Autism Risk Across Generations A Population-Based Study of Advancing Grandpaternal and Paternal Age Autism Risk

Frans EM, Sandin S, Reichenberg A, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

Advancing paternal age has been linked to autism.

Objective

To further expand knowledge about the association between paternal age and autism by studying the effect of grandfathers' age on childhood autism.

Design

Population-based, multigenerational, case-control study.

Setting

Nationwide multigeneration and patient registers in Sweden.

Participants

We conducted a study of individuals born in Sweden since 1932. Parental age at birth was obtained for more than 90% of the cohort. Grandparental age at the time of birth of the parent was obtained for a smaller subset (5936 cases and 30 923 controls).

Main Outcome and Measure

International Classification of Diseases diagnosis of childhood autism in the patient registry.

Results

A statistically significant monotonic association was found between advancing grandpaternal age at the time of birth of the parent and risk of autism in grandchildren. Men who had fathered a daughter when they were 50 years or older were 1.79 times (95% CI, 1.35-2.37; P < .001) more likely to have a grandchild with autism, and men who had fathered a son when they were 50 years or older were 1.67 times (95% CI, 1.35-2.37; P < .001) more likely to have a grandchild with autism, compared with men who had fathered children when they were 20 to 24 years old, after controlling for birth year and sex of the child, age of the spouse, family history of psychiatric disorders, highest family educational level, and residential county. A statistically significant monotonic association was also found between advancing paternal age and risk of autism in the offspring. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on grandparental age.

Conclusions and Relevance

Advanced grandparental age was associated with increased risk of autism, suggesting that risk of autism could develop over generations. The results are consistent with mutations and/or epigenetic alterations associated with advancing paternal age.

Association of Maternal Exposure to Childhood Abuse With Elevated Risk for Autism in Offspring Autism and Maternal Exposure to Childhood Abuse

Roberts AL, Lyall K, Rich-Edwards JW, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

Adverse perinatal circumstances have been associated with increased risk for autism in offspring. Women exposed to childhood abuse experience more adverse perinatal circumstances than women unexposed, but whether maternal abuse is associated with autism in offspring is unknown.

Objectives

To determine whether maternal exposure to childhood abuse is associated with risk for autism in offspring and whether possible increased risk is accounted for by a higher prevalence of adverse perinatal circumstances among abused women, including toxemia, low birth weight, gestational diabetes, previous induced abortion, intimate partner abuse, pregnancy length shorter than 37 weeks, selective serotonin reuptake inhibitor use, and alcohol use and smoking during pregnancy.

Design and Setting

Nurses' Health Study II, a population-based longitudinal cohort of 116 430 women.

Participants

Nurses with data on maternal childhood abuse and child's autism status (97.0% were of white race/ethnicity). Controls were randomly selected from among children of women who did not report autism in offspring (participants included 451 mothers of children with autism and 52 498 mothers of children without autism).

Main Outcome Measures

Autism spectrum disorder in offspring, assessed by maternal report and validated with the Autism Diagnostic Interview–Revised in a subsample.

Results

Exposure to abuse was associated with increased risk for autism in children in a monotonically increasing fashion. The highest level of abuse was associated with the greatest prevalence of autism (1.8% vs 0.7% among women not abused, P = .005) and with the greatest risk for autism adjusted for demographic factors (risk ratio, 3.7; 95% CI, 2.3-5.8). All adverse perinatal circumstances except low birth weight were more prevalent among women abused in childhood. Adjusted for perinatal factors, the association of maternal childhood abuse with autism in offspring was slightly attenuated (risk ratio for highest level of abuse, 3.0; 95% CI, 1.9-4.8).

Conclusions and Relevance

We identify an intergenerational association between maternal exposure to childhood abuse and risk for autism in the subsequent generation. Adverse perinatal circumstances accounted for only a small portion of this increased risk.

JAMA Psychiatry: Autism Spectrum Disorders Topic Collection

Autism Risk Across Generations A Population-Based Study of Advancing Grandpaternal and Paternal Age Autism Risk

Association of Maternal Exposure to Childhood Abuse With Elevated Risk for Autism in Offspring Autism and Maternal Exposure to Childhood Abuse