Paternal age and birth defects: how strong is the association?

Abstract

Infants born to older fathers have a slightly increased risk of birth defects. Young paternal age is also associated with slightly increased risk of several selected birth defects in their offspring. However, given the weak association, paternal age appears to play a small role in the aetiology of birth defects.

The effect of father’s age in fertile, subfertile, and assisted reproductive technology pregnancies: A population based cohort study

“…Other studies have linked paternal age to increased miscarriage rates [8], as well as birth defects and autism [11-15, 21, 23]. Yang et al [12] reviewed literature on birth defects as a function of paternal age and found a weak but consistent association. Unfortunately, the national SART CORS and NASS datasets lack information on the male partner.…”

“…A paternal age >40 may contribute to increased miscarriage rates, particularly when the woman is also of advanced age [8] but studies differ on the effect of paternal age on ART success rates [9,10]. In addition, rates of birth defects and autism may also be increased with advanced paternal age [11][12][13][14][15]. Guidelines on advanced age and fertility treatment released in 2011 by the Society of Obstetricians and Gynaecologists of Canada [6] focused primarily on older age in women, but summarized the known data on advanced age in men in the following statement:…”

Paternal age and reproduction

“…All autosomal monosomies are lethal and only fetuses with autosomal trisomies 13, 18 and 21 can survive to term. Trisomy 21 is the most common trisomy in newborns and its incidence is increased with higher maternal age, whereas the influence of paternal age is controversially discussed (Sloter et al, 2004;Yang et al, 2007;Crane and Morris, 2007). A recent evaluation of 3419 affected subjects, however, revealed that trisomy 21 and higher paternal age are only associated when mothers are aged 35 years or older.…”

“…Increased risk for heart defects, circulatory/respiratory defects, diaphragmatic hernia, tracheo-oesophageal fistulas, musculo-sceletal anomalies (data extracted from Yang et al, 2007). 2005a, b). Zhu et al analyzed data of 70 347 singleton births in Denmark, but only women aged 20 -29 years and fathers older than 19 years were included.…”

“…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.…”