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

doi:10.3877/cma.j.issn.1673-5250.2022.04.007

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

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)
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)	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

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)
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)	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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