The impact of maternal antenatal treatment with two doses of azithromycin and monthly sulphadoxine-pyrimethamine on child weight, mid-upper arm circumference and head circumference: A randomized controlled trial

PLoS One. 2019 May 7;14(5):e0216536. doi: 10.1371/journal.pone.0216536. eCollection 2019.

Abstract

Aim: Intermittent preventive treatment in pregnancy (IPTp) with azithromycin and monthly sulfadoxine-pyrimethamine increased the mean child weight, mid-upper arm and head circumference at four weeks of age in a rural low-income setting. Now we assess for how long these gains were sustained during 0-5 years of age.

Methods: We enrolled 1320 pregnant Malawian women in a randomized trial and treated them with two doses of sulfadoxine-pyrimethamine (control) or monthly sulfadoxine-pyrimethamine as IPTp against malaria, or monthly sulfadoxine-pyrimethamine and two doses of azithromycin (AZI-SP) as IPTp against malaria and reproductive tract infections. Child weight, mid-upper arm circumference, head circumference and weight-for-height Z-score were recorded at one, six, 12, 24, 36, 48, and 60 months.

Results: Throughout follow-up, the mean child weight was approximately 100 g higher (difference in means 0.12 kg, 95% CI 0.04-0.20, P = 0.003 at one month; 0.19 kg, 95% CI 0.05-0.33, P = 0.007, at six months), mean head circumference 2 mm larger (0.3 cm, 95% CI 0.1 to 0.5, P = 0.004 at one month) and the cumulative incidence of underweight by five years of age was lower (hazard ratio 0.74, 95% CI 0.60 to 0.90, P = 0.002) in the AZI-SP group than in the control group. The 2 mm difference in the mean mid-upper arm circumference at one month (0.2 cm, 95% CI 0.0 to 0.3, P = 0.007) disappeared after three years of age. There was no difference in mean weight-for-height Z-score at any time point.

Conclusion: In Malawi, IPTp with azithromycin and monthly sulfadoxine-pyrimethamine has a modest, 3-5-year positive impact on child weight, mid-upper arm circumference and head circumference, but not on weight-for-height Z-score.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Antimalarials / administration & dosage
  • Arm / anatomy & histology*
  • Azithromycin / administration & dosage*
  • Birth Weight / drug effects*
  • Child
  • Child, Preschool
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Head / anatomy & histology*
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Malaria / epidemiology
  • Malaria / prevention & control*
  • Malawi
  • Male
  • Pregnancy
  • Pregnancy Complications, Infectious / epidemiology
  • Pregnancy Complications, Infectious / prevention & control
  • Pregnancy Complications, Parasitic / epidemiology
  • Pregnancy Complications, Parasitic / prevention & control
  • Pyrimethamine / administration & dosage*
  • Respiratory Tract Infections / epidemiology
  • Respiratory Tract Infections / prevention & control*
  • Sulfadoxine / administration & dosage*

Substances

  • Anti-Bacterial Agents
  • Antimalarials
  • Drug Combinations
  • fanasil, pyrimethamine drug combination
  • Azithromycin
  • Sulfadoxine
  • Pyrimethamine

Grants and funding

This study was funded by grants from the Academy of Finland (79787 and 207010), the Foundation for Pediatric Research in Finland and the Medical Research Fund of Tampere University Hospital (9S001). The analysis of the follow-up study was carried out by LH with funding from the Office of Health, Infectious Diseases, and Nutrition, Bureau for Global Health, United States Agency for International Development (USAID) under terms of Cooperative Agreement No. AID-OAA-A-12-00005, through the Food and Nutrition Technical Assistance III Project (FANTA), managed by FHI 360. The contents of this article are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government. Azithromycin and its placebo used in the study were provided free of charge by Pfizer Inc (New York), which had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.