Eggs for Improving Nutrition, cognitive development and reducing linear growth retardation among Infants and young Children (ENRICH): protocol of an egg supplementation trial among children aged 9-18 months in Hyderabad, India.

INTRODUCTION: Evidence on the impact of nutrient-rich animal source foods such as eggs for improving child growth and cognition is inconsistent. This study aims to examine the impact of an egg intervention in children, along with behaviour change communication (BCC) to the mother, on linear growth and cognition, and nutritional status in children aged 9-18 months. METHODS AND ANALYSIS: A 9-month open-labelled randomised controlled trial will be conducted in three urban slums in Hyderabad, India, as a substudy of an observational cohort study (n=350) following pregnant women and their children until 18 months of age in a population at risk of stunting. The children born to women enrolled during the third trimester of pregnancy will be block randomised in a 1:4 ratio into the intervention (n=70) and control (n=280) groups. Children in the intervention group will be supplemented with one egg per day starting from 9 months until 18 months of age. BCC designed to enhance adherence to the intervention will be used. The control group will be a part of the observational cohort and will not receive any intervention from the study team. The primary outcome will be length-for-age z-scores, and the secondary outcomes will include cognition, blood biomarkers of nutritional status including fatty acid profile and epigenetic signatures linked with linear growth and cognition. Multivariate intention-to-treat analyses will be conducted to assess the effect of the intervention. ETHICS AND DISSEMINATION: The study is approved by the Institutional ethics committees of ICMR-National Institute of Nutrition, Hyderabad, India and London School of Hygiene and Tropical Medicine, UK. The results will be published in peer-reviewed journals and disseminated to policy-makers. Findings will also be shared with study participants and community leaders. TRIAL REGISTRATION NUMBER: CTRI/2021/11/038208.

Meeting the fetal requirement for polyunsaturated fatty acids in pregnancy.

PURPOSE OF REVIEW: The aim of this review is to summarize recent evidence on the importance of individual long chain polyunsaturated fatty acid (LCPUFA) to the developing fetus and the maternal dietary requirement for these. RECENT FINDINGS: Large-scale randomized controlled trials and innovative genetic and stable isotope studies are providing new insights in this field. SUMMARY: Large randomized controlled trials of LCPUFA supplementation in pregnancy suggest that higher n-3 LCPUFA intake reduces the risk of preterm birth and increases the length of gestation, with secondary effects on birth weight. There is little evidence of an effect on postnatal visual function and cognition, but interpretation is complicated by maternal metabolic adaptations and adipose tissue status in the newborn. The links between polymorphisms in the FADS genes and tissue fatty acid composition suggest that LCPUFA synthesis influences overall availability. Stable isotope studies have also demonstrated the capacity for LCPUFA synthesis in pregnancy, the fact that n-6 synthesis is greater than n-3, metabolic channeling of individual fatty acids to different fates, and selective placental transfer. Studies linking FADS genotype to cognition imply that n-3 LCPUFA synthesis could have an effect on infant cognition, but more large-scale genetic studies are needed.

Folate in pregnancy and imprinted gene and repeat element methylation in the offspring.

BACKGROUND: Epigenetic regulation of imprinted genes and transposable elements has been implicated in human disease and may be affected by maternal diet. OBJECTIVE: The objective was to determine the effect on offspring epigenetic status of nutritional and genetic factors that influence folate exposure in pregnancy. DESIGN: We measured folate intake from diet, the use of folic acid supplements and the period of consumption, maternal and cord red blood cell (RBC) folate, and genotypes for 5 methylation cycle enzymes in a prospective cohort study of pregnancies in the United Kingdom between 2000 and 2006. We related these to offspring methylation status within 3 maternally methylated imprinted genes: paternally expressed gene 3 (PEG3), insulin-like growth factor 2 (IGF2), and small nuclear ribonucleoprotein polypeptide N, and the long interspersed nuclear element 1 (LINE-1) in genomic DNA extracted from whole blood in 913 pregnancies. RESULTS: Supplement use after 12 wk of gestation was associated with a higher level of methylation in IGF2 (+0.7%; 95% CI: 0.02, 1.4; P = 0.044) and reduced methylation in both PEG3 (-0.5%; 95% CI: -0.9, -0.1; P = 0.018) and LINE-1 (-0.3%; 95% CI: -0.6, -0.04; P = 0.029). The same pattern was observed in relation to RBC folate in the cord blood at birth: IGF2 (P = 0.038), PEG3 (P < 0.001), and LINE-1 (P < 0.001). LINE-1 methylation was related to maternal RBC folate (P = 0.001) at 19 wk. No effect of supplement use up to 12 wk (current recommendation) was found. CONCLUSIONS: Folic acid use after 12 wk of gestation influences offspring repeat element and imprinted gene methylation. We need to understand the consequences of these epigenetic effects.

Vitamin D in pregnancy at high latitude in Scotland.

The aims of the present study were to determine compliance with current advice on vitamin D and to assess the influence of season, dietary intake, supplement use and deprivation on vitamin D status in pregnant mothers and newborns in the north of Scotland where sunlight exposure is low. Pregnant women (n 1205) and their singleton newborns were studied in the Aberdeen Maternity Hospital (latitude 57°N) between 2000 and 2006. Plasma 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 were measured at 19 weeks of gestation in mothers and at delivery in newborns. During pregnancy, 21·0 (95 % CI 18·5, 23·5) % of women took vitamin D supplements. The median intake was 5 µg/d and only 0·6 (95 % CI 0·1, 1·0) % took the recommended 10 µg/d. Supplement use, adjusted for season, dietary intake and deprivation, significantly increased maternal 25-hydroxyvitamin D (25(OH)D) by 10·5 (95 % CI 5·7, 15·2) nmol/l (P< 0·001); however, there was no significant effect on cord 25(OH)D (1·4 (95 % CI - 1·8, 4·5) nmol/l). The biggest influence on both maternal and cord 25(OH)D was season of birth (P< 0·001). Compared with the least deprived women (top three deciles), the most deprived pregnancies (bottom three deciles) were characterised by a significantly lower seasonally adjusted 25(OH)D ( - 11·6 (95 % CI - 7·5, - 15·7) nmol/l in the mother and - 5·8 (95 % CI - 2·3, - 9·4) nmol/l in the cord), and a lower level of supplement use (10 (95 % CI 4, 17) v. 23 (95 % CI 20, 26) %). More should be done to promote vitamin D supplement use in pregnancy but the critical importance of endogenous vitamin D synthesis, and known adaptations of fat metabolism specific to pregnancy, suggest that safe sun advice may be a useful additional strategy, even at high latitude.

Diet and deprivation in pregnancy.

Deprivation is associated with poor pregnancy outcome but the role of nutrition as a mediating factor is not well understood. We carried out a prospective cohort study of 1461 singleton pregnancies in Aberdeen, UK during 2000-6. We measured nutrient intake and supplement use, B vitamin and homocysteine status, birth weight, gestational age, neonatal treatment and socio-economic deprivation status. Women in the most deprived deciles were approximately 6 years younger and half as likely to take folic acid supplements periconceptually as the least deprived mothers. Deprivation was associated with low blood folate, high homocysteine and diets low in protein, fibre and many of the vitamins and minerals. The diets of the more deprived women were also characterised by low intakes of fruit, vegetables and oily fish and higher intakes of processed meat, fried potatoes, crisps and snacks. Deprivation was related to preterm birth (OR 1.14 (95 % CI 1.03, 1.25); P = 0.009) and whether the baby required neonatal treatment (OR 1.07 (95 % CI 1.01, 1.14); P = 0.028). Low birth weight was more common in women consuming diets low in vitamin C (OR 0.79 (95 % CI 0.64, 0.97); P = 0.028), riboflavin (OR 0.77 (95 % CI 0.63, 0.93); P = 0.008), pantothenic acid (OR 0.79 (95 % CI 0.65, 0.97); P = 0.023) and sugars (OR 0.78 (95 % CI 0.64, 0.96); P = 0.017) even after adjustment for deprivation index, smoking, marital status and parity. Deprivation in pregnancy is associated with diets poor in specific nutrients and poor diet appears to contribute to inequalities in pregnancy outcome. Improving the nutrient intake of disadvantaged women of childbearing age may potentially improve pregnancy outcome.

A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis.

Nationwide fortification of enriched uncooked cereal grains with folic acid began in the United States and Canada in 1996 and 1997, respectively, and became mandatory in 1998. The rationale was to reduce the number of births complicated by neural tube defects. Concurrently, the United States and Canada experienced abrupt reversals of the downward trend in colorectal cancer (CRC) incidence that the two countries had enjoyed in the preceding decade: absolute rates of CRC began to increase in 1996 (United States) and 1998 (Canada), peaked in 1998 (United States) and 2000 (Canada), and have continued to exceed the pre-1996/1997 trends by 4 to 6 additional cases per 100,000 individuals. In each country, the increase in CRC incidence from the prefortification trend falls significantly outside of the downward linear fit based on nonparametric 95% confidence intervals. The statistically significant increase in rates is also evident when the data for each country are analyzed separately for men and women. Changes in the rate of colorectal endoscopic procedures do not seem to account for this increase in CRC incidence. These observations alone do not prove causality but are consistent with the known effects of folate on existing neoplasms, as shown in both preclinical and clinical studies. We therefore hypothesize that the institution of folic acid fortification may have been wholly or partly responsible for the observed increase in CRC rates in the mid-1990s. Further work is needed to definitively establish the nature of this relationship. In the meantime, deliberations about the institution or enhancement of fortification programs should be undertaken with these considerations in mind.