What prenatal exposures increase the risk of Autism Spectrum Disorder (ASD)?

From the Guidelines

Prenatal exposure to organophosphate pesticides has been linked to an increased risk of Autism Spectrum Disorder (ASD) in children, as evidenced by a systematic review of epidemiologic studies and experimental animal studies 1. Several prenatal exposures have been associated with increased risk of Autism Spectrum Disorder (ASD).

• Maternal infections during pregnancy, particularly those accompanied by high fever or immune activation, may increase ASD risk.
• Certain medications taken during pregnancy pose concerns, including valproic acid (an anticonvulsant), with doses above 1000mg daily carrying higher risk; thalidomide if taken during days 20-35 of gestation; and misoprostol if used in unsuccessful abortion attempts.
• Environmental toxins such as air pollution, pesticides, and heavy metals (particularly mercury and lead) have shown associations with ASD development.
• Advanced parental age (maternal age over 35 or paternal age over 40) correlates with increased risk.
• Maternal metabolic conditions including diabetes, obesity, and hypertension during pregnancy may also contribute to ASD risk.
• Extreme prematurity (birth before 26 weeks) and very low birth weight (under 1500g) are additional risk factors. These associations likely involve complex interactions between genetic susceptibility and environmental triggers that disrupt normal neurodevelopment during critical periods of brain formation.

However, it's essential to note that the evidence on prenatal antidepressant use during pregnancy and offspring neurodevelopmental problems is still limited and inconclusive 1.

• Some studies suggest that prenatal antidepressant exposure may be associated with an increased risk of ASD and ADHD, but the evidence is not strong, and the associations may be due to confounding factors rather than a causal effect of the exposure.
• Other studies have found no significant association between prenatal antidepressant exposure and neurodevelopmental problems in offspring. Therefore, the current evidence does not support a strong causal link between prenatal antidepressant exposure and ASD risk, and more research is needed to fully understand the relationship between prenatal exposures and neurodevelopmental outcomes 1.

From the FDA Drug Label

VALPROATE CAN PRODUCE TERATOGENIC EFFECTS ... THERE HAVE BEEN REPORTS OF DEVELOPMENTAL DELAY, AUTISM AND/OR AUTISM SPECTRUM DISORDER IN THE OFFSPRING OF WOMEN EXPOSED TO VALPROATE DURING PREGNANCY

• Prenatal exposure to valproic acid is associated with an increased risk of Autism Spectrum Disorder (ASD) in the offspring.
• The exact mechanism is unknown, but valproic acid has been shown to have teratogenic effects.
• Women of childbearing potential should be thoroughly informed of the risks and benefits of valproate treatment before initiating therapy 2.
• The use of folic acid supplementation may reduce the risk of congenital neural tube defects, but its effect on ASD risk is unknown.

From the Research

Prenatal Exposures and ASD Risk

Prenatal exposures that increase the risk of Autism Spectrum Disorder (ASD) include:

• Pesticide exposure, particularly pyrethroid and organophosphate, during pregnancy 3
• Air pollution, including particulate matter and heavy metals, during the prenatal period 4, 5
• Maternal immune activation (MIA) conditions, such as infection, hypertension, and autoimmune diseases, during pregnancy 5
• Certain drugs and dietary nutrients that may affect epigenetic regulation during pregnancy 6

Protective Factors

Some prenatal exposures may reduce the risk of ASD, including:

• Folic acid supplements taken around the time of conception 7
• Maternal intake of certain nutrients and supplements, such as periconceptional folic acid supplements 4

Key Findings

• Pregnancy seems to be the time when pesticide exposure has the greatest impact on the onset of ASD in children 3
• MIA-related conditions and pregnancy PM2.5 were independently associated with ASD risk, but there were no interactions between the two 5
• Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder 7