骨化三醇对极低出生体重儿骨代谢与合并症的影响

The Effects of Calcitriol on Bone Metabolism and Diseases in VLBWI

摘要: 目的：通过对极低出生体重儿(Very low birth weight infants, VLBWI)补充骨化三醇与维生素D3的临床对照研究，探讨活性维生素D制剂对VLBWI骨代谢及相关疾病的影响。方法：前瞻性对照研究，选择2019年1月~2019年10月期间入住青岛大学附属医院NICU、并取得家长知情同意的40例VLBWI为骨化三醇组，随其后入院的第1个VLBWI 40例为对照组。两组VLBWI在喂养耐受后(骨化三醇组为10.26 ± 3.76天，对照组为10.65 ± 5.20天)均给予维生素AD每日1粒(含维生素D 500 IU、维生素A 1500 IU)，骨化三醇组每日加服骨化三醇(0.125 ug)，对照组每日加服维生素D3 (400 IU)。两组VLBWI在生后24小时内及生后1月时分别测定血清25-(OH)D、碱性磷酸酶(Alkaline phosphatase, ALP)、血磷、血钙水平，矫正胎龄(Corrected gestational age, CGA) 40周时测量身长、体重、头围体格发育指标，并收集两组VLBWI住院期间临床资料。进行统计学处理。结果：1) 骨代谢指标比较：两组生后24小时及1月龄时血清25-(OH)D、血ALP、血钙、血磷水平差异均无统计学意义(P > 0.05)；两组喂养方式、TPN时间及钙磷摄入差异无统计学意义(P > 0.05)；CGA 40周时身长、体重、头围比较差异无统计学意义(P > 均0.05)。2) 围产期合并症比较：骨化三醇组机械通气时间(2.5 ± 0.5 vs 5.8 ± 0.8 d)及住院时间(49.50 ± 2.8 vs 56.00 ± 3.5 d)均低于对照组，差异有统计学意义(P < 0.05)。两组支气管肺发育不良(Bronchopulmonary dysplasia, BPD)总体发生率(23.68% vs 35.14%)，差异无统计学意义(P > 0.05)，但骨化三醇组轻度BPD发生率显著高于对照组(88.89% vs 38.46%)，中度BPD发生率明显低于对照组(0% vs 46.15%)，差异均有统计学意义(P < 0.05)；骨化三醇组败血症发生率较对照组低(10.53% vs 32.43%)，差异有统计学意义(P < 0.05)；两组VLBWI无创通气时间以及新生儿呼吸窘迫综合征(Respiratory distress syndrome, RDS)、代谢性骨病(Metabolic bone disease, MBD)发生率比较，差异无统计学意义(P > 0.05)。结论：1) VLBWI生后补充骨化三醇替代补充维生素D3对骨代谢的影响无明显差异。2) VLBWI补充骨化三醇可以缩短机械通气时间及住院时间，减轻BPD的严重程度，降低败血症的发生率。

Abstract: Objective: To explore the effects of active vitamin D preparation on bone metabolism and diseases in very low birth weight infants (VLBWI), through a clinical controlled study of calcitriol and vitamin D3 supplementation. Methods: A prospective observational study was conducted in the NICU at the Affiliated Hospital of Qingdao University between January and October 2019. The VLBWI whose parents signed an informed consent form was included in the calcitriol group (n = 40); the next VLBWI admitted to the NICU following the calcitriol group was included in the control group (n = 40). Both groups of premature infants were given vitamin AD (vitamin D 500 IU, vitamin A 1500 IU) 1 capsule per day after gestational tolerance (the calcitriol group 10.26 ± 3.76 days, the control group 10.65 ± 5.20 days), the calcitriol group added calcitriol 0.125 ug per day and the control group added vitamin D3 400 IU per day. Serum 25-(OH)D, alkaline phosphatase (ALP), calcium and phosphorus levels were measured within 24 h and 1 month after birth. The length, weight and head circumference were measured at 40 weeks of corrected gestational age. The clinical data of two groups during hospitalization were recorded and statistically processed. Results: 1) Comparison of bone metabolic indexes: there was no significant difference in serum 25-(OH)D level, vitamin D status, serum ALP, serum calcium and phosphorus levels between the two groups at 1 month after birth (P > 0.05); there was no significant difference in length, weight, and head circumference between the two groups at 40 weeks of corrected gestational age (P > 0.05). 2) Comparison of perinatal comorbidities: the mechanical ventilation time (2.5 ± 0.5 vs 5.8 ± 3.2 d) and hospital stay (49.50 ± 2.8 vs 56.00 ± 3.5 d) in the calcitrol group were significantly lower than those in the control group, with statistical significance (P < 0.05). The overall incidence of bronchopulmonary dysplasia (BPD) between the two groups was 23.68% vs 35.14% (P > 0.05), but the incidence of mild BPD in the calcitriol group was significantly higher than that in the control group (88.89% vs 38.46%), and the incidence of moderate BPD in the calcitriol group was significantly lower than that in the control group (0% vs 46.15%), both of which were statistically significant (P < 0.05). The incidence of sepsis in the calcitriol group was lower than that in the control group (10.53% vs 32.43%), and the difference was statistically significant (P < 0.05). There were no significant differences in VLBWI noninvasive ventilation time, the incidence of respiratory distress syndrome (RDS) and metabolic bone disease (MBD) between the two groups (P > 0.05). Conclusions: 1) There is no significant difference in the effects of calcitriol supplementation and vitamin D3 supplementation on bone metabolism in very low birth weight infants. 2) Calcitriol supplementation in very low birth weight infants can not only shorten the duration of mechanical ventilation and hospital stay, but also reduce the severity of BPD and the incidence of sepsis.