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.
Key words
autism spectrum disorder /
gastrointestinal comorbidity /
antibiotics /
morbidity risk /
early life
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
[1] Hyman SL, Levy SE, Myers SM.Identification, evaluation, and management of children with autism spectrum disorder[J].Pediatrics, 2020, 145(1):e20193447.
[2] Lord C, Charman T, Havdahl A, et al.The Lancet Commission on the future of care and clinical research in autism[J].Lancet, 2022, 399(10321):271-334.
[3] Wang J, Ma B, Wang J, et al.Global prevalence of autism spectrum disorder and its gastrointestinal symptoms: A systematic review and Meta-analysis[J].Front Psychiatry, 2022, 13: 963102.
[4] Diamanti T, Prete R, Battista N, et al.Exposure to antibiotics and neurodevelopmental disorders: Could probiotics modulate the gut-brain axis?[J].Antibiotics (Basel), 2022, 11(12):1767.
[5] Lin YC, Lin CH, Lin MC.The association of prenatal antibiotic use with attention deficit and autism spectrum disorders: A nationwide cohort study[J].Children (Basel), 2023, 10(7):1128.
[6] Gómez-Vallejo S, Leoni M, Ronald A, et al.Autism spectrum disorder and obstetric optimality: A twin study and Meta-analysis of sibling studies[J].J Child Psychol Psychiatry, 2021, 62(11):1353-1362.
[7] Nitschke AS, do Valle HA, Vallance BA, et al.Association between prenatal antibiotic exposure and autism spectrum disorder among term births: A population-based cohort study[J].Paediatr Perinat Epidemiol, 2023, 37(6):516-526.
[8] American Psychiatric Association.Diagnostic and statistical manual of mental disorders[M].5th ed.Arlington, VA: American Psychiatric Association, 2013.
[9] Hyams JS, Di Lorenzo C, Saps M, et al.Childhood functional gastrointestinal disorders: Child/adolescent[J].Gastroenterology 2016; 130(5): 1527-1537.
[10] Cheng B, Zhu J, Yang T, et al.Vitamin A deficiency increases the risk of gastrointestinal comorbidity and exacerbates core symptoms in children with autism spectrum disorder[J].Pediatr Res, 2021, 89(1): 211-216.
[11] Njotto LL, Simin J, Fornes R, et al.Maternal and early-life exposure to antibiotics and the risk of autism and attention-deficit hyperactivity disorder in childhood: A Swedish population-based cohort study[J].Drug Saf, 2023, 46(5):467-478.
[12] Delara M, McMillan DE, Nickel NC, et al.Early life exposure to antibiotics and the risk of mood and anxiety disorders in children and adolescents: A population-based cohort study[J].J Psychiatr Res, 2021, 137: 621633.
[13] Margetaki K, Stratakis N, Roumeliotaki T, et al.Prenatal and infant antibiotic exposure and childhood growth, obesity and cardiovascular risk factors: The Rhea mother-child cohort study, Crete, Greece[J].Pediatr Obes, 2022, 17(1):e12843.
[14] Slob EMA, Brew BK, Vijverberg SJH, et al.Early-life antibiotic use and risk of attention-deficit hyperactivity disorder and autism spectrum disorder: Results of a discordant twin study[J].Int J Epidemiol, 2021, 50(2): 475-484.
[15] Bistoletti M, Caputi V, Baranzini N, et al.Antibiotic treatment-induced dysbiosis differently affects BDNF and TrkB expression in the brain and in the gut of juvenile mice[J].PLoS One 2019, 14(2):e0212856.
[16] Guida F, Turco F, Iannotta M, et al.Antibiotic-induced microbiota perturbation causes gut endocannabinoidome changes, hippocampal neuroglial reorganization and depression in mice[J].Brain Behav Immun,2018, 67: 230-245.
[17] Vargason T, McGuinness DL, Hahn J.Gastrointestinal symptoms and oral antibiotic use in children with autism spectrum disorder: Retrospective analysis of a privately insured U.S.population[J].J Autism Dev Disord, 2019, 49(2):647-659.
[18] Chaaban H, Patel MM, Burge K, et al.Early antibiotic exposure alters intestinal development and increases susceptibility to necrotizing enterocolitis: A mechanistic study[J].Microorganisms, 2022, 10(3):519.
[19] Volkova A, Ruggles K, Schulfer A, et al.Effects of early-life penicillin exposure on the gut microbiome and frontal cortex and amygdala gene expression[J].iScience, 2021, 24(7):102797.
[20] Shi F, Huang Y, Yang M, et al.Antibiotic-induced alternations in gut microflora are associated with the suppression of immune-related pathways in grass carp (Ctenopharyngodon idellus)[J].Front Immunol, 2022, 13: 970125.
[21] Dash S, Syed YA, Khan MR.Understanding the role of the gut microbiome in brain development and its association with neurodevelopmental psychiatric disorders[J].Front Cell Dev Biol,2022, 10: 880544.
PDF(610 KB)
