Maternal Vitamin D Supplementation and Infantile Rickets: Secondary Analysis of a Randomized Trial.

BACKGROUND: The role of maternal vitamin D supplementation in the prevention of infantile rickets is unknown, particularly in low- and middle-income countries without routine infant vitamin D supplementation. Through secondary analysis of a randomized, placebo-controlled trial in Bangladesh, we examined the dose-ranging effects of maternal vitamin D supplementation on the risk of biochemical rickets at 6 to 12 months of age. METHODS: Pregnant women (n = 1300) were randomized into 5 groups: placebo, or vitamin D 4200 IU/week, 16 800 IU/week, or 28 000 IU/week from second trimester to delivery and placebo until 6 months postpartum; or 28 000 IU/week prenatally and until 6 months postpartum. Infants underwent biochemical rickets screening from 6 to 12 months of age (n = 790). Relative risks (RR) and 95% confidence intervals (95% CI) of biochemical rickets were estimated for each group versus placebo. RESULTS: Overall, 39/790 (4.9%) infants had biochemical rickets. Prevalence was highest in the placebo group (7.8%), and the risk was significantly lower among infants whose mothers received combined prenatal and postpartum vitamin D at 28 000 IU/week (1.3%; RR, 0.16; 95% CI, 0.03-0.72). Risks among infants whose mothers received only prenatal supplementation (4200 IU, 16 800 IU, 28 000 IU weekly) were not significantly different from placebo: 3.8% (RR, 0.48; 95% CI, 0.19-1.22), 5.8% (RR, 0.74; 95% CI, 0.33-1.69), and 5.7% (RR, 0.73; 95% CI, 0.32-1.65), respectively. CONCLUSIONS: Maternal vitamin D supplementation (28 000 IU/week) during the third trimester of pregnancy until 6 months postpartum reduced the risk of infantile biochemical rickets. Further research is needed to define optimal postpartum supplementation dosing during lactation.

Maternal diabetes and fracture risk in offspring: a population-based analysis.

Factors affecting intrauterine environment exerts influence on skeletal health and fracture risk in later life. Diabetes during pregnancy is known to influence birth weight and is associated with fetal overgrowth. However, the effects of maternal diabetes on fracture risk in offspring is unknown. This study was aimed to evaluate the association between maternal diabetes and fracture risk in offspring. Using population-based administrative health data for Manitoba, Canada, we identified deliveries complicated by gestational diabetes and type 2 diabetes between April 1, 1980 and March 31, 2020. The cohort was followed for a median of 15.8 years. The primary outcome was any incident fracture in offspring. Secondary outcomes were long bone upper extremity fracture, long bone lower extremity fracture, vertebral fracture, and any non-trauma fractures. Cox proportional hazard regression models were used to estimate fracture risk in offspring by maternal diabetes status adjusted for relevant covariates. Of 585 176 deliveries, 26 397 offspring were born to women with diabetes (3.0% gestational diabetes and 1.5% type 2 diabetes) and 558 779 were born to women without diabetes. The adjusted risk for any fracture was 7% (HR 1.07; 95% CI, 2.7-11.5%) higher in offspring of mothers with diabetes than offspring of mothers without diabetes. Types of fractures were similar between the two groups with a predominance of long-bone upper extremity fractures. In conclusion, maternal diabetes was associated with a modest increase in fracture risk in offspring. Longitudinal prospective studies are needed to understand intrauterine and post-natal factors that may influence fracture risk in offspring of mothers with diabetes.

Bone Health in Osteosarcoma at Presentation and Its Impact on Cancer Treatment: A Case Series of 3 Pediatric Patients.

Osteosarcoma is the most common pediatric malignant bone tumor. Concomitant osteoporosis has typically been attributed to oncologic therapy. The present case series is aimed to describe 3 patients who presented with osteoporosis or osteopenia before, or early in, their oncology treatment. In our patients, bone health and its complications had significant impacts including pain, reduced mobility, prolonged admission, and delays in recovery. Our patients experienced improvement with resection of their primary tumor and with bisphosphonate infusion. Future studies are required to determine the prevalence osteoporosis at presentation of osteosarcoma and the role of bisphosphonates.

A closer look at rickets and vitamin D deficiency in Manitoba: The tip of the iceberg.

OBJECTIVES: Vitamin D deficiency rickets remains a problem in Canada. Our primary objective was to determine the annual incidence of rickets and/or early vitamin D deficiency in Manitoba. Secondarily, we investigated if there was an increase in the annual incidence. METHODS: A retrospective chart review was undertaken to identify cases in our catchment area from 2003 to 2015. Data sources included endocrine and hospital charts and radiology reports. Early vitamin D deficiency was determined by review of all 25(OH)D tests from 2011 to 2015. Values less than 30 nmol/L with an elevated bone marker prompted a chart review in children under 7 years. RESULTS: We identified 46 cases of rickets and 68 with early vitamin D deficiency. For Manitoba, the annual incidence of rickets was 8.2 cases per 100,000 in infants, and 1.6 per 100,000 in children aged 1 to 7 years. Those with early vitamin D deficiency had annual incidences of 2.7 per 100,000 infants and 9.9 per 100,000 Manitoban children. No temporal trends were noted for either. For both disorders, most cases were from northern or rural locales; about 50% were of self-declared Indigenous or Inuit heritage, and the majority (>75%) of children were from families with high material deprivation using area-based socioeconomic measures. CONCLUSION: Despite several decades of preventative efforts, the incidence of rickets was comparable to previous Canadian reports, particularly in infants. Greater education across the lifespan and engagement with communities and public health agencies will be needed to reduce the high incidence of this preventable disease.

Efficacy and safety of metformin during pregnancy in women with gestational diabetes mellitus or polycystic ovary syndrome: a systematic review.

BACKGROUND: Metformin is an effective oral anti-hyperglycemic agent that is widely used to manage diabetes mellitus type 2 in the general population and more recently, in pregnancy. However, as metformin crosses the placenta, its use during pregnancy raises concerns regarding potential adverse effects on the mother and fetus. OBJECTIVE: (i) To provide background for the use of metformin during pregnancy through a narrative review and (ii) to critically appraise the published evidence on the efficacy and safety of using metformin during pregnancy through a systematic review. RESULTS: Metformin appears to be effective and safe for the treatment of gestational diabetes mellitus (GDM), particularly for overweight or obese women. However, patients with multiple risk factors for insulin resistance may not meet their treatment goals with metformin alone and may require supplementary insulin. Evidence suggests that there are potential advantages for the use of metformin over insulin in GDM with respect to maternal weight gain and neonatal outcomes. Furthermore, patients are more accepting of metformin than insulin. The use of metformin throughout pregnancy in women with polycystic ovary syndrome reduces the rates of early pregnancy loss and preterm labor and protects against fetal growth restriction. There have been no demonstrable teratogenic effects, intra-uterine deaths or developmental delays with the use of metformin. CONCLUSIONS: The publications reviewed in this paper support the efficacy and safety of metformin during pregnancy with respect to immediate pregnancy outcomes. Because there are no guidelines for the continuous use of metformin in pregnancy, the duration of treatment is based on clinical judgment and experience on a case-by-case basis.

Galanin is highly expressed in bone marrow mesenchymal stem cells and facilitates migration of cells both in vitro and in vivo.

Galanin peptide has recently been found to be highly abundant in early embryonic mouse mesenchyme, while galanin and its receptors are expressed in embryonic mouse stem cells. Bone marrow mesenchymal stem cells (BMMSCs) represent the primary source for adult stem cell therapy. In this study we examined the abundance of galanin and its receptors in BMMSCs and evaluated its possible function. Galanin mRNA and protein were highly expressed in BMMSCs cultures up to four passages, while among the three galanin receptor subtypes (GalR1, GalR2, and GalR3) only GalR2 and to a lesser extent GalR3 were expressed. Using chemotaxis and wound assays we found that galanin protein increased the migration of BMMSCs. Furthermore, increased serum galanin levels in a galanin transgenic model enhanced the mobilization (homing) of injected BMMSCs in vivo. These data suggest a role for galanin in BMMSC migration, probably through activation of the GalR2 receptor.