The Effect of Parental Age on the Probability of Having Healthy Offspring: A Literature Review
This article focuses on problems that can occur in a reproductive process: conception, pregnancy, and infant health. This literature review examines recent scientific studies on the effects of parental age on each of these problems. I found the studies through relevant keyword searches. The brief summary is as follows.
The results of the studies show that the probability of a woman getting pregnant in one year of trying (sex every 3 days) drops from 71% (at 20 years old) to 55% (at 40 years old). The probability of miscarriage also increases from 10% to 25%, while the probability of a birth defect rises from 1% to 15%, with an acceleration in this trend after the age of 40.
To illustrate the probability of having a healthy offspring within a year, a chart was constructed based on the following formula: (probability of successful pregnancy in one year) * (probability of no miscarriage) * (probability of no birth defects). However, the father's age was not included in this calculation, as I did not find these data in the studies. The intention of the chart is to illustrate the trend, not to indicate the exact numbers.
While the effect of age on male fertility is not as pronounced as it is for women, studies show that fertility decreases, miscarriage rates increase, and the probability of birth defects rises with increasing age. However, noticeable trends tend to appear after the age of 40.
For men, the probability of making a woman pregnant within a year decreases by approximately 10% after the age of 40, compared to the age of 30. However, older men also tend to have less sex than younger ones. After 40, men increase the probability of miscarriage by 1.23 times (how I understood, it increases from 10% to 12% for a partner in her 20s, could be wrong) compared to 25-29. Finally, advanced paternal age has a significant positive effect on the rate of birth defects. However, the rate is generally low. For example, orofacial clefts have a probability lower than 0.2%. For fathers over 45, this probability is up to 0.3%.
The rest of this post provides evidence for these statements.
Fertility
“Most couples will get pregnant within a year if they have regular sex and don't use contraception.
But women become less fertile as they get older.
The effect of age on men's fertility is less clear.
Having regular sex means having sex every 2 to 3 days throughout the month.” [19]
“Across a population, women younger than 35 and men younger than 40 have a better chance of having a child than people who are older. This is true for natural pregnancies and for pregnancies conceived through assisted reproductive treatments such as IVF (in-vitro fertilisation).” [5]
Women
On average women give birth to the first kid when they are 30 years old [1].
If you look here, you’ll see data from the American Society of Reproductive Medicine (ASRM) on the odds of natural pregnancy by age each month.
Age (years) Odds of a Natural Pregnancy by Age each Month
25 25%
30 20%
35 <15%
40 <5%
Below, you’ll see data on the odds of natural pregnancy by age within one year of trying.
Women’s Age Chance of Getting Pregnant by Age Within 1 Year
20-24 86%
25-29 78%
30-34 63%
35-39 52%
Taken from [2]
Chances for the older age (within 1 year): “40-45 55%” [3]
"the cumulative pregnancy proportion at 12 cycles of attempt time ranged from 79.3% (age 25–27 years) to 55.5% (age 40–45 years)" [29]
Chart from [6].
“A woman is born with all the eggs she will ever have. As she ages her eggs age with her and their number and quality reduces over time. This is why her chance of having a baby also reduces over time, especially for women older than 35 years of age.” [5]
Men
“The chart above shows men’s likelihood of having a child decreases sharply after 30, but that is more closely related to lifestyle factors than infertility. Advanced paternal age is generally considered “above 40” or “above 45” by most doctors and fertility studies.” [4]
“Men younger than 40 have a better chance of fathering a child than those older than 40. The quality of the sperm men produce seems to decline as they get older.” [5]
“One study showed after adjusting for female age, conception during a 12-month period was 30% less likely for men over the age of 40 compared with men younger than 30.” [7]
“Further evidence of this negative impact was identified in an observational study of pregnant women, in which a fivefold increase in the time to achieve pregnancy was observed when the man's age was >45 years.47 Moreover, when compared with men <25 years old, men of APA (>45 years) were 4.6 times more likely not to induce pregnancy until after 1 year of regular unprotected intercourse. When those men who took longer than 2 years to induce a pregnancy with their partners were examined, men of APA (>45 years) were 12.5 times more likely to be included.47” [18]
“These results were confirmed in retrospective data from 6188 randomly selected women, showing that paternal age over 40 years was a significant risk factor for infertility after 12 months, but only in women aged 35 years or older (adjusted OR 3.02 compared with men <40 years) (de La Rochebrochard and Thonneau, 2003).” [22]
Male fertility is based on the annual number of birth per father’s age. [24]
From [25]
From [26]
"Male age was not appreciably associated with fecundability after adjustment for female age, although the number of men over age 45 years was small (n=37)." [29]
Pregnancy
“For women who know they’re pregnant, about 10 to 20 in 100 pregnancies (10 to 20 percent) end in miscarriage.” [20]
In 2021, in women over 34 years 25.4% of deliveries end in c-section [1].
Women
Miscarriage
“Risk of miscarriage according to maternal age. The bars for each point reflect the 95% confidence intervals” [8].
Premature birth
“During 2018-2020 (average) in the United States, preterm birth rates were highest for women ages 40 and older (14.4%), followed by women under age 20 (10.4%), ages 30-39 (10.3%) and ages 20-29 (9.6%).” [9]
Men
Miscarriage
“Advanced paternal age was found to be associated with an increased risk of miscarriage. Pooled risk estimates for miscarriage for age categories 30–34, 35–39, 40–44 and ≥45 years of age were 1.04 (95% CI 0.90, 1.21), 1.15 (0.92, 1.43), 1.23 (1.06, 1.43) and 1.43 (1.13, 1.81) respectively (reference category 25–29 years).” [10]
“fathers between 40-44 years of age were 23% more likely to contribute to the incidence of spontaneous miscarriage before 20 weeks of gestation than their younger peers. Similarly, when the paternal age was over 45 years the risk for pregnancy loss before 20 weeks was increased by 43% and before 13 weeks by 74%.” [11]
Premature birth
“The risk of preterm birth increased with paternal age, almost entirely resulting from an association for very preterm birth. Compared with fathers age 20-24 years, ORs for very preterm birth were 1.3 (age 25-29), 1.4 (age 35-39), 1.7 (age 40-44), 1.6 (age 45-49), and 2.1 (age 50+) (test for trend: P = 0.01).” [12]
Infant health
“Birth defects affect 1 in every 33 babies born in the United States each year.” [21]
Most common: Down syndrome (Trisomy 21). FragileX syndrome. Klinefelter syndrome. Triple-X syndrome. Turner syndrome. Trisomy 18. Trisomy 13.
The effect of parental age on genetic defects might be stronger than reported, because existing literature is based on comparison of children across families that can differ in many other ways too [28].
Women
“The chance of having a child affected by Down syndrome increases from about 1 in 1,250 for a woman who conceives at age 25, to about 1 in 100 for a woman who conceives at age 40.” [8]
“The average age of women giving birth has increased over the last few decades from 24.6 years to 27.2 years. To go along with this, birth rates have risen in women age 30-34 and 35-39. For moms ages 35-39, the prevalence of birth defects ranges from 32-44 per 1000 births. When compared with moms aged 25-29, there is an extra 5 to 12 non-chromosomal birth defects for every 1000 births. In moms 40 years and older 24-50 per 1000 births are affected by these non-chromosomal abnormalities. This is an increase of about 6-11 birth defects for every 1000 births.
Some specific abnormalities found to be associated with advanced maternal age include congenital heart defects, hypospadias (abnormal male urethra), craniosynostosis (abnormal skull growth), club foot, and diaphragmatic hernia. Women ages 35-39 will deliver 1 to 4 additional cases of congenital heart defects per 1000 births. In age 40 and over, that number jumps to 30.” [14]
Risk of making a baby with down syndrome [26]:
At age 20, 1 in 2000
At age 24, 1 in 1300
At age 25, 1 in 1200
At age 29, 1 in 950
At age 30, 1 in 900
At age 34, 1 in 450
At age 35, 1 in 350
At age 39, 1 in 150
At age 40, 1 in 100
At age 44, 1 in 40
At age 45, 1 in 30
At age 49, 1 in 10
Overall, the risk of any birth defects for female age [27]:
before 35: 0.9%
35-39: 4.75%
40-44: 15%
>=45: 26%
Men
“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.” [15]
“Only 6% to 10% of all trisomy 21 cases are due to errors in spermatogenesis (15). Oldereid et al. (8) summarized the studies in their meta-analysis of data from the Nordic countries (8). A small but statistically significant increase was noted by high paternal age (≥40 years) (pooled estimate 1.13; 95% confidence interval [CI], 1.05–1.23).” [16]
Based on [16]:
birth defect - slight increase
congenital heart defects - no association
Paternal age was investigated in the recent systematic review and meta-analysis of Oldereid et al. (8) who found a small but statistically significant increase in children's orofacial clefts for fathers older than 45 years (pooled estimate 1.14; 95% CI, 1.02–1.29).
Two studies, from the United States and Canada 28, 29, found a statistically significantly higher risk, up to 1.5 times, for gastroschisis in offspring when the father is a young man. This was confirmed in the meta-analysis by Oldereid et al. (8) (pooled estimate 0.88; 95% CI, 0.78–1.00) (≥35 years). Although the risk increased with younger fathers, it was much less pronounced than it was for young mothers.
Few studies were identified that addressed a possible association between hypospadias and paternal age, and no clear results were found.
In a systematic review and meta-analysis on paternal age and risk of cancer in offspring, higher paternal age was not associated with a risk of childhood cancer (8). Further, a Danish study (38) found no association between paternal age and cancer. A U.S. study (39) found that compared with children born to fathers aged 20–24 years, those born to fathers in older age groups had a 5% to 15% higher risk of childhood cancer; per 5-year increase in paternal age and after adjustment including maternal age, a statistically significant increase was noted (aOR 1.03; 95% CI, 1.02–1.05).
Any Childhood Cancer - increased risk for advanced paternal age
CNS Tumors - unclear
diabetes - Increasing parental age and especially increasing maternal age seem to be associated with a week but significantly increased risk of type 1 DM in childhood.
Asthma - Young parental age is probably associated with an increased risk of asthma in offspring.
Cerebral palsy - No studies of sufficient quality were found on the effect of paternal age on CP in children.
Neurodevelopment - A protective effect of increasing maternal age has been found for behavioral problems, but divergent results have been shown for paternal age.
Autism - Higher parental age seems to be associated with an increase in ASD but with no clear age cutoff.
Schizophrenia - The risk of schizophrenia seems to be increased in mothers younger than 20 years, but for advanced maternal age the results are conflicting. Advanced paternal age is associated with an increased risk of schizophrenia in the children, with various risk estimates depending on the paternal age category.
Bipolar disorders - There is no convincing evidence of an association between parental age and BPD.
Mental retardation - From the limited literature available, there is no clear association between parental age and mental retardation.
“Higher paternal age was associated with an increased risk of premature birth, low birth weight, and low Apgar score. After adjustment for maternal age, infants born to fathers aged 45 years or older had 14% higher odds of premature birth (odds ratio 1.14, 95% confidence interval 1.13 to 1.15), independent of gestational age, and 18% higher odds of seizures (1.18, 0.97 to 1.44) compared with infants of fathers aged 25 to 34 years. The odds of gestational diabetes was 34% higher (1.34, 1.29 to 1.38) in mothers with the oldest partners. 13.2% (95% confidence interval 12.5% to 13.9%) of premature births and 18.2% (17.5% to 18.9%) of gestational diabetes in births associated with older fathers were estimated to be attributable to advanced paternal age.” [17]
References
https://rmanetwork.com/blog/what-are-my-odds-of-getting-pregnant-at-any-age/
https://sofatinfertility.com/news/how-women-infertility-chart-changes-with-age/
https://theconversation.com/male-fertility-how-age-affects-mens-chances-of-having-children-156411
https://www.marchofdimes.org/peristats/data?reg=99&top=3&stop=61&lev=1&slev=4&obj=1
https://www.focusonreproduction.eu/article/News-in-Reproduction-Miscarriage-2
https://www.chop.edu/conditions-diseases/pregnancy-over-age-30
https://academic.oup.com/humrep/article/22/3/696/608685?login=false
Schoumaker, B. (2019). Male fertility around the world and over time: How different is it from female fertility?. Population and Development Review, 459-487.
https://www.britishfertilitysociety.org.uk/fei/at-what-age-does-fertility-begin-to-decrease/
Демикова, Н. С., Подольная, М. А., & Лапина, А. С. (2020). Возраст матери как фактор риска врожденных пороков развития. Российский вестник перинатологии и педиатрии, 65(2), 34-39.
https://link.springer.com/article/10.1007/s10654-021-00734-8
Wesselink, A. K., Rothman, K. J., Hatch, E. E., Mikkelsen, E. M., Sørensen, H. T., & Wise, L. A. (2017). Age and fecundability in a North American preconception cohort study. American journal of obstetrics and gynecology, 217(6), 667-e1.
https://academic.oup.com/humupd/article/11/3/261/759255?login=false
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