Reduced T2*-weighted placental MRI predicts foetal growth restriction in women with chronic rheumatic disease-a Danish explorative study.

OBJECTIVES: Women with chronic rheumatic disease (CRD) are at greater risk of foetal growth restriction than their healthy peers. T2*-weighted magnetic resonance imaging of placenta (T2*P-MRI) is superior to conventional ultrasonography in predicting birth weight and works as a proxy metabolic mirror of the placental function. We aimed to compare T2*P-MRI in pregnant women with CRD and healthy controls. In addition, we aimed to investigate the correlation between T2*P-MRI and birth weight. METHODS: Using a General Electric (GE) 1.5 Tesla, we consecutively performed T2*-weighted placental MRI in 10 women with CRD and 18 healthy controls at gestational week (GW)24 and GW32. We prospectively collected clinical parameters during pregnancy including birth outcome and placental weight. RESULTS: Women with CRD had significantly lower T2*P-MRI values at GW24 than healthy controls (median T2*(IQR) 92.1 ms (81.6; 122.4) versus 118.6 ms (105.1; 129.1), p = 0.03). T2*P-MRI values at GW24 showed a significant correlation with birth weight, as the T2*P-MRI value was reduced in all four pregnancies complicated by SGA at birth. Three out of four pregnancies complicated by SGA at birth remained undetected by routine antenatal ultrasound. CONCLUSION: This study demonstrates reduced T2*P-MRI values and a high proportion of SGA at birth in CRD pregnancies compared to controls, suggesting an increased risk of placental dysfunction in CRD pregnancies. T2*P-MRI may have the potential to focus clinical vigilance by identifying pregnancies at risk of SGA as early as GW24. Key Points • Placenta-related causes of foetal growth restriction in women with rheumatic disease remain to be investigated. • T2*P-MRI values at gestational week 24 predicted foetuses small for gestational age at birth. • T2*P-MRI may indicate pregnant women with chronic rheumatic disease (CRD) in need of treatment optimization.

Preterm Birth and in Utero Exposure to Corticosteroids Are Associated With Increased Infection Risk in Children of Mothers With IBD.

BACKGROUND: Corticosteroids, thiopurines, and biologics may come into play during pregnancy in women with inflammatory bowel disease and potentially impact the developing fetal immune system. We aimed to assess the risk of serious infections in children stratified by in utero exposure to biologics and immunomodulators or concomitant treatment with corticosteroids. METHODS: All singleton IBD pregnancies between 2008 and 2022 at a tertiary IBD center in Denmark were included. Maternal and offspring demographics, maternal disease activity, antenatal medical treatment, and infant infections resulting in hospital admission were recorded after review of medical records. RESULTS: In 602 live births (99.0%), we registered exposure to antenatal treatment as follows: biological monotherapy (n = 61, 10.2%), thiopurines (n = 110, 17.9%), biologics and concomitant thiopurines (n = 63, 10.3%), and controls (ie, no treatment with biological and/or thiopurines; n = 369, 60.6%). Preterm delivery (<37 gestational weeks) and systemic steroid administration during the third trimester were associated with an increased risk of serious infection in the offspring immediately after birth (relative risk = 17.5; 95% confidence interval, 7.8-39.8; P < .001, and relative risk = 4.8; 95% confidence interval, 1.5-12.7; P = 0.003, respectively).Intra-uterine exposure to biologics or combination treatment were not associated with a statistically significant higher risk of serious infections compared with controls; however, combination treatment showed an inclination towards an increased risk across analyses. CONCLUSION: Preterm birth and systemic corticosteroid administration late in pregnancy are significant risk factors for serious infections in the offspring of IBD mothers.

Preterm birth and systemic corticosteroid administration late in pregnancy are significant risk factors for serious infections in the offspring of IBD mothers.

Time to Diagnosis and Birth Outcomes of Pregnancy-onset IBD.

BACKGROUND: Pregnancy-onset inflammatory bowel disease (PO-IBD) may pose a clinical challenge. We investigated the clinical course of PO-IBD, including time to diagnosis, medical treatment, and the impact on birth outcomes. METHODS: All pregnancies in women with IBD at a tertiary IBD center in Denmark were identified from 2008 to 2021. Maternal and offspring outcome data, retrieved from medical records of women with new onset IBD during pregnancy, were compared with the outcomes of women with IBD diagnosed prior to pregnancy (controls). Outcomes included subtype of IBD, disease location, medical treatment, birth weight, intrauterine growth retardation (IUGR), gestational age at birth, caesarean section, stillbirth, congenital malformations, and time elapsed from onset of symptoms to diagnosis. RESULTS: In total, 378 women contributed with 583 pregnancies. Pregnancy-onset IBD affected 34 (9.0%) women. Ulcerative colitis (UC; n = 32) was more prevalent than Chron's disease (CD; n = 2). Birth outcomes in pregnancies affected by PO-IBD were comparable to that of the 549 controls. Women with PO-IBD received more corticosteroids and biologics following their diagnosis than did the controls (5 [14.7%] vs 2 [2.9%]; P = .07; and 14 [41.2%] vs 9 [13.2%]; P = .003, respectively). Concerning time to IBD diagnosis, there was no statistically significant difference between the 2 groups (PO-IBD, 2.5 months, interquartile range [2-6] vs controls 2 months [1-4.5]; P = .27). CONCLUSION: Although we observed a trend towards a diagnostic delay, PO-IBD was not associated with a significantly increased time to diagnosis. Birth outcomes in women with PO-IBD were comparable to those diagnosed with IBD prior to pregnancy.

Pregnancy-Onset IBD (PO-IBD) is rare and can be difficult to diagnose. The present study however reveals no significant difference in time-to-diagnosis between women with PO-IBD and women diagnosed with IBD while not pregnant.

Predictors of disease activity during pregnancy in women with inflammatory bowel disease-a Danish cohort study.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) activity during pregnancy is associated with adverse pregnancy outcomes. We aimed to identify key clinical characteristics that predict disease activity during pregnancy. METHODS: Between January 2008 through 2021, we identified all singleton pregnancies among women with IBD recorded in patient and birth registries at a tertiary IBD centre in Denmark. Maternal and infant data were retrieved from medical records. Demographics, Physicians Global Assessment (PGA) of disease activity 6 months prior to pregnancy and in all three trimesters of pregnancy and pregnancy outcomes were recorded. RESULTS: In 609 pregnancies, we observed 603 (99.0%) live births. Disease activity in one or more trimesters was seen in 283 women (46.5%). UC phenotype was associated with an increase in risk of disease activity (adjusted OR = 2.6 [1.8-3.9]; p < 0.001). Disease activity within 6 months prior to conceiving (169 women [27.7%]) was associated with an increased risk of continuous disease activity during pregnancy (adjusted OR of 5.3 [3.5-8.2]; p < 0.001). Disease activity during a previous pregnancy was associated with an increased risk of flares in subsequent pregnancies (adjusted OR of 3.2 [1.5-6.6]; p = 0.002). Sustained clinical remission throughout pregnancy was associated with an increased probability of normal birth term, birthweight and low risk of fetal growth restriction (FGR) and stillbirth. CONCLUSION: Predictors for disease activity include disease activity in a previous pregnancy and/or prior to conception, as well as UC phenotype. Reassuringly, women with IBD in remission are not at increased risk of adverse pregnancy outcomes.

Vedolizumab clearance in neonates, susceptibility to infections and developmental milestones: a prospective multicentre population-based cohort study.

BACKGROUND: Little is known about the consequences of intrauterine exposure to, and the post-natal clearance of, vedolizumab. AIMS: To investigate the levels of vedolizumab in umbilical cord blood of newborns and rates of clearance after birth, as well as how these correlated with maternal drug levels, risk of infection and developmental milestones during the first year of life METHODS: Vedolizumab-treated pregnant women with inflammatory bowel disease were prospectively recruited from 12 hospitals in Denmark and Canada in 2016-2020. Demographics were collected from medical records. Infant developmental milestones were evaluated by the Ages and Stages Questionnaire (ASQ-3). Vedolizumab levels were measured at delivery and, in infants, every third month until clearance. Non-linear regression analysis was applied to estimate clearance. RESULTS: In 50 vedolizumab-exposed pregnancies, we observed 43 (86%) live births, seven (14%) miscarriages, no congenital malformations and low risk of adverse pregnancy outcomes. Median infant:mother vedolizumab ratio at birth was 0.44 (95% confidence interval [CI], 0.32-0.56). The mean time to vedolizumab clearance in infants was 3.8 months (95% CI, 3.1-4.4). No infant had detectable levels of vedolizumab at 6 months of age. Developmental milestones at 12 months were normal or above average. Neither vedolizumab exposure in the third trimester (RR 0.54, 95% CI, 0.28-1.03) nor combination therapy with thiopurines (RR 1.29, 95% CI, 0.60-2.77) seemed to increase the risk of infections in the offspring. CONCLUSIONS: Neonatal vedolizumab clearance following intrauterine exposure is rapid. Infant vedolizumab levels did not correlate with the risk of infections during the first year of life. Continuation of vedolizumab throughout pregnancy is safe.

Anti-TNF Therapy in Pregnant Women With Inflammatory Bowel Disease: Effects of Therapeutic Strategies on Disease Behavior and Birth Outcomes.

BACKGROUND: Active inflammatory bowel disease (IBD) adversely affects pregnancy outcomes. Little is known about the risk of relapse after stopping anti-tumor necrosis factor (anti-TNF) treatment during pregnancy. We assessed the risk of relapse before delivery in women who discontinued anti-TNF treatment before gestational week (GW) 30, predictors of reduced infant birth weight, a marker associated with long-term adverse outcomes, and rates and satisfaction with counseling. METHODS: Pregnant women with IBD receiving anti-TNF treatment were prospectively invited to participate in an electronic questionnaire carried out in 22 hospitals in Denmark, Australia, and New Zealand from 2011 to 2015. Risk estimates were calculated, and birth weight was investigated using t tests and linear regression. RESULTS: Of 175 women invited, 153 (87%) responded. In women in remission, the relapse rate did not differ significantly between those who discontinued anti-TNF before GW 30 (1/46, 2%) compared with those who continued treatment (8/74, 11%; relative risk, 0.20; 95% confidence interval [CI], 0.02 to 1.56; P = 0.08). Relapse (P = 0.001) and continuation of anti-TNF therapy after GW 30 (P = 0.007) were independently associated with reduced mean birth weight by 367 g (95% CI, 145 to 589 g; relapse) and 274 g (95% CI, 77 to 471 g; anti-TNF exposure after GW 30). Of 134 (88%) women who received counseling, 116 (87%) were satisfied with the information provided. CONCLUSIONS: To minimize fetal exposure in women in remission, discontinuation of anti-TNF before GW 30 seems safe. Relapse and continuation of anti-TNF therapy after GW 30 were each independently associated with lower birth weight, although without an increased risk for birth weight <2500 g. Most women received and were satisfied with counseling.

Semen Quality and Sperm DNA Integrity in Patients With Severe Active Inflammatory Bowel Disease and Effects of Tumour Necrosis Factor-alpha Inhibitors.

BACKGROUND AND AIMS: The impact of severe inflammation on semen quality, including sperm DNA integrity, in men with inflammatory bowel disease [IBD] is unknown, as are the potential effects of anti-tumour necrosis factor-alpha [TNF-alpha] therapy. We investigated the influence of severe active IBD and anti-TNF-alpha treatment on semen quality. METHODS: We prospectively included 20 patients admitted with severe active IBD. Further, 19 patients who initiated and 17 who stopped anti-TNF-alpha therapy were included. Semen samples were obtained during active disease, and on/off treatment. For paired comparisons, samples were collected not less than 3 months after achieving remission, after treatment initiation, or after treatment cessation. Sperm DNA Fragmentation Index [DFI], concentration, morphology, and motility were evaluated. Sex hormones and seminal plasma anti-TNF-alpha drug levels were measured. RESULTS: In patients with severe disease, progressive sperm motility was impaired and increased significantly [from 28.4% to 37.4%, p = 0.045] during remission. There was no difference in DFI [12.5% versus 12.0%, p = 0.55], concentration [55.0 mill/ml versus 70.0 mill/ml, p = 0.39], or normal morphology [4.7% versus 5.1%, p = 0.51] in these patients. During active disease, testosterone was decreased, and normalised after obtaining remission. Patients who started anti-TNF-alpha therapy had a statistically significant, but clinically irrelevant, reduction in DFI after treatment initiation [12.8% versus 10.0%, p = 0.02]. All other semen parameters were unaffected by therapy. Anti-TNF-alpha drugs were excreted in negligible amounts in semen. CONCLUSIONS: Severe active IBD reduces progressive sperm motility and testosterone levels, but sperm DNA integrity is unaffected by active disease. Anti-TNF-alpha therapy does not impair sperm quality.

Fecal Calprotectin Is Not Affected by Pregnancy: Clinical Implications for the Management of Pregnant Patients with Inflammatory Bowel Disease.

BACKGROUND: Noninvasive biomarkers of inflammation for monitoring inflammatory bowel disease (IBD) are important in pregnancy. Clinical and laboratory markers are often affected by the physiological adaption that occurs during pregnancy, although, few, if any, data exist on fecal calprotectin (FC). We investigated FC concentrations in pregnant controls and IBD women, and whether FC correlated with physician global assessment (PGA), C-reactive protein (CRP), and Harvey-Bradshaw Index (HBI)/Simple Clinical Colitis Activity Index (SCCAI) before and after pregnancy, as well as during each trimester. METHODS: The study is a prospective multicenter study of 46 pregnant women with and 21 without IBD in Denmark, Australia, and New Zealand. Demographics, clinical parameters, and HBI/SCCAI were recorded. Stool and blood samples were obtained to determine FC and CRP concentrations. RESULTS: From pregnant IBD women and pregnant controls, 174 and 21 fecal samples were collected, respectively. The median FC concentration in pregnant IBD women was 131 µg/g (range 0-3600) and in controls 0 µg/g (range 0-84) (P < 0.0001). FC strongly correlated with PGA at all 5 timepoints (r ≥ 0.80; P < 0.0001) and with HBI/SCCAI before (r = 0.66; P < 0.0001) and after pregnancy (r = 0.47; P < 0.003) but not during pregnancy (P > 0.05). An FC cutoff concentration of 250 µg/g significantly correlated with active disease according to PGA in all 5 periods (P ≤ 0.0002). CRP only significantly correlated with FC (P = 0.0007) and PGA in the second trimester (P = 0.0003). No significant correlation was found between CRP and HBI/SCCAI at any timepoint (P > 0.05). CONCLUSIONS: The physiological changes that occur during pregnancy do not affect FC, in contrast to CRP and HBI/SCCAI. The combined use of FC and PGA seems optimal to assess disease activity in IBD during pregnancy.

Adherence and quality of care in IBD.

OBJECTIVE: In inflammatory bowel disease (IBD), adherence to both medical treatment and other aspects of care has a substantial impact on the course of the disease. Most studies of medical adherence have reported that 30-45% of patients with IBD were non-adherent. Our study aimed to investigate the different aspects of adherence and to identify predictors of non-adherence, including the quality of care, for outpatients with IBD. MATERIALS AND METHODS: An anonymous electronic questionnaire was used to investigate different aspects of adherence, the quality of care, patient involvement and shared decision making among 377 IBD outpatients. RESULTS: Three hundred (80%) filled in the questionnaire. The overall adherence rate was 93%. Young age (< 35 years old) and smoking were significantly associated with non-adherence (prevalence odds ratio (POR) 2.98, 95% CI 1.04-8.52, p < 0.05 and POR 3.88, 95% CI 1.36-11.05, p < 0.05, respectively). The lowest medical adherence rates were found for 5-ASA and topical treatments among patients with inactive disease. A large majority of patients stated that treatment strategies were agreed upon as a shared decision between the patient and the health care professionals. CONCLUSIONS: Predictors for non-adherence were young age and smoking. High adherence rates could be explained by a high patient satisfaction and a high degree of shared decision making.

[Starvation is a rare cause of metabolic ketoacidosis].

A 79-year-old woman with no medical history was admitted under the diagnosis of stroke. Two months prior she had a fractured tibia, complicated by osteomyelitis. Physical examination showed dehydration and malnourishment. Chest X-ray revealed pneumonia and laboratory data revealed signs of infection, dehydration and normoglycaemic metabolic acidosis with elevated P-3-hydroxybutyrate. The case presents a starvation- (weight loss ~ 13 kg) and infection-induced non-diabetic metabolic ketoacidosis treated with intravenous supplementation of isotonic saline, potassium, bicarbonate and insulin.

[Indication of treatment with Warfarin should be stated explicitly].

Warfarin has a narrow therapeutic window and side effects include bleeding causing e.g. hospital admission and death. Monitoring of treatment and review of indication are mandatory. We report a case of more than four years of warfarin treatment without indication. Treatment was not discontinued due to inadequate medical record keeping and communication among health-care providers. Medical-record keeping should follow guidelines from the National Board of Health. In addition, clearly stated treatment duration and indication may prevent unwarranted or premature termination of treatment.