Dataset Information

Thymic size is increased by infancy, but not pregnancy, nutritional supplementation in rural Gambian children: a randomized clinical trial.

ABSTRACT:

Background

Thymic size in early infancy predicts subsequent survival in low-income settings. The human thymus develops from early gestation, is most active in early life and is highly sensitive to malnutrition. Our objective was to test whether thymic size in infancy could be increased by maternal and/or infant nutritional supplementation.

Methods

The Early Nutrition and Immune Development (ENID) Trial was a randomized 2?×?2?×?2 factorial, partially blinded trial of nutritional supplementation conducted in rural Gambia, West Africa. Pregnant women (N?=?875) were randomized to four intervention groups (iron-folate (standard care), multiple micronutrients, protein energy or protein energy + multiple micronutrients at 'booking' (mean gestational age at enrolment?=?13.6?weeks, range 8-20?weeks) until delivery. The iron-folate and multiple micronutrient arms were administered in tablet form and the protein energy arms as a lipid-based nutritional supplement. All intervention arms contained 60?mg iron and 400??g folic acid per daily dose. From 24 to 52?weeks of age, infants from all groups were randomized to receive a daily lipid-based nutritional supplement, with or without additional micronutrients. Thymic size was assessed by ultrasonography at 1, 8, 24 and 52?weeks of infant age, and a volume-related thymic index calculated. Detailed data on infant growth, feeding status and morbidity were collected.

Results

A total of 724 (82.7%) mother-infant pairs completed the trial to infant age 52?weeks. Thymic size in infancy was not significantly associated with maternal supplement group at any post-natal time point. Infants who received the daily LNS with additional micronutrients had a significantly larger thymic index at 52?weeks of age (equivalent to an 8.0% increase in thymic index [95% CI 2.89, 13.4], P?=?0.002). No interaction was observed between maternal and infant supplement groups.

Conclusions

A micronutrient-fortified lipid-based supplement given in the latter half of infancy increased thymic size, a key mediator of immune function. Improving the micronutrient status of infants from populations with marginal micronutrient status may improve immune development and survival.

Trial registration

ISRCTN registry (controlled-trials.com) Identifier: ISRCTN49285450.

SUBMITTER: Moore SE

PROVIDER: S-EPMC6378709 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Thymic size is increased by infancy, but not pregnancy, nutritional supplementation in rural Gambian children: a randomized clinical trial.

Moore Sophie E SE Fulford Anthony J C AJC Sosseh Fatou F Nshe Patrick P Darboe Momodou K MK Prentice Andrew M AM

BMC medicine 20190218 1

<h4>Background</h4>Thymic size in early infancy predicts subsequent survival in low-income settings. The human thymus develops from early gestation, is most active in early life and is highly sensitive to malnutrition. Our objective was to test whether thymic size in infancy could be increased by maternal and/or infant nutritional supplementation.<h4>Methods</h4>The Early Nutrition and Immune Development (ENID) Trial was a randomized 2 × 2 × 2 factorial, partially blinded trial of nutritional su ...[more]

PMID: 30773140

Similar Datasets

Project description:BackgroundVitamin D is important to maternal, fetal, and infant health, but quality data on vitamin D status in low- and middle-income countries and response to cholecalciferol supplementation in pregnancy are sparse.ObjectiveWe characterized vitamin D status and vitamin D metabolite change across pregnancy and in response to cholecalciferol supplementation in rural Gambia.MethodsThis study was a secondary analysis of samples collected in a 4-arm trial of maternal nutritional supplementation [iron folic acid (FeFol); multiple micronutrients (MMN); protein energy (PE) as lipid-based supplement; PE + MMN]; MMN included 10 ?g/d cholecalciferol. Plasma 25-hydroxycholecalciferol [25(OH)D3], 24,25-dihydroxycholecalciferol [24,25(OH)2D3], and C3-epimer-25-hydroxycholecalciferol [3-epi-25(OH)D3] were measured by LC-MS/MS in 863 women [aged 30 ± 7 y (mean ± SD)] in early pregnancy (presupplementation) and late pregnancy, (gestational age 14 ± 3 and 30 ± 1 wk). Changes in 25(OH)D3 and vitamin D metabolite concentrations and associations with pregnancy stage and maternal age and anthropometry were tested.ResultsEarly pregnancy 25(OH)D3 concentration was 70 ± 15 nmol/L and increased according to pregnancy stage (82 ± 18 and 87 ± 17 nmol/L in the FeFol and PE-arms) and to cholecalciferol supplementation (95 ± 19 and 90 ± 20 nmol/L in the MMN and PE + MMN-arms) (P < 0.0001). There was no difference between supplemented groups. Early pregnancy 25(OH)D3 was positively associated with maternal age and gestational age. Change in 25(OH)D3 was negatively associated with late pregnancy, but not early pregnancy, triceps skinfold thickness. The pattern of change of 24,25(OH)2D3 mirrored that of 25(OH)D3 and appeared to flatten as pregnancy progressed, whereas 3-epi-25(OH)D3 concentration increased across pregnancy.ConclusionThis study provides important data on the vitamin D status of a large cohort of healthy pregnant women in rural Africa. Without supplementation, vitamin D status increased during pregnancy, demonstrating that pregnancy stage should be considered when assessing vitamin D status. Nutritionally relevant cholecalciferol supplementation further increased vitamin D status. These data are relevant to the development of fortification and supplementation policies in pregnant women in West Africa.

Project description:BackgroundVitamin A deficiency (VAD) impairs T-cell-mediated immunity. In regions where VAD is prevalent, vitamin A supplementation (VAS) reduces child mortality, perhaps by improving immune function.ObjectiveOur objective was to determine if neonatal VAS would improve thymic function in Bangladeshi infants, and to determine if such effects differed by sex or nutritional status (i.e., birth weight above/below the median).MethodsThree hundred and six infants were randomly assigned to 50,000 IU vitamin A (VA) or placebo (PL) within 48 h of birth. Primary outcomes were measured at multiple ages and included 1) thymic index (TI) at 1, 6, 10, and 15 wk; 2) T-cell receptor excision circles (TREC), an index of thymic output of naïve T cells; and 3) total/naïve T cells in peripheral blood at 6 wk, 15 wk, and 2 y. A mixed linear model for repeated measures was used to assess group differences at each age and identify interactions with sex and birth weight.ResultsVAS did not significantly (P = 0.21) affect TI overall (i.e., at all ages) but decreased TI by 7.8% (P = 0.029) at 6 wk: adjusted TI means for the PL and VA groups at 1, 6, 10, and 15 wk were 4.09 compared with 3.80 cm2, 7.78 compared with 7.18 cm2, 8.11 compared with 7.84 cm2, and 7.91 compared with 7.97 cm2, respectively. VAS did not significantly (P = 0.25) affect TREC overall but decreased TREC by 19% (P = 0.029) at 15 wk: adjusted TREC means for the PL and VA groups at 6 wk, 15 wk, and 2 y were 13.6 compared with 16.1 copies/pg DNA, 19.4 compared with 15.7 copies/pg DNA, and 11.8 compared with 10.0 copies/pg DNA, respectively. VAS did not significantly affect overall total (P = 0.10) or naïve (P = 0.092) T cells: adjusted naïve T-cell means for the PL and VA groups at 6 wk, 15 wk, and 2 y were 3259 compared with 3109 cells/µL, 3771 compared with 3487 cells/µL, and 1976 compared with 1898 cells/µL, respectively.ConclusionIn contrast to our hypothesis, VAS decreased thymic function early in infancy but health effects are presumably negligible owing to the transience and small magnitude of this effect. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610.

Project description:OBJECTIVES:A high prevalence of rickets of unknown aetiology has been reported in Chakaria, Bangladesh. Classically, rickets is caused by vitamin D deficiency but increasing evidence from Africa and Asia points towards other nutritional deficiencies or excessive exposure to some metals. The aim of this study was to investigate the aetiology of rickets in rural Bangladeshi children. METHODS:64 cases with rickets-like deformities were recruited at first presentation together with age-sex-village matched controls. Data and sample acquisition included anthropometry, radiographs, fasted plasma and urinary samples, 24 h weighed dietary intake together with a 24 h urine collection, and 13C-breath tests to detect Helicobacter (H.) pylori infection. RESULTS:One child had active rickets and frank hypovitaminosis D (F, n = 1) and one had deformities with radiological features of Blount disease (M, n = 1). The remaining cases were grouped into those with active rickets, defined as a radiographic Thacher score ?1.5 (Group A, n = 24, 12M, 12F) and rickets-like bone deformities but not active rickets (Group B, n = 38, 28M, 10F). All children had a low dietary calcium intake, but this was lower in Group A than their controls (mean (SD): 156 (80) versus 323 (249) mg/day, p = 0.005). Plasma 25-hydroxyvitamin D (25OHD) was lower in Group A compared to controls; 63% of Group A and 8% of controls had a concentration <25 nmol/L (p ? 0.0001). There was, however, no evidence of differences in skin sunshine exposure. Group A had lower plasma calcium and phosphate and higher 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH). 88% of Group A and 0% of controls had undetectable plasma intact fibroblast growth factor (iFGF23), with c-terminal FGF23 (cFGF23) concentrations in the normal range. Urinary phosphate and daily outputs of environmental metals relative to creatinine were higher and tubular maximal phosphate reabsorption per unit glomerular filtration rate (TmP/GFR) was lower in Group A compared to controls. Although less pronounced than Group A, Group B had higher alkaline phosphatase, 1,25(OH)2D and PTH concentrations than controls but similar calcium intake, TmP/GFR, iFGF23 and cFGF23 concentrations. Mean 25OHD concentrations were also similar to controls and there was no significant difference in the percentage <25 nmol/L (Group B: 13%, controls: 5%, p = 0.2) No group differences were seen in prevalence of anaemia, iron deficiency or H. pylori infection. CONCLUSION:Nutritional rickets in this region is likely to be predominantly due to low calcium intake in the context of poor vitamin D status and exposure to environmental metals, but not H. pylori infection, anaemia or iron deficiency.

Project description:BackgroundGrowth faltering remains common in children in sub-Saharan Africa and is associated with substantial morbidity and mortality. Due to a very slow decline in the prevalence of stunting, the total number of children with stunting continues to rise in sub-Saharan Africa. Identification of effective interventions remains a challenge.MethodsWe analysed the effect of 36 years of intensive health interventions on growth in infants and young children from three rural Gambian villages. Routine growth data from birth to age 2 years were available for 3659 children between 1976 and 2012. Z scores for weight-for-age, length-for-age, weight-for-length, mid-upper-arm circumference, and head circumference were calculated using the WHO 2006 growth standards. Seasonal patterns of mean Z scores were obtained by Fourier regression. We additionally defined growth faltering as fall in Z score between 3 months and 21 months of age.FindingsWe noted secular improvements in all postnatal growth parameters (except weight-for-length), accompanied by declines over time in seasonal variability. The proportion of children with underweight or stunting at 2 years of age halved during four decades of the study period, from 38·7% (95% CI 33·5-44·0) for underweight and 57·1% (51·9-62·4) for stunting. However, despite unprecedented levels of intervention, postnatal growth faltering persisted, leading to poor nutritional status at 24 months (length-for-age Z score -1·36, 95% CI -1·44 to -1·27, weight-for-age Z score -1·20, -1·28 to -1·11, and head circumference Z score -0·51, -0·59 to -0·43). The prevalence of stunting and underweight remained unacceptably high (30·0%, 95% CI 27·0-33·0, for stunting and 22·1%, 19·4 to 24·8, for underweight).InterpretationA combination of nutrition-sensitive and nutrition-specific interventions has achieved a halving of undernutrition rates, but despite these intensive interventions substantial growth faltering remains. We need to understand the missing contributors to growth faltering to guide development of new interventions.FundingUK Medical Research Council, UK Department for International Development.

Project description:BackgroundPregnancy is a critical period for both woman and baby from a nutritional perspective. Nutritional education is considered an important tool for promoting a healthy lifestyle, but has not been studied as a determinant for maternal use of supplements during pregnancy, especially in Romania, where evidence about pregnancy and nutrition is scarce. This study aimed to evaluate the relationship between nutritional knowledge and the use of folic acid, iron and multivitamin supplements during pregnancy and to assess the influence of socio-demographic factors and prenatal care.MethodsWe conducted a cross-sectional study on a sample of 400 pregnant women admitted to the Cuza-Vodă Obstetrics and Gynaecology Clinical Hospital in Iaşi, Romania, during August-September 2010. We collected self-reported data regarding socio-demographic characteristics, number of prenatal check-ups and the use of folic acid, iron and multivitamin supplements during pregnancy. We assessed nutritional knowledge using a standardized questionnaire divided into three sections: general nutritional recommendations for pregnant women; the roles of nutrients; and sources of nutrients. We used logistic regression to analyse the associations between these factors.ResultsThe prevalence of the use of supplements during pregnancy was 48% for folic acid, 45.3% for iron and 68% for multivitamins. Above-average nutritional knowledge was independently associated with the use of folic acid (aOR, 4.7; 95% CI, 1.6-13.8), iron (aOR, 2.6; 95% CI, 1.2-5.7) and multivitamins (aOR, 2.8; 95% CI, 1.2-6.8). The use of folic acid was independently associated with a higher level of formal education (aOR, 5.2; 95% CI, 2.1-12.8) and an early start in prenatal care (aOR, 3.4; 95% CI, 1.0-11.1). Women with a higher education (aOR, 2.3; 95% CI, 1.1-4.9), more than 10 prenatal visits (aOR, 7.2; 95% CI, 3.4-15.0) and those who received advice on breastfeeding (aOR, 2.0; 95% CI, 1.1-3.5) were more likely to use iron during pregnancy. Similar results were found when analysing the contributing factors for the use of multivitamins: more than 12 years of schooling (aOR, 3.4; 95% CI, 1.4-7.9) and appropriate prenatal care (aOR, 9.4; 95% CI, 4.5-19.5).ConclusionsLevel of nutritional knowledge has a strong independent association with the use of supplements during pregnancy.

Dataset Information

Thymic size is increased by infancy, but not pregnancy, nutritional supplementation in rural Gambian children: a randomized clinical trial.

Background

Methods

Results

Conclusions

Trial registration

Publications

Thymic size is increased by infancy, but not pregnancy, nutritional supplementation in rural Gambian children: a randomized clinical trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets