Health-related quality of life in the first 5 years of the children born to mothers with IBD does not differ from children born to healthy mothers.

OBJECTIVE: Inflammatory bowel disease (IBD) is often diagnosed in women in their reproductive years of life and therefore children are born to mothers with IBD. Health outcomes of children born to mothers with IBD seem favorable. However, little is known about the quality of life related to their health compared to children born to healthy mothers. Therefore, our first objective was to investigate the effect of having IBD during pregnancy on the health-related quality of life (HRQoL) of children born to mothers with IBD in the first 5 years of age compared to children born to healthy mothers. Secondly, we studied the effect of the different IBD related factors on the HRQoL. METHODS: We prospectively followed 264 women with IBD, who visited the preconception outpatient clinic at our tertiary health center in the Netherlands from April 2013 through November 2016. Women of children aged 1-5 years were approached to fill in a 43-item validated TNO-AZL Preschool Children Quality of Life questionnaire (TAPQOL) to assess HRQoL (Fekkes et al., 2000; Bunge et al., 2005 [1,2]). Outcomes were compared to children of mothers without IBD. RESULTS: One-hundred-eighty-two women completed the TAPQOL questionnaire. In total 182 children of mothers with IBD were included [median age 3.0 years (IQR 2-4)]. From 70 healthy mothers, 70 children were included as controls. There was no significant difference in the HRQoL between children who were and were not born to mothers with IBD (P = .18). Also, no effect of the different IBD related factors was found. CONCLUSION: In this study, we found no effect of having IBD during pregnancy on the health-related quality of life of children in the first 5 years of life.

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.

Hepatitis B Vaccination Effective in Children Exposed to Anti-Tumour Necrosis Factor Alpha in Utero.

INTRODUCTION: Neonates exposed to tumour necrosis factor [TNF] alpha inhibitors in utero are born with detectable drug levels which can still be detected throughout the first year of life. Since 2011, the hepatitis B virus [HBV] vaccine is routinely administered to all newborns in the Netherlands. Adults treated with anti-TNF have been reported to respond inadequately to the HBV vaccine. The aim of this study was to compare anti-HB levels in anti-TNF-exposed children with non-exposed children following routine Dutch HBV vaccination. METHODS: We performed a cross-sectional, controlled cohort study from 2014 to 2017 in a single, tertiary referral centre. Pregnant women treated with anti-TNF for inflammatory bowel disease [IBD] and their subsequent children were recruited from the IBD preconception outpatient clinic. Pregnant women not treated with anti-TNF for IBD and their subsequent children were eligible as controls. Adherence to the Dutch National Vaccination Programme was mandatory for participation in this study. A venous blood sample was obtained 1 month after final HBV vaccination. Anti-HB levels were measured by enzyme-linked immunosorbent assay. RESULTS: Anti-HB levels at 12 months did not differ between the anti-TNF-exposed [n = 15] and the control group [n = 12] [> 1000 IU/l vs > 1000 IU/l, p = 0.59]. All children were successfully immunized against HBV, defined as anti-HB > 10 IU/l. Median anti-TNF levels determined in cord blood at birth were 9.0 µg/ml [interquartile range: 3.0-15.0 µg/ml] for infliximab and 0.4. µg/ml [interquartile range: 0.3-0.6 µg/ml] for adalimumab. There were no differences in general birth and health outcomes. CONCLUSION: Children born with detectable anti-TNF levels can be effectively vaccinated against HBV.

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.

Drug therapies for ulcerative proctitis: systematic review and meta-analysis.

BACKGROUND: Patients with ulcerative colitis limited to the proctum are considered to have ulcerative proctitis (UP). In patients with more extensive ulcerative colitis, treatment occurs in a step-up fashion (5-ASA, corticosteroids, thiopurines, anti-TNF-α agents), a strategy which has proven effective. Although treatment of UP occurs using the same step-up design, the efficacy of these therapies in UP is scarcely studied. The objectives were to systematically review the literature for randomized controlled trials studying drug therapies for induction and maintenance of remission in patients with UP. METHODS: Electronic databases and reference lists of review articles were searched. The primary outcomes were clinical remission induction rate and the maintained clinical remission rate. Secondary outcomes were induction and maintenance of endoscopic and histological remission. Relative risks (RR) and 95% confidence intervals (CI) for were calculated. RESULTS: Twenty-three studies (1834 patients) were included. Eighteen trials investigated induction and 5 studied maintenance of remission. Topical 5-ASA was significantly superior to placebo for induction (RR, 2.39; 95% CI, 1.63-3.51) and maintenance (RR, 2.80; 95% CI, 1.21-6.45) of clinical remission, regardless of dose or formulation. Subgroup analysis of 5-ASA suppositories also showed superiority over placebo for induction of clinical (RR, 3.07; 95% CI, 1.70-5.55) and endoscopic remission (RR, 2.64; 95% CI, 1.85-3.77). CONCLUSIONS: Topical 5-ASA is superior to placebo for the induction and maintenance of clinical remission and for the induction of endoscopic remission. The efficacy of corticosteroids, thiopurines, and anti-TNFα has been insufficiently studied in patients with UP.

Double sampling of a faecal immunochemical test is not superior to single sampling for detection of colorectal neoplasia: a colonoscopy controlled prospective cohort study.

BACKGROUND: A single sampled faecal immunochemical test (FIT) has moderate sensitivity for colorectal cancer and advanced adenomas. Repeated FIT sampling could improve test sensitivity. The aim of the present study is to determine whether any of three different strategies of double FIT sampling has a better combination of sensitivity and specificity than single FIT sampling. METHODS: Test performance of single FIT sampling in subjects scheduled for colonoscopy was compared to double FIT sampling intra-individually. Test positivity of double FIT sampling was evaluated in three different ways: 1) "one of two FITs+" when at least one out of two measurements exceeded the cut-off value, 2) "two of two FITs+" when both measurements exceeded the cut-off value, 3) "mean of two FITs+" when the geometric mean of two FITs exceeded the cut-off value. Receiver operator curves were calculated and sensitivity of single and the three strategies of double FIT sampling were compared at a fixed level of specificity. RESULTS: In 124 of 1096 subjects, screen relevant neoplasia (SRN) were found (i.e. early stage CRC or advanced adenomas). At any cut-off, "two of two FITs+" resulted in the lowest and "one of two FITs+" in the highest sensitivity for SRN (range 35-44% and 42%-54% respectively). ROC's of double FIT sampling were similar to single FIT sampling. At specificities of 85/90/95%, sensitivity of any double FIT sampling strategy did not differ significantly from single FIT (p-values 0.07-1). CONCLUSION: At any cut off, "one of two FITs+" is the most sensitive double FIT sampling strategy. However, at a given specificity level, sensitivity of any double FIT sampling strategy for SRN is comparable to single FIT sampling at a different cut-off value. None of the double FIT strategies has a superior combination of sensitivity and specificity over single FIT.

Higher fecal immunochemical test cutoff levels: lower positivity rates but still acceptable detection rates for early-stage colorectal cancers.

BACKGROUND: Adjusting the threshold for positivity of quantitative fecal immunochemical tests (FIT) allows for controlling the number of follow-up colonoscopies in a screening program. However, it is unknown to what extent higher cutoff levels affect detection rates of screen-relevant neoplasia. This study aimed to assess the effect of higher cutoff levels of a quantitative FIT on test positivity rate and detection rate of early-stage colorectal cancers (CRC). METHODS: Subjects above 40 years old scheduled for colonoscopy in 5 hospitals were asked to sample a single FIT (OC sensor) before colonoscopy. Screen-relevant neoplasia were defined as advanced adenoma or early-stage cancer (stage I and II). Positivity rate, sensitivity, and specificity were evaluated at increasing cutoff levels of 50 to 200 ng/mL. RESULTS: In 2,145 individuals who underwent total colonoscopy, 79 patients were diagnosed with CRC, 38 of which were with early-stage disease. Advanced adenomas were found in 236 patients. When varying cutoff levels from ≥ 50 to ≥ 200 ng/mL, positivity rates ranged from 16.5% to 10.2%. With increasing cutoff levels, sensitivity for early-stage CRCs and for screen-relevant neoplasia ranged from 84.2% to 78.9% and 47.1% to 37.2%, respectively. CONCLUSIONS: Higher FIT cutoff levels substantially decrease test positivity rates with only limited effects on detection rates of early-stage CRCs. However, spectrum bias resulting in higher estimates of sensitivity than would be expected in a screening population may be present. IMPACT: Higher cutoff levels can reduce strain on colonoscopy capacity with only a modest decrease in sensitivity for curable cancers.