Do Women with Polycystic Ovary Syndrome (PCOS) and Their Children Have Elevated Rates of Autism? an Electronic Health Records Study in the UK

Background:  Elevated levels of prenatal testosterone may increase the risk for autism spectrum conditions (autism). There is also an association between autism and polycystic ovarian syndrome (PCOS) in women with autism and mothers with a child with autism, although the extent of this association remains obscure. Given that PCOS is also associated with elevated prenatal and circulating testosterone, hyperandrogenism in PCOS may be implicated in the development of autistic traits in women with PCOS and their children.

Objectives:  1. To examine the prevalence of autism in women with PCOS, and conversely, PCOS in women with autism. 2. To calculate the odds of developing autism in first-born children of women with PCOS.

Methods:  Using electronic health records obtained from the Clinical Practice Research Datalink (CPRD) in the UK, we conducted two matched case-control studies. 1. We examined the prevalence and risk of PCOS in women with autism and vice versa in a sample of n = 791 and n = 22,263 women, respectively, compared to up to five times as many age and GP practice matched controls. Frequency tables were calculated and differences tested using Chi-Square Test for Proportions. 2. We examined the risk of autism in first-born children of women with PCOS in a population of n = 8,611 children with mothers with PCOS matched to up to five times as many controls. Cases and controls were linked to mothers using the Mother-Baby Link within the CPRD. Controls were matched on gender, GP practice, and year of birth within ± two years. Two models adjusting for covariates were generated using conditional logistic regression. The first adjusted for maternal age, marital status, and maternal psychiatric diagnoses, while the second also included obstetric complications and metabolic conditions. Autism diagnoses were based on previously validated Read code lists (Fombonne et al., 2004; Smeeth et al., 2004). PCOS was defined according to Read code PCOS diagnoses (polycystic ovarian syndrome, C165.00, and Stein-Leventhal syndrome, C164.12), as well as by phenotypic parameters, where women with a PCO diagnosis, in addition to ovulatory dysfunction and/or hyperandrogenism, according to Rotterdam criteria, were included.

Results: 1. We found significantly increased rates of PCOS in women with autism (2.3% vs. 1.1%, P = 0.006) and significantly elevated rates of autism in women with PCOS (0.23% compared with 0.09%, P < 0.001). 2. The odds of having a child with autism for mothers with PCOS was also significantly increased, both in the unadjusted model and following adjustment for marital status, maternal psychiatric diagnoses, obstetric complications, and metabolic conditions (unadj. OR: 1.58, 95% CI: 1.27 – 1.98; adj. OR: 1.35, 95% CI: 1.06 – 1.71).

Conclusions:  These two large-scale epidemiological studies present evidence that women with PCOS and their children have a greater prevalence of autism. Prenatal and maternal sex-steroids may be a potential source of this association.