Z Geburtshilfe Neonatol 2013; 217(02): 50-55
DOI: 10.1055/s-0032-1331231
Review
© Georg Thieme Verlag KG Stuttgart · New York

Hyperglycaemia and Preterm Infants: A Chapter of its Own

Hyperglykämie und Frühgeborene: Ein Kapitel für sich
K. Heimann
1   University Children’s Hospital, Department of Neonatology, RWTH Aachen University, D-52074 Aachen, Germany
,
B. Karges
2   Division of Endocrinology and Diabetes, RWTH Aachen University, D-52074 Aachen, Germany
,
T. W. Goecke
3   Prenatal Diagnosis and Obstetrics, Department of Gynaecology and Obstetrics, RWTH Aachen University, D-52074 Aachen, Germany
,
T. Orlikowsky
1   University Children’s Hospital, Department of Neonatology, RWTH Aachen University, D-52074 Aachen, Germany
› Author Affiliations
Further Information

Publication History

received 27 July 2012

accepted 19 October 2012

Publication Date:
26 April 2013 (online)

Abstract

Antenatally, glucose maintenance takes place via transplacental transfer from mother to fetus. In the third trimester, the amount of glucose transported increases, while glycogen and fat stores are developed. After delivery a continuous and sufficient glucose supply for vital organs and brain is essential. In term infants hormonal and metabolic adaption is well-coordinated, involving adrenal gland, pancreas and liver. However, in preterm infants, mainly during first week of life, there is a high risk of abnormalities in glucose homeostasis. Due to limited glycogen and fat stores, hypoglycaemia may occur which is avoided by continuous glucose infusion. An underestimated risk is hyperglycaemia due to a combination of relative insulin deficiency and insulin resistance, associated with increased mortality and morbidity. Management of hyperglycaemia is one of the topics in neonatology and is still being discussed controversially. This review approaches different therapeutic strategies and gives an overview about the current recommendations in the literature.

Zusammenfassung

Während der Schwangerschaft erhält der Fetus die zu Aufrechterhaltung des Metabolismus und Wachstums notwendigen Glukosemengen diaplazentar über die Mutter. Im letzten Drittel der Schwangerschaft wird die diaplazentare Glukosemenge erhöht, während gleichzeitig Glykogen- und Fettspeicher angelegt und ausgebaut werden. Nach der Geburt ist eine kontinuierliche und suffiziente Glukoseversorgung für die Organe vor allem für das Gehirn essentiell. Bei reifen Neugeborenen erfolgt die hormonelle und metabolische Anpassung unter Einbeziehung der Nebenniere, des Pankreas und der Leber. Bei Frühgeborenen dagegen besteht vor allem in der ersten Lebenswoche ein hohes Risiko für eine gestörte Glukose-Homöostase. Aufgrund kaum vorhandener Glykogen- und Fettspeicher entsteht eine Hypoglykämieneigung, weshalb oft kontinuierlich Glukose intravenös verabreicht werden muss. Häufig wird eine reaktive Hyperglykämie beobachtet, die als Kombination aus relativem Insulinmangel und Insulinresistenz entsteht und mit einer erhöhten Mortalität und Morbidität einhergeht. Da Prävention und Behandlung der Hyperglykämie des Frühgeborenen ein in der Neonatologie kontrovers diskutiertes Thema ist, soll dieser Artikel die unterschiedlichen therapeutischen Strategien beleuchten und eine Übersicht über die aktuellen Empfehlungen in der Literatur geben.

 
  • References

  • 1 Huppertz-Kessler CJ, Verveuer D, Pöschl J. Intensivmedizinisches Reizumfeld und Stressoren – welchen Einfluss haben Sie auf die Gehrinentwicklung frühgeborener Kinder?. Klin Padiatr 2010; 222: 236-242
  • 2 Cotterill A, Cowley D, Greer R. Hypoglycaemia: Assessment and management. In: Brook’s Clinical Pediatric Endocrinology. (eds.). Brook C, Clayton P, Brown R. 6th Ed. 2009: 505-529
  • 3 Hay Jr WW. Strategies for feeding the preterm infant. Neonatology 2008; 94: 245-254
  • 4 Hey E. Hyperglycaemia in the very preterm baby. Semin Fetal Neonatal Med 2005; 10: 377-387
  • 5 Mitanchez D. Glucose regulation in the preterm newborn infants. Horm Res 2007; 68: 265-271
  • 6 Mitanchez-Mokhtari D, Lahlou N, Kieffer F et al. Both relative insulin resistance and defective islet beta-cell processing of proinsulin are responsible for transient hyperglycaemia in extremely preterm infants. Pediatrics 2004; 113: 537-541
  • 7 Binder N, Raschko F, Benda GI et al. Insulin infusion with parenetral nutrition in extremely low birthweight infants with hyperglycaemia. J Pediatr 1989; 114: 273-280
  • 8 Ng SM, May JE, Emmerson AJ. Continuous insulin infusion in extremely-low-birth-weight neonates. Biol Neonate 2005; 87: 269-272
  • 9 Heimann K, Peschgens T, Kwiecien R et al. Are recurrent hyperglycemic episodes and median blood glucose level a prognostic factor for increased morbidity and mortality in premature infants ≤1 500 g?. J Perinat Med 2007; 35: 245-248
  • 10 Ogilvy-Stuart AL, Beardsall K. Management of hyperglycaemia in the preterm infant. Arch Dis Child Fetal Neonatal Ed 2010; 95: 126-131
  • 11 Baerdsall K, Vanhaesbrouck S, Ogilvy-Stuart AL et al. Early insulin therapy in very-low birth weight infants. N Eng J Med 2008; 359: 1873-1884
  • 12 van Aerde JE, Wilke MS, Feldman L et al. Accretion of lipid in the fetus and newborn. In: Polin RA, Fox WW, Abman SH. eds. Fetal and neonatal physiology. Vol. 1 3rd edn. Philadelphia, Pensylvania, USA: Saunders; 2003: 388-404
  • 13 Dumortier O, Blondeau B, Duvillie B et al. Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet. Diabetologia 2007; 50: 2495-2503
  • 14 Schwitzgebel VM, Somm E, Klee P. Modeling intrauterine growth retardation in rodents: Impact on pancreas development and glucose homeostasis. Mol Cell Endocrinol. 2009. 25; 304. 78-83
  • 15 Thorn SR, Brown LD, Rozance PJ et al. Increased hepatic glucose production in fetal sheep with intrauterine growth restriction is not suppressed by insulin. Diabetes Aug 28 2012; [Epub ahead of print]
  • 16 deVries A, Holmes MC, Heijnis A et al. Prenatal dexamethasone exposure induces changes in nonhuman primate offspring cardiometabolic and hypothalamic-pituitary-adrenal axis function. J Clin Invest 2007; 117: 1058-1067
  • 17 Reynolds RM. Glucocorticoid excess and the developmental origins of disease: Two decades of testing the hypothesis. Psychoneuroendocrinology Sep 18 2012; [Epub ahead of print]
  • 18 Harmon KA, Gerard L, Jensen DR et al. Continuous glucose profiles in obese and normal-weight pregnant women on a controlled diet: metabolic determinants of fetal growth. Diabetes Care 2011; 34: 2198-2204
  • 19 Lawlor DA, Relton C, Sattar N et al. Maternal adiposity – a determinant of perinatal and offspring outcomes?. Nat Rev Endocrinol 2012; 8: 679-699
  • 20 Hawdon JM, Hubbard M, Hales CN et al. Use of specific immunoradiometric assay to dertermine preterm neonatal insulin-glucose relations. Arch Dis Child Fetal Neonatal Ed 1995; 73: 166-169
  • 21 Hawdon JM, Ward Platt MP, Aynsley-Green A. Patterns of metabolic adaption for preterm and term infants in the first neonatal week. Arch Dis Child 1992; 67: 357-365
  • 22 Belik J, Musey J, Trusell K. Continuous infusion of glucagon induces severe hyponatremia and thrombocytopenia in a premature neonate. Pediatrics 2001; 107: 595-597
  • 23 Collins JW, Hoppe M, Brown K et al. A controlled trial of insulin infusion and parenteral nutrition in extremely low birth weight infants with glucose intolerance. J Pediatr 1991; 118: 921-927
  • 24 Hume R, Burchell A. Abnormal expression of the glucose-6-phosphatase in preterm infants. Arch Dis Child 1993; 68: 202-204
  • 25 Charsha DS, McKinley PS, Whitfield JM. Glucagon infusion for treatment of hypoglycaemia: Efficacy and safety in sick, preterm infants. Pediatrics 2003; 111: 220-221
  • 26 Jackson L, Burchell A, McGeechan A et al. An inadequate glycaemic response to glucagon is linked to insulin resistance in preterm infants?. Arch Dis Child Fetal Neonatal Ed 2003; 88: 62-66
  • 27 Sunehag AL. Parenteral glycerol enhances gluconeogenesis in very premature infants. Pediatr Res 2003; 53: 641-653
  • 28 Alexandrou G, Skiöld B, Karlén J et al. Early hyperglycaemia is a risk factor for death and white matter reduction in preterm infants. Pediatrcs 2010; 125: 584-591
  • 29 Blanco CL, Baillargeon JG, Morrison RL et al. Hyperglycaemia in extremely low birth weigh infants in a predominantly Hispanic population and related morbidities. J Perinatol 2006; 26: 737-741
  • 30 Ertl T, Gyarmati J, Gaal V et al. Relationship between hyperglycemia and retinopathy of prematurity in very low birth weight infants. Biol Neonat 2006; 89: 56-59
  • 31 Garg R, Agthe AG, Donehue PK et al. Hyperglycemia and retinopathy of prematurity in very low birthweight infants. J Perinatol 2003; 23: 186-194
  • 32 Hall NJ, Peters M, Eaton S et al. Hyperglycemia is associated with increased morbidity and mortality rates in neonates with necrotizing enterocolitis. J Pediatr Surg 2004; 113: 898-901
  • 33 Kao LS, Morris BH, Lally KP et al. Hyperglycaemia and morbidity and mortality in extremely low birth weight infants. J Perinatol 2006; 26: 730-736
  • 34 Manzoni P, Castagnola E, Motert M et al. Hyperglycaemia as a possible marker for invasive fungal infection in preterm neonates. Acta Paediatrica 2006; 95: 486-493
  • 35 Rowen JL, Atkins JT, Levy ML et al. Invasive fungal dermatitis in the ≤1 000-gram neonate. Pediatrics 1995; 95: 682-687
  • 36 Pollak A, Cowett RM, Schwartz R et al. Glucose disposal in low-birth weigh infants during steady state hyperglycaemia: effects of exogenous insulin administration. Pediatrics 1978; 61: 546-549
  • 37 Tyrala EE, Chen X, Boden G. Glucose metabolism in the infant weighing less than 1,100 grams. J Pediatr 1994; 125: 283-287
  • 38 Dweck H, Cassady G. Glucose intolerance in infant of very low birth weight 1 100 g or less. Pediatrics 1974; 53: 189-195
  • 39 Farrag HM, Cowett RM. Glucose homeostasis in the micropremie. Clin Perinatol 2000; 27: 1-22
  • 40 Hays SP, Smith EO, Sunehag AL. Hyperglycaemia is a risk factor for early death and morbidity in extremely low birth-weight infants. Pediatrics 2006; 118: 1811-1818
  • 41 Mc Cowen KC, Malhorta A, Bistrian BR. Stress-induced hyperglycaemia. Crit Care Clin 2001; 17: 107-124
  • 42 Chakravarthy MV, Zhu Y, Wice MB et al. Decreased fetal size is associated with beta-cell hyperfunction in early life and failure with age. Diabetes 2009; 57: 2698-2707
  • 43 Craig ME, Hattersley A, Donaghue KC. Definition, epidemiology and classification of diabetes in children and adolescents. Pediatr Diabetes 2009; 10 (Suppl. 12) 3-12
  • 44 Holterhus PM, Beyer P, Bürger-Büsing J et al. Diagnostik, Therapie und Verlaufskontrolle des Diabetes mellitus im Kindes- und Jugendalter. S3-Leitlinie. http://www.deutsche-diabetesgesellschaft.de/redaktion/mitteilungen/leitlinien/EBL_Kindesalter_2009.pdf 2009
  • 45 Roth-Kleiner M, Stadelmann Diaw C, Urfer J et al. Evaluation of different POCT devices for glucose measurement in a clinical neonatal setting. Eur J Pediatr 2010; 169: 1387-1395
  • 46 Pittas AG, Siegel RD, Lau J. Insulin therapy for critically ill hospitalized patients: a meta-analysis of randomized controlled trials. Arch Intern Med 2004; 164: 2005-2011
  • 47 Sinclair JC, Bittino M, Cowett RM. Interventions for prevention of neonatal hyperglycaemia in very low birth weight infants. Cochrane Database Syst Rev. Jul 8 2009; CD007615, Review
  • 48 Kaempf JW, Kaempf AJ, Wu Y et al. Hyperglycaemia, insulin and slower growth velocity may increase the risk of retinopathy of prematurity. J Perinatol 2011; 31: 251-257
  • 49 Wikström S, Lundin F, Ley D et al. Carbon dioxide and glucose affect electrocortical backround in extremely preterm infants. Pediatrics 2011; 127: e1028-e1034 Epub 2011 Mar 28
  • 50 van der Lugt NM, Smits-Wintjens VE, van Zwieten PH et al. Short and long term outcome of neonatal hyperglycaemia in very preterm infants: a retrospective follow-up study. BMC Pediatr 2010; 10: 52
  • 51 Hattersley A, Bruining J, Shield J et al. The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes 2009; 10 (Suppl. 12) 33-42
  • 52 Karges B, Meissner T, Icks A et al. Management of diabetes mellitus in infants. Nat Rev Endocrinol 2011; DOI: 10.1038/nrendo.2011.204.
  • 53 Holl RW. Diabetes mellitus beim Frühgeborenen: Erstmalige Behandlung mit Sulfonylharnstoff. Klin Padiatr 2009; 221: 52-53
  • 54 Wendelin G, Haim M, Reiterer F et al. Diabetes mellitus beim Frühgeborenen: Erstmalige Behandlung mit Sulfonylharnstoff. Klin Padiatr 2009; 221: 100
  • 55 Ostertag SG, Jovanovic L, Lewis B et al. Insulin pump therapy in the very low birth weight infant. Pediatrics 1986; 78: 625-630
  • 56 Pointexter BB, Karn CA, Denne SC. Exogenous insulin reduces proteolysis and protein synthesis in extremely low birth weight infants. J Pediatr 1998; 132: 948-935
  • 57 Beardsall K, Ogilvy-Stuart AL, Frystyk J et al. Early elective insulin therapy can reduce hyperglycaemia and increase insulin-like-growth factor-I levels in very low birth weight infants. J Pediatr 2007; 151: 611-617
  • 58 Beardsall K, Vanhaesbrouck S, Ogilvy-Stuart AL et al. A randomised controlled trial of early insulin therapy in very low birth weight infants, “NIRTURE” (neonatal insulin replacement therapy in Europe). BMC Pediatr 2007; 7: 29