Children of men over 40 have an increased risk of autism spectrum disorders compared with those whose fathers are under 30, according to an article in the Archives of General Psychiatry based on a study of Israeli children born in the Eighties.
Autism and related conditions, known collectively as autism spectrum disorders, have become increasingly common, affecting 50 in every 10,000 children as compared with five two decades ago. This increase is partially due to higher levels of awareness and changes in diagnostic processes, but could also reflect an increase in incidence, according to the authors. Older parental age has previously been linked to abnormalities in brain development, but few studies have examined the effect of parents' ages on autism.
Dr. Abraham Reichenberg of the Mount Sinai School of Medicine in New York and the Institute of Psychiatry at King's College London and colleagues evaluated this association in children born in Israel some two decades ago. All men and three-fourths of the women born in these years were assessed by the draft board at age 17, during which time any psychiatric disorders were recorded. Reichenberg and colleagues thus obtained draft board information and the age of the father for 318,506 individuals; the age of the mother was available for 132,271 of those.
Two hundred and eight individuals in the larger group (a rate of 6.5 per 10,000) and 110 in the group with both maternal and paternal ages (8.3 per 10,000) had a diagnosis of autism spectrum disorder, according to the draft board registry. Among the paternal age groups of 15 to 29 years, 30 to 39 years, 40 to 49 years and older than 50 years, there were 34 cases, 62 cases, 13 cases and one case, respectively, of autism spectrum disorders. Advancing age among fathers was associated with increased risk of autism, such that the odds of autism spectrum disorder were nearly six times greater among children of men 40 and older than those of men 29 years and younger. Older age among mothers was not associated with autism after researchers factored in the effect of the father's age.
The authors discuss several possible genetic mechanisms for the effect, including spontaneous mutations in sperm-producing cells or alterations in genetic "imprinting," which affects gene expression. "It is important to keep in mind, however, that age at paternity varies across societies and over time," they continue. "In a given population, a change in the cultural environment could produce a change in paternal age. In theory, it could thereby lead to a change in the incidence of autism. Although further work is necessary to confirm this interpretation, we believe that our study provides the first convincing evidence that advanced paternal age is a risk factor for autism spectrum disorder," they conclude.
DRUG THAT REDUCES COLON
CANCER MAY POSE OTHER RISKS
A well-known drug for arthritis pain - Pfizer's Celebrex (generically known as celecoxib) - can slow the recurrence of polyps in the colon for those at risk of colon cancer. But a study published recently in the New England Journal of Medicine cautions about an increased risk of heart attack and stroke, so the drug shouldn't automatically be taken as a preventive measure.
The Prevention of Spontaneous Adenomatous Polyps (PreSAP) study, involving more than 1,550 participants on six continents, was led by Dr. Nadir Arber, chairman of the Integrated Cancer Prevention Center and professor of medicine and gastroenterology at the Tel Aviv Sourasky Medical Center and Dr. Bernard Levin, vice president of Cancer Prevention and Population Sciences at the University of Texas M. D. Anderson Cancer Center. "Celecoxib 400 mg once daily significantly reduced colorectal adenoma occurrence, with a greater effect on advanced adenomas," said Arber. "There is no doubt that celecoxib is an effective agent in reducing the size and occurrence of adenomas in patients with higher risks for colorectal cancer," added Levin. "Low-dose aspirin also has been shown to reduce adenoma formation in individuals with a prior history of polyps, and has the potential to decrease cardiovascular disease risk. However, its use is associated with an increased risk of upper-gastrointestinal bleeding and stroke."
As excess amounts of the protein cyclooxygenase (COX-2) are associated with adenomas and colon cancer, PreSAP researchers studied celecoxib - a selective COX-2 inhibitor - to prevent the pre-cancerous lesions. At the conclusion of the trial, the cumulative adenoma rate for the celecoxib study group was 33.6%, while the cumulative rate of adenoma development in the placebo group was 49.3% (a 36% reduction). Celecoxib administration was associated with a 50% reduction in larger, potentially more dangerous adenomas.
An editorial in the journal said because of the cardiovascular risk, Celebrex and its generic version has "no role" in preventing cancer in those who don't face high risk of colon cancer. Instead, screening for occult blood in the stool and colonoscopy is recommended.