Lower birth weight-for-age and length-for-age z-scores in infants with in-utero HIV and ART exposure: a prospective study in Cape Town, South Africa

Nyemba, Dorothy; Kalk, Emma; Madlala, Hlengiwe P.; Malaba, Thokozile R; Slogrove, Amy L.; Davies, Mary‐Ann; Boulle, Andrew; Myer, Landon; Powis, Kathleen M.

doi:10.1186/s12884-021-03836-z

Cited by 19 publications

(20 citation statements)

References 21 publications

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“…4 A). Our finding of lower WAZ at birth among HEU infants is consistent with several other studies conducted in African populations [ 27 , 30 , 58 – 60 ]. When our HEU infants were grouped by breastfeeding status, the breastfeeding HEU infants had significantly higher WAZ at 6 weeks postpartum compared to non-breastfeeding HEU infants (Fig.…”

Section: Discussionsupporting

confidence: 93%

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Dynamics of the infant gut microbiota in the first 18 months of life: the impact of maternal HIV infection and breastfeeding

et al. 2022

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Background Access to antiretroviral therapy (ART) during pregnancy and breastfeeding for mothers with HIV has resulted in fewer children acquiring HIV peri- and postnatally, resulting in an increase in the number of children who are exposed to the virus but are not infected (HEU). HEU infants have an increased likelihood of childhood infections and adverse growth outcomes, as well as increased mortality compared to their HIV-unexposed (HUU) peers. We explored potential differences in the gut microbiota in a cohort of 272 Nigerian infants born to HIV-positive and negative mothers in this study during the first 18 months of life. Results The taxonomic composition of the maternal vaginal and gut microbiota showed no significant differences based on HIV status, and the composition of the infant gut microbiota at birth was similar between HUU and HEU. Longitudinal taxonomic composition of the infant gut microbiota and weight-for-age z-scores (WAZ) differed depending on access to breast milk. HEU infants displayed overall lower WAZ than HUU infants at all time points. We observed a significantly lower relative abundance of Bifidobacterium in HEU infants at 6 months postpartum. Breast milk composition also differed by time point and HIV infection status. The antiretroviral therapy drugs, lamivudine and nevirapine, as well as kynurenine, were significantly more abundant in the breast milk of mothers with HIV. Levels of tiglyl carnitine (C5) were significantly lower in the breast milk of mothers without HIV. ART drugs in the breast milk of mothers with HIV were associated with a lower relative abundance of Bifidobacterium longum. Conclusions Maternal HIV infection was associated with adverse growth outcomes of HEU infants in this study, and these differences persist from birth through at least 18 months, which is a critical window for the development of the immune and central nervous systems. We observed that the relative abundance of Bifidobacterium spp. was significantly lower in the gut microbiota of all HEU infants over the first 6 months postpartum, even if HEU infants were receiving breast milk. Breastfeeding was of benefit in our HEU infant cohort in the first weeks postpartum; however, ART drug metabolites in breast milk were associated with a lower abundance of Bifidobacterium.

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Section: Discussionsupporting

confidence: 93%

“…Previous studies have shown that HEU infants have lower WAZ compared to HUU infants [ 27 – 30 ]. Our results are also consistent with those findings (Fig.…”

Section: Resultsmentioning

confidence: 99%

Dynamics of the infant gut microbiota in the first 18 months of life: the impact of maternal HIV infection and breastfeeding

et al. 2022

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“…Thus, residual confounding cannot be excluded. For example, we could not assess the effect of maternal viral loads and CD4 cell counts due to limited reporting and lack of adjustment for these confounders in most of the studies include d. 17,21,[30][31][32]34,37,43,44,[46][47][48][49][50][51][52][53][54] Still, for some of the outcomes studied, such as PTB, the risk was significantly elevated in the majority of the studies with narrow CIs. Third, some of the measured outcomes, such as preeclampsia, 17,21,31,33,36,37,39 were reported by only a few studies (seven).…”

Section: Discussionmentioning

confidence: 99%

Perinatal outcomes in women living with HIV‐1 and receiving antiretroviral therapy—a systematic review and meta‐analysis

Shinar

Agrawal

Ryu

et al. 2021

Acta Obstet Gynecol Scand

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Introduction Antiretroviral therapy‐naïve pregnant women living with HIV are at an increased risk for adverse pregnancy outcomes. It remains controversial whether this risk persists with antiretroviral therapy. We conducted a systematic review and meta‐analysis to evaluate whether pregnant women living with HIV and receiving antiretroviral therapy antenatally, are at an increased risk of adverse outcomes compared with HIV‐negative controls. Material and methods We searched MEDLINE, Embase, International Pharmaceutical Abstracts, EBM Reviews, PubMed (non‐MEDLINE records), EBSCO CINAHL Complete, Clarivate Web of Science, African Index Medicus, LILACS and Google Scholar for all observational studies comparing pregnant women living with HIV on antiretroviral therapy with HIV‐negative controls from 1 January 1994 to 10 August 2021 with no language or geographic restrictions. Perinatal outcomes included preterm birth (PTB), low birthweight, small‐for‐gestational age and preeclampsia. Using a random‐effects model we pooled raw data to generate odds ratio (OR) with 95% confidence intervals (CI) for each outcome. Sub‐analyses for high and low resource countries and time of antiretroviral therapy initiation were performed. This systematic review and meta‐analysis is registered with PROSPERO, number CRD42020182722. Results Of the 7900 citations identified, 27 were eligible for analysis (12 636 pregnant women living with HIV on antiretroviral therapy and 7 812 115 HIV‐negative controls). ORs (95% CI) of PTB (1.88 [1.63–2.17]), small‐for‐gestational age (1.60 [1.18–2.17]) and low birthweight (2.15 [1.58–2.92]) were significantly higher in pregnant women living with HIV than in HIV‐negative women, while the risk of preeclampsia (0.86 [0.57–1.30]) was comparable. The risk of PTB and low birthweight was higher in both high resource and low resource countries, while the risk of small‐for‐gestational age was higher only in the former. Preconceptional antiretroviral therapy was associated with a higher risk of PTB compared with antenatal initiation. Conclusions Pregnant women living with HIV on antiretroviral therapy have an increased risk of PTB, low birthweight and small‐for‐gestational age in high resource countries, as well as PTB and low birthweight in low income countries compared with HIV‐negative controls.

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“…All covariates in univariable analyses with a p -value of 0.10 were included in multivariable analyses. Additionally, an a priori decision was made to include maternal age in the multivariable model, regardless of univariable p-value [ 3 , 32 , 33 ]. Infant feeding practice was defined as exclusive breastfeeding, formula feeding, or mixed feeding based on maternal report.…”

Section: Methodsmentioning

confidence: 99%

Growth patterns of infants with in- utero HIV and ARV exposure in Cape Town, South Africa and Lusaka, Zambia

et al. 2022

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Background Infants born HIV-exposed yet remain uninfected (HEU) are at increased risk of poorer growth and health compared to infants born HIV-unexposed (HU). Whether maternal antiretroviral treatment (ART) in pregnancy ameliorates this risk of poorer growth is not well understood. Furthermore, whether risks are similar across high burden HIV settings has not been extensively explored. Methods We harmonized data from two prospective observational studies conducted in Cape Town, South Africa, and Lusaka, Zambia, to compare weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) Z-scores between infants who were HEU and HU, converting infant anthropometric measures using World Health Organisation Growth Standards adjusted for age and sex. Linear mixed effects models were fit to identify risk factors for differences in anthropometrics at 6–10 weeks and 6 months by infant HIV exposures status and by timing of exposure to maternal ART, either from conception or later in gestation. Results Overall 773 mother-infant pairs were included across two countries: women living with HIV (WLHIV), 51% (n = 395) with 65% on ART at conception and 35% initiating treatment in pregnancy. In linear mixed effects models, WAZ and WLZ at 6–10 weeks were lower among infants who were HEU vs HU [β = − 0.29 (95% CI: − 0.46, − 0.12) and [β = − 0.42 (95% CI: − 0.68, − 0.16)] respectively after adjusting for maternal characteristics and infant feeding with a random intercept for country. At 6 months, LAZ was lower [β = − 0.28 CI: − 0.50, − 0.06)] among infants who were HEU, adjusting for the same variables, with no differences in WAZ and WLZ. Within cohort evaluations identified different results with higher LAZ among infants who were HEU from Zambia at 6–10 weeks, [β = + 0.34 CI: + 0.01, + 0.68)] and lower LAZ among infants who were HEU from South Africa [β = − 0.30 CI: − 0.59, − 0.01)] at 6 months, without other anthropometric differences at either site. Conclusion Infant growth trajectories differed by country, highlighting the importance of studying contextual influences on outcomes of infants who were HEU.

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Lower birth weight-for-age and length-for-age z-scores in infants with in-utero HIV and ART exposure: a prospective study in Cape Town, South Africa

Cited by 19 publications

References 21 publications

Dynamics of the infant gut microbiota in the first 18 months of life: the impact of maternal HIV infection and breastfeeding

Dynamics of the infant gut microbiota in the first 18 months of life: the impact of maternal HIV infection and breastfeeding

Perinatal outcomes in women living with HIV‐1 and receiving antiretroviral therapy—a systematic review and meta‐analysis

Growth patterns of infants with in- utero HIV and ARV exposure in Cape Town, South Africa and Lusaka, Zambia

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