Effect of Low-Dose Iron Supplementation on Early Development in Breastfed Infants: A Randomized Clinical Trial.

Importance: Breastfed infants are at risk of iron deficiency, which is associated with suboptimal development. There is a paucity of evidence on the effects of iron supplementation on child development, and current guidelines are divergent. Objective: To assess whether daily iron supplementation, 1 mg/kg, between 4 and 9 months in exclusively or predominantly breastfed infants improves psychomotor development at 12 months. Design, Setting, and Participants: This was a randomized, double-blind, placebo-controlled trial conducted between December 2015 and May 2020 with follow-up through May 2023 in an outpatient setting in Poland and Sweden. Participants were healthy singleton infants born at term with birth weight greater than 2500 g who were exclusively or predominantly breastfed (>50%) and did not have anemia (hemoglobin >10.5 g/dL) at age 4 months. Exclusion criteria included major illness, congenital anomaly, food allergy, and difficulty communicating with caregivers. Interventions: Iron (micronized microencapsulated ferric pyrophosphate), 1 mg/kg, or placebo (maltodextrin) once daily from age 4 to 9 months. Main Outcomes and Measures: The primary outcome was psychomotor development assessed by motor score of Bayley Scales of Infant and Toddler Development III at 12 months, adjusted for gestational age, sex, and maternal education. Secondary outcomes included cognitive and language scores at 12 months; motor, cognitive, and language scores at 24 and 36 months; iron deficiency (serum ferritin <12 ng/mL), and iron deficiency anemia (iron deficiency and hemoglobin <10.5 g/dL) at 12 months. Results: Of 221 randomized infants (111 female), 200 (90%) were included in the intention-to-treat analysis (mean [SD] age, 12.4 [0.8] months). Iron supplementation (n = 104) compared to placebo (n = 96) had no effect on psychomotor development (mean difference [MD] for motor score, -1.07 points; 95% CI, -4.69 to 2.55), cognitive score (MD, -1.14; 95% CI, -4.26 to 1.99), or language score (MD, 0.75; 95% CI, -2.31 to 3.82) at 12 months. There were no significant differences at 24 and 36 months. The intervention did not reduce the risk for iron deficiency (relative risk [RR], 0.46; 95% CI, 0.16 to 1.30) or iron deficiency anemia (RR, 0.78; 95% CI, 0.05 to 12.46) at 12 months. Conclusion and Relevance: No benefit was found with daily low-dose iron supplementation between 4 and 9 months with respect to psychomotor development, risk of iron deficiency, or iron deficiency anemia among breastfed infants in a setting of low risk of anemia. Trial Registration: ClinicalTrials.gov Identifier: NCT02242188.

Reevaluating the FDA's warning against the use of probiotics in preterm neonates: A societal statement by ESPGHAN and EFCNI.

The recent advisory issued by the United States Food and Drug Administration, cautioning against the routine administration of probiotics in preterm neonates, has sparked a lively debate within the scientific community. This commentary presents a perspective from members of the Special Interest Group on Gut Microbiota and Modifications within the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and other authors who contributed to the ESPGHAN position paper on probiotics for preterm infants, as well as representatives from the European Foundation for the Care of Newborn Infants. We advocate for a more nuanced and supportive approach to the use of certain probiotics in this vulnerable population, balancing the demonstrated benefits and risks.

Effect of human milk-based fortification in extremely preterm infants fed exclusively with breast milk: a randomised controlled trial.

Background: Mortality and severe morbidity remain high in extremely preterm infants. Human milk-based nutrient fortifiers may prevent serious complications and death. We aimed to investigate whether supplementation with human milk-based fortifier (HMBF), as compared to bovine milk-based fortifier (BMBF), reduced the incidence of the composite outcome of necrotising enterocolitis (NEC), sepsis, and mortality in extremely preterm infants exclusively fed human milk. Methods: In this multicentre, randomised controlled trial at 24 neonatal units in Sweden, extremely preterm infants born between gestational week 22 + 0 and 27 + 6 fed exclusively human breast milk (mother's own and/or donor milk), were randomly assigned (1:1) to receive targeted fortification with either HMBF or BMBF. Randomisation was conducted before the enteral feeds reached 100 mL/kg/day, and was stratified by enrolment site, gestational age, singleton/twin, and sex. The allocation was concealed before inclusion, but after randomisation the study was not blinded for the clinical staff. For the NEC diagnosis, the study group was masked to an independent radiologist, and the final assessment of NEC and culture-proven sepsis was done by a blinded consensus panel review. The primary outcome was the composite of NEC stage II-III, culture-proven sepsis, and mortality from inclusion to discharge, no longer than postmenstrual week 44 + 0, in the intention-to-treat population (ClinicalTrials.gov, NCT03797157). Findings: Between February 21st, 2019, and May 21st, 2021, 229 neonates were randomly assigned (115 HMBF, 114 BMBF). After exclusion of one infant due to parents' withdrawal of consent, 228 infants were included in the intention-to-treat analysis. Of the 115 infants assigned to HMBF, 41 (35.7%) fulfilled the criteria of either NEC, sepsis, or death, compared with 39 (34.5%) of 113 infants assigned to BMBF (OR 1.05, 95% CI 0.61-1.81, p = 0.86). Adverse events did not differ significantly between groups. Interpretation: Supplementation with HMBF, as compared with BMBF, did not reduce the incidence of the composite outcome of NEC, sepsis, or death. Our results do not support routine supplementation with HMBF as a nutritional strategy to prevent NEC, sepsis, or death in extremely preterm infants exclusively fed human milk. Funding: ALF grant, Prolacta Bioscience, Swedish Research Council, and Research Council for Southeast Sweden.

Insulin resistance prior to term age in very low birthweight infants: a prospective study.

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.

An ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow's Milk Allergy.

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.

Iron - a background article for the Nordic Nutrition Recommendations 2023.

Iron absorption from foods is generally lower than that of most other nutrients and is highly variable depending on individual iron status and iron bioavailability in the meal. Several large population groups in the Nordic and Baltic countries are at risk of iron deficiency, including infants, young children, menstruating females, pregnant women as well as vegetarians. Iron deficiency leads to anemia, fatigue, and limited capacity for physical activity. Of particular concern is that iron deficiency anemia in young children is associated with impaired neurodevelopment. A comprehensive literature search has been performed and summarized. New factorial calculations have been performed considering iron losses, iron absorption and iron requirements in various population groups. Recent data on iron intakes and the prevalence of iron deficiency in the Nordic countries are presented. Average requirements and tentative recommended intakes are presented for 12 different population groups. Pregnant women and those with high menstrual blood losses should consume iron-rich food and undergo screening for iron deficiency. Infants should consume iron-rich complementary foods and cow's milk should be avoided as a drink before 12 months of age and limited to < 500 mL/day in toddlers. Vegetarians should consume a diet including wholegrains, legumes, seeds, and green vegetables together with iron absorption enhancers. There is no evidence that iron intake per se increases the risk of cancer or diabetes. Iron absorption from foods is generally lower than that of most other nutrients and can vary between <2 and 50% depending on individual iron status and iron bioavailability in the meal.

Prebiotics in the management of pediatric gastrointestinal disorders: Position paper of the ESPGHAN special interest group on gut microbiota and modifications.

Prebiotics are substrates that are selectively utilized by host microorganisms conferring a health benefit. Compared to probiotics there are few studies with prebiotics in children. Most studies have been performed using infant formula supplemented with prebiotics, while add-on prebiotic supplementation as prevention or treatment of childhood gastrointestinal disorders has rarely been reported. The aim of this position paper was to summarize evidence and make recommendations for prebiotic supplementation in children with gastrointestinal diseases. Recommendations made are based on publications up to January 1, 2023. Within the scope of the European Society for Paediatric Gastroenterology Hepatology and Nutrition Special Interest Group on Gut Microbiota and Modifications, as in our previous biotic recommendations, at least two randomized controlled clinical trials were required for recommendation. There are some studies showing benefits of prebiotics on selected outcomes; however, we cannot give any positive recommendations for supplementing prebiotics in children with gastrointestinal disorders.

Neonatal outcome following metformin-treated gestational diabetes mellitus: A population-based cohort study.

INTRODUCTION: Neonatal hypoglycemia is a common complication associated with gestational diabetes and therefore relevant to consider in evaluations of maternal treatment. We aimed to investigate the risk of neonatal hypoglycemia in offspring exposed to metformin treatment alone (MT) or combined with insulin (MIT) in comparison with nutrition therapy alone (NT), and insulin treatment alone (IT). In addition, we investigated MT in comparison with MIT. Secondary outcomes included neonatal anthropometrics, respiratory morbidity, hyperbilirubinemia, 5-min Apgar score, and preterm birth. MATERIAL AND METHODS: This Swedish population-based cohort included 16 181 women diagnosed with gestational diabetes, and their singleton offspring born in 2019-2021. We estimated risk as adjusted odds ratio (aOR) with 95% confidence interval (CI), using individual-level, linkage register-data in multivariable logistic regression models. RESULTS: In the main analysis, MT was associated with a lower risk of neonatal hypoglycemia vs NT (aOR 0.85, 95% CI: 0.74-0.96), vs MIT (0.74 [0.64-0.87]), and vs IT (0.47 [0.40-0.55]), whereas MIT was associated with a similar risk of neonatal hypoglycemia vs NT (1.14 [0.99-1.30]) and with lower risk vs IT (0.63 [0.53-0.75]). However, supplemental feeding rates were lower for NT vs pharmacological treatments (p < 0.001). In post hoc subgroup analyses including only exclusively breastfed offspring, the risk of neonatal hypoglycemia was modified and similar among MT and NT, and higher in MIT vs NT. Insulin exposure, alone or combined with metformin, was associated with increased risk of being large for gestational age. Compared with NT, exposure to any pharmacological treatment was associated with significantly lower risk of 5-min Apgar score < 4. All other secondary outcomes were comparable among the treatment categories. CONCLUSIONS: The risk of neonatal hypoglycemia appears to be comparable among offspring exposed to single metformin treatment and nutrition therapy alone, and the lower risk that we observed in favor of metformin is probably explained by a difference in supplemental feeding practices rather than metformin per se. By contrast, the lower risk favoring metformin exposure over insulin exposure was not explained by supplemental feeding. However, further investigations are required to determine whether the difference is an effect of metformin per se or mediated by other external factors.

Polychlorinated alkanes in paired blood serum and breast milk in a Swedish cohort study: Matrix dependent partitioning differences compared to legacy POPs.

BACKGROUND: Polychlorinated alkanes (PCAs) constitute a large group of individual congeners originating from commercial chlorinated paraffin (CP) products with carbon chain lengths of PCAs-C10-13, PCAs-C14-17, and PCAs-C18-32, occasionally containing PCAs-C6-9 impurities. The extensive use of CPs has led to global environmental pollution of PCAs. This study aimed to quantify PCAs in paired serum and breast milk of lactating Swedish mothers, exploring their concentration relationship. METHODS: Twenty-five paired samples of mothers' blood serum and breast milk were analysed and concentrations were determined for PCAs C6-32 and compared to 4,4'-DDE, the PCB congener 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), and hexachlorobenzene (HCB). RESULTS: The median concentrations of PCAs-C6-9, PCAs-C10-13, PCAs-C14-17, PCAs-C18-32 and ΣPCAs in serum were 14, 790, 520, 16 and 1350 ng/g lipid weight (lw), respectively, and in breast milk 0.84, 36, 63, 6.0 and 107 ng/g lw. Levels of 4,4'-DDE, CB-153 and HCB were comparable in the two matrices, serum and breast milk at 17, 12 and 4.9 ng/g lw. The results show significant differences of PCAs-C10-13 and PCAs-C14-17 in breast milk with 22- and 6.2-times lower lw-based concentrations than those measured in serum. On wet weight the differences serum/breast milk ratios of PCAs-C6-9, PCAs-C10-13, PCAs-C14-17, PCAs-C18-32 and ΣPCAs were 1.7, 3.2, 1.0, 0.4 and 1.6, respectively, while the ratio for 4,4'-DDE, CB-153 and HCB were each close to 0.1. CONCLUSION: Swedish lactating mothers had high serum concentrations of PCAs-C10-13 and PCAs-C14-17, with the ΣPCAs median serum concentration of 1350 ng/g lw. The breast milk concentration, although considerably lower at 107 ng/g lw, still surpassed those of 4,4'-DDE, CB-153 and HCB, suggesting an exposure risk of infants to PCAs. The variation in blood and breast milk accumulation between PCAs and studied legacy POPs, is rarely discussed but warrants further studies on partitioning properties as well as associated toxicological implications.

Arachidonic and docosahexaenoic acid supplementation and brain maturation in preterm infants; a double blind RCT.

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.

Revised Swedish infant feeding guidelines are associated with earlier introduction of allergenic foods.

BACKGROUND: Randomized controlled trials have demonstrated that early introduction of allergenic foods, such as peanut and egg, can reduce food allergy in high-risk children. Many international guidelines recommend introduction of allergenic foods in the first year of life, and accordingly, the Swedish National Food agency released updated guidelines in June 2019. OBJECTIVE: Our aim was to examine whether the age at introduction and consumption frequency of allergenic foods have changed since release of the revised national guidelines on the introduction of solid foods in Sweden. METHODS: Children born between June 2016 and December 2018 (n = 1925) were compared with children born between June 2019 and April 2021 (n = 1761) by using data from the NorthPop Birth Cohort study. Data on food introduction, eczema, and food allergy were prospectively collected until age 18 months by using web-based questionnaires. IgE sensitization was assessed at 18 age months. RESULTS: The proportion of participants who had been introduced to egg, legume, soy products, peanut, almond, and cashew nut during the first year of life increased after implementation of the revised national guidelines. The most significant changes were seen for legume (from 55.2% to 69.8% [adjusted odds ratio = 1.90 (95% CI = 1.62-2.24)]) and peanut (from 29.2% to 43.2% adjusted odds ratio = 1.87 (95% CI = 1.55-2.24)]); consumption frequency had also increased. No differences in the prevalence of eczema, food allergy, or sensitization to the foods of interest were found. CONCLUSION: Since release of the revised guidelines, infants in the general population are introduced to and consume a variety of allergenic foods earlier and more frequently; however, early manifestations of allergic disease have remained unchanged.

Effect of arachidonic and docosahexaenoic acid supplementation on quality of growth in preterm infants: A secondary analysis of a randomized controlled trial.

BACKGROUND & AIMS: A balanced supply of arachidonic acid (ARA) and docosahexaenoic acid (DHA) may be crucial for quality of growth in preterm infants. This secondary analysis of a randomized controlled trial aimed to determine the effect of enhanced ARA and DHA supplementation on growth and body composition in infants born before 29 weeks of gestation. Furthermore, we aimed to study associations between human milk feeding, growth patterns and body composition. METHODS: The ImNuT-trial randomized 121 infants to receive a daily supplement with medium chain triglycerides (control) or 100 mg/kg ARA and 50 mg/kg DHA (ARA:DHA group) from the second day of life until 36 weeks postmenstrual age. Growth and body composition were evaluated up to 3 months corrected age. RESULTS: The ARA:DHA group showed better linear growth from birth to term equivalent age compared to the control group; mean difference in z score change from birth for length was 0.74 ([95% CI, 0.17-1.3]; p = 0.010). There were no differences in growth and body composition outcomes at 3 months corrected age between the groups. An increase in z score for weight after 36 weeks postmenstrual age and breastfeeding at 3 months corrected age were the strongest positive predictors of fat mass% at 3 months corrected age (both, p < 0.001). CONCLUSION: Early enhanced supplementation of ARA and DHA may be beneficial with respect to somatic growth in very preterm infants. CLINICAL TRIAL REGISTRATION: The trial has been registered on www. CLINICALTRIALS: gov, ID: NCT03555019.

Factors associated with the increased incidence of necrotising enterocolitis in extremely preterm infants in Sweden between two population-based national cohorts (2004-2007 vs 2014-2016).

OBJECTIVE: To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants. DESIGN: Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage ≥II) were validated against hospital records. PATIENTS: All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden. MAIN OUTCOME MEASURES: NEC incidence. RESULTS: The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047). CONCLUSIONS: The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.

Fruit Pouch Consumption Does Not Associate with Early Manifestations of Allergic Disease.

Consumption of acidic fruit pouches in infancy may damage the epithelial barrier in the gastrointestinal tract and is suggested to increase allergy risk. We aimed to explore if a high fruit pouch consumption is associated with a higher incidence of early allergic manifestations. We included 2959 parent-child dyads from the Swedish prospective, population-based NorthPop birth cohort study with parentally reported data on frequency of fruit pouch consumption at 9 months of age, as well as parentally reported eczema, wheeze, physician-diagnosed asthma, and food allergy in the first 18 months of life. Immunoglobulin E levels (IgE) in serum (n = 1792), as response to a food mix and an inhalant mix, were determined at age 18 months. Compared with no consumption, daily consumption of one or more pouches at 9 months of age was associated with inhalant sensitization (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.06-4.87, n = 1792) but did not remain significant in the multivariable adjusted model (aOR 2.08, 95% CI 0.95-4.53, n = 1679). There were no associations between fruit pouch consumption and allergic manifestations at this young age. This study suggests that fruit pouch consumption is not associated with allergic phenotypes or IgE sensitization in early childhood.

A follow up on the feasibility after national implementation of magnesium sulfate for neuroprotection prior to preterm birth.

INTRODUCTION: The risk for brain injury manifested as cerebral palsy is higher in very preterm born children than in term. Prenatal administration of magnesium sulfate (MgSO4 ) has been shown to be neuroprotective and reduces the proportion of very preterm born children later diagnosed with cerebral palsy. A Swedish national clinical practice guideline was implemented in March 2020, stipulating the administration of a single intravenous dose of 6 g MgSO4 1-24 h prior to delivery before gestational age 32+0, aiming for 90% treatment coverage. The aim of this study was to evaluate the feasibility of this new clinical practice guideline in the first year of its implementation. MATERIAL AND METHODS: Data on MgSO4 treatment were collected by reviewing the medical charts of women who gave birth to live born children in gestational age 22+0-31+6 during the period of March 1, 2020 to February 28, 2021, at five Swedish university hospitals. Women with pre-eclampsia, eclampsia, or high elevated liver enzymes low platelets (HELLP) were excluded. RESULTS: A total of 388 women were eligible and 79% received treatment with MgSO4 . Of the 21% not receiving treatment, 9% did not receive treatment due to lack of knowledge about the clinical practice guideline, 9% were not possible to treat and 3% had missing data. The proportion treated increased from 72% to 87% from the first to the last 3 months. Of those treated, 81% received the drug within the stipulated timeframe (mean 8.7 h, median 3.4 h). CONCLUSIONS: There was a positive trend over time in the proportion of women receiving MgSO4 treatment, but the a priori target of 90% was not reached during the first year of implementation. Our findings indicate that this target could be reached with additional information to clinicians.

An ESPGHAN position paper on the diagnosis, management and prevention of cow's milk allergy.

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 1 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.

Genetic Preference for Sweet Taste in Mothers Associates with Mother-Child Preference and Intake.

Taste perception is a well-documented driving force in food selection, with variations in, e.g., taste receptor encoding and glucose transporter genes conferring differences in taste sensitivity and food intake. We explored the impact of maternal innate driving forces on sweet taste preference and intake and assessed whether their children differed in their intake of sweet foods or traits related to sweet intake. A total of 133 single nucleotide polymorphisms (SNPs) in genes reported to associate with eating preferences were sequenced from saliva-DNA from 187 mother-and-child pairs. Preference and intake of sweet-, bitter-, sour-, and umami-tasting foods were estimated from questionnaires. A total of 32 SNP variants associated with a preference for sweet taste or intake at a p-value < 0.05 in additive, dominant major, or dominant minor allele models, with two passing corrections for multiple testing (q < 0.05). These were rs7513755 in the TAS1R2 gene and rs34162196 in the OR10G3 gene. Having the T allele of rs34162196 was associated with higher sweet intake in mothers and their children, along with a higher BMI in mothers. Having the G allele of rs7513755 was associated with a higher preference for sweets in the mothers. The rs34162196 might be a candidate for a genetic score for sweet intake to complement self-reported intakes.

One-year survival and outcomes of infants born at 22 and 23 weeks of gestation in Sweden 2004-2007, 2014-2016 and 2017-2019.

OBJECTIVE: To explore associations between perinatal activity and survival in infants born at 22 and 23 weeks of gestation in Sweden. DESIGN/SETTING: Data on all births at 22 and 23 weeks' gestational age (GA) were prospectively collected in 2004-2007 (T1) or obtained from national registers in 2014-2016 (T2) and 2017-2019 (T3). Infants were assigned perinatal activity scores based on 3 key obstetric and 4 neonatal interventions. MAIN OUTCOME: One-year survival and survival without major neonatal morbidities (MNM): intraventricular haemorrhage grade 3-4, cystic periventricular leucomalacia, surgical necrotising enterocolitis, retinopathy of prematurity stage 3-5 or severe bronchopulmonary dysplasia. The association of GA-specific perinatal activity score and 1-year survival was also determined. RESULTS: 977 infants (567 live births and 410 stillbirths) were included: 323 born in T1, 347 in T2 and 307 in T3. Among live-born infants, survival at 22 weeks was 5/49 (10%) in T1 and rose significantly to 29/74 (39%) in T2 and 31/80 (39%) in T3. Survival was not significantly different between epochs at 23 weeks (53%, 61% and 67%). Among survivors, the proportions without MNM in T1, T2 and T3 were 20%, 17% and 19% for 22 weeks and 17%, 25% and 25% for 23 weeks' infants (p>0.05 for all comparisons). Each 5-point increment in GA-specific perinatal activity score increased the odds for survival in first 12 hours of life (adjusted OR (aOR) 1.4; 95% CI 1.3 to 1.6) in addition to 1-year survival (aOR 1.2; 95% CI 1.1 to 1.3), and among live-born infants it was associated with increased survival without MNM (aOR 1.3; 95% CI 1.1 to 1.4). CONCLUSION: Increased perinatal activity was associated with reduced mortality and increased chances of survival without MNM in infants born at 22 and 23 weeks of GA.

Nutrition and Intestinal Rehabilitation of Children With Short Bowel Syndrome: A Position Paper of the ESPGHAN Committee on Nutrition. Part 2: Long-Term Follow-Up on Home Parenteral Nutrition.

Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The preferred treatment for IF is parenteral nutrition which may be required until adulthood. The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their expertise. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE, and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-center experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached >90% agreement. This second part of the position paper is dedicated to the long-term management of children with SBS-IF. The paper mainly focuses on how to achieve intestinal rehabilitation, treatment of complications, and on possible surgical and medical management to increase intestinal absorption.