Thursday, January 25, 2007

Paternal Age Above 35

Paternal Ages Above and below 35 are associated with a different risk of schizophrenia
concerned heart View Delete
1: Eur Psychiatry. 2006 Dec 1; [Epub ahead of print] Links
Paternal ages below or above 35 years old are associated with a different risk of schizophrenia in the offspring.Wohl M, Gorwood P.
INSERM U675, 16 rue Henri Huchard 75018 Paris, France; AP-HP (Paris VII), C.H.U Louis Mourier, Service de psychiatrie du Professeur Ades, 178 rue des Renouillers, 92701 Colombes Cedex, France.

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.

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Monday, January 15, 2007

"I noticed that many children with schizophrenia had old fathers" Christina Dallman physician

Father's age raises schizophrenia risk

September 06 2002 at 06:55PM

Stockholm - Swedish scientists have found that older men face a much greater risk of fathering schizophrenic children than younger men.

Schizophrenia is a widespread and debilitating form of mental disease with symptoms ranging from delusions and an altered sense of self to apathy and social withdrawal.

Scientists at Sweden's Karolinska Institute found that children fathered by men aged 45 or older were three times as likely to develop schizophrenia as offspring of men aged 20-24.

"We already knew there was an increased risk when older women have children," Christina Dahlman, the physician who led the study, said.

"When I looked closer at the men, I noticed that many children with schizophrenia had old fathers."

The findings, released this week, support earlier studies by Israeli and American scientists.

As in many Western countries, couples in Sweden are delaying having their first child. In the past three decades, the average age of a first-time mother has risen by five years to 28,5 years.

Dahlman and colleague Peter Allebeck studied 524 schizophrenics for more than seven years and found that being fathered by an older man doubled the risk of developing the disease.

As most older men tended to have older wives, the cumulative risk was three times greater.

The reasons for the link were unclear, but Dahlman said sperm cell mutations, which increase with a man's age, have been known to cause various other diseases.

Children of older men may also lose their fathers at an early age, possibly increasing the risk of schizophrenia.

Around 24 million people worldwide suffer from schizophrenia, according to the World Health Organisation. Symptoms can be treated but there is no cure.

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Like 35 and Down Syndrome for Women

Old fathers raise risk of brain disorder
By Jacqueline Maley
October 23, 2004
There is a "strong association" between men who become fathers after the age of 50 and of schizophrenia in their children, a study has found.

Swedish research that tracked over 700,000 young people found 15 per cent of schizophrenia cases could be attributed to older fathers. Researchers believe the link may be due to sperm mutations, which accumulate as men get older.

Compared with men who become fathers between 21 and 24, those who father children at the age of 50 or older have four to five times the chance of their offspring developing schizophrenia. The link was stronger if there was no family history of the disorder.

The link between schizophrenia and older paternity had been made before, but this was the first large study to look at a range of factors that could confound the results, said Professor John McGrath, a psychiatric epidemiologist at the Queensland Centre for Mental Health Research.

"If all babies had fathers less than 30, the paper suggests, the incidence of schizophrenia would reduce by 15 per cent," he said.

In the 1970s it was commonly believed that mothers caused their children's schizophrenia, Professor McGrath said. "There is now an interesting new lead looking at father's age, and this study adds weight to that.

"Schizophrenia is a group of brain disorders, and we're struggling to find out what causes them. This study ... will help to tease apart the causal pathway."

In Australia about 1 per cent of people develop schizophrenia. A study published in 2002 in People and Place, a Monash University journal, found consecutive generations of Australian men were becoming parents later.

In 2002 the average age of fathers was 32, compared with an average age of 29 in 1982, according to data from the Australian Bureau of Statistics.

The executive director of the mental health lobby group SANE Australia, Barbara Hocking, said the Swedish research, published in the British medical journal BMJ, was "major, major stuff".

She likened the research to the link between mothers over 35 and an increased risk of Down syndrome in their children. "It helps people understand what risk factors may be, so you can take action to reduce them."

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Excepts from the Harvard Mental Health Letter September 2006

Minding Your Mind

New Key to Autism

September 25, 2006

By Michael Craig Miller, M.D.
Harvard Medical School

Convincing Evidence
What Causes These Genetic Errors?
Should Older Men Stop Fathering Babies?
A study published in the September, 2006 issue of the Archives of General Psychiatry may give older prospective fathers pause before plunging into biological parenthood. The authors found a significant increase in the risk of autism and similar disorders as fathers got older

This is not the first discovery of its type. Healthcare professionals have long known that as parents age, the risk of giving birth to a child with certain illnesses goes up. Older mothers, for example, are more likely to have a child with Down syndrome. In recent years, studies have revealed a link between aging fathers and schizophrenia.

Until recently, health care professionals have focused almost exclusively on the mother's age as a risk factor for health problems in the child. But we now know that the father's age also adds to the risk of potentially devastating diseases. And there is no practical way to detect these illnesses during pregnancy. For those weighing the risks, the decision can be wrenching. Adoption and in some instances a sperm donation may be acceptable alternatives to older fathers wanting to build a healthy family.

Michael Craig Miller, M.D. is Editor in Chief of the Harvard Mental Health Letter. He is also associate physician at Beth Israel Deaconess Medical Center and assistant professor at Harvard Medical School. He has been practicing psychiatry for more than 25 years and teaches in the Harvard Longwood Psychiatry Residency Program.

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Lance Armstrong has three healthy children from cryopreservation of his semen

Sperm have always been much easier to freeze and there are documented
pregnancies resulting from semen samples frozen for over 20 years. In
my opinion, freezing sperm for men who choose to delay fatherhood is
not a bad idea, but convincing men that it is in their best interest
would be a grand obstacle with which to struggle.

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Saturday, January 13, 2007

Birth Characteristics and Subsequent Risk for Breast Cancer in Very Young Women
Kim Innes1, Tim Byers1 and Maria Schymura2
1 Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, CO.
2 New York State Cancer Registry, New York State Department of Health, Albany, NY.

'There is growing evidence that prenatal exposures may influence later breast cancer risk. This matched case-control study used linked New York State birth and tumor registry data to examine the association between birth characteristics and breast cancer risk among women aged 14–37 years. Cases were women diagnosed with breast cancer between 1978 and 1995 who were also born in New York after 1957 (n = 484). For each case, selected controls were the next six liveborn females with the same maternal county of residence. The authors found a J-shaped association between birth weight and breast cancer risk, and very high birth weight (4,500 g) was associated with the greatest elevation in risk (adjusted odds ratio (OR) = 3.10, 95% confidence interval (CI): 1.18, 7.97). The association of maternal age with breast cancer risk was also J-shaped, with maternal age of more than 24 years showing a positive, linear association (adjusted OR = 1.94, 95% CI: 1.18, 3.18 for maternal age 35 vs. 20–24 years; p for trend = 0.02)........ " American Journal of Epidemiology 2000 Vol. 152 No 12



Letters to the Editor

Paternal Age as a Risk Factor
Dear Editor:

Recent research reports have focused attention on the association between advanced paternal age and increased risk of schizophrenia in offspring (1,2). In addition to schizophrenia, numerous genetic illnesses are reported to have the same association with increased paternal age (3). An increased mutation rate related to increased paternal age has been documented in the male gametogenesis (4). Most of these illnesses are autosomal-dominant disorders (5). Two x-linked recessive illnesses—hemophilia A and Lesch-Nyhan disease—have been frequently found with increased maternal grandpaternal age (6–8). It is proposed that the origin of schizophrenia can in some cases be related to a mutation in the gametogenesis of the father that is related to aging. It is further proposed that, as with hemophilia A and Lesch-Nyhan disease, the mutated gene or genes in some cases of schizophrenia and other genetic illnesses can be transmitted to future generations. In such cases, the illness could be expressed in a distant relative far removed in time from the original mutational event. Further genetic research on germline mutations related to paternal age is needed to establish the significance of paternal age as a risk factor.

1. Malaspina D, Harlap S, Fennig S, Heiman D, Nahon D, Feldman D, and others. Advancing paternal age and the risk of schizophrenia. Arch Gen Psychiatry 2001;58:361–7.

2. Raschka LB. Parental age and schizophrenia. Magyar Andrologia [Hungarian Andrology] 1998;111:47–50.

3. Tarin JJ, Brines J, Cano A. Long-term effects of delayed parenthood. Hum Reprod 1998;13:2371–6.

4. Crow JF. How much do we know about spontaneious human mutation rates? Environ Mol Mutagen 1993;21:122–9.

5. Carothers AD, McAllion SJ, Paterson CR. Risk of dominant mutation in older fathers: evidence from osteogenesis imperfecta. J Med Genet 1986;23:227–30.

6. Rimoin DL. Mutation in man. In: Emery AEH, Rimoin DA, editors. Principles and practice of medical genetics. Edinburgh (UK): Churchill Livingstone; 1983. p 32–3.

7. Crow JF. The high spontaneious mutation rate: is it a risk? Proc Natl Acad Sic USA 1997;94:8380–6.

8. Prevention of avoidable mutational disease: memorandum from a WHO meeting. Bull World Health Organ 1986;64:205–16.

Leslie B Raschka, MD, FRCPC
Toronto, Ontario

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Paternal Age Effect and Disorders Known in 1999

Table II. Long-term effects of paternal ageing on offspring from table on page 2373 of Long –term effects of delayed parenthood by J.J. Tarin, J. Brines, and A. Cano

Dominant disorders
Wilms tumour, thanatophoric dysplasia, retinitis pigmentosa, osteogenisis imperfecta type IIA, acrodysostosis, achondroplasia, Apert’s disease, fibrodysplasia ossificans progressiva, aniridia, bilateral retinoblastoma, multiple exostoses, Marfan’s, Lesch-Nyan’s, Pfeiffer’s, Wardenburg’s, Treacher-Collins, Soto’s, and Crouzon’s syndromes, basel cell nevus, cleidocranial dysostosis, polyposis coli, oculodentodigital syndrome, Costello syndrome , progeria, Recklinghausen’s neurofibromatosis, tuberous sclerosis and renal polycystic kidney disease.

X-linked recessive diseases
Haemophilia A and Duchenne’s muscular dystrophy

Non-cytogenetic congential defects
Congential cataracts, reduction defects of the upper limb, nasal aplasia, pulmonic and urethtal stenosis, perauricular cyst, cleft palate,1 neural tube defects

Athetoid /dystonic cerebral palsy and congenital hemiplegia

Psychotic disorders

Decreased learning capacity and/or mental retardation


Epidemiological evidence of perinatal influence in the etiology of adult cancers

1: J Clin Epidemiol. 1989;42(2):151-7. Links
Epidemiologic evidence of perinatal influence in the etiology of adult cancers.Janerich DT, Hayden CL, Thompson WD, Selenskas SL, Mettlin C.
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06510.

Using data from 5489 cancer patients and 2647 patients without cancer we investigated whether parental age at the birth of the patient or the patient's rank within his sibship was related to the risk of cancer during adulthood. An increase of 10 years in maternal age was associated with an increase of 24% for the incidence of breast cancer (odds ratio = 1.24%; 95% CI = 1.09-1.41); the corresponding increase for paternal age was 19% (odds ratio = 1.19; 95% CI = 1.07-1.33). There was some evidence that the age of each parent may make an independent contribution to the risk of breast cancer. For certain types of genito-urinary cancers, the risk was higher when the parents were relatively young at the birth of the patient. These cancers included tumors arising in the prostate (odds ratios = 0.71 and 0.55 for maternal and paternal ages, respectively), testis (odds ratios = 0.57 and 0.52), penis (odds ratios = 0.37 and 0.45), kidney (odds ratios = 0.66 and 0.60), and bladder (odds ratio = 0.79 and 0.85). The associations for cancer of the prostate and bladder were stronger among patients who were diagnosed at a relatively young age. No statistically significant effects were found for birth order relative to adult cancers. The authors conclude that environmental factors that affect the parents or that operate in the perinatal period may have stronger influences on the incidence of adult cancers than have been previously recognized.

PMID: 2918324 [PubMed - indexed for MEDLINE]


Tuesday, January 02, 2007

The Korean Breast Cancer Study

This is the first and largest report about paternal and maternal ages and breast cancer in Asian women. These findings suggest that paternal age is associated with an increased risk of breast cancer in female offspring. However, further prospective study is needed to verify the present findings.

BMC Cancer. 2005; 5: 143.
Published online 2005 October 31. doi: 10.1186/1471-2407-5-143.
Copyright © 2005 Choi et al; licensee BioMed Central Ltd.

Association of paternal age at birth and the risk of breast cancer in offspring: a case control study
Ji-Yeob Choi,1 Kyoung-Mu Lee,1 Sue Kyung Park,1 Dong-Young Noh,2 Sei-Hyun Ahn,3 Keun-Young Yoo,1 and Daehee Kang1,4

1Department of Preventive Medicine, Seoul National University College of Medicine, 28 Yongon-Dong Chongno-Gu, Seoul 110-799 Korea
2Department of General Surgery, Seoul National University College of Medicine, 28 Yongon-Dong Chongno-Gu, Seoul 110-799 Korea
3Department of General Surgery, Ulsan University College of Medicine, 388-1 Pungnap-2dong Songpa-gu, Seoul 138-736, Korea
4Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-Dong Chongno-Gu, Seoul 110-799 Korea

Corresponding author.

Ji-Yeob Choi:; Kyoung-Mu Lee:; Sue Kyung Park:; Dong-Young Noh:; Sei-Hyun Ahn:; Keun-Young Yoo:; Daehee Kang:

Received July 8, 2005; Accepted October 31, 2005.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Multiple Sclerosis and Paternal Age

Parental Age, Family Size, and Risk of Multiple Sclerosis.

Original Article

Epidemiology. 15(6):717-723, November 2004.
Montgomery, Scott M. *+; Lambe, Mats ++; Olsson, Tomas [S]; Ekbom, Anders *++

Methods: Using the Swedish Inpatient Register, we identified 4443 patients with a diagnosis of MS. From the general Swedish population, using birth and death registers, we selected 24,194 controls with similar characteristics for year, county of birth, and survival until at least age at diagnosis of the matched cases. The Multi-Generation Register linked data on siblings and parents. The Census provided father's social class based on occupation.

. The risk of MS increased steadily with father's age but not mother's age, up to 2.00 (1.35-2.96) for 51- to 55-year-old fathers (compared with 21- to 25-year-old fathers).

Conclusions: Parents who have offspring with MS may have subtly impaired fertility. The unexpected association with paternal age may be the result of an increased risk of accumulating germ cell mutations among older males.


Diabetes Type 1 and Paternal Age

1: Eur J Pediatr. 1999 May;158(5):362-6. Links
Risk factors for type I diabetes mellitus in children in Austria.Rami B, Schneider U, Imhof A, Waldhor T, Schober E.
University Children's Hospital Vienna, Austria.

The aim of this study was to investigate environmental risk factors in the development of type 1 diabetes mellitus in a population-based case-control study. Parents of all patients with manifestation of type 1 diabetes between 1989 and 1994 in Vienna were asked to complete a questionnaire (n = 114). Control children (n = 495), matched for age and sex, were randomly recruited from all schools in Vienna. Fathers of diabetic children were significantly older at the time their children were born than fathers of control children (P = 0.015). Children with diabetes were more likely to be second- or third-born children (P<0.05) and fewer went to kindergarten than the control group children (P = 0.007). No significant difference in duration of gestation, percentage of delivery by caesarean section, birth weight or length was found. Neonatal jaundice was more often observed in the patient group (P = 0.038). Breast feeding was reported by 82.7% of mothers of diabetic children and by 81% of mothers of control children, and the duration of breast feeding was longer in patients than in controls (n.s.). CONCLUSION: In our study, the development of type 1 diabetes mellitus was associated with higher paternal age and neonatal jaundice. No correlation could be found with dietary intake of cow's milk products in early infancy, vaccination and other environmental factors.

PMID: 10333115 [PubMed - indexed for MEDLINE]

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