Adherence to Vitamin D Supplementation Recommendations for Breastfed Infants and Young Children: An Analysis of Canadian Community Health Survey Data Cycles From 2015 to 2018.

BACKGROUND: In Canada, nutrition policy, as outlined in the Nutrition for Healthy Term Infants recommendations, includes a daily vitamin D supplement of 10 µg (400 IU) for breastfed infants and young children to support adequate vitamin D status. OBJECTIVES: This study aimed to report on adherence to vitamin D supplementation recommendations for breastfed infants (≤12 months); and for children breastfed >12 mo. METHODS: Canadian Community Health Survey (paired-cycles 2015/2016 and 2017/2018) maternal experiences data for infants born 2012-2018 who received any breastmilk formed the sample (n = 7079). Whether the infant was given a vitamin D supplement (yes/no) and the frequency (daily/almost every day, 1-2/wk, or <1/wk) were surveyed. Weighted data (95% CI) were summarized according to breastfeeding history (exclusive to 6 mo and continuing; partial to 6 mo and continuing; and stopped ≤6 mo). Correlates of supplement adherence were explored using logistic regression. RESULTS: Overall, 87.1% (95% CI: 85.9%, 88.3%) of participants reported giving their infant (≤12 mo) a vitamin D supplement, and of these, 83.3% (95% CI: 81.9%, 84.7%) did so daily/almost every day, 12.4% (95% CI: 11.1%, 13.7%) did so 1-2/wk, and 4.3% (95% CI: 3.6%, 5.0%) did so <1/wk. Lower adjusted odds of adherence were observed among participants reporting: stopped breastfeeding ≤6 mo, lower education or income, recent immigration, and overweight prepregnancy body mass index; higher odds of adherence were observed in the western provinces. Regarding mothers of children >12 mo and breastfed (n = 2312), 58.0% (95% CI: 54.9%, 61.1%) gave a vitamin D supplement daily/almost every day. CONCLUSIONS: Adherence to providing a vitamin D supplement to breastfed infants is high in Canada. Nonetheless, we estimate that ∼27% of mothers are nonadherent to daily/almost every day administration of a vitamin D supplement and that adherence declines in children breastfed >12 mo. Further promotion to support uptake of the current guidance may be necessary, particularly for parents of recent immigration or lower socioeconomic status.

A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

BACKGROUND: Vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (ICU) and associated with worse clinical course. Trials in adult ICU demonstrate rapid restoration of vitamin D status using an enteral loading dose is safe and may improve outcomes. There have been no published trials of rapid normalization of VDD in the pediatric ICU. METHODS: We conducted a multicenter placebo-controlled phase II pilot feasibility randomized clinical trial from 2016 to 2017. We randomized 67 critically ill children with VDD from ICUs in Canada, Chile and Austria using a 2:1 randomization ratio to receive a loading dose of enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or placebo. Participants, care givers, and outcomes assessors were blinded. The primary objective was to determine whether the loading dose normalized vitamin D status (25(OH)D > 75 nmol/L). Secondary objectives were to evaluate for adverse events and assess the feasibility of a phase III trial. RESULTS: Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary analyses (40 treatment, 19 placebo). Thirty-one/38 (81.6%) participants in the treatment arm achieved a plasma 25(OH)D concentration > 75 nmol/L versus 1/18 (5.6%) the placebo arm. The mean 25(OH)D concentration in the treatment arm was 125.9 nmol/L (SD 63.4). There was no evidence of vitamin D toxicity and no major drug or safety protocol violations. The accrual rate was 3.4 patients/month, supporting feasibility of a larger trial. A day 7 blood sample was collected for 84% of patients. A survey administered to 40 participating families showed that health-related quality of life (HRQL) was the most important outcome for families for the main trial (30, 75%). CONCLUSIONS: A single 10,000 IU/kg dose can rapidly and safely normalize plasma 25(OH)D concentrations in critically ill children with VDD, but with significant variability in 25(OH)D concentrations. We established that a phase III multicentre trial is feasible. Using an outcome collected after hospital discharge (HRQL) will require strategies to minimize loss-to-follow-up. CLINICALTRIALS: gov NCT02452762 Registered 25/05/2015.

Effect of Vitamin D Supplementation on Bone Mass in Infants With 25-Hydroxyvitamin D Concentrations Less Than 50 nmol/L: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

Importance: The dose of supplemental vitamin D needed in infants born with serum 25-hydroxyvitamin D (25[OH]D) concentrations less than 50 nmol/L (ie, 20 ng/mL) is unclear. Objective: To determine whether a higher dose (1000 IU vs 400 IU per day) is required in infants born with 25(OH)D concentrations less than 50 nmol/L for bone mineral accretion across infancy. Design, Setting, and Participants: In this prespecified secondary analysis of a double-blinded randomized clinical trial, conducted from March 2016 to March 2019 in a single center in Greater Montreal, Quebec, Canada, a consecutive sample of 139 healthy term singletons were recruited from 866 infants screened for vitamin D status at birth. Data were analyzed from June 2021 to November 2022. Interventions: Capillary blood was collected 24 to 36 hours after birth to measure serum total 25(OH)D concentrations. Infants with 25(OH)D concentrations less than 50 nmol/L were randomized to receive either 1000 IU or 400 IU per day of oral vitamin D3 supplementation from age 1 to 12 months. Infants with 25(OH)D concentrations of 50 nmol/L or greater formed a reference group. Main Outcomes and Measures: Measures at age 1, 3, 6, and 12 months were preplanned and included whole-body bone mineral content, lumbar spine bone mineral content, and bone mineral density using dual-energy x-ray absorptiometry, and serum 25(OH)D3 using liquid chromatography tandem mass spectrometry. Results: Of 139 included infants, 81 (58.3%) were male, and the median (IQR) gestational age at birth was 39.6 (38.9-40.6) weeks. A total of 49 infants were included in the 1000 IU per day group, 49 infants in the 400 IU per day group, and 41 in the reference group. Mean (SD) whole-body bone mineral content was not different between trial groups over time (1000 IU per day, 173.09 [2.36] g; 400 IU per day, 165.94 [66.08] g). Similarly, no differences were observed in lumbar spine bone mineral content or density. Mean (SD) serum 25(OH)D3 concentrations were significantly higher in the 1000 IU per day group from age 3 to 12 months (3 months, 115.2 [35.3] nmol/L; 6 months, 121.6 [34.4] nmol/L; 12 months, 99.6 [28.8] nmol/L) compared with the 400 IU per day trial group (3 months, 77.4 [23.3] nmol/L; 6 months, 85.1 [18.6] nmol/L; 12 months, 82.3 [14.3] nmol/L). Conclusions and Relevance: In this study, a higher dose of vitamin D supplementation in infants born with 25(OH)D concentrations less than 50 nmol/L did not present advantages to bone mass in infancy. This study supports a standard dose of 400 IU per day of vitamin D supplementation for breastfed infants in Montreal. Trial Registration: ClinicalTrials.gov Identifier: NCT02563015.

Vitamin D Status of People 3 to 79 Years of Age from the Canadian Health Measures Survey 2012-2019.

BACKGROUND: Vitamin D is recognized in bone health and the prevention of rickets and osteomalacia. OBJECTIVE: This study aimed to assess vitamin D status of people in Canada and to identify factors associated with vitamin D inadequacy and deficiency. METHODS: Serum 25-hydroxyvitamin D (25(OH)D) from the Canadian Health Measures Survey (cycles 3-6, n = 21,770, 3-79 y) were evaluated for geometric means and proportions <40 (inadequate) and <30 (risk of deficiency) nmol/L. Factors associated with inadequacy or deficiency were tested using logistic regression. RESULTS: Mean serum 25(OH)D was 57.9 (95% CI: 55.4, 60.5) nmol/L; the prevalence of inadequacy was 19.0% (95% CI: 15.7, 22.3) and risk of deficiency was 8.4% (95% CI: 6.5, 10.3). Prominent dietary factors associated with inadequacy in adults included: not consuming fish compared with ≥1/wk (adjusted ORadj: 1.60; 95% CI: 1.21, 2.11), none compared with ≥1/d for cow's milk (ORadj: 1.41; 95% CI: 1.02, 1.94) or margarine (ORadj: 1.42; 95% CI: 1.08, 1.88); or nonuser compared with user of vitamin D supplements (ORadj: 5.21; 95% CI: 3.88, 7.01). Notable demographic factors included: younger adults compared with 71 to 79 y (19-30 y ORadj: 2.33; 95% CI: 1.66, 3.29); BMI ≥30 compared with <25 kg/m2 (ORadj: 2.30; 95% CI: 1.79, 2.95); lower household income quartile 1 compared with 4 (ORadj: 1.46; 95% CI: 1.00, 2.15); and self-reported Black (ORadj: 8.06; 95% CI: 4.71, 13.81), East/Southeast Asian (ORadj: 3.83; 95% CI: 2.14, 6.85), Middle Eastern (ORadj: 4.57; 95% CI: 3.02, 6.92), and South Asian (ORadj: 4.63; 95% CI: 2.62, 8.19) race compared with White. Similar factors were observed in children and for deficiency. CONCLUSIONS: Most people in Canada have adequate vitamin D status; nonetheless, racialized groups have an elevated prevalence of inadequacy. Further research is required to evaluate if current strategies to improve vitamin D status, including increasing vitamin D in fortified foods and supplements, and dietary guidance to include a source of vitamin D every day help to reduce health inequality in Canada.

Vitamin D supplementation and gross motor development: A 3-year follow-up of a randomized trial.

BACKGROUND: Vitamin D status during pregnancy, early childhood and season-at-birth are implicated in gross motor development (GMD). AIM: To test whether vitamin D intake in infancy and season-at-birth affect GMD in early childhood. STUDY DESIGN: 3-year follow up study of a single-center trial. SUBJECTS: Healthy infants (n = 116) were allocated to 400 (standard-of-care), 800 or 1200 IU/day of vitamin D3 supplementation from 1 to 12 months; n = 70 returned for follow-up at 3-years. OUTCOME MEASURES: The main outcome was GMD using the Peabody Developmental Motor Scales-2 which includes gross motor quotient (GMQ) and stationary, locomotion and object manipulation subtests. RESULTS: GMQ scores were normal (≥85) in 94 %. An interaction between dosage group and season-at-birth (p = 0.01) was observed for GMQ and stationary standardized score; among winter/spring born children, the 1200 IU/d scored higher vs. 400 and 800 IU/d groups. Object manipulation standardized score was higher (p = 0.04) in children in the 1200 vs. 400 IU/d group, without interaction with season-at-birth. CONCLUSIONS: GMD in young children who received 400 IU/d of supplemental vitamin D in infancy is not influenced by season-at-birth. This dose of vitamin D of 400 IU/d as recommended in North America adequately supports GMD. The modest enhancement in GMD with 1200 IU/d in winter/spring born children requires further study.

Correction of neonatal vitamin D status using 1000 IU vitamin D/d increased lean body mass by 12 months of age compared with 400 IU/d: a randomized controlled trial.

BACKGROUND: Intrauterine exposure to maternal vitamin D status <50 nmol/L of serum 25-hydroxyvitamin D [25(OH)D] may adversely affect infant body composition. Whether postnatal interventions can reprogram for a leaner body phenotype is unknown. OBJECTIVES: The primary objective was to test whether 1000 IU/d of supplemental vitamin D (compared with 400 IU/d) improves lean mass in infants born with serum 25(OH)D <50 nmol/L. METHODS: Healthy, term, breastfed infants (Montréal, Canada, March 2016-2019) were assessed for serum 25(OH)D (immunoassay) 24-36 h postpartum. Infants with serum 25(OH)D <50nmol/L at 24-36 h were eligible for the trial and randomly assigned at baseline (1 mo postpartum) to 400 (29 males, 20 females) or 1000 IU/d (29 males, 20 females) of vitamin D until 12 mo. Infants (23 males, 18 females) with 25(OH)D ≥50 nmol/L (sufficient) formed a nonrandomized reference group provided 400 IU/d. Anthropometry, body composition (DXA), and serum 25(OH)D concentrations were measured at 1, 3, 6, and 12 mo. RESULTS: At baseline, mean ± SD serum 25(OH)D concentrations in infants allocated to the 400 and 1000 IU/d vitamin D groups were 45.8 ± 14.1 and 47.6 ± 13.4, respectively; for the reference group it was 69.2 ± 16.4 nmol/L. Serum 25(OH)D concentration increased on average to ≥50 nmol/L in the trial groups at 3-12 mo. Lean mass varied differently between groups over time; at 12 mo it was higher in the 1000 IU/d vitamin D group than in the 400 IU/d group (mean ± SD: 7013 ± 904.6 compared with 6690.4 ± 1121.7 g, P = 0.0428), but not the reference group (mean ± SD: 6715.1 ± 784.6 g, P = 0.19). Whole-body fat mass was not different between the groups over time. CONCLUSIONS: Vitamin D supplementation (400 or 1000 IU/d) during infancy readily corrects vitamin D status, whereas 1000 IU/d modestly increases lean mass by 12 mo. The long-term implications require further research. This trial was registered at clinicaltrials.gov as NCT02563015.

Maternal excess adiposity and serum 25-hydroxyvitamin D < 50 nmol/L are associated with elevated whole body fat mass in healthy breastfed neonates.

BACKGROUND: Vitamin D status of pregnant women is associated with body composition of the offspring. The objective of this study was to assess whether the association between maternal vitamin D status and neonatal adiposity is modified by maternal adiposity preconception. METHODS: Healthy mothers and their term appropriate weight for gestational age (AGA) infants (n = 142; 59% male, Greater Montreal, March 2016-2019) were studied at birth and 1 month postpartum (2-6 weeks). Newborn (24-36 h) serum was collected to measure total 25-hydroxyvitamin D [25(OH)D] (immunoassay); maternal pre-pregnancy BMI was obtained from the medical record. Anthropometry, body composition (dual-energy X-ray absorptiometry) and serum 25(OH)D were measured at 2-6 weeks postpartum in mothers and infants. Mothers were grouped into 4 categories based on their vitamin D status (sufficient 25(OH)D ≥ 50 nmol/L vs. at risk of being insufficient < 50 nmol/L) and pre-pregnancy BMI (< 25 vs. ≥25 kg/m2): insufficient-recommended weight (I-RW, n = 24); insufficient-overweight/obese (I-OW/O, n = 21); sufficient-recommended weight (S-RW, n = 69); and sufficient-overweight/obese (S-OW/O, n = 28). Partial correlation and linear fixed effects model were used while adjusting for covariates. RESULTS: At birth, infant serum 25(OH)D mean concentrations were below 50 nmol/L, the cut-point for sufficiency, for both maternal pre-pregnancy BMI categories; 47.8 [95%CI: 43.8, 51.9] nmol/L if BMI < 25 kg/m2 and 38.1 [95%CI: 33.5, 42.7] nmol/L if BMI ≥25 kg/m2. Infant serum 25(OH)D concentrations at birth (r = 0.77; P < 0.0001) and 1 month (r = 0.59, P < 0.0001) were positively correlated with maternal postpartum serum 25(OH)D concentrations. Maternal serum 25(OH)D concentration was weakly correlated with maternal percent whole body fat mass (r = - 0.26, P = 0.002). Infants of mothers in I-OW/O had higher fat mass versus those of mothers in S-OW/O (914.0 [95%CI: 766.4, 1061.6] vs. 780.7 [95%CI: 659.3, 902.0] g; effect size [Hedges' g: 0.42]; P = 0.04 adjusting for covariates) with magnitude of difference of 220.4 g or ~ 28% difference. CONCLUSIONS: Maternal and neonatal vitamin D status are positively correlated. In this study, maternal adiposity and serum 25(OH)D < 50 nmol/L are dual exposures for neonatal adiposity. These findings reinforce the importance of vitamin D supplementation early in infancy irrespective of vitamin D stores acquired in utero and maternal weight status.

Disparities in Vitamin D Status of Newborn Infants from a Diverse Sociodemographic Population in Montreal, Canada.

BACKGROUND: Vitamin D status at birth is reliant on maternal-fetal transfer of vitamin D during gestation. OBJECTIVES: We aimed to examine the vitamin D status of newborn infants in a diverse population and to subsequently identify the modifiable correlates of vitamin D status. METHODS: In this cross-sectional study, healthy mother-infant dyads (n = 1035) were recruited within 36 h after term delivery (March 2016-March 2019). Demographic and lifestyle factors were surveyed. Newborn serum 25-hydroxyvitamin D [25(OH)D] was measured (standardized chemiluminescence immunoassay) and categorized as deficient [serum 25(OH)D <30 nmol/L] or adequate (≥40 nmol/L). Serum 25(OH)D was compared among categories of maternal characteristics using ANOVA; each characteristic was tested in a separate model. Subgroups (use of multivitamins preconception and continued in pregnancy compared with during pregnancy only) were matched (n = 352/group) for maternal factors (ancestry, age, income, education, parity, and prepregnancy BMI) using propensity scores; logistic regression models were generated for odds of deficiency or adequacy. RESULTS: Infants' mean serum 25(OH)D was 45.9 nmol/L (95% CI: 44.7, 47.0 nmol/L) (n = 1035), with 20.8% (95% CI: 18.3%, 23.2%) deficient and 60.7% (95% CI: 55.2%, 66.2%) adequate. Deficiency prevalence ranged from 14.6% of white infants to 41.7% of black infants. Serum 25(OH)D was higher (P < 0.0001) in infants of mothers with higher income, BMI < 25 kg/m2, exercise and sun exposure in pregnancy, and use of multivitamins preconception. In the matched-subgroup analysis, multivitamin supplementation preconception plus during pregnancy relative to only during pregnancy was associated with lower odds for vitamin D deficiency (ORadj: 0.55; 95% CI: 0.36, 0.86) and higher odds for adequate vitamin D status (ORadj: 1.47; 95% CI: 1.04, 2.07). CONCLUSIONS: In this study most newborn infants had adequate vitamin D status, yet one-fifth were vitamin D deficient with disparities between population groups. Guidelines for a healthy pregnancy recommend maternal use of multivitamins preconception and continuing in pregnancy. An emphasis on preconception use may help to achieve adequate neonatal vitamin D status.This trial was registered at clinicaltrials.gov as NCT02563015.

Vitamin D Status of Infants of Mothers with Gestational Diabetes: Status at Birth and a Randomized Controlled Trial of Vitamin D Supplementation across Infancy.

BACKGROUND: Vitamin D status and requirements of infants of women with gestational diabetes mellitus (GDM) are unclear. OBJECTIVES: The objectives were to assess vitamin D status in infants of mothers with GDM and compare vitamin D status in response to 400 vs. 1000 IU/d vitamin D supplementation in infants born with serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L. METHODS: Women with GDM delivering full-term infants (n = 98; March 2017-2019, Montreal, Canada) were surveyed for demographic and lifestyle factors. Pregnancy history was obtained from medical records. Newborn serum 25(OH)D was measured (immunoassay) and categorized as <30 (deficient) or ≥40 nmol/L (adequate). Breastfed neonates (n = 16) with serum 25(OH)D <50 nmol/L at birth were randomly assigned to 400 or 1000 IU/d of supplemental cholecalciferol (vitamin D3), and serum 25(OH)D was measured at baseline (≤1 mo) and 3, 6, and 12 mo of age. Groups were compared using a linear mixed-effects model and Tukey-Kramer post hoc tests. RESULTS: Mean newborn serum 25(OH)D was 46.4 (95% CI: 43.9, 49.9) nmol/L, with 15.3% (95% CI: 8.2%, 22.4%) <30 nmol/L and 61.2% (95% CI: 51.6%, 70.9%) ≥40 nmol/L. During the trial, most infants were breastfed to 3 mo (400 IU/d: 87.5%; 1000 IU/d: 75.0%). Mean (± SEM) infant serum 25(OH)D was higher in the 1000-IU/d group at 3 mo (79.9 ± 5.9 vs. 111.5 ± 15.2 nmol/L; P = 0.0263), and although not different at 6-12 mo, was maintained at >50 nmol/L. CONCLUSIONS: Most infants of women with GDM had adequate vitamin D status in this study. In those born with serum 25(OH)D <50 nmol/L, vitamin D status was corrected by 3 mo of age in response to 400 or 1000 IU/d of supplemental vitamin D. Dietary guidance should continue to recommend that all women who could become pregnant take a multivitamin supplement and that breastfed infants receive 400 IU/d of supplemental vitamin D. This study and ancillary trial were registered at clinicaltrials.gov (https://www. CLINICALTRIALS: gov/ct2/show/NCT02563015) as NCT02563015.

Patterns of Bone Mineral Accretion and Sex Differences in Healthy Term Vitamin D Replete and Breastfed Infants From Montreal, Canada: Bone Mass Reference Data.

Infancy is a period of rapid bone growth and mineral accretion; nonetheless, reference data remain scarce for this age group. The purpose of this report is to generate reference data for bone mass in breastfed vitamin D replete infants and investigate patterns of bone mineral accretion and sex differences. This is a secondary analysis from a double-blinded randomized controlled trial (NCT00381914). Healthy term breastfed (exclusively or mixed) infants were randomized to different doses of oral vitamin D supplementation (400-1600 IU/d) and followed prospectively from 1 to 12 mo. Plasma 25-hydroxyvitamin D (LC-MS/MS), bone mineral content (BMC; whole body (WB) and lumbar spine (LS)) and bone mineral density (BMD; LS) were measured at 1, 3, 6, 9, and 12 mo by dual-energy x-ray absorptiometry (Hologic Discovery 4500A) with no effect of supplementation on bone outcomes. For the purpose of this analysis, 63 infants with adequate plasma 25-hydroxyvitamin D ≥ 50 nmol/L at baseline, were included. Differences over time and between sexes were tested using mixed model repeated measures ANOVA. Infants (31 males, 32 females) were 39.5 ± 1.1 wk gestational age at birth and appropriate for gestational age. WB BMC, LS BMC, and LS BMD increased by 143.2%, 116.8%, and 31.1% respectively across infancy. WB BMC was higher (4.2% - 9.4%; p = 0.03) in males than in females across the study. After adjusting WB BMC for weight, length or head BMC, sex differences were not evident. LS BMC and LS BMD did not vary by sex. LS BMD growth charts for both sexes combined, were generated using LMS chartmaker. WB BMC more than doubles during the first year of life confirming the importance of skeletal growth and the need for age-specific reference data in infancy. Sex differences in BMC, if any, are mostly driven by differences in body size.

Inadequate vitamin D status is associated with lower food plus supplemental intake of vitamin D in children of South Asian ethnicity living in the National Capital Region of Canada.

Vitamin D status, measured in a Vitamin D Standardization Program certified laboratory, was assessed among children of South Asian and European ethnicity living in the national capital region of Canada to explore factors that may account for inadequate status. Demographic information, dietary and supplemental vitamin D over 30 d prior to measurement of serum 25-hydroxyvitamin D (25OHD), and anthropometry were measured (age 6.0-18.9 y; n = 58/group; February-March 2015). No group related differences in age, height and body mass index (BMI) Z-scores or in food vitamin D intakes were observed. Standardized serum 25OHD was lower in South Asian children (mean ± SD: 39.0 ± 16.8 nmol/L vs. European: 58.4 ± 15.8 nmol/L). A greater proportion of South Asian children had serum 25OHD <40 nmol/L (56.9 vs. 8.6%, P < 0.0001) and fewer took supplements (31 vs. 50%, P = 0.0389). In a multi-factorial model (r2 = 0.54), lower vitamin D status was associated with overweight/obese BMI and older age (14-18 y); no interaction with ethnicity was observed. Lower vitamin D status was associated with lower total vitamin D intake only in South Asian children. This study reinforces the importance of public health actions towards meeting vitamin D intake recommendations among those of high-risk deficiency. Novelty: A higher proportion of South Asian vs. European children had inadequate vitamin D status. Lower vitamin D status was associated with a BMI in the overweight/obese range. Lower vitamin D status was associated with lower total vitamin D intake in South Asian but not European children.

Early prenatal use of a multivitamin diminishes the risk for inadequate vitamin D status in pregnant women: results from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort study.

BACKGROUND: Reports on the adequacy of vitamin D status of pregnant women are not available in Canada. OBJECTIVES: The objectives of this study were to examine vitamin D status across pregnancy and identify the correlates of vitamin D status of pregnant women in Canada. METHODS: Pregnant women (≥18 years) from 6 provinces (2008-2011) participating in a longitudinal cohort were studied. Sociodemographic data, obstetrical histories, and dietary and supplemental vitamin D intakes were surveyed. Plasma 25-hydroxyvitamin D (25OHD) was measured using an immunoassay standardized to LC-MS/MS from samples collected during the first (n = 1905) and third trimesters (n = 1649) and at delivery (n = 1543). The proportion of women with ≥40 nmol/L of plasma 25OHD (adequate status) was estimated at each time point, and factors related to achieving this cut point were identified using repeated-measures logistic regression. Differences in 25OHD concentrations across trimesters and at delivery were tested a using repeated-measures ANOVA with a post hoc Tukey's test. RESULTS: In the first trimester, 93.4% (95% CI: 92.3%-94.5%) of participants had 25OHD ≥40 nmol/L. The mean plasma 25OHD concentration increased from the first to the third trimester and then declined by delivery (69.8 ± 0.5 nmol/L, 78.6 ± 0.7 nmol/L, and 75.7 ± 0.7 nmol/L, respectively; P < 0.0001). A lack of multivitamin use early in pregnancy reduced the odds of achieving 25OHD ≥40 nmol/L (ORadj = 0.33; 95% CI: 0.25-0.42) across all time points. Factors associated with not using a prenatal multivitamin included multiparity (ORadj = 2.08; 95% CI: 1.42-3.02) and a below-median income (ORadj = 1.39; 95% CI: 1.02-1.89). CONCLUSIONS: The results from this cohort demonstrate the importance of early multivitamin supplement use to achieve an adequate vitamin D status in pregnant women.

Longitudinal Assessment of Vitamin D Status across Trimesters of Pregnancy.

BACKGROUND: The evolution of vitamin D status across pregnancy trimesters and its association with prepregnancy body mass index (ppBMI; in kg/m2) remain unclear. OBJECTIVES: We aimed to 1) assess trimester-specific serum total 25-hydroxyvitamin D [25(OH)D] concentrations, 2) compare those concentrations between ppBMI categories, and 3) examine associations between 25(OH)D concentrations, ppBMI, and vitamin D intake. METHODS: As part of a prospective cohort study, 79 pregnant women with a mean age of 32.1 y and ppBMI of 25.7 kg/m2 were recruited in their first trimester (average 9.3 weeks of gestation). Each trimester, vitamin D intake was assessed by 3 Web-based 24-h recalls and a Web questionnaire on supplement use. Serum total 25(OH)D was measured by LC-tandem MS. Repeated-measures ANOVA was performed to assess the evolution of 25(OH)D concentrations across trimesters of pregnancy and comparisons of 25(OH)D concentrations between ppBMI categories were assessed by 1-factor ANOVAs. Stepwise regression analyses were used to identify determinants of 25(OH)D concentrations in the third trimester. RESULTS: Mean ± SD serum total 25(OH)D concentrations increased across trimesters, even after adjustments for ppBMI, seasonal variation, and vitamin D intake from supplements (67.5 ± 20.4, 86.5 ± 30.9, and 88.3 ± 29.0 nmol/L at mean ± SD 12.6 ± 0.8, 22.5 ± 0.8, and 33.0 ± 0.6 weeks of gestation, respectively; P < 0.0001). In the first and third trimesters, women with a ppBMI ≥30 had lower serum total 25(OH)D concentrations than women with a ppBMI <25 (P < 0.05); however, most had concentrations >40nmol/L by the second trimester. Vitamin D intake from supplements was the strongest determinant of third-trimester serum total 25(OH)D concentrations (r2 = 0.246, ß = 0.51; P < 0.0001). CONCLUSIONS: There was an increase in serum total 25(OH)D concentrations across trimesters, independent of ppBMI, seasonal variation, and vitamin D intake from supplements. Almost all women had serum total 25(OH)D concentrations over the 40- and 50-nmol/L thresholds, thus our study supports the prenatal use of a multivitamin across pregnancy.

Effect of Vitamin D Supplementation in Early Life on Children's Growth and Body Composition: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Vitamin D deficiency during pregnancy or infancy is associated with adverse growth in children. No systematic review has been conducted to summarize available evidence on the effect of vitamin D supplementation in pregnancy and infancy on growth and body composition in children. OBJECTIVE: We aim to summarize the available evidence on the effect of vitamin D supplementation in pregnancy and infancy on child growth and body composition. METHOD: A systematic review and meta-analysis were performed on the effects of vitamin D supplementation during early life on children's growth and body composition (bone, lean and fat). A literature search of randomized controlled trials (RCTs) was conducted to identify relevant studies on the effects of vitamin D supplementation during pregnancy and infancy on children's body composition (bone, lean and fat) in PubMed, EMBASE and Cochrane Library from inception to 31 December 2020. A Cochrane Risk Assessment Tool was used for quality assessment. The comparison was vitamin D supplementation vs. placebo or standard care. Random-effects and fixed-effect meta-analyses were conducted. The effects are presented as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 3960 participants from eleven randomized controlled trials were eligible for inclusion. Vitamin D supplementation during pregnancy was associated with higher triceps skinfold thickness (mm) (MD 0.33, 95% CI, 0.12, 0.54; I2 = 34%) in neonates. Vitamin D supplementation during pregnancy or infancy was associated with significantly increased length for age z-score in infants at 1 year of age (MD 0.29, 95% CI, 0.03, 0.54; I2 = 0%), and was associated with lower body mass index (BMI) (kg/m2) (MD -0.19, 95% CI -0.34, -0.04; I2 = 0%) and body mass index z-score (BMIZ) (MD -0.12, 95% CI -0.21, -0.04; I2 = 0%) in offspring at 3-6 years of age. Vitamin D supplementation during early life was not observed to be associated with children's bone, lean or fat mass. CONCLUSION: Vitamin D supplementation during pregnancy or infancy may be associated with reduced adiposity in childhood. Further large clinical trials of the effects of vitamin D supplementation on childhood body composition are warranted.

Individual participant data (IPD)-level meta-analysis of randomised controlled trials with vitamin D-fortified foods to estimate Dietary Reference Values for vitamin D.

CONTEXT AND PURPOSE: Individual participant data-level meta-regression (IPD) analysis is superior to meta-regression based on aggregate data in determining Dietary Reference Values (DRV) for vitamin D. Using data from randomized controlled trials (RCTs) with vitamin D3-fortified foods, we undertook an IPD analysis of the response of winter serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among children and adults and derived DRV for vitamin D. METHODS: IPD analysis using data from 1429 participants (ages 2-89 years) in 11 RCTs with vitamin D-fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D DRV estimates across a range of serum 25(OH)D thresholds using unadjusted and adjusted models. RESULTS: Our IPD-derived estimates of vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25 and ≥ 30 nmol/L are 6 and 12 µg/day, respectively (unadjusted model). The intake estimates to maintain 90%, 95% and 97.5% of concentrations ≥ 50 nmol/L are 33.4, 57.5 and 92.3 µg/day, respectively (unadjusted) and 17.0, 28.1 and 43.6 µg/day, respectively (adjusted for mean values for baseline serum 25(OH)D, age and BMI). CONCLUSIONS: IPD-derived vitamin D intakes required to maintain 90%, 95% and 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L are much higher than those derived from standard meta-regression based on aggregate data, due to the inability of the latter to capture between person-variability. Our IPD provides further evidence that using food-based approaches to achieve an intake of 12 µg/day could prevent vitamin D deficiency (i.e., serum 25(OH)D < 30 nmol/L) in the general population.

Increased adiposity in children with obesity is associated with low red blood cell omega-3 fatty acid status and inadequate polyunsaturated fatty acid dietary intake.

The association between total dietary fat intake and measures of body fatness in children with obesity remains inconsistent. This study aimed to determine whether dietary long-chain polyunsaturated fatty acids (LCPUFA) and LCPUFA status relate to body composition in children with obesity. Children (n = 63, 9.0 ± 0.2 year, BMI Z-score 3.1 ± 0.2) were divided into tertiles of percentage body fat assessed by dual-energy X-ray absorptiometry. Diet was assessed 3-days food diaries. Fatty acid proportions in red blood cells (RBC) were measured by gas chromatography. Data stratified by sex and Tanner stages were compared with a MIXED model ANOVA. Associations between RBC fatty acid status and dietary intakes were examined with Spearman correlation. Moderate correlations were observed between RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) proportions, dietary EPA and DHA (r = 0.39, P < .05) as well as fish servings (r = 0.33, P < .05). Dietary LCPUFA did not differ among tertiles. Children in tertile 3 had lower RBC α-linolenic acid (-40%) and EPA + DHA (-15%) proportions adjusted for age, Tanner stages and race compared with tertile 1. The lower omega-3 LCPUFA status in children with greater adiposity is consistent with suboptimal intakes of omega-3 LCPUFA and fish in the diet.

Lean body mass accretion is elevated in response to dietary vitamin D: A dose-response study in female weanling rats.

Vitamin D status positively relates to lean body mass in infants. This study tested the effect of vitamin D on body composition and growth-related hormones. It was hypothesized that low vitamin D status programs for higher fat mass accretion. Female weanling Sprague-Dawley rats (4 weeks; n = 6/diet) were randomized to AIN-93G diets with modified vitamin D contents for 8 weeks: group 1 (1 IU vitamin D3/g diet), group 2 (2 IU vitamin D3/g diet), and group 3 (4 IU vitamin D3/g diet). At week 0, 4, and 8 of study, measurements included: serum 25(OH)D3, IGF-1, IGFBP3, leptin, and whole body composition assessed with DXA. Differences among groups were tested using mixed model ANOVA with Tukey's post hoc t-tests. No differences were observed in baseline body composition and biomarkers, nor did body weight and food intake differ over the study. At week 8, serum 25(OH)D3 in group 3 was higher (P < .0001) compared to groups 1 and 2. At 8 weeks, lean mass (P < .05) and lean mass accretion (P < .05) were significantly higher in groups 2 and 3 compared to group 1. Serum IGF-1 concentration declined over time (P < .001) with smaller declines at week 8 in group 3 (P < .05). Serum IGFBP3 concentration was lower at week 4 in group 2 compared to groups 1 and 3. Serum leptin concentration and fat mass were not affected by diet. These results suggested that the achievement of higher vitamin D status may support a lean body phenotype without altering weight gain.

Maternal risk factors and newborn infant vitamin D status: a scoping literature review.

Low vitamin D (VitD) status is common among newborn infants, more so in temperate latitudes with evidence that maternal VitD deficiency is a major risk factor given that the neonate relies solely on maternal-fetal transfer of VitD. This scoping review was conducted to provide an overview of the latest evidence from studies regarding the impact of maternal risk factors on infant 25-hydryoxyvitamin D [25(OH)D] concentrations with a focus on studies in Canada and the United States. Several maternal risk factors that contribute to low maternal-fetal 25(OH)D concentrations have been reported over many decades, but no clear pattern has been established for multiethnic populations. For example, darker skin pigmentation and ethnicity are common risk factors for low VitD status. Studies in predominantly white women showed that supplementation of VitD during pregnancy causes significant increases in maternal serum 25(OH)D which often improves cord serum 25(OH)D values. In addition, VitD recommendations by health care professionals and adherence to supplementation by pregnant women appear to positively influence maternal and infant 25(OH)D concentrations. Conversely, winter season, obesity, lower socioeconomic status including lifestyle factors (smoking), and use of medication pose risk for lower maternal-fetal transfer of VitD. However, there is still a dearth of pertinent data on the relationship between some of the maternal risk factors and newborn 25(OH)D concentrations, for instance, relationships between gestational diabetes and neonatal VitD status. Additional research is required to determine if the same target for 25(OH)D concentrations applies for pregnant women, neonates, and infants.

Effect of Vitamin D Supplementation, Food Fortification, or Bolus Injection on Vitamin D Status in Children Aged 2-18 Years: A Meta-Analysis.

Meta-analyses on the effect of vitamin D intake on status in children are lacking, especially those focused on vitamin D-fortified foods. The objective of this meta-analysis was to investigate the effect of vitamin D interventions (fortified foods, supplements, bolus injections) on vitamin D status in children 2-18 y of age. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, literature searches were conducted up to December 2016. Randomized placebo-controlled vitamin D interventions in healthy children aged 2-18 y were included. A random-effects model was used with I2 assessing heterogeneity. We included 26 trials (5403 children) with interventions (n = 9 fortified foods, n = 15 supplements, n = 2 bolus injections) from 100-4000 IU vitamin D/d over 4 wk to 2 y. The serum 25-hydroxyvitamin D [25(OH)D] weighted mean difference for all 26 trials (23.5 nmol/L; 95% CI: 20.7, 26.3 nmol/L; I2 = 99.9%) resulted in a mean increase of 1.0 nmol/L (95% CI: 0.3, 1.7 nmol/L) for each increase of 100 IU vitamin D/d (per 1 µg/d : 0.4 nmol/L; 95% CI: 0.1, 0.7 nmol/L). The response per 100 IU vitamin D/d was greater in trials with a mean baseline serum 25(OH)D <30 nmol/L, with the use of fortified foods and with baseline vitamin D intakes <100 IU/d. In conclusion, the serum 25(OH)D response to vitamin D intake differs on the basis of baseline status, intakes, and delivery mode, but not age, sex, or latitude.

Vitamin D Status and Immune Health Outcomes in a Cross-Sectional Study and a Randomized Trial of Healthy Young Children.

In young children, the relationship between vitamin D and biomarkers of immune function is not well elucidated. The objective was to investigate relationships between vitamin D and immune function in young children. Data were from a cross-sectional study (study 1) of healthy children 1.8⁻5.9 years (n = 457) and a 12 weeks trial using vitamin D fortified foods (study 2) in healthy 1.8⁻8.7 years old (n = 77) in Montreal, Canada. Vitamin D status and ex vivo immune function were assessed. In study 1 (male: n = 242; 53%), plasma IL-6, TNFα and CRP were significantly higher (p < 0.05) in children with 25-hydroxyvitamin D (25(OH)D) ≥ 75 nmol/L compared to.