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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.

Background and 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

Importance: Vitamin D may be important for neurodevelopment. The optimal daily dose of vitamin D for early brain development is not known. Objectives: To test whether a higher (1200 IU) vs standard (400 IU) dose of vitamin D₃ has beneficial effects on neurodevelopment in the first 2 years of life and whether serum 25-hydroxyvitamin D concentration is associated with neurodevelopment. Design, Setting, and Participants: This double-blind, interventional randomized clinical trial involved healthy infants born full-term between January 1, 2013, and June 30, 2014, at a maternity hospital in Helsinki, Finland, at the 60th northern latitude. Two-year follow-up was conducted by May 30, 2016. Data analysis was by the intention-to-treat principle. Data were analyzed from November 1, 2020, to May 31, 2021. Interventions: Randomization of 404 infants to receive 400 IU of oral vitamin D₃ supplementation daily and 397 infants to receive 1200 IU of oral vitamin D3 supplementation daily from 2 weeks to 24 months of age. Main Outcomes and Measures: Primary outcomes were child total developmental milestone scores at 12 and 24 months of age measured using the Ages and Stages Questionnaire (total score is calculated as a mean of the 5 subscale scores: total score range, 0–60, where 0 indicates delay in all developmental domains and 60 indicates that the child can master all age-specific skills) as well as externalizing, internalizing, and dysregulation problems and competencies scores at 24 months measured using the Infant-Toddler Social and Emotional Assessment (range 0–2, where 0 indicates no problems or no competencies and 2 indicates a high level of problems or a high level of competencies; variables were standardized to the mean [SD] of 0 [1]). Secondary outcomes were specific skills, problems, and competencies derived from these questionnaires. Results: Of the 987 families recruited, 495 children were randomly assigned to receive 400 IU of vitamin D₃, and 492 children were randomly assigned to receive 1200 IU of vitamin D₃. A total of 801 families participated in the follow-up at 12 and/or 24 months, with 404 children (207 girls [51.2%]) in the 400-IU group and 397 children (198 girls [49.9%]) in the 1200-IU group. All children were of Northern European ethnicity. No differences were found between the 400-IU group and the 1200-IU group in the mean (SD) adjusted Ages and Stages Questionnaire total score at 12 months (45.0 [7.1] vs 46.2 [7.9]; mean difference [MD], 1.17 [95% CI, –0.06 to 2.38]) or 24 months (50.9 [5.3] vs 51.5 [5.5]; MD, 0.48 [95% CI, –0.40 to 1.36]). No differences were found between the 400-IU group and the 1200-IU group at 24 months in the mean (SD) adjusted Infant-Toddler Social and Emotional Assessment externalizing domain score (–0.07 [1.00] vs 0.07 [0.98]; MD, 0.15 [95% CI, –0.01 to 0.31]), internalizing domain score (0.04 [1.06] vs –0.02 [0.98]; MD, –0.07 [95% CI, –0.24 to 0.1.0]), dysregulation domain score (–0.00 [1.04] vs 0.02 [0.96]; MD, 0.02 [95% CI, –0.14 to 0.18]), or competencies score (–0.02 [1.02] vs 0.01 [1.02]; MD, 0.03 [95% CI, –0.13 to 0.20]). The 1200-IU group did have a higher risk in the adjusted model of scoring 1.5 SDs or more on the externalizing domain score (odds ratio, 2.33 [95% CI, 1.19–4.56]; P = .01). Levels of serum 25-hydroxyvitamin D were not associated with the primary outcomes. Conclusions and Relevance: Higher-than-standard vitamin D₃ doses provide no systematic benefits for child neurodevelopment up to 2 years of age. However, the potential disadvantageous effects of higher doses could not be fully excluded; even if minimal, the potential nonbeneficial effects of higher-than-standard doses warrant further studies in which both safety and benefits should be evaluated. Trial Registration: ClinicalTrials.gov Identifier: NCT01723852

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.