The study findings provide a detailed mapping of the connections between maternal health during pregnancy and autism in childhood, bringing more clarity to the mechanisms involved. In addition, they reinforce the importance of considering genetic and family environmental factors when interpreting these associations, to avoid hasty conclusions about direct causes.
Autism is a neurodevelopmental disorder that is usually identified in the first years of life. It is characterized by difficulties in social communication and the presence of repetitive and restrictive behaviors.
Since its origin is linked to early brain development and the intrauterine environment, many studies seek to understand how non-genetic factors, especially those related to the mother's health during pregnancy, can influence a child's risk of developing autism.
In this context, throughout the study, the term "autism" will be used to refer to Autism Spectrum Disorder (ASD), its formal clinical nomenclature.
Several studies have already identified relationships between certain maternal conditions during pregnancy and an increased risk of autism in children. For example, epidemiological studies suggest that mothers who had depression, diabetes, immune system diseases, or infections during pregnancy may have children who are more likely to receive a diagnosis of ASD.
However, there are still many uncertainties about this topic. One of the main challenges is that other maternal medical conditions have not been studied in this context, and many of them can occur simultaneously, making it difficult to analyze the isolated impacts of each one.
Furthermore, even when an association between a maternal illness and autism is identified, it is not clear whether this relationship is cause and effect or whether it is due to other common factors in the family.
Maternal medical conditions can affect the baby directly, either through physiological changes associated with the illness or through the use of medications. This direct impact is plausible, since substances present in the mother's blood can cross the placenta and reach the fetus, influencing its development.
Furthermore, the blood-brain barrier, which protects the baby's brain from potentially harmful substances, is only fully formed during pregnancy, making the brain more vulnerable in the early stages.
However, these associations can also be explained by familial factors shared between mother and child, such as genetic predisposition or exposure to a common environment, such as air pollution or socioeconomic status.
Previous research suggests that there may be a genetic link between some maternal conditions and autism. For example, some psychiatric and metabolic conditions that occur in mothers are also more common in relatives of autistic individuals.
This suggests that inherited genetic variations may play a role in both maternal health and ASD risk. Furthermore, even when a condition is not directly inherited, the mother’s genes may influence the intrauterine environment indirectly.
It is therefore essential to understand to what extent the observed effects are caused by the condition itself or whether they simply reflect a genetic predisposition shared between mother and child. Different research approaches are needed to distinguish between these possibilities.
One effective method is to compare siblings born to the same mother, where one has autism and the other does not. This allows us to control for genetic and family environmental factors that remain constant across siblings.
Another strategy is to use the father as a negative control: if a particular maternal condition is associated with autism but a similar condition in the father is not, this may indicate a direct effect of pregnancy.
Using these strategies, combined with traditional observational studies, helps shed light on the true influence of maternal health on the development of autism.
In the current study, researchers from NYU Grossman School of Medicine, USA, analyzed a large database from Denmark, including medical records of more than 1.1 million children born between 1998 and 2015, as well as detailed information about their mothers' health during pregnancy.
This database, linked to national health registries, allowed an in-depth examination of the relationship between different maternal conditions and the diagnosis of autism in childhood, taking into account demographic and socioeconomic factors.
In addition, the researchers analyzed the presence of comorbidities, that is, the occurrence of multiple medical conditions at the same time, and investigated whether these associations varied according to the sex of the child and the presence of intellectual disability.
The results revealed that, among the 1,131,899 children followed, 18,374 (approximately 1.6%) received a diagnosis of ASD. The average age of diagnosis was 8.3 years, but this average varied over the study period, reflecting both an increase in early diagnosis and differences in the duration of follow-up for each child.
The researchers analyzed 236 different maternal conditions, of which 30 showed a statistically significant association with autism, even after adjusting for demographic factors and comorbidities. Among these conditions, obstetric, cardiometabolic and psychiatric diseases, such as gestational diabetes and depression, stood out.
The researchers used methods that take into account genetic factors and family characteristics to analyze the relationship between the health conditions of mothers during pregnancy and autism in their children.
They found that many of these associations did not indicate a cause-and-effect relationship. That is, just because a mother had a certain condition during pregnancy does not necessarily mean that the condition caused the child’s autism.
Instead, the results suggest that the increased risk of autism in children of mothers with certain conditions may be related to inherited genetic traits or to factors in the family environment that influence both the mother’s health and the child’s development.
For example, some psychiatric and metabolic conditions may have a shared genetic basis between mother and child, and factors such as socioeconomic status and exposure to environmental pollutants may also be involved.
Therefore, although the data show that some maternal conditions are statistically associated with autism in offspring, this relationship appears to be explained primarily by genetic predisposition and familial influences, rather than a direct effect of the mother’s condition on the baby during pregnancy.
This reinforces the importance of interpreting these associations with caution and considering other factors that may be influencing the results.
The study findings provide a detailed mapping of the connections between maternal health during pregnancy and autism in childhood, bringing more clarity to the mechanisms involved.
They also reinforce the importance of considering genetic and family environmental factors when interpreting these associations, to avoid hasty conclusions about direct causes.
This type of research can help direct future investigations and inform public policies and maternal and child health strategies, ensuring that medical recommendations are based on solid evidence.
READ MORE:
Familial confounding in the associations between maternal health and autism
Vahe Khachadourian, Elias Speleman Arildskov, Jakob Grove, Paul F. O’Reilly, Joseph D. Buxbaum, Abraham Reichenberg, Sven Sandin, Lisa A. Croen, Diana Schendel, Stefan Nygaard Hansen & Magdalena Janecka
Nature Medicine (2025)
Abstract:
Evidence suggests that maternal health in pregnancy is associated with autism in the offspring. However, most diagnoses in pregnant women have not been examined, and the role of familial confounding remains unknown. Our cohort included all children born in Denmark between 1998 and 2015 (n = 1,131,899) and their parents. We fitted Cox proportional hazard regression models to estimate the likelihood of autism associated with each maternal prenatal ICD-10 diagnosis, accounting for disease chronicity and comorbidity, familial correlations and sociodemographic factors. We examined the evidence for familial confounding using discordant sibling and paternal negative control designs. Among the 1,131,899 individuals in our sample, 18,374 (1.6%) were diagnosed with autism by the end of follow-up. Across 236 maternal diagnoses we tested (prevalence ≥0.1%), 30 were significantly associated with autism after accounting for sociodemographic factors, disorder chronicity and comorbidity, and correction for multiple testing. This included obstetric, cardiometabolic and psychiatric disorders (for example, diabetes in pregnancy (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.08–1.31) and depression (HR 1.49, 95% CI 1.27–1.75)), previously shown to be associated with autism. Family-based analyses provided strong evidence for familial confounding in most of the observed associations. Our findings indicate pervasive associations between maternal health in pregnancy and offspring autism and underscore that these associations are largely attributable to familial confounding.
Comments