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Original Investigation |

Evidence of Reproductive Stoppage in Families With Autism Spectrum Disorder:  A Large, Population-Based Cohort Study

Thomas J. Hoffmann, PhD1,2; Gayle C. Windham, PhD3; Meredith Anderson, MA3; Lisa A. Croen, PhD4; Judith K. Grether, PhD3; Neil Risch, PhD1,2,4
[+] Author Affiliations
1Institute for Human Genetics, University of California, San Francisco
2Department of Epidemiology and Biostatistics, University of California, San Francisco
3Environmental Health Investigations Branch, California Department of Public Health, Richmond
4Division of Research, Kaiser Permanente, Oakland, California
JAMA Psychiatry. 2014;71(8):943-951. doi:10.1001/jamapsychiatry.2014.420.
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Importance  Few studies have examined the curtailment of reproduction (ie, stoppage) after the diagnosis of a child with autism spectrum disorder (ASD).

Objective  To examine stoppage in a large, population-based cohort of families in which a child has received a diagnosis of ASD.

Design, Setting, and Participants  Individuals with ASD born from January 1, 1990, through December 31, 2003, were identified in the California Department of Developmental Services records, which were then linked to state birth certificates to identify full sibs and half-sibs and to obtain information on birth order and demographics. A total of 19 710 case families in which the first birth occurred within the study period was identified. These families included 39 361 individuals (sibs and half-sibs). Control individuals were randomly sampled from birth certificates and matched 2:1 to cases by sex, birth year, and maternal age, self-reported race/ethnicity, and county of birth after removal of children receiving services from the California Department of Developmental Services. Using similar linkage methods as for case families, 36 215 pure control families (including 75 724 total individuals) were identified that had no individuals with an ASD diagnosis.

Exposures  History of affected children.

Main Outcomes and Measures  Stoppage was investigated by comparing the reproductive behaviors of parents after the birth of a child with ASD vs an unaffected child using a survival analysis framework for time to next birth and adjusting for demographic variables.

Results  For the first few years after the birth of a child with ASD, the parents’ reproductive behavior was similar to that of control parents. However, birth rates differed in subsequent years; overall, families whose first child had ASD had a second child at a rate of 0.668 (95% CI, 0.635-0.701) that of control families, adjusted for birth year, birth weight, maternal age, and self-reported maternal race/ethnicity. Results were similar when a later-born child was the first affected child in the family. Reproductive curtailment was slightly stronger among women who changed partners (relative rate for second-born children, 0.553 [95% CI, 0.498-0.614]).

Conclusions and Relevance  These results provide the first quantitative assessment and convincing statistical evidence of reproductive stoppage related to ASD. These findings have implications for recurrence risk estimation and genetic counseling.

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Figure 1.
Process of Identifying Case and Control Families

We linked California Department of Developmental Services (DDS) and birth records to identify the study population.aMatched for sex, birth year, and maternal age, race/ethnicity, and county of residence.bFor example, individual A is a full sib of individual B and B is a full sib of individual C, but A is a half-sib of C.cFor example, families for whom the first sib was born before 1990.dFor example, families with first and third sibs but no second sib.

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Figure 2.
Kaplan-Meier Curves for Time to Next Birth to Assess Stoppage in Families With Full Sibs

A, Time to second child. B, Time to third child (from second child). C, Time to fourth child (from third child). No history indicates no history of autism spectrum disorder (ASD) in offspring; affected indicates 1 or more children with a diagnosis of ASD.

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Figure 3.
Kaplan-Meier Curves for Time to Next Birth to Assess Stoppage Among Mothers Who Switched Partners

Offspring included in assessment are half-sibs. A, Time to first half-sib, second maternal birth order. B, Time to first half-sib, third maternal birth order (from second child). No history indicates no history of autism spectrum disorder (ASD) in offspring; affected indicates 1 or more children with a diagnosis of ASD.

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