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  • 1.
    Berglund, Staffan K.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Chmielewska, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersson, Ola
    Hepcidin is a relevant iron status indicator in infancy: results from a randomized trial of early vs. delayed cord clamping2021In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 89, no 5, p. 1216-1221Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to evaluate whether serum hepcidin is a useful indicator of iron status in infants.

    Methods: Term infants (n = 400) were randomized to delayed (≥180 s) or early (≤10 s) cord clamping (CC). Iron status was assessed at 4 and 12 months. In all cases with iron depletion or iron deficiency (ID) (as defined in “Methods”) (n = 30) and 97 randomly selected iron-replete infants, we analyzed hepcidin and explored its correlation to the intervention, iron status, and perinatal factors.

    Results: Serum hepcidin concentrations were significantly lower in the early CC group at both time points and in ID infants at 4 months. Median (2.5th–97.5th percentile) hepcidin in non-ID infants in the delayed CC group (suggested reference) was 64.5 (10.9–142.1), 39.5 (3.5–157.7), and 32.9 (11.2–124.2) ng/mL in the cord blood and at 4 and 12 months, respectively. The value of 16 ng/mL was a threshold detecting all cases of iron depletion/ID at 4 months. No similar threshold for ID was observed at 12 months. The strongest predictor of hepcidin at both ages was ferritin.

    Conclusions: Hepcidin is relevant as iron status indicator in early infancy and may be useful to detect ID. Levels <16 ng/mL at 4 months of age indicates ID.

    Impact

    • Serum hepcidin is a relevant indicator of iron status in early infancy.
    • Normal reference in healthy infants is suggested in this study.
    • Serum hepcidin may be useful in clinical practice to detect iron deficiency.
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  • 2.
    Berglund, Staffan K.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Chmielewska, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Starnberg, Josefine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Björn
    Hägglöf, Bruno
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Norman, Mikael
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of iron supplementation of low-birth-weight infants on cognition and behavior at 7 years: a randomized controlled trial2018In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 83, p. 111-118Article in journal (Refereed)
    Abstract [en]

    Background Low-birth-weight infants (LBW) are at an increased risk of iron deficiency that has been associated with impaired neurodevelopment. We hypothesized that iron supplementation of LBW infants improves cognitive scores and reduces behavioral problems until school age.

    Methods We randomized 285 marginally LBW (2,000-2,500 g) infants to receive 0, 1, or 2 mg/kg/day of iron supplements from 6 weeks to 6 months of age. At 7 years of age, 205 participants were assessed regarding cognition using Wechsler Intelligence Scale for Children (WISC-IV) and behavior using the parental questionnaires Child Behavior Checklist (CBCL) and Five to Fifteen (FTF).

    Results There were no significant differences between the intervention groups in WISC-IV or FTF. However, the CBCL scores for externalizing problems were significantly different, in favor of supplemented children (P=0.045). When combining the supplemented groups, they had significantly lower scores for externalizing behavior compared with placebo (median (interquartile range): 44 [34;51] vs. 48.5 [41;56] P=0.013), and their risk ratio (95% confidence interval) for a total behavioral score above the cutoff for clinical problems was 0.31 (0.09-1.0), P=0.054.

    Conclusion Lower scores of externalizing behavior in supplemented children support our previous findings at 3 years, and suggest that iron supplementation may have long-lasting effects on behavioral functions.

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  • 3.
    Bäckström, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Chmielewska, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Berglund, Staffan K.
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Normal range and predictors of serum erythroferrone in infants2023In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 94, no 3, p. 965-970Article in journal (Refereed)
    Abstract [en]

    Background: Erythroferrone (ERFE) has been identified as a hepcidin-regulating hormone synthetized by erythroblasts correlating to the erythropoietic activity and the needs for iron substrate in bone marrow of adults. The present study aimed to assess the ERFE serum concentrations and its predictors in infants.

    Methods: ERFE was explored at 4 time points during the first year of life in 45 healthy, breastfed, normal birth weight (NBW) infants, and 136 marginally low birth weight infants (LBW, 2000–2500 g) receiving iron (N = 58) or placebo (N = 78) between 6 weeks and 6 months of age.

    Results: ERFE concentrations were low at birth, increasing gradually during the first year of life. In NBW infants, reference ranges (5th to 95th percentile) were at 6 weeks <0.005–0.99 ng/mL and at 12 months <0.005–33.7 ng/mL. ERFE was higher in LBW infants at 6 weeks but lower at 12 months compared to NBW and minimally affected by iron supplementation among LBW infants. Correlations of ERFE with erythropoietic and iron status markers were weak and inconsistent.

    Conclusions: The role of ERFE in the crosstalk of erythropoiesis and iron homeostasis remains unclear in infants and further studies on ERFE in infants and older children are warranted within the framework of the erythropoietin–ERFE–hepcidin axis.

    Impact: Normal range of erythroferrone in healthy infants is described for the first time. Erythroferrone in infants lacks correlation to iron status and markers of erythropoiesis. The findings indicate differences in infant regulation of iron homeostasis as compared to adults. The findings point to a need to study infant erythropoiesis separately from its adult counterpart. The findings may have clinical impact on management strategies of iron-loading anemia in infancy.

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  • 4.
    Chmielewska, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Berglund, Staffan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lindberg, Josefine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Mikael, N.
    Westrup, B.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    HEAD GROWTH AND NEURODEVELOPMENT UNTIL 7 YEARS OF AGE: A STUDY IN LOW BIRTH WEIGHT INFANTS2016In: EUROPEAN JOURNAL OF PEDIATRICS, ISSN 0340-6199, Vol. 175, no 11, p. 1485-1485Article in journal (Refereed)
  • 5.
    Chmielewska, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Chmielewski, Grzegorz
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lewandowski, Zbigniew
    Szajewska, Hania
    Effect of iron supplementation on psychomotor development of non-anaemic, exclusively or predominantly breastfed infants: a randomised, controlled trial2015In: BMJ Open, E-ISSN 2044-6055, Vol. 5, no 11, article id e009441Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Uncertainty exists regarding the effects of iron supplementation during infancy on neurodevelopmental outcomes in the absence of anaemia. The aim of the study is to establish whether psychomotor and mental development is influenced by early iron supplementation in healthy, non-anaemic, exclusively or predominantly breastfed infants.

    METHODS AND ANALYSIS: Healthy term infants will be recruited. If exclusively or predominantly breast fed (>50% of daily feedings) and not anaemic at 4 months, they will be randomised to receive either iron pyrophosphate (approximately 1 mg/kg) or placebo daily until 9 months of age. The primary outcome measure is neurodevelopment assessed with the Bayley Scales of Infant and Toddler Development (Bayley-III) at 12 months, and repeated at 24 and 36 months of age. Haematological parameters of iron metabolism also will be measured.

    ETHICS AND DISSEMINATION: The Bioethics Committee of the Medical University of Warsaw approved the study protocol before recruitment started. Study results will be submitted to peer-reviewed journals in the fields of paediatrics and nutrition, and presented at relevant conferences.

    TRIAL REGISTRATION NUMBER: NCT02242188.

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  • 6.
    Chmielewska, Anna
    et al.
    Department of Paediatrics, The Medical University of Warsaw, Dzialdowska 1, Warsaw 01-184, Poland.
    Dziechciarz, Piotr
    Department of Paediatrics, The Medical University of Warsaw, Dzialdowska 1, Warsaw 01-184, Poland.
    Gieruszczak-Białek, Dorota
    Department of Paediatrics, The Medical University of Warsaw, Dzialdowska 1, Warsaw 01-184, Poland.
    Horvath, Andrea
    Department of Paediatrics, The Medical University of Warsaw, Dzialdowska 1, Warsaw 01-184, Poland.
    Pieścik-Lech, Małgorzata
    Department of Paediatrics, The Medical University of Warsaw, Dzialdowska 1, Warsaw 01-184, Poland.
    Ruszczyński, Marek
    Department of Paediatrics, The Medical University of Warsaw, Dzialdowska 1, Warsaw 01-184, Poland.
    Skórka, Agata
    Department of Paediatrics, The Medical University of Warsaw, Dzialdowska 1, Warsaw 01-184, Poland.
    Szajewska, Hania
    Department of Paediatrics, The Medical University of Warsaw, Dzialdowska 1, Warsaw 01-184, Poland.
    Effects of prenatal and/or postnatal supplementation with iron, PUFA or folic acid on neurodevelopment: update2019In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 122, no s1, p. S10-S15Article in journal (Refereed)
    Abstract [en]

    Neurodevelopment has been linked, among other factors, to maternal and early infant diets. The objective of this review, which is part of the NUTRIMENTHE research project 'The effect of diet on the mental performance of children' (www.nutrimenthe.com), was to update current evidence on the effects of nutritional interventions such as iron, folic acid or n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy and/or in early life on the mental performance and psychomotor development of children. In May 2014, we searched MEDLINE and The Cochrane Database of Systematic Reviews for relevant studies published since 2009. The limited updated evidence suggests that iron supplementation of infants may positively influence the psychomotor development of children, although it does not seem to alter their mental development or behaviour. The use of multivitamin-containing folic acid supplements during pregnancy did not benefit the mental performance of the offspring. Evidence from randomised controlled trials (RCT) did not show a clear and consistent benefit of n-3 LCPUFA supplementation during pregnancy and/or lactation on childhood cognitive and visual development. Caution is needed when interpreting current evidence, as many of the included trials had methodological limitations such as small sample sizes, high attrition rates, and no intention-to-treat analyses. Taken together, the evidence is still inconclusive. Large, high-quality RCT to assess the effects of supplementation with iron, LCPUFA or folic acid are still needed to further clarify the effects of these, and other nutrients, on neurodevelopment. Recent recommendations from scientific societies are briefly presented.

  • 7.
    Chmielewska, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Farooqi, Aijaz
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lean Tissue Deficit in Preterm Infants Persists up to 4 Months of Age: Results from a Swedish Longitudinal Study2020In: Neonatology, ISSN 1661-7800, E-ISSN 1661-7819, Vol. 117, no 1, p. 80-87Article in journal (Refereed)
    Abstract [en]

    Background: At term-equivalent age, infants born prematurely are shorter, lighter and have more adipose tissue compared to term counterparts. Little is known on whether the differences in body composition persist in later age. 

    Methods: We prospectively recruited 33 preterm infants (<32 weeks gestational age, mean gestational age 28.1 weeks) and 69 term controls. Anthropometry and body composition (air displacement plethysmography) were monitored up to 4 months of age. Nutrient intakes from preterm infants were collected from clinical records. 

    Results: At 4 months of age preterm infants were lighter and shorter than term controls (mean weight-for-age z-score: –0.73 vs. 0.06, p = 0.001; mean length-for-age z-score: –1.31 vs. 0.29, p < 0.0001). The significantly greater percentage of total body fat seen in preterm infants at term-equivalent age (20.2 vs. 11.7%, p < 0.0001) was no longer observed at 4 months. A deficit of fat-free mass persisted until 4 months of age (fat-free mass at term-equivalent age: 2.71 vs. 3.18 kg, p < 0.0001; at 4 months: 4.3 vs. 4.78 kg, p < 0.0001). The fat mass index and fat-free mass index (taking length into account) did not differ between the groups. Nutrition had little effect on body composition. Higher protein intake at week 2 was a negative predictor of fat-free mass at discharge. 

    Conclusions: At 4 months corrected age, preterm infants were both lighter and shorter than term controls and the absolute fat-free mass deficit remained until this age. Little effect of nutrition on body composition was observed.

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  • 8.
    Chmielewska, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Pediatrics, The Medical University of Warsaw, Warsaw, Poland .
    Piescik-Lech, Malgorzata
    Shamir, Raanan
    Szajewska, Hania
    Systematic review: Early infant feeding practices and the risk of wheat allergy2017In: Journal of Paediatrics and Child Health, ISSN 1034-4810, E-ISSN 1440-1754, Vol. 53, no 9, p. 889-896Article, review/survey (Refereed)
    Abstract [en]

    Aim: Wheat is a common allergen. Early feeding practices (breastfeeding, potentially allergenic foods) might affect the risk of allergy. To systematically evaluate the association between early feeding practices and the risk of wheat allergy and sensitisation. Methods: Five databases were searched for studies of any design up to July 2015. Results: We included seven studies (five observational, low to moderate quality, two randomised controlled trials (RCTs), high quality). The results come from observational studies unless stated otherwise. Longer breastfeeding was associated with wheat allergy (two studies,n = 1847) and sensitisation (one study, n = 3781). Evidence for exclusive breastfeeding was contradictory; longer exclusive breastfeeding wasassociated with either lower (one study, n = 408) or higher (one study, n = 3781) risk of wheat sensitisation. Breastfeeding at gluten introductiondid not affect the risk of wheat allergy (two studies, n = 2581). Introducing cereal ≥7 months of age increased the risk of wheat allergy (onestudy, n = 1612), but results from an RCT (n = 1303) showed no effect. Early introduction of gluten was associated with a reduced risk of wheat sensitisation up to 5 years in one observational study (n = 3781) but not in RCTs (n = 1303). Conclusions: Based on limited evidence, the influence of breastfeeding and an early exposure to gluten on the risk of wheat allergy remain uncertain. There is no evidence supporting breastfeeding at gluten introduction as modifying the risk. Early introduction of gluten might reducethe risk of sensitisation, but currently, no evidence exists that it affects the risk of wheat allergy.

  • 9. Manousou, Sofia
    et al.
    Johansson, Birgitta
    Chmielewska, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Pediatrics, Medical University of Warsaw, Warsaw, Poland.
    Eriksson, Janna
    Gutefeldt, Kerstin
    Tornhage, Carl-Johan
    Eggertsen, Robert
    Malmgren, Helge
    Hulthen, Lena
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nyström Filipsson, Helena
    Role of iodine-containing multivitamins during pregnancy for children’s brain function: protocol of an ongoing randomised controlled trial: the SWIDDICH study2018In: BMJ Open, E-ISSN 2044-6055, Vol. 8, no 4, article id e019945Article in journal (Refereed)
    Abstract [en]

    Introduction: Iodine is essential for normal brain development. Moderate and severe fetal iodine deficiency results in substantial to serious developmental delay in children. Mild iodine deficiency in pregnancy is associated with neurodevelopmental deficits in the offspring, but evidence from randomised trials is lacking. The aim of the Swedish Iodine in Pregnancy and Development in Children study is to determine the effect of daily supplementation with 150 µg iodine during pregnancy on the offspring’s neuropsychological development up to 14 years of age.

    Methods and analysis: Thyroid healthy pregnant women (n=1275: age range 18–40 years) at ≤12 weeks gestation will be randomly assigned to receive multivitamin supplements containing 150 µg iodine or non-iodine-containing multivitamin daily throughout pregnancy. As a primary outcome, IQ will be measured in the offspring at 7 years (Wechsler Intelligence Scale for Children-V). As secondary outcomes, IQ will be measured at 3.5 and 14 years, psychomotor development at 18 months and 7 years, and behaviour at 3.5, 7 and 14 years. Iodine status (urinary iodine concentration) will be measured during pregnancy and in the offspring at 3.5, 7 and 14 years. Thyroid function (thyroid hormones, thyroglobulin), and deiodinase type 2 polymorphisms will be measured during pregnancy and in the offspring at 7 and 14 years. Structural MRI or other relevant structural or functional brain imaging procedures will be performed in a subgroup of children at 7 and 14 years. Background and socioeconomic information will be collected at all follow-up times.

    Ethics and dissemination: This study is approved by the Ethics Committee in Göteborg, Sweden (Diary numbers: 431-12 approved 18 June 2012 (pregnancy part) and 1089-16 approved 8 February 2017 (children follow-up)). According to Swedish regulations, dietary supplements are governed by the National Food Agency and not by the Medical Product Agency. Therefore, there is no requirement for a monitoring committee and the National Food Agency does not perform any audits of trial conduct. The trial will be conducted in accordance with the Declaration of Helsinki. The participating sites will be contacted regarding important protocol changes, both orally and in writing, and the trial registry database will be updated accordingly. Study results will be presented at relevant conferences, and submitted to peer-reviewed journals with open access in the fields of endocrinology, paediatrics and nutrition. After the appropriate embargo period, the results will be communicated to participants, healthcare professionals at the maternal healthcare centres, the public and other relevant groups, such as the national guideline group for thyroid and pregnancy and the National Food Agency.

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  • 10.
    Pieścik-Lech, Małgorzata
    et al.
    Department of Paediatrics, The Medical University of Warsaw, Poland.
    Chmielewska, Anna
    Department of Paediatrics, The Medical University of Warsaw, Poland.
    Shamir, Raanan
    Institute for Gastroenterology, Nutrition and Liver Diseases, Schneider Children’s Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
    Szajewska, Hania
    Department of Paediatrics, The Medical University of Warsaw, Poland.
    Systematic Review: Early Infant Feeding and the Risk of Type 1 Diabetes2017In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 64, no 3, p. 454-459Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: In addition to genetic background, a number of environmental factors have been claimed to influence the development of type 1 diabetes (T1D), including infant diet.

    OBJECTIVE: The aim of the study was to systematically update evidence on the possible relation between early feeding practices and the risk of T1D.

    METHODS: The Cochrane Library, MEDLINE, EMBASE, Web of Science, and CINAHL were searched for studies of any design up to July 2015. MEDLINE and EMBASE were additionally searched in March 2016. The primary outcome measures were the development of T1D or T1D-associated autoimmunity (T1DA).

    RESULTS: Nine publications were identified. Breastfeeding at the time of gluten introduction, as compared to gluten introduction after weaning, did not reduce the risk of developing T1DA or T1D. In children at high risk of developing T1D, except for gluten introduction at 3 months or younger age compared with gluten introduction at older than 3 months, which increased the risk of T1DA, the age of gluten introduction in infants had no effect on the risk of developing T1DA.

    CONCLUSIONS: Current evidence, mainly from observational studies, does not support the claim that early infant feeding practices, such as breastfeeding at gluten introduction or the age of the infant at the time of gluten introduction, may decrease the risk of developing T1D. More robust data are needed from randomized controlled trials.

  • 11. Seliga-Siwecka, Joanna
    et al.
    Chmielewska, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jasinska, Katarzyna
    Effect of targeted vs standard fortification of breast milk on growth and development of preterm infants (<= 32weeks): study protocol for a randomized controlled trial2020In: Trials, E-ISSN 1745-6215, Vol. 21, no 1, article id 946Article in journal (Refereed)
    Abstract [en]

    Background: Human milk is recommended for all very low birth weight infants. Breastmilk is highly variable in nutrient content, failing to meet the nutritional demands of this group. Fortification of human milk is recommended to prevent extrauterine growth retardation and associated poor neurodevelopmental outcome. However, standard fortification with fixed dose multicomponent fortifier does not account for the variability in milk composition. Targeted fortification is a promising alternative and needs further investigation.

    Methods: This randomized controlled trial will recruit preterm infants (≤ 32 weeks of gestation) within the first 7 days of life. After reaching 80 ml/kg/day of enteral feeding, patients will be randomized to receive standard fortification (HMF, Nutricia) or targeted fortification (modular components: Bebilon Bialka, Nutricia—protein; Polycal, Nutricia—carbohydrates; Calogen, Nutricia—lipids). The intervention will continue until 37 weeks of post-conception age or hospital discharge. Parents and outcome assessors will be blinded to the intervention. The primary outcome measure is velocity of weight, length, and head growth until 36 weeks post-conceptional age or discharge. Secondary outcomes include neurodevelopment at 12 months assessed with Bayley Scale of Development III, repeated at 36 months; body composition at discharge and at 4 months; and incidence of necrotizing enterocolitis, sepsis, retinopathy of prematurity, and bronchopulmonary dysplasia.

    Discussion: Targeted fortification has previously been shown as doable in the neonatal intensive care unit context. If it shows to improve growth and neonatal outcome, choosing the targeted fortification as a first line nutritional approach in very low birth weight infants may become a recommendation.

    Trial registration: ClinicalTrials.govNCT03775785, Registered on July 2019.

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  • 12.
    Seliga-Siwecka, Joanna
    et al.
    Department of Neonatology and Neonatal Intensive Care, Medical University of Warsaw, Warszawa, Poland.
    Fiałkowska, Justyna
    Department of Neonatology and Neonatal Intensive Care, Medical University of Warsaw, Warszawa, Poland.
    Chmielewska, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effect of targeted vs. standard fortification of breast milk on growth and development of preterm infants (≤32 weeks): results from an interrupted randomized controlled trial2023In: Nutrients, E-ISSN 2072-6643, Vol. 15, no 3Article in journal (Refereed)
    Abstract [en]

    Human milk is recommended for very low birth weight infants. Their nutritional needs are high, and the fortification of human milk is a standard procedure to optimize growth. Targeted fortification accounts for the variability in human milk composition. It has been a promising alternative to standard fixed-dose fortification, potentially improving short-term growth. In this trial, preterm infants (≤32 weeks of gestation) were randomized to receive human milk after standard fortification (HMF, Nutricia) or tailored fortification with modular components of proteins (Bebilon Bialko, Nutricia), carbohydrates (Polycal, Nutricia), and lipids (Calogen, Nutricia). The intervention started when preterms reached 80 mL/kg/day enteral feeds. Of the target number of 220 newborns, 39 were randomized. The trial was interrupted due to serious intolerance in five cases. There was no significant difference in velocity of weight gain during the supplementation period (primary outcome) in the tailored vs. standard fortification group: 27.01 ± 10.19 g/d vs. 25.84 ± 13.45 g/d, p = 0.0776. Length and head circumference were not significantly different between the groups. We found the feasibility of targeted fortification to be limited in neonatal intensive care unit practice. The trial was registered at clinicaltrials.gov NCT:03775785.

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  • 13.
    Szajewska, Hania
    et al.
    Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland.
    Shamir, Raanan
    Schneider Children’s Medical Center of Israel, Institute of Gastroenterology, Nutrition and Liver Diseases, Petach Tikva, Israel.
    Chmielewska, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stróżyk, Agata
    Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland.
    Zalewski, Bartłomiej M.
    Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland.
    Auricchio, Renata
    Pediatric Section European Laboratory for the Investigation of Food Induced Disease (ELFID), Department of Translation Medical Science, University Federico II, Naples, Italy.
    Koletzko, Sibylle
    Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany; Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland.
    Korponay-Szabo, Ilma R.
    Department of Pediatrics, Faculty of Medicine and Clinical Center, University of Debrecen, Debrecen, Hungary; Celiac Disease Center, Heim Pál Children’s Hospital, Budapest, Hungary.
    Mearin, Luisa
    Department of Pediatrics, Leiden University Medical Center, Willem Alexander Children’s Hospital, Leiden, Netherlands.
    Meijer, Caroline
    Department of Pediatrics, Leiden University Medical Center, Willem Alexander Children’s Hospital, Leiden, Netherlands.
    Ribes-Koninckx, Carmen
    Pediatric Gastroenterology and Hepatology, La Fe University Hospital, Valencia, Spain.
    Troncone, Riccardo
    Pediatric Section European Laboratory for the Investigation of Food Induced Disease (ELFID), Department of Translation Medical Science, University Federico II, Naples, Italy.
    Early Feeding Practices and Celiac Disease Prevention: Protocol for an Updated and Revised Systematic Review and Meta-Analysis2022In: Nutrients, E-ISSN 2072-6643, Vol. 14, no 5, article id 1040Article, review/survey (Refereed)
    Abstract [en]

    Uncertainty remains in regard to when, how, and in what form gluten should be introduced into the diet, particularly of infants genetically predisposed to developing celiac disease (CD). MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials databases will be searched from inception. Randomized controlled trials (RCTs) and observational studies (cohort, case-control, or cross-sectional studies) investigating the association between early feeding practices and the risk of CD and/or CD autoimmunity will be included. In prospective studies, participants will be infants regardless of the risk of developing CD. For retrospective studies, participants will be children or adults with CD or presenting with positive serology indicative of CD. Interventions will be gluten-containing products of any type. Exposures will be breastfeeding and/or the introduction of gluten-containing products of any type. In control groups, there will be no exposure, different degrees of exposure (partial vs. exclusive breastfeeding, different amounts of gluten, etc.), or a placebo. The primary outcome measure will be CD or CD autoimmunity (i.e., anti-transglutaminase or anti-endomysial antibodies). At least two reviewers will independently assess the risk of bias using a validated risk assessment tool depending on study design. Disagreements will be resolved by discussion to achieve a consensus with the involvement of one or more additional reviewers if required. If appropriate, data will be pooled. If not, a narrative synthesis will be performed. The findings will be submitted to a peer-reviewed journal.

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  • 14.
    Szajewska, Hania
    et al.
    Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland.
    Shamir, Raanan
    Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
    Stróżyk, Agata
    Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland.
    Chmielewska, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Zalewski, Bartłomiej M.
    Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland.
    Auricchio, Renata
    Department of Translation Medical Science, Pediatric Section European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy.
    Koletzko, Sibylle
    Dr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital, LMU Munich, Munich, Germany; School of Medicine Collegium Medicum, Department of Pediatrics, Gastroenterology and Nutrition, University of Warmia and Mazury, Olsztyn, Poland.
    Korponay-Szabo, Ilma R.
    Department of Pediatrics, Faculty of Medicine and Clinical Center, University of Debrecen, Debrecen, Hungary; Celiac Disease Center, Heim Pál National Paediatric Institute, Budapest, Hungary.
    Mearin, M. Luisa
    Willem Alexander Children's Hospital, Leiden University Medical Center, Leiden, Netherlands.
    Meijer, Caroline
    Willem Alexander Children's Hospital, Leiden University Medical Center, Leiden, Netherlands.
    Ribes-Koninckx, Carmen
    Pediatric Gastroenterology and Hepatology & Instituto de Investigacion Sanitaria, La Fe University Hospital, Valencia, Spain.
    Troncone, Riccardo
    Department of Translation Medical Science, Pediatric Section European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy.
    Systematic review: early feeding practices and the risk of coeliac disease. A 2022 update and revision2022In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 57, no 1, p. 8-22Article, review/survey (Refereed)
    Abstract [en]

    Background: The effects of early feeding practices on the risk of coeliac disease (CD) remain debated.

    Aims: To update evidence on these practices on the risk of CD and/or CD-related autoimmunity (CDA), defined as anti-transglutaminase or anti-endomysial antibody positivity.

    Methods: We searched MEDLINE, EMBASE and the Cochrane Library to May 2022 for randomised controlled trials (RCTs) and observational studies.

    Results: We included 36 publications (30 studies). In the population at genetic risk of developing CD (HLA DQ2/DQ8-positive), exclusive or any breastfeeding and longer breastfeeding duration did not reduce the risk of developing CD/CDA during childhood. While a meta-analysis of four case–control studies showed a decreased risk for CD when gluten was introduced during breastfeeding, this was not shown in RCTs and cohort studies. Age at gluten introduction was not associated with cumulative CD/CDA risk, although two RCTs suggested that earlier gluten introduction was associated with earlier CDA appearance. Evidence from six observational studies suggests that consumption of a higher amount of gluten at weaning and/or thereafter may increase CD risk. There is insufficient evidence to determine the amount of gluten associated with an increased CD/CDA risk. Regarding whether infant feeding practices modulate the risk conferred by different HLA genotypes results were inconsistent.

    Conclusions: For the population at genetic risk of CD, breastfeeding and age at gluten introduction have no effect on its cumulative incidence during childhood. There is some evidence for an effect of the amount of gluten consumed at weaning and/or thereafter on CD/CDA risk.

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