title: An unexpected finding: younger fathers have a higher risk for offspring with chromosomal aneuploidies.
abstract: The past decades have seen a remarkable shift in the demographics of childbearing in Western countries. The risk for offspring with chromosomal aneuploidies with advancing maternal age is well known, but most studies failed to demonstrate a paternal age effect. Retrospectively, we analyzed two case data sets containing parental ages from pre- and postnatal cases with trisomies 21, 13 and 18. The reference data set contains the parental ages of the general Swiss population. We dichotomized all couples into two distinct groups. In the first group, the mothers' integral age was as least as the father's age or older. We compared the frequency of cases in nine 5-year intervals of maternal age. In addition, we computed logistic regression models for the binary endpoint aneuploidy yes/no where paternal ages were incorporated as linear or quadratic, as well as smooth functions within a generalized additive model framework. We demonstrated that the proportion of younger fathers is uniformly different between cases and controls of live-born trisomy 21 as well, although not reaching significance, for fetuses over all mother's ages. Logistic regression models with different strategies to incorporate paternal ages confirmed our findings. The negative paternal age effect was also found in pre- and postnatal cases taken together with trisomies 13 and 18. The couples with younger fathers face almost twofold odds for a child with Down syndrome (DS). We estimated odds curves for parental ages. If confirmation of these findings can be achieved, the management of couples at risk needs a major correction of the risk stratification.
authors.affiliation: Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Steiner
authors.affiliation: Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland.
authors.forename: Rahim
authors.initials: R
authors.lastname: Masood
authors.affiliation: Biostatistics Unit, Institute for Social and Preventive Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Kaspar
authors.initials: K
authors.lastname: Rufibach
authors.affiliation: Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland.
authors.forename: Dunja
authors.initials: D
authors.lastname: Niedrist
authors.affiliation: Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kundert
authors.affiliation: Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland.
authors.forename: Mariluce
authors.initials: M
authors.lastname: Riegel
authors.affiliation: Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland.
authors.forename: Albert
authors.initials: A
authors.lastname: Schinzel
mesh_terms: D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D025063:Chromosome Disorders / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D003710:Demography; D004314:Down Syndrome / Q000235:genetics; D005220:Fathers; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008423:Maternal Age; D008875:Middle Aged; D009035:Mothers; D010331:Paternal Age; D012189:Retrospective Studies; D012307:Risk Factors; D013557:Switzerland; D014314:Trisomy / Q000235:genetics; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome; D055815:Young Adult