早期抗生素暴露与孤独症谱系障碍及胃肠合并症发生风险关联分析

Association of early antibiotic exposure with risks of autism spectrum disorder and gastrointestinal comorbidities

摘要

目的 探讨生后早期抗生素暴露与孤独症谱系障碍(ASD)及ASD胃肠合并症发生的关联,为部分ASD的预防提供理论依据。方法 采用病例对照研究,纳入2022年1月—2023年12月于川北医学院附属医院儿童心理行为门诊就诊的ASD儿童为ASD组(n=497),并同期在儿童保健门诊招募性别及年龄相似的健康儿童为对照组(n=506)。采用问卷调查的方式收集儿童一般情况、胃肠症状及2岁内抗生素暴露情况。采用logistic回归分析探讨早期抗生素暴露与ASD发生的关联,以及在ASD合并胃肠症状中的作用。结果 ASD组早期抗生素暴露比例显著高于对照组(37.2% vs.18.8%, χ²=42.407, P<0.001)。有早期抗生素暴露的ASD组总胃肠症状、便秘、腹痛、恶心呕吐及大便恶臭的发生率均显著高于无早期抗生素暴露的ASD组(67.6%、42.2%、25.4%、9.7%、17.3% vs. 39.4%、25.3%、8.7%、5.1%、7.1%,P<0.05)。在校正性别、年龄、早期居住地、母亲文化、母亲怀孕年龄、胎龄、出生方式、喂养方式和早期家庭年收入后,logistic回归分析显示早期抗生素暴露是ASD的危险因素(OR=2.21, 95%CI: 1.61~3.05, P<0.001),也是ASD胃肠合并症的危险因素(OR=3.17, 95%CI: 2.14~4.70, P<0.001)。对于具体的胃肠症状,未校正和校正模型均提示早期抗生素暴露增加ASD儿童便秘(OR=2.03)、腹痛(OR=3.90)及大便恶臭(OR=3.06)的发生风险(P<0.001)。结论 生后早期抗生素暴露可能增加ASD及ASD胃肠合并症的发生风险,应避免早期不必要的抗生素使用。

Abstract

Objective To explore the association of early postnatal antibiotic exposure with the development of autism spectrum disorder (ASD) and the occurrence of gastrointestinal comorbidities in ASD, so as to provide theoretical basis for the prevention of certain cases of ASD. Methods A case-control study was conducted, including children diagnosed with ASD at the Child Psychology Clinic of the Affiliated Hospital of North Sichuan Medical College from January 2022 to December 2023 as the ASD group.Healthy children of similar gender and age were recruited from the Child Health Clinic during the same period as the control group.Data on general information, gastrointestinal symptoms, and antibiotic exposure within the first two years of life were collected through questionnaires.Logistic regression analysis was employed to explore the association between early antibiotic exposure and the occurrence of ASD, as well as its role in gastrointestinal symptoms comorbid with ASD. Results The proportion of early antibiotic exposure was significantly higher in the ASD group compared to the control group (37.2% vs. 18.8%, χ²=42.407, P<0.001).The incidence rates of overall gastrointestinal symptoms, constipation, abdominal pain, nausea and vomiting, and foul-smelling stools were significantly higher in the antibiotic-exposed ASD group compared to the non-exposed ASD group (67.6%, 42.2%, 25.4%, 9.7%, 17.3% vs. 39.4%, 25.3%, 8.7%, 5.1%, 7.1%, respectively, P<0.05).After adjusting for gender, age, early residence, maternal education, maternal age at pregnancy, gestational age, delivery mode, feeding method, and early family annual income, logistic regression analysis revealed that early antibiotic exposure was a risk factor for ASD (OR=2.21, 95%CI: 1.61 - 3.05, P<0.001) and for gastrointestinal comorbidities in ASD (OR=3.17, 95%CI: 2.14 - 4.70, P<0.001).For specific gastrointestinal symptoms, both unadjusted and adjusted models indicated that early antibiotic exposure increased the risk of constipation (OR=2.03), abdominal pain (OR=3.90), and foul-smelling stools (OR=3.06) in children with ASD(P<0.001). Conclusions Early antibiotic exposure may increase the risk of ASD and gastrointestinal comorbidities in ASD.Therefore, unnecessary antibiotic use in early life should be avoided.

关键词

孤独症谱系障碍 / 胃肠合并症 / 抗生素 / 发病风险 / 生命早期

Key words

autism spectrum disorder / gastrointestinal comorbidity / antibiotics / morbidity risk / early life

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基金资助

四川省自然科学基金(2024NSFSC1670);南充市市校科技战略合作专项资金(20SXZRKX0007);川北医学院附属医院博士启动资金(202004);川北医学院重点培育项目(CBY23-ZDA05)