Paternal age equal or greater than 50 years and a 320% increase in congenital malformations in offspring compared to 20-29

1: Hum Reprod. 2005 Nov;20(11):3173-7. Epub 2005 Jul 8. Links
Paternal age and congenital malformations.Zhu JL, Madsen KM, Vestergaard M, Olesen AV, Basso O, Olsen J.
The Danish Epidemiology Science Centre, University of Aarhus, Denmark.

BACKGROUND: Spontaneous mutations in germ cells increase with male age, but an association between paternal age and congenital malformations is not well established. We conducted a population-based cohort study to estimate this association. METHODS: A study population of couples and their firstborn children were identified in the Danish Fertility Database between 1980 and 1996 (n = 71937). Diagnoses of congenital malformations in children were obtained by linkage to the nationwide hospital register (1980-1999). RESULTS: Overall, there were no differences in the prevalence of malformations as a function of paternal age. However, the prevalence of malformations of extremities and syndromes of multiple systems, as well as Down's syndrome, increased with increasing paternal age. For example, in comparison with fathers age 20-29 years, adjusted hazard ratio of syndromes of multiple systems was 1.15 [95% confidence interval (CI) 0.81-1.65] for age 35-39 years, 1.33 (95% CI 0.79-2.25) for age 40-44 years, 1.73 (95% CI 0.82-3.65) for age 45-49 years, and 3.20 (95% CI 1.37-7.48) for age > or = 50 years (test for trend P = 0.01). CONCLUSIONS: Our data suggest that advanced paternal age may be associated with an excess occurrence of some specific malformations. The association could be caused by mutations of the gametes in men induced by biological or environmental factors.

PMID: 16006461 [PubMed - indexed for MEDLINE]

MOREOVER IN ANIMAL AND IN MAN, PATERNAL AGEING SEEMS RESPONSIBLE FOR A GRADUAL LOWERING IN THE LEVEL OF PROGENY CEREBRAL FUNCTIONS

1: Contracept Fertil Sex. 1993 May;21(5):382-5. Links
[Age of the father and development][Article in French]
Auroux M.
Biologie de la Reproduction et du Developpement, CHU Bicetre.

Testicular ageing affects at the same time the individual and his lineage. In the individual, vascular, endocrine, blood testis barrier and Sertoli cells changes because of age lead a decrease of spermatozoa number and an alteration in their form and motility. These changes lead a gradual decrease of fertility. In the progeny, paternal ageing is responsible for new dominant autosomic mutations which themselves cause different malformations, as achondroplasia, Apert or Recklinghausen disease, Marfan Syndrome etc. and perhaps for certain chromosome X linked recessive mutations as Duchenne myopathy or hemophily A. Moreover, in animal and man, paternal ageing seems responsible for a gradual lowering in the level of progeny cerebral functions. In man, very youthful age is also related to these effects. Thus, the curve corresponding to this phenomenon presents an inverted U-Shape, of which the top corresponds to about thirty years of paternal age. Maternal age does not appear to play a part in this event. On the whole, these results pose the problem of the optimum age for fatherhood.

PMID: 7920923 [PubMed - indexed for MEDLINE

Do we know or act on the risks of age, toxins more than 3 cups of coffee per day on sperm DNA? Not usually

Reprod Toxicol. 1992;6(4):289-92. Links
Male-mediated teratogenesis and other reproductive effects: biologic and epidemiologic findings and a plea for clinical research.Davis DL, Friedler G, Mattison D, Morris R.
This paper reviews biologic and epidemiologic evidence that prefertilization and perifertilization exposures to fathers influence a variety of reproductive outcomes, including fertilization, miscarriage, low birth weight, congenital anomalies, cancer, and neurodevelopmental and other childhood health problems. Males and females bring an equal number of chromosomes to their progeny, but their genomes may affect different aspects of reproduction. While the key male role principally ends at fertilization, there is growing experimental and human evidence that factors relating both to prefertilization and perifertilization exposure also play a role post fertilization. Some negative human epidemiologic findings reflect the fact that routinely gathered information usually generates detailed descriptions of maternal exposures and does not collect records regarding prefertilization paternal exposures. The absence of extensive human evidence should be interpreted as a deficiency in research rather than an absence of male-mediated adverse reproductive outcomes. More than 60 different compounds or industrial processes have been identified as increasing defects in human sperm and possibly increasing the risk to offspring from male-mediated exposures. Further research needs to include better characterizations of both maternal and paternal prefertilization and perifertilization exposures, in order to assess more accurately their relative effects. Pediatricians confronted with adverse pregnancy and antenatal health outcomes should obtain detailed information on relevant prefertilization exposures of both parents.

FATHERS 34 AND OVER WERE 90% MORE LIKELY THAN FATHERS AGE 20 TO 34 YEARS TO HAVE LOW-BIRTHWEIGHT BABIES

May 2006, Vol 96, No. 5 | American Journal of Public Health 862-866
© 2006 American Public Health Association
DOI: 10.2105/AJPH.2005.066324

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RESEARCH AND PRACTICE
Paternal Age as a Risk Factor for Low Birthweight
Nancy E. Reichman, PhD and Julien O. Teitler, PhD

Nancy E. Reichman is with the Department of Pediatrics, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick. Julien O. Teitler is with the School of Social Work, Columbia University, New York, NY.

Correspondence: Requests for reprints should be sent to Nancy E. Reichman, PhD, Department of Pediatrics, Robert Wood Johnson Medical School, 97 Paterson St, Room 435, New Brunswick, NJ 08903 (e-mail: nancy.reichman@umdnj.edu).



Objectives. We examined associations between paternal age and low birth-weight in the US urban population.

Methods. Using a population-based sample of 4621 births, we used multiple logistic regression analysis to estimate associations between paternal age and low birthweight, controlling for maternal age, other demographic factors, and the child’s gender.

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

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