Prevalence and risk factors for vitamin D deficiency among Tanzanian HIV-exposed uninfected infants.
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ABSTRACT:
SUBMITTER: Rwebembera A
PROVIDER: S-EPMC3789521 | biostudies-literature | 2013 Oct
REPOSITORIES: biostudies-literature
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Prevalence and risk factors for vitamin D deficiency among Tanzanian HIV-exposed uninfected infants.
Rwebembera Anath A Sudfeld Christopher R CR Manji Karim P KP Duggan Christopher C Aboud Said S Fawzi Wafaie W WW
Journal of tropical pediatrics 20130424 5
Vitamin D is essential for bone development and may also play an integral role in control of intracellular pathogens. Serum 25-hydroxyvitamin D levels were assessed at 6 months of age for 191 HIV-exposed uninfected infants enrolled in a trial of multivitamins (not including vitamin D) in Tanzania. A total of 66 infants (34.6%) were classified as vitamin D deficient (<20 ng/ml), 93 (48.7%) as vitamin D insufficient (20-30 ng/ml) and 32 (16.8%) as vitamin D sufficient (≥30 ng/ml). Independent risk ...[more]
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Project description:Immunization and nutritional interventions are mainstays of child health programs in sub-Saharan Africa, yet few published data exist on their interactions. HIV-exposed (but uninfected) infants enrolled in a randomized placebo-controlled trial of multivitamin supplements (vitamins B complex, C, and E) conducted in Tanzania were sampled for an assessment of measles IgG quantity and avidity at 15 to 18 months. Infants were vaccinated between 8.5 and 12 months of age, and all mothers received high-dose multivitamins as the standard of care. Of 201 HIV-exposed infants who were enrolled, 138 (68.7%) were seropositive for measles. There were no effects of infant multivitamin supplementation on measles seroconversion proportions, IgG concentrations, or IgG avidity (P > 0.05). The measles seroconversion proportion was greater for HIV-exposed infants vaccinated at 10 to 11 months of age than for those vaccinated at 8.5 to 10 months (P = 0.032) and greater for infants whose mothers had a CD4 T-cell count of <200 cells/?l than for infants whose mothers had a CD4 T-cell count of >350 cells/?l (P = 0.039). Stunted infants had a significantly decreased IgG quantity compared to nonstunted infants (P = 0.012). As for measles avidity, HIV-exposed infants vaccinated at 10 to 11 months had increased antibody avidity compared to those vaccinated at 8.5 to 10 months (P = 0.031). Maternal CD4 T-cell counts of <200 cells/?l were associated with decreased avidity compared to counts of >350 cells/?l (P = 0.047), as were lower infant height-for-age z-scores (P = 0.016). Supplementation with multivitamins containing B complex, C, and E does not appear to improve measles vaccine responses for HIV-exposed infants. Studies are needed to better characterize the impact of maternal HIV disease severity on the immune system development of HIV-exposed infants and the effect of malnutrition interventions on vaccine responses. (This study has been registered at ClinicalTrials.gov under registration no. NCT00197730.).
| S-EPMC3754503 | biostudies-literature
Project description:BackgroundThis study evaluated maternal factors associated with infant neurodevelopmental outcomes among HIV-exposed uninfected (HEU) infants in rural South Africa. This study followed pregnant women living with HIV pre- and postpartum and evaluated sociodemographic factors, use of antiretrovirals (ARVs), and mental health factors as predictors of HEU infant developmental outcomes (cognitive, receptive, and expressive communication, fine and gross motor skills).MethodsParticipants were 80 mother-infant dyads. Mothers were assessed during pregnancy, and HEU infant development was assessed at a mean (SD) of 13.36 (1.89) months of age.ResultsWomen were an average (SD) of 28.9 (5.2) years of age, and infants were on average 13.4 (1.9) months old. An analysis of covariance indicated that infants whose mothers had ARV detected in dry blood spots at 32 weeks of pregnancy had lower functioning scores in the cognitive domain than those with undetected ARV (n = 14; M, 15.3 vs 17.2; P = .048). Antenatal physical intimate partner violence was also associated with delayed cognitive functioning (F (1, 74), 4.96; P = .029).ConclusionsThis study found risks for delayed infant cognitive development to be associated with the use of ARV during pregnancy and intimate partner violence, although findings merit replication due to the low sample size. Given the growing number of HEU infants, the necessity to better understand the potential toxicity of ARV exposure in utero is apparent. Similarly, the need for preventing intimate partner violence and screening for, and managing, developmental delays among these infants is increasing.
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Project description:With expanded HIV treatment and prevention programmes, most infants born to HIV-positive women are uninfected, but the patterns and determinants of their growth are not well described. This study aimed to assess growth patterns in a cohort of HIV-exposed uninfected (HEU) infants who participated in an experimental HIV vaccine trial and to test for associations with maternal and infant factors, including in-utero exposure to antiretroviral therapy (ART), mode of delivery, exclusive breastfeeding, mother's education and receipt of the vaccine. Infants in the trial were seen at regular clinic visits from birth to 48 weeks of age. From the anthropometric measurements at these visits, weight-for-age z-scores (WAZ), weight-for-length z-scores (WLZ) and length-for-age z-scores (LAZ) were computed using World Health Organization (WHO) software and reference tables. Growth patterns were investigated with respect to maternal and infant factors, using linear mixed regression models. From 94 infants included at birth, growth data were available for 75.5% at 48 weeks. The determinants of infant growth in this population are multifactorial: infant LAZ during the first year was significantly lower among infants delivered by caesarean section (p = 0.043); both WAZ and LAZ were depressed among infants with longer exposure to maternal ART (WAZ: p = 0.015; LAZ: p < 0.0001) and among infants of mothers with lower educational level (WAZ: p = 0.038; LAZ: p < 0.0001); the effect of maternal education was modified by breastfeeding practice, with no differences seen in exclusively breastfed infants. These findings inform intervention strategies to preserve growth in this vulnerable infant population.
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Project description:IntroductionVitamin D deficiency is highly prevalent and is associated with bone disease, cardiovascular disease, metabolic syndrome and malignancy. Injection drug users (IDUs), with or without HIV infection, are at risk for these conditions; however, limited data on vitamin D deficiency exist in this population. We determined the prevalence and correlates of vitamin D deficiency among urban IDUs in the AIDS Linked to the IntraVenous Experience (ALIVE) Study cohort.MethodsFor this cross-sectional sub-study, vitamin D deficiency was defined as a serum 25(OH)-vitamin D level <20 ng/mL. Multivariable logistic regression was used to identify factors independently associated with vitamin D deficiency.ResultsOf 950 individuals analyzed, 29% were HIV-infected. The median age was 49 years; 65% were male, and 91% were black. The median vitamin D level was 13.5 ng/mL (IQR, 9.0-20.3); 74% were deficient (68% in HIV-infected vs. 76% in HIV-uninfected, p?=?0.01). Non-black race, fall/winter season, multivitamin intake, higher serum albumin, HCV seropositivity and HIV-infection were associated with significantly lower odds of vitamin D deficiency.ConclusionsVitamin D deficiency is prevalent among IDUs. Notably, HIV-infected IDUs were less likely to be vitamin D deficient. Higher vitamin D levels were associated with multivitamin intake and with higher albumin levels, suggesting that nutritional status contributes substantially to deficiency. The association between HCV serostatus and vitamin D level remains unclear. Further investigation is needed to define the clinical implications of the heavy burden of vitamin D deficiency in this high-risk, aging population with significant co-morbidities.
| S-EPMC3995810 | biostudies-literature
Project description:As prevention of mother-to-child HIV-1 transmission (PMTCT) programs decrease the numbers of HIV-1-infected infants, it remains important to improve growth in HIV-1-exposed, uninfected (EU) infants. To determine the growth rate and predictors of growth faltering in breast-fed and formula-fed EU infants, growth analyses [weight-for-age (WAZ), weight-for-length (WLZ), and length-for-age (LAZ) Z-scores] were conducted by using data from a randomized feeding trial in HIV-1-infected women in Kenya. Growth faltering in EU infants was compared based on randomization to breastfeeding (BF) or formula feeding (FF) using Cox proportional hazards regression models. Linear mixed-effects models determined rate and cofactors of length growth. Among 338 EU infants, 164 (49%) were breast-fed and 174 (51%) formula-fed. In both arms, growth declined steadily during follow-up. By 2 y, 29% of children were underweight (WAZ < -2), 18% were wasted (WLZ < -2), and 58% were stunted (LAZ < -2), with no differences by feeding arm. Higher maternal education (y) and taller stature (cm) were associated with a decreased risk of underweight and stunting [underweight: adjusted HR (aHR) = 0.90 (95% CI: 0.83, 0.99), P = 0.03, and aHR = 0.92 (95% CI: 0.87, 0.97), P = 0.002; and stunting: aHR = 0.91 (95% CI: 0.85, 0.97), P = 0.003, and aHR = 0.96 (95% CI: 0.92, 0.99), P = 0.02, respectively]. Diarrhea was associated with an increased risk of wasting [aHR = 2.26 (95% CI: 1.11, 4.62), P = 0.03]. In multivariate analyses, FF was associated with slower declines in length velocity [0.24 LAZ/y (95% CI: 0.06, 0.43), P = 0.009]. Despite being uninfected, HIV-1-exposed infants showed frequent growth faltering, suggesting the need for vigilance in recognizing stunting within PMTCT programs. The slower rate of decline in length growth with FF may reflect benefits of micronutrients. Because BF is the best option for HIV-1-infected mothers in resource-limited settings, nutritional interventions should be examined for their impact on growth in EU breast-fed infants.
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Project description:ObjectivesHIV-exposed uninfected (HEU) infants have higher rates of severe and fatal infections compared with HIV-unexposed (HUU) infants, likely due to immune perturbations. We hypothesized that alterations in natural killer (NK) cell activity might occur in HEU infants and predispose them to severe infections.DesignCase-control study using cryopreserved peripheral blood mononuclear cells (PBMCs) at birth and 6 months from HEU infants enrolled from 2002 to 2009 and HUU infants enrolled from 2011 to 2013.MethodsNK cell phenotype and function were assessed by flow cytometry after 20-h incubation with and without K562 cells.ResultsThe proportion of NK cells among PBMCs was lower at birth in 12 HEU vs. 22 HUU (1.68 vs. 10.30%, p < 0.0001) and at 6 months in 52 HEU vs. 72 HUU (3.09 vs. 4.65%, p = 0.0005). At birth, HEU NK cells demonstrated increased killing of K562 target cells (p < 0.0001) and increased expression of CD107a (21.65 vs. 12.70%, p = 0.047), but these differences resolved by 6 months. Stimulated HEU NK cells produced less interferon (IFN)γ at birth (0.77 vs. 2.64%, p = 0.008) and at 6 months (4.12 vs. 8.39%, p = 0.001), and showed reduced perforin staining at 6 months (66.95 vs. 77.30%, p = 0.0008). Analysis of cell culture supernatants indicated that lower NK cell activity in HEU was associated with reduced interleukin (IL)-12, IL-15, and IL-18. Addition of recombinant human IL-12 to stimulated HEU PBMCs restored IFNγ production to that seen in stimulated HUU cultures.ConclusionNK cell proportion, phenotype, and function are altered in HEU infants. NK cell cytotoxicity and degranulation are increased in HEU at birth, but HEU NK cells have reduced IFNγ and perforin production, suggesting an adequate initial response, but decreased functional reserve. NK cell function improved with addition of exogenous IL-12, implicating impaired production of IL-12 by accessory cells. Alterations in NK cell and accessory cell function may contribute to the increased susceptibility to infection in HEU infants.
| S-EPMC5403425 | biostudies-literature
Project description:HIV-exposed uninfected infants (HEU) have higher infectious morbidity than HIV-unexposed infants (HUU). HEU have multiple immune defects of unknown origin. We hypothesized that HEU have higher regulatory T cells (Treg) than HUU, which may dampen their immune defenses against pathogens. We compared 25 Treg subsets between HEU and HUU and sought the factors that may affect Treg frequencies. At birth, 3 Treg subsets, including CD4 + FOXP3 + and CD4 + FOXP3 + CD25+, had higher frequencies in 123 HEU than 117 HUU and 3 subsets were higher in HUU. At 28 and 62 weeks of life, 5 Treg subsets were higher in HEU, and none were higher in HUU. The frequencies of the discrepant Treg subsets correlated at birth with differential abundances of bacterial taxas in maternal gut microbiome and at subsequent visits in infant gut microbiomes. In vitro, bacterial taxa most abundant in HEU expanded Treg subsets with higher frequencies in HEU, recapitulating the in vivo observations. Other factors that correlated with increased Treg were low maternal CD4 + T cells in HEU at birth and male sex in HUU at 28 weeks. We conclude that maternal and infant gut dysbiosis are central to the Treg increase in HEU and may be targeted by mitigating interventions.
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Project description:BackgroundProphylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia.MethodsWe compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana.ResultsA total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure-risk difference, -0.69% (95% confidence interval [CI] -2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI -1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93).ConclusionsSevere anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1-6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants. CLINICALTRIAL.SGOV REGISTRATION NUMBERS: NCT01086878 (http://clinicaltrials.gov/show/NCT01086878), NCT00197587 (http://clinicaltrials.gov/show/NCT00197587), and NCT00270296 (http://clinicaltrials.gov/show/NCT00270296).
| S-EPMC3781096 | biostudies-literature