E. coli Infection Quadruples Risk Of Cerebral Palsy

OB/GYN News, Sept 15, 2001 by Kathryn Demott

Group B Strep. infection of the amniochorionic membranes triples risk.

QUEBEC CITY -- Very-low-birth-weight infants with Escherichia coli of the amniochorionic membranes are at more than four times the risk of having cerebral palsy, compared with those without the infection, Helen M. McDonald, Ph.D., said.

And those whose membranes are infected with group B streptococcus (GBS) have nearly three times the risk, she reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

Although these findings may someday have important clinical implications, for now, routine practice shouldn't change. Suppression of labor is already ill advised in the woman who has threatened preterm labor and signs of infection. But as this study shows, "a lot of times we really don't know that infection is present," she said.

Dr. McDonald and her associates at the University of Adelaide (Australia) were among the first investigators to home in on the link between specific pathogens and cerebral palsy.

"This is such a tremendous accomplishment and contribution to this area to begin to draw that link between inflammation to the organisms that might be involved," one attendee noted.

Previous studies in humans and animal models established that intrauterine infection plays a role in cerebral palsy, especially in low-birth-weight babies.

The study compared labor and delivery records of 82 children with cerebral palsy confirmed at age 5 with those of 183 control children without the disorder. All children were of very-low birth weight and were followed until age 7. Under a protocol at the hospital where the study was conducted, most very-low-birth-weight babies had their placentas cultured and examined histologically, focusing specifically on the interface between the amniochorionic membranes.

After analyzing 92 variables for their association with cerebral palsy, the investigators found that the presence of E. coli or GBS in the placenta had the strongest association: A total of 19.4% of all infants with cerebral palsy had positive placental cultures for E.coli, compared with 4.9% of those children who didn't have cerebral palsy, for an odds ratio of 4.4.

GBS was found in 12.9% of infants with cerebral palsy and 4.9% of those without it, for an odds ratio of 2.7.

Taken together, more than one-quarter (25.8%) of those children with cerebral palsy had E. coli or GBS placental infections, compared with 9.5% of children without the neurologic defect (odds ratio of 3.3).

Infants with a history of threatened preterm delivery without actually delivering early were also almost three times more likely to develop cerebral palsy than were those who didn't have such a history (odds ratio of 2.7).

These findings support the hypothesis that maternal infection appears to cause an elevation in fetal brain cytokines, which in turn leads to damage in the fetal brain.

On the other hand, among all babies with placental evidence of infection, only 1 in 10 mothers had clinical signs of infection.

"We know that E. coli and CBS can cause ascending infection," and often when it does so, there are no signs--overt or subclinical--of the infection, and yet this degree of infection can lead to brain damage.

Genetic factors may also play a role. Some fetuses may have a genetic predisposition to have an unregulated response to cytokines.

"Not a single study to date has really been able to address the pathophysiology of cerebral palsy and intracellular infection," noted Dr. Michael Gravett of Oregon Health Sciences University, Portland.

The pathophysiology of cerebral palsy may be related to cytokine-induced apoptosis, or it may be related to endotoxin and hypertension, hypoxemia, and reperfusion. The new findings "suggest that there's a clustering of E. coli that may be related to a hypoxemia-reperfusion phenomenon," he said.