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中华妇幼临床医学杂志(电子版)

中华妇幼临床医学杂志(电子版) ›› 2022, Vol. 18 ›› Issue (04) : 419 -426. doi: 10.3877/cma.j.issn.1673-5250.2022.04.007

论著

极早产儿支气管肺发育不良影响因素的多中心临床研究
刘燕1,†(), 赵铭1, 姜红1, 陈晨2, 王小琴3, 张磊4   
  1. 1青岛大学附属医院儿童医学中心新生儿科，青岛　266003
    2济宁市第一人民医院新生儿科，济宁　272002
    3青岛市市立医院儿科，青岛　266071
    4枣庄市妇幼保健院新生儿科，枣庄　261031
  • 收稿日期:2021-12-11 修回日期:2022-06-08 出版日期:2022-08-01
  • 通信作者: 刘燕

Risk factors of bronchopulmonary dysplasia in very preterm infants: a multicenter study

Yan Liu1,†(), Ming Zhao1, Hong Jiang1, Chen Chen2, Xiaoqin Wang3, Lei Zhang4   

  1. 1Department of Neonatology, Children′s Medical Center, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
    2Department of Neonatology, Jining No.1 People′s Hospital, Jining 272002, Shandong Province, China
    3Department of Pediatrics, Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, China
    4Department of Neonatology, Maternity and Child Health Care of Zaozhuang, Zaozhuang 261031, Shandong Province, China
  • Received:2021-12-11 Revised:2022-06-08 Published:2022-08-01
  • Corresponding author: Yan Liu
  • Supported by:
    Shandong Provincial Medical Health Technology Development Project(2016WS0267)
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引用本文：

刘燕, 赵铭, 姜红, 陈晨, 王小琴, 张磊. 极早产儿支气管肺发育不良影响因素的多中心临床研究[J/OL]. 中华妇幼临床医学杂志(电子版), 2022, 18(04): 419-426.

Yan Liu, Ming Zhao, Hong Jiang, Chen Chen, Xiaoqin Wang, Lei Zhang. Risk factors of bronchopulmonary dysplasia in very preterm infants: a multicenter study[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2022, 18(04): 419-426.

目的

探讨极早产儿发生支气管肺发育不良(BPD)的影响因素。

方法

选择2020年1月1日至12月31日，于青岛大学附属医院、青岛市市立医院、济宁市第一人民医院及枣庄市妇幼保健院出生并接受治疗的208例极早产儿为研究对象。根据是否发生BPD，将其分为BPD组(n＝153)和非BPD组(n＝55)；再根据BPD严重程度分度，将BPD组极早产儿分为Ⅰ度BPD亚组(n＝31)、Ⅱ度BPD亚组(n＝17)及Ⅲ度BPD亚组(n＝7)。采用回顾性分析法，统计学比较BPD组与非BPD组，以及3个BPD亚组极早产儿出生与治疗情况、生后14 d内液体摄入量等。采用多因素非条件logistic回归分析，探讨极早产儿发生BPD及BPD极早产儿发生Ⅲ度BPD的影响因素。本研究经青岛大学附属医院医学伦理委员会批准(审批文号：QYFYWZLL26841)，并且与所有患儿监护人签署临床研究知情同意书。

结果

①BPD组极早产儿出生胎龄、体重、头围及身长，以及生后1、5、10 min Apgar评分，均小于、轻于、短于、低于非BPD组；而孕母产前激素使用率，极早产儿出生窒息率、肺表面活性剂(PS)使用率及早发型败血症(EOS)发生率，以及有创及无创机械通气时间，均高于、长于非BPD组，并且差异均有统计学意义(P<0.05)。②BPD组极早产儿生后第2、4、5、7、11、12天的总液体摄入量，以及生后第6、8~14天肠外液体静脉输注量，均多于非BPD组；生后第1~14天肠内液体摄入量，则均少于非BPD组，并且上述差异均有统计学意义(P<0.05)。③多因素非条件logistic回归分析：极早产儿生后1 min Apgar评分低(OR＝1.866，95%CI：1.063~3.274，P＝0.030)，有创机械通气时间长(OR＝1.834，95%CI：1.158~2.905，P＝0.010)，无创机械通气时间长(OR＝1.163，95%CI：1.067~1.267，P＝0.001)，发生EOS(OR＝0.071，95%CI：0.011~0.465，P＝0.006)是极早产儿发生BPD的独立危险因素；生后第3、4、5天肠内液体摄入量多(OR＝0.671、0.708、0.746，95%CI：0.483~0.932、0.511~0.846、0.583~0.955，P＝0.017、0.004、0.020)，是极早产儿发生BPD的独立保护因素。④3个BPD亚组极早产儿出生胎龄、孕母产前激素使用率、出生窒息率、EOS发生率及有创机械通气时间，生后第1、2、4、5、6天总液体摄入量及肠外液体静脉输注量，以及生后第1天肠内液体摄入量比较，差异均有统计学意义(均为P<0.05)。但是，这16项因素均不是BPD极早产儿发生Ⅲ度BPD的独立影响因素。

结论

极早产儿发生BPD是多种因素共同作用的结果，减少出生窒息及EOS发生率，优化呼吸支持策略，增加生后第3~5天肠内液体摄入量，有望降低极早产儿BPD发生率。

关键词: 支气管肺发育不良, 液体摄入, 危险因素, 呼吸，人工, 婴儿，极度早产
Objective

To explore influencing factors of bronchopulmonary dysplasia (BPD) in very premature infants.

Methods

From 1 January to 31 December 2020, a total of 208 very premature infants who were born and treated in the Affiliated Hospital of Qingdao University, Jining No.1 People′s Hospital, Qingdao Municipal Hospital and Maternity and Child Health Care of Zaozhuang, were chosen as research subjects. According to whether BPD occurred or not, they were divided into BPD group (n=153) and non-BPD group (n=55). Then according to severity degree of BPD, very premature infants in BPD group were divided into grade Ⅰ BPD subgroup (n=31), grade Ⅱ BPD subgroup (n=17) and grade Ⅲ BPD subgroup (n=7). Clinical data of 208 very premature infants were retrospectively analyzed. Conditions at birth and of treatment, and fluid intake within 14 d after birth of very premature infants were statistically compared between BPD and non-BPD groups, and among 3 BPD subgroups. Multivariate unconditional logistic regression analysis was used to investigate the influencing factors of BPD occurence in very premature infants and grade Ⅲ BPD occurence in BPD very premature infants. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University (Approval No. QYFYWZll26841). All the guardians of the infants signed the informed consents of clinical study.

Results

① The gestational age, weight, head circumference and body length at birth, and 1, 5, 10 min Apgar scores of very premature infants in BPD group were smaller, lighter, shorter, lower than those in non-BPD group; while the usage of prenatal hormones to mother, the incidence of birth asphyxia, usage of pulmonary surfactant (PS), incidence of early onset sepsis (EOS), usage time of invasive and non-invasive ventilation of very premature infants, were higher or longer than those in non-BPD group. And the above differences were statistically significant (P<0.05). ② The total fluid intake at 2, 4, 5, 7, 11, 12 d after birth, and intravenous infusion volume of parenteral fluid at 6 d, 8-14 d after birth of very premature infants in BPD group were more than those in non-BPD group; while the enteral fluid intake at 1-14 d after birth were less than those in non-BPD group. And the above differences were statistically significant (P<0.05). ③ Multivariate unconditional logistic regression analysis showed that lower 1 min Apgar score (OR=1.866, 95%CI: 1.063-3.274, P=0.030), longer duration of invasive ventilation (OR=1.834, 95%CI: 1.158-2.905, P=0.010), longer duration of non-invasive ventilation (OR=1.163, 95%CI: 1.067-1.267, P=0.001), EOS occurence (OR=0.071, 95%CI: 0.011-0.465, P=0.006) were independent risk factors of BPD occurrence in very premature infants. The larger volume of enteral fluid intake at 3, 4, 5 d after birth (OR=0.671, 0.708, 0.746; 95%CI: 0.483-0.932, 0.511-0.846, 0.583-0.955; P=0.017, 0.004, 0.020) were independent protective factors of BPD occurrence in very premature infants. ④ There were significant differences among grade Ⅰ, Ⅱ and Ⅲ BPD subgroups in gestational age at birth, prenatal hormone application to mother, birth asphyxia rate, incidence of EOS and duration of invasive mechanical ventilation, also in total fluid intake and intravenous infusion volume of parenteral fluid at 1, 2, 4, 5, 6 d after birth, and enteral fluid intake at 1 d after birth (all P<0.05). However, these 16 indicators were not independent influencing factors of grade Ⅲ BPD occurrence in BPD very premature infants.

Conclusions

The occurrence of BPD in very premature infants is the result of multiple factors. Reducing incidence of birth asphyxia and EOS, optimizing respiratory support strategies, and increasing enteral fluid intake at 3-5 d after birth, would be expected to reduce incidence of BPD in very premature infants.

Key words: Bronchopulmonary dysplasia, Fluid intake, Risk factors, Respiration, artificial, Infant, extremely premature
表1 BPD与非BPD组极早产儿一般临床资料及治疗情况比较
组别 例数 出生胎龄(周，±s) 男性[例数(%)] BW(g，±s) 出生头围[cm，M(Q1，Q3)] 出生身长[cm，M(Q1，Q3)] 生后1 min Apgar评分[分，M(Q1，Q3)] 生后5 min Apgar评分[分，M(Q1，Q3)]
BPD组 55 29.5±1.7 32(58.2) 1 198±279 28(26，29) 37(35，40) 8(5，9) 9(7，9)
非BPD组 153 31.1±1.6 95(62.1) 1 467±283 28(29，30) 40(38，42) 9(7，10) 10(8，10)
统计量   t＝6.446 χ2＝0.209 t＝6.143 Z＝－4.445 Z＝－5.424 Z＝－3.280 Z＝－4.044
P值   <0.001 0.672 <0.001 <0.001 <0.001 0.001 <0.001
组别 例数 生后10 min Apgar评分[分，M(Q1，Q3)] 合并PDA[例数(%)] 小于胎龄儿[例数(%)] 剖宫产娩出[例数(%)] 多胎儿[例数(%)] 孕母胎膜早破[例数(%)] 孕母产前使用激素[例数(%)]
BPD组 55 9(9，10) 15(27.3) 8(14.6) 42(76.4) 8(14.6) 16(29.1) 31(58.5)
非BPD组 153 10(9，10) 41(26.8) 13(8.5) 116(75.8) 35(22.9) 41(26.8) 59(38.6)
统计量   Z＝－4.286 χ2＝0.005 χ2＝1.631 χ2＝0.007 χ2＝1.712 χ2＝0.107 χ2＝5.223
P值   <0.001 0.946 0.202 0.935 0.191 0.744 0.022
组别 例数 出生窒息[例数(%)] 孕母妊娠期高血压疾病[例数(%)] 孕母妊娠期糖尿病[例数(%)] 使用PS[例数(%)] 发生EOS[例数(%)] 有创机械通气时间(d，±s) 无创机械通气时间(d，±s)
BPD组 55 21(39.6) 14(26.4) 7(13.2) 35(63.6) 23(43.4) 8.89±1.21 25.1±3.7
非BPD组 153 24(15.7) 40(26.1) 34(22.2) 39(25.5) 37(24.2) 0.36±0.15 10.8±2.4
统计量   χ2＝12.076 χ2＝0.010 χ2＝2.305 χ2＝25.685 χ2＝6.130 t＝－85.743 t＝－32.580
P值   0.001 0.920 0.129 <0.001 0.013 <0.001 <0.001
图1 BPD与非BPD组极早产儿生后14 d内液体摄入量比较(图1A：每日液体总摄入量；图1B：每日肠外液体静脉输注量；图1C：每日肠内液体摄入量)注：a表示BPD与非BPD组比较，P<0.05。BPD为支气管肺发育不良
表2 极早产儿发生BPD的多因素非条件logistic回归分析结果a
影响因素 B SE Wald值 P值 OR值 OR值95%CI
生后1 min Apgar评分 0.624 0.287 4.726 0.030 1.866 1.063~3.274
有创机械通气时间 0.607 0.235 6.686 0.010 1.834 1.158~2.905
无创机械通气时间 0.151 0.044 11.836 0.001 1.163 1.067~1.267
发生EOS －2.644 0.959 7.608 0.006 0.071 0.011~0.465
生后第3天肠内液体摄入量 －0.400 0.168 5.670 0.017 0.671 0.483~0.932
生后第4天肠内液体摄入量 0.346 0.120 8.335 0.004 1.413 1.117~1.787
生后第5天肠内液体摄入量 －0.292 0.126 5.400 0.020 0.746 0.583~0.955
常数项 －4.618 12.563 0.135 0.713 0.010 —
表3 3个BPD亚组极早产儿一般临床资料及治疗情况比较
组别 例数 出生胎龄(周，±s) BW(g，±s) 出生头围(cm，±s) 出生身长(cm，±s) Apgar评分(分，±s)
生后1 min 生后5 min 生后10 min
Ⅰ度BPD亚组 31 29.1±1.4 1 175±271 27.2±2.2 36.8±2.9 6.9±2.2 7.9±1.6 9.1±0.6
Ⅱ度BPD亚组 17 30.6±1.2 1 246±217 27.5±2.1 37.9±2.5 7.3±2.6 8.6±1.6 9.1±1.0
Ⅲ度BPD亚组 7 28.6±2.4 1 184±414 25.7±3.5 36.1±4.8 6.1±3.6 7.3±3.7 8.1±2.7
F值   7.129 0.372 1.558 1.117 0.506 1.300 1.897
P值   0.002 0.691 0.220 0.335 0.606 0.281 0.162
组别 例数 孕母产前使用激素[例数(%)] 出生窒息[例数(%)] 使用PS[例数(%)] 发生EOS[例数(%)] 有创机械通气时间(d，±s) 无创机械通气时间(d，±s)
Ⅰ度BPD亚组 31 12(38.7) 6(19.4) 21(67.7) 7(22.6) 2.5±1.2 24.1±1.4
Ⅱ度BPD亚组 17 12(70.6) 8(47.1) 9(52.9) 11(64.7) 2.6±0.5 25.7±5.0
Ⅲ度BPD亚组 7 7(100.0) 7(100.0) 5(71.4) 5(71.4) 52.7±15.3 28.1±8.2
F值   10.746 16.556 1.250 10.898 276.455 3.032
P值   0.005 <0.001 0.535 0.004 <0.001 0.057
图2 3个BPD亚组极早产儿生后14 d内液体摄入量比较(图2A：每日液体总摄入量；图2B：每日肠外液体静脉输注量；图2C：每日肠内液体摄入量)注：a表示3个BPD亚组比较的P<0.05。BPD为支气管肺发育不良
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