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The impact of nutrition on growth, biomarkers, and health outcomes in preterm infants
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction: Nutrients play a crucial role for growth and brain development after preterm birth. Meeting the nutritional needs of preterm infants is challenging. Particularly, the most immature infants have a high risk of malnutrition and poor growth during hospital care. To meet recommended energy and nutrient intakes during early postnatal life, a concentrated parenteral nutrition (PN) regimen was implemented in clinical use in 2012 at the neonatal intensive care unit at Umeå University Hospital (Umeå, Sweden). However, electrolyte homeostasis is labile after preterm birth and infants require an electrolyte supply that corresponds to their energy and protein intakes to avoid electrolyte disturbances. Although sodium imbalances such as hyper- and hyponatremia are common in the most immature preterm infants, there is limited knowledge to what extent these imbalances are affected by fluid volume and sodium supply. Furthermore, it is unclear whether the early high sodium concentrations lead to any adverse effects, including intraventricular hemorrhage, or simply reflect immediate adaptive processes after preterm birth.

Aim: This thesis investigates the impact of nutrition on growth, nutritional biomarkers, and health outcomes in preterm infants born with a birth weight below 1500 g.

Methods: We used data from two study populations. First, we collected data for all very low birth weight infants (< 1500 g) born between 2010 and 2013 and treated at Umeå University Hospital (Umeå, Sweden; n = 134). Second, we used data from the EXtremly PREterm infants in Sweden Study (EXPRESS). We included all infants born before 27 gestational weeks in Sweden between 2004 and 2007 who survived the first 24 h (n = 602). Data collection for both study populations included a) intakes of all parenteral and enteral nutritional products and other fluids during the first 28 postnatal days, b) all anthropometric measurements during hospital stay, c) perinatal data, and d) neonatal morbidity.

Results: The concentrated PN regimen improved early energy and macronutrient intakes in very low birth weight infants. Furthermore, weight and length growth from postnatal week two to a postmenstrual age of 36 weeks improved in very low birth weight infants who received the concentrated PN regimen compared with infants who received the previous original PN regimen (Paper I). Increased parenteral energy and protein intakes provided by the concentrated PN regimen, did not induce a higher occurrence of electrolyte imbalances as electrolytes were supplied according to the current recommendations (Paper II). In the EXPRESS cohort, the majority of extremely preterm infants had hypernatremia during the first and hyponatremia during the second postnatal week. Gestational age and supply of sodium, rather than fluid volume, were the major factors determining the risks of hyper- and hyponatremia (Paper III). High total supply of sodium was significantly correlated with severe intraventricular hemorrhage if mostly mediated by blood product transfusions (Paper IV).

Conclusions: Our results suggest that in very immature preterm infants a concentrated PN regimen improves early nutrient intakes and postnatal growth without causing electrolyte disturbances. Hyper- and hyponatremia are common and the supply of sodium is a major predictor. The impact of sodium on severe intraventricular hemorrhage needs further investigation.

Abstract [sv]

Introduktion: Att möta energi- och näringsbehovet hos barn som föds för tidigt är utmanande, framförallt för de allra minsta barnen som på grund av omogenhet har hög risk för undernäring och dålig tillväxt. Med syfte att möta det rekommenderade energi- och näringsbehovet direkt efter födelsen hos för tidigt födda barn implementerades därför en koncentrerad parenteral näringslösning (PN) på den neonatala intensivvårdsavdelningen vid Umeå universitetssjukhus i februari 2012. Även elektrolytobalans är vanligt hos för tidigt födda barn. För att undvika denna obalans behöver för tidigt födda barn en elektrolytförsörjning som motsvarar energi- och proteinintaget. Både högt och lågt natrium (hyper- och hyponatremi) är vanliga tillstånd hos de mest omogna barnen men det finns begränsad kunskap i vilken utsträckning dessa obalanser påverkas av vätskevolym och natriumintag. Vidare är det oklart om höga natriumkoncentrationer leder till negativa konsekvenser, som exempelvis intraventrikulär blödning, eller om natriumobalanser enbart återspeglar en omedelbar anpassning efter för tidig födelse.

Syfte: Denna avhandling undersöker energi- och näringsintag och dess samband med tillväxt, näringsrelaterade biomarkörer och hälsoutfall hos för tidigt födda barn med en födelsevikt under 1500 gram.

Metoder: Två studiepopulationer användes. Alla barn som föddes med en födelsevikt under 1500 gram mellan 2010 och 2013, vårdade på Umeå universitetssjukhus utgjorde den ena studiepopulationen (n = 134). Den andra studiepopulationen utgjordes av data från Extremely PREterm infants in Sweden Study (EXPRESS) där alla barn födda före 27 graviditetsveckor mellan 2004 och 2007 ingick. Från EXPRESS inkluderades barn som överlevde de första 24 timmarna (n = 602). Datainsamlingen för båda studiepopulationerna inkluderade a) intag av alla parenterala och enterala näringsprodukter samt andra vätskor under de första 28 levnadsdagarna, b) alla antropometriska mätningar under sjukhusvistelsen, c) perinatal data och d) neonatal sjuklighet.

Resultat: Koncentrerad PN förbättrade det tidiga energi- och makronutrientintaget hos barn med en födelsevikt under 1500 gram. Vikt- och längdtillväxten förbättrades från andra levnadsveckan till 36 veckor postmenstrual ålder hos barn som fick koncentrerad PN jämfört med barn som fick ursprunglig PN (Delarbete I). Det ökade parenterala energi- och proteinintaget var inte associerat med högre förekomst av elektrolytobalanser eftersom elektrolyter gavs enligt aktuella rekommendationer (Delarbete II). I EXPRESS kohorten hade majoriteten av barnen hypernatremi under den första levnadsveckan och hyponatremi under den andra levnadsveckan. Ålder vid födelse och natriumtillförsel, snarare än vätskevolym, var faktorer som bidrog till hyper- och hyponatremi (Delarbete III). Hög total natriumtillförsel var associerat med svår intraventrikulär blödning men detta samband var främst medierat av natrium från transfusioner av blodprodukter (Delarbete IV).

Slutsatser: En koncentrerad PN förbättrar tidigt energi- och näringsintag samt tillväxt hos för tidigt födda barn utan att orsaka elektrolytobalans. Hyper- och hyponatremi är vanligt och tillförseln av natrium är en viktig faktor. Samband mellan högt natriumintag och svår intraventrikulär blödning behöver ytterligare undersökas.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2019. , p. 50
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2055
Keywords [en]
Preterm infant, parenteral nutrition, energy intake, nutrient intakes, postnatal growth, electrolyte imbalances, sodium supply, hypernatremia, intraventricular hemorrhage
National Category
Pediatrics Nutrition and Dietetics
Research subject
Pediatrics; Nutrition
Identifiers
URN: urn:nbn:se:umu:diva-164834ISBN: 978-91-7855-093-7 (print)OAI: oai:DiVA.org:umu-164834DiVA, id: diva2:1367523
Public defence
2019-11-29, Stora hörsalen, målpunkt P, byggnad 5B, plan 6, Norrlands universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2019-11-08 Created: 2019-11-04 Last updated: 2019-11-06Bibliographically approved
List of papers
1. Use of concentrated parenteral nutrition solutions is associated with improved nutrient intakes and postnatal growth in very low-birth-weight infants
Open this publication in new window or tab >>Use of concentrated parenteral nutrition solutions is associated with improved nutrient intakes and postnatal growth in very low-birth-weight infants
2019 (English)In: JPEN - Journal of Parenteral and Enteral Nutrition, ISSN 0148-6071, E-ISSN 1941-2444Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: Evidence showing the beneficial effects of enhanced parenteral nutrition (PN) to very low-birth-weight (VLBW,<1500 g) infants is accumulating. However, PN composition and its impact on growth outcomes are questioned. This study aimed to investigate the associations between administration of a concentrated PN regime and intakes of energy and macronutrients as well as postnatal growth in VLBW infants. 

Methods: We compared 2 cohorts of VLBW infants born before (n = 74) and after (n =44) a concentrated PN regime was introduced into clinical use. Daily nutrition and fluid intake during the first 28 postnatal days and all available growth measurements during hospitalization were retrospectively collected from clinical charts. 

Results: Infants who received concentrated PN compared with original PN had higher parenteral intakes of energy (56 vs 45 kcal/kg/d, P < 0.001), protein (2.6 vs 2.2 g/kg/d, P = 0.008), and fat (1.5 vs 0.7 g/kg/d, P < 0.001) during the first postnatal week. Changes in standard deviation scores for weight and length from birth to postnatal day 28 were more positive in the concentrated PN group (mean [95% CI]; weight change: –0.77 [–1.02 to –0.52] vs –1.29 [–1.33 to –1.05], P = 0.005; length change: –1.01 [–1.36 to –0.65] vs –1.60 [–1.95 to –1.25], P = 0.025). There were no significant differences in fluid intake and infant morbidity between the groups. 

Conclusion: Our results suggest that concentrated PN is useful and seems to be safe for improving early nutrition and growth in VLBW infants.

National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-148009 (URN)10.1002/jpen.1522 (DOI)
Available from: 2018-05-24 Created: 2018-05-24 Last updated: 2019-11-04
2. Effects of two different parenteral nutrition regimen on plasma electrolyte concentrations in very low birth weight infants
Open this publication in new window or tab >>Effects of two different parenteral nutrition regimen on plasma electrolyte concentrations in very low birth weight infants
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Introduction: Recent studies demonstrated an increased prevalence of electrolyte imbalances in preterm infants who received enhanced amounts of energy and protein within the first days after birth. The aim of this study was to investigate the effect of two parenteral nutritional (PN) regimen, which differ in energy and protein content, on intakes and plasma concentrations of electrolytes in very low birth weight (VLBW, < 1500 g) infants.

Methods: We collected daily nutritional, growth, and nutritional biomarker data retrospectively from clinical charts for VLBW infants born before (n = 81) and after (n = 53) the implementation of a concentrated PN regimen at the neonatal intensive care unit at Umeå University Hospital (Umeå, Sweden).

Results: During the first postnatal week, intakes of energy, protein, sodium, potassium, calcium, and phosphorous were significantly higher in infants who received the concentrated PN regimen compared with infants who received the original PN regimen. The prevalence of hypernatremia, hypophosphatemia, and hypercalcemia did not differ significantly between the groups. However, infants who received concentrated PN were less likely to develop hypokalaemia during the first postnatal week compared with infants who received original PN (30 vs. 76%, P < 0.001).

Conclusion: A concentrated, energy- and protein-optimized, PN regimen requires careful adjustments of electrolytes in VLBW infants. During the first three postnatal days, a minimum potassium intake of 1 mmol/kg/d might be necessary to prevent early hypokalaemia. The risk of early hypernatremia was not affected by different sodium intakes.

Keywords
Preterm infants, parenteral nutrition, nutrient intakes, plasma electrolyte concentrations
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-164832 (URN)
Available from: 2019-11-04 Created: 2019-11-04 Last updated: 2019-11-14Bibliographically approved
3. Sodium supply influences plasma sodium concentration and the risks of hyper- and hyponatremia in extremely preterm infants
Open this publication in new window or tab >>Sodium supply influences plasma sodium concentration and the risks of hyper- and hyponatremia in extremely preterm infants
Show others...
2017 (English)In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 81, p. 455-460Article in journal (Refereed) Published
Abstract [en]

Background: Hyper- and hyponatremia occur frequently in extremely preterm infants. Our purpose was to investigate plasma sodium (P-Na) concentrations, the incidence of hyper and hyponatremia, and the impact of possible predisposing factors in extremely preterm infants.

Methods: In this observational study, we analyzed data from the EXtremely PREterm (< 27 wk.) infants in Sweden Study (EXPRESS, n = 707). Detailed nutritional, laboratory, and weight data were collected retrospectively from patient records.

Results: Mean ± SD P-Na increased from 135.5 ± 3.0 at birth to 144.3 ± 6.1 mmol/l at a postnatal age of 3 d and decreased thereafter. Fifty percent of infants had hypernatremia (P-Na >145 mmol/l) during the first week of life while 79% displayed hyponatremia (P-Na < 135 mmol/l) during week 2. Initially, the main sodium sources were blood products and saline injections/infusions, gradually shifting to parenteral and enteral nutrition towards the end of the first week. The major determinant of P-Na and the risks of hyper- and hyponatremia was sodium supply. Fluid volume provision was associated with postnatal weight change but not with P-Na.

Conclusion: The supply of sodium, rather than fluid volume, is the major factor determining P-Na concentrations and the risks of hyper- and hyponatremia.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
urn:nbn:se:umu:diva-128245 (URN)10.1038/pr.2016.264 (DOI)000396297000016 ()
Available from: 2016-11-30 Created: 2016-11-30 Last updated: 2019-11-04Bibliographically approved
4. Associations between sodium supply, sodium imbalances and severe intraventricular haemorrhage in extremely preterm infants: A nested case-control study
Open this publication in new window or tab >>Associations between sodium supply, sodium imbalances and severe intraventricular haemorrhage in extremely preterm infants: A nested case-control study
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Severe intraventricular haemorrhage (IVH) is a serious neonatal morbidity among extremely preterm infants that has been associated with adverse neurodevelopmental consequences. We aimed to explore the associations between sodium supply, sodium imbalances and severe IVH.

Methods: We used data from the EXtremely PREterm Infants in Sweden Study (EXPRESS) including all extremely preterm infants (< 27 weeks) born during 2004 and 2007 in Sweden (n = 707) and conducted a nested case-control study. For every infant with severe IVH (grades 3 to 4, n = 70) one control infant with a normal cranial ultrasound, a birthday closest to the case infant, and matched for hospital, sex, gestational age, and birth weight was selected.

Results: Sodium supply was higher in infants with severe IVH compared with controls [Daily sodium supply until postnatal day 2: Mean ± SD (mmol/kg/d): 5.49 ± 2.53 vs. 3.95 ± 1.91, P = 0.009]. This association did not remain significant when we excluded the amount of sodium delivered from transfused blood products from total sodium supply. High concentrations of or large fluctuations in plasma sodium were not related to severe IVH.

Conclusion: Although our results suggest a relationship between sodium supply and severe IVH via blood product transfusions, it is unclear whether this represents an effect of solute or volume load.

Keywords
Preterm infants, sodium supply, sodium imbalances, intraventricular haemorrhage
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-164833 (URN)
Available from: 2019-11-04 Created: 2019-11-04 Last updated: 2019-11-14Bibliographically approved

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