Supplementation In Early Life Research Articles

Early childhood multiple micronutrient supplementation is associated with lower obesity prevalence in later childhood, compared with iron and vitamin A supplementation only

We examined whether multiple micronutrient (MM) supplementation in early childhood has any lasting effect on child size in later childhood. In a randomized, double‐blind controlled trial in Mexico, infants (n=650) from a prenatal supplementation trial (MM or iron only) received either MM or iron and vitamin A (Fe‐A) supplements for 6d/wk from 3–24mo of age. Child height (ht) and weight (wt) were measured in a 2008 follow‐up visit (n=607; mean age 8.5 ± 0.9y). Using intent to treat analysis [4 group comparisons (by mother and child group) and by child group only] we found no significant differences (p>.1) in child wt, ht, ht‐for‐age or wt‐for‐age Z‐scores (HAZ or WAZ), or prevalence of stunting (HAZ<−2), underweight (WAZ<−2), thinness (BMI‐forage Z‐score (BAZ)< −2) or overweight (BAZ +1 to +1.9). However, the child MM group had significantly lower BMI, BAZ and obesity prevalence (BAZ>+2) than the child Fe‐A group (mean BMI 17.3 ± 2.7 vs. 17.8 ± 2.9 kg/m2, mean BAZ 0.5 ± 1.1 vs. 0.8 ± 1.2, obesity 10.2 vs. 17.3%; all p<.05). Analysis by 4 groups showed a similar, though not statistically significant trend (p=.07); children who received MM (in utero and early childhood) had the lowest obesity prevalence (9.2%) and those who received Fe only in utero and Fe‐A in childhood had the highest prevalence (18.3%). Results are consistent with our findings at 2y of age and suggest long term benefits of MM supplementation in early life. Further analysis is required to adjust for contextual factors that may have contributed to this difference after supplementation was completed.Funding: MI; Thrasher Research Fund; UNICEF; CONACYT; INSP Mexico; UC Berkeley; Emory University

A differential effect of 2 probiotics in the prevention of eczema and atopy: A double-blind, randomized, placebo-controlled trial

The role of probiotics in prevention of allergic disease is still not clearly established, although early reports suggested Lactobacillus GG halved the risk of eczema at 2 years. To determine whether probiotic supplementation in early life could prevent development of eczema and atopy at 2 years. Double-blind, randomized placebo-controlled trial of infants at risk of allergic disease. Pregnant women were randomized to take Lactobacillus rhamnosus HN001 (L rhamnosus), Bifidobacterium animalis subsp lactis strain HN019 or placebo daily from 35 weeks gestation until 6 months if breast-feeding, and their infants were randomized to receive the same treatment from birth to 2 years (n = 474). The infant's cumulative prevalence of eczema and point prevalence of atopy, using skin prick tests to common allergens, was assessed at 2 years. Infants receiving L rhamnosus had a significantly (P = .01) reduced risk of eczema (hazard ratio [HR], 0.51; 95% CI, 0.30-0.85) compared with placebo, but this was not the case for B animalis subsp lactis (HR, 0.90; 95% CI, 0.58-1.41). There was no significant effect of L rhamnosus (HR, 0.74; 95% CI, 0.46-1.18) or B animalis subsp lactis (HR, 0.82; 95% CI, 0.52-1.28) on atopy. L rhamnosus (71.5%) was more likely than B animalis subsp lactis (22.6%) to be present in the feces at 3 months, although detection rates were similar by 24 months. We found that supplementation with L rhamnosus, but not B animalis subsp lactis, substantially reduced the cumulative prevalence of eczema, but not atopy, by 2 years. Understanding how Lactobacilli act to prevent eczema requires further investigation.

Neonatal-Age Treatment with Vitamin A Delays Postweaning Vitamin A Deficiency and Increases the Antibody Response to T-cell Dependent Antigens in Young Adult Rats Fed a Vitamin A-Deficient Diet

Vitamin A supplementation for infants and young children is recommended by WHO/UNICEF for countries with a high prevalence of vitamin A deficiency, and vitamin A is often administered at immunization contacts. Using a rat model, we tested whether supplementation with vitamin A or other retinoids at the time of neonatal immunization has prospective benefit in terms of preventing postweaning vitamin A deficiency and promoting antibody responses to T-cell dependent (TD) antigens administered at the neonatal stage and at the young adult stage. Rats were treated orally on postnatal d 6–8 with oil (placebo control), vitamin A, retinoic acid, or a combination of both (VARA) (n ≥ 12/group), and immunized with tetanus toxoid (TT) on d 7. The primary anti-TT response was measured on d 21, after which weanling rats were fed the vitamin A-deficient diet until ∼10 wk. At 8 wk, rats were immunized again with TT to determine the recall response, and with a novel TD antigen, keyhole limpet hemocyanin (KLH), to assess the adult primary response. None of the supplements affected the plasma titer of anti-TT immunoglobulin G (IgG) on d 21 (P = 0.25). However, neonatal-age supplementation with vitamin A or VARA at the young adult stage resulted in: >5 times higher anti-TT IgG recall response (P < 0.01); 5- and 9-times higher anti-KLH primary IgM and IgG responses, respectively (P < 0.05), and plasma retinol in the normal range (∼1.0 μmol/L vs. ∼0.35 μmol/L in retinoic acid-treated and control groups, P < 0.0001). We conclude that early-life supplementation with vitamin A or VARA can prospectively benefit the primary and recall antibody responses to TD antigens administered at the young adult stage, which may involve the maintenance of normal plasma retinol levels.

Early-life supplementation of vitamins A and D, in water-soluble form or in peanut oil, and allergic diseases during childhood

Early vitamin supplementation is given routinely to infants in many countries, but it is unclear whether this affects the risk of allergic diseases. We sought to study the association between early-life supplementation of vitamins A and D in water-soluble form or in peanut oil and allergic diseases up to 4 years of age. A prospective birth cohort of 4089 newborn infants was followed for 4 years using parental questionnaires repeatedly to collect information on exposure and health. At 4 years, the response rate was 90%, and allergen-specific IgE levels to food and airborne allergens were measured in 2614 of the participating children. Vitamins A and D were given to 98% of the children in infancy, and vitamins based in peanut oil dominated (90%). Children supplemented with vitamins A and D in water-soluble form during the first year of life had an almost 2-fold increased risk of asthma (adjusted odds ratio [OD], 2.18; 95% CI, 1.45-3.28), food hypersensitivity (adjusted OR, 1.89; 95% CI, 1.33-2.65), and sensitization to common food and airborne allergens (adjusted OR, 1.88; 95% CI, 1.34-2.64) at age 4 years compared with those receiving vitamins in peanut oil. No increased risk of IgE antibodies to peanut was seen in children receiving vitamins in peanut oil. Supplementation of vitamins A and D in water-soluble form seems to increase the risk of allergic disease up to the age of 4 years compared with supplementation with the same vitamins given in peanut oil. Vitamins A and D in oil does not seem to increase the risk of allergic disease during childhood.

Lack of effect of vitamin D administration during pregnancy and early life on diabetes incidence in the non-obese diabetic mouse.

Several studies have suggested that vitamin D supplementation in early life may reduce the risk of developing type 1 diabetes in later life. The non-obese diabetic (NOD) mouse is a model of spontaneous type 1 diabetes currently used for testing hypothesis/compounds aimed at disease prevention. In this study, we tested the effect of vitamin D (16 IU by gavage) on diabetes incidence in NOD/Ba mice treated from conception with olive oil containing vitamin D via maternal dosing up to 10 weeks of age and followed up until 32 weeks of age. Twelve breeding pairs were administered olive oil containing vitamin D during pregnancy, 15 days following the birth of the pups and for the next 10 weeks subsequently. The same breeding pairs were bred again after a clearance period of 15 days using a control solution to produce a control litter. This control group received a control solution for the same period of time. Diabetes incidence, degree of insulitis, and insulin content in the pancreas were investigated in the two groups. 12 vitamin D-treated NOD mice developed diabetes compared to 15 animals in the control group (Log rank test p = 0.899, NS). There were no significant differences between the groups in diabetes incidence, time of onset of the disease, degree of insulitis, or the insulin content in the pancreas. Vitamin D administered in utero and in the early stages of life at the dosage used does not change the incidence of diabetes or modify the disease process that leads to beta cell destruction in the NOD mouse.

Comparison of Linear Growth Patterns in the First Three Years of Life Across Two Generations in Guatemala

The secular increase in height is assumed to result from long-term improvements in nutritional intakes and reductions in infectious disease burdens. Nutritional supplementation in early life reduces stunting in chronically undernourished populations. It is not known whether these improvements have an impact on the growth of subsequent generations. Our objective was to estimate the intergenerational effect on offspring length of improved nutrition in the mother's early childhood. We studied 283 mother-child pairs (mothers born 1969-1977; children born 1996-1999). The mothers had received nutritional supplementation--either atole (enhanced protein-energy) or fresco (moderate energy, no protein), with both containing vitamins and minerals--prenatally and up to age 7 y as part of a community trial conducted in 4 villages in Guatemala. Length was measured on repeated occasions to 36 months of age in both mothers and children. Growth was modeled as a fractional polynomial. Children grew faster than their mothers. Children of mothers who received atole grew faster than children of women who received fresco. In both groups, lengths of individual children were positively correlated with lengths of their own mothers at the same ages. Correlations were generally stronger when the mothers had received atole in early life. We have confirmed a secular trend in growth of children in a developing country setting. The rate of child growth reflects, in part, the growth pattern of the mother, including improvements to that pattern resulting from nutritional supplementation.

Prospective study of protein-energy supplementation early in life and of growth in the subsequent generation in Guatemala

The secular increase in height is assumed to result from long-term improvements in nutritional intakes and reductions in infectious disease burdens. Nutritional supplementation in early life reduces stunting in chronically undernourished populations. It is unknown whether these improvements can be transmitted to subsequent generations. Our objective was to estimate the intergenerational effect on offspring length of improved nutrition in the mother's childhood. We studied 263 children born in 1996-1999 to 231 women who had received nutritional supplementation, ie, atole (high-protein, moderate-energy drink) or fresco (nonprotein, low-energy drink), prenatally and up to age 7 y as part of a community trial in Guatemala between 1969 and 1977. Child length was measured at different times to age 36 mo. Children born to women who received the enhanced supplement were taller (age-adjusted difference: 0.80 cm; 95% CI: 0.16, 1.44 cm) than were children whose mothers received the low-energy supplement. This increment was independent of the children's birth weight or socioeconomic status but was substantially attenuated and no longer significant after adjustment for maternal height (adjusted difference: 0.43 cm; 95% CI: -0.10, 0.96 cm; P > 0.10). The effect of maternal nutritional supplementation was more pronounced in boys than in girls (P for interaction < 0.10) and in children born to women who received supplements at ages 3-7 y than in children born to women who received supplements at ages 0-3 y (P for interaction < 0.01). Nutritional supplementation in childhood has positive effects on both the supplemented persons and on the subsequent generation.