Exposure to measles in utero and Crohn's disease: Danish register study

Introduction

It has been suggested that people exposed to measles in utero may be at high risk of developing Crohn's disease in adulthood.1 2 Swedish investigators have reported an increased incidence of Crohn's disease in individuals born shortly after a measles epidemic,3 and they later described four pregnant women with measles, three of whose offspring developed Crohn's disease as adults.4

Subjects, methods, and results

To test this surprisingly strong association we conducted a record linkage study in Denmark. Hospital records from the Blegdamshospital (until 1976 the main hospital for treatment of infectious diseases in Copenhagen county) for 1915-66 were screened to identify pregnant women aged 15-43 years with measles. Their children were identified through the Copenhagen civil register (or church registers for those born before 1923) and linked through their civil registration system numbers with the national hospital discharge, cancer, and inflammatory bowel disease registries. Offspring who died before 31 December 1995 were identified through death certificates. For those with a gastrointestinal diagnosis, we contacted the patient's doctor for more information.

We identified 472 women aged 15 to 43 years who had been admitted with measles. Thirty three were pregnant: 11 developed measles during the first trimester, 9 during the second, 6 during the third, and 9 had exanthema less than 14 days after delivery. All but three women were identified in the civil registers. Four first trimester pregnancies were never registered and one child could not be found in any register.

Of the 26 offspring identified (including one set of twins), four died, one in infancy. The diagnoses of the other three, who died as adults, did not suggest inflammatory bowel disease (drug addiction, lung cancer, and heart disease). Among individuals still alive (median age 51.4 (36-79) years) none were registered as having Crohn's disease in either the inflammatory bowel disease register for Copenhagen or the national hospital discharge register. Three had gastrointestinal diagnoses: colon cancer 51 years ago at age 28, benign rectal neoplasm 8 years ago at age 44, and proctitis haemorrhagica 19 years ago at age 21. These patients’ general practitioners confirmed that none had developed inflammatory bowel disease.

Comment

We identified the offspring of 25 women who had had measles during pregnancy and found no association between exposure to measles and Crohn's disease. Based on a binomial distribution, the upper 95% confidence limit of our observed zero cases was 2.8 cases, which is far from the 18.8 cases expected (3/4 x 25 exposed) from the report by Ekbom et al.4

We are confident about the diagnoses made at the Blegdamshospital and the recording of the pregnancies. We cannot exclude the possibility that other women treated for measles at the hospital were in fact pregnant. However, all the records contained information on last day of menstruation and if one period was missed we considered the woman possibly pregnant; according to the civil registers none of these women gave birth.

Subjects exposed to measles in utero were followed long past the age in which Crohn's disease peaks (1). Even if they had developed Crohn's disease before 1977, when the discharge registry was established, Crohn's disease is a chronic disease which often results in admission so those affected would probably have appeared in the discharge register at some time after this date. Proctitis haemorrhagica and colon cancer could both be associated with ulcerative colitis, but the patients admitted several times to hospital were never treated for colitis or an associated problem.

Follow up of subjects exposed to measles in utero. Each line represents subjects followed from birth until 1995 or death. The age interval 15-30 years (within which the incidence of inflammatory bowel disease peaks) is shown. Year that registers were established is also indicated (CR=cancer register, IBDR=inflammatory bowel disease register, CRS=civil registration system, NHDR=national hospital discharge register)

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We have no clear explanation for the discrepancy between our results and those of Ekbom et al. However, our findings agree with those of Jones et al,5 who followed the offspring of 47 women with measles in pregnancy; none of their offspring developed Crohn's disease after an average follow up of 33 years. Measles infection in their study was self reported or diagnosed by a general practitioner and was presumably less severe than in our group of hospitalised women. In conclusion, exposure to measles in utero does not seem to be strongly associated with the development of Crohn's disease later in life.