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  • 1. Agostoni, C
    et al.
    Buonocore, G
    Carnielli, VP
    De Curtis, M
    Darmaun, D
    Decsi, T
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, ND
    Fusch, C
    Genzel-Boroviczeny, O
    Goulet, O
    Kalhan, SC
    Kolacek, S
    Koletzko, B
    Lapillonne, A
    Mihatsch, W
    Moreno, L
    Neu, J
    Poindexter, B
    Puntis, J
    Putet, G
    Rigo, J
    Riskin, A
    Salle, B
    Sauer, P
    Shamir, R
    Szajewska, H
    Thureen, P
    Turck, D
    van Goudoever, JB
    Ziegler, EE
    Enteral nutrient supply for preterm infants: commentary from the European society of paediatric gastroenterology, hepatology and nutrition committee on nutrition2010In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 50, no 1, p. 85-91Article in journal (Refereed)
    Abstract [en]

    The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

  • 2. Agostoni, Carlo
    et al.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Infant formulae: from ESPGAN recommendations towards ESPGHAN-coordinated global standards.2005In: Journal of pediatric gastroenterology and nutrition, ISSN 0277-2116, Vol. 41, no 5, p. 580-3Article in journal (Other academic)
  • 3. Andersson, Ola
    et al.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersson, Dan
    Hellstrom-Westas, Lena
    Effect of Delayed vs Early Umbilical Cord Clamping on Iron Status and Neurodevelopment at Age 12 Months A Randomized Clinical Trial2014In: JAMA Pediatrics, ISSN 2168-6203, Vol. 168, no 6, p. 547-554Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Prevention of iron deficiency in infancy may promote neurodevelopment. Delayed cord clamping (DCC) can prevent iron deficiency during the first 6 months of life. However, no data are available on long-term effects on infant outcomes in relation to time for umbilical cord clamping. OBJECTIVE To investigate effects of DCC, as compared with early cord clamping (ECC), on infant iron status and neurodevelopment at age 12 months in a European setting. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 382 full-term infants born after a low-risk pregnancy at a Swedish county hospital. Follow-up at 12 months included evaluation of iron status (ferritin level, transferrin saturation, transferrin receptor level, reticulocyte hemoglobin level, and mean cell volume) and parental assessment of neurodevelopment by the Ages and Stages Questionnaire, second edition (ASQ). INTERVENTIONS Infants were randomized to DCC (>= 180 seconds after delivery) or ECC (<= 10 seconds after delivery). MAIN OUTCOMES AND MEASURES The main outcome was iron status at age 12 months; the secondary outcome was ASQ score. RESULTS In total, 347 of 382 infants (90.8%) were assessed. The DCC and ECC groups did not differ in iron status (mean ferritin level, 35.4 vs 33.6 ng/mL, respectively; P =.40) or neurodevelopment (mean ASQ total score, 229.6 vs 233.1, respectively; P =.42) at age 12 months. Predictors of ferritin levels were infant sex and ferritin in umbilical cord blood. Predictors of ASQ score were infant sex and breastfeeding within 1 hour after birth. For both outcomes, being a boy was associated with lower results. Interaction analysis showed that DCC was associated with an ASQ score 5 points higher among boys (mean [SD] score, 229 [43] for DCC vs 224 [39] for ECC) but 12 points lower among girls (mean [SD] score, 230 [39] for DCC vs 242 [36] for ECC), out of a maximum of 300 points (P =.04 for the interaction term). CONCLUSIONS AND RELEVANCE Delayed cord clamping did not affect iron status or neurodevelopment at age 12 months in a selected population of healthy term-born infants. However, it may not be possible to demonstrate minor effects on neurodevelopment with the size of the study population and the chosen method for assessment. The current data indicate that sex may influence the effects on infant development after DCC in different directions. The magnitude and biological reason for this finding remain to be investigated.

  • 4. Andersson, Ola
    et al.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersson, Dan
    Hellström-Westas, Lena
    Effects of delayed cord clamping on neurodevelopment and infection at four months of age: a randomised trial2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 5, p. 525-531Article in journal (Refereed)
    Abstract [en]

    Aim To investigate the effect that delayed and early umbilical cord clamping have on neurodevelopment, immunoglobulin G (IgG) and symptoms of infection during the first 4months of life.

    Methods Full-term infants (n=382) were randomised to delayed (180sec) or early cord clamping (10sec). The Ages and Stages Questionnaire (ASQ) was used to assess neurodevelopment at 4months. Immunoglobulin G was measured at birth, 23days and 4months. Parents recorded any symptoms indicating infection during the first 4months of life.

    Results The total scores from the ASQ did not differ between groups. However, the delayed cord clamping (DCC) group had a higher mean (SD) score in the problem-solving domain [55.3 (7.2) vs. 53.5 (8.2), p=0.03] at 4months and a lower mean (SD) score in the personal-social domain [49.5 (9.3) vs. 51.8 (8.1), p=0.01]. The IgG level was higher in the DCC group at 23days (11.7 vs. 11.0g/L, p=0.004), but did not differ between the groups at 4months. Symptoms of infection were comparable between the groups.

    Conclusion Delayed cord clamping did not affect overall neurodevelopment or symptoms of infection up to 4months of age, but may have an impact on specific neurodevelopmental domains.

  • 5. Andersson, Ola
    et al.
    Hellstrom-Westas, Lena
    Andersson, Dan
    Clausen, Jesper
    Domellof, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling: a randomized trial2013In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 5, p. 567-574Article in journal (Refereed)
    Abstract [en]

    Objective. To investigate the effect of delayed cord clamping (DCC) compared with early cord clamping (ECC) on maternal postpartum hemorrhage (PPH) and umbilical cord blood gas sampling. Design. Secondary analysis of a parallel-group, single-center, randomized controlled trial. Setting. Swedish county hospital. Population. 382 term deliveries after a low-risk pregnancy. Methods. Deliveries were randomized to DCC (>= 180 seconds, n = 193) or ECC (<= 10 seconds, n = 189). Maternal blood loss was estimated by the midwife. Samples for blood gas analysis were taken from one umbilical artery and the umbilical vein, from the pulsating unclamped cord in the DCC group and from the double-clamped cord in the ECC group. Samples were classified as valid when the arterial-venous difference was -0.02 or less for pH and 0.5 kPa or more for pCO(2). Main outcome measures. PPH and proportion of valid blood gas samples. Results. The differences between the DCC and ECC groups with regard to PPH(1.2%, p = 0.8) and severe PPH(-2.7%, p = 0.3) were small and non-significant. The proportion of valid blood gas samples was similar between theDCC (67%, n = 130) and ECC (74%, n = 139) groups, with 6% (95% confidence interval: -4%-16%, p = 0.2) fewer valid samples after DCC. Conclusions. Delayed cord clamping, compared with early, did not have a significant effect on maternal postpartum hemorrhage or on the proportion of valid blood gas samples. We conclude that delayed cord clamping is a feasible method from an obstetric perspective.

  • 6. Andersson, Ola
    et al.
    Hellstrom-Westas, Lena
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Elective caesarean: does delay in cord clamping for 30 s ensure sufficient iron stores at 4 months of age? A historical cohort control study2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 11, article id e012995Article in journal (Refereed)
    Abstract [en]

    Objective: To compare iron stores in infants born after elective caesarean section (CS) and a 30 s delay of umbilical cord clamping with those born vaginally after early (<= 10 s) or delayed (>= 180 s) cord clamping. Design: Prospective observational study with historical control. Setting: Swedish county hospital. Population: 64 infants born after elective CS were compared with a historical control of 166 early clamped and 168 delayed clamped after vaginal birth. Methods: Blood and iron status were measured in blood samples collected at birth, 48-96 hours after birth, 4 and 12 months of age. Primary and secondary outcome measures: Ferritin at 4 months of age was the primary outcome, second outcome measures were other indicators of iron status, and haemoglobin, at 4 and 12 months of age, as well as respiratory distress at 1 and 6 hours after birth. Results: At 4 months infants born by elective CS had better iron status than those born vaginally subjected to early cord clamping, shown by higher adjusted mean difference of ferritin concentration (39 mu g/L (95% CI 10 to 60)) and mean cell volume (1.8 fL (95% CI 0.6 to 3.0)); and lower levels of transferrin receptors (-0.39 mg/L (95% CI -0.69 to -0.08)). No differences were seen between infants born after elective CS and delayed clamped vaginally born infants at 4 months. No differences were found between groups at 12 months of age. Conclusions: Waiting to clamp the umbilical cord for 30 s after elective CS results in higher iron stores at 4 months of age compared with early cord clamping after vaginal birth, and seems to ensure iron status comparable with those achieved after 180 s delayed cord clamping after vaginal birth.

  • 7. Andersson, Ola
    et al.
    Hellström-Westas, Lena
    Andersson, Dan
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial2011In: BMJ. British Medical Journal (International Ed.), ISSN 0959-8146, E-ISSN 0959-535X, Vol. 343, p. d7157-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the effects of delayed umbilical cord clamping, compared with early clamping, on infant iron status at 4 months of age in a European setting.

    DESIGN: Randomised controlled trial.

    SETTING: Swedish county hospital.

    PARTICIPANTS: 400 full term infants born after a low risk pregnancy.

    INTERVENTION: Infants were randomised to delayed umbilical cord clamping (≥180 seconds after delivery) or early clamping (≤10 seconds after delivery).

    MAIN OUTCOME MEASURES: Haemoglobin and iron status at 4 months of age with the power estimate based on serum ferritin levels. Secondary outcomes included neonatal anaemia, early respiratory symptoms, polycythaemia, and need for phototherapy.

    RESULTS: At 4 months of age, infants showed no significant differences in haemoglobin concentration between the groups, but infants subjected to delayed cord clamping had 45% (95% confidence interval 23% to 71%) higher mean ferritin concentration (117 μg/L v 81 μg/L, P<0.001) and a lower prevalence of iron deficiency (1 (0.6%) v 10 (5.7%), P=0.01, relative risk reduction 0.90; number needed to treat=20 (17 to 67)). As for secondary outcomes, the delayed cord clamping group had lower prevalence of neonatal anaemia at 2 days of age (2 (1.2%) v 10 (6.3%), P=0.02, relative risk reduction 0.80, number needed to treat 20 (15 to 111)). There were no significant differences between groups in postnatal respiratory symptoms, polycythaemia, or hyperbilirubinaemia requiring phototherapy.

    CONCLUSIONS: Delayed cord clamping, compared with early clamping, resulted in improved iron status and reduced prevalence of iron deficiency at 4 months of age, and reduced prevalence of neonatal anaemia, without demonstrable adverse effects. As iron deficiency in infants even without anaemia has been associated with impaired development, delayed cord clamping seems to benefit full term infants even in regions with a relatively low prevalence of iron deficiency anaemia. Trial registration Clinical Trials NCT01245296.

  • 8. Andersson, Ola
    et al.
    Lindquist, Barbro
    Lindgren, Magnus
    Stjernqvist, Karin
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hellstrom-Westas, Lena
    Effect of Delayed Cord Clamping on Neurodevelopment at 4 Years of Age: A Randomized Clinical Trial2015In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 169, no 7, p. 631-638Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Prevention of iron deficiency in infancy may promote neurodevelopment. Delayuci umbilical cord clamping (CC) prevents iron deficiency at 4 to 6 months of age, but long-term effects after 12 months of age have not been reported. OBJECTIVE To investigate the effects of delayed CC compared with early CC on neurodevelopment at 4 years of age. DESIGN, SETTING, AND PARTICIPANTS Follow-up of a randomized clinical trial conducted from April 16, 2008, through May 21, 2010, at a Swedish county hospital. Children who were included in the original study (n = 382) as full-term infants born after a low-risk pregnancy were invited to return for follow-up at 4 years of age. Wechsler Preschool and Primary Scale of Intelligence (WPPSI-111) and Movement Assessment Battery for Children (Movement ABC) scores (collected between April 18, 2012, and July 5, 2013) were assessed by a blinded psychologist. Between April 11, 2012, and August 13, 2013, parents recorded their child's development using the Ages and Stages Questionnaire, Third Edition (ASQ) and behavior using the Strengths and Difficulties Questionnaire. All data were analyzed by intention to treat. INTERVENTIONS Randomization to delayed CC (>= 180 seconds after delivery) or early CC (<= 10 seconds after delivery). MAIN OUTCOMES AND MEASURES The main outcome was full-scale IQ as assessed by the were development as assessed by the scales from the WPPSI-III and Movement ABC, development as recorded using the ASQ, and behavior using the Strengths and Difficulties Questionnaire. RESULTS We assessed 263 children (68.8%). No differences were found in WPPSI-III scores between groups. Delayed CC improved the adjusted mean differences (AMDs) in the ASQ personal-social (AMD, 2.8; 95% Cl, 0.8-4.7) and fine-motor (AMD, 2.1; 95% Cl, 0.2-4.0) domains and the Strengths and Difficulties Questionnaire prosocial subscale (AMD, 0.5; 95% Cl, >0.0-0.9). Fewer children in the delayed-CC group had results below the cutoff in the ASQ fine-motor domain (11.0% vs 3.7%; P =.02) and the Movement ABC bicycle-trail task (12.9% vs 3.8%; P =.02). Boys who received delayed CC had significantly higher AMDs in the WPPSI-III processing-speed quotient (AMD, 4.2; 95% Cl, 0.8-7.6; P =.02), Movement ABC bicycle-trail task (AMD, 0.8; 95% Cl, 0.1-1.5; P =.03), and fine-motor (AMD, 4.7; 95% Cl, 1.0-8.4; P =.01) and personal-social (AMD, 4.9; 95% Cl, 1.6-8.3; P =.004) domains of the ASQ. CONCLUSIONS AND RELEVANCE Delayed CC compared with early CC improved scores in the fine-motor at 4 years of age, especially in boys, indicating that optimizing the time to CC may affect neurodevelopment in a low-risk population of children born in a high-income country.

  • 9. Arslanoglu, Sertac
    et al.
    Corpeleijn, Willemijn
    Moro, Guido
    Braegger, Christian
    Campoy, Cristina
    Colomb, Virginie
    Decsi, Tamas
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fewtrell, Mary
    Hojsak, Iva
    Mihatsch, Walter
    Molgaard, Christian
    Shamir, Raanan
    Turck, Dominique
    van Goudoever, Johannes
    Donor Human Milk for Preterm Infants: Current Evidence and Research Directions2013In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 57, no 4, p. 535-542Article in journal (Other academic)
    Abstract [en]

    The Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition aims to document the existing evidence of the benefits and common concerns deriving from the use of donor human milk (DHM) in preterm infants. The comment also outlines gaps in knowledge and gives recommendations for practice and suggestions for future research directions. Protection against necrotizing enterocolitis is the major clinical benefit deriving from the use of DHM when compared with formula. Limited data also suggest unfortified DHM to be associated with improved feeding tolerance and with reduced cardiovascular risk factors during adolescence. Presence of a human milk bank (HMB) does not decrease breast-feeding rates at discharge, but decreases the use of formula during the first weeks of life. This commentary emphasizes that fresh own mother's milk (OMM) is the first choice in preterm infant feeding and strong efforts should be made to promote lactation. When OMM is not available, DHM is the recommended alternative. When neither OMM nor DHM is available, preterm formula should be used. DHM should be provided from an established HMB, which follows specific safety guidelines. Storage and processing of human milk reduces some biological components, which may diminish its health benefits. From a nutritional point of view, DHM, like HM, does not meet the requirements of preterm infants, necessitating a specific fortification regimen to optimize growth. Future research should focus on the improvement of milk processing in HMB, particularly of heat treatment; on the optimization of HM fortification; and on further evaluation of the potential clinical benefits of processed and fortified DHM.

  • 10. Askelöf, Ulrica
    et al.
    Andersson, Ola
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fasth, Anders
    Hallberg, Boubou
    Hellström-Westas, Lena
    Pettersson, Karin
    Westgren, Magnus
    Wiklund, Ingela E.
    Götherström, Cecilia
    Wait a minute?: An observational cohort study comparing iron stores in healthy Swedish infants at 4 months of age after 10-, 60-and 180-second umbilical cord clamping2017In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 12, article id e017215Article in journal (Refereed)
    Abstract [en]

    Background and objective: Umbilical cord blood (UCB) is a valuable stem cell source used for transplantation. Immediate umbilical cord (UC) clamping is widely practised, but delayed UC clamping is increasingly advocated to reduce possible infant anaemia. The aim of this study was to investigate an intermediate UC clamping time point and to evaluate iron status at the age of 4 months in infants who had the UC clamped after 60 s and compare the results with immediate and late UC clamping.

    Design: Prospective observational study with two historical controls.

    Setting: A university hospital in Stockholm, Sweden, and a county hospital in Halland, Sweden.

    Methods: Iron status was assessed at 4 months in 200 prospectively recruited term infants whose UC was clamped 60 s after birth. The newborn baby was held below the uterine level for the first 30 s before placing the infant on the mother's abdomen for additional 30 s. The results were compared with data from a previously conducted randomised controlled trial including infants subjected to UC clamping at <= 10 s (n= 200) or >= 180 s (n= 200) after delivery.

    Results: After adjustment for age differences at the time of follow- up, serum ferritin concentrations were 77, 103 and 114 mu g/L in the 10, 60 and 180 s groups, respectively. The adjusted ferritin concentration was significantly higher in the 60 s group compared with the 10 s group (P=0.002), while the difference between the 60 and 180 s groups was not significant (P=0.29).

    Conclusion: In this study of healthy term infants, 60 s UC clamping with 30 s lowering of the baby below the uterine level resulted in higher serum ferritin concentrations at 4 months compared with 10 s UC clamping. The results suggest that delaying the UC clamping for 60 s reduces the risk for iron deficiency.

  • 11. Bentsen, Beint
    et al.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Finkel, Yigael
    Fläring, Urban
    Torp Hansen, Kari
    Kok, Karin
    Moltu, Sissel
    Petrini, Pia
    Thomassen, Rut Anne
    Pediatrisk parenteral nutrition.: Nordisk handbok.2010In: Pediatrisk parenteral nutrition.: Nordisk handbok. / [ed] Yigael Finkel, Uppsala: Fresenius Kabi , 2010Chapter in book (Refereed)
  • 12.
    Berglund, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Barns järnbehov och hur vi bäst kan skydda barnhjärnan2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 11, p. 460-463Article in journal (Refereed)
  • 13.
    Berglund, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Meeting iron needs for infants and children2014In: Current opinion in clinical nutrition and metabolic care, ISSN 1363-1950, E-ISSN 1473-6519, Vol. 17, no 3, p. 267-272Article, review/survey (Refereed)
    Abstract [en]

    Purpose of reviewIron deficiency early in life is associated with impaired neurological development. This study reviews the latest research on how to best meet iron requirements in infants and children.Recent findingsThere is concurrent evidence that delayed cord clamping is well tolerated and improves infant iron stores. Iron supplements or enriched complementary foods starting before 6 months of life do not reduce iron deficiency prevalence in low-risk populations. However, for low birth weight infants, iron supplements before 6 months of life have long-term benefits. Iron deficiency anaemia (IDA) during the second half year of life is rare in countries with high compliance to iron-rich complementary foods, but remains a major problem globally. In high-risk populations, iron supplementation reduces IDA and possibly improves growth. However, increased risk of infections is a concern and optimal preventive strategies have not yet been determined. Finally, there is concurrent evidence that iron supplementation of anaemic school-aged children reduces IDA and possibly improves neuropsychological outcomes.SummaryInterventions for prevention of iron deficiency should be prioritized in risk groups. However, the unclear long-term benefits and possible risk of adverse effects, particularly increased infections in developing countries, prompt further large-scale, double-blinded trials.

  • 14.
    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.

  • 15.
    Berglund, Staffan K.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Björn, Matias
    Lindberg, Josefine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Björn
    Norman, Mikael
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Marginally low birth weight increases the risk of underweight and short stature at three and a half years of age2016In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 105, no 6, p. 610-617Article in journal (Refereed)
    Abstract [en]

    AIM: Little is known about the long-term health of marginally low birth weight (LBW) children. This study characterised growth among infants weighing 2,000g-2,500g and explored the prevalence and predictors of sustained growth restriction.

    METHOD: This prospective observational trial followed the weight and height of 281 Swedish marginally LBW children from birth to 3.5 years of age. Children with a standard deviation score (SDS) for body mass index or height below -2 were considered underweight and short respectively.

    RESULTS: The mean SDS for weight and height showed a rapid increase before 12-19 weeks of age. The most rapid weight gain was in infants born small for gestational age. However, at 3.5 years of age, 9.5% of the children remained underweight and 6.5% had short stature. Regression models showed that slow weight gain before 19 weeks of age was the strongest predictor for lasting underweight, while slow height gain before 19 weeks of age and male sex were associated with short stature.

    CONCLUSION: Marginally LBW infants were more likely to be underweight and have a short stature at 3.5 years of age and the absence of catch-up growth during the first five months after birth identified those at highest risk.

  • 16.
    Berglund, Staffan K
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lindberg, Josefine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Bjorn
    Department of Women and Child Health, Division of Neonatology, Karolinska Institute, Stockholm, Sweden.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of iron supplements and perinatal factors on fetal hemoglobin disappearance in LBW infants2014In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 76, no 5, p. 477-482Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:The homeostatic mechanisms of iron metabolism and erythropoiesis in infants are unclear. Infants synthesize both fetal hemoglobin (HbF) and adult hemoglobin (HbA), and it is not known how the hemoglobin switch is regulated. We hypothesized that iron supplements to infants affect the disappearance of HbF. METHODS: We randomized 285 low-birth-weight infants (2,000-2,500g) into three intervention groups receiving 0, 1, or 2 mg/kg/d of iron supplements from 6 wk to 6 mo of age. In the present secondary analysis, we analyzed iron status, total hemoglobin (Hb), and HbF fraction at 6 wk, 12 wk, and at 6 mo and calculated absolute levels of HbF. RESULTS: We observed dose-dependent increased levels of Hb in iron-supplemented groups at 6 mo of age. However, for absolute HbF concentration, there was no similar effect of intervention. Mean (SD) HbF was 81.2 (16.8), 37.0 (13.8), and 8.1 (5.6) g/l at 6 wk, 12 wk, and 6 mo, respectively, similar in all groups. In linear regression analyses, postconceptional age turned out as the major predictor of HbF, independent of gestational age at birth. CONCLUSION: Our hypothesis was rejected. Instead, we confirmed a close correlation to postconceptional age, supporting a genetically programmed switch, insensitive to most environmental factors including birth.

  • 17.
    Berglund, Staffan K
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Björn
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Iron Supplementation Until 6 Months Protects Marginally Low-Birth-Weight Infants From Iron Deficiency During Their First Year of Life2015In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, no 3, p. 390-395Article in journal (Refereed)
    Abstract [en]

    Objectives: Low-birth-weight (LBW) infants (<2500 g) have an increased risk of iron deficiency (ID) during their first 6 months of life. The optimal dose and duration of iron supplementation to LBW infants are, however, unknown. The objective of the present study was to investigate the long-term effect on iron status and growth in marginally LBW (2000-2500 g) infants, of iron supplements given until 6 months of life. Methods: In a randomized controlled trial, 285 healthy marginally LBW infants received 0, 1, or 2 mg . kg(-1).day(-1) of iron supplements from 6 weeks to 6 months of age: At 12 months and 3.5 years of life we measured length, weight, head circumference, and indicators of iron status (hemoglobin, ferritin, mean corpuscular volume, and transferrin saturation) and assessed the prevalence of iron depletion, functional ID, and ID anemia. Results: At 12 months of age, there was a significant difference in ferritin between the groups (P = 0.00 6). Furthermore, there was a significant difference in the prevalence of iron depletion (23.7%, 10.6%, and 6.8%, respectively, in the placebo, 1-mg, and 2-mg groups, P = 0.009) and similar nonsignificant trends for functional ID and ID anemia. At 3.5 years of life there were no significant differences in iron status and the mean prevalence of iron depletion was 3.2%. Anthropometric data were not affected by the intervention. Conclusions: Iron supplements with 2 mg . kg(-1) . day(-1) until 6 months of life effectively reduces the risk of ID during the first 12 months of life and is an effective intervention for preventing early ID in marginally LBW infants.

  • 18.
    Berglund, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    The Department of Nutrition, University of California, Davis, CA, USA.
    Westrup, Björn
    The Department of Women and Child Health, Division of Neonatology, Karolinska Institute, Stockholm, Sweden.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of iron supplementation on serum hepcidin and serum erythropoietin in low-birth-weight infants2011In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 94, no 6, p. 1553-1561Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The iron-regulatory hormone hepcidin has not been studied in infants, who experience large physiologic changes in iron status. OBJECTIVE: The objective was to study hepcidin and erythropoietin and their correlation with iron status in iron-replete and iron-deficient low-birth-weight (LBW) infants-a group at particular risk of iron deficiency (ID). DESIGN: We randomly assigned 285 otherwise healthy LBW infants to receive, from 6 wk to 6 mo of age, 3 doses of iron supplements: 0 (placebo), 1, or 2 mg/kg daily. Hepcidin, erythropoietin, hemoglobin, and variables of iron status were analyzed. RESULTS: Serum hepcidin did not change over time in the placebo group, despite a rapid decrease in serum ferritin. In iron-supplemented infants, hepcidin increased significantly, reaching a mean (±SD) concentration of 19.2 ± 2.5 ng/mL in the 2-mg/kg group compared with 13.0 ± 2.6 ng/mL in the placebo group at age 6 mo (P < 0.001). The difference was even larger between iron-deficient and iron-replete infants. Hepcidin was independently positively correlated with ferritin at all ages and was negatively correlated with the transferrin receptor concentration at age 6 wk and with transferrin at age 6 mo. Erythropoietin was initially similar between groups but decreased significantly in iron-supplemented infants. In addition to being negatively correlated with hemoglobin, it was also independently negatively correlated with indicators of iron status. CONCLUSIONS: Hepcidin is closely associated with iron status and may be a useful indicator of iron stores and ID in infants. Erythropoietin is negatively correlated with iron status, which suggests a feedback mechanism that needs further study. This trial is registered at clinicaltrials.gov as NCT00558454.

  • 19.
    Berglund, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Bjorn
    Department of Women and Child Health, Karolinska Institute, SE-182 88 Stockholm, Sweden.
    Haraldsson, Elisabet
    Department of Audiology, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
    Engstrom, Berit
    Department of Audiology, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
    Domellof, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of iron supplementation on auditory brainstem response in marginally LBW infants2011In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 70, no 6, p. 601-606Article in journal (Refereed)
    Abstract [en]

    LBW infants are at risk of iron deficiency (ID), which is associated with impaired nervous system development and may lead to prolonged auditory brainstem response (ABR) latencies. We hypothesized that iron supplementation shortens ABR latencies in marginally LBW (MLBW, 2000-2500 g) infants. In a randomized, controlled trial, 285 healthy MLBW infants received 0, 1, or 2 mg iron/kg/d of iron supplements from 6 wk to 6 mo of age. ABR absolute wave V latencies and central conduction time (CCT) were measured at the endpoint. There were no significant differences between groups in ABR wave V latencies (n = 218). Furthermore, there were no significantly prolonged ABR latencies in infants with ID (n = 32). CCT was significantly higher in the 2 mg group than in the placebo group (n = 126). However, there were no significant correlations between CCT and iron intake or any iron status variable, suggesting that differences in CCT were not caused by iron. We conclude that iron supplements did not improve ABR latencies, and iron-deficient MLBW infants did not have impaired ABR latencies at 6 mo, suggesting that ABR is not a sensitive measure of impaired neurological development or that mild/moderate ID causes no such impairment in MLBW infants.

  • 20.
    Berglund, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Björn
    Department of Women and Child Health, Division of Neonatology, Karolinska Institute, Stockholm, Sweden.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Iron supplements reduce the risk of iron deficiency anemia in marginally low birth weight infants2010In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 126, no 4, p. e874-e883Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Low birth weight infants are at risk for iron deficiency (ID). Most LBW infants have marginally low birth weight (MLBW, 2000–2500 g) and it is not known whether they benefit from iron supplements. The objective of this trial was to study the effects of iron supplementation in MLBW infants.

    METHOD: In a randomized controlled trial, we assigned 285 healthy, MLBW infants to receive iron supplements at a dose of 0 (placebo), 1, or 2 mg/kg per day between 6 weeks and 6 months of age. Hemoglobin levels, ferritin levels, transferrin saturation, mean cell volume, and transferrin receptor levels were analyzed at 6 months. Growth and morbidity were monitored.

    RESULTS: Iron supplementation resulted in significant dose-dependent effects on hemoglobin and all iron status indicators at 6 months. The prevalence of ID at 6 months was 36% in the placebo group, 8.2% in the 1 mg/kg per day group, and 3.8% in the 2 mg/kg per day group (P < .001). The prevalence rates of ID anemia (IDA) were 9.9%, 2.7%, and 0%, respectively (P = .004). Among infants who were exclusively breastfed at 6 weeks, the prevalence of IDA was 18% in the placebo group. There were no significant differences between groups in growth or morbidity.

    CONCLUSIONS: MLBW infants have relatively high risks of ID and IDA, especially if they are breastfed. Iron supplementation at 2 mg/kg per day from 6 weeks to 6 months reduces this risk effectively, with no short-term adverse effects on morbidity or growth.

  • 21.
    Berglund, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Björn
    Division of Neonatology, Department of Women and Child Health, Karolinska Institute, Stockholm, Sweden.
    Hägglöf, Bruno
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of iron supplementation of LBW infants on cognition and behavior at 3 years2013In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 131, p. 47-55Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Low birth weight (LBW) infants are at increased risk of cognitive and behavioral problems and at risk for iron deficiency, which is associated with impaired neurodevelopment. We hypothesized that iron supplementation of LBW infants would improve cognitive scores and reduce behavioral problems. METHODS: In a randomized controlled trial, 285 marginally LBW (2000-2500 g) infants received 0, 1, or 2 mg/kg/day of iron supplements from 6 weeks to 6 months of age. At 3.5 years of age, these infants and 95 normal birth weight controls were assessed with a psychometric test (Wechsler Preschool and Primary Scale of Intelligence) and a questionnaire of behavioral problems (Child Behavior Checklist; CBCL). RESULTS: There were no significant differences in IQ between the LBW groups or LBW infants versus controls. Mean (SD) full-scale IQ was 105.2 (14.5), 104.2 (14.7), and 104.5 (12.7) in the placebo, 1 mg, and 2 mg groups, respectively (P = .924). However, for behavioral problems, there was a significant effect of intervention. The prevalence of children with CBCL scores above the US subclinical cutoff was 12.7%, 2.9%, and 2.7% in the placebo, 1-mg, and 2-mg groups, respectively (P = .027), compared with 3.2% in controls. Relative risk (95% confidence interval) for CBCL score above cutoff in placebo-treated children versus supplemented was 4.5 (1.4-14.2). CONCLUSIONS: Early iron supplementation of marginally LBW infants does not affect cognitive functions at 3.5 years of age but significantly reduces the prevalence of behavioral problems. The study suggests a causal relation between infant iron deficiency and later behavioral problems.

  • 22. Bhatia, Jatinder
    et al.
    Griffin, Ian
    Anderson, Diane
    Kler, Neelam
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Selected macro/micronutrient needs of the routine preterm infant2013In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 162, no 3, p. S48-S55Article in journal (Refereed)
    Abstract [en]

    Requirements for optimal nutrition, especially for micronutrients, are not well defined for premature infants. The "reference fetus," developed by Ziegler et al,(1) has served as a model to define nutritional needs and studies designed to determine nutrient requirements. Revision of nutrient requirements and provision of optimal nutrition may lead to improved outcomes in preterm infants. Appropriate provision of nutrients also may help prevent nutritional disorders, such as metabolic bone disease and anemia. In this review, we discuss calcium, phosphorus, magnesium, vitamin D, iron, and copper, and define optimal intakes based on the available published data. (J Pediatr 2013;162:S48-55).

  • 23.
    Björkström, Markus V
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hall, Lina
    Söderlund, Stina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Håkansson, Eva Grahn
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Håkansson, Stellan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Intestinal flora in very low-birth weight infants2009In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 98, no 11, p. 1762-1767Article in journal (Refereed)
    Abstract [en]

    AIM: To study the early faecal microbiota in very low-birth weight infants (VLBW, <1500 g), possible associations between faecal microbiota and faecal calprotectin (f-calprotectin) and to describe the faecal microbiota in cases with necrotizing enterocolitis (NEC) before diagnosis. METHODS: Stool samples from the first weeks of life were analysed in 48 VLBW infants. Bacterial cultures were performed and f-calprotectin concentrations were measured. In three NEC cases, cultures were performed on stool samples obtained before diagnosis. RESULTS: Bifidobacteria and lactobacilli were often identified in the first stool sample, 55% and 71% of cases, respectively within the first week of life. A positive correlation between lactic acid bacteria (LAB) and volume of enteral feed was found. Other bacteria often identified were Escherichia coli, Enterococcus and Staphyloccus sp. F-calprotectin was not associated with any bacterial species. All NEC cases had an early colonization of LAB. Prior to onset of disease, all cases had a high colonization of non-E. coli Gram-negative species. CONCLUSION: In contrast to the previous studies in VLBW infants, we found an early colonization with LAB. We speculate that this may be due to early feeding of non-pasteurized breast milk.

  • 24. Bonamy, Anna-Karin Edstedt
    et al.
    Mohlkert, Lilly-Ann
    Hallberg, Jenny
    Liuba, Petru
    Fellman, Vineta
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Norman, Mikael
    Blood Pressure in 6-Year-Old Children Born Extremely Preterm2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 8, article id e005858Article in journal (Refereed)
    Abstract [en]

    Background-Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. Methods and Results-We measured casual blood pressures (BPs) in a population-based cohort of 6-year-old survivors of extremely preterm birth (< 27 gestational weeks; n=171) and in age-and sex-matched controls born at term (n=172). Measured BP did not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow-up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week-longer gestation. Conclusions-Six-year-old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow-up at older age is warranted.

  • 25. Braegger, Christian
    et al.
    Campoy, Cristina
    Colomb, Virginie
    Decsi, Tamas
    Domellof, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fewtrell, Mary
    Hojsak, Iva
    Mihatsch, Walter
    Molgaard, Christian
    Shamir, Raanan
    Turck, Dominique
    van Goudoever, Johannes
    Vitamin D in the Healthy European Paediatric Population2013In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 56, no 6, p. 692-701Article in journal (Refereed)
    Abstract [en]

    In recent years, reports suggesting a resurgence of vitamin D deficiency in the Western world, combined with various proposed health benefits for vitamin D supplementation, have resulted in increased interest from health care professionals, the media, and the public. The aim of this position paper is to summarise the published data on vitamin D intake and prevalence of vitamin D deficiency in the healthy European paediatric population, to discuss the health benefits of vitamin D and to provide recommendations for the prevention of vitamin D deficiency in this population. Vitamin D plays a key role in calcium and phosphate metabolism and is essential for bone health. There is insufficient evidence from interventional studies to support vitamin D supplementation for other health benefits in infants, children, and adolescents. The pragmatic use of a serum concentration >50 nmol/L to indicate sufficiency and a serum concentration <25 nmol/L to indicate severe deficiency is recommended. Vitamin D deficiency occurs commonly among healthy European infants, children, and adolescents, especially in certain risk groups, including breast-fed infants, not adhering to the present recommendation for vitamin D supplementation, children and adolescents with dark skin living in northern countries, children and adolescents without adequate sun exposure, and obese children. Infants should receive an oral supplementation of 400 IU/day of vitamin D. The implementation should be promoted and supervised by paediatricians and other health care professionals. Healthy children and adolescents should be encouraged to follow a healthy lifestyle associated with a normal body mass index, including a varied diet with vitamin D-containing foods (fish, eggs, dairy products) and adequate outdoor activities with associated sun exposure. For children in risk groups identified above, an oral supplementation of vitamin D must be considered beyond 1 year of age. National authorities should adopt policies aimed at improving vitamin D status using measures such as dietary recommendations, food fortification, vitamin D supplementation, and judicious sun exposure, depending on local circumstances.

  • 26. Bronsky, J.
    et al.
    Campoy, C.
    Braegger, C.
    Braegger, Christian
    Bronsky, Jiri
    Cai, Wei
    Campoy, Cristina
    Carnielli, Virgilio
    Darmaun, Dominique
    Decsi, Tamas
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, Nicholas
    Fewtrell, Mary
    Fidler Mis, Natasa
    Franz, Axel
    Goulet, Olivier
    Hartman, Corina
    Hill, Susan
    Hojsak, Iva
    Iacobelli, Silvia
    Jochum, Frank
    Joosten, Koen
    Kolacek, Sanja
    Koletzko, Berthold
    Ksiazyk, Janusz
    Lapillonne, Alexandre
    Lohner, Szimonetta
    Mesuiten, Dieter
    Mihalyi, Krisztina
    Mihatsch, Walter A.
    Mimouni, Francis
    Molgaard, Christian
    Moltu, Sissel J.
    Nomayo, Antonia
    Picaud, Jean Charles
    Prell, Christine
    John, Puntis
    Arieh, Riskin
    Saenz De Pipaon, Miguel
    Senterre, Thibault
    Shamir, Raanan
    Simchowitz, Venetia
    Szitanyi, Peter
    Tabbers, Merit M.
    Van Den Akker, Chris H. B.
    Van Goudoever, Johannes B.
    Van Kempen, Anne
    Ver-Bruggen, Sascha
    Wu, Jiang
    Weihui, Yan
    ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Vitamins2018In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 37, no 6, p. 2366-2378Article in journal (Refereed)
  • 27. Bronsky, Jiri
    et al.
    Campoy, Cristina
    Embleton, Nicholas
    Fewtrell, Mary
    Mis, Nataša Fidler
    Gerasimidis, Konstantinos
    Hojsak, Iva
    Hulst, Jessie
    Indrio, Flavia
    Lapillonne, Alexandre
    Molgaard, Christian
    Moltu, Sissel Jennifer
    Verduci, Elvira
    Vora, Rakesh
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Palm Oil and Beta-palmitate in Infant Formula: A Position Paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition2019In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 68, no 5, p. 742-760Article in journal (Refereed)
    Abstract [en]

    Background: Palm oil (PO) is used in infant formulas in order to achieve palmitic acid (PA) levels similar to those in human milk. PA in PO is esterified predominantly at the SN-1,3 position of triacylglycerol (TAG), and infant formulas are now available in which a greater proportion of PA is in the SN-2 position (typical configuration in human milk). As there are some concerns about the use of PO, we aimed to review literature on health effects of PO and SN-2-palmitate in infant formulas. Methods: PubMed and Cochrane Database of Systematic Reviews were systematically searched for relevant studies on possible beneficial effects or harms of either PO or SN-2-palmitate in infant formula on various health outcomes. Results: We identified 12 relevant studies using PO and 21 studies using SN-2-palmitate. Published studies have variable methodology, subject characteristics, and some are underpowered for the key outcomes. PO is associated with harder stools and SN-2-palmitate use may lead to softer stool consistency. Bone effects seem to be short-lasting. For some outcomes (infant colic, faecal microbiota, lipid metabolism), the number of studies is very limited and summary evidence inconclusive. Growth of infants is not influenced. There are no studies published on the effect on markers of later diseases. Conclusions: There is insufficient evidence to suggest that PO should be avoided as a source of fat in infant formulas for health reasons. Inclusion of high SN-2-palmitate fat blend in infant formulas may have short-term effects on stool consistency but cannot be considered essential.

  • 28. Bruun, Signe
    et al.
    Gouveia-Figueira, Sandra
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Husby, Steffen
    Jacobsen, Lotte Neergaard
    Michaelsen, Kim F.
    Fowler, Christopher J
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Zachariassen, Gitte
    Satiety Factors Oleoylethanolamide, Stearoylethanolamide, and Palmitoylethanolamide in Mother's Milk Are Strongly Associated with Infant Weight at Four Months of Age: data from the Odense Child Cohort2018In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 10, no 11, article id 1747Article in journal (Refereed)
    Abstract [en]

    Regulation of appetite and food intake is partly regulated by N-acylethanolamine lipids oleoylethanolamide (OEA), stearoylethanolamide (SEA), and palmitoylethanolamide (PEA), which induce satiety through endogenous formation in the small intestine upon feeding, but also when orally or systemic administered. OEA, SEA, and PEA are present in human milk, and we hypothesized that the content of OEA, SEA, and PEA in mother's milk differed for infants being heavy (high weight-for-age Z-score (WAZ)) or light (low WAZ) at time of milk sample collection. Ultra-high performance liquid chromatography-mass spectrometry was used to determine the concentration of OEA, SEA, and PEA in milk samples collected four months postpartum from mothers to high (n = 50) or low (n = 50) WAZ infants. Associations between OEA, SEA, and PEA concentration and infant anthropometry at four months of age as well as growth from birth were investigated using linear and logistic regression analyses, adjusted for birth weight, early infant formula supplementation, and maternal pre-pregnancy body mass index. Mean OEA, SEA, and PEA concentrations were lower in the high compared to the low WAZ group (all p < 0.02), and a higher concentration of SEA was associated with lower anthropometric measures, e.g., triceps skinfold thickness (mm) (β = -2.235, 95% CI = -4.04, -0.43, p = 0.016), and weight gain per day since birth (g) (β = -8.169, 95% CI = -15.26, -1.08, p = 0.024). This raises the possibility, that the content of satiety factors OEA, SEA, and PEA in human milk may affect infant growth.

  • 29.
    Buttner, Barbara E.
    et al.
    Department of Food Science, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Witthoft, Cornelia M.
    Department of Food Science, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effect of type of heat treatment of breastmilk on folate content and pattern2014In: Breastfeeding medicine, ISSN 1556-8253, Vol. 9, no 2, p. 86-91Article in journal (Refereed)
    Abstract [en]

    Background: Breastmilk is the recommended aliment for preterm infants. Milk banks provide donated breastmilk for the neonatal care of preterm infants when mother's own milk is not is available. To avoid pathogen transmission, donated breastmilk is heat-treated according to different procedures before administration. There is varying information on the effect of heat treatment on folate in breastmilk. Sufficient folate intake, however, is essential for normal growth and brain development. This study determined and compared the effects of different heat treatments on breastmilk folate content and pattern of individual folate forms. Materials and Methods: Donated Swedish breastmilk samples were heat-treated according to three procedures: two low temperature treatments (57 degrees C, 23 minutes; 62.5 degrees C, 12 minutes) and a rapid high temperature treatment (heating to 73 degrees C in boiling water). The folate content and pattern were determined before and after treatment by high-performance liquid chromatography. Results: The folate content in 38 untreated Swedish breastmilk samples was 15046nmol/L. Two different folate vitamers were detected: 5-methyltetrahydrofolate (78 +/- 7%) and tetrahydrofolate (22 +/- 7%). Heat treatment affected only tetrahydrofolate stability and decreased folate content by 15-24%; however, the effects on folate content did not differ among the investigated heat treatment procedures. Conclusions: Folate losses during heat treatment of human milk were considered acceptable. Yet, native folate content of heat-treated, non-fortified breastmilk supplied only 25% of the recommended daily intake for preterm infants.

  • 30.
    Challis, Pontus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Larsson, Linn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stoltz Sjöström, Elisabeth
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Serenius, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Elfvin, Anders
    Validation of the diagnosis of necrotising enterocolitis in a Swedish population-based observational study2019In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, no 5, p. 835-841Article in journal (Refereed)
    Abstract [en]

    Aim: The definition of necrotising enterocolitis (NEC) is based on clinical and radiological signs that can be difficult to interpret. The aim of the present study was to validate the incidence of NEC in the Extremely Preterm Infants in Sweden Study (EXPRESS)

    Methods: The EXPRESS study consisted of all 707 infants born before 27 + 0 gestational weeks during the years 2004–2007 in Sweden. Of these infants, 38 were recorded as having NEC of Bell stage II or higher. Hospital records were obtained for these infants. Furthermore, to identify missed cases, all infants with a sudden reduction of enteral nutrition, in the EXPRESS study were identified (n = 71). Hospital records for these infants were obtained. Thus, 108 hospital records were obtained and scored independently by two neonatologists for NEC.

    Results: Of 38 NEC cases in the EXPRESS study, 26 were classified as NEC after validation. Four cases not recorded in the EXPRESS study were found. The incidence of NEC decreased from 6.3% to 4.3%.

    Conclusion: Validation of the incidence of NEC revealed over- and underestimation of NEC in the EXPRESS study despite carefully collected data. Similar problems may occur in other national data sets or quality registers.

  • 31.
    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)
  • 32.
    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, ISSN 2044-6055, 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.

  • 33. Dewey, Kathryn G
    et al.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Cohen, Roberta J
    Landa Rivera, Leonardo
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Iron supplementation affects growth and morbidity of breast-fed infants: results of a randomized trial in Sweden and Honduras.2002In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 132, no 11, p. 3249-3255Article in journal (Refereed)
    Abstract [en]

    Iron supplements are often prescribed during infancy but their benefits and risks have not been well documented. We examined whether iron supplements affect growth or morbidity of breast-fed infants. Full-term infants in Sweden (n = 101) and Honduras (n = 131) were randomly assigned to three groups at 4 mo of age: 1) placebo from 4 to 9 mo; 2) placebo from 4 to 6 mo and iron supplements [1 mg/(kg. d)] from 6 to 9 mo; or 3) iron supplements from 4 to 9 mo. All infants were exclusively or nearly exclusively breast-fed to 6 mo and continued to be breast-fed to at least 9 mo. Growth was measured monthly and morbidity data were collected every 2 wk. Among the Swedish infants, gains in length and head circumference were significantly lower in those who received iron than in those given placebo from 4 to 9 mo. The same effect on length was seen in Honduras, but only at 4-6 mo among those with initial hemoglobin (Hb) > or =110 g/L. There was no significant main effect of iron supplementation on morbidity, nor any significant interaction between iron supplementation and site, but for diarrhea (with both sites combined), there was an interaction between iron supplementation and initial Hb. Among infants with Hb < 110 g/L at 4 mo, diarrhea was less common among those given iron than in those given placebo from 4-9 mo, whereas the opposite was true among those with Hb > or = 110 g/L (P < 0.05). We conclude that routine iron supplementation of breast-fed infants may benefit those with low Hb but may present risks for those with normal Hb.

  • 34.
    Domellöf, Erik
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Johansson, Anna-Maria
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Farooqi, Aijaz
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rönnqvist, Louise
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Improved fine motor performance in children born preterm: a longitudinal study of upper-limb kinematics from 4 to 8 years2015Conference paper (Refereed)
    Abstract [en]

    Introduction:

    Although children born preterm (PT) are at known risk for impaired neuromotor development, longitudinal studies using detailed measurements of motor performance are rare. This study investigated developmental changes in goal-directed upper-limb kinematics from 4-8 years old in a sample of children born fullterm (FT) and PT without known developmental disabilities.

    Participants and Methods:

    3D kinematic recordings of performance with either arm/hand during a goal-directed unimanual precision task were carried out at 4 and 8 years in 37 children (13 very PT, V-PT, < 32 GW; 5 moderately PT, M-PT, 33-35 GW; 19 FT).

    Results:

    Repeated measures ANOVA revealed significant main effects for group and occasion, and interaction effects between group and occasion, for distal movement duration (p < .0001) and segmentation in terms of movement units (MUs, p < .0001). From initially having displayed less proficient movement organization at 4 years than both children born FT and M-PT, the children born V-PT showed a marked catch-up at 8 years, where no significant group differences remained. The mean between-occasion difference was substantial for both duration and segmentation in V-PT relative the other groups, although with noticeably higher within-group variability (MSD = 1.2 s/7.8 MUs) than M-PT (MSD = 0.5 s/2.5 MUs) and FT (MSD = 0.5 s/4.2 MUs).

    Conclusion:

    The children born PT, V-PT in particular, generally displayed a considerable gain in fine motor performance from preschool to school age. Compared with the FT and M-PT groups, however, the rate of improvement appears more heterogeneous in the V-PT group

  • 35.
    Domellöf, Erik
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology. Research and Development Unit, Kolbäcken Child Rehabilitation Centre, Umeå, Sweden.
    Johansson, Anna-Maria
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Farooqi, Aijaz
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rönnqvist, Louise
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Relations Among Upper-Limb Movement Organization and Cognitive Function at School Age in Children Born Preterm2013In: Journal of Developmental and Behavioral Pediatrics, ISSN 0196-206X, E-ISSN 1536-7312, Vol. 34, no 5, p. 344-352Article in journal (Refereed)
    Abstract [en]

    Objective: To explore relations between aspects of upper-body spatiotemporal movement organization and intelligence in children born preterm at school age.

    Methods: Three-dimensional (3D) kinematic recordings of arm and head movements during a unimanual precision task were related to performance on the Wechsler Intelligence Scale for Children, 4th edition, in a sample of 32 children born preterm (gestational age, mean: 31.5 weeks [range: 22-35 weeks]; birth weight, mean: 1699 g [range: 404-2962 g]) at 6 years to 8 years with no diagnosed cognitive, sensory, or motor impairments compared with 40 age-matched control children born fullterm.

    Results: In the children born preterm, upper-limb movement duration and segmentation of movement trajectories were significantly associated with full-scale intelligence quotient independent of gestational age (GA) and sex. These effects pertained to the preferred side, characterized by more effective movement organization being linked with increased intelligence scores. The same relations were not seen in the controls. Within the children born preterm, a significant effect of GA was also found for some aspects of upper-limb movement organization. Full-scale intelligence quotient was within normal limits for both groups but significantly lower in the preterm (mean: 94.5 [range: 72-120]) compared with the fullterm (mean: 101.7 [range: 76-119]) born children.

    Conclusions: The findings demonstrate that, independent of GA, the spatiotemporal organization of upper-limb movements is partly associated with cognitive performance in children born preterm.

  • 36.
    Domellöf, Erik
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Timby, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Department of Nutrition, University of California, Davis, USA.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Formula feeding supplemented with milk fat globule membranes  improves cognitive score in term infants at 12 months2013In: Developmental Medicine & Child Neurology, 55 (Suppl. S2): Abstracts of the European Academy of Childhood Disability 25th Annual Meeting, 10-12 October 2013, Newcastle-Gateshead, UK, Mac Keith Press , 2013, p. 50-50Conference paper (Refereed)
    Abstract [en]

    Introduction: Findings of enhanced cognitive development in breast‐fed compared with formula‐fed infants suggest that breast milk contains neurodevelopmentally beneficial components. Animal studies report positive behavioral effects of supplementation with components included in the bovine milkfat globule membrane fraction (MFGM). Behavioral effects of MFGM supplemented formula in human infants have not been studied. This study tested the hypothesis that infants fed an experimental formula (EF) supplemented with a bovine MFGM fraction would display a more favorable neurofunctional development than infants fed a standard formula (SF) at 12 months.

    Participants and Methods: Healthy term formula‐fed infants (n = 160) and a breast‐fed reference (BFR) group (n = 80) were included in a prospective double blind randomized trial before 2 months of age. Formula‐fed infants were randomized to receive EF or SF from inclusion until 6 months. At 12 months, cognitive, motor and verbal functions were tested using the Bayley Scales of Infant and Toddler Development‐III.

    Results: The cognitive score was significantly higher in the EF (105.8 ± 9.2) than SF (101.8 ± 8.0) group, but equal between the EF and BFR groups. No differences were found in motor or verbal score between the formula groups. The BFR group displayed higher verbal but not motor scores than the formula groups.

    Conclusion: In keeping with the hypothesis, feeding infants MFGM supplemented formula resulted in improved cognitive function at 12 months compared with a standard formula. The difference in cognitive score between the EF and SF groups is compliant with calculated differences between formula‐fed and breast‐fed infants in previous studies.

  • 37.
    Domellöf, M
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Neonatal hematology2006In: Acta Paediatrica, Vol. 95, p. 765-Article, book review (Other academic)
    Abstract [en]

    No abstract avilable

  • 38.
    Domellöf, M
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Dewey, KG
    Lönnerdal, B
    Hernell, O
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Prophylactic iron supplementation in infancy:: Safety issues2006In: Acta Paediatrica, Vol. 95, no 8Article in journal (Other academic)
    Abstract [en]

    No abstract available

  • 39.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Benefits and harms of iron supplementation in iron-deficient and iron-sufficient children2010In: Nestlé Nutrition workshop series. Paediatric programme, ISSN 1661-6677, Vol. 65, p. 153-165Article in journal (Refereed)
    Abstract [en]

    Due to high iron requirements, young children are at risk for iron deficiency anemia. Iron supplements are therefore often recommended, especially since iron deficiency anemia in children is associated with poor neurodevelopment. However, in contrast to most other nutrients, excess iron cannot be excreted by the human body and it has recently been suggested that excessive iron supplementation of young children may have adverse effects on growth, risk of infections, and even on cognitive development. Recent studies support that iron supplements are beneficial in iron-deficient children but there is a risk of adverse effects in those who are iron replete. In populations with a low prevalence of iron deficiency, general supplementation should therefore be avoided. Iron-fortified foods can still be generally recommended since they seem to be safer than medicinal iron supplements, but the level of iron fortification should be limited. General iron supplementation is recommended in areas with a high prevalence of iron deficiency, with the exception of malarious areas where a cautious supplementation approach needs to be adopted, based either on screening or a combination of iron supplements and infection control measures. More studies are urgently needed to better determine the risks and benefits of iron supplementation and iron-fortified foods given to iron-deficient and iron-sufficient children.

  • 40.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Iron and Other Micronutrient Deficiencies in Low-Birthweight Infants2013In: Maternal and child nutrition: the first 1,000 days / [ed] Jatinder Bhatia, Zulfiqar A. Bhutta, Satish C. Kalhan, 2013, p. 197-206Conference paper (Refereed)
    Abstract [en]

    Low birthweight (LBW), defined as birthweight <2,500 g, is a major global public health problem and is associated with lifelong cognitive and behavioral problems. Very LBW (VLBW) infants (<1,500 g) are at high risk of multiple macro- and micronutrient deficiencies, but most LBW infants are larger (1,500-2,500 g), and the most common nutritional problem of those infants is iron deficiency (ID). Globally, about 25% of pre-school children have ID anemia (IDA), the most severe form of ID, and there is good evidence that ID is associated with impaired brain development. However, adverse effects of excessive iron supplementation have been observed. Delayed umbilical cord clamping, which increases infant iron stores, should be recommended for all newborns. There is good evidence that intakes of 2 mg of dietary iron per kg daily prevents IDA in LBW infants without causing adverse effects. A recent study shows that this dose of iron supplementation also reduces the risk of behavioral problems at 3 years in infants with birthweights 2,000-2,500 g.VLBW infants need 2-3 mg/kg per day. To achieve these intakes, breastfed LBW infants should receive iron supplements, and formula-fed LBW infants should receive an iron-fortified infant formula.

  • 41.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Iron requirements, absorption and metabolism in infancy and childhood.2007In: Curr Opin Clin Nutr Metab Care, ISSN 1363-1950, Vol. 10, no 3, p. 329-35Article in journal (Other academic)
    Abstract [en]

    PURPOSE OF REVIEW: Iron deficiency is a significant public health problem in young children due to their high iron requirements, and iron supplements are therefore often recommended. During the time period in focus for this review (2005-2006), there have been additional advances in our understanding of the molecular mechanisms of iron absorption and metabolism. It has also been suggested that iron supplements may have adverse effects in children. RECENT FINDINGS: Recently discovered molecules, for example hepcidin, lactoferrin receptor and heme carrier protein may be important for iron metabolism in children. There are possible metabolic interactions between iron and several other minerals. Many studies show that iron deficiency in young children is associated with impaired neurodevelopment but it is not clear whether this can be prevented by iron supplementation. Oral iron supplements given to young children in malarious regions may lead to increased risk of death or severe infections, especially in those who are iron replete. SUMMARY: More research is needed to identify those children who will benefit from iron supplementation and to better determine iron requirements during early life. Clinical trials should include functional outcomes. Better knowledge about molecular mechanisms and nutrient interactions may lead to new diagnostic tests and preventive strategies.

  • 42.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Iron requirements in infancy2011In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 59, no 1, p. 59-63Article in journal (Refereed)
    Abstract [en]

    Iron deficiency anemia is the most common micronutrient deficiency worldwide and infants constitute a risk group due to their high iron requirements. Iron is critical for brain development, and case control studies have shown a consistent association between iron deficiency anemia in infancy and poor neurodevelopment, suggesting that it is important to prevent iron deficiency anemia in infants. However, it is also important to avoid excessive iron intakes which may have adverse effects on growth. Due to redistribution of iron from hemoglobin to iron stores, healthy, term, normal birth weight infants are virtually self-sufficient with regard to iron during the first 6 months of life. After that age, iron becomes a critical nutrient. The estimated daily iron requirements at the age of 6-12 months (0.9-1.3 mg/kg body weight) are higher than during any other period of life. Exclusively breast-fed infants normally do not need additional iron until 6 months of life. Formula-fed infants should receive iron-fortified formula. Low birth weight infants should receive additional iron supplements from an early age. From 6 months of age, all infants should receive a sufficient intake of iron-rich (complementary) foods, which may be meat products or iron-fortified foods. The estimations of iron requirements in infants have a weak evidence base and current European and American recommendations for infants differ significantly. To further clarify iron requirements in infants, there is clearly a need for randomized, controlled trials assessing the effects of different iron intake on anemia, neurodevelopment, and other health outcomes.

  • 43.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Iron requirements of term, breast-fed infants: a study in Sweden and Honduras2001Doctoral thesis, comprehensive summary (Other academic)
  • 44.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Meeting the iron needs of low and very low birth weight infants2017In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 71, p. 16-23Article in journal (Refereed)
    Abstract [en]

    Low birth weight (LBW), defined as a birth weight of < 2,500 g, affects 16% of all newborns and is a risk factor for impaired neurodevelopment as well as adverse cardiovascular and metabolic outcomes, including hypertension. LBW infants include both term, small for gestational age infants and preterm infants. Most LBW infants have only marginally LBW (2,000-2,500 g). Recent advances in neonatal care have significantly improved the survival of very LBW (VLBW) infants (< 1,500 g). LBW infants are at high risk of iron deficiency due to low iron stores at birth and higher iron requirements due to rapid growth. Using a factorial approach, iron requirements of LBW infants have been estimated to be 1-2 mg/kg/day, which is much higher than the requirements of term, normal birth weight infants, who need almost no dietary iron during the first 6 months of life. In VLBW infants, blood losses and blood transfusions related to neonatal intensive care, as well as erythropoietin treatment, will greatly influence iron status and iron requirements. The timing of umbilical cord clamping at birth is of great importance for the amount of blood transfused from the placenta to the newborn and thereby total body iron. Delayed cord clamping of LBW infants is associated with less need for blood transfusion, less intraventricular hemorrhage, and less necrotizing enterocolitis. Randomized controlled trials have shown that an iron intake of 1-3 mg/kg/day (1-2 mg for marginally LBW and 2-3 mg for VLBW) is needed to effectively prevent iron deficiency. There is some recent evidence that these levels of iron intake will prevent some of the negative health consequences associated with LBW, especially behavioral problems and other neurodevelopmental outcomes and possibly even hypertension. However, it is also important to avoid excessive iron intakes which have been associated with adverse effects in LBW infants.

  • 45.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nutritional care of premature infants: microminerals2014In: Nutritional care of preterm infants: scientific basis and practical guidelines / [ed] Koletzko, B, Poindexter, B, Uauy, R, Basel: S. Karger, 2014, p. 121-139Chapter in book (Refereed)
    Abstract [en]

    Microminerals, including iron, zinc, copper, selenium, manganese, iodine, chromium and molybdenum, are essential for a remarkable array of critical functions and need to be supplied in adequate amounts to preterm infants. Very low birth weight (VLBW) infants carry a very high risk of developing iron deficiency which can adversely affect neurodevelopment. However, a too high iron supply in iron-replete VLBW infants may induce adverse effects such as increased infection risks and impaired growth. Iron needs are influenced by birth weight, growth rates, blood losses (phlebotomy) and blood transfusions. An enteral iron intake of 2 mg/kg/day for infants with a birth weight of 1,500-2,500 g and 2-3 mg/kg/ day for VLBW infants is recommended. Higher doses up to 6 mg/kg/day are needed in infants receiving erythropoietin treatment. Regular monitoring of serum ferritin during the hospital stay is advisable. Routine provision of iron with parenteral nutrition for VLBW infants is not recommended. Less certainty exists for the advisable intakes of other microminerals. It appears prudent to provide enterally fed VLBW infants with daily amounts per kilogram body weight of 1.4-2.5 mu g zinc, 100-230 mu g copper, 5-10 mu g selenium, 1-15 mu g manganese, 10-55 mu g iodine, 0.03-2.25 mu g chromium, and 0.3-5 mu g molybdenum. Future scientific findings may justify deviations from these suggested ranges.

  • 46.
    Domellöf, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Braegger, Christian
    Campoy, Cristina
    Colomb, Virginie
    Decsi, Tamas
    Fewtrell, Mary
    Hojsak, Iva
    Mihatsch, Walter
    Molgaard, Christian
    Shamir, Raanan
    Turck, Dominique
    van Goudoever, Johannes
    Iron Requirements of Infants and Toddlers2014In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 58, no 1, p. 119-129Article in journal (Refereed)
    Abstract [en]

    Iron deficiency (ID) is the most common micronutrient deficiency worldwide and young children are a special risk group because their rapid growth leads to high iron requirements. Risk factors associated with a higher prevalence of ID anemia (IDA) include low birth weight, high cow's-milk intake, low intake of iron-rich complementary foods, low socioeconomic status, and immigrant status. The aim of this position paper was to review the field and provide recommendations regarding iron requirements in infants and toddlers, including those of moderately or marginally low birth weight. There is no evidence that iron supplementation of pregnant women improves iron status in their offspring in a European setting. Delayed cord clamping reduces the risk of ID. There is insufficient evidence to support general iron supplementation of healthy European infants and toddlers of normal birth weight. Formula-fed infants up to 6 months of age should receive iron-fortified infant formula, with an iron content of 4 to 8 mg/L (0.6-1.2 mg <bold></bold> kg(-1) <bold></bold> day(-1)). Marginally low-birth-weight infants (2000-2500 g) should receive iron supplements of 1-2 mg <bold></bold> kg(-1) <bold></bold> day(-1). Follow-on formulas should be iron-fortified; however, there is not enough evidence to determine the optimal iron concentration in follow-on formula. From the age of 6 months, all infants and toddlers should receive iron-rich (complementary) foods, including meat products and/or iron-fortified foods. Unmodified cow's milk should not be fed as the main milk drink to infants before the age of 12 months and intake should be limited to <500 mL/day in toddlers. It is important to ensure that this dietary advice reaches high-risk groups such as socioeconomically disadvantaged families and immigrant families.

  • 47.
    Domellöf, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Cohen, R J
    Dewey, K G
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rivera, L L
    Lönnerdal, B
    Iron supplementation of breast-fed Honduran and Swedish infants from 4 to 9 months of age.2001In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 138, no 5, p. 679-687Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The objective was to study the effects of iron supplementation on hemoglobin and iron status in 2 different populations. Study design: In a randomized, placebo-controlled, masked clinical trial, we assigned term Swedish (n = 101) and Honduran (n = 131) infants to 3 groups at 4 months of age: (1) iron supplements, 1 mg/kg/d, from 4 to 9 months, (2) placebo, 4 to 6 months and iron, 6 to 9 months, and (3) placebo, 4 to 9 months. All infants were breast-fed exclusively to 6 months and partially to 9 months. RESULTS: From 4 to 6 months, the effect of iron (group 1 vs 2 + 3) was significant and similar in both populations for hemoglobin, ferritin, and zinc protoporphyrin. From 6 to 9 months, the effect (group 2 vs group 3) was significant and similar at both sites for all iron status variables except hemoglobin, for which there was a significant effect only in Honduras. In Honduras, the prevalence of iron deficiency anemia at 9 months was 29% in the placebo group and 9% in the supplemented groups. In Sweden, iron supplements caused no reduction in the already low prevalence of iron deficiency anemia at 9 months (<3%). CONCLUSION: Iron supplementation from 4 to 9 months or 6 to 9 months significantly reduced iron deficiency anemia in Honduran breast-fed infants. The unexpected hemoglobin response at 4 to 6 months in both populations suggests that regulation of hemoglobin synthesis is immature at this age.

  • 48.
    Domellöf, Magnus
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Dewey, Kathryn G
    Cohen, Roberta J
    Lönnerdal, Bo
    Hernell, Olle
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Iron supplements reduce erythrocyte copper-zinc superoxide dismutase activity in term, breastfed infants.2005In: Acta Paediatr, ISSN 0803-5253, Vol. 94, no 11, p. 1578-82Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate whether iron supplements compromise copper status in infants. METHODS: 214 healthy, term, breastfed Swedish and Honduran infants were randomized to (1) iron supplements (1 mg/kg/d) from 4-9 mo of age, (2) iron supplements from 6-9 mo, or (3) placebo. Blood samples were obtained at 4, 6, and 9 mo and analyzed for plasma copper (p-Cu) and, at 9 mo, for copper/zinc-dependent superoxide dismutase (CuZn-SOD) activity. RESULTS: P-Cu increased with infant age. At 9 mo, Honduran infants had significantly higher p-Cu (1.40+/-0.29 vs 1.09+/-0.22 mg/l, p<0.001) and CuZn-SOD activity (1.09+/-0.29 vs 0.93+/-0.21 U/mg Hb, p<0.001) than Swedish infants. Infants receiving iron supplements from 4-9 mo had significantly lower CuZn-SOD at 9 mo of age (0.95+/-0.27 vs 1.08+/-0.24 U/mg Hb, p=0.023) than those receiving placebo.CONCLUSION: There is a physiologic increase in p-Cu during the first 9 mo of life. Differences in copper status between Swedish and Honduran infants may be due to genetic or nutritional differences. Iron supplementation decreases CuZn-SOD activity, probably due to a negative effect on copper status. Possible clinical implications remain to be elucidated.

  • 49.
    Domellöf, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Dewey, Kathryn G
    Lönnerdal, Bo
    Cohen, Roberta J
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    The diagnostic criteria for iron deficiency in infants should be reevaluated.2002In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 132, no 12, p. 3680-3686Article in journal (Refereed)
    Abstract [en]

    Diagnostic criteria for iron deficiency (ID) and iron deficiency anemia (IDA) in infants are poorly defined. Our aim was to establish appropriate cut-off values for hemoglobin (Hb), plasma ferritin, erythrocyte mean cell volume (MCV), zinc protoporphyrin (ZPP) and soluble transferrin receptors (TfR) in infancy. Exclusively breast-fed infants (n = 263) in Honduras and Sweden were randomly assigned to receive iron supplementation or placebo, and blood samples were obtained at 4, 6 and 9 mo of age. Reference ranges were determined using three different approaches for defining iron-replete infants. The usefulness of several variables for predicting the Hb response to iron was evaluated. We found the following 2 SD cut-off values in iron-replete infants: Hb <105 g/L at 4-6 mo and <100 g/L at 9 mo; ZPP >75 micro mol/mol heme at 4-6 mo and >90 micro mol/mol heme at 9 mo; ferritin <20 micro g/L at 4 mo, <9 micro g/L at 6 mo and <5 micro g/L at 9 mo; and TfR >11 mg/L at 4-9 mo. The Hb response to iron was not a useful definition of IDA at 4 mo of age. Hb, MCV and ZPP at 6 mo as well as growth variables predicted the Hb response at 6-9 mo, but ferritin and TfR at 6 mo did not. We conclude that there is need for a reevaluation of the definitions of ID and IDA in infants.

  • 50.
    Domellöf, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Georgieff, Michael K.
    University of Minnesota School of Medicine, Minneapolis, MN.
    Postdischarge Iron Requirements of the Preterm Infant2015In: Journal of Pediatric Surgery Case Reports, ISSN 0022-3476, E-ISSN 2213-5766, Vol. 167, no 4, Supplement, p. S31-S35Article in journal (Refereed)
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