Anti-TNF Levels in Cord Blood at Birth are Associated with Anti-TNF Type.

BACKGROUND AND AIMS: Pregnancy guidelines for women with inflammatory bowel disease [IBD] provide recommendations regarding anti-TNF cessation during pregnancy, in order to limit foetal exposure. Although infliximab [IFX] leads to higher anti-TNF concentrations in cord blood than adalimumab [ADA], the recommendations are similar. We aimed to demonstrate the effect of anti-TNF cessation during pregnancy on foetal exposure, for IFX and ADA separately. METHODS: We conducted a prospective single-center cohort study. Women with IBD, using IFX or ADA, were followed-up during pregnancy. In case of sustained disease remission, anti-TNF was stopped in the third trimester. At the birth, the anti-TNF concentration was measured in the cord blood. A linear regression model was developed to demonstrate anti-TNF concentration in cord blood at birth. In addition, outcomes such as disease activity, pregnancy outcomes and 1-year health outcomes of infants were collected. RESULTS: We included 131 pregnancies that resulted in a live birth [73 IFX, 58 ADA]. At birth, 94 cord blood samples were obtained [52 IFX, 42 ADA], showing significantly higher levels of IFX than ADA [p < 0.0001]. Anti-TNF type and stop week were used in the linear regression model. During the third trimester, IFX transportation over the placenta increased exponentially; however, ADA transportation was limited and increased in a linear fashion. Overall, health outcomes were comparable. CONCLUSIONS: Our linear regression model shows that ADA may be continued longer during pregnancy, because transportation over the placenta is lower than for IFX. This may reduce relapse risk of the mother, without increasing foetal anti-TNF exposure.

Use of Thiopurines During Conception and Pregnancy Is Not Associated With Adverse Pregnancy Outcomes or Health of Infants at One Year in a Prospective Study.

BACKGROUND & AIMS: Most data on the safety of thiopurine therapy for inflammatory bowel disease (IBD) during pregnancy come from retrospective studies, which makes it difficult to adjust for confounding factors. We performed a prospective cohort study to determine whether thiopurine use affects pregnancy outcomes or health outcomes of children. METHODS: We performed a prospective study of all women who visited the IBD preconception outpatient clinic at our tertiary health center in The Netherlands from December 2008 through May 2016. Patients were counseled before pregnancy and seen bimonthly during pregnancy. We collected and analyzed data on medication use, as well as lifestyle and clinical factors, during conception and pregnancy. Pregnancy outcomes (live birth, spontaneous abortion, elective abortion, and stillbirth), birth outcomes (gestational age, birth weight, and congenital abnormalities), and health outcomes of infants 1 year after birth were compared between women who did and did not use a thiopurine during conception and pregnancy. In addition, health outcomes of infants 1 year after birth were compared with infants born to mothers without IBD from the same geographic region. RESULTS: Our study comprised 309 women with confirmed IBD (216 with Crohn's disease, 85 with ulcerative colitis, and 8 with IBD unclassified). During the study period, 311 pregnancies of 232 women resulted in a live birth; a thiopurine was used during 108 pregnancies (35%). After correction for diagnosis, fertility treatment, and disease activity, there was no association between thiopurine use and spontaneous abortions. Birth outcomes were similar between women who did and did not use a thiopurine. Among infants 1 year of age, there were no differences in median growth, number of infections, allergies, adverse reactions to vaccinations, or chronic diseases between those born to women who did and did not use a thiopurine or between women with and without IBD. CONCLUSIONS: In this prospective cohort study, we found no association between maternal thiopurine use during pregnancy and increased spontaneous abortions, adverse birth outcomes, or adverse health outcomes of infants 1 year after birth.

The Effects of Active IBD During Pregnancy in the Era of Novel IBD Therapies.

OBJECTIVES: Previous data on inflammatory bowel disease (IBD) relapse during pregnancy mainly originate from retrospective studies. The aim of this study was therefore (i) to evaluate the effect of active disease at conception and IBD disease type on disease relapse during pregnancy and (ii) to study the effects of disease relapse during pregnancy on birth outcomes in a prospective cohort with adequate representation of current treatments. METHODS: From 2008 to 2014, IBD women were recruited from an ongoing prospective clinical cohort. All patients with confirmed IBD diagnosis with a pregnancy wish or pregnancy were prospectively followed-up until pregnancy and delivery. Disease relapse was measured at each visit. Birth outcomes were recorded from the obstetrician. RESULTS: A total of 298 pregnancies were observed in 229 IBD patients (157 Crohn's disease (CD), 66 ulcerative colitis (UC), and 6 IBD unclassified), resulting in 226 live births. Active disease at conception was strongly associated with disease relapse during pregnancy (aOR=7.66, 95% confidence interval (CI): 3.77-15.54). UC patients experienced relapse during pregnancy more often than CD patients, independent of maternal age, smoking, periconceptional disease activity, previous IBD surgery, and the use of immunosuppressives or anti-tumor necrosis factor (TNF) (aOR=3.71, 95% CI:1.86-7.40). Disease relapse was not associated with adverse birth outcomes such as spontaneous abortion, low-birth weight, or preterm birth. CONCLUSIONS: This study confirms that active disease around conception increases the risk of disease relapse during pregnancy. In addition, UC patients relapse more often during pregnancy than CD patients. Birth outcomes were excellent, reflecting the stringent follow-up and treatment of this group of patients.