Fortmann Ingmar, Welp Amrei, Hoffmann Nele, Faust Kirstin, Silwedel Christine, Retzmann Jana, Gembicki Michael, Köstlin-Gille Natascha, Häfke Anna, Zemlin Michael, Marissen Janina, Bossung Verena, Soler Wenglein Janina, Scharf Jan-Lennard, Weichert Jan, Müller Andreas, Ricklefs Isabell, Rody Achim, Pirr Sabine, Boutin Sebastien, Rupp Jan, Brinkmann Folke, Heideking Martin, Stichtenoth Guido, Göpel Wolfgang, Herting Egbert, Hanke Kathrin, Härtel Christoph
Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Lübeck and Borstel, Germany.
JAMA Netw Open. 2025 May 1;8(5):e259647. doi: 10.1001/jamanetworkopen.2025.9647.
Animal models suggest a link between early antibiotic exposure and obstructive airway disease, but corresponding data for premature infants are lacking.
To investigate whether repeated perinatal antibiotic exposure in preterm neonates with very low birth weight (VLBW) is associated with obstructive airway disease at early school age.
DESIGN, SETTING, AND PARTICIPANTS: In this population-based, multicenter cohort study, VLBW preterm neonates (22 weeks 0 days' to 36 weeks 6 days' gestation with birth weight <1500 g) were enrolled in 58 German Neonatal Network (GNN) centers from January 2009 to March 2017 and received a standardized follow-up at 5 to 7 years of age. To assess the sequential outcomes of antibiotic exposures, the post hoc analysis was restricted to participants born by cesarean delivery. Data were analyzed from May 2024 to February 2025.
Perinatal antibiotic exposure, defined by an antibiotic risk score (ARS).
The primary end point was the forced expiratory volume in 1 second (FEV1) z score at 5 to 7 years of age. The low-risk (ARS I) group was exclusively exposed to surgical antimicrobial prophylaxis (SAP) given to the mother before cesarean delivery. The intermediate-risk (ARS II) group was exposed to maternal SAP and postnatal antibiotic treatment of the neonate, while the high-risk (ARS III) group was additionally exposed to antenatal maternal treatment. Secondary outcomes included forced vital capacity (FVC) z score and childhood asthma episodes. Univariate and linear regression models were used to analyze outcome measures.
Of 3820 VLBW preterm-born children with follow-up at age 5 to 7 years (median gestational age, 28.4 weeks [IQR, 26.6-30.3 weeks]; 1948 [51.0%] male; 1382 [36.2%] from a multiple birth), 3109 (81.4%) were born by cesarean delivery. Of these children, 292 (9.4%) were classified into ARS I, 1329 (42.7%) into ARS II, and 1488 (47.9%) into ARS III. Higher ARS levels were associated with lower FEV1 z scores at early school age (ARS II vs I: β, -0.31 [95% CI, -0.59 to -0.02]; P = .03; ARS III vs II: β, -0.27 [95% CI, -0.46 to -0.08]; P = .006). In the secondary analysis, a higher exposure level (ARS III vs II) was associated with impaired FVC z scores (β, -0.23; 95% CI, -0.43 to -0.03; P = .02) and an increased risk of early childhood asthma episodes (odds ratio, 1.91; 95% CI, 1.32-2.76; P = .001).
In this GNN cohort study, multiple episodes of perinatal antibiotic exposure were associated with impaired lung function in preterm-born children at early school age. Early identification of high-risk neonates may enable targeted strategies to support respiratory health and optimize long-term outcomes.
动物模型表明早期抗生素暴露与阻塞性气道疾病之间存在联系，但缺乏早产儿的相应数据。
探讨极低出生体重（VLBW）早产儿围产期反复接触抗生素是否与学龄早期的阻塞性气道疾病有关。
设计、设置和参与者：在这项基于人群的多中心队列研究中，2009年1月至2017年3月期间，58个德国新生儿网络（GNN）中心纳入了VLBW早产儿（妊娠22周0天至36周6天，出生体重<1500 g），并在5至7岁时接受了标准化随访。为了评估抗生素暴露的连续结果，事后分析仅限于剖宫产出生的参与者。2024年5月至2025年2月对数据进行了分析。
围产期抗生素暴露，由抗生素风险评分（ARS）定义。
主要终点是5至7岁时的1秒用力呼气量（FEV1）z评分。低风险（ARS I）组仅在剖宫产术前接受了母亲的手术抗菌预防（SAP）。中风险（ARS II）组接受了母亲的SAP和新生儿的产后抗生素治疗，而高风险（ARS III）组还接受了产前母亲治疗。次要结局包括用力肺活量（FVC）z评分和儿童哮喘发作次数。使用单变量和线性回归模型分析结局指标。
在3820名5至7岁接受随访的VLBW早产儿中（中位胎龄28.4周[IQR，26.6 - 30.3周]；1948名[51.0%]为男性；1382名[36.2%]来自多胞胎），3109名（81.4%）通过剖宫产出生。在这些儿童中，292名（9.4%）被归类为ARS I，1329名（42.7%）被归类为ARS II，1488名（47.9%）被归类为ARS III。较高的ARS水平与学龄早期较低的FEV1 z评分相关（ARS II与I相比：β， - 0.31 [95% CI， - 0.59至 - 0.02]；P = 0.03；ARS III与II相比：β， - 0.27 [95% CI， - 0.46至 - 0.08]；P = 0.006）。在次要分析中，较高的暴露水平（ARS III与II相比）与FVC z评分受损相关（β， - 0.23；95% CI， - 0.43至 - 0.03；P = 0.02）以及幼儿哮喘发作风险增加相关（比值比，1.91；95% CI，1.32 - 2.76；P = 0.001）。
在这项GNN队列研究中，围产期多次接触抗生素与早产儿童学龄早期的肺功能受损有关。早期识别高危新生儿可能有助于制定有针对性的策略，以支持呼吸道健康并优化长期结局。
