Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social interaction and communication, and by the presence of restrictive repetitive behavior. The precise cause of ASD is largely unknown, but is thought to be due to genetic predisposition combined with environmental factors. Emerging epidemiological studies have identified several non-genetic risk factors for ASD, many of which may have their origins during prenatal and early postnatal periods. Among these, nutritional and metabolic factors during critical early life windows may be important, but they have not been well studied in a prospective birth cohort.
To address some of these knowledge gaps, this dissertation focused on the prospective associations between: 1) maternal folate and vitamin B12 status and development of ASD in children (specific aim 1); and 2) child’s leptin and adiponectin levels and development of ASD (specific aims 2 and 3). Data from the Boston Birth Cohort (BBC), a large prospective birth cohort, consisting of a predominantly urban, low-income minority population, were used. The BBC recruited mother-child pairs at birth and followed them from birth onwards for pediatric outcomes including ASD. Electronic Medical Records were used to identify children with ASD and other neurodevelopmental disorders.
For specific aim 1, maternal folate status was defined using two complementary measures: maternal self-reported intake via questionnaire and maternal plasma biomarker of folate and vitamin B12 levels. Mothers’ supplement intake during pregnancy was associated with a ‘U-shaped’ relationship in ASD risk in their children. In addition, extremely high maternal plasma folate and vitamin B12 levels were associated with a greater risk of developing ASD in children.
For specific aims 2 and 3, the child’s plasma leptin and adiponectin levels were measured at two-time points: cord blood collected at delivery and venous blood collected in early childhood. Children with highest early childhood leptin levels (quartile 4), when compared to those with lowest levels (quartile 1), showed an increased risk of developing ASD. Extremely rapid weight gain during 1st year of life was associated with a greater ASD risk, when compared to those children whose growth was on track and this association persisted after adjusting for pertinent confounders. Early childhood leptin partially mediated the association between 1st year weight gain and ASD. However, no association with ASD was found for fetal growth pattern and cord leptin levels. On the other hand, cord adiponectin levels were inversely associated with ASD risk and this was independent of preterm birth, early childhood adiponectin and other known ASD risk factors. While higher early childhood adiponectin was also associated with a lower risk of ASD, the association attenuated after adjusting for cord adiponectin.
The findings from this dissertation, if confirmed by future studies, could have important clinical and public health implications. Notably, findings from specific aim 1 underscore the need to 1) regularly monitor folate levels in women of reproductive age (both at clinical and population level); and 2) identify an optimal plasma folate levels, so that adverse effects of both low and high levels of folate can be averted. Findings from specific aims 2 and 3 provide a basis to further explore whether biomarkers such as leptin and adiponectin, in combination with early life growth pattern can improve our ability to detect children at high risk of developing ASD at the earliest possible age, to inform targets for early prevention
