Early child development in children who are HIV-exposed uninfected compared to children who are HIV-unexposed: observational sub-study of a cluster-randomized trial in rural Zimbabwe

Abstract

Introduction: Exposure to maternal HIV may affect early child development (ECD), although previous studies have reported heterogeneous findings. We evaluated ECD among children who were HIV-exposed uninfected (CHEU) and children who were HIV-unexposed (CHU) recruited to the SHINE trial in rural Zimbabwe.

Methods: SHINE was a community-based cluster-randomized trial of improved infant feeding and/or improved water, sanitation and hygiene. Pregnant women were enrolled between 2012 and 2015. We assessed ECD in a sub-study at 24 months of age, between 2016 and 2017, using the Malawi Developmental Assessment Tool (MDAT; assessing motor, cognitive, language and social development); MacArthur-Bates Communicative Development Inventory (CDI) (assessing vocabulary and grammar); A-not-B test (assessing object permanence); and a self-control task. Mothers and infants were tested longitudinally for HIV. We used generalized estimating equations to compare ECD scores between CHEU and CHU, accounting for the cluster-randomized design. Primary results were adjusted for trial-related factors that could affect measurement reliability of ECD: study nurse, age of child, calendar month of birth, sex and randomized arm.

Results: A total of 205 CHEU and 1175 CHU were evaluated. Mean total MDAT score was 90.6 (SD 8.7) in CHEU compared to 92.4 (9.1) in CHU (adjusted mean difference -1.3, 95% CI: -2.3, -0.3), driven mostly by differences in gross motor (-0.5, 95% CI: -0.9, -0.2) and language scores (-0.6, 95% CI: -1.1, -0.1). There was evidence that fine motor scores were lower in CHEU (adjusted mean difference -0.4, 95% CI: -0.8, 0.0) but no evidence of a difference in social scores (0.1, 95% CI: -0.2, 0.4). Mean MacArthur-Bates CDI vocabulary score was 57.9 (SD 19.2) in CHEU compared to 61.3 (18.8) in CHU (adjusted mean difference -2.9 words, 95% CI: -5.7, -0.1). Object permanence and self-control scores were similar between groups.

Conclusions: CHEU in rural Zimbabwe had total child development and vocabulary scores that were approximately 0.15 standard deviations lower than CHU at two years of age. More detailed and specific studies are now needed to unravel the reasons for developmental delay in CHEU and the likelihood that these delays persist in the longer term.

Trial registration: ClinicalTrials.gov NCT01824940.

Keywords: HIV-exposed uninfected; Zimbabwe; child development; language; motor; self-control.

Figure 1

Flow of participants through the SHINE early child development (ECD) sub‐study. ¹In all, 212 clusters were randomized, 53 in each of the four trial arms. After randomization, 1 cluster was excluded as it was determined to be in an urban area, 1 cluster was excluded as the village health worker covering it mainly had clients outside the study area, and 1 more was merged into a neighbouring cluster based on subsequent data on village health worker coverage. Three new cluster designations were created due to anomalies in the original mapping: for 2 of these, the trial arm was clear; the third contained areas that were in 2 trial arms, and was assigned to the underrepresented arm, resulting in 53 clusters in each arm. All of this occurred before enrolment began. When enrolment was completed, however, there was 1 standard‐of‐care cluster in which no women were enrolled, leaving a total of 211 clusters available for analysis. ²Children were not eligible for the ECD sub‐study if they turned two years of age (allowable range 102 to 112 weeks) before 1 March 2016. ³Children were eligible for the ECD sub‐study if they turned two years of age (allowable range 102 to 112 weeks) between 1 March 2016, and April 30, 2017. ⁴Children were eligible for the ECD sub‐study because they turned two years of age (allowable range 102 to 112 weeks) between 1 March 2016, and 30 April 2017, but they were not contactable or were not approached for consent because the number of children becoming 102 to 112 weeks of age between 1 March 2016, and 30 April 2017, exceeded the capacity of the 11 ECD‐trained nurses. ⁵Children in the WASH plus IYCF combined arm were excluded from this analysis because of an interaction between HIV exposure and IYCF plus WASH for the total MDAT score (p = 0.008, Wald test). IYCF: infant and young child feeding; SOC: standard of care; WASH: water, sanitation and hygiene.