[This corrects the article DOI: 10.1016/j.eclinm.2025.103682.].

BACKGROUND:Randomised trials have shown that pregnancy vitamin D supplementation results in greater offspring bone mineral density (BMD) in childhood. The effect of this intervention on bone microarchitecture, a further determinant of bone strength, and possible interactions with genetic variation in vitamin D metabolism, have not previously been investigated. We investigated these in a post hoc analysis of a randomised controlled trial. METHODS:MAVIDOS was a randomised placebo-controlled trial of 1000 IU/day cholecalciferol from 14 to 17 weeks' gestation until delivery. Offspring tibial bone microarchitecture was assessed at age 6-7 years using high resolution peripheral quantitative computed tomography (HR-pQCT; Stratec Xtreme CTII). Maternal and child genotype at four single nucleotide polymorphisms (SNPs) [rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), rs2282679 (GC)] was determined using serum samples. Differences in bone microarchitecture by randomisation were assessed using linear regression, and additionally across clusters of bone microarchitecture phenotypes generated using cluster analysis approaches. RESULTS:222 children (placebo n = 110, cholecalciferol n = 112) were included. No significant differences in cross-sectional area, cortical thickness or porosity, trabecular thickness or number, or volumetric BMD (total, cortical or trabecular) were found using linear regression, and there was no interaction with either maternal or offspring SNP genetic variants. Three phenotypic bone clusters were generated. Differences in child anthropometry were evident across clusters, but the proportion of mothers randomised to cholecalciferol was similar across the clusters (p = 1.0). CONCLUSION:In this subset of children born to mothers participating in a trial of vitamin D supplementation in pregnancy, no effect of the supplementation on tibial microarchitecture was observed.

The effect of pregnancy vitamin D supplementation on bone mineral density (BMD) in the mother immediately after delivery and at 4 years after delivery was assessed in a randomised placebo-controlled trial. The mothers’ BMD did not differ between the two intervention groups. Vitamin D supplementation during pregnancy has positive effects on the offspring’s bone development and bone mineral density (BMD) in childhood, but there are limited data on the effects on the mother’s skeleton. We assessed this in a post hoc follow-up of a randomised trial. MAVIDOS was a randomised placebo-controlled trial of 1000 IU/day cholecalciferol from 14 to 17 weeks gestation until delivery. Participants were invited to have a dual-energy X-ray absorptiometry (DXA) scan of the whole body, lumbar spine (LS) and left hip within 2 weeks after delivery and again 4 years after delivery. BMD was compared between the cholecalciferol and placebo groups; in women with DXA at both time points, the effect of cholecalciferol was assessed using mixed effects modelling to account for repeated measures. Four hundred one and 443 participants had a DXA within 2 weeks after delivery and at a mean of 4.1 years after delivery, respectively. Cholecalciferol supplementation increased serum 25-hydroxyvitamin D status in late pregnancy compared to placebo. BMD at all sites was similar between the two randomisation groups at both time points (p > 0.05 for all). Two hundred sixty-three participants had a DXA at both birth and 4 years. BMD increased between 1 and 6

We aimed to investigate associations between diabetes mellitus and incident fracture, stratified by diabetes type (1 or 2), disease duration and microvascular complications of diabetes. This prospective cohort analysis used data from the UK Biobank, a large population-based cohort of participants recruited 2006-2010 at age 40-69 yr. The exposure was type 1 or type 2 diabetes at baseline, with the outcome of first incident osteoporotic fracture. Poisson regression was used to calculate incidence rate ratios (IRRs) for osteoporotic fracture to investigate prospective relationships between diabetes type 1 or 2 and fracture risk independent of traditional clinical risk factors, estimated BMD by heel ultrasound (eBMD), adiposity, and C-reactive protein (CRP). The role of diabetic microvascular complications and associations between diabetes duration and fracture risk were studied. There were 498 949 participants (271 882 women, mean age 56 yr; 227 067 men, 57 yr). In fully adjusted models, type 1 and 2 diabetes were associated with increased fracture risk [type 1; IRR: 2.93 (95% CI: 2.37, 3.62); type 2: 1.25 (1.14, 1.38)], similar by sex. The magnitude of risk associated with type 2 diabetes increased with the duration of disease. Increasing number of microvascular complications was associated with greater fracture risk [any vs no complications, IRR 2.03 (1.57, 2.62)]. Diabetes is associated with increased risk of fracture (magnitude of effect greater in type 1 than type 2 diabetes). Associations were partly independent of traditional risk factors, adiposity, eBMD, and CRP. Type 2 diabetes disease duration and the presence of microvascular complications in both types were dose-dependent risk factors for fracture.

Observational studies have suggested negative associations between maternal 25-hydroxyvitamin D (25(OH)D) status and risk of hypertensive disorders of pregnancy [pregnancy-induced hypertension (PIH) and preeclampsia (PET)]. Data from intervention studies are limited. We hypothesised that vitamin D supplementation would lower maternal blood pressure (BP) during pregnancy and reduce the incidence of hypertensive disorders of pregnancy. The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a randomised placebo-controlled trial. Pregnant women with a baseline 25(OH)D of 25–100 nmol/l were randomized to either 1000 IU/day cholecalciferol or placebo from 14 to 17 weeks’ gestation until delivery. BP recordings documented during routine clinical pregnancy care were obtained from clinical records and grouped into gestational windows based on the schedule for routine antenatal care in the United Kingdom (23+0–24+6, 27+0–28+6, 33+0–35+6, 37+0–38+6, 39+0–40+6 and ≥ 41+0 weeks+days). Systolic and diastolic BP measurements in these gestational windows were compared between randomisation groups. Diagnoses of PIH or PET (in accordance with national guidelines) and the use of antihypertensive agents were also noted and compared between groups. Data for 734 women (366 cholecalciferol, 368 placebo) were included. Maternal mean systolic and diastolic BP did not differ between the randomization groups at any of the gestations studied. The incidences of PIH (placebo 1.6

Smoking in adulthood increases fracture risk. In a prospective birth cohort study including 1966 children, we found that smoking before and during pregnancy were positively associated with the offspring BMD in childhood, but with attenuation by weight. This highlights the complex relationship between maternal smoking and offspring bone development. Inconsistent relationships between smoking in pregnancy and offspring bone mineral density (BMD) have been reported. We investigated the relationships between maternal smoking before and during pregnancy with offspring bone outcomes measured by dual-energy X-ray absorptiometry (DXA) during early childhood. In the Southampton Women’s Survey, maternal smoking was determined before pregnancy and at 11 and 34 weeks’ gestation. Offspring had DXA at birth (whole body), 4, 6–7 and 8–9 years (whole-body-less-head). Linear regression was used to examine the associations between maternal smoking and standardised bone area (BA), bone mineral content (BMC), BMD and bone mineral apparent density (BMAD). Adjustment for maternal educational qualification, diet, ethnicity, age and parity (all identified by directed acyclic graph) and offspring age and sex was performed. The child’s weight was additionally added to assess mediation of the association. A total of 1966 mother–offspring dyads were included; 25.7

Background: Findings from the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial demonstrated a positive effect of gestational cholecalciferol supplementation on offspring bone mineral density (BMD) at age 4 y. Demonstrating the persistence of this effect is important to understanding whether maternal vitamin D supplementation could be a useful public health strategy to improving bone health. Objectives: We investigated whether gestational vitamin D supplementation increases offspring BMD at ages 6-7 y in an exploratory post-hoc analysis of an existing trial. Methods: In the MAVIDOS randomized controlled trial, pregnant females < 14 wk' gestation with a singleton pregnancy and serum 25-hydroxyvitamin D 25-100nmol/l at 3 United Kingdom hospitals (Southampton, Sheffield, and Oxford) were randomly assigned to either 1000 IU/d cholecalciferol or placebo from 14 to 17-wk gestation until delivery. Offspring born at term to participants recruited in Southampton were invited to the childhood follow-up at ages 4 and 6-7 y. The children had a dual-energy X-ray absorptiometry (DXA, Hologic discovery) scan of whole-body-less-head (WBLH) and lumbar spine, from which bone area, bone mineral content (BMC), BMD, and bone mineral apparent density (BMAD) were derived. Linear regression was used to compare the 2 groups adjusting for age, sex, height, weight, duration of consumption of human milk, and vitamin D use at 6-7 y. Results: A total of 454 children were followed up at ages 6-7 y, of whom 447 had a usable DXA scan. Gestational cholecalciferol supplementation resulted in higher WBLH BMC [0.15 SD, 95% confidence interval (CI): 0.04, 0.26], BMD (0.18 SD, 95% CI: 0.06, 0.31), BMAD (0.18 SD, 95% CI: 0.04, 0.32), and lean mass (0.09 SD, 95% CI: 0.00, 0.17) compared with placebo. The effect of pregnancy cholecalciferol on bone outcomes was similar at ages 4 and 6-7 y. Conclusions: Supplementation with cholecalciferol 1000 IU/d during pregnancy resulted in greater offspring BMD and lean mass in mid-childhood compared with placebo in this exploratory post-hoc analysis. These findings suggest that pregnancy vitamin D supplementation may be an important population health strategy to improve bone health.

Introduction: Poor cognitive function and osteoporosis commonly co-exist in later life. In women, this is often attributed to post-menopausal estrogen loss. However, a common early life origin for these conditions and the associations between cognitive function and bone mineral density (BMD) in childhood have not previously been explored. We examined these relationships at age 6-7 years in the Southampton Women's Survey (SWS) motheroffspring cohort. Methods: Child occipitofrontal circumference (OFC), a proxy for brain volume, intelligence quotient (IQ) [Wechsler Abbreviated Scale of Intelligence] and visual recognition and working memory [CANTAB (R) Delayed Matching to Sample (DMS) and Spatial Span Length (SSP), respectively] were assessed. Whole-body-less-head (WBLH) and lumbar spine dual-energy X-ray absorptiometry [Hologic Discovery] (DXA) were performed to measure bone area (BA), bone mineral content (BMC), BMD and bone mineral apparent density (BMAD). Linear regression was used to examine associations between age and sex standardized variables (beta represent standard deviation (SD) difference per SD of cognitive function). Results: DXA was performed in 1331 children (mean (SD) age 6.8 (0.33) years, 51.5 % male), with OFC, IQ, DMS and SSP assessed in 1250, 551, 490 and 460, respectively. OFC (beta = 0.25 SD/SD, 95%CI 0.20,0.30), IQ (beta = 0.11 SD/SD, 95%CI 0.02,0.19), and DMS (beta = 0.11, SD/SD, 95%CI 0.01,0.20) were positively associated with WBLH BA, with similar associations for lumbar spine BA. OFC and DMS were also positively associated with WBLH BMC, but only OFC was associated with BMD (WBLH: beta = 0.38 SD/SD, 95%CI 0.33,0.43; LS: beta = 0.19 SD/SD, 95%CI 0.13,0.24). Conclusion: Childhood brain volume was positively associated with measures of skeletal size and BMD, whereas IQ and memory were associated only with skeletal size. These findings suggest that common early life determinants for skeletal growth and BMD and cognitive function should be explored to identify potential early-life approaches to preventing osteoporosis and cognitive decline.

Objectives: Hypothalamic hamartoma (HH) typically presents with gonadotrophin-dependent precocious puberty and/or seizures. Other endocrine disturbances are rare. We describe an infant with syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) and a HH.Case presentation: A 6-week-old infant presented with seizures and life-threatening hyponatremia. A HH was identified on magnetic resonance imaging. Clinical examination and biochemistry were consistent with SIADH, and serum copeptin was high during hyponatremia, further supporting this diagnosis. Tolvaptan was effective in normalizing plasma sodium and enabling liberalization of fluids to ensure sufficient nutritional intake and weight gain and manage hunger.Conclusions: Hyponatremia due to SIADH is novel at presentation of a HH, and can be challenging to diagnose and manage. Successful management of hyponatremia in this case was achieved using tolvaptan.