A systematic review of maternal exposures and the risk of autism spectrum disorders in their infants

Abstract

Maternal exposures associated with autism spectrum disorder remain poorly understood. The purpose of this systematic review was to assess the current understanding of maternal exposures and their associations with increased or decreased risk of infant autism. We searched Ovid MEDLINE databases and reference lists in 2021 for studies looking at maternal factors analyzed for an association with ASD. The primary outcome was autism or autism spectrum disorder diagnosis. Exposures were grouped as biomarkers, environmental, occupational, medication, genetic variability, and maternal illnesses and conditions. PRISMA guidelines were followed. Descriptive summary statistics were evaluated. Of 433 reports identified, 47 studies published between 2006 and 2021 fulfilled the inclusion criteria. Exposures consistently associated with a significant increased risk of autism spectrum disorder outcomes included: benzoate, 10-hydroxydecanoate, methyl jasmonate, 1-methylhistidine, nonanoic acid, organohalogens, ornithine, polyunsaturated fatty acids, agricultural pesticides, heavy metals (arsenic, cadmium, chromium, lead, low levels of manganese, tin), cigarette smoking, hypotaurine, indoor household pesticides, methanol, newborn complications at delivery, occupational exposures, solvents, strontium, urate, antibiotics, placental differently methylated regions, diabetes, maternal fever, maternal depression, androgen-associated conditions and psychiatric disorders. Factors consistently associated with a significant decreased risk included: quinoline, air conditioning, cesium, copper, 3-hydroxybutanic acid, maternal fruit consumption, mercury, and phenylalanine. This review provides evidence that there are several potential pregnancy exposures and biomarkers associated with an autism spectrum disorder diagnosis in children. Genetic mutations may play role in impact of exposures’ risks. Continued work on identifying potential exposures and biomarkers is needed to better counsel pregnant individuals.