Factors Associated with Inflammatory Bowel Disease Flare During Pregnancy Among Women with Preconception Remission.

BACKGROUND: The factors associated with inflammatory bowel diseases (IBD) relapse throughout gestation in those with preconception remission remain unknown. AIMS: We aimed to investigate disease and pregnancy course among IBD women with quiescent disease at conception. METHODS: Women with IBD attending a multidisciplinary clinic for preconception, antenatal and postnatal treatment were prospectively recruited during 2011-2018. RESULTS: Overall, 298 women with IBD with quiescent disease at the time of conception constituted the study cohort. Of these, 112 (37.6%) women experienced disease flare during pregnancy. The risk of disease relapse was higher in those with ulcerative colitis (UC) as compared to those with Crohn's disease (CD) (48.1% vs. 31.8%, P = 0.005). The proportion of women with prior IBD-related gastrointestinal surgery was lower in those who experienced disease flare up (13.4% vs. 26.3%, P = 0.009). The use of biologic therapy at the time of conception was associated with lower rates of disease relapse (25.0% vs. 43.9%, P = 0.001). In multivariate analysis, use of conventional medications or no treatment (aOR [95% CI]: 2.0 (1.12, 3.57), P = 0.02) and lack of prior history of IBD-related surgery (aOR [95% CI]: 3.13 (1.37, 7.14), P = 0.007) were independently positively associated with disease relapse. Rates of hospitalization during pregnancy (21.4% vs. 2.2%, P < 0.001) and preterm delivery (22.3% vs. 9.1%, P = 0.002) were higher, and birthweight was lower (median 2987 vs. 3153 grams, P = 0.05) in those with disease flare as compared to those who maintained remission. CONCLUSION: Prior IBD-related surgery and biologic therapy were found as independent protective factors against relapse during pregnancy among women with quiescent disease at conception.

Disease flare at prior pregnancy and disease activity at conception are important determinants of disease relapse at subsequent pregnancy in women with inflammatory bowel diseases.

PURPOSE: Disease flare throughout gestation are not uncommon among women with inflammatory bowel diseases (IBD), and can substantially affect pregnancy outcomes. We aimed to evaluate the effect of prior pregnancy outcome on the risk of disease flare at subsequent pregnancy in women with IBD. METHODS: Women with IBD attending a multidisciplinary clinic for the preconception, antenatal and postnatal treatment were prospectively recruited during 2011-2018. RESULTS: Overall, 476 IBD women were followed during the study period. Of them, 69 (14.5%) had two pregnancies throughout follow-up period and constituted the study cohort. Among these 69 women, 48 (69.6%) had Crohn's disease and 21 (30.4%) ulcerative colitis. The median interpregnancy interval was 20 [11-32] months. Overall, 34 (49.3%) women experienced disease flare at the subsequent pregnancy. In multivariate analysis, active disease at conception (odds ratio [95% CI]: 25.65 (3.05, 25.52), P < 0.001) and history of disease flare at the previous pregnancy (odds ratio [95% CI]: 4.21 (1.10, 16.58), P < 0.001) were the only independent predictors of disease relapse in current gestation. Rates of hospitalization during pregnancy (14.7% vs. 0, P = 0.02) and preterm delivery (32.4% vs. 5.7%, P = 0.006) were higher, and neonatal birth weight was lower (median 3039 vs. 3300 g, P = 0.03), in those with disease flare as compared to those with maintained remission. CONCLUSION: History of disease relapse at previous gestation and periconception disease activity were found as important predictors of disease flare among IBD women. These data would facilitate adequate counseling and informed management decisions among reproductive-aged IBD women and their treating physicians.

Ustekinumab during pregnancy in patients with inflammatory bowel disease: a prospective multicentre cohort study.

BACKGROUND: Women with inflammatory bowel diseases (IBD) often receive biologics to maintain remission during pregnancy. AIMS: To assess maternal and neonatal outcomes in patients with IBD treated with ustekinumab (UST) during pregnancy METHODS: In a multicentre, prospective cohort study, we recruited women with IBD treated with UST during pregnancy between 2019 and 2021. Outcomes were compared among patients treated with UST, anti-tumour necrosis factor α, (anti-TNF) and non-UST, non-anti-TNF therapies. UST-treated patients were matched 1:2 to controls according to age, body mass index and parity. Newborns were followed up to 12 months. RESULTS: We recruited 129 pregnant patients: UST 27; anti-TNF 52; non-UST, non-anti-TNF 50 (thiopurine or mesalazine 30, no therapy 20); Crohn's disease 25 (96.9%). Overall, pregnancy, neonatal and newborn outcomes were satisfactory, with no significant differences among patients treated with UST, anti-TNF and non-UST non-anti-TNF agents for obstetrical maternal complications [UST 3 (11.5%), anti TNF 12 (23.1%), non UST, non-anti-TNF 4 (8.2%), p = 0.095], pre-term delivery [1 (4.3%), 9 (18.4%), 4 (5.7%), p = 0.133], low birth weight [1 (4.2%), 5 (10.2%), 4 (8.3%), p = 0.679], or first year newborn hospitalisation [2 (9.1%), 4 (8.2%), 3 (6.1%), p = 0.885]. CONCLUSION: Pregnant patients with IBD treated with UST demonstrated favourable pregnancy and neonatal outcomes that were comparable with those in patients treated with anti-TNF or other therapy. Data are reassuring for patients with IBD and their physicians when considering UST during pregnancy.

SARS-CoV-2 IgG Antibody Levels in Women with IBD Vaccinated during Pregnancy.

INTRODUCTION: Regulatory agencies supported vaccination of pregnant women with SARS-CoV-2 mRNA vaccines, including patients with IBD. No data exist regarding these vaccines in IBD during pregnancy. AIM: To assess the serologic response to two doses of the mRNA SARS-CoV-2 BNT162b2 vaccine in pregnant women with IBD vaccinated during pregnancy, compared to that of pregnant women without IBD, and non-pregnant women with IBD. METHODS: Anti-spike antibody levels were assessed in all women and in cord blood of consenting women. RESULTS: From December 2020 to December 2021, 139 women were assessed: pregnant with IBD-36, pregnant without IBD-61, and not pregnant with IBD-42. Antibodies were assessed in cords of two and nine newborns of women with and without IBD, respectively. Mean gestational ages at administration of the second vaccine doses were 22.0 weeks in IBD and 23.2 weeks in non-IBD, respectively. Mean (SD) duration from the second vaccine dose to serology analysis in pregnant women with IBD, without IBD, and in non-pregnant women with IBD was 10.6 (4.9), 16.4 (6.3), and 4.3 (1.0) weeks, respectively. All women mounted a serologic response. In multivariable analysis, no correlation was found between the specific group and antibody levels. In both pregnancy groups, an inverse correlation between antibody levels and the interval from the second vaccine dose was demonstrated. Cord blood antibody levels exceeded maternal levels in women with and without IBD. CONCLUSION: All patients with IBD mounted a serologic response. The interval between vaccine administration to serology assessment was the most important factor determining antibody levels. A third vaccine dose should be considered in pregnant women with IBD vaccinated at early stages of pregnancy.

A unique sonographic presentation of prenatal volvulus associated with malrotation.

This is a unique case of prenatal diagnosis of bowel malrotation suspected by an abnormal course of the duodenum. Early detection of volvulus was enabled, leading to timely intervention and a favorable outcome.

Clinical utility of fecal calprotectin in monitoring disease activity and predicting relapse in pregnant patients with inflammatory bowel diseases.

OBJECTIVES: Inflammatory bowel diseases (IBDs) are commonly diagnosed in reproductive-aged women and can substantially affect pregnancy outcomes. Non-invasive monitoring of IBD during the prenatal course is particularly challenging as traditional laboratory biomarkers are often affected by pregnancy-related physiologic changes. We aimed to evaluate the role of fecal calprotectin (FC) in monitoring disease activity and predicting relapse among IBD women throughout gestation. METHODS: Women with IBD attending a multidisciplinary clinic for the preconception, antenatal and postnatal treatment were prospectively recruited during 2014-2018. FC levels were determined with an enzyme-linked immunoassay. RESULTS: A total of 265 FC (preconception, n = 41; 1st trimester, n = 48; 2nd trimester, n = 84; 3rd trimester, n = 76; postpartum, n = 16) measurements were obtained in 157 pregnancies. Higher FC concentrations were found in all time points in those with active disease than those in remission as assessed by either physician global assessment or disease clinical scores. FC levels were significantly correlated with physician global assessment and disease activity indices in all 5 periods of investigation. Excluding those with disease flare at the time of conception, disease relapse was encountered during the prenatal course in 40 (31.5%) of the remaining 127 pregnancies. FC levels were significantly higher in those who experienced a disease flare later in the course of gestation as compared to those who maintained clinical remission (median 341 vs. 224 µg/g, P = 0.04). CONCLUSION: FC appears to be a reliable marker of ongoing disease activity throughout the prenatal course as well as a predictor of imminent disease flare among IBD pregnant patients.

Assessment of the procoagulant potential and associated risk factors in pregnant patients with inflammatory bowel diseases.

OBJECTIVE: Both inflammatory bowel diseases (IBDs) and pregnancy are established risk factors for thrombotic complications, thus IBD pregnant patients can be considered at even greater risk for thrombosis as compared to non IBD pregnant women. We aimed to evaluate the risk factors associated with this prothrombotic tendency among IBD women throughout gestation. METHODS: Women with IBD attending a multidisciplinary clinic for the preconception,antenatal and postnatal treatment were prospectively recruited during 2017-2018. Prothrombotic tendency was assessed by thrombin generation, a global marker of the activation of the coagulation system, expressed as the endogenous thrombin potential (ETP). RESULTS: Overall, 145 IBD women and 50 healthy control subjects were enrolled in this study. Body mass index (BMI) and gestational age were comparable between the groups. ETP level was significantly higher in women with IBD compared to control subjects in all time period (P < .0001). Among women with IBD, ETP level positively correlated with disease activity, as assessed by physician global assessment (P = .005), gestational age (P < .0001), extra-intestinal involvement (P = .04), C-reactive protein level (P < .0001), erythrocyte sedimentation rate (P < .0001), white blood cell count (P = .008), BMI (P = .02) and was inversely correlated with hemoglobin level (P < .0001). ETP level did not correlate with the occurrence of adverse pregnancy outcomes. In a multivariate analysis, active disease (ß = 0.20, P = .009), gestational age (ß = 0.45, P < .0001), extra-intestinal involvement (ß = 0.17, P = .02) and BMI (ß = 0.15, P = .05) retained independent predictors of high ETP levels. CONCLUSION: As determined by thrombin generation, the procoagulant potential among IBD pregnant patients was independently associated with disease activity, BMI and extra-intestinal disease involvement.