Introduction

There is a need for a fast, efficient and safe way to induce tolerance in patients with severe allergic rhinitis. Intralymphatic immune therapy has been shown to be effective.

Methods

Patients with severe birch and timothy allergy were randomized and received three doses of 0.1 ml of birch and 5-grass allergen extracts (10,000 SQ units/ml, ALK-Abello), or birch and placebo or 5-grass and placebo by ultrasound-guided injections into inguinal lymph nodes at monthly intervals. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were evaluated before treatment and after each birch and grass pollen season during three subsequent years. Circulating proportions of T helper subsets and allergen-induced cytokine and chemokine production were analysed by flow cytometry and Luminex.

Results

The three groups reported fewer symptoms, lower use of medication and improved quality of life during the birch and grass pollen seasons each year after treatment at an almost similar rate independently of treatment with one or two allergens. Mild local pain was the most common adverse event. IgE levels to birch decreased, whereas birch-induced IL-10 secretion increased in all three groups. IgG4 levels to birch and timothy and skin prick test reactivity remained mainly unchanged. Conjunctival challenge tests with timothy extract showed a higher threshold for allergen. In all three groups, regulatory T cell frequencies were increased 3 years after treatment.

Conclusions

Intralymphatic immunotherapy with one or two allergens in patients with grass and birch pollen allergy was safe, effective and may be associated with bystander immune modulatory responses.

Background Although controversial, lower maternal intake of n-3 polyunsaturated fatty acid (PUFA) during pregnancy and lower levels of omega-3 PUFA in serum phospholipids during childhood have been related to obesity. The main source of omega-3 PUFA is fatty fish in the diet. Objectives To assess the relationship between overweight/obesity and the intake of fatty fish in maternal diet during pregnancy and in children up to 8 years of age. Methods The prospective cohort All Children in South-East Sweden (ABIS) followed babies from birth to 8 years of age. A total of 6749 children at 5 years of age (boys 52.6%) and 3017 children at 8 years (boys 52.3%) participated. A “fatty-fish index” was constructed on the basis of self-reports of nutritional habits. Results The prevalence of overweight and obesity in children at 5 years were 12.9% and 4.2%, respectively. At 8 years, 12.2% of the children presented overweight and 2.3% obesity. Girls were more affected than boys by overweight/obesity. A higher fish index during pregnancy was not related to overweight/obesity in the children, whereas a higher fish index in the children during the first years of life was related to obesity at 5 and 8 years of age. This relationship disappeared in a multivariable analysis. Maternal body mass index (BMI), maternal education, maternal smoking during pregnancy, birth weight, and physical activity all remained related to overweight/obesity at both 5 and 8 years of age. Conclusion No relationships were found between a lower intake of fatty fish in the diet, neither in mothers during pregnancy nor in early childhood, and increased risk of overweight/obesity.

INTRODUCTION: Four-hour voiding observation with provocation test (VOP) using a scale, a damp detector and ultrasound for determination of residuals, is an easily performed non-invasive method for the evaluation of bladder function in newborns. Neonatal bladder function evaluated with VOP has been described for healthy newborns (HN) but not for children with spinal dysraphism (SD), for whom early bladder evaluation is essential for decisions regarding Clean Intermittent Catheterization and follow-up. The aim of the present study was to describe voiding observation with provocation test in newborns with spinal dysraphism and compare with corresponding data for healthy newborns.

METHODS AND MATERIALS: At a tertiary hospital, a 4 h voiding observation with provocation (VOP) was performed in 50 neonates (22 girls, 28 boys) with spinal dysraphism (37 open SD, 13 closed SD) consecutively evaluated for possible neurogenic bladder-sphincter dysfunction (1998-2019). All newborns with open SD and 4/13 with closed SD had been through postnatal neurosurgery before the test. Mean age was 10 days. Voiding observation was performed during 4 h with visual observation the fourth hour recording behavior and urinary flow (e.g. stream, dribbling). Finally, bladder provocations (e.g. suprapubic compression) were performed, and any leakage was noted. Findings were compared to those of 50 healthy newborns (HN) earlier published (Gladh et al., 2002). There were no significant differences in background data such as gender, age or diuresis between newborns with SD and HN.

RESULTS AND DISCUSSION: Voiding observation with provocation test of children with SD revealed significant differences compared to HN see summary table. Some children with SD had frequent small voids/leakages and low bladder volumes while three had no voiding and high volumes. Leakage during bladder provocation test and not voiding with a stream was not seen in HN but were common in newborns with SD (69% resp. 74%) (p < 0.01). A child with these findings should thus be investigated further. Identifying children needing Clean Intermittent Catheterization is important as well as being able to postpone or refrain from invasive urodynamic studies if not strongly indicated. VOP may give valuable information for these judgements.

CONCLUSION: Newborns with spinal dysraphism differ from healthy newborns in many aspects of bladder function. Bladder function varies between newborns with closed and open spinal dysraphism. Many newborns with spinal dysraphism leak at bladder provocation and void without a stream but healthy newborns do not. Early determination of post-void residuals is mandatory in children with spinal dysraphism and non-invasive VOP gives this information in a standardized way, also adding information on frequency, voiding with a stream and leakage at provocation.

Background: A relationship between overweight and obesity early in life and adolescence has been reported. The aim of this study was to track changes in overweight/obesity in children and to assess risk factors related to the persistence of overweight/obesity between 2.5 and 8 years. Study design: Children who participated in all three follow-ups at 2.5, 5 and 8 years in the prospective cohort All Children in Southeast Sweden (ABIS) (N = 2245, 52.1% boys and 47.9% girls) were classified as underweight, normal, overweight or with obesity, and changes within categories with age were related to risk factors for development of obesity in a multivariate analysis. Results: The prevalence of overweight and obesity between 2.5 and 8 years was 11%-12% and 2%-3%, respectively. Children with normal weight remained in the same category over the years, 86% between 2.5 to 5 years and 87% between 5 and 8 years. Overweight and obesity at 5 and 8 years were positively related to each other (p < 0.0001 for both). High level of TV watching at 8 years and high maternal body mass index (BMI) when the child was 5 years were related to lower probability to a normalized ISO-BMI between 5 and 8 years of age (p < 0.05 for both). Conclusion: Children with ISO-BMI 18.5 to 24.9 remain in that range during the first 8 years of life. Children with overweight early in life gain weight and develop obesity, and children with obesity tend to remain with obesity up to 8 years of age. TV watching and high maternal BMI were related to lower probability to weight normalization between 5 and 8 years of age. A multidisciplinary approach to promote dietary and physical activity changes in the entire family should be used for the treatment and prevention of overweight and obesity in early childhood.

Background: Overweight among children and adolescents related to social inequality, as well as age and gender differences, may contribute to poor self-image, thereby raising important public health concerns. This study explores social inequality in relation to overweight and perception of overweight among 263 boys and girls, age 7 to 17, in Vaxjo, Sweden. Methods: Data were obtained through a questionnaire and from physical measurements of height, weight and waist circumference [WC]. To assess social, age and gender differences in relation to overweight, the independent sample t- and chi-square tests were used, while logistic regression modeling was used to study determinants for perception of overweight. Results: Social inequality and gender differences as they relate to high ISO-BMI [Body Mass Index for children] and WC were associated with low maternal socioeconomic status [SES] among boys less than 13 years [mean age = 10.4; n = 65] and with low paternal education level among boys = 13 years [mean age = 15.0; n = 39] [p less than 0.05]. One suggested explanation for this finding is maternal impact on boys during childhood and the influence of the father as a role model for adolescent boys. The only association found among girls was between high ISO-BMI in girls = 13 years [mean age = 15.0; n = 74] and low paternal occupational status. Concerning perception of overweight, age and gender differences were found, but social inequality was not the case. Among boys and girls less than 13 years, perception of overweight increased only when overweight was actually present according to BMI or WC [p less than 0.01]. Girls = 13 years [mean age = 15.0] were more likely to unrealistically perceive themselves as overweight or "too fat," despite factual measurements to the contrary, than boys [p less than 0.05] and girls less than 13 years [mean age = 10.4; n = 83] [p less than 0.001]. Conclusions: The association between social inequality and overweight in adolescence in this study is age-and gender-specific. Gender differences, especially in perception of overweight, tend to increase with age, indicating that adolescence is a crucial period. When planning interventions to prevent overweight and obesity among children and adolescents, parental SES as well as age and gender-specific differences in social norms and perception of body weight status should be taken into account.

PROBLEM: How maternal allergy affects the systemic and local immunological environment during pregnancy and the immune development of the offspring is unclear.

METHOD OF STUDY: Expression of 40 genes was quantified by PCR arrays in placenta, peripheral blood mononuclear cells (PBMC), and cord blood mononuclear cells (CBMC) from 7 allergic and 12 non-allergic women and their offspring.

RESULTS: Placental gene expression was dominated by a Th2-/anti-inflammatory profile, irrespectively of maternal allergy, as compared to gene expression in PBMC. p35 expression in placenta correlated with fetal Tbx21 (ρ = -0.88, P < 0.001) and IL-5 expression in PBMC with fetal galectin1 (ρ = 0.91, P < 0.001). Increased expression of Th2-associated CCL22 in CBMC preceded allergy development.

CONCLUSIONS: Gene expression locally and systemically during pregnancy was partly associated with the offspring's gene expression, possibly indicating that the immunological milieu is important for fetal immune development. Maternal allergy was not associated with an enhanced Th2 immunity in placenta or PBMC, while a marked prenatal Th2 skewing, shown as increased CCL22 mRNA expression, might contribute to postnatal allergy development.

Background: The influence of maternal allergy on the development of immune responses and allergy in the offspring is not understood.

Objective: To investigate (i) if maternal allergy influences the gene expression locally in placenta, systemically in peripheral blood mononuclear cells (PBMC) and fetally in cord blood mononuclear cells (CBMC), (ii) if the gene expression in the placenta and PBMC influences the gene expression in CBMC and (iii) how the gene expression at birth relates to allergy development during  childhood.

Methods: A real-time PCR array was used to quantify forty immune regulatory genes in placenta, PBMC (gestational week 39) and in CBMC from 7 allergic and 12 non-allergic women and their offspring. Furthermore, quantitative real-time PCR was used to measure mRNA expression of Tbx21, GATA-3, Foxp3, RORC and CCL22 in CBMC, selected based on present PCR array results and previous protein findings in cord blood, in 13 children who developed and 11 children who did not develop allergy during childhood.

Results: The gene expression profile in the placenta revealed a T-helper (Th) 2-/anti-inflammatory environment as compared with gene expression systemically, in PBMC. Maternal allergy was associated with increased expression of p35 in PBMC and CBMC and p40 in placenta. Placental p35 expression correlated with fetal Tbx21 expression (Rho=-0.88, p<0.001) and maternal IL-5 expression in PBMC with fetal Galectin-1 (Rho=0.91, p<0.001) expression. Allergy development in the children was preceded by high mRNA expression of the Th2-associated chemokine CCL22 at birth.

Conclusion and clinical relevance: Gene expression locally and systemically during pregnancy influenced the offspring’s gene expression at birth, indicating an interplay between maternal and fetal immunity. Children developing allergy during childhood had an increased expression of the Th2-associated chemokine CCL22 at birth, indicating a Th2 skewing before disease onset. Maternal allergy was not associated with a Th2-dominance in placenta, PBMC or CBMC.

Background: Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results. Objectives: We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years). Methods: First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age less than 37 weeks) and low birth weight (less than 2500 g) with childhood asthma outcomes. Results: Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P less than. 05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27). Conclusion: Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.

Cord serum (CS) phospholipid fatty acid composition is associated with maternal diet during foetal life, and maternal intake of linoleic acid (LA, C18:2 omega-6) and alpha-linolenic acid (LNA, C18:3 omega-3) has been shown to influence the LA and LNA levels in CS. A possible connection between the increased incidence of atopic diseases and increased intake of LA and decreased intake of LNA in the Western world has been proposed. less thanbrgreater than less thanbrgreater thanThe aim of this study was to explore phospholipid fatty acid proportions and total IgE levels in CS from Swedish children, collected from 1985 to 2005, a period with increasing frequency of allergic diseases in Sweden, and reveal possible changes over time. less thanbrgreater than less thanbrgreater thanPhospholipid fatty acids and total IgE antibodies were analysed with gas chromatography and UniCAP(A (R)) technology, respectively, in 300 CS samples. less thanbrgreater than less thanbrgreater thanThe proportions of LA and LNA decreased significantly from 1985 to 2005 (p andlt; 0.001 for both). However, the LA/LNA ratio did increase (p andlt; 0.001), revealing a relatively larger decrease in LNA than in LA. No correlations were found between omega-6 and omega-3 fatty acids and total IgE antibodies in CS from newborn children. less thanbrgreater than less thanbrgreater thanThe LA/LNA ratio increased (p andlt; 0.001) in cord serum samples collected between 1985 and 2005, and no correlations between fatty acids and total IgE were found.

The increasing allergy prevalence in affluent countries may be caused by reduced microbial stimulation and a decreased dietary ω-3/ω-6 long-chain polyunsaturated fatty acid (LCPUFA) ratio, resulting in an abnormal postnatal immune maturation. The timing of allergy-preventive probiotic and ω-3 LCPUFA interventions is critical, as early-life events occurring during critical windows of immune vulnerability can have long-term impact on immune development. The maternal dietary and microbial environment during pregnancy may programme the immune development of the child. Prenatal environmental exposures may alter gene expression via epigenetic mechanisms, aiming to induce physiological adaptations to the anticipated postnatal environment, but potentially also increasing disease susceptibility in the offspring if exposures are mismatched. Although the importance of fetal programming mostly has been studied in cardiovascular and metabolic disease, this hypothesis is also very attractive in the context of environmentally influenced immune-mediated diseases. This review focuses on how prenatal, perinatal or postnatal ω-3 LCPUFA interventions regulate childhood immune and allergy development, and if synergistic effects may be obtained by simultaneous probiotic supplementation. We propose that combined pre- and postnatal preventive measures may be most efficacious. Increasing knowledge on the immunomodulatory effects of prenatal, perinatal and postnatal interventions will help to direct future strategies to combat the allergy epidemic.