CHICAGO—Infants who are susceptible to diabetes and are initially exposed to cereal before four months, or after six months of age, have an increased risk of developing antibodies to islet cells (cells in the pancreas that produce insulin), which is thought to precede the development of diabetes, according to an article in the October 1 issue of The Journal of the American Medical Association (JAMA).

According to background information in the article, dietary exposures in infancy have been implicated, although not consistently, as a factor in type 1 diabetes mellitus (DM).

Jill M. Norris, M.P.H., Ph.D., of the University of Colorado Health Sciences Center, Denver, and colleagues examined the association between exposure to cereals in the infant diet and appearance of islet autoantibodies (IA) in a birth cohort of children at increased risk of type 1 DM, based on genotype and family history of DM. Islet autoantibodies are a type of antibodies associated with diabetes, and can be present for years prior to the diagnosis of type 1 DM.

The study included 1,183 children at increased risk of type 1 DM. The researchers obtained exposure and outcome measures on 76 percent of enrolled children. The study was conducted from 1994 to 2002 with an average follow-up of four years.

After adjusting for covariates and confounders, the researchers found that compared with children who were exposed to cereal between ages 4 and 6 months, children exposed to any cereals before 4 months of age had a 4.32 times greater risk for IA, and those who were first exposed at 7 months or older had a 5.36 times increased risk for IA.

CHICAGO—An updated analysis of data from the Women's Health Initiative study shows that estrogen plus progestin reduces the risk of fracture in healthy postmenopausal women, but the increased risk of other disease outcomes results in no net benefit. The study appears in the October 1 issue of The Journal of the American Medical Association (JAMA).

Jane A. Cauley, Dr.P.H., from the University of Pittsburgh, and other investigators from the Women's Health Initiative (WHI), analyzed data from the randomized clinical trial to determine if the relative risk reduction of estrogen plus progestin on fractures differed by risk factors for fracture. The WHI enrolled 16,608 postmenopausal women aged 50 to 79 years who were randomized to receive either 0.625 mg/d (milligrams per day) of estrogen plus 2.5 mg/d of progestin or a placebo and followed-up for an average of 5.6 years.

The study looking at the effects of combination hormone therapy on various chronic diseases of older women was stopped three years earlier than planned because of safety concerns, including an increase in risks of cardiovascular disease and breast cancer. The main study results were published in July 2002, and showed that hip and clinical vertebral fractures were significantly reduced by 34 percent and total osteoporotic fractures by 24 percent, according to the authors. The estrogen-only arm of the WHI trial is continuing and is scheduled to be completed in 2005. Researchers are also looking at the rate of fractures in that trial.

In this current updated study, the authors report: "A total of 733 women (8.6 percent) in the estrogen-plus-progestin group and 896 (11.1 percent) in the placebo group experienced a fracture during the follow-up period of 5.6 years. ... Estrogen plus progestin reduced the risk of hip fracture by 33 percent." Overall fractures were reduced by 24 percent. The combination hormone therapy also showed consistent positive effects on hip and lumbar spine bone mineral density (BMD).

CHICAGO—Continuous combined estrogen plus progestin therapy may increase the risk of ovarian cancer and may also increase the number of endometrial biopsies used to diagnose cancers, according to a study based on a new analysis of data from the Women's Health Initiative and published in the October 1 issue of The Journal of the American Medical Association (JAMA).

"For years, there has been concern about possible associations of gynecologic malignancies with postmenopausal hormone therapy," the authors provide as background information. "The Women's Health Initiative (WHI) trial of estrogen plus progestin provides the first opportunity to examine possible associations of gynecologic malignancies with continuous combined postmenopausal hormone therapy in a large, randomized, double-blind, placebo-controlled setting." The trial was stopped early because health risks (e.g., increased risk of breast cancer) were found to outweigh the benefits of the therapy, and the main study results were published in July, 2002.

Garnet L. Anderson, Ph.D., from the Fred Hutchinson Cancer Research Center, Seattle, and colleagues performed this study to determine the possible associations of estrogen plus progestin on gynecologic cancers and related diagnostic procedures.

The WHI trial involved 16,608 postmenopausal women at 40 U.S. clinical centers who had not had a hysterectomy. The women were randomized in two groups - one that received a placebo and the other a single tablet of 0.625 mg/d (milligrams per day) of conjugated equine estrogens plus 2.5 mg/d of medroxyprogesterone acetate (Prempro). Women who had a prior hysterectomy were randomized to a parallel trial of estrogen alone and that trial is continuing until 2005.

In 5.6 years of follow-up, estrogen plus progestin reduced endometrial cancer rates by 19 percent, but increased ovarian cancer rates by 58 percent. These differences were not statistically significant, however. No evidence of a difference was found between treatment groups in the distribution of tumor anatomy, grade, or stage of disease at diagnosis. The numbers of other gynecologic cancers were too small to make reliable conclusions.

There were 27 ovarian cancers diagnosed per 100,000 women per year in women randomized to placebo. With estrogen plus progestin use, this rate was increased to 42 cancers in 100,000 women per year. Thus even if the observed effect is real, ovarian cancer remains a rare disease in women taking these hormones, the authors state.

Though combined hormones appear to have a slightly protective effect on endometrial cancer, this therapy does not completely prevent the disease. The authors note that the vaginal bleeding that commonly occurs with this therapy must be monitored. In the trial, "Women randomized to continuous combined hormones were subjected to more endometrial biopsies and vaginal ultrasounds and were more frequently found to have mild abnormalities in routine Papanicolaou [Pap] tests," the authors found.

CHICAGO—Researchers have found no association between thimerosal-containing vaccines and the development of autism in children who received the vaccine, according to an article in the October 1 issue of The Journal of the American Medical Association (JAMA).

According to background information in the article, thimerosal, a preservative used in some vaccine formulations, contains ethylmercury. At high doses, mercuric compounds can cause toxic effects in the kidneys and nervous system. It has been suggested that childhood vaccination with thimerosal-containing vaccine could be causally related to neurodevelopmental disorders such as autism, attention deficit/hyperactivity disorder, and language and speech delay.

Anders Hviid, M.Sc., and colleagues from the Statens Serum Institut, Copenhagen, Denmark, studied children who were vaccinated with a thimerosal-containing pertussis vaccine and children vaccinated with the same pertussis vaccine formulated without thimerosal and compared these two groups with respect to development of autism and other autistic-spectrum disorders. The study included all children born in Denmark from January 1, 1990, until December 31, 1996 (n=467,450).

The researchers identified 440 autism cases and 787 cases of other autistic-spectrum disorders. The risk of autism and other autistic-spectrum disorders did not differ significantly between children vaccinated with thimerosal-containing vaccine and children vaccinated with thimerosal-free vaccine. Furthermore, there was no indication of a dose-response association between autism and the amount of ethylmercury received through thimerosal.

INFANT CEREAL LINKED TO INCREASED RISK OF TYPE I DIABETES AGE OF INTRODUCTION IS CRITICAL FACTOR