Kids of Older Dads at Risk for 'Serious' Psychiatric Problems

Megan Brooks

February 26, 2014

Men who delay starting a family risk having a child with a variety of psychiatric problems and academic difficulties.

Results from a Swedish population-based study show that siblings born to fathers aged 45 years and older were at higher risk for autism, attention deficit/hyperactivity disorder (ADHD), psychosis, bipolar disorder, suicide attempts, substance abuse, failing a grade, and low educational attainment compared with siblings born to fathers in their early 20s.

"We are not saying that all offspring born to older fathers will have psychiatric or educational problems," first author Brian D'Onofrio, PhD, associate professor, Department of Psychological and Brain Sciences, Indiana University in Bloomington, told Medscape Medical News.

"Rather, the study found that advancing paternal age at childbearing is associated with greater risk for serious problems in offspring that cause great impairment. As such, the study adds to a growing body of research that suggests families, doctors, and society as a whole must consider both the pros and cons of delaying childbearing," Dr. D'Onofrio said.

The study was published online February 26 in JAMA Psychiatry.

Magnitude of Risk

The researchers estimated the risk for a variety of psychiatric and academic problems associated with advancing paternal age using several quasiexperimental designs, including the comparison of differentially exposed siblings, cousins, and first-born cousins. Participants included all individuals born in Sweden from 1973 to 2001 (about 2.6 million).

Paternal age of 45 years and older was associated with increased risk for psychiatric morbidity in offspring in within-sibling comparisons.

Psychiatric Outcome Hazard Ratio 95% CI
Autism 3.45 1.62 - 7.33
ADHD 13.13 6.85 - 25.16
Psychosis 2.07 1.35 - 3.20
Bipolar disorder 24.70 12.12 - 50.31
Suicide attempt 2.72 2.08 - 3.56
Substance abuse 2.44 1.98 - 2.99

CI, confidence interval

Advancing paternal age was also associated with greater odds of failing a grade (odds ratio [OR], 1.59; 95% CI, 1.37 - 1.85) and low educational attainment (OR, 1.70; 95% CI, 1.50 - 1.93) in within-sibling comparisons.

"Additional analyses using several quasi-experimental designs obtained commensurate results, further strengthening the internal and external validity of the findings," the authors write.

The magnitude of risk was as large as or larger than previous estimates, they note.

Novel Findings

"The findings are consistent with the hypothesis that de novo mutations during spermatogenesis associated with advancing paternal age influence offspring morbidity, which should be investigated in molecular genetic studies of psychiatric disorders," Brian Miller, MD, assistant professor, Department of Psychiatry and Health Behavior, Georgia Regents University in Augusta, told Medscape Medical News.

Dr. Miller was a peer reviewer on the study and has a research interest in paternal age and psychiatric morbidity. He said this new study yields "several novel findings."

"The authors investigated associations between advancing paternal age and indices of morbidity that have not previously been explored, including ADHD, suicidality, substance use, and academic problems," Dr. Miller said.

"The case-sibling analysis," he added, "strongly suggests that neither 'selection into late fatherhood' (which posits that increased liability for offspring morbidity in the form of personality traits results in a tendency to postpone childbearing) nor unmeasured genetic and environmental factors shared by siblings explains the observed associations with advancing paternal age."

"The authors also found a robust dose-response association with offspring morbidity, suggesting that there is not an obvious cutoff point above which paternal age should be considered 'advanced.' "

The study was supported by a grant from the National Institute of Child Health and Human Development, the Swedish Research Council, and the Swedish Council for Working Life and Social Research. The authors and Dr. Miller report no relevant financial relationships.

JAMA Psychiatry. Published online February 26, 2014. Abstract


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