This project seeks to expand on the success of an exploratory R21 grant previously awarded to establish capacity to link complex administrative data sets from three separate sources reporting births, conceptions from assisted reproductive technology (ART), and autism diagnoses in California. The goal of this research is to build and analyze the largest and most detailed dataset in existence on ART and developmental disabilities including autism, intellectual disability, and cerebral palsy, in a large and diverse state, with the ultimate aim of understanding the relationship between ART and risk of these disorders. We have successfully linked the California Birth Master Files to the CDC's National Assisted Reproductive Technology Surveillance System registry for California fertility clinics and to outcome data on autism and receipt of developmental services for the 1996 to 2007 birth cohorts, and published initial findings from this dataset. We seek next to expand the project significantly in order to assess in greater detail the relationship between ART and autism as well as other developmental disabilities. First, we propose to incorporate additional cohorts of California births and conceptions through at least 2016, and outcomes through at least 2020. This will expand the data set to more than eleven million births, about 123,000 ART births, and about 65,000 autism cases. This will also expand our follow-up period into early adulthood, an unprecedented feature in a population-based dataset this large that allows us to examine long-term developmental consequences of ART. In addition, we will include data on diagnoses of cerebral palsy and intellectual disability. Next, we will expand our analyses in several ways: 1) strengthen our preliminary findings in this much larger dataset by analyzing variation in the association among subgroups of infertility and ART procedure as well as potential mediating variables like obstetric complications and effect modifiers like maternal obesity; 2) model the long-term symptom expression of autism through adolescence, and test whether these patterns differ by conception group; 3) use sibling pairs discordant for ART conception to assess the role of confounding by family characteristics; 4) examine the association between ART and intellectual disability and cerebral palsy; and 5) assess the role that neighborhood characteristics play in the association between ART and developmental disabilities. Against the background of rapidly rising autism prevalence and the increasingly important role of ART in reproductive decision-making, this research has notable scientific and public health implications. By elucidating the long term developmental risks associated with specific treatments/subsets of ART patients, this project has the potential to make significant contributions to our understanding of the etiology of autism and other developmental disabilities, and to risk-benefit considerations for the recommendation and usage of specific procedures.
The prevalence of autism has increased rapidly in recent decades and its causes remain poorly understood; meanwhile the use of Assisted Reproductive Technology (ART) has also increased, although the long-term risks to children conceived this way remain largely unknown. This project will contribute to public health by building and analyzing a unique population-level dataset designed to assess the association between ART and its subtypes and Autism, Intellectual Disability, and Cerebral Palsy as well as investigate heterogeneity in risk and the factors that may affect the associations. This will better enable individuals and their health care providers to weigh the risks and benefits of ART procedures and to identify potential modifiable risk factors for autism and other developmental disabilities.
