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NEONATAL HYPOGLYCEMIA

NEONATAL HYPOGLYCEMIA. MAJID MOHAMMADIZADEH MD ISFAHAN UNIVERSITY OF MEDICAL SCIENCES DEPARTMENT OF PEDIATRICS DIVISION OF NEONATOLOGY. را شامل می شود term و late preterm این بحث نوزادان. References.

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NEONATAL HYPOGLYCEMIA

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  1. NEONATAL HYPOGLYCEMIA MAJID MOHAMMADIZADEH MD ISFAHAN UNIVERSITY OF MEDICAL SCIENCES DEPARTMENT OF PEDIATRICS DIVISION OF NEONATOLOGY M. MOHAMMADIZADEH

  2. را شامل می شود term و late pretermاین بحث نوزادان M. MOHAMMADIZADEH

  3. References • Tin W. Defining neonatal hypoglycemia: a continuing debate. Seminars Fetal Neonatal Med 2014;19: 27-32 • Hawdon JM. Neonatal hypoglycemia: Are evidence- based clinical guidelines achievable? Neoreviews 2014; 15(3): e91- 8 • Adamkin DH and the committee on fetus and newborn. Clinical report- Postnatal glucose homeostasis in late preterm and term infants. Pediatrics 2011;127: 575- 9 • Aziz K, Canadian Pediatric Society- Fetus and Newborn Committee. Pediatric Child Health 2004; 9(10): 723- 9. Reaffirmed at 2013 by this committee M. MOHAMMADIZADEH

  4. چرا هیپوگلیسمی نوزادی مهم و قابل توجه است؟ M. MOHAMMADIZADEH

  5. Hypoglycemia is one of the most frequent metabolic problems in neonatal medicine • Maintainingglucose homeostasis is one of the important physiological events during fetal-to-neonatal transition M. MOHAMMADIZADEH

  6. Neonatal glucose concentrations decrease after birth to as low as 30 mg/dL during the first 1 to 2 hours after birth • It then increase to higher and relatively more stable concentrations, generally above 45 mg/dL by 12 hours after birth M. MOHAMMADIZADEH

  7. هموستاز گلوکز و سازگاری متابولیک طی انتقال از زندگی جنینی به نوزادی M. MOHAMMADIZADEH

  8. Endocrine and MetabolicChanges ofNeonatal MetabolicAdaptation M. MOHAMMADIZADEH

  9. Numerical definition of hypoglycemia/ determination of a cut- off valueIs it true? M. MOHAMMADIZADEH

  10. Four different approaches to define neonatal hypoglycemiaby Marvin Cornblath and his six co-investigators • Approach based on clinical manifestation • Approach based on epidemiological data • Approach based on acute changes in physiological responses • Approach based on neurologic and developmental outcomes M. MOHAMMADIZADEH

  11. Approach based on neurologic and developmental outcomes • Data for this functional definition that correlates the glucose concentration with adverse neurodevelopmental outcome is still very limited • It is confounded by: • the use of various cut-off glucose levels • the duration and frequency of ‘hypoglycemia’ in different studies • Furthermore, most data from the observational studies have failed to include ‘non-hypoglycemic controls’ M. MOHAMMADIZADEH

  12. Approach based on neurologic and developmental outcomes • Boluyt et al: identified 18 observational studies that correlate ‘neonatal hypoglycaemia’ and neurodevelopmental outcome • Overall quality and methodology was considered poor in 16 of them • There was a major clinical and methodological heterogeneity of the other two high-quality studies • No studies provided a valid estimate of the effect of neonatal hypoglycaemia on neurodevelopment M. MOHAMMADIZADEH

  13. Approach based on neurologic and developmental outcomes • This statement remains unchanged by more recently published evidence from a 15-year follow-up cohort of preterm infants (<32 weeks of gestation) with frequent low blood glucose measurements in the first 10 days and their carefully matched controls M. MOHAMMADIZADEH

  14. Of concern is the widespread adoption of a single numerical value based on two published papers (whose results are now generally considered not to justify their conclusions) that a level of less than 2.6mmol/L (<47 mg/dL) should be used to define neonatal hypoglycemia M. MOHAMMADIZADEH

  15. The two published papers M. MOHAMMADIZADEH

  16. First • The numerical ‘cut off’ value of the definition was widely adopted as <2.6 mmol/l (47 mg/dl) from the late 1980s, influenced by an important publication in 1988 by Lucas et al. • They reported serious impairment in motor and cognitive development at 18 months in babies with recurrent ‘asymptomatic hypoglycemia’. M. MOHAMMADIZADEH

  17. They stated that: • ‘the association between modest hypoglycemia and poor neurodevelopment reported here might not be causal and might reflect our failure to adjust adequately for confounding factors’ • They also stressed in a letter published later about the difficulty in proving causation by the observational study: • ‘when such observations generate hypotheses or legitimate clinical concerns, this should stimulate future studies’ M. MOHAMMADIZADEH

  18. However, most readers were attracted only to the final statement of the abstract: • ‘These data suggest that, contrary to general belief, moderate hypoglycemia may have serious neurodevelopmental consequences and reappraisal of current management is urgently required’ M. MOHAMMADIZADEH

  19. Second • The report by Lucas et al. was soon followed by the publication of a paper: • auditory and somatosensory evoked brain stem potentials in five babies were delayed or blocked when the blood glucose level fell to <2.6 mmol/l (47 mg/dl) • Subsequent studies using the same approach failed to support this finding M. MOHAMMADIZADEH

  20. The study by:Northern Neonatal Nursing Initiative Trial Group M. MOHAMMADIZADEH

  21. Comparison of mean Griffiths Development Quotients at 2 years of age M. MOHAMMADIZADEH

  22. Comparison of Wechsler Intelligence Scale for Children (WISC-III) at 15 years of age M. MOHAMMADIZADEH

  23. Summary of assessments at 15 years of the studied children M. MOHAMMADIZADEH

  24. چرا به دنبال تعریف عددی هیپوگلیسمی نوزادی نباشیم؟ • نوع مطالعات مورد اشاره • تفاوت علت هیپوگلیسمی • تفاوت مدت هیپوگلیسمی • تفاوت در امکان استفاده از سوخت های جایگزین M. MOHAMMADIZADEH

  25. There is no single ‘cut-off’ blood glucose value that can be used to define clinically significant neonatal hypoglycemia • There is no justifiable reason to continue using the most widely adopted numerical value of blood glucose <2.6 mmol/l (47 mg/dl) as the definition M. MOHAMMADIZADEH

  26. Attempts to arrive at a single definition, usually to 1 decimal place in the context of devices that cannot measure accurately to ±0.5 mmol/L (± 9 mg/dL) and failing to take into account biological variability, have no rational basis M. MOHAMMADIZADEH

  27. The most widely accepted lower limit of blood glucose, <2.6 mmol/l (47 mg/dl), was derived from observational studies that at best can only provide a ‘hypothesis’ • Turning this hypothesis into a belief may have trapped us in a clinical conundrum with a fear of allegations of medical malpractice M. MOHAMMADIZADEH

  28. Perhaps, more importantly, many newborn babies (and their families) have also been ensnared in such confusing conundrums, and subjected to potentially harmful effects • Many newborn babies are subjected to overdiagnosis, investigation, and treatment for ‘neonatal hypoglycemia’ M. MOHAMMADIZADEH

  29. Operational thresholds M. MOHAMMADIZADEH

  30. Operational thresholds The blood glucose thresholds for taking action M. MOHAMMADIZADEH

  31. It is important to prevent potentially damaging hypoglycemia in vulnerable infants • But this goal must be balanced against the risks of overly invasive management: • separation of mother and infant • placing at risk the establishment of breastfeeding • unnecessary administration of formula or intravenous glucose, which in turn impairs metabolic adaptation to postnatal life M. MOHAMMADIZADEH

  32. تعریف و اهداف • شناسایی و مونیتورینگ نوزادان در معرض خطر و مداخله به هنگام برای پیشگیری و/ یا درمان هیپوگلیسمی • اندازه گیری قند خون در نوزاد علامت دار و مداخله درمانی در صورت نیاز M. MOHAMMADIZADEH

  33. شناسایی و مونیتورینگ نوزادان در معرض خطر و مداخله به هنگام برای پیشگیری و/ یا درمان هیپوگلیسمی M. MOHAMMADIZADEH

  34. نوزادان در معرض خطر کدامند؟ • پاتوفیزیولوژی • 4 دسته نوزادان: • Late preterm • LGA • SGA • Infant of diabetic mother • آیا با در نظر گرفتن این گروه ها نوزادان دیگری را با هیپوگلیسمی از دست می دهیم؟ • نوع و نحوه تغذیه این نوزادان M. MOHAMMADIZADEH

  35. نوع و نحوه تغذیه • All infants who are expected to tolerate enteral feedings should be fed with milk as soon as possible after birth and then at frequent intervals thereafter • Infants who are capable of sucking should be offered the breast at each feeding (if this is the mother’s wish) M. MOHAMMADIZADEH

  36. If it is likely that infants will need supplementary formula feedings, maternal human milk expression should be encouraged • The requirement for formula feedings must be titrated against the clinical condition of the infant, blood glucose monitoring, and the supply of maternal human milk • In the breastfed infant, formula intake should be kept to the minimum necessary, with the goal of enhancing breastfeeding and avoiding suppression of normal metabolic adaptation M. MOHAMMADIZADEH

  37. زمان اندازه گیری اولین قند خون پس از تولد • تغذیه در ساعت اول تولد و اندازه گیری نیم ساعت بعد • تغذیه در ساعت اول تولد و اندازه گیری پیش از نوبت بعدی تغذیه • تغذیه و سپس اندازه گیری در ساعت 2 تولد M. MOHAMMADIZADEH

  38. تا چه زمانی اندازه گیری را ادامه دهیم؟ • اگر قند خون در محدوده طبیعی بود و در نهایت به 47-45 میلی گرم در دسی لیتر رسید: • نوزاد مادر دیابتی و LGA: تا ساعت 12 تولد • نوزاد Late pretermو SGA: حداقل تا ساعت 24تولد/ + دو نوبت تا ساعت 36 تولد به شرط برقراری تغذیه مناسب M. MOHAMMADIZADEH

  39. روش اندازه گیری قند خون • When NH is suspected, the plasma or blood glucose concentration must be determined immediately by using one of the laboratory enzymatic methods (eg, glucose oxidase, hexokinase, or dehydrogenase method) • Plasma blood glucose values tend to be approximately 10% to 18% higher than whole-blood values because of the higher water content of plasma M. MOHAMMADIZADEH

  40. روش اندازه گیری قند خون • To prevent delays in the initiation of treatment, bedside reagent test-stripglucose analyzers can be used if the test is performed carefully and the clinician is aware of the limited accuracy of these devices M. MOHAMMADIZADEH

  41. Test-strip results demonstrate a reasonable correlation with actual plasma glucose concentrations • But the variation from the actual level may be as much as 10 to 20 mg/dL • Unfortunately, this variation is greatest at low glucose concentrations M. MOHAMMADIZADEH

  42. Because of limitations with “rapid” bedside methods, the blood or plasma glucose concentration must be confirmed by laboratory testing ordered stat • A long delay in processing the specimen can result in a falsely low concentration as erythrocytes in the sample metabolize the glucose in the plasma • This problem can be avoided by transporting the blood in tubes that contain a glycolytic inhibitor such as fluoride M. MOHAMMADIZADEH

  43. فاصله اندازه گیری قند خون و زمان آن نسبت به نوبت تغذیه • بستگی دارد به: • میزان قند خون • نیاز یا عدم نیاز به مداخله M. MOHAMMADIZADEH

  44. میزان گلوکز خون در محدوده قابل قبول است • زمان اندازه گیری: • پیش از نوبت بعدی تغذیه • فاصله اندازه گیری: • هر 3-2 ساعت یک بار • هر 4 ساعت یک بار • هر 6-3 ساعت یک بار M. MOHAMMADIZADEH

  45. میزان گلوکز خون نیاز به مداخله دارد(آکادمی کودکان آمریکا) M. MOHAMMADIZADEH

  46. میزان گلوکز خون نیاز به مداخله دارد(انجمن کودکان کانادا) • At-risk babies who have a blood glucose of less than 1.8 mmol/L at 2 h of age despite one feed or less than 2.0 mmol/L after subsequent feeding, should receive an intravenous dextrose infusion • At-risk babies who repeatedly have blood glucose levels of less than 2.6 mmol/L despite subsequent feeding should also be considered for intravenous therapy M. MOHAMMADIZADEH

  47. میزان گلوکز خون نیاز به مداخله دارد(انجمن کودکان کانادا) M. MOHAMMADIZADEH

  48. میزان گلوکز خون نیاز به مداخله دارد (گروه پزشکان آمریکا و انگلستان) • The suggested blood glucose operational threshold concentrationsat which clinicians should consider intervention are: • A single measurement of blood glucose <1 mmol/l (18 mg/dl) • Blood glucose level <2 mmol/l (36 mg/dl), that remains belowthe same value at the next measurement • A single measurement of <2.5 mmol/l (45 mg/dl) in a newbornwith abnormal clinical signs M. MOHAMMADIZADEH

  49. میزان گلوکز خون نیاز به مداخله دارد • تا چه زمانی اندازه گیری را ادامه دهیم؟ • The clinician must be certain that the infant can maintain normal plasma glucose concentrations on a routine diet for a reasonably extended period (through at least 3 feed-fast periods) before discharge • نوع تغذیه M. MOHAMMADIZADEH

  50. اندازه گیری قند خون در نوزاد علامت دار و مداخله درمانی در صورت نیاز M. MOHAMMADIZADEH

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