Accuracy of third trimester ultrasound in predicting neonatal birthweight in patients with inflammatory bowel disease

Author(s):  
Christine Roy-McMahon ◽  
Patricia Rekawek ◽  
Catherine Anne Bigelow ◽  
Samantha Raymond ◽  
Jessica R. Overbey ◽  
...  
2020 ◽  
pp. 205064062096461
Author(s):  
Ana-Marija Grišić ◽  
Maria Dorn-Rasmussen ◽  
Bella Ungar ◽  
Jørn Brynskov ◽  
Johan F K F Ilvemark ◽  
...  

Background Infliximab therapy during pregnancy in inflammatory bowel disease is challenged by a dilemma between maintaining adequate maternal disease control while minimizing fetal infliximab exposure. We investigated the effects of pregnancy on infliximab pharmacokinetics. Methods The study population comprised 23 retrospectively identified pregnancies. Patients with inflammatory bowel disease were generally in clinical remission at pregnancy conception (74%) and received steady infliximab maintenance therapy (5 mg/kg q8w n = 17; q6w n = 4; q10w n = 1; 10 mg/kg q8w n = 1). Trough blood samples had been obtained in the same patients prior to pregnancy ( n = 119), the first trimester ( n = 16), second trimester ( n = 18), third trimester ( n = 7), and post-pregnancy ( n = 12). Data were analyzed using nonlinear mixed-effects population pharmacokinetic modelling. Results Dose-normalized infliximab concentrations were significantly higher during the second trimester (median 15 µg/mL/kg, interquartile range 10–21) compared to pre-pregnancy (7, 2–12; p = 0.003), the first trimester (9, 1–12; p = 0.04), or post-pregnancy (6, interquartile range 3–11; p > 0.05) in patients with inflammatory bowel disease. Similar trends were observed in the third trimester (13, 7–36; p > 0.05). A one-compartment model with linear elimination described the pharmacokinetics of infliximab (volume of distribution = 18.2 L; clearance 0.61 L/day). Maternal infliximab exposure was influenced by the second and third trimester of pregnancy and anti-infliximab antibodies, and not by pregnancy-imposed physiological changes in, for example, body weight or albumin. Infliximab clearance decreased significantly during the second and third trimesters by up to 15% as compared to pre- and post-pregnancy and the first trimester. The increased maternal infliximab exposure was weakly associated with lowered clinical disease activity. Pharmacokinetic model simulations of virtual patients indicated the increased maternal infliximab trough concentrations imposed by pregnancy will not completely counteract the decrease in infliximab concentration if therapy is paused in the third trimester. Conclusion Infliximab clearance decreases significantly in the second and third trimesters, leading to increasing maternal infliximab concentrations in any given regimen. Maternal infliximab levels may thus be maintained as constant in a de-intensified regimen by therapeutic drug monitoring guidance in inflammatory bowel disease.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S391-S393
Author(s):  
F de Voogd ◽  
H Joshi ◽  
E Van Wassenaer ◽  
G D’Haens ◽  
K Gecse

Abstract Background Disease activity during pregnancy in women with inflammatory bowel disease (IBD) is associated with miscarriage, preterm delivery and low birth weight. Monitoring disease activity throughout the pregnancy is therefore important. Gastrointestinal ultrasound (GIUS) has a high potential as a point-of-care tool for monitoring disease activity in IBD as it has been shown to correlate well with endoscopy and magnetic resonance imaging. However, data are scarce on the use of GIUS in IBD throughout pregnancy. The aim of this prospective study is to determine the feasibility and reliability of GIUS in pregnant IBD patients. Methods Patients were included when visiting the outpatient IBD pregnancy clinic. At each trimester, clinical and biochemical disease activity was evaluated and GIUS was performed. Feasibility was assessed by the ability to visualise each bowel segment (terminal ileum (TI), ascending (AC), transverse (TC), descending (DC) and sigmoid colon (SC)). Reliability was evaluated by using clinical and biochemical disease activity as a gold standard. This was defined as a Harvey–Bradshaw Index ≥4 in Crohn’s disease (CD) or a Simple Clinical Colitis Activity Index ≥5 in ulcerative colitis and a faecal calprotectin (FCP)³ 250 mg/g. Bowel wall thickness (BWT) of > 3 mm in the colon and > 2mm in the terminal ileum was considered as signs of active inflammation on ultrasound. A Mann–Whitney U-test and chi-square were used for statistical analysis. Results Thirty-two IBD patients (54% CD) were studied. Both a GIUS and FCP was available in 18, 11 and 6 patients for the first, second and third trimester, respectively. Eleven of 32 (34%) patients had clinically active disease at least at one time point during the pregnancy. Table 1 shows the visibility per segment. When the active disease was defined as an FCP ≥ 250 mg/g, GIUS could distinguish active from the non-active disease in the first, second and third trimester with a sensitivity of 80%, 75% and 75% and specificity of 85%, 86% and 100%, respectively. FCP levels were significantly higher in patients with an active disease on GIUS regardless of the trimester (mean 1095.5 ± 1453.8 mg/g vs. 265.25 ± 649.8 mg/g, p < 0.0001). Conclusion GIUS is accurate to distinguish active from the quiescent disease in pregnancy. Feasibility to visualise the TI and the SC decreased during the second and third trimester, although active disease could still be detected. Consequently, GIUS is feasible and reliable to assess disease activity throughout pregnancy in IBD.


2020 ◽  
Vol 26 (12) ◽  
pp. 1926-1932 ◽  
Author(s):  
Amy Yu ◽  
Sonia Friedman ◽  
Ashwin N Ananthakrishnan

Abstract Background The postpartum period is marked by physiological and psychological stresses that may impact activity in inflammatory bowel disease. The predictors and outcomes of disease activity during this period have not been well characterized. Methods We performed a retrospective review of inflammatory bowel disease patients who underwent successful pregnancy and live birth at 2 referral institutions. Data on patient and disease factors including disease activity before and during pregnancy were abstracted from the medical records. We noted whether therapy was dose-reduced or stopped during pregnancy at each trimester and after delivery. Multivariable logistic regression of independent predictors of postpartum flare was performed, adjusting for relevant covariates. Results We identified a total of 206 eligible women (mean age, 33.2 years). Of these, 97 (47%) had a diagnosis of Crohn’s disease, whereas the remainder had ulcerative colitis. Nearly half the women delivered vaginally (53%), and the rest delivered by Caesarean section (47%). In the entire cohort, 65 (31.6%) experienced a postpartum flare within the year after delivery. In multivariable analysis, development of a postpartum flare was predicted by disease activity during the third trimester (odds ratio [OR], 6.27; 95% confidence interval [CI], 2.81–17.27), therapy de-escalation during pregnancy (OR, 3.00; 95% CI, 1.03–8.68), and therapy de-escalation after pregnancy (OR, 4.43; 95% CI, 1.55–12.65). Postpartum disease flare was not related to disease type, duration of disease, or mode of childbirth. Conclusions One-third of women with inflammatory bowel disease may experience disease flare during the postpartum year. Continued optimization of therapy before, during, and after pregnancy is essential to prevent this morbidity.


Author(s):  
Floris De Voogd ◽  
Harshad Joshi ◽  
Elsa Van Wassenaer ◽  
Steven Bots ◽  
Geert D’Haens ◽  
...  

Abstract Introduction Active disease in inflammatory bowel disease patients during pregnancy is associated with poor maternal and fetal outcomes. Objective evaluation of disease activity is a core strategy in IBD, and during pregnancy noninvasive modalities are preferred. We aimed to evaluate feasibility and accuracy of intestinal ultrasound (IUS) to objectify disease activity throughout pregnancy. Methods Pregnant patients with known IBD were included and followed throughout pregnancy for clinical disease activity, with fecal calprotectin (FCP) and with IUS every trimester. Feasibility of IUS was assessed for all colonic segments and terminal ileum (TI). Intestinal ultrasound outcomes to detect active disease and treatment response were compared with clinical scores combined with FCP. Results In total, 38 patients (22 CD, 16 UC) were included, with 27 patients having serial IUS. Feasibility of IUS decreases significantly in third trimester for TI (first vs third trimester: 91.3% vs 21.7%, P < .0001) and sigmoid (first vs third trimester: 95.6% vs 69.5%, P = .023). Intestinal ultrasound activity showed moderate to strong correlation with clinical activity (r = 0.60, P < .0001) and FCP (r = 0.73, P < .0001). Throughout pregnancy, IUS distinguished active from quiescent disease with 84% sensitivity and 98% specificity according to FCP combined with clinical activity. IUS showed disease activity in >1 segment in 52% of patients and detected treatment response with 80% sensitivity and 92% specificity. Conclusions IUS is feasible and accurate throughout pregnancy, although visualization of the sigmoid and TI decreases in the third trimester. IUS provides objective information on disease activity, extent, and treatment response, even during second and third trimester, and offers a noninvasive strategy to closely monitor patients during pregnancy.


2020 ◽  
Vol 14 (12) ◽  
pp. 1780-1784 ◽  
Author(s):  
Sang Hyoung Park ◽  
Hyo Jong Kim ◽  
Chang Kyun Lee ◽  
Eun Mi Song ◽  
Sang-Bum Kang ◽  
...  

Abstract Backgrounds and Aims We aimed to evaluate the safety of Bacille Calmette–Guérin [BCG] vaccination in infants born to mothers receiving anti-tumour necrosis factor [anti-TNF] therapy for inflammatory bowel disease. Methods Adverse events of BCG vaccination were evaluated in 90 infants who were last exposed to anti-TNF agents at a median of gestational week 30. Results After receiving BCG vaccination at a median age of 6 months [range, 0.25–11 months], three infants [3.3%] showed injection site swelling, two of whom also showed axillar lymphadenopathy. The rates of adverse events were similar between infants who were last exposed to anti-TNF agents before the third trimester [n = 35] and those who were last exposed in the third trimester [n = 55] [2.9% vs 3.6%; p = 1.00]. All adverse events were spontaneously resolved and there were no serious adverse events such as active tuberculosis infection or death. Conclusions BCG vaccination after 6 months of age is of low risk in infants exposed to anti-TNF agents in utero.


2014 ◽  
Vol 28 (9) ◽  
pp. 505-509 ◽  
Author(s):  
Yvette PY Leung ◽  
Remo Panaccione ◽  
Subrata Ghosh ◽  
Cynthia H Seow

Antitumour necrosis factor (anti-TNF) therapy has been a major advance in the treatment of inflammatory bowel disease (IBD) by improving rates of mucosal healing, steroid-free remission, and decreasing rates of hospitalization and surgery. Because IBD affects women in their reproductive years, clinicians have and will continue to be asked in the future about the safety profile of these agents and their potential impact on pregnancy, the developing fetus and newborn. Immunoglobulin G transfer from the mother to fetus begins in the second trimester, with an elevation starting at 22 weeks of gestation and the largest amount transferred in the third trimester. Although research investigating the long-term outcomes of children exposed to anti-TNF therapy in utero is limited, there is no known adverse effect on either pregnancy or newborn outcomes including infectious complications with this class of drugs. The World Congress of Gastroenterology consensus statement on biological therapy for IBD considered infliximab and adalimumab to be low risk and compatible with use during conception and during pregnancy in at least the first two trimesters. Based on a clinical algorithm used at the University of Calgary Pregnancy and IBD clinic (Calgary, Alberta), recommendations have been provided on the management of pregnant patients on anti-TNF therapy, particularly with regard to third-trimester dosing, taking into account disease characteristics of individual patients. When educated about the safety of anti-TNF therapy during pregnancy, patients often choose to continue on therapy during the third trimester.


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