Mortality, Morbidity, and Developmental Outcomes in Infants Born to Women Who Received Either Mefloquine or Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment of Malaria in Pregnancy: A Cohort Study

Maria Rosario ,Raquel González,Manfred Accrombessi,Clara Menéndez,Achille Massougbodji,Michel Cot,Mwaka A Kakolwa,Abdunoor M Kabanywanyi,Esperança Sevene,Peter G Kremsner,Rella Manego Zoleko,John J Aponte,Valérie Briand,Ghyslain Mombo-Ngoma,Smaïla Ouédraogo,Salim Abdulla,Michael Ramharter,Eusébio Macete,Ayôla Akim Adegnika ,Anifa Valá

doi:10.1371/journal.pmed.1001964

Abstract

BackgroundLittle is known about the effects of intermittent preventive treatment of malaria in pregnancy (IPTp) on the health of sub-Saharan African infants. We have evaluated the safety of IPTp with mefloquine (MQ) compared to sulfadoxine-pyrimethamine (SP) for important infant health and developmental outcomes.Methods and FindingsIn the context of a multicenter randomized controlled trial evaluating the safety and efficacy of IPTp with MQ compared to SP in pregnancy carried out in four sub-Saharan countries (Mozambique, Benin, Gabon, and Tanzania), 4,247 newborns, 2,815 born to women who received MQ and 1,432 born to women who received SP for IPTp, were followed up until 12 mo of age. Anthropometric parameters and psychomotor development were assessed at 1, 9, and 12 mo of age, and the incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were determined until 12 mo of age. No significant differences were found in the proportion of infants with stunting, underweight, wasting, and severe acute malnutrition at 1, 9, and 12 mo of age between infants born to women who were on IPTp with MQ versus SP. Except for three items evaluated at 9 mo of age, no significant differences were observed in the psychomotor development milestones assessed. Incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were similar between the two groups. Information on the outcomes at 12 mo of age was unavailable in 26% of the infants, 761 (27%) from the MQ group and 377 (26%) from the SP group. Reasons for not completing the study were death (4% of total study population), study withdrawal (6%), migration (8%), and loss to follow-up (9%).ConclusionsNo significant differences were found between IPTp with MQ and SP administered in pregnancy on infant mortality, morbidity, and nutritional outcomes. The poorer performance on certain psychomotor development milestones at 9 mo of age in children born to women in the MQ group compared to those in the SP group may deserve further studies.Trial registrationClinicalTrials.gov NCT00811421

Highlights

Malaria infection in pregnancy is a significant public health problem in endemic regions, especially in sub-Saharan Africa, where there are nearly 30 million pregnancies at risk of infection every year [1]
No significant differences were found between intermittent preventive treatment of malaria in pregnancy (IPTp) with MQ and SP administered in pregnancy on infant mortality, morbidity, and nutritional outcomes
To prevent maternal infection in malaria endemic areas in Africa, World Health Organization (WHO) recommends the use of insecticide-treated bed nets and the administration of intermittent preventive treatment of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) [16]

Summary

Introduction

Malaria infection in pregnancy is a significant public health problem in endemic regions, especially in sub-Saharan Africa, where there are nearly 30 million pregnancies at risk of infection every year [1]. Infection with malaria during pregnancy can cause severe maternal anemia (reduced red blood cell numbers), stillbirths, and pre-term and low-birth-weight babies, and is responsible for the deaths of many women and their babies To prevent this loss of life, the World Health Organization (WHO) recommends that pregnant women living in areas of moderate to high transmission in Africa receive the antimalarial drug sulfadoxinepyrimethamine (SP) at each scheduled antenatal visit after the first trimester (intermittent preventive treatment of malaria in pregnancy [IPTp]). Because malaria parasites are becoming resistant to SP, other antimalarial drugs are being investigated for use in IPTp. A recent randomized controlled trial (a study that compares outcomes in participants assigned at random to receive different interventions) compared the efficacy and safety of IPTp with SP and with mefloquine (MQ, an antimalarial drug that, like SP, is considered safe throughout pregnancy) in pregnant women living in four countries in sub-Saharan Africa. By following the babies born to the women participating in this trial for up to 12 months, the researchers evaluate the longer term effects of IPTp with SP and MQ during pregnancy on infant health and development

Methods

Results

Conclusion