广谱抗生素使用时间对极低出生体重早产儿炎症因子水平及支气管肺发育不良的影响

Effect of broad-spectrum antibiotics usage duration on inflammatory factor levels and bronchopulmonary dysplasia in very low birth weight premature infants

摘要

目的 探究广谱抗生素(ABX)使用时间对极低出生体重(VLBW)早产儿炎症因子水平及支气管肺发育不良(BPD)的影响。方法 选择2021年6月至2023年6月宿迁市第一人民医院收治的VLBW早产儿(n=105)为研究对象。根据BPD诊断标准,分为BPD组(n=42)和非BPD组(n=63)。根据生后14 d内ABX使用时间,分为≤7 d组(n=51)和>7 d组(n=54)。采用Pearson相关系数法分析相关性。采用多因素Logistic回归分析ABX使用时间与BPD风险的关联。采用广义多因子降维模型(GMDR)分析ABX使用时间与出生2周血清炎症标志物水平对BPD的交互作用。结果 与ABX使用≤7 d组相比,ABX使用>7 d组患儿出生2周的白细胞介素-6(IL-6)、IL-8、肿瘤坏死因子α(TNF-α)、降钙素原(PCT)水平均更高(t介于2.113到9.254之间,P<0.05),IL-10水平更低(t=7.042,P<0.05),差异均有统计学意义。ABX使用时间与出生2周IL-6、IL-8、TNF-α、PCT均呈正相关(r介于0.304到0.560之间,P<0.05),与出生2周IL-10呈负相关(r=-0.402,P<0.05)。与非BPD组相比,BPD组患儿的出生体重、Apgar评分均更低,有创机械通气(IMV)时间、住院时间、ABX使用时间更长,阴道分娩、IMV、吸入高浓度氧、肺表面活性物质(PS)使用、宫内感染、新生儿窒息的患儿比例均更高,差异均有统计学意义(t/χ²介于2.324到49.388之间,P<0.05)。与非BPD组相比,BPD组患儿出生时的IL-6、IL-8、TNF-α、PCT水平均更高,IL-10水平更低,差异均有统计学意义(t介于2.637到27.382之间,P<0.05);出生2周的IL-8、PCT水平均更高,IL-10水平更低,差异均有统计学意义(t介于3.656到20.420之间,P<0.05)。多因素Logistic回归分析显示,ABX使用时间与BPD风险存在独立相关性(OR=1.518,95%CI:1.260~1.626,P<0.05),且ABX使用时间从低到高四分位数组趋势性检验差异有统计学意义(P趋势<0.05)。GMDR分析显示,调整混杂因素后,最佳交互作用模型为ABX使用时间与出生2周IL-8、IL-10、PCT之间的交互作用(P<0.05)。结论 广谱抗生素使用时间延长与极低出生体重早产儿的血清炎症标志物水平异常表达显著相关,并与支气管肺发育不良风险独立相关,临床应控制广谱抗生素使用时间以降低支气管肺发育不良风险。

Abstract

Objective To explore effect of broad-spectrum antibiotics (abbreviated as ABX) usage duration on inflammatory cytokine levels and bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) premature infants. Methods 105 VLBW premature infants who admitted to Suqian First People's Hospital from June 2021 to June 2023 were selected as research subjects. According to diagnostic criteria for BPD,they were divided into BPD group (n=42) and non-BPD group (n=63). According to duration of ABX use within 14 days after birth,they were divided into ABX usage duration ≤7 d group (n=51) and ABX usage duration >7 d group (n=54). Pearson correlation coefficient method was used to analyze correlations between ABX usage duration and serum inflammatory cytokine levels. Multiple Logistic regression was used to analyze association between ABX usage duration and risk for BPD. Generalized multi-factor dimension reduction model (GMDR) was used to analyze interactions of ABX usage duration and serum inflammatory marker levels at 2 weeks after birth with BPD. Results Compared with the ABX usage duration ≤7 d group,the VLBW premature infants in the ABX usage duration >7 d group had higher serum levels of interleukin-6 (IL-6),interleukin-8 (IL-8),tumor necrosis factor-α (TNF-α),and procalcitonin (PCT) at 2 weeks after birth (t=2.113-9.254,all P<0.05),while they had lower serum level of interleukin-10 (IL-10)(t=7.042,P<0.05),there were statistically significant differences. ABX usage duration was positively correlated with IL-6,IL-8,TNF-α and PCT at 2 weeks after birth (r=0.304-0.560,all P<0.05),and negatively correlated with IL-10 at 2 weeks after birth (r=-0.402,P<0.05). Compared with the non-BPD group,the VLBW premature infants in the BPD group had lower birth weight and Apgar score,longer invasive mechanical ventilation (IMV) time,hospital stay and ABX usage duration,and higher proportion of VLBW premature infants undergoing vaginal delivery,IMV,inhaling higher concentration oxygen,using pulmonary surfactant (PS),suffering from intrauterine infection and neonatal asphyxia,and there were statistically significant differences (t/χ ²=2.324-49.388,all P<0.05). Compared with the non-BPD group,the VLBW premature infants in the BPD group had higher serum levels of IL-6,IL-8,TNF-α and PCT,and lower serum level of IL-10 at birth,there were statistically significant differences (t=2.637-27.382,all P<0.05). At 2 weeks after birth,the serum levels of IL-8 and PCT of the VLBW premature infants in the BPD group were significantly higher,while their serum level of IL-10 was significantly lower,and the differences were statistically significant (t=3.656-20.420,all P<0.05). Multiple Logistic regression analysis showed an independent correlation between ABX usage duration and BPD risk (OR=1.518,95%CI:1.260-1.626,P<0.05),and the trend test of ABX usage duration from low quartiles to high quartiles showed statistically significant differences (P_trend<0.05). GMDR analysis showed that after adjusting for confounding factors,the optimal interaction model was the interaction model between ABX usage duration and serum IL-8,IL-10 and PCT at 2 weeks after birth (P<0.05). Conclusion The prolonged use of ABX is significantly correlated with abnormal expression of serum inflammatory markers in VLBW preterm infants and independently associated with the risk of BPD,and clinical control of ABX use time should be implemented to reduce the risk of BPD.

关键词

极低出生体重 / 早产儿 / 支气管肺发育不良 / 抗生素 / 炎症因子

Key words

very low birth weight / premature infant / bronchopulmonary dysplasia / antibiotics / inflammatory cytokine

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基金资助

江苏省妇幼健康科研项目(F201643)