早产儿血清25-羟维生素D和维生素D结合蛋白水平与支气管肺发育不良的关系

The clinical significance of serum 25-hydroxy vitamin D and vitamin D binding protein in premature infants with bronchopulmonary dysplasia

目的探讨早产儿血清25-羟维生素D [25-hydroxy vitamin D,25-(OH)D]和维生素D结合蛋白(vitamin D binding protein,DBP)水平与支气管肺发育不良(bronchopulmonary dysplasia,BPD)的关系。方法前瞻性选取2017年3月至2018年9月郑州大学第三附属医院新生儿科收治的胎龄<32周早产儿,生后1周开始补充维生素D 800 IU/d至出院,于出生时和生后28 d采集静脉血检测血清25-(OH)D和DBP水平。根据生后28 d是否发生BPD分为BPD组和非BPD组,比较两组血清25-(OH)D和DBP水平的差异。结果共纳入胎龄<32周早产儿170例,其中BPD组56例,胎龄(29.8±1.2)周,出生体重(1 198±157)g,轻度BPD 32例,中重度BPD 24例;非BPD组114例,胎龄(30.2±1.5)周,出生体重(1 243±146)g。BPD组1、5 min Apgar评分低于非BPD组,合并新生儿肺炎、败血症、窒息、动脉导管未闭比例高于非BPD组,机械通气时间、辅助通气时间、总吸氧时间、住院时间长于非BPD组,差异有统计学意义(P<0.05)。两组性别、胎龄、出生体重、剖宫产、母孕期并发症比较,差异均无统计学意义(P>0.05)。BPD组出生时和生后28 d血清25-(OH)D水平均低于非BPD组[(27.8±5.9)nmol/L比(30.4±1.1)nmol/L,(77.5±11.7)nmol/L比(83.8±11.6)nmol/L],两组生后28 d血清25-(OH)D水平均较出生时明显升高,差异有统计学意义(P<0.05)。生后28 d BPD组血清DBP水平低于非BPD组且低于出生时,差异有统计学意义(P<0.05)。中重度BPD组出生时血清25-(OH)D水平和生后28 d血清DBP水平均低于轻度BPD组[(25.3±4.9)nmol/L比(29.7±5.9)nmol/L,(373.9±19.1)μg/ml比(391.4±23.6)μg/ml],差异有统计学意义(P<0.05)。多因素分析显示,新生儿肺炎(OR=4.331,95%CI 1.269~14.784)、败血症(OR=4.020,95%CI 1.153~14.015)是早产儿发生BPD的危险因素;出生时血清25-(OH)D水平高(OR=0.827,95%CI 0.693~0.987)是早产儿发生BPD的保护性因素。结论早产儿出生时血清25-(OH)D水平高是发生BPD的保护性因素,合并新生儿肺炎和败血症是发生BPD的危险因素;出生时血清25-(OH)D及生后28 d血清DBP水平低下可能对评估BPD患儿病情严重程度有一定的参考价值。

Objective To study the relationship of serum 25-hydroxy vitamin D [25-(OH) D] and vitamin D binding protein (DBP) in premature infants with bronchopulmonary dysplasia (BPD) and their clinical significance. Method From March 2017 to September 2018, the premature infants with gestational age (GA)<32 weeks admitted to the neonatal department of our hospital were prospectively studied. All the premature infants were given 800 IU/d vitamin D supplement from one week after birth. Venous blood sample were collected at birth and 28 d after birth to measure 25-(OH) D and DBP levels. The infants were evaluated for BPD at 28 d after birth and then assigned into the BPD group and the non-BPD group. The differences of 25-(OH) D and DBP levels were compared. Result A total of 170 premature infants (GA<32 weeks) were included, including 56 cases in the BPD group and 114 cases in the non-BPD group. The BPD group had 34 males, the GA was (29.8±1.2) weeks, the birth weight (BW) was (1 198±157) g. The non-BPD group had 95 males, the GA was (30.2±1.5) weeks, the BW was (1 243±146) g. No significant differences existed in GA, BW and male gender proportion between BPD group and non-BPD group (P>0.05). The BPD group had a lower levels of serum 25-(OH) D at birth [(27.8±5.9) nmol/L vs.(30.4±1.1) nmol/L, P<0.05]. The levels of serum 25-(OH) D in moderate/severe BPD group were significantly lower than mild BPD group [(25.3±4.9) nmol/L vs.(29.7±5.9) nmol/L, P<0.05];25-(OH) D in BPD group was still lower than the non-BPD group at 28 days after birth (after vitamin D supplement)[(77.5±11.7) nmol/L vs.(83.8±11.6) nmol/L, P<0.05]. Comparison of serum DBP levels between the two groups showed that, DBP at 28 d after birth in BPD group were significantly lower than the non-BPD group, and DBP in moderate/severe BPD group were significantly lower than the mild BPD group [(373.9±19.1)μg/ml vs.(391.4±23.6)μg/ml], the differences were both statistically significant (P<0.05). Multivariate analysis showed that the high serum 25-(OH)D level at birth (OR=0.827, 95%CI 0.693~0.987) was protective factors for BPD, while neonatal pneumonia (OR=4.331, 95%CI 1.269~14.784) and neonatal sepsis (OR=4.020, 95%CI 1.153~14.015) were risk factors for BPD. Conclusion The high serum 25-(OH) D level at birth in preterm infants was protective factors for BPD, while neonatal pneumonia and sepsis were the risk factors for BPD. Moreover, low serum 25-(OH) D level at birth and low serum DBP level at 28 d after birth maybe useful indicators for the severity of BPD.