Autism risk linked to age of parents Written by Matthew Hogg

Autism risk linked to age of parents
News - Autism News
Written by Matthew Hogg
Thursday, 30 October 2008




A new study finds that the age of both mothers and fathers is a major factor in the risk that a child will develop an autism spectrum disorder.



A major epidemiological study of American children published in the latest issue of the American Journal of Epidemiology has found that older parents, both mothers and fathers, are more likely to have a child with an autism spectrum disorder (ASD).



The study results suggest that mothers aged 35 or older have a 30% greater chance of having an autistic child compared to mothers aged 25 to 29, while fathers older than 40 had a 40% higher risk than those aged 25 to 29.



In addition, the study noted that firstborn children were the most likely to be affected by ASDs; firstborn offspring of 2 older parents being 3 times more likely to develop autism than third or later-born offspring of mothers aged 20–34 and fathers aged less than 40.



The study was conducted by Dr Maureen Durkin and colleagues from the University of Wisconsin School of Medicine and Public Health and was funded by the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.



The researchers looked at data from 10 US study sites participating in the CDC's Autism and Developmental Disabilities Monitoring Network. Out of 253,347 children born at the study sites who had complete parental age information 1,251 were identified as having an autism spectrum disorder at age 8 using the Autism and Developmental Disabilities Monitoring Network. ASDs refer to autistic disorder, pervasive developmental disorder not otherwise specified (PDD-NOS), and Asperger’s syndrome. The diagnoses were all made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria.



With this data in hand the researchers reviewed the parental age information to look for a correlation with ASD incidence to come up with their conclusions. Other factors such as gender, gestational age, birth weight, multiple births, maternal ethnicity, education and site of recruitment were all taken into account. This was done to insure that the age of mothers and fathers could be said with some degree of certainty to be an independant risk factor for the development of ASDs.



The researchers however did note drawbacks to their study design which may have affected the reliability of the results. For example they did not take into account infertility treatments and rates of mental illness or personality traits amongst the parents.



It was also noted that older parents may be more knowledgeable and aware of the signs of developmental disorders and therefore be more likely to seek medical advice and a diagnosis for their child. This could account for at least some of the differences in ASD rates among children of parents in different age groups.



Despite the limitations of the study Dr. Durkin and colleagues conclude that the results provide the "most compelling evidence to date that autistic spectrum disorder risk is linked to both maternal and paternal age, and decreases with birth order”.



They also say that “the increase in a rise with both maternal and paternal age has potential implications for public health planning and investigations of autism.”



The apparent rise in ASDs in the western world has coincided with a trend towards parents having children at an older age, together with a decline in the size of families, so the study results support this potential connection.



The link between autism and the age of parents is currently unclear, but the researchers speculate that the sperm of older men may be more susceptible to uncorrected genetic mutations which are passed on to the child. In older women, age related complications and chromosome alterations are suggested as possibilities.



The study although flawed does provide compelling evidence for a link between the age of both parents and ASDs, but as the researchers themselves admit, large long-term studies of well-characterised birth cohorts are needed to confirm the findings.

US Press Fails To Cover CDC Funded Study Finding Older Parental Age and Autism Spectrum Disorder Go Together

First-born children of older parents are more likely to be autistic
A major US study has provided the strongest evidence yet that older mothers and fathers are more likely to have a child with autism.

By Roger Dobson
Last Updated: 11:10AM GMT 26 Oct 2008

First-born children of older parents were three times more likely to develop autism than later children of younger parents, researchers found.

"The results provide the most compelling evidence to date that autism risk increases with both maternal and paternal age, and decreases with birth order," according to the research team, whose study was funded by the US Centers for Disease Control and Prevention.

The findings could help to provide an explanation for the recent increase in the number of children diagnosed with autism, which has coincided with a trend towards parents having children at an older age, and to smaller family sizes.

The researchers say in their paper, reported in the American Journal of Epidemiology: "The increase in autism risk with both maternal and paternal age has potential implications for public health planning and investigations of autism."

In the study, the researchers examined records of 240,000 children born in 1994, and identified 1,251 as having autism. After taking into account a range of factors, both maternal and paternal age were found to be independently associated with autism.

For mothers aged 35 or over, the risk of having an autistic child was 30 per cent higher than for mothers aged 25 to 29. Mothers under 20 had a 30 per cent lower risk than those aged 35 to 29. Fathers aged 40 or over had a 40 per cent higher risk of having an autistic child than fathers aged 25 to 29.

Many western countries have seen a trend for women to have their first child later in life, while the decline in average family size means that a higher proportion of today's children are first-born.

There is no clear explanation for why parental age increases the risk of having an autistic child. The researchers speculate that older fathers could be more likely to pass on gene mutations, while older mothers may be more prone to age-related chromasome changes or pregnancy complications. Older parents are also more likely to have undergone fertility treatment.

Another theory is that older parents may be more aware of developmental abnormalities, and therefore more likely to seek treatment and have their child diagnosed with disorders such as autism.

Firstborn children are also more prone to suffer from other childhood disorders, including type I diabetes. One possible explanation is the so-called "hygiene hypothesis", which suggests that firstborns are exposed to fewer infections from other children early in childhood and as a result are more likely to develop autoimmune diseases.

Autism study findings

http://www.nurseryworld.co.uk/news/login/857820/


Autism study findings
Nursery World, 30 October 2008
First-born children with older mothers and fathers have a greater risk of developing autism than later children of young parents, according to a new study. Funded by the US Centers for Disease Control and Prevention, the study, published in the American Journal of Epidemiology, looked at the records of 240,000 children born in 1994, identifying 1,251 as having autism. Researchers said that the study provided evidence that maternal and paternal age are associated with autism. Mothers surveyed aged 35 or over had a 30 per cent increased risk of having an autistic child, while the fathers aged over 40 had...

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Parental age increases autism risk in first born

Parental age increases autism risk in first born
by Neharika Sabharwal
Published on October 27, 2008 - 1 comments

United States, October 26: A recent study has revealed a strong possibility that parental age is the major predictor of autism, a development disorder. US researchers, analyzing the incidence of autism, observed, that it was three times more prevalent in the first born child, than the later born off-springs of younger parents.

During examination of the records of 240,000 children born in 1994, nearly 1,251 showed symptoms of autism. The data reinforces the claim that parenthood in advanced age is indeed a risk factor in the development of an autistic condition among kids.

Research throws light on the aspect that older parents, though independently, were associated with autism. Mothers above 35 years had a 30 percent risk bearing an autistic child as compared to one in her 20’s. For a father in his forties, the estimated risk was 40 percent higher of inflicting the child with the disorder.

The study published in the American Journal of Epidemiology, provided an explanation to the reason behind the increase in the number of children diagnosed with the ailment. The apparent rise in the condition in the western world coincided with the trend towards parents having children at an older age, together with a decline in the size of families.

Another theory propounded is that older parents are more likely to notice development difficulties in their children and seek treatment for a disorder like autism.

Autism, a brain disorder, causes different kinds of abnormalities, including communication problems, social interaction and repetitive pattern of behavior.

It affects an estimated 5 out of every 10,000 people and is more likely to occur in boys than girls.

While the reason for the autism age link is not clear, the researchers speculate that as men age their DNA (deoxyribonucleic acid) may lose some ability to repair itself. Spontaneous mutations in sperm carrying cells may be passed on rather than corrected. In older women, age related complications and chromosome alterations may be the possibility.

The researchers say, “The increase in a rise with both maternal and paternal age has potential implications for public health planning and investigations of autism.”

Although further work is necessary to confirm this interpretation, the study provides convincing evidence that paternal age is a risk factor for autism spectrum disorder.

Facing Autism in New Brunswick --A Father Who Wants to Know

Facing Autism in New Brunswick
Autism News and Opinion
Sunday, October 26, 2008

Autism, Parental Age and Birth Order
A study in the United States has found a link between higher parental age and the likelihood of first born children of older parents developing autism. The study, Advanced Parental Age and the Risk of Autism Spectrum Disorder, by Maureen S. Durkin, Matthew J. Maenner, Craig J. Newschaffer, Li-Ching Lee, Christopher M. Cunniff, Julie L. Daniels, Russell S. Kirby, Lewis Leavitt, Lisa Miller, Walter Zahorodny, and Laura A. Schieve is published in the advance access section of the online edition of the American Journal of Epidemiology, October 21, 2008.
The study defined "older" parents as mothers aged 35 or older and fathers aged 40 or older (maternal age 35, paternal age 40 years). The risk of developing ASD increased significantly with each 10-year increase in both maternal age and paternal age. Each 10-year increase in maternal age was associated with a 20% increase in ASD risk while each 10-year increase in paternal age was associated with a 30% increase in ASD risk.The study also confirmed earlier studies showing greater risk of ASD development amongst first born children of older parents:"The risk of ASD within each of 3 parental age categories (both parents "younger," 1 parent "older," and both parents "older") was highest among firstborn children and declined with increasing birth order" ....... The results of this study provide the most compelling evidence to date that ASD risk increases with both maternal and paternal age and decreases with birth order."
What I find curious is the greater risk of autism development amongst firstborn children given that the parental age will always be greater amongst the subsequently born children than amongst first born. The authors of the study offer no conclusion on this point but provide several existing hypotheses as possible explanations:The observation in this and at least 2 previous studies (2, 4) that the risk of developing ASD was highest for firstborn children and declined with increasing birth order is a pattern also observed for other childhood disorders, including type I diabetes and atopy, and is cited as support for the "hygiene hypothesis." According to this hypothesis, firstborn children are exposed to fewer infections from other children early in childhood and, because of delayed immunologic challenge, may be more likely to develop autoimmune responses including those that may adversely affect neurodevelopment (29). Another possible factor that could lead to the observed birth-order effect is exposure to potentially neurotoxic, fat-soluble chemicals accumulated in maternal tissue that have been passed to offspring transplacentally or through breast milk (30). Because of accumulation over a lifetime, the load of such neurotoxins transmitted might be expected to be highest for firstborn children, particularly when combined with advanced maternal age. Another possible explanation for the observed birth order effect is "stoppage" or a tendency for parents of 1 child with ASD not to have subsequent children because of the demands of parenting a child with a disability or concerns about genetic susceptibility (31), thus increasing the likelihood in the cohort as a whole that a child with ASD will have a low birth order. Information available for the present study did not allow examination of these hypotheses.
I was 42 when my younger son Conor, subsequently diagnosed with Autistic Disorder, was born. As an older father within the definition of this study I hope that this line of study continues to be explored objectively and professionally and is not derailed or distorted by the anger, from all "sides", that afflicts much public discussion of autism causes and treatments.
Anyone interested in following this issue in the "blogosphere" should check out the blog AUTISM PREVENTION FATHER BABIES 25-33 PATERNAL AGE IS A KEY IN NON-FAMILIAL AUTISMVaccines by concernedheart which is listed on my Autism Blog List in the right side bar of this blog. Concernedheart has been following this area for awhile and updates regularly.
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Rutgers Rakes in $58M of NIMH, NIDDK Funding for 'Omics Studies No Coverage that Autism, schizophrenia, biopolar diabetes increase with paternal age

sometimes maternal age is also a cause according to the plethora of studies. Rutgers is the recipient, but the public looses. All one needs to do to have healthier babies is know your own genetic history and have your children in your 20s and very, very early 30s to prevent these disorders. This includes kidney diseases which increase in offspring of older fathers too.
Rutgers Rakes in $58M of NIMH, NIDDK Funding for 'Omics Studies
[
By a GenomeWeb staff reporter
NEW YORK (GenomeWeb News) – Rutgers University has reeled in nearly $58 million from the National Institutes of Health to fund two research programs to conduct genomics studies of mental disorders and of metabolic and digestive diseases, the university said today.

Rutgers said it will use a $42.4 million five-year grant, and a supplemental award of $1.2 million, to create a Center for Genomic Studies on Mental Disorders at the university. The funding for the genomics center will support maintenance of a comprehensive lab, clinical databases, and computational infrastructure to fund national and international research focused on autism, bipolar disorder, depression, obsessive-compulsive disorder, and schizophrenia.

That grant also includes subcontracts to the Washington University School of Medicine to establish clinical and genetic databases, and to the Information Sciences Institute of the University of Southern California, which will study computational technology.
Rutgers also will use a five-year, $14 million contract from the National Institute of Diabetes and Digestive and Kidney Diseases to fund services and infrastructure costs for a cellular and molecular biology lab used for studying digestive, liver, and kidney diseases, and diabetes.

Autism and parental age

http://www.nhs.uk/news/2008/10October/Pages/Autismandparentalage.aspx
Monday October 27 2008
Autism and parental age

ASD probably has several causes
“First-born children of older parents are more likely to be autistic,” warned The Daily Telegraph. It reported on a study that examined the medical records of 240,000 children born in the US in 1994, and found that both maternal and paternal age were independently associated with autism. It said mothers aged 35 or older had a 30% higher chance of having an autistic child compared to mothers aged 25 to 29, while Fathers over 40 years had a 40% higher risk than those aged 25 to 29.
The study quoted in this news piece was not limited to autism but looked at the broader condition of autistic spectrum disorder (ASD). The study’s limitations mean that a definitive conclusion cannot be drawn about the contribution of parental age to overall risk for ASD. Its cause is still largely unknown, and it is unlikely that one factor alone will be responsible. The researchers themselves say that large long-term studies of well-characterised birth cohorts are needed to confirm these findings.Where did the story come from?
Dr Maureen Durkin and colleagues from the University of Wisconsin School of Medicine and Public Health carried out this study. The work was funded by the Center for Disease Control and Prevention in Atlanta. The study was published in the peer-reviewed medical journal, American Journal of Epidemiology.What kind of scientific study was this?
In this case-cohort study, the researchers were interested in the effects of parental age on the risk of autism spectrum disorder in the offspring. In this sort of study, both cases and controls come from the same cohort (population group).
The population comprised all 253,347 live births that took place in 1994 to women living in 10 areas around the US, (including Alabama, Arizona, Arkansas, Colorado, Georgia, Maryland, Missouri, New Jersey, North Carolina and Wisconsin). Information on these births was obtained from birth records held at the Wisconsin Department of Health and Family Services, and birth data from the National Center for Health Statistics. The records included information on the age of the mother and father, birth order, and other important variables.
From this population, the researchers identified children who had been diagnosed with autism in 2002 (at age eight) using the Autism and Developmental Disabilities Monitoring Network. This gave a total of 2,142 children with a ‘diagnosis’ of autistic spectrum disorder [ASD], namely autistic disorder, pervasive developmental disorder not otherwise specified, or Asperger’s syndrome.
Birth certificate information and information on birth order and parental age was only available for 1,251 of the children diagnosed with autism (58% of the total number of cases), so only these children were used in analysis as the ‘cases’. A ‘diagnosis’ was made if there was documented classification of a disorder, or if there was evidence from a medical or educational setting that indicated ‘unusual behaviours consistent with ASD’.
The researchers then assessed whether the age of the child’s parents had any effect on whether they went on to develop an autistic spectrum disorder. They took into account (i.e. adjusted for) other factors such as gender, gestational age, birth weight, multiple birth, maternal ethnicity, education and site of recruitment.What were the results of the study?
The researchers found a link between increasing parental age and odds of ‘diagnosis’ of autistic spectrum disorder by age eight. First-born children to mothers aged 35 years and over who also had fathers aged 40 years and over were at the greatest risk of autism (triple the likelihood). This was compared with children who were third or more in order of birth to younger parents (mother aged 20-34 years and father younger than 40 years). In separate analyses, there were generally “modest” links between autism and other parental age groups and other birth orders, ranging from 1.4 times as likely to 2.3 times.What interpretations did the researchers draw from these results?
The researchers conclude that these results provide the “most compelling evidence to date that autistic spectrum disorder risk is linked to both maternal and paternal age, and decreases with birth order”. They say that the increased risk of autism with both maternal and paternal age has implications for public health planning.What does the NHS Knowledge Service make of this study?
This case-cohort study concluded that there is a link between maternal and paternal age and risk of developing autistic spectrum disorder. In a study of this design, it is important to measure and adjust for other factors that may be responsible for the link. Here, the researchers have adjusted for a number of these factors, but they note that they did not adjust for infertility treatments and psychopathology or behavioural traits of parents. The researchers also note that their study cannot control for the fact that older parents may have more knowledge of developmental disorders and therefore be more likely to seek a diagnosis for their child. Therefore, it is possible that the different numbers of autistic children diagnosed to parents of different ages may be a result of this different rate of diagnosis.
The researchers identify other shortcomings of their study, saying that measures of parity (numbers of children) only relates to mothers and does not account for other children of the fathers in the cohort. They also say that other confounders may not have been measured, including possible misclassification of ASD, and an inability to adjust for paternal education due to missing information.
Importantly, the study assessed the link between parental age and autistic spectrum disorders, and this includes a wide range of conditions, including typical autism. However, the researchers note that 80% of the ASD cases were autistic disorder, and among the remaining 20% they could not differentiate between autism, PDD-NOS and Asperger’s. The ‘diagnosis’ of ASD was not necessarily reliant on a clinical process, and the researchers relied on school or medical evaluations to determine the diagnosis themselves in 35% of the participating children. The accuracy of this process is questionable.
Another important point is that only 58% of the actual ‘cases’ were included in the analyses because of missing information from birth certificates, maternal or paternal age and birth order. Although the researchers state that their final sample was comparable to the total population of ASD cases regarding demographic factors and ASD case characteristics, differences in the factors being measured between the children who were included and those who were excluded would have biased the results. The researchers have considered this however, and say that the exclusion for missing information applied to both ‘cases’ and the comparison cohort, so it is unlikely to have affected the cases differently.
What causes ASD is largely unknown, but it is likely that several factors are responsible. The study has too many limitations for a definitive conclusion to be drawn about the contribution of parental age to overall risk for ASD. As the researchers say, large long-term studies of well-characterised birth cohorts are needed to confirm these findings.
Links to the headlines
First-born children of older parents are more likely to be autistic. The Daily Telegraph, October 26 2008
Links to the science
Durkin MS, Maenner MJ, Newschaffer CJ et al. Advanced Parental Age and the Risk of Autism Spectrum Disorder. American Journal of Epidemiology 2008; Advance Access published online on October 21
Analysis by
Edited by NHS Choices

the study provides convincing evidence that paternal age is a risk factor for autism spectrum disorder.

Parental age increases autism risk in first born

by Neharika Sabharwal
Published on October 27, 2008 - 0 comments
United States, October 26: A recent study has revealed a strong possibility that parental age is the major predictor of autism, a development disorder. US researchers, analyzing the incidence of autism, observed, that it was three times more prevalent in the first born child, than the later born off-springs of younger parents. " alt="Parental age increases autism risk in first born" src="http://www.themedguru.com/files/pregnant_mom_child.jpg">
window.google_render_ad();
United States, October 26: A recent study has revealed a strong possibility that parental age is the major predictor of autism, a development disorder. US researchers, analyzing the incidence of autism, observed, that it was three times more prevalent in the first born child, than the later born off-springs of younger parents.
During examination of the records of 240,000 children born in 1994, nearly 1,251 showed symptoms of autism. The data reinforces the claim that parenthood in advanced age is indeed a risk factor in the development of an autistic condition among kids.
Research throws light on the aspect that older parents, though independently, were associated with autism. Mothers above 35 years had a 30 percent risk bearing an autistic child as compared to one in her 20’s. For a father in his forties, the estimated risk was 40 percent higher of inflicting the child with the disorder.
The study published in the American Journal of Epidemiology, provided an explanation to the reason behind the increase in the number of children diagnosed with the ailment. The apparent rise in the condition in the western world coincided with the trend towards parents having children at an older age, together with a decline in the size of families.
Another theory propounded is that older parents are more likely to notice development difficulties in their children and seek treatment for a disorder like autism.
Autism, a brain disorder, causes different kinds of abnormalities, including communication problems, social interaction and repetitive pattern of behavior.
It affects an estimated 5 out of every 10,000 people and is more likely to occur in boys than girls.
While the reason for the autism age link is not clear, the researchers speculate that as men age their DNA (deoxyribonucleic acid) may lose some ability to repair itself. Spontaneous mutations in sperm carrying cells may be passed on rather than corrected. In older women, age related complications and chromosome alterations may be the possibility.
The researchers say, “The increase in a rise with both maternal and paternal age has potential implications for public health planning and investigations of autism.”
Although further work is necessary to confirm this interpretation, the study provides convincing evidence that paternal age is a risk factor for autism spectrum disorder.

The CDC Study Showing Offspring of Older Parents More Likely To Be Autistic Not Told To Americans

This study is all over the Indian press, published in Scotland, England, Thailand but not in America. Why have no newspapers in the USA picked this up?

Kids of older parents likely to be autistic

Kids of older parents likely to be autistic
26 Oct 2008, 1637 hrs IST, ANI





Older mothers and fathers are more likely to have a child with autism, according to a new US study.First-born kids of older parents likely to develop autism (Getty Images)



In the study, researchers found that first-born children of older parents were three times more likely to develop autism than later children of younger parents. "The results provide the most compelling evidence to date that autism risk increases with both maternal and paternal age, and decreases with birth order," the Telegraph quoted researchers, as saying.

“The increase in autism risk with both maternal and paternal age has potential implications for public health planning and investigations of autism," they added.

In the study, the researchers examined records of 240,000 children born in 1994, and identified 1,251 as having autism. After adjusting for a range of factors, both maternal and paternal age were found to be independently linked to autism.

The study revealed that for mothers aged 35 or over, the risk of having an autistic child was 30 per cent higher than for mothers aged 25 to 29.

Mothers under 20 had a 30 per cent lower risk than those aged 35 to 29. Fathers aged 40 or over had a 40 per cent higher risk of having an autistic child than fathers aged 25 to 29.

However, there is no clear explanation for why parental age increases the risk of having an autistic child.

The study is published in the American Journal of Epidemiology.




Click here to comment on this story.

Risk of Autism Increases with Parental Age -

RSSRisk of Autism Increases with Parental Age - But No One Knows Why
http://autism.about.com/b/2008/10/26/risk-of-autism-increases-with-parental-age-but-no-one-knows-why.htmBy Lisa Jo Rudy, About.com Guide to Autism
Risk of Autism Increases with Parental Age - But No One Knows Why
Sunday October 26, 2008
The UK's Telegraph has done a nice job of summarizing the findings of an American study focused on the risk of autism relative to the ages of parents. The findings are not new; rather, they are confirmation of earlier findings which suggest that older parents are more likely to produce children with autism.
Interestingly, though, this study adds another rather odd bit of information: apparently, FIRST children of older parents are more likely to be autistic than later children. In other words, as the parents grow older and have more children, their age apparently ceases to be as much of an issue.

For mothers aged 35 or over, the risk of having an autistic child was 30 per cent higher than for mothers aged 25 to 29. Mothers under 20 had a 30 per cent lower risk than those aged 35 to 29. Fathers aged 40 or over had a 40 per cent higher risk of having an autistic child than fathers aged 25 to 29.
Many western countries have seen a trend for women to have their first child later in life, while the decline in average family size means that a higher proportion of today's children are first-born.

There is no clear explanation for why parental age increases the risk of having an autistic child. The researchers speculate that older fathers could be more likely to pass on gene mutations, while older mothers may be more prone to age-related chromasome changes or pregnancy complications. Older parents are also more likely to have undergone fertility treatment.

Another theory is that older parents may be more aware of developmental abnormalities, and therefore more likely to seek treatment and have their child diagnosed with disorders such as autism.

Before parents draw too many conclusions from these findings, it's important to make a couple of points.
First, while first-time parents in developed nations are older overall than they were decades ago, the difference in age is minor (about two years). The average age of a first-time parent is nowhere near 35. Thus, while the parental age/autism link may be significant, it certainly wouldn't explain a huge rise in diagnoses (assuming that the rise in diagnoses indicates a real rise in incidence).

Second, some have posited the idea that older parents may have met and married later because of social and communications challenges. If such is the case, then older parents may be more likely to have autistic traits - and thus may be more likely to transmit those traits to their children. This possibility seems to me to have legs - though I don't have research studies to cite on the subject.

As it happens, we were older (I was 36) when my son with autism was born - and 39 when my daughter withOUT autism was born. So these statistics reflect our reality 100%. Does it reflect yours? Or - are you an older adult considering parenthood, and worrying about these new findings? Share your thoughts!

Autism link to firstborn of older parents

Autism link to firstborn of older parents



« Previous « PreviousNext » Next »View GalleryPublished Date: 26 October 2008
By Liz Longden
FIRSTBORN children of older parents have three times as much chance of being diagnosed with autism than later born children of younger parents, new research has revealed.

A study of 240,000 teenagers carried out by researchers in the US has found a strong link between the likelihood of developing the condition and a higher age of parents.

Mothers aged 35 and over were cited as having a 30% higher risk of having an ADVERTISEMENTautistic child than mothers in their twenties, while for fathers in their forties and over the risk was estimated to be even greater at around 40% higher when compared with fathers aged under 30.

The study also suggested that later born children were less likely to be afflicted with autistic disorders than firstborn offspring.

The research team behind the study has claimed their work provides "the most compelling evidence to date that autism risk increases with both maternal and paternal age, and decreases with birth order".

The study, published in the American Journal of Epidemiology, has been hailed as a possible explanation for the apparent increase in incidence of the condition in the western world, where social trends mean increasing numbers of couples put off having children until later in life, and tend to opt for smaller families – meaning a higher proportion of babies are firstborn or only children.

There is no clue to suggest why parental age should increase the risk of a child being autistic, but the authors suggest the sperm of older fathers could be more likely to pass on genetic mutations, while older mothers might be more susceptible to chromosome alterations. Another theory suggests that older parents may be more likely to spot developmental difficulties in their children, and therefore more likely to seek help and a formal diagnosis.

Firstborn children are also more prone to suffer from other childhood disorders, including type I diabetes. One theory to explain the phenomenon is the "hygiene hypothesis", which suggests that first-time parents are more protective and expose their children to fewer infections in early childhood, making them likely to develop autoimmune diseases.

First-born children of older parents were three times more likely to develop autism than later children of younger parents, researchers found.

First-born children of older parents are more likely to be autistic
A major US study has provided the strongest evidence yet that older mothers and fathers are more likely to have a child with autism.

By Roger Dobson
Last Updated: 7:48PM BST 25 Oct 2008

First-born children of older parents were three times more likely to develop autism than later children of younger parents, researchers found.

"The results provide the most compelling evidence to date that autism risk increases with both maternal and paternal age, and decreases with birth order," according to the research team, whose study was funded by the US Centers for Disease Control and Prevention.

The findings could help to provide an explanation for the recent increase in the number of children diagnosed with autism, which has coincided with a trend towards parents having children at an older age, and to smaller family sizes.

The researchers say in their paper, reported in the American Journal of Epidemiology: "The increase in autism risk with both maternal and paternal age has potential implications for public health planning and investigations of autism."

In the study, the researchers examined records of 240,000 children born in 1994, and identified 1,251 as having autism. After taking into account a range of factors, both maternal and paternal age were found to be independently associated with autism.

For mothers aged 35 or over, the risk of having an autistic child was 30 per cent higher than for mothers aged 25 to 29. Mothers under 20 had a 30 per cent lower risk than those aged 35 to 29. Fathers aged 40 or over had a 40 per cent higher risk of having an autistic child than fathers aged 25 to 29.

Many western countries have seen a trend for women to have their first child later in life, while the decline in average family size means that a higher proportion of today's children are first-born.

There is no clear explanation for why parental age increases the risk of having an autistic child. The researchers speculate that older fathers could be more likely to pass on gene mutations, while older mothers may be more prone to age-related chromasome changes or pregnancy complications. Older parents are also more likely to have undergone fertility treatment.

Another theory is that older parents may be more aware of developmental abnormalities, and therefore more likely to seek treatment and have their child diagnosed with disorders such as autism.

Firstborn children are also more prone to suffer from other childhood disorders, including type I diabetes. One possible explanation is the so-called "hygiene hypothesis", which suggests that firstborns are exposed to fewer infections from other children early in childhood and as a result are more likely to develop autoimmune diseases.

Advanced Parental Age and the Risk of Autism Spectrum Disorder

Oxford Journals Medicine American Journal of Epidemiology American Journal of Epidemiology Advance Access 10.1093/aje/kwn250


American Journal of Epidemiology Advance Access published online on October 21, 2008
American Journal of Epidemiology, doi:10.1093/aje/kwn250
This Article

Abstract
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American Journal of Epidemiology © 2008 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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ORIGINAL CONTRIBUTION


Advanced Parental Age and the Risk of Autism Spectrum Disorder
Maureen S. Durkin, Matthew J. Maenner, Craig J. Newschaffer, Li-Ching Lee, Christopher M. Cunniff, Julie L. Daniels, Russell S. Kirby, Lewis Leavitt, Lisa Miller, Walter Zahorodny and Laura A. Schieve
Correspondence to Dr. Maureen Durkin, Waisman Center and Departments of Population Health Sciences and Pediatrics, University of Wisconsin School of Medicine and Public Health, 789 WARF, 610 Walnut Street, Madison, WI 53726 (e-mail: mdurkin@wisc.edu).

Received for publication March 21, 2008. Accepted for publication July 16, 2008.


ABSTRACT
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
References


This study evaluated independent effects of maternal and paternal age on risk of autism spectrum disorder. A case-cohort design was implemented using data from 10 US study sites participating in the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network. The 1994 birth cohort included 253,347 study-site births with complete parental age information. Cases included 1,251 children aged 8 years with complete parental age information from the same birth cohort and identified as having an autism spectrum disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. After adjustment for the other parent's age, birth order, maternal education, and other covariates, both maternal and paternal age were independently associated with autism (adjusted odds ratio for maternal age 35 vs. 25–29 years = 1.3, 95% confidence interval: 1.1, 1.6; adjusted odds ratio for paternal age 40 years vs. 25–29 years = 1.4, 95% confidence interval: 1.1, 1.8). Firstborn offspring of 2 older parents were 3 times more likely to develop autism than were third- or later-born offspring of mothers aged 20–34 years and fathers aged <40 years (odds ratio = 3.1, 95% confidence interval: 2.0, 4.7). The increase in autism risk with both maternal and paternal age has potential implications for public health planning and investigations of autism etiology.


autistic disorder; birth order; maternal age; paternal age


Abbreviations: ASD, autism spectrum disorder; PDD-NOS, pervasive developmental disorders-not otherwise specified


INTRODUCTION
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ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
References


This paper examines the relation between parental age at delivery and the prevalence of autism spectrum disorder (ASD). The possibility that autism is more common in offspring of older parents has generated considerable interest (1–6). Confirmation of such an association could have important public health implications in light of increasing trends in recent decades regarding both maternal and paternal age (7). In addition, evidence of paternal and maternal age effects on autism risk may provide clues to the etiology of a class of neurodevelopmental disorder that is still poorly understood and thought to be complex and multifactoral.

In evaluating the association between parental age and autism risk, it is important to account for other variables related to both parental age and autism or that may modify the association. Birth order is a potentially confounding factor because it is positively associated with parental age and has been reported in some studies to be associated with autism risk, with at least 3 studies reporting firstborn children to be at increased risk of autism (1, 2, 4). The goal of this study was to determine, in a large, population-based cohort of US children, whether advancing maternal and paternal age each independently increase a child's risk of developing autism after controlling for the other parent's age, birth order, and other risk factors.


MATERIALS AND METHODS
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ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
References


Study design and sample
We implemented a population-based, case-cohort design in which the comparison group was a cohort of all livebirths in 1994 in 10 geographically defined study areas participating in the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network (8). The 10 areas are all sites with deidentified birth certificate information on parental age and other relevant variables included in the Network database and include sites in Alabama, Arizona, Arkansas, Colorado, Georgia, Maryland, Missouri, New Jersey, North Carolina, and Wisconsin.

The cohort serving as the comparison group includes all livebirths to mothers residing in any 1 of the study areas in 1994, with complete information available from birth certificates on maternal and paternal age, birth order, and other variables. We used 2 data sources to construct the cohort: 1994 deidentified birth records for the Wisconsin study area provided by the Wisconsin Department of Health and Family Services and, for the remaining sites, the National Center for Health Statistics public use natality data files (9). The public use file includes county of residence for births in densely populated counties, which enabled us to ascertain deidentified birth information for all births in most of the counties. We were unable to precisely obtain counts of births occurring in sparsely populated counties in which 13,043 (4.1%) of the study-area births occurred in 1994. For these counties, we obtained county-level aggregate information on the total number of births in 1994 and their distribution by variables such as maternal marital status, ethnicity, and age and selected a stratified random sample of deidentified birth records (equal in number and similar in distribution by maternal marital status, ethnicity, and age to all livebirths occurring in the respective counties in 1994) from sparsely populated counties of the state in which the study area was located. The full cohort included 326,785 livebirths, of which 73,438 (22.5%) were excluded because of missing paternal age. The cohort serving as the comparison group thus included the 253,347 livebirths with complete information on parental age and other key variables (Table 1).




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Table 1. Characteristics of the 1994 Birth Cohort and ASD Cases, 10 Study Sites From the US Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network




The total number of children aged 8 years residing in the study areas in 2002 determined by the Autism and Developmental Disabilities Monitoring Network surveillance system to have an ASD was 2,142. Birth certificate information was available for 1,517 (70.8%) of these children, who were born in the same state as their state of residence in 2002. The remaining 29.2% of cases were excluded from this analysis because of missing birth certificate information. The case group for the present analysis was further restricted to the 1,251 children (58.4% of the total ASD case group) for whom information on both parents' age as well as birth order and gestational age was available. Our final sample was comparable to the total population of ASD cases regarding demographic factors and ASD case characteristics (Table 1).
Case definition
ASDs include behaviorally defined neurodevelopmental disorders diagnosed through clinical observation, and they encompass impairments in social, communicative, and behavioral development, often accompanied by abnormalities in intellectual functioning, learning, attention, and sensory processing. For this study, children with ASD included members of the birth cohort residing in the study area in 2002 who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for autistic disorder; pervasive developmental disorders-not otherwise specified (PDD-NOS (http://www.cdc.gov/ncbddd/autism/overview_diagnostic_criteria.htm), including atypical autism); or Asperger's disorder (10) based on a comprehensive review of educational and clinical records by trained clinicians. Children were classified by clinician reviewers as having an ASD if they had either a documented previous classification of ASD (65%) or an evaluation record from an educational or medical setting indicating unusual behaviors consistent with ASD (35%). For children previously identified as having an ASD, case status was confirmed on the basis of evaluation records. For children without a documented ASD classification, data were abstracted on all relevant ASD and developmental behaviors from education or medical evaluations to determine whether behaviors described in the evaluations by clinical reviewers were consistent with the diagnostic criteria. Because case status was determined solely on the basis of information contained in evaluation records, and because Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria are less well defined for PDD-NOS than for autistic disorder, the surveillance protocol for determining whether a child could be classified as having PDD-NOS required documentation of at least 1 behavior considered to be an ASD discriminator, such as being oblivious to others when there is a clear social opportunity or demonstrating atypical and persistent focus on sensory input (11).

Of the 1,251 ASD cases, 80.7% were determined to meet criteria for autistic disorder, while there was insufficient information for those remaining to distinguish between autistic disorder, Asperger's disorder, or PDD-NOS. Information from standardized intelligence tests was available for approximately 75% of the ASD cases. On the basis of this information, children with ASD were classified as having intellectual impairment (an IQ of <70) versus normal intelligence. Further details regarding the 2002 Autism and Developmental Disabilities Monitoring Network sample and methodology have been reported previously (8, 11).

Analytic strategy and statistical methods
Potential for confounding effects of birth order, gender, and other variables was evaluated by first examining unadjusted associations between each potential confounder and the independent variables of maternal and paternal age as well as the dependent variable, ASD case status. Variables were considered to be potentially confounding factors if they were associated with both parental age and ASD. Unadjusted odds ratios with confidence intervals were computed to evaluate the magnitude of these associations, and unconditional logistic regression models were fit to estimate adjusted odds ratios and 95% confidence intervals. Statistical significance was evaluated by using chi-square tests for categorical variables and analysis of variance for continuous variables.

To enhance the comparability of our findings with those from other studies, we fit 2 types of models, 1 with parental ages categorized into 6 categories: <20, 20–24, 25–29, 30–34, 35–39, 40 years; and the other with parental age as a continuous variable with the odds ratio scaled to reflect a 10-year difference in age (4). Although we found the association between parental age and autism risk to be similar across the 10 sites, to adjust for potential site-to-site variability we included site dummy variables in all multivariable models. To evaluate interaction or modifying effects of each covariate and of ASD subtypes on the associations between parental age and ASD, we performed stratified analyses. We also tested interaction terms for maternal age by paternal age and 2-way and 3-way interaction terms for each parent's age by the other covariates in the regression models, but we identified no significant interactions. SAS version 9.1.3 software (SAS Institute, Inc., Cary, North Carolina) was used for all statistical analyses.

This research involved secondary analysis of deidentified data and was approved by the University of Wisconsin Institutional Review Board.


RESULTS
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In unadjusted analyses, both mean maternal age and mean paternal age were significantly higher for ASD cases than for the birth cohort as a whole (Table 2). Table 2 also shows that mean parental ages differed significantly in unadjusted analyses across categories of birth order, maternal education, ethnicity, multiple birth, gestational age, and birth weight for gestational age, but not for gender. With parental age 25–29 years as the reference group, the odds of developing ASD was significantly reduced for parental age <20 years and increased for maternal age 35 and paternal age 40 years (Table 3, unadjusted odds ratios). We therefore used these age cutoffs (maternal age 35, paternal age 40 years) to classify each parent's age as "older" versus "younger." Other significant predictors of ASD in unadjusted analyses included low birth order, male gender, advanced maternal education, and preterm birth (Table 3).




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Table 2. Unadjusted Mean Maternal and Paternal Ages at Delivery for ASD Cases Compared With the Cohort as a Whole, and in the Cohort as a Whole Stratified by Covariate Categories, 1994 Birth Cohort From 10 Study Sites From the US Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network






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Table 3. Distribution of ASD Cases and Birth Cohort Comparison Group by Parental Age Categories and Other Independent Variables, and Unadjusted and Adjusted Odds Ratios With 95% Confidence Intervals, 1994 Birth Cohort From 10 Study Sites From the US Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network




Multivariable analysis of parental ages modeled as categorical variables
After we adjusted for the other parent's age and other covariates, the increases in ASD risk associated with maternal age 35 years and paternal age 40 years (relative to age 25–29 years) were slightly reduced compared with the unadjusted analysis (Table 3). In contrast, the results for birth order suggest that the decline in ASD risk associated with increasing birth order is somewhat stronger in the adjusted analysis than in the unadjusted analysis (Table 3). In addition, the apparent increase in ASD risk associated with higher levels of maternal education in the unadjusted analysis is no longer evident in the adjusted model, suggesting that the apparent maternal education effect is due to its association with parental age (Table 3).
Parental ages modeled as continuous variables
In unadjusted analyses, the risk of developing ASD increased significantly with each 10-year increase in both maternal age and paternal age. After adjustment for age of the other parent and other covariates, each 10-year increase in maternal age was associated with a 20% increase in ASD risk (odds ratio = 1.2, 95% confidence interval: 1.1, 1.4) while each 10-year increase in paternal age was associated with a 30% increase in ASD risk (odds ratio = 1.3, 95% confidence interval: 1.1, 1.5).

Combined effects of parental age and birth order
The risk of ASD within each of 3 parental age categories (both parents "younger," 1 parent "older," and both parents "older") was highest among firstborn children and declined with increasing birth order (Table 4). Considering the combined effects of parental age and birth order, we excluded from the analysis births to mothers aged <20 years and found the lowest risk group to be third- or later-born offspring of mothers aged 20–34 years and fathers aged <40 years. Compared with that for this group, the risk of ASD increased with both declining birth order and increasing number of older parents. The highest risk group included firstborn offspring of mothers aged 35 years and fathers aged 40 years, with a risk 3 times that of the reference group (Table 4).




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Table 4. Adjusted Odds Ratiosa With 95% Confidence Intervals Indicating Increasing Risk of ASD With Parental Ageb and Decreasing Risk With Birth Order, 1994 Birth Cohort From 10 Study Sites From the US Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network





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Our findings are consistent with those recently reported from a large study of members of a California health maintenance organization (4) that found the risk of ASD to be positively and independently associated with both maternal and paternal age, with adjusted odds ratios nearly identical to those reported here. These findings contrast somewhat with 5 other recent epidemiologic studies that found only 1 or neither parent's age to be associated with ASD risk after controlling for the other parent's age (2, 3, 12–14).
The lack of consistency across studies could be due to limitations of sample size and of population representation of previous studies as well as other methodological differences, including autism case definitions and inclusion criteria and the ability to control for important variables. The present study included a large sample of children with sufficient information to enable evaluation of separate and combined effects of each parent's age as well as birth order and other variables. With more than 1,200 cases, it included over 50% more cases and thus more statistical power than any of the previous studies examining independent effects of maternal and paternal age on ASD risk.

Another advantage of this study is the population-based nature and diversity of the cohort, allowing control for factors that may confound the association between parental age and ASD. Maternal education is 1 variable we considered to be a potentially confounding factor because it is associated with maternal age and has been observed to be related to ASD risk (15). Our results, however, suggest that the association between advanced maternal education and ASD risk observed in unadjusted analysis may be spurious and due to confounding by parental age.

The results of this study also demonstrate the importance of controlling for birth order in evaluating independent effects of parental age on ASD risk. Because birth order increases with parental age and, in this and other studies, has been found to be negatively associated with ASD risk, failure to control for birth order may mask a positive association between parental age and ASD risk. Two of the previous studies reporting an association between advancing maternal age and ASD (2, 4) also had adjusted for birth order and, similar to the present study, found birth order to be negatively associated with ASD.

An additional advantage of this study is its restriction to a single birth year, thereby controlling for temporal trends in recent decades in both ASD prevalence and parental ages at the birth of their children. This feature of the study allows estimation of the association between parental age and ASD risk independently of temporal trends in diagnostic practices or other factors.

Public health implications
The strength of the independent associations between maternal and paternal age and ASD risk, as indicated by the odds ratios in the range of 1.2–1.4 reported here, is modest. However, the observation that these effects are independent of each other and of low birth order raises the likelihood that the combined effects of parental age and birth order may have important public health implications. Mean maternal age in the United States has increased steadily since the 1970s, particularly for firstborn children, for whom mean maternal age at delivery increased by 3.8 years between 1970 and 2004 (16). In addition, the proportion of births to women aged 35 years began increasing in the United States after 1980, when it was 5%; by 2004, it had increased to 14.2% (17, 18). During this same period, fertility rates for men aged 40 years also increased each year, while fertility among men aged <30 years declined (16). With the decline in average family size in recent decades, we would also expect the proportion of children who are firstborn to have increased. Similar trends are occurring in other developed countries (7). The results of this study raise the question of whether some portion of the recent rise in ASD prevalence (19) may be linked to recent trends in parental age and family size. A further question is whether a modest increase in prevalence associated with advancing parental age and low birth order may have contributed to a greater awareness of ASD and, in turn, increases in measured prevalence. The tendency for older parents of firstborn children to have higher levels of educational achievement and resources than other parents could further contribute to increased awareness and an expansion of the diagnosis of ASD.

Potential etiologic implications of parental age effects
Because we observed independent effects of the age of each parent on ASD risk, the possible mechanisms for these effects could include a broad range of processes associated with either or both maternal and paternal age. The observed paternal age effect independent of maternal age could point to a causal role of gene mutations in male germ cells, because the probability or selection of these mutations increases as men age (20, 21). The independent effect of maternal age, on the other hand, may point to age-related chromosome changes, pregnancy complications, or environmental exposures during pregnancy. Independent effects of 1 or both parents' ages also could point to a role of accumulated environmental exposures that may have mutagenic effects on gametes or could result from a combination of mechanisms (21, 22).

The association between advanced maternal and paternal age and ASD is also consistent with a potential role of infertility treatments or assisted reproductive technologies, the uses of which have increased in the past decade, especially by women and men of advanced reproductive age (23). Numerous studies have found associations between these technologies and adverse pregnancy outcomes, including those due to epigenetic effects (24–27), although a recent review found no evidence of elevated rates of autism among children born after in vitro fertilization techniques (28). Even though we have no information about exposure to these treatments in our cohort, the observation that firstborn children of older parents had the highest ASD risk is consistent with a possible infertility treatment effect because women who give birth after infertility treatment are more likely to be primiparous than those represented in the general birth cohort. However, the association between multiple birth and ASD in this study was weak and not statistically significant (Table 3, unadjusted odds ratio), whereas assisted reproduction technologies are strongly associated with multiple birth (23).

Another unmeasured factor in the present study potentially associated with both advanced parental age and ASD risk in offspring is psychopathology or behavioral traits of parents that may result in both delayed parenthood and genetic susceptibility to autism in offspring (14).

Birth-order effects
The observation in this and at least 2 previous studies (2, 4) that the risk of developing ASD was highest for firstborn children and declined with increasing birth order is a pattern also observed for other childhood disorders, including type I diabetes and atopy, and is cited as support for the "hygiene hypothesis." According to this hypothesis, firstborn children are exposed to fewer infections from other children early in childhood and, because of delayed immunologic challenge, may be more likely to develop autoimmune responses including those that may adversely affect neurodevelopment (29). Another possible factor that could lead to the observed birth-order effect is exposure to potentially neurotoxic, fat-soluble chemicals accumulated in maternal tissue that have been passed to offspring transplacentally or through breast milk (30). Because of accumulation over a lifetime, the load of such neurotoxins transmitted might be expected to be highest for firstborn children, particularly when combined with advanced maternal age. Another possible explanation for the observed birth order effect is "stoppage" or a tendency for parents of 1 child with ASD not to have subsequent children because of the demands of parenting a child with a disability or concerns about genetic susceptibility (31), thus increasing the likelihood in the cohort as a whole that a child with ASD will have a low birth order. Information available for the present study did not allow examination of these hypotheses.

Another important limitation of this study is that the cohort available for analysis excludes births with missing paternal age information. Because this exclusion applied to both the ASD cases and the comparison group (Table 1), we would not expect it to have resulted in biased estimates of the association between ASD and parental age. In a separate analysis, we examined the association between maternal age and ASD without adjusting for paternal age and including the full birth cohort, and we found the association between maternal age and ASD to be the same as that observed in the subcohort with paternal age.

Another limitation is that the birth cohort comparison group includes about 1% of births of children who died postnatally in addition to an undetermined number who moved out of the study area between birth and the age of 8 years, whereas children who died postnatally and those moving out of the study area after birth are excluded from the case group. Because of this limitation, we could not estimate cumulative incidence of ASD. Nonetheless, this limitation is unlikely to have biased the estimated odds ratios reported in this study, particularly those adjusted for factors such as gestational age and birth weight for gestational age, which are strongly associated with postnatal mortality. Another possible explanation for the increase in ASD among offspring of older parents, but one we cannot evaluate with the data available, is that, compared with younger parents, older parents may be more aware of developmental abnormalities and better able to access diagnostic and special educational services. Other limitations are that parity pertains to only mothers and does not take into account the number of previous births fathered by the fathers represented in the cohort, potential for residual confounding by factors not measured in the present study, possible misclassification of ASD case status, and missing information on paternal education.

Conclusion
The results of this study provide the most compelling evidence to date that ASD risk increases with both maternal and paternal age and decreases with birth order. Further research involving large, well-characterized birth cohorts followed longitudinally will be required to confirm these findings and adequately evaluate the range of alternative genetic and environmental hypotheses that this and other studies raise regarding parental age and birth-order effects on ASD risk. Smaller, focused studies may also be useful, such as Crow's idea to look for mutations responsible for complex disorders of unknown etiology and with parental age effects by studying affected families with older parents (20).






ACKNOWLEDGMENTS

Author affiliations: Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (Maureen S. Durkin, Matthew J. Maenner); Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (Maureen S. Durkin, Lewis Leavitt); Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin (Maureen S. Durkin, Matthew J. Maenner, Lewis Leavitt); Department of Epidemiology, Drexel University, Philadelphia, Pennsylvania (Craig J. Newschaffer); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Li-Ching Lee); Department of Pediatrics, University of Arizona College of Medicine, Tucson, Arizona (Christopher M. Cunniff); Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (Julie L. Daniels); Department of Maternal and Child Health, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama (Russell S. Kirby); Department of Public Health and Environment, State of Colorado, Denver, Colorado (Lisa Miller); Department of Pediatrics, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Trenton, New Jersey (Walter Zahorodny); and National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia (Laura A. Schieve).

This work was funded by the Centers for Disease Control and Prevention, Cooperative Agreements UR3/CCU523235 and UR3/DD000078. Additional funding for graduate student support for data analysis was provided by the University of Wisconsin.

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

Conflict of interest: none declared.


References
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CiteULike Connotea Del.icio.us What's this?

Am J Epidemiol. 2008 Oct 21. [Epub ahead of print]

Am J Epidemiol. 2008 Oct 21. [Epub ahead of print]
Advanced Parental Age and the Risk of Autism Spectrum Disorder.Durkin MS, Maenner MJ, Newschaffer CJ, Lee LC, Cunniff CM, Daniels JL, Kirby RS, Leavitt L, Miller L, Zahorodny W, Schieve LA.
This study evaluated independent effects of maternal and paternal age on risk of autism spectrum disorder. A case-cohort design was implemented using data from 10 US study sites participating in the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network. The 1994 birth cohort included 253,347 study-site births with complete parental age information. Cases included 1,251 children aged 8 years with complete parental age information from the same birth cohort and identified as having an autism spectrum disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. After adjustment for the other parent's age, birth order, maternal education, and other covariates, both maternal and paternal age were independently associated with autism (adjusted odds ratio for maternal age >/=35 vs. 25-29 years = 1.3, 95% confidence interval: 1.1, 1.6; adjusted odds ratio for paternal age >/=40 years vs. 25-29 years = 1.4, 95% confidence interval: 1.1, 1.8). Firstborn offspring of 2 older parents were 3 times more likely to develop autism than were third- or later-born offspring of mothers aged 20-34 years and fathers aged <40 years (odds ratio = 3.1, 95% confidence interval: 2.0, 4.7). The increase in autism risk with both maternal and paternal age has potential implications for public health planning and investigations of autism etiology.
PMID: 18945690 [PubMed - as supplied by publisher]

Pressure on men to have children before they hit 40, before they hit 35,

Women not the only ones with ticking Biological ClockBy Silberstein Awad & Miklos(Jennybeth) All of these factparents. ...ors are bound to put more pressure on men to have children before they hit 40, and to listen to the ticking of their own biological clock. Birth defects and miscarriages are not always the fault of the

Dr Bowman said couples should consider becoming parents earlier

Sperm damage rises from 35: study
-->-->24th October 2008, 7:45 WST -->


Older women are not alone in their fertility troubles, according to Australian research confirming the male biological clock is ticking too.
A new study has found a man's fertility starts a steady decline from his mid-30s when sperm starts to fragment.
Researchers at Sydney IVF analysed the DNA of semen samples taken from 3,300 men in NSW and Tasmania, and found older men had less chance of fathering a child.
The find, presented at a fertility conference in Brisbane this week, is the biggest in Australia to show infertility dogs both sexes as they age.
"Drops in fertility from the age of 35 have been traditionally thought of as a fact of life for women but our study shows the same is true of men," said the centre's medical director Dr Mark Bowman.
The study showed that from the age of 35, a significant proportion of men's sperm is damaged, a process called DNA fragmentation. And the percentage of damaged sperm climbs from about 17 per cent at 35 to 22 per cent at 45.
"What this means is that even if a man produces the average of 40 million sperm per ejaculation, many of those sperm will not be able to fertilise an egg normally," Dr Bowman said.
"He will have a lower fertility potential and be less likely to father a child."
One in six Australian couples experience infertility, defined as attempting to conceive for one year without success, and specialists say delaying parenthood into the late 30s and 40s is a leading factor.
About 40 per cent of couples seeking IVF treatment do so due to a male fertility problem.
Dr Bowman said couples should consider becoming parents earlier.
"Australian men need to take their fertility seriously," he said.
"They need to be aware of their potential to become fathers and not assume that they'll be OK as their age advances."
Studies have shown that lifestyle changes, particularly giving up smoking, limiting alcohol, eating well and taking antioxidants, can help slow changes in male fertility.
Professor Rob McLachlan, director of Andrology Australia in Melbourne, said the issue of male infertility was often overshadowed.
"In the past, women have tended to be front and centre when it comes to identifying and treating infertility," Prof McLachlan said.
"Gender equality in the delivery of fertility services should be the goal of all assisted reproductive technology programs, and we need a commitment to make it happen."AAP -->
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The report said there was significant DNA damage to sperm in samples from men over the age of 35.

Oct
23
2008
Men have their own biological clock
Published by Times of the Internet at 3:34 am under Top News

SYDNEY, Oct. 22 (UPI) —


An Australian study suggests men have a biological clock that signals a drop in fertility after the age of 35.



Researchers at Sydney IVF said sperm and DNA samples from more than 3,000 men shows DNA fragmentation of sperm increased with age, the Australian Broadcasting Corp. reported Wednesday.



The report said there was significant DNA damage to sperm in samples from men over the age of 35.



They cannot take fertility absolutely for granted, there is also an impact of male age on fertility, Mark Bowman of Sydney IVF said.



Copyright 2008 by United Press International
All Rights Reserved.

Dr Kylie de Boer says the samples showed that as men age their sperm starts to fragment or break down,

Biological clock ticking for men too
By medical reporter Sophie Scott

Posted 4 hours 49 minutes ago

Video: Male biological clock ticking too (ABC News) Map: Sydney 2000
The drop off in fertility for women after the age of 35 is well known. Now Australian researchers have found that men face a similar decline at the same age.

Sydney IVF researchers took sperm samples from more than 3,000 men and their DNA or genetic make-up was examined.

Mark Bowman from Sydney IVF says they found older men had less chance of fathering a child.

"They cannot take fertility absolutely for granted, there is also an impact of male age on fertility," he said.

Dr Kylie de Boer says the samples showed that as men age their sperm starts to fragment or break down, which makes the sperm less viable for fertilising the egg.

The older the man, the more damage, researchers found.

"The rate of DNA fragmentation of sperm increased with age and there was a significant DNA damage to sperm when the man was above the age of 35," Mr Bowman said.

And while the Rupert Murdochs of this world have fathered children later in life, the new research suggests they are the exception, not the rule.

One in six Australian couples end up seeking medical treatment because they cannot conceive and in almost half of those cases it is due to male infertility.

Mr Bowman says a healthy lifestyle is one way of holding back the years.

"The messages would be limit alcohol, don't smoke, eat a healthy diet, take anti-oxidants and probably spend more time with your partner," he said.


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Long-term effects of delayed fatherhood in mice on postnatal

Long-term effects of delayed fatherhood in mice on postnatal
development and behavioral traits of offspring1
Short title: Long-term effects of paternal age on offspring
Summary sentence: Delayed fatherhood has long-term effects on preweaning development,
spontaneous motor activity and passive-avoidance learning capacity of offspring in the mouse
model
Key words: delayed fatherhood long-term effects offspring
Silvia García-Palomares3, José F. Pertusa3, José Miñarro4, Miguel A. García-Pérez5,6,
Carlos Hermenegildo5,7, Francisco Rausell3, Antonio Cano8 and Juan J. Tarín2,3
1Supported by grant BFI2003-04761 from “Ministerio de Ciencia y Tecnología”, cofinanced by
the “Fondo Europeo de Desarrollo Regional (FEDER); grant ISCIII2006-PI0405 from “Instituto
de Salud Carlos III, Fondo de Investigación Sanitaria, Ministerio de Sanidad y Consumo”,
cofinanced by the FEDER; and grants GV2004-B-206 and AE/2007/001 from “Generalitat
Valenciana, Conselleria d’Émpresa, Universitat i Ciencia”.
2Correspondence: Juan J. Tarín, Department of Functional Biology and Physical Anthropology,
Faculty of Biological Sciences, University of Valencia, Dr. Moliner 50, 46100 Burjassot,
Valencia, Spain; Tel. 34-96-354 3221; E-mail: tarinjj@uv.es
3Department of Functional Biology and Physical Anthropology, Faculty of Biological Sciences,
University of Valencia, Burjassot, 46100 Valencia, Spain










1: Biol Reprod. 2008 Oct 15. [Epub ahead of print]
Links
Long-Term Effects of Delayed Fatherhood in Mice on Postnatal Development and Behavioral Traits of Offspring.
García-Palomares S, Pertusa JF, Miñarro J, García-Pérez MA, Hermenegildo C, Rausell F, Cano A, Tarín JJ.
This study aims to analyze, in mice, the long-term effects of delayed fatherhood on postnatal development, spontaneous motor activity and learning capacity of offspring. Hybrid parental-generation (F0) males, at the age of 12, 70, 100, and 120 weeks, were individually housed with a randomly-selected 12 week-old hybrid female. The resulting first-generation (F1) offspring were tested for several developmental and behavioral variables. Cumulative percentage of F1 pups that attained immediate righting in the 120-week group was lower than that found in the 12-, 70- and 100-week groups. Furthermore, the postnatal day of attaining immediate righting was higher in pups from the 120-week group when compared to pups from the other age groups. At the age of 20 weeks, F1 offspring from the 120-week group displayed lower counts of motor activity than offspring from the 12-, 70- and 100-week groups. One week later, a higher percentage of offspring from the 100- and 120- groups entered the dark compartment during the retention trial of the passive avoidance test when compared to offspring from the 12-week group. Offspring from the 120-week group exhibited also lower step-through latency in the retention trial than offspring from the 12-, 70- and 100-week groups. These results show that advanced paternal age at conception has long-term effects on preweaning development, spontaneous motor activity and reduced passive-avoidance learning capacity of mouse offspring.
PMID: 18923158 [PubMed - as supplied by publisher]

. The results indicate that advanced paternal age at conception has negative long-term effects on reproductive fitness and longevity of offspring in

the mouse model.


Delayed fatherhood in mice decreases reproductive fitness
and longevity of offspring1
Short title: Long-term effects of paternal age on offspring
Summary sentence: Delayed fatherhood decreases reproductive fitness and longevity of
offspring in the mouse model
Key words: delayed fatherhood long-term effects offspring
Silvia García-Palomares3, Samuel Navarro4, José F. Pertusa3, Carlos Hermenegildo5,6,
Miguel A. García-Pérez5,7, Francisco Rausell3, Antonio Cano8 and Juan J. Tarín2,3
1Supported by grant BFI2003-04761 from “Ministerio de Ciencia y Tecnología”, cofinanced by
the “Fondo Europeo de Desarrollo Regional (FEDER); grant ISCIII2006-PI0405 from “Instituto
de Salud Carlos III, Fondo de Investigación Sanitaria, Ministerio de Sanidad y Consumo”,
cofinanced by the FEDER; and grants GV2004-B-206 and AE/2007/001 from “Generalitat
Valenciana, Conselleria d’Émpresa, Universitat i Ciencia”.
2Correspondence: Juan J. Tarín, Department of Functional Biology and Physical Anthropology,
Faculty of Biological Sciences, University of Valencia, Dr. Moliner 50, 46100 Burjassot,
Valencia, Spain; Tel. 34-96-354 3221; E-mail: tarinjj@uv.es
3Department of Functional Biology and Physical Anthropology, Faculty of Biological Sciences,
University of Valencia, Burjassot, 46100 Valencia, Spain
4Department of Pathology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
5Research Unit, Hospital Clínico de Valencia, 46010 Valencia, Spain
BOR Papers in Press. Published on October 15, 2008 as DOI:10.1095/biolreprod.108.073395
Copyright 2008



1: Biol Reprod. 2008 Oct 15. [Epub ahead of print]
Links
Delayed Fatherhood in Mice Decreases Reproductive Fitness and Longevity of Offspring.
García-Palomares S, Navarro S, Pertusa JF, Hermenegildo C, García-Pérez MA, Rausell F, Cano A, Tarín JJ.
This study aims to analyze, in mice, the long-term effects of delayed fatherhood on reproductive fitness and longevity of offspring. Hybrid parental-generation (F0) males, at the age of 12, 70, 100, and 120 weeks, were individually housed with a randomly-selected 12 week-old hybrid female. The reproductive fitness of first-generation (F1) females was tested from the age of 25 weeks until the end of their reproductive life. In F1 males, the testing period ranged from the age of 52 weeks until death. Breeding F1 females from the 120-week group displayed interbirth intervals longer than females from the 12-, 70- and 100-week groups. Furthermore, F2 pups begotten by F1 studs exhibited weaning weights lower than pups from the 12- and 70-week groups. Offspring from the 120-week group exhibited shorter survival times associated with lower incidence of tumorigenesis and higher loss of body weight when approaching death when compared to F1 offspring from younger age groups. The results indicate that advanced paternal age at conception has negative long-term effects on reproductive fitness and longevity of offspring in the mouse model.
PMID: 18923156 [PubMed - as supplied by publisher]