Hormonal, electrolyte disturbances and features of hemostasis in term newborn infants of mothers with gestational diabetes mellitus.

The article reviews the available data on investigations in the field of electrolyte (calcium, magnesium), hormonal (insulin, leptin) and hemostasis disturbances in term newborns from women with gestational diabetes; possible mechanisms of their development are also highlighted. The review describes changes in blood glucose concentration in term newborns from women with gestational diabetes, and their impact on the child's condition. In addition to already known factors causing macrosomia and other metabolic disorders in term neonates, the role of leptin (peptide hormone that regulates energy metabolism) is quite discussable. Low leptin levels lead to the development of obesity. It is also confirmed, that leptin influences brain development of the newborn, leading to later cognitive deficits in children from women with GDM.
The aim of the review is to summarize the available data on investigations in the field of electrolyte (calcium, magnesium), hormonal (insulin, leptin) and hemostasis disturbances in term newborns from women with gestational diabetes.

term newborn, magnesium, calcium, glucose, leptin, insulin, hemostasis, gestational diabetes

1. Рагозин А.К., Арбатская Н.Ю., Демидова И.Ю., Колегаева О.И. Гестационный сахарный диабет: патогенез, диагностика, протокол ведения. Доступно по: www.med-m.su/publikatsii-v-presse/blog) [Ragozin AK, Arbatskaya NY, Demidova IY, Kolegaeva OI. Gestational diabetes: pathogenesis, diagnosis, management protocols. Available from: www.med-m.su/publikatsii-v-presse/blog]

2. Metzger B, Oats J, Coustan D, Hod M. Results of the HAPO study: progress towards a new paradigm for detection & diagnosis of GDM. Proceedings of the 5th International simposium on Diabetes and pregnancy; 2009. Italy, Sorrento.

3. Hyperglycemia and Adverse Pregnancy Outcomes. New England Journal of Medicine. 2008;358(19):1991–2002. doi: 10.1056/NEJMoa0707943

4. Cundy T, Gamble G, Townend K, et al. Perinatal mortality in Type 2 diabetes mellitus. Diabetic Medicine. 2000;17(1):33–39. doi: 10.1046/j.1464-5491.2000.00215.x

5. Андреева Е.В. и др. Состояние фето-плацентарной системы при гестационном сахарном диабете. / Материалы IV съезда акушеров-гинекологов России; 2008. С. 11. [Andreeva EV, Dobrokhotova YE, Yushina MV, et al. Sostoyanie feto-platsentarnoy sistemy pri gestatsionnom sakharnom diabete. Proceedings of IV Russian Conference of obstetrics and gynecologists. Moscow; 2008. 11 p.]

6. Евсюкова И.И., Кошелева Н.Г. Сахарный диабет: беременные и новорожденные. – М.: Специальная литература; 2009. С. 272. [Evsyukova II, Kosheleva NG. Diabetes mellitus: pregnant women and newborns. Moscow: Special literature; 2009. 272 p.]

7. Campbell IW, Duncan C, Urquhart R, Evans M. Placental dysfunction and stillbirth in gestational diabetes mellitus. The British Journal of Diabetes & Vascular Disease. 2009;9(1):38–40. doi: 10.1177/1474651408101348

8. BjØRstad AR, Irgens-Hansen K, Daltveit AK, Irgens LM. Macrosomia: mode of delivery and pregnancy outcome. Acta Obstetricia et Gynecologica Scandinavica. 2010;89(5):664–669. doi: 10.3109/00016341003686099

9. Дементьева Г.М. Оценка физического развития новорожденных: пособие для врачей. – М.: НИИ-ПиДХ МЗ РФ; 2000. – С. 25. [Dementieva GM. Evaluation of physical development of infants: a manual for physicians. Moscow: NII-PiDH Ministry of Health; 2000. 25p.]

10. Дедов И.И., Петеркова В.А. Руководство по детской эндокринологии. – М.: Универсум Паблишинг; 2006. 595 с. [Dedov II, Peterkova VA. Pediatric Endocrinology Manual. Moscow: Universum Pablishing; 2006. 595 p.]

11. Краснопольский В.И., Петрухин В.А., Бурумкулова Ф.Ф. Гестационный сахарный диабет: новый взгляд на старую проблему. // Акушерство и гинекология. – 2010. – №2 – С. 3–6. [Krasnopolsky VI, Petrukhin VA, Burumkulova FF. Gestational diabetes: a new view of an old problem. Akusherstvo i ginekologii︠a︡. 2010;(2):3–6.]

12. Петрухин В.А., Куликов И.А., Бурумкулова Ф.Ф., Котов Ю.Б. Гестационный сахарный диабет: факторы риска, контроль гликемии и профилактика диабетической фетопатии. // Российский вестник акушера-гинеколога. – 2007. – Т. 7. – №3 – С. 47–51. [Petrukhin VA, Kulikov IA, Burumkulova FF, Kotov Y.B. Gestational diabetes mellitus: risk factors, glycemia monitoring, prevention of diabetic fetopathy. Rossiĭskiĭ vestnik akushera-ginekologa. 2007;7(3):47–51.]

13. Skitek M. Scrining for gestational diabetes mellitus. Clinical Chemical Laboratory Medicine. 2005;43(6):664–666. doi: 10.1515/CCLM.2005.114

14. Колесникова М.Б., Килина А.В. Антенатальное развитие и течение адаптационного периода новорожденных, родившихся у матерей с гестационным сахарным диабетом. // Вопросы современной педиатрии. – 2008. – Т. 7. – №2. – С. 111–114. [Kilina AV, Kolesnikova MB. Antenatal development and adaptation period of infants born by mothers with gestational diabetes. Voprosy sovremennoĭ pediatrii. 2008;7(2):111–114.]

15. Троицкая М.В. Особенности ранней постнатальной адаптации новорожденных от матерей с разными типами сахарного диабета: Автореф. дис. ... канд. мед. наук. – М.; 2001. 23 с. [Troitskaya MV. Especially early postnatal adaptation of newborns from mothers with different types of diabetes. [dissertation abstract] Moscow; 2001. 23 p.]

16. Schneider S, Hoeft B, Freerksen N, et al. Neonatal complications and risk factors among women with gestational diabetes mellitus. Acta Obstetricia et Gynecologica Scandinavica. 2011;90(3):231–237. doi: 10.1111/j.1600-0412.2010.01040.x

17. Шабалов Н.П. Неонатология: Учебное пособие. – М.: МЕДпресс информ. – 2009. [Shabalov NP. Neonatology. Handbook. Moscow: MEDpress Inform; 2009.]

18. Бурумкулова Ф.Ф., Петрухин В.А. Гестационный сахарный диабет: эндокринологические и акушерские аспекты. // Врач. – 2012. – №9 – С. 2–5. [Burumkulova FF, Petrukhin VA. Gestational diabetes mellitus: endocrinological and obstetric aspects. Vrach. 2012;(9):2–5.]

19. Володин Н.Н. Неонатология: национальное руководство. – М.: ГЭОТАР-Медиа; 2009. С. 848. [Volodin NN. Neonatology: national guidelines. Moscow: GEOTAR-Media; 2007. 848 p.]

20. Логутова Л.С., Петрухин В.А., Бочарова И.И. Мониторинг новорожденных, родившихся у матерей с гестационным сахарным диабетом. // Российский вестник акушера-гинеколога. – 2013. – Т. 13. – №2 – С. 89–94. [Logutova LS, Petrukhin VA, Bocharova II. Monitoring of newborn infants born to mothers with gestational diabetes mellitus. Rossiĭskiĭ vestnik akushera-ginekologa. 2013;13(2):89–94.]

21. Mountain KR. The infant of the diabetic mother. Bailliere's clinical obstetrics and gynaecology. 1991;5(2):413–442.

22. Ведмедь А.А., Шапошникова Е.В. Особенности течения беременности, родов и состояния новорожденных у пациенток с гестационным сахарным диабетом. // Вестник Российского университета дружбы народов. – 2009. – Т. 7. – №348. – С. 51. [Vedmed AA, Shaposhnikov EV. Peculiarities of pregnancy, childbirth and neonatal status in patients with gestational diabetes mellitus. Bulletin of the Russian People's Friendship University. 2009;7(348):51.]

23. Esakoff TF, Cheng YW, Sparks TN, Caughey AB. The association between birthweight 4000 g or greater and perinatal outcomes in patients with and without gestational diabetes mellitus. American Journal of Obstetrics & Gynecology. 2009; 200(6):672.e671–672.e674. doi: 10.1016/j.ajog.2009.02.035

24. Сорокина А.В. Крупный плод: мифы и реальность. // Российский вестник акушера-гинеколога. – 2013. – Т. 13. – №. 4. – С. 86–88. [Sorokina AV. A large fetus: myths and realities. Rossiĭskiĭ vestnik akushera-ginekologa. 2013;13(4):86–88.]

25. Das SU, Ankola P. Infants Born to Mothers with Pre-Gestational Diabetes Have a Higher Risk of Developing Neonatal Hypocalcemia Compared to Mothers with Gestational Diabetes. Journal of Neonatology Research. 2012;2(3):130–133.

26. Mitanchez D. Management of infants born to mothers with gestational diabetes. Paediatric environment. Diabetes & metabolism. 2010;36(6 Pt 2):587–594. doi: 10.1016/j.diabet.2010.11.012

27. Van Howe RS, Storms MR. Hypoglycemia in infants of diabetic mothers: experience in a rural hospital. American journal of perinatology. 2006;23(2):105–110. doi: 10.1055/s-2006-931913

28. Deshpande S, Ward Platt M. The investigation and management of neonatal hypoglycaemia. Seminars in fetal & neonatal medicine. 2005;10(4):351–361. doi: 10.1016/j.siny.2005.04.002

29. Flores-le Roux JA, Sagarra E, Benaiges D, et al. A prospective evaluation of neonatal hypoglycaemia in infants of women with gestational diabetes mellitus. Diabetes research and clinical practice. 2012;97(2):217–222. doi: 10.1016/j.diabres.2012.03.011

30. Зернова Л.Ю., Коваленко Т.В. Постнатальная адаптация новорожденных у матерей с ожирением: клинические и метаболические особенности. // Российский вестник перинатологии и педиатрии. – 2011. – Т. 56. – №6 – С. 10–15. [Zernova LYu, Kovalenko TV. Postnatal adaptation of neonatal infants of obese mothers: clinical and metabolic features. Rossiĭskiĭ vestnik perinatologii i pediatrii. 2011;56(6):10–15.]

31. Vela-Huerta MM, Amador-Licona N, Anaya-Aguirre S, et al. Insulin and Leptin Levels in Appropriate-for-Gestational-Age Infants of Diabetic Mother. Iranian journal of pediatrics. 2012;22(4):475–480.

32. Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425–432. doi: 10.1038/372425a0

33. Okereke NC, Uvena-Celebrezze J, Hutson-Presley L, et al. The effect of gender and gestational diabetes mellitus on cord leptin concentration. American journal of obstetrics and gynecology. 2002;187(3):798–803.

34. Nelson CA, Wewerka S, Thomas KM, et al. Neurocognitive sequelae of infants of diabetic mothers. Behavioral neuroscience. 2000;114(5):950–956.

35. Harvey J, Shanley LJ, O'Malley D, Irving AJ. Leptin: a potential cognitive enhancer? Biochemical Society transactions. 2005;33(Pt 5):1029–1032. doi: 10.1042/BST20051029

36. Farr SA, Banks WA, Morley JE. Effects of leptin on memory processing. Peptides. 2006;27(6):1420–1425. doi: 10.1016/j.peptides.2005.10.006

37. Chen Z, Zhao Y, Yang Y, Li Z. Leptin withdrawal after birth: A neglected factor account for cognitive deficit in offspring of GDM mother. Medical hypotheses. 2011;77(1):125–127.

38. Lin X, Taguchi A, Park S, et al. Dysregulation of insulin receptor substrate 2 in β cells and brain causes obesity and diabetes. The Journal of Clinical Investigation. 2004;114(7):908.

39. Kubota N, Terauchi Y, Tobe K, et al. Insulin receptor substrate 2 plays a crucial role in beta cells and the hypothalamus. The Journal of Clinical Investigation. 2004;114(7):917–927. doi: 10.1172/JCI21484

40. Choudhury AI, Heffron H, Smith MA, et al. The role of insulin receptor substrate 2 in hypothalamic and β cell function. Journal of Clinical Investigation. 2005;115(4):940.

41. Orkin SH, Nathan DG, Ginsburg D, et al. Nathan and Oski's hematology of infancy and childhood. Elsevier Health Sciences; 2008.

42. Andrew M, Paes B, Milner R, et al. Development of the human coagulation system in the full-term infant. Blood. 1987;70(1):165–172.

43. Monagle P, Barnes C, Ignjatovic V, et al. Developmental haemostasis. Impact for clinical haemostasis laboratories. Thrombosis and haemostasis. 2006;95(2):362–372. doi: 10.1267/THRO06020362.

44. Del Vecchio A, Latini G, Henry E, Christensen R. Template bleeding times of 240 neonates born at 24 to 41 weeks gestation. Journal of perinatology. 2008;28(6):427–431.

45. Wiedmeier SE, Henry E, Sola-Visner M, Christensen R. Platelet reference ranges for neonates, defined using data from over 47 000 patients in a multihospital healthcare system. Journal of perinatology. 2009;29(2):130–136.

46. Saxonhouse MA, Sola MC. Platelet function in term and preterm neonates. Clinics in perinatology. 2004;31(1):15–28. doi: 10.1016/j.clp.2004.03.009.

47. Mankin P, Maragos J, Akhand M, Saving KL. Impaired platelet-dense granule release in neonates. Journal of pediatric hematology/oncology. 2000;22(2):143–147.

48. Šimák J, Holada K, Janota J, Straňák Z. Surface expression of major membrane glycoproteins on resting and TRAP-activated neonatal platelets. Pediatric research. 1999;46(4):445–445.

49. Dardik R, Kaufmann Y, Savion N, et al. Platelets mediate tumor cell adhesion to the subendothelium under flow conditions: Involvement of platelet GPIIbIIIa and tumor cell αv integrins. International journal of cancer. 1997;70(2):201–207.

50. Linder N, Shenkman B, Levin E, et al. Deposition of whole blood platelets on extracellular matrix under flow conditions in preterm infants. Archives of Disease in Childhood-Fetal and Neonatal Edition. 2002;86(2):F127–F130.

51. Hézard N, Potron G, Schlegel N, et al. Unexpected persistence of platelet hyporeactivity beyond the neonatal period: a flow cytometric study in neonates, infants and older children. Thrombosis and haemostasis. 2003;90(1):116–123.

52. Kenet G, Lubetsky A, Shenkman B, et al. Cone and platelet analyser (CPA): a new test for the prediction of bleeding among thrombocytopenic patients. British journal of haematology. 1998;101(2):255–259.

53. Levy-Shraga Y, Maayan-Metzger A, Lubetsky A, et al. Platelet Function of Newborns as Tested by Cone and Plate(let) Analyzer Correlates with Gestational Age. Acta Haematologica. 2006;115(3–4):152–156.

54. Rajasekhar D, Kestin A, Bednarek F, et al. Neonatal platelets are less reactive than adult platelets to physiological agonists in whole blood. Thrombosis and haemostasis. 1994;72(6):957–963.

55. Strauss T, Maayan-Metzger A, Simchen MJ, et al. Impaired platelet function in neonates born to mothers with diabetes or hypertension during pregnancy. Klinische Padiatrie. 2010;222(3):154–157. doi: 10.1055/s-0030-1249092

56. Knobler H, Savion N, Shenkman B, et al. Shear-induced platelet adhesion and aggregation on subendothelium are increased in diabetic patients. Thrombosis research. 1998;90(4):181–190.

57. Kudoloa GB, Koopmans SJ, Haywood JR, DeFronzo RA. Chronic hyperinsulinernia inhibits platelet-activating factor (PAF) biosynthesis in the rat kidney. Journal of lipid mediators and cell signalling. 1997;16(1):23–37.