Association of celiac disease with eosinophilic esophagitis: Nationwide register-based cohort study with sibling analyses.

Background: Celiac disease (CeD) is associated with several immune-mediated disorders, but it is unclear whether it is associated with eosinophilic esophagitis (EoE). Objective: We sought to examine the risk of EoE in patients with biopsy-verified CeD compared with matched controls and siblings. Methods: Using nationwide population-based histopathology data, we identified 27,338 patients with CeD diagnosed in the period 2002 to 2017 in Sweden. Patients with CeD were age- and sex-matched with up to 5 reference individuals (n = 134,987) from the general population. Cox Regression was used to estimate hazard ratios (HRs) for developing biopsy-verified EoE. In a secondary analysis, we used unaffected siblings of patients with CeD as comparators to adjust for intrafamilial confounding. Results: The median age at CeD diagnosis was 27 years, and 63.3% were female patients. During a median follow-up of 8.1 years, 17 patients with CeD and 13 matched reference individuals were diagnosed with EoE. This corresponded to incidence rates of 0.08 versus 0.01 per 1000 person-years, respectively, and an adjusted HR for EoE of 6.65 (95% CI, 3.26-13.81). Compared with their siblings without CeD, patients with CeD were however at a no increased risk of EoE (HR, 1.39; 95% CI, 0.55-3.51). Conclusions: In this study, individuals with CeD were at a 6.6-fold increased risk of later EoE compared with the general population. This association might be explained by an altered health-seeking behavior or through shared genetic or early environmental factors because the excess risk disappeared in sibling analyses.

Exposure to Allergen-Specific Immunotherapy in Pregnancy and Risk of Congenital Malformations and Other Adverse Pregnancy Outcomes.

BACKGROUND: Owing to insufficient data, current guidelines recommend against initiating allergen-specific immunotherapy (AIT) during pregnancy but suggest that well-tolerated ongoing immunotherapy may be continued. OBJECTIVE: To evaluate the safety of AIT in pregnancy, especially the risk for congenital malformations. METHODS: This nationwide Swedish cohort study identified pregnancies exposed to AIT, both subcutaneous and sublingual, through the Swedish Medical Birth register and the Prescribed Drug Register between 2005 and 2014. Information on congenital malformations in offspring was retrieved from the National Patient Register. Using the personal identity number, we linked data between registers. Using logistic regression, we calculated odds ratios (ORs) with 95% CIs for congenital malformations and other adverse pregnancy outcomes after adjusting for potential confounders. RESULTS: From 2005 to 2014, we identified 924,790 singleton pregnancies. Among these, 743 pregnancies had been exposed to AIT 3 months before conception up until gestational week 22. Allergen-specific immunotherapy in pregnancy was not linked to congenital malformations (OR = 0.90; 95% CI, 0.63-1.27) or other adverse pregnancy outcomes (preterm birth: OR = 0.98; 95% CI, 0.71-1.35; stillbirth: OR = 0.79; 95% CI, 0.26-2.47; or cesarean delivery: OR = 0.91; 95% CI, 0.76-1.09). Stratification by route of immunotherapy, subcutaneous or sublingual, resulted in similar ORs. Restricting the pregnancy cohort to women with asthma or pulmonary disease, nulliparous women, births in 2012 to 2014, or Swedish-born women yielded similar results. CONCLUSIONS: This nationwide study found no evidence of congenital malformations or other adverse pregnancy outcomes in women treated with AIT in pregnancy.

Preterm birth reduces the risk of IgE sensitization up to early adulthood: A population-based birth cohort study.

BACKGROUND: Immunoglobulin E (IgE) sensitization is associated with asthma and allergic diseases. Gestational age influences early immune system development, thereby potentially affecting the process of tolerance induction to allergens. OBJECTIVE: To study IgE sensitization to common allergens by gestational age from childhood up to early adulthood. METHODS: Population-based birth cohort, data from the Swedish BAMSE study were used. Allergen-specific IgE antibodies to a mix of common food (fx5) and inhalant (Phadiatop) allergens were analysed at 4, 8, 16 and 24 years. Sensitization was defined as allergen-specific IgE ≥0.35 kUA /L to fx5 and/or Phadiatop at each time point. Using logistic regression and generalized estimated equations, adjusted odds ratios (aORs) for sensitization in relation to gestational age were calculated. Replication was sought within the Swedish twin study STOPPA. RESULTS: In BAMSE, 3522 participants were screened for IgE antibodies during follow-up; of these, 197 (5.6%) were born preterm (<37 gestational weeks) and 330 (9.4%) post-term (≥42 weeks). Preterm birth reduced the risk of sensitization to common food and/or inhalant allergens up to early adulthood by 29% (overall aOR = 0.71; 95% CI: 0.52-0.98), and to food allergens specifically by 40% (overall aOR = 0.60; 95% CI: 0.38-0.93). No relation was found between post-term birth and IgE sensitization at any time point. Replication analyses in STOPPA (N = 675) showed similar risk estimates for sensitization to food and/or inhalant allergens (aOR = 0.72; 95% CI: 0.42-1.21), which resulted in a combined meta-analysis aOR = 0.71 (95% CI: 0.54-0.94). CONCLUSIONS: Our study suggests an inverse association between preterm birth and long-term IgE sensitization.

Adverse pregnancy outcomes and risk of later allergic rhinitis-Nationwide Swedish cohort study.

BACKGROUND: Perinatal conditions may be associated with future allergic disease; however, data are conflicting and incomplete for childhood allergic rhinitis (AR). The aim of this study was to examine pregnancy outcome (cesarean delivery, preterm birth, low birthweight) and offspring AR as defined by national registers. METHODS: Nationwide longitudinal cohort study using prospectively recorded register data from 1 059 600 singleton livebirths born in Sweden in 2001-2012. Cox regression adjusted for infant sex and maternal factors (age at delivery, country of birth, parity, smoking, body mass index, and asthma/pulmonary disease) estimated hazard ratios (HRs) for AR during childhood. RESULTS: During the study period 2001-2013, 22 386 (2.11%) children were diagnosed with AR. AR was more common in infants born through cesarean delivery (2.34%) than in those born vaginally (2.10%) (HR = 1.12; 95% confidence interval [95% CI] = 1.08-1.16). This was equivalent to one extra case of AR in 383 children followed up in our study. AR was also associated with moderately preterm birth (≥32-36 weeks of gestation: HR = 1.12, 95% CI = 1.04-1.20), large for gestational age (HR = 1.05, 95% CI = 1.01-1.10), and low (<7) 5-minute Apgar score (HR = 1.15, 95% CI = 1.02-1.30). Similar risk estimates were obtained when we restricted the outcome to ≥2 hospital-based records of AR. No association was observed between very preterm birth, post-term birth, low birthweight, or small for gestational age and AR. CONCLUSION: Our study indicates an association between pregnancy outcomes and childhood AR, although observed effect sizes were generally modest.

Cesarean delivery, preterm birth, and risk of food allergy: Nationwide Swedish cohort study of more than 1 million children.

BACKGROUND: Little is known about early-life risk factors for food allergy in children. OBJECTIVES: We examined the association between perinatal characteristics and future risk of food allergy in offspring. METHODS: This nationwide Swedish cohort study of 1,086,378 children born in Sweden in 2001-2012 used prospectively recorded data from health care registers. Using Cox regression, we estimated hazard ratios (HRs) with 95% CIs for the association between perinatal characteristics (eg, cesarean delivery and preterm birth) and food allergy as defined by diagnoses in the National Patient Register, adjusting for infant sex and maternal factors (age at delivery, country of birth, parity, smoking, body mass index, and asthma/pulmonary disease). RESULTS: During the 13-year follow-up, 26,732 (2.5%) children were given a diagnosis of food allergy. Food allergy was positively associated with cesarean delivery (HR, 1.21; 95% CI, 1.18-1.25), large for gestational age (HR, 1.15; 95% CI, 1.10-1.19), and low 5-minute Apgar score (HR, 1.22; 95% CI, 1.10-1.36) but negatively associated with very preterm birth (<32 weeks of gestation: HR, 0.74; 95% CI, 0.56-0.98). No association was found between food allergy and moderately preterm birth, low birth weight, or small for gestational age. Risk estimates were similar when the outcome was restricted to 2 records of diagnosed food allergy. In 1,000 children undergoing cesarean delivery, an extra 5 developed food allergy compared with the reference group, suggesting that 17% of food allergy in children born by means of cesarean delivery can be explained by this exposure (attributable fraction). CONCLUSIONS: Cesarean delivery was associated with increased risk of food allergy, whereas very preterm birth decreased risk.

Spacers versus nebulizers in treatment of acute asthma - a prospective randomized study in preschool children.

OBJECTIVE: To compare administration of bronchodilators by nebulizers with delivery by metered dose inhalers (MDIs) with spacers and to evaluate the clinical effect of the treatment of acute asthma in preschool children. METHODS: A prospective randomized clinical trial in a pediatric emergency department (PED). Preschool children who were admitted for virus induced wheezing or acute asthma exacerbation were randomly allocated to receive bronchodilator treatment by nebulizer or by metered dose inhaler. The accompanying parents completed a questionnaire. RESULTS: The length of stay in the PED and the hospitalization rate were similar and no difference was seen in the parents' view of ease of use and device acceptance. Baseline data were similar for both groups apart from the family history of asthma and atopic disease that was greater in the nebulizer group. No significant differences were seen in heart rate, respiratory rate and oxygen saturation at baseline and after the treatment. According to the parents 40% of the participants had asthma diagnosis though up to 66% had some kind of asthma medication. CONCLUSIONS: Our data suggests that MDIs with spacers are at least as effective as nebulizers in the delivery of beta agonists to treat preschool children with virus induced wheezing or acute exacerbations of asthma in the PED. Parents may underestimate the gravity of their children's asthma. It is mandatory to provide adequate information to the staff and parents in order to treat pediatric acute asthma successfully.