What causes autism in pregnancy and how can a pregnant woman minimize the risk of having a child with autism?

Causes of Autism During Pregnancy

Autism spectrum disorder results primarily from genetic factors, but multiple prenatal environmental exposures and maternal conditions during pregnancy can increase risk, though no single factor "causes" autism in isolation. 1

Genetic Factors (Primary Contributors)

Genetics represent the strongest risk factor for autism, with heritability estimates of 50-90% based on twin and population studies. 2, 3

• Multiple genes contribute to autism risk through both common genetic variations and rare mutations with large effect sizes 2
• Sibling recurrence risk ranges from 6-19% with one affected child, escalating to 32-50% when two or more children are affected 1, 3
• Advanced maternal and paternal age significantly increases autism risk through accumulation of de novo genetic mutations 2

Maternal Medical Conditions During Pregnancy

Several maternal health conditions during pregnancy are associated with increased autism risk:

• Gestational diabetes mellitus is a significant predictor of severe autism (4.5-fold increased risk) 4, 5, 6
• Pregestational diabetes mellitus also shows strong associations with autism 5, 6
• Maternal autoimmune diseases, particularly antiphospholipid syndrome with anti-β2GP1 IgG antibodies and thyroid disease with anti-TPO antibodies 6
• Maternal infections during pregnancy, especially rubella and cytomegalovirus with direct fetal brain injury 5, 6
• Prolonged maternal fever and systemic inflammation, which alter inflammatory cytokines that cross the placenta 5, 6
• Preeclampsia has documented associations with increased autism risk 6

Medication Exposures During Pregnancy

Certain medications taken during pregnancy show established or probable associations with autism:

• Valproic acid (antiepileptic drug) has the strongest evidence for autism risk 5, 6
• Thalidomide shows documented associations 5, 6
• Misoprostol has possible associations requiring further study 5, 6
• Selective serotonin reuptake inhibitors (SSRIs) remain controversial, with conflicting evidence about whether associations reflect the medication itself versus the underlying maternal psychiatric condition 1, 6

Critical caveat: The maternal psychiatric condition (depression, anxiety) itself is associated with increased autism risk independent of medication use, making it difficult to isolate medication effects 1

Environmental Chemical Exposures

Growing evidence implicates specific environmental chemicals during the prenatal period:

• Heavy exposure to pesticides during pregnancy, particularly chlorpyrifos, shows associations with autism 1, 2, 6
• Air pollution exposure, especially particulate matter <2.5 and 10 μm diameter (PM2.5 and PM10), demonstrates consistent associations 2, 6
• Heavy metals including lead show documented relationships 1, 2
• Polychlorinated biphenyls (PCBs) have been recommended for systematic review 2
• Bisphenol A (BPA) and phthalates may target autism-related genes 1, 2

The prenatal period represents a critical window of vulnerability when the developing brain is particularly susceptible to chemical disruptions. 1, 2

Substance Use During Pregnancy

• Ethanol (alcohol) shows documented associations with autism 5, 6
• Cocaine use has described associations 5, 6
• Heavy smoking shows possible associations, though direct causation is not established 7, 5

Nutritional Factors

• Folic acid deficiency during pregnancy is associated with increased autism risk 5, 6
• Poor maternal nutrition overall has been linked to neurodevelopmental problems 1

Birth-Related Factors

• Extremely premature birth (<26 weeks gestational age) significantly increases autism risk 2
• Birth oxygen desaturation is a significant predictor of severe autism (4.1-fold increased risk) 4
• Meconium aspiration syndrome, abnormal birth weight, and prolonged labor time show associations 7
• Closer spacing between pregnancies increases autism risk 2

Maternal Stress and Psychiatric Conditions

Maternal depression, anxiety, and stress during pregnancy are independently associated with increased autism risk, separate from medication effects:

• These conditions may operate through altered parenting practices, adverse birth outcomes, or direct effects on fetal neurodevelopment 1
• Stressful life events during pregnancy show documented associations 1
• Low socioeconomic status predicts both maternal depression and reduced access to healthy nutrition, creating multiple risk pathways 1

How to Minimize Risk During Pregnancy

Based on the evidence, pregnant women can take these specific steps:

Medical Management

• Achieve optimal glycemic control if diabetic before and during pregnancy 4, 5, 6
• Treat maternal infections promptly and manage fever aggressively 5, 6
• Avoid valproic acid for epilepsy management when alternative antiepileptic drugs are available 5, 6
• Discuss SSRI use with your physician, weighing risks of untreated maternal depression against potential medication effects 1

Nutritional Interventions

• Take prenatal vitamins with adequate folic acid throughout pregnancy 5, 6
• Maintain adequate nutrition and avoid deficiencies 1, 5

Environmental Exposure Reduction

• Minimize exposure to pesticides by choosing organic produce when possible and avoiding agricultural areas 1, 2, 6
• Reduce air pollution exposure by avoiding high-traffic areas and using air filtration indoors 2, 6
• Avoid heavy metals including lead exposure 1, 2
• Minimize use of products containing BPA and phthalates 1, 2

Substance Avoidance

• Completely avoid alcohol during pregnancy 5, 6
• Avoid cocaine and illicit drug use 5, 6
• Minimize or eliminate smoking 5, 6

Lifestyle Factors

• Manage maternal stress through appropriate support and interventions 1
• Treat underlying psychiatric conditions with appropriate medical supervision 1
• Optimize pregnancy spacing (avoid very close consecutive pregnancies) 2

Critical Understanding

The dramatic rise in autism prevalence from 1 in 150 (2002) to 1 in 59 (2014) cannot be explained by genetics or diagnostic changes alone, strongly implicating environmental factors and gene-environment interactions. 1, 2

No single environmental factor "causes" autism—the disorder results from complex interactions between genetic susceptibility and multiple environmental influences during critical developmental windows. 1, 8 The prenatal period represents the most vulnerable time when interventions can potentially reduce risk 1, 2, 8

Males are affected 3-4.5 times more frequently than females, suggesting hormonal and sex-specific protective factors play important roles. 1, 2 Increased fetal testosterone exposure, measured by digit ratio, is associated with autism diagnosis 1