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The influence of paternal age on down syndrome
Harry Fisch1, Grace Hyun, Robert Golden
1Department of Urology, Columbia-Presbyterian Medical Center, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Insights
Advanced paternal age significantly increases Down syndrome risk, especially when mothers are 35 or older. This combined parental age effect highlights risks for genetic abnormalities in children born to older parents.
Area of Science:
- Genetics
- Reproductive Health
- Pediatrics
Background:
- Advanced parental age is linked to increased genetic abnormality risks in offspring.
- Maternal age's influence on Down syndrome is established, but paternal age effects are less understood.
Purpose of the Study:
- To investigate the impact of advanced paternal age on Down syndrome incidence.
- To determine if paternal age contributes to Down syndrome risk, particularly in conjunction with maternal age.
Main Methods:
- Analysis of Down syndrome cases (n=3,419) from 1983-1997 using the NY State Congenital Malformations Registry.
- Modeling parental age effects using individual age groups and a linear covariate.
- Statistical evaluation using log linear chi-square tests to assess significance.
Main Results:
- A notable increase in births to parents aged 35+ was observed between 1983-1997.
- Paternal age showed no influence on Down syndrome risk until maternal age reached 35.
- The paternal contribution to Down syndrome was 50% when mothers were 40+, indicating a significant combined effect.
Conclusions:
- Advanced paternal age, in combination with advanced maternal age, significantly elevates Down syndrome incidence.
- This finding suggests a broader paradigm for genetic risks associated with older fathers for other conditions.
Purpose:
Children born to older parents are at greater risk for genetic abnormalities, such as Down syndrome. The influence of maternal age on Down syndrome is well established but little is known about the genetic consequences of advanced paternal age.
Materials And Methods:
Data on the incidence of Down syndrome from 1983 to 1997 (3,419 cases) were obtained from the New York State Department of Health congenital malformations registry. Parental age was modeled as individual age groups and by a single linear covariate (drift model). The log linear chi-square test and a test of significance of different explanatory variables were used to evaluate these models to determine significance. We compared actual Down syndrome rates by maternal age with the estimated rate corrected for paternal age.
Results:
From 1983 to 1997 a dramatic increase in the number of infants born to parents 35 years or older was observed. During the 15-year study period there was an increase of 111% and 60% in the number of mothers and fathers 35 years old or older, respectively. There was no parental age influence on Down syndrome until age 35 years and older. A paternal age effect was seen in association with a maternal age of 35 years and older, and it was most pronounced when maternal age was 40 years and older (p = 0.0004). In this later maternal age group the paternal contribution to Down syndrome was 50%.
Conclusions:
Advanced paternal age combined with maternal age significantly influences the incidence of Down syndrome. This effect may represent a paradigm for other genetic abnormalities in children of older fathers.