Association of paternal age with prevalence of selected birth defects

Abstract

BACKGROUND: Unlike maternal age, the effect of paternal age on birth defect prevalence has not been well examined. We used cases from the Texas birth defect registry, born during 1996-2002, to evaluate the association of paternal age with the prevalence of selected structural birth defects. METHODS: Poisson regression was used to calculate prevalence ratios (PRs) and 95% confidence intervals (CIs) associated with paternal age for each birth defect, adjusting for maternal age, race/ethnicity, and parity. RESULTS: Relative to fathers ages 25-29 years, fathers 20-24 years of age were more likely to have offspring with gastroschisis (PR 1.47, 95% CI: 1.12-1.94), and fathers 40þ years old were less likely to have offspring with trisomy 13 (PR 0.40, 95% CI: 0.16-0.96). No association was seen between paternal age and prevalence of anencephaly and encephalocele. A selection bias was observed for the other birth defects in which cases of younger fathers were more often excluded from study. CONCLUSIONS: In studies of birth defect risk and paternal age, the source of information may affect the validity of findings.

Paternal age and reproduction

“…The incidence of trisomy 18 in newborns is not affected by paternal age (Naguib et al, 1999), whereas fathers older than 39 years are less likely to have children with trisomy 13 (prevalence ratio 0.4, 95% CI: 0.16 -0.96) in comparison to fathers aged 25-29 years (Archer et al, 2007). Hatch et al (1990) evaluated autosomal trisomies (all autosomes except chromosome 1) in spontaneous miscarriages and found no significant paternal age effects (Hatch et al, 1990).…”

“…Nonetheless, children of older fathers are not only more likely to have several diseases of clear genetic cause (Kühnert and Nieschlag, 2004;Lambert et al, 2006), they show also an increased risk for multifactorial diseases such as birth defects (Olshan et al, 1994;McIntosh et al, 1995;Kazaura et al, 2004;Bille et al, 2005;Zhu et al, 2005a, b;Archer et al, 2007;Yang et al, 2007), childhood cancers (Moll et al, 1996;Hemminki et al, 1999;Sharpe et al, 1999;Murray et al, 2002;Yip et al, 2006), prostate cancer (Zhang et al, 1999), breast cancer (controversial) (Colditz et al, 1991;Choi et al, 2005), diabetes mellitus type l (Bingley et al, 2000;Cardwell et al, 2005), multiple sclerosis (Montgomery et al, 2004), some forms of cerebral palsy (Fletcher and Foley, 1993), schizophrenia (Malaspina, 2001), bipolar disorder (Frans et al, 2008), autism (Reichenberg et al, 2006), epilepsy (Vestergaard et al, 2005), Alzheimer disease (Whalley et al, 1995) and lower intelligence quotients (Malaspina et al, 2005;Saha et al, 2009). However, some of the reported associations need to be considered with caution for methodological reasons in the statistical analysis, especially in regard to the validity of the data sources (Kirby, 2007) (Fig.…”

The effects of advanced paternal age on fertility

“…70,71 Fathers of APA were less likely to sire offspring with trisomy 13 and no relationship has been shown between APA and the birth of an offspring with anencephaly or encephalocele. 69 With regard to Klinefelter syndrome, the population risk is around 1 in 500, 72 and one study found this to be increased to 1 in 312 in men of APA .50 years old. 73 Other work has suggested that there is no significant relationship of APA with either the paternal or maternal age in Klinefelter syndrome.…”

Is There a Paternal Age Effect for Aneuploidy?

“…Therefore with advanced age, the level of mutations in spermatozoa is comparatively high due to the larger number of divisions they have undergone with age [Penrose, 1955;Archer et al, 2007]. In addition, excessive lifestyle, drinking, drug abuse, smoking, and exposure to other DNA-damaging agents are well-known factors causing an increase in sperm aneuploidy, and older men may have progressively exposed themselves to such agents throughout their lifetime.…”