Survival and Reproduction Among Males With Birth Defects 

and Risk of Recurrence in Their Children 

JAMA v.285 n.6, 14feb01

[ abstract below ]

Offspring of Men With Birth Defects Twice as Likely to Have Defects

Press Release / NIEHS 13feb01

Men born with a birth defect have a substantially increased risk of having a child with a birth defect, a large population study revealed today. Compared with other fathers, the risk was doubled.

The second-generation risk also appeared higher - at least for dissimilar birth defects - than for the offspring of mothers who had been born with birth defects.

Scientists at the U.S. National Institute of Environmental Health Sciences and Norway's University of Bergen reviewed Norwegian births since 1967. They compared 12,000 men who had been born with a recognized defect with nearly a half-million unaffected men. The scientists reported today in the Journal of the American Medical Association for Feb. 14 that the men had fathered 1,265 children and that:

• Twenty-one of these children (1.6 percent) had been born with the same defect as their father's. This is about seven times the risk of those same defects in the general population but is about the same risk as a previous study showed for the children of women with birth defects.

• However, the children of fathers with birth defects also had a higher risk of having different, unrelated birth defects. Forty-three children (3.4 percent) had defects that were not like their father's, compared to an expected number of 24 (1.9 percent). This result was in contrast to the findings of the previous women's study in which the children of women with defects appeared to have no increased risk of babies with defects different from the mother's.

• The total risk of birth defects was 5.1 percent among the offspring of fathers with defects, or twice the 2.1 percent risk of the offspring of other fathers. The risk was spread out across categories of defects, not concentrated in any one category.

"Five percent of children with birth defects is not a whole lot," Allen J. Wilcox, M.D., Ph.D., said, "but it still is more than double what we see in the children of unaffected fathers." Dr. Wilcox is chief of epidemiology at the National Institute of Environmental Health Sciences, one of the U.S. National Institutes of Health.

"What surprised us," Dr. Wilcox continued, "is that the children of the affected fathers had a higher risk of all kinds of defects, not just the same defect as their father. In our earlier study of women with birth defects, this did not appear to be the case: The children seemed to have no special risk of birth defects except for the specific defect of the mother."

Dr. Wilcox' co-researchers are Rolv T. Lie, Ph.D., and Rolv Skjaerven, Ph.D., both professors at the University of Bergen. Their studies are based on the Medical Birth Registry of Norway which links the birth records of fathers, mothers and offspring through the Norwegian system of unique personal identification numbers.

The investigators grouped the birth defects recorded into 24 categories. Cleft lip, genitalia defects, limb defects and clubfoot (in which the foot is twisted out of position) were the four most common recurring defects that recurred in the offspring of affected fathers. In many cases, these defects can be surgically repaired.

In their report, the three said they had expected an excess in defects of the same type as the fathers because many birth defects are heritable. They said they had no explanation for the increased rate of dissimilar effects.

In the study, boys with birth defects had a lower-than-normal survival rate to age 20. Even if they survived to adulthood, they were 30 percent less likely to father a child than other men. This pattern of reduced reproduction (which the authors said presumably reflects social factors as well as biological) had also been seen among affected women.

The scientists said the higher death rates among babies with birth defects, as well as the reduced likelihood that the survivors will have children, reduces the impact of parents with defects on the next generation.

"We also need to put this into perspective," Dr. Wilcox said. "More than 95 percent of all babies with birth defects are born to parents who have no known birth defects themselves. Measles, a lack of folate in the diet, and heavy alcohol use are factors for some defects, but the causes of most birth defects, environmental as well as genetic, are not known. We have a lot to learn - still - about the cause and prevention of birth defects."

source http://www.niehs.nih.gov/oc/news/dadbd.htm 13feb01
Media Contact: Bill Grigg (301) 402-3378, (301)496-3512 grigg@niehs.nih.gov

Survival and Reproduction Among Males With Birth Defects and

Risk of Recurrence in Their Children

JAMA v.285 n.6, 14feb01

Rolv T. Lie, PhD; Allen J. Wilcox, MD, PhD; Rolv Skjærven, PhD

Context  Few systematic data exist on survival and reproduction among males with birth defects and their contribution to occurrence of birth defects in the next generation.

Objective  To estimate survival of males with registered birth defects, their subsequent reproduction rates, and their risk of transmitting birth defects to their offspring.

Design and Setting  Population-based cohort study of data from the Medical Birth Registry of Norway.

Subjects  A total of 486 207 males born in Norway between 1967 and 1982, 12 292 of whom had a recorded birth defect.

Main Outcome Measures  Survival rates through 1992, reproduction rates through 1998, and risk of birth defects among offspring of males with vs without birth defects.

Results  Survival through 1992 was lower among males with birth defects (84% vs 97%). Compared with males without birth defects, affected males were 28% less likely to have had a child. Among offspring of affected males, 5.1% had a registered birth defect compared with 2.1% of offspring of males without birth defects (relative risk [RR], 2.4; 95% confidence interval [CI], 1.9-3.0). Offspring of affected fathers had an increased risk of the same defect as their fathers (RR, 6.5; 95% CI, 4.0-10.4) and an increased risk of dissimilar defects (RR, 1.8; 95% CI, 1.3-2.5).

Conclusions  Compared with unaffected males, males with birth defects have higher mortality and survivors are less likely to have a child. Fathers with birth defects are significantly more likely than unaffected fathers to have an affected child.

JAMA. 2001;285:755-760

Author/Article Information

Author Affiliations: Section for Medical Statistics and Medical Birth Registry of Norway, University of Bergen, Norway (Drs Lie and Skjærven); and the National Institute of Environmental Health Sciences, Research Triangle Park, NC (Dr Wilcox).
 
Corresponding Author and Reprints: Rolv T. Lie, PhD, Section for Medical Statistics, University of Bergen, Armauer Hansens Bldg, 5021 Bergen, Norway (e-mail: Rolv.Lie@smis.uib.no).

Author Contributions: Dr Lie participated in study concept and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and statistical expertise.

Dr Wilcox participated in study concept and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and medical expertise.

Dr Skjærven participated in study concept and design, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, and statistical expertise.

Acknowledgment: We are indebted to Donna D. Baird, PhD, Olga Basso, PhD, Ruth Little, ScD, and Stein Emil Vollset, MD, DrPH, for helpful comments.