updated 8/16/2004 5:25:20 PM ET 2004-08-16T21:25:20

A new study adds more evidence to a body of research that suggests the children of some women who get the flu while pregnant are at higher risk of developing schizophrenia.

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The latest study examined the women’s blood samples, which indicated that those who had the flu during the first half of pregnancy were three times more likely than non-infected women to have children who developed schizophrenia later in life, the researchers said.

They emphasized that the overall risks are still quite small. Only about 1 percent of the U.S. population has schizophrenia and the results suggest that about 97 percent of babies born to women who had the flu while pregnant will not develop schizophrenia.

Lead author Dr. Alan Brown theorized that the damage occurs only in a small number of genetically susceptible fetuses since most pregnant women with the flu end up with healthy children. He said more research is needed to confirm the link.

However, Dr. Robert Yolken, a Johns Hopkins University scientist who has long studied the role viruses may play in mental illness, said the latest findings along with previous evidence make it “pretty clear that influenza infection during pregnancy is a risk factor, probably one of several risk factors” for schizophrenia.

Yolken said the added knowledge might lead to interventions to help keep pregnant women healthy. Already, women who will be more than three months pregnant during the flu season are urged to get the flu shot.

Virtually all previous studies had relied on recollections from mothers of schizophrenics about flu exposure during pregnancy, or on evidence that mothers had been pregnant during flu outbreaks, Brown said.

By contrast, Brown and his colleagues were able to analyze blood samples taken decades earlier from pregnant women participating in a separate study. In the women’s blood serum, the researchers measured levels of antibodies to strains of flu viruses that had been prevalent during 1959 through 1966, when the women were pregnant.

The study, which appears in August’s Archives of General Psychiatry, is “thus far the most robust evidence” of the flu-schizophrenia connection, said Brown, a psychiatrist at New York Psychiatric Institute and Columbia University.

Biggest risk during first trimester
Compared with women who hadn’t been infected, women with flu antibodies during the first half of pregnancy had a threefold risk of having children who developed schizophrenia. An even bigger, sevenfold risk occurred during the first trimester, a critical period for fetal development, though those results were less statistically certain because there were fewer first-trimester blood samples, Brown said.

The study involved 189 women — 64 of whom had children who developed schizophrenia and 125 whose children did not.

The disease, among the most severe mental illnesses, typically involves delusions, hallucinations and disordered thinking. Schizophrenia usually first appears in adolescence or early adulthood and affects about 2 million Americans.

It is thought to be caused by a combination of genetic and environmental factors, including obstetric complications during pregnancy; Brown said his research suggests that up to about 14 percent of cases may be linked with prenatal exposure to influenza.

Other research has suggested infections other than flu might be involved, including measles and genital herpes during pregnancy, which may adversely affect the developing fetal brain.

Brown said he suspects that in the case of influenza, antibodies or proteins called cytokines produced by the mother’s immune system in response to the infection pass through the placenta into the fetus and disrupt brain development.

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