Scientists reveal dangers of older fathers

Scientists reveal dangers of older fathers
By Laura Donnelly, Health Correspondent
Last Updated: 10:18PM BST 31/05/2008
Children are almost twice as likely to die before adulthood if they have a father over 45, research has shown.
A mass study found that deaths of children fathered by over-45s occurred at almost twice the rate of those fathered by men aged between 25 and 30.

Scientists believe that children of older fathers are more likely to suffer particular congenital defects as well as autism, schizophrenia and epilepsy. The study was the first of its kind of such magnitude in the West, and researchers believe the findings are linked to the declining quality of sperm as men age.

A total of 100,000 children born between 1980 and 1996 were examined, of whom 830 have so far died before they reached 18, the majority when they were less than a year old.

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The deaths of many of the children of the older fathers were related to congenital defects such as problems of the heart and spine, which increase the risk of infant mortality. But there were also higher rates of accidental death, which the researchers believe might be explained by the increased likelihood of suffering from autism, epilepsy or schizophrenia.

Most research into older parents has, until now, focused on the risks passed on by older mothers. But the new study, published in the European Journal of Epidemiology, was adjusted to take account of maternal age and socio-economic differences.

The research also found higher death rates among children of the youngest fathers, especially those below the age of 19. However, the study said these differences were explained by the risks of teenage motherhood and poorer diet and lifestyle.

Previous research using the same data found that older men were four times as likely to father a child with Down's syndrome, while other studies have found that the genetic quality of sperm deteriorates as men age.

More than 75,000 babies in Britain are born to fathers aged 40 and over each year, or more than one in 10 of all births. This includes more than 6,000 born to fathers aged 50 or over. The average age of fathering a child in this country is 32.

Dr Allan Pacey, senior lecturer in andrology – the medical specialty dealing with male reproduction – at the University of Sheffield, said: "A lot of people know that there are risks for the child that come from having an older mother, but children of older fathers also carry an increased risk. These sorts of results provide another good reason to have children early, when possible."

Dr Pacey, who is secretary of the British Fertility Society, said scientists were unsure exactly what impact the ageing process had on the quality of sperm, making it impossible to detect defects before conception.

Dr Jin Liang Zhu, from the Danish Epidemiology Science Centre, which carried out the research, said: "The risks of older fatherhood can be very profound, and it is not something that people are always aware of."

The mother's age still has the bigger impact on child health, however. About one in 900 babies born to women under 30 have Down's syndrome – a figure which reaches one in 100 by the age of 40. The number of over-40s giving birth in Britain each year has doubled in the past decade to 16,000. The risk of miscarriage rises sharply with age.

Spontaneous Mutations = in Schizophrenia are they due to Older Paternal Age

Science News Share Blog Mutations Responsible For 10 Percent Of Schizophrenia Pinpointed
ScienceDaily (May 30, 2008) — People with schizophrenia from families with no history of the illness were found to harbor eight times more spontaneous mutations -- most in pathways affecting brain development -- than healthy controls. By contrast, no spontaneous mutations were found in people with schizophrenia who had family histories of the illness. The findings strongly suggest that rare, spontaneous mutations likely contribute to vulnerability in cases of schizophrenia from previously unaffected families.



Scans of the genome of patients with schizophrenia have revealed rare spontaneous copy number mutations that account for at least 10 percent of the non-familial cases of the disease. Researchers describe specific genetic mutations present in individuals who have schizophrenia, but not present in their biological parents who do not have the disease.

This new data will help researchers account for the persistence of schizophrenia in the population despite low birth rates among people with the disease.

Researchers at Columbia University Medical Center scanned the genome of 1,077 people which included 152 individuals with schizophrenia, 159 individuals without schizophrenia, and both of their biological parents for copy number mutations. They found mutations, either a gain or loss of genes, in 15 individuals diagnosed with schizophrenia that were not present in the chromosomes of either biological unaffected parent. Only two of such mutations were found in those without schizophrenia. Study subjects were from the European-origin Afrikaner population in South Africa, a genetically homogenous population that is ideal for genetic evaluation.

"We now know the cause of around 10 percent of the cases of sporadic schizophrenia," said Maria Karayiorgou, M.D., professor of psychiatry, Columbia University Medical Center, the senior author on the study. "Schizophrenia is not as much of a 'big black box' as it used to be. The identification of these genes lets us know what brain development pathways are involved in disease onset, so that in the future we can look at better ways of treating this devastating disease."

Schizophrenia affects approximately 1 percent of the population worldwide. About 40 percent of the disease is thought to be inherited, with the other 60 percent sporadically showing up in people whose family history does not include the disease.

One of the new or de novo mutations researchers found in more than one affected individual in this study was a deletion of a region of chromosome 22. Dr. Karayiorgou had previously provided evidence that loss of genes in this region, 22q11.2, was responsible for introducing "new" or sporadic cases of schizophrenia in the population. This confirms 22q11.2 as the only known recurrent such mutation linked to schizophrenia.

"We have already demonstrated 22q11.2 to be involved in sporadic schizophrenia and we have made considerable progress in understanding the underlying biological mechanisms," said Dr. Gogos. "Now, we have a new set of mutations that we can investigate. The more information we have about the biological basis for this disease, the more information we can provide to those who suffer from it and their families."

"Such abnormal deletions or duplications of genetic material are increasingly being implicated in schizophrenia and autism," explains National Institute of Mental Health Director Thomas R. Insel, M.D. "Now we have a dramatic demonstration that genetic vulnerabilities for these illnesses may stem from both hereditary and non-hereditary processes. This line of research holds promise for improved treatments -- and perhaps someday even prevention -- of developmental brain disorders."

Karayiorgou and co-senior author Joseph A. Gogos, M.D., Ph.D., associate professor of physiology and neuroscience at Columbia University Medical Center, agree that the goal is for psychiatrists to be able to inform patients that they have a mutation that is causing their disease and ultimately to be able to tailor treatments to individual patients based on their specific mutation. This tailored treatment is a ways off, according to Dr. Karayiorgou, but she says patients and their families are relieved to know that there is a biological cause of their illness.

The researchers plan to extend their screen for additional de novo mutations by using increased resolution scans to study additional families. They also plan to scrutinize further genes affected by the identified mutations through human genetics and animal model approaches.

This study was supported by the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH) and the Lieber Center for Schizophrenia Research at Columbia University Medical Center.


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Journal reference:

Xu B, Roos JL, Levy S, van Rensburg EJ, Gogos JA, Karayiorgou M.. Strong association of de novo copy number mutations with sporadic schizophrenia.. Nature Genetics, May 30, 2008
Adapted from materials provided by Columbia University Medical Center.
Need to cite this story in your essay, paper, or report? Use one of the following formats:
APA

MLA Columbia University Medical Center (2008, May 30). Gene Mutations Responsible For 10 Percent Of Schizophrenia Pinpointed. ScienceDaily. Retrieved May 30, 2008, from http://www.sciencedaily.com­ /releases/2008/05/080530132220.htmenlarge

A. Genetic mutations that result in fewer than two (middle offspring) or more than two (right offspring) genomic copies of a chromosomal region, are present in individuals who have schizophrenia, but not present in their biological parents who do not have the disease. For comparison, a family with an unaffected offspring is indicated at the left. B. A schematic representation of a spontaneous copy number mutation found in one individual with schizophrenia. This mutation results in loss of genes, including a gene affecting neurodevelopment (EPHB1). (Credit: P. Alexander Arguello, Copyright Columbia University Medical Center, May 2008)
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We propose that de novo genetic alterations in the paternal germline cause an independent and common variant of schizophrenia and that abnormal methy

Novartis Found Symp. 2008;289:196-203; discussion 203-7, 238-40.
Growth and schizophrenia: aetiology, epidemiology and epigenetics.
Malaspina D, Perrin M, Kleinhaus KR, Opler M, Harlap S.
Department of Psychiatry, New York University School ofMedicine, New York, NY 10016, USA.
There is a strong genetic component for schizophrenia risk, but it is unclear how the illness is maintained in the population given the significantly reduced fertility of those with the disorder. One possibility is that new mutations occur in schizophrenia vulnerability genes. If so, then those with schizophrenia may have older fathers, since advancing paternal age is the major source of new mutations in humans. We found that paternal age at conception is a robust risk factor for schizophrenia, explaining perhaps a quarter of all cases. The predisposing genetic events appear to occur stochastically in proportion to advancing paternal age, and the possible mechanisms include de novo point mutations or defective epigenetic regulation of paternal genes. The risk might also be related to paternal toxic exposures, nutritional deficiencies, suboptimal DNA repair enzymes or other factors that influence the fidelity of genetic information in the constantly replicating male germ line. We propose that de novo genetic alterations in the paternal germline cause an independent and common variant of schizophrenia and that abnormal methylation of paternally imprinted genes could be the mechanism. These findings suggest exciting new directions for research into the aetiology of schizophrenia.
PMID: 18497104 [PubMed - in process]

Disease-causing genetic mutations in sperm increase with men's age

Disease-causing genetic mutations in sperm increase with men's age



There's a lot said about a woman's ticking biological clock, but male biology doesn't age as gracefully as men might like to think. By analyzing sperm from men of various ages, scientists from the McKusick-Nathans Institute for Genetic Medicine at Johns Hopkins have discovered that older men's sperm is more likely to contain disease-causing genetic mutations that also seem to increase a sperm's chances of fertilizing an egg. The findings, which appear in the advance online section of the American Journal of Human Genetics, emerged during efforts to explain why a rare genetic disease is more common in children born to older fathers. The disease, Apert syndrome, leads to webbed fingers and early fusion of the skull bones, which must be surgically corrected. The researchers found that mutation rates in sperm increased as men aged, but not enough to fully account for the increased incidence of Apert syndrome in children born to older fathers, leading to the suspicion that the disease-causing mutations confer some benefit to the sperm, despite the mutations' effects on the resulting baby. 'Mutations causing this disease occur more frequently in the sperm of older men, but the mutation rate isn't quite as high as the incidence of Apert syndrome,' says Ethylin Jabs, M.D., director of the Center for Craniofacial Development and Disorders at Johns Hopkins. 'For some reason, a sperm with one of these mutations is more likely to be used to make a baby than normal sperm.' While Apert syndrome itself affects only 1 in 160,000 births, the scientists believe a combination of increased mutation rate and 'mutation advantage' might also be behind some of the 20 or so other genetic conditions linked to older fathers, including achrondroplasia dwarfism. These disorders begin to increase rapidly with the father's age at about the same time as maternal risks increase -- age 33 to 35. Most of the evidence for paternal age effects has come from determining how many children with these conditions are born to fathers of various ages. For the current study, the Hopkins scientists studied sperm from 148 men of various ages and looked for two genetic changes that are responsible for 99 percent of Apert syndrome cases. They found that men over 60 were, on average, three times as likely as men under 30 to have sperm with at least one of these changes. The mutations didn't appear in the men's blood. 'Men over age 52 are six times more likely than a 27-year-old to have a child with Apert syndrome, so the mutation rate alone can't account for the condition's link to paternal age,' says first author Rivka Glaser, a graduate student in the human genetics and molecular biology program at Johns Hopkins. 'Literally hundreds of millions of sperm are made in each batch, so in most cases there are still many normal sperm available,' adds Jabs, also a professor of pediatrics. 'Because the few mutated sperm are more likely to be used to make a baby than would be expected, the mutation must provide them some competitive advantage over their normal counterparts.' The two genetic mutations that cause most cases of Apert syndrome affect a protein called fibroblast growth-factor receptor-2 (FGFR2). The mutated versions of FGFR-2 don't bind to its usual targets with the same affinity, perhaps contributing to the sperm's likelihood of fertilizing an egg, the researchers suggest. The scientists looked for the two FGFR2 mutations in sperm from two groups of men who did not have children with Apert syndrome. These controls -- 57 from a Johns Hopkins study and 76 from an ongoing study at Lawrence Livermore National Laboratory -- were asked to provide sperm and blood samples and to complete a health survey. They also analyzed sperm from 15 fathers of children with Apert syndrome.

Significantly increased paternal age was found in the paternally derived cases of Kleinfelter

Hum Genet. 1992 Jul;89(5):524-30.Links
Reduced recombination and paternal age effect in Klinefelter syndrome.Lorda-Sanchez I, Binkert F, Maechler M, Robinson WP, Schinzel AA.
Institut für Medizinische Genetik, Universität, Zürich, Switzerland.

The parental origin of the additional sex chromosome was studied in 47 cases with an XXY sex chromosome constitution. In 23 cases (49%), the error occurred during the first paternal meiotic division. Maternal origin of the additional chromosome was found in the remaining 24 cases (51%). Centromeric homo- versus heterozygosity could be determined in 18 out of the 24 maternally derived cases. According to the centromeric status and recombination rate, the nondisjunction was attributable in 9 cases (50%) to an error at the first maternal meiotic division, in 7 cases (39%) to an error at the second maternal meiotic division and in 2 cases (11%) to a nullo-chiasmata nondisjunction at meiosis II or to postzygotic mitotic error. No recombination, and in particular none in the pericentromeric region, was found in any of the 9 cases due to nondisjunction at the first maternal meiotic division. Significantly increased paternal age was found in the paternally derived cases. Maternal age was significantly higher in the maternally derived cases due to a meiotic I error compared with those due to a meiotic II error. There were no significant clinical differences between patients with respect to the origin of the additional X chromosome.

PMID: 1353053 [PubMed - indexed for MEDLINE]

Is the prevalence of Klinefelter syndrome increasing?

1: Eur J Hum Genet. 2008 Feb;16(2):163-70. Epub 2007 Nov 14. Links
Is the prevalence of Klinefelter syndrome increasing?Morris JK, Alberman E, Scott C, Jacobs P.
Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Barts and the London, Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK. j.k.morris@qmul.ac.uk

The birth prevalence of sex chromosome trisomies (SCT), that is individuals with an XYY, XXY or XXX sex chromosome constitution, is traditionally based on six surveys of unselected newborns carried out in the 1960s and early 1970s. All three SCTs had a prevalence of 1 in 1000 same sex births. We re-examined these prevalences based on additional cytogenetic studies of newborn surveys, spontaneous abortions, perinatal deaths and prenatal diagnoses. The more recent newborn surveys suggest there has been an increase in the prevalence of XXYs, but not of the other two SCTs since the original newborn series. The prevalence of XXYs has risen from 1.09 to 1.72 per 1000 male births (P=0.023). We suggest that such an increase, in the absence of an increase in the prevalence of XXX, is unlikely to be due to increased maternal age. As XXY is the only chromosome abnormality known where a substantial proportion ( approximately 50%) arise as the result of non-disjunction at the first paternal meiotic division, we speculate that some factor may be interfering with pairing and/or recombination of the sex bivalent at the paternal MI division.

Is paternal age playing a role in the changing prevalence of Klinefelter syndrome?

Eur J Hum Genet. 2008 May 21. [Epub ahead of print]
Is paternal age playing a role in the changing prevalence of Klinefelter syndrome?Herlihy AS, Halliday J.
[1] 1Public Health Genetics, Murdoch Childrens Research Institute, Parkville, Victoria, Australia [2] 2Andrology Australia, Clayton, Victoria, Australia.

PMID: 18493264 [PubMed - as supplied by publisher]

Paternal age causes more CAG repeats and can lead to sporadic Huntington's

What causes dementia, Alzheimer’s, Parkinson’s, Huntington’s, autism, ADD, ADHD and other neurodegen

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Comments by J. C. Spencer

This article helps us understand what is causing Dementia, Alzheimer’s, Parkinson’s, Huntington’s, Autism, ADD, ADHD, and other neurodegenerative challenges which may be caused by a misfolded (mutated) toxic proteins.


Trehalose deals with toxicityAn article was released today by ScienceDaily on the story we reported recently about what scientists are now saying causes neurodegenerative diseases. Connect the dots and they lead to sugars, specifically trehalose for helping correct the gene expression caused by the toxicity in the RNA. Bottom line: Get the toxin out.

Lowering the cost of healthcare starts with cutting off the supply line of toxins coming into the body. The second and third steps are to get the toxins out of the system and get good nutrients into the body.

How RNA Toxicity Contributes To Neurodegenerative Disease.

ScienceDaily (May 21, 2008) — Expanding on prior research . . .

. . .performed at the University of Pennsylvania, Penn biologists have determined that faulty RNA, the blueprint that creates mutated, toxic proteins, contributes to a family of neurodegenerative disorders in humans. Nancy Bonini, professor in the Department of Biology at Penn and an investigator of the Howard Hughes Medical Institute, and her team previously showed that the gene that codes for the ataxin-3 protein, responsible for the inherited neurodegenerative disorder Spinocerebellar ataxia type 3, or SCA3, can cause the disease in the model organism Drosophila. SCA3 is one of a class of human diseases known as polyglutamine repeat diseases, which includes Huntington's disease. Previous studies had suggested that the disease is caused largely by the toxic polyglutamine protein encoded by the gene.

The current study, which appears in the journal Nature, demonstrates that faulty RNA, the blueprint for the toxic polyglutamine protein, also assists in the onset and progression of disease in fruit fly models.

“The challenge for many researchers is coupling the power of a simple genetic model, in this case the fruit fly, to the enormous problem of human neurodegenerative disease,” Bonini said. “By recreating in the fly various human diseases, we have found that, while the mutated protein is a toxic entity, toxicity is also going on at the RNA level to contribute to the disease.”

To identify potential contributors to ataxin-3 pathogenesis, Bonini and her team performed a genetic screen with the fruit fly model of ataxin-3 to find genes that could change the toxicity. The study produced one new gene that dramatically enhanced neurodegeneration. Molecular analysis showed that the gene affected was muscleblind, a gene previously implicated as a modifier of toxicity in a different class of human disease due to a toxic RNA. These results suggested the possibility that RNA toxicity may also occur in the polyglutamine disease situation.

The findings indicated that an RNA containing a long CAG repeat, which encodes the polyglutamine stretch in the toxic polyglutamine protein, may contribute to neurodegeneration beyond being the blueprint for that protein. This raised the possibility that expression of the RNA alone may be damaging.

Long CAG repeat sequences can bind together to form hairpins, dangerous molecular shapes. The researchers therefore tested the role of the RNA by altering the CAG repeat sequence to be an interrupted CAACAG repeat that could no longer form a hairpin. Such an RNA strand, however, would still be a blueprint for an identical protein. The researchers found that this altered gene caused dramatically reduced neurodegeneration, indicating that altering the RNA structure mitigated toxicity.

To further implicate the RNA in the disease progression, the researchers then expressed just a toxic RNA alone, one that was unable to code for a protein at all. This also caused neuronal degeneration. These findings revealed a toxic role for the RNA in polyglutamine disease, highlighting common components between different types of human triplet repeat expansion diseases. Such diseases include not only the polyglutamine diseases but also diseases like myotonic dystrophy and fragile X.

The family of diseases called polyglutamine repeat disorders arise when the genetic code of a CAG repeat for the amino acid glutamine stutters like a broken record within the gene, becoming very long. This leads to an RNA — the blueprint for the protein — with a similar long run of CAG. During protein synthesis, the long run of CAG repeats are translated into a long uninterrupted run of glutamine residues, forming what is known as a polyglutamine tract. The expanded polyglutamine tract causes the errant protein to fold improperly, leading to a glut of misfolded protein collecting in cells of the nervous system, much like what occurs in Alzheimer's and Parkinson's diseases.

Polyglutamine disorders are genetically inherited ataxias, neurodegenerative disorders marked by a gradual decay of muscle coordination, typically appearing in adulthood. They are progressive diseases, with a correlation between the number of CAG repeats within the gene, the severity of disease and age at onset.

In addition to Bonini, researchers whose work contributed to this study are Ling-Bo Li, formerly in the Department of Biology at Penn and now with the Department of Biochemistry at the University of Utah, and Zhenming Yu and Xiuyin Teng of the Department of Biology at Penn and the Howard Hughes Medical Institute.

Funding for this study was provided by the National Institute of Neurological Disorders and Stroke.

Adapted from materials provided by University of Pennsylvania.

http://www.sciencedaily.com/releases/2008/05/080521105243.htm

Last Updated ( May 22, 2008 at 02:20 PM )

Mother Told She'd Be Arrested for Bringing Autistic Son to Church

FOXNEWS.COM HOME > U.S.

Mother Told She'd Be Arrested for Bringing Autistic Son to Church
Monday, May 19, 2008


BERTHA, Minn. — The mother of a 13-year-old autistic boy says she wanted to take him to Mass on Sunday despite a court order that bans him from her church.

Carol Race ended up attending a different church — after the Todd County, Minn., sheriff stopped her and said she'd be arrested if she brought Adam to the Church of St. Joseph in Bertha.

There is a restraining order barring Race's son from St. Joseph's. The Reverend Daniel Walz wrote in court documents that Adam's behavior was disruptive and dangerous. Adam is more than 6 feet tall and over 225 pounds.

The pastor wrote that Adam spits, urinates and once struck a child during Mass.

Race says Adam doesn't spit, and that the urination is incontinence. She admits he once struck a child.

Race has already violated the restraining order once, and is scheduled to appear in court for that on Monday.

James F. Crow on the Paternal Age Effect in 1994

I don't find this nonlinear effect at all surprising. Everything gets worse with age, so I fully expect fidelity of replication, efficiency of editing, and error correction to deteriorate with age. For a man of age 20, the male mutation rate is about 8 times the female rate. With a linear increase, in a man at age 30, the ratio is 430/24 = 18, at age 45 it is 770/24 = 32. With nonlinearity, these ratios are much larger, some 30-fold at age 30 and as much as two orders of magnitude at age 40. Examples such as MEN2A, MEN2B, and Apert syndrome, in which a total of 92 new mutations were all paternal, are therefore not so surprising. Whatever selective forces reduced the mutation rate in our distant past, at a time when most reproduction must have been very early, were not effective for older males.

I conclude that for a number of diseases the mutation rate increases with age and at a rate much faster than linear. This suggests that the greatest mutational health hazard in the human population at present is fertile old males

Births to women over age 40 soaring, and so is birth rate (and so is autism)

http://www.lcsun-news.com/ci_9303163



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Births to women over age 40 soaring, and so is birth rate
By ANNE CONSTABLE The Santa Fe New Mexican
Article Launched: 05/18/2008 11:30:17 AM MDT


SANTA FE, N.M.—Barton Bond is looking forward to coaching his son's football team. His wife, Joyce, can't wait to sew Halloween costumes when their children are old enough to go trick-or-treating.
The Bonds sound like typical new parents, but they're not.

They've been married 32 years, but have no other children. Barton has retired from one job and now teaches part-time at Central New Mexico Community College. Joyce is just two and a half years away from retirement from her job as marketing manager for the city of Santa Fe.

Last July, she gave birth to triplets, Jayci Clare, Dallas Witt and Marie Patrice.

At a time when most people their age would be looking forward to being grandparents, they are feeding, changing and burping their merry trio.

At 53, Joyce is part of a new, growing demographic. Births to women over age 40 are soaring and so is the birth rate.

In obstetrical terms, a woman of 35 is considered to have reached "advanced maternal age." And a woman over 40, well, she might be scaling 13,000-foot peaks or swimming laps three times a week, but her eggs are senior citizens. Her biological clock has virtually stopped.

A woman's fertility starts to decline around age


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27. According to the American Fertility Association, the chance she will get pregnant is 20-to-30 percent per cycle until her 30s and by age 40 falls to 5 percent.
But many women are lengthening their childbearing years through assisted reproductive technologies such as fertility treatments, egg donation and in vitro fertilization, in which egg cells are fertilized by sperm outside the woman's womb and then implanted in her uterus.

In 1995 and 2006, for example, the number of babies born to women 40 to 44 grew from 67,250 to 105,476. And the number of babies born to women older than that increased from 2,727 to 6,958, according to the federal Centers for Disease Control's National Vital Statistics System.

The birth rate of the women 40 to 44 grew by 45 percent in that time, and the birth rate for the oldest group doubled.

More babies are born to women having their first child over age 40 as well. The number of these births increased from 20,096 in 2000 to 24,284 in 2006.

"There's a lot more you can do. The biologic clock has changed," said Jim Thompson, a fertility specialist with the Center for Reproductive Medicine in Albuquerque.

Women in their late 40s and even their early 50s can have babies using donor eggs or embryos so long as they have a healthy uterus, Thompson said.

Artificial insemination and in vitro fertilization become less efficient, however, because of the declining quality of a woman's eggs, he said. Women in their mid-40s have a 60 percent chance of getting pregnant with an egg donor, compared to 1 or 2 percent with their own eggs.

Pregnancy carries a higher risk among older women who are more likely to experience complications such as pregnancy-induced hypertension, high blood pressure, placental separation and low birth weight.

"That being said," Thompson said, "most women do fine in their mid- to late 40s, even their early 50s."

The Bonds' living room in their home is full of baby equipment. Jayci and Dallas are swaying back and forth in their swings. Marie is bobbing in a walker. Nobody is crying.

"We're running out of room," said Joyce as she surveyed the multiple pieces of baby equipment.

Her mother was 45 when Joyce was born. "I loved having an older mother. I felt that my brother and I (who is six years older than Joyce) kept Mom and Dad young," she said.

But Joyce and Barton, who is 55, "didn't suddenly sit down at the kitchen table and say, 'Let's have babies in our 50s.'"

Life happened. A new job, a move, illness in the family, Joyce's hormonal imbalance, Barton's bout with cancer—all intervened.

"There was always a life event when we got serious about having children," she said.

When they were finally ready, their ages were against them. Joyce was one year shy of the cutoff age for patients at the Center for Reproductive Medicine when three embryos were implanted in her uterus in January of 2007. If this didn't work, she figured, "it was not meant to be."

When she found out she was having triplets, she said, "I didn't know whether to laugh or cry."

Her pregnancy went well, but like many high-risk moms, she spent the last month before the birth in the hospital where blood flow in the umbilical artery of one of the babies was tested daily.

The babies were born by emergency caesarian section on July 25 at 29 weeks and three days. Each was a little over 2 pounds. All the children are thriving.

Joyce, who returned to work full time, gets the babies up in the morning and gives Marie a treatment for her lungs. By the time she returns home, the triplets are ready to go to sleep for the night. "I want to be in their vision in the morning and the evening when they go to bed," she said.

Barton, who teaches film two evenings a week in Albuquerque, cares for the babies during the day with the help of the family's Bolivian au pair, Teresa Villarroel. Volunteers from Many Mothers visit weekly to give Villarroel a break.

Joyce's hair was gray during her pregnancy, and in the hospital, she was sometimes mistaken for her children's grandmother. The news took many family members and friends aback. "What are you thinking?" they wondered.

But Joyce and Barton are relaxed about raising children into their "golden years."

"I wouldn't do it if I didn't think I could," said Joyce.

"We are going to be older when they're in their teens," she said, "But I'm just trying to stay young. I don't consider myself the typical grandmotherly type."

Barton is clearly over the moon.

"I'd rather hold a baby than anything. That's the best part of the whole package," he said. Cuddling Dallas, he talks to his son about the Cubs and the Kansas City Chiefs. "We lay there. That's the best."

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Parental age and risk of childhood cancers: a population-based cohort study from Sweden

1: Int J Epidemiol. 2006 Dec;35(6):1495-503. Epub 2006 Sep 28. Links

Comment in:
Int J Epidemiol. 2007 Jun;36(3):691-2.
Parental age and risk of childhood cancers: a population-based cohort study from Sweden.Yip BH, Pawitan Y, Czene K.
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, 171 77 Stockholm, Sweden.

BACKGROUND: Frequent germ line cells mutations were previously demonstrated to be associated with aging. This suggests a higher incidence of childhood cancer among children of older parents. A population-based cohort study of parental ages and other prenatal risk factors for five main childhood cancers was performed with the use of a linkage between several national-based registries. METHODS: In total, about 4.3 million children with their parents, born between 1961 and 2000, were included in the study. Multivariate Poisson regression was used to obtain the incidence rate ratios (IRR) and 95% confidence interval (CI). Children <5 years of age and children 5-14 years of age were analysed independently. RESULTS: There was no significant result for children 5-14 years of age. For children <5 years of age, maternal age were associated with elevated risk of retinoblastoma (oldest age group's IRR = 2.39, 95%CI = 1.17-4.85) and leukaemia (oldest age group's IRR = 1.44, 95%CI = 1.01-2.05). Paternal age was significantly associated with leukaemia (oldest age group's IRR = 1.31, 95%CI = 1.04-1.66). For central nervous system cancer, the effect of paternal age was found to be significant (oldest age group's IRR = 1.69, 95%CI = 1.21-2.35) when maternal age was included in the analysis. CONCLUSION: Our findings indicate that advanced parental age might be associated with an increased risk of early childhood cancers.

New findings help resolve a long-standing debate in immunology over what type of cells are behind the progression of type-1 diabetes:

NewsBlog:
Autoimmune debate resolved?Posted by Edyta Zielinska
[Entry posted at 8th May 2008 05:04 PM GMT]
Comment on this blog

New findings help resolve a long-standing debate in immunology over what type of cells are behind the progression of type-1 diabetes: attacker or protector cells.

Scientists found that autoimmune destruction is likely due to a defect in levels of a cytokine within insulin-producing islets that reduce the numbers of protector cells. The research was published in today's online issue of Immunity.

IL-2 is a cytokine that paradoxically affects both the immune cells that protect the insulin producing beta-cells, the T regulatory (Tregs) cells, and the ones that attack them, the T-effector (Teff) cells.

Some reports have shown that Treg numbers increased with diabetes onset, while other papers have shown a decrease in Treg numbers. After painstaking quantitative thin-section analysis in NOD mice, a model system for type 1 diabetes, researchers realized that numbers of Tregs were high in some areas and low in others. "You cannot find a defect in these cells [Tregs] anywhere in the body -- except inside the islets," where there was a marked decrease, said Qizhi Tang from University of California, San Francisco, one of the two first authors on the report.

Tregs depend on signals, like IL-2 produced by other immune cells, for their survival. However, researchers found abnormally low levels of IL-2 production in the pancreatic islets. When they injected early diabetic mice with low levels of IL-2, the disease progression was halted. "Here they're showing that the reduced IL-2 production is linked to survival of Tregs," said Roland Tisch, a professor of microbiology and immunology at the University of North Carolina at Chapel Hill, who was not involved in the study. Without a sufficient number of healthy Tregs supported by IL-2 in the pancreatic islets, the destruction of the islet cells continues.

"You could treat diabetic patients," with this approach, said Tang, but it would be "really critical to determine the right dosing." Given IL-2's dual role -- promoting Treg survival at low levels, but activating destructive Teff proliferation at high levels -- the cytokine could not be used in patients as a stand-alone treatment, and would have to include another drug that reduced the chances of activating Teff cells, said Tang.

It's the Sperm DNA that Collects Errors with Age and Exposure to Toxins

Dr Miriam
Todays health topic: The pros and cons of being an older dad
7/05/2008

It's 28 years since Les Dennis held his last baby (son Philip, by his first wife Lynne). And judging by his tired demeanour, looking after 13-day-old Eleanor Grace has been a bit of a jolt.
A month ago, the 53-year-old comedian said he felt the happiest and most contented he'd ever been. But snapped earlier this week at a north London cafe, with baby Eleanor and fiancee Claire Nicholson, he looked totally worn out.
Some would argue that few men of Les's age have the energy to deal with a new baby. But there are now more older dads than ever - the average age of dads in the UK has increased from 29 to 32 since 1980.
But before becoming an older dad, here are a few points to weigh up first...



Reduced fertility
It's not just women whose fertility falls with age. In the US, tests on 100 healthy men aged 22 to 80 found that by the time a man is 40, 60 per cent of his sperm is unhealthy or abnormal compared to 25 per cent of that of a 22-year-old.
Lifespan
Although we're living longer than ever, the later you become a dad, the less likely you are to still be around into your offspring's middle age.
Health consequences





Babies of older dads are at greater risk of:
Autism-a 2006 US study reported that men aged 40 and over have a two-and-a-half times greater risk of fathering an autistic child than those under 30.
Schizophrenia - one in six cases of schizophrenia may have been due to having a father aged over 30, according to research published in the BMJ, and involving more than 700,000 people.
Alzheimer's - in a study involving more than 200 people with Alzheimer's, researchers at Munich University found that children born to older dads had a slightly higher risk of developing the condition.
The theory is that as we age, damage builds up in our DNA and this is passed on to a child. So the older the dad, the more time there has been for DNA damage to accumulate.
The upside
But it's not all doom and gloom. Research has also established that older dads tend to be more nurturing, affectionate and gentle.
One theory is that the calm approach of older dads is thought to be due to a drop in their testosterone levels And studies show that older dads are three times more likely to share in nappy changing, feeding, bath times, story reading and bedtimes.
Sure enough, Les showed his caring side when he interrupted his brunch with Claire to walk around the restaurant with Eleanor.
This is also good news for little Eleanor because many respected studies have shown that the children of involved dads do well in life - they have more confidence, higher self-esteem, greater sense of security and are better able to cope with stress.

Paternal age is independently and positively associated with the probability of low birthweight

Am J Public Health. 2006 May; 96(5): 862–866.
doi: 10.2105/AJPH.2005.066324. PMCID: PMC1470584

Copyright © American Journal of Public Health 2006
Paternal Age as a Risk Factor for Low Birthweight
Nancy E. Reichman, PhD and Julien O. Teitler, PhD
Nancy E. Reichman is with the Department of Pediatrics, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick. Julien O. Teitler is with the School of Social Work, Columbia University, New York, NY.
Requests for reprints should be sent to Nancy E. Reichman, PhD, Department of Pediatrics, Robert Wood Johnson Medical School, 97 Paterson St, Room 435, New Brunswick, NJ 08903 (e-mail: nancy.reichman@umdnj.edu).
Accepted May 17, 2005.
This article has been cited by other articles in PMC.
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Abstract
METHODS
RESULTS
DISCUSSION
References AbstractObjectives. We examined associations between paternal age and low birth-weight in the US urban population.
Methods. Using a population-based sample of 4621 births, we used multiple logistic regression analysis to estimate associations between paternal age and low birthweight, controlling for maternal age, other demographic factors, and the child’s gender.

Results. When the child’s gender and the mother’s race/ethnicity, birthplace, parity, marital status, and health insurance type were controlled, teenaged fathers were 20% less likely and fathers older than 34 years were 90% more likely than fathers aged 20 to 34 years to have low-birthweight babies. The associations were significant when maternal age was also controlled. No racial/ethnic differences in associations between paternal age and low birthweight were found.

Conclusions. We identified paternal age as an independent risk factor for low birthweight in the US urban population, suggesting that more attention needs to be paid to paternal influences on birth outcomes and to the interactive effects of urban environments and individual risk factors on health.

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References Low birthweight is a leading cause of infant mortality in the United States and can lead to debilitating and costly long-term health problems for infants who survive. Low birthweight is associated with cerebral palsy, deafness, blindness, epilepsy, chronic lung disease, learning disabilities, and attention deficit disorder.1,2 The annual cost of low birthweight in 1988 was estimated at $5.5 to $6 billion3; an updated estimate probably would be much higher.
Generally, teenaged mothers and older mothers are at higher risk of delivering low-birthweight babies than mothers aged 20 to 34 years.4 However, for Black or disadvantaged mothers, the risk of low birthweight has been found to increase with age even at the low end of the age distribution. This phenomenon has been attributed to “weathering”—a premature deterioration of health among individuals who are exposed to harsh living conditions.5,6

Paternal age has received less attention than maternal age in studies of low birth-weight, even though advanced paternal age has been linked to sperm abnormalities and gene mutations,7–9 preeclampsia,10 miscarriage,11 and some birth defects.12–15 One recent study found a positive association between paternal age and preterm birth in Denmark.16 The few previous studies of the association between paternal age and birth-weight in the United States or Canada found no evidence of a detrimental effect of increased paternal age.17–20 However, those studies focused on national, state, or low-risk populations. None focused on urban or disadvantaged populations at high risk of weathering.21 Additionally, they relied on birth certificate data, which in the United States have high rates of missing data on paternal age.4

This is the first study to investigate the association between paternal age and low birth-weight in an urban population. Using a national sample of urban births between 1998 and 2000, we compared associations between paternal age and low birthweight with associations between maternal age and low birthweight. We also explored racial/ethnic differences in the associations between low birthweight and parents’ ages.

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Abstract
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RESULTS
DISCUSSION
References METHODS
Sample
As part of a national longitudinal birth cohort study, births were randomly selected from each of 75 hospitals in 20 US cities with populations greater than 200 000. The field periods for the different hospitals were staggered between 1998 and 2000. Births to unmarried women were oversampled. While still in the hospital after giving birth, mothers were approached by a professional survey interviewer and screened for eligibility. If eligible, they were asked to participate in a national survey about the conditions and capabilities of new parents, their relationships, and their children’s well-being. A mother was eligible for the study if both she and the baby’s father were at least 18 years old or, if they were minors, the hospital allowed recruitment of minors into the study; if she was able to complete the interview in either English or Spanish; if the father of the newborn was living; and if they were not planning to place the child for adoption. The fathers were also asked to participate in an interview. Informed consent was obtained. A total of 4898 mothers (86% of those eligible) were interviewed between the spring of 1998 and the fall of 2000; 78% of the fathers were interviewed.22
Of the 4898 mothers who agreed to participate, 4621 were included in the analysis; 95 were excluded because the birth was a multiple birth, 27 were excluded because of missing birthweight, 74 were excluded because of missing maternal or paternal age, and 81 were excluded because of missing data on other analysis variables.



Characteristics
Maternal age, obtained from the mother’s report, was categorized as younger than 20 years, 20 to 34 years (the reference group), or 35 years and older to capture the nonlinear association between age and low birth-weight described earlier. Paternal age was obtained from the mother’s report and categorized in the same way, because there was little existing work in this area to guide us (we assessed the sensitivity of the results to alternative age categorizations; see the “Results” section). Maternal reports of paternal age were validated against self-reports of fathers who completed interviews. The correlation of paternal ages from the 2 sources was 0.98.
Low birthweight was defined as less than 2500 g. Birthweights were obtained from mothers’ reports and converted from pounds and ounces to grams. These were validated against birthweights recorded by hospital staff for a subset of 2305 births for which medical records were reviewed. The correlation of birthweights from the 2 sources was 0.98. The rate of low birthweight in this sample from 20 large US cities (10.1%) is slightly higher than the rate found for the 100 largest US cities and their suburbs in 2000 (8.9%).23

Maternal demographic characteristics, health insurance status, and the child’s gender were obtained from maternal reports. Maternal race/ethnicity was categorized as non-Hispanic White, non-Hispanic Black, Hispanic, or other. For maternal birthplace, we distinguished between US-born and foreign-born mothers. For parity, we distinguished between first births and births to women who had previously given birth to other children. Marital status referred to whether the mother was married to the baby’s father at the time of the birth. Mother’s health insurance status was used instead of education as a control for socioeconomic status because of the high correlation of education and very young age. Health insurance status was categorized as private, Medicaid (in California, Medi-Cal), or other (other government, charity, uninsured, or self-pay).



Analysis
We used multiple logistic regression to estimate the associations of both maternal and paternal age with low birthweight. Stata/SE version 8 software (StataCorp LP, College Station, Tex) was used to conduct all statistical analyses. We calculated odds ratios (ORs) and 95% confidence intervals (CIs; 2-tailed) for 3 models. The first model examined the association between mother’s age and low birth-weight, with adjustment for maternal demographic characteristics and the child’s gender. The second model examined the association between father’s age and low birthweight, with adjustment for maternal demographic characteristics (other than age) and the child’s gender. The last model included maternal and paternal age in addition to the other maternal demographic variables and the child’s gender. Model 3 therefore indicated the association between father’s age and low birth-weight, with mother’s age and other covariates controlled. Because associations between maternal age and low birthweight differ by race, we also calculated odds ratios and confidence intervals separately for non-Hispanic Whites and non-Hispanic Blacks, as well as for Hispanic mothers, for whom less is known about age patterns in low birthweight.

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DISCUSSION
References RESULTSThe distributions of maternal and paternal ages are shown in Table 1 . Eighteen percent of the mothers and 8% of the fathers were aged younger than 20 years at the time of their child’s birth, 73% of the mothers and fathers were 20 to 34 years old, and 9% of the mothers and 19% of the fathers were aged 35 years or older. Almost three quarters (73%) of the fathers were in the same age group as their baby’s mother. The age distributions of non-Hispanic Whites, non-Hispanic Blacks, and Hispanics were very similar to those of the full sample (figures for mothers not shown).

TABLE 1—
Distribution (No. [%]) of Maternal Characteristics and Child’s Gender, by Paternal Age Group: Sample of Births in 20 US Cities With Populations Greater Than 200 000, 1998–2000

The paternal age groups differed with regard to all covariates. Increased paternal age was significantly associated with mother’s age, race/ethnicity, parity, marital status, birthplace, and health insurance status (P<.001 in each case) and with the child’s gender (P<.05). The directions of the associations were largely as expected: The likelihood that the mother was US-born, married, had other children, and had private health insurance increased with paternal age. Partners of non-Hispanic White mothers were the most likely, and partners of Hispanic mothers were the least likely, to be older than 34 years.

After adjusting for maternal race/ethnicity, birthplace, parity, marital status, health insurance status, and the child’s gender, we found that mothers aged 35 years and older were more likely than mothers aged 20 to 34 years to have low-birthweight babies (Table 2 , model 1; OR = 2.1, 95% CI = 1.5, 2.8; P< .001). The association was reduced by half when we adjusted for paternal age (model 3; OR = 1.5, 95% CI = 1.0, 2.1; P< .05). In this sample, mothers aged younger than 20 years were neither significantly more nor significantly less likely than mothers aged 20 to 34 years to have low-birthweight babies.

TABLE 2—
Odds Ratios (With 95% Confidence Intervals [CIs]) From Multiple Logistic Regression Analysis of Associations Between Parents’ Age and Low Birthweight and Between Other Covariates and Low Birthweight: Sample of Births in 20 US Cities With Populations (more ...)

The associations between paternal age and low birthweight were as strong as those between maternal age and low birthweight. When we controlled only for the mother’s demographic characteristics (other than age) and the child’s gender, we found that teenaged fathers were less likely than fathers aged 20 to 34 years (the reference group) to have low-birthweight babies, although the association was not statistically significant (Table 2 , model 2). When we adjusted for the mother’s age in addition to the other covariates, we found that teenaged fathers were 70% as likely as fathers aged 20 to 34 years to have low-birthweight babies (Table 2 , model 3; OR = 0.7, 95% CI = 0.5, 1.0; P< .10). Fathers aged 35 years or older were 1.9 times as likely (P< .001) as fathers aged 20 to 34 years to have low-birthweight babies, after adjustment for maternal demographic characteristics (other than age) and the child’s gender (Table 2 , model 2). This association was only slightly reduced when we adjusted for maternal age (Table 2 , model 3).

The directions of the associations between the other covariates and low birthweight were similar to those described in previous research.2 Non-Hispanic Black mothers were more likely than non-Hispanic White mothers to deliver low-birthweight babies. Hispanic mothers were less likely than their non-Hispanic White counterparts to deliver low-birthweight babies. Being born in the United States and being poor (having Medic-aid coverage for the birth) were risk factors for low birthweight; having had previous children, being married, and having a male child decreased the likelihood of low birthweight.

The patterns were generally similar across racial/ethnic groups, although the small sample sizes (particularly for non-Hispanic Whites) made statistically significant results less likely (Table 3 ). When we controlled for maternal demographic characteristics, the child’s gender, and paternal age, we found that maternal age older than 34 years was a significant risk factor for low birthweight among non-Hispanic Blacks and Hispanics. For each racial/ethnic subgroup, the association between paternal age older than 34 years and low birthweight was virtually identical to that for the full sample (Table 2 , model 3; OR=1.7, 95% CI=1.3, 2.2). The associations between paternal age younger than 20 years and low birthweight, though not significant for any racial/ethnic subgroup, were negative in all models.

TABLE 3—
Odds Ratios (With 95% Confidence Intervals [CIs]) From Multiple Logistic Regression Analysis of Associations Between Parents’ Ages and Low Birthweight, by Race/Ethnicity of Mother: Sample of Births in 20 US Cities With Populations Greater Than (more ...)

Because there was little previous research to guide us in the specification of paternal age categories, we assessed the sensitivity of the results to a number of different age breakdowns. Alternative sets of models were estimated with (1) 3 categories for paternal age (<20, 20–34, ≥35 years), with a continuous characterization of maternal age (the models included terms for age in years and age squared); (2) 4 age categories for both parents (<18, 18–21, 22–34, ≥35 years); (3) 5 age categories for both parents (<20, 20–24, 25–29, 30–34, ≥35 years); and (4) the 5 age categories for fathers, with the continuous characterization of maternal age. Regardless of age breakdown or reference group, fathers aged 35 years or older were at greatest risk of having low-birthweight babies, after mother’s age and other demographic characteristics and the child’s gender were controlled. The odds ratios for low birthweight among fathers aged 35 years or older ranged from 1.3 to 1.8.

We calculated odds ratios and confidence intervals, separately, (1) for parents aged at least 18 years, (2) with adjustment for maternal education in addition to health insurance status and the other measures, and (3) for full-term (at least 37 weeks’ gestation) births, using the subsample of 2305 births for which medical records were available. The findings were consistent across specifications, indicating that the associations we found for teenaged parents apply to 18 and 19 year-olds but not necessarily to parents aged younger than 18 years, who were underrepresented in our sample; the associations overall were not driven by the measure of socioeconomic status we used; and paternal age is associated with low birthweight, even among births that are not preterm, suggesting that paternal age may reduce birthweight through retarded fetal growth. (Results from the supplementary analyses are available from the authors.)

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Abstract
METHODS
RESULTS
DISCUSSION
References DISCUSSIONUsing a population-based urban sample and adjusting for maternal age and other risk factors, we found that increased paternal age is positively associated with the probability of low birthweight. The paternal age associations are as large as those of maternal age and are substantial compared with those of other known risk factors for low birthweight, such as race, which have received substantial public health attention. It is important to note, however, that comparisons of regression estimates do not provide information on the relative risks attributable to different factors, which depend not only on effect sizes but also on the prevalence of the different risk factors in the population.

Geronimus found a paradoxical birth outcome advantage among Black teenaged mothers relative to older Black mothers.5,6 She suggested that this finding may reflect a more rapid deterioration in health with age among Black women than among White women, owing to Black women’s greater cumulative exposure to harsh living conditions. She coined the term “weathering” to describe this phenomenon. She also found that residents of persistently impoverished urban areas, particularly Black men, are at extremely high risk for morbidity at early ages and suggested that weathering, caused by cumulative exposure to hazards in residential and work environments or to chronic stress, is a potential explanation.21

Our finding that paternal age is independently and positively associated with the probability of low birthweight suggests a possible paternal weathering phenomenon. Several previous studies found detrimental effects of paternal age on infant outcomes, but they did not investigate associations between paternal age and birthweight.12–15 The few studies that specifically looked at paternal age and birthweight17–20 did not find adverse effects of increased age, but those studies used vital statistics data and focused on low-risk samples. In 2000, paternal age was not reported for 24% of births to all women aged younger than 25 years and for 39% of all births to unmarried women in the United States.4 Two of the studies17,19 focused on births to married women for this reason, and therefore underrepresented the urban poor. The other 2 studies were based on statewide samples of births in North Dakota18 and North Carolina,20 states in which 0% and 20% of the population, respectively, resides in cities of more than 100 000 people (authors’ computations from 2000 US census data24,25). It is therefore possible that these studies did not detect paternal age effects because they focused on low-risk populations. Ours is the first study to examine the association between paternal age and low birth-weight in an urban population. The absence of associations in low-risk populations and the presence of a positive association between paternal age and low birthweight in our urban sample are consistent with a paternal weathering effect.

A number of potential mechanisms could underlie the association between paternal age and low birthweight. Some involve direct biological effects of male aging, which may be hastened by exposure to harsh living conditions. Age-associated sperm abnormalities or chromosomal mutations may affect fetal growth. For example, increases with age in the number of paternal germ cell divisions have been hypothesized to increase the risk for spontaneous mutation, which may lead to genetically based fetal developmental disorders.26,27 Some mutations may confer a survival benefit to sperm within the cellular environment of the testes, as has been found in the case of the FGFR2 mutation associated with Apert syndrome.8

Paternal genes may affect placental growth, as has been found in mice.28 It is also possible that the sustained nature of spermatogenesis is associated with age-related vulnerability to compromised DNA-protective mechanisms29 or environmental exposures that impede fetal development. Whether such vulnerabilities occur at earlier ages among disadvantaged (potentially weathered) fathers is an empirical question that has not been explored. Paternal substance use over a prolonged period of time may adversely affect sperm. Previous studies have found associations between paternal smoking12,30 and alcohol use12,31 and adverse reproductive outcomes, although little is known about potential mechanisms that might underlie these associations.

Paternal aging may also affect low birth-weight indirectly, through its effects, biological or social, on the mother’s health. One study found an association between paternal age and preeclampsia,10 a known risk factor for low birthweight. Potential social mechanisms may involve the dynamics of the parents’ relationship. For example, domestic violence or lack of financial or emotional support could affect mothers’ physical, emotional, and reproductive health, possibly through increased stress, involvement in substance use, or lack of medical care. The extent to which paternal age or age differences between the parents is associated with such risk factors has been little explored.

As far as we know, this was the first study to document a positive association between paternal age and low birthweight in the United States. It should be replicated and the association further explored. Our study was subject to some limitations. The sample underrepresented parents aged younger than 18 years. Sample sizes precluded us from testing for interaction effects between more refined age and racial/ethnic categories. Health insurance status is an imperfect proxy for socioeconomic status. Finally, although we have established associations, we cannot investigate the underlying causal mechanisms or rule out the possibility that the associations are confounded by unmeasured factors. The absence of measures of parents’ cumulative exposure to harsh living conditions precluded us from directly testing the paternal weathering hypothesis.

Our finding that paternal age is an independent risk factor for low birthweight in an urban population suggests that more attention needs to be paid to paternal influences on birth outcomes and, more generally, to the interactive effects of urban environments and individual risk factors on health.

Acknowledgments
This research was funded by the National Institute of Child Health and Human Development (grant R01HD35301).

The authors are grateful to Jennifer Borkowski, who implemented the statistical analyses, and to Steven Schinke for comments on an earlier version of the article.


NotesPeer Reviewed
Contributors
Both authors contributed to the design of the study, the analysis and interpretation of the data, and the writing and revision of the article.
Human Participant Protection
This study received institutional review board approval from Robert Wood Johnson Medical School and Columbia University.
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References References1.Hack M, Klein NK, Taylor HG. Long-term developmental outcomes of low birthweight infants. Future Child. 1995;5:176–96. [PubMed].
2.Reichman N. Low birthweight and school readiness. Future Child. 2005;15:91–116. [PubMed].
3.Lewit EM, Baker LS, Corman H, Shiono PH. The direct costs of low birthweight. Future Child. 1995;5: 35–56. [PubMed].
4.Martin J, Hamilton B, Ventura S, Menacker F, Park M. Births: final data for 2000. Natl Vital Stat Rep. 2002;50:(5):1–101.
5.Geronimus AT. The weathering hypothesis and the health of African-American women and infants: evidence and speculations. Ethn Dis. 1992;2:207–221. [PubMed].
6.Geronimus AT. Black/white differences in the relationship of maternal age to birthweight: a population-based test of the weathering hypothesis. Soc Sci Med. 1996;42:589–597. [PubMed].
7.Bujan L, Mieusset R, Mondinat C, Mansat A, Pontonnier F. Sperm morphology in fertile men and its age related variation. Andrologia. 1988;20:121–128. [PubMed].
8.Goriely A, McVean GA, Rojmyr M, Ingemarsson B, Wilkie AO. Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. Science. 2003;301:643–646. [PubMed].
9.Glaser RL, Broman KW, Schulman RL, Eskenazi B, Wyrobek AJ, Jabs EW. The paternal-age effect in Apert syndrome is due, in part, to the increased frequency of mutations in sperm. Am J Hum Genet. 2003;73: 939–947. [PubMed].
10.Harlap S, Paltiel O, Deutsch L, et al. Paternal age and preeclampsia. Epidemiology. 2002;13:660–667. [PubMed].
11.de la Rochebrochard E, Thonneau P. Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study. Hum Reprod. 2002;17:1649–1656. [PubMed].
12.Savitz DA, Schwingl P, Keels MA. Influence of paternal age, smoking, and alcohol consumption on congenital anomalies. Teratology. 1991;44:429–440. [PubMed].
13.Friedman JM. Genetic disease in the offspring of older fathers. Obstet Gynecol. 1981;57:745–749. [PubMed].
14.Olshan AF, Schnitzer PG, Baird PA. Paternal age and the risk of congenital heart defects. Teratology. 1994;50:80–84. [PubMed].
15.Lian Z-H, Zack MM, Erickson JD. Paternal age and the occurrence of birth defects. Am J Hum Genet. 1986;39:648–660. [PubMed].
16.Zhu JL, Madsen KM, Vestergaard M, Basso O, Olsen J. Paternal age and preterm birth. Epidemiology. 2005;16:259–262. [PubMed].
17.Parker JD, Schoendorf KC. Influence of paternal characteristics on the risk of low birthweight. Am J Epidemiol. 1992;136:399–407. [PubMed].
18.Abel EL, Krueger M, Burd L. Effects of maternal and paternal age on Caucasian and Native American preterm births and birthweights. Am J Perinatol. 2002; 19:49–54. [PubMed].
19.Tough SC, Faber AJ, Svenson LW, Johnston DW. Is paternal age associated with an increased risk of low birthweight, preterm delivery, and multiple birth? Can J Public Health. 2003;94:88–92. [PubMed].
20.Olshan AF, Ananth CV, Savitz DA. Intrauterine growth retardation as an endpoint in mutation epidemiology: an evaluation based on paternal age. Mutat Res. 1995;344:89–94. [PubMed].
21.Geronimus AT. Economic inequality and social differentials in mortality. Federal Reserve Bank of New York Econ Policy Rev. 1999;5:(3):23–36.
22.Reichman NE, Teitler JO, Garfinkel I, McLanahan SS. Fragile Families: sample and design. Child Youth Serv Rev. 2001;23:303–326.
23.Duchon LM, Andrulis DP, Reid HM. Measuring progress in meeting Healthy People goals for low birth-weight and infant mortality among the 100 largest cities and their suburbs. J Urban Health. 2004;81: 323–339. [PubMed].
24.Cities and towns. Places over 100 000: 2000 to 2004. Available at: http://www.census.gov/popest/cities/SUB-EST2004.html. Accessed March 29, 2004.
25.GCT-T1. Population estimates [table]. Available at: http://factfinder.census.gov/servlet/DatasetMainPageServlet?_program=DEC&_submenuId=datasets_0&_lang=en. Accessed March 29, 2004.
26.Glaser RL, Jabs EW. Dear old dad. Sci Aging Knowledge Environ. 2004;3:re1. [PubMed].
27.Jung A, Schuppe HC, Schill WB. Are children of older fathers at risk for genetic disorders? Andrologia. 2003;35:191–199. [PubMed].
28.Frank D, Fortino W, Clark L, et al. Placental overgrowth in mice lacking the imprinted gene Ipl. Proc Natl Acad Sci U S A. 2002;99:7490–7495. [PubMed].
29.Walter CA, Walter RB, McCarrey JR. Germline genomes—a biological fountain of youth? Sci Aging Knowledge Environ. 2003;26:PE4. [PubMed].
30.Vine MV. Smoking and male reproduction: a review. Int J Androl. 1996;19:323–337. [PubMed].
31.Little RE, Sing CF. Association of father’s drinking and infant’s birthweight. N Engl J Med. 1986;314: 1644–1645. [PubMed].

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It is also recognized that paternal age is increased among affected children."

1: Nat Rev Genet. 2008 May;9(5):341-55. Links
Advances in autism genetics: on the threshold of a new neurobiology.Abrahams BS, Geschwind DH.
Neurology Department, and Semel Institute for Neuroscience and Behaviour, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1769 USA. brett.abrahams@gmail.com


Autism is a heterogeneous syndrome defined by impairments in three core domains: social interaction, language and range of interests. Recent work has led to the identification of several autism susceptibility genes and an increased appreciation of the contribution of de novo and inherited copy number variation. Promising strategies are also being applied to identify common genetic risk variants. Systems biology approaches, including array-based expression profiling, are poised to provide additional insights into this group of disorders, in which heterogeneity, both genetic and phenotypic, is emerging as a dominant theme.

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