Advanced Paternal Age
Should older men who want to be fathers be worried about the health of their offspring? We never thought about this before, so why now? Because it’s only been the last 100 years in the history of mankind that we have been living long enough to even think about advanced paternal age issues. And, given the fact the age at fatherhood has risen consistently over the last 2 generations, this question is now a real one.
What is Advanced Paternal Age?
Advanced paternal age is defined as a father over 40 years of age. Sperm banks that sell donated sperm typically do not accept donors over the age of 50 years. It’s well known that as men get older, their fertility declines, but at a later age, and to a lesser degree, than women. Here’s what happens to fertility as men age:
- Testosterone levels fall about 1% per year after age 40.
- Daily sperm production remains relatively constant.
- Sperm motility falls about 7% per year.
- Ejaculate volume falls with age.
- DNA damage, a measure of sperm “robustness,” increases with age.
The effects of these changes on fertility are hard to assess since erectile dysfunction, decreasing frequency of intercourse and partner’s maternal age can also affect fertility as men age.
Paternal Age and Sperm
As men age, the quality control processes during sperm production are taxed, often heavily, since 1000 sperm are produced per heartbeart in normal men. Because of this, genetic alterations occur more frequently in sperm as men age:
- Sperm chromosomal abnormalities increase, especially among the sex chromosomes X and Y, which can be transmitted to offspring.
- Single gene mutations occur in sperm DNA. This causes a handful of rare but debilitating diseases in offspring (Table 1).
Paternal Age and Pregnancy Outcomes
Even after successful conception, paternal age has been linked to other pregnancy issues:
- Spontaneous miscarriage rates are twice as common in partners of men age 50 years or older.
- Early births (< 32 weeks) and fetal deaths are twice as high in older compared to younger fathers.
So, even after “fertility” is achieved, male partner age can influence the eventual success of pregnancies.
Paternal Age and Birth Defects
In addition to the single gene disorders in offspring (Table 1), various other complex disorders and birth defects have also been linked to paternal age (Table 2) with an overall estimated increased risk of 20% as men age.
Importantly, there is now solid evidence that being an older father leads to an increase in several adult diseases in offspring. These cognitive disorders include schizophrenia (5 fold higher), autism (4 fold higher), bipolar disorder (2 fold higher) and the spectrum of attention deficit disorders (ADHD, 2 fold higher) and are listed in Table 3.
What Should You Do?
Based on current, developing knowledge, men should understand that they too have a “biological clock” and proceed to become fathers with caution. Still, you should know that the overall risk is still quite low. And, currently, there is no testing to assess the risk beforehand. For concerned individuals, the pregnancy should be treated like a “high-risk” pregnancy, and the mother should have the appropriate prenatal screenings and tests that women receive for a high-risk pregnancy.
Table 1. Single gene disorders in offspring linked to paternal age
- Apert syndrome
- Bilateral retinoblastoma
- Crouzon syndrome
- Fibrodysplasia ossificans
- Gardner Syndrome (Adenomatous Polyposis)
- Hemophilia A
- Lesch Nyhan syndrome
- Marfan syndrome
- Multiple Endocrine Neoplasia 2A,2B
- Neurofibromatosis 1
- Oculodentodigital syndrome
- Osteogenesis imperfect
- Pfeiffer syndrome
- Polycystic kidney disease
- Thanatophoric dysplasia
- Treacher-Collins syndrome
- Tuberous sclerosis
- Wardenburg syndrome
Table 2. Birth defects in offspring associated with advanced paternal age
- Tracheoesophageal Fistula
- Atrial Septal Defect
- Ventricular Septal Defect
- Diaphragmatic Hernia
- Cleft Palate and Cleft Lip
- Pulmonary Stenosis
- Spina Bifida
Table 3. Cognitive disorders in offspring associated with advanced paternal age
- Alzheimer’s Disease (AD)
- Attention Deficit Disorders (ADHD)
- Autism and Autism Spectrum Disorder
- Bipolar Disorder