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We compared postnatal growth in the first 18-months of life between children who are HIV-exposed uninfected (CHEU) with fetal exposure to ARV drugs (prophylaxis or triple-drug therapy (ART)) and CHEU not exposed to ARVs. We also examined other independent predictors of postnatal growth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analysed data from a national prospective cohort study of 2526 CHEU enrolled at 6-weeks and followed up 3-monthly till 18-months postpartum, between October 2012 and September 2014. Infant anthropometry was measured, and weight-for-age (WAZ) and length-for-age (LAZ) Z-scores calculated. Generalized estimation equation models were used to compare Z-scores between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 2526 CHEU, 617 (24.4%) were exposed to ART since -pregnancy (pre-conception ART), 782 (31.0%) to ART commencing post-conception, 879 (34.8%) to maternal ARV prophylaxis (Azidothymidine (AZT)), and 248 (9.8%) had no ARV exposure. In unadjusted analyses, preterm birth rates were higher among CHEU with no ARV exposure than in other groups. Adjusting for infant age, the\u00a0mean WAZ profile\u00a0was lower among CHEU exposed to pre-conception ART [-0.13 (95% confidence interval \u2212\u20090.26; \u2212\u20090.01)] than the referent AZT prophylaxis group; no differences in mean WAZ profiles\u00a0were observed for the post-conception ART (\u2212\u20090.05 (\u2212\u20090.16; 0.07)), None (\u2212\u20090.05 (\u2212\u20090.26; 0.16)) and newly-infected (\u2212\u20090.18 (\u2212\u20090.48; 0.13)) groups. Mean LAZ profiles\u00a0were similar across all groups. In multivariable analyses, mean WAZ and LAZ profiles\u00a0\u00a0for the ARV exposure groups\u00a0were completely aligned. Several non-ARV factors including child, maternal, and socio-demographic factors independently predicted mean WAZ. These include child male (0.45 (0.35; 0.56)) versus female, higher maternal education grade 7\u201312 (0.28 (0.14; 0.42) and 12\u2009+\u2009(0.36 (0.06; 0.66)) versus\u2009\u2264\u2009grade7, employment (0.16 (0.04; 0.28) versus unemployment, and household food security (0.17 (0.03; 0.31). Similar predictors were observed for mean LAZ.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Findings provide evidence for initiating all pregnant women living with HIV on ART as fetal exposure had no demonstrable adverse effects on postnatal growth. Several non-HIV-related maternal, child and socio-demographic factors were independently associated with growth, highlighting the need for multi-sectoral interventions. Longer-term monitoring of CHEU children is recommended.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12879-022-07847-9","type":"journal-article","created":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T08:04:04Z","timestamp":1670313844000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Impact of antenatal antiretroviral drug exposure on the growth of children who are HIV-exposed uninfected: the national South African Prevention of Mother to Child Evaluation cohort study"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9596-1909","authenticated-orcid":false,"given":"Vundli","family":"Ramokolo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Kuhn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Lombard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ameena E.","family":"Goga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,6]]},"reference":[{"issue":"4","key":"7847_CR1","first-page":"527","volume":"64","author":"H Peters","year":"2017","unstructured":"Peters H, Francis K, Sconza R, Horn A, Peckham SC, Tookey PA, et al. 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This project was reviewed in accordance with CDC human research protection procedures and was determined to be research, but CDC investigators did not interact with participants or have access to identifiable data or specimens for research purposes. Participants provided written informed consent. Consent from a parent or legal guardian was obtained if the participant was a minor (aged\u2009<\u200918\u00a0years).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"908"}}