Middle ear effusion, ventilation tubes and neurological development in childhood.

BACKGROUND: Otitis media with middle ear effusion (MEE) can be treated with ventilation tubes (VT) insertion, and it has been speculated that prolonged MEE in childhood can affect neurological development, which in turn may be important for later academic achievements. OBJECTIVE: To investigate the association between middle ear effusion (MEE), treatment with ventilation tubes (VT) and childhood neurological development. STUDY DESIGN: We examined 663 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) unselected mother-child cohort study. Children were followed by study pediatricians with regular visits from pregnancy until 3 years of age. MEE was diagnosed using tympanometry at age 1, 2 and 3 years. Information regarding VT from age 0-3 years was obtained from national registries. We assessed age at achievement of gross motor milestones from birth, language scores at 1 and 2 years, cognitive score at 2.5 years and general development score at age 3 years using standardized quantitative tests. RESULTS: Children with MEE had a lower 1-year word production vs. children with no disease: (median 2, IQR [0-6] vs. 4, IQR [1-7]; p = 0.017), and a lower 1-year word comprehension (median 36; IQR [21-63] vs. 47, IQR [27-84]; p = 0.03). Children with VT had a lower 2-5-year cognitive score vs. children with no disease; estimate -2.34; 95% CI [-4.56;-0.12]; p = 0.039. No differences were found between children with vs. without middle ear disease regarding age at achievement of gross motor milestones, word production at 2 years or the general developmental score at 3 years. CONCLUSION: Our study supports the previous findings of an association between MEE and concurrent early language development, but not later neurological endpoints up to the age of 3. As VT can be a treatment of those with symptoms of delayed development, we cannot conclude whether treatment with VT had positive or negative effects on neurodevelopment.

Early life bacterial airway colonization, local immune mediator response and risk of otitis media.

Introduction. Acute otitis media (AOM) is the most common bacterial infection in early childhood, but the underlying mechanisms making some children more susceptible are poorly understood.Aim. To examine the associations between bacterial airway colonization in early life and the risk of AOM and tympanostomy tube insertion (TTI), and whether such associations are modulated by an insufficient local immune mediator response to bacterial colonization.Methodology. Bacterial cultures from hypopharyngeal samples were obtained at 1 week, 1 month and 3 months of age in the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort comprising 700 children. Twenty immune mediators were quantified from airway mucosal lining fluid sampled at 1 month. AOM symptoms were registered in a daily diary until 3 years. Information on TTI in the first 3 years was obtained from national registers.Results. Children colonized with Streptococcus pneumoniae at 1 month of age had increased incidence of AOM [aIRR 2.43 (1.14-5.21)] and children colonized with Moraxella catarrhalis at 1 month or Haemophilus influenzae at 3 months had an increased risk of TTI [aHR 1.45 (1.00-2.10) and 1.73 (1.10-2.71)]. There were no associations between the local immune mediator response to colonization and risk of AOM or TTI.Conclusion. Pathogenic bacterial airway colonization in early life was found to be associated with an increased risk of otitis media, albeit not consistently. These associations were independent of the local immune response to colonization.

Distinct immune phenotypes in infants developing asthma during childhood.

Early exposure to environmental triggers may elicit trajectories to chronic inflammatory disease through deregulated immune responses. To address relations between early immune competence and development of childhood asthma, we performed functional immune profiling of 186 parameters in blood of 541 18-month-old infants and examined links between their response phenotype and development of transient or persistent disease at 6 years of age. An abnormal neutrophil-linked antiviral response was associated with increased risk of transient asthma. Children who exhibited persistent asthma at year 6 showed enhanced interleukin-5 (IL-5) and IL-13 production in stimulated T cells at 18 months of age, which was associated with early life bacterial colonization of the airways. These findings highlight the early appearance of distinct immune characteristics in infants developing different asthma endotypes during childhood.

Infectious diseases detected by screening after arrival to Denmark in internationally adopted children.

AIM: To show the prevalence of selected infectious diseases among internationally adopted children (IAC) in Denmark. BACKGROUND: Each year approximately 200 IAC arrive in Denmark. These are at increased risk of infectious diseases rarely seen in Danish children. Studies from the 1990s showed that 60% of IAC had infectious diseases and that the majority of these were undetected without screening. METHODS: The study is a prospective study of medical records from children seen in the adoption clinic at Copenhagen University Hospital in the period 2009-2013. Screening was done for hepatitis A (HAV), B (HBV) and C (HCV), syphilis, HIV, tuberculosis (TB) and intestinal parasites. RESULTS: In 245 IAC tested, 2% had evidence of recent HAV infection, 3% with HBV and one child with HCV, and no cases of HIV were found. One child had antibodies against syphilis (anti-Trpa AB positivity), and 2% were latently infected with tuberculosis. We found 30% infected with pathogenic intestinal parasites. Only 46% had serologic evidence of immunisation against HBV. CONCLUSION: The prevalence of infections in IAC was lower than previously reported but compared to the general population, a higher prevalence of intestinal parasites, hepatitis and tuberculosis was found. We recommend that IAC are offered screening shortly after arrival.

Antibiotics in Pregnancy Increase Children's Risk of Otitis Media and Ventilation Tubes.

OBJECTIVES: To study the association between antibiotic intake in pregnancy and the development of otitis media and placement of ventilation tubes (VTs) in the offspring under the hypothesis that antibiotics in pregnancy may alter the offspring's propensity for disease. STUDY DESIGN: Data from the 700 children in the Copenhagen Prospective Studies on Asthma in Childhood 2010 unselected birth cohort study were used. Information on maternal antibiotic use and other exposures during pregnancy was collected prospectively from interviews and validated in national registries. Otitis media episodes were registered in a prospective diary for 3 years. Information regarding children's VTs was obtained from national registries. RESULTS: There were 514 children who had diary information and were included in the analysis regarding otitis media episodes. For VTs analysis, 699 children were included. Thirty-seven percent of the mothers received antibiotics during pregnancy, and this was associated with increased risk of otitis media (adjusted hazard ratio 1.30; 95% CI 1.04-1.63; P = .02). The risk of receiving VTs was especially associated with third trimester antibiotics (adjusted hazard ratio 1.60; 95% CI 1.08-2.36, P = .02). The risk of otitis media increased with increasing number of treatments (per-level adjusted hazard ratio 1.20; 95% CI 1.04-1.40; P = .02), but for VTs this association was not significant after adjustment. CONCLUSION: Maternal use of antibiotics during pregnancy is associated with an increased risk of otitis media and VT insertions in the offspring. Antibiotics late in pregnancy mainly contributed to these effects, pointing toward potential transmission of an unfavorable microbiome from mother to child.

Incidence and Determinants of Ventilation Tubes in Denmark.

BACKGROUND AND OBJECTIVES: Many children are treated for recurrent acute otitis media and middle ear effusion with ventilation tubes (VT). The objectives are to describe the incidence of VT in Denmark during 1997-2011 from national register data, furthermore, to analyze the determinants for VT in the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) birth cohort. METHODS: The incidence of VT in all children under 16 years from 1997-2011 were calculated in the Danish national registries. Determinants of VT were studied in the COPSAC2010 birth cohort of 700 children. RESULTS: Nationwide the prevalence of VT was 24% in children aged 0 to 3 three years, with a significant increase over the study period. For all children 0-15 years, the incidence of VT was 35/1,000. In the VT population, 57% was male and 43% females. In the COPSAC2010 birth cohort, the prevalence of VT during the first 3 years of life was 29%. Determinants of VT were: maternal history of middle ear disease; aHR 2.07, 95% CI [1.45-2.96] and siblings history of middle ear disease; aHR 3.02, [2.11-4.32]. Paternal history of middle ear disease, presence of older siblings in the home and diagnosis of persistent wheeze were significant in the univariate analysis but the association did not persist after adjustment. CONCLUSION: The incidence of VT is still increasing in the youngest age group in Denmark, demonstrating the highest incidence recorded in the world. Family history of middle ear disease and older siblings are the main determinants for VT.

Effect of Vitamin D3 Supplementation During Pregnancy on Risk of Persistent Wheeze in the Offspring: A Randomized Clinical Trial.

IMPORTANCE: Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of vitamin D supplementation to pregnant women is unknown. OBJECTIVE: To determine whether supplementation of vitamin D3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, single-center, randomized clinical trial conducted within the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. Enrollment began March 2009 with a goal of 708 participants, but due to delayed ethical approval, only 623 women were recruited at 24 weeks of pregnancy. Follow-up of the children (N = 581) was completed when the youngest child reached age 3 years in March 2014. INTERVENTIONS: Vitamin D3 (2400 IU/d; n = 315) or matching placebo tablets (n = 308) from pregnancy week 24 to 1 week postpartum. All women received 400 IU/d of vitamin D3 as part of usual pregnancy care. MAIN OUTCOMES AND MEASURES: Age at onset of persistent wheeze in the first 3 years of life. Secondary outcomes included number of episodes of troublesome lung symptoms, asthma, respiratory tract infections, and neonatal airway immunology. Adverse events were assessed. RESULTS: Of the 581 children, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16%) in the vitamin D3 group and 57 children (20%) in the control group. Vitamin D3 supplementation was not associated with the risk of persistent wheeze, but the number of episodes of troublesome lung symptoms was reduced, and the airway immune profile was up-regulated (principal component analysis, P = .04). There was no effect on additional end points. Intrauterine death was observed in 1 fetus (<1%) in the vitamin D3 group vs 3 fetuses (1%) in the control group and congenital malformations in 17 neonates (5%) in the vitamin D3 group vs 23 neonates (8%) in the control group. [table: see text]. CONCLUSIONS AND RELEVANCE: The use of 2800 IU/d of vitamin D3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years. However, interpretation of the study is limited by a wide CI that includes a clinically important protective effect. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00856947.

[The risk of infections in internationally adopted children is real]. / Infektionsrisikoen hos internationale adoptivbørn er reel.

Each year approximately 400 internationally adopted children (IAC) come to Denmark from countries with high prevalences of infectious diseases. Former studies of IAC have shown that approximately 1% of the IAC are infected with Hepatitis A, 3-6% with Hepatitis B, mostly asymptomatic infections. 8-27% have gastrointestinal parasites and 1-7% have tuberculosis, but 3-21% have a positive Mantoux test. The studies found none with HIV or HCV and only a few with syphilis. The vaccination status was often deficient and the serology results did not match the vaccination records. All studies conclude that screening of IAC is recommended.