Observational studies suggest that vitamin D deficiency among people living with HIV is associated with a greater risk of disease progression and death. Low levels of vitamin D in pregnancy are also ...associated with poor fetal and infant growth. Therefore, vitamin D supplementation may improve clinical outcomes for pregnant women living with HIV and improve fetal and postnatal growth for their infants.
We conducted a randomized, triple-blind, placebo-controlled trial of vitamin D3 supplementation among pregnant and lactating women living with HIV in Dar es Salaam, Tanzania (ClinicalTrials.gov NCT02305927). Participants were randomized with 1:1 allocation stratified by study clinic to receive either daily 3,000 IU vitamin D3 supplements or matching placebo supplements from the second trimester of pregnancy (12-27 weeks) until 1 year postpartum. The primary outcomes were (i) maternal HIV progression or death, (ii) small-for-gestational-age (SGA) live births (<10th percentile), and (iii) infant stunting at 1 year of age (length-for-age z-score < -2). We also examined the effect of vitamin D3 supplementation on secondary maternal and infant health outcomes, maternal and infant serum 25-hydroxyvitamin D (25OHD) concentrations, and maternal hypercalcemia. An intent-to-treat analysis was used as the primary analytic approach. We enrolled 2,300 pregnant women between June 15, 2015, and April 17, 2018, and follow-up of mothers and infants was completed on October 20, 2019. There were 1,148 pregnant women randomly assigned to the vitamin D3 group, and 1,152 to the placebo group. The proportion of mothers lost to follow-up at 1 year postpartum was 6.6% in the vitamin D3 group (83 of 1,148) and 6.6% in the placebo group (76 of 1,152). The proportion of children lost to follow-up at 1 year of age was 5.5% in the vitamin D3 group (59 of 1,074 live births) and 5.2% in the placebo group (57 of 1,093 live births). There was no difference in the risk of maternal HIV progression or death, with 166 events during 1,461 person-years of follow-up in the vitamin D3 group and 141 events during 1,469 person-years of follow-up in the placebo group (hazard ratio 1.21, 95% CI 0.97 to 1.52, p = 0.09). There was no difference in the risk of SGA birth between the vitamin D3 (229 SGA births among 1,070 live births) and placebo groups (236 SGA births among 1,091 live births) (relative risk 1.03, 95% CI 0.87 to 1.22, p = 0.70). There was also no difference in the risk of infant stunting at 1 year of age between the vitamin D3 (407 events among 867 infants) and placebo groups (413 events among 873 infants) (relative risk 1.00, 95% CI 0.92 to 1.10, p = 0.95). In terms of adverse events, no cases of maternal hypercalcemia were identified. One hypersensitivity reaction to the trial supplements occurred for a pregnant woman in the placebo group. A limitation of our study is that our findings may not be generalizable to HIV-negative pregnant women or contexts where severe vitamin D deficiency is prevalent.
The trial findings do not support routine vitamin D supplementation for pregnant and lactating women living with HIV in Tanzania.
ClinicalTrials.gov Identifier: NCT02305927.
Approximately 20.5 million infants were born weighing <2500 g (defined as low birthweight or LBW) in 2015, primarily in low- and middle-income countries (LMICs). Infants born LBW, including those ...born preterm (<37 weeks gestation), are at increased risk for numerous consequences, including neonatal mortality and morbidity as well as suboptimal health and nutritional status later in life. The objective of this study was to identify predictors of LBW and preterm birth among infants in rural Uganda.
Data were derived from a prospective birth cohort study conducted from 2014-2016 in 12 districts across northern and southwestern Uganda. Birth weights were measured in triplicate to the nearest 0.1 kg by trained enumerators within 72 hours of delivery. Gestational age was calculated from the first day of last menstrual period (LMP). Associations between household, maternal, and infant characteristics and birth outcomes (LBW and preterm birth) were assessed using bivariate and multivariable logistic regression with stepwise, backward selection analyses.
Among infants in the study, 4.3% were born LBW (143/3,337), and 19.4% were born preterm (744/3,841). In multivariable analysis, mothers who were taller (>150 cm) (adjusted Odds Ratio (aOR) = 0.42 (95% CI = 0.24, 0.72)), multigravida (aOR = 0.62 (95% CI = 0.39, 0.97)), or with adequate birth spacing (>24 months) (aOR = 0.60 (95% CI = 0.39, 0.92)) had lower odds of delivering a LBW infant Mothers with severe household food insecurity (aOR = 1.84 (95% CI = 1.22, 2.79)) or who tested positive for malaria during pregnancy (aOR = 2.06 (95% CI = 1.10, 3.85)) had higher odds of delivering a LBW infant. In addition, in multivariable analysis, mothers who resided in the Southwest (aOR = 0.64 (95% CI = 0.54, 0.76)), were ≥20 years old (aOR = 0.76 (95% CI = 0.61, 0.94)), with adequate birth spacing (aOR = 0.76 (95% CI = 0.63, 0.93)), or attended ≥4 antenatal care (ANC) visits (aOR = 0.56 (95% CI = 0.47, 0.67)) had lower odds of delivering a preterm infant; mothers who were neither married nor cohabitating (aOR = 1.42 (95% CI = 1.00, 2.00)) or delivered at home (aOR = 1.25 (95% CI = 1.04, 1.51)) had higher odds.
In rural Uganda, severe household food insecurity, adolescent pregnancy, inadequate birth spacing, malaria infection, suboptimal ANC attendance, and home delivery represent modifiable risk factors associated with higher rates of LBW and/or preterm birth. Future studies on interventions to address these risk factors may be warranted.
(1) Background: The effects of zinc supplementation on child growth, and prior reviews of these studies, have shown mixed results. We aim to systematically review and meta-analyze randomized ...controlled trials evaluating effects of preventive zinc supplementation for 3 months or longer during pregnancy or in children up to age 5 years on pregnancy outcomes and child growth; (2) Methods: We searched PubMed, EMBASE, Cochrane Library, Web of Science, and trial registries for eligible trials up to October 10, 2017. Inclusion selection and data extractions were performed independently and in duplicate. Study quality was evaluated by the Cochrane Risk of Bias tool. Findings were pooled using random effects meta-analysis, with heterogeneity assessed by
² and τ² statistic, stratified analyses, and meta-regression, and publication bias by Egger's and Begg's tests; (3) Results: Seventy-eight trials with 34,352 unique participants were identified, including 24 during pregnancy and 54 in infancy/childhood. Maternal zinc supplementation did not significantly increase birth weight (weighted mean difference (WMD) = 0.08 kg, 95%CI: -0.05, 0.22) or decrease the risk of low birth weight (RR = 0.76, 95%CI: 0.52-1.11). Zinc supplementation after birth increased height (WMD = 0.23 cm, 95%CI: 0.09-0.38), weight (WMD = 0.14 kg, 95%CI: 0.07-0.21), and weight-for-age
-score (WMD = 0.04, 95%CI: 0.001-0.087), but not height-for-age
-score (WMD = 0.02, 95%CI: -0.01-0.06) or weight-for-height Z score (WMD = 0.02, 95%CI: -0.03-0.06). Child age at zinc supplementation appeared to modify the effects on height (
-interaction = 0.002) and HAZ (
-interaction = 0.06), with larger effects of supplementation starting at age ≥2 years (WMD for height = 1.37 cm, 95%CI: 0.50-2.25; WMD for HAZ = 0.12, 95%CI: 0.05-0.19). No significant effects of supplementation were found on the risk of stunting, underweight or wasting; (4) Conclusion: Although the possibility of publication bias and small study effect could not be excluded, the current meta-analysis indicates that zinc supplementation in infants and early childhood, but not pregnancy, increases specific growth outcomes, with evidence for a potentially stronger effect after 2 years of age. These findings inform recommendation and policy development for zinc supplementation to improve growth among young children.
Environmental enteric dysfunction (EED) may contribute to poor growth and development in young children. While validated EED biomarkers are currently lacking, multiplex assays are able to capture ...multiple domains of the condition. The purpose of this exploratory study was to examine the relationship between biomarkers of EED and subsequent growth and development among Tanzanian HIV-exposed uninfected (HEU) infants.
We enrolled 467 infants of mothers living with HIV who had participated in a trial of vitamin D3 supplementation during pregnancy. Infant serum samples collected at 6 weeks (n = 365) and 6 months (n = 266) were analyzed for anti-flagellin and anti-lipopolysaccharide (LPS) IgA and IgG via ELISA as well as the 11-plex Micronutrient and EED Assessment Tool (MEEDAT), which incorporates two biomarkers of EED intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14). Outcomes were 12-month growth length-for-age z-score (LAZ), weight-for-length z-score (WLZ), and weight-for-age z-score (WAZ) and development Caregiver Reported Early Development Instruments (CREDI) z-scores and were assessed using linear regression.
In primary analyses, higher quartiles of 6-month anti-LPS IgG concentrations were significantly associated with lower LAZ at 12 months (ptrend = 0.040). In secondary analyses, higher log2-transformed 6-week anti-flagellin IgA and 6-month anti-LPS IgA concentrations were significantly associated with lower LAZ at 12 months. No associations were observed between I-FABP or sCD14 and infant growth. However, higher log2-transformed 6-week sCD14 concentrations were significantly associated with lower overall CREDI z-scores, while higher log2-transformed 6-month I-FABP concentrations were significantly associated with higher overall CREDI z-scores.
Unlike anti-flagellin and anti-LPS Igs, MEEDAT's biomarkers of EED (I-FABP and sCD14) were not associated with subsequent linear growth among HEU infants in Tanzania. The relationship between EED and infant development warrants further study.
Environmental Enteric Dysfunction (EED) is an acquired small intestinal inflammatory condition underlying high rates of stunting in children <5 years of age in low- and middle-income countries. ...Children with EED are known to have repeated exposures to enteropathogens and environmental toxins that leads to malabsorptive syndrome. We aimed to characterize association of linear growth faltering with enteropathogen burden and subsequent changes in EED biomarkers. In a longitudinal birth cohort (n = 272), monthly anthropometric measurements (Length for Age Z score- LAZ) of asymptomatic children were obtained up to 18 months. Biological samples were collected at 6 and 9 months for the assessment of biomarkers. A customized TaqMan array card was used to target 40 enteropathogens in fecal samples. Linear regression was applied to study the effect of specific enteropathogen infection on change in linear growth (ΔLAZ). Presence of any pathogen in fecal sample correlated with serum flagellin IgA (6 mo, r = 0.19, p = 0.002), fecal Reg 1b (6 mo, r = 0.16, p = 0.01; 9mo, r = 0.16, p = 0.008) and serum Reg 1b (6 mo, r = 0.26, p<0.0001; 9 mo, r = 0.15, p = 0.008). At 6 months, presence of Campylobacter β (SE) 7751.2 (2608.5), p = 0.003 and ETEC LT β (SE) 7089.2 (3015.04), p = 0.019 was associated with increase in MPO. Giardia was associated with increase in Reg1b β (SE) 72.189 (26.394), p = 0.006 and anti-flic IgAβ (SE) 0.054 (0.021), p = 0.0091. Multiple enteropathogen infections in early life negatively correlated with ΔLAZ, and simultaneous changes in gut inflammatory and permeability markers. A combination vaccine targeting enteropathogens in early life could help in the prevention of future stunting.
An acute shortage of infant formulas in the United States occurred in early 2022, exacerbating a longer-standing, less severe shortage that has occurred over the last several years. The shortage has ...been particularly problematic for specialized formulas such as those needed for infants and children with food allergies, intestinal failure, kidney disease, and metabolic disorders. Although undoubtedly the magnitude of the current shortage will abate over time, it has affected many children and caused tremendous distress for thousands of families. We propose a series of interventions to be undertaken as soon as feasible to help ensure that the conditions that led to this problem do not recur and families regain confidence in the safety and supply reliability of formulas for infants and young children regardless of their medical needs.
Moderate acute malnutrition (MAM) affects over 30 million children aged < 5 years worldwide. MAM may confer a greater risk of developing severe malnutrition and even mortality in children. Assessing ...risk factors for MAM may allow for earlier recognition of children at risk of deleterious health outcomes.
To determine risk factors associated with the prevalence and development of MAM among children aged 6 to 59 months with acute diarrhoea who received treatment with oral rehydration solution and zinc supplementation.
We conducted a secondary analysis of data from a randomized, dose-finding trial of zinc among children with acute diarrhoea in India and Tanzania. We used regression models to assess risk factors for prevalent MAM at the start of diarrhoea treatment and to identify risk factors associated with the development of MAM at 60 days. MAM was defined as weight for length (or height) Z score ≤-2 and > -3 or mid-upper arm circumference < 12.5 and ≥ 11.5 cm.
A total of 4,500 children were enrolled; 593 (13.2%) had MAM at the baseline. MAM at baseline was significantly less common among children in Tanzania than in India (adjusted risk ratio aRR 0.37, 95% confidence interval CI: 0.30, 0.44, P < 0.001), in children aged 24- < 60 months versus 6- < 12 months (aRR 0.46, 95% CI: 0.38, 0.56, P < 0.001), and in families with household wealth index higher than the median (aRR 0.79, 95% CI: 0.68, 0.92, P = 0.002). Sixty days after outpatient treatment and follow-up, 87 (2.5%) children developed MAM. When compared to children aged 6- < 12 months, children aged 24- < 60 months had a 52% lower risk of developing MAM. Every one unit increase in weight for length (or height) Z score at enrolment was associated with a 93% lower risk of developing MAM during follow-up.
Among children with diarrhoea, younger children and those from households with lower wealth were at greater risk of MAM. These children may benefit from targeted interventions focusing on feeding (targeted nutrition support for at-risk households) and follow up in order to reduce the occurrence of MAM and its consequences.
Background High energy requirements and poor feeding can lead to growth failure in patients with ventricular septal defect (VSD), but effects of preoperative malnutrition on surgical outcomes are ...poorly understood, especially in low‐resource settings. Methods and Results We analyzed a cohort of children <5 years of age undergoing VSD closure at 60 global centers participating in the International Quality Improvement Collaborative for Congenital Heart Disease, 2015 to 2020. We calculated adjusted odds ratios (ORs) for in‐hospital death and major infection and adjusted coefficients for duration of intensive care unit stay for 4 measures of malnutrition: severe wasting (weight‐for‐height Z score, <−3), moderate wasting (−3<weight‐for‐height Z score≤−2), underweight (weight‐for‐age Z score, ≤−2), and stunting (height‐for‐age Z score, ≤−2) according to World Health Organization Child Growth Standards. Among 10 966 children undergoing VSD closure in the analyzed cohort, 8136 (74%) were membranous VSDs. Median age was 9.6 months (interquartile range, 3.6–12.0), and 4088 (37.3%) had wasting/severe wasting, 5029 (45.9%) had underweight, and 3515 (32.1%) had stunting. There were 4749 (43.3%) children who met the criteria for ≥2 malnutrition categories. Overall, 84 patients (0.8%) died in‐hospital, and 199 (1.8%) had major infection. Severe wasting (OR, 3.38 95% CI, 1.55–7.35; P =0.002), underweight (OR, 6.46 95% CI, 2.81–14.8; P <0.001), and stunting (OR, 2.73 95% CI, 1.40–5.34; P =0.003) were independent predictors of mortality. Similar results were observed for infection and duration of intensive care unit stay. Underweight was the strongest predictor of adverse outcomes. Children meeting criteria for all 3 (stunting, wasting, and underweight) had 17.2 times higher odds of mortality ( P <0.001) than nonmalnourished children. Conclusions Malnutrition was associated with mortality, infection, and longer intensive care unit stay in a global cohort of children undergoing VSD closure.
Onward and upward Duggan, Christopher P
The American journal of clinical nutrition,
February 2019, 20190201, 2019-02-01, 2019-02-00, Letnik:
109, Številka:
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Journal Article
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