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中华妇幼临床医学杂志(电子版) ›› 2023, Vol. 19 ›› Issue (02) : 202 -211. doi: 10.3877/cma.j.issn.1673-5250.2023.02.012

论著

早产儿支气管肺发育不良合并代谢性骨病的影响因素
杨萍, 许世敏, 李亮亮, 尹向云, 锡洪敏, 马丽丽, 李向红†()   
  1. 青岛大学附属医院新生儿科，青岛　266555
  • 收稿日期:2022-11-01 修回日期:2023-02-19 出版日期:2023-04-01
  • 通信作者: 李向红

Influencing factors of bronchopulmonary dysplasia complicated with metabolic bone disease in preterm infants

Ping Yang, Shimin Xu, Liangliang Li, Xiangyun Yin, Hongmin Xi, Lili Ma, Xianghong Li†()   

  1. Neonatal Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao 266555, Shandong Province, China
  • Received:2022-11-01 Revised:2023-02-19 Published:2023-04-01
  • Corresponding author: Xianghong Li
  • Supported by:
    Medical and Health Science and Technology Development Program of Shandong Province(2016WS0278)
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引用本文：

杨萍, 许世敏, 李亮亮, 尹向云, 锡洪敏, 马丽丽, 李向红. 早产儿支气管肺发育不良合并代谢性骨病的影响因素[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(02): 202-211.

Ping Yang, Shimin Xu, Liangliang Li, Xiangyun Yin, Hongmin Xi, Lili Ma, Xianghong Li. Influencing factors of bronchopulmonary dysplasia complicated with metabolic bone disease in preterm infants[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(02): 202-211.

目的

探讨早产儿支气管肺发育不良(BPD)合并代谢性骨病(MBD)的临床高危因素。

方法

选取青岛大学附属医院新生儿重症监护病房(NICU)于2018年1月1日至2020年12月31日收治的151例BPD早产儿为研究对象，按照BPD早产儿是否合并MBD，将其分为BPD合并MBD组(n＝41)和单纯BPD组(n＝110)。采取回顾性分析法，对2组患儿的临床病例资料、除MBD外的其他并发症发生情况、无创正压通气与有创机械通气治疗时间、药物治疗情况、血清生化指标、肠内与肠外营养情况等进行分析。采用Pearson列联系数，对2组患儿的BPD严重程度与MBD相关性进行分析。再将单因素分析中有统计学意义的变量，纳入多因素非条件logistic回归分析，探讨BPD早产儿合并MBD的影响因素。本研究遵循的研究程序经青岛大学附属医院医学伦理委员会审批(QYFY WZLL 26771)，并与所有患儿监护人签署书面知情同意书。

结果

①BPD合并MBD组患儿出生胎龄、出生体重，均低于单纯BPD组，并且差异有统计学意义(P<0.05)。②BPD合并MBD组早产儿无创正压通气时间和住院时间，均长于单纯BPD组，并且差异有统计学意义(P<0.05)；BPD合并MBD组患儿住院期间新生儿败血症和新生儿坏死性小肠结肠炎(NEC)发生率，均高于单纯BPD组，并且差异亦有统计学意义(P<0.05)。③2组患儿生后第1、21天时，25-羟维生素D[25(OH)D]浓度、血清碱性磷酸酶(ALP)及血磷水平比较，差异均有统计学意义(P<0.05)。④BPD合并MBD组的患儿肠外营养时间和母乳喂养时间与达全肠内喂养日龄，均长于单纯BPD组，并且差异均有统计学意义(P<0.05)；BPD合并MBD组生后第28天时，摄入总热量、肠内营养热量、肠内蛋白质及肠外氨基酸，均低于单纯BPD组，并且差异亦均有统计学意义(P<0.05)。⑤BPD合并MBD患儿的BPD严重程度与MBD呈显著正相关关系(r＝0.381，P<0.001)。⑥BPD早产儿合并MBD影响因素的多因素非条件logistic回归分析结果显示，无创正压通气时间长(OR＝1.043，95%CI：1.015~1.072，P＝0.003)和肠外营养时间长(OR＝1.041，95%CI：1.008~1.075，P＝0.014)，均为导致BPD早产儿发生MBD的独立危险因素；出生第21天时，BPD早产儿的血清25(OH)D水平升高是导致其发生MBD的独立保护因素(OR＝0.919，95%CI：0.858~0.984，P＝0.015)。

结论

生后3周内血清25(OH)D水平升高，可降低BPD早产儿发生MBD风险。对BPD早产儿生后早期，给予积极肠内营养支持，保证适宜的血清25(OH)D水平，并定期评估骨代谢指标，以期降低BPD早产儿发生MBD的几率，对已发生MBD的BPD合并MBD患儿，可改善其预后及远期结局。

关键词: 支气管肺发育不良, 骨疾病，代谢性, 碱性磷酸酶, 胃肠外营养, 危险因素, 保护因素, 婴儿，早产
Objective

To investigate the risk factors for bronchopulmonary dysplasia (BPD) combined with metabolic bone disease (MBD) in premature infants.

Methods

A total of 151 preterm infants with BPD admitted to Neonatal Intensive Care Unit (NICU) of the Affiliated Hospital of Qingdao University from January 1, 2018 to December 31, 2020 were selected into this study. According to whether BPD infants had MBD or not, they were divided into BPD complicated with MBD group (n=41) and BPD alone group (n=110). Retrospective analysis was performed to analyze the clinical case data, the occurrence of other complications except MBD, the treatment time of non-invasive positive pressure ventilation and invasive mechanical ventilation, drug treatment, serum biochemical indexes, enteral and parenteral nutrition between two groups.Pearson column correlation number was used to analyze the correlation between the severity of BPD and MBD between two groups. The statistically significant variables in the univariate analysis were included in the multivariate unconditional logistic regression analysis to explore influencing factors of BPD combined with MBD in preterm infants.The research procedures followed in this study were approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University (QYFY WZLL 26771), and written informed consents were obtained from all guardians of the children.

Results

① The gestational age and birth weight of BPD complicated with MBD group were lower than those of BDP alone group, and the differences were statistically significant (P<0.05). ② The duration of non-invasive positive pressure ventilation and hospital stay of BPD complicated with MBD group were both longer than those in BPD alone group, and the difference was statistically significant (P<0.05). The incidence of neonatal sepsis and neonatal necrotizing enterocolitis (NEC) in BPD complicated with MBD group during hospitalization were higher than those in BPD alone group, and the difference were statistically significant (P<0.05). ③ There were statistically significant differences in the concentration of 25-hydroxyvitamin D[25 (OH) D], serum alkaline phosphatase (ALP) and blood phosphorus between two groups at the first and 21st day after the birth (P<0.05). ④ The parenteral nutrition time and breastfeeding time of BPD complicated with MBD group were longer than those of BPD alone group, and the differences were statistically significant (P<0.05). On the 28th day after birth, total calories, enteral nutrient calories, enteral protein and parenteral amino acids in BPD complicated with MBD group were lower than those in BPD alone group, and the differences were statistically significant (P<0.05). ⑤ There was a significant positive correlation between the severity of BPD and MBD in premature infants of BPD complicated with MBD (r=0.381, P<0.05). ⑥ Multivariate logistic regression analysis of MBD in premature infants with BPD showed that non-invasive positive pressure ventilation time (OR=1.043, 95%CI: 1.015-1.072, P=0.003) and parenteral nutrition time (OR=1.041, 95%CI: 1.008-1.075, P=0.014), all of which were independent risk factors for MBD in premature infants with BPD. Serum 25(OH)D level at day 21 of birth was an independent protective factor for MBD in premature infants with BPD (OR=0.919, 95%CI: 0.858 ~ 0.984, P=0.015).

Conclusions

Increased serum 25(OH)D level within 3 weeks after birth can reduce the risk of MBD in preterm infants with BPD. Early after birth, premature infants with BPD should be given active enteral nutrition support to ensure appropriate serum 25(OH)D level, and bone metabolism indexes should be evaluated regularly, so as to reduce the probability of developing MBD in premature infants with BPD, and to improve the prognosis and long-term outcome of children with BPD and MBD.

Key words: Bronchopulmonary dysplasia, Bone diseases, metabolic, Alkaline phosphatase, Parenteral nutrition, Risk factors, Protective factors, Infant, premature
表1 2组BPD早产儿及其母亲一般情况比较
组别 例数 性别[例数(%)] 出生胎龄(周，±s) 出生体重(g，±s) 多胎[例数(%)] Apgar评分(分，±s)
男 女 生后1 min 生后5 min
单纯BPD组 110 64(58.2) 46(41.8) 28.7±1.5 1 110.8±260.8 22(20.0) 6.7±2.2 8.1±1.6
BPD合并MBD组 41 28(68.3) 13(31.7) 27.5±1.7 968.2±230.3 11(26.8) 6.7±2.1 8.2±1.3
统计值   χ2＝1.28 t＝－3.52 t＝－3.09 χ2＝0.82 t＝－0.02 t＝－0.01
P值   0.257 <0.001 0.002 0.366 0.983 0.991
组别 例数 剖宫产术娩出[例数(%)] 胎膜早破[例数(%)] 胎盘异常[例数(%)] 母亲妊娠期高血压疾病[例数(%)] 母亲妊娠期糖尿病[例数(%)] 母亲产前使用激素[例数(%)] SGA儿[例数(%)]
单纯BPD组 110 74(67.3) 25(22.7) 9(8.2) 32(29.1) 23(20.9) 86(78.2) 13(11.8)
BPD合并MBD组 41 24(58.5) 13(31.7) 3(7.3) 9(22.0) 9(22.0) 33(80.5) 5(12.2)
统计值   χ2＝1.00 χ2＝1.28 — χ2＝0.77 χ2＝0.02 χ2＝0.10 —
P值   0.317 0.258 0.260 0.380 0.890 0.758 0.220
表2 2组BPD早产儿住院期间并发症发生率及辅助通气治疗时间比较
组别 例数 有创机械通气时间[d, M(Q1，Q3)] 无创正压通气时间[d, ±s] PDA[例数(%)] 新生儿败血症[例数(%)] PNAC[例数(%)]
单纯BPD组 110 0(0，0.8) 36.6±16.4 49(44.5) 16(39.0) 24(21.8)
BPD合并MBD组 41 0(0，4.4) 52.8±19.5 22(53.7) 24(21.8) 9(22.0)
统计值   t＝－1.64 t＝－5.11 χ2＝0.99 χ2＝4.54 χ2<0.001
P值   0.101 <0.001 0.318 0.033 0.986
组别 例数 IVH[例数(%)] NEC[例数(%)] 低钙血症[例数(%)] EUGR[例数(%)] 住院时间(d, ±s)
单纯BPD组 110 7(6.4) 1(0.9) 2(1.8) 59(53.6) 76.4±25.9
BPD合并MBD组 41 4(9.8) 4(9.8) 1(2.4) 23(56.1) 99.3±36.1
统计值   — — — χ2＝0.07 t＝－4.40
P值   0.491 0.019 0.441 0.787 <0.001
表3 2组BPD早产儿住院期间药物使用情况比较[例数(%)]
组别 例数 咖啡因 地塞米松 利尿剂 PS
单纯BPD组 110 105(95.5) 48(43.6) 80(72.7) 67(60.9)
BPD合并MBD组 41 40(97.6) 24(58.5) 33(80.5) 27(65.9)
χ2值   — 2.36 0.96 0.31
P值   0.340 0.124 0.328 0.577
表4 2组BPD早产儿出生第1、21天生化指标比较(±s)
组别 例数 生后血清25(OH)D(ng/mL) 血清ALP(IU/L)a 血磷(mmol/L)a 血镁(mmol/L)a 血钙(mmol/L)a 尿素氮(mmol/L)a 直接胆红素(mmol/L)a
第1天 第21天
单纯BPD组 110 11.8±5.1 17.4±8.4 411.9±136.9 1.9±0.3 0.9±0.1 2.3±0.2 2.5±1.2 18.6±12.9
BPD合并MBD组 41 9.4±3.6 13.2±5.6 710.6±150.3 1.3±0.4 0.9±0.1 2.3±0.2 2.8±1.6 21.1±18.9
t值   －2.73 －3.17 －8.08 －7.61 －0.72 －0.75 －0.84 －0.67
P值   0.006 0.002 <0.001 <0.001 0.471 0.451 0.398 0.503
表5 BPD早产儿肠内、外营养比较
组别 例数 生后第7天
摄入总热量[kCal/(kg·d), ±s] 肠内营养热量[kCal/(kg·d), ±s] 肠内蛋白质[g/(kg·d), M(Q1，Q3)] 肠外氨基酸[g/(kg·d)，M(Q1，Q3)]
单纯BPD组 110 91.4±14.1 12.4(4.7，22.3) 0.5(0.2，0.9) 3.3(2.9，3.5)
BPD合并MBD组 41 91.0±18.1 9.9(4.2，25.3) 0.4(0.2，1.0) 3.3(2.8，3.5)
统计值   t＝0.13 Z＝－0.13 Z＝－0.13 Z＝－0.23
P值   0.900 0.898 0.897 0.816
组别 例数 生后第14天
摄入总热量[kCal/(kg·d), ±s] 肠内营养热量[kCal/(kg·d), ±s] 肠内蛋白质[g/(kg·d), ±s] 肠外氨基酸[g/(kg·d), M(Q1，Q3)]
单纯BPD组 110 106.0±13.6 53.9±35.4 2.2±1.4 2.4(1.2，2.9)
BPD合并MBD组 41 102.3±14.5 44.9±30.2 1.8±1.2 2.6(1.77，3.2)
统计值   t＝1.43 t＝1.46 t＝1.49 Z＝－1.46
P值   0.156 0.148 0.139 0.144
组别 例数 生后第28天
摄入总热量[kCal/(kg·d), ±s] 肠内营养热量[kCal/(kg·d), ±s] 肠内蛋白质[g/(kg·d), M(Q1，Q3)] 肠外氨基酸[g/(kg·d), M(Q1，Q3)]
单纯BPD组 110 118.3±16.6 102.8±37.6 4.3(3.2, 4.8) 0(0，1.3)
BPD合并MBD组 41 108.7±22.3 76.9±50.2 3.0(1.2, 4.3) 1.4(0，2.7)
统计值   t＝2.87 t＝－2.64 Z＝－3.62 Z＝－3.55
P值   0.005 0.008 <0.001 <0.001
组别 例数 母乳喂养时间[d, M(Q1，Q3)] 肠外营养时间[d, M(Q1，Q3)] 添加母乳强化剂[例数(%)] 达全肠内喂养日龄[d, M(Q1，Q3)]
单纯BPD组 110 52.0(8.0，67.1) 23.5(17.0，33.2) 70(63.6) 23.5(17.0，33.2)
BPD合并MBD组 41 66.5(35.5，92.5) 39.0(25.0，52.5) 29(70.7) 39.0(25.0，52.5)
统计值   －2.89 －4.42 0.67 －4.42
P值   0.004 <0.001 0.414 <0.001
表6 BPD严重程度与MBD相关性分析[例数(%)]
BPD分级 例数 非MBD MBD
I 54 50(33.1) 4(2.6)
Ⅱ 66 47(31.1) 19(12.6)
Ⅲ 31 13(8.6) 18(11.9)
合计 151 110(72.8) 41(27.2)
表7 BPD早产儿合并MBD影响因素的多因素非条件logistic回归分析结果
相关因素 B SE Wald值 P值 OR值 OR值95%CI
无创正压通气时间 0.042 0.014 8.923 0.003 1.043 1.015~1.072
出生第21天25(OH)D水平 —0.085 0.035 5.904 0.015 0.919 0.858~0.984
肠外营养时间 0.040 0.016 6.098 0.014 1.041 1.008~1.075
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