Painkillers during pregnancy increase risk of schizophrenia by four times
Nov 2, 2004 - 3:16:38 PM

Children born to mothers who took analgesics in the second three months of pregnancy run a more than four-fold greater risk of developing schizophrenia, a new study from Denmark has found.

Published in the November issue of the British Journal of Psychiatry, the study set out to shed light on the hypothesis that prenatal exposure to analgesics may affect the development of the nervous system of the foetus, leading to an increased risk of schizophrenia in adulthood.

The researchers analysed data from the Copenhagen Perinatal Cohort, which consists of 9125 individuals delivered by 8949 pregnant women between October 1959 and December 1961. A total of 8400 infants survived the first month after birth.

Information on exposure to analgesics and psychiatric hospitalisation was available for 7999 people from the Perinatal Cohort. It was found that the prevalence of exposure to analgesics at any time during the first trimester was 0.9%; during the second trimester 1.8%; and during the third, 2.0%.

A total of 116 cases of schizophrenia were identified. For the first trimester, the risk was only significant for the third month, and was not significant for the third trimester. However, the incidence of schizophrenia in both males and females in the analgesic exposure group during the second trimester was more than four times higher than in the non-exposure group during that period.

The association was slightly stronger in females than males. Importantly, it was independent of maternal schizophrenia, which was the strongest risk factor for schizophrenia in this study.

Other known risk factors, such as parental history of schizophrenia, second-trimester viral infections, treatment with other drugs, pregnancy complications, parental social status and parental age were all taken into account. The link between prenatal exposure to analgesics and schizophrenia was found to be independent of all these risk factors.

The authors comment that during the second trimester of pregnancy a part of the brain called the cortical subplate reaches its peak of development. This may be a period when the immature foetal brain is particularly sensitive to a range of environmental influences.

It was previously found from data from the Copenhagen Perinatal Cohort that the risk of having malformed children was over twice as high in mothers who took analgesics during pregnancy. This discovery is of potential relevance to theories on causal factors in schizophrenia, as well.

A large number of physical defects, such as cleft palate, large or small distance between tear ducts and adherent earlobes have been linked to schizophrenia-spectrum disorders in a sample of the Copenhagen Perinatal Cohort.

The researchers also found that taking psychiatric medications during the second trimester was associated with intake of analgesics during the same period. Taking both these medications could be associated with increased levels of psychiatric problems and/or a tendency to consult a physician more often.

However, it would have required a larger cohort study and the collection of additional prenatal and perinatal data to disentangle effects of prenatal exposure to analgesic drugs from the effects of the somatic and psychosomatic conditions prompting their use.

The authors of the study caution that as only 6.9% of all the cohort members with schizophrenia had been exposed to analgesics in the second trimester, this research needs to be replicated before prenatal exposure to analgesics can be added to the list of demonstrated risk factors for schizophrenia.

Holger J, Sorensen E L, Mortensen L, Reinisch J M and Mednick S A (2004) Association between prenatal exposure to analgesics and risk of schizophrenia. British Journal of Psychiatry, 185, 366-371.

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