Autism spectrum disorder (ASD) is a complex developmental condition that affects how a person communicates with and relates to other people, and how they experience the world around them. ASD is considered a “spectrum” disorder because it affects each individual differently and to varying degrees. The causes of ASD are still not fully understood, but research suggests that both genetic and environmental factors play important roles. This article will examine what is currently known about potential causes and risk factors for ASD that originate during pregnancy.
Genetic Factors
Genetics are believed to be one of the primary causes of ASD. If one identical twin has autism, there is a 36-95% chance the other twin will also have it. For fraternal twins, that risk is lower at 0-31%. Researchers have identified a number of genes associated with ASD, but each gene variant only accounts for a small fraction of cases. This suggests that ASD is caused by a combination of common genetic variants working together. Some of the main genetic factors linked to ASD risk include:
– Inherited Mutations – Rare mutations in genes involved in brain development, like CHD8, SCN2A, and SHANK3 can be passed down and significantly increase ASD risk. However, these mutations only account for 1-2% of ASD cases.
– Common Genetic Variants – More common variants in over 100 genes involved in synapse formation, neuronal communication, and chromatin remodeling can interact to influence ASD susceptibility.
– Spontaneous Mutations – De novo genetic changes that occur spontaneously in parents’ sperm or eggs cells account for a significant portion of ASD risk. Having older parents increases chances of detrimental spontaneous mutations.
– Genetic Syndromes – There are several genetic syndromes like Fragile X, Rett Syndrome, and Tuberous Sclerosis caused by known mutations that have ASD as a common symptom.
While ASD has a strong genetic basis, the majority of risk is polygenic, meaning many genes are involved. The interplay between genetic factors accumulated through generations and environmental influences ultimately determines if ASD develops.
Advanced Parental Age
Multiple studies have found links between advanced maternal and paternal age at conception and increased risk of having a child with ASD. A meta-analysis found mothers over 35 had a 1.5 times higher chance of having a child with ASD compared to younger mothers. For fathers over 50, the risk was 1.66 times higher. Older parents are at greater risk for spontaneous genetic mutations in sperm and egg cells that may contribute to ASD development. The accumulating effects of environmental toxins over time may also play a role.
Pregnancy Complications
Certain prenatal and perinatal complications have been associated with higher ASD risk. These include:
Maternal Infections
Activation of the mother’s immune system and inflammation responses to infectious diseases may affect fetal neurological development. Rubella, cytomegalovirus (CMV), and herpes infections during pregnancy have been linked to increased ASD risk. Autoimmune conditions like diabetes, rheumatoid arthritis, and celiac disease in the mother may also be risk factors.
Bleeding and Gestational Diabetes
Vaginal bleeding, placental abnormalities, preeclampsia, and gestational diabetes can reduce oxygen and nutrients to the fetus and disrupt brain development. Children born to mothers with gestational diabetes have a higher risk of developing autism.
Premature Birth
Babies born more than 3 weeks premature have a 31% higher risk of ASD. Preemies often experience maternal infection, fetal distress, and other complications that may impact development.
Low Birth Weight & Fetal Growth Restriction
Weighing less than 5.5 pounds at birth and having poor growth in the womb have been associated with greater ASD risk. This may reflect underlying problems with placental function, genetics, or other factors interfering with fetal development.
Birth Trauma
Experiencing lack of oxygen, trauma during delivery, cord complications, or distress right before or after birth may contribute to atypical development of ASD. However, more research is needed to confirm these relationships.
Medications, Alcohol & Smoking During Pregnancy
Certain prenatal exposures may influence ASD risk, especially during first and second trimesters when the brain is rapidly developing:
Valproic Acid
This medication used to treat epilepsy, bipolar disorder, and migraines has been linked to higher autism risk with first trimester exposure. However, risks must be weighed against benefits for each pregnancy.
SSRIs
Some studies find an association between prenatal SSRI antidepressants like fluoxetine and increased ASD risk, while others find no link. More research is needed to clarify this relationship.
Thalidomide
This medication historically used to treat nausea in pregnancy causes severe birth defects. It may also be linked to increased autism risk.
Alcohol
Drinking during pregnancy can disrupt fetal brain development. Moderate to heavy alcohol use is associated with higher ASD risk compared to light or no drinking.
Smoking
NICU studies found higher autism rates in babies whose mothers smoked during pregnancy compared to those who didn’t. Toxins in cigarettes may affect fetal brain development.
However, it’s difficult to isolate these exposures from other genetic and environmental confounding factors in human studies. More research is needed to better understand any association with ASD.
Environmental Toxins
Exposure to certain environmental toxins and pollutants during pregnancy could influence ASD risk by disrupting fetal brain development. More research is needed, but potential risks may include:
– Air pollution – Exposure to high levels of air pollution including particulate matter, nitrogen oxides, and volatile organic compounds has been associated with higher ASD risk.
– Heavy metals – Metals like arsenic, lead, mercury, and cadmium can cross the placenta and accumulate in the fetal brain. Studies are mixed on links to ASD.
– Pesticides – Insecticides, herbicides, and fungicides may impact fetal neurodevelopment. More study is needed on links to ASD.
– Phthalates & BPA – These chemicals found in plastics, personal care products, and more may have neurodevelopmental effects. Findings on links to ASD are still inconsistent.
– Other endocrine disruptors – Compounds like PBDEs used as flame retardants could have neurological effects but more research is needed.
While these associations are concerning, more work is needed to establish causal relationships between toxins and ASD risk. Reducing exposure to harmful chemicals during pregnancy is still recommended.
Maternal Immune System Dysregulation
Growing evidence suggests the mother’s immune activity during pregnancy may influence ASD development. Researchers propose several theories:
Maternal Autoantibodies
Autoantibodies directed against fetal brain proteins have been found more often in the blood of mothers with autistic children. These antibodies may cross the placenta and interfere with healthy neurodevelopment.
Inflammation
Elevated inflammatory markers like cytokines and chemokines in the mother’s blood may denote an overactive inflammatory response that creates a suboptimal fetal environment.
Maternal Infection
Infections during pregnancy activate the mother’s immune defenses. While protecting mom, some of these immune factors like cytokines may cross the placenta and alter fetal neurodevelopment.
Allergies & Asthma
Women with allergies, asthma, or autoimmune diseases have more active immune systems, which could theoretically affect fetal development. Some studies find higher ASD rates among offspring of women with these conditions.
More research is underway to better understand if immune dysregulation during gestation contributes to ASD risk. If so, it may lead to preventative approaches.
Nutritional Deficiencies
Insufficient levels of key nutrients during pregnancy may impact fetal brain development and increase ASD risk in offspring. Some of the main nutritional deficiencies potentially linked to ASD include:
Folate
Folate is a B vitamin crucial for fetal neurological development. Deficiency has been associated with increased ASD risk in several studies. Getting adequate folate before and during pregnancy is recommended to reduce risks.
Vitamin D
Some research indicates vitamin D deficiency in pregnancy may be associated with greater chances of having a child with autism. More study is underway on this link.
Iron & Zinc
Iron supports healthy fetal brain growth, while zinc is involved in neuron development. Deficiencies in pregnancy may potentially impact ASD risk. However, more research is needed.
Omega-3s
Omega-3 fatty acids support fetal brain development and neuron function. Lower maternal levels during pregnancy have been associated with increased ASD risk in some studies.
Following nutritional guidelines and taking prenatal vitamins containing these key nutrients can help reduce associated risks. Eating plenty of leafy greens, beans, lentils, fish, nuts and seeds can help prevent deficiencies.
Conclusion
While much has been learned, the exact causes of ASD are complex and not fully understood. Current research suggests ASD likely develops from a combination of inherited genetic factors and non-genetic influences encountered during prenatal development. Key risks associated with ASD include advanced parental age, pregnancy complications, prenatal medication exposures, maternal immune activation, toxins, and nutritional deficiencies. Identifying these risk factors will hopefully allow clinicians to develop better screening tools and preventative interventions to reduce ASD prevalence in future generations. Expectant mothers should follow all medical guidelines for a healthy pregnancy and limit exposure to potential toxins/infections that may impact fetal development. While not all ASD cases are preventable, minimizing risks during pregnancy and promptly addressing developmental delays can potentially lead to the best outcomes.