早期经验性抗生素延长暴露对早产儿住院结局的影响

doi:10.3969/j.issn.1004-583X.2024.08.008

摘要/Abstract

摘要：

目的回顾性分析胎龄<32周或出生体重<1 500 g早产儿的临床资料,探讨早产儿早期经验性抗生素延长暴露对早产儿住院结局的影响,进一步指导早产儿抗生素的合理应用。方法收集青岛大学附属医院2018年1月1日到2020年12月31日收治的胎龄<32周或出生体重<1 500 g的早产儿临床资料。按照生后早期经验性抗生素应用时间分为短期暴露组(≤5 d)和长期暴露组(>5 d),分析比较两组早产儿住院期间并发症。结果共291例,男166例,女125例。抗生素短期暴露组抗生素使用中位时间为3 d,长期暴露组抗生素使用中位时间为9 d。与短期暴露组相比,长期暴露组早产儿喂养不耐受(feeding intolerance,FI)发生率明显增加,达半量肠内喂养时间、达全肠内喂养时间及住院时间明显延长(P<0.05),长期暴露组早产儿支气管肺发育不良(bronchopulmonary dysplasia,BPD)、晚发败血症(late-onset sepsis,LOS)的发生率明显升高(P<0.05)。单因素logistic回归分析显示,抗生素延长暴露与住院期间FI、BPD、LOS、复合不良结局发生率增加均相关。多因素logistic回归分析显示经验性抗生素延长暴露是FI、BPD的独立危险因素,多元线性回归分析显示抗生素暴露时间越长,住院时间及达全肠内喂养时间越长。结论经验性抗生素延长暴露可增加早产儿BPD风险,影响肠道喂养,导致住院时间延长。

关键词: 婴儿, 早产, 婴儿, 极低出生体重, 经验性抗生素, 不良结局

Abstract:

Objective To explore the effect of prolonged early empirical antibiotic exposures on the hospitalization outcome of preterm infants by retrospectively analyzing the clinical data of preterm infants born with gestational age <32 weeks or birth weight < 1500 g, and to further guide the rational application of antibiotics in preterm infants. Methods Clinical data of preterm infants born with gestational age <32 weeks or birth weight <1500 g in the Affiliated Hospital of Qingdao University from January 1, 2018 to December 31, 2020 were collected. They were divided into short-term exposure group (≤5 days) and long-term exposure group (>5 days) according to the duration of empirical antibiotic application in the early postnatal period. The complications during hospitalization between the two groups were analyzed and compared. Results A total of 291 cases were retrospectively included, involving 166 males and 125 females. The median duration of antibiotic use in the short-term and long-term exposure groups was 3 days and 9 days, respectively. Compared with those of the short-term exposure group, cases in the long-term exposure group presented significantly higher incidence of feeding intolerance (FI), and longer duration of half-intestinal feeding, full intestinal feeding and the length of stay (P<0.05). The incidence of bronchopulmonary dysplasia (BPD) and late-onset sepsis (LOS) was significantly higher in the long-term exposure group than that of the short-term exposure group (P<0.05). Univariate Logistic regression analysis showed that prolonged antibiotic exposure was associated with increased incidences of FI, BPD, LOS, and composite outcomes during hospitalization. Multivariate Logistic regression analysis showed that prolonged exposure of empirical antibiotics was an independent risk factor for FI and BPD. Multiple linear regression analysis showed that the duration of antibiotic use was positively correlated with the length of stay and the length of whole intestinal feeding. Conclusion Prolonged early empirical antibiotic exposures can increase the risk of BPD in preterm infants, affect intestinal feeding, and lead to a longer length of stay.

Key words: infant, premature, infant, very low birth weight, empirical antibiotics, adverse outcome

中图分类号:

R722

徐元媛, 于见梅, 张秀丽, 李亮亮, 尹向云, 李向红. 早期经验性抗生素延长暴露对早产儿住院结局的影响[J]. 临床荟萃, 2024, 39(8): 728-733.

Xu Yuanyuan, Yu Jianmei, Zhang Xiuli, Li Liangliang, Yin Xiangyun, Li Xianghong. Effect of prolonged early empirical antibiotic exposures on hospitalization outcomes of premature infants[J]. Clinical Focus, 2024, 39(8): 728-733.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2024.08.008

https://huicui.hebmu.edu.cn/CN/Y2024/V39/I8/728

图/表 5

表1 两组早产儿基本资料比较

Tab.1 Basic data of the two groups

组别	例数	产前激素 [例(%)]	产前抗生素 [例(%)]		剖宫产 [例(%)]	妊高症 [例(%)]		妊娠期糖尿病 [例(%)]		胎膜早破 [例(%)]	产前发热或绒毛膜炎 [例(%)]
短期暴露组	104	73(70.2)	43(41.4)		78(75.0)	27(26.0)		33(31.7)		18(17.3)	2(1.9)
长期暴露组	187	143(76.5)	46(24.6)		140(74.9)	55(29.4)		59(31.6)		31(16.6)	6(3.2)
统计值		χ²=1.377	χ²=8.829		χ²=0.001	χ²=0.393		χ²=0.001		χ²=0.025	χ²=0.072
$P$ 值		0.241	0.003		0.980	0.531		0.975		0.873	0.788
组别	胎龄(w)			出生体重(g)			性别男 [例(%)]		多胎 [例(%)]			SGA [例(%)]
短期暴露组	30.00(30.00,31.00)			1450.00(1280.00,1590.00)			57(54, 8)		25(24.0)			5(4.8)
长期暴露组	30.00(29.00,31.00)			1300.00(1110.00,1480.00)			109(58.3)		45(24.1)			32(17.1)
统计值	$Z$ =-1.136			$Z$ =-3.847			χ²=0.331		χ²=0.000			χ²=9.117
$P$ 值	0.256			<0.01			0.565		0.996			0.003
组别	1分钟APGAR评分 (分)			5分钟APGAR评分 (分)			PS应用 [例(%)]		机械通气 [例(%)]			母乳喂养 [例(%)]
短期暴露组	9.00(7.00,10.00)			10.00(9.00,10.00)			30(28.8)		8(7.7)			39(37.5)
长期暴露组	7.00(6.00,9.00)			9.00(8.00,10.00)			65(34.8)		34(18.2)			78(41.7)
统计值	$Z$ =-4.699			$Z$ =-4.371			χ²=1.063		χ²=5.954			χ²=0.493
$P$ 值	<0.01			<0.01			0.303		0.015			0.483

表1 两组早产儿基本资料比较

Tab.1 Basic data of the two groups

组别	例数	产前激素 [例(%)]	产前抗生素 [例(%)]		剖宫产 [例(%)]	妊高症 [例(%)]		妊娠期糖尿病 [例(%)]		胎膜早破 [例(%)]	产前发热或绒毛膜炎 [例(%)]
短期暴露组	104	73(70.2)	43(41.4)		78(75.0)	27(26.0)		33(31.7)		18(17.3)	2(1.9)
长期暴露组	187	143(76.5)	46(24.6)		140(74.9)	55(29.4)		59(31.6)		31(16.6)	6(3.2)
统计值		χ²=1.377	χ²=8.829		χ²=0.001	χ²=0.393		χ²=0.001		χ²=0.025	χ²=0.072
$P$ 值		0.241	0.003		0.980	0.531		0.975		0.873	0.788
组别	胎龄(w)			出生体重(g)			性别男 [例(%)]		多胎 [例(%)]			SGA [例(%)]
短期暴露组	30.00(30.00,31.00)			1450.00(1280.00,1590.00)			57(54, 8)		25(24.0)			5(4.8)
长期暴露组	30.00(29.00,31.00)			1300.00(1110.00,1480.00)			109(58.3)		45(24.1)			32(17.1)
统计值	$Z$ =-1.136			$Z$ =-3.847			χ²=0.331		χ²=0.000			χ²=9.117
$P$ 值	0.256			<0.01			0.565		0.996			0.003
组别	1分钟APGAR评分 (分)			5分钟APGAR评分 (分)			PS应用 [例(%)]		机械通气 [例(%)]			母乳喂养 [例(%)]
短期暴露组	9.00(7.00,10.00)			10.00(9.00,10.00)			30(28.8)		8(7.7)			39(37.5)
长期暴露组	7.00(6.00,9.00)			9.00(8.00,10.00)			65(34.8)		34(18.2)			78(41.7)
统计值	$Z$ =-4.699			$Z$ =-4.371			χ²=1.063		χ²=5.954			χ²=0.493
$P$ 值	<0.01			<0.01			0.303		0.015			0.483

表2 两组早产儿住院不良结局比较[例(%)]

Tab.2 Adverse hospitalization outcomes between groups

组别	例数	BPD	ROP	LOS	NEC	死亡	复合不良结局
短期暴露组	104	15(14.4)	6(5.8)	10(9.6)	3(2.9)	1(1.0)	26(24.0)
长期暴露组	187	63(33.7)	13(7.0)	40(21.4)	12(6.4)	6(3.2)	83(44.4)
统计值		χ²=12.645	χ²=0.153	χ²=6.512	χ²=1.706	χ²=1.437	χ²=10.720
$P$ 值		<0.01	0.696	0.011	0.192	0.231	0.001

表2 两组早产儿住院不良结局比较[例(%)]

Tab.2 Adverse hospitalization outcomes between groups

组别	例数	BPD	ROP	LOS	NEC	死亡	复合不良结局
短期暴露组	104	15(14.4)	6(5.8)	10(9.6)	3(2.9)	1(1.0)	26(24.0)
长期暴露组	187	63(33.7)	13(7.0)	40(21.4)	12(6.4)	6(3.2)	83(44.4)
统计值		χ²=12.645	χ²=0.153	χ²=6.512	χ²=1.706	χ²=1.437	χ²=10.720
$P$ 值		<0.01	0.696	0.011	0.192	0.231	0.001

表3 两组早产儿肠道喂养及住院时间比较

Tab.3 Enteral feeding and hospitalization time between groups

组别	例数	FI[例(%)]	达半量肠道喂养时间(d)	达全肠道喂养时间(d)	住院时间(d)
短期暴露组	104	22(21.2)	10.00(8.00, 14.00)	16.00(13.00, 20.00)	44.00(34.00, 58.00)
长期暴露组	187	85(45.4)	12.00(8.50, 18.00)	23.00(17.00, 33.50)	55.00(43.00, 70.00)
统计值		χ²=16.975	$Z$ =-2.768	$Z$ =-6.032	$Z$ =-3.955
$P$ 值		<0.01	0.006	<0.01	<0.01

表3 两组早产儿肠道喂养及住院时间比较

Tab.3 Enteral feeding and hospitalization time between groups

组别	例数	FI[例(%)]	达半量肠道喂养时间(d)	达全肠道喂养时间(d)	住院时间(d)
短期暴露组	104	22(21.2)	10.00(8.00, 14.00)	16.00(13.00, 20.00)	44.00(34.00, 58.00)
长期暴露组	187	85(45.4)	12.00(8.50, 18.00)	23.00(17.00, 33.50)	55.00(43.00, 70.00)
统计值		χ²=16.975	$Z$ =-2.768	$Z$ =-6.032	$Z$ =-3.955
$P$ 值		<0.01	0.006	<0.01	<0.01

表4 早期经验性抗生素暴露与FI及主要结局的回归分析

Tab.4 Regression analysis of early empirical antibiotic exposures with FI and primary outcomes

指标	回归系数	标准误	Wald χ²值	校正前 $P$ 值	校正前 $O R$ 值	校正前 $O R$ 的95% $C I$		校正后 $P$ 值	校正后 $O R$ 值	校正后 $O R$ 的95% $C I$
指标	回归系数	标准误	Wald χ²值	校正前 $P$ 值	校正前 $O R$ 值	下限	上限	校正后 $P$ 值	校正后 $O R$ 值	下限	上限
FI	0.876	0.305	8.267	0.000	3.106	1.789	5.392	0.004	2.401	1.322	4.362
BPD	1.227	0.430	8.151	0.001	3.015	1.613	5.635	0.004	3.412	1.469	7.924
ROP	-0.515	0.713	0.520	0.696	1.220	0.450	3.312	0.471	0.598	0.148	2.419
LOS	0.736	0.407	3.270	0.013	2.558	1.221	5.360	0.071	2.088	0.940	4.636
NEC	0.383	0.705	0.295	0.203	2.309	0.636	8.375	0.587	1.467	0.369	5.837
死亡	0.078	1.329	0.003	0.259	3.414	0.405	28.754	0.953	1.081	0.080	14.622
复合不良结局	0.803	0.335	5.740	0.001	2.394	1.410	4.065	0.017	2.232	1.157	4.306

表4 早期经验性抗生素暴露与FI及主要结局的回归分析

Tab.4 Regression analysis of early empirical antibiotic exposures with FI and primary outcomes

指标	回归系数	标准误	Wald χ²值	校正前 $P$ 值	校正前 $O R$ 值	校正前 $O R$ 的95% $C I$		校正后 $P$ 值	校正后 $O R$ 值	校正后 $O R$ 的95% $C I$
指标	回归系数	标准误	Wald χ²值	校正前 $P$ 值	校正前 $O R$ 值	下限	上限	校正后 $P$ 值	校正后 $O R$ 值	下限	上限
FI	0.876	0.305	8.267	0.000	3.106	1.789	5.392	0.004	2.401	1.322	4.362
BPD	1.227	0.430	8.151	0.001	3.015	1.613	5.635	0.004	3.412	1.469	7.924
ROP	-0.515	0.713	0.520	0.696	1.220	0.450	3.312	0.471	0.598	0.148	2.419
LOS	0.736	0.407	3.270	0.013	2.558	1.221	5.360	0.071	2.088	0.940	4.636
NEC	0.383	0.705	0.295	0.203	2.309	0.636	8.375	0.587	1.467	0.369	5.837
死亡	0.078	1.329	0.003	0.259	3.414	0.405	28.754	0.953	1.081	0.080	14.622
复合不良结局	0.803	0.335	5.740	0.001	2.394	1.410	4.065	0.017	2.232	1.157	4.306

表5 早期经验性抗生素暴露与次要结局的回归分析

Tab.5 Regression analysis of early empirical antibiotic exposures and secondary outcomes

指标	未标准化系数	标准化系数	标准误	$t$ 值	校正前 $P$ 值	校正后 $P$ 值	校正前β的95% $C I$		校正后β的95% $C I$
指标	未标准化系数	标准化系数	标准误	$t$ 值	校正前 $P$ 值	校正后 $P$ 值	下限	上限	下限	上限
达半量肠内喂养时间	0.985	0.070	0.803	1.227	0.003	0.221	0.803	4.007	-0.595	2.565
达全肠内喂养时间	5.246	0.221	1.288	4.071	<0.01	<0.01	5.040	10.282	2.709	7.782
住院时间	5.215	0.113	1.552	3.361	<0.01	0.001	5.786	16.188	2.160	8.269

表5 早期经验性抗生素暴露与次要结局的回归分析

Tab.5 Regression analysis of early empirical antibiotic exposures and secondary outcomes

指标	未标准化系数	标准化系数	标准误	$t$ 值	校正前 $P$ 值	校正后 $P$ 值	校正前β的95% $C I$		校正后β的95% $C I$
指标	未标准化系数	标准化系数	标准误	$t$ 值	校正前 $P$ 值	校正后 $P$ 值	下限	上限	下限	上限
达半量肠内喂养时间	0.985	0.070	0.803	1.227	0.003	0.221	0.803	4.007	-0.595	2.565
达全肠内喂养时间	5.246	0.221	1.288	4.071	<0.01	<0.01	5.040	10.282	2.709	7.782
住院时间	5.215	0.113	1.552	3.361	<0.01	0.001	5.786	16.188	2.160	8.269

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