Gestational vitamin D and offspring fracture risk: do associations persist into mid adolescence?

BACKGROUND: Previous studies report that maternal vitamin D exposure during pregnancy is associated with offspring later-life bone health. A study in the Vitamin D in Pregnancy (VIP) cohort reported sexually dimorphic effects of maternal 25-hydroxyvitamin-D (25(OH)D) and offspring fracture profiles at 10 years of age. We, therefore, aimed to determine associations between maternal 25(OH)D status and offspring fracture risk at 16 years of age in this cohort. METHODS: In total, 475 mother-child pairs were recruited to the VIP study in southeastern Australia. Maternal serum samples were obtained at recruitment (<16 weeks' gestation) and/or 28-32 weeks' gestation and analysed for 25(OH)D. Radiologically-confirmed incident fractures in children were ascertained from date of birth (2002-2004) until July 16, 2019. Cox proportional hazard models were used to determine associations between maternal 25(OH)D and childhood fracture risk, and final models included maternal age at recruitment, offspring sex, birth weight, gestation length and season of 25(OH)D sample. RESULTS: Data were available for 400 children (mean age 16.1 years). There were 122 (30.5%) children who sustained at least one fracture. Higher maternal 25(OH)D (per 10 nmol/L) in early gestation was associated with a decreased fracture risk in boys (HR 0.87; 95% CI: 0.77, 0.99); the pattern was reversed in girls (HR 1.10; 95% CI 1.00, 1.22). At late gestation, higher maternal 25(OH)D was associated with an increased fracture risk in girls (HR 1.14; 95% CI: 1.04, 1.24). CONCLUSIONS: While our findings must be interpreted within the constraints of our limitations, we report that the contradictory risk profiles observed at early childhood in this cohort remain in adolescence.

Incidence and severity of cytomegalovirus infection in seropositive heart transplant recipients.

BACKGROUND: The frequency and significance of cytomegalovirus (CMV) infection in seropositive (R+) heart transplant recipients (HTR) is unclear, with preventative recommendations mostly extrapolated from other groups. We evaluated the incidence and severity of CMV infection in R+ HTR, to identify risk factors and describe outcomes. METHODS: R+ HTR from 2010 to 2019 were included. Antiviral prophylaxis was not routinely used, with clinically guided monitoring the local standard of care. The primary outcome was CMV infection within one-year post-transplant; secondary outcomes included other herpesvirus infections and mortality. RESULTS: CMV infection occurred in 27/155 (17%) R+ HTR. Patients with CMV had a longer hospitalization (27 vs. 20 days, unadjusted HR 1.02, 95% CI 1.00-1.02, p = .01), higher rate of intensive care readmission (26% vs. 9%, unadjusted HR 3.46, 1.46-8.20, p = .005), and increased mortality (33% vs. 8%, unadjusted HR 10.60, 4.52-24.88, p < .001). The association between CMV and death persisted after adjusting for multiple confounders (HR 24.19, 95% CI 7.47-78.30, p < .001). Valganciclovir prophylaxis was used in 35/155 (23%) and was protective against CMV (infection rate 4% vs. 27%, adjusted HR .07, .01-.72, p = .025), even though those receiving it were more likely to have received thymoglobulin (adjusted OR 10.5, 95% CI 2.01-55.0, p = .005). CONCLUSIONS: CMV infection is common in R+ HTR and is associated with a high burden of disease and increased mortality. Patients who received valganciclovir prophylaxis were less likely to develop CMV infection, despite being at higher risk. These findings support the routine use of antiviral prophylaxis following heart transplantation in all CMV R+ patients.

Maternal vitamin D and offspring fracture risk: the Vitamin D in Pregnancy study.

Vitamin D is important for bone health and strength. Previous studies report 25-hydroxyvitamin D (25(OH)D) exposure during pregnancy may impact offspring bone health later in life. In this study, maternal 25(OH)D at recruitment was associated with a lower fracture risk in boys and an increased fracture risk in girls at 28-32 weeks gestation. PURPOSE: Maternal 25-hydroxyvitamin D (25(OH)D) in pregnancy has been shown to be associated with offspring bone measures in some studies, but few have examined fracture risk. We aimed to determine associations between maternal vitamin D status and offspring fracture risk. METHODS: In total, 475 mother-child pairs participating in the Vitamin D in Pregnancy study in southeastern Australia were recruited. Maternal serum samples were taken at recruitment (< 16 weeks gestation) and/or 28-32 weeks gestation and analysed for 25(OH)D. Incident fractures in children were ascertained from date of birth (2002-2004) until December 31, 2012. Cox proportional hazard models included maternal age at recruitment, offspring sex, birth weight, gestation length and season of vitamin D sample. RESULTS: Complete follow-up data were available for 400 children (median age = 9.5 years). There were 68 (17.0%) children who sustained at least one fracture. Higher maternal 25(OH)D (per 10 nmol/L) in early gestation was weakly associated with a decreased fracture risk in boys (HR 0.82; 95% CI 0.68, 0.99; p = 0.048) but not girls (HR 1.10; 95% CI 0.98, 1.25; p = 0.11). At late gestation, higher maternal 25(OH)D was associated with increased fracture risk in girls (HR 1.11; 95% CI 1.01, 1.23; p = 0.038) but not boys (HR 0.94; 95% CI 0.80, 1.10; p = 0.42). No statistically significant relationships were detected in analyses investigating 25(OH)D as a categorical variable. CONCLUSION: There is some evidence that higher maternal 25(OH)D at recruitment was associated with lower fracture risk in boys, while higher maternal 25(OH)D at 28-32 weeks gestation was associated with an increased fracture risk in girls.

Gestational Folate and Offspring Bone Health; The Vitamin D in Pregnancy Study.

Maternal nutritional intake, such as folate and folic acid supplementation, during pregnancy may affect offspring bone health during childhood. We aimed to determine the associations between maternal dietary and supplementary folate intake and offspring bone health measures, including fracture risk. Data were obtained from 160 of 475 mother-child pairs who had returned for the 11-year follow up of the Vitamin D in Pregnancy Study, an observational cohort study. Incident fractures were ascertained from radiological records and dual X-ray absorptiometry was used to measure bone mineral density and content at 11 years of age. Maternal dietary folate intake during pregnancy was determined by Food Frequency Questionnaire and folate supplementation was determined through self-report. Both measures were undertaken at recruitment (before 16 weeks gestation) and at 28-32 weeks' gestation. Multivariable linear regression models and Cox regression models were used to examine associations. Results are presented as per 1000 µg folate for dietary measures. There were significant associations between maternal folate supplementation in early pregnancy (< 16 weeks gestation) and offspring spine bone mineral content (BMC) (ß = 1.53, 95% CI 0.21, 2.86), spine area (ß = 1.10, 95% CI 0.37, 1.82) and total body less head area (ß = 329.30, 95% CI 3.50, 55.20) at the 11-year follow-up. The association between spine BMC was attenuated after adjustment for bone size (ß = 0.13 95% CI - 0.85, 1.10). There was no association between maternal folate supplementation at 28-32 weeks' or maternal dietary intake at either time point with any offspring bone outcome. These data suggest that folate supplementation in early pregnancy may be associated with offspring bone size, but not other bone measures.