Context

Thiopurines and anti-TNF are increasingly used during the pregnancy of women with inflammatory bowel disease (IBD). These drugs do not increase the rate of malformations and serious infections in children who have been exposed in utero. Yet, recent large-scale studies have shown that thiopurines are associated with increased rates of stillbirths, preterm births and large for gestational age infants, while combination of thiopurines and anti TNF are associated with increased rates of serious infections during the first year of life

Objective

The aim of the present study was to assess the risk of malignancies in children born to mothers with IBD and exposed in utero to thiopurines or anti-TNF.

Results

Of a total of 35,071 pregnancies, 35,772 children born from 26,092 women with IBD were included. Among them, 4,994 had been exposed in utero to thiopurines, 5,725 to anti-TNF, and 26,092 to neither of these (1,039 had been exposed to both drugs).

A total of 59 malignancies occurred during follow-up: 17 leukemias, 8 lymphomas, 9 central nervous system tumors, 7 neuroblastomas, 3 retinoblastomas, 2 renal tumors, 2 hepatic tumors, 3 malignant bone tumors, 2 extraosseous sarcomas, 3 germ cell tumors, and 3 othermalignant epithelial neoplasms. Median age at cancer diagnosis was 2.7 years. The overall rate of malignancies was 269/million person-year (PY). This rate was 270/million-PY in children exposed to thiopurines, 135/million-PY in children exposed to anti-TNF, and 270/million-PY in children unexposed to thiopurine or anti-TNF. No malignancy occurred among children exposed to both thiopurine and anti-TNF. The overall risk of malignancy did not differ between children unexposed to thiopurine and anti-TNF and those exposed to thiopurines or to anti-TNF.

Conclusions

Prenatal exposure to thiopurines or anti-TNF does not appear to increase the risk of earlylife malignancy. In this study, the overall incidence rate of childhood malignancy in children born to mothers with IBD was of 269/million-PY, close to that reported in the French general population over the same years (181/million-PY).