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.

Lotta Hallamaa,Charles Mangani,Per Ashorn,Ulla Ashorn,Yin Bun Cheung,Mari Luntamo,Teija Kulmala,Julie Gutman

doi:10.1371/journal.pone.0216536

Abstract

AimIntermittent 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.MethodsWe 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.ResultsThroughout 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.ConclusionIn 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.

Highlights

Childhood growth failure is common, especially in sub-Saharan Africa and in southern Asia
Throughout follow-up, the mean child weight was approximately 100 g higher, 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 in the AZI-SP group than in the control group
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

Summary

Introduction

Childhood growth failure is common, especially in sub-Saharan Africa and in southern Asia. We have previously reported results from the “Lungwena Antenatal Intervention Study” (LAIS), that suggest that birth and neonatal size can be increased with intensive maternal infection control during pregnancy[1,2]. We have shown that the length gain attained during fetal period is sustained during the first five years of life[3]. Results of the follow-up study suggested that increased length in bone is not lost during childhood. The situation might be different with child weight, mid-upper arm circumference (MUAC) and head circumference (HC). This is suggested by results from studies using maternal dietary supplementation with energy and/or nutrients, where fetal-period gains have largely been lost within a year or two after birth[4,5]

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