Case-Control Analysis of Paternal Age and Trisomic Anomalies.

Objectives 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.
Design 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.
Setting Data from 22 EUROCAT congenital anomaly
registers in 12 European countries.
Participants 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.
Main outcome measures 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 signifi cant
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.