Antibiotic exposure during pregnancy or early infancy is not associated with increased risks of autism spectrum disorder (ASD), intellectual disorder, or language disorder in children, according to a recent study published in BMJ.1
Takeaways
- The study found no significant association between antibiotic exposure during pregnancy or early infancy and increased risks of autism spectrum disorder (ASD), intellectual disorder, or language disorder in children.
- While most neurodevelopmental disorders showed no increased risk, the study observed a slight increase in the risk of epilepsy associated with antibiotic exposure during infancy.
- The analysis included a large sample size, with 3.67 million children in the pregnancy cohort and 3.94 million in the infant cohort, providing robust data for the conclusions.
- To ensure accurate comparisons, the study used 1-to-1 score matching, resulting in 980,872 pairs in the pregnancy cohort and 804,887 pairs in the infant cohort, balancing baseline characteristics between groups.
- Despite the general findings, the study noted substantial associations in subgroup analyses and emphasized the necessity for further research, particularly regarding the slight increase in epilepsy risk.
Neurodevelopmental disorders have a lasting impact among patients, making them a public health issue that must be addressed in children. Additionally, the prevalence of these disorders has increased over time, and data has indicated a potential association with changes in the microbiome.
Antibiotics are often used during pregnancy and infancy to manage infections but have been linked to disturbances in the microbiome. This has led to concern about a potential association between prenatal antibiotic use and neurodevelopmental disorder development.
Currently, antibiotics are frequently used in primary care, especially for the treatment of respiratory infections.2 Investigators have recommended limiting antibiotic use to reduce the prevalence of antibiotic resistance. However, data about its association with neurodevelopmental disorders remains limited.1
To evaluate the link between antibiotic exposure in pregnancy and early infancy with subsequent neurodevelopmental disorder development, investigators conducted a nationwide retrospective cohort study. Data from 2008 to 2021 was obtained from the National Health Insurance Service (NHIS) mother-child linked database.
Births from April 1, 2009, to December 31, 2020, recorded in the NHIS were included in the analysis. Exclusion criteria included chromosomal abnormalities and antibiotic use in the months before pregnancy but not during pregnancy.
In the initial study cohort, antibiotic exposure during pregnancy was evaluated. In the second cohort, antibiotic exposure during infancy was evaluated, with children who died in the first 6 months of life, presenting with chromosomal abnormalities, and diagnosed with a study outcome in the first 6 months of life excluded.
Antibiotic exposure was determined by the presence of 1 or more systemic antibiotic prescription. A maternal prescription during pregnancy determined exposure in the first cohort while a child prescription within the first 6 months of life determined exposure in the second cohort.
ASD, intellectual disorder, language disorder, and epilepsy were the primary outcomes of the analysis. These outcomes were often diagnosed by psychiatrists or pediatricians.
Covariates included demographics, indications for antibiotic use, infection related to health care use, maternal conditions, medication use, obstetrics conditions, measures of health care use, smoking status, and body mass index.
There were 3,665,246 children in the pregnancy cohort and 3,944,731 in the infant cohort, with antibiotic exposure reported in 45% and 50.1%, respectively. Following 1-to-1 score matching, the cohorts included 980,872 and 804,887 pairs, respectively. Baseline differences were observed between groups, but characteristics were balanced after matching.
In the pregnancy cohort, a rate difference of 0.15 per 1000 person years for ASD was reported, as well as 0.09 for intellectual disorder, 0.21 for language disorder, and 0.09 for epilepsy. Similar figures were reported in the infant cohort, at 0.05, 0.13, 0.13, and 0.22, respectively.
Antibiotic exposure was linked to increased risks of all study outcomes. Adjusted hazard ratios ranged from 1.08 for epilepsy to 1.17 for intellectual disorders in the pregnancy cohort and from 1.04 for ASD to 1.28 for epilepsy in the infant cohort.
During sibling analysis, substantial associations were reported. The pregnancy cohort had hazard ratios of 1.06 for ASD, 1.00 for intellectual disorder, 1.05 for language disorder, and 1.03 for epilepsy. In the infant cohort, these ratios were 1.00, 1.07, 1.04, and 1.13, respectively. Only epilepsy risk in the infant cohort remained slightly increased.
These results indicated no general associations between antibiotic exposure and ASD, intellectual disorders, and language disorders. However, associations were found among subgroups, and an association remained for epilepsy, indicated a need for further research.
References
- Choi A, Lee H, Jeong HE, et al. Association between exposure to antibiotics during pregnancy or early infancy and risk of autism spectrum disorder, intellectual disorder, language disorder, and epilepsy in children: population based cohort study. BMJ. 2024;385:e076885 doi:10.1136/bmj-2023-076885
- Del Mar C. Antibiotics for acute respiratory tract infections in primary care. BMJ. 2016;354:i3482. doi:10.1136/bmj.i3482
