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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.

PURPOSE OF REVIEW: Iron deficiency (ID) affects one in five children before they reach preschool age. Existing evidence on ID contributing to suboptimal development and neurodevelopmental disorders come mostly from mechanistic and observational studies. Recommendations for screening and treatment are diverging, emphasizing the knowledge gap. The purpose of this review is to summarize recent evidence on ID in infants and children, its possible role in developmental disorders, and effects of iron supplementation.

RECENT FINDINGS: Recent well powered randomized controlled trials showed no effect of early iron supplementation on psychomotor development in infants, neither in populations at high nor low risk of ID. Treatment of nonanemic ID in children 1-3 years did not improve their cognitive scores. Evidence from observational and imaging studies suggests association of brain ID and attention deficit hyperactivity disorder in children (ADHD).

SUMMARY: Universal prophylactic iron supplementation in infants is not supported by current evidence. Whether non anemic ID needs to be treated is uncertain and so is the legitimacy and timing of screening for ID and anemia. The role of ID and iron availability for the brain in pathogenesis of neurodevelopmental conditions such as ADHD requires further studies.

Aim: Neonatal hyperglycaemia is associated with a multitude of adverse outcomes, including mortality and impaired neurological development. The aim of this study was to characterise the current management of neonatal hyperglycaemia in Swedish neonatal units.

Methods: A digital survey was sent to 27 Swedish neonatal units providing care to preterm infants born before 32 completed gestational weeks.

Results: Sixty-eight responses were collected from 21 different units. Thirty-two percent (22/68) of clinicians reported having a local treatment guideline for neonatal hyperglycaemia. Hyperglycaemia was defined as a glucose concentration above a value in the range of 8.0–10.0 mmol/L by 62.5% of clinicians, while 16.7% and 21.8% used a definition between 10.1 and 12.0 mmol/L and > 12 mmol/L, respectively. Intravenous glucose reduction was initiated at higher glucose concentrations by clinicians working at university hospital units (p = 0.006). Glucose concentration threshold for initiation of insulin treatment varied between 8 and 30 mmol/L. Three clinicians (3/35 (8.5%)) reported having experienced problems with frequent hypoglycaemia during ongoing insulin treatment.

Conclusions: This study demonstrates extensive differences in clinical practice regarding neonatal hyperglycaemia both within and between neonatal units in Sweden. Randomised controlled trials are needed to provide evidence for clinical guidelines and to improve and standardise the care of these infants.

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.

Background: Our aim was to evaluate if increased survival and new ventilation strategies were accompanied by a changed incidence of bronchopulmonary dysplasia (BPD) in Sweden over a decade.

Methods: Data from two Swedish population-based studies of live-born infants with gestational age (GA) 22–26 weeks, born during 2004–2007 (n=702) and 2014–2016 (n=885), were compared for survival, any BPD, moderate BPD and severe BPD and the composite outcomes of any BPD or death and severe BPD or death at 36 weeks postmenstrual age (PMA). Ventilation strategies and interventions were analysed. Any BPD was defined as the use of supplemental oxygen or any respiratory support at 36 weeks PMA, moderate BPD as nasal cannula with <30% oxygen and severe BPD as ≽30% oxygen, continuous positive airway pressure (CPAP) or mechanical ventilation.

Results: Survival to 36 weeks PMA increased from 72% to 81% (p<0.001). Total days on mechanical ventilation increased from a median of 9 to 16 days (p<0.001). High-flow nasal cannula (HFNC) was introduced between the cohorts, and days of CPAP and HFNC increased from 44 to 50 days (p<0.001). Any BPD was unchanged at 65% versus 68%. Moderate BPD increased from 37% to 47% (p=0.003), while the incidence of severe BPD decreased from 28% to 23% (p<0.046). Severe BPD or death decreased from 48% to 37% (p<0.001), while any BPD or death remained unchanged at 74% versus 75%.

Conclusion: Even though an increased survival of infants born at 22–26 weeks GA was accompanied by an increased duration of invasive and non-invasive respiratory support, the incidence of any BPD remained unchanged, while severe BPD decreased in infants alive at 36 weeks PMA.

This technical review, one of five developed by the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) special interest group (SIG) on gut microbiota and modifications (GMM), supports the creation of a position paper on the use of biotic-supplemented formulas, including those containing human milk oligosaccharides (HMOs) produced through chemical synthesis or microbial biotechnology. Though these oligosaccharides are identical to the HMOs found in human milk, they do not originate from it. Therefore, we used human-identical milk oligosaccharides (HiMOs). This review focuses on the clinical outcomes related to the supplementation of infant formulas with these HiMOs. The ESPGHAN SIG-GMM conducted a systematic review to evaluate the clinical outcomes of HiMO-supplemented infant formulas in healthy infants (0–12 months) published before 2024. Six RCTs and two mechanistic substudies met the inclusion criteria and investigated different combinations of HiMOs added to the formula. The HiMOs studied so far show no difference compared to the control formula in outcomes such as: anthropometric data, regurgitation-related symptoms, crying, fussiness, or colic. A specific combination of five HMO-analogues (2′fucosyllactose [FL], 3-FL, lacto-N-tetraose [LNT], 3′-sialyllactose [SL], and 6′-SL) suggest a softer stool consistency and more frequent defecation in presumable healthy infants, but these studies also used the highest amount of HiMOs; however, the clinical relevance of this finding remains uncertain. Regarding infection prevention, no clear conclusion can be drawn. There was no difference in tolerability and no safety concerns were raised with the HiMO studied so far. This technical report serves as the background for formulating recommendations on the use of HiMOs-supplemented infant formula in healthy infants studied so far.

A previous guideline on cow's milk allergy (CMA) developed by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) was published in 2012. This position paper provides an update on the diagnosis, treatment, and prevention of CMA with focus on gastrointestinal manifestations. All systematic reviews and meta-analyses regarding prevalence, pathophysiology, symptoms, and diagnosis of CMA published after the previous ESPGHAN document were considered. Medline was searched from inception until May 2022 for topics that were not covered in the previous document. After reaching consensus on the manuscript, statements were formulated and voted on each of them with a score between 0 and 9. A score of ≥6 was arbitrarily considered as agreement. Available evidence on the role of dietary practice in the prevention, diagnosis, and management of CMA was updated and recommendations formulated. CMA in exclusively breastfed infants exists, but is uncommon and suffers from over-diagnosis. CMA is also over-diagnosed in formula and mixed fed infants. Changes in stool characteristics, feeding aversion, or occasional spots of blood in stool are common and in general should not be considered as diagnostic of CMA, irrespective of preceding consumption of cow's milk. Over-diagnosis of CMA occurs much more frequently than under-diagnosis; both have potentially harmful consequences. Therefore, the necessity of a challenge test after a short diagnostic elimination diet of 2–4 weeks is recommended as the cornerstone of the diagnosis. This position paper contains sections on nutrition, growth, cost, and quality of life.

Background: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important structural components of neural cellular membranes and possess anti-inflammatory properties. Very preterm infants are deprived of the enhanced placental supply of these fatty acids, but the benefit of postnatal supplementation on brain development is uncertain. The aim of this study was to test the hypothesis that early enteral supplementation with ARA and DHA in preterm infants improves white matter (WM) microstructure assessed by diffusion-weighted MRI at term equivalent age.

Methods: In this double-blind, randomized controlled trial, infants born before 29 weeks gestational age were allocated to either 100 mg/kg ARA and 50 mg/kg DHA (ARA:DHA group) or medium chain triglycerides (control). Supplements were started on the second day of life and provided until 36 weeks postmenstrual age. The primary outcome was brain maturation assessed by diffusion tensor imaging (DTI) using Tract-Based Spatial Statistics (TBSS) analysis.

Results: We included 120 infants (60 per group) in the trial; mean (range) gestational age was 26+3 (22+6 - 28+6) weeks and postmenstrual age at scan was 41+3 (39+1 - 47+0) weeks. Ninety-two infants underwent MRI imaging, and of these, 90 had successful T1/T2 weighted MR images and 74 had DTI data of acceptable quality. TBSS did not show significant differences in mean or axial diffusivity between the groups, but demonstrated significantly higher fractional anisotropy in several large WM tracts in the ARA:DHA group, including corpus callosum, the anterior and posterior limb of the internal capsula, inferior occipitofrontal fasciculus, uncinate fasciculus, and the inferior longitudinal fasciculus. Radial diffusivity was also significantly lower in several of the same WM tracts in the ARA:DHA group.

Conclusion: This study suggests that supplementation with ARA and DHA at doses matching estimated fetal accretion rates improves WM maturation compared to control treatment, but further studies are needed to ascertain any functional benefit.

Clinical trial registration: www.clinicaltrials.gov; ID:NCT03555019.

Aim: We evaluated the increased centralisation of extremely preterm (EPT) births in Sweden in relation to the changes in mortality and morbidity.

Methods: Population-based data covering Swedish live births from 22 + 0 to 26 + 6 weeks of gestation during 2004–2007 and 2014–2016 were analysed for associations between time-period, birth within (inborn) or outside (outborn) regional centres, and outcomes.

Results: Among 1626 liveborn infants, 703 were born in 2004–2007 and 923 in 2014–2016. Birth outside (vs. within) regional centres was associated with a higher infant mortality even after adjustment for birth cohort, gestational age, birthweight standard deviation score and infant sex (adjusted odds ratio 2.01, 95% confidence interval 1.31–3.07, p = 0.001). The higher 1-year mortality in outborn infants was mainly due to more deaths within 24 h after birth. Outborn infants had a higher incidence of intraventricular haemorrhage grade 3–4 than inborn infants (22% vs. 14% in 2004–2007, and 22% vs. 13% in 2014–2016, both p < 0.05). While survival to 1 year without major morbidity increased in inborn infants (33%–40%, p = 0.008), it remained unchanged in outborn infants (29% vs. 30%, p = 0.88).

Conclusion: Centralisation of EPT births contributed to a lower 1-year mortality in 2014–2016 than that in 2004–2007, attributed to a decrease in deaths before 24 h among inborn infants.