Parathyroid hormone-vitamin D dynamics vary according to the definition of vitamin D deficiency in newborn infants.

BACKGROUND: Parathyroid hormone (PTH) is an indirect functional indicator of vitamin D status. Risk of vitamin D deficiency, assessed using circulating 25-hydroxyvitamin D (25(OH)D), is defined as <30 nmol/L by the National Academy of Medicine and alternatively <25 nmol/L in the global consensus recommendation on prevention and management of nutritional rickets. OBJECTIVE: To test PTH concentrations and the odds for elevated values according to vitamin D deficiency cut-points (<30 nmol/L, or <25 nmol/L) in newborn infants. METHODS: Healthy term-born infants (n = 858) were recruited from Montreal, Canada (2016-2019). Obstetric data were obtained from medical records, and demographic factors surveyed. Immunoassays were used to measure newborn (24-36 h) serum PTH and 25(OH)D; 25(OH)D was standardized to National Institute of Standards and Technology (NIST) standard reference materials. Serum PTH was log-transformed before comparing serum 25(OH)D groups (<30 vs. ≥30; or <25 vs. ≥25 nmol/L) using ANCOVA adjusted for infant sex, type of delivery, parity, race, and family income. The odds of elevated PTH (>71.48 pg/mL) were tested using logistic regression, adjusted for the same covariates. RESULTS: Infants (50.2 % female) were 39.6 ± 1.0 weeks gestational age (mean ± SD), and 3.41 ± 0.38 kg. Median serum 25(OH)D was 45.4 (IQR 23.2) nmol/L; 20.5 % had serum 25(OH)D < 30 nmol/L, and 12.4 % <25 nmol/L. Median serum PTH was 30.72 (IQR 33.90) pg/mL, elevated in 12.7 % overall, and higher in infants born with serum 25(OH)D < 25 vs. ≥25 nmol/L (35.96 (IQR 39.20) vs. 30.36 (IQR 32.93) pg/mL, p = 0.0158). The odds of elevated PTH were higher when serum 25(OH)D was <25 nmol/L (ORadj 2.13, 95 % CI: 1.23, 3.69). PTH concentration and the odds of being elevated did not differ according to the 30 nmol/L cut-point. CONCLUSIONS: Based on this study, the definition of vitamin D deficiency relative to bone health as set by the National Academy of Medicine (<30 nmol/L) exceeds the threshold at which PTH is elevated in newborn infants.

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.

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.

Iodine Status of Mother-Infant Dyads from Montréal, Canada: Secondary Analyses of a Vitamin D Supplementation Trial in Breastfed Infants.

BACKGROUND: Most pregnant or lactating women in Canada will not meet iodine requirements without iodine supplementation. OBJECTIVES: To assess the iodine status of 132 mother-infant pairs based on secondary analyses of a vitamin D supplementation trial in breastfed infants from Montréal, Canada. METHODS: Maternal iodine status was assessed using the breastmilk iodine concentration (BMIC). Singleton, term-born infants were studied from 1-36 months of age. Usual (adjusted for within-person variation) iodine intakes were estimated from urinary iodine and creatinine concentrations. Iodine status was assessed using median urinary iodine concentrations (UICs) and by estimating inadequate intakes by the cut-point method using a proposed Estimated Average Requirement for infants 0-6 months of age (72 µg/d). RESULTS: At 1, 3, and 6 months of age, 70%, 63%, and 3% of infants, respectively, were exclusively breastfed. From 1-36 months of age (n = 82-129), the median UICs were ≥100 µg/L (range, 246-403 µg/L), which is the cutoff for adequate intakes set by the WHO for children <2 years. Almost all (98%-99%) infants at 1 and 2 months, 2 and 3 months, and 3 and 6 months of age had usual creatinine-adjusted iodine intakes ≥ 72 µg/d. The median BMIC was higher (P < 0.001) at 1 month compared to 6 months of lactation [1 month, 198 µg/kg (IQR, 124-274; n = 105) and 6 months, 109 µg/kg (IQR, 67-168; n = 78)]. At 1 and 6 months, 96% and 79% of mothers, respectively, had a BMIC ≥ 60 µg/kg, the lower limit of a normal reference range. The percentages of mothers that used a multivitamin-mineral (MVM) supplement containing iodine were 90% in pregnancy and 79% and 59% at 1 and 6 months of lactation, respectively. CONCLUSIONS: The iodine status of infants was adequate throughout infancy. These results support a recommendation that all women who could become pregnant, who are pregnant, or who are breastfeeding take a daily MVM supplement containing iodine.

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.

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.

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.

Maternal Vitamin D Status and Gestational Weight Gain as Correlates of Neonatal Bone Mass in Healthy Term Breastfed Young Infants from Montreal, Canada.

The implications of maternal gestational weight gain (GWG) and vitamin D status to neonatal bone health are unclear. We tested whether maternal 25-hydroxyvitamin D (25(OH)D) and GWG relate to neonatal bone mineral content (BMC) and bone mineral density (BMD). Healthy term appropriate for gestational age breastfed neonates (n = 142) and their mothers were recruited 24-36 h after delivery and followed at 1.0 ± 0.5 month. At birth, obstetric data were collected and newborn serum 25(OH)D was measured. At 1 month, neonatal whole-body (WB) BMC, WB BMC relative to body weight (WB BMC/kg), lumbar spine BMC and BMD, maternal and neonatal 25(OH)D concentrations, and anthropometry were measured. Infant BMC and BMD between maternal 25(OH)D (<50, ≥50 nmol/L) and GWG (insufficient, adequate, and excessive) categories were compared. Maternal 25(OH)D was not related to infant whole-body BMC, BMC/kg, lumbar spine BMC, and BMD. Infants in the excessive maternal GWG category had greater (p = 0.0003) whole-body BMC and BMC/kg and lumbar spine BMC and BMD than inadequate GWG, and greater (p = 0.0063) whole-body BMC/kg and lumbar spine BMC and BMD than adequate GWG. These results suggest that maternal GWG, but not vitamin D status, modestly relates to bone mass in neonates.

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.

Effects of Recording Food Intake Using Cell Phone Camera Pictures on Energy Intake and Food Choice.

BACKGROUND: The well-documented increases in obesity and unhealthy dietary practices substantiate the need for evidence-based tools that can help people improve their dietary habits. The current spread of mobile phone-embedded cameras offers new opportunities for recording food intake. Moreover, the act of taking pictures of food consumed may enhance visual consciousness of food choice and quantity. The present study aimed to assess the effect of using cell phone pictures to record food intake on energy intake and food choice in college students. The effectiveness and acceptability of cell phone picture-based diet recording also was assessed. METHODS: A repeated measures crossover design was used. One group of participants entered their food intake online during 3 days based on their memory, although a second group recorded their food intake using cell phone pictures as their reference. Participants then crossed over to complete 3 more days of diet recording using the alternate method. Focus groups were conducted to obtain feedback on the effectiveness and acceptability of cell phone picture-based diet recording. RESULTS: Intake of meat and vegetable servings were significantly higher in the memory period compared with the cell phone period, regardless of the order. Results from the focus group indicated a positive attitude toward the use of cell phone pictures in recording food intake and an increased awareness of food choice and portion size. LINKING EVIDENCE TO ACTION: Cell phone pictures may be an easy, relevant, and accessible method of diet self-monitoring when aiming at dietary changes. Future trials should combine this technique with healthy eating education.