Advanced Grandparental Age as a Risk Factor for Autism

Advanced Grandparental Age as a Risk Factor for Autism

This study is currently recruiting patients.
Verified by University of Mississippi Medical Center April 2007

Sponsored by: University of Mississippi Medical Center
Information provided by: University of Mississippi Medical Center
ClinicalTrials.gov Identifier: NCT00464477


Purpose



The Division of Medical Genetics at the University of Mississippi Medical Center is recruiting parents of children with a pervasive developmental disorder (including autism, autistic spectrum disorder, PDD-NOS, Asperger syndrome, childhood disintegrative disorder, and Rett syndrome) to participate in a study to help determine potential causes of the increasing prevalence of these disorders. The study is being conducted using an anonymous on-line survey available to parents through a secure link.

The study consists of approximately 90 questions about the affected child, siblings, parents, and grandparents, which will take roughly 10-15 minutes to complete. Several families will also be invited to participate in a phone interview. Both the survey and the phone interview are conducted using a self-designated code to protect anonymity and patient privacy. No identifying information such as name, date of birth, address, or phone number will be asked. Only questions regarding the year of birth of family members will be asked.

Condition
Autistic Disorder
Pervasive Developmental Disorder
Asperger Syndrome
Childhood Disintegrative Disorder
Rett Syndrome


MedlinePlus related topics: Asperger's Syndrome; Autism; Mental Health; Rett Syndrome
Genetics Home Reference related topics: Rett syndrome

Study Type: Observational
Study Design: Natural History, Cross-Sectional, Random Sample, Retrospective Study

Official Title: Advanced Grandparental Age as a Risk Factor for Autism and Other Pervasive Developmental Disorders

Further study details as provided by University of Mississippi Medical Center:
Study start: March 2007; Expected completion: May 2007


Autism is a genetically heterogeneous entity. Although numerous studies have demonstrated a strong genetic basis, no clear etiology has been identified to date. Recently, two studies have demonstrated an increased risk of autism in children born to fathers over the age of 40. However, given the large male-to-female predominance of autism, it is likely that new mutations on the X chromosome account for a significant number of affected cases. Due to the maternal origin of the X chromosome in males, we hypothesize that advanced maternal-grandpaternal age may also be a risk factor for autism. Precedence for this theory exists with other X-linked disorders such as Duchenne muscular dystrophy and Rett syndrome. Additionally, it has been demonstrated that maternal psychiatric illness, but not paternal psychiatric illness, is more prevalent among parents of children with autism. Using anonymous surveys of families with autistic children, we seek to identify the ages of grandparents at the time the parents were born in order to determine if advanced maternal-grandpaternal age is associated with an increased risk for autism when adjusted for advanced maternal and paternal age. Additionally, we will seek out sister-pairs in order to identify any statistical significance between the ages of the maternal grandfather at delivery of each sister. If advanced maternal-grandpaternal age is, in fact, a risk factor, it would help direct molecular researchers towards genes on the X chromosome as potential etiologies for autism. Also, further study of potential mutagenic exposures in the environment of grandparents may help elucidate the reason for the increasing incidence of autism in recent decades.
Eligibility

Genders Eligible for Study: Both
Criteria
Inclusion Criteria:

Individuals of any age with autism, autistic disorder, autistic spectrum disorder, Asperger syndrome, pervasive developmental disorder, PDD-NOS, Rett syndrome, or Childhood disintegrative disorder
Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier NCT00464477

Omar Abdul-Rahman, MD 601-984-1900 OAbdulrahman@prevmed.umsmed.edu


United States, Mississippi
University of Mississippi Medical Center, Jackson, Mississippi, 39216, United States; Recruiting
Omar Abdul-Rahman, MD 601-984-1900 OAbdulrahman@prevmed.umsmed.edu



Study chairs or principal investigators

Omar Abdul-Rahman, MD, Principal Investigator, University of Mississippi Medical Center

Daughters Get Retts an X-linked Dominant Disorder Because Daughters Receive the X Chromosome With The Dominant Mutation From Their Fathers ?

1: Am J Hum Genet. 1996 Jun;58(6):1364-8. Links
High male:female ratio of germ-line mutations: an alternative explanation for postulated gestational lethality in males in X-linked dominant disorders.Thomas GH.
Department of Pediatrics, The John Hopkins University School of Medicine, Baltimore, MD, USA


In this paper I suggest that a vastly higher rate of de novo mutations in males than in females would explain some, if not most, X-linked dominant disorders associated with a low incidence of affected males. It is the inclusion of the impact of a high ratio of male:female de novo germ-line mutations that makes this model new and unique. Specifically, it is concluded that, if an X-linked disorder results in a dominant phenotype with a significant reproductive disadvantage (genetic lethality), affected females will, in virtually all cases, arise from de novo germ-line mutations inherited from their fathers rather than from their mothers. Under this hypothesis, the absence of affected males is explained by the simple fact that sons do not inherit their X chromosome (normal or abnormal) from their fathers. Because females who are heterozygous for a dominant disorder will be clinically affected and will, in most cases, either be infertile or lack reproductive opportunities, the mutant gene will not be transmitted by them to the next generation (i.e., it will be a genetic lethal). This, not gestational lethality in males, may explain the absence of affected males in most, if not all, of the 13 known X-linked dominant diseases characterized by high ratios of affected female to male individuals. Evidence suggesting that this mechanism could explain the findings in the Rett syndrome is reviewed in detail.

PMID: 8651313 [PubMed - indexed for MEDLINE


For one thing, Rett syndrome occurs sporadically more than 99% of the time



HERE IS THE ANSWER ONE MAN TWO DAUGHTERS WITH DIFFERENT MOTHERS BOTH DAUGHTERS WITH RETTS "WE SHOW THAT THE MUTATION IS PRESENT AT A LOW LEVEL IN THE DNA EXTRACT FROM THE FATHER'S(PATIENT'S) SPERM"


Clin Genet. 2006 Oct;70(4):336-8.
Germline mosaicism for a MECP2 mutation in a man with two Rett daughters
Evans JC, Archer HL, Whatley SD, Clarke A.
Department of Medical Genetics, Cardiff University, Cardiff, UK.
Abstract
Rett syndrome is a severe neurodevelopmental disorder that is caused by mutations in the X-linked gene, methyl-CpG binding protein 2 (MECP2). The majority of cases are sporadic, but rarely germline mosaicism can lead to familial cases. Here, we report the first case where germline mosaicism for a MECP2 mutation has been shown in a man. He has two affected daughters who are half sisters, and both have the c.808delC mutation. We show that this mutation is present at a low level in DNA extracted from the patient's semen. This case has implications for genetic counseling, and pre-natal testing should be offered for the partners of men who have a daughter with Rett syndrome.

Lay Summary
The vast majority of MeCP2 mutations in Rett Syndrome are sporadic mutations – that is, they are novel mutations. However, a few familial Rett Syndrome cases have been reported. In four cases, the mother was a non-symptomatic carrier; in four other cases, a “germline mosaicism” in the mother was hypothesized. That is, in a “germline mosaicism” only the germline cells (sperm, eggs) possess the mutation, and not the other cells of the body. In this study, the authors describe the first case of a germline mosaicism for Rett Syndrome in a man. Specifically, this case study describes a father with two daughters with Rett Syndrome, from two different mothers. Despite having different mothers, it was found that the Rett daughters share the similar uncommon MeCP2 mutation. Further genetic testing revealed that the mutation had been transmitted from the father’s germline – the mutation was present in DNA extracted from his sperm. As a result, the authors suggest that genetic counselling and prenatal testing should be available for men with an affected child.

Readers of this Blog May Be Interested in Reading About Single Gene Disorders Related To Advancing Paternal Age

Mutat Res. 1997 Jun 9;377(1):61-2. Links
Mutation load and human longevity.Gavrilov LA, Gavrilova NS, Kroutko VN, Evdokushkina GN, Semyonova VG, Gavrilova AL, Lapshin EV, Evdokushkina NN, Kushnareva YE.
Center for Longevity Research at A.N. Belozersky Institute, Moscow State University, Russia. gavrilov@glas.apc.org

Since paternal age at reproduction is considered to be the main factor determining human spontaneous mutation rate (Crow, J. (1993) Environ. Mol. Mutagenesis, 21, 122-129), the effect of paternal age on human longevity was studied on 8,518 adult persons (at age 30 and above) from European aristocratic families with well-known genealogy. The daughters born to old fathers (50-59 years) lose about 4.4 years of their life compared to daughters of young fathers (20-29 years) and these losses are highly statistically significant, while sons are not significantly affected. Since only daughters inherit the paternal X chromosome, this sex-specific decrease in daughters' longevity might indicate that human longevity genes (crucial, house-keeping genes) sensitive to mutational load might be located in this chromosome.

PMID: 9219579 [PubMed - indexed for MEDLINE]

May 2007 PATERNAL AGE AND AUTISM ARE ASSOCIATED IN A FAMILY-BASED SAMPLE

Letter to the Editor
Molecular Psychiatry (2007) 12, 419–421. doi:10.1038/sj.mp.4001966

Paternal age and autism are associated in a family-based sample
R M Cantor1,2,3, J L Yoon1, J Furr4 and C M Lajonchere3,4,5

1Department of Human Genetics, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA, USA
2Department of Pediatrics, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA, USA
3AGRE Consortium, Los Angeles, CA, USA
4Autism Genetic Resource Exchange, Cure Autism Now, Los Angeles, CA, USA
5Department of Pediatrics, Keck School of Medicine, University of Southern California, CA, USA
Correspondence: RM Cantor, E-mail: rcantor@mednet.ucla.edu


PMID: 17453057 [PubMed - as supplied by publisher]

The paternal age distribution of the AGRE fathers, whose first child is autistic differs significantly from that of the 'control' sample (P=0.005). A 2 goodness-of-fit test with 2 degrees of freedom was conducted using percents in the 'control' group age categories to calculate the expected values in the AGRE sample. The shift toward higher paternal ages in those with an affected first-born is seen most dramatically in the group of AGRE fathers who are 30–39 years inclusive, which is 54.7% of the distribution compared with the 41.9 % that is expected. We interpret this shifted age distribution to provide support for the recently reported finding by Reichenberg and co-workers that autism risk is associated with advancing paternal age.

What is the first mention in historical literature of the paternal age effect?

From a paper, "Human Longevity and Parental Age at Conception",by L.A. Gavrilov and N.S. Gavrilova, 2000

Thank you to Dr. Leonid Gavrilov for sending me the link to his paper because I was wondering what the early written observations of the problems of children of advanced paternal age were.


Wilhelm Weinberg (1862 — 1937)couldn't have been the first to write of the deleterious effects of older fathers on offspring.
The Gavrilovs have a section in their paper on the historical background.

"The first mention in the historical literature suggesting a possible life-shortening effect on offspring of delayed parenting was made by the French naturalist Buffon(1826), who noted that when old men procreate "they often engender monsters, deformed children, still more defective than their father"(see Robine and Allard 1997).


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HITLER'S FATHER WAS 51 WHEN HE WAS BORN!

DID ADVANCING PATERNAL AGE CAUSE THE GUNMAN TO BE BORN WITH NEUROCOGNITIVE DEVELOPMENTAL PROBLEMS? CAN WE CHANGE THE AGE THAT WE FATHER BABIES?

WHAT ARE THE DANGERS TO SOCIETY OF MEN FATHERING BABIES LATER AND LATER IN LIFE?
IS THE AUTISM EPIDEMIC CAUSED IN LARGE PART BY SO MANY MEN FATHERING BABIES PAST THE AGE OF 35?
IS THE DIABETES TYPE 1 EPIDEMIC ALSO CAUSED BY THE EPIDEMIC OF LATER FATHERING OF BABIES?

CAN WE OPEN CRYOBANKS FOR HEALTHY YOUNG MEN TO BANK SPERM FOR THEMSELVES FOR LATER FATHERING OF BABIES? YOUNG MEN ARE DOING THIS KIND SPERM BANKING FOR THEMSELVES NOW IN NEW DELHI AND MUMBAI.

IS SPORADIC DIABETES TYPE 1, AUTISM, SCHIZOPHRENIA, PROSTATE CANCER,OTHER CANCERS, MS, ALZHEIMER'S, INFERTILITY, HEMOPHILIA, DUCHENNE'S MUSCULAR DYSTROPHY, EVEN MAJOR DEPRESSION RELATED TO GENETIC MUTATIONS FROM OLDER MEN FATHERING BABIES?

IS ANYONE LOOKING FOR A PATERNAL AGE EFFECT IN THE MUTATIONS TO GENES IN TYPE 2 DIABETES? OR CROHN'S, OR LUPUS, OR RHEUMATOID ARTHRITIS, OR FIBROMYALGIA, ETC. ETC.

ADVANCED PATERNAL AGE: How old is too old?
Isabelle Bray, David Gunnel and George Davey Smith
Department of Social Medicine, University of Bristol, UK

Journal of Epidemiology amd Community Health 2006;60:851-853

"Average paternal age in the UK is increasing. The public health implications of this trend have not been widely anticipated or debated. .....Accumulated chromosomal aberrations and mutations occurring during the maturation of the male germ cells are thought to be responsible for the increased risk of certain conditions with older fathers. Growing evidence shows that the offspring of older fathers have reduced fertility and an increased risk of birth defects, some cancers and schizophrenia." ......

Classical Autism, Asperger's Syndrome, Early Childhood Schizophrenia?

What's in a name?

The term autism used to refer to "classical autism" defined by Leo Kanner.



Asperger's was defined by Hans Asperger.

Asperger syndrome
Asperger published the first definition of Asperger syndrome in 1944. In four boys, he identified a pattern of behavior and abilities that he called "autistic psychopathy", meaning autism (self) and psychopathy (personality disease). The pattern included "a lack of empathy, little ability to form friendships, one-sided conversation, intense absorption in a special interest, and clumsy movements." Asperger called children with AS "little professors" because of their ability to talk about their favorite subject in great detail. It is commonly said that the paper was based on only four boys. However, Dr. Günter Krämer, of Zürich, who knew Asperger, states that it "was based on investigations of more than 400 children".

Asperger was convinced that many of the children he identified as having autistic symptoms would use their special talents in adulthood. He followed one child, Fritz V., into adulthood. Fritz V. became a professor of astronomy and solved an error in Newton’s work he originally noticed as a child. Hans Asperger’s positive outlook contrasts strikingly with Leo Kanner's description of autism, of which Asperger's is often considered to be a high-functioning form.
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Early childhood schizophrenia.

Click on any of the links below to perform a new search
ERIC #: ED067804
Title: Early Childhood Psychosis: Infantile Autism, Childhood Schizophrenia and Related Disorders. An Annotated Bibliography 1964 to 1969.
Authors: Bryson, Carolyn Q.; Hingtgen, Joseph N.
Descriptors: Annotated Bibliographies; Autism; Clinical Diagnosis; Emotional Disturbances; Exceptional Child Education; Handicapped Children; Identification; Infants; Intellectual Development; Language Acquisition; Neurology; Perceptual Development; Psychosis; Schizophrenia; Theories; Therapy; Young Children
Source: N/A
Peer-Reviewed: N/A
Publisher: Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402 ($1.25)
Publication Date: 1972-00-00
Pages: 135
Pub Types: N/A
Abstract: The annotated bibliography on early childhood psychosis (infantile autism, childhood schizophrenia, and related disorders) contains 424 entries (books, journal articles, conference and research reports) dating from 1964 through the first 6 months of 1970, which pertain to theory, research, and treatment. Number of entries for each subject is noted in parentheses. The following topics serve to organize the entries: descriptive studies (36), differential diagnosis (27), family characteristics (21), behavioral characteristics (19), followup studies (13), intellectual development (12), perceptual processes (28), language (20), neurobiological correlates (seven), drug studies (12), electroencephalogram studies (13), skeletal, cell, biochemical, and other studies (19), psychotherapy (50), behavior therapy (78), educational programs (20), evaluation of therapy (six), and theory (43). Included is an author index. (GW)
Abstractor: N/A
Reference Count: N/A

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Lumping people with Asperger's syndrome and classical autism, and early childhood schizophrenia and mild autism into a diagnosis of autism or ASD is not at all helpful for communication. We are talking about vastly different people. Heung-sui Cho and Temple Grandin are worlds and worlds apart. Let's call Seung-hui Cho, someone who was born with childhood schizophrenia/autism in today's lingo.

They ARE probably all caused by paternal age effects over sometimes over generations, but they vary with the family and the age of the father and the family history. A son of an engineer and an uneducated woman who conceived him when he was 34 will differ from a son of a very simple man and woman who fathered him after 35. The paternal age effect on the DNA of sperm making cells over time is not good for the non-verbal intelligence or the emotional intelligence as defined by Daniel Goleman, of offspring. This may not manifest until more generations have gone by. The rule is, from my point of view, for the health of future generations, father all babies by 32 or cryobank semen in your mid 20s to 30 for any later fathering of babies. Of course the ages that I pick are not exact. In some families boys will be fine if their fathers are older than 35. There are families where the results of later paternal age do not result in mental illness, but may result in de novo Alzheimer's.



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ADVANCING PATERNAL AGE IS FOUND TO BE A RISK FACTOR FOR AUTISM IN ALL THE STUDIES THAT LOOK FOR PATERNAL AGE IN AUTISM

PRENATAL AND PERINATAL RISK FACTORS FOR AUTISM

A REVIEW and INTEGRATION OF FINDINGS

Alexander Kolevzon, MD; Raz Gross, MD, MPH; Abraham Reichenberg, PhD


Arch Pediatr Adolesc Med. 2007;161:326-333.

Objective To review the evidence for the presence of prenatal and perinatal factors that affect the risk of autism and autism spectrum disorders.

Data Sources Relevant articles were identified by searching MEDLINE, screening reference lists of original studies, and searching major journals likely to publish epidemiological studies on the topic.

.............................
Main Exposures Parental characteristics and obstetric complications.

Main Outcome Measures Rates of autism and autism spectrum disorders.

Results Seven epidemiological studies were identified that fulfilled inclusion criteria. The parental characteristics associated with an increased risk of autism and autism spectrum disorders included advanced maternal age, advanced paternal age, and maternal place of birth outside Europe or North America. The obstetric conditions that emerged as significant fell into 2 categories: (1) birth weight and duration of gestation and (2) intrapartum hypoxia.

Conclusions Evidence to suggest that parental age and obstetric conditions are associated with an increased risk of autism and autism spectrum disorders is accumulating. Although not proven as independent risk factors for autism, these variables should be examined in future studies that use large, population-based birth cohorts with precise assessments of exposures and potential confounders.

The results of this review show that 3 of the 4 population-based studies28-29,32 to examine paternal age reported a significant association with risk of autism and ASDs. The fourth study31 also found that paternal age was older in fathers of case patients with autism compared with fathers of controls, although this relationship was statistically weaker in the adjusted analysis. Thus, advancing paternal age is consistently associated with increased risk of autism and ASDs.
Advanced paternal age has been associated with several congenital disorders, including Apert syndrome,40 craniosynostosis,41 situs inversus,42 syndactyly,43 cleft lip and/or palate,44-45 hydrocephalus,44 neural tube defects,46 and Down syndrome.47 In addition, advanced paternal age has been associated with schizophrenia15 and decreased intellectual capacities in the offspring.48 The most widely proposed mechanism underlying these congenital anomalies is known as the "copy error" hypothesis, first proposed by Penrose.49 After puberty, spermatocytes divide every 16 days, and by the age of 35 years, approximately 540 cell divisions have occurred. As a result, de novo genetic mutations that result from replication errors and defective DNA repair mechanisms are believed to propagate in successive clones of spermatocytes. These mutations accumulate with advancing paternal age and thus help explain how this disorder, which has a large genetic component, can be maintained in the population despite reduced reproduction in affected individuals.






This study does not differeniate between familial and non-familial autism.

Low Birthweight and advancing paternal age have been found to go together.

DO DEFFECTS IN THE MANY GENES GOVERNING MYELIN FORMATION PLAY A LARGE ROLE IN A BOY LIKE SEUNG-HUI CHO'S MAKEUP?

George Bartzokis,M.D.


Visiting Professor

Laboratory of Neuro Imaging,
Department of Neurology, UCLA School of Medicine
635 Charles Young Drive South, Suite 225
Los Angeles, CA 90095-7332



Education

1975-1979, BA Harvard University, Cambridge, MA
1979-1983, MD Yale Medical School, New Haven, CT
1983-1984, Internship, UCLA/WLA VA, Los Angeles, CA
1984-1987, Psychiatry Residency, UCLA NPI, Los Angeles, CA
1987-1990, Schizophrenia Research Fellow, UCLA Dept of Psychology, Los Angeles, CA


Research

Development of brain imaging biomarkers for use in diagnosis of neuropsychiatric disorders and medication development
Assessing brain maturation and degeneration trajectories over the life-span in normal populations and how neuropsychiatric disorders interact with these processes


Projects

Myelin breakdown in aging and Alzheimer's disease
In vivo quantification of age-related increases in brain iron levels
Evaluation of brain maturational trajectories in normal adults and patientss with neuropsychiatrc diseases


Skills

Quantification of brain iron levels
Quantification of limbic structures volumes
Quantification of brain myelination
Quantification of myelin integrity
Clinical trials
Administration of multidisciplinary teams


Honors

U.S. Patent, Method for Quantitatively Measuring Stored Iron in Tissue Using MRI










This quote is not from a published paper.
I had asked Dr. Bartzokis why risk of non-familial autism, schizophrenia, MS, and Alzheimer's risk increases with the age of the father at a person's birth.



"The issue is that the older man will have sperm that has undergone more divisions and therefore had more chances to have mutations.
The COMPLEXITY of the myelination process makes it more vulnerable to mutations. I am not talking of one specific mutation. Many things could MANIFEST in the myelination or myelin breakdown process because it is so vulnerable - something going slightly wrong will impact it while it will not impact bone growth or the heart. A good example is ApoE4 - whatever else it may affect, it manifests in the reduced capacity of myelin repair and earlier onset of AD."

All donors are between 18 and 35 years of age in order to minimize age related genetic abnormalities.

Northwest Andrology & Cryobank Inc. sperm bank is committed to providing the industry's highest level of professional services for our donors and clients.




Donor Standards

Our donors are recruited from the Northwest US. Most of our donors are either starting, currently involved with, or have finished their higher education at the time of their participation in our donor program. All donors are between 18 and 35 years of age in order to minimize age related genetic abnormalities.

POLICE IDENTIFIED THE SHOOTER'S FATHER AS CHO SEONG-TAE, 61

Father's age:


South Korea's largest newspaper Chosun Ilbo reported that Cho's family was poor when they lived in a Seoul suburb and decided to emigrate to seek a better life.

The family lived in a rented, basement apartment - usually the cheapest unit in a multi-apartment building, the newspaper reported quoting building owner Lim Bong-ae, 67. Police identified the shooter's father as Cho Seong-tae, 61.

"I didn't know what (Cho's father) did for a living. But they lived a poor life," Lim told the newspaper. "While emigrating, (Cho's father) said they were going to America because it is difficult to live here and that it's better to live in a place where he is unknown."

Meanwhile, South Korean President Roh Moo-hyun held a special meeting with aides today to discuss the shooting, as the public expressed shame over a South Korean citizen being identified as the gunman.

Roh was to speak publicly about the tragedy later in the day, his office said, without elaborating on what the president discussed at the meeting with aides.

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Sung Cho, 61, and Hyang Cho, 56, kept a low profile in the small town, attending services at the Korean Presbyterian Church and planting lettuce in the backyard of their home.

"The most irrefutable finding is our demonstration that a father’s age is a major risk factor for schizophrenia."

The title is a quote from Dr. Dolores Malaspina


Poor, rural roots

Cho's parents have always struggled to make ends meet.

Sung-tae Cho, the killer's father, came from a poor rural area. He was a "country bumpkin" and considerably older than his wife, the daughter of a refugee, said Seung-hui Cho's great-aunt, Kim Yang-soon. "We practically forced her to get married."

Hyang-im's father had fled south during the Korean War that separated the south from its communist northern neighbor, according to Korean news reports.

Sung-tae and Hyang-im Cho were ambitious and apparently educated because after they settled on the still semi-rural outskirts of Seoul, they bought a used-book store. One could make a decent living selling secondhand books in the 1970s, before South Korea's economy began to boom. But one relative said the bookstore just eked out a profit.

To ease his family's plight, Sung-tae Cho left his wife behind to be a laborer in the Middle East, working on oil fields and construction sites in Saudi Arabia for most of the 1980s.

Back home, his wife gave birth March 22, 1982, to their daughter, Sun-kyung. On Jan. 18, 1984, Seung-hui was born.

For the first few years of Seung-hui Cho's life, the family lived in a dark, damp basement apartment on a busy commercial street in Shinchang, a suburb of Seoul. They lived at the bottom of a three-story, red-brick home, and paid $150 a month, a bargain even then.

Cho attended an elementary school a short walk from his home. About 950 students attend today, about half the number when Cho was there. The cluster of three-story buildings frames a large, U-shaped dirt courtyard.

The school files contain only a single sheet of paper on Cho, showing he left the school in August 1992, at age 8, after partially completing second grade.

"We don't know anything about that student," said the vice principal, who refused to identify himself. "And I'd like to point out that he did not graduate from here."

Sung-Tai Cho, the Killer's Father ....He Was a "Country Bumpkin" and CONSIDERABLY OLDER THAN CHO'S MOTHER

Sung-Tae Cho, the killer's father, came from a poor rural area. He was a "country bumpkin" and considerably older than Cho's mother, Hyang-Im Kim, the daughter of a refugee, said Cho's great-aunt, Kim Yan-Soon. "We practically forced her to get married."

A Vivid Portrait - Paternal Age? Family History?

THE NEW YORK TIMES

April 22, 2007


Before Deadly Rage, a Life Consumed by a Troubling Silence



By N. R. KLEINFIELD
Published: April 22, 2007
From the beginning, he did not talk. Not to other children, not to his own family. Everyone saw this. In Seoul, South Korea, where Seung-Hui Cho grew up, his mother agonized over his sullen, brooding behavior and empty face. Talk, she just wanted him to talk.




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An Isolated Boy in a World of Strangers
Cho's Behavior Alarmed Some Who Knew Him; Family 'Humbled by This Darkness'

By David Cho and Amy Gardner
Washington Post Staff Writers
Saturday, April 21, 2007; Page A01

Warning signs about Seung Hui Cho came early in his life.

Cho was unusually quiet as a child, relatives said. He did not respond to greetings. He did not want to be hugged. But when Cho fought with his older sister, he would punch her with shocking violence.


Kim Yang Soon, a great-aunt in Korea, said Cho's mother told her the boy had autism. After the family immigrated to the United States in 1992, when Cho was 8, Kim would call his mother and ask how the boy was doing. "She only talked about her daughter," Kim said. "We knew something was wrong."

neuroendocrine cells of the intestinal epithelium have a role to play in Crohn's Disease

Another neuroendocrine disorder probably due to increased paternal age. I've heard there is an epidemic of children with Crohn's.


Researchers Discover Genes Associated with Crohn’s Disease
Apr 17 2007, 12:38 PM EST
GEN News Highlights


A search of the entire human genome revealed three genes linked to increase the risk of developing inflammatory bowel disease. Additionally, the study identified two regions of the genome where genetic risk factors are located but no known genes were implicated.

The researchers found that PHOX2B, NCF4, and ATG16L1 constitute genetic risk factors for Crohn's disease or colitis as well as numerous biological pathways not previously thought to play a role in Crohn's disease.

"The identification of the PHOX2B gene in this study may implicate a role for neuroendocrine cells of the intestinal epithelium as having a role to play in Crohn's Disease,” reports John D. Rioux, Ph.D., associate professor of medicine at the Montreal Heart Institute and the Universite de Montreal.

“In addition, the identification of the NCF4 gene indicates that altered reactive oxygen species production, important in the generation of an effective antimicrobial response, may lead to increased risk of developing the disease.”

The fact that the authors also found strong association of the ATG16L1 gene provides further evidence that an individual's response to microbes has an influence on susceptibility to Crohn's disease.

In addition to demonstrating its association to the disease, the authors found that ATG16L1 is essential for the normal autophagic process used to degrade worn-out cellular components and help eliminate some pathogenic bacteria. "We propose that genetic variation in the ATG16L1 gene leads to alterations in how the body uses autophagy and therefore may result in increased persistence of both cellular and bacterial components, leading to inappropriate immune activation and increased risk of Crohn's disease" adds Dr. Rioux.

The report appears in the April 15 online edition of Nature Genetics.

Researchers Discover Genes Associated with Crohn’s Disease
Apr 17 2007, 12:38 PM EST
GEN News Highlights


A search of the entire human genome revealed three genes linked to increase the risk of developing nflammatory bowel disease. Additionally, the study identified two regions of the genome where genetic risk factors are located but no known genes were implicated.

The researchers found that PHOX2B, NCF4, and ATG16L1 constitute genetic risk factors for Crohn's disease or colitis as well as numerous biological pathways not previously thought to play a role in Crohn's disease.

"The identification of the PHOX2B gene in this study may implicate a role for neuroendocrine cells of the intestinal epithelium as having a role to play in Crohn's Disease,” reports John D. Rioux, Ph.D., associate professor of medicine at the Montreal Heart Institute and the Universite de Montreal.

“In addition, the identification of the NCF4 gene indicates that altered reactive oxygen species production, important in the generation of an effective antimicrobial response, may lead to increased risk of developing the disease.”

The fact that the authors also found strong association of the ATG16L1 gene provides further evidence that an individual's response to microbes has an influence on susceptibility to Crohn's disease.

In addition to demonstrating its association to the disease, the authors found that ATG16L1 is essential for the normal autophagic process used to degrade worn-out cellular components and help eliminate some pathogenic bacteria. "We propose that genetic variation in the ATG16L1 gene leads to alterations in how the body uses autophagy and therefore may result in increased persistence of both cellular and bacterial components, leading to inappropriate immune activation and increased risk of Crohn's disease" adds Dr. Rioux.

The report appears in the April 15 online edition of Nature Genetics.

Cho Seung-Hui Diagnosed With Autism As A Child

AutismLink Reacts to Diagnosis of Autism in Virginia Tech Shooter



PITTSBURGH, April 19 /PRNewswire-USNewswire/ -- AutismLink and Autism
Center of Pittsburgh Director Cindy Waeltermann today issued a statement
regarding the recent revelation that Virginia Tech shooter Cho Seung-Hui
was diagnosed with autism as a child.
"While the entire autism community in Pittsburgh and across the nation
are devastated by the recent events at Virginia Tech, we would like to
caution the public not to stigmatize children or individuals with autism.
Cho likely did not receive the help and support that he needed early on --
that is why early intervention is so important, and that is why places like
the Autism Center of Pittsburgh exist. The act of one individual should not
reflect upon the entire autistic population.
It is unfair to blame Cho's actions on autism when he was clearly
psychologically impaired and likely had another disorder in addition to his
autism. His psychological evaluations apparently revealed a dark history
that concluded that he was an imminent danger to himself and others and was
also depressed.
This is a wake up call that stresses the importance of early
intervention, research, and appropriate treatment strategies. Many strides
have been made in autism spectrum disorders and research has consistently
shown that when children receive the help that they need early on they are
more likely to become more adept at social and communication skills.
Autism affects 1 in 150 children and is now the most commonly diagnosed
developmental disability in the world. It is time to recognize autism for
the epidemic it is."


-------------------------------------------------------------------------------------

Cho's great-aunt, Kim Yang-soon, said Cho was diagnosed with autism after coming to U.S. in 1992. Speaking from her home in South Korea, she described Cho as "very cold" and said her niece was constantly worried about him.

Meta Win ((R)) Was Performed-PATERNAL AGE 35 AND ABOVE-HIGHER RATE FOR SCHIZOPHRENIA

WHY WASN'T THIS A HEADLINE IN ALL THE PAPERS LIKE THE ANTIDEPRESSENT STORY APRIL 18TH?


Eur Psychiatry. 2006 Dec 1; : 17142012
Paternal ages below or above 35 years old are associated with a different risk of schizophrenia in the offspring.
[My paper] M Wohl , P Gorwood
BACKGROUND: A link between older age of fatherhood and an increased risk of schizophrenia was detected in 1958. Since then, 10 studies attempted to replicate this result with different methods, on samples with different origins, using different age classes. Defining a cut-off at which the risk is significantly increased in the offspring could have an important impact on public health. METHODS: A meta-analysis (Meta Win((R))) was performed, assessing the mean effect size for each age class, taking into account the difference in age class references, and the study design. RESULTS: An increased risk is detected when paternal age is below 20 (compared to 20-24), over 35 (compared to below 35), 39 (compared to less than 30), and 54 years old (compared to less than 25). Interestingly, 35 years appears nevertheless to be the lowest cut-off where the OR is always above 1, whatever the age class reference, and the smallest value where offspring of fathers below or above this age have a significantly different risk of schizophrenia. CONCLUSION: No threshold can be precisely defined, but convergent elements indicate ages below or above 35 years. Using homogeneous age ranges in future studies could help to clarify a precise threshold.

Non-Verbal Child

"Seung-Hui troubled his parents when he was young because he wouldn't talk, but he was well-behaved. I don't know how I can compensate for the responsibility for raising my kids improperly," Mr Kim told the Dong-A Ilbo newspaper.

Kim's sister said she remembered Seung-Hui as a quiet child.

"He was a good-looking boy but he wouldn't talk. If I nudged him and tried to talk with him, he wouldn't answer," Kim Yang-soon, 84, told Reuters Television.

The apartment owner says Cho's father told him it would be better to live in "a place where he is unknown."


The gunman's family lived in an off-white, two-story townhouse in Centreville.
"He was very quiet, always by himself," neighbor Abdul Shash said of the gunman.
Shash said the gunman spent a lot of his free time playing basketball, and wouldn't respond if someone greeted him. He described the family as quiet

But she said friends of hers who went to middle school with Cho told her they recalled him getting picked on there.

"There were just some people who were really mean to him and they would push him down and laugh at him," Roberts said Wednesday. "He didn't speak English really well and they would really make fun of him."

More Information About PERC/DRY CLEANING

Acute Exposure


VIRGINIA TECH GUNMAN ---- HIS EXPOSURE TO PERC SINCE CHILDHOOD COULD BE THE CAUSE OF HIS MENTAL DERANGEMENT


Tetrachloroethylene probably depresses the CNS through a solvent effect on lipids and protein components of neural membranes. It defats the skin, causing redness, blistering, and scaling. Organ damage, primarily liver and kidney, may occasionally be seen. CNS effects appear immediately during and following exposure, while organ damage may be delayed for hours to days. Most inhaled or ingested tetrachloroethylene leaves the body unchanged in exhaled air. Only 1% to 3% is metabolized (though there is considerable individual variation), and residual organ damage is not commonly observed.

Children do not always respond to chemicals in the same way that adults do. Different protocols for managing their care may be needed.

CNS
Tetrachloroethylene causes dose-related CNS and respiratory depression, but transient initial CNS excitation can also occur. Symptoms can include irritability, impaired coordination, lightheadedness, headache, slurred speech, malaise, nausea, ataxia, sedation, coma, and death. Sublethal CNS effects generally resolve quickly when the victim is removed from further exposure, but may be delayed due to fat uptake. CNS effects can also be prolonged following ingestion exposure.



A CBS PIECE ON THE DANGERS OF PERC


According to the EPA's Web site, "Breathing PERC for short periods of time can adversely affect the human nervous system. Effects range from dizziness, fatigue, headaches, and sweating, to incoordination and unconsciousness. Contact with PERC vapor irritates the skin, eyes, nose, and throat. These effects are not likely to occur at levels of PERC that are normally found in the environment. Breathing PERC over longer periods of time can cause liver and kidney damage in humans. Workers repeatedly exposed to large amounts of PERC in air can also experience memory loss and confusion. Laboratory studies show that PERC causes kidney and liver damage and cancer in animals exposed repeatedly by inhalation and by mouth. Repeat exposure to large amounts of PERC in air may likewise cause cancer in humans."

You may have gotten a whiff of PERC's strong, fresh scent at your cleaners but, once PERC evaporates into the air, you can't always smell it.

Mickelson had no idea her home was so contaminated until, one day, she literally collapsed from the fumes, and was rushed to the hospital.

"The city Department of Health did tests on us and our neighbors, and it was in our breath and our urine and in my breast milk and my neighbor's breast milk; it was basically everywhere," she says.

Even wearing dry cleaned clothes may put you at risk, Smith observes.

In the first study of its kind, Consumer Reports magazine measured PERC emissions from freshly dry-cleaned blazers and the results, Smith says, were "startling."

The magazine's Jean Halloran says, "We found that there was a small, but definitely increased risk of cancer from wearing freshly dry-cleaned clothes once or twice a week."

The industry calls that junk science.

"When handled properly, PERC is "extremely safe," says Nora Nealis, who runs the National Cleaners Association."

She says studies of workers at dry cleaners have found no increased risk of cancer, even after years of PERC exposure.

"I have friends and neighbors and family members who are in the dry cleaning industry," Nealis adds, "and I have no compunction whatsoever about their health or safety."

But some regulators aren't buying that.

Last month, California became the first state in the nation to ban PERC, calling it a public health threat. They ordered it phased out at dry cleaners over the next 15 years.


California phases out dry-cleaning solvent
SACRAMENTO, Jan. 26 (UPI) -- California is the first state to enact a gradual ban on a dry-cleaning solvent that has been linked to several cancers.

The California Air Resources Board voted 9-0 to ban the purchase of new machines that use the chemical perchloroethylene, or perc, as of 2008, The Los Angeles Times reported Friday.

All perc machines are to be phased out by 2023.

"It's very important to public health to move in the direction of eliminating perc from dry-cleaning facilities in California. ... But a lot of people are going to be affected by what we do today. There has to be a sense of fairness," said board member Barbara Riordan, one of four board members who voted Thursday against a quicker ban supported by environmental groups, the Times said.

The U.S. Environmental Protection Agency has rejected a ban on perc machines, instead phasing them out only at dry cleaners in residential buildings.

"Tightening the rules for dry cleaners is an important step in the agency's comprehensive strategy to protect public health. EPA remains committed to the phase-out in residential buildings," spokeswoman Jessica Emond told the Times.

Copyright 2007 by United Press International. All Rights Reserved.



The South Coast Air Quality Management District (SCAQMD) in Diamond Bar, CA, which oversees the Los Angeles area, has approved a first-of-its-kind plan to ban the use of the solvent Perchloroethylene (perc) in drycleaners by 2020, despite strong opposition from perc producers. The plan ..



Some studies suggest that repeated, frequent overexposure to some organic solvents over months or years may have long-lasting and possibly permanent effects on the nervous system. The exposure levels at which these effects occur are not known, and the effects have not been studied in workers exposed only to perc.

The symptoms of these long-term effects include fatigue, poor muscle coordination, difficulty in concentrating, loss of short-term memory, and personality changes such as increased anxiety, nervousness and irritability.








WEB EXCLUSIVE
By Jamie Reno
Newsweek
Updated: 4:49 p.m. PT Feb 21, 2007
Feb. 21, 2007 - It wasn't exactly "Mr. Smith Goes to Washington," but when Gordon Shaw appeared last month at the California Air Resources Board meeting in Sacramento to extol the virtues of his environmentally friendly dry-cleaning operation, he spoke with almost Capraesque idealism. "I opened the first 100 percent all-natural liquid carbon dioxide dry cleaner on the West Coast to create a competitive advantage, and to try to positively revolutionize my industry," he told the seven-member board, which monitors California air pollution and related health issues. "I get a tremendous sense of fulfillment as





What are the human health concerns associated with perc?
The extent of any health effects from perc exposure depends on the amount of perc and how long the exposure lasts. People exposed to high levels of perc, even for brief periods, may experience serious symptoms. Those include dizziness, fatigue, headaches, confusion, nausea, and skin, lung, eye and mucous membrane irritation. Repeated exposure to high levels can also irritate the skin, eyes, nose and mouth, and can cause liver damage and respiratory failure. Perc might cause effects at lower levels as well.

Studies in laboratory animals indicate that exposures to high levels of perc can produce effects on the developing fetus that include altered growth, birth defects, and death. While there have been studies of people who are exposed to high levels of perc, the studies are limited and inconclusive. Scientists have not yet determined whether perc exposures can cause such adverse effects in pregnant women as increased incidence of miscarriage or reproductive effects, affect women's fertility, or affect children born to parents exposed to high levels of perc

Risk of Schizophrenia in Offspring of Dry Cleaners Very High

Tetrachloroethylene use by dry cleaners and Schizophrenia risk in offspring:
It has been reported that the VT gunman's parents own a dry cleaners shop.






Schizophr Res. 2007 Feb;90(1-3):251-4. Epub 2006 Nov 17. Links
Tetrachloroethylene exposure and risk of schizophrenia: offspring of dry cleaners in a population birth cohort, preliminary findings.Perrin MC, Opler MG, Harlap S, Harkavy-Friedman J, Kleinhaus K, Nahon D, Fennig S, Susser ES, Malaspina D.
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, 10032, USA. mcp20@columbia.edu

Tetrachloroethylene is a solvent used in dry cleaning with reported neurotoxic effects. Using proportional hazard methods, we examined the relationship between parental occupation as a dry cleaner and risk for schizophrenia in a prospective population-based cohort of 88,829 offspring born in Jerusalem from 1964 through 1976, followed from birth to age 21-33 years. Of 144 offspring whose parents were dry cleaners, 4 developed schizophrenia. We observed an increased incidence of schizophrenia in offspring of parents who were dry cleaners (RR=3.4, 95% CI, 1.3-9.2, p=0.01). Tetrachloroethylene exposure warrants further investigation as a risk factor for schizophrenia.

PMID: 17113267 [PubMed - in process]


PERC—A STAIN ON THE DRY CLEANING INDUSTRY
New Types of Dry Cleaning That Are Better for the Environment and Safer for You
Darn that stain Uncle Harry got on your best sweater when he spilled his home-brewed honey-rutabaga beer on you at the family's holiday get-together. Curse the lingering scent of "Eau de Midnight Pasture" perfume that Grandma Jean's hug left on your sport coat. Well, off to the cleaners!

There are over 30,000 dry cleaning facilities for you to choose from in the United States, but 95 percent of them use the toxic chemical perchloroethylene (perc) as the primary cleaning solvent. Exposure to perc is a significant risk to the workers who dry clean the clothes, and it's also a health risk to you and the loved ones who share your home. Once you get the dry-cleaned clothes home, they continue to off-gas perc into the air in your abode.

The National Institute of Environmental Health Sciences states that: "Short-term exposure to PERC can cause adverse health effects on the nervous system that include dizziness, fatigue, headaches, sweating, incoordination, and unconsciousness. Long-term exposure can cause liver and kidney damage." The International Association for Research on Cancer classifies perc as a probable carcinogen.

Fortunately, there are healthier (and greener) dry-cleaning alternatives. Here they are:

The actual percentage of cases with paternal germ line-derived schizophrenia in given population will depend on demographics of paternal childbearing

Is there going to be more violence because we have ignored the science of the male biological clock? If there is so much more autism, so much more diabetes type 1, how much more schizophrenia is there in the USA? Men could change the age they fathered babies if the knew the repercussions. There is the option for cryobanking sperm.


Schizophrenia Risk and the Paternal Germ Line
By Dolores Malaspina


Dolores Malaspina
Paternal age at conception is a robust risk factor for schizophrenia. Possible mechanisms include de novo point mutations or defective epigenetic regulation of paternal genes. The predisposing genetic events appear to occur probabilistically (stochastically) in proportion to advancing paternal age, but might also be induced by 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 germ line cause an independent and common variant of schizophrenia.

Seminal findings
We initially examined the relationship between paternal age and the risk for schizophrenia because it is well established that paternal age is the major source of de novo mutations in the human population, and most schizophrenia cases have no family history of psychosis. In 2001, we demonstrated a monotonic increase in the risk of schizophrenia as paternal age advanced in the rich database of the Jerusalem Perinatal Cohort. Compared with the offspring of fathers aged 20-24 years, in well-controlled analyses, each decade of paternal age multiplied the risk for schizophrenia by 1.4 (95 percent confidence interval: 1.2-1.7), so that the relative risk (RR) for offspring of fathers aged 45+ was 3.0 (1.6-5.5), with 1/46 of these offspring developing schizophrenia. There were no comparable maternal age effects (Malaspina et al., 2001).

There seems to be an interest in a maternal age effect

Some papers have found differing maternal age effects in a daughter's risk of breast cancer. Here is one that claims that a daughter's risk rises with maternal age. I have found great differences in the findings in this regard. Some research have found a U shape some a J shape. It does seem that increased maternal and paternal ages have an effect on the risk for non-familial breast cancer.

Maternal age, parity, and pregnancy estrogens
Journal Cancer Causes and Control
Publisher Springer Netherlands
ISSN 0957-5243 (Print) 1573-7225 (Online)
Subject Biomedical and Life Sciences
Issue Volume 1, Number 2 / September, 1990
Category Research Papers
DOI 10.1007/BF00053162
Pages 119-124
SpringerLink Date Thursday, November 04, 2004

Maternal age, parity, and pregnancy estrogens
Kelly Panagiotopoulou, Klea Katsouyanni, Eleni Petridou, Yannis Garas, Anastasia Tzonou and Dimitrios Trichopoulos

Received: 29 March 1990 Accepted: 11 June 1990

Total estrogens (TE), estradiol (E2), estriol (E3), and human placental lactogen (hPL) were determined by radioimmunoassay in the blood of 126 pregnant women during their 26th and 31st weeks of pregnancy and the results were studied in relation to maternal age and parity. Total estrogens and E2 were lowest among the youngest women (<20 years) and highest among women aged 20–24 years, whereas older women (25 + years) had, on the average, intermediate values. For E3 the pattern was qualitatively similar to that of TE and E2 but less striking, and no maternal age pattern was evident with respect to hPL. Within maternal age groups, TE and E2 were higher among women in the first, than among those in their second, full-term pregnancy; the difference was about seven percent for TE (P=0.14) and about 14 percent for E2 (P=0.05). No parity patterns were evident with respect to E3 and hPL. There were fairly strong correlations between the determinations of the same hormone in the same woman during the 26th and 31st weeks of pregnancy; Pearson correlation coefficients were 0.60 for TE, 0.78 for E2, 0.60 for E3, and 0.72 for hPL. Since the risk of breast cancer increases apparently monotonically with maternal age at birth, the present data are equivocal with respect to the hypothesis linking levels of pregnancy estrogens to risk of breast cancer in the offspring. However, the data are compatible with hypotheses linking excessive pregnancy-estrogen exposure to conditions more common among first-born individuals, including testicular cancer and cryptorchidism.
Key words Breast neoplasms - estrogens - maternal age - parity

Drs Panagiotopoulou, Katsouyanni, Petridou, Garas, and

WHY DOESN'T THE CDC OR THE MARCH OF DIMES WARN ABOUT THE REALITY OF PATERNAL AGE and GENETIC DISORDERS?

1: World J Urol. 1993;11(2):137-40. Links
The effect of age on male reproductive function.Murray MJ, Meacham RB.
Department of Surgery, University of Colorado, Health Sciences Center, Denver 80262.

When couples elect to defer child bearing, the effects of age on reproductive potential must be considered. The impact of advancing age on female reproductive potential has been well documented. Relatively less attention, however, has been directed toward the effect of age on male reproductive function. Although less pronounced than its effect on female fertility, advancing age does have an impact on male reproduction. Among men, increasing age is associated with a decrease in sexual function as well as changes in testicular histology and a decline in basic fertility parameters. Additionally, there is an identifiable association between advanced paternal age and subsequent birth defects. These issues should be borne in mind when men are counseled regarding the age at which they elect to establish families.

PMID: 8343797 [PubMed - indexed for MEDLINE]










FMI | One On One | Problem Solver | Medical Watch | Arrest Logs | ABC News Feeds




By Deanna Lambert
E-mail | Biography
One in eight babies is born premature every year in the United States. On January 22, 2005 Joe Watson became one of those babies. He weighed only 2 pounds when he was born at 26 weeks, but Joe was fighting desperatly to hang on to life.

His mother, Glenda Watson says at first the doctors said her son wouldn't survive. "When I first went into labor, the doctors said there wasn't much chance at him making it unless I stayed in bed, kept pregnancy on a little longer."

Joe's father, Doug Watson recalls his son's birth as scary. "Well it was all pretty scary. He was almost 3 months early and we didn't know what kinds of problems we might face."

Glenda found out she was pregnant at the age of 47. A mother's age is a risk factor for preterm birth according to information from the March of Dimes.

Between 2002-2004 in Florida, 17% of premature babies were born to mothers over the age of 40, followed by 15% to teenage moms.

Joe may have been born small and weak, wearing diapers about the size of a business card, but today he's grown into one of the strongest advocates for the March of Dimes. He is this year's 2008 March of Dimes Ambassador for the March for Babies.

Joe is now 3 years old and on April 26th, he will lead the line of marchers in Panama City for this year's March for Babies.

All money raised by teams go to support the March of Dimes, which is an organization that the Watsons' credit with saving thier son's life.

Glenda says, "I say without the March of Dimes, doctors, and of course God, we wouldn't have Joe. The March of Dimes has done a lot of research, come up with a lot of drugs that helped his lungs while he was inside me and after he was born." Doug agrees. "10 or 15 years ago, there probably wouldn't be near the survival rate there is now. It's because of the research of the March of Dimes who help babies like Joe come into the world and be healthy."

Bay County's March for Babies will be on Saturday April 26, 2008 at McKenzie Park in Panama City. Registration begins at 8 am. The walk sarts at 9am.

You can register a team by clicking here. For more information about the March of Dimes and how to volunteer in our area, call their office at (850) 785-6460.

The March of Dimes Never mentions this study:




Paternal Age and Preterm Birth.
Brief Reports Epidemiology. 16(2):259-262, March 2005.Zhu, Jin Liang *; Madsen, Kreesten M. *; Vestergaard, Mogens +; Basso, Olga *; Olsen, Jorn *
Abstract: Background: There is growing evidence that advanced paternal age can be a reproductive hazard.
Methods: We studied couples and their first children using nationwide registers in Denmark between 1980 and 1996. We restricted the analysis to mother's age 20-29 years. We estimated odds ratios (ORs) of preterm (<37 weeks gestation) and very preterm birth (<32 weeks) as a function of paternal age using logistic regression to adjust for potential confounding variables.
Results: The risk of preterm birth increased with paternal age, almost entirely resulting from an association for very preterm birth. Compared with fathers age 20-24 years, ORs for very preterm birth were 1.3 (age 25-29), 1.4 (age 35-39), 1.7 (age 40-44), 1.6 (age 45-49), and 2.1 (age 50+) (test for trend: P = 0.01).
Conclusions: Risk of very preterm birth increases among older fathers, perhaps as a result of a paternal placental effect.
(C) 2005 Lippincott Williams & Wilkins, Inc.
Copyright © 2007, Lippincott Williams & Wilkins. All rights reserved.Published by Lippincott Williams & Wilkins.Copyright/Disclaimer Notice • Privacy Policy Subscribe

These findings suggest that older fathers produce higher frequencies of XY sperm,

1: Am J Hum Genet. 2001 Nov;69(5):1046-54. Epub 2001 Oct 1. Links
Frequency of XY sperm increases with age in fathers of boys with Klinefelter syndrome.Lowe X, Eskenazi B, Nelson DO, Kidd S, Alme A, Wyrobek AJ.
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.

With increasing availability of drugs for impotence and advanced reproductive technologies for the treatment of subfertility, more men are fathering children at advanced ages. We conducted a study of the chromosomal content of sperm of healthy men aged 24-57 years to (a) determine whether father's age was associated with increasing frequencies of aneuploid sperm including XY, disomy X, disomy Y, disomy 21, and sperm diploidy, and (b) examine the association between the frequencies of disomy 21 and sex-chromosomal aneuploidies. The study group consisted of 38 fathers of boys with Klinefelter syndrome (47, XXY) recruited nationwide, and sperm aneuploidy was assessed using multicolor X-Y-21 sperm FISH ( approximately 10,000 sperm per donor). Paternal age was significantly correlated with the sex ratio of sperm (Y/X; P=.006) and with the frequency of XY sperm (P=.02), with a clear trend with age by decades (P<.006). Compared with fathers in their 20s (who had an average frequency of 7.5 XY sperm per 10,000), the frequencies of XY sperm were 10% higher among fathers in their 30s, 31% higher among those in their 40s, and 160% higher among those in their 50s (95% CI 69%-300%). However, there was no evidence for age effects on frequencies of sperm carrying nullisomy sex; disomies X, Y, or 21; or meiosis I or II diploidies. The frequencies of disomy 21 sperm were significantly associated with sex-chromosomal aneuploidy (P=.04)-in particular, with disomy X (P=.004), but disomy 21 sperm did not preferentially carry either sex chromosome. These findings suggest that older fathers produce higher frequencies of XY sperm, which may place them at higher risk of fathering boys with Klinefelter syndrome, and that age effects on sperm aneuploidy are chromosome specific.

PMID: 11582569 [PubMed - indexed for MEDLINE]

Mean paternal age 38.7 in Thai children with Crouzon and Apert sydromes

: J Craniofac Surg. 2003 Jan;14(1):101-4; discussion 105-7. Links
FGFR2 mutations among Thai children with Crouzon and Apert syndromes.Shotelersuk V, Mahatumarat C, Ittiwut C, Rojvachiranonda N, Srivuthana S, Wacharasindhu S, Tongkobpetch S.
Chulalongkorn Craniofacial Center, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. vorasuk.s@chula.ac.th

Crouzon and Apert syndromes have been reported to be associated with mutations in Fibroblast Growth Factor Receptor 2 (FGFR2) gene in various ethnic groups, but never in Southeast Asian subjects. Therefore, the authors conducted a study to characterize 11 Thai patients: four with Crouzon syndrome and seven with Apert syndrome. All cases are sporadic. Mean paternal and maternal ages were 38.7 and 28.6 years, respectively. Molecularly, all patients were found to have mutations in the FGFR2 gene. Three mutations (C278F, S347C, S351C) were detected in all Crouzon patients with two having S351C. The seven patients with Apert syndrome have either S252W or P253R mutation. The authors' findings that sporadic cases were associated with advanced paternal age and that they all had mutations in FGFR2 are consistent with previous reports. This is another observation supporting the causative role of FGFR2 mutations in Crouzon and Apert syndromes.

KAISER STUDY FINDS PATERNAL AGE AND MATERNAL AGE RISK FACTORS FOR AUTISM

Vol. 161 No.4 April, 2007

Maternal and Paternal Age and Risk of Autism Spectrum Disorders
Lisa A. Croen, PhD; Daniel V. Najjar, MS; Bruce Fireman, MA; Judith K. Grether, PhD


Arch Pediatr Adolesc Med. 2007;161:334-340.

Objective To explore the association between maternal and paternal age and risk of autism spectrum disorders (ASDs) in offspring.

Design Historical birth cohort study.

Setting Kaiser Permanente (KP) in Northern California.

Participants All singleton children born at KP from January 1, 1995, to December 31, 1999, were included in the study. We identified 593 children who had ASD diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification, code 299.0 or 299.8) recorded 2 or more times in KP outpatient databases before May 2005. These children were compared with all 132 251 remaining singleton KP births.

Main Exposures Maternal and paternal age at birth of offspring.

Results Risk of ASDs increased significantly with each 10-year increase in maternal age (adjusted RR, 1.31; 95% confidence interval [CI], 1.07-1.62) and paternal age (RR, 1.28; 95% CI, 1.09-1.51). Adjusted RRs for both maternal and paternal age were elevated for children with autistic disorder (maternal age: RR, 1.18; 95% CI, 0.87-1.60; paternal age: RR, 1.34; 95% CI, 1.06-1.69) and children with Asperger disorder or pervasive developmental disorder not otherwise specified (maternal age: RR, 1.45; 95% CI, 1.09-1.93; paternal age: RR, 1.24; 95% CI, 0.99-1.55). Associations with parental age were somewhat stronger for girls than for boys, although sex differences were not statistically significant.

4 Epidemiological Studies Say Paternal Age Is A Risk Factor For Autism

Prenatal and Perinatal Risk Factors for Autism
A Review and Integration of Findings

Alexander Kolevzon, MD; Raz Gross, MD, MPH; Abraham Reichenberg, PhD


Arch Pediatr Adolesc Med. 2007;161:326-333.

Objective To review the evidence for the presence of prenatal and perinatal factors that affect the risk of autism and autism spectrum disorders.

Data Sources Relevant articles were identified by searching MEDLINE, screening reference lists of original studies, and searching major journals likely to publish epidemiological studies on the topic.

Study Selection For inclusion in this review, studies required (1) a well-defined sample of cases drawn from population-based registers or cohorts; (2) standardized, prospectively collected obstetric information from birth records or registers; (3) comparison subjects drawn from the general population with information on obstetric complications collected from the same source; and (4) a standardized format for presentation of data, allowing for comparisons among studies.

Main Exposures Parental characteristics and obstetric complications.

Main Outcome Measures Rates of autism and autism spectrum disorders.

Results Seven epidemiological studies were identified that fulfilled inclusion criteria. The parental characteristics associated with an increased risk of autism and autism spectrum disorders included advanced maternal age, advanced paternal age, and maternal place of birth outside Europe or North America. The obstetric conditions that emerged as significant fell into 2 categories: (1) birth weight and duration of gestation and (2) intrapartum hypoxia.

Paternal Age as a Risk Factor for Low Birthweight

Low Birth Weight is often observed in babies who go on to manifest paternal age related autism and schizophrenia.



--------------------------------------------------------------------------------
AJPH First Look, published online ahead of print Mar 29, 2006
American Journal of Public Health, 10.2105/AJPH.2005.066324
Research and Practice
Paternal Age as a Risk Factor for Low Birthweight
Nancy E. Reichman 1* Julien O. Teitler 2

1 Robert Wood Johnson Medical School
2 Columbia University


Abstract



Objectives. We examined associations between paternal age and low birthweight 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.

Key Words: Birth Outcomes, Socioeconomic Factors