Objective
HIV‐exposed but HIV‐uninfected (HEU) children are widely considered at increased risk of mortality and morbidity. Recent advances in prevention of mother‐to‐child HIV transmission (PMTCT) ...strategies, incorporating life‐long universal maternal antiretroviral therapy (ART, “Option B+”) with extended breastfeeding, may improve HEU child health substantially. We critically reviewed reports of mortality/morbidity among HEU and HIV‐unexposed (HU) children in sub‐Saharan Africa.
Methods
We searched Medline, EMBASE, CINAHL, PsycINFO, Academic Search Premier, Global Health & Psychosocial Instruments databases, conference s, and reference lists for longitudinal studies from sub‐Saharan Africa reporting mortality and clinical morbidity among HIV‐uninfected children aged ≤10 years, by maternal HIV status. Studies were appraised by Newcastle‐Ottawa Scale and ACROBAT‐NRSI. Due to substantial heterogeneity of study designs, populations and results (I2 = 75%), data were not synthesised.
Results
We included 37 reports (28 studies, 11 164 HEU children); methodological and reporting quality were variable. Most reports came from settings without universal access to maternal ART (n = 35). Results were conflicting, with some studies indicating increased risk of mortality, hospitalisation and/or under‐nutrition among HEU children, while others found no evidence of increased risk. In subanalyses, improved maternal health, ART use and breastfeeding were strongly protective for all outcomes. Only 39% (11/28) of studies adjusted for major confounders. Reports from settings using universal maternal ART with breastfeeding (n = 2) found no differences in growth or development but did not report mortality or infectious morbidity.
Conclusions
The existing literature provides little insight into HEU child health under recently adopted PMTCT strategies. There is a need for robust comparative data on HEU and HIV‐unexposed child health outcomes under Option B+; optimising breastfeeding practices and increasing maternal use of ART should be urgent public health priorities.
Objectif
Les enfants exposés au VIH mais non infectés (ENI) sont largement considérés comme à risque accru de mortalité et de morbidité. Nous avons examiné les rapports de mortalité/morbidité chez les enfants ENI et ceux non exposées au VIH en Afrique subsaharienne.
Méthodes
Nous avons effectué des recherches dans les bases de données Medline, EMBASE, CINAHL, PsycINFO, Academic Search Premier, Global Health & Psychosocial Instruments, les résumés de conférences, les listes de références pour les études longitudinales en Afrique subsaharienne rapportant sur la mortalité et la morbidité clinique chez les enfants non infectés âgés ≤ 10 ans, selon le statut VIH de la mère. Les études ont été évaluées par l’échelle de Newcastle‐Ottawa et ACROBAT‐NSRI. En raison de l'hétérogénéité importante entre les conceptions des études, les populations et les résultats (I2 = 75%), les données n'ont pas été synthétisées.
Résultats
Nous avons inclus 37 rapports (28 études, 11.164 enfants ENI); la qualité méthodologique et des rapports était variable. La plupart des rapports provenaient de régions sans accès universel à l’ART maternelle (n = 35). Les résultats étaient contradictoires, certaines études indiquant un risque accru de mortalité, d'hospitalisation et/ou de sous‐alimentation chez les enfants ENI tandis que d'autres n'ont trouvé aucune preuve d'un risque accru. Dans les sous‐analyses, l'amélioration de la santé maternelle, l'utilisation de l’ART et l'allaitement étaient fortement protecteurs pour tous les résultats. Seules 39% (11/28) des études ont corrigé pour les facteurs confusionnels majeurs. Les rapports provenant de régions avec accès à l’ART maternelle universelle avec l'allaitement maternel (n = 2) n'ont trouvé aucune différence dans la croissance ou le développement, mais n'ont pas rapporté sur la mortalité ou la morbidité infectieuse.
Conclusions
La littérature existante fournit peu d'informations sur la santé des enfants ENI dans les stratégies PTME récemment adoptées. Des données comparatives fiables sur les résultats de santé des enfants ENI et ceux non exposés aux VIH sous Option B+ sont nécessaires. L'optimisation des pratiques d'allaitement et l'augmentation de l'utilisation de l’ART maternelle devraient être des priorités urgentes de santé publique.
Objetivo
Los niños expuestos al VIH pero sin infectar (ESI) se consideran hoy en día en mayor riesgo de mortalidad y morbilidad. Hemos revisado de forma crítica los informes sobre mortalidad/morbilidad de niños ESI y niños sin exposición al VIH en África subsahariana.
Métodos
Hemos buscado en las bases de datos de Medline, EMBASE, CINAHL, PsycINFO, Academic Search Premier, Global Health & Psychosocial Instruments, resúmenes de conferencias; listas de referencia para estudios longitudinales en África subsahariana que reportaban mortalidad y morbilidad clínica en niños sin infección por VIH con edades ≤ 10 años, según estatus materno de VIH. Los estudios fueron valorados con las escalas de Newcastle‐Ottawa y ACROBAT‐NSRI. Debido a una heterogeneidad sustancial en el diseño de los estudios, las poblaciones y los resultados (I2=75%), no se incluyeron los datos.
Resultados
Incluimos 37 informes (28 estudios, 11 164 niños ESI); las calidades metodológicas y de los informes eran variables. La mayoría de los informes eran de lugares sin acceso universal al TAR materno (n=35). Los resultados eran conflictivos, con algunos estudios indicando un riesgo aumentado de mortalidad, hospitalización y/o desnutrición entre los niños ESI, mientras que otros no encontraban evidencia alguna sobre un riesgo aumentado. En sub‐análisis, una mejor salud materna, el uso de TAR y la lactancia eran resultados protectores para todos los resultados. Solo un 39% (11/28) de los estudios hacia ajustes para los principales factores de confusión. Los informes de lugares con un programa universal de TAR y lactancia (n=2) no encontraron diferencias en el crecimiento o desarrollo, pero no reportaba ni mortalidad ni morbilidad por infecciones.
Conclusiones
La literatura existente aporta poca visión sobre la salud de niños ESI bajo la reciente adopción de estrategias de prevención de la transmisión madre‐hijo. Existe una necesidad de datos comparativos robustos sobre los resultados de la salud de niños ESI y niños sin exponer al VIH bajo la Opción B+. Unas prácticas de lactancia mejoradas y un aumento en el uso materno del TAR deberían ser prioridades urgentes de salud pública.
Introduction
Several HIV‐related syndemics have been described among adults. We investigated syndemic vulnerability to hazardous drinking (HD), intimate partner violence (IPV) and household food ...insecurity (HFIS) in breastfed children born without HIV in urban South Africa. We compared those who were perinatally HIV exposed (CHEU) to those who were not (CHU), under conditions of universal maternal antiretroviral therapy (ART) and breastfeeding.
Methods
A prospective cohort of pregnant women living with HIV (WLHIV), and without HIV, were enrolled and followed with their infants for 12 months postpartum (2013–2017). All WLHIV initiated antenatal efavirenz‐based ART. Measurements of growth (∼3 monthly), infectious cause hospitalisation, ambulatory childhood illness (2‐week recall) and neurodevelopment (BSID‐III, measured at ∼12 months’ age) were compared across bio‐social strata using generalised linear regression models, with interaction terms; maternal data included interview‐based measures for HD (AUDIT‐C), IPV (WHO VAW) and HFIS.
Results
Among 872 breastfeeding mother‐infant pairs (n = 461 CHEU, n = 411 CHU), WLHIV (vs. HIV negative) reported more unemployment (279/461, 60% vs. 217/411, 53%; p = 0.02), incomplete secondary education (347/461, 75% vs. 227/411, 55%; p < 0.0001), HD (25%, 117/459 vs. 7%, 30/411; p < 0.0001) and IPV (22%, 101/457 vs. 8%, 32/411; p < 0.0001) at enrolment; and HFIS at 12 months (45%, 172/386 vs. 30%, 105/352; p > 0.0001). There were positive interactions between maternal HIV and other characteristics. Compared to food secure CHU, the mean difference (95% CI) in weight‐for‐age Z‐score (WAZ) was 0.06 (−0.14; 0.25) for food insecure CHU; −0.26 (−0.42; −0.10) for food secure CHEU; and −0.43 (−0.61; −0.25), for food insecure CHEU. Results were similar for underweight (WAZ < −2), infectious‐cause hospitalisation, cognitive and motor delay. HIV‐IPV interactions were evident for ambulatory diarrhoea and motor delay. There were HIV‐HD interactions for odds of underweight, stunting, cognitive and motor delay. Compared to HD‐unexposed CHU, the odds ratios (95% CI) of underweight were 2.31 (1.11; 4.82) for HD‐exposed CHU; 3.57 (0.84; 15.13) for HD‐unexposed CHEU and 6.01 (2.22; 16.22) for HD‐exposed CHEU.
Conclusions
These data suggest that maternal HIV‐related syndemics may partly drive excess CHEU health risks, highlighting an urgent need for holistic maternal and family care and support alongside ART to optimise the health of CHEU.
OBJECTIVES:To assess neurodevelopment of breastfed HIV-exposed uninfected (HEU) and breastfed HIV-unexposed children in the context of universal maternal antiretroviral therapy (ART).
...DESIGN:Prospective study with antenatal enrolment and follow-up of breastfeeding HEU and HIV-unexposed mother–infant pairs through 12–18 months postpartum.
SETTING:Peri-urban community, Cape Town, South Africa.
PARTICIPANTS:HEU (n = 215) and HIV-unexposed (n = 306) children.
MAIN OUTCOME MEASURES:Cognitive, motor and language development at median 13 (interquartile range 12–14) months of agecontinuous and dichotomous Bayley Scales of Infant and Toddler Development Third Edition (delay defined as composite score <85).
RESULTS:Incidence of preterm delivery (<37 weeks) was similar among HEU and HIV-unexposed children (11 vs. 9%, P = 0.31; median gestation 39 weeks); 48% were boys. Median breastfeeding duration was shorter among HEU vs. HIV-unexposed children (6 vs. 10 months). All HIV-infected mothers initiated lifelong ART (tenofovir–emtricitabine–efavirenz) antenatally. HEU (vs. HIV-unexposed) children had higher odds of cognitive delay odds ratio (OR) 2.28 (95% confidence interval (CI) 1.13–4.60) and motor delay OR 2.10 (95% CI 1.03–4.28), but not language delay, in crude and adjusted analysis. Preterm delivery modified this relationship for motor developmentcompared with term HIV-unexposed children, term HEU children had similar odds of delay, preterm HIV-unexposed children had five-fold increased odds of delay (adjusted OR 4.73, 95% CI 1.32; 16.91) and preterm HEU children, 16-fold increased odds of delay (adjusted OR 16.35, 95% CI 5.19; 51.54).
CONCLUSION:Young HEU children may be at increased risk for cognitive and motor delay despite universal maternal ART and breastfeeding; those born preterm may be particularly vulnerable.
BACKGROUND:Prevention of mother-to-child transmission of HIV implementation faces significant challenges globally, particularly in the context of universal lifelong antiretroviral therapy (ART) for ...all HIV-infected pregnant women.
METHODS:We describe the rationale and methods of the Maternal and Child Health-Antiretroviral Therapy (MCH-ART) study, an implementation science project examining strategies for providing HIV care and treatment to HIV-infected women who initiate ART during pregnancy and their HIV-exposed infants.
RESULTS:MCH-ART is composed of 3 interrelated study designs across the antenatal and postnatal periods. Phase 1 is a cross-sectional evaluation of consecutive HIV-infected pregnant women seeking antenatal care; phase 2 is an observational cohort of all women from phase 1 who are eligible for initiation of ART following local guidelines; and phase 3 is a randomized trial of strategies for delivering ART to breastfeeding women from phase 2 during the postpartum period. During each phase, a set of study measurement visits is carried out separately from antenatal care and ART services; a maximum of 9 visits takes place from the beginning of antenatal care through 12 months postpartum. In parallel, in-depth interviews are used to examine issues of ART adherence and retention qualitatively, and costs and cost-effectiveness of models of care are examined. Separate substudies examine health outcomes in HIV-uninfected women and their HIV-unexposed infants, and the role of the adherence club model for long-term adherence and retention.
DISCUSSION:Combining observational and experimental components, the MCH-ART study presents a novel approach to understand and optimize ART delivery for MCH.
To compare short-term outcomes of very low birthweight (VBLW, <1500 g) neonates by maternal HIV status.
Retrospective hospital-based cohort in Cape Town, South Africa.
Of 1579 mothers, 316 (20%) were ...HIV-positive; 183/316 (58%) received ≥8 weeks of antenatal antiretrovirals. HIV-exposed neonates (HIVE, vs HIV-unexposed, HIVU) had increased risk of necrotising enterocolitis (NEC; OR 1.93, 95% CI 1.27-2.92) and invasive ventilation (OR 1.35, 95% CI 1.01-1.79). Extremely low birthweight (ELBW, <1000 g) modified the HIV-exposure-mortality relationship: among ELBW neonates, HIVE vs HIVU mortality OR 1.75 (95% CI 1.13-2.69); among non-ELBW, OR 0.89 (95% CI 0.54-1.49). Antiretrovirals (≥8 vs <8 weeks/none) reduced NEC (OR 0.46, 95% CI 0.22-0.97) and invasive ventilation risks (OR 0.57, 95% CI 0.32-0.99). HIV-PCR results were available for 228/316 (72%) HIVE neonates; 11/228 (5%) tested positive.
Among VLBW neonates, HIV-exposure was associated with increased risk of adverse short-term outcomes; antenatal antiretrovirals were protective.
Despite widespread concerns about HIV incidence in pregnant and postpartum women, there are few data from Africa on HIV acquisition in breastfeeding and subsequent mother-to-child transmission. We ...measured HIV incidence in a prospective cohort of 413 peripartum and breastfeeding women who tested HIV-negative during pregnancy. In 377 woman-years accrued postpartum (median duration of follow-up, 1 year), there were seven women infected after delivery (postpartum incidence, 1.86/100 person-years; 95% confidence interval 0.88–3.89) with transmission to 2/7 (28%) infants.
Background
South Africa faces dual epidemics of HIV and obesity; however, little research has explored whether HIV status influences associations between pre‐pregnancy body mass index (BMI) and ...adverse birth outcomes.
Objectives
To examine associations between pre‐pregnancy body mass index (BMI) and adverse birth outcomes, and if they differ by HIV status.
Methods
We followed HIV‐uninfected and ‐infected pregnant women initiating antiretroviral therapy (ART) from first antenatal visit through delivery. HIV‐infected women initiated ART (tenofovir‐emtricitabine/lamivudine‐efavirenz) in pregnancy. Estimated pre‐pregnancy BMI (kg/m2) was categorised as underweight (<18.5), normal (18.5‐24.9), overweight (25.0‐29.9), and obese (≥30.0). We used modified Poisson regression to estimate risk ratios (RR) for associations between pre‐pregnancy BMI and adverse birth outcomes and explored modification by HIV status.
Results
Among 1116 women (53% HIV‐infected), 44% of HIV‐uninfected women and 36% of HIV‐infected women were classified as obese; 4% of women were underweight. Overall, 12% of infants were delivered preterm (<37 weeks), 10% small for gestational age (SGA, <10th percentile), and 9% large for gestational age (LGA, >90th percentile). Compared to HIV‐uninfected women, HIV‐infected women on ART had less LGA (5% vs 13%) but more SGA (12% vs 8%), and a similar proportion of preterm (13% vs 11%) infants. Pre‐pregnancy BMI was not associated with preterm birth. Among HIV‐uninfected women, obesity modestly increased the risk of LGA (RR 1.34, 95% confidence interval CI 0.82, 2.19), and underweight modestly elevated the risk of SGA (RR 1.66, 95% CI 0.79, 3.46). These associations were attenuated among HIV‐infected women (RR 1.07, 95% CI 0.44, 2.64 for LGA, and RR 1.34, 95% CI 0.49, 3.64 for SGA).
Conclusions
In this urban African setting of high HIV prevalence, pre‐pregnancy obesity was common and did not vary by HIV status. In HIV‐uninfected women, obesity increased the risk of LGA and being underweight the risk of SGA, compared with among HIV‐uninfected women.
Background
Maternal HIV and antiretroviral therapy (ART) exposure in utero may influence infant weight, but the contribution of maternal y body mass index (BMI) to early life overweight and obesity ...is not clear.
Objective
To estimate associations between maternal BMI at entry to antenatal care (ANC) and infant weight through approximately 1 year of age and to evaluate whether associations were modified by maternal HIV status, maternal HIV and viral load, breastfeeding intensity through 6 months or timing of entry into ANC.
Methods
We followed HIV‐uninfected and ‐infected pregnant women initiating efavirenz‐based ART from first antenatal visit through 12 months postpartum. Infant weight was assessed via World Health Organization BMI and weight‐for‐length z‐scores (WLZ) at 6 weeks, 3, 6, 9 and 12 months. We used multivariable linear mixed‐effects models to estimate associations between maternal BMI and infant z‐scores over time.
Results
In 861 HIV‐uninfected infants (454 HIV‐exposed; 407 HIV‐unexposed), nearly 20% of infants were overweight or obese by 12 months of age, regardless of HIV exposure status. In multivariable analyses, increasing maternal BMI category was positively associated with higher infant BMIZ and WLZ scores between 6 weeks and 12 months of age and did not differ by HIV exposure status. However, HIV‐exposed infants had slightly lower BMIZ and WLZ trajectories through 12 months of age, compared with HIV‐unexposed infants across all maternal BMI categories. Differences in BMIZ and WLZ scores by HIV exposure were not explained by timing of entry into ANC or maternal viral load pre‐ART initiation, but z‐scores were slightly higher for HIV‐exposed infants who were predominantly or exclusively versus partially breastfed.
Conclusions
These findings suggest maternal BMI influences early infant weight gain, regardless of infant HIV exposure status. Intervention to reduce maternal BMI may help to address growing concerns about obesity among HIV‐uninfected children.
OBJECTIVE:Tenofovir (TDF) affects bone health and is widely used in pregnancy but data are limited on the effects of TDF exposure in utero. We examined the association between duration of in-utero ...TDF exposure and linear growth in HIV-exposed, uninfected (HEU) infants.
DESIGN:A prospective cohort of pregnant women initiating TDF-containing regimens at primary care services in Cape Town, South Africa, were enrolled and followed with their breastfeeding infants through 12 months postpartum.
METHODS:Length-for-age z scores (LAZ) were calculated from infant lengths reported at birth and measured at 6, 12, 24, 36 and 48 weeks, using Fenton and WHO standards. Linear mixed-effects models were used to examine the association between duration of TDF exposure and LAZ over time.
RESULTS:In 464 singleton mother–infant pairs (median CD4 at ART initiation, 346 cells/μl; viral load (VL), 4.0 log10 copies/ml), the median duration of in-utero TDF exposure was 16.7 weeks (interquartile range, IQR 11.0–22.0) with 31, 44 and 25% of infants exposed to less than 12, 12–22 and more than 22 weeks of TDF, respectively. Overall, 12% of children were stunted (LAZ < −2) at 48 weeks. Duration of exposure was not associated with LAZadjusted mean difference for more than 22 vs less than 12 weeks, −0.12 (95% CI −0.47 to 0.23); 12–22 vs less than 12 weeks, −0.06 (95% CI −0.35 to 0.24). Mean LAZ was 0.15 lower per log increase in maternal VL at ART initiation (95% CI −0.29 to −0.0001).
CONCLUSION:These data suggest no association between duration of TDF exposure in utero and early linear growth.
BACKGROUND:Elevated HIV viral load (VL) in pregnancy has been linked to increased risk of mortality, immunologic abnormalities, infectious morbidity and restricted growth among HIV-exposed uninfected ...(HEU) children, but little is known about effects on child development.
METHODS:HIV-infected women initiating lifelong antiretroviral therapy (ART; tenofovir + emtricitabine + efavirenz) antenatally were followed from first antenatal visit through delivery and with their breastfed infants postpartum. Cognitive, motor and expressive language development (Bayley Scales of Infant and Toddler Development-Third Edition; delay defined as score <85) were assessed on a subset of HEU infants. HIV VL was measured at ART initiation, in third trimester and around delivery. Cumulative viremia in pregnancy was expressed as log10 VL copies × year/mL viremia copy-years (VCY). Relationships between VCY and development were examined after adjusting for socioeconomic, behavioral and psychosocial confounders.
RESULTS:Women (median pre-ART log10 VL 4.1, CD4 349 cells/mm) commonly reported adverse social circumstances (44% informal housing, 63% unemployed, 29% risky drinking). Among 214 infants (median age, 13 months; 53% male; 13% born <37 weeks’ gestation), viremia predicted lower motor and expressive language, but not cognitive, scores in crude and adjusted analysis per log10 VCY increase, αβ (95% confidence interval CI)motor, −2.94 (−5.77 to −0.11); language, −3.71 (−6.73 to −0.69) and cognitive −2.19 (−5.02 to 0.65). Increasing VCY also predicted higher relative odds of motor delay adjusted odds ratio (aOR)3.32; 95% CI1.36–8.14) and expressive language delay (aOR2.79; 95% CI1.57–4.94), but not cognitive delay (aOR1.68; 95% CI0.84–3.34).
CONCLUSIONS:Cumulative maternal HIV viremia in pregnancy may have adverse implications for HEU child development.
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