Objective To determine reference blood pressure (BP) values in a cohort of healthy infants at 3, 6 and 12 months of age. Design An antenatally recruited population-based mother–child cohort study. Setting The multicentre Preventing Atopic Dermatitis and ALLergies in children study, recruiting non-selected pregnant women in Norway and Sweden between 2014 and 2016. Infant oscillometric BP was measured at clinical follow-up visits at 3, 6 and 12 months of age. Patients In total, 2100 infants had BP readings available during infancy. Main outcome measures Systolic, diastolic and mean arterial BP at each follow-up visit based on successful BP measurements defined as three readings obtained in a calm state with systolic BP within a 20 mm Hg range. Results Successful BP measurements were obtained in 1778 infants at 3, 6 and/or 12 months of age. Median systolic/diastolic BP (mean arterial pressure) was 95/56 (69) mm Hg at age 3 months, 96/57 (72) mm Hg at 6 months and 95/57 (71) mm Hg at 12 months. Conclusions This study establishes reference values for oscillometric BP in healthy infants and shows consistent measurements across 3, 6 and 12 months of age.

PURPOSE:To determine the molecular cause of the two epithelial recurrent erosion dystrophies, Dystrophia Smolandiensis and Dystrophia Helsinglandica, and to identify phenotypic differences between the two conditions. METHODS:DNA samples and clinical data from structured interview records were obtained from the Swedish families in which Dystrophia Smolandiensis and Dystrophia Helsinglandica were originally characterized. Candidate variant detection was performed using combinations of linkage analysis, Sanger sequencing, exome sequencing and genome sequencing. Differences in age of onset and precipitating factors of erosive episodes were assessed using the Wilcoxon rank sum test and Fisher's exact test. RESULTS:In Dystrophia Smolandiensis, the novel candidate variant NQO1 c.535 T>A p.(Phe179Ile) co-segregated with disease across 49 informative meioses. In Dystrophia Helsinglandica, the known pathogenic splice variant COL17A1 c.3156C>T was identified. There were significant phenotypic differences between the two conditions. The median age of onset was lower in Dystrophia Smolandiensis (2.5 years vs. 6 years, p = 0.00065). Cigarette smoke, intense sunlight and pregnancy were distinct precipitating factors of erosive episodes in Dystrophia Smolandiensis (p = 0.0010, p < 0.0001 and p = 0.016, respectively), whereas minor trauma to the eye was specific to Dystrophia Helsinglandica (p < 0.0001). CONCLUSION:NQO1 is a candidate gene for Dystrophia Smolandiensis, while Dystrophia Helsinglandica is synonymous with COL17A1-associated ERED. The two conditions are characterized by distinct phenotypic differences. Based on these findings, we suggest a reclassification of epithelial recurrent erosion dystrophies guided by genetics. We propose designating COL17A1-associated epithelial recurrent erosion dystrophy as ERED1 and NQO1-associated epithelial recurrent erosion dystrophy as ERED2.

Background Previously identified asthma-susceptibility genes account for a small part of asthma heritability and their role in asthma pathogenesis is unclear. We explored associations between genetic variants in the 17q21 locus, CDHR3 (cadherin-related family member 3) , coding a receptor for Rhinovirus-C, preschool wheeze and asthma at 7 years. Methods Four genetic variants in the 17q21 locus (rs8076131, rs12603332, rs8079416, rs3859192) and rs6967330 in CDHR3 were studied regarding associations with preschool wheeze and asthma at 7 years. We compared 125 cases, enrolled during an acute wheezing episode, with 96 healthy controls at preschool age (6-45 months). At 7 years cases with asthma (N=68) and without asthma (N=31) were compared regarding genetic variants and other clinical parameters. Results Rs8076131 (AA vs GG) was associated with preschool wheeze (OR 3.50, p=0.001), and asthma at 7 years (OR 8.55, p=0.002). Rs12603332 (CC vs TT) was related to asthma at 7 years irrespective of rhinovirus infection at inclusion or current signs of airborne allergy (aOR 7.17, p=0.016). The association of rs6967330 with asthma was restricted to children with specific genotypes in the 17q21 locus; rs8076131-AA ( p=0.028) , rs8079416-CC (p=0.006), and rs3859192-TT (p=0.042). Rhinovirus infection at inclusion was significantly related to asthma exclusively in homozygotes rs8079416-CC (p=0.032) and rs3859192-TT (p=0.027). Conclusion Our results highlight the impact of asthma heritability by reporting strong associations between 17q21 locus and asthma in a high-risk cohort. The association of rs6967330 in CDHR3 and early-life rhinovirus infection with asthma at school age might be dependent on specific genotypes in the 17q21 locus.

Background:Childhood atopic dermatitis is associated with maternal gestational weight gain, whereas an association with prepregnancy body mass index (ppBMI) or fetal and newborn anthropometric measurements is unclear. Objective:Our aim was to determine whether, primarily, maternal ppBMI and, secondarily, offspring newborn anthropometric measurements or fetal growth are associated with atopic dermatitis by age 3 years. Methods:In 2107 mother-child pairs (54% boys) from the general population-based Scandinavian PreventADALL (Preventing Atopic Dermatitis and Allergies) cohort, maternal ppBMI was reported at time of enrollment (at midpregnancy). Thoracic and abdominal circumferences were measured by ultrasound at midpregnancy and again at birth, as were weight and length. Fetal growth, including thoracic and abdominal growth and fetal weight gain, was estimated from midpregnancy to birth. Atopic dermatitis was diagnosed using standard criteria at 3, 6, 12, 24, and age 36 months. Results:Atopic dermatitis was diagnosed in 525 of the 2107 children (25%) by age 3 years, with a positive association with increasing maternal BMI (adjusted odds ratio [aOR] per BMI unit = 1.03 [95% CI = 1.00-1.06]). Furthermore, increasing birth length (mean = 50.5 ± 2.0 cm) was positively associated with atopic dermatitis (aOR = 1.06 [95% CI = 1.01-1.12]), whereas short birth length (<48 cm) was inversely associated with atopic dermatitis (aOR = 0.71 [95% CI = 0.51-1.0]). Neither birth weight nor thoracic, abdominal, or upper arm circumference at birth nor fetal growth was associated with atopic dermatitis. Conclusion:Increasing maternal ppBMI and increasing birth length were positively associated with offspring atopic dermatitis by age 3 years, whereas short birth length was associated with a lower risk of atopic dermatitis.

Background Pollen sensitization may be directed toward proteins also found in plant foods. Objective We explored whether early food introduction and skin emollients prevented birch and grass sensitization at age 3 years and whether the effect was mediated by skin barrier function or modified by season of birth. Methods In the population-based, randomized, controlled Preventing Atopic Dermatitis and Allergy in Children trial, information on allergic sensitization by age 3 years was available in 2,066 children. Newborns were randomized (1:1:1:1) to no (controls); to food (tastes of peanut, cow’s milk, wheat, and egg from 3 months) or skin (oil baths and facial cream from 2 weeks); or to both interventions. Sensitization was defined as specific IgE 0.1 kUA/L or greater and/or skin prick test wheal 3 mm or greater. A mediator analysis assessed the skin intervention’s effect through transepidermal water loss at 3 months. An interaction analysis estimated effect modification by month of birth. Results At age 3 years, 117 of 1,492 children (7.8%) were sensitized to birch and 40 of 1,482 children (2.7%) to timothy. Compared with controls, crude odds ratio (95% CI) in the food, skin, and combined intervention groups, respectively, was 1.10 (0.63-1.93), 2.38 (1.43-3.95), and 0.70 (0.37-1.34) for birch, and 0.58 (0.21-1.60), 1.73 (0.77-3.91), and 1.00 (0.40-2.49) for grass sensitization. A significant indirect effect of the skin intervention through transepidermal water loss was observed, but there was no significant modification by month of birth for either intervention. Conclusions Early food introduction did not affect the risk of pollen sensitization. Infants with skin intervention had increased risk only of birch sensitization, mediated by reduced skin barrier function in early infancy.

Introduction Asthma is a leading cause of morbidity and healthcare use among children. Risk factors of childhood asthma include atopic predisposition and severe wheezing episodes caused by rhinovirus infection in early life. In children with first-time rhinovirus-induced wheezing, we aim to study the response of a short corticosteroid treatment to prevent recurrent wheezing and asthma.Method and analysis This is a double-blind, randomised, placebo-controlled, phase IV, international multicentre trial involving eight sites in Norway, Sweden and Finland. Two hundred and eighty 3–23 months old steroid-naïve children are randomised 1:1 to receive oral dexamethasone (0.3 mg/kg/day) versus placebo in 3 days for their first wheezing episode and rhinovirus infection. Rhinovirus is diagnosed with multiplex PCR. The two co-primary outcomes are time to next physician-confirmed wheezing episode, and time to asthma, within 24 months from inclusion. Asthma is defined as fulfilment of the 2007 National Asthma Education and Prevention Program—criteria for initiating asthma controller medication in children aged 0–4 years. Primary interaction analyses are age, gender, atopic predisposition, risk genotypes and viral co-detection. The optimal cut-off on the rhinovirus genome load used to define a true rhinovirus infection will be assessed by exploring interactions between rhinovirus genomic loads and study drug on the co-primary outcomes. Secondary outcomes are number of wheezing episodes, duration and severity of each wheezing episode, bronchial hyperreactivity, quality of life and safety (height/weight development) at 24 months from inclusion.Ethics and dissemination Rhinovirus positive children with acute wheezing fulfilling inclusion and exclusion criteria are enrolled after informed consent from both caregivers. This trial has received ethical approval from all sites. Results will be submitted to Competent Authorities and disseminated via peer-reviewed publications and conferences within paediatrics and other relevant fields. If proven effective, findings may be implemented directly into paediatric clinical guidelines.Trial registration number NCT03889743.

Introduction: Placental function differs by fetal sex, and placental dysfunction is associated with adverse pregnancy outcomes. We aimed to investigate the role of midpregnancy maternal circulating placenta-associated angiogenic biomarkers and fetal sex in relation to placental dysfunction-related pregnancy complications. Methods: The Preventing Atopic Dermatitis and Allergies in children birth cohort study provided maternal serum from 2511 pregnancies at gestational weeks 16-22. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were analyzed by immunoassays. Pregnancy complications (n = 385) included gestational hypertension, preeclampsia, preterm delivery, and/or newborn weight <10th percentile; categorized as 'uncomplicated', 'complicated' and 'severely complicated' pregnancies by zero, one or two or more complications. The risk of 'any number of pregnancy complications' by biomarkers tertiles were assessed in multivariable logistic regression models with interaction analyses of fetal sex. Results: Midpregnancy median PlGF was lower and sFlt-1 higher in pregnancies with a female versus a male fetus, with median (interquartile range) sFlt-1/PlGF-ratio being 7.2 (4.9-10.2) versus 6.4 (4.3-9.0) in 'uncomplicated', 7.3 (4.7-10.7) versus 6.4 (4.5-9.0) in 'complicated', and 11.2 (5.4-22.7) versus 5.9 (4.8-13.4) in 'severely complicated' pregnancies. The risks of 'any number of pregnancy complications' were highest in the lowest tertile of PlGF (adjusted odds ratio (aOR) 1.6, 95 % confidence interval (CI): 1.2-2.2) and sFlt-1 (aOR 1.4, 95 % CI: 1.0-1.9) without influence of fetal sex (all, pinteractions >0.05). Conclusion: Circulating midpregnancy placenta-associated angiogenic biomarkers differed by fetal sex and pregnancy complications. The higher risk of pregnancy complications with low midpregnancy PlGF and/or sFlt-1 levels was not influenced by fetal sex.

BACKGROUND:Multiple environmental and genetic factors play a role in the pathogenesis of atopic eczema (AE). We aimed to investigate gene-environment interactions (G × E) to improve understanding of the pathophysiology. METHODS:We analysed data from 16 European studies to test for interaction between the 24 most significant AE-associated loci identified from genome-wide association studies and 18 early-life environmental factors. We tested for replication using a further 10 studies and in vitro modeling to independently assess findings. RESULTS:The discovery analysis (including 25,339 individuals) showed suggestive evidence for interaction (p < 0.05) between seven environmental factors (antibiotic use, cat ownership, dog ownership, breastfeeding, elder sibling, smoking and washing practices) and at least one established variant for AE, 14 interactions in total. In the replication analysis (254,532 individuals) dog exposure × rs10214237 (on chromosome 5p13.2 near IL7R) was nominally significant (ORinteraction = 0.91 [0.83-0.99] p = 0.025), with a risk effect of the T allele observed only in those not exposed to dogs. A similar interaction with rs10214237 was observed for siblings in the discovery analysis (ORinteraction = 0.84 [0.75-0.94] p = 0.003), but replication analysis was under-powered (ORinteraction = 1.09 [0.82-1.46]). rs10214237 homozygous risk genotype is associated with lower IL-7R expression in human keratinocytes, and dog exposure modelled in vitro showed a differential response according to rs10214237 genotype. CONCLUSION:Interaction analysis and functional assessment provide preliminary evidence that early-life dog exposure may modify the genetic effect of rs10214237 on AE via IL7R, supporting observational epidemiology showing a protective effect for dog ownership. The lack of evidence for other G × E studied here implies only weak effects are likely to occur.

Background Smoking in pregnancy has detrimental effects on infant respiratory health, while the effects of other nicotine-containing products on infant lung function are unclear. We aimed to explore if smokeless tobacco such as snus used in pregnancy increased the risk of lower lung function in infancy and if the associations differed by sex. Methods From the Scandinavian population-based Preventing Atopic Dermatitis and ALLergies in Children birth cohort, we included 1163 infants with available tidal flow-volume measurements at 3 months of age and maternal self-reported use of nicotine-containing products in pregnancy. The risk of a ratio of time to peak tidal expiratory flow to total expiratory time <25th percentile by any nicotine exposure, snus exclusively and cigarette smoking with or without other nicotine-containing products was explored by regression analyses adjusting for maternal age, education and asthma. Results Overall 120 out of 1163 (10.3%) infants were exposed to any nicotine in utero , 71 out of 120 by snus exclusively and 49 out of 120 by smoking, with six also exposed to snus. By pregnancy week 6, 85.8% of mothers reported stopping nicotine use. The risk of lower lung function was higher in children exposed in utero to nicotine-containing products with an odds ratio (OR) of 1.63 (95% confidence interval (CI) 1.02–2.59) with a similar tendency for snus exclusively (OR 1.55, 95% CI 0.88–2.71) and smoking (OR 1.79, 0.84–3.84). Effect estimates were similar after adjusting for covariates. No differences of the effect by sex were observed. Conclusion Our study suggests that in utero exposure to not only cigarettes, but also snus, may negatively affect infant lung function.

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.

BackgroundSpinocerebellar ataxia 4 (SCA4), characterized in 1996, features adult-onset ataxia, polyneuropathy, and linkage to chromosome 16q22.1; its underlying mutation has remained elusive. ObjectiveTo explore the radiological and neuropathological abnormalities in the entire neuroaxis in SCA4 and search for its mutation. MethodsThree Swedish families with undiagnosed ataxia went through clinical, neurophysiological, and neuroimaging tests, including PET studies and genetic investigations. In four cases, neuropathological assessments of the neuroaxis were performed. Genetic testing included short read whole genome sequencing, short tandem repeat analysis with ExpansionHunter de novo, and long read sequencing. ResultsNovel features for SCA4 include dysautonomia, motor neuron affection, and abnormal eye movements. We found evidence of anticipation; neuroimaging demonstrated atrophy in the cerebellum, brainstem, and spinal cord. [18F]FDG-PET demonstrated brain hypometabolism and [11C]Flumazenil-PET reduced binding in several brain lobes, insula, thalamus, hypothalamus, and cerebellum. Moderate to severe loss of Purkinje cells in the cerebellum and of motor neurons in the anterior horns of the spinal cord along with pronounced degeneration of posterior tracts was also found. Intranuclear, mainly neuronal, inclusions positive for p62 and ubiquitin were sparse but widespread in the CNS. This finding prompted assessment for nucleotide expansions. A polyglycine stretch encoding GGC expansions in the last exon of the zink finger homeobox 3 gene was identified segregating with disease and not found in 1000 controls. ConclusionsSCA4 is a neurodegenerative disease caused by a novel GGC expansion in the coding region of ZFHX3, and its spectrum is expanded to include dysautonomia and neuromuscular manifestations.

Abstract Background Human papillomaviruses are common in the urogenital tract amongst women of childbearing age. A few studies indicate a possible association between human papillomavirus infections in pregnancy and adverse pregnancy outcomes whilst other studies find no such association. We aimed to investigate the association between human papillomavirus infections during pregnancy and adverse pregnancy outcomes linked to placental dysfunction, including hypertensive disorders of pregnancy, gestational diabetes mellitus and newborns small for gestational age. Materials and methods Pregnant women from the general population in Norway and Sweden were enrolled at the time of routine mid-gestational ultrasound examination. Urine samples collected at mid-gestation in 950 and at delivery in 753 participants, were analyzed for 28 human papillomavirus genotypes, including 12 high-risk genotypes. Participants completed electronic questionnaires at enrollment and medical records were reviewed for background characteristics and for the following adverse pregnancy outcomes: hypertensive disorders of pregnancy including gestational hypertension, preeclampsia, superimposed preeclampsia, eclampsia and Hemolysis Elevated Liver enzymes and Low Platelets (HELLP) syndrome, gestational diabetes mellitus, and newborns small for gestational age. Associations between adverse pregnancy outcomes and (a) any human papillomavirus, high-risk human papillomavirus and human papillomavirus genotype 16 infection at mid-gestation, (b) multiple genotype infections at mid-gestation, and (c) persisting infections during pregnancy were assessed with univariable and multivariable logistic regression models. Missing covariates were imputed using multiple imputation. Results At mid-gestation, 40% (377/950) of women were positive for any of the 28 genotypes, 24% (231/950) for high-risk genotypes and human papillomavirus 16 was found in 6% (59/950) of the women. Hypertensive disorders of pregnancy was observed in 9% (83/950), gestational diabetes mellitus in 4% (40/950) and newborns small for gestational age in 7% (67/950). Human papillomavirus infection with any genotype, high-risk or human papillomavirus genotype 16 at mid-gestation was not associated with adverse pregnancy outcomes. No associations were found for multiple genotype infections at mid-gestation or persisting infections. Conclusion In a general population of pregnant women, we found no evidence of human papillomavirus infections during pregnancy being associated with hypertensive disorders of pregnancy, gestational diabetes mellitus, or newborns small for gestational age. Trial registration Trial registration The study is registered at ClincialTrials.gov; NCT02449850 on May 19th, 2015. Graphical Abstract

Abstract Background Asthma is the most common chronic disease in children with an increasing prevalence. Its development is caused by genetic and environmental factors and allergic sensitization is a known trigger. Dog allergens affect up to 30% of all children and dog dander‐sensitized children show increased expression of cystatin‐1 (CST1) and eotaxin‐3 (CCL26) in nasal epithelium. The aim of our study was to investigate the functional mechanism of CST1 and CCL26 in the alveolar basal epithelial cell line A549. Methods A549 cells were transfected with individual overexpression vectors for CST1 and CCL26 and RNA sequencing was performed to examine the transcriptomics. edgeR was used to identify differentially expressed genes (= DEG, |log2FC | ≥ 2, FDR < 0.01). The protein expression levels of A549 cells overexpressing CST1 and CCL26 were analyzed using the Target 96 inflammation panel from OLINK (antibody‐mediated proximity extension–based assay; OLINK Proteomics). Differentially expressed proteins were considered with a |log2FC| ≥ 1, p < .05. Results The overexpression of CST1 resulted in a total of 27 DEG (1 upregulated and 26 downregulated) and the overexpression of CCL26 in a total of 137 DEG (0 upregulated and 137 downregulated). The gene ontology enrichment analysis showed a significant downregulation of type I and III interferon signaling pathway genes as well as interferon‐stimulated genes. At the protein level, overexpression of CST1 induced a significantly increased expression of CCL3, whereas CCL26 overexpression led to increased expression of HGF, and a decrease of CXCL11, CCL20, CCL3 and CXCL10. Conclusion Our results indicate that an overexpression of CST1 and CCL26 cause a downregulation of interferon related genes and inflammatory proteins. It might cause a higher disease susceptibility, mainly for allergic asthma, as CCL26 is an agonist for CCR‐3‐carrying cells, such as eosinophils and Th2 lymphocytes, mostly active in allergic asthma.

Atopic dermatitis (AD) affects approximately 20% of children in industrialized countries. AD causes dry, itchy skin and can increase the chance of infections.This study was a substudy of the large Scandinavian PreventADALL trial, including 2394 infants, recruited from the general population between 2014 and 2016. Children in this trial were allocated randomly to receive either a skin intervention, food intervention, combined intervention, or no intervention. Children were examined at 3, 6 and 12 months of age. The examinations involved an investigation of the skin, to evaluate dry skin and skin barrier function by transepidermal water loss (TEWL) in the outer layers of the skin (higher TEWL suggests decreased skin barrier function). The skin intervention consisted of oil baths at least 4 times per week from 2 weeks of age through 8 months of age, and have previously not been shown to prevent AD by 1 and 3 years of age. We aimed to investigate whether frequent oil baths had any effect on TEWL and dry skin.We found that the skin intervention increased TEWL in the first year of life, especially at 3 months of age. Dry skin was less common in the skin intervention groups compared with the groups with no skin intervention. Infants with mutations in the gene coding for a skin barrier protein, called filaggrin, were associated with increased TEWL; however, in the skin intervention group, TEWL was similar among the infants with or without filaggrin mutations. Our findings suggest that oil baths several times per week from early infancy transiently decreases skin barrier function. Background In the general population randomized controlled trial PreventADALL, frequent emollient bath additives from 2 weeks of age did not prevent atopic dermatitis, while the effect on skin barrier function throughout infancy is not established.Objectives The primary aim of this exploratory substudy was to assess the effect of mineral-based oil baths on transepidermal water loss (TEWL) and dry skin through infancy, and secondarily to explore if filaggrin (FLG) mutations modified the effect.Methods Overall, 2153 infants were included and randomized to either the 'Skin intervention' (SI) group (n = 995) (oil bath 4 times weekly from 2 weeks through 8 months) or 'No skin intervention' (NSI) group (n = 1158), with TEWL measurements at 3, 6 and/or 12 months of age. Information on FLG mutation status was available for 1683 of these infants. Effects of the skin intervention on TEWL and dry skin through infancy were assessed by mixed-effects regression modelling. Background characteristics and protocol adherence were collected from electronic questionnaires, birth records and weekly diaries.Results The TEWL (95% confidence interval) was on average 0.42 g m-2 h-1 (0.13-0.70, P = 0.004) higher in the SI group compared with the NSI group through the first year of life, with significantly higher levels at 3 months [8.6 (8.3-9.0) vs. 7.6 (7.3-7.9)], but similar at 6 and 12 months. Dry skin was observed significantly more often in the NSI group compared with the SI group at 3 months (59% vs. 51%) and at 6 months of age (63% vs. 53%), while at 12 months of age, the difference was no longer significant. At 3 months, the TEWL of FLG mutation carriers was similar to the TEWL in the SI group. No interaction between SI and FLG mutation was found in the first year of life.Conclusions Infants given frequent oil baths from 2 weeks of age had reduced skin barrier function through infancy compared with controls, largely attributed to higher TEWL at 3 months of age, while the skin at 3 and 6 months appeared less dry in infants subjected to the skin intervention. In a general population cohort, 2153 infants with frequent oil baths from 2 weeks of age had reduced skin barrier function through infancy compared with controls, largely attributed to higher TEWL at 3 months of age. Dry skin at 3 and 6 months was less common in infants subjected to the skin intervention.

Preschool children with wheezing disorders pose diagnostic and therapeutic challenges and consume substantial healthcare resources. Peripheral eosinophil blood count (EBC) has been proposed as a potential indicator for future asthma development. This review by the European Academy of Allergy and Clinical Immunology (EAACI) Preschool Wheeze Task Force aimed to provide systematic evidence for the association between increased EBC and the risk of future asthma, as well as to identify potential cutoff values. In February 2023, a search of PubMed, EMBASE, and Cochrane Library databases was conducted to identify studies comparing EBCs in preschool children with wheezing who continued to wheeze later in life and those who did not. Included observational studies focused on children aged <6 years with a wheezing disorder, assessment of their EBCs, and subsequent asthma status. No language or publication date restrictions were applied. Among the initial 3394 studies screened, 10 were included in the final analysis, involving 1225 patients. The data from these studies demonstrated that high EBC in preschool children with wheezing is associated with future asthma development, with odds ratios of 1.90 (95% CI: 0.45-7.98, p = .38), 2.87 (95% CI: 1.38-5.95, p < .05), and 3.38 (95% CI: 1.72-6.64, p < .05) for cutoff values in the <300, 300-449, and ≥450 cells/μL ranges, respectively. Defining a specific cutoff point for an elevated EBC lacks consistency, but children with EBC >300 cells/μL are at increased risk of asthma. However, further research is needed due to the limitations of the included studies. Future investigations are necessary to fully elucidate the discussed association.

AimOur aim was to investigate whether risk factors, including selected genetic variants, appeared with the same frequency in preterm-born and term-born children with respiratory symptoms.MethodsWe conducted an observational study on a cohort at Copenhagen University Hospital Hiller & oslash;d, Denmark, consisting of 63 preterm-born and 86 term-born children who were included at birth and followed to 6 years of age. Odd ratios (OR) and 95% CIs were calculated.ResultsValid genotyping data were obtained from 135 children and 126 and 64 parents completed questionnaires at the 1-year and 6-year follows-ups, respectively. The C allele of rs3751972 was associated with an increased wheezing risk at 6 years of age in term-born children, but not in preterm-born children (OR 8.84, 95% CI 1.02-76.72, p = 0.05 versus OR 2.33, 95% CI 0.59-9.20, p = 0.23, respectively). At 1 year of age, preterm-born children with respiratory symptoms were three times as likely to have parents who smoked than those without such symptoms (65% and 21%, respectively, p = 0.005).ConclusionGenetic variants known to affect the risk of respiratory symptoms did not seem to affect the risk of wheezing in preterm children. Parental smoking was a significant risk factor for respiratory symptoms.

AIM:This study explored whether early-life factors, such as rhinovirus-induced wheeze and allergic sensitisation, were related to asthma at 11 years of age. METHODS:We focused on 107 children aged 6-48 months, who attended the paediatric emergency department at Astrid Lindgren's Children's Hospital in Stockholm, Sweden, with acute wheeze in 2008-2012. They also attended follow-up visits at 11 years of age and were compared with 46 age-matched healthy controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with logistic regression. RESULTS:We found that 62.6% of the acute wheeze cases had asthma at 11 years of age. Rhinoviruses at inclusion were the only common airway viruses associated with an increased asthma risk (OR 2.4, 95% CI 1.02-5.6). Other increased risks were parental heredity for asthma and/or allergies (adjusted OR 3.4, 95% CI 1.1-9.9) and allergic sensitisation at 2 years of age (adjusted OR 3.0, 95% CI 1.02-8.7). The highest prevalence of asthma was when children had both rhinovirus-induced wheeze at inclusion and allergic sensitisation at 7 years of age. CONCLUSION:Our findings highlight the importance of hereditary factors and allergic sensitisation on the development of asthma and suggest that rhinoviruses are associated with asthma development in predisposed children.

BACKGROUND:Human papillomaviruses are common in the urogenital tract amongst women of childbearing age. A few studies indicate a possible association between human papillomavirus infections in pregnancy and adverse pregnancy outcomes whilst other studies find no such association. We aimed to investigate the association between human papillomavirus infections during pregnancy and adverse pregnancy outcomes linked to placental dysfunction, including hypertensive disorders of pregnancy, gestational diabetes mellitus and newborns small for gestational age. MATERIALS AND METHODS:Pregnant women from the general population in Norway and Sweden were enrolled at the time of routine mid-gestational ultrasound examination. Urine samples collected at mid-gestation in 950 and at delivery in 753 participants, were analyzed for 28 human papillomavirus genotypes, including 12 high-risk genotypes. Participants completed electronic questionnaires at enrollment and medical records were reviewed for background characteristics and for the following adverse pregnancy outcomes: hypertensive disorders of pregnancy including gestational hypertension, preeclampsia, superimposed preeclampsia, eclampsia and Hemolysis Elevated Liver enzymes and Low Platelets (HELLP) syndrome, gestational diabetes mellitus, and newborns small for gestational age. Associations between adverse pregnancy outcomes and (a) any human papillomavirus, high-risk human papillomavirus and human papillomavirus genotype 16 infection at mid-gestation, (b) multiple genotype infections at mid-gestation, and (c) persisting infections during pregnancy were assessed with univariable and multivariable logistic regression models. Missing covariates were imputed using multiple imputation. RESULTS:At mid-gestation, 40% (377/950) of women were positive for any of the 28 genotypes, 24% (231/950) for high-risk genotypes and human papillomavirus 16 was found in 6% (59/950) of the women. Hypertensive disorders of pregnancy was observed in 9% (83/950), gestational diabetes mellitus in 4% (40/950) and newborns small for gestational age in 7% (67/950). Human papillomavirus infection with any genotype, high-risk or human papillomavirus genotype 16 at mid-gestation was not associated with adverse pregnancy outcomes. No associations were found for multiple genotype infections at mid-gestation or persisting infections. CONCLUSION:In a general population of pregnant women, we found no evidence of human papillomavirus infections during pregnancy being associated with hypertensive disorders of pregnancy, gestational diabetes mellitus, or newborns small for gestational age. TRIAL REGISTRATION:Trial registration The study is registered at ClincialTrials.gov; NCT02449850 on May 19th, 2015.