Artemisinin-based combination therapy during pregnancy: outcome of pregnancy and infant mortality: a cohort study

Michael Nambozi, Halidou Tinto, Victor Mwapasa, Harry Tagbor, Jean-Bertin Bukasa Kabuya, Sebastian Hachizovu, Maminata Traoré, Innocent Valea, Marc Christian Tahita, Gifty Ampofo, Jozefien Buyze, Raffaella Ravinetto, Diana Arango, Kamala Thriemer, Modest Mulenga, Jean-Pierre van Geertruyden, Umberto D'Alessandro, Michael Nambozi, Halidou Tinto, Victor Mwapasa, Harry Tagbor, Jean-Bertin Bukasa Kabuya, Sebastian Hachizovu, Maminata Traoré, Innocent Valea, Marc Christian Tahita, Gifty Ampofo, Jozefien Buyze, Raffaella Ravinetto, Diana Arango, Kamala Thriemer, Modest Mulenga, Jean-Pierre van Geertruyden, Umberto D'Alessandro

Abstract

Background: The World Health Organization (WHO) recommendation of treating uncomplicated malaria during the second and third trimester of pregnancy with an artemisinin-based combination therapy (ACT) has already been implemented by all sub-Saharan African countries. However, there is limited knowledge on the effect of ACT on pregnancy outcomes, and on newborn and infant's health.

Methods: Pregnant women with malaria in four countries (Burkina Faso, Ghana, Malawi and Zambia) were treated with either artemether-lumefantrine (AL), amodiaquine-artesunate (ASAQ), mefloquine-artesunate (MQAS), or dihydroartemisinin-piperaquine (DHA-PQ); 3127 live new-borns (822 in the AL, 775 in the ASAQ, 765 in the MQAS and 765 in the DHAPQ arms) were followed-up until their first birthday.

Results: Prevalence of placental malaria and low birth weight were 28.0% (738/2646) and 16.0% (480/2999), respectively, with no significant differences between treatment arms. No differences in congenital malformations (p = 0.35), perinatal mortality (p = 0.77), neonatal mortality (p = 0.21), and infant mortality (p = 0.96) were found.

Conclusions: Outcome of pregnancy and infant survival were similar between treatment arms indicating that any of the four artemisinin-based combinations could be safely used during the second and third trimester of pregnancy without any adverse effect on the baby. Nevertheless, smaller safety differences between artemisinin-based combinations cannot be excluded; country-wide post-marketing surveillance would be very helpful to confirm such findings. Trial registration ClinicalTrials.gov, NCT00852423, Registered on 27 February 2009, https://ichgcp.net/clinical-trials-registry/NCT00852423.

Conflict of interest statement

No competing interest stated except UDA who reports receiving grant support from Sigma-Tau Industrie Farmaceutiche Riunite.

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