Studies tying large health databases with disease registries continue to
provide evidence for the association of stresses during pregnancy and the
occurrence of psychiatric disorders among affected offspring, but the low
prevalence of those disorders, even in studies based on large populations,
still leaves room for uncertainty.
"Aberrations in fetal experience in a subset of persons, whether
caused by stress, infections, or famine, alter the neurodevelopment of the
fetus," explained epidemiologist and developmental psychologist Stephen
Buka, Sc.D., a professor of community health at Brown University Medical
School. "That should be considered established."
"When you connect what we know about neuroanatomy with the
pathophysiology of schizophrenia, it seems quite logical and is supported by
the evidence that some portion of those brain abnormalities in adults have
their origins early in fetal development," said Buka.
Recent studies illuminate both the promise and the pitfalls of such
The results of a pilot study linked a short-lived, prenatal societal
stressor with incidence of schizophrenia. In it, U.S. and Israeli researchers
compared data from the Jerusalem Perinatal Cohort Study with records in
Israel's national Psychiatric Registry covering all admissions to
psychiatric wards and day-treatment facilities in the country.
Dolores Malaspina, M.D., M.P.H., Susan Harlap, M.B.B.S., both professors of
psychiatry at New York University School of Medicine, and colleagues
investigated whether women who were pregnant at the time of the Arab-Israeli
war in June 1967 were more likely to give birth to children who later were
diagnosed with schizophrenia.
They found no differences when analyzing results by trimester, but did see
a significant increase in schizophrenia-related diagnoses among children born
in January 1968, corresponding to a gestational age of two months in June
"[A] time-limited threat likely to have caused severe anxiety in
pregnant women was associated with an altered incidence of schizophrenia in
the offspring," wrote Malaspina and colleagues in the online,
open-access journal BMC Psychiatry on August
They also found that a disproportionate number of girls developed the
disorder. The sex difference may be due to increased vulnerability to stress
or to a greater mortality of vulnerable males, they suggested.
They traced 88,829 offspring included in the Jerusalem Perinatal Cohort,
which covered births from 1964 to 1976 in western (Israeli) Jerusalem.
Overall, 637 of the children developed schizophrenia, and 676 developed other
psychiatric disorders by age 30. The stressor faced by the mothers was the
three-week period leading up to and including the war, from May 18, 1967, to
June 11, 1967.
They found that nine of the 493 births in January 1968 (based on standard
month of birth) eventually were diagnosed with schizophrenia or related
illnesses, compared with two to five births in the previous and following two
months. Although absolute numbers were low, the differences were statistically
significant, the researchers said.
However, other factors might have affected these results, pointing out
problems common to this research field, said Buka, who was not involved with
the Jerusalem study.
"The definition used of schizophrenia included not only schizophrenia
but also schizotypal disorder, delusional disorders, nonaffective psychoses,
and schizoaffective disorder," he pointed out. In addition, if the
estimated gestational age was off and the babies were born prematurely, they
might well have been conceived in June 1967 by parents who were not mobilized
for war, either for reasons of age or poor health, he said.
Malaspina and Harlap were careful not to overinterpret their findings.
"[O]ur results should be regarded as 'hypothesis generating' rather
than proof that the greatest vulnerability to schizophrenia occurs in the
second, rather than any other, gestational month," they said.
The first trimester of fetal development has received the most attention
because that is when most organogenesis happens, especially in the brain, said
Katherine Abel, Ph.D., of the Centre for Women's Mental Health Research
at the University of Manchester in England, in an interview with
Researchers must be cautious about attributing population-wide stressors to
individuals, she said. Abel and several colleagues published a study of the
effects of antenatal stress on risk of schizophrenia in the February
Archives of General Psychiatry.
They studied a cohort of 1.38 million births recorded in Denmark's
Medical Birth Registry from 1973 to 1995. They found a slight increase (1.67)
in adjusted relative risk among mothers exposed to the death of a first-degree
relative in the first trimester of pregnancy.
That study ties the exposure to a stressor specific to the individual
woman, said Abel. War or famine may affect people differently, depending on
any number of intermediary factors, such as socioeconomic status, she said.
Furthermore, many genetic, behavioral, and environmental effects probably
combine to cause what, in the end, is a fairly rare event.
Abel is now involved in an even larger study based on health registries in
Sweden and hopes that the larger size and increased power will provide better
data on gender and timing of prenatal influences on the origins of
While conclusive research tying psychiatric epidemiology to developmental
stages remains in the future, some practical lessons can be drawn from the
current state of knowledge, said Buka and Abel.
"Women's condition in pregnancy has an important effect on
outcomes, so holistic care of pregnant women is important," said
"We should enhance the pregnancies of women at high risk because of
environmental stressors or family history by intervening to reduce stress,
ensuring that they have a good diet, and checking frequently for
infection—especially in the first trimester," agreed Buka.
"Acute Maternal Stress in Pregnancy and Schizophrenia in
Offspring: A Cohort Prospective Study" is posted at<www.biomedcentral.com/content/pdf/1471-244x-8-71.pdf>.▪