Palivizumab Exposure and the Risk of Autoimmune Disease: A Cross-National Cohort Study.

BACKGROUND: Treatment with biologic pharmaceuticals may be associated with an increased risk of immune-mediated disease. Palivizumab is a humanized monoclonal antibody designed to provide passive immunity against respiratory syncytial virus infection. Palivizumab is primarily used in preterm children known to be immunologically immature. The long-term effect of palivizumab in terms of autoimmune diseases has not yet been investigated. AIM: Our objective was to investigate whether exposure to palivizumab was associated with the development of autoimmune diseases in children. METHODS: This was a population-based cohort study including data from 769,523 Danish children born between 1 January 1999 and 31 December 2010 and data from 581,742 Swedish children born between 1 July 2005 and 31 December 2010. RESULTS: Of the 1,351,265 children included, 1192 (0.09 %) were exposed to palivizumab. Nine cases of autoimmune disease were diagnosed among palivizumab-exposed children during the period of observation. Among the children exposed to palivizumab, one child in Denmark developed inflammatory bowel disease; in Sweden, children developed juvenile arthritis (one child), diabetes mellitus (two children), celiac disease (four children), and inflammatory bowel disease (one child). The risk of autoimmune disease was not significantly increased after palivizumab exposure (hazard ratio adjusted for age and country: 1.54; 95 % confidence interval 0.80-2.95). CONCLUSION: The risk of autoimmune disease was not increased after palivizumab exposure. Given the small number of incident cases of autoimmune disease observed, this finding should be interpreted with caution.

Cesarean section and disease associated with immune function.

BACKGROUND: Earlier studies have shown that delivery by cesarean section (CS) is associated with an increased risk of disease associated with immune function in the offspring, but these studies have generally not discriminated between the effect of acute and elective CS. OBJECTIVE: We sought to further explore these associations using discrimination between the effects of acute versus elective CS. METHODS: We performed a population- and national register-based cohort study including all children born in Denmark from January 1997 through December 2012. Hazard ratios for diseases associated with immune function in children delivered by acute and elective CS with vaginal delivery as the reference were calculated by using Cox regression. All analyses were adjusted for gestational age, sex, birth weight, maternal age, maternal smoking during pregnancy, and complications during pregnancy (preeclampsia, eclampsia, hemorrhage, and hyperemesis). RESULTS: A total of 750,569 children aged 0 to 14 years were included. Children delivered by both acute and elective CS had an increased risk of asthma, laryngitis, and gastroenteritis. Children delivered by acute CS had an increased risk of ulcerative colitis and celiac disease, whereas children delivered by elective CS had an increased risk of lower respiratory tract infection and juvenile idiopathic arthritis. The effect of elective CS was higher than the effect of acute CS on the risk of asthma. CONCLUSION: Children delivered by CS are at increased risk of disease associated with immune function. The effect is mainly on diseases involving the mucosal immune system.

The Danish National Prescription Registry in studies of a biological pharmaceutical: palivizumab - validation against two external data sources.

BACKGROUND: National prescription databases are important tools in pharmacoepidemiological studies investigating potential long-term adverse events after drug use. Palivizumab is a biological pharmaceutical used as passive prophylaxis against severe infection with respiratory syncytial virus in high-risk children. OBJECTIVE: To assess the registration of palivizumab in the Danish National Prescription Registry (DNPR) and to examine if palivizumab reimbursement data obtained from the Danish Health and Medicines Authority could serve as a supplement to data from the DNPR. METHODS: Registration of palivizumab exposure in the DNPR between 1999 and 2010 was compared to two external data sources: registration of palivizumab exposure in medical records, and palivizumab reimbursement data. RESULTS: During the study period, 182 children with palivizumab exposure were registered in the DNPR. A total of 207 children were registered for palivizumab reimbursement. The sensitivity of palivizumab registration in the DNPR was 26% (20%-34%), and the specificity of no palivizumab registration in the DNPR was 97% (94%-99%), with data from the medical record as the reference. Palivizumab registration sensitivity in reimbursement data was 29% (22%-36%), and the specificity of no palivizumab registration in the DNPR was 97% (94%-99%), with data from the medical record as the reference. CONCLUSION: Exposure to palivizumab was underestimated in the DNPR. Reimbursement data are a readily accessible data supplement, which only slightly increased the sensitivity of palivizumab registration in the DNPR. Our findings underline the need to improve DNPR information concerning drugs administered in hospitals.

Incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in Danish and Swedish children.

BACKGROUND: Several studies have shown that the prevalence of the frequent chronic conditions of atopic dermatitis, asthma, and allergy has increased substantially for reasons not fully understood. Atopic diseases affect quality of life in both children and their family members. OBJECTIVE: Using national registers, we sought to establish up-to-date incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in the Danish and Swedish child populations. METHODS: Children born in Denmark from 1997 to 2011 or born in Sweden from 2006 to 2010 participated in this cross-national, population-based cohort study. Incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in the Danish and Swedish child cohorts were ascertained through disease-specific dispensed prescribed medication, specific hospital contacts, or both. RESULTS: In both countries the incidence rate of atopic dermatitis was stable during the study periods. The incidence rate of asthma increased until 2006 and stabilized for the rest of the study period in Denmark and increased in Sweden. The incidence rate of allergic rhinoconjunctivitis decreased in both countries. CONCLUSION: The study revealed similar trends, with stable incidence rates of atopic dermatitis in both Danish and Swedish children, an increase and then stabilization in asthma incidence rates in Denmark and an increase in Sweden, and a decrease in allergic rhinoconjunctivitis incidence rates. At age 5 years, one third of all children were affected with at least one of the conditions of atopic dermatitis, asthma, or allergic rhinoconjunctivitis.

Medical augmentation of labor and the risk of ADHD in offspring: a population-based study.

BACKGROUND AND OBJECTIVE: Oxytocin for labor augmentation is widely used in obstetric care in Western countries. Two recent, smaller studies found opposing results regarding the association between prenatal exposure to oxytocin for labor augmentation and attention-deficit/hyperactivity disorder (ADHD). In Denmark, oxytocin is the medication used for nearly all medical augmentations of labor, and we examined the association between medical augmentation of labor and ADHD in a large cohort study based on national register data. METHODS: All singletons born after spontaneous onset of labor in Denmark between 2000 and 2008 (N = 546 146) were included in the study. Data from the Danish Medical Birth Registry on medical augmentation of labor (yes/no) were used to identify exposed children. ADHD was defined based on the diagnostic codes of International Classification of Diseases, 10th Revision, for hyperkinetic disorder and information on dispensed ADHD medication. A multivariate proportional hazards regression model was used to test the association. RESULTS: Among 546 146 deliveries, 26% included medical augmentation of labor, and 0.9% of the children were identified as having ADHD (n = 4617). We found no association between augmentation of labor and ADHD in the offspring (hazard ratio: 1.05 [95% confidence interval: 0.98-1.13]). CONCLUSIONS: Our study does not support an association between medical augmentation of labor and ADHD in the child.

Does internal podalic version of the non-vertex second twin still have a place in obstetrics? A Danish national retrospective cohort study.

OBJECTIVE: Investigate the rate of internal podalic version followed by breech extraction for a second non-vertex twin with the first delivered vaginally, and compare neonatal outcome with emergency cesarean section. DESIGN: Cohort study. SETTING: National Danish Registers. POPULATION: Twin pregnancies (1997-2012) with gestational age ≥34 weeks; first twin delivered vaginally, second by internal podalic version and breech extraction or cesarean section. METHODS: Data were collected from the Danish National Patient Register and the Danish National Birth Register. MAIN OUTCOME MEASURES: Rates of delivery mode, 5-min Apgar score, asphyxia, umbilical cord pH, admission to neonatal intensive care unit, treatment by mechanical ventilation, and experience level of obstetricians performing internal podalic version. RESULTS: 457 births were available for analysis: 39 cases of internal podalic version and breech extraction and 418 cesarean section cases for second twin. Compared with the cesarean section group, the internal podalic version group had lower rates of asphyxia. Apgar scores and umbilical cord pH levels were not significantly different, although with a tendency to be higher in the internal version than the cesarean section group, however, fewer cases needed mechanical ventilation. Thirty internal versions and breech extractions were performed by obstetricians with >5 years clinical experience and three by trainees. CONCLUSION: Cesarean sections for a second twin seem to have been frequent during the last 15 years while internal podalic version is a vanishing procedure. A slight tendency for better neonatal outcome was found in the internal podalic version and extraction group than cesarean section.