Just weeks before her 50th birthday, pop-icon Janet Jackson announced that she is pregnant with her first child. Jackson is part of a trend towards women starting their families at an advanced age.
While Janet and her husband appear thrilled to be parents, rumors are swirling that many in the Jackson family are not. The ever-reliable “family source” claims that many relatives worry Janet is too old to be having a child and is putting her health and the health of the baby in jeopardy.
Putting aside the rumor mill, it’s not an uncommon fear, as there is a widespread popular belief that advanced maternal age can be dangerous to both mom and her fetus—with good reason. The risk for having a baby with down syndrome goes way up with maternal age and the mother’s risk for conditions like stroke, gestational diabetes, and pre-eclampsia.
One largely unexplored image is whether aging fathers contribute to the risk of birth defects. Janet’s husband and the baby’s father is billionaire businessman Wissam Al Mana—aged 41. Should he and other older dad’s be concerned? The science is less than settled and relies heavily on the controversial field of epigenetics.
If it’s ‘no’ from mom—go ask dad?
Births by women ages 50 to 54 rose by more than 165 percent from the year 2000 (255 births) to 2013 (677 births), according to the Centers for Disease Control and Prevention. The overall increase in fertility rates for women 35 and older during the last two decades is linked, in large degree, to IVF. The first child born through the fertility-enhanced method was in 1978 in England. From 2008 to 2012, the birth rate in England doubled for women 50 and older. In 2013, an average of 13 children were born every week to mothers 50 and older, most of whom used in vitro fertilization.
Maria del Carmen Bousada de Lara is the oldest verified mother; she was aged 66 years 358 days when she gave birth to twins; she was 130 days older than Adriana Iliescu, who gave birth in 2005 to a baby girl. In both cases the children were conceived through IVF with donor eggs. The oldest verified mother to conceive naturally (listed currently in the Guinness Records) is Dawn Brooke (UK), who conceived a son at the age of 59 years in 1997 while taking estrogen.
For years, scientists and physicians have focused exclusively on the age of mom, the primary reason being that for women, all their eggs are set before birth. The eggs sit there until puberty, when menstruation begins. During the decades that the eggs are stagnant, scientists believe the egg’s chromosomes are susceptible to more and more genetic damage. Other’s posit that as a woman ages, there are fewer ‘good’ eggs to pick from for use in IVF.
Whatever the reason, the data certainly backs up the notion that older mothers are at risk of having babies with genetic based disorders. For example, a 2015 Dutch study that included over 5 million families found a strong link between maternal age and autism risk—a mother in her 40’s had a 15 percent higher chance of having an autistic child than a mother in her 20’s.
But this wasn’t really news. It’s been standard-operating-procedure for physicians to advise mothers over the age of 35 of the risks of advanced age pregnancy and to recommend testing the developing fetuses for genetic abnormalities for decades. What was more interesting was that dad’s over the age of 50 had a two-thirds higher chance of having a child with autism than those in their 20’s. Unlike women, men continuously make new sperm (and then discard them) that’s why for a long time no one was really studying older dads—until recently.
A number of recent studies have found correlations between the children of older dads and an increased risk for mental health issues like schizophrenia, autism and ADHD. Authors of one of these major studies theorized that, similar to women, over time mutations can build up in the cells that give rise to new sperm. A small study of Icelandic men did find a correlation between the age of a man and the accumulation of mutations in a his sperm.
This idea is highly controversial, partly because an increase in mutation rate does not directly mean an increase in schizophrenia or any other disease. Furthermore, many of these conditions have very weak genetic connections. Another argument proposed is that epigenetics is the mechanism that decreases sperm quality as a man ages. In short, epigenetics is a way in which cells turn off and on genes. Each cell in your body has a complete genome, but your neurons don’t need to know how to make antibodies. So epigenetic modifications allow cells to shut down the genes it does need and access the genes it does need more readily. There is a growing belief, not necessarily substantiated by a lot of hard evidence, that environmental factors (diet, stress, exposure to toxins) can also influence these modifications.
Some data have shown that many factors can influence methylation patterns (a popular epigenetic modification which leads to a gene being shut off or silenced) in sperm cells like obesity and alcoholism. A few small studies have even claimed that obesity can be inherited via these epigenetic marks on a man’s sperm. This evidence has led some to believe that as men age and accumulate more of these these epigenetic marks on their sperm, the cumulative effects lead to the increased risks for diseases seen in children of older dads.
However, there are a few problems here that scientists must address before we can start telling older dads their sperm might be tainted. The first is that a process called epigenetic reprogramming virtually wipes out all the epigenetic marks on a new embryo, making passing on these epigenetic marks directly very difficult, if not impossible. Some scientists believe that some marks aren’t removed or that cells ‘know how to re-add’ certain ones, however other studies find zero evidence this is happening in sperm. Epigenetic changes are also very transient and can be removed by any cell fairly easily. Furthermore, some scientists have suggested the placement of these epigenetic marks may be entirely or mostly driven by genetic sequences we don’t fully understand yet and not by environmental factors. Needless to say the science is out.
Reason to worry or statistical noise?
But back to the question at hand: Should Janet and her husband—as well as other older parents—be concerned about the health of their babies? While the prevailing scientific belief may suggest so, there are a number of studies that state otherwise. A study of over one million Swedish children found that kids of older mothers were more successful academically (and taller) than those from younger moms. And that 2015 Dutch study found an 18 percent higher autism risk for teen moms when compared to moms in their 20s—that rate is actually slightly higher than for mom’s in their 40s. That would seem to stand in contradiction to the idea of eggs sitting around picking up mutations and chromosomal damage as the years go on.
In fact, most children with down syndrome (a disease characterized by a chromosomal abnormality) are born to mom’s under the age of 35. While that’s mostly because the overwhelming majority of children are born to moms under the age of 35, the fact that there are a lot of women in their “reproductive prime” having children with genetic and chromosomal disorders would seem to point the story away from age being the driving factor.
Perhaps, this is why, despite the agreed upon risk of advanced maternal and paternal risk, no health care provider explicitly states women shouldn’t have kids after their 20s. Dr. Karen O’Brien, a high-risk pregnancy specialist at Beth Israel Deaconess Medical Center in Boston, MA says, “Couples shouldn’t be so concerned about the risks that they don’t complete their family, the vast majority of patients over 35 have very good outcomes, they just need a little closer attention paid to them.”
Today extra attention means amniocentesis and keeping mom and dad in good health—but the future may mean gene editing and CRISP too.
Nicholas Staropoli is the associate director of GLP and director of the Epigenetics Literacy Project. He has an M.A. in biology from DePaul University and a B.S. in biomedical sciences from Marist College. Follow him on twitter @NickfrmBoston.
(Author’s disclosure: I am the child of parents of a semi-advanced age—mom 32 and dad 38 at the time of my birth)