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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.

Background: Diet during pregnancy significantly influences maternal and offspring health outcomes, including long-term risk of obesity, cardiovascular disease, asthma, allergic disease and diabetes. Food frequency questionnaires (FFQs) are cost-effective tools for dietary assessment but require validation to ensure accuracy. The objective of this study was to assess the validity of an FFQ developed for pregnant women in the NorthPop Birth Cohort Study (NorthPop) in Sweden.

Methods: Pregnant women (n = 96) were recruited from NorthPop. Nutrient and food group intakes assessed by the FFQ were compared with intakes assessed by three 24-hour dietary recalls (24HR) using group mean comparisons, Spearman correlation coefficients, cross-classification, and Bland-Altman analysis.

Results: The FFQ showed acceptable to very good correlations for most nutrients and food groups. Mean deattenuated correlation coefficients were 0.45 (0.15 to 0.73) for nutrients and 0.55 (0.32 to 0.80) for food groups. Energy adjustment altered individual nutrient correlations, but the overall mean remained unchanged at 0.45 (0.11 to 0.84); however, it reduced the mean correlation for food groups to 0.49 (0.17 to 0.70). Analyses of mean intake, cross-classification, and Bland-Altman plots showed acceptable agreement between the FFQ and the 24HR reference method.

Conclusions: The FFQ evaluated in this study is a valid tool for assessing dietary intake at the group level among pregnant women in the NorthPop cohort. The results support the use of this FFQ to study relationships between diet and disease and to identify dietary factors during pregnancy.

The purpose of the study is to assess the prevalence of glucose disturbances (dysglycemia) in very low birth weight (VLBW) infants at 36 weeks postmenstrual age (PMA) using a continuous glucose monitoring (CGM) system and to identify possible risk factors for these disturbances. A prospective observational cohort study (VLBW Infants—Glucose and Hormonal Profiles over Time; LIGHT) included 35 VLBW infants admitted to a single tertiary neonatal intensive care unit during 2016–2019. Perinatal data were registered prospectively. CGM registration was performed at 36 weeks PMA for a period of 48 h. Protracted hyperglycemia and hypoglycemia were defined as > 30 min with glucose concentrations > 8 mmol/L or < 2.6 mmol/L, respectively. A total of 19,907 measurements were retrieved and analyzed. Protracted dysglycemia was found in 68.6% of infants, with 51% of infants experiencing hyperglycemia (4.5% of registration time) and 40% experiencing hypoglycemia (1.2% of registration time). Male sex was associated with longer time spent in hyperglycemia. Insulin treatment prior to 36 weeks PMA was associated with longer time spent in hypoglycemia. CGM values correlated strongly with capillary glucose measurements, and no values fell within clinically dangerous ranges.

Conclusion: Protracted dysglycemia is common in VLBW infants even at 36 weeks PMA. Identification of risk factors for dysglycemia might help delineate certain patients in need of careful monitoring of glucose concentrations even when nearing term age. CGM is a promising tool for glucose monitoring in the neonatal intensive care unit.

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).

Aim: To describe glucose homeostasis disturbances (dysglycaemia) in very low-birthweight infants (<1500 g) during the admission period and explore associated risk factors.

Methods: The LIGHT (very low-birthweight infants - glucose and hormonal profile over time) study was a prospective observational cohort study that included 49 very low-birthweight infants admitted to the tertiary neonatal intensive care unit in Umeå, Sweden, during 2016–2019. All glucose concentrations (n = 3515) sampled during the admission period were registered.

Results: Hyperglycaemia >10 mmol/L and hypoglycaemia <2.6 mmol/L were registered in 63% and 55% of the infants, respectively. Onset of dysglycaemia occurred almost exclusively in the first postnatal week. Hyperglycaemia followed 15% of corticosteroid doses given; all were preceded by pre-existing hyperglycaemia. Pre-existing hyperglycaemia was found in 66.7% of hyperglycaemic infants who received inotrope treatment. Upon commencement, 72.5% of antimicrobial treatments given were neither preceded nor followed by hyperglycaemia.

Conclusion: Dysglycaemia was common in very low-birthweight infants. Daily means of glucose concentrations seemed to follow a postmenstrual age-dependent pattern, decreasing towards term age suggesting a postmenstrual age-dependent developmental mechanism. The primary mechanism causing hyperglycaemia was independent of sepsis, and corticosteroid and inotrope treatments. No hypoglycaemia was registered during ongoing insulin treatment.

Objective: To evaluate whether implementing a nutritional care bundle is associated with growth and morbidity in very preterm (VPT) infants.

Study design: This study compared 87 VPT infants (<32 gestational weeks) born 2018 (Before group) with 75 infants born 2020 (After group), treated at a single center in the Czech Republic. A nutritional care bundle was implemented during 2019.

Results: Median gestational age (weeks) was 30.0 [IQR 27.6-31.1] for the Before group and 29.9 [IQR 27.9-30.6] for the After group. During postnatal days 1-14, parenteral fluid intake was significantly lower in the After group compared to the Before group and conversely for enteral fluid intake. Infants in the After group achieved full enteral feeds by postnatal day 14 (72.9 % vs. Before group 51.9 %). Weight z-scores decreased significantly less from birth to 36 weeks postmenstrual age in the After group (-0.8 [IQR -1.3 to -0.5]) compared to the Before group (-1.5 [IQR -2.0 to -1.2]). Head circumference z-scores decreased significantly less in the After group (-0.8±0.9) than the Before group (-1.6±1.1). Decreased rate of patent ductus arteriosus (PDA) requiring treatment was observed in the After group (P < 0.001).

Conclusions: Implementation of a nutritional care bundle in VPT infants was associated with improved postnatal growth and may reduce treatment-requiring PDA.

Objectives: Practices for fortifying human milk vary among neonatal intensive care units (NICUs). It is unclear whether enteral energy intake above 140 kcal/kg/day with increased fat supplementation, leads to greater weight gain in breast milk fed extremely preterm infants (EPT).

Methods: Anthropometric and nutritional data were collected from clinical records for Swedish EPT infants born between gestational weeks 26+0 and 27+6. Included infants were treated at NICU A (n=17) or NICU B (n=39). The primary outcome was change in standard deviation scores (ΔSDS) for weight between postmenstrual weeks 29+0 and 34+0.

Results: At birth, the mean gestational age was 26.9 (±0.45 SD) weeks, and the mean birthweight was 969 (±107 SD) grams. Between postmenstrual weeks 29+0 and 33+6, the energy intake was significantly higher at NICU B: mean (SD) 149 (±14.9) vs 132 (±11.2) kcal/kg/day, p=<0.001. This was driven by a higher fat intake at NICU B: mean (SD) 7.97 (±1.05) vs 6.20 (±0.92) grams/kg/day, p=<0.001, which in turn was explained by more liberal use of lipid supplements at NICU B. No significant differences were found in ΔSDS for weight, length, or head circumference between the two NICUs.

Conclusions: Despite considerable differences in energy intake due to the use of enteral lipid supplements, our study showed no differences in ΔSDS for weight, length, or head circumference. This may be due to limited fat absorption in infants already receiving adequate energy and fat, and poor absorption of fat from human donor milk. 

Objective: To explore the glucose-related hormone profile of very low birthweight (VLBW) infants and assess the association between neonatal hyperglycaemia and insulin resistance during the admission period.

Design: A prospective observational study—the Very Low Birth Weight Infants, Glucose and Hormonal Profiles over Time study.

Setting: A tertiary neonatal intensive care unit and four neonatal units in county hospitals in Sweden.

Patients: 48 infants born <1500 g (VLBW) during 2016–2019.

Outcome measures: Plasma concentrations of glucose-related hormones and proteins (C-peptide, insulin, ghrelin, glucagon-like peptide 1 (GLP-1), glucagon, leptin, resistin and proinsulin), insulin:C-peptide and proinsulin:insulin ratios, Homoeostatic Model Assessment 2 (HOMA2) and Quantitative Insulin Sensitivity Check (QUICKI) indices, measured on day of life (DOL) 7 and at postmenstrual age 36 weeks.

Results: Lower gestational age was significantly associated with higher glucose, C-peptide, insulin, proinsulin, leptin, ghrelin, resistin and GLP-1 concentrations, increased HOMA2 index, and decreased QUICKI index and proinsulin:insulin ratio. Hyperglycaemic infants had significantly higher glucose, C-peptide, insulin, leptin and proinsulin concentrations, and lower QUICKI index, than normoglycaemic infants. Higher glucose and proinsulin concentrations and insulin:C-peptide ratio, and lower QUICKI index on DOL 7 were significantly associated with longer duration of hyperglycaemia during the admission period.

Conclusions: VLBW infants seem to have a hormone profile consistent with insulin resistance. Lower gestational age and hyperglycaemia are associated with higher concentrations of insulin resistance markers.

Background & aims: Previous studies have observed changes in fat and fat-free mass among preterm infants when compared to term-born infants. However, these studies have mainly focused on moderate or very preterm infants, with a scope limited to the first few years of life. We aimed to compare body composition in extremely preterm infants to term-born infants in early childhood. Additionally, we investigated whether early neonatal nutrition was associated with the distribution of fat- and fat-free mass in later life.

Methods: The study used dual-energy x-ray absorptiometry to evaluate the body composition of 52 children aged 6–9-years, of whom 35 were born extremely preterm and 17 were born at term and was analyzed using multivariate linear regression. Nutritional intakes of fluids, energy, and macronutrients during the first eight postnatal weeks for 26 extremely preterm infants were investigated in relation to body composition at age 6–9 years using Bayesian regression analysis and Gradient Boosting Machine.

Results: Children born extremely preterm had smaller head circumference (confidence interval −8.7 to −1.7), shorter height (confidence interval −2.7 to −0.6), higher waist to height ratio (confidence interval 0.01–0.05) and lower fat-free mass (confidence interval −3.9 to −0.49), compared to children born at full-term. Children born extremely preterm had a differing response to amount of fluid and macronutrient intake for both fat mass index and fat-free mass index. A bimodal response showed high intake of fluid and macronutrients as associated with high fat mass index for some children, whereas others demonstrated an inverse association, suggesting analysis on cohort-level as problematic.

Conclusions: Childhood body composition differs between extremely preterm infants and term-born infants. Extremely preterm infants display differing responses in their body composition to varying levels of fluids and macronutrient intake during the neonatal period.

Background: Extremely preterm infants, defined as those born before 28 weeks’ gestational age, are a very vulnerable patient group at high risk for adverse outcomes, such as necrotizing enterocolitis and death. Necrotizing enterocolitis is an inflammatory gastrointestinal disease with high incidence in this cohort and has severe implications on morbidity and mortality. Previous randomized controlled trials have shown reduced incidence of necrotizing enterocolitis among older preterm infants following probiotic supplementation. However, these trials were underpowered for extremely preterm infants, rendering evidence for probiotic supplementation in this population insufficient to date.

Methods: The Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial is a multicenter, double-blinded, placebo-controlled and registry-based randomized controlled trial conducted among extremely preterm infants (n = 1620) born at six tertiary neonatal units in Sweden and four units in Denmark. Enrolled infants will be allocated to receive either probiotic supplementation with ProPrems® (Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus) diluted in 3 mL breastmilk or placebo (0.5 g maltodextrin powder) diluted in 3 mL breastmilk per day until gestational week 34. The primary composite outcome is incidence of necrotizing enterocolitis and/or mortality. Secondary outcomes include incidence of late-onset sepsis, length of hospitalization, use of antibiotics, feeding tolerance, growth, and body composition at age of full-term and 3 months corrected age after hospital discharge.

Discussion: Current recommendations for probiotic supplementation in Sweden and Denmark do not include extremely preterm infants due to lack of evidence in this population. However, this young subgroup is notably the most at risk for experiencing adverse outcomes. This trial aims to investigate the effects of probiotic supplementation on necrotizing enterocolitis, death, and other relevant outcomes to provide sufficiently powered, high-quality evidence to inform probiotic supplementation guidelines in this population. The results could have implications for clinical practice both in Sweden and Denmark and worldwide.