Parents’ age tied to risk of oral birth defects

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New research suggests that the older parents are, the higher the risk that their child will be born with a Cleft lip and palate, congenital malformations that affect the mouth and face.

These birth defects arise when the lips or palate fail to fuse properly early in fetal development. A cleft lip appears as a split in the upper lip, often including the gums and bones of the upper jaw, while a cleft palate involves an opening in the roof of the mouth. The two defects can arise alone, but more often occur together—sometimes as part of a syndrome marked by a number of congenital anomalies.

Exactly why some children develop oral clefts is unclear, but scientists have discovered some genes that seem to be involved, while other research has pointed to certain environmental factors, including mothers’ smoking and, possibly, dietary deficiencies in folic acid early in pregnancy.

In the new study, Danish researchers found that a child’s risk of being born with a cleft lip, with or without a cleft palate, increased in tandem with parents’ age. The risk was 20 percent greater, for example, for a 40-year-old mother than for a 30-year-old. Similarly, each 10-year increase in a father’s age between the ages of 20 and 50 was associated with a 12-percent increase in the risk of cleft lip.

However, the heightened risk vanished if one parent was significantly younger, according to the researchers led by Camilla Bille of the University of Southern Denmark in Odense.

A different pattern emerged for cases of isolated cleft palate, in which only the father’s age seemed to matter. A child’s risk of the birth defect rose 27 percent with each 10-year increase in a father’s age, the researchers found.

The findings are published in the May issue of the journal Epidemiology.

It’s not surprising that parental age had different influences on the risk of isolated cleft palate and that of cleft lip with or without the palate malformation, according to Bille. Studies have suggested that the two birth defects are distinct and arise through different mechanisms, she told Reuters Health.

Bille’s group’s findings are based on records for nearly 1.5 million births in Denmark between 1973 and 1996. Overall, 1,920 children were born with “nonsyndromic” cleft lip, with or without a cleft palate—meaning the child had no other major birth defects. Another 956 children were born with nonsyndromic cleft palate.

Oral clefts occur in one to two per 1,000 live births. It’s thought that genes play the primary role in the risk of the birth defects, but researchers have yet to pinpoint the various other factors that may be involved.

Maternal smoking, Bille said, is the only environmental factor that studies have consistently tied to the risk of oral clefts, and it seems to exert only a moderate influence.

Exactly why parents’ ages may sway the risk - and why a father’s age alone factored into isolated cleft palate—is not fully clear. Older fathers, Bille noted, may be more likely than younger men to have genetic abnormalities in their sperm that could contribute to oral clefts.

She pointed out that certain syndromes caused by a mutation in a single gene, including one called Apert syndrome, which often includes oral clefts-may mainly originate from abnormalities in the father’s sperm cells.

Parents’ age alone, however, does not seem to be a strong risk factor for oral clefts, according to Bille. Instead, she said, genetics, parental age, maternal smoking and other yet-to-be-identified factors appear to work in concert to give rise to the birth defects.

SOURCE: Epidemiology, May 2005. 

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