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IBD with onset during childhood seems to represent a severe disease phenotype with increased morbidity. We have previously demonstrated that children with IBD have significantly lower final grades in compulsory school compared to healthy peers.To evaluate the association of childhood-onset IBD with a later professional career and subsequent earnings METHODS: We identified 5404 individuals diagnosed with childhood-onset (18 years) IBD between 1990 and 2014 (2818 with ulcerative colitis and 2328 with Crohn's disease) in the Swedish National Patient Register. Patients were matched with 10 general population reference individuals by sex, birth year, and place of residence (n = 51,295). Data on earnings during 1992-2017 were obtained through the longitudinal integration database for health insurance and labour market studies. Earnings were converted into Euros (inflation-adjusted to 2019). The differences in earnings between patients and general population reference individuals were calculated through quantile regression.Patients with childhood-onset IBD had significantly lower annual taxable earnings from ages 20 to 30 (adjusted median annual income difference (AMAID) at age 30: -5.4% [95% CI -9.1% to -1.8%]). In particular, annual taxable earnings through early adult age were lower in patients who, during childhood, had had surgery or long-term inpatient treatment for IBD (AMAID at age 30: -16.3% [95% CI -24.7% to -7.9%]).Overall, the negative influence of disease on earnings in early adult age was modest for patients with childhood-onset IBD. The markedly larger negative income gap from ages 20 to 30 in patients with more severe IBD during childhood should be recognised.

Patients with celiac disease (CD) have an increased risk of encapsulated bacterial infections. Less is known about other serious infections in CD, especially in patients diagnosed in the 21st century.We contacted all 28 pathology departments in Sweden through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort study and identified 20,088 individuals with CD (defined as villous atrophy) diagnosed in 2002-2017. Patients were matched for sex, age, and calendar year to 80,152 general population comparators and followed up until December 31, 2019. Serious infections were defined as having a hospital-based (inpatient and outpatient) diagnosis in the National Patient Register. Cox regression yielded adjusted hazard ratios (aHR) controlling for education, country of birth, and comorbidities.During 173,695 person-years of follow-up, 6,167 individuals with CD (35.5/1,000 person-years) had a serious infection. This was compared with 19,131 infections during 743,260 person-years (25.7/1,000 person-years) in matched comparators, corresponding to an aHR of 1.29 (95% confidence interval [CI] = 1.25-1.33). aHR were similar when restricted to infection requiring hospital admission (1.23; 95% CI = 1.17-1.29). The excess risk of serious infections also persisted beyond the first year after CD diagnosis (aHR = 1.24; 95% CI = 1.20-1.29). Patients with CD were at risk of sepsis (aHR = 1.26; 95% CI = 1.09-1.45) and gastrointestinal infections (1.60; 95% CI = 1.47-1.74). Mucosal healing during CD follow-up did not influence the risk of subsequent serious infections.This nationwide study of patients with celiac disease diagnosed in the 21st century revealed a significantly increased risk of serious infections. While absolute risks were modest, vaccinations should be considered during CD follow-up care.

Background Both testicular germ cell tumours (TGCT) and neurodevelopmental disorders are associated with urogenital malformations. Few studies have investigated the association between psychiatric disorders and TGCT. We investigated whether history of any psychiatric or neurodevelopmental disorder is associated with increased risk or mortality of TGCT. Method This is a nested case–control study including 6166 TGCT patients diagnosed during 1992–2014, individually matched for age and calendar period to 61,660 controls. We calculated odds ratios (ORs) for the association between type of psychiatric diagnoses and TGCT risk. Among the cases, we used a cohort design and calculated hazard ratios (HRs) of the association between psychiatric diagnose and all-cause and TGCT-specific death. Results History of a neurodevelopmental disorder (attention deficit hyperactivity disorder, autism spectrum disorder and intellectual disabilities) was associated with an increased risk of seminoma (OR: 1.54; 1.09–2.19). Seminoma patients with neurodevelopmental disorders were younger (34 versus 38 years, p = 0.004) and had more stage IV disease (5.4% versus 1.2%) than those without. Psychiatric history overall was not associated with TGCT. Patient history of any psychiatric disorder was associated with an increased all-cause and TGCT-specific death. Conclusions We report an association between neurodevelopmental disorders and testicular seminoma, and an increased TGCT-specific mortality for TGCT patients with psychiatric disorders.

Background Inflammatory bowel disease [IBD] has been linked to an increased risk of colorectal neoplasia. However, the types and risks of specific polyp types in IBD are less clear. Methods We identified 41 880 individuals with IBD (Crohn’s disease [CD: n = 12 850]; ulcerative colitis [UC]: n = 29 030]) from Sweden matched with 41 880 reference individuals. Using Cox regression, we calculated adjusted hazard ratios [aHRs] for neoplastic colorectal polyps [tubular, serrated/sessile, advanced and villous] defined by histopathology codes. Results During follow-up, 1648 [3.9%] IBD patients and 1143 [2.7%] reference individuals had an incident neoplastic colorectal polyp, corresponding to an incidence rate of 46.1 and 34.2 per 10 000 person-years, respectively. This correlated to an aHR of 1.23 (95% confidence interval [CI] 1.12–1.35) with the highest HRs seen for sessile serrated polyps [8.50, 95% CI 1.10–65.90] and traditional serrated adenomas [1.72, 95% CI 1.02–2.91]. aHRs for colorectal polyps were particularly elevated in those diagnosed with IBD at a young age and at 10 years after diagnosis. Both absolute and relative risks of colorectal polyps were higher in UC than in CD [aHRs 1.31 vs 1.06, respectively], with a 20-year cumulative risk difference of 4.4% in UC and 1.5% in CD, corresponding to one extra polyp in 23 patients with UC and one in 67 CD patients during the first 20 years after IBD diagnosis. Conclusions In this nationwide population-based study, there was an increased risk of neoplastic colorectal polyps in IBD patients. Colonoscopic surveillance in IBD appears important, especially in UC and after 10 years of disease.

To determine the risk of inflammatory bowel disease (IBD) in patients with celiac disease (CeD) (and vice versa ) compared with general-population comparators.Using Swedish histopathology and healthcare register data, we identified 48,551 patients with CeD and 83,529 with IBD diagnosed in 1969-2016. Each patient was compared with age- and sex-matched general-population comparators (CeD: n = 240,136; IBD: n = 408,195). Cox regression estimated hazard ratios (HRs) for IBD in patients with CeD and vice versa . Our main analyses were limited to events beyond the first year of follow-up to reduce potential surveillance bias.During follow-up, 784 (1.6%) patients with CeD were diagnosed with IBD compared with 1,015 (0.4%) matched comparators. In patients with CeD, the HR for IBD was 3.91 (95% confidence interval [CI] 3.56-4.31), with largely similar HRs for Crohn's disease (4.36; 3.72-5.11) and ulcerative colitis (3.40; 3.00-3.85). During follow-up, 644 (0.8%) patients with IBD and 597 (0.1%) comparators were diagnosed with CeD. The HR for CeD in patients with IBD was 5.49 (95% CI 4.90-6.16), with the highest risk estimates seen in ulcerative colitis (HR = 6.99; 6.07-8.05), and the HR for Crohn's disease was 3.31 (2.69-4.06). In patients with CeD and IBD, the diagnostic interval was usuallylt;1 year; however, HRs of 3-4 were seen even after 10 years of follow-up. During 20 years of follow-up, 2.5% of patients with CeD developed incident IBD, and 1.3% of patients with IBD developed CeD.The bidirectional association between CeD diagnosis and IBD warrants attention in the initial assessment and follow-up of these conditions. Their co-occurrence, independent of temporal sequence, suggests shared etiology.

Background and Purpose: Ischemic stroke is a common cause of death in adults, however, mortality after pediatric ischemic stroke is not well explored. We investigate long-term and cause-specific mortality in children with ischemic stroke and their first-degree relatives. Methods: Through nationwide Swedish registers, we identified 1606 individuals Results: The mortality rate in the first 6 months was 40.1 (95% CI, 24.7–55.6) per 1000 person-years compared with 1.1/1000 in controls (95% CI, 0.3–1.9). The overall mortality risk was hazard ratio (HR)=10.8 (95% CI, 8.1–14.3) and remained elevated beyond 20 years (HR=3.9 [95% CI, 2.1–7.1]). Children with ischemic stroke were at increased risk of death from neurological diseases (HR=29.9 [95% CI, 12.7–70.3]), cardiovascular diseases (HR=6.2 [95% CI, 1.8–22.2]), cancers (HR=6.5 [95% CI, 2.6–15.9]) and endocrine, nutritional and metabolic diseases (HR=49.2 [95% CI, 5.7–420.8]). First-degree relatives to children with ischemic stroke had an increased mortality risk (HR=1.21 [95% CI, 1.05–1.39]), with the highest risk among siblings (HR=1.52 [95% CI, 1.09–2.11]) and relatives to individuals with ischemic stroke >28 days of age (HR=1.23 [95% CI, 1.06–1.42]) compared with the relatives of the controls. Conclusions: Long-term mortality increased after pediatric ischemic stroke, even 20 years later, with neurological diseases as the most frequent cause of death.

Background and Aims: The risk for infection in alcohol-related liver disease (ALD) has rarely been investigated at a population level, nor if the underlying liver histopathology is associated with infection risk. We examined the rate of hospital-based infections in a nationwide cohort of biopsy-proven ALD, and the subsequent risk of death. Methods: Population-based cohort study in Sweden comparing 4028 individuals with an international classification of disease (ICD) code for ALD and a liver biopsy from 1969 to 2017 with 19,296 matched general population individuals. Swedish national registers were used to ascertain incident infections in secondary or tertiary care and subsequent mortality until 2019. We used Cox regression, adjusted for sex, age, education, country of birth, diabetes, and number of hospitalizations in the year preceding liver biopsy date, to estimate hazard ratios (HRs) in ALD and histopathological subgroups compared to reference individuals. Results: Median age at ALD diagnosis was 59 years, 65% were men and 59% had cirrhosis at baseline. Infections were more common in patients with ALD (84 cases/1000 person-years [PY]) compared to reference individuals (29/1000 PYs; adjusted hazard ratio [aHR] 3.06, 95% CI = 2.85–3.29). This excess risk corresponded to one additional infection per 18 ALD patients each year. The rate of infections was particularly high in individuals with cirrhosis (aHR = 3.46) and in those with decompensation (aHR = 5.20). Restricting our data to those with an infection, ALD (aHR = 3.63, 95%CI = 3.36–3.93), and especially ALD cirrhosis (aHR = 4.31, 95%CI = 3.89–4.78) were linked to subsequent death. Conclusions: Individuals with biopsy-proven ALD have a three-fold increased rate of infections compared with the general population. The risk of death after an infection is also considerably higher in individuals with ALD.

Introduction: A detailed understanding of respiratory support patterns in preterm infants is lacking. The aim was to explore and visualize this practice in Sweden. Methods: Preterm infants with gestational ages of 22–31 weeks, admitted to neonatal units reporting daily to the Swedish Neonatal Quality Register and discharged alive in November 2015–April 2022, were included in this descriptive cohort study. Proportions receiving mechanical ventilation, noninvasive support, or supplemental oxygen were calculated and graphically displayed for each gestational week and postnatal day (range 0–97) up to hospital discharge or 36 weeks of postmenstrual age. Results: Respiratory support in 148,515 days of care (3,368 infants; 54% males; median [interquartile range] birthweight = 1,215 [900–1,525] g) was evaluated. Trajectories showed distinct nonlinear patterns for each category of respiratory support, but differences in respiratory support over the gestational age range were linear: the proportion of infants on mechanical ventilation decreased by −11.7 to −7.3% (variability in estimates related to the postnatal day chosen for regression analysis) for each week higher gestational age (r = −0.99 to −0.87, p ≤ 0.001). The corresponding proportions of infants with supplemental oxygen decreased by −12.4% to −4.5% for each week higher gestational age (r = −0.98 to −0.94, p < 0.001). At 36 weeks of postmenstrual age, dependencies on mechanical ventilation, noninvasive support, and supplemental oxygen varied from 3%, 84%, and 94% at 22 weeks to 0%, 3%, and 5% at 31 weeks of gestational age, respectively. Conclusions: Respiratory support patterns in very preterm infants follow nonlinear, gestational age-specific postnatal trajectories in a dose-response-related fashion.

Introduction : Symptoms of irritable bowel syndrome (IBS) are common reasons for endoscopic procedures. We examined the yield of colonoscopy and upper endoscopy in IBS for several organic diseases. Methods : Matched population-based prevalence study in Sweden. We identified 21,944 participants diagnosed with IBS from 1987 to 2016 undergoing colonoscopy with a biopsy from all of Sweden's 28 pathology departments within 6 months of diagnosis. We compared prevalence of histopathology-proven diagnoses of inflammatory bowel disease (IBD), colorectal cancer, precancerous polyps, and microscopic colitis between patients recently diagnosed with IBS and matched controls without IBS (n = 81,101) undergoing colonoscopy. We also compared prevalence of celiac disease between patients diagnosed with IBS (n = 9,965) and matched controls (n = 45,584) undergoing upper endoscopy with biopsy. IBS patients were also compared to their siblings. Conditioned logistic regression estimated adjusted odds ratios (aORs). Results : Biopsy-proven IBD was seen in 1.6% of IBS and in 5.9% of controls (aOR=0.21; 95%CI=0.19–0.24). The prevalence of precancerous polyps was 4.1% vs. 13.0% (aOR=0.28; 95%CI=0.26–0.30), colorectal cancer 0.8% vs. 6.3% (aOR=0.17; 95%CI=0.14–0.20) and celiac disease 1.9% vs. 3.4% (aOR=0.54; 95%CI=0.47–0.63). Conversely, the prevalence of microscopic colitis was 2.9% vs. 1.7% (aOR=1.77; 95%CI=1.61–1.95), with higher prevalence in older patients and patients with IBS with diarrhea. Yield of colonoscopy for precancerous polyps, colorectal cancer, and microscopic colitis increased by age. Our findings were consistent using unaffected siblings as the comparator group. Discussion : The diagnostic yield of upper endoscopy and colonoscopy for organic disease is low in patients with a first-time diagnosis of IBS, though increases with age.

The totality of the societal and individual impact of treatment-resistant depression (TRD) is unknown, as is the potential to prognosticate TRD. The generalizability of many observational studies on TRD is limited.To estimate the burden of TRD in a large population-wide cohort in an area with universal health care by including data from both health care types (psychiatric and nonpsychiatric) and, further, to develop a prognostic model for clinical use.This cohort study, a population-based observational study, assessed data from the Stockholm MDD Cohort for episodes of major depressive disorder (MDD) between 2010 and 2017 that fulfilled predefined criteria for TRD (≥3 consecutive antidepressant treatments). Data analysis was performed from August 2020 to May 2022.Outcomes were psychiatric and nonpsychiatric comorbid conditions, antidepressant treatments, health care resource utilization, lost workdays, all-cause mortality, and intentional self-harm and, in the prognostic model, TRD.A total of 158 169 unipolar MDD episodes (in 145 577 patients) were identified between January 1, 2012, and December 31, 2017 (64.7% women; median [IQR] age, 42 years [30-56]). Of these, 12 793 episodes (11%) fulfilled criteria for TRD. The median (IQR) time from the start of MDD episode to TRD was 552 days (294-932). Selective serotonin reuptake inhibitor was the most common class of antidepressant treatment in all treatment steps, and 5907 patients (46.2%) received psychotherapy at some point before initiation of the third pharmacological antidepressant treatment. Compared with matched non-TRD episodes, TRD episodes had more inpatient bed-days (mean, 3.9 days; 95% CI, 3.6-4.1, vs 1.3 days; 95% CI, 1.2-1.4) and more lost workdays (mean, 132.3 days; 95% CI, 129.5-135.1, vs 58.7 days; 95% CI, 56.8-60.6) 12 months after the index date. Anxiety, stress, sleep disorder, and substance use disorder were all more common comorbid conditions in TRD episodes. Intentional self-harm was more than 4 times more common in TRD episodes. The all-cause mortality rate for patients with MDD with TRD episodes was 10.7/1000 person-years at risk, compared with 8.7/1000 person-years at risk for patients with MDD without TRD episodes (hazard ratio, 1.23; 95% CI, 1.07-1.41). Median time from start of the first antidepressant treatment to start of the second, and from start of the second antidepressant treatment to start of the third, was 165 and 197 days, respectively. The severity of MDD, defined using the self-rating Montgomery-Åsberg Depression Rating Scale (MADRS-S) at time of MDD diagnosis, was found to be the most important prognostic factor for TRD (C index = 0.69).In this cohort study, TRD was a common variant of MDD when including patients from both health care types, which is associated with a high disease burden for both patients and society. The median time between initiation of new antidepressant treatments was longer than recommended in current treatment guidelines, suggesting room for more structured and timely depression care.

Objective To assess associations of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and pregnancy outcomes considering testing policy and test‐positivity‐to‐delivery interval. Design Nationwide cohort study. Setting Sweden. Population From the Pregnancy‐Register we identified 88 593 singleton births, 11 March 2020–31 January 2021, linked to data on SARS‐CoV‐2‐positivity from the Public Health Agency, and information on neonatal care admission from the Neonatal Quality Register. Adjusted odds ratios (aORs) were estimated stratified by testing‐policy and test‐positivity‐to‐delivery interval. Main outcome measures Five‐minute Apgar score, neonatal care admission, stillbirth and preterm birth. Results During pregnancy, SARS‐CoV‐2 test‐positivity was 5.4% (794/14 665) under universal testing and 1.9% (1402/73 928) under non‐universal testing. There were generally lower risks associated with SARS‐CoV‐2 under universal than non‐universal testing. In women testing positive >10 days from delivery, generally no significant differences in risk were observed under either testing policy. Neonatal care admission was more common (15.3% versus 8.0%; aOR 2.24, 95% CI 1.62–3.11) in women testing positive ≤10 days before delivery under universal testing. There was no significant association with 5‐minute Apgar score below 7 (1.0% versus 1.7%; aOR 0.64, 95% CI 0.24–1.72) or stillbirth (0.3% versus 0.4%; aOR 0.72, 95% CI 0.10–5.20). Compared with term births (2.1%), test‐positivity was higher in medically indicated preterm birth (5.7%; aOR 2.70, 95% CI 1.60–4.58) but not significantly increased in spontaneous preterm birth (2.3%; aOR 1.12, 95% CI 0.62–2.02). Conclusions Testing policy and timing of test‐positivity impact associations between SARS‐CoV‐2‐positivity and pregnancy outcomes. Under non‐universal testing, women with complications near delivery are more likely to be tested than women without complications, thereby inflating any association with adverse pregnancy outcomes compared with findings under universal testing. Tweetable abstract Testing policy and time from SARS‐CoV‐2 infection to delivery influence the association with pregnancy outcomes., Tweetable abstract Testing policy and time from SARS‐CoV‐2 infection to delivery influence the association with pregnancy outcomes.

Background Restorative surgery after colectomy due to ulcerative colitis (UC) may be performed simultaneously with colectomy (primary) or as a staged procedure. Risk factors for failure after restorative surgery are not fully explored. This study aimed to compare the risk of failure after primary and staged reconstruction. Methods This is a national register-based cohort study of all patients 15 to 69 years old in Sweden treated with colectomy due to UC and who received an ileorectal anastomosis (IRA) or ileal pouch-anal anastomosis (IPAA) between 1997 and 2017. Failure was defined as a reoperation with new ileostomy after restorative surgery or a remaining defunctioning ileostomy after 2 years. Risk of failure was calculated using the Kaplan-Meier method and Cox regression adjusted for sex, age, calendar period, primary sclerosing cholangitis, and duration of UC. Results Of 2172 included patients, 843 (38.8%) underwent primary reconstruction, and 1329 (61.2%) staged reconstruction. Staged reconstruction was associated with a decreased risk of failure compared with primary reconstruction (hazard ratio, 0.73; 95% CI, 0.58–0.91). The 10-year cumulative risk of failure was 15% vs 20% after staged and primary reconstruction, respectively. In all, 1141 patients (52.5%) received an IPAA and 1031 (47.5%) an IRA. In stratified multivariable models, staged reconstruction was more successful than primary reconstruction in both IRA (hazard ratio, 0.75; 95% CI, 0.54–1.04) and IPAA (hazard ratio, 0.73; 95% CI, 0.52–1.01), although risk estimates failed to attain statistical significance. Conclusions In UC patients undergoing colectomy, postponing restorative surgery may decrease the risk of failure.

Background and Purpose: The risk of epilepsy after stroke has not been thoroughly explored in pediatric ischemic stroke. We examined the risk of epilepsy in children with ischemic stroke as well as in their first-degree relatives. Methods: In Swedish National Registers, we identified 1220 children Results: Through this nationwide population-based study, 219 (18.0%) children with ischemic stroke and 91 (0.7%) comparators were diagnosed with epilepsy during follow-up corresponding to a 27.8-fold increased risk of future epilepsy (95% CI, 21.5–36.0). The risk of epilepsy was still elevated after 20 years (hazard ratio [HR], 7.9 [95% CI, 3.3–19.0]), although the highest HR was seen in the first 6 months (HR, 119.4 [95% CI, 48.0–297.4]). The overall incidence rate of epilepsy was 27.0 per 100 000 person-years (95% CI, 21.1–32.8) after ischemic stroke diagnosed ≤day 28 after birth (perinatal) and 11.6 per 100 000 person-years (95% CI, 9.6–13.5) after ischemic stroke diagnosed ≥day 29 after birth (childhood). Siblings and parents, but not offspring, to children with ischemic stroke were at increased risk of epilepsy (siblings: HR, 1.64 [95% CI, 1.08–2.48] and parents: HR, 1.41 [95% CI, 1.01–1.98]). Conclusions: The risk of epilepsy after ischemic stroke in children is increased, especially after perinatal ischemic stroke. The risk of epilepsy was highest during the first 6 months but remained elevated even 20 years after stroke which should be taken into account in future planning for children affected by stroke.

We aimed to determine the risk of incident cancer in autoimmune hepatitis (AIH) compared with the general population and siblings. AIH was defined by the presence of a medical diagnosis of AIH and results of examination of a liver biopsy specimen in a nationwide Swedish population-based cohort study. We identified 5,268 adults with AIH diagnosed during 1969–2016 and 22,996 matched, general population, reference individuals and 4,170 sibling comparators. Using Cox regression, hazard ratios were determined for any incident cancer, and subtypes were determined from the Swedish Cancer Register. During follow-up, a cancer diagnosis was made in 1,119 individuals with AIH (17.2 per 1,000 person-years) and 4,450 reference individuals (12.0 per 1,000 person-years). This corresponded to a hazard ratio of 1.53 (95% confidence interval: 1.42, 1.66). Cancer risk was highest in those with cirrhosis. There was a 29.18-fold increased risk of hepatocellular carcinoma (HCC) (95% confidence interval: 17.52, 48.61). The annual incidence risk of HCC in individuals with AIH who had cirrhosis was 1.1% per year. AIH was also linked to nonmelanoma skin cancer (hazard ratio (HR) = 2.69) and lymphoma (HR = 1.89). Sibling analyses yielded similar risk estimates for any cancer (HR = 1.84) and HCC (HR = 23.10). AIH is associated with an increased risk of any cancer, in particular, HCC and extrahepatic malignancies. The highest risk for cancer, especially HCC, is in patients with cirrhosis.

Background There are concerns that individuals with chronic immune‐mediated diseases are at increased risk of COVID‐19 and related severe adverse outcome, including intensive care admission or death. We aimed to explore the absolute and relative risk of severe COVID‐19 in inflammatory bowel disease (IBD). Methods This population‐based cohort study used nationwide registers in Sweden, with 67,292 individuals with a diagnosis of IBD 1969–2017 (Crohn's disease, n = 21,599; ulcerative colitis: n = 43,622; IBD‐unclassified: n = 2071) and alive on 1 February 2020. Patients with IBD were matched to up to five controls from the general population (n = 297,910). Cox regression estimated hazard ratios (HRs) for (i) hospital admission with laboratory‐confirmed COVID‐19 as the primary diagnosis, and (ii) severe COVID‐19 (composite outcome consisting of (a) COVID‐19 intensive care admission, or (b) death from COVID‐19 or (c) death within 30 days of COVID‐19 hospital admission), were calculated. Analyses were conditioned on age, sex, calendar period, and county and adjusted for other comorbidities. Results Between 1 February and 31 July 2020, 179 (0.27%) IBD patients and 500 (0.17%) general population controls were admitted to hospital with COVID‐19 (adjusted HR [aHR] = 1.43; 95% CI = 1.19–1.72). The corresponding numbers for severe COVID‐19 was 65 (0.10%) and 183 (0.06%; aHR = 1.11; 95% CI = 0.81–1.52). Adjusted HRs were similar in Crohn's disease and ulcerative colitis. In a propensity score‐matched model taking comorbidity into account until 2016, the increased risk for COVID‐19 hospital admission remained (aHR = 1.32; 1.12–1.56), but there was no increased risk of severe COVID‐19 (aHR = 1.12; 0.85–1.47). Conclusions While individuals with IBD were more likely to be admitted to hospital for COVID‐19 than the general population, the risk of severe COVID‐19 was not higher., Key Summary Summarise the established knowledge on this subject Individuals with inflammatory bowel disease (IBD) are at increased risk of infections.COVID‐19 is a pandemic, affecting millions of people.COVID‐19 can have gastrointestinal manifestations.While IBD does not seem to influence the prognosis in COVID‐19 positive individuals, data are scarce about the relative and absolute risk of severe COVID‐19 in IBD compared with that in the general population. What are the significant and/or new findings of this study? Compared to the general population, individuals with IBD were at increased risk of hospital admission from COVID‐19, and this risk increase remained when taking comorbidity into account in a propensity score model.However, they were at no increased risk of severe COVID‐19 defined as intensive care or death from COVID‐19.Compared to siblings, individuals with IBD were at no increased risk of hospital admission from COVID‐19 or severe COVID‐19.Even in a country (Sweden) with extensive COVID‐19, the absolute risk of severe COVID‐19 seems low in IBD. This is comforting to patients and their families.

ObjectiveTo study the association between SARS-CoV-2 infection and newly diagnosed hypertension during pregnancy.DesignProspective, population based cohort study.SettingAll singleton pregnancies after 22 completed gestational weeks registered in the Swedish Pregnancy Register and the Medical Birth Registry of Norway, from 1 March 2020 to 24 May 2022.Participants312 456 individuals available for analysis (201 770 in Sweden and 110 686 in Norway), with pregnancies that reached 42 completed gestational weeks by the end of follow-up in the pregnancy registries, excluding individuals with SARS-CoV-2 infection before pregnancy and those with a diagnosis of pre-existing hypertension or onset of hypertension before 20 gestational weeks.Main outcome measuresNewly diagnosed hypertension during pregnancy was defined as a composite outcome of a diagnosis of gestational hypertension, pre-eclampsia, HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome, or eclampsia, from gestational week 20 to one week after delivery. The association between SARS-CoV-2 infection and hypertension during pregnancy was investigated with a stratified Cox proportional hazard model, adjusting for maternal age, body mass index, parity, smoking, region of birth, education, income, coexisting medical conditions, previous hypertension during pregnancy, number of healthcare visits during the past year, and vaccination against SARS-CoV-2. Pre-eclampsia was also analysed as a separate outcome.ResultsOf 312 456 individuals available for analysis, 8% (n=24 566) had SARS-CoV-2 infection any time during pregnancy, 6% (n=18 051) had a diagnosis of hypertension during pregnancy, and 3% (9899) had pre-eclampsia. SARS-CoV-2 infection during pregnancy was not associated with an increased risk of hypertension during pregnancy (adjusted hazard ratio 0.99, 95% confidence interval 0.93 to 1.04) or pre-eclampsia (0.98, 0.87 to 1.10). The results were similar for SARS-CoV-2 infection in all gestational trimesters and in different time periods that corresponded to dominance of different variants of the SARS-CoV-2 virus.ConclusionsThis population based study did not find any evidence of an association between SARS-CoV-2 infection during pregnancy and an increased risk of hypertension during pregnancy or pre-eclampsia.

Benjamin Lebwohl,1,2 Emma Larsson,3 Jonas Söderling,4 Bjorn Roelstraete,4 Joseph A Murray,5 Peter HR Green,1 Jonas F Ludvigsson1,4,6 1Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, NY, USA; 2Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; 3Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden; 4Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; 5Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; 6Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, SwedenCorrespondence: Jonas F LudvigssonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, PO Box 281, Stockholm, SE-17177, SwedenTel +46-19-6021000Email jonasludvigsson@yahoo.comBackground: Patients with celiac disease (CeD) are at increased risk of certain viral infections and of pneumococcal pneumonia, raising concerns that they may be susceptible to severe coronavirus disease 2019 (Covid-19). We aimed to quantify the association between CeD and severe outcomes related to Covid-19.Methods: We performed a population-based cohort study, identifying individuals with CeD in Sweden, as defined by small intestinal villus atrophy diagnosed at all (n=28) Swedish pathology departments during the years spanning 1969– 2017, and alive on February 1, 2020. We compared these patients to controls matched by sex, age, county, and calendar period. We performed Cox proportional hazards with follow-up through July 31, 2020, assessing risk of 1) hospital admission with a primary diagnosis of laboratory-confirmed Covid-19 (co-primary outcome); and 2) severe disease as defined by admission to intensive care unit and/or death attributed to Covid-19 (co-primary outcome).Results: Among patients with CeD (n=40,963) and controls (n=183,892), the risk of hospital admission for Covid-19 was 2.9 and 2.2 per 1000 person-years respectively. After adjusting for comorbidities, the risk of hospitalization for Covid-19 was not significantly increased in patients with CeD (HR 1.10; 95% CI 0.80– 1.50), nor was the risk of severe Covid-19 increased (HR 0.97; 95% CI 0.59– 1.59). Results were similarly null when we compared CeD patients to their non-CeD siblings with regard to these outcomes. Among all patients with CeD and controls hospitalized with a diagnosis of Covid-19 (n=58 and n=202, respectively), there was no significant difference in mortality (HR for CeD compared to controls 0.96; 95% CI 0.46– 2.02).Conclusion: In this population-based study, CeD was not associated with an increased risk of hospitalization for Covid-19 or intensive care unit and/or death attributed to Covid-19.Keywords: Covid-19, celiac disease, epidemiology, infection, SARS-CoV-2

BACKGROUND To avoid a permanent stoma, restorative surgery is performed after the colectomy. Previous studies have shown that less than half of patients with ulcerative colitis undergo restorative surgery. OBJECTIVE The primary aim was to explore the association between socioeconomic status and restorative surgery after colectomy. DESIGN This was a nationwide register-based cohort study. SETTINGS The study was conducted in Sweden. PATIENTS All Swedish patients with ulcerative colitis who underwent colectomy between 1990 and 2017 at the age of 15 to 69 years were included. MAIN OUTCOME MEASURES The main outcome was restorative surgery, and the secondary outcome was failure of the reconstruction (defined as the need for a new ileostomy after the reconstruction or nonreversal of a defunctioning stoma within 2 years of the reconstruction). To calculate HRs for restorative surgery after colectomy, as well as failure after restorative surgery, multivariable Cox regression models were performed (adjusted for sex, year of colectomy, colorectal cancer diagnosis, education, civil status, country of birth, income (quartiles 1 to 4, where Q4 represents highest income), hospital volume, and stratified by age). RESULTS In all, 5969 patients with ulcerative colitis underwent colectomy, and of those, 2794 (46.8%) underwent restorative surgery. Restorative surgery was more common in patients with a high income at the time of colectomy (quartile 1, reference; quartile 2, 1.09 (0.98-1.21); quartile 3, 1.20 (1.07-1.34); quartile 4, 1.27 (1.13-1.43)) and less common in those born in a Nordic country than in immigrants born in a non-Nordic country (0.86 (0.74-0.99)), whereas no association was seen with educational level and civil status. There was no association between socioeconomic status and the risk of failure after restorative surgery. LIMITATIONS The study was restricted to register data. CONCLUSIONS Restorative surgery in ulcerative colitis appears to be more common in patients with a high income and patients born in a non-Nordic country, indicating inequality in the provided care. See Video Abstract at http://links.lww.com/DCR/B433. LA CIRUGA RESTAURADORA ES MS COMN EN PACIENTES CON COLITIS ULCEROSA CON INGRESOS ALTOS UN ESTUDIO POBLACIONAL ANTECEDENTES:Para evitar un estoma permanente, se realiza una cirugia reparadora despues de la colectomia. Estudios anteriores han demostrado que menos de la mitad de los pacientes con colitis ulcerosa se someten a cirugia reconstituyente.OBJETIVO:El objetivo principal fue explorar la asociacion entre el nivel socioeconomico y la cirugia reconstituyente despues de la colectomia.DISENO:Estudio de cohorte basado en registros a nivel nacional.MARCO:Suecia.PACIENTES:Todos los pacientes Suecos con colitis ulcerosa que se sometieron a colectomia desde el 1990 a 2017 a la edad de 15 a 69 anos.MEDIDAS DE RESULTADOS PRINCIPALES:El resultado principal fue la cirugia restaurativa y el resultado secundario fue el fracaso de la reconstruccion (definida como la necesidad de una nueva ileostomia despues de la reconstruccion o la no-reversion de un estoma disfuncional dentro de los dos anos posteriores a la reconstruccion). Para calcular los cocientes de riesgo para la cirugia restauradora despues de la colectomia, asi como el fracaso despues de la cirugia restauradora, se realizaron modelos de regresion de Cox multivariables (ajustados por sexo, ano de colectomia, diagnostico de cancer colorrectal, educacion, estado civil, pais de nacimiento e ingresos (cuartiles 1- 4; donde Q4 representa los mayores ingresos), volumen de hospitales y estratificado por edad).RESULTADOS:En total 5969 pacientes con colitis ulcerosa se sometieron a colectomia, y de ellos 2794 (46,8%) se sometieron a cirugia restauradora. La cirugia restauradora fue mas comun en pacientes con altos ingresos en el momento de la colectomia (referencia del cuartil 1, cuartil 2: 1,09 (0,98-1,21), cuartil 3: 1,20 (1,07-1,34), cuartil 4: 1,27 (1,13-1,43)), y menos comun en los nacidos en un pais nordico que en los inmigrantes nacidos en un pais no-nordico (0,86 (0,74-0,99)), mientras que no se observo asociacion con el nivel educativo y el estado civil. No hubo asociacion entre el nivel socioeconomico y el riesgo de fracaso despues de la cirugia reparadora.LIMITACIONES:Restriccion para registrar datos.CONCLUSIONES:La cirugia reparadora en colitis ulcerosa parece ser mas comun en pacientes con ingresos altos y en pacientes nacidos en un pais no-nordico, lo que indica desigualdad en la atencion brindada. Consulte Video Resumen en http://links.lww.com/DCR/B433.

Patients with alcohol-related liver disease (ALD) frequently have risk factors for cardiovascular disease (CVD), but their long-term risk of CVD is not well-known, especially considering the competing risk of death from liver-related causes. It is further unknown if any excess risk varies across histological subgroups.We investigated the risk of CVD outcomes in 3488 persons with ALD and an available liver biopsy in Sweden between 1969 and 2016, compared with a matched reference population (n = 15,461). Administrative coding from national diagnostic and histopathology registers were used to define exposures and outcomes. Competing risk regression, taking non-CVD death into account and adjusting for potential confounders, was used to estimate subdistribution hazard ratios for incident CVD up until Dec 31, 2019.At baseline, patients with ALD had a median age of 58 years, 64% were men, and 2039 (58%) had cirrhosis on histology. The incidence rate of CVD was 35.6 per 1000 person-years in ALD compared with 19.0 per 1000 person-years in reference individuals. ALD was associated with a 2-fold increased short-term risk for CVD compared with matched reference individuals (subdistribution hazard ratio during the first year after diagnosis, 2.29; 95% confidence interval, 1.79-2.95), but this risk decreased with time. Incidence rates of CVD were comparable across histological subgroups (ranging from 27.4 CVD cases per 1000 person-years in those with normal histology to 39.2 cases per 1000 person-years in those with cirrhosis).Persons with biopsy-proven ALD have increased rates of CVD across histological subgroups compared with matched reference individuals, particularly just after ALD diagnosis. Active surveillance of modifiable CVD risk factors should be considered by clinicians treating patients with ALD.

Celiac disease (CD) is associated with many immune-mediated conditions, but a definitive epidemiological association between CD and juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) has not been established. We quantified the risk of JIA and RA among patients with CD using a population-based cohort.We identified patients diagnosed with biopsy-proven CD between 2004 and 2017 using data from a national histopathology cohort in Sweden. Each patient was matched by age, sex, calendar year, and geographic region to reference individuals in the general population. We calculated the incidence and estimated the relative risk, through Cox proportional hazards models, of JIA in individuals with CD aged18 and of RA in individuals with CD aged ≥18.We identified 24,014 individuals with CD who were matched to 117,397 reference individuals from the general population. Among individuals aged18, the incidence rate of JIA was 5.9 per 10,000 person-years in patients with CD and 2.2 per 10,000 person-years in the general population (n events = 40 and 73, respectively; hazard ratio [HR] 2.68, 95% confidence interval 1.82-3.95) over a follow-up of 7.0 years. Among individuals aged ≥ 18, the incidence of RA was 8.4 per 10,000 person-years in CD and 5.1 per 10,000 person-years in matched comparators (n events = 110 and 322, respectively; HR 1.70, 95% confidence interval 1.36-2.12) over a follow-up of 8.8 years.Among children with CD, JIA develops nearly 3 times as often as it does in the general population, and among adults with CD, RA occurs nearly 2 times as often. Clinicians caring for patients with CD with joint symptoms should have a low threshold to evaluate for JIA or RA.

Early detection of attention-deficit/hyperactivity disorder (ADHD) plays a crucial role in reducing negative effects on everyday life, including academic failure and poor social functioning. Children who survive ischemic strokes risk major disabilities, but their risk of ADHD has not been studied in nationwide cohorts.To assess the risk of ADHD in children after pediatric ischemic stroke.Participants in this Swedish nationwide cohort study included 1320 children diagnosed with ischemic stroke recorded in linked Swedish national registers from January 1, 1969, to December 31, 2016, without prior ADHD diagnosis. Ten matched controls were identified for each index case, and first-degree relatives were identified for index individuals and controls. Analyses were stratified by perinatal and childhood strokes and presence of comorbid adverse motor outcomes and/or epilepsy. End of follow-up was the date of ADHD diagnosis, death, or December 31, 2016, whichever occurred first. Data analyses were performed August 1 to 28, 2021.Pediatric ischemic stroke.Attention-deficit/hyperactivity disorder identified using codes from the International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, and/or prescribed ADHD medication recorded in the Medical Birth Register, National Patient Register, or Prescribed Drug Register after stroke. Cox proportional hazards regression was used to assess adjusted hazard ratios (aHRs) for ADHD after pediatric stroke, adjusting for parental age and ADHD in first-degree relatives.Of 1320 children with stroke included in the analysis (701 boys [53.1%]), 75 (45 boys [60.0%]) were diagnosed with ADHD after stroke compared with 376 (252 boys [67.0%]) among the controls (aHR, 2.00 [95% CI, 1.54-2.60]). The risk was increased after both perinatal (aHR, 2.75 [95% CI ,1.65-4.60]) and childhood (aHR, 1.82 [95% CI, 1.34-2.48]) strokes and were similar if children born preterm or small for gestational age were excluded. Compared with controls, risks of ADHD were higher among children with perinatal stroke and adverse motor outcomes and/or epilepsy (aHR, 6.17 [95% CI, 2.80-13.62]) than among those without these comorbidities (aHR, 1.65 [95% CI, 0.80-3.42]). However, findings were similar in childhood stroke for children with adverse motor outcomes and/or epilepsy (aHR, 1.80 [95% CI, 1.12-2.89]) and among those without these comorbidities (aHR, 1.92 [95% CI, 1.28-2.90]).This cohort study of 1320 children with pediatric ischemic stroke suggests that there is an increased risk of ADHD, particularly in children with adverse motor outcomes and/or epilepsy, compared with controls. The risk increases after childhood strokes regardless of comorbidities.

Background and Aims Patients with inflammatory bowel disease [IBD] are subject to more work disability than the general population. We aimed to estimate the monetary cost of IBD for the individual through assessment of earnings in relation to diagnosis. Methods Through linkage of national registers, we identified patients aged 30–55 years at first IBD diagnosis in Sweden in 2002–2011, and same-sex IBD-free siblings. We estimated taxable earnings and disposable income from 5 years before to 5 years after diagnosis. Results The 5961 patients [27% Crohn’s disease, 68% ulcerative colitis, 4.3% IBD unclassified] had similar taxable earnings to their 7810 siblings until the year of diagnosis, when earnings decreased and remained lower than for siblings during follow-up. The adjusted difference in earnings over the entire 5-year period after diagnosis was −5% [−8212€; 95% confidence interval: −11 458 to −4967€]. The difference was greater in women than in men, and greater in Crohn’s disease than in ulcerative colitis. When stratifying for sex and IBD subtype and comparing earnings during each year of follow-up, median annual earnings were lower in women with Crohn’s disease and ulcerative colitis than in their sisters during all years of follow-up, whereas the men had similar annual taxable earnings to their brothers. Disposable income was similar between patients and siblings during the investigated time period. Conclusion From the year of diagnosis and at least 5 years onwards, patients with IBD had 5% lower earnings than siblings, mainly explained by differences between women with IBD and their sisters. However, there were no differences in disposable income.

INTRODUCTION Celiac disease (CD) affects 1% of the population. Its effect on healthcare cost, however, is barely understood. We estimated healthcare use and cost in CD, including their temporal relationship to diagnosis. METHODS Through biopsy reports from Sweden's 28 pathology departments, we identified 40,951 prevalent patients with CD (villous atrophy) as of January 1, 2015, and 15,086 incident patients with CD diagnosed in 2008-2015, including 2,663 who underwent a follow-up biopsy to document mucosal healing. Each patient was compared with age- and sex-matched general population comparators (n = 187,542). Using nationwide health registers, we retrieved data on all inpatient and nonprimary outpatient care, prescribed diets, and drugs. RESULTS Compared with comparators, healthcare costs in 2015 were, on average, $1,075 (95% confidence interval, $864-1,278) higher in prevalent patients with CD aged

ObjectivePatients with alcohol-related liver disease (ALD) are at increased risk of death, but studies have rarely investigated the significance of histological severity or estimated relative risks compared with a general population. We examined mortality in a nationwide cohort of biopsy-proven ALD.DesignPopulation-based cohort study in Sweden comparing 3453 individuals with an International Classification of Disease (ICD) code for ALD and a liver biopsy from 1969 to 2017 with 16 535 matched general population individuals. Swedish national registers were used to ascertain overall and disease-specific mortality, starting follow-up at the latest of first ICD diagnosis or liver biopsy plus 3 months. Cox regression adjusted for relevant confounders was used to estimate HRs in ALD and histopathological subgroups.ResultsMedian age at diagnosis was 58 years, 65% were men and 52% had cirrhosis at baseline. Five-year cumulative mortality was 40.9% in patients with ALD compared with 5.8% in reference individuals. The risk for overall mortality was significantly increased (adjusted HR (aHR)=4.70, 95% CI 4.35 to 5.08). The risk of liver-related death was particularly high (43% of all deaths, aHR=167.6, 95% CI 101.7 to 276.3). Mortality was significantly increased also in patients with ALD without cirrhosis and was highest in the first year after baseline but persisted after ≥10 years of follow-up (aHR=2.74, 95% CI 2.37 to 3.16).ConclusionIndividuals with biopsy-proven ALD have a near fivefold increased risk of death compared with the general population. Individuals with ALD without cirrhosis were also at increased risk of death, reaffirming the need to increase vigilance in the management of these individuals.

Introduction Mortality concern is a frequent driver of care seeking in patients with irritable bowel syndrome (IBS). Data on mortality in IBS are scarce, and population-based studies have been limited in size. We examined mortality in IBS. Methods A nationwide, matched, population-based cohort study was conducted in Sweden. We identified 45,524 patients undergoing a colorectal biopsy at any of Sweden's 28 pathology departments and with a diagnosis of IBS from 2002 to 2016 according to the National Patient Register, a nationwide registry of inpatient and outpatient specialty care. We compared the mortality risk between these individuals with IBS and age- and sex-matched reference individuals (n = 217,316) from the general population and siblings (n = 53,228). In separate analyses, we examined the role of mucosal appearance for mortality in IBS. Finally, we examined mortality in 41,427 patients with IBS not undergoing a colorectal biopsy. Cox regression estimated hazard ratios (HRs) for death. Results During follow-up, there were 3,290 deaths in individuals with IBS (9.4/1,000 person-years) compared with 13,255 deaths in reference individuals (7.9/1,000 person-years), resulting in an HR of 1.10 (95% confidence interval [CI] = 1.05-1.14). After adjustment for confounders, IBS was not linked to mortality (HR = 0.96; 95% CI = 0.92-1.00). The risk estimates were neutral when patients with IBS were compared with their siblings. The underlying mucosal appearance on biopsy had only a marginal impact on mortality, and patients with IBS not undergoing a colorectal biopsy were at no increased risk of death (HR = 1.02; 95% CI = 0.99-1.06). Discussion IBS does not seem to confer an increased risk of death.

Objective Major depressive disorder (MDD) is a highly prevalent condition and a significant contributor to global disability. The vast majority of MDD is handled by primary care, but most real-life studies on MDD only include data from secondary care. The aim of this study was therefore to estimate the total clinical and societal burden of incident MDD including data from all healthcare levels in a large well-defined western European healthcare region. Methods Population-wide observational study included healthcare data from Region Stockholm, Sweden's largest region with approximately 2.4 million inhabitants. All patients in Region Stockholm having their first unipolar MDD episode between January 1, 2012, and December 31, 2018, were included. The sample also included matched study population controls. Outcomes were psychiatric and non-psychiatric comorbid conditions, antidepressant therapy use, healthcare resource utilization, work loss, and all-cause mortality. Results In the study period, 137,822 patients in Region Stockholm were diagnosed with their first unipolar MDD episode. Compared with matched controls, MDD patients had a higher burden of non-psychiatric and psychiatric comorbid conditions, 3.2 times higher outpatient healthcare resource utilization and 8.6 times more work loss. MDD was also associated with a doubled all-cause mortality compared with matched controls (HR: 2.2 [95% CI: 2.0-2.4]). Conclusions The high mortality, morbidity, healthcare resource utilization, and work loss found in this study confirms that MDD is associated with individual suffering and low functioning leading to substantial costs for patients and society. These findings should motivate additional efforts in improving outcomes for MDD patients.

Background Surgery rates in patients with Crohn’s disease have decreased during the last few decades, and use of antitumor necrosis agents (anti-TNF) has increased. Whether these changes correlate with a decreased probability of stoma is unknown. The objective of this study was to investigate the incidence of stoma in patients with Crohn’s disease over time. Methods Through linkage of national registers, we identified patients who were diagnosed with Crohn’s disease in 2003–2014 and were followed through 2019. We compared formation and closure of stomas over the calendar periods of diagnosis (2003–2006, 2007–2010, and 2011–2014). Results In a nationwide cohort of 18,815 incident patients with a minimum 5 years of follow-up, 652 (3.5%) underwent formation of a stoma. This was mostly performed in conjunction with ileocolic resection (39%). The 5-year cumulative incidence of stoma formation was 2.5%, with no differences between calendar periods (P = .61). Less than half of the patients (44%) had their stoma reversed. Stomas were more common in elderly-onset compared with pediatric-onset disease: 5-year cumulative incidence 3.6% vs 1.3%. Ileostomies were most common (64%), and 24.5% of the patients who underwent stoma surgery had perianal disease at end of follow-up. Within 5 years of diagnosis, 0.8% of the incident patients had a permanent stoma, and 0.05% had undergone proctectomy. The time from diagnosis to start of anti-TNF treatment decreased over calendar periods (P < .001). Conclusions Despite increasing use of anti-TNF and a low rate of proctectomy, the cumulative incidence of stoma formation within 5 years of Crohn’s disease diagnosis has not decreased from 2003 to 2019.

Introduction: A revised intrapartum cardiotocography (CTG) classification was introduced in Sweden in 2017. The aims of the revision were to adapt to the international guideline published in 2015 and to adjust the classification of CTG patterns to current evidence regarding intrapartum fetal physiology. This study aimed to investigate adverse neonatal outcomes before and after implementation of the revised CTG classification. Material and Methods: A before-and-after design was used. Cohort I (n = 160 210) included births from June 1, 2014 through May 31, 2016 using the former CTG classification, and cohort II (n = 166 558) included births from June 1, 2018 through May 31, 2020 with the revised classification. Data were collected from the Swedish Pregnancy and Neonatal Registers. The primary outcome was moderate to severe neonatal hypoxic ischemic encephalopathy (HIE 2-3). Secondary outcomes were birth acidemia (umbilical artery pH

Background: Although some studies have reported a decrease in preterm birth following the start of the COVID-19 pandemic, the findings are inconsistent. Objective: This study aimed to compare the incidences of preterm birth before and after the introduction of COVID-19 mitigation measures in Scandinavian countries using robust population-based registry data. Study Design: This was a registry-based difference-in-differences study using births from January 2014 through December 2020 in Norway, Sweden, and Denmark. The changes in the preterm birth (

Background: Autoimmune hepatitis (AIH) is a chronic inflammatory liver condition that predominantly affects women. However, pregnancy risks remain unclear in these women. Methods: A nationwide population-based cohort study (ESPRESSO) in Sweden 1992-2016 including 309 singleton births in women with AIH and 1,532 matched births in women from the general population was performed. AIH was diagnosed as a combination of administrative coding from medical diagnosis of AIH and liver biopsy data from Sweden’s 28 pathology departments. Using conditional logistic regression, odds ratios (ORs) for adverse pregnancy outcomes were determined. Findings: Among 306 live births to AIH women, 51 (16.7%) were preterm compared to 70 out of 1,524 (4.6%) reference births. This corresponded to an OR of 5.10 for preterm birth (95%CI=3.29-7.92), with similar odds seen when using sibling comparators. AIH women with and without cirrhosis had similar odds for preterm birth. The AIH association was particularly strong with medically indicated preterm birth (OR=13.01; 95%CI=5.50-30.79). In addition, AIH was associated with offspring low birth weight (OR=5.31; 95%CI=2.82-9.99) and low 5-min Apgar score (OR=3.46; 95%CI=1.14-10.49), but we found no association with congenital malformations (OR=1.14; 95%CI=0.68-1.91), small for gestational age (OR=1.04; 95%CI=0.38-2.85), stillbirth (OR=0.59; 95%CI=0.02-18.88), or neonatal death (OR=7.42; 95%CI=0.65-84.25). Maternal AIH was linked to an increased odds of cesarean section (OR=1.44; 5%CI=1.04-2.00) and preeclampsia (OR=3.65; 95%CI=2.01-6.64), but not to gestational diabetes. Interpretation: Maternal AIH was associated with a 5-fold higher odds of preterm birth, and future studies are needed to elucidate mechanisms and identify interventions that can reduce this risk. Funding: This project received funding through the Karolinska Institutet and Columbia University Irving Medical Center. Declaration of Interest: Jonas F Ludvigsson coordinates a study on behalf of the Swedish IBD quality register (SWIBREG). This study has received funding from Janssen corporation. Rajani Sharma is a speaker for Takeda on educational lectures, unrelated to this research. Hannes Hagstrom’s institution has received research funding from Intercept, Astra Zeneca and Gilead. Hannes Hagstrom has served as a scientific board advisor for BMS and Gilead. None of these are deemed relevant for the current study. Elizabeth C Verna is on the Gilead advisory board and receives Salix research support. Tracey G Simon reports grants to the institution from Amgen, and has previously served as a consultant to Aetion, for work unrelated to this manuscript. This study did not receive any support from these organizations and these organizations did not have a role in the design and conduct of the study. Authors not named here have disclosed no conflicts of interest. Ethical Approval: The ESPRESSO cohort was reviewed by the Stockholm Ethics Board (No. 2014/1287-31/4) approved on August 27, 2014.

IntroductionDespite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies.MethodsWe screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale.ResultsWe screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection—as compared with uninfected pregnant women—were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias.ConclusionsThis analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

Purpose: Early-onset colorectal cancer (CRC diagnosed before age 50) has risen worldwide, with an increasing number of survivors of reproductive age. We aimed to investigate the risk of adverse pregnancy and neonatal outcomes among early-onset CRC survivors. Methods: We conducted a nationwide case-control study of 207 births in women with early-onset CRC and 1019 births in women without CRC from the general Swedish population (1992-2019), matched on age, calendar year of birth, parity, and county of residence. To control for genetic susceptibility and shared childhood exposures, we additionally identified 146 births in female siblings of the CRC survivors. Early-onset CRC cases were identified through the Swedish Cancer Register (1969-2019), and siblings were identified through the Swedish Multi-generation Register. Maternal characteristics and neonatal outcomes were retrieved from the Swedish Medical Birth Register and National Patient Register. Using conditional logistic regression, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: Compared to women without prior CRC, early-onset CRC survivors who gave birth had increased risk of pre-eclampsia (aOR 2.52, 95% CI 1.25 to 5.08), induced labor (aOR 1.64, 95% CI 1.09 to 2.46) and emergency Cesarean section (aOR 1.79, 95% CI 1.17 to 2.75), after adjustment for maternal education level, country of birth, body mass index and smoking in early pregnancy, and comorbidities. Sibling analyses showed similar trends, especially for higher risk of induced labor (aOR 2.58, 95% CI 1.03 to 6.49). Maternal history of early-onset CRC was also associated with offspring preterm birth (aOR 2.31, 95% CI 1.34 to 3.99) and low birth weight (aOR 2.95, 95% CI 1.40 to 6.21), and risks were particularly pronounced for medically indicated preterm birth (aOR 4.48, 95% CI 2.05 to 9.79). No significant associations were found for small for gestational age birth, low Apgar score, and congenital malformations. Conclusion: In this population-based study, history of early-onset CRC was associated with increased risk of adverse pregnancy outcomes, including pre-eclampsia, induction of labor, and emergency Cesarean section. Offspring to mothers with early-onset CRC also had increased risk of medically indicated preterm birth and neonatal low birth weight. Citation Format: Yin Cao, Stephanie Zhao, Tomas S. Bexelius, Jonas Söderling, Mengyao Shi, Bjorn Roelstraete, Barbara B. Warner, Olof Stephansson, Jonas F. Ludvigsson. Pregnancy and neonatal outcomes among early-onset colorectal cancer survivors: a nationwide case-control study. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P074.

Ischemic stroke increases the risk of neurodevelopmental disorders; however, the risk of autism is not thoroughly explored. Our aim was to evaluate risk of autism and risk factors for autism in children with pediatric ischemic stroke and in their first-degree relatives.In this cohort study, individuals with ischemic stroke from 1969 to 2016,18 years of age, alive 1 week after stroke, and without prior autism were identified in Swedish national registers. Ten matched controls per index individual and all first-degree relatives of index individuals and controls were identified. Conditional Cox regression was used to calculate the risk of autism. Unconditional logistic regression was performed to analyze sex, gestational age, age at stroke diagnoses, comorbid adverse motor outcome, comorbid epilepsy, and a sibling with autism as risk factors for autism in children with ischemic stroke.Of the 1,322 index individuals, 46 (3.5%) were diagnosed with autism compared to 161 (1.2%) controls (adjusted hazard ratio [aHR] 3.02, 95% CI 2.15-4.25). There was no significant difference in risk of autism according to age at stroke: perinatal (aHR 2.69, 95% CI 1.44-5.03) and childhood stroke (aHR 3.18, 95% CI 2.12-4.78). The increased risk remained after exclusion of children born preterm or small for gestational age (aHR 3.78, 95% CI 2.55-5.60) and when children with stroke diagnosed from 1997 to 2014 were analyzed (aHR 2.91, 95% CI = 1.95-4.35). Compared to controls, the risk of autism was increased in individuals with ischemic stroke and comorbid epilepsy (aHR 7.05, 95% CI 3.74-13.30), as well as adverse motor outcome (aHR 4.28, 95% CI 2.44-7.51). When individuals with adverse motor outcome and epilepsy were censored, the risk of autism was still increased (aHR 2.37, 95% CI 1.45-3.85). Sex, gestational age, and having a sibling with autism were not associated with autism in individuals with pediatric ischemic stroke.An increased risk of autism was seen after pediatric ischemic stroke, particularly in individuals with comorbid epilepsy, and could not be explained by being born preterm or small for gestational age. The risk was increased also in individuals free from epilepsy and adverse motor outcome, implying that all children with ischemic stroke should be readily screened for autism if the disorder is suspected.

Inflammatory bowel disease (IBD) has been linked to adverse pregnancy outcomes, but it is unclear how risks vary by histological activity.We performed a nationwide study of Swedish women diagnosed with IBD 1990-2016 and a pre-pregnancy (12 months) colorectal biopsy with vs. without histological inflammation (1223 and 630 births, respectively). We also examined pregnancy outcomes in 2007-2016 of women with vs. without clinically active IBD (i.e., IBD-related hospitalization, surgery, or medication escalation)12 months before pregnancy (2110 and 4993 births, respectively). Accounting for smoking, socio-demographics, and comorbidities, generalized linear models estimated adjusted risk ratios (aRRs) for preterm birth (37 gestational weeks) and small-for-gestational age (SGA,10th percentile weight for age).Of infants to women with vs. without histological inflammation, 9.6% (n = 117) and 6.5% (n = 41) were preterm, respectively (aRR = 1.46; 95%CI = 1.03-2.06). Histological inflammation was associated with preterm birth in ulcerative colitis (UC) (aRR = 1.64; 95%CI = 1.07-2.52), especially extensive colitis (aRR = 2.37; 95%CI = 1.12-5.02), but not in Crohn's disease (aRR = 0.99; 95%CI = 0.55-1.78). Of infants to women with vs. without histological inflammation, 116 (9.6%) and 56 (8.9%), respectively, were SGA (aRR = 1.09; 95%CI = 0.81-1.47). Clinically active disease before pregnancy was linked to preterm birth (aRR = 1.42; 95%CI = 1.20-1.69), but not to SGA birth (aRR = 1.13; 95%CI = 0.96-1.32). Finally, of infants to women without clinical activity, histological inflammation was not significantly associated with preterm birth (aRR = 1.20; 95%CI = 0.68-2.13).Histological and clinical activity in IBD, especially in UC, were risk factors for preterm birth. Further research is needed to determine the importance of pre-pregnancy histological activity in women without clinically-defined disease activity.The Swedish Society of Medicine.