Genetic factors likely confound the link between c-sections and offspring mental health

A new study published in Psychiatry Research indicates that the observed link between cesarean sections and mental disorders in offspring may be partially explained by shared genetics rather than the birth procedure itself. The research indicates that individuals born via planned cesarean delivery tend to carry a higher genetic liability for conditions such as schizophrenia, bipolar disorder, and depression. These findings suggest that previous associations between birth mode and mental health could be confounded by hereditary factors.

Observational studies have reported that children born by cesarean section face a higher statistical risk of developing psychiatric disorders later in life. This correlation has raised concerns among medical professionals and expectant parents regarding the potential long-term neurodevelopmental consequences of surgical delivery. The prevalence of cesarean sections continues to rise globally, making the safety of the procedure a priority for public health monitoring.

“We ran this study because prior work has shown that cesarean delivery is associated with increased risk of mental disorders in offspring,” said study author Søren Dinesen Østergaard, a professor at the Department for Affective Disorder at Aarhus University Hospital in Denmark. “This is sometimes interpreted as a causal effect, but there is an alternative/competing explanation, namely that this is confounded by genetic liability to mental disorder. We tested this hypothesis by investigating whether cesarean delivery was associated with increased genetic liability to mental disorder in the offspring. This turned out to be the case.”

The existence of a statistical link does not necessarily imply that the surgery causes the mental health condition. A competing hypothesis suggests that the association is a result of familial confounding. This theory proposes that the same factors influencing a mother’s need or choice for a cesarean section might also be related to genetic traits passed down to the child.

For instance, a mother with a high genetic predisposition for certain psychiatric conditions might experience pregnancy or delivery in a way that makes a planned cesarean section more likely. If she passes those genetic risks to her child, the child may eventually develop a mental disorder. In this scenario, the cesarean section acts as a marker for the genetic risk rather than the direct cause of the disorder.

Past research using sibling comparisons has supported this idea. These studies found that when scientists account for shared family factors, the association between cesarean births and offspring mental illness diminishes significantly. The authors of the current study aimed to test this genetic hypothesis directly by analyzing DNA data from a large population.

The researchers utilized data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). This is a comprehensive Danish population-based cohort. The study sample included 17,050 individuals born in Denmark between 1996 and 2008.

The sample was nearly evenly split between sexes, with 8,382 females and 8,668 males. To assess genetic predisposition, the investigators calculated polygenic risk scores for five major mental disorders. These disorders included schizophrenia, bipolar disorder, depression, autism, and attention-deficit/hyperactivity disorder (ADHD).

A polygenic risk score is a numerical value that summarizes an individual’s estimated genetic liability for a specific trait or disease. It is calculated by summing the effects of thousands of common genetic variants across the entire genome. While a high score does not guarantee a person will develop a disorder, it indicates a higher biological susceptibility compared to the general population.

The researchers obtained information on the mode of delivery from the Danish National Patient Register. They categorized births into three distinct groups: vaginal deliveries, planned cesarean sections, and acute cesarean sections. Vaginal delivery served as the reference group for all statistical comparisons.

Among the 17,050 participants, 2,929 were delivered via cesarean section. This subgroup consisted of 1,252 planned procedures and 1,739 acute procedures. The analysis used statistical models that adjusted for relevant factors such as sex, birth year, birth order, and maternal age to isolate the relationship between birth mode and genetics.

When the researchers analyzed all cesarean sections together as a single category, they found no significant association with the polygenic risk scores for any of the five mental disorders. The genetic profiles of those born via cesarean section did not differ substantially from those born vaginally in the aggregate analysis. A more nuanced picture emerged when the team separated planned cesarean sections from acute ones.

The study revealed a positive association between being born via planned cesarean section and having higher polygenic risk scores for severe psychiatric disorders. Specifically, individuals delivered by planned surgery had significantly higher genetic liability for schizophrenia, bipolar disorder, and depression. The statistical analysis showed adjusted odds ratios of approximately 1.07 for schizophrenia and bipolar disorder, and 1.06 for depression.

These numbers indicate that the genetic risk for these conditions was slightly elevated in the planned cesarean group compared to the vaginal delivery group. Importantly, this pattern was not observed for acute cesarean sections. The genetic risk scores for individuals born via emergency or acute surgery did not differ significantly from those born vaginally.

The researchers also examined genetic risk scores for neurodevelopmental disorders. They found no significant association between planned cesarean delivery and genetic liability for autism or ADHD. The link appeared specific to the genetic risks for affective and psychotic disorders.

To ensure the reliability of their findings, the authors conducted robustness analyses. They repeated the statistical tests after excluding participants whose parents had been diagnosed with a mental disorder prior to the child’s birth. This step was intended to see if the results were driven solely by parents with known psychiatric histories.

The positive associations generally persisted even after these exclusions. This suggests that the link is not merely a reflection of diagnosed parental illness but likely involves broader, sub-clinical genetic liabilities. The findings support the hypothesis that unmeasured familial factors confound the relationship between birth mode and mental health.

The distinction between planned and acute cesarean sections is significant. Acute cesarean sections are typically performed due to immediate obstetric emergencies, such as labor complications or fetal distress. These events are often biologically random or strictly physical in nature.

In contrast, planned cesarean sections involve a decision-making process prior to labor. This decision can be influenced by maternal preferences, psychological factors, or medical recommendations related to the mother’s health status. The study suggests that the factors leading to a planned cesarean are more likely to correlate with genetic liabilities for mental health conditions.

The lack of association with ADHD genetic risk is noteworthy. The authors speculate that this might be due to the nature of ADHD symptoms. Symptoms of ADHD often wane or change as individuals reach adulthood and reproductive age.

Consequently, the traits associated with ADHD might not influence the decision-making process regarding delivery mode as strongly as traits associated with depression or anxiety. The genetic liability for conditions like schizophrenia and bipolar disorder, which often manifest in early adulthood, appeared to have a stronger connection to the circumstances surrounding planned births.

The findings demonstrate that “the relationship between cesarean delivery and mental disorder in offspring is more complex than previously thought,” Østergaard told PsyPost.

The study does have some limitations. Polygenic risk scores currently explain only a small fraction of the total genetic variance for mental disorders. This means they are not comprehensive measures of an individual’s full genetic potential for a condition.

Additionally, the observed associations were statistically significant but relatively weak in magnitude. This indicates that while genetics plays a role, it is likely one of many complex factors involved. The study was also restricted to Danish individuals. The findings may not necessarily apply to populations with different genetic backgrounds.

Despite these limitations, the study offers a critical perspective on the “nature versus nurture” debate regarding birth modes. It highlights the importance of accounting for genetic factors when interpreting observational health data. Future research on the long-term effects of cesarean sections should consider genetic liability to avoid overestimating the causal impact of the surgery itself.

“We have done what we can here,” Østergaard said. “I hope that research groups from other countries with available genetic data at the same scale will test whether the findings can be replicated.”

The study, “Genetic liability to mental disorders and being delivered via cesarean section,” was authored by Søren Dinesen Østergaard, Maria Speed, Alisha Silvia Mercedes Hall, Esben Agerbo, and Katherine L. Musliner.

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