hypoglycemia of newborn

Hypoglycemia of Newborn

Dr. Ilya Rozin

הצגת מקרה

בהריונה הראשון 30תאומים, בן ובת, נולדו לאם בת (IVF .)

.מעקב הריון תקין עקב יתר לחץ-דם. מספר שעות 32 אם אושפזה בשבוע

טרם הלידה היתה ירידת מים. ילדה בניתוח קיסרי.9 ו-8 גרם, אפגר 1825הבת, מצג ראש, משקל לידה ,

נזקקה למעט חמצן.-סבלה מRDS אינטובציה כשעה לאחר הלידה, קיבלה ,

סורפקטנט, הונשמה למשך יממה.

הצגת מקרה

10 ו-9 גרם, אפגר 1600הבן, מצג ראש, משקל.החל לקבל כלכלה )חלב אם( ביום השני לחיים. •ביממה הרביעית היו ערכי גלוקוז גבוהים בסטיק.•בדיקה גופנית – תקינה, בדיקות דם – תקינות, תרביות דם •

עקרות. עקב היפרגליקמיה עקשנית הוחל במתן אינסולין, למרות •

זאת ערכי גלוקוז המשיכו להיות גבוהים. ביממה הששית התינוק נראה חולה מאוד והחל לפרכס. •

נעשה ברור זיהומי מלא – שלילי. מג%, 234מג%, בסטיק בדם – 12 גלוקוזCSF -ב•

מג%.39גלוקוז במעבדה

הצגת מקרה

הבת החלה לקבל חלב אם ביום השלישי לחיים.•ביממה החמישית הופיעו ערכי סוכר גבוהים •

בסטיק. בהדרגה נראתה פחות טוב: חוורת, אפטית, ירדה •

ממשקל לידה. 13%קיבלה עירוי של גלוקוז בריכוז נמוך עם אינסולין. •

עקב החמרה כללית במצב ואפנאות הונשמה.נעשה ברור זיהומי – שלילי. • מג196 מג%, גלוקוז בדם בסטיק 1סוכר CSFב-•

מג%.%14, גלוקוז במעבדה –

הצגת מקרה

פער בין בדיקת הסוכר במעבדה ובסטיק.

.הסטיק בודק חומרים מחזרים ולא גלוקוז בלבד

-נשלח דם לGalactose 1-Phosphate Uridyltransferase ונמצאה פעילות נמוכה מאוד

של האנזים. :אבחנהClassical Galactosemia

הצגת מקרה

,הוחל במתן גלוקוז בריכוזים עולים הופסק אינסולין, בהמשך קבלו כלכלה נטולת

galactose.US .מוח ביום השני לחיים לשניהם תקין US מוח בשחרור: אזורים אקוגנים סביב החדרים

עם ציסטות דו צדדיות. במעקב: בעיות טונוס קשות, תנועות עיניים

.CPאבנורמליות, פיגור קוגניטיבי,

HYPOGLYCEMIA IN THE NEWBORN INFANT

Glucose metabolism in the fetus Glucose metabolism in the neonate Definition of hypoglycemia in the newborn Etiology and types of hypoglycemia Clinical presentation of hypoglycemia Infant of diabetic mother Management and outcome

Glucose metabolism in the fetus

Maternal glucose is the major substrate delivered to the human fetus for energy metabolism.

Fetal uptake of glucose is regulated by maternal glucose concentration.

Glucose transport: concentration gradient – facilitated diffusion. Fetal plasma glucose is ~ 70%-80% of mother’s. When gestational age increases, uterine blood flow increases,

therefore, blood flow to the fetus increases. Glucose transport to the fetus is only 40-50% of the total

uptake by the placenta.


Insulin in the 8 weeks of gestation and in 13-18 weeks fetal Insulin response to maternal hyperglycemia.

Insulin: stimulates glucose incorporation into liver glycogen, acts as growth hormone

Growth Hormone in the 9 weeks and rapidly increased between 11-16 weeks of gestation.

Fetal GH level is high to maternal plasma.


Hepatic glycogen content is low in early gestation and increases slowly ) between 15-20 weeks of gestation(.

Glycogenolysis and glycogenesis enzymes are present and increase slowly through pregnancy.

Absence of gluconeogenesis )gluconeogenesis enzymes are not active in utero(.

80% of fetal glucose to energy 20% of fetal glucose to lactate, amino acid and other

means.

Glucose metabolism in the newborn:At birth…

Discontinuation of maternal substrates and nutrient supply: need to mobilize glucose or other substrates to meet energy requirements.

Glucose falls )nadir ~ 1-2 hours of age( and rises by 2-4 hours in all infants.

Glucoregulatory hormones )epinephrine, norepinephrine, glucagon( rise rapidly, insulin decreases )mobilization of glycogen and fatty acids(.

Levels of hormones and metabolic fuels change after birth

Glucose metabolism in the newborn

Breast milk provides lactose but not more than 50% of glucose utilization rate.

Therefore, neonates are markedly dependent on active gluconeogenesis to maintain hepatic glucose production.

Role of elevated Growth Hormone is not defined. In first 48-72 hours level is low with elevation in the 8 weeks after birth.

Glucose kinetics in the newborn

Rates of glucose production and utilization in the newborn are between 4-6 mg/kg/min

Rates are higher in the newborn compared with adults due to:- Higher metabolic rate- Higher brain-to-body weight ratio of the newborn brain

After 2 days, with the introduction of feeding, the normal infant maintains plasma glucose at 40-70 mg/dl )2.5-6 mmol /L(.

Definition of neonatal hypoglycemia

Statistical approach. Clinical approach

)Most infants recover after birth, lack of correlation with CNS side effects, lack of outcome studies, studies based on different populations, changes in mothers’ and infants’ care(.

Most investigators would consider serum glucose concentration < 2.5 mmol/L or 45 mg/dl to be low in the first 72 hours of life.

The definition is the same for term and preterm infants. Differ to transient and persistent ,symptomatic and

asymptomatic hypoglycemia.

Etiology of neonatal hypoglycemia

I. TRANSIENT HYPOGLYCEMIA

A. Changes in maternal metabolism: 1. Intrapartum administration of glucose 2. Drugs: terbutalin, ritodrin, propranolol

3. Diabetes in pregnancy )IDM(

B. Neonatal problems: 1. IUGR/SGA infant 5. Preterm infant 2. Birth asphyxia 6. Rh-incompatibility 3. Infection 7. Hyperviscosity 4. Hypothermia 8. Cardiac malformations 9. Iatrogenic causes

II. Persistent or recurrent hypoglycemia

A. Hyperinsulinism: 1. Beta-cell hyperplasia: nesidioblastosis -adenoma spectrum,

sulfonylurea receptor defect. 2. Beckwith- Wiedemann Syndrome.

B. Endocrine disorders:1. Pituitary insufficiency.2. Cortisol deficiency.3. Congenital glucagon deficiency.

4. Epinephrine deficiency. C. Inborn errors of metabolism:

1. Carbohydrate metabolism – galactosemia, fructose intolerance, glycogen storage disease, gluconeogenesis disorders.2. Amino-acid metabolism – Maple-syrup urine disease, aminoacidopathies3. Fatty-acid metabolism – carnitine defects, acyl-CoA dehydrogenase defects.

D. Nerohypoglycemia )hypoglycorrhahia(: defective glucose transport.

Beckwith’s syndrome with glossoptosis

Incidence of hypoglycemia according to birth weight and gestational age

Symptoms and signs of neonatal hypoglycemia

Abnormal cry Apnea, cyanosis Feeding difficulties Respiratory distress Hypothermia Hypotonia

Irritability Jitteriness, tremor Lethargy, stupor Seizures Sweating Tachycardia

Infants of Diabetic Mothers

Macrosomy, visceromegaly, unexplained fetal demise

congenital anomalies:congenital anomalies:

Cardiac – VSD, TGA, TOF, double-outlet..

Skeletal and CNS – caudal regression

Gastrointestinal – small left colon

organs and systems organs and systems abnormalities:abnormalities:

HypoglycemiaHeart failure, septal hypertrophyPolycythemiaHyperbilirubinemiaHypocalcemiaRenal vein thrombosis

Infants of Diabetic Mothers

Maternal hyperglycemia

Fetal hyperglycemia

Fetal Hyperinsulinism

Increased fetal substrate uptake

Activity hepaticenzymes

Lipid synthesis

Macrosomia

Cardiomegaly

Adipose tissue

Metabolic rate

Oxygen consumption

Hypoxemia

Synthesis of erythropoietin

RBC mass - polycythemia

Suppressed production of surfactant

RDS

Stillbirth?

Blood-work in neonatal hypoglycemia

Glucose to lab (ASAP, on ice)

Electrolytes +chloride Cortisol, growth

hormone Insulin level Blood gases Lactate + pyruvate Ammonia

Free fatty acid Amino acids Acetoacetate/beta

hydroxybutirate Urine:

Ketones, organic acids, reducing substances

TSH

Management of neonatal hypoglycemia

Anticipation in the high-risk group:LGA/SGA infants, IDM, acutely ill neonates, preterm infant, weight <2500 or > 4000 gr.

Treatment: transient vs. persistent symptomatic vs. asymptomatic

Investigation and treatment of the underlying cause


I. TRANSIENT HYPOGLYCEMIA:

Most are early, Asymptomatic and will recover with early feeding

Symptomatic Hypoglycemia: Bolus of 2 ml/kg glucose 10%. If seizure 4 ml/kg of glucose 10%. All infants, irrespective of cause and age should be treated with parenteral

glucose infusion: 6-8 mg/kg/min of dextrose 10%.

THE AIM: To maintain serum glucose above 45 mg/dl. Therefore: Glucose should be monitored frequently

No response: Bolus of 2 ml/kg glucose 10% Increase rate or concentration.

When blood glucose is stable for 4-6 hours feeding can be initiated and infusion can be weaned.


Persistent hypoglycemia glucose infusion rate > 12 mg/kg/min

Consider a diagnosis of hyperinsulinism, hormonal or metabolic disorders.

Add other drugs: - Hydrocortisone - Glucagon - Diazoxide - Somatostatin - Octreotide Pancreatectomy

תופעות לוואי מינון תרופה

עליה בלחץ דם-היפרגליקמיה, היפוקלאמיה-

כאבי ראש, אי שקט-

1-2 mg/kg/dose 3-4 / day I.V. Hydrocortisone

רטנציה של נתרן ומים – בצקות-היפרגליקמיה-צהבת של ילוד-

אריטמיה, טכיקרדיה-ירדה בלחץ דם-

Initial: 5-10 mg/kg/day in 2-3 doseIn Hyperinsulinemia: 10-15

mg/kg/day – 8-12 hr. P.O. or I.V.

Diazoxide

הקאות, שלשול-תפיחות בטן-

Initial: 1 mcg/kg/dose – 4/day with titration.

Max. dose: 10 mcg/kg/day S/C or I.V.

Somatostatin ( Octreotide )

הקאות, בחילות-טכיקרדיה, ירידה בלחץ דם-

רגישות יתר-

0.1-0.3 mg/kg/doseMax. dose: 1 mg/dose I.V. I.M. S/C.

Glucagon

Prognosis and outcome in neonatal hypoglycemia

Even asymptomatic hypoglycemia in healthy full term infants can be associated with abnormal neurologic exam )VEP(.

Preterm infants have lower IQ results when exposed to recurrent hypoglycemia. They may be asymptomatic for long periods and need to be monitored.

IDM with hypoglycemia in the past, suffer lower school achievements compared with healthy newborns

Attention should be put when dealing with early discharge. Brain MRI’S: damage of posterior hemispheres )occipital and

parietal(.

Polycythemia

Hematocrit greatly exceeds normal values for gestational and postnatal age.

Affects approximately 1% to 5% of newborns. Many affected infants are asymptomatic. Mean Ht and Hb from capillary samples at

birth are 61% +/- 7.4 and 19.3 g/dl +/- 2.2. The diagnosis is based upon peripheral

venous samples.

Polycythemia

Polycythemia must be distinguished from hyperviscosity: if greater than 12 centipoise, measured at shear rate of 11.5 per sec ) 6 centipoise at rate of 106 per sec(.

Viscosity and Ht have linear relationship when Ht is less than 60%.

Hyperviscosity occurred in only 47% of infant with polycythemia.

Polycythemia

Incidence 1%-5% of healthy newborns screened. Factors of influence the Ht during the first day after

birth: - time delay between birth and clamping of the

umbilical cord, - site of blood sampling, - age of the time sampling, - method of Ht measurement.

Polycythemia

Pathophysiology

Hyperviscosity

Reduced blood flow to organ

Poor tissue perfusion

Polycythemia

Causes

Two major mechanism:

- active ) increased intrauterine erythropoesis(

- passive ) erythrocyte transfusion (

Polycythemia

Causes Passive: Daley clamping of the umbilical cord – most

common. Intrapartum hypoxia )increased placental

transfusion(. Twin-to-twin transfusion )10%-15% of monochorionic

twin(. Maternal-fetal transfusion.

Polycythemia

Causes Active: Chronic intrauterine hypoxia and placental insufficiency: - SGA. - maternal preeclampsia or other vascular disorder. - maternal hypoxemia due to cardiac or pulmonary disorders. - drugs – propranolol. - smoking, high altitude, postterm date. - diabetic mother, LGA, Beckwith-Wiedemann syndrome. Endocrine abnormalities: congenital adrenal hyperplasia,

hypothyroidism, hyperthyroidism. Chromosomal abnormalities: trisomy 21,18,13.

Polycythemia

Clinical features Often begin by two hours after birth. May delayed to the 2-3 day because of excessive

extracellular fluid loss. Infants with no symptoms by 48 to 72 hours of age

are likely to remain asymptomatic. Signs and symptoms usually due to reduced tissue

perfusion or associated metabolic abnormalities.

Polycythemia - Clinical features

CVS & Respiratory:- acrocyanosis and sluggish peripheral perfusion,

- plethora,

- cyanosis )17%(,

- tachypnea & distress,

- heart murmur, heart failure and increased vascular resistance.


Neurologic effects:- irritability,

- abnormal cry,

- jitteriness,

- lethargy,

- hypotonia,

- apnea.

)associated with reduce cerebral blood flow(


Gastrointestinal disorder:

- abdominal distention,

- poor feeding.

- NEC ) sometimes(.

) in 20% of affected infants(.


Genitourinary:-hematuria, proteinuria, RVT. Hypoglycemia:- common, in 14%-40%, - Increased Gluc. utilization. Hyperbilirubinemia:-in 1/3 of infants, -breakdown and

increased number of circulated RBC. Thrombocytopenia:- one report ) 6 of 32 ( - if Ht > 70% - Plt. <100.K

Polycythemia

Diagnosis

Should be in infant who appear plethoric or who have signs or symptoms my be due to polycythemia.

Ht on a capillary blood sample from a wormed heel. If Ht capillary > 65% - repeat on a venous blood. Diagnosis of polycythemia if the venous Ht is > 65%.

Management of polycythemia

Controversial – uncertain whether intervention affect long-term outcome, may be associated with some GIT morbidity.

Asymptomatic newborn with polycythemia do not appear to benefit from treatment.

All polycythemic infant should be monitoring to hypoglycemia and hyperbilirubinemia.


Asymptomatic: Ht between 60%-70% - observation, adequate hydration and glucose intake

)oral intake, body weight, urine output(, - repeat Ht in 12 – 24 hours. Ht > 70% - many clinicians perform Partial Exchange

Transfusion; - however, continued observation with hydration may

be appropriate.


Symptomatic: If Ht > 65%

- partial exchange transfusion )PET(,

- or observation with I.V. fluids for first 24-48 hours of age at rate 100 cc/kg/day, with glucose rate of 6-8 mg/kg/min.

If worsening of symptoms – PET.

Partial exchange transfusion

Reduced Ht without causing hypovolemia. Reverses the reduction in cerebral blood

flow, cardiac index and oxygen transport attributed to hyperviscosity.

Dose not appear to affect long-term outcome. My be increased risk of NEC after treatment.

Partial exchange transfusion

Exchange volume =

[)observed Ht-desire Ht( x blood volume] / observed Ht.

Blood volume – 80 ml ) to 100 (/kg of BW.

Desire Ht – 45%. With NaCl 0.9% only. Through peripheral or central vein and artery.

Outcome of polycythemia

Outcome depend more upon associated condition, such as hypoglycemia, or underline disorder, such as placental insufficiency.

Important benefit from PET has not been show.

Infant with hyperviscosity have poorer neurologic outcome )lower IQ, lower score in spilling and arithmetical achievement(.

hypoglycemia of newborn

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