore, Kerryn A.
Alessandro, Umberto d'
Nosten, François
Ter Kuile, Feiko
Stergachis, Andy
Keywords: Embaràs
Medicaments
Malària
Pregnancy
Drugs
Malaria
Issue Date: 2-May-2017
Publisher: Public Library of Science (PLoS)
Abstract: Background Animal embryotoxicity data, and the scarcity of safety data in human pregnancies, have prevented artemisinin derivatives from being recommended for malaria treatment in the first trimester except in lifesaving circumstances. We conducted a meta-analysis of prospective observational studies comparing the risk of miscarriage, stillbirth, and major congenital anomaly (primary outcomes) among first-trimester pregnancies treated with artemisinin derivatives versus quinine or no antimalarial treatment. Methods and findings Electronic databases including Medline, Embase, and Malaria in Pregnancy Library were searched, and investigators contacted. Five studies involving 30,618 pregnancies were included; four from sub-Saharan Africa (n = 6,666 pregnancies, six sites) and one from Thailand (n = 23,952). Antimalarial exposures were ascertained by self-report or active detection and confirmed by prescriptions, clinic cards, and outpatient registers. Cox proportional hazards models, accounting for time under observation and gestational age at enrollment, were used to calculate hazard ratios. Individual participant data (IPD) meta-analysis was used to combine the African studies, and the results were then combined with those from Thailand using aggregated data meta-analysis with a random effects model. There was no difference in the risk of miscarriage associated with the use of artemisinins anytime during the first trimester (n = 37/671) compared with quinine (n = 96/945; adjusted hazard ratio [aHR] = 0.73 [95% CI 0.44, 1.21], I2 = 0%, p = 0.228), in the risk of stillbirth (artemisinins, n = 10/654; quinine, n = 11/615; aHR = 0.29 [95% CI 0.08–1.02], p = 0.053), or in the risk of miscarriage and stillbirth combined (pregnancy loss) (aHR = 0.58 [95% CI 0.36–1.02], p = 0.099). The corresponding risks of miscarriage, stillbirth, and pregnancy loss in a sensitivity analysis restricted to artemisinin exposures during the embryo sensitive period (6–12 wk gestation) were as follows: aHR = 1.04 (95% CI 0.54–2.01), I2 = 0%, p = 0.910; aHR = 0.73 (95% CI 0.26–2.06), p = 0.551; and aHR = 0.98 (95% CI 0.52–2.04), p = 0.603. The prevalence of major congenital anomalies was similar for first-trimester artemisinin (1.5% [95% CI 0.6%–3.5%]) and quinine exposures (1.2% [95% CI 0.6%–2.4%]). Key limitations of the study include the inability to control for confounding by indication in the African studies, the paucity of data on potential confounders, the limited statistical power to detect differences in congenital anomalies, and the lack of assessment of cardiovascular defects in newborns. Conclusions Compared to quinine, artemisinin treatment in the first trimester was not associated with an increased risk of miscarriage or stillbirth. While the data are limited, they indicate no difference in the prevalence of major congenital anomalies between treatment groups. The benefits of 3-d artemisinin combination therapy regimens to treat malaria in early pregnancy are likely to outweigh the adverse outcomes of partially treated malaria, which can occur with oral quinine because of the known poor adherence to 7-d regimens
Note: Reproducció del document publicat a: https://doi.org/10.1371/journal.pmed.1002290
It is part of: PLoS Medicine, 2017, vol. 14, num. 5, p. e1002290
Related resource: https://doi.org/10.1371/journal.pmed.1002290
URI: http://hdl.handle.net/2445/114457
ISSN: 1549-1277
Appears in Collections:Articles publicats en revistes (ISGlobal)

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