Child growth and neurodevelopment after maternal antenatal antibiotic treatment

Abstract

Objective: To assess whether intermittent preventive treatment of pregnant women (IPTp) with sulfadoxine-pyrimethamine (SP) and azithromycin (AZI) in a malaria-endemic area leads to sustained gains in linear growth and development in their offspring.

Design: Follow-up study of a randomised trial.

Setting: Mangochi District in rural southern Malawi.

Participants: 1320 pregnant women and their offspring.

Interventions: IPTp monthly with SP and twice with AZI (AZI-SP group), monthly with SP but no AZI (monthly SP), or twice with SP (control). No intervention was given to children.

Main outcome measures: Cognitive performance using Raven's Coloured Progressive Matrices (CPM) at 13 years of age; mean height and height-for-age Z-score (HAZ), cumulative incidence and prevalence of stunting (HAZ <-2); weight, body mass index, mid-upper-arm circumference and head circumference.

Results: At approximately 13 years of age, the mean CPM score was 14.3 (SD 3.8, range 6-29, maximum 36), with no differences between groups. Children in the AZI-SP group were on average 0.4 cm (95% CI -0.9 to 1.7, p=0.6) taller than those in the control group. For cumulative incidence of stunting, the HR in the AZI-SP group was 0.72 (95% CI 0.61 to 0.84, p<0.001) compared with the control and 0.76 (95% CI 0.65 to 0.90, p<0.001) compared with the monthly SP groups. There was no intergroup difference in stunting prevalence or anthropometric measurements.

Conclusions: In rural Malawi, maternal intensified infection control during pregnancy reduces offspring's cumulative incidence of ever being stunted by 13 years of age. In this study, there was no evidence of a positive impact on cognitive performance.

Trial registration number: NCT00131235.

Keywords: adolescent health; child development; growth; neurology.

Figure 1

Follow-up of live-born children. Figure created by the authors. AZI-SP, intervention group with monthly SP and two doses of azithromycin; BMI, body mass index; SP, sulfadoxine-pyrimethamine.

Figure 2

Differences between means in the AZI-SP and control groups and 95% CI in height; measurement points from 1 month to approximately 13 years. Figure created by the authors. AZI-SP, intervention group with monthly sulfadoxine-pyrimethamine and two doses of azithromycin.

Figure 3

Cumulative incidence of stunting (HAZ <−2SD) and severe stunting (HAZ <−3SD) from 1 month to approximately 13 years of age by intervention group. Stunting (HAZ <−2, upper sets of lines) and severe stunting (HAZ <−3, lower sets of lines) are shown. Figure created by the authors. AZI-SP, intervention group with monthly SP and two doses of azithromycin; HAZ, height-for-age Z-score; SP, sulfadoxine-pyrimethamine.