Risk of Miscarriage and Older Fathers Old News Worn out Pasta Machine Analogy

Thursday, April 24, 2008


The biological clock may no longer be ticking on just the woman's side of the bed.

If current research is correct, a man's baby-making alarm may start to ring not too long after a woman's chimes its final warning toll -- around age 40.

"I don't want there to be a panic, but I think it's safe to say that the father's age should be one of many factors couples should put into the equation when planning a family," says Karine Kleinhaus, MD, PhD, a researcher at Columbia University who recently spearheaded a study on paternal age and miscarriage.

Over the past decade -- and particularly during the last five years -- studies have been mounting indicating that the age of the father may affect the health of the offspring in more ways than one.

Risk of Birth Defects
Associations have been made between paternal age and the risk of birth defects and developmental disorders such as autism and Apert's syndrome, as well as mental illnesses like schizophrenia. Moreover, studies conducted by Kleinhaus and colleagues at Columbia University looked at some 90,000 births and concluded the older a man is when he conceives a child, the more likely his partner is to miscarry -- even when she is young, healthy, and has no other risk factors.

Many believe this is just the beginning of what there is to learn.

"What we know now may be just the tip of the iceberg, particularly regarding birth issues we don't fully understand. We are just beginning to look at the role of a father's age. And as time goes by it's likely we are going to learn a lot more," says Jeremy Silverman, PhD, a professor of psychiatry at Mt. Sinai Medical Center in New York City, and the researcher of a study that associated paternal age with risks of autism.

Aging Dads: What Goes Wrong
Like every system in the body, experts say the male reproductive organs have not been spared the ravages of time.

"First there seems to be some clear changes that happen on a purely chemical level as a man ages. He has lower testosterone levels, lower DHEA, lower estrogen, plus higher levels of FSH and LH, which signal pretty much the same thing in men as in women -- reproductive failure," says Hackensack University embryologist Dave McCulloh, PhD, director of laboratory services at University Reproductive Associates in Hasbrouck Heights, N.J.

In a French study of nearly 2,000 men published in 2005 in the journal Fertility and Sterility, doctors concluded that even in couples undergoing IVF an aging father could figure into the pattern of pregnancy failure, more than previously thought.

But it's not just the idea of making fewer babies that is of concern. The new research is also tampering with conventional fertility wisdom, which has long asserted that because new sperm is made daily, male fertility remains untouchable.

And while the notion of unending sperm production hasn't changed, some researchers now believe that as a man ages, the task of churning out that daily supply is a little like trying to make a fresh batch of macaroni in a worn-out pasta machine.

In short, while the ingredients may be fresh, the mechanism that puts it all together gets slower and works less efficiently with age. And that means far fewer perfect macaroni -- and sperm -- to show for it.

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Public release date: 3-Aug-2006
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Contact: Stephanie Berger
sb2247@columbia.edu
212-305-4372
Columbia University's Mailman School of Public Health

Miscarriage significantly associated with increasing paternal age
In a study conducted at Columbia University's Mailman School of Public Health and the New York Psychiatric Institute researchers found that increasing paternal age is significantly associated with increased rates of spontaneous abortion, a pregnancy loss occurring before twenty weeks of gestation. Results indicate that as the male partner ages there is a steady increase in rate of miscarriage. Women with partners aged 35 or older had nearly three times as many miscarriages as compared with women conceiving with men younger than 25 years of age. This finding is independent of the woman's age and not explained by other factors such as diabetes, smoking, or previous spontaneous abortions, and adds to the growing realization of the importance of paternal characteristics for successful reproductive outcome.

"There has been a tremendous amount of research on women, and how their characteristics affect pregnancy outcomes. Of course, women's importance and centrality to pregnancy cannot be overstated. However, scientists seem to have forgotten that men are equal partners in reproduction, and their influence should be studied to the same degree. Our group has focused on men's influence on the health of their offspring, and we have made some fascinating discoveries," said Karine Kleinhaus, MD, MPH currently in Columbia's Department of Psychiatry and first author of the study. "This study shows how a man's age affects the likelihood of miscarriage."

Earlier research by the Columbia scientists showed that older men's wives suffer from preeclampsia, while the offspring of older men are more likely to get schizophrenia. "This is not as surprising as it may sound at first, as it was already shown by other researchers that older men have more abnormalities in their sperm, and that their children are more susceptible to certain birth defects," observes Dr. Klienhaus. In fact, the American Society for Reproductive Medicine has set an upper age limit of 40 years old for semen donors because of the increased risk of genetic abnormalities in the offspring of older fathers.

The international team of scientists involved in the study used a large historical data set containing information on many characteristics of mothers and fathers that might contribute to spontaneous abortion. The researchers analyzed data from the ante-natal or post-partum interviews of 13,865 women. This data was recorded in the Jerusalem Perinatal Study, a population-based cohort derived from 92,408 births in Jerusalem in 1964-1976.

Accordingly, the study, which focused exclusively on spontaneous abortion as the outcome, has as one of its strengths its large sample size and its extensive data, which permit consideration of important potential confounders not included together in other analyses. These include variables such as maternal diabetes, parity, history of prior spontaneous and induced abortions, and history of maternal smoking, and socioeconomic status.

The cohort used for this study is unique, with immigrants from many origins, including Iran, Iraq, Afghanistan and countries of North Africa, as well as Central and Eastern Europe. "This broad mix of backgrounds makes our study findings more generalizable," observed Susan Harlap, MD, professor of clinical epidemiology in the Mailman School of Public Health's Department of Epidemiology, and the leader of this research team. "While several previous studies suggested that father's age might contribute to miscarriage, they failed to clarify whether there is a cut-off age or a progressive trend over the whole range of ages."

The study findings generate strong support for the association of increasing paternal age with increasing rates of spontaneous abortion, and are corroborated by other published studies. "Advanced paternal age may result in only a slight increase in the chance of spontaneous abortion for a specific couple. Nevertheless, as child bearing is increasingly delayed in Western societies, this study provides important information for people who are planning their families," said Dr. Kleinhaus. "The study also adds to a growing understanding of how men's age, health, and occupations can affect their partner's pregnancies and the offspring's future development."


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In addition to the Mailman School of Public Health and the New York Psychiatric Institute, the international team of scientists included researchers from Braun School of Public Health and Community Medicine and the Department of Hematology, Hebrew University-Hadassah, Jerusalem, Israel.

The Jerusalem Perinatal Cohort, is among those being followed by the life course studies program within the Mailman School's Department of Epidemiology. Department Chair Ezra Susser, MD, DrPH, has been building a program of life course research -- called the Imprints Center -- in which epidemiologists seek to uncover the causes of a broad range of disease and health outcomes, following individuals from an early point in life and examining their risks for disease. Life course studies are particularly well positioned to examine the interplay of genetic and environmental risk factors - the key to understanding many complex diseases.

The study findings are published in the August 1, 2006 issue of Obstetrics & Gynecology 2006;108:369-377 ?2006 by The American College of Obstetricians and Gynecologists.

About the Mailman School of Public Health
The only accredited school of public health in New York City, and among the first in the nation, Columbia University's Mailman School of Public Health provides instruction and research opportunities to more than 950 graduate students in pursuit of masters and doctoral degrees. Its students and more than 270 multi-disciplinary faculty engage in research and service in the city, nation, and around the world, concentrating on biostatistics, environmental health sciences, epidemiology, health policy and management, population and family health, and sociomedical sciences. http://www.mailman.hs.columbia.edu/

Founded in 1896, the New York State Psychiatric Institute (PI) continues to contribute importantly to knowledge about understanding and treating psychiatric disorder and is ranked among the best psychiatric research facilities in the world today. Noted for its research on depression and suicide, schizophrenia, anxiety and child psychiatric disorders, PI is also at the forefront of research dedicated to unraveling the brain's mysteries. Its scientists constitute the core of the Department of Psychiatry at Columbia University. In 2000, Dr. Eric Kandel was awarded the Nobel Prize in Physiology or Medicine for research in his labs at PI on the cellular basis of memory. http://www.nyspi.org/



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