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

PLoS Med. 2016 Feb 23;13(2):e1001964. doi: 10.1371/journal.pmed.1001964. eCollection 2016 Feb.

Abstract

Background: Little 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 findings: In 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%).

Conclusions: No 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 registration: ClinicalTrials.gov NCT00811421.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Africa, Southern / epidemiology
  • Antimalarials / therapeutic use
  • Child
  • Child Development / drug effects*
  • Drug Combinations
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Malaria / prevention & control*
  • Maternal Exposure / adverse effects*
  • Mefloquine / adverse effects*
  • Mefloquine / therapeutic use
  • Morbidity / trends
  • Pregnancy
  • Pregnancy Complications, Parasitic / prevention & control*
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Pyrimethamine / therapeutic use*
  • Sulfadoxine / therapeutic use*
  • Survival Rate / trends
  • Treatment Outcome

Substances

  • Antimalarials
  • Drug Combinations
  • fanasil, pyrimethamine drug combination
  • Sulfadoxine
  • Mefloquine
  • Pyrimethamine

Associated data

  • ClinicalTrials.gov/NCT00811421

Grant support

This study was funded by the European Developing Countries Clinical Trials Partnership (EDCTP; IP.2007.31080.002), the Malaria in Pregnancy Consortium and the following national agencies: Instituto de Salud Carlos III (PI08/0564), Spain; Federal Ministry of Education and Research (BMBF FKZ: da01KA0803), Germany; Institut de Recherche pour le Développement (IRD), France. CANTAM provided infrastructure help in the study. RG and MRu were partially supported by grants from the Spanish Ministry of Health (ref. CM07/0015 and CM11/00278, respectively). The CISM receives core funding from the Spanish Agency for International Cooperation (AECI). LLITNs (Permanet) were donated by Vestergaard Fransen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.