Case-control analysis of paternal age and trisomic anomalies.
OBJECTIVE
To determine whether older paternal age increases the risk of fathering a pregnancy with Patau (trisomy 13), Edwards (trisomy 18), Klinefelter (XXY) or XYY syndrome.


METHODS
Case-control: cases with each of these syndromes were matched to four controls with Down syndrome from within the same congenital anomaly register and with maternal age within 6 months.


METHODS
Data from 22 EUROCAT congenital anomaly registers in 12 European countries.


METHODS
Diagnoses with observed or (for terminations) predicted year of birth from 1980 to 2005, comprising live births, fetal deaths with gestational age ≥ 20 weeks and terminations after prenatal diagnosis of the anomaly. Data include 374 cases of Patau syndrome, 929 of Edwards syndrome, 295 of Klinefelter syndrome, 28 of XYY syndrome and 5627 controls with Down syndrome.


METHODS
Odds ratio (OR) associated with a 10-year increase in paternal age for each anomaly was estimated using conditional logistic regression. Results were adjusted to take account of the estimated association of paternal age with Down syndrome (1.11; 95% CI 1.01 to 1.23).


RESULTS
The OR for Patau syndrome was 1.10 (95% CI 0.83 to 1.45); for Edwards syndrome, 1.15 (0.96 to 1.38); for Klinefelter syndrome, 1.35 (1.02 to 1.79); and for XYY syndrome, 1.99 (0.75 to 5.26).


CONCLUSIONS
There was a statistically significant increase in the odds of Klinefelter syndrome with increasing paternal age. The larger positive associations of Klinefelter and XYY syndromes with paternal age compared with Patau and Edwards syndromes are consistent with the greater percentage of these sex chromosome anomalies being of paternal origin.
De Souza
E
E
Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Wolfson Institute of Preventive Medicine, Charterhouse Square, London, UK.
Morris
J K
JK
D000328:Adult; D025063:Chromosome Disorders / Q000453:epidemiology / Q000209:etiology; D002882:Chromosomes, Human, Pair 13; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004314:Down Syndrome / Q000453:epidemiology / Q000209:etiology; D004812:Epidemiologic Methods; D005060:Europe / Q000453:epidemiology; D006801:Humans; D007713:Klinefelter Syndrome / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008423:Maternal Age; D010331:Paternal Age; D014314:Trisomy; D000073839:Trisomy 13 Syndrome