BACKGROUND: Pooled analyses summarising long-term growth outcomes in children who are HIV-exposed uninfected (HEU) compared with children who are HIV-unexposed (HU) are lacking. We aimed to summarise the existing literature on growth outcomes. METHODS: We did a systematic review and meta-analysis of published literature on 60-month growth outcomes (length-for-age Z score [LAZ], weight-for-age Z score [WAZ], weight-for-length Z score [WLZ], head circumference-for-age Z score [HCAZ], stunting [LAZ<
-2], wasting [WLZ<
-2], underweight [WAZ<
-2], and microcephaly [HCAZ<
-2]) in children who were HEU compared with children who were HU. Medline, EMBASE, Cochrane Library, WHO Global Index Medicus and Web of Science were searched from Jan 1, 1989 to Dec 31, 2022. Randomised controlled trials and cohort studies comparing growth in children who were HEU versus children who were HU were included. Study-specific estimates were pooled by use of random-effects and fixed-effect meta-analysis. Results were stratified by age (birth
0-5 months
6-11 months
12-17 months
18-23 months
and 24-60 months) and antiretroviral therapy (ART) period (pre-ART [before 2003]
ART [2003 onwards]). This study is registered with PROSPERO, CRD42018091762. FINDINGS: 28 studies were included
25 (90%) were done in Africa and 23 (82%) in the ART period, reporting growth outcomes on 11 794 children who were HEU and 23 826 children who were HU from 15 countries. Across all ages in the pre-ART and ART periods, children who were HEU had significantly lower LAZ compared with children who were HU. In the ART period, children who were HEU were more likely to be stunted at all ages except for 0-5 months. Pre-ART, significantly lower WAZ was found in children who were HEU from 6-11 months to 18-23 months, and at all ages during the ART period. Children who were HEU had significantly higher odds of underweight at birth than children who were HU
this difference persisted to age 2 years. Pre-ART and ART HCAZ were significantly lower for children who were HEU at all ages, except for 24-60 months, even though heterogeneity was high. No differences in WLZ were found between groups. Differences between children who were HEU and children who were HU tended to be more pronounced during the ART period compared with the pre-ART period, particularly at younger ages. INTERPRETATION: Children who are HEU have more growth faltering than children who are HU, which is present at birth and persists over the first 24 months. These growth disparities remain evident during the ART period. Interventions to promote healthy growth probably need to start antenatally. FUNDING: None.