Effects of vitamin D supplementation during pregnancy on bone health and offspring growth: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Whether vitamin D supplementation during pregnancy is beneficial to bone health and offspring growth remains controversial. Moreover, there is no universal agreement regarding the appropriate dose and the time of commencement of vitamin D supplementation during pregnancy. OBJECTIVE: We aimed to systematically review the effects of vitamin D supplementation during pregnancy on bone development and offspring growth. METHODS: A literature search for randomized controlled trials (RCTs) was performed in 7 electronic databases to identify relevant studies about the effects of vitamin D supplementation during pregnancy on bone development and offspring growth from inception to May 22, 2022. A Cochrane Risk Assessment Tool was used for quality assessment. Vitamin D supplementation was compared with placebo or standard supplements. The effects are presented as the mean differences (MDs) with 95% CIs. The outcomes include bone mineral content (BMC), bone mineral density (BMD), bone area (BA), femur length (FL) and humeral length (HL); measurement indicators of growth, including length, weight and head circumference; and secondary outcome measures, including biochemical indicators of bone health, such as the serum 25(OH)D concentration. Additionally, subgroup analyses were carried out to evaluate the impact of different doses and different initiation times of supplementation with vitamin D. RESULTS: Twenty-three studies with 5390 participants met our inclusion criteria. Vitamin D supplementation during pregnancy was associated with increased humeral length (HL) (MD 0.13, 95% CI 0.06, 0.21, I2 = 0, P = 0.0007) during the fetal period (third trimester). Vitamin D supplementation during pregnancy was associated with a significantly increased length at birth (MD 0.14, 95% CI 0.04, 0.24, I2 = 24%, P = 0.005) and was associated with a higher cord blood 25(OH)D concentration (MD 48.74, 95% CI 8.47, 89.01, I2 = 100%, P = 0.02). Additionally, subgroup analysis revealed that birth length was significantly higher in the vitamin D intervention groups of ≤1000 IU/day and ≥4001 IU/day compared with the control group. Prenatal (third trimester) vitamin D supplementation was associated with a significant increase in birth length, while prenatal (second trimester) vitamin D supplementation was associated with a significant increase in birth weight. CONCLUSION: Vitamin D supplementation during pregnancy may be associated with increased humeral length (HL) in the uterus, increased body length at birth and higher cord blood 25(OH)D concentration. Evidence of its effect on long-term growth in children is lacking. Additional rigorous high-quality, long-term and larger randomized trials are required to more fully investigate the effects of vitamin D supplementation during pregnancy.

Variability of serum phosphorus and its association with mortality among hemodialysis patients
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OBJECTIVE: To determine the relationship between the variability of serum phosphorus and mortality among maintenance hemodialysis (MHD) patients. MATERIALS AND METHODS: A total of 502 MHD cases were studied from the Shanghai Renal Registry Network. Serum phosphorus variability was indicated by a coefficient of variation (CV). According to the CV median of serum phosphorus, patients were divided into two groups: a high-variability group (CV ≥ 0.226 mmol/L) and a low-variability group (CV < 0.226 mmol/L). Average phosphorus ≤ 1.78 mmol/L was defined as the standard phosphorus group and serum phosphorus > 1.78 mmol/L was defined as the non-standard phosphorus group. The relationship between serum phosphorus variability and all-cause and cardiovascular disease (CVD) mortality was assessed. RESULTS: In the 502 MHD cases, the average age of patients was 63.9 ± 14.60 years, and dialysis vintage was 82.0 (43.0 - 139.0) months. 118 patients (23.5%) died, succumbing to all-cause mortality, while 64 patients (14.3%) died from CVD. The high-variability group had increased all-cause mortality (27.7% vs. 19.3%, p = 0.028). Death from CVD was increased in the high-variability group, but had no statistical significance (15.4% vs. 10.0%, p = 0.082). Cox regression analysis showed that older age, low hemoglobin levels, a higher phosphorus CV, and low serum albumin were independent risk factors for all-cause and CVD mortality. The standard group with low-phosphorus variability had a decreased mortality compared with the non-standard group with high variability (15.3 vs. 29.2%, p = 0.047 and 6.0 vs. 15.0%, p = 0.033, respectively). The Kaplan-Meier method revealed that patients with low phosphorus variability had a decreased all-cause and CVD mortality (p = 0.023 and p = 0.047, respectively) compared with high phosphorus variability patients. CONCLUSION: Higher phosphorus CV was independently correlated with all-cause and CVD mortality. Low phosphorus variability with on-target levels resulted in decreased patient mortality. Thus, stable serum phosphorus levels may improve survival in MHD patients.
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