Developmental origins of autism: A population level linked data study of potentially modifiable risk factors
1. Can we develop algorithms for case ascertainment of ASD using administrative health and education data? Are these algorithms valid, sensitive and specific?
2. What is the prevalence and incidence of ASD in British Columbia? Has it increased over time?
3. What is the rate of prenatal exposure to exogenous oxytocin in British Columbia? Has this changed over time? Is oxytocin being used appropriately in BC?
4. Does prenatal exposure to exogenous oxytocin increase the risk of ASD?
5. Does a maternal mood disturbance during pregnancy increase the risk of ASD in the child? Does the treatment of a maternal mood disturbance with a psychotropic medicine increase the risk of ASD during early childhood?
6. Can we distinguish the effect of prenatal psychotropic medicine exposure from the effect of antenatal maternal mood disturbances on risk of ASD?
7. What is the role of timing, duration and polypsychopharmacotherapy (treatment with more one category of psychotropic medicine) on the risk of ASD?
8. Is exposure to airborne pollutants, including PM2.5, nitrogen dioxide and other airborne pollutants, during early pregnancy associated with a higher risk for the development of ASD?
9. Is exposure to maternal epilepsy and/or anticonvulsants in utero associated increase risk of ASD?
10. Can we distinguish between the effect of prenatal anticonvulsant exposure from the effect of antenatal maternal epilepsy on risk of ASD?
11. What are the developmental trajectories of children diagnosed with ASD in regard to their social, emotional, and cognitive-academic development, social relationships, and participation during the elementary school years?
12. Is there a relationship between gestational age and indicators of intrauterine growth (e.g. small for gestational age birth) and ASD? Are they associated with different comorbidities among children with ASD and with different deficits comprising ASD?
1. We hypothesize that algorithms using a combination of health and education data may be valid indicators of ASD status in a child.
2. We hypothesize that the prevalence of ASD has increased in BC over the time period of our study; however, this may not represent a true increase in the incidence of autism as reporting changes and differing definitions of ASD may all play a role.
3. We hypothesize that the exposure to exogenous oxytocin through induction and augmentation of labour has increased during our study period.
4. We hypothesize that after properly controlling for all relevant confounders and accurately identifying the exposure and the outcome, that there will no increased risk of ASD associated with prenatal exposure to exogenous oxytocin.
5. We hypothesize that prenatal exposure to an SRI antidepressant will be associated with an increased for risk for ASD in childhood, above and beyond the risk associated with exposure to a maternal mood disturbance. We are uncertain whether prenatal exposure to other psychotropic medicines will increase the risk for ASD.
6. SRIs play a role in the development of an ASD that is distinct from the underlying maternal mood disturbance, such that even after accounting for maternal illness severity, the rate of ASD will be statistically significantly higher among children born to mothers using SRIs in pregnancy as compared to equally depressed mothers not using SRIs. We are uncertain whether other psychotropic medicines will play a role above and beyond the mood disorder they are treating
7. a) While brain growth spans all of gestation, we expect that continuous (all trimesters) prenatal SRI exposure will increase the risk of ASD compared with exposure in the first or third trimesters alone.
b)We hypothesize that increased ASD symptom severity will be associated with prolonged continuous prenatal SRI exposure compared with exposure in the first or third trimesters alone.
c) Prenatal exposure to polypsychopharmacotherapy (including an SRI) will be associated with an increased risk for ASD when compared to SRI monotherapy.
8. We hypothesize that mothers of children who are diagnosed with ASD had significantly higher exposures to PM2.5, an indicator of traffic pollutants, during early pregnancy than control mothers.
9. We hypothesize that exposure to maternal epilepsy is not associated with increased risk of ASD, but that exposure to anticonvulsants are associated with increased risk of ASD.
10. We expect that using some sophisticated analytic techniques, we will be able to distinguish the effect of maternal epilepsy from exposure to anticonvulsants.
11. We hypothesize that there are many different developmental trajectories of children with ASD.
12. We hypothesize that (1) ASD diagnosis will increase in a linear fashion with decreasing gestational age at birth and with indicators of inadequate intrauterine growth; (2) more preterm children and those with inadequate uterine growth will be diagnosed with ASD will have co-morbid condition(s) including cognitive impairment [IQ