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Background: A novel maternal diet index (MDI), characterizing offspring asthma- and allergy-associated maternal intake during pregnancy was constructed and validated in Healthy Start, USA. This study aims to (1) externally validate the asthma findings from Healthy Start in the NorthPop Birth Cohort Study (NorthPop) in Sweden; and (2) characterize the diet and demographics of the two cohorts.

Methods: The MDI was computed as a weighted combination of seven components associated with offspring allergies and asthma, including vegetables and yogurt (associated with decreased odds) and cold cereals, fried potatoes, juice, red meat, and rice (associated with increased odds). Doctor diagnoses provided childhood asthma incidence and timing. Parametric Weibull time-to-event analysis evaluated associations between the MDI, dichotomized at the median (72.2) for Healthy Start, and offspring asthma.

Results: The NorthPop and Healthy Start mean MDI values differed significantly (p < 0.001) and in NorthPop, only 6.1% had MDI < 72.2. Data from 6446 mother-child dyads in NorthPop yielded a crude hazard ratio (HR) for asthma of 0.70 (95% confidence interval [CI] 0.50–0.98, p = 0.037) and a fully adjusted HR of 0.84 (0.55–1.29; p = 0.428) for MDI > 72.2 versus < 72.2 (n = 4655). The fully adjusted HR for 945 Healthy Start dyads was significant at HR 0.41 (0.29–0.57; p < 0.0001).

Conclusions: Results show that in a population with different maternal dietary patterns and demographics compared to the source population, MDI > 72.2 was not an independent predictor of offspring asthma. Further proof of the utility and generalizability of the MDI needs to be tested in other populations.

Background: Behaviour-based physical intensity evaluation requires rigorous calibration before application in long-term recordings of children's sleep/activity patterns. This study aimed at (i) calibrating activity counts of motor behaviour measured simultaneously with MotionWatch 8 (MW8) and ActiGraph (GT3X) in 3-year-old children, (ii) documenting movement intensities in 30s-epochs at wrist/hip positions, and (iii) evaluating the accuracy of cut-off agreements between different behavioural activities.

Methods: Thirty 3-year-old children of the NorthPop cohort performed six directed behavioural activities individually, each for 8-10 minutes while wearing two pairs of devices at hip and wrist position. These naturally-occurring behaviours were aligned to movement intensities from 'motionless' (watching cartoons) and 'sedentary' (recumbent story listening, sit and handcraft) to 'light activity' (floor play with toys), 'moderate activity' (engaging in a brisk walk) and 'vigorous activity (a sprinting game). Time-keeping was ensured using direct observation by an observer. Receiver-Operating-Curve classification was applied to determine activity thresholds and to assign two composite movement classes.

Results: Activity counts of MW8 and GT3X pairs of wrist-worn (rho = 0.94) and hip-worn (rho = 0.90) devices correlated significantly (p < 0.001). Activity counts at hip position were significantly lower compared to those at the wrist position (p < 0.001), irrespective of device type. Sprinting, floorball/walk and floorplay assigned as 'physically mobile' classes achieved outstanding accuracy (AUC > 0.9) and two sedentary and a motionless activities assigned into 'physically stationary' classes achieved excellent accuracy (AUC > 0.8).

Conclusion: This calibration provides useful cut-offs for physical activity levels of preschool children. Contextual information of behaviour is advantageous over intensity classifications only, because interventions will focus on behaviour-allocated time to reduce a sedentary lifestyle. Our comparative calibration is one step forward to behaviour-based movement guidelines for 3-year-old children.

Introduction: Diet diversity (DD) in infancy may be protective for early food allergy (FA) but there is limited knowledge about how DD incorporating consumption frequency influences FA risk.

Methods: Three measures of DD were investigated in 2060 infants at 6 and/or at 9 months of age within the NorthPop Birth Cohort Study: a weighted DD score based on intake frequency, the number of introduced foods, and the number of introduced allergenic foods. In multivariable logistic regression models based on directed acyclic graphs, associations to parentally reported physician-diagnosed FA at age 9 and 18 months were estimated, including sensitivity and stratified analyses.

Results: High weighted DD scores (24-31p) at age 9 months were associated with 61% decreased odds of FA at age 18 months [OR (95% CI) = 0.39 0.18–0.88] compared with infants with the lowest DD scores (0-17p). The association remained significant after exclusion of early FA cases. Having introduced 13–14 foods at age 9 months, independent of consumption frequency, was associated with 45% decreased odds of FA [OR (95% CI) = 0.55 (0.31–0.98)] compared to having introduced 0–10 foods. When stratifying, significantly reduced odds for FA were seen for children with eczema and for children with no FA history in the family. No association was seen between DD at age 6 months and FA at age 18 months.

Conclusion: A diverse diet at age 9 months may prevent FA at age 18 months. Our results underscore the need for additional investigations on the impact of consumption frequency in infancy.

Background: Early gastrointestinal microbiota establishment is crucial for host metabolism and immune development, with delivery mode and breastfeeding playing key roles. Vaginal delivery promotes colonization by maternal vaginal and gut microbes, while Caesarean section delivery leads to exposures of environmental and skin-derived microbiota. Although maternal contributions have been studied, the role of paternal exposure in shaping infant microbiota remains underexplored. We hypothesized that both parents influence infant microbiota establishment and therefore investigated the contributions of maternal and paternal microbes, as well as delivery mode, on infant oral and fecal microbiota within 48 h of birth and at 1 month of age.

Methods: We analysed the gut and oral microbiota of 264 pregnant women, 261 partners, and 266 infants using 16S rRNA gene amplicon sequencing. α-diversity (Shannon Index) was compared using Wilcoxon tests, and β-diversity (Bray–Curtis dissimilarity) was assessed with PERMANOVA and PERMDISP. Principal component analysis (PCA) based on centered log-ratio (CLR)-transformed genus-level data was used for ordination and visualisation of taxonomic structure. Differentially abundant taxa across niches and delivery modes were identified using Kruskal–Wallis and Wilcoxon tests with false discovery rate (FDR) correction, followed by linear discriminant analysis (LDA). Putative amplicon sequence variant (ASV) sharing between infants and family members was explored using tree-based phylogenetic plots showing taxon presence and relative abundance across sample types. All analyses were performed in R using established packages.

Results: Adults showed significantly higher microbial α-diversity than infants in both gut and oral samples. β-diversity analyses revealed distinct microbial community structures influenced by ecological niches and delivery mode. Within the first 48 h after birth, differential abundance analyses identified Lactobacillus crispatus in meconium and Blautia_A in oral swabs enriched in vaginally delivered infants. L. crispatus also emerged as a key marker of the vaginal microbiota in our cohort-wide comparison, while Blautia, typically a gut-associated genus, was also detected in parental rectal and meconium samples. This co-occurrence may reflect transient microbial seeding during vaginal delivery. However, due to the limited resolution of 16S rRNA gene sequencing, these patterns suggest ecological overlap rather than definitive evidence of vertical transmission.

Conclusions: Our findings demonstrate that delivery mode influences early gut and oral microbiota composition, with vaginal delivery associated with taxa also found in maternal samples. While we observed microbial continuity between infant and parental niches, we could not clearly distinguish partner-specific contributions—likely due to the limited resolution of 16S rRNA gene sequencing. These results highlight the importance of delivery-associated exposures in early microbial development and underscore the need for high-resolution approaches to better resolve microbial acquisition within families.

Aim: To investigate possible differences in neurodevelopment between lockdown-exposed and non-exposed 18-month-old toddlers in Sweden.

Methods: Data were extracted from the prospective NorthPop Birth Cohort Study in Sweden. Neurodevelopment was assessed using the Ages and Stages Questionnaire Third Edition (ASQ-3) and a clinical routine evaluation at the child health care centre for additional validation. Statistical analyses were performed using IBM SPSS Statistics.

Results: More lockdown-exposed toddlers fell below the cut-off score on the ASQ-3 “Gross motor function” assessment at 18 months, compared to the pre-lockdown category (5.1% vs. 3.6%, adjusted p = 0.002). Conversely, fewer lockdown-exposed toddlers failed the fine motor task “Can draw scribble” versus the pre-lockdown category (1.4% vs. 2.4% adjusted p = 0.014).

Conclusions: Toddlers who were lockdown-exposed had lower gross motor function but were more successful in the fine motor task at 18 months.

Objectives: Breast-fed (BF) have lower risk of infections during infancy compared to those formula-fed (FF). A higher content of alpha-lactalbumin (α-lac) in breast milk, which may promote a more favorable gut microbiota, could be one reason. In this study, we evaluated whether increased concentration of α-lac in low-protein infant formula affects the immune response and the incidence of infections during infancy.

Methods: In a double-blinded randomized controlled trial, healthy-term infants (n = 245) received low-protein infant formulas with α-lac-enriched whey (α-lac-EW; 1.75 g protein/100 kcal, 27% α-lac) or casein glycomacropeptide-reduced whey (CGMP-RW; 1.76 g protein/100 kcal, 14% α-lac), or standard formula (SF; 2.2 g protein/100 kcal, 10% α-lac) from 2 to 6 months. BF constituted a reference group. Cytokines and high-sensitivity C-reactive protein (hsCRP) were measured during intervention and infection-related morbidity, and treatment was evaluated until 12 months.

Results: Serum interleukin-6 (IL-6) was lower in BF than in all FF groups during intervention (p < 0.001). No other differences in cytokines (tumor necrosis factor alpha [TNF-α], transforming growth factor beta 1 [TGF-β1], TGF-β2, IL-1, IL-10, IL-12, interferon gamma [INF-γ]) or hsCRP were found among the study groups. Infection-related morbidity did not differ among study groups, except slight differences in the use of antibiotics during (α-lac-EW vs. CGMP-RW [p = 0.008]) and after intervention (α-lac-EW vs. BF [p = 0.016]).

Conclusions: Increased α-lac concentration in low-protein infant formula to levels similar to breast milk did not affect the cytokine profile and had minor effect on infection-related morbidity. The higher IL-6 concentrations in FF than in BF needs further investigation.

Background: Prenatal exposure to maternal asthma may influence DNA methylation patterns in offspring, potentially affecting their susceptibility to later diseases including asthma.

Objective: To investigate the relationship between parental asthma and newborn blood DNA methylation.

Methods: Epigenome-wide association analyses were conducted in 13 cohorts on 7433 newborns with blood methylation data from the Illumina450K or EPIC array. We used fixed effects meta-analyses to identify differentially methylated CpGs (DMCs) and comb-p to identify differentially methylated regions (DMRs) associated with maternal asthma during pregnancy and maternal asthma ever. Paternal asthma was analyzed for comparison. Models were adjusted for covariates and cell-type composition. We examined whether implicated sites related to gene expression analyses in publicly available data for childhood blood and adult lung.

Results: We identified 27 CpGs associated with maternal asthma during pregnancy at False Discovery Rate < 0.05 but none for maternal asthma ever. Two distinct CpGs were associated with paternal asthma. We observed 5 DMRs associated with maternal asthma during pregnancy 3 associated with maternal asthma ever and 13 DMRs associated with paternal asthma. Gene expression analysis using data in blood from 832 children and lung from 424 adults showed associations between identified DMCs using maternal asthma and expression of several genes, including HLA genes and HOXA5, previously implicated in asthma or lung function.

Conclusion: Parental asthma, especially maternal asthma during pregnancy, may be associated with alterations in newborn DNA methylation. These findings might shed light on underlying mechanisms for asthma susceptibility.

Background: Maternal diet during pregnancy is considered a potential modifiable risk factor for allergic diseases in offspring. The dietary inflammatory index (DII) is a tool to assess the inflammatory potential of the diet and has been suggested to be associated with offspring allergy development. Its association with food allergy and immunoglobulin E (IgE) sensitization in children remains understudied.

Methods: This study analyzed 4709 mother-partner-child triads from the NorthPop Birth Cohort in Sweden. Maternal DII scores were calculated from a food frequency questionnaire administered at gestational week 34. Allergy outcomes at 18 months included parent-reported physician-diagnosed food allergy, parent-reported eczema and atopic eczema according to UK Working Party criteria, parent-reported ever wheeze, parent-reported physician-diagnosed asthma, and IgE sensitization to food and airborne allergens. Associations between maternal DII scores (continuous and quartiles) and allergic outcomes were assessed using logistic regression, adjusting for maternal age, allergic heredity, farm living, region of birth, siblings, and education.

Results: At age 18 months, 4.9% of children had physician-diagnosed food allergy, 30.6% had eczema, 11.4% had atopic eczema, 15.9% reported ever wheeze, 4.1% had physician-diagnosed asthma, and 19% were IgE sensitized. No significant associations were found between maternal DII scores and the allergic outcomes of interest.

Conclusion: This large birth cohort study found no association between maternal DII during pregnancy and allergic diseases or IgE sensitization in 18-month-old children, suggesting that a proinflammatory diet during pregnancy does not influence early allergic outcomes. Further research is needed to clarify the role of maternal diet in offspring immune development.

Background: Non-communicable diseases (NCDs) are a global health issue, posing a substantial burden on the individual, community, and public health. The risk of developing NCDs is influenced by a complex interplay between genetic, epigenetic, and environmental factors.

Methods: The NorthPop Birth Cohort Study (NorthPop) constitutes an infrastructure enabling cutting-edge research on the foundational pathways to NCDs in childhood, including allergic diseases and asthma, overweight/obesity, cognitive and neurodevelopmental dysfunction, gastrointestinal disorders, and caries. NorthPop aims at recruiting 10,000 families. Pregnant women and their partners residing in Västerbotten County, Sweden are eligible. Recruitment started in 2016 and is anticipated to end in 2025. Extensive data on parental, fetal and child health outcomes, lifestyle, diet, and environmental exposures are prospectively collected using web-based questionnaires in pregnancy and childhood until the children turn 7 years old. Urine samples are collected from the pregnant woman at gestational age 14–24 weeks. Blood samples are collected at gestational age 28 weeks. Placenta and cord blood are collected at birth. A breast milk sample is collected 1 month postpartum. Blood samples from the children are collected at 18 months and 7 years of age. Oral swabs and fecal samples are collected from the children within 48 h of birth, at 1, 9 and 18 months, 3 and 7 years of age. At age 7 years, children are invited to a follow-up visit, including measurements of weight, height, blood pressure, pulse, hand grip strength, working memory, skin prick test and saliva sampling. Additional measurements, such as sleep–wake and light exposure, and additional biological samples are collected in sub-cohorts. Permission for linkage to medical records and national registers e.g., the Swedish Pregnancy Register, the National Patient Register, the Longitudinal Integration Database for Health insurance and Labor market studies and the Swedish Prescribed Drug Register has been granted.

Discussion: Our multidisciplinary approach allows us to study how early life exposures, as well as parental health and lifestyle, influence future health in the offspring. Our results are anticipated to contribute to the understanding of disease risk and may inform future strategies aimed at risk reduction, highly significant for public health.

Trial registration: Retrospectively registered at Researchweb 11 November 2024 (project number 279272).

Background: Respiratory infections in early life are an identified risk factor for asthma. We hypothesized that infection-prevention measures during the coronavirus disease 2019 (COVID-19) pandemic influenced the risk of respiratory morbidity and aeroallergen sensitization in early childhood. Objective: We compared respiratory morbidity and aeroallergen sensitization in children born before and during the pandemic. Methods: We compared a COVID-19 category (exposed children; n = 1661) to a pre–COVID-19 category (nonexposed children; n = 1676) by using data from the prospective population-based NorthPop Birth Cohort study in Sweden. Data on respiratory morbidity and concomitant medication were retrieved from national registers. Prospectively collected data on respiratory morbidity using web-based questionnaires at 9 and 18 months of age were applied. At age 18 months, serum IgE levels to aeroallergens were determined (n = 1702). Results: The risk of developing any respiratory tract infection (adjusted odds ratio [aOR] = 0.33 [95% CI, 0.26-0.42]), bronchitis (aOR = 0.50 [95% CI, 0.27-0.95]) and croup (aOR = 0.59 [95% CI, 0.37-0.94]) were decreased in the COVID-19 category. The risk of wheeze in the first 9 months was lower in the COVID-19 category (aOR = 0.70 [95% CI, 0.55-0.89]). There were also fewer prescriptions of antibiotics in the COVID-19 category. The prevalence of aeroallergen sensitization was similar between categories. Conclusion: Children born during the COVID-19 pandemic demonstrated significantly decreased risks of respiratory infections and prescribed antibiotics until 18 months of age compared to children born before the COVID-19 pandemic. Whether this will affect the risk of developing asthma in childhood is being followed.