Anti-TNF-alpha and/or thiopurines in IBD during pregnancy without negative consequences for mother and child
A new study was published that looked at the adverse effects of treating inflammatory bowel disease (IBD) with anti-TNF-alpha or thiopurine drugs.
Study on inflammatory bowel disease
Good news is good news. And this is especially true when it does not only concern individual patients, but always pairs of patients - that is: pregnant women with inflammatory bowel diseases and their children.
Such "doubly good" news has just been published in the scientific journal Gut.1 A retrospective multicentre study was published that looked at the adverse effects of treating inflammatory bowel disease (IBD) with anti-TNF-alpha or thiopurine drugs. The retrospective study, which was conducted at a total of 20 Dutch clinics, recorded the health consequences for 1,000 children and their 626 mothers who had taken corresponding therapies during their pregnancy. The children were followed up until the age of five.
And the result of the study is that no negative consequences for the children are to be expected.
What was evaluated
Of the 1,000 children included in the study, 564 had not been exposed to either anti-TNF-alpha or thiopurine drugs during pregnancy. These children served as a control group for the 436 children who had had contact with the respective substances in the womb. In addition, the average values of the Dutch general population could and were used as a comparison for some parameters.
The following was recorded for the children study:
- Antibiotic-treated infections: An increased incidence of infections requiring antibiotics was only found in children of mothers who actively smoked during pregnancy. In contrast, such infections occurred less frequently if the mothers had breastfed their child for at least one month. An increase in antibiotic-requiring infections was not observed even if the mothers continued a previously started anti-TNF-alpha therapy in the third trimester of pregnancy.
- Hospitalisations due to severe infections: With regard to this parameter, the researchers were also unable to detect any abnormalities when comparing the children in the verum and control groups. This also applied in the same way to the subgroup of children who were exposed to anti-TNF-alpha drugs during pregnancy.
- Vaccination side effects: In total, only seven severe vaccination reactions were observed in the children. Four of the children had to be hospitalised due to high fever, but no life-threatening vaccine side effects occurred. According to the authors of the study, these figures do not allow an association of drug exposure with frequently occurring severe vaccination side effects. This also applied to children whose mothers had developed intrahepatic cholestasis (ICP) during pregnancy.
- Growth: A total of 16 (1.6%) of the children showed a growth disorder. This is close to the average value in the Dutch general population. An association with the mothers' IBD medication during pregnancy could not be demonstrated. None of the children of mothers with ICP developed growth retardation.
- Autoimmune diseases: One of the children (0.1%) developed an autoimmune disease in the form of type 1 diabetes mellitus. However, his mother had not taken any IBD medication during pregnancy and had not had an episode of the disease. The researchers therefore assume that the medications studied do not lead to an increased incidence of autoimmune diseases.
- Malignancies: Two (0.2%) children developed malignancies in the form of rhabdomyosarcoma of the left orbit and leukaemia, respectively. The number of affected children again corresponds to the Dutch average for the general population. Both mothers had taken cortisone during pregnancy, the mother of the child with rhabdomyosarcoma also azathioprine. The researchers concluded, however, that even in these cases there was no evidence for an association of the medication intake with the observed malignancies.
Other findings
The authors of the study also identified other associations between risk factors and pregnancy complications. For example, the administration of systemic corticosteroids was associated with preterm births. A more detailed analysis of this association by pregnancy trimester was not possible because of the small number of cases.
Women who took a thiopurine during pregnancy had an increased risk of intrahepatic cholestasis. This could lead to an increased concentration of 6-methylmercaptopurines (6-MMP), the authors say. They therefore recommend prophylactically monitoring the corresponding 6-MMP levels in the patients.
Despite all the positive results of the study, the authors point out two weaknesses of the study. Firstly, there was no comparison group that was not affected by IBD. In addition, the bias that could have entered the study as a result of patient selection seems worth mentioning to the authors. Only 34% of the women contacted for the study had agreed to participate in the study in the end.
This study is the largest of its kind to date.
Reference:
1. Kanis SL, et al. Health outcomes of 1000 children born to mothers with inflammatory bowel disease in their first 5 years of life. Gut 2021; 70: 1266-1274.