Infant lung function and early skin barrier impairment in the development of asthma at age 3 years.

BACKGROUND: Largely unexplored, we investigated if lower lung function, impaired skin barrier function by transepidermal water loss (TEWL), eczema, and filaggrin (FLG) mutations in infancy were associated with asthma in early childhood. METHODS: From the factorially designed randomized controlled intervention study PreventADALL, we evaluated 1337/2394 children from all randomization groups with information on asthma at age 3 years, and at age 3 months either lung function, TEWL, eczema, and/or FLG mutations. Lower lung function was defined as the time to peak tidal expiratory flow to expiratory time (tPTEF /tE ) <0.25, and skin barrier impairment as a high TEWL >9.50 g/m2 /h. Eczema was clinically observed, and DNA genotyped for FLG mutations. Asthma was defined as asthma-like symptoms (≥3 episodes of bronchial obstruction) between age 2-3 years as well as a history of doctor-diagnosed asthma and/or asthma medication use. Associations were analyzed in logistic regression models, presented with adjusted ORs (aOR) and 95% confidence intervals (CI). RESULTS: Lower lung function and skin barrier impairment were associated with asthma in general; aOR (95% CI) 5.4 (2.1, 13.7) and 1.6 (1.1, 2.5), while eczema and FLG mutations were associated with asthma in children with atopic dermatitis or allergic sensitization only. Stratifying for sex, the risk of asthma was only increased in boys with lower lung function; aOR (95% CI) 7.7 (2.5, 23.6), and in girls with FLG mutations; aOR (95% CI) 3.5 (1.5, 8.2). CONCLUSION: Lower lung function and impaired skin barrier function in infancy may increase the risk of asthma at age 3 years.

Feeding Practices and Dietary Diversity in the First Year of Life: PreventADALL, a Scandinavian Randomized Controlled Trial and Birth Cohort Study.

BACKGROUND: Breastmik is considered the optimal source of nutrition in early infancy. However, recommendations and practices for when and how complementary food should be introduced in the first year of life vary worldwide. Early introduction of allergenic foods may prevent food allergies, but if early food introduction influences infant feeding practices is less known. OBJECTIVES: We sought to assess infant feeding practices in the first year of life and to determine if early interventional food introduction influences breastfeeding and dietary diversity. METHODS: Dietary intake was assessed in infants from the population-based clinical trial Preventing Atopic Dermatitis and ALLergies (PreventADALL) in children study. A total of 2397 infants were cluster-randomized at birth into 4 different groups: 1) control, 2) skin intervention, 3) introduction to 4 allergenic foods between 3 and 4 mo of age: peanut, cow milk, wheat, and egg, as small tastings until 6 mo, and 4) combined skin and food interventions. Dietary data were available from at least one of the 3-, 6-, 9-, and 12-mo questionnaires in 2059 infants. In the present analysis, groups 1 and 2 constitute the No Food Intervention group, whereas groups 3 and 4 constitute the Food Intervention group. We used the log-rank test and Cox regression to assess the impact of food intervention on age of breastfeeding cessation. Mixed effects logistic regression was used to compare dietary diversity, defined as the number of food categories consumed, between intervention groups. RESULTS: At 3, 6, 9, and 12 mo, 95%, 88%, 67%, and 51% were breastfed, respectively, and breastfeeding duration was not affected by the food intervention. In the No Food Intervention group, mean age of complementary food introduction was 18.3 wk (confidence interval [CI]: 18.1, 18.5). In the Food Intervention group, the dietary diversity score was 1.39 units (CI: 1.16, 1.62) higher at 9 mo (P < 0.001) and 0.7 units (CI: 0.5, 0.9) higher at 12 mo (P < 0.001) compared to the No Food Intervention group. CONCLUSIONS: Early food intervention did not affect breastfeeding rates and increased dietary diversity at 9 and 12 mo.

Skin care interventions in infants for preventing eczema and food allergy.

BACKGROUND: Eczema and food allergy are common health conditions that usually begin in early childhood and often occur in the same people. They can be associated with an impaired skin barrier in early infancy. It is unclear whether trying to prevent or reverse an impaired skin barrier soon after birth is effective for preventing eczema or food allergy. OBJECTIVES: Primary objective To assess the effects of skin care interventions such as emollients for primary prevention of eczema and food allergy in infants. Secondary objective To identify features of study populations such as age, hereditary risk, and adherence to interventions that are associated with the greatest treatment benefit or harm for both eczema and food allergy. SEARCH METHODS: We performed an updated search of the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase in September 2021. We searched two trials registers in July 2021. We checked the reference lists of included studies and relevant systematic reviews, and scanned conference proceedings to identify further references to relevant randomised controlled trials (RCTs).  SELECTION CRITERIA: We included RCTs of skin care interventions that could potentially enhance skin barrier function, reduce dryness, or reduce subclinical inflammation in healthy term (> 37 weeks) infants (≤ 12 months) without pre-existing eczema, food allergy, or other skin condition. Eligible comparisons were standard care in the locality or no treatment. Types of skin care interventions could include moisturisers/emollients; bathing products; advice regarding reducing soap exposure and bathing frequency; and use of water softeners. No minimum follow-up was required. DATA COLLECTION AND ANALYSIS: This is a prospective individual participant data (IPD) meta-analysis. We used standard Cochrane methodological procedures, and primary analyses used the IPD dataset. Primary outcomes were cumulative incidence of eczema and cumulative incidence of immunoglobulin (Ig)E-mediated food allergy by one to three years, both measured at the closest available time point to two years. Secondary outcomes included adverse events during the intervention period; eczema severity (clinician-assessed); parent report of eczema severity; time to onset of eczema; parent report of immediate food allergy; and allergic sensitisation to food or inhalant allergen. MAIN RESULTS: We identified 33 RCTs comprising 25,827 participants. Of these, 17 studies randomising 5823 participants reported information on one or more outcomes specified in this review.  We included 11 studies, randomising 5217 participants, in one or more meta-analyses (range 2 to 9 studies per individual meta-analysis), with 10 of these studies providing IPD; the remaining 6 studies were included in the narrative results only.   Most studies were conducted at children's hospitals. Twenty-five studies, including all those contributing data to meta-analyses, randomised newborns up to age three weeks to receive a skin care intervention or standard infant skin care. Eight of the 11 studies contributing to meta-analyses recruited infants at high risk of developing eczema or food allergy, although the definition of high risk varied between studies. Durations of intervention and follow-up ranged from 24 hours to three years. All interventions were compared against no skin care intervention or local standard care. Of the 17 studies that reported information on our prespecified outcomes, 13 assessed emollients. We assessed most of the evidence in the review as low certainty and had some concerns about risk of bias. A rating of some concerns was most often due to lack of blinding of outcome assessors or significant missing data, which could have impacted outcome measurement but was judged unlikely to have done so. We assessed the evidence for the primary food allergy outcome as high risk of bias due to the inclusion of only one trial, where findings varied based on different assumptions about missing data. Skin care interventions during infancy probably do not change the risk of eczema by one to three years of age (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.81 to 1.31; risk difference 5 more cases per 1000 infants, 95% CI 28 less to 47 more; moderate-certainty evidence; 3075 participants, 7 trials) or time to onset of eczema (hazard ratio 0.86, 95% CI 0.65 to 1.14; moderate-certainty evidence; 3349 participants, 9 trials). Skin care interventions during infancy may increase the risk of IgE-mediated food allergy by one to three years of age (RR 2.53, 95% CI 0.99 to 6.49; low-certainty evidence; 976 participants, 1 trial) but may not change risk of allergic sensitisation to a food allergen by age one to three years (RR 1.05, 95% CI 0.64 to 1.71; low-certainty evidence; 1794 participants, 3 trials). Skin care interventions during infancy may slightly increase risk of parent report of immediate reaction to a common food allergen at two years (RR 1.27, 95% CI 1.00 to 1.61; low-certainty evidence; 1171 participants, 1 trial); however, this was only seen for cow's milk, and may be unreliable due to over-reporting of milk allergy in infants. Skin care interventions during infancy probably increase risk of skin infection over the intervention period (RR 1.33, 95% CI 1.01 to 1.75; risk difference 17 more cases per 1000 infants, 95% CI one more to 38 more; moderate-certainty evidence; 2728 participants, 6 trials) and may increase the risk of infant slippage over the intervention period (RR 1.42, 95% CI 0.67 to 2.99; low-certainty evidence; 2538 participants, 4 trials) and stinging/allergic reactions to moisturisers (RR 2.24, 95% 0.67 to 7.43; low-certainty evidence; 343 participants, 4 trials), although CIs for slippages and stinging/allergic reactions were wide and include the possibility of no effect or reduced risk. Preplanned subgroup analyses showed that the effects of interventions were not influenced by age, duration of intervention, hereditary risk, filaggrin (FLG) mutation, chromosome 11 intergenic variant rs2212434, or classification of intervention type for risk of developing eczema. We could not evaluate these effects on risk of food allergy. Evidence was insufficient to show whether adherence to interventions influenced the relationship between skin care interventions and eczema or food allergy development. AUTHORS' CONCLUSIONS: Based on low- to moderate-certainty evidence, skin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema; may increase risk of food allergy; and probably increase risk of skin infection. Further study is needed to understand whether different approaches to infant skin care might prevent eczema or food allergy.

Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial.

BACKGROUND: Skin emollients applied during early infancy could prevent atopic dermatitis, and early complementary food introduction might reduce food allergy in high-risk infants. The study aimed to determine if either regular skin emollients applied from 2 weeks of age, or early complementary feeding introduced between 12 and 16 weeks of age, reduced development of atopic dermatitis by age 12 months in the general infant population. METHODS: This population-based 2×2 factorial, randomised clinical trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway; and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine ultrasound pregnancy screening at 18 weeks were cluster-randomised at birth from 2015 to 2017 to the following groups: (1) controls with no specific advice on skin care while advised to follow national guidelines on infant nutrition (no intervention group); (2) skin emollients (bath additives and facial cream; skin intervention group); (3) early complementary feeding of peanut, cow's milk, wheat, and egg (food intervention group); or (4) combined skin and food interventions (combined intervention group). Participants were randomly assigned (1:1:1:1) using computer- generated cluster randomisation based on 92 geographical living area blocks as well as eight 3-month time blocks. Carers were instructed to apply the interventions on at least 4 days per week. Atopic dermatitis by age 12 months was the primary outcome, based on clinical investigations at 3, 6 and 12 months by investigators masked to group allocation. Atopic dermatitis was assessed after completing the 12-month investigations and diagnosed if either of the UK Working Party and Hanifin and Rajka (12 months only) diagnostic criteria were fulfilled. The primary efficacy analyses was done by intention-to-treat analysis on all randomly assigned participants. Food allergy results will be reported once all investigations at age 3 years are completed in 2020. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). The study is registered at clinicaltrials.gov, NCT02449850. FINDINGS: 2697 women were recruited between Dec 9, 2014, and Oct 31, 2016, from whom 2397 newborn infants were enrolled from April 14, 2015, to April 11, 2017. Atopic dermatitis was observed in 48 (8%) of 596 infants in the no intervention group, 64 (11%) of 575 in the skin intervention group, 58 (9%) of 642 in the food intervention group, and 31 (5%) of 583 in the combined intervention group. Neither skin emollients nor early complementary feeding reduced development of atopic dermatitis, with a risk difference of 3·1% (95% CI -0·3 to 6·5) for skin intervention and 1·0% (-2·1 to 4·1) for food intervention, in favour of control. No safety concerns with the interventions were identified. Reported skin symptoms and signs (including itching, oedema, exanthema, dry skin, and urticaria) were no more frequent in the skin, food, and combined intervention groups than in the no intervention group. INTERPRETATION: Neither early skin emollients nor early complementary feeding reduced development of atopic dermatitis by age 12 months. Our study does not support the use of these interventions to prevent atopic dermatitis by 12 months of age in infants. FUNDING: The study was funded by several public and private funding bodies: The Regional Health Board South East, The Norwegian Research Council, Health and Rehabilitation Norway, The Foundation for Healthcare and Allergy Research in Sweden-Vårdalstiftelsen, Swedish Asthma and Allergy Association's Research Foundation, Swedish Research Council-the Initiative for Clinical Therapy Research, The Swedish Heart-Lung Foundation, SFO-V at the Karolinska Institute, Freemason Child House Foundation in Stockholm, Swedish Research Council for Health, Working Life and Welfare-FORTE, Oslo University Hospital, the University of Oslo, and Østfold Hospital Trust.

Parent and child perception of quality of life in a randomized controlled peanut oral immunotherapy trial.

BACKGROUND: Improved quality of life (QoL) after oral immunotherapy (OIT) in peanut allergic children is often reported by their parents, while the child's perspective is less clear. OBJECTIVE: We aimed to explore whether 2 years of OIT improved QoL in children with peanut allergy and to identify factors influencing change in QoL. METHODS: In the open-labeled TAKE-AWAY peanut OIT trial including children with anaphylaxis to peanuts, 57 were randomized to OIT and 20 to observation. The Pediatric Quality of Life Inventory Version 4.0 was completed by parents and children at enrollment (Y0 ), after 1 year (end of updosing; Y1 ) and after 2 years (Y2 ) of OIT. Minimally clinically important difference (MCID) is ≥5.3. Perceived treatment burden was recorded by visual analogue scales, including adverse events (AEs). An open food challenge (OFC) was performed at Y2 . RESULTS: At Y2 , 18 children had discontinued OIT and 2 of 39 OIT children refused OFC, while 35 of 37 were desensitized to 7500 mg peanut protein. From Y0 to Y2, the mean change (95% confidence intervals) in QoL was 4.4 (0.5, 8.3) among child self-reports and twice as large among parental proxy reports (9.3 [4.3, 14.3]; both P < 0.0001), without significant improvement among the controls. The change in QoL was significantly different from the controls for the parental proxy reports only (P = 0.002). Neither treatment burden nor AEs significantly predicted changes in QoL. CONCLUSION: Two years of OIT improved child-QoL as reported by parents, but not by the children, suggesting that parents may overestimate improvement in child-QoL by OIT.

Emollient creams and bath oils do not prevent atopic eczema. / Fuktighetskrem og oljebad forebygger ikke atopisk eksem.

Emollient creams and bath oils do not prevent atopic eczema in infants. Emollients are nevertheless important for those who suffer from eczema.

Asthma with allergic comorbidities in adolescence is associated with bronchial responsiveness and airways inflammation.

BACKGROUND: Childhood asthma frequently has allergic comorbidities. However, there is limited knowledge of the longitudinal development of asthma comorbidites and their association to bronchial hyper-responsiveness (BHR) and airway inflammation markers. We therefore aimed to assess the association between childhood asthma with allergic comorbidities and BHR and fractional exhaled nitric oxide (FE(NO)) and the impact of gender on these associations. METHODS: Based on data from 550 adolescents in the prospective birth cohort 'Environment and Childhood Asthma' study, asthma was defined for the three time periods 0-2, 2-10 and 10-16 years of age, using recurrent bronchial obstruction (rBO) 0-2 years of age as a proxy for early asthma. Asthma comorbidities included atopic dermatitis (AD) and allergic rhinitis (AR) from 10 to 16 years. At age 16 years BHR, assessed by metacholine bronchial challenge, and airway inflammation, assessed by FE(NO), were compared between the groups of asthma with or without the two comorbidities, to a reference group with no never asthma, and subsequently stratified by gender. RESULTS: Boys with asthma and AR, regardless of AD had significantly more severe BHR and higher FE(NO) than the other asthma phenotypes. Almost half of the children remained in the asthma and AR category from 10 to 16 years, the entire difference being determined by new incident cases from 10 to 16 years. CONCLUSIONS: Asthma phenotypes characterized by allergic comorbidities and AR in particular appears closely associated with BHR and FE(NO), especially among boys.

Home-Based Double-Blind, Placebo-Controlled Challenges for Diagnosis of Delayed Gluten/Milk Hypersensitivity in Children.

BACKGROUND: Delayed hypersensitivity to gluten and milk protein is frequently reported but may be difficult to diagnose. OBJECTIVE: We aimed to explore if a method of home-based double-blind placebo-controlled food challenges (H-FC) can identify and reduce unnecessary elimination diets in children. METHODS: We included 73 of 92 children aged 1 to 17 years referred to a tertiary allergy clinic from 2011 to 2021 due to self-reported, delayed symptoms to gluten or milk. The children were randomized to H-FC, receiving gluten/milk protein or placebo for 5 to 7 days in a double-blind crossover manner, separated by 3 washout weeks. Patients/parents recorded symptoms using standardized forms. Two crossover periods were used from 2011 to 2016 and 3 periods from 2017 to 2021. A positive challenge required significantly more symptoms during the active period versus the placebo period. After the challenge, reintroduction of milk/gluten was assessed by a follow-up interview. The primary outcome was the proportion of children with a positive challenge. RESULTS: The children, with a mean age of 11 years, had followed a strict gluten-free or milk-protein-free diet for a median duration of 24 months (range: 3-180 months). A positive challenge was observed in 18 of 73 children (25%), more often using 2 (35%) compared with 3 challenge periods (12%). At follow-up, 44 of 55 (80%) children with a negative challenge had successfully reintroduced milk/gluten. CONCLUSIONS: H-FC may be an effective method in avoiding unnecessary elimination diets in children. Only 25% of the challenges were positive, and 80% of the children with negative challenges succeeded in reintroducing the food. Three challenge periods may be necessary to reduce false-positive outcomes.

Lung function in preterm infants at 3 months corrected age after neonatal LC-PUFA supplementation.

OBJECTIVE: To test the hypothesis that long-chain polyunsaturated fatty acid (LC-PUFA) supplementation improves lung function at 3 months corrected age (CA) compared with standard treatment in very preterm infants. We also aimed to investigate the association between bronchopulmonary dysplasia (BPD), longitudinal growth, and lung function at 3 months CA. METHODS: A secondary analysis from the ImNuT trial, in which 121 infants with gestational age <29 weeks were randomized to a daily supplement with arachidonic acid (ARA) and docosahexaenoic acid (DHA) (ARA:DHA group) or MCT-oil (control group) from birth up to 36 weeks postmenstrual age (PMA). Lung function was assessed at 3 months CA by tidal flow volume loops and the outcomes were the ratio of time to peak tidal expiratory flow to expiratory time (tPTEF /tE ) and tidal volume (VT ) per body weight (mL/kg). RESULTS: Thirty-nine infants in the ARA:DHA group versus 51 in the control group had a successful lung function test. There was no mean difference (MD) in tPTEF /tE ratio (MD: 0.01, 95% confidence interval [CI]: -0.04 to 0.05; p = .77) or VT (MD: 0.09 mL/kg, 95% CI: -0.79 to 0.62; p = .81) between the study groups. The multivariable regression model showed that BPD was associated with tPTEF /tE ratio ≤ 0.25 (p = .03) and that an increase in z score for length after 36 weeks PMA correlated positively with VT (mL/kg) (p = .03). CONCLUSION: Neonatal LC-PUFA supplementation did not improve lung function at 3 months CA in very preterm infants. BPD was independently associated with reduced lung function, while improved linear growth correlated with higher tidal volumes.

Use of Swedish smokeless tobacco during pregnancy: A systematic review of pregnancy and early life health risk.

BACKGROUND AND AIMS: Smokeless tobacco is a heterogeneous product group with diverse composition and prevalence globally. Tobacco use during pregnancy is concerning due to the risk of adverse pregnancy outcomes and effects on child health. Nicotine may mediate several of these effects. This systematic review measured health outcomes from Swedish smokeless tobacco (snus) use during pregnancy. METHOD: Literature search was conducted by an information specialist in May 2022. We included human studies of snus use during pregnancy compared with no tobacco use, assessed risk of bias, conducted a meta-analysis and assessed confidence in effect-estimates using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). RESULTS: We included 18 cohort studies (42 to 1 006 398 participants). Snus use during pregnancy probably (moderate confidence in risk estimates) increase the risk of neonatal apnea, adjusted odds ratio 95% confidence interval [aOR (95% CI)] 1.96 (1.30 to 2.96). Snus use during pregnancy possibly (low confidence in risk estimates) increase the risk of stillbirths aOR 1.43 (1.02 to 1.99), extremely premature births aOR 1.69 (1.17 to 2.45), moderately premature birth aOR 1.26 (1.15 to 1.38), SGA aOR 1.26 (1.09 to 1.46), reduced birth weight mean difference of 72.47 g (110.58 g to 34.35 g reduction) and oral cleft malformations aOR 1.48 (1.00 to 2.21). It is uncertain (low confidence in risk estimates, CI crossing 1) whether snus use during pregnancy affects risk of preeclampsia aOR 1.11 (0.97 to 1.28), antenatal bleeding aOR 1.15 (0.92 to 1.44) and very premature birth aOR 1.26 (0.95 to 1.66). Risk of early neonatal mortality and altered heart rate variability is uncertain, very low confidence. Snus using mothers had increased prevalence of caesarean sections, low confidence. CONCLUSIONS: This systematic review reveals that use of smokeless tobacco (snus) during pregnancy may adversely impact the developing child.

Third trimester fetal lung volume, thoracic circumference, and early infant lung function.

BACKGROUND: We aimed to investigate the relationship between fetal third trimester lung volume (LV), thoracic circumference (TC), fetal weight, as well as fetal thoracic and weight growth, and early infant lung function. METHODS: Fetal LV, TC and estimated weight were measured with ultrasound at 30 gestational weeks in 257 fetuses from the general population-based prospective cohort study Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL). Fetal thoracic growth rate and weight increase were calculated using TC and estimated fetal weight measured by ultrasound during pregnancy, and TC and birthweight of the newborn. Lung function was assessed by tidal flow-volume measurement in awake infants at 3 months of age. The associations between fetal size (LV, TC, and estimated weight) and growth (thoracic growth rate and fetal weight increase) measures and the time to peak tidal expiratory flow to expiratory time ratio (tPTEF /tE ) as well as tidal volume standardized for body weight (VT /kg) were analyzed using linear and logistic regression models. RESULTS: We observed no associations between fetal LV, TC or estimated fetal weight and tPTEF /tE as a continuous variable, tPTEF /tE < 25th percentile, or VT /kg. Similarly, fetal thoracic growth and weight increase were not associated with infant lung function. Analyses stratified for sex showed a significant inverse association between fetal weight increase and VT /kg (p = 0.02) in girls. CONCLUSION: Overall, fetal third trimester LV, TC, estimated fetal weight, thoracic growth rate and weight increase were not associated with infant lung function at 3 months of age.

Pet keeping and tobacco exposure influence CD14 methylation in childhood.

BACKGROUND: Several CD14 gene-environment interactions in relation to the development of allergic diseases have been reported, but the underlying biological mechanisms are unclear. We recently showed that CD14 methylation increased during childhood, parallelling a decreased impact of CD14 polymorphisms on soluble CD14 levels. Here, we aim to explore whether environmental stimuli during childhood affects CD14 methylation, thereby providing a biological mechanism through which environment may modulate genetic effect. METHODS: CD14 methylation levels were quantified in 157 children from the prospective Environment and Childhood Asthma birth cohort at ages 2 and 10. Associations between CD14 methylation levels and house dust levels of endotoxin, ß(1,3)-glucans (at 2 yr only), allergens (dog, cat, and house dust mite), pet keeping and tobacco smoke exposure (TSE; questionnaire data) at 2 and 10 yr were explored. RESULTS: Children in homes without pets had larger increases in CD14 methylation through childhood (2-10 yr) compared with children with pets (2.1% increase (p = 0.003) vs. 0.4% decrease (n.s.), global p = 0.04). At 10 yr of age, lower CD14 methylation values were found in children with pets compared with children without pets at both 2 and 10 yr (5.4% vs. 7.5% [p = 0.02]). A similar trend was detected for TSE; children not exposed show larger increases in CD14 methylation, most pronounced in school-age girls exposed vs. not exposed to tobacco (5.5% vs. 7.5% methylation, p = 0.037). CONCLUSION: Pet keeping and TSE appears to limit increase in CD14 methylation from 2 to 10 yr of age. This may partly explain the diverging CD14 allele associations with allergic diseases detected in different environments.

Skin Barrier Function and Infant Tidal Flow-Volume Loops-A Population-Based Observational Study.

Background: The relationship between the skin barrier- and lung function in infancy is largely unexplored. We aimed to explore if reduced skin barrier function by high transepidermal water loss (TEWL), or manifestations of eczema or Filaggrin (FLG) mutations, were associated with lower lung function in three-month-old infants. Methods: From the population-based PreventADALL cohort, 899 infants with lung function measurements and information on either TEWL, eczema at three months of age and/or FLG mutations were included. Lower lung function by tidal flow-volume loops was defined as a ratio of time to peak tidal expiratory flow to expiratory time (tPTEF/tE) <0.25 and a tPTEF <0.17 s (<25th percentile). A high TEWL >8.83 g/m2/h (>75th percentile) denoted reduced skin barrier function, and DNA was genotyped for FLG mutations (R501X, 2282del4 and R2447X). Results: Neither a high TEWL, nor eczema or FLG mutations, were associated with a lower tPTEF/tE. While a high TEWL was associated with a lower tPTEF; adjusted OR (95% CI) 1.61 (1.08, 2.42), the presence of eczema or FLG mutations were not. Conclusions: Overall, a high TEWL, eczema or FLG mutations were not associated with lower lung function in healthy three-month-old infants. However, an inverse association between high TEWL and tPTEF was observed, indicating a possible link between the skin barrier- and lung function in early infancy.

Altered oxidative state in schoolchildren with asthma and allergic rhinitis.

Oxidative stress may be defined as a disruption of the balance between the level of oxidants and reductants (antioxidants), and oxidative state in children may influence the risk of asthma and allergic disease. We investigated serum antioxidant levels: selenium, vitamin E, bilirubin, albumin, uric acid and transferrin as well as the oxidant ferritin and their association with asthma and allergic rhinitis. Children of 7-12 yr with asthma (n = 50) and no asthma (controls) (n = 52) underwent skin prick test, lung function, fractional exhaled nitric oxide (FeNO) measurements and blood sampling. Allergic rhinitis was found in 23 children, 19 with asthma and four controls. Healthy children were controls without rhinitis. Asthma was associated with reduced albumin (g/l), adjusted odds ratio (aOR) (95% CI) 0.81 (0.66, 0.99) (p = 0.048) compared with healthy children in a regression analysis adjusted for age and gender. Asthma with high FeNO ≥20 ppb was associated with reduced albumin, aOR 0.60 (0.40, 0.89) (p = 0.012) compared to controls with FeNO <20. Asthma with allergic rhinitis had reduced albumin, aOR = 0.70 (0.50, 0.99) (p = 0.04), and higher ferritin levels (mg/l) [aOR = 1.04 (1.00, 1.09) p = 0.03] compared to healthy children. Poorly controlled asthma was associated with lower vitamin E levels, aOR 0.79 (0.65, 0.95) (p = 0.02), lower transferrin levels, aOR 0.72 (0.57, 0.92) (p < 0.01), and higher albumin levels, aOR 1.53 (1.03, 2.28) (p = 0.04), compared to well controlled asthma. In conclusion, schoolchildren with asthma and rhinitis had reduced levels of the major serum antioxidant albumin, and poorly controlled asthma was associated with decreased vitamin E and transferrin levels. Reduced albumin was associated with increased FeNO, a marker of allergic inflammation in asthma, although the discriminatory value of this finding should be further assessed in population studies.

Paracetamol in early infancy: the risk of childhood allergy and asthma.

AIM: We investigated whether paracetamol exposure in pregnancy and until 6 months of age was associated with allergic disease in school children. METHODS: In a prospective birth cohort study in Oslo, 1016 children included at birth were re-investigated at 10 years. Paracetamol exposure in pregnancy and until 6 months of age was registered. Outcomes at 10 years included current asthma, a history of asthma, allergic sensitization and allergic rhinitis. RESULTS: Maternal paracetamol use in the first trimester increased the risk for allergic rhinitis at 10 years OR (odds ratio) (95%CI) 2.30 (1.06, 4.97) in boys and girls. Paracetamol use until 6 months in girls increased the risk for allergic sensitization OR 2.20 (1.15, 4.22) and a history of asthma OR 2.20 (1.13, 4.30). The ORs for allergic sensitization and history of asthma in girls remained unchanged adjusting for upper or lower airway infections during the first 6 months of life. CONCLUSION: Paracetamol exposure in pregnancy was associated with allergic rhinitis, but not with asthma or allergic sensitization at 10 years of age. Paracetamol used until 6 months of age was associated with allergic sensitization and having a history of asthma in girls at 10 years of age, even considering concomitant airway infections.

Maternal human papillomavirus infections at mid-pregnancy and delivery in a Scandinavian mother-child cohort study.

OBJECTIVES: Human papillomavirus (HPV) infections are common, especially during women's reproductive years, with unclear obstetrical impact. This study aimed to identify HPV prevalence at mid-gestation and delivery, type-specific persistence from mid-gestation to delivery, and risk factors for HPV infection and persistence. METHODS: In 757 women from a Scandinavian prospective mother-child cohort, HPV was analyzed in first-void urine samples at mid-gestation and delivery. We used Seegene Anyplex II HPV28 PCR assay for genotyping and semi-quantifying 28 genital HPV genotypes, including 12 high-risk HPVs (HR-HPV). Socio-demographic and health data were collected through e-questionnaires. RESULTS: Any-HPV genotype (any of 28 assessed) was detected in 38% of the study cohort at mid-gestation and 28% at delivery, and HR-HPVs in 24% and 16%, respectively. The most prevalent genotype was HPV16: 6% at mid-gestation and 4% at delivery. Persistence of Any-HPV genotype was 52%, as was HR-HPV genotype-specific persistence. A short pre-conception relationship with the child's father and alcohol intake during pregnancy increased HPV infection risk at both time points. Low viral load at mid-gestation was associated with clearance of HPV infections at delivery. CONCLUSION: HPV prevalence was higher at mid-gestation compared with delivery, and low viral load was associated with clearance of HPV at delivery.

Rhinitis in children: co-morbidities and phenotypes.

Rhinitis and its co-morbidities affect quality of life; and in children, little is known. We therefore aimed to describe the co-morbidities and phenotypes of current rhinitis in 10-yr-old Norwegian children. We used information on rhinitis, asthma, allergic sensitization, anaphylaxis, and lung function tests from clinical examinations and structured parental interviews of 1019 children included in the birth cohort study, the Environment and Childhood Asthma Study, in Oslo. Current rhinitis was reported in 254 (25.0%) of the children, and 87.4% had at least one allergy-related co-morbidity of rhinitis, with conjunctivitis the most prevalent (75.6%). Overall, 11.8% of the children had conjunctivitis combined with current asthma and atopic eczema. Children with rhinitis were also more likely to have severe bronchial hyperresponsiveness (BHR) (PD(20)