Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that affects communication, social interaction, and behavior. These traits typically become apparent and are formally diagnosed during early childhood, often around two years of age. Currently, no standard clinical test can reliably screen for or diagnose ASD in a fetus during pregnancy. Research is intensely focused on understanding the various genetic and environmental factors that increase the likelihood of developing ASD in an effort to identify risk markers long before a behavioral diagnosis is possible.
Why Standard Prenatal Tests Cannot Detect Autism
Standard prenatal screening tools are not designed to detect a condition like ASD, which is defined by a collection of behavioral traits rather than a single structural defect. Tests like Non-Invasive Prenatal Testing (NIPT), which analyzes fetal DNA in the mother’s blood, primarily screen for common chromosomal abnormalities such as Down syndrome (Trisomy 21). NIPT may detect some rare genetic syndromes associated with a high probability of ASD, but it cannot screen for ASD itself.
Diagnostic tests such as amniocentesis or chorionic villus sampling (CVS) are used to detect specific chromosomal changes or single-gene disorders. While these tests can identify conditions that significantly increase the risk for ASD, they cannot offer a definitive autism diagnosis. ASD diagnosis is complicated because it is often polygenic, involving the subtle effects of many different genes, or it is idiopathic, with no clear genetic cause identified.
Standard anatomy ultrasounds, which check for major physical malformations like heart defects, cannot visualize the subtle brain differences that underlie ASD. Autism is a neurodevelopmental condition involving the organization and function of the brain. This complexity cannot be resolved by current routine imaging for diagnostic purposes.
Genetic Contributions to Risk
Genetic factors are considered the primary contributor to ASD risk, with heritability estimates sometimes as high as 85 percent. The genetic basis for ASD is highly heterogeneous, meaning it can arise from many different genetic variations, making a single prenatal test impossible. Much of the risk comes from polygenic risk, which is the cumulative effect of hundreds or thousands of common genetic variants (single nucleotide polymorphisms or SNPs), each having a tiny effect.
These common variants are measured using a Polygenic Risk Score (PRS), which calculates an individual’s overall genetic probability for the condition. While a high PRS indicates an increased probability, it cannot predict a diagnosis, especially for the general population.
A smaller percentage of ASD cases are linked to monogenic syndromes or rare, high-impact genetic changes. Examples include Fragile X syndrome or Tuberous Sclerosis Complex, which are caused by a single gene mutation and carry a high probability of co-occurring with ASD. These specific mutations can sometimes be identified through prenatal genetic testing, but the test result is for the syndrome itself, not a definitive diagnosis of ASD.
Environmental and Developmental Factors
Beyond genetics, a range of non-genetic factors encountered during pregnancy and early life are known to slightly increase the likelihood of ASD. These environmental factors interact with an individual’s genetic predisposition, influencing how the condition may develop. Advanced parental age, particularly paternal age, is a consistently noted factor associated with a higher risk.
Maternal health conditions, such as gestational diabetes, obesity, and hypertension, have been linked to increased ASD risk, possibly due to associated inflammation and altered hormonal states.
Exposure to certain medications, most notably the anti-epileptic drug valproate, during pregnancy significantly raises the risk. Maternal infections like rubella or influenza can also trigger a maternal immune response that may interfere with fetal brain development.
Researchers are also tracking subtle differences in fetal development as potential early indicators of risk. One study found that approximately 30 percent of fetuses who later developed ASD had anomalies in the heart, kidneys, and head detected during a second-trimester anatomy ultrasound. These findings do not diagnose ASD but suggest that developmental differences associated with the condition may begin prenatally, often involving multiple organ systems.
Emerging Research and Biomarkers
Current research is actively exploring novel biomarkers—measurable biological indicators—that could eventually lead to earlier identification of risk. One promising area involves looking at specific maternal autoantibodies in the mother’s blood that target fetal brain proteins, potentially predicting a higher risk of ASD before birth. Other investigations focus on metabolomics, which analyzes the profile of small molecules like amino acids and lipids in maternal or amniotic fluid. Distinct patterns of certain metabolites have been identified, suggesting a possible metabolic signature of ASD risk.
Advanced imaging techniques, such as specialized fetal MRI or ultrasound, are also being studied to detect subtle differences in brain region growth or connectivity in high-risk fetuses. These cutting-edge tools are currently research-only and have not been validated for clinical use in diagnosing or screening for ASD.