Pregnancy, stress and schizophrenia

“Children born to women who suffer severe stress early in pregnancy are at increased risk of developing schizophrenia later in life,” The Daily Telegraph reports.

The newspaper said that a Danish study of 1.38 million births from 1973 to 1995 found the risk of schizophrenia increased by 67 per cent among the offspring of women who experienced the death of a relative during early pregnancy.

The BBC said that researchers found that the risk did not increase at any other time during pregancy or in the six months leading up to it.

This large study looked at schizophrenia in the children of pregnant mothers who experienced the death or serious illness of a close relative before or during pregnancy. It  did not look at all types of mental illness and the only stressful event recorded was the death or illness of a relative.

Many factors, including genetic and environmental ones, are likely to play a role in the risk of developing schizophrenia as an adult. Prospective mothers should bear in mind that for each individual the overall risk of developing schizophrenia is low.

Where did the story come from?

Ali Khashan and colleagues from University of Manchester, Cork University in Ireland, and University of Aarhus in Denmark carried out the research. The study was funded by Tommy’s the Baby Charity and the Stanley Medical Research Institute. The study was published in the peer-reviewed medical journal: Archives of General Psychiatry.

What kind of scientific study was this?

In this retrospective cohort study, the researchers used Danish population registers to see whether maternal exposure to stressful events affected the risk of schizophrenia in offspring.

Using the register of all births in Denmark, the researchers identified 1.38 million women who had given birth between January 1 1973 and June 30 1995. National registries were used to identify the women’s close relatives (parents, siblings, spouses, and other children), and to see if any of these relatives had died, or had serious illnesses such as heart attacks, cancer, or a stroke. Using this data the researchers identified women who had experienced the death or serious illness of a close relative either during their pregnancy or in the six months before pregnancy.

The researchers then used the Danish Psychiatric Central Register, which records all admissions to psychiatric inpatient units since 1969 and all outpatient visits to psychiatric units since 1995, to see whether the women’s children had been diagnosed with schizophrenia between the age of 10 and death, loss to follow up (being unable to be traced by the researchers), migration, or the end of the study (June 30 2005).

The risk of the offspring developing schizophrenia if their mothers had had a close relative get seriously ill or die during pregnancy was then compared with those whose mothers had not. The researchers also looked at whether the risk varied depending on when the mother was exposed to the traumatic event (in the six months before pregnancy, first trimester, second trimester, or third trimester) and the type of event (illness or death). Factors that could have affected the results were taken into account, such as family history of schizophrenia or other mental illnesses, place of birth, offspring age and gender, maternal age, not being able to identify the father of the child, and year of diagnosis.

What were the results of the study?

Just over 36,000 of the 1.38 million women had a close relative get seriously ill or die in the six months before pregnancy or during pregnancy. Of the children of the 1.38 million women, 7,331 developed schizophrenia, and 122 of these had mothers who had been exposed to these traumatic life events during or just before pregnancy.

Overall, the researchers found no significant association between maternal exposure to a traumatic life event (both a close relative dying and getting ill) just before or during pregnancy and the risk of schizophrenia in the offspring. The researchers then looked at the effects of a close relative dying or getting ill separately. When this was done, no significant association was found between serious illness in a close relative and risk of schizophrenia in offspring.

However, there was an increased risk of the children developing schizophrenia if the mother had had a close relative die during their first trimester, but not in other trimesters or just before pregnancy. This increase remained even if the researchers looked only at people with no family history of schizophrenia. The researchers estimated that maternal exposure to death during the first trimester could be responsible for three in every 1,000 cases of schizophrenia.

What interpretations did the researchers draw from these results?

The researchers concluded that exposure to severe stress during the first trimester of pregnancy “may alter the risk of schizophrenia in offspring”.

What does the NHS Knowledge Service make of this study?

This study has the advantage of being based on an entire population. However, there are some limitations to bear in mind:

• This study was based on information collected in various Danish national registers. The accuracy of the study’s results is dependent on the accuracy and completeness of the information recorded in these registers. For example, it is likely that some cases of schizophrenia have been missed as the registers did not capture outpatient visits for schizophrenia before 1995. In addition, some women's close relatives could not be identified.
• As with any study where the participants are not randomly chosen, these results could have been caused by other differences between the groups. Although efforts were made to take these into account, they may not have been adequate, especially as some information in the registries may have been incomplete, such as whether or not there was a family history of schizophrenia.
• Although the study looked at a large group of people, few developed schizophrenia. These small numbers mean that it is difficult to make an accurate estimate of how different factors contribute to the risk of the disease, as analyses will not be able to detect small effects. It is also more likely for significant effects to occur by chance.
• Because registry data was the sole source of information, it is unknown if the mothers experienced traumas other than the death or illness of a close relative during pregnancy.
• These results may not apply to different populations of women.

Many factors, including genetics and the environment, are likely to play a role in the risk of developing schizophrenia, and it is worth bearing in mind that the overall risk for developing this disease is low.