Antibiotic use during pregnancy linked to slightly increased risk of ADHD

A new comprehensive analysis suggests that maternal use of antibiotics during pregnancy is associated with a slightly elevated likelihood of the child receiving a diagnosis of attention-deficit/hyperactivity disorder (ADHD). The research indicates that this statistical link is stronger when antibiotics are administered during the second or third trimesters. These findings were published recently in the Journal of Affective Disorders.

ADHD is a neurodevelopmental condition that has become increasingly common in recent years. It is characterized by symptoms such as difficulty sustaining attention, impulsive actions, and hyperactivity. While genetics play a major role in the development of the disorder, scientists believe that environmental factors also contribute. Researchers have increasingly focused on exposures that occur before birth.

Antibiotics are among the most frequently prescribed medications for pregnant women. They are essential for treating bacterial infections that could otherwise harm the mother or the fetus. However, these drugs do not only target harmful bacteria. They also affect the vast community of helpful microbes living in the human gut, known as the microbiota.

There is a growing body of evidence suggesting a connection between the gut and the brain. This concept is often referred to as the gut-brain axis. The theory posits that the composition of gut bacteria can influence brain development and function. This influence may occur through various biological pathways, such as the production of neurotransmitters or the regulation of inflammation.

Mothers pass aspects of their microbiota to their children. Additionally, the environment within the womb influences the initial development of the fetus’s own biological systems. Consequently, some scientists hypothesize that disrupting the maternal microbiome with antibiotics could have downstream effects on the child’s neurodevelopment. Previous studies on this topic have produced conflicting results, with some finding a risk and others finding none.

To address these inconsistencies, a research team led by Jiali Fan from West China Second University Hospital at Sichuan University initiated a new investigation. They sought to clarify the potential relationship by combining data from many different sources. This approach allows for a more robust statistical analysis than any single study could provide on its own.

The researchers conducted a meta-analysis. This is a scientific method that pools statistical data from multiple independent studies to identify broader trends. The team searched major medical databases for observational cohort studies published up to October 2024. They followed strict guidelines to select high-quality research.

The final analysis included nine major studies. These studies represented a massive combined pool of participants, totaling more than 6.1 million mother-child pairs. The data encompassed populations from several different regions. These included countries in North America, Europe, and Asia.

The researchers used a scoring system called the Newcastle-Ottawa Scale to evaluate the quality of the included research. This scale assesses how well a study selected its participants and how accurately it measured outcomes. The team found that the included studies were generally of moderate to high methodological quality.

The primary finding of the analysis identified a positive association. The overall data showed that children exposed to antibiotics in the womb had a hazard ratio of 1.15 compared to those who were not exposed. This figure represents a 15 percent increase in the relative risk of developing ADHD. Another statistical measure used in the study, the odds ratio, placed this increased likelihood at 28 percent.

The researchers then broke down the data to see if the timing of the exposure mattered. Pregnancy is divided into three distinct periods known as trimesters. The analysis found no statistical connection between antibiotic use in the first trimester and a later ADHD diagnosis. This lack of association in early pregnancy was consistent across the data.

However, a different pattern emerged for the later stages of pregnancy. The study identified a link when antibiotics were used during the mid-pregnancy period. A similar association was observed for antibiotic use during late pregnancy. This suggests that the timing of exposure may be a relevant factor in this potential relationship.

In addition to timing, the team investigated the frequency of antibiotic use. They wanted to know if taking more courses of medication changed the risk profile. The data showed that a single course of antibiotics was not statistically linked to an increased risk of ADHD. The association only became apparent with repeated use.

When mothers received two separate courses of antibiotics, the risk of their children developing ADHD rose. The risk appeared to increase further for those who received three or more courses. This finding hints at a potential cumulative effect. It suggests that more frequent disruptions to the maternal microbiome might correspond to a higher probability of the neurodevelopmental outcome.

The researchers performed sensitivity analyses to test the strength of their conclusions. This process involves removing one study at a time from the calculations to ensure no single dataset is skewing the results. The findings remained stable throughout this process. This consistency suggests that the observed link is robust across the different study populations included.

Despite these findings, the authors emphasize that the results must be interpreted with caution. The study design is observational. This means it can detect a correlation between two events, but it cannot prove that one caused the other. There are other factors that could explain the association.

The most prominent alternative explanation is the underlying infection itself. Women are prescribed antibiotics because they are sick. Infections trigger immune responses and inflammation in the body. It is possible that the maternal fever or inflammation affects fetal brain development, rather than the medication.

Some of the studies included in the analysis attempted to adjust for this factor. For instance, one study accounted for maternal infection and still found a link to the medication. However, not all studies could fully separate the effects of the illness from the effects of the cure. This remains a primary challenge in this field of research.

Another limitation of the analysis is the lack of detail regarding specific drugs. Antibiotics are a diverse class of medications. Different types of antibiotics target bacteria in different ways and have varying effects on the microbiome. The current data did not allow the researchers to determine if specific classes of drugs carried higher risks than others.

The study also lacked precise information on dosages. Without knowing the exact amount of medication taken, it is difficult to determine a precise biological threshold for risk. The researchers relied on prescription records and medical files. These records confirm a prescription was filled but do not always guarantee it was taken as directed.

The biological mechanisms remain theoretical. While animal studies have shown that antibiotics can alter behavior in mice by changing gut bacteria, this has not been definitively proven in humans. The pathway from maternal gut bacteria to fetal brain development is a subject of ongoing scientific inquiry.

The authors recommend that future research should be prospective in nature. This means designing studies that recruit pregnant women and follow them forward in time. Such studies should meticulously record the specific type, dosage, and duration of antibiotic use. This would allow for a much finer-grained analysis of the risks.

The researchers also suggest using advanced study designs to rule out genetic factors. Sibling comparisons can be a powerful tool. By comparing one sibling who was exposed to antibiotics to another who was not, scientists can control for shared genetics and household environments. This would help isolate the effect of the medication.

In clinical practice, antibiotics remain vital tools. The risks of leaving a bacterial infection untreated during pregnancy are well-documented and can be severe. The authors state that their findings should not discourage necessary treatment. Instead, they suggest the results highlight the need for prudent prescribing.

Physicians should continue to weigh the benefits and risks. The study supports the idea that antibiotics should be used only when clearly indicated. Avoiding unnecessary or repeated courses of these drugs may be beneficial. This aligns with general medical guidance regarding antibiotic stewardship.

The study, “Meta-analysis of the association between prenatal antibiotic exposure and risk of childhood attention-deficit/hyperactivity disorder,” was authored by Jiali Fan, Shanshan Wu, Chengshuang Huang, Dongqiong Xiao, and Fajuan Tang.