Complex Neonates: Hypoglycemia & Risk Factors

Complex Neonates

Topics Covered

• Jaundice is a topic for discussion
• Hypoglycaemia is a topic for discussion
• Neonatal Infection or Sepsis is a topic for discussion
• Meconium is a topic for discussion

Hypoglycemia

Risk Factors that lead to neurological sequelae

• Fetal growth restriction indicated by birth weight being less than second centile
  • Small for gestational age
  • Clinically wasted with over two centiles discrepancy between occipital frontal circumference and weight, measured using age and sex normalised data
• Infants of mothers with diabetes
• Infants of mothers consuming beta-blockers in third trimester or at birth

Birth Weight by Gestational Age

• Second centile birth weights are defined for boys and girls
• 37 weeks: 2.10 kg for boys, 2.00 kg for girls
• 38 weeks: 2.30 kg for boys, 2.20 kg for girls
• 39 weeks: 2.50 kg for boys, 2.45 kg for girls
• 40 weeks: 2.65 kg for boys, 2.60 kg for girls
• 41 weeks: 2.80 kg for boys, 2.75 kg for girls
• 42 weeks: 2.90 kg for boys, 2.85 kg for girls

Measurement of BG Concentration

• BG concentration gets checked for perinatal acidosis, indicated by cord arterial or infant pH below 7.1 with base deficit greater or equal to -12mmol/L
• Hypothermia under 36.5°C attributed not to environmental factors
• Suspected or confirmed early onset neonatal infection
• Central cyanosis
• Apnoea
• Altered level of consciousness
• Seizures
• Hypotonia
• Lethargy
• High pitched cry
• Abnormal feeding behaviour, when feeding normally, suggests consideration of BG measurement

Abnormal Feeding Behaviour

• Not waking for feeds can be a sign
  • Babies waking only 3-5 times in first 24 hours.
  • Healthy newborns should feed at least eight times in the first 24 hours.
• Very frequent feeding can be a sign
  • Babies breastfeed but do not appear satisfied
  • Baby gets tired or stops feeding within five minutes
• Not sucking effectively, indicated by weak suck or inability to suck

Glucose Metabolism

• At birth, babies must switch from placental glucose acquisition to independent glucose production
• Shift can result in initial drop in blood glucose levels
• Blood glucose should rise ≈3-4 hours after birth

Hypoglycemia

• Low blood glucose levels with a cut-off used at <2.6mmol/L
• Prematurity and/or intrauterine growth restriction decreases stores of glycogen and fat and impairs hormonal responses
• Maternal diabetes increases metabolic rate and brown fat metabolism and causes fetal hyperinsulinemia
• Maternal beta blockers causes fetal hyperinsulinemia and suppresses catecholamine responses
• Perinatal hypoxia causes anaerobic metabolism, exhausting stores
• Hypothermia increases the metabolic rate
• Sepsis or infection results in poor feeding

Temperature Regulation

• Hypothermia increases metabolism and glucose and glycogen mobilization
• Hypothermia can cause pulmonary vasoconstriction and may affect surfactant production
• Hypothermia elevates brown fat metabolism and oxygen consumption, driving respiratory work and potentially distress
• As bodily glucose regulation suffers, outcomes can include hypoxia and eventually hypoxemia

Hyperglycaemia Prevention

• Prevention is better than cure
• Temperature control through skin-to-skin contact
• Early breastfeeding within the first hour
• Frequent Feeding, no longer than three hours between feeds
• Blood Glucose Assessment can be performed before second feed, two to four hours after birth

Case Study 1

• Claire gave birth to their first baby after an induction of labour, at 39+6 weeks gestation, for Gestational Diabetes
• Assess risks to infant and care and management plan if breastfeeding
• Consider and utilize UNICEF breastfeeding tools

Identifying if Baby is Feeding Well

• The table provides information about key signs to observe and questions to ask:
• Your Baby: 8-12 feeds in 24 hours. Baby calms/relaxes when feeding, and remains content after most feeds
• Baby takes deep, rhythmic sucks and you hear swallowing sounds
• The baby should generally feed for between 5 and 40 minutes before coming off the breast
• The baby should have normal skin color, and is alert and waking for feeds. Weight loss is less than 10%
• Baby's Nappies: At least 5-6 heavy, wet nappies in 24 hours
• There are at least two dirty nappies in 24 hours, at least £2 coin size, yellow and runny
• Breasts/Nipples: Both breasts and nipples are comfortable, and nipples are the same shape at the end of the feed as at the start.

Flowchart A - Management from Birth

• For 24 hours for term infants at risk of hypoglycaemia
• Dry and skin-to-skin care in warm, draught free room
• After drying, put on a hat and cover with warm blanket
• For breastfeeding mothers with at risk infants should breastfeeding in the first hour
• Should formula be required, give volume appropriate for 40-60ml/kg/day
• Parent education to prevent Hypoglycaemia must be performed
• Check the pre-feed blood glucose level prior to the second feed (two to four hours post-birth). If blood glucose exceeds 2.0mmol/l, frequent feeding and blood assessment can performed by 24 hrs
  • For those woman who choose to formula feed can give, 40 to 60ml, over the first 24 hours

Box 1 - Infants who need Routine Blood Glucose monitoring

• Fetal growth restriction under 2 centile
• Infants of mothers with diabetes
• Infants of mothers talking beta-blockers in the 3rd trimester or/and at time of birth

Box 2 - Signs that may indicate Hypoglycemia

• Lethargy
• Abnormal feeding after a period of feeding well
• High pitched cry
• Altered level of consciousness
• Hypotonia
• Seizures
• Hypothermia <36.5°C
• Cyanosis
• Apnea

Flowchart B - Pre-Feed BG 1.0 to 1.9 mmol/l, Birth to 72 hours

• Assess baby for clinical signs of hypoglycaemia
• If no, administers glucose and assess need to feed
• If formula, give 40-60 ml
• Recheck blood glucose before third feed no later than 8 hours after birth
  • If no, perform rechecks

Flowchart C - Blood Glucose 1.0mmol/l and/or Clinical signs consistent with Hypoglycemia

• Get IV access. Collect BGs
• Administer 10% Glucose and admit to neonatal unit
• If IV not possible, offer Glucose and do not hold on getting milk

Jaundice

• Yellow colouration of skin/sclera, caused by accumulation of bilirubin skin and mucous membranes
• Raised levels of bilirubin (hyperbilirubinaemia)
• Neonates produce more bilirubin due to high turnover of RBCs and combined with immature intestinal processes = risk of hyperbilirubinemia

Jaundice Development

• Approximately 60% of term and 80% pre-term, develops jaundice in first week of life
• Approximately 10% of solely breastfed babies are jaundiced at age one month
• However, some babies can develop very high levels of bilirubin, which can be harmful, indicating a more serious underlying disorder
• Pathological jaundice occurs within 24 hours after birth.

Causes

• Blood group incompatibility
• Infection/Sepsis
• Liver disease
• Bruising
• Metabolic disorders
• Enzyme deficiency
• Hypoxia
• Hypothermia
• SGA
• Prematurity
• Polycythaemia
• Poor feeding
• Breastfeeding
• Immature liver
• Increased red blood cell load
• Shorter red cell span
• Low levels of albumin
• Increased entero-hepatic circulation
• Ventouse extraction
• Optimal cord clamping

Risk Factors

• Gestational age under 38 weeks
• A previous sibling with neonatal jaundice needing phototherapy
• Present Jaundice in newborn babies under 28 days
• Mother's intention to breastfeed exclusively
• Jaundice in the first 24 hours of life

Physiology

• Bilirubin is the by-product of RBC breakdown released it in an unconjugated and fat-soluble form
• Unconjugated bilirubin binds to albumin, travels to the liver, where receptor proteins Y & Z take in the unconjugated bilirubin
• Within the liver, Glucuronyl Tranferase binds bilirubin to Glucuronic acid, becoming water soluble
• Is excreted through the gut (stercobilinogin) and kidneys(urobilinogin)

Unconjugated

• Product of haemoglobin metabolism within reticuloendothelial system
• Cannot be readily excreted in bile or urine; must undergo conjugation in the liver before excretion is possible
• Can cross the blood-brain barrier and accumulate in the brain which can cause bilirubin encephalopathy or kernicterus
• Mostly bound to albumin in the plasma, while a small amount is unbound

Conjugated

• Direct product of bilirubin metabolism within the liver
• Water soluble
• Readily excreted into bile, stool, and urine
• Unable to cross blood brain barrier into brain tissues
• High amounts can indicate liver disease

Unconjugated hyperbilirubinemia is from:

• Increased red cell breakdown
  • Birth trauma
  • Infections
  • Rh isoimmunisation or ABO incompatibility
  • Polycythaemia
  • G6PD deficiency
• Failure of Conjugation can have genetic reasons, and Breastmilk may inhibit glucuronosyltransferase action
• Increased Enterohepatic Circulation through Delayed intestinal transit

Conjugated Hyperbilirubinemia

• Idiopathic neonatal (unknown)
• Total Parenteral Nutrition-associated cholestasis
• Congenital Infection, like CMV
• Neonatal liver issues like Hepatitis
• Bile duct abnormalities like biliary atresia
• Metabolic disorders like hypothyroidism

Kernicterus

• Describes yellow staining of the basal ganglia seen at autopsy in babies who have had severe jaundice
• The term is also used to describe long-term clinical effects of severe hyperbilirubinemia
• Life-long severe neurological disability affects cerebral palsy, with poor movement control, and involuntary movements and sensorineural deafness.

Benefits of Bilirubin

• Questions may consider hyperbilirubinemia
• Early in life confers may have biological advantage
• This can have potent antioxidant which helps protect the baby from oxidative and cell damaging free radicals
• These higher ranges of bilirubin protect the antioxidant effects for breast-fed infants
• The higher bilirubin levels will lower the risk for those with heart disease

Red Blood Cell Physiology

• Haem into biliverdin into unconjugated bilirubin
• Globin converts into amino acids
• Iron is stored in the body for RBC

How Jaundice Affects the Body

• Unconjugated bilirubin reaches spleen to the liver
• Liver converts it to canaliculi from Hepatocytes
• Goes to duodenum with Bile Duct
• Terminal ileum for reduction by Gut Bateria and sterobilinogen
• Enters Kidneys for Urobilinogen

Evaluating Jaundice (History)

• Maternal risks – rhesus status, ABO
• Neonatal risks – types of delivery, i.e. bruising
• Ethnicity-types of anaemia
• Infection
• Feeding and behaviour

Evaluating Jaundice (Inspection)

• Stools
• Urine
• Inspect with Natural light
• Blanching of skin and gums and sclera

When to use Bilirubin test

• Check if Bilurubinometer is accurate first
• Or Serum Bilirubin levels (SBG)

Evaluating Jaundice with Kramer's Rule

• Zones indicate the bilirubin range associated with each zone
• In micromol/L
  • Zone 1 has range of 100
  • Zone 2 has range of 150
  • Zone 3 has range of 200
  • Zone 4 has range of 250
  • Zone 5 has range of more than 250

Notes about Kramer's Rule

• Jaundice is confirmed by revealing the skin and the subcutaneous tissue at distinct zones by whitening skin with digital pressure
• This approach is focused to the distal of Jaundice based on the cephalocaudal distribution
• Visual examination of newborn must be confirmed with further serum and transcutaneous examinations
• Keep in mind that visual evaluation decreases as bilirubin levels raise

Action and Treatment

• Repeat bilirubin measurement every 6-12 hours
• Repeat and consider using phototherapy
• Consider blood transfusion
• Do not use direct sunlight

Treatment

• Always first test for serum Bilirubin measurement
• Test if under 24 hour of life OR gestational age under 35/40
• Test if over 35/40 and 24 hours and more
  • Start with transcutaneous bilirubin
  • If not available measure serum bilirubin
  • Use serum measurement for treatment

Underlying Assessments for Jaundice

• Check blood group of mother and baby
• DAT also named 'Coombs test' is also viable. Full body exam and full blood count. Check blood count

Management

Tests for long term are: full blood exam and film, for G6 levels

• Also full blood, and puncture

Exchange Transfusion for Jaundice

• Only used if severe
• Consists of
  • Removing baby's blood
  • Adding maternal Antibiotics
  • Adding the blood which may be rh or the bilirubin

Phototherapy Care

• Be aware treatment applies to surface level of the baby skin
• Need to be able to provide eye protection
• And ensure that baby is in thermoneutral environment

Expert Advise Needed if baby has Conjugated Bilirubin

• Consider care of babies with conjugated bilirubin high level
• Check pale stools and test for conjugated bilirubin. May need screening

Biliary Artesia

• Is a congenital case for live births
• Will cause a rise in the blood stream from what goes into bloodstream

Screening tests for neonates with prolonged jaundice:

• Split SBR - unconjugated and conjugated serum bilirubin
• Liver function tests - Obstructive jaundice is characterised by elevated plasma conjugated bilirubin and marked elevation of plasma alkaline phosphatase
• Thyroxine and thyroid-stimulating hormone - rule out hypothyroidism and hypopituitarism
• Urine and blood cultures to rule out bacterial infection
• TORCH screen to exclude common congenital viral and bacterial infections
• Stool and Urine specimens

TORCH Details:

• Toxoplasmosis causes a singular celled organism to found in faeces of unpasteurised goats milk and cats' soils
• Infections in Parvovirus or Chicken Pox
• Congenital rubella
• First trimester of rubella can affect baby
• CMV a more herpes virus for infections

Sally, Evie Case:

• For vaginal delivery, with a 3 kilogram weighing by 39 weeks. Note physiology of the jaundice and what potential causes, and what care would be appropriate for Evie if breastfeeding

Newborn Immunity

• Immune system is fully integrated from roughly the first year of age. The neonate mainly relies immunoglobins
  • igG through placenta, with passive immunity for what diseases mother have
  • igM also synthesized by fetus
  • igA in the colon system

Acquisition of Infections

• First onset comes near 24