Iron status in early childhood is modified by diet, sex and growth : Secondary analysis of a randomized controlled vitamin D trial

Background & aims: During early childhood the risk of iron deficiency (ID) is high. Serum ferritin serves as a marker of iron status. We explored prevalence of ID and iron deficiency anemia (IDA), and identified determinants of iron status in infants and toddlers. Methods: We performed a secondary analysis of the Vitamin D intervention in infants (VIDI) study in Finnish healthy term infants. According to study protocol, at 12- and 24-months of age iron status, growth and dietary intakes were evaluated. ID was defined as serum ferritin Results: ID prevalence increased from 14% in infants to 20% in toddlers. IDA prevalence was 3% at both time points. In infants, ID and IDA were more common in boys than in girls (19% vs. 9%, p = 0.001 and 5% vs. 1%, p = 0.039) but no sex-difference in toddlers was observed. Of infants, 30% had daily iron intake below average requirement of 5 mg/day. Higher daily iron intake per body weight (mg/kg) independently associated with higher infant serum ferritin (B (95% CI) 0.30 (0.04, 0.56), p = 0.026). Correlation between iron intake and ferritin was stronger in infants with ID than in infants without ID. Breastfeeding was more common (63% vs. 35%, p < 0.001) among ID infants than in infants without ID. In toddlers, frequent consumption of milk products independently associated with lower ferritin (B (95% CI) -0.03 (-0.05, -0.01), p = 0.001). Consumption of meat and fish associated with better iron status. Serum ferritin at both time points associated with duration of gestation and growth. The association of growth and ferritin was age-dependent in boys, while in girls, faster growth associated consistently with lower ferritin. Conclusions: In Northern European healthy infants and toddlers ID is common. The intake of iron remains below recommendations and food consumption and iron intake associate with iron status. Further studies are warranted to assess significance of ID on child development and clinical health outcomes. (C) 2021 The Authors. Published by Elsevier Ltd.Peer reviewe

The Effects of Vitamin D Supplementation During Infancy on Growth During the First 2 Years of Life

Context: The relationship between maternal and infant vitamin D and early childhood growth remains inadequately understood. Objective: This work aimed to investigate how maternal and child 25-hydroxyvitamin D (25[OH]D) and vitamin D supplementation affect growth during the first 2 years of life. Methods: A randomized, double-blinded, single-center intervention study was conducted from pregnancy until offspring age 2 years. Altogether 812 term-born children with complete data were recruited at a maternity hospital. Children received daily vitamin D-3 supplementation of 10 mu g (group 10) or 30 mu g (group 30) from age 2 weeks to 2 years. Anthropometry and growth rate were measured at age 1 and 2 years. Results: Toddlers born to mothers with pregnancy 25(OH)D greater than 125 nmol/L were at 2 years lighter and thinner than the reference group with 25(OH)D of 50 to 74.9 nmol/L (P .053), but group 30 had slower growth in length and head circumference between 6 months and 1 year (P 121 nmol/L) were shorter (mean difference 0.2 SD score [SDS], P = .021), lighter (mean difference 0.4 SDS, P = .001), and thinner (in length-adjusted weight) (mean difference 0.4 SDS, P = .003) compared with the lowest quartile (< 81.2 nmol/L). Conclusion: Vitamin D and early childhood growth may have an inverse U-shaped relationship.Peer reviewe

Collagen X Biomarker (CXM), Linear Growth, and Bone Development in a Vitamin D Intervention Study in Infants

Publisher Copyright: © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).Collagen X biomarker (CXM) is suggested to be a biomarker of linear growth velocity. However, early childhood data are limited. This study examines the relationship of CXM to the linear growth rate and bone development, including the possible modifying effects of vitamin D supplementation. We analyzed a cohort of 276 term-born children participating in the Vitamin D Intervention in Infants (VIDI) study. Infants received 10 μg/d (group-10) or 30 μg/d (group-30) vitamin D3 supplementation for the first 2 years of life. CXM and length were measured at 12 and 24 months of age. Tibial bone mineral content (BMC), volumetric bone mineral density (vBMD), cross-sectional area (CSA), polar moment of inertia (PMI), and periosteal circumference (PsC) were measured using peripheral quantitative computed tomography (pQCT) at 12 and 24 months. We calculated linear growth as length velocity (cm/year) and the growth rate in length (SD unit). The mean (SD) CXM values were 40.2 (17.4) ng/mL at 12 months and 38.1 (12.0) ng/mL at 24 months of age (p = 0.12). CXM associated with linear growth during the 2-year follow-up (p = 0.041) but not with bone (p = 0.53). Infants in group-30 in the highest tertile of CXM exhibited an accelerated mean growth rate in length compared with the intermediate tertile (mean difference [95% CI] −0.50 [−0.98, −0.01] SD unit, p = 0.044) but not in the group-10 (p = 0.062) at 12 months. Linear association of CXM and growth rate until 12 months was weak, but at 24 months CXM associated with both length velocity (B for 1 increment of √CXM [95% CI] 0.32 [0.12, 0.52] cm/yr, p = 0.002) and growth rate in length (0.20 [0.08, 0.32] SD unit, p = 0.002). To conclude, CXM may not reliably reflect linear growth from birth to 12 months of age, but its correlation with growth velocity improves during the second year of life.Peer reviewe

Maternal vitamin D status, gestational diabetes and infant birth size

Background: Maternal vitamin D status has been associated with both gestational diabetes mellitus (GDM) and fetal growth restriction, however, the evidence is inconsistent. In Finland, maternal vitamin D status has improved considerably due to national health policies. Our objective was to compare maternal 25-hydroxy vitamin D concentrations [25(OH)D] between mothers with and without GDM, and to investigate if an association existed between maternal vitamin D concentration and infant birth size. Methods: This cross-sectional study included 723 mother-child pairs. Mothers were of Caucasian origin, and infants were born at term with normal birth weight. GDM diagnosis and birth size were obtained from medical records. Maternal 25(OH)D was determined on average at 11 weeks of gestation in pregnancy and in umbilical cord blood (UCB) at birth. Results: GDM was observed in 81 of the 723 women (11%). Of the study population, 97% were vitamin D sufficient [25(OH)D >= 50 nmol/L]. There was no difference in pregnancy 25(OH)D concentration between GDM and non-GDM mothers (82 vs 82 nmol/L, P = 0.99). Regression analysis confirmed no association between oral glucose tolerance test results and maternal 25(OH)D (P > 0.53). Regarding the birth size, mothers with optimal pregnancy 25(OH)D (>= 80 nmol/L) had heavier newborns than those with suboptimal pregnancy 25(OH)D (P = 0.010). However, mothers with optimal UCB 25(OH) D had newborns with smaller head circumference than those with suboptimal 25(OH)D (P = 0.003), which was further confirmed as a linear association (P = 0.024). Conclusions: Maternal vitamin D concentration was similar in mothers with and without GDM in a mostly vitamin D sufficient population. Associations between maternal vitamin D status and birth size were inconsistent. A sufficient maternal vitamin D status, specified as 25(OH)D above 50 nmol/L, may be a threshold above which the physiological requirements of pregnancy are achieved.Peer reviewe

Food and Nutrient Intake and Nutrient Sources in 1-Year-Old Infants in Finland : A Cross-Sectional Analysis

The infant diet has short- and long-term health consequences. Updated data regarding the dietary intake of Finnish infants are lacking. The objectives of this study were to describe infant food and nutrient intake and to identify food sources of the nutrients. Altogether, 739 healthy infants were studied. Dietary intake and breastfeeding frequency were assessed with a three-day food record at 1 year of age. Dietary intake was calculated separately for non-breastfed and breastfed infants. One-third (36%) of the infants were partially breastfed and 95% consumed mass-produced baby foods. The infants' diet consisted mainly of infant formula, dairy milk, porridges, fruit and berry foods, and meat dishes. The mean vegetable, fruit and berry consumption was 199 g/day. Most nutrient intakes were adequate except for fat, linoleic acid, vitamin D and iron from food. Mean sucrose intake, as a percentage of total energy intake (E%), was 5-6 E%. High protein intake (>20 E%) was observed in 19% of non-breastfed infants. Overall, the infants' diet was favorable since vegetable and fruit consumption was reasonably high and nutrient intake was mostly adequate. However, the fat intake was lower, and protein intake higher than recommended. Increasing the consumption of vegetable oils and reducing the intake of red meat and dairy milk may further improve the diet of 1-year-olds.Peer reviewe

High Pregnancy, Cord Blood, and Infant Vitamin D Concentrations May Predict Slower Infant Growth

Context: The relationship of maternal and infant 25-hydroxyvitamin D concentration [25(OH)D] with infant growth is unclear. Objective: Our objective was to explore whether 25(OH)D in pregnancy, umbilical cord blood (UCB), or in infancy was associated with infant growth. Design: This study involved 798 healthy infants and their mothers in Finland. We assessed 25(OH)D during pregnancy, from UCB at birth, and from the infant at the age of 12 months. Main Outcome Measures: Infant length, weight, length-adjusted weight, and head circumference at 6 and 12 months and midupper-arm circumference at 12 months. Results: Of the mothers and infants, 96% and 99% were vitamin D sufficient [25(OH)D >= 50 nmol/L], respectively. Mothers with pregnancy 25(OH)D >125 nmol/L had the shortest, lightest (in weight), and thinnest (in length-adjusted weight) infants at 6 months (P for all <0.05). For each 10 nmol/L higher UCB 25(OH)D, the infants were 0.03 SD score (SDS) shorter at 6 months (95% CI -0.05 to -0.01), adjusted for birth size, infant 25(OH)D, and parental height. Higher UCB 25(OH)D associated with smaller head circumference at 6 and 12 months (P for all 125 nmol/L had the thinnest infants at 12 months (P = 0.021). For each 10 nmol/L higher infant 25(OH)D, the infants were 0.03 SDS lighter (-0.05 to -0.01) and 0.03 SDS thinner (-0.05 to 0.00) at 12 months. Conclusions: Our results suggest that high pregnancy, cord blood, and infant vitamin D concentration may have disadvantageous effects on infant growth.Peer reviewe

Season, dietary factors, and physical activity modify 25-hydroxyvitamin D concentration during pregnancy

Peer reviewe

Genetic variants for head size share genes and pathways with cancer

The size of the human head is determined by growth in the first years of life, while the rest of the body typically grows until early adulthood1. Such complex developmental processes are regulated by various genes and growth pathways2. Rare genetic syndromes have revealed genes that affect head size3, but the genetic drivers of variation in head size within the general population remain largely unknown. To elucidate biological pathways underlying the growth of the human head, we performed the largest genome-wide association study on human head size to date (N = 79,107). We identified 67 genetic loci, 50 of which are novel, and found that these loci are preferentially associated with head size and mostly independent from height. In subsequent neuroimaging analyses, the majority of genetic variants demonstrated widespread effects on the brain, whereas the effects of 17 variants could be localized to one or two specific brain regions. Through hypothesis-free approaches, we find a strong overlap of head size variants with both cancer pathways and cancer genes. Gene set analyses showed enrichment for different types of cancer and the p53, Wnt and ErbB signalling pathway. Genes overlapping or close to lead variants – such as TP53, PTEN and APC – were enriched for genes involved in macrocephaly syndromes (up to 37-fold) and high-fidelity cancer genes (up to 9-fold), whereas this enrichment was not seen for human height variants. This indicates that genes regulating early brain and cranial growth are associated with a propensity to neoplasia later in life, irrespective of height. Our results warrant further investigations of the link between head size and cancer, as well as its clinical implications in the general population

Genetic variants for head size share genes and pathways with cancer

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer

Genetic Variants For Head Size Share Genes and Pathways With Cancer

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer