Stress during pregnancy might raise the risk that a baby will have asthma, and a mother's flu during pregnancy possibly could increase an offspring's risk of schizophrenia, separate new studies say.

In the stress-asthma study, researchers at Brigham and Women's Hospital and Harvard Medical School, both in Boston, investigated differences in immune function markers in cord blood between infants born to mothers in high stress environments and those born to mothers with lower stress. They say they found marked differences in patterns that might be associated with asthma risk later in life.

The findings have been published online ahead of print publication in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

Asthma is known to be more prevalent among ethnic minorities and disadvantaged urban communities, but the disparity isn't explained completely by known physical factors. Urban women living in the inner city also experience significant stress, particularly minority women.

The role of stress in asthma development is poorly understood, but animal studies have suggested that a mother's stress during pregnancy can influence her offspring's immune system, starting in the womb.

To determine whether a similar transference of stress-mediated immune differences might occur with humans, Dr. Rosalind Wright, of Brigham and Women's Hospital, and colleagues recruited pregnant women in several cities, including Boston, Baltimore, New York, and St. Louis. Their families were largely ethnic minorities, 20 percent of whom were living below the poverty level. Each child's mother or father had a history of asthma or allergy.

In total, 557 families answered detailed questions about the various stressors in their lives, at home (including domestic violence), in their financial situations, and in their neighborhoods (community violence). When the infants were born, their cord blood was collected and isolated immune cells were stimulated with a number of factors—allergens such as dust, cockroach, viral, and bacterial stimulants—and then analyzed for the production of various cord blood cytokines as indicators of how the child's immune system was primed to respond to the environment. Cytokines basically are proteins that serve as molecular messengers between cells.

The researchers found that the patterns of cytokines related to certain stimulants differed based on the level of stress mothers had reported.

"The ctyokine patterns seen in the higher stress groups, which are an indication of how the child's immune system is functioning at birth, may be a marker of increased risk for developing asthma and allergy as they get older," Wright says.

"For example, while the debate continues as to whether primary sensitization to allergens begins before birth, these findings suggest the possibility that prenatal stress may enhance the neonates' response to inhalant antigens, specifically those antigens that the fetus is likely to encounter more directly in utero, like dust mite."

The research, funded by the National Institute of Allergy and Infectious Diseases, will continue as the infants grow up to determine whether maternal stress levels do indeed have an impact on asthma development.

"The current findings suggest that psychological stress is involved in programming of the infant immune response and that this influence begins during pregnancy," Wright says. "As these infants mature, we will learn how these factors manifest later in terms of the development of asthma and allergy."

Flu-schizophrenia study

The other study, conducted at the University of Wisconsin-Madison in collaboration with the University of North Carolina at Chapel Hill, found that rhesus monkey babies born to mothers that had the flu while pregnant had smaller brains and showed other brain changes similar to those observed in human patients with schizophrenia.

Published online by the journal Biological Psychiatry, it's claimed to be the first study done with monkeys that examines the effects of flu during pregnancy. Results from the study support findings from rodent studies suggesting this type of infection may increase the risk of schizophrenia in offspring, says lead author Sarah J. Short.

Short worked on the study while earning her doctorate at Wisconsin and now is a post-doctoral fellow at UNC working with Dr. John H. Gilmore, professor of psychiatry in the UNC School of Medicine.

"This was a relatively mild flu infection, but it had a significant effect on the brains of the babies," Short says. "While these results aren't directly applicable to humans, I do think they reinforce the idea, as recommended by the Centers for Disease Control and Prevention, that pregnant women should get flu shots, before they get sick."

In the study, 12 rhesus macaques were infected with a mild influenza A virus one month before their baby's due date, early in the third trimester of pregnancy. For comparison, the study also included seven pregnant monkeys that did not have the flu.

When the babies were 1 year old, magnetic resonance imaging (MRI) scans were taken of their brains. Researchers also assessed the babies' behavioral development at that time.

The babies born to flu-infected mothers showed no evidence of direct viral exposure. Their birth weight, gestation length, and neuromotor, behavioral, and endocrine responses were all normal.

However, the MRI scans revealed significant reductions in overall brain size in the flu-exposed babies. In addition, the scans found significant reductions of "gray matter," or the portion of brain tissue that is dark in color, especially in areas of the brain called the cingulate and parietal lobe. They also showed significant reductions of "white matter," or brain tissue that is lighter in color, in the parietal lobe.

The cingulate is located in the middle of the brain, but spans a broad distance from front to back and relays information from both halves of the brain. This structure is important for numerous cognitive function related to emotions, learning, memory, and executive control of these processes to aid in decision-making and anticipation of rewards.

In addition, this structure also plays a role in regulating autonomic processes, such as blood pressure and respiratory control. The parietal lobe comprises a large section on both sides of the brain between the frontal lobes and the occipital lobes, in the back of the brain. This part of the brain integrates information from all the senses and is especially important for combining visual and spatial information.

"The brain changes that we found in the monkey babies are similar to what we typically see in MRI scans of humans with schizophrenia," Gilmore says. "This suggests that human babies whose mothers had the flu while pregnant may have a greater risk of developing schizophrenia later in life than babies whose mothers did not have the flu. Normally that risk affects about one of every 100 births. Studies in humans suggest that for flu-exposed babies, the risk is two or three per 100 births."

Most of the work of the study was done at the Harlow Center for Biological Psychology, which is part of Wisconsin's Department of Psychology.

The center's director, Christopher Coe, is senior author of the study. Gilmore, a schizophrenia researcher who has led several studies that used MRI scans of newborn human brains, led the analysis of MRI data in the pregnancy and influenza study.