Autism spectrum disorder (ASD) refers to a range of conditions characterized by challenges with social skills, repetitive behaviors, speech and nonverbal communication. The causes of autism are still not fully understood, but research suggests that genetic and environmental factors play a role. Some people believe that maternal stress during pregnancy may be one of the environmental risk factors that contributes to autism. In this article, we’ll explore the evidence around prenatal stress as a potential cause of autism.
The Stress Hypothesis
The idea that prenatal stress could contribute to autism first emerged in the 1960s. Some researchers proposed that high levels of maternal stress hormones like cortisol crossing the placenta may affect fetal brain development. This could disrupt processes that are important for social and communication skills.
Since then, a number of studies have investigated whether stressful life events during pregnancy are associated with an increased risk of autism in children. Stressful life events could include things like the death of a close relative, job loss, divorce or domestic violence. The hypothesis is that when a pregnant woman experiences intense or chronic stress, it may create changes in the intrauterine environment that adversely impact fetal neurodevelopment.
Evidence from Human Studies
A number of human epidemiological studies have found associations between prenatal stress and autism, but results have been mixed.
Positive Associations
Some studies have found evidence for increased autism risk with prenatal stress:
- A 2013 study of over 1.2 million children in Sweden found that mothers who lost a close relative during pregnancy were 1.5 times more likely to have a child with autism.
- A small 2019 study of 98 mother-child pairs in Egypt found that women who experienced stress during pregnancy, measured by self-reported questionnaires, had a higher likelihood of having a child diagnosed with autism.
- A 2020 meta-analysis of 12 studies with over 80,000 participants found a modest but statistically significant association between prenatal stress and autism risk.
Null Findings
However, other studies have not found a link between prenatal stress and autism:
- A 2015 study of over 95,000 children in Denmark found no association between mothers experiencing bereavement during pregnancy and autism risk.
- A 2020 study of over 260,000 births in California did not find an increased risk of autism in children whose mothers experienced severe life events during pregnancy like death of a close relative or job loss.
- A 2022 study of prenatal exposure to a major ice storm in Canada did not find associations with autism diagnoses in exposed children.
Overall, human studies present a mixed picture when it comes to maternal prenatal stress and autism risk. Some find evidence for an association while others do not.
Animal Studies
Animal studies allow researchers to better control variables and directly test whether prenatal stress exposure causes autism-like behaviors. However, we have to be cautious about generalizing animal findings to humans.
Some key animal studies on prenatal stress and autism-like effects include:
- A 2006 study found that pregnant mice exposed to simulated stress had offspring with impaired social behaviors and habit formation.
- A 2007 rat study found that male offspring of stressed mothers had reduced social interaction and increased repetitive behaviors.
- However, a 2016 study in mice did not find that prenatal stress induced clear autism-like behaviors in offspring.
As with human studies, the animal literature presents mixed results. Some studies in rodents demonstrate that prenatal stress can cause neurological and behavioral changes reminiscent of autism spectrum disorder. However, other studies do not replicate these findings.
Potential Biological Mechanisms
If prenatal stress does contribute to autism risk, what are the biological mechanisms? Research suggests a few possibilities:
Stress Hormones
As mentioned earlier, prenatal stress leads to the release of cortisol and other stress hormones. These could cross the placenta and directly impact fetal brain development.
Inflammation
Stress activates the mother’s immune system, leading to increased inflammation. Inflammatory proteins called cytokines may cross into the fetal brain and promote abnormal neural connectivity.
Gene Expression
Stress hormones may alter gene expression in the fetal brain, affecting processes like neuron migration, synapse formation and pruning. This could underlie changes in behavior and cognition.
However, the exact mechanisms remain poorly understood. More research in animals and humans is needed to elucidate how maternal stress signaling could lead to neurodevelopmental disorders like autism.
Timing of Stress Exposure
Some research suggests the timing of prenatal stress exposure matters. The fetal brain may be particularly vulnerable to maternal stress during certain sensitive windows of development.
For example, a 2010 study found that women exposed to a stressful event in the first or second trimester had a higher likelihood of having a child with autism. Other work suggests stress in the second and third trimester may have the greatest impact.
More research is needed to clarify whether certain periods of prenatal development are especially susceptible. It’s also important to consider that susceptibility may depend on genetic and other factors.
Interaction With Genetics
There is likely interplay between prenatal stress exposure and genetic vulnerability. Some work suggests stress may more strongly influence autism risk among fetuses already genetically predisposed to the condition.
For example, a 2005 study found prenatal stress was associated with autism only in children who also had particular genetic variants associated with serotonin and oxytocin, two neurotransmitters involved in social behavior.
More research on gene-environment interactions could help identify biological subgroups most susceptible to environmental stressors.
Potential Confounding Factors
It’s challenging to isolate prenatal stress as an independent risk factor for autism in humans. Some potential confounding factors to consider:
- Genetics – Family history of autism may underlie both autism risk and maternal stress levels.
- Other factors – Various prenatal, perinatal, and postnatal variables could be the real causal factors.
- Reporting bias – Retrospective self-report of stress levels may be inaccurate.
Researchers attempt to control for confounders in various ways, but it remains difficult to make definitive conclusions from human observational studies.
Limitations of Existing Research
While the stress hypothesis is biologically plausible, there are limitations in the research to date:
- Inconsistent findings across human studies.
- Mixed results from animal models.
- Limited mechanistic understanding from biological studies.
- Need for more rigorously controlled studies ruling out confounders.
- Lack of randomized controlled trials manipulating prenatal stress.
More high-quality studies are needed to firmly establish maternal stress as a causal risk factor for autism spectrum disorder.
Conclusion
In summary, there is some evidence that high levels of maternal stress during pregnancy could be one of the many factors that contributes to autism risk. However, the research literature remains inconclusive overall. Some well-designed studies find associations, while others do not. Potential mechanisms like changes in stress hormones, inflammation, and gene expression have been proposed, but direct biological evidence in humans is lacking. Animal studies demonstrate that prenatal stress can induce autism-like neurological and behavioral changes in offspring, but extrapolating these findings to humans is difficult.
Given the current state of the evidence, prenatal stress exposure should be considered a potential but unconfirmed risk factor for autism. More large-scale studies controlling for confounding variables and exploring gene-environment interactions are needed to elucidate the relationship. The hypothesis that maternal stress contributes to autism also needs to be more rigorously tested in biological experiments. While reducing pregnancy stress and anxiety is advisable for the sake of mothers’ health, the direct impact on autism risk reduction remains uncertain based on current evidence.