An infection in a woman about to give birth may increase the risk of cerebral palsy in her baby, according to a new study by the California Birth Defects Monitoring Program.
The study in today's Journal of the American Medical Assn. found that babies of women who showed signs of certain infections--such as in the uterus or urinary tract--during labor and delivery were almost eight times more likely to have cerebral palsy.
The finding, while not definitive proof that infections can cause the disorder, throws into doubt a long-standing theory that cerebral palsy in full-term, normal birth-weight babies is caused by a lack of oxygen during birth.
Cerebral palsy is one of the most common childhood disabilities, affecting 1 to 2 in 1,000 children. About 7,000 babies born each year in the United States develop the disorder; about 40% of those cases are premature babies.
Cerebral palsy is caused by damage to the brain that can leave a child with difficulty walking, talking and swallowing. The cause of the disorder has been poorly understood, particularly for normal birth-weight babies, but the usual reason given involves lack of oxygen during birth.
"The important message of this study is that babies who have been called birth asphixia [lack of oxygen] may instead have damage caused by maternal infection. It's a major change in thinking about what makes these babies so sick," said epidemiologist Judith K. Grether of the California Birth Defects Monitoring Program. Grether co-authored the study with Dr. Karin B. Nelson of the National Institute of Neurological Disorders and Stroke.
The statistical association between infection and cerebral palsy warrants a full-scale investigation, Dr. David A. Eschenbach of the University of Washington in Seattle wrote in an accompanying editorial.
"The work of Grether and Nelson clarifies some issues, but new questions arise. . . . We need a better understanding of the pre-term and [full-] term fetal and maternal responses to infection," Eschenbach said.
Because cerebral palsy is rare in normal birth-weight babies, studying its causes is difficult. Today's study was drawn from data available through the California Birth Defects Monitoring Program, which is operated by the state Department of Health Services and the March of Dimes Birth Defects Foundation.
Grether and Nelson began their research with a database of 155,000 births from 1983-85 among women in four Northern California counties. Analysis of medical records showed 46 normal birth-weight children with moderate or severe cerebral palsy. The researchers compared this group to a control group of 378 unaffected children.
The analysis of the medical records of the births revealed that the mothers of the children with cerebral palsy were more likely to have chorioamnionitis, an infection in the uterus; bladder or kidney infections; or sepsis, an infection of the bloodstream. In some cases, the medical records revealed only symptoms of an infection in the mother, such as fever, foul-smelling amniotic fluid or inflammation of the placenta or umbilical cord.
Overall, one or more indicators of maternal infection were present in 10 of the 46 children with cerebral palsy, compared with only 11 of the 378 healthy children-- about an eightfold difference.
"We thought there might be an association, but we were very surprised by how large it was," Nelson said. "This really ups the ante on research on infection. But it comes at a time when there is a large and rapidly growing body of research on infection and how it may influence the developing brain."
Scientists do not understand how an infection in a pregnant mother might damage her baby's brain, Nelson said.
"It will be important to know if there are certain bacteria that are causing the problem, or whether it might be viral infections as well. But the other real possibility is that it is the response to the infection by the mother or baby that is causing the damage," she said.
When fighting an infection, the immune system releases substances called inflammatory mediators that, Nelson said, "protect the body up to a point." But this immunological response may ultimately be harmful to the fetus.
"The babies themselves do not have signs of infection," Grether said. "In the past, we felt if we can't find infection in the babies then [the cause of cerebral palsy] must be something else."
The study also found that the babies who were eventually found to have cerebral palsy looked very sick at birth, exhibiting wide-ranging problems, such as poor Apgar scores (measurements of various aspects of the baby's health), difficulties in breathing, low blood pressure or seizures. In the past, these symptoms in children who developed cerebral palsy have been attributed to a lack of oxygen at birth.
The babies with cerebral palsy were also found to have a high incidence of a particular form of the affliction called spastic quadriplegia, in which abnormal muscle control is present in all four limbs.
"This tells us that both sides of the brain experienced damage, as opposed to one side of the brain," Grether said.
Because so many questions remain about the effects of infection during pregnancy, experts can offer little specific advice to pregnant women and their obstetricians.
"The mother and physician being alert to minor signs of maternal infection and the initiation of prompt treatment are essential to help prevent developmental brain damage of the newborn," said Dr. Murray Goldstein, medical director of the United Cerebral Palsy Research and Education Foundation. "This is true for both premature and full-term infants, for both low birth-weight and normal birth-weight infants."
If the infection link to cerebral palsy is confirmed, more research will be needed to find what treatments might reduce the risk, Grether said. To protect a baby, obstetricians sometimes perform a caesarean section on a woman with an infection, but the study did not have enough information to determine whether C-sections or antibiotic treatment alters the risk of cerebral palsy.
"Those will be very important questions to address," Grether said.