The study is not the first to suggest that a mother's psychological state can influence her unborn child's brain development, but it is the largest, involving nearly 1.4 million Danish children followed for decades.
But researchers say the study adds to the evidence that severe stress early in pregnancy -- in this case the death of a parent, sibling, spouse, or child -- may negatively impact fetal brain development.
"We did not see this association in the months before pregnancy, or after the first trimester," says study co-author Kathryn M. Abel, PhD, of the University of Manchester.
Stress and Schizophrenia
Abel and colleagues from the University's Center for Women's Mental Health Research examined data from a comprehensive, nationwide Danish health registry, which recorded about 1.38 million births in the country between 1973 and 1995.
The same registry was used to determine if mothers who gave birth during this time had first-degree relatives who died, received a diagnosis of cancer, or had a heart attack or stroke during their pregnancies.
Roughly 22,000 women experienced the death of a close relative during pregnancy, and about 14,000 had a relative treated for a life-threatening illness.
A total of 7,331 schizophrenia cases were identified among Danes born between 1973 and 1995 over at least two decades of follow-up.
Being born to a mother who had a close relative die during her first trimester was found to be associated with a 67% increased risk for schizophrenia.
But a similar death up to six months before conception or at any other time during pregnancy did not appear to elevate risk, nor did having a seriously ill relative during pregnancy.
Abel tells WebMD that the research team plans to repeat the study using the Swedish health registry, which is more than twice the size of the Danish one.
The newly published study appears in the February issue of the journal Archives of General Psychiatry.
"We also want to expand the research to look for other mental health outcomes," Abel says. "I think it is highly likely that if we look at a broader spectrum of psychiatric disorders we will find that those are increased as well."
Some Stress May Be Good
Developmental psychologist Janet DiPietro, PhD, who also studies the impact of maternal stress on fetal brain development, says even if major traumatic events such as the death of a loved one do influence schizophrenia risk, the risk is still very small.
Having a family history of schizophrenia or another mental illness was associated with a much larger risk, in this study and in others.
DiPietro says much of the research linking pregnancy stress to negative outcomes has focused on early child development and relied on mothers' perceptions of their children's behavior.
"The problem is that mothers who are more anxious and stressed are more likely to view their child as having behavioral problems," she says.
In her own 2006 study, in which child behavior was independently assessed, moderate stress during pregnancy was actually associated with a good outcome -- advanced development at age 2.
One possible reason for this is that the chemicals the body produces in response to stress also play a role in fetal maturation, she tells WebMD.
DiPietro is associate dean for research and a professor at Baltimore's Johns Hopkins School of Public Health.
"The knee-jerk reaction is to think that all stress is bad, but this may not be so in pregnancy," she says. "The fetus is not as vulnerable as we may think to the day-to-day stresses women deal with, like working and meeting deadlines."