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BACKGROUND: In Sweden, the incidence of necrotising enterocolitis (NEC) in extremely preterm infants has increased from 6 to10% over a decade. We examined whether changes in enteral nutrition during the first 2 weeks were associated with growth and development of NEC.

METHODS: The EXPRESS (2004–2007) and EXPRESS 2 (2014–2016) cohorts included infants <27 gestational weeks. NEC diagnoses were validated. Nutritional data were retrieved from four of the six healthcare regions (n = 815). Growth and NEC incidence were compared between cohorts, and odds ratios (OR) were adjusted for early risk factors in a logistic regression model.

RESULTS: In EXPRESS 2, during the first postnatal week, feeding advancement was more rapid (10 vs. 8 ml/kg/d, p < 0.001) and fortification more common (27% vs. 3.6%, p < 0.001). Growth improved from birth to 28 days (delta z-scores: weight, –2.18 vs. –1.49,p < 0.001; length, –2.22 vs. –1.96, p = 0.013) and to 36 weeks’ postmenstrual age. Neither feeding advancement nor fortification was associated with increased NEC risk >7 d (n = 44; aOR 0.96, 95% CI 0.91–1.01, p = 0.15; aOR 1.33, 95% CI 0.57–2.79, p = 0.50).

CONCLUSION: A more active early enteral nutrition policy in Sweden was associated with faster feeding advancement, earlier fortification, increased protein intake, and improved growth without increased NEC risk.

Objective: To compare neurodevelopmental outcomes in extremely preterm (EPT) children born across two epochs in Sweden.

Design and setting: Nationwide population-based cohorts of infants born at 22–26 weeks’ gestation in 2004–2007 (Cohort 1) and 2014–2016 (Cohort 2), comprising 1606 live births. Survivors were assessed at 2–2.5 years’ corrected age using the same protocol design.

Main outcome: The primary outcome was neurodevelopmental impairment (NDI), defined as a composite of moderate–severe cerebral palsy (CP), visual or hearing deficits, or moderate–severe cognitive, language or motor impairment assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III). For children not assessed with Bayley-III, NDI was defined as moderate–severe speech delay, general developmental delay or categories of CP, vision and hearing impairment. Outcomes were compared using logistic regression to evaluate differences between cohorts and perinatal and socioeconomic risk factors.

Results: Of 1188 eligible survivors, 1062 (89.3%) were assessed (mean gestational age (GA) 24.8 weeks; 54.9% male). The prevalence of moderate–severe NDI at 22, 23, 24, 25 and 26 weeks’ gestation was 60% vs 52%, 51% vs 51%, 34% vs 42%, 27% vs 32% and 17% vs 24% in Cohorts 1 and 2, respectively. Overall prevalence did not differ significantly (27% vs 35%; adjusted OR (AOR) 1.2, 95% CI 0.94 to 1.6). Among 724 (68%) children assessed with Bayley III, Cohort 2 had higher rates of cognitive delay (21.6% vs 11.3%; AOR 1.8, 95% CI 1.1 to 3.4) and language delay (40.9% vs 16.1%; AOR 3.3, 95% CI 1.4 to 4.1). Low GA and maternal country of birth outside the Nordic region were the strongest predictors of NDI and cognitive delay, the latter association confined to Cohort 2.

Conclusion: Although survival of EPT infants in Sweden has improved, long-term neurodevelopmental outcomes have not. The root causes of failed improvements in long-term outcomes for EPT infants are complex and need further clarification.

For many years, biotics (including probiotics, prebiotics, human identical milk oligosaccharides, synbiotics, and postbiotics) have been added to infant formula to influence the gut microbiota of formula-fed infants, aiming to bring it closer to that of breastfed infants. The Special Interest Group on Gut Microbiota and Modifications (SIG-GMM) of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) evaluated clinical outcomes from studies on biotic-supplemented infant formulas. A modified Delphi process was used to establish consensus on recommendations. This document is supported by separately published technical reviews, which synthesize the available evidence, analyze its limitations, and identify research gaps. ESPGHAN SIG-GMM concludes that infant formulas supplemented with one or more of the biotics evaluated so far fed to healthy infants do not raise safety concerns regarding growth, tolerance, and adverse effects. Based on available evidence, for some prebiotics (short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides), a weak recommendation in favor can be formulated because they soften stools by reducing stool consistency, and, to a lesser extent, increase stool frequency in presumed healthy infants. However, due to variability in study designs, intervention types, and measured outcomes, no clear conclusions can be drawn about their overall clinical benefits. Due to differences in interventions (e.g., duration, amount, and composition), inclusion criteria, and primary and secondary outcomes, for most biotics evaluated so far, no recommendations can actually be made “in favor” or “against.” This conclusion may reflect the limited data on specific biotics and outcomes because of the heterogeneity in the randomized controlled trials, rather than an actual lack of effect.

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.

Objectives: The aim of the manuscript is to provide evidence-based or expert consensus-based recommendations for growth assessment and nutritional management of preterm-born infants during the post-discharge period.

Methods: The search was conducted in Pubmed, MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews using the MESH terms: infant, preterm infant, low birth weight, infant food, nutritional status, nutrients, breast feeding, infant formula, human milk, dietary supplements, vitamins, iron, vitamin D, minerals, energy intake, weaning, and baby led. Overall, 402 papers were identified and screened, from which 101 publications were included in the present position paper. In the absence of evidence, recommendations reflect the authors' combined expert opinion. Final consensus was obtained through multiple e-mail exchanges and meetings with the Committee of Nutrition of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition.

Results: Continuous growth monitoring through measurements of weight, length, and HC post-discharge is recommended to identify growth faltering (GF) or undernutrition. To prevent disproportionate growth, weight-for-length z-scores should be included in the assessment when term equivalent age is reached. Infants discharged with a significant drop in weight and length, exceeding a −2 standard deviation loss, require tailored nutritional support to address long-term growth challenges and to support recovery to normal growth rates. Breastfeeding is highly recommended for all infants when feasible. Infants needing to catch up in growth should be given supplements, such as HMF For those fed with formula, an adequate protein: energy ratio, minerals, and trace elements should be supplied to facilitate catch-up growth. The start of solid foods should coincide with the infant's neurological developmental milestones, rather than adhering strictly to a set age. Vitamin D and iron supplementation (with regular ferritin monitoring) is recommended through at least 12 months CA.

Conclusion: For preterm infants, close monitoring of growth after discharge and nutritional assessment is essential to identify those at high risk for GF or undernutrition and to provide individualized nutritional support when needed. These patients should either be referred to a specialized center for pediatric nutritional care or, alternatively, their general pediatrician should receive appropriate training on the subject.

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.

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.

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.