Paternal use of selective serotonin reuptake inhibitors and adverse health outcomes: A nationwide cohort study on 13,547 exposed children.

BACKGROUND: The use of selective serotonin reuptake inhibitors (SSRIs) has increased over time. Several studies indicate that paternal use of medication may adversely affect the developing fetus. Only a few studies have investigated the association between preconceptional paternal exposure to SSRIs and the risks of adverse health outcomes in children. OBJECTIVES: This study aimed to assess adverse birth outcomes and adverse early life events in children fathered by men using SSRIs prior to conception. MATERIALS AND METHODS: All live-born singleton children born in Denmark from 1997 until 2019 and their parents were included. The exposed cohort comprised all children fathered by men using SSRIs 3 months prior to conception and the unexposed cohort comprised all other children. We estimated the odds ratios for adverse birth outcomes: small for gestational age (SGA), preterm birth, low Apgar score, and major congenital malformations. Furthermore, we estimated the hazard ratios for adverse early life events of infections and hospitalizations within 1 year from birth. We also examined adverse birth outcomes and the adverse early life events according to SSRI subgroups. RESULTS: There was a statistically significantly increased odds ratio 1.15 (confidence interval, CI: 1.06-1.23) for preterm birth. No significant results were found for SGA, low Apgar score, and major congenital malformations. The adjusted hazard ratios for hospitalizations and infections were 1.06 (CI: 1.02-1.11) and 1.02 (CI: 0.97-1.07), respectively. There was a statistically significantly increased odds ratio for preterm birth with respect to the SSRI subgroups citalopram and escitalopram, and for hospitalizations with respect to citalopram. DISCUSSION AND CONCLUSION: Although the risks of certain adverse birth and adverse early life outcomes were statistically significantly increased, the ratios were small and may have limited clinical importance. Paternal use of SSRI was in general safe in the preconceptual period.

Does Surgery Before Pregnancy in Women With Inflammatory Bowel Disease Increase the Risk of Adverse Maternal and Fetal Outcomes? A Danish National Cohort Study.

INTRODUCTION: Up to 15% of women with Crohn's disease (CD) or ulcerative colitis (UC) undergo bowel surgery before pregnancy, and there is little data on pregnancy outcomes in this population. We aimed to assess maternal/fetal outcomes in women with CD or UC who underwent surgeries before pregnancy. METHODS: In this nationwide study, we included all pregnancies in women with CD or UC from 1997 to 2022 and examined 6 categories of CD and UC surgeries before pregnancy. We used multilevel logistic regression to compute crude and adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) for the risk of pregnancy and offspring complications in women who did, vs did not, undergo surgery before pregnancy. RESULTS: There were 833 UC and 3,150 CD pregnancies with prior surgery and 12,883 UC and CD 6,972 pregnancies without surgery. For UC, prior surgery was associated with Cesarian section (C-section) (ileoanal pouch: aOR: 20.03 [95% CI 10.33-38.83]; functional ileostomy: aOR:8.55 [6.10-11.98]; diverting ileostomy: aOR: 38.96 [17.05-89.01]) and preterm birth (aOR: 2.25 [1.48-3.75]; 3.25 [2.31-4.59]; and 2.17 [1.17-4.00]) respectively. For CD and prior intestinal surgery, the risks of C-section (aOR: 1.94 [1.66-2.27]), preterm birth (aOR: 1.30 [1.04-1.61]), and low 5-minute Apgar (aOR: 1.95 [95% CI 1.07-3.54]) increased and premature rupture of membranes (aOR: 0.68 [0.52-0.89]) decreased. For CD with only prior perianal surgery, the risk of C-section (aOR: 3.02 [2.31-3.95]) increased and risk of gestational hypertension/preeclampsia/eclampsia (aOR: 0.52 [0.30-0.89]) decreased. DISCUSSION: Providers should be aware there is an increased likelihood of C-section and certain perinatal complications in patients with CD or UC surgery before pregnancy.

Longitudinal Measurements of Blood Biomarkers in Patients with Crohn's Disease or Ulcerative Colitis Treated with Infliximab: Only the Latest Values in the Induction Period Predict Treatment Failure.

Background: Few studies have incorporated longitudinal assessments or used combinations of blood biomarkers as predictors of loss of response to biologic therapy for patients with Crohn's disease (CD) or ulcerative colitis (UC). Methods: This is a population-based cohort study comprising Danish patients with CD or UC from 2008 to 2018. We used logistic regression to analyze whether levels and changes in levels of C-reactive protein (CRP), serum albumin, and hemoglobin, routinely measured during a 14-week infliximab induction period, predicted a change to another biologic medication or cessation of biologic therapy. Results: During the induction period, 2883 (1626 CD, 1257 UC) patients had 12,730, 12,040, and 13,538 specimens with CRP, serum albumin, and hemoglobin, respectively. In all, 284 patients (9.9%) switched to another biologic medication, and 139 (4.8%) ceased biologic therapy in the follow-up period. Only the most recent CRP and hemoglobin levels predicted the efficacy of infliximab treatment at approximately 14 weeks, a time point when the clinician often determines whether to continue treatment. Conclusion: Measurement of blood biomarkers prior to the clinical assessment does not predict the effectiveness of infliximab.

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.

Vitamin D and Marine n-3 Fatty Acids for Autoimmune Disease Prevention: Outcomes Two Years After Completion of a Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: In the 5.3-year randomized, 2 × 2 factorial, double-blind, placebo-controlled Vitamin D and Omega-3 Trial (VITAL), vitamin D supplementation reduced autoimmune disease (AD) incidence (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.61-0.99). Omega-3 (n-3) fatty acid supplementation showed a statistically nonsignificant reduction (HR 0.85, 95% CI 0.67-1.08). We aimed to confirm further AD cases arising during and after randomization and assess sustained effects with two years of postintervention observation. METHODS: Of the 12,786 men aged ≥50 and 13,085 women aged ≥55 initially randomized, we observed surviving and willing participants for two more years. We continued to confirm annual participant-reported new AD by medical record review. Cox models calculated HRs for all confirmed incident AD, (and secondary endpoints, including probable cases, and individual ADs), during the observational and randomized periods. RESULTS: A total of 21,592 participants (83.5%) were observed for two more years; 514 participants developed incident confirmed AD (236 since prior report), of whom 255 had been randomized to vitamin D versus 259 to vitamin D placebo (HR 0.98 [95% CI 0.83-1.17] at 7 years). AD was confirmed in 234 participants initially randomized to n-3 fatty acids versus 280 randomized to its placebo (HR 0.83 [95% CI 0.70-0.99] at 7 years). Of newly confirmed cases, 65 had onset during randomization; their inclusion changed randomized results as follows: HR 0.85 (95% CI 0.70-1.04) for vitamin D and HR 0.87 (95% CI 0.71-1.06) for n-3 fatty acids. CONCLUSION: Two years after trial termination, the protective effects of 2000 IU/day of vitamin D dissipated, but 1,000 mg/day of n-3 fatty acids had a sustained effect in reducing AD incidence.

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.

Older Adult-Onset of Inflammatory Bowel Diseases Is Associated With Higher Utilization of Analgesics: A Nationwide Cohort Study.

INTRODUCTION: Patients with inflammatory bowel diseases (IBD) commonly require analgesic medications to treat pain, which may be associated with complications. We examined trends of analgesic use according to age at IBD onset. METHODS: This nationwide cohort study included adults diagnosed with IBD between 1996 and 2021 in Denmark. Patients were stratified according to their age at IBD onset: 18-39 years (young adult), 40-59 years (adult), and older than 60 years (older adult). We examined the proportion of patients who received prescriptions for analgesic medications within 1 year after IBD diagnosis: strong opioids, tramadol, codeine, nonsteroidal anti-inflammatory drugs, and paracetamol. Multivariable logistic regression analysis was performed to examine the association between age at IBD onset and strong opioid prescriptions and the composite of strong opioid/tramadol/codeine prescriptions. RESULTS: We identified 54,216 adults with IBD. Among them, 25,184 (46.5%) were young adults, 16,106 (29.7%) were adults, and 12,926 (23.8%) were older adults at IBD onset. Older adults most commonly received analgesic prescriptions of every class. Between 1996 and 2021, strong opioid, tramadol, and codeine prescriptions were stable, while paracetamol prescriptions increased and nonsteroidal anti-inflammatory drug prescriptions decreased. After multivariable logistic regression analysis, older adults had higher adjusted odds of receiving strong opioid prescriptions (adjusted odds ratio 1.95, 95% confidence interval 1.77-2.15) and the composite of strong opioid/tramadol/codeine prescriptions (adjusted odds ratio 1.93, 95% confidence interval 1.81-2.06) within 1 year after IBD diagnosis compared with adults. DISCUSSION: In this nationwide cohort, older adults most commonly received analgesic prescriptions within 1 year after IBD diagnosis. Additional research is needed to examine the etiology and sequelae of increased analgesic prescribing to this demographic.

Dynamics of the Gut Mycobiome in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Intestinal fungi have been implicated in the pathogenesis of ulcerative colitis (UC). However, it remains unclear if fungal composition is altered during active versus quiescent disease. METHODS: We analyzed clinical and metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD), available via the IBD Plexus Program of the Crohn's & Colitis Foundation. We evaluated the fungal composition of fecal samples from 421 patients with UC during clinical activity and remission. Within a longitudinal subcohort (n = 52), we assessed for dynamic taxonomic changes across alterations in clinical activity over time. We examined if fungal amplicon sequence variants and fungal-bacterial relationships were altered during activity versus remission. Finally, we classified activity in UC using a supervised machine learning random forest model trained on fungal abundance data. RESULTS: During clinical activity, the relative abundance of genus Candida was increased 3.5-fold (P-adj < 1 × 10-4) compared with during remission. Patients with longitudinal reductions in clinical activity demonstrated parallel reductions in Candida relative abundance (P < .05). Candida relative abundance correlated with Parabacteroides diastonis, Faecalibacterium prausnitzii, and Bacteroides dorei relative abundance (P < .05) during remission; however, these correlations were disrupted during activity. Fungal abundance data successfully classified patients with active or quiescent UC (area under the curve ∼0.80), with Candida relative abundance critical to the success of the model. CONCLUSIONS: Clinical activity in UC is associated with an increased relative abundance of Candida, cross-sectionally and dynamically over time. The role of fecal Candida as a target for therapeutics in UC should be evaluated.

Use of Tramadol vs Traditional Opioids and Adverse Outcomes in Patients with Inflammatory Bowel Disease: A Danish Nationwide Cohort Study.

BACKGROUND: Use of traditional opioids (TOs) for pain management has been associated with adverse outcomes among patients with inflammatory bowel diseases (IBDs). It is unknown if similar associations exist for tramadol, a partial opioid agonist and serotonin and norephinephrine reuptake inhibitor. We sought to compare adverse outcomes associated with tramadol vs TOs in an IBD population. METHODS: This nationwide cohort study included adults with IBD diagnosed from 1995 to 2021 in Denmark with subsequent prescriptions for tramadol or TOs. For each analgesic, 2 populations were assessed: initial users (first prescription) and persistent users (first 3 consecutive prescriptions within 365 days). Outcomes included infection, bowel obstruction/ileus, IBD surgery, and mortality within 90 days after the initial use index date (date of first prescription) and within 365 days after the persistent use index date (date of third prescription). Odds ratios adjusted for demographics, comorbidities, and IBD severity were calculated using multivariable logistic regression. RESULTS: We identified 37 377 initial users and 15 237 persistent users of tramadol or TOs. Initial users of tramadol had lower adjusted odds of infection (adjusted odds ratio [OR], 0.80; 95% confidence interval [CI], 0.65-0.99), bowel obstruction/ileus (aOR, 0.74; 95% CI, 0.53-1.03), and mortality (aOR, 0.43; 95% CI, 0.35-0.55), and a higher adjusted odds of IBD-related surgery (aOR, 1.27; 95% CI, 1.02-1.60) vs initial users of TOs. Similar results were found for persistent users. CONCLUSIONS: Tramadol was associated with lower odds of infection, bowel obstruction/ileus, and mortality vs TOs among patients with IBD. These associations may be impacted by residual confounding.

Adverse birth outcomes and early-life infections after in utero exposure to corticosteroids for inflammatory bowel disease: a Danish nationwide cohort study.

BACKGROUND: Systemic corticosteroids are often used to treat inflammatory bowel disease (IBD) flares during pregnancy as maintenance of disease remission is crucial to optimize pregnancy outcomes. However, there is little data regarding the effect of in utero exposure to corticosteroids on the risk of adverse birth outcomes and early-life infections in the offspring. METHODS: We used the Danish national registries to establish a nationwide cohort of all singleton live births in women with IBD from 1995 to 2015. Outcomes in children exposed in utero to corticosteroids were compared to those who were not exposed. In logistic and Cox proportional hazard regression models, we adjusted the outcomes (major congenital malformation, preterm birth, small for gestational age, low 5-min Apgar score, and infections) for confounders such as body mass index, smoking, comorbidity, and additional medical IBD treatment. RESULTS: After in utero exposure to corticosteroids at any time between 30 days prior to conception through the first trimester (n = 707), the adjusted hazard ratio of major congenital malformation was 1.28 (95% CI: 0.82-2.00) compared to children born to women with IBD, but not exposed to corticosteroids in utero (n = 9371). After in utero exposure to corticosteroids at any time during pregnancy (n = 1336), the adjusted odds ratios for preterm birth, small for gestational age, and low 5-min Apgar score were 2.45 (95% CI: 1.91-3.13), 1.21 (95% CI: 0.76-1.90), and 0.91 (95% CI: 0.33-2.52), respectively. Finally, the adjusted hazard ratio of overall infections in the first year of life was 1.14 (95% CI: 0.94-1.39). CONCLUSIONS: This nationwide cohort study suggests that children of women with IBD exposed to corticosteroids in utero had an almost 2.5-fold increased risk of preterm birth. Use of corticosteroids is closely related to disease activity and we cannot adjust for the independent role of disease activity. It is however reassuring that the other examined birth and early-life outcomes were not statistically significantly increased.

Increased Risk of Postpartum Infections After Caesarian and Vaginal Delivery in Women With Inflammatory Bowel Disease: A Danish Nationwide Cohort Study.

BACKGROUND: There is lack of knowledge concerning postpartum infections in women with inflammatory bowel disease (IBD). Our aim is to determine the 30-day postpartum infectious complications in women with and without IBD who have a caesarian section, normal vaginal delivery, or assisted vaginal delivery. METHODS: We used Danish national registries to establish a study population of liveborn, singleton births from January 1, 1997, through December 31, 2015. We examined 30-day postpartum maternal infectious complications in women with and without IBD, according to the mode of delivery. Statistical models were adjusted for multiple confounders. RESULTS: In all, 3255 women with and 207 608 without IBD had a caesarian section. Within 30 days postpartum, 4.5% of women with and 3.7% without IBD had an infectious complication. Increased infectious complications included overall infections (adjusted OR [aOR], 1.83; 95% confidence interval [CI], 1.35-2.47), infections of the gastrointestinal tract (aOR, 4.36, 95% CI 2.34-8.10), and infections of the skin and subcutaneous tissue (aOR, 4.45; 95% CI, 2.30-8.50). Other puerperal infections, urological and gynecological, and other infections were increased, although not significantly. For vaginal deliveries, 1.6% of 5771 women with IBD and 1.3% of 793 110 women without IBD had an infectious complication, and the aOR of infections of the gastrointestinal tract was 3.17 (95% CI, 1.47-6.85). There were too few outcomes to calculate the risk of infections after assisted vaginal delivery. CONCLUSIONS: The risk of a 30-day postpartum infectious complication is increased in women with IBD. Physicians should carefully monitor their patients postpartum to prevent these adverse outcomes.

Women with inflammatory bowel disease who have a caesarean section or a vaginal delivery are at increased risk for infections within the 30-day postpartum period. Physicians should be aware of this increased risk and work to minimize infectious complications after delivery.

Challenges and Opportunities for Advancing Research and Improving Care for Sexual and Gender Minorities With Inflammatory Bowel Disease.

Within the field of gastroenterology and inflammatory bowel disease specifically, there has been little research exploring the healthcare experiences of LGBTQIA+ individuals. This article describes unique clinical challenges and research opportunities that exist particularly at the intersection of inflammatory bowel disease and sexual health.

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.

Sexual Dysfunction in Female Patients with Inflammatory Bowel Disease: An Overview.

Sexual dysfunction is common among females with inflammatory bowel disease and may result in issues involving intimacy, sexual activity, and satisfaction, as well both the formation and preservation of personal relationships. Risk factors for sexual dysfunction include select surgical interventions, medications, mental illnesses, and IBD-related intestinal and extraintestinal comorbidities. In addition, certain demographic factors such as age, disease type and activity may influence the severity of sexual dysfunction. Evaluation of sexual dysfunction may include the use of validated sexual functioning questionnaires, a brief mental health assessment, initial inquiry into vulvovaginal or perineal symptoms, and a gynecologic and GI-focused physical exam. An interdisciplinary care team involving IBD specialists, obstetrician-gynecologists, pelvic floor physical therapists, and primary care physicians may be best suited to provide optimal care and treatment recommendations for patients with sexual dysfunction. Options for management often include pelvic floor physical therapy, biofeedback, and mental health support. Further research is necessary to delineate the impact of IBD activity on sexual dysfunction, to determine if health outcome differences exist depending on surgical approaches utilized during J-pouch operations, and finally to evaluate the care and perceptions of patients with IBD who identify as sexual and gender minorities.

The safety of paternal and maternal use of 5-aminosalicylic acid during conception and pregnancy: a nationwide cohort study.

BACKGROUND: Data on the safety of paternal use of 5-aminosalicylic acid (5-ASA) prior to conception are lacking, and the safety of maternal use of 5-ASA during pregnancy has not been examined in nationwide data. AIMS: To examine offspring outcomes after paternal pre-conception use of 5-ASA, and after maternal use during pregnancy METHODS: This nationwide cohort study was based on Danish health registries. The study population included live born singletons of patients with ulcerative colitis (UC) or Crohn's disease (CD). Paternal exposure included 2168 children fathered by men treated with 5-ASA, and 7732 unexposed. Maternal exposure included 3618 children exposed in utero to 5-ASA, and 7128 unexposed. The outcomes were pre-term birth, small for gestational age (SGA), low Apgar score and major congenital abnormalities (CAs) according to EUROCAT guidelines. RESULTS: The vast majority of fathers and mothers used mesalazine. In children fathered by men with UC using 5-ASA, we found no increased risk of pre-term birth, SGA or low Apgar score. The hazard ratio (HR) of CAs was 1.30 (95% CI 0.92-1.85). In children of fathers with CD, the odds ratio (OR) of SGA was 1.52 (95% CI 0.65-3.55). After maternal 5-ASA exposure, the OR of SGA in children of women with UC was 1.46 (95% CI: 0.93-2.30); for CAs in children of women with CD, HR was 1.44 (95% CI 0.84-2.47). CONCLUSIONS: Paternal and maternal use of 5-ASA was safe across offspring outcomes; none of the findings reached statistical significance. The safety of 5-ASA formulations that are used infrequently cannot be settled here.

Paternal use of medications for inflammatory bowel disease and the risk of hospital-diagnosed infections in the offspring: a nationwide cohort study.

BACKGROUND: Information regarding the impact of paternal inflammatory bowel disease (IBD) medications on child outcomes is scarce. AIM: To examine the risk of childhood infections associated with fathers' use of anti-inflammatory/immunosuppressive medications taken before conception. METHODS: This is a nationwide cohort study based on Danish health registries, comprising all live-born singleton children born between January 1997 and February 2019 who were fathered by men with IBD. Exposed cohorts included children fathered by men treated with 5-aminosalicylates (5-ASAs), thiopurines, corticosteroids or anti-tumour necrosis factor-α (anti-TNF-α) agents within 3 months before conception. The unexposed cohort included children not exposed to paternal IBD medications. Outcomes were the first infection, diagnosed in the hospital setting in the first year of life, and from the age of 1 to 3 years. RESULTS: In all, 2178 children were fathered by men exposed to 5-ASAs, 843 to thiopurines, 417 to systemic corticosteroids and 436 to anti-TNF-α agents; 6799 children were unexposed. The adjusted hazard ratio (aHR) for infections within the first year of life for 5-ASAs was 0.78 (95% CI, 0.66-0.91), thiopurines 0.89 (95% CI, 0.73-1.09), systemic corticosteroids 0.95 (95% CI, 0.70-1.29), and anti-TNF-α agents 1.17 (95% CI, 0.94-1.46). The aHR for infections from 1 to 3 years for 5-ASAs was 0.97 (95% CI, 0.83-1.13), thiopurines 0.87 (95% CI, 0.71-1.07), systemic corticosteroids 1.25 (95% CI, 0.94-1.65), and anti-TNF-α agents 0.79 (95% CI, 0.60-1.03). CONCLUSION: Fathers' use of anti-inflammatory/immunosuppressive medications before conception was not significantly associated with childhood infections. These results fill an important research gap regarding paternal medication safety.

Infliximab Is Not Associated With a General Long-Term Weight Gain in Patients With Inflammatory Bowel Disease: A Nationwide Study.

INTRODUCTION: Patients with Crohn's disease (CD) and ulcerative colitis (UC) may lose weight during periods of active disease and may gain weight when inflammation heals. Studies have hypothesized an association between antitumor necrosis factor-alpha (anti-TNF-α) and unintended weight gain during maintenance therapy, and this association has not been previously clarified. METHODS: In a nationwide observational study based on Danish national health registries, we included patients who initiated therapy with infliximab and followed changes in weight during induction therapy (0-90 days) and maintenance therapy (91-270 days). The association between the use of infliximab and weight gain was analyzed by a multilevel mixed-effects linear regression model. RESULTS: Among 851 patients with CD and UC who initiated infliximab therapy, long-term weight gain was not observed during maintenance therapy in most of the patients. Women with CD who were underweight at the initiation of therapy had an average weight gain of 7.5 kg. Men and women with CD and UC with normal or increased body mass index had an average weight gain of <2 kg during maintenance therapy. Underweight men with CD and UC gained 2.9 kg (95% confidence interval 2.1-3.6) and 2.9 kg (95% confidence interval 1.9-3.9), respectively, in the first 90 days, although neither group had statistically significant weight gain in the maintenance period. Less than 3% of the patients had weight gain greater than 10% of their baseline body weight during the study period. DISCUSSION: Weight gain among patients treated with anti-TNF-α therapies is unlikely to be due to an effect from anti-TNF-α therapy.