Prenatal nutrition supplementation and growth biomarkers in preadolescent Bangladeshi children: A birth cohort study.

Little is known about the usefulness of biomarkers to study the influence of prenatal nutrition supplementation in improving child growth. Anthropometry is not always straightforward to understand how nutrition might impact growth, especially in settings with high rates of malnutrition and infections. We examined the effects of prenatal supplementation on growth and growth biomarkers and the relationship between anthropometric measures and growth biomarkers of children at 4.5 and 9 years of age. Children were enrolled from a longitudinal cohort, where mothers were randomized into daily supplementation with either early-food (≤9 gestation week [GW]) or usual-food (~20 GW) (608 kcal 6 days/week); they were further randomized to receive 30-mg or 60-mg iron with 400-µg folic acid, or multiple micronutrients (MM) in rural Bangladesh. Anthropometric data were collected from mothers at GW8 and children at 4.5 (n = 640) and 9 years (n = 536). Fasting blood was collected from children at each age. Early-food supplementation showed reduced stunting and underweight at 4.5 and 9 years age respectively compared to usual-food. Prenatal supplementations did not have any effect on growth biomarkers except for STAT5b expression which was lower in the early-food compared to the usual-food group (ß = -0.21; 95 CI% = -0.36, -0.07). Plasma concentrations of 25-hydroxy vitamin D and calcium were both inversely associated with weight-for-age and body mass index-for-age Z-scores at 9 years, particularly in early-food and MM groups. Although there was minimal effect on child growth by prenatal supplementations, the associations of biomarkers with anthropometric indices were predominantly driven by timing of food or MM supplementations.

High-Dose Neonatal Vitamin A Supplementation to Bangladeshi Infants Increases the Percentage of CCR9-Positive Treg Cells in Infants with Lower Birthweight in Early Infancy, and Decreases Plasma sCD14 Concentration and the Prevalence of Vitamin A Deficiency at Two Years of Age.

BACKGROUND: Vitamin A (VA) stores are low in early infancy and may impair development of the immune system. OBJECTIVE: This study determined if neonatal VA supplementation (VAS) affects the following: 1) development of regulatory T (Treg) cells; 2) chemokine receptor 9 (CCR9) expression, which directs mucosal targeting of immune cells; and 3) systemic endotoxin exposure as indicated by changed plasma concentrations of soluble CD14 (sCD14). Secondarily, VA status, growth, and systemic inflammation were investigated. METHODS: In total, 306 Bangladeshi infants were randomly assigned to receive 50,000 IU VA or placebo (PL) within 48 h of birth, and immune function was assessed at 6 wk, 15 wk, and 2 y. Primary outcomes included the following: 1) peripheral blood Treg cells; 2) percentage of Treg, T, and B cells expressing CCR9; and 3) plasma sCD14. Secondary outcomes included the following: 4) VA status measured using the modified relative dose-response (MRDR) test and plasma retinol; 5) infant growth; and 6) plasma C-reactive protein (CRP). Statistical analysis identified group differences and interactions with sex and birthweight. RESULTS: VAS increased (P = 0.004) the percentage of CCR9+ Treg cells (13.2 ± 1.37%) relative to PL (9.17 ± 1.15%) in children below the median birthweight but had the opposite effect (P = 0.04) in those with higher birthweight (VA, 9.13 ± 0.89; PL, 12.1 ± 1.31%) at 6 and 15 wk (values are combined mean ± SE). VAS decreased (P = 0.003) plasma sCD14 (1.56 ± 0.025 mg/L) relative to PL (1.67 ± 0.032 mg/L) and decreased (P = 0.034) the prevalence of VA deficiency (2.3%) relative to PL (9.2%) at 2 y. CONCLUSIONS: Neonatal VAS enhanced mucosal targeting of Treg cells in low-birthweight infants. The decreased systemic exposure to endotoxin and improved VA status at 2 y may have been due to VA-mediated improvements in gut development resulting in improved barrier function and nutrient absorption. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610.

Infant cortisol stress-response is associated with thymic function and vaccine response.

Stress can impair T cell-mediated immunity. To determine if infants with high stress responses had deficits in T-cell mediated immunity, we examined the association of pain-induced cortisol responsiveness with thymic function and vaccine responses in infants. This study was performed among 306 (male = 153 and female = 153) participants of a randomized, controlled trial examining the effect of neonatal vitamin A supplementation on immune function in Bangladesh (NCT01583972). Salivary cortisol was measured before and 20 min after a needle stick (vaccination) at 6 weeks of age. The thymic index (TI) was determined by ultrasonography at 1, 6, 10 and 15 weeks. T-cell receptor excision circle and blood T-cell concentrations were measured at 6 and 15 weeks. Responses to Bacillus Calmette-Guérin (BCG), tetanus toxoid, hepatitis B virus and oral poliovirus vaccination were assayed at 6 and 15 weeks. Cortisol responsiveness was negatively associated with TI at all ages (p < .01) in boys only, was negatively associated with naïve helper T-cell concentrations in both sexes at both 6 (p = .0035) and 15 weeks (p = .0083), and was negatively associated with the delayed-type hypersensitivity (DTH) skin test response to BCG vaccination at 15 weeks (p = .034) in both sexes. Infants with a higher cortisol response to pain have differences in the T-cell compartment and a lower DTH response to vaccination. Sex differences in the immune system were seen as early as 6 weeks of age in these healthy infants.