Neurodevelopmental disorders (NDDs) have emerged as a significant public health concern due to their profound and lasting impact on individuals and society. The global prevalence of these disorders, including autism spectrum disorder (ASD), has been steadily increasing, highlighting the urgent need for a comprehensive understanding and effective intervention strategies. Although the causes of NDDs are complex and multifactorial, several risk factors have been identified, including advanced maternal age, preterm birth, environmental influences, and changes in the microbiome. Evidence increasingly suggests that microbiome disturbances during critical developmental periods may play a key role in the onset of NDDs.
Antibiotics and Child Development
Antibiotics, widely used during pregnancy and infancy to treat bacterial infections, have raised concerns about their unintended consequences, particularly their impact on the gut microbiome. The foetal and early-life periods are critical for microbiome development, and disruptions during these stages may have significant implications for neurodevelopment. Despite these concerns, studies investigating the relationship between antibiotics and NDDs, such as ASD, intellectual disorder, and language disorder, have yielded mixed and often inconclusive results. Factors such as infection severity, genetic predispositions, and shared familial influences complicate the task of isolating the effects of antibiotics.
Microbiome disruption is a central concern in this context. The gut microbiota plays a vital role in the gut-brain axis, a bidirectional communication pathway between the gastrointestinal system and the central nervous system. Changes in microbiome composition during sensitive developmental windows may influence immune responses, neurotransmitter production, and overall brain development. For instance, certain gut bacteria produce metabolites capable of crossing the blood-brain barrier and modulating neural activity. Antibiotics, by altering gut microbial balance, may inadvertently disrupt these processes.
South Korean Study
A South Korean study aimed to assess whether exposure to antibiotics during pregnancy or early infancy was associated with the development of ASD, intellectual disorder, or language disorder in children. Using a nationwide database, researchers tracked antibiotic prescriptions and their potential links to developmental outcomes. To address confounding factors, the study employed a propensity score-matched cohort design and a sibling analysis. These methods helped distinguish the effects of antibiotics from other variables such as genetic and familial factors.
The findings revealed no significant association between antibiotic use during pregnancy or infancy and the development of ASD, intellectual disorder, or language disorder. Small increased risks observed in general population analyses were reduced in sibling analyses, suggesting that familial factors might explain these results.
Intellectual and Language Disorders
Intellectual and language disorders have received less attention in studies of antibiotic exposure. This study found no significant association between antibiotic use and these outcomes, indicating that antibiotics are unlikely to play a major role. However, given the increasing recognition of these disorders as common developmental challenges, further research is needed to confirm these findings and identify other contributing factors.
Language and intellectual development are influenced by a combination of genetic, environmental, and social factors. Although antibiotics may not directly affect these domains, their impact on overall health and early-life infections could indirectly influence developmental trajectories. Severe infections requiring antibiotic treatment, for example, might lead to missed developmental milestones or prolonged illness, hindering cognitive and linguistic growth.
Strengths and Limitations of the Research
The study’s large sample size and rigorous methodologies add significant value to its findings. By utilising a nationwide database, researchers minimised biases related to selection and recall. The sibling analyses further strengthened the study by controlling for shared familial factors, allowing for a clearer assessment of the effects of antibiotics.
However, limitations remain. Defining antibiotic exposure based on prescription records rather than actual use could lead to misclassification. Similarly, outcome misclassification may occur, particularly for conditions not validated with diagnostic tools. While the study accounted for many confounders, gaps in data, such as incomplete information on paternal characteristics and maternal smoking, leave room for residual confounding. Additionally, the study did not explore the cumulative effects of repeated antibiotic courses, a potentially important factor in understanding microbiome disruption and its impact on neurodevelopment.
Implications for Parents and Healthcare Providers
The findings highlight the importance of evidence-based antibiotic use during pregnancy and infancy. Antibiotics remain essential for treating bacterial infections, but their overuse raises concerns about antibiotic resistance and potential developmental risks. The study noted that nearly half of all pregnancies and infants were exposed to antibiotics, often for respiratory tract infections that may not require antibiotic treatment. This emphasises the need for adherence to prescribing guidelines and careful risk-benefit assessments.
Healthcare providers play a crucial role in educating families about appropriate antibiotic use. Clear communication regarding when antibiotics are necessary and the potential risks of overuse can help families make informed decisions. Encouraging the use of probiotics during or after antibiotic courses may help mitigate microbiome disruptions, though further research is needed to validate their effectiveness.
Future Directions
While the South Korean study offers valuable insights, more research is needed to address unresolved questions. Future studies should focus on intellectual and language disorders, which remain underexplored in this context. Research should also investigate interactions between antibiotics and other factors, such as diet, breastfeeding, and exposure to other medications, to better understand their combined influence on neurodevelopment.
Another promising area for investigation is the differential impact of antibiotic classes on the microbiome. Identifying specific antibiotics that pose higher risks could guide more targeted prescribing practices, reducing unnecessary exposure while preserving the efficacy of these essential medications.
Conclusion
The study provided a nuanced understanding of the relationship between antibiotics and neurodevelopmental disorders. While antibiotics are lifesaving tools, their use should be guided by evidence-based practices to minimise risks and safeguard the health of mothers and children. By promoting antibiotic stewardship and fostering awareness among healthcare providers and families, it is possible to balance the need for effective infection treatment with the goal of supporting healthy neurodevelopment in children.
Reference
Choi, A., Lee, H., Jeong, H. E., Lee, S.-Y., Kwon, J. S., Han, J. Y., Choe, Y. J., & Shin, J.-Y. (2024). 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 (Clinical Research Ed.), 385, e076885. https://doi.org/10.1136/bmj-2023-076885