Dataset Information

Biomarkers of environmental enteric dysfunction are not consistently associated with linear growth velocity in rural Zimbabwean infants.

ABSTRACT:

Background

Child stunting remains a poorly understood, prevalent public health problem. Environmental enteric dysfunction (EED) is hypothesized to be an important underlying cause.

Objectives

Within a subgroup of 1169 children enrolled in the SHINE (Sanitation Hygiene Infant Nutrition Efficacy) trial in rural Zimbabwe, followed longitudinally from birth to 18 mo of age, we evaluated associations between the concentration of 11 EED biomarkers and linear growth velocity.

Methods

At infant ages 1, 3, 6, 12, and 18 mo, nurses measured child length and collected stool and blood; the lactulose-mannitol urine test was also conducted at all visits except at 1 mo. Stool neopterin, α-1 antitrypsin, myeloperoxidase, and regenerating gene 1β protein; urinary lactulose and mannitol; and plasma kynurenine, tryptophan, C-reactive protein, insulin-like growth factor-1 (IGF-1), soluble CD14, intestinal fatty acid binding protein, and citrulline were measured. We analyzed the change in relative [∆ length-for-age z score (LAZ)/mo] and absolute (∆ length/mo) growth velocity during 4 age intervals (1-3 mo; 3-6 mo; 6-12 mo; and 12-18 mo) per SD increase in biomarker concentration at the start of each age interval.

Results

In fully adjusted models, we observed only 3 small, statistically significant associations: kynurenine:tryptophan ratio at 12 mo was associated with decreased mean LAZ velocity during the 12-18 mo interval (-0.015 LAZ/mo; 95% CI: -0.029, -0.001 LAZ/mo); mannitol excretion at 6 mo was associated with increased LAZ velocity during the 6-12 mo interval (0.013 LAZ/mo; 95% CI: 0.001, 0.025 LAZ/mo), and plasma IGF-1 at 1 mo was associated with increased LAZ velocity during the 1-3 mo interval (0.118 LAZ/mo; 95% CI: 0.024, 0.211 LAZ/mo). Results for absolute growth velocity were similar, except IGF-1 was also associated with growth during the 12-18 mo interval. We found no other associations between any EED biomarker and linear growth velocity.

Conclusions

None of 11 biomarkers of EED were consistently associated with linear growth among Zimbabwean children.This trial was registered at clinicaltrials.gov as NCT01824940.

SUBMITTER: Mutasa K

PROVIDER: S-EPMC8106752 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:OBJECTIVES:Environmental enteric dysfunction (EED) may inhibit growth and development in low- and middle-income countries, but available assessment methodologies limit its study. In rural Bangladesh, we measured EED using the widely used lactulose mannitol ratio (L:M) test and a panel of intestinal and systemic health biomarkers to evaluate convergence among biomarkers and describe risk factors for EED. METHODS:In 539 18-month-old children finishing participation in a randomized food supplementation trial, serum, stool, and urine collected after lactulose and mannitol dosing were analyzed for biomarkers of intestinal absorption, inflammation, permeability and repair, and systemic inflammation. EED scores for each participant were developed using principal component analysis and partial least squares regression. Associations between scores and L:M and with child sociodemographic and health characteristics were evaluated using regression analysis. RESULTS:EED prevalence (L:M?>?0.07) was 39.0%; 60% had elevated acute phase proteins (C-reactive protein >5 mg/L or ?-1 acid glycoprotein >100 mg/dL). Correlations between intestinal biomarkers were low, with the highest between myeloperoxidase and ?-1 antitrypsin (r?=?0.33, P?<?0.01), and biomarker values did not differ by supplementation history. A 1-factor partial least squares model with L:M as the dependent variable explained only 8.6% of L:M variability. In adjusted models, L:M was associated with child sex and socioeconomic status index, whereas systemic inflammation was predicted mainly by recent illness, not EED. CONCLUSIONS:Impaired intestinal health is widespread in this setting of prevalent stunting, but a panel of serum and stool biomarkers demonstrated poor agreement with L:M. Etiologies of intestinal and systemic inflammation are likely numerous and complex in resource-poor settings, underscoring the need for a better case definition with corresponding diagnostic methods to further the study of EED.

Project description:BackgroundUndernutrition in early life underlies 45% of child deaths globally. Stunting malnutrition (suboptimal linear growth) also has long-term negative effects on childhood development. Linear growth deficits accrue in the first 1000 d of life. Understanding the patterns and timing of linear growth faltering or recovery during this period is critical to inform interventions to improve infant nutritional status.ObjectiveWe aimed to identify the pattern and determinants of linear growth trajectories from birth through 24 mo of age in a cohort of Zimbabwean infants.DesignWe performed a secondary analysis of longitudinal data from a subset of 3338 HIV-unexposed infants in the Zimbabwe Vitamin A for Mothers and Babies trial. We used k-means clustering for longitudinal data to identify linear growth trajectories and multinomial logistic regression to identify covariates that were associated with each trajectory group.ResultsFor the entire population, the mean length-for-age z score declined from -0.6 to -1.4 between birth and 24 mo of age. Within the population, 4 growth patterns were identified that were each characterized by worsening linear growth restriction but varied in the timing and severity of growth declines. In our multivariable model, 1-U increments in maternal height and education and infant birth weight and length were associated with greater relative odds of membership in the least-growth restricted groups (A and B) and reduced odds of membership in the more-growth restricted groups (C and D). Male infant sex was associated with reduced odds of membership in groups A and B but with increased odds of membership in groups C and D.ConclusionIn this population, all children were experiencing growth restriction but differences in magnitude were influenced by maternal height and education and infant sex, birth weight, and birth length, which suggest that key determinants of linear growth may already be established by the time of birth. This trial was registered at clinicaltrials.gov as NCT00198718.

Project description:BackgroundThe underperformance of oral vaccines in children of low- and middle-income countries is partly attributable to underlying environmental enteric dysfunction (EED).MethodologyWe conducted a longitudinal, community-based study to evaluate the association of oral rotavirus vaccine (Rotarix®) seroconversion with growth anthropometrics, EED biomarkers and intestinal enteropathogens in Pakistani infants. Children were enrolled between three to six months of their age based on their nutritional status. We measured serum anti-rotavirus immunoglobulin A (IgA) at enrollment and nine months of age with EED biomarkers and intestinal enteropathogens.ResultsA total of 391 infants received two doses of rotavirus (RV) vaccine. 331/391 provided paired blood samples. Of these 331 children, 45% seroconverted at 9 months of age, 35% did not seroconvert and 20% were seropositive at baseline. Non-seroconverted children were more likely to be stunted, wasted and underweight at enrollment. In univariate analysis, insulin-like growth factor (IGF) concentration at 6 months were higher in seroconverters, median (25th, 75th percentile): 26.3 (16.5, 43.5) ng/ml vs. 22.5 (13.6, 36.3) ng/ml for non-seroconverters, p-value = 0.024. At nine months, fecal myeloperoxidase (MPO) concentrations were significantly lower in seroconverters, 3050(1250, 7587) ng/ml vs. 4623.3 (2189, 11650) ng/ml in non-seroconverted children, p-value = 0.017. In multivariable logistic regression analysis, alpha-1 acid glycoprotein (AGP) and IGF-1 concentrations were positively associated with seroconversion at six months. The presence of sapovirus and rotavirus in fecal samples at the time of rotavirus administration, was associated with non-seroconversion and seroconversion, respectively.ConclusionWe detected high baseline RV seropositivity and impaired RV vaccine immunogenicity in this high-risk group of children. Healthy growth, serum IGF-1 and AGP, and fecal shedding of rotavirus were positively associated with RV IgA seroconversion following immunization, whereas the presence of sapovirus was more common in non-seroconverters.Trial registrationClinical Trials ID: NCT03588013.

Project description:IntroductionDeployment of rotavirus vaccines has contributed to significant declines in diarrheal morbidity and mortality globally. Unfortunately, vaccine performance in low-middle income countries (LMICs) is generally lower than in developed countries. The cause for this has been associated with several host and maternal factors including poor water sanitation and hygiene (WASH) status, which are predominant in LMICs. More recently, environmental enteric dysfunction (EED) has specifically been hypothesized to contribute to poor vaccine uptake and response. The aim of this study was to examine the association between serological biomarkers of EED and seroconversion to rotavirus vaccine in Zambian infants.MethodsThis was a retrospective cohort study of 142 infants who had been fully immunized with Rotarix™, and had known seroconversion status. Seroconversion was defined as 4-fold or more increase in rotavirus-specific IgA titres between pre-vaccination and one month post-dose two vaccination. We performed ELISA assays to assess soluble CD14 (sCD14), Endotoxin Core IgG Antibodies (EndoCAb), intestinal fatty acid binding protein (i-FABP) and Zonulin according to the manufacturers protocols. Generalised linear model with family-poisson, link-log and robust standard error was used to estimate the independent effects of biomarkers on seroconversion adjusting for important cofounders.ResultsThe median concentration of Zonulin, Soluble CD14, EndoCaB, and IFABP were 209.3 (IQR = 39.7, 395.1), 21.5 (IQR = 21.5, 21.5), 0.3 (IQR = 0.3, 0.3), and 107.7 (IQR = 6.4, 1141.4) respectively. In multivariable analyses adjusting for the independent effect of other biomarkers and confounders (i.e. age of child at vaccination, breast-milk anti-rotavirus IgA, infant serum anti-rotavirus IgG, and IgA seropositivity at baseline), there was strong evidence of about 24% increase in seroconversion due to doubling Zonulin concentration (Adjusted risk ratio (aRR) = 1.24; 95% CI = 1.12 to1.37; p<0.0001). Similarly, we found about 7% increase in seroconversion due to doubling IFABP concentration (aRR = 1.07; 95% CI = 1.02 to 1.13; p = 0.006).ConclusionWe found that high levels of zonulin and IFABP played a role in seroconversion. It is plausible that increased gut permeability in EED allows greater uptake of the live virus within the vaccine, but later consequences result in deleterious local structural distortions and malabsorption syndromes.

Project description:BackgroundAdverse birth outcomes, including preterm birth and stunting at birth, have long-term health implications. The relation between adverse birth outcomes and chronic, asymptomatic gastrointestinal inflammation (environmental enteric dysfunction-EED) is poorly understood.ObjectiveWe aimed to examine the relation between maternal EED and adverse birth outcomes in a sample of pregnant Ugandan women and their newborn infants.DesignWe conducted a prospective cohort study in Mukono, Uganda. A total of 258 pregnant women were enrolled at their first prenatal visit (?18 weeks of gestation). EED was measured by urinary lactulose:mannitol (L:M) ratio and serum concentrations of antibodies to the bacterial components flagellin and LPS. Covariates were obtained from survey data collected at 2 time points. Associations were assessed through the use of unadjusted and adjusted simple linear regression models.ResultsComplete birth outcome data were recorded for 220 infants within 48 h of delivery. Mean ± SD gestational age was 39.7 ± 2.1 wk, and 7% were born preterm. Mean ± SD length and length-for-age z score (LAZ) at birth were 48.1 ± 3.2 cm and -0.44 ± 1.07, respectively. L:M ratio was not associated with any birth outcome. In adjusted models, higher concentrations of natural log-transformed anti-flagellin immunoglobin G (IgG) and anti-LPS IgG were significantly associated with shorter length of gestation (?: -0.89 wk; 95% CI: -1.77, -0.01 wk, and ?: -1.01 wk; 95% CI: -1.87, -0.17 wk, respectively) and with reduced length (?: -0.80 cm; 95% CI: -1.55, -0.05 cm, and ?: -0.79 cm; 95% CI: -1.54, -0.04 cm, respectively) and LAZ at birth (? -0.44 z score; 95% CI: -0.83, -0.05, and ?: -0.40 z score; 95% CI: -0.79, -0.01, respectively).ConclusionMaternal anti-flagellin and anti-LPS IgG concentrations in pregnancy, but not L:M ratio, were associated with shorter gestation and reduced infant length at birth. Further research on the relation between maternal EED and birth outcomes is warranted.