Paediatrics 1

NEONATOLOGY

1. Classification of newborns. Basic concepts of perinatology

  • Important terms
    • Live birth = presence of vital signs at birth
    • Miscarriage = absence of vital signs and pregnancy loss before week 20
    • Stillbirth = absence of vital signs and pregnancy loss after week 20
  • Classification according to age
    • Newborn = child < 28 days of age
    • Infant = child < 1 year of age
  • Classification according to term
    • Preterm infant = infant born before 37 weeks of gestation
    • Term infant = infant born between 37 and 42 weeks of gestation
    • Post term infant = infant born after 42 weeks of gestation
  • Classification according to weight depending on gestational age
    • Small-for-gestational age (SGA) infant = birthweight < 10th percentile for gestational age
    • Appropriate-for-gestational age (AGA) infant = birthweight 10th – 90th percentile
    • Large-for-gestational age (LGA) infant = birthweight > 90th percentile
  • Classification according to weight independent of gestational age
    • Low birth weight = birthweight 1500 – 2500 g
    • Very low birth weight = birthweight 1000 – 1500 g
    • Extremely low birth weight = birthweight < 1000 g
  • Definitions
    • Congenital = contracted in utero
    • Perinatal = from 24 weeks of gestation until 4 weeks after birth
    • Antenatal = before birth
    • Postnatal = after birth
    • Neonatal = from birth until 4 weeks after birth

2. The characteristics of the premature and intrauterine growth restriction infants

  • Premature (pre-term) infant
    • Physical characteristics
      • Big head, short trunk
      • Immature extremities
      • Nails not covering tip of fingers
      • Oedematous, pinkish, thin skin with subcutaneous fat missing
      • No testes in scrotum
      • Presence of lanugo (small hairs)
      • Labia majora don’t cover labia minora
      • Few palmar creases
    • Immature breathing mechanism (weak cry) -> require artificial respiration
    • Immature heat regulation -> require incubator for weeks or months
    • Immature GI tract -> require parenteral nutrition
  • Intrauterine growth restriction (IUGR)
    • = foetus does not achieve its intrauterine growth potential
      • Does not achieve the size its genetics would allow it to, if all factors were optimal
    • Usually defined as being small for gestation age (SGA) + decreased growth velocity
    • Ponderal index = body weight/height3
      • Foetal weight is estimated during antenatal ultrasound
    • Symmetric IUGR
      • = whole body is smaller, but proportional
      • 20 – 30% of cases
      • Etiology
        • Chromosomal abnormalities
        • Congenital infection
        • Genetic syndromes
      • Clinical features
        • Occurs in early stages of gestation
        • Normal ponderal index
    • Asymmetric IUGR
      • = body is disproportionally smaller
        • Head circumference normal, length slightly decreased, weight significantly decreased
      • 70 – 80% of cases
      • Due to placental insufficiency, due to:
        • Chronic hypoxia
        • Preeclampsia
        • Chronic hypertension
        • Malnutrition
      • Clinical features
        • Occurs in the later stages of gestation
        • Low ponderal index
        • Normal-sized head with small body and limbs
  • Complications of IUGR
    • Mortality rate 5 – 20x higher
    • Perinatal asphyxia
    • Hypoglycaemia
    • Hyperviscosity/polycythaemia
    • Abnormal temperature regulation
    • Pulmonary haemorrhage
    • Persistent pulmonary hypertension in the neonate
  • Difference between intrauterine growth restriction (IUGR) and small for gestational age (SGA)
    • IUGR is a reduction in the foetal growth rate, unrelated to the actual weight at birth
      • IUGR is always pathological
    • SGA is a reduction in birth weight
      • SGA is physiological in constitutionally small foetuses (some families are just small)
      • SGA is pathological if it follows IUGR
    • A foetus can have IUGR but not be SGA at birth
    • A foetus can be SGA at birth without having had IUGR

3. The characteristics of the mature newborn

  • Mature (term) infants
    • Measurements
      • Bodyweight – 3000 – 4000 g
      • Length – 47 – 55 cm
      • Head circumference – ~36 cm
      • Heart rate – 120-160/min
      • Respiratory rate – 40-60/min
    • Physical characteristic
      • Nails cover tip of fingers
      • Good skin turgor
      • Body covered by mucous
      • Testicles in scrotum
      • Labia minora covered by labia majora
      • Strong cry immediately after birth
      • Plantar creases cover the soles of the feet
      • Reacts to strong stimuli
      • React to the environment (e.g. taste awareness)
  • Infant mortality
    • Mostly in < 1 month old
    • Mortality > 1 year is mostly due to socio-economic factors
    • Major causes of infant mortality
      • Preterm birth
      • Development anomalies
      • Perinatal asphyxia

4. The first evaluation of the newborn baby, routine delivery room and initial care

  • First evaluation
    • Ask the following three questions.
      • Is the infant term?
      • Does the infant have good muscle tone?
      • Is the infant breathing or crying?
    • If answers to all are “yes”, the newborn does not need resuscitation. Proceed to routine care
    • If not, stabilize as necessary
      • Maintain temperature
      • A – clear airways
      • B – breathing – ventilation and oxygenation
      • C – chest compressions
      • Administer epinephrine or fluids
  • Routine care
    • Drying the newborn
    • Clearing airway secretions
      • By wiping, not by suction
    • Maintain temperature
    • Clamp and cut the umbilical cord
    • Skin-to-skin contact with mother
    • Vitamin K shot
    • Ophthalmic antibiotic drops
  • Apgar score
    • Performed at 1 and 5 minutes after birth
    • Used to evaluate status of the newborn and its adaptation to the environment
    • Score
      • Normal: 7 -10
      • Moderately abnormal: 4 – 6
      • Low – 0 – 3
Component 0 points 1 point 2 points
Appearance (skin colour) Cyanotic or pale Acrocyanosis Pink body and extremities
Pulse (heart rate) None < 100/min > 100/min
Grimace (reflex response to irritable stimuli) None Whimpering, grimace Crying, active withdrawal
Activity (muscle tone, movement) No movement, hypotonia Some flexion Active motion
Respirations None Weak crying, irregular/slow/weak breathing or gasping Regular breathing, strong cry
  • Other
    • General appearance
      • Is the newborn well, cooperative, agitated, weak, irritable, serious, life-threatening, etc.
      • Sex
      • Identification of deformations or malformations
      • Determination of state of foetal nutrition
        • Amount of subcutaneous fat on thigh and glutes
        • Amount of Wharton’s jelly in umbilical cord
      • Signs of respiratory distress
        • Paradoxical breathing is normal
    • Measurements
      • Length
      • Weight
      • Head circumference
    • Vital signs
      • Axillary temp (36,5 – 37,5)
      • Respiratory rate (40 – 60)
      • Heart rate (120 – 160)
      • Blood pressure (65-85/45-55)
    • Skin
      • Colour
        • Should be rose-pale
        • Acrocyanosis normal in the first days
        • Central cyanosis never normal
        • Jaundice in the first 24 hours is pathological
        • Physiological jaundice in days 3 – 8
        • Greenish discoloration is meconium
      • Lesions or pigmentation changes
      • Examine turgor
    • Head
      • Size and shape
      • Palpate fontanelles
        • Bulging when infant is sitting -> Increased ICP
        • Depressed -> dehydration
      • Palpate sutures
    • Face and mouth
      • Facial palsy
      • Position, symmetry of eyes
      • Examination of the red-light reflex
      • Colour of lips
      • Cleft palate or lip
      • Examine tonsils and palate
    • Respiratory system
      • Size and symmetry of thorax
        • Small -> pulmonary hypoplasia
        • Pectus excavatum or carinatum
      • Breathing movements
      • Use of accessory breathing muscles
      • Auscultation
        • Symmetrical, equal breathing sounds
    • Cardiovascular system
      • Palpation of peripheral pulses
      • Auscultation
        • Murmurs in the first few days are normal
    • Abdomen
      • Slightly protruding abdomen is normal
      • Umbilicus
        • Look for infection or hernia
      • Palpation of liver, spleen, kidneys
      • Diastasis recti (nonunion of the two rectus muscles) is common and spontaneously resolves
      • Auscultation
    • Musculoskeletal
      • Sacral dimple
        • May indicate underlying neural tube defect
      • Structure of spine (kyphosis, lordosis, scoliosis)
      • Joints (position, motion, stability, swelling, tenderness)
        • Valgus/varus
        • Developmental dysplasia of the hip
      • Number of digits
    • Neurological
      • Muscle tone, strength
      • Deep tendon reflexes
      • Superficial reflexes (abdominal and cremasteric)
      • Neonatal (primitive) reflexes
        • These are present at birth but resolve after a few months
        • They are abnormal if absent in the first months, asymmetric, or persist after the first few months
        • Moro reflex (startle reflex)
          • When the head suddenly falls back, arms are abducted and extended, and legs are flexed
        • Stepping reflex
          • Holding infant upright with feet on flat surface elicits a walking movement
        • Grasp reflex
          • Touching the palm elicits grasping
    • Genitourinary
      • Presence and description of external genitalia
      • Hernias and hydrocoeles
      • Presence of cryptorchidism
      • Presence of hypospadias and epispadias

5. Birth injuries

  • Risk factors for birth injuries
    • Large-for-date infants
      • Especially > 4500 g
    • Forceps-assisted or vacuum-assisted delivery
      • Very high risk if combined
    • Breech presentation
    • Excessive traction during delivery
  • Extracranial injuries
    • Cephalohaematoma
      • = haematoma between skull and periosteum
      • Most common during forceps or vacuum delivery
      • 1 – 2% of deliveries
      • Clinical features
        • Most commonly unilateral
        • Limited by suture lines (does not cross them) -> blood loss limited
        • If large -> jaundice, anaemia
      • Treatment
        • Self-limiting after weeks/months
        • Usually don’t require treatment, only observation
    • Subgaleal haematoma
      • = haematoma in loose tissue between skull periosteum and epicranial aponeurosis
      • Most common during vacuum delivery
      • Clinical features
        • Large haematoma, can cause hypovolaemic shock
        • Not limited by suture lines -> no barrier -> large blood loss possible
        • 20 – 40% of neonatal blood volume can be lost
      • Treatment
        • Volume resuscitation (transfusion or saline, depending on labs)
  • Neurologic injuries
    • Facial nerve palsy
      • Most common during forceps delivery
      • Clinical features
        • A peripheral type of facial nerve palsy
        • Loss of nasolabial fold
        • Partial closing of eye
        • “Drooping” mouth
      • Treatment
        • No treatment
        • Spontaneously resolves within 2 weeks
    • Neonatal brachial plexus palsy
      • 1 – 2 / 1000 births
      • Due to stretching of brachial plexus during vaginal birth
      • Clinical features
        • Most commonly affects C5, C6 (= Erb’s palsy)
          • Adducted, internally rotated arm
          • Extended forearm
          • Normal hand and wrist movement
          • Grasp reflex present
        • Rarely affects C7 – Th1 (= Klumpke’s palsy)
          • Weakness of hand muscles
          • Grasp reflex absent
          • Horner syndrome may occur
        • Rarely (10%) affects whole brachial plexus
        • Can occur with fractured clavicle, humerus, or other injuries
      • Treatment
        • Spontaneously resolves in 90% of cases
    • Phrenic nerve palsy
      • Causes respiratory distress
      • Decreased breathing sounds on one side
      • Spontaneously resolves
    • Fractures of clavicle, humerus, femur
      • Clavicle fracture -> observation only. Resolves.
      • Humerus, femur fracture -> immobilization. Resolves.

6. Hypoxic-ischemic encephalopathy, intracranial haemorrhage, and its complications

  • Hypoxic-ischaemic encephalopathy
    • = neonatal encephalopathy due to perinatal asphyxia (hypoxia or ischaemia)
    • Antepartum risk factors
      • Intrauterine growth restriction (strongest risk factor)
      • Preeclampsia
      • Abnormal placenta
      • Maternal thyroid disease
    • Intrapartum events (risk factors)
      • Uterine rupture
      • Placental abruption
      • Umbilical cord prolapse
      • Shoulder dystocia
      • Maternal infection
    • In most cases of hypoxic-ischaemic encephalopathy, there is no acute intrapartum event, only antepartum risk factors
    • Clinical features
      • Can be anywhere from mild and transient to multi-organ failure
      • Abnormal behaviour
      • Lethargy
      • Hypotonia
      • Absent reflexes
      • Coma
    • Diagnosis
      • Apgar score < 5
      • Low umbilical cord pH
      • Typical clinical features
      • Typical radiological features
    • Treatment
      • Initial stabilization
      • Therapeutic hypothermia
      • Supportive measures
    • Complications
      • Mortality rate 25 – 50%
      • Abnormal psychomotor and mental development
      • Cerebral palsy
      • Epilepsy
  • Intracranial haemorrhage
    • Etiology
      • Operative delivery (vacuum or forceps)
      • Prematurity -> intraventricular h.
    • Types (in decreasing order of incidence)
      • Subdural haemorrhage
      • Subarachnoid haemorrhage
      • Intraventricular haemorrhage
      • Epidural haemorrhage
    • Clinical features
      • Small -> no problem
      • Large -> increased ICP, apnoea, respiratory depression, seizure
    • Diagnosis
      • CT (if emergent)
      • MRI
    • Treatment
      • Small -> just observation
      • Large -> emergency surgical evacuation

7. Persistent pulmonary hypertension of the newborns. Patent ductus arteriosus.

  • Persistent pulmonary hypertension of the newborn (PPHN)
    • Epidemiology
      • Occurs in term or late preterm infants
    • Etiology
      • Idiopathic
      • Pulmonary hypoplasia
      • Intrauterine growth restriction
      • Bacterial infection
    • Pathomechanism
      • Abnormal pulmonary vasculature -> pulmonary vascular resistance doesn’t decrease after birth -> right-to-left shunting of blood through the ductus arteriosus or foramen ovale
    • Clinical features
      • Symptoms begin within 24 hours of birth
      • Cyanosis
      • Respiratory distress
    • Diagnosis
      • Echocardiography shows pulmonary hypertension
    • Treatment
      • 100% oxygen
      • Inhaled NO
      • Mechanical ventilation
      • Extracorporeal membrane oxygenation
    • Complications
      • 10% mortality
      • Developmental delay
      • Motor disability
  • Patent ductus arteriosus
    • Sometimes called ductus botalli persistens (DBP) in Hungarian literature
    • Clinical features
      • Often small and asymptomatic
      • If larger -> dyspnoea, cyanosis
    • Diagnosis
      • Physical examination
        • Loud continuous murmur in left infraclavicular region
      • Echocardiography for definitive diagnosis
    • Treatment
      • Observation
        • If small PDA
      • Pharmacological closure
        • If symptomatic or large
        • In premature infants
        • With IV indomethacin or ibuprofen
      • Percutaneous closure
        • If symptomatic or large
    • Complications
      • Pulmonary hypertension
      • Heart failure
      • Eisenmenger syndrome

8. Polycythaemia. Hyperviscocity syndrome.

  • Definition of polycythaemia
    • Venous haematocrit > 65% OR:
    • Hb > 220 g/L
  • Definition of hyperviscosity syndrome
    • The clinical features which occur due to hyperviscosity
  • Polycythaemia is the most important cause of hyperviscosity syndrome
    • However, not all infants with polycythaemia develop hyperviscosity syndrome
  • Etiology
    • Delayed cord clamping
      • Especially if the foetus is held at a level below the mother before clamping
    • Twin-twin transfusion syndrome
    • Placental insufficiency
    • Maternal diabetes
  • Pathogenesis
    • Increased blood volume -> increased viscosity -> decreased blood flow -> decreased oxygen transport
      • -> decreased tissue oxygenation
      • -> formation of microthrombi
    • Neonatal RBCs are less deformable than adult RBCs
  • Clinical features of polycythaemia/hyperviscosity syndrome
    • Often asymptomatic
    • Cyanosis
    • Apnoea
    • Vomiting
    • Poor feeding
    • Hypoglycaemia
  • Treatment
    • Target Htc: 60%
    • Asymptomatic, Htc 60 – 70% -> IV fluids
    • Asymptomatic, Htc > 70% -> partial exchange transfusion (?)
    • Symptomatic -> partial exchange transfusion

9. Jaundice and hyperbilirubinaemia in the newborn. Kernicterus

  • Jaundice
    • 1/3 of infants experience jaundice
    • Occurs when total bilirubin reaches > 7 mg/dL
      • Can be measured transcutaneously (POC test) or in blood
      • Physical examination is not reliable
  • Physiologic hyperbilirubinaemia
    • Most infants experience some degree of hyperbilirubinaemia
    • < 12 mg/dL total bilirubin
    • Occurs between day 3 – 8 in term infants
    • Mechanism
      • RBCs of newborn have short lifespan
      • Newborns have impaired bilirubin conjugation
      • Newborns have decreased excretion of bilirubin
    • No treatment needed
  • Pathological hyperbilirubinaemia
    • Any neonatal hyperbilirubinaemia with any of the following conditions:
      • Onset before 24 hours of age
      • Rapid elevation of bilirubin
      • Levels high enough to warrant treatment
      • Signs of underlying illness
      • Persisting jaundice
    • Etiology
      • Conjugated hyperbilirubinaemia
        • See topic 10
      • Unconjugated hyperbilirubinaemia
        • Haemolysis
          • Infection
          • Haemolytic disease of the newborn
          • G6PD deficiency
        • Polycythaemia
        • Haematoma
        • Impaired conjugation
          • Crigler-Najjar syndrome
          • Gilbert syndrome
        • Impaired gastric motility
    • Treatment
      • Modality depends on:
        • Bilirubin level (if above a certain threshold, which depends on the age of the neonate)
        • Whether conjugated or unconjugated
        • Risk factors
        • The condition of the infant
      • Phototherapy
        • Only for unconjugated hyperbilirubinaemia
        • Irradiation with light breaks down unconjugated bilirubin into water-soluble products
      • Exchange transfusion
        • Indications
          • Phototherapy ineffective
          • Severe anaemia
          • In immune-mediated haemolysis
        • Mechanism
          • Antibody-coated RBCs, unattached antibodies, and bilirubin is removed
          • RBCs from donor blood are infused
  • Neonatal bilirubin toxicity
    • Only unconjugated bilirubin crosses the BBB and causes neurotoxicity
    • Prevention: phototherapy
    • Acute bilirubin encephalopathy
      • Lethargy
      • Hypotonia
      • Fever
      • Seizures
    • Kernicterus (chronic bilirubin encephalopathy)
      • Cerebral paresis
      • Hearing loss
      • Gaze palsy
      • Dental dysplasia

10. Most common causes of direct hyperbilirubinemia

  • Biliary obstruction
    • Biliary atresia
    • Choledochal cyst
    • Tumour
  • Infection
    • TORCH
    • Sepsis
    • UTI
  • Metabolic disorder
    • Alpha-1 antitrypsin deficiency
    • Cystic fibrosis
    • Galactosaemia
    • Tyrosinaemia

11. Neonatal hypoglycaemia, hypocalcaemia

  • Neonatal hypoglycaemia
    • Definition
      • Newborns have a tendency to develop transient low blood sugar level physiologically
      • There is no specific cut-off value at which blood sugar level in infants is pathological
        • Teacher said hypoglycaemia is < 2,6 mM
    • Etiology
      • Hypoglycaemia without acidaemia
        • Free fatty acids increased -> fatty acid oxidation defects
        • Free fatty acids decreased -> insulin-mediated hypoglycaemia
          • Congenital hyperinsulinism
          • Insulinoma
      • Hypoglycaemia with acidaemia
        • Ketones increased -> ketotic hypoglycaemia
          • Glycogen storage disease (types 0, III, VI, IX)
          • Growth hormone deficiency
          • Cortisol deficiency
        • Lactate increased -> disorder of gluconeogenesis
          • Glycogen storage disease (type I)
          • Fructose 1,6-bisphosphatase deficiency
          • Pyruvate carboxylase deficiency
      • Other causes of hypoglycaemia
        • Ingestion of antidiabetics, ethanol, beta blockers
        • Liver failure
        • Sepsis
    • Clinical features
      • Lethargy
      • Irritability
      • Tremor
      • Hypotonia
      • Decreased consciousness
      • Bradycardia
      • Cyanosis
      • Seizures
    • Screening
      • By POC test from capillary blood
        • POC tests are not accurate for low blood sugar values and should only be used for screening
      • Indicated in:
        • Infants with symptoms
        • Preterm and post-term infants
        • Large for gestational age infants
        • Small for gestational age infants
        • Infants of mothers with diabetes
    • Diagnosis
      • By plasma glucose level
        • More accurate than POCT
      • Look for underlying cause
        • Measure FFA, lactose, pH, ketones, etc.
    • Treatment
      • Symptomatic infants -> IV dextrose
        • 20% dextrose rather than the normal 5%
      • Asymptomatic infants -> oral feeding
      • Continuous monitoring
  • Neonatal hypocalcaemia
    • Etiology
      • Early hypocalcaemia (first two-three days)
        • Prematurity
        • Maternal diabetes
        • Perinatal asphyxia
        • Intrauterine growth restriction
        • Hypoparathyroidism
        • DiGeorge syndrome
      • Late hypocalcaemia (day 3 – 7)
        • High phosphate intake (cow milk intake)
        • Acute kidney injury
    • Clinical features
      • Most are asymptomatic
      • Jitteriness
      • Muscle jerking
      • Seizures
    • Screening
      • Indicated in
        • Very low birth weight infants
        • Infants with congenital heart disease
        • Symptomatic infants
    • Diagnosis
      • By plasma ionized or total Ca2+ level
        • Total Ca2+ < 2 mM
        • Ionized Ca2+ < 1,1 mM
      • Also measure phosphate, vitamin D, PTH
    • Treatment
      • Asymptomatic -> oral feeding
      • Symptomatic -> IV calcium solution

12. Neonatal convulsions, differential diagnosis, and treatment

  • Not all seizures or convulsions are epileptic; it’s important to distinguish those which are from those which aren’t
    • The same pathologies can cause both epileptic and non-epileptic seizures, but the prognosis and treatment are different
  • Epileptic neonatal seizures
    • Can be clinical or subclinical, but there are always EEG changes
    • Epidemiology
      • 1 – 3 / 1000 live birth
    • Etiology
      • Hypoxic-ischaemic encephalopathy
      • Metabolic disturbance (hypoglycaemia, hypocalcaemia, etc.)
      • Epilepsy syndromes
      • Inborn errors of metabolism
      • Ischaemic stroke
      • Intracranial haemorrhage
      • CNS infection
    • Clinical features
      • Subtle seizures
        • Most common
        • Abnormal, rapid eye movements
        • Lip smacking
        • Swimming or pedalling movement
      • Clonic seizures
        • Second most common
        • Repetitive muscle contractions (2 – 3 per second)
      • Tonic seizures
        • Sustained, transient muscle contractions
      • Myoclonic seizures
        • Sporadic (isolated) muscle contractions
      • Subclinical seizures
        • No clinical signs, just present on EEG
      • Never generalized tonic-clonic (grand mal)!
    • Diagnosis
      • Video-EEG
        • A video is made of the infant while EEG is taken
    • Differential diagnosis
      • Must be differentiated from non-epileptic paroxysmal disorders
    • Treatment
      • Treat underlying cause
      • Phenobarbital or other antiepileptics
  • Non-epileptic paroxysmal disorders
    • More common than epileptic neonatal convulsions
    • Not epileptic in origin
    • Can occur with or without underlying disease
    • Etiology
      • Metabolic disturbances
      • Hypoxic-ischaemic encephalopathy
      • Intracranial haemorrhage
      • Sepsis
      • Drug withdrawal
    • Clinical features
      • These movements can be similar to epileptic convulsions
      • Apnoeic episodes
      • Jitteriness
      • Benign myoclonus during sleep
    • Diagnosis
      • No EEG changes!
    • Treatment
      • Treat underlying disease, if present

(Respiratory distress)

  • Respiratory distress
    • = a condition where the patient has trouble maintaining normal gas exchange and oxygenation
    • This term is important to know but doesn’t specifically belong under any topic
    • Etiology
      • Infant/neonatal respiratory distress syndrome (IRDS/NRDS)
      • Transient tachypnoea of the newborn
      • Meconium aspiration syndrome
      • Pulmonary air leaks
      • Choanal atresia
      • Pneumonia
      • Pulmonary hypoplasia
      • Diaphragmatic malformation
    • Clinical features
      • Tachypnoea (RR > 60)
      • Shallow breathing
      • Expiratory grunting (forced expiration against closed glottis)
      • Nasal flaring
      • Chest retraction
      • Cyanosis

13. Transient tachypnoea of the newborn. Meconium aspiration.

  • Transient tachypnoea of the newborn
    • Common cause of respiratory distress
    • Also called “wet lung disease”
    • Occurs in term or near-term infants
    • Risk factors
      • C-section
      • Maternal diabetes
    • Pathogenesis
      • Delayed resorption of lung fluid -> transient pulmonary oedema
      • C-section causes the infant to miss out on contractions, which may help the resorption of fluid
    • Clinical features
      • Tachypnoea which begins within 2 hours of delivery
      • Mild – moderate respiratory distress
      • Symptoms persist for 12 – 48 hours
    • Diagnosis
      • X-ray
        • Fluid in interlobar fissure
        • Hyperinflated lung
        • Perihilar streaking (sun-burst pattern)
      • Blood culture and lab tests
        • To exclude other causes of respiratory distress
    • Treatment
      • Supportive and observation
  • Meconium aspiration syndrome (MAS)
    • Occurs mostly in post-term infants
    • Etiology
      • Idiopathic
      • Hypoxia
      • After spinal cord/head compression
      • Infection
    • Pathomechanism
      • Post-term infants have overmatured GI tracts, which release the meconium before birth
      • Foetus aspirates meconium
      • Obstruction causes atelectasis or interstitial emphysema -> inhomogeneous lung parenchyma
      • Aspirated meconium inactivates surfactant
    • Clinical features
      • Green amniotic fluid (stained by meconium)
      • Respiratory distress, which starts right after birth
    • Diagnosis
      • Presence of meconium-stained amniotic fluid
      • Respiratory failure on blood gas
      • X-ray
        • Hyperinflation of lung and emphysema
        • Irregular patchy infiltrate
    • Complications
      • Pneumonitis, pneumonia
      • Pneumothorax
      • Persistent pulmonary hypertension
    • Treatment
      • General supportive care
        • Warm environment
        • Ensure normal hydration
        • Provide protein and calorie intake
      • Empiric antibiotics
      • Surfactant administration, if necessary
      • Suction, if necessary
      • Respiratory support, if necessary
    • Prevention
      • Identify high-risk pregnancies (post-term, maternal HT, diabetes, smoking)
      • Prevent post-term birth by inducing birth at week 41
  • (Choanal atresia)
    • (Included in lecture but not mentioned in topic name)
    • = congenital malformation with bony or soft tissue obstruction of the choanae
    • Can be uni-or-bilateral
    • Bilateral
      • Neonates are obligate nasal breathers, so it’s life-threatening
      • Intermittent cyanosis, especially when eating and sleeping
      • Cyanosis improves when crying, as they can breathe with their mouth when crying
      • Nasal catheterisation immediately after delivery
      • Later surgical perforation
    • Unilateral
      • Chronic rhinitis
      • Surgical perforation after 1 – 2 years
  • (Air leak syndrome)
    • (Included in lecture but not mentioned in topic name)
    • Includes pneumothorax, pulmonary interstitial emphysema, pneumopericardium, pneumomediastinum, pneumoperitoneum, subcutaneous emphysema
    • Includes all diseases where alveoli rupture and air escapes into:
      • Interstitium -> decreased lung compliance
      • Pleural space -> atelectasis
      • Mediastinum and pericardial space -> circulatory collapse
    • Risk factors
      • NRDS
      • Meconium aspiration syndrome
      • Pneumonia
      • Procedures like intubation, suction, mechanical ventilation
    • Spontaneous PTX
      • Not life-threatening
      • Often asymptomatic
      • Can resolve spontaneously
    • Tension PTX
      • Life-threatening
      • The amount of air in the pleural space increases with each breath -> high pressure in pleural space
        • -> lung collapse -> respiratory collapse
        • -> compression of vessels -> circulatory collapse
      • Diagnosis
        • Physical examination shows shifted heart sounds, chest asymmetry
        • X-ray or transillumination
      • Treatment
        • Emergency thoracentesis -> chest tube with suction

14. Respiratory distress syndrome and its treatment

  • Infant/neonatal respiratory distress syndrome (IRDS/NRDS)
    • Also called “hyaline membrane disease”
  • Leading cause of preterm neonate morbidity and mortality
  • Risk factors
    • Low gestational age
      • < 28 weeks of gestation: 60 – 80%
      • 28 – 32 weeks of gestation: 30 – 60%
      • 32 – 36 weeks of gestation: 15 – 30%
    • C section
    • Maternal diabetes
    • Twins
  • Pathogenesis
    • Surfactant
      • Deficiency -> increased surface tension -> atelectasis
      • Present in foetal lung at week 20, levels increase every week until it reaches mature level at week 35
    • Premature infants have higher chest wall compliance than term infants
      • This increases the tendency of atelectasis
    • Atelectasis
      • -> decreased lung compliance and functional residual capacity -> V/Q mismatch -> hypoxaemia & hypercapnia -> acidosis and pulmonary vasoconstriction -> lung injury
        • Acute consequence of lung injury: protein exudate -> hyaline membrane formation
        • Chronic consequence of lung injury: -> bronchopulmonary dysplasia
  • Clinical features
    • Respiratory distress within minutes or hours
    • Symptoms progress and peak within 3 days
    • Hypoperfusion, oliguria
  • Diagnosis
    • X-ray
      • Ground-glass opacities
      • “White lung”/completely opaque lung (in severe cases)
    • Blood gas
      • Hypoxaemia
      • Hypercapnia
      • Acidosis
  • Scoring system
    • Silvermann-Anderson scoring
    • Scores severity of NRDS
  • Prevention
    • Prenatal amniocentesis
      • Assesses foetal lung maturity
      • Lecithin/sphingomyelin (L/S) ratio in amniotic fluid
        • Ratio > 2 -> low risk
        • Ratio < 1,5 -> high risk
    • Prevent premature birth
    • Antenatal (48 hours before delivery) corticosteroid to mother
      • Betamethasone
      • Stimulates infant lung maturation
      • Indicated in pregnant women between 24 – 34 weeks gestation with high risk of preterm birth in the next 7 days
      • Optimal benefit after 24 – 48 hours, so delivery should be delayed until then if possible
  • Treatment
    • General care
      • Warm environment
      • Ensure normal hydration
      • Provide protein and calorie intake
      • Antibiotics if risk for infection
    • Oxygen therapy
      • By warm, humidified gas
      • Maintain O2 saturation in low 90s (too high cause oxygen toxicity)
    • Respiratory therapy
      • Prefer non-invasive, lung-protective methods like
        • nCPAP – nasal continuous positive airway pressure
        • BiPAP – bi-level positive airway pressure
      • In severe NRDS/impending respiratory failure -> mechanical ventilation
    • Surfactant replacement
      • Administration of exogenous surfactant into airways and lung
      • Natural (better) or synthetic
      • Administered non-invasively by thin catheter after direct laryngoscopy

15. Nosocomial infections in neonates (pathogens, treatment, prevention)

  • = all neonatal infections where there is no evidence of transplacental transmission
  • Etiology
    • Risk factors
      • Prematurity
      • Very low birth weight
      • Endotracheal tube
      • Admission into neonatal ICU
      • Central catheter
      • Broad-spectrum antibiotic use
    • Pathogens
      • Coagulase-negative staphylococci (CONS) (70% of cases)
        • The most common CONS is staphylococcus epidermidis
      • Staphylococcus aureus
      • Gram negative rods
  • Infections
    • Ventilator-associated pneumonia
    • Central line-associated bloodstream infection (CLABSI)
    • Urinary tract infection
    • Sepsis
  • Treatment
    • Empiric antibiotic until culture result is available
  • Prevention
    • Hand hygiene
    • Maternal breast milk feeding
    • Correct technique when inserting and maintaining catheters, tubes
    • Avoid broad-spectrum antibiotics

16. Clinical symptoms, diagnostic features, and treatment of sepsis in the newborn period

  • Etiology
    • Group B streptococcus (GBS, strep. agalactiae)
      • Most common
    • E. coli
    • Listeria monocytogenes
    • Proteus, Klebsiella
  • Risk factors
    • Maternal risk factors
      • Traumatic delivery
      • Prolonged rupture of membranes
      • Maternal colonization of GBS
        • In urine, GI tract, vaginal tract, rectum, etc.
        • Up to 30% of pregnant women are colonised by GBS
    • Neonatal risk factors
      • Prematurity (5x higher)
  • Pathogenesis
    • Early-onset sepsis, at least for GBS, is primarily an intra-uterine infection
      • Probably ascending from contaminated amniotic fluid
    • Infection route for late-onset sepsis is unclear
  • Clinical features
    • Respiratory distress
    • Temperature instability (Fever/hypothermia)
    • Lethargy
    • Poor feeding
    • Jaundice
    • Vomiting
  • Types
    • Early-onset sepsis
      • 3/4 of all cases
      • In first week, most often first day
      • Fulminant, multisystem, severe
      • Mortality rate up to 50%
    • Late-onset sepsis
      • 1/4 of all cases
      • From second week to three months, most often in weeks 3 – 4
      • Slowly progressing
      • Single or few organ systems affected
      • Mortality rate up to 20%
  • Diagnosis
    • Non-specific clinical symptoms; high index of suspicion necessary
    • Maternal or infant antibiotic treatment (for different reason) can make diagnosis of sepsis difficult
    • Blood culture
    • Other cultures
      • Ear swab
      • Umbilical swab
      • Gastric aspirate
  • Treatment
    • Ampicillin + gentamycin until culture results are available
  • Prevention
    • Rectal and vaginal GBS cultures and urinary culture for all pregnant women
      • Should be taken toward the end of term (week 35)
      • Positive culture -> IV penicillin G
    • GBS bacteriuria -> IV penicillin G
    • Women with previous child with GBS sepsis -> IV penicillin G

17. Meningitis in the newborn period

  • Bacterial meningitis
    • Epidemiology
      • Bacterial meningitis is more common in the first month than at any other time in life
    • Etiology
      • Risk factors
        • Low birth weight
        • Prematurity
        • Traumatic delivery
      • Pathogens
        • Group B streptococcus (GBS)
        • E. coli
    • Types
      • Early-onset infection
        • Within first six days
        • Due to vertical transmission from maternal genital tract
      • Late-onset infection
        • After day 6
        • Due to nosocomial, community, or maternally acquired pathogens
    • Clinical features
      • Temperature instability (Fever/hypothermia)
      • Irritability
      • Lethargy
      • Hypotonia
      • Seizures
      • Poor feeding
    • Diagnosis
      • High/low WBC in blood
      • High WBC in CSF
      • High protein in CSF
      • Decreased glucose in CSF
      • Blood culture
      • Gram staining of CSF
      • Definitive diagnosis: CSF culture after LP
    • Treatment
      • Empiric treatment
        • Initiated if bacterial meningitis is suspected but not yet confirmed by culture
        • Typically ampicillin + gentamicin + cefotaxime
      • Specific treatment
        • After culture results are available
  • Viral meningitis
    • Not frequent in newborns
    • Most commonly due to HSV or enterovirus
    • Similar clinical features as bacterial meningitis
    • Treatment usually includes acyclovir

18. Neonatal necrotizing enterocolitis

  • Epidemiology
    • The most common GI emergency in neonates
    • 90% of cases occur in premature infants
  • Etiology
    • Prematurity
    • Antibiotic use
    • Not feeding with human breast milk
  • Pathomechanism
    • Susceptible host + GI dysbiosis + mucosal injury -> Ischaemic necrosis of intestinal mucosa
  • Clinical features
    • Occurs during weeks 2 – 4
    • Sudden onset of symptoms in a previously healthy infant
    • Abdominal distension
    • Gastroparesis
    • Abdominal tenderness
    • Rectal bleeding
    • Vomiting, usually bilious
    • Nonspecific signs
      • Poor feeding
      • Lethargy
      • Respiratory failure
  • Diagnosis
    • Typical clinical symptoms
    • Definitive diagnosis: pneumatosis intestinalis on x-ray
      • Air inside the intestinal wall
  • Treatment
    • Supportive care
    • No oral feeding + parenteral nutrition
    • Gastric decompression
    • Broad-spectrum antibiotics
    • Severe cases -> surgery

19. Congenital and connatal infections

  • General
    • Mechanisms of infection
      • Intrauterine
        • Transplacental by blood
        • Ascending from vaginal tract
      • During delivery
      • Postnatal
        • Breast milk
        • Cross infection
        • From environment
    • Important to know regarding these infections
      • The nature of the damage to the foetus
      • The treatment, if available
      • Preventative measure
    • Antenatal screening programmes
      • Mandatory for
        • Rubella
        • Hepatitis B
        • HIV
        • Syphilis
      • Not mandatory, but screened in certain groups
        • Hepatitis C
        • CMV
        • Herpes simplex virus
        • Parvovirus B19
        • Toxoplasmosis
    • Most congenital infections cause nonspecific symptoms, like
      • Petechiae, purpurae
      • Hepatosplenomegaly
      • Small for gestational age
      • Seizures
      • Haematological abnormalities
      • Pneumonia
  • Congenital rubella infection
    • Epidemiology
      • Very rare in countries with vaccination programmes
      • Especially mandatory vaccination programmes, like Hungary
    • Route of transmission
      • Transplacental
    • Period of susceptibility
      • First 20 weeks
      • Highest in the first 8 weeks (80%)
      • Risk decreases from week 8 to 20
    • Clinical features in foetus
      • Rubella syndrome
        • Patent ductus arteriosus (PDA)
        • Cataracts
        • Encephalitis
        • Interstitial pneumonia
        • Sensory abnormality of eye, ear
        • Bony radiolucency
      • Expanded rubella syndrome
        • Small for gestational age
        • Microcephaly
        • Patent ductus arteriosus (PDA)
        • Pulmonary stenosis
        • Hepatosplenomegaly
        • Lymphadenomegaly
    • Clinical features in mother
      • Fever
      • Sore throat
      • Rash
      • Red, itchy eyes
    • Diagnosis
      • Of mother or neonate: PCR of throat swab
      • Of foetus: IgM serology of amniotic fluid
    • Prevention
      • Vaccination programmes
        • MMR vaccine at 15 months and 4 years
      • Mandatory antenatal screening
      • Non-immunized women are offered the vaccine postnatally
  • Congenital cytomegalovirus infection
    • Epidemiology
      • The most common congenital infection
      • 1% of live births in the US
    • Route of transmission
      • Transplacental
    • Clinical features in foetus
      • 95% asymptomatic at birth, 10% of these develop late complication
      • Hearing loss
      • Intrauterine growth restriction
      • CNS abnormalities
        • Microcephaly, hydrocephalus
        • Periventricular calcification
        • Cerebral palsy
    • Clinical features in mother
      • Usually asymptomatic
      • Mononucleosis-like symptoms
    • Prevention
      • No prevention available
    • Treatment
      • IV ganciclovir in newborn
  • Congenital toxoplasmosis
    • Cat is the primary host
    • Route of transmission:
      • Transplacental
    • Clinical features in foetus
      • Classical triad
        • Hydrocephalus
        • Chorioretinitis (posterior uveitis)
        • Intracranial calcifications
      • Non-specific features
        • Hepatosplenomegaly
        • Thrombocytopaenia
        • Growth retardation
    • Clinical features in mother
      • Usually asymptomatic
      • Mononucleosis-like symptoms
    • Prevention
      • Pregnant women should avoid contact with cat litter and eating undercooked food
    • Treatment
      • Pyrimethamine, sulfadiazine, and folinic acid (leucovorin)
        • May be effective in utero
        • Definitely effective postnatally
  • Congenital syphilis
    • Epidemiology
      • More common in children of mothers who don’t receive antenatal care
    • Route of transmission
      • Transplacental
      • Contact with infected fluids during birth
    • Period of susceptibility
      • Whole pregnancy (?)
    • Clinical features in foetus
      • Miscarriage
      • Stillbirth
      • Most are asymptomatic at birth but manifest later
      • Late manifestations (> 2 years of age)
        • Saddle nose
        • Prominent forehead
        • Hutchinson teeth (notched, widely spaced teeth)
        • Mulberry molars (poorly developed first molars)
        • Hearing loss
        • Gummas
    • Prevention
      • Mandatory antenatal serology
      • AB treatment for all mothers with positive serology
        • Unless they can document previous successful treatment
    • Treatment
      • 10 days of IV penicillin G or single-dose IM penicillin G for pregnant women and newborns
  • Congenital listeriosis
    • Route of transmission
      • Transplacental
      • Contact with infected fluids during birth
    • Clinical features in foetus
      • Stillbirth
      • Congenital listeriosis: Widespread abscesses
      • Perinatal listeriosis: Meningitis
    • Prevention
      • Pregnant women should avoid soft cheeses and meats
  • Congenital parvovirus B19
    • Epidemiology
      • 33% of positive, non-immune pregnant women transmit the virus transplacentally
    • Route of transmission
      • Transplacental
    • Clinical features in foetus
      • Miscarriage/stillbirth
      • Severe anaemia
      • Foetal hydrops
      • Cardiomyopathy
    • Clinical features in childhood
      • Flu-like symptoms
      • “Lacy” rash
    • Treatment
      • Intrauterine exchange transfusion for anaemia
  • Congenital varicella zoster
    • Epidemiology
      • Most mothers have been vaccinated, so congenital infection is rare
      • Only 2% of positive mothers transmit it transplacentally
    • Route of transmission
      • Transplacental
    • Period of susceptibility
      • First 20 weeks
      • Right before delivery
    • Clinical features in foetus
      • Congenital varicella syndrome (infection during first 20 weeks)
        • Hypertrophic scars
        • Limb abnormalities
        • Eye abnormalities
        • CNS abnormalities
      • Neonatal varicella (infection right before delivery)
        • Severe infection
        • Mortality rate 30%
    • Prevention
      • IV acyclovir for infected pregnant women and neonates
      • If maternal symptoms right before delivery: administer anti-VZV immunoglobulins
  • Congenital herpes simplex
    • Genital herpes, most commonly HSV2
    • Route of transmission
      • During birth
    • Clinical features in neonate
      • Typical skin lesions
      • Meningoencephalitis
    • Diagnosis
      • Of mother: Clinical diagnosis
      • Of neonate: Viral culture from skin lesions
    • Prevention
      • Caesarean section if genital herpes symptoms are present at time of delivery
  • Hepatitis B
    • Route of transmission
      • Transplacental
      • During birth
      • During breastfeeding
    • Prevention
      • Mandatory antenatal screening for HBsAg
      • Positive mother: neonate gets HBV vaccine and anti-HBV immunoglobulin
  • Hepatitis C
    • Route of transmission
      • During birth
    • Prevention
      • Cure mother before pregnancy
      • No treatment for infected children
  • HIV
    • Epidemiology
      • > 90% of paediatric cases are due to vertical transmission
    • Route of transmission
      • During birth
      • Breastfeeding
    • Prevention
      • C-section in some cases
      • Anti-retroviral to pregnant mother
      • Anti-retroviral to infant first 4 weeks
  • Chlamydia trachomatis
    • Route of transmission
      • During birth
    • Clinical features in neonate
      • Conjunctivitis
      • Pneumonia
    • Prevention
      • Screening for women at risk for chlamydia and becoming pregnant

20. Inborn errors of metabolism

  • = enzyme deficiencies
  • Phenylketonuria (PKU)
    • Epidemiology
      • 1:9000 live births
      • 98% have classical PKU
    • Pathophysiology
      • A normal diet contains large amounts of phenylalanine
      • Decreased conversion of phenylalanine to tyrosine ->
        • Phenylalanine accumulation -> presence of abnormal phenylalanine metabolites
        • Tyrosine deficiency -> catecholamine, melanin deficiency
      • Classical PKU = Deficiency of phenylalanine hydroxylase, which converts phenylalanine into tyrosine
      • Atypical PKU = Deficiency of tetrahydrobiopterin (THB), a cofactor for phenylalanine hydroxylase
    • Clinical features
      • Thanks to newborn screening resulting in early treatment, clinical features are rarely seen nowadays
      • Mental retardation
      • Growth restriction
      • Psychomotor delay
      • Seizures
      • Microcephaly
      • Vomiting
      • Fair skin, blue eyes, pale hair
    • Diagnosis
      • Newborn screening
        • Measurement of serum phenylalanine on day 2 or 3
    • Treatment
      • Diet low in phenylalanine and high in tyrosine
        • Eat only special medical foods including amino acids mixtures without phenylalanine
        • Aspartame, an artificial sweetener, contains phenylalanine and must be avoided
  • Galactosaemia
    • Epidemiology
      • 1:60 000 live births
    • Pathophysiology
      • Deficiency of enzymes involved in galactose metabolism
        • Galactose is a monosaccharaide found in lactose found in dairy products
      • 5 enzymes are involved in galactose metabolism, each of which can be deficient
      • > 90% have deficiency of galactose 1-phosphate uridyltransferase (GALT) -> classic galactosaemia
    • Clinical features
      • Even with close follow-up most adults end up developing problems
      • Poor feeding, poor weight gain
      • Vomiting
      • Cataract
      • Liver abnormalities
        • Hepatomegaly
        • Jaundice
        • Hypoglycaemia
      • CNS abnormalities
        • Lethargy
        • Cognitive impairment
    • Diagnosis
      • Newborn screening
        • Serum measurement of galactose and its metabolites
      • Definitive diagnosis
        • Measure enzyme activity in RBCs
    • Treatment
      • Avoid foods with lactose and galactose, including breastmilk
      • Galactosaemia is one of the few contraindications to breastfeeding
  • Glycogen storage disorders
    • Characterised by defects in enzymes of glycogenolysis or glycolysis
    • Many different types
    • Clinical features
      • Hypoglycaemia
      • Hepatomegaly
      • Cardiomyopathy
      • Hyperlipidaemia
      • Exercise intolerance
    • Management
      • Special diet
      • Enzyme replacement therapy (for some types)

21. Late complications of neonatal diseases (ROP, BPD)

  • Retinopathy of prematurity (ROP)
    • Etiology
      • Prematurity
      • Very low birth weight
      • Supplementation with high O2
    • Pathomechanism
      • Fluctuating levels of oxygen in the blood -> pathological extraretinal neovascularization -> haemorrhage
      • Can cause visual abnormalities or blindness later
    • Screening
      • Performed by ophthalmologist
      • Indicated in
        • Very low birth weight infants
        • Gestational age of 30 weeks or less
    • Treatment
      • Not severe ROP -> surveillance with regular check-up
      • Severe ROP
        • Laser photocoagulation
        • Intravitreal injection of anti-VEGF therapy
  • Bronchopulmonary dysplasia
    • = chronic lung disease in preterm infants which develops due to abnormal lung development or lung injury
    • Definition
      • Usually defined as requiring oxygen support at 28 days of age
    • Etiology
      • Prematurity (always)
      • Intrauterine growth restriction
      • Maternal smoking
      • Mechanical ventilation
      • Supplementation with high O2
    • Pathomechanism
      • Abnormal lung development or lung injury -> atelectasis, inflammation, pulmonary oedema
    • Clinical features
      • Tachypnoea
      • Respiratory distress
    • Diagnosis
      • Oxygen reduction test
        • If the O2 saturation falls below 90% within 60 minutes of being in room air (no oxygen support), test is positive
      • X-ray
        • Diffuse haziness, coarse interstitial pattern
    • Treatment
      • Supportive care
      • Ensure proper food intake
      • Fluid restriction
      • In severe cases, steroids and bronchodilators may be used
    • Prevention
      • In infants needing ventilation, use as little ventilation as needed
    • Complications
      • Pulmonary hypertension
      • Cor pulmonale

22. Congenital anomalies of the gastrointestinal tract (oesophagus, stomach, intestines)

  • Oesophageal atresia
    • = oesophagus ends blindly instead of leading to the stomach
    • Epidemiology
      • 1 in 4500 live births
    • Different types (according to Gross classification)
      • Classified according to the arrangement of the tracheoesophageal fistula
      • Five types (A – E), but type C is the most important
      • Type C (90% of cases)
        • Tracheoesophageal fistula connects to the distal segment of the oesophagus
    • Pathomechanism
      • Abnormal development of the tracheoesophageal septum causes abnormal separation of the trachea and oesophagus
      • Foetus can’t swallow amniotic fluid -> polyhydramnios
      • Secretions from proximal blind oesophagus can enter lung or mouth
      • Air enters stomach -> gastric distension
      • Gastric secretions can enter lung -> aspiration, aspiration pneumonia
    • Clinical features
      • Prenatal: Polyhydramnios (increased amniotic fluid)
      • Postnatal:
        • Symptomatic immediately after birth
        • Cyanotic attack
        • Dyspnoea
        • Inability to feed
        • Inability to pass feeding tube (more than 10 – 15 cm)
        • Gastric distension
    • Associated abnormalities (VACTERL)
      • 50 – 70% of patients have one or more of these
      • Vertebral anomaly
      • Anorectal malformations
      • Cardiac anomaly
      • Tracheoesophageal fistula
      • Esophageal atresia
      • Renal anomaly
      • Limb malformation
    • Diagnosis
      • Prenatal: polyhydramnios on ultrasound
      • X-ray
        • Oesophageal pouch
        • Air in stomach and intestines
      • Water-soluble contrast study of upper GI tract
      • Look for associated abnormalities
        • Echocardiography
        • Renal US
    • Treatment
      • Prenatal diagnosis: transfer to centre which can operate
      • No oral feeding
      • Continuous suction of proximal oesophagus
      • Endotracheal intubation
      • Surgery
        • Ligation of tracheoesophageal fistula
        • Primary anastomosis of oesophageal segments
    • Prognosis
      • Very high survival (close to 100% for term)
      • Nowadays complications are rare, but still possible:
        • Oesophageal stricture
        • Recurrent fistula
        • Anastomotic leak
  • Duodenal atresia and stenosis
    • Atresia = complete occlusion or absence of lumen
    • Stenosis = narrowing of lumen
    • 1 in 2500 – 5000 live births
    • Etiology
      • 30% of cases occur in Down syndrome
    • Clinical features
      • Obstruction can occur at any level of duodenum
      • Prenatal: Polyhydramnios
      • Vomiting
        • If obstruction distal to Vater papilla -> bile in vomit
        • -> hyponatraemia, dehydration
      • Distended upper abdomen
    • Diagnosis
      • Prenatal ultrasound:
        • “Double bubble” sign
          • (two air bubbles, one being stomach and the other being the distended duodenum proximal to the obstruction)
        • Polyhydramnios
      • X-ray
        • “Double bubble” sign
        • Gasless distal bowel
      • Search for associated anomalies
    • Treatment
      • Duodeno-duodenal anastomosis
      • Excision of the narrowing parts
  • Small bowel atresia and stenosis
    • Less common than duodenal or oesophageal obstruction
    • Clinical features
      • Prenatal: Polyhydramnios
      • Bile in vomit
      • Abdominal distension
    • Diagnosis
      • X-ray
      • Distended, air-filled bowels proximal to obstruction
    • Treatment
      • Nasogastric tube
      • IV fluids
      • Antibiotics
      • Surgery
        • Primary anastomosis or temporary stoma
  • Anorectal malformations
    • Types in girls
      • No anus, fistula between rectum and perineum
      • No anus, fistula between rectum and vestibule
      • Rectum, urethra, vagina, all open into a common opening called “cloaca”
    • Types in boys
      • No anus, fistula between rectum and perineum
      • No anus, fistula between rectum and bulbar urethra
      • No anus, fistula between rectum and prostatic urethra
    • Diagnosis
      • Lateral X-ray after 18 hours after birth
        • Must wait for air to reach the rectum
      • Look for associated malformations (VACTERL)
    • Treatment
      • Surgery (exact procedure depends on malformation)
    • Prognosis
      • The lower (more distal) the malformation is, the better the prognosis
      • Faecal or urinary incontinence

23. Omphalocele, gastroschisis

  • Abdominal wall defects
    • = omphalocoele, gastroschisis
    • In both conditions abdominal contents herniate through the abdominal wall
    • 1 in 4000 live births
    • Treatment
      • Preoperative
        • Wrap bowel with sterile saline dressings covered in plastic wrap
        • Nasogastric tube to decompress
        • IV fluids
        • Ensure normothermia
        • IV antibiotics
        • Rectal irrigation
      • Surgery
        • Return contents into bowel
        • Primary suture of abdominal wall defect
        • If any bowels can’t fit in abdominal cavity during surgery, they’re covered by a plastic bag called a silo. The other end of the silo is hung up, so that the bowels will return into the abdominal cavity after a few days due to gravity
  • Omphalocoele
    • Pathomechanism
      • Due to failure of the midgut to return to the abdominal cavity after physiological herniation
      • Herniation of abdominal organs through abdominal wall at umbilicus
      • Organs are covered by amniotic membrane and peritoneum
      • Exposed bowel -> increased fluid loss
    • Clinical features
      • Larger than gastroschisis (> 2,5 cm)
      • Covered by amniotic membrane
      • Umbilical cord at the top
    • Associated anomalies
      • Very frequent (50 – 60%)
      • Malrotation of intestines
      • Cardiac anomalies
      • Renal anomalies
      • Trisomies
      • Beckwith-Wiedemann syndrome
  • Gastroschisis
    • Pathomechanism
      • Peritoneal cavity too small for developing organs -> anterior abdominal wall ruptures at its weakest point, to the right of the umbilicus
      • Exposed bowel -> increased fluid loss
    • Clinical features
      • 2 – 4 cm defect in abdominal wall
        • Defect to the right of the umbilicus
      • Not covered by any membrane
    • Associated anomalies rare
    • Complications
      • Intestinal stenosis or atresia
      • Volvulus
      • Non-rotation of intestines

24. Diaphragmatic hernia

  • It’s not specified in the topic name, but the topic is about congenital diaphragmatic hernia
  • Epidemiology
    • One in 3000 live births
  • Pathomechanism
    • Impaired development of pleuroperitoneal membrane -> defect in diaphragm
      • 90% of cases occur on the left side
    • Abdominal contents herniate into pleural cavity
    • Lung gets compressed in utero -> pulmonary hypoplasia, surfactant deficiency, left ventricular hypoplasia -> respiratory failure
  • Types
    • Bochdalek hernia
      • Most common (90% of cases)
      • Defect in posterolateral part of diaphragm
    • Morgagni hernia
      • Rare (5%)
      • Defect in sternocostal part of diaphragm
  • Clinical features
    • Symptoms depend on degree of pulmonary hypoplasia
    • In first few hours or days
    • Respiratory distress
  • Diagnosis
    • Prenatal ultrasound
      • Bowel in thorax
      • Mediastinal shift
      • Lung-to-head ratio < 1 (indicates pulmonary hypoplasia)
    • Auscultation of bowel sounds in chest and absent breathing sounds
    • X-ray
      • Bowel in thorax
  • Treatment
    • The surgery itself is simple – the problem is stabilizing the neonate first
    • Stabilization
      • Endotracheal tube intubation (NEVER mask ventilation)
        • Mask ventilation forces air into intestines, further compressing the lung
      • Nasogastric tube with continuous suction
        • Decompresses the intestines
      • High-frequency oscillatory ventilation
    • Surgery
      • Surgery can wait up to approx. 10 days
      • Repositioning of the herniated organs
      • Simple primary closure of diaphragmatic defect
      • If big defect: closure with patch
  • Complications
    • Pulmonary hypertension
    • Chronic lung disease

25. Acyanotic congenital heart diseases

  • Pre- and postnatal circulation
    • In the prenatal circulation both ventricles work in parallel helping each other -> problem with one side of the heart can be compensated by the other
    • In the postnatal circulation the ventricles work in series -> problem with one side can’t be compensated and will affect the other
    • For this reason, most congenital heart diseases become apparent after birth
  • Congenital heart disease occurs in 8/1000 live births
    • 2/1000 live births have severe congenital heart disease, needing intervention in the neonatal period
  • Acyanotic congenital heart diseases
    • = left-to-right shunting
    • Risk factors
      • Trisomies (esp. 21)
      • Maternal infections
      • Maternal drugs or alcohol during pregnancy
    • Types
      • Ventricular septal defect (VSD)
      • Atrial septal defect (ASD)
      • Patent ductus arteriosus (PDA)
      • AV canal
    • These CHDs don’t cause cyanosis, but can cause symptoms like
      • Exercise intolerance
      • Growth restriction
      • Symptoms of heart failure
    • If severe, acyanotic CHDs can cause Eisenmenger syndrome
    • Definite diagnosis is made by echocardiography
    • Smaller defects are often asymptomatic and don’t require treatment
  • Ventricular septal defect (VSD)
    • Most common CHD
    • Clinical features
      • Often small and asymptomatic
      • If larger -> heart failure by the age of 2 – 3 months
    • Diagnosis
      • Physical examination
        • Holosystolic regurgitation murmur on left lower sternal border
        • Mid-diastolic murmur on apex of heart
      • Echocardiography for definitive diagnosis
    • Treatment
      • Surgical repair with patch
        • Indicated if defect is large
  • Atrial septal defect (ASD)
    • Second most common CHD
    • Types
      • Ostium primum type ASD (ASD I)
        • ~20% of ASDs
      • Ostium secundum type ASD (ASD II)
        • ~70% of ASDs
    • Clinical features
      • Often small and asymptomatic
      • If larger -> symptomatic, potentially heart failure
    • Diagnosis
      • Physical examination
        • Widely split second heart sound which does not change with respiration (it’s fixed)
        • Systolic ejection murmur over second ICS on left side
      • X-ray
        • Cardiomegaly
        • Prominent pulmonary vessels
      • Echocardiography for definitive diagnosis
    • Treatment
      • Amplatzer closure device
        • By percutaneous interventional catheterization
        • Indicated if the ASD causes significant shunt
  • Patent ductus arteriosus (PDA)
    • See topic 7

26. Cyanotic congenital heart diseases

  • Cyanotic congenital heart disease
    • = right-to-left shunting
    • Risk factors
      • Trisomies
        • Especially Down syndrome
      • Maternal infections
      • Maternal drugs or alcohol during pregnancy
    • Types
      • The 5 T’s
        • Transposition of the great vessels
        • Tetralogy of Fallot
        • Truncus arteriosus
        • Tricuspid atresia
        • Total anomalous pulmonary venous connection
      • Other types
        • Pulmonary atresia
        • Hypoplastic left heart syndrome
        • Coarctation of the aorta
    • Ductal-dependant CHDs
      • These CHDs are only compatible with life as long as a left-to-right shunt like the ductus arteriosus persists
      • Tetralogy of Fallot with severe RVOT
      • Hypoplastic left heart syndrome
      • Transposition of great arteries
      • Pulmonary atresia
      • Critical coarctation of the aorta
      • Critical aortic stenosis
      • Critical pulmonary stenosis
    • Clinical features
      • Can cause cyanotic and hypoxaemic emergencies in infancy
      • Hypoxia -> cyanosis
        • = deoxygenated haemoglobin > 5 g/dL
      • Hypoxaemia
        • = arterial pO2 < 65 mmHg
    • Treatment
      • See treatment of heart failure (topic 1 in general paediatrics)
      • Prostaglandin E1 (alprostadil) for ductal-dependent congenital heart defects
        • Keeps the ductus arteriosus open until surgical repair
      • Repair by interventional catheterisation or surgery
  • Tetralogy of Fallot
    • Most common cyanotic CHD
    • Ductal-dependent if RVOT is severe
    • Includes:
      • Right ventricular outflow tract obstruction (RVOT)
      • Right ventricular hypertrophy
      • Ventricular septal defect
      • Overriding aorta
    • Clinical features
      • Persistent mild cyanosis
      • “Tet” spells
        • Intermittent episodes of hypercyanosis and hypoxia during psychological or physiological stress
      • Child prefers to sit in a squatting position
        • Squatting reduces the right-to-left shunt
    • Diagnosis
      • X-ray: “boot-shaped” heart
      • Echocardiography for definitive diagnosis
    • Treatment
      • “Tet” spells
        • Administer O2
        • Assume squat position
        • IV fluid and morphine
      • Permanent
        • Prostaglandin E1 until surgery
        • Surgical patching of VSD and correction of RVOT
  • Transposition of the great vessels
    • = aorta arises from right ventricle and the pulmonary trunk from the left
    • Ductal-dependent CHD
    • “Egg on a string” appearance on x-ray
    • Treatment: arterial switch procedure
  • Tricuspid atresia
    • = absent tricuspid valve, resulting in no flow between right atrium and ventricle
    • Ductal-dependent CHD
    • Right ventricle usually hypoplastic
    • Treatment
      • Three different procedures to separate the pulmonary and systemic circulations
      • Norwood, Glenn, and Fontan procedures
  • Truncus arteriosus
    • = Aorticopulmonary septum doesn’t develop, forming a single truncus arteriosus which receives blood from both ventricles
  • Total anomalous pulmonary venous connection
    • = All pulmonary veins drain into the systemic venous circulation instead of the left atrium
    • Not ductal-dependent, but requires interatrial shunting by the way of a foramen ovale or ASD

27. Infant nutrition. Comparison of breastfeeding and formula feeding. Feeding of the premature babies

  • Infant nutrition
    • Ideally:
      • Exclusively breastfeeding first 6 months
      • Partial breastfeeding, partial vegetables and fruits from month 6 to 12
    • Very few clinical situations exclude breastfeeding
      • Maternal HIV
      • Maternal active TB
      • Maternal cytostatic treatment
      • Infantile galactosaemia
    • More than 99% of infants have no reason to not be exclusively breastfed
      • Hungarian data
        • More than 90% of infants are at least partially fed by formula
        • Only approx. 60% are exclusively breastfed during the first month, and this number decreases with age
        • Only approx. 40% are exclusively breastfed in the first sixth months
      • In Scandinavia and Germany, the percentage is over 90%
    • Replacements for breast milk
      • Many replacements for breast milk were tried in the 1800s
      • Cow’s milk was the obvious choice, but infants died days after being fed cow’s milk
      • It turned out that cow’s milk has 3x the protein content of breast milk, which is problematic
      • They tried diluting cow’s milk 3x, but this solution didn’t contain enough energy
      • 3x diluted cow’s milk with added carbohydrates worked as a replacement for breast milk and became the standard substitution
  • Breastfeeding
    • Pros vs formula feeding
      • Pros for the infant
        • Contains oligosaccharides which help develop a healthy intestinal bacterial flora
        • Contains IgA antibodies, complement factors, and lactoferrin (antimicrobial protein) -> passive immunity
        • Contains proteins which increase iron absorption
        • Skin-to-skin contact
        • Prevents acute infections (like otitis media, pneumonia)
        • Lower risk of asthma, allergy, obesity, diabetes mellitus, IBD
      • Pros for the mother
        • Faster uterus involution
        • Longer postpartum anovulation
        • Faster weight loss back to baseline
        • Lower risk of breast cancer, endometrial cancer, ovarian cancer, type 2 diabetes
        • Cheaper, more practical
    • The intestinal flora of breastfed infants has mostly bifidobacteria, lactobacillus -> good
    • Breast milk contains enough energy and nutrients for the infant for the first 6 months, but after this the infant needs additional food to cover their needs
    • Exclusively breastfed infants should daily vitamin D supplementation, as breast milk doesn’t contain enough vitamin D
  • Formula feeding
    • The composition of formulas can’t be exactly equal to that of breast milk and will always be inferior
    • Protein content
      • Infant formula is still based on cow’s milk, and therefore contains cow’s milk proteins
      • These proteins can be recognized as foreign by the infant -> cow’s milk allergy or intolerance
      • Enzymatic hydrolysis of the cow’s milk protein breaks down epitopes, preventing the infant from recognizing them, but creates an unpalatable formula -> formulas are only partially hydrolysed, leaving some epitopes
    • Fat content
      • It’s difficult to mimic the fat composition of breast milk, especially the composition of polyunsaturated fatty acids
      • Formulas (sold in Europe) must have essential polyunsaturated fatty acids added
    • The intestinal flora of formula-fed infants consists of mostly E. coli -> not good
    • Many formulas contain probiotics or prebiotics
  • Comparison
Breast-feeding Formula feeding
Nutrient composition Physiological Non-physiological
Maintenance of sterility Easy Difficult
Protective immunity IgA, complement factors, lactoferrin None
Allergic proteins None Cow milk/soy
Resulting intestinal flora Lactobacillus, bifidobacteria E. coli and coliform strains
Mother-infant relation Very close, skin-to-skin contact Impersonal
Taste Variable Always the same
Cost Very cheap Expensive
Practicality Very practical Impractical
  • Feeding of premature infants
    • Unlike term infants, preterm infants have no energy store and require nutrients immediately after birth
    • Infants < 32 weeks or < 1800 g require at least one month of special nutrition
    • Most preterm infants can’t feed directly from the breast -> milk should be expressed and fed by nasogastric tube during steps 4 – 6
    • Six steps of feeding premature infants
      • 1 – Parenteral glucose and electrolytes
        • Immediately after birth
      • 2 – Add parenteral amino acids and vitamin
        • ASAP, but within 48 hours
      • 3 – Add parenteral lipids
        • After 2 days
      • 4 – Add minimal enteral nutrition
        • Only 12 – 24 mL of breast milk daily
        • Stimulates the GI tract function and development
      • 5 – Combine parenteral and enteral nutrition
        • Lasts for several weeks
      • 6 – Only enteral nutrition
        • Very variable when this stage is reached

XXVII. Foetal erythropoiesis and haematology

  • This is not a topic on the topic list, but it was discussed in the lectures this semester so it might be good to know
  • Place of foetal erythropoiesis
    • Weeks 2 – 10: Yolk sac
    • Weeks 10 – 26: Liver
    • Weeks 18 onwards: Bone marrow
  • Foetal erythropoiesis does not depend significantly on the maternal nutritional status
    • The foetus, like the parasite it is, is very good at trapping iron, folate, B12 from the mother
  • Timing of umbilical cord clamping
    • Right after birth, a lot of blood is moved from the placenta to the foetus through the umbilical cord = placental transfusion
    • Clamping the umbilical cord too early prevents placental transfusion, lowering the blood volume of the neonate
    • However, clamping too late causes polycythaemia
  • Haemoglobin structure
    • Foetal haemoglobin (α2γ2) has different structure than adult haemoglobin (α2β2)
    • Foetal Hb has greater affinity for oxygen, increasing oxygen uptake from maternal blood in the placenta but decreasing peripheral oxygen delivery
    • After delivery, synthesis of γ chains decrease while β chains increase, eventually making all Hb molecules in the body α2β2
  • Oxygen saturation
    • In utero oxygen saturation is 45 – 60% (relative hypoxia compared to adult life)
    • After birth, rises to 95%

XXIX. Neonatal anaemia

  • Also not a topic on the topic list, but it may be on next semesters list?
  • Etiology
    • Blood loss
      • Abruptio placentae
      • Placenta praevia
      • Twin-to-twin transfusion syndrome
      • Ruptured lived or spleen
    • Haemolysis
      • Haemolytic disease of the newborn (Rh, ABO incompatibility)
      • G6PD deficiency
      • Haemoglobinopathies
    • Diminished RBC production
      • Blackfan-Diamond syndrome
      • Infections
      • Anaemia of prematurity
      • Physiologic anaemia
  • Neonatal blood transfusion
    • In severe anaemia blood transfusions are necessary, but these transfusions also cause severe side effects in the neonates and should only be used when absolutely necessary
    • For this reason, there are strict guidelines regarding when to transfuse neonates
  • Physiologic anaemia
    • Normocytic normochromic anaemia which is physiological in neonates
    • Pathogenesis
      • With the onset of respiration, O2 saturation increases -> EPO production decreases -> RBC production decreases
      • During growth after birth, plasma volume increases faster than the RBC mass, causing haemodilution
    • Requires no treatment
  • Anaemia of prematurity
    • = an exaggeration of physiologic anaemia in preterm infants
    • Occurs at 3 – 12 weeks after birth in < 32 week preterm infants
    • Pathogenesis
      • Impaired EPO production for unknown reasons
      • Many blood tests taken from preterm infants -> iatrogenic “phlebotomy”
      • RBCs of preterm infants have lower lifespan
      • Preterm infants grow relatively faster than term infants -> haemodilution
      • Preterm infants have more foetal haemoglobin than term infants, so anaemia impairs peripheral oxygenation more in preterms than terms
    • Diagnosis
      • Hb 60 – 80 g/L
    • Clinical features
      • Often asymptomatic
      • Apnoea
      • Tachycardia
      • Tachypnoea
    • Prevention
      • Delay cord clamping
      • Reduce number of blood tests taken
  • Haemolytic disease of the newborn
    • Major problem in the past, nowadays not
    • Pathogenesis
      • Maternal exposure to foetal antigens on RBCs -> maternal production of antibodies, which cross placenta -> haemolysis of foetal RBCs
      • Maternal exposure to foetal RBCs occurs most commonly during birth, so it’s too late for the antibodies to affect the present foetus
        • However, if the mother has another foetus with the same RBC antigens, that foetus can be affected
      • Incompatibility in ABO antigens -> more common, but mild disease
        • Example: Mother O, foetus A
      • Incompatibility in Rh antigens -> severe disease, but nowadays prevented
        • In Rh- mother with Rh+ foetus
    • Clinical features
      • Hydrops foetalis
        • Only in Rh incompatibility
      • Neonatal anaemia
      • Jaundice
    • Diagnosis
      • Signs of haemolysis -> Coombs test
        • Positive -> Rh incompatibility
        • Negative or weak positive -> ABO incompatibility
    • Treatment
      • Most cases, even Coombs positive ones, don’t require treatment
      • Intrauterine blood transfusion
        • Only in severe cases
      • Phototherapy for hyperbilirubinaemia
    • Prevention
      • Rh- mothers are screened for anti-D antibodies
        • No anti-D antibodies (unsensitized mothers) -> receive anti-D immunoglobulin
          • These immunoglobulins will destroy the foetal RBCs during birth before they can sensitize the mother
        • Anti-D antibodies present (sensitized mothers) -> monitor foetus for haemolysis

XXX. Haemorrhagic disease of the newborn

  • = Vitamin K deficiency bleeding of the newborn
  • Pathomechanism
    • Neonates have low vitamin K, due to limited transport across placenta, low vit K content in breast milk, and sterile gut
  • “Early” type haemorrhagic disease
    • Within 24 hours of life
    • Due to maternal use of drugs with anti-vitamin K effect
      • Warfarin
      • Phenytoin
      • Phenobarbital
  • “Classic” type haemorrhagic disease
    • Between day 1 and 7
    • Due to exclusive breastfeeding and/or no vitamin K prophylaxis
  • “Late” type haemorrhagic disease
    • Between 3 weeks and 8 months
    • Due to exclusive breastfeeding and/or no vitamin K prophylaxis
    • Can also be due to fat malabsorption, AB treatment
  • Clinical features
    • Bleeding of umbilicus
    • Cephalohaematoma
    • Intracranial haemorrhage
  • Prevention
    • All term infants: 2 mg oral vitamin K (Konakion)
    • All preterm infants: 1 mg IV vitamin K
    • Infants who are exclusively breastfed should get 2 mg oral vitamin K weekly
  • Treatment
    • Repeat IV vitamin K
    • Fresh frozen plasma transfusion

XXXI. Neural tube defects

  • Risk factors
    • Maternal folic acid deficiency
    • Drugs affecting folate metabolism
  • Prevention
    • Folic acid before planned pregnancy and during pregnancy
  • Myelomeningocele
    • = protrusion of both meninges and spinal cord through a defect in the back
    • Epidemiology
      • 1 – 2 / 1000 live births
    • Clinical features
      • Paraparesis
      • Clubfoot

XXXII. Neonatal hypotonia

  • Hypotonia = reduced resistance to passive range of motion in joints
  • Sometimes called floppy baby syndrome
  • Etiology
    • CNS hypoxia/ischaemia
    • Genetic syndromes
      • Down syndrome
      • Prader-Willi syndrome
    • Spinal muscle atrophy
    • Congenital myasthenia gravis
    • Muscular dystrophy
    • Metabolic myopathy
  • Diagnosis
    • Infant’s body forms an upside-down U-shape when held at abdomen or back

XXIII. Periventricular leukomalacia and hydrocephalus

  • Periventricular leukomalacia (= encephalopathy of prematurity)
    • Mainly affects premature infants
      • The lower the birth weight, the higher risk
      • 5% of very low birth weight (< 1500 g) infants
    • Pathomechanism
      • Hypoxia, ischaemia, or inflammation cause focal necrosis of periventricular white matter
    • Clinical features
      • Infants rarely show signs, but they appear later
      • Typically causes spastic diplegia of the legs
      • Can cause weakness of arms and face if severe
    • Diagnosis
      • Typically diagnosed during routine screening ultrasound
  • Hydrocephalus
    • = enlarged ventricles due to excess CSF
    • 2 types, although a mixture of both types often occurs
    • Etiology
      • Interventricular haemorrhage
      • Infection
        • TORCH
      • Choroid plexus tumour
      • Brain tumour
      • Development malformations
        • Neural tube defects
        • Aqueductal stenosis
        • Arnold-Chiari malformation
        • Dandy-Walker malformation
    • Noncommunicating or obstructive hydrocephalus
      • More common than communicating
      • Something obstructs the CSF circulation at the point of foramen of Monro, aqueduct of Sylvius, or fourth ventricle
    • Communicating hydrocephalus
      • Less common than noncommunicating
      • Blood or debris obstruct and inflame the arachnoid villi, preventing CSF absorption
      • Local inflammation -> inflamed arachnoid villi -> decreased CSF absorption
    • Treatment
      • Ventriculoperitoneal shunt
        • One-way shunt which drains CSF into the peritoneum

GENERAL PAEDIATRICS

History taking in paediatrics

  • Not a topic, but should be known
  • Maternal history
    • Age
    • Chronic diseases
    • Number of pregnancies
    • Number of children
    • Medications
    • Problems during pregnancy
      • Bleeding
      • Trauma
      • Hypertension
      • Infection
    • Drug/alcohol/smoking abuse
  • Labour history
    • Length of labour
    • Type of delivery
    • Use of forceps/vacuum
    • Use of anaesthesia
    • Gestational age (pre-term/mature/post-term)
    • Birth weight and length
    • APGAR score
  • Neonatal history
    • Any problems in neonatal period
    • Breathing problems
    • Use of oxygen
    • Need for intensive care
    • Need for phototherapy
    • Feeding problems
  • Feeding history
    • Breastfed/bottle fed
    • Use of formula
    • Frequency, amount
      • Should be approx. 150 mL/kg body weight/day
  • Other history
    • Vaccination history
    • Chronic diseases
    • Medications
    • Allergies
    • Family history
    • Social history

1. Heart failure

  • Etiology
    • Structurally normal heart
      • Cardiomyopathy
      • Myocarditis
      • Myocardial infarction
      • Arrhythmias
    • Congenital heart defects
  • Clinical features
    • In infancy
      • Hepatomegaly
      • Significant tachypnoea (> 60/min)
      • Feeding difficulty
      • Increased sweating
      • Tachycardia
      • Growth retardation
    • In childhood
      • Fatigue
      • GI symptoms
      • Tachycardia
      • Tachypnoea
      • Growth retardation
  • Diagnosis
    • Physical examination
      • May give clue for diagnosis
      • Cool extremities
      • Decreased capillary refill
      • Wheezing and rales on auscultation
      • Hepatomegaly
      • Peripheral oedema
    • Echocardiography
      • Gold standard
    • X-ray
      • Cardiomegaly
      • Prominent pulmonary vasculature
      • Features of underlying disease
    • ECG – generally not useful
    • Labs
      • NT-proBNP
      • Electrolytes
      • Renal function
      • Liver function
      • Iron studies
  • Treatment
    • Treat underlying or contributing conditions
    • Diuretics
    • ACE inhibitor/ARB
    • Beta blockers
    • Digoxin

2. Infective endocarditis, myocarditis, pericarditis in childhood

  • Infective endocarditis
    • Epidemiology
      • ~1 – 3 per 100 000 children
      • Approx. 90% occurs in children with structural heart disease
      • Approx. 10% occurs in children without
    • Etiology
      • Congenital heart disease
      • Prosthetic valve
      • Dental procedures or other surgical procedures
      • Central venous catheters
    • Infectious agents
      • Streptococcus viridans
        • In children with congenital heart disease
      • Staphylococcus aureus and coagulase-negative staphylococci (CONS)
        • In children who had cardiac surgery
        • In children who have prosthetic material in the heart
    • Clinical features
      • Subacute infective endocarditis
        • Usually nonspecific symptoms
        • Low fever
        • Malaise
        • Weight loss
      • Acute infective endocarditis
        • Rapidly progressive symptoms
        • High fever
        • Haemodynamic instability
        • Heart failure
      • New heart murmur
      • Embolic phenomena
        • Osler nodes – painful red lesions on hands, fee
        • Roth spots – spots on retina
        • Janeway lesions – painless lesions on hands, feet
        • Splinter haemorrhages – under nails
    • Diagnosis
      • Based on the Duke criteria, where the major criteria include
        • Positive blood culture
        • Positive echocardiography
          • Preferably transoesophageal
      • Elevated inflammatory markers
    • Treatment
      • Severely ill patients
        • Stabilize cardiac function (heart failure, pulmonary oedema, etc.)
        • Give empiric antibiotics immediately after obtaining blood cultures
      • Not severely ill patients
        • Wait for blood culture results before starting antibiotics
        • Bactericidal antibiotics are preferred
        • Treatment lasts long (4 – 8 weeks)
      • Surgery
        • In case of unsuccessful antibiotic treatment, endocardial abscess, valve rupture, or valvular insufficiency
    • Complications
      • Heart failure
      • Perivalvular abscess
      • Metastatic infection
      • Organ infarction
    • Prevention
      • Good oral hygiene for all patients at risk
      • Prophylactic antibiotics before dental and other procedures in high-risk patients
  • Myocarditis
    • Epidemiology
      • 1 – 2 per 100 000 children
    • Etiology
      • Most commonly due to virus
      • Coxsackie group B
      • Adenovirus
    • Clinical features
      • Anywhere from nonspecific symptoms to cardiogenic shock and arrhythmias
      • Two phases, which overlap:
      • Viral infection phase
        • Fever
        • Myalgia
        • Malaise
      • Autoimmunity and inflammatory phase
        • Symptoms of heart failure
        • Arrhythmias
    • Diagnosis
      • Definitive diagnosis based on endomyocardial biopsy or MRI
        • MRI is more commonly used
      • Viral swabs from rectal and nasal mucosa to confirm viral etiology
    • Treatment
      • There is no curative therapy. The goal is to stabilize while we wait for it to resolve
      • Stabilize cardiac function (heart failure, cardiogenic shock, etc.)
        • Diuretics, afterload-reducing agents
        • Inotropic drugs, mechanical ventilation
      • Intravenous immunoglobulin (IVIG)
        • May improve prognosis
      • Limit physical activity for 6 months after onset of disease
    • Prognosis
      • Some never fully recover cardiac function, leading to dilatative cardiomyopathy
      • 5 – 10% mortality rate
      • 5 – 20% require cardiac transplant
  • Pericarditis
    • Etiology
      • Most commonly due to virus
      • Staph. aureus, strep. pneumoniae
      • Uraemia
      • Heart surgery (-> postpericardiotomy syndrome)
      • Rheumatic diseases
    • Clinical features
      • Symptoms are worse in cases where the pericardial effusion is large, especially if it accumulates quickly
      • Symptoms worsen when lying down
      • Pleuritic chest pain
        • Sharp and piercing
        • Worsens on deep inspiration
      • Dyspnoea
      • Fever
      • Distant heart sounds
      • Pericardial friction rub
      • Tachycardia
    • Diagnosis
      • Clinical diagnosis based on 2 of these 4 criteria
        • Typical chest pain
        • Pericardial friction rub
        • Typical ECG changes
        • Pericardial effusion
      • Echocardiography
        • Shows pericardial effusion
      • X-ray
        • Cardiomegaly
      • ECG
        • Reduced QRS amplitude
        • Widespread ST elevation
    • Treatment
      • Pericardiocentesis
        • In cases of significant effusions
      • NSAIDs
      • Pericardiectomy
        • For refractory pericarditis

3. Otitis, sinusitis

  • Acute (suppurative) otitis media
    • Epidemiology
      • More common in the cold season
      • Most common in 1 – 4-year olds
    • Clinical features
      • Ear pain
      • Hearing loss
      • Otorrhoea
    • Diagnosis
      • With otoscope
      • Bulging and white or yellow tympanic membrane
    • Treatment
      • Ibuprofen/paracetamol for pain
      • Topical anaesthetic
        • Not if tympanic membrane is perforated
      • Antibiotics
        • Amoxicillin
        • For children < 2 years
        • For children > 2 years if any of the following are present:
          • Persistent symptoms
          • High fever
          • Otorrhoea
          • Bilateral
      • Paracentesis/tympanocentesis
        • If treatment fails, to collect sample for bacterial culture
        • If severe symptoms
    • Complications
      • Acute mastoiditis -> mastoidectomy needed
  • Otitis media with effusion
    • Epidemiology
      • Very common, affects almost 90% of children by the age of 4
    • Develops due to malfunction of eustachian tube, preventing ventilation of the middle ear
    • Clinical features
      • Mostly asymptomatic
      • Hearing loss
      • Tinnitus
      • Poor or delayed speech development
    • Diagnosis
      • With otoscope
      • Bubbles or air-fluid level behind tympanic membrane
      • No signs of infection (see acute otitis media)
    • Treatment
      • Usually resolves spontaneously within six weeks
      • Tympanostomy tube may be placed
        • Remains for 6 – 9 months
      • Adenoidectomy may be performed
  • Otitis externa (= swimmer’s ear)
    • Epidemiology
      • More common in summer
    • Etiology
      • Bacterial infections (pseudomonas, staph, …)
    • Clinical features
      • Severe ear pain
      • Otorrhoea
      • Tender tragus and auricle
    • Diagnosis
      • With otoscope
      • Inflamed external ear canal
    • Treatment
      • Suction of discharge, cleaning ear canal
      • Topical antibiotics, steroids, antiseptic, depending on severity
  • Chronic suppurative otitis media
    • Etiology
      • Usually due to untreated acute otitis media
    • Clinical features
      • Chronic (> 6 wks) purulent otorrhoea
      • Hearing loss
      • Usually no pain
      • Cholesteatoma may be present
        • -> destruction of ossicles
        • -> facial palsy
    • Diagnosis
      • With otoscope
      • Central perforation of tympanic membrane
      • Purulent discharge from middle ear
    • Treatment
      • Tympanoplasty
      • Surgical removal of cholesteatoma
  • Acute bacterial rhinosinusitis
    • Etiology
      • Secondary bacterial infection after a viral upper respiratory tract infection
      • Haemophilus, strep. pneumoniae, Moraxella, etc.
    • Clinical features
      • Facial pain
      • Headache
      • Purulent nasal discharge
      • Obstructed nose
      • Cough
    • Complications
      • Orbital cellulitis
      • Abscess
      • Sinus thrombosis
      • Meningitis
      • Cerebral abscess
    • Diagnosis
      • Symptoms of sinus inflammation (cough or nasal symptoms) + one of the following
        • Symptoms not improving for more than 10 days
        • Severe symptoms (ill appearance, high fever) with purulent nasal discharge
        • Worsening symptoms
      • Or 3/5 of the following symptoms
        • Purulent nasal discharge
        • Severe pain over a paranasal sinus
        • Fever
        • Elevated ESR and CRP
        • “Double sickening” = symptoms initially improve before they worsen
    • Treatment
      • Antibiotics (amoxicillin-clavulanate)
      • Topical saline
      • If patient is in severe condition: hospitalization
  • Chronic bacterial rhinosinusitis
    • Similar to acute bacterial rhinosinusitis, but symptoms last for > 12 weeks
    • Types
      • Chronic rhinosinusitis with nasal polyps
      • Chronic rhinosinusitis without nasal polyps
    • Treatment:
      • Functional endoscopic sinus surgery (FESS)

4. Epiglottitis, laryngitis

  • Epiglottitis
    • A medical emergency, as the airways suddenly can become obstructed
    • Nowadays rare due to haemophilus vaccine
    • Etiology
      • Group A streptococcus
      • Staphylococcus aureus
      • Haemophilus influenzae in unvaccinated patients
    • Clinical features
      • Fever
      • Inspiratory stridor
      • Drooling
      • Respiratory distress
      • “Sniffing” posture
        • Head forward, mouth open, jaw forward
    • Diagnosis
      • By direct observation of inflamed, swollen, cherry red epiglottis, aryepiglottic folds
        • Should only be performed in operating room where intubation can be performed, as the laryngoscopy can trigger airway obstruction
        • If findings show epiglottitis -> immediate intubation or tracheostomy
      • Lateral x-ray may show enlarged epiglottis
      • Blood culture and epiglottic culture to determine etiology
    • Treatment
      • Airway maintenance is the first priority
        • Endotracheal intubation for almost all patients
      • Admission to ICU
      • Antibiotics
        • Empiric after airway is secured and cultures are taken
        • Targeted antibiotics after culture results are available
  • Croup (acute laryngotracheitis)
    • Epidemiology
      • Very common
      • Occurs in children 6 months to 3 – 6 year
      • Usually in fall and winter
    • Etiology
      • Virus, most commonly parainfluenza
      • Can occur after a cold
    • Clinical features
      • Often mild
      • Inspiratory stridor
      • Hoarseness
      • Barking cough
      • If severe
        • Respiratory distress
        • Dyspnoea
        • Respiratory failure
    • Diagnosis
      • Based on clinical features
      • X-ray may show subglottic narrowing
    • Treatment
      • Usually mild, self-limiting after 5 days
      • Calm the child down
        • Anxiety worsens airway obstruction
      • Give nebulized racemic epinephrine inhalation
      • Give cool, humid air inhalation
      • IM or oral dexamethasone
      • Severe cases should be admitted and observed

5. Pharyngitis, tonsillitis

  • Viral pharyngitis
    • Epidemiology
      • More common than bacterial pharyngitis
    • Etiology
      • Adenovirus
      • Rhinovirus
      • Coronavirus
    • Clinical features
      • Rhinorrhoea
      • Conjunctivitis
      • Cough
      • Herpangina (ulcerative vesicles in mouth)
    • Treatment
      • No specific treatment
  • Streptococcal (tonsillo-)pharyngitis
    • Epidemiology
      • 15 – 30% of childhood pharyngitis
      • Most common during winter and early spring
    • Etiology
      • Group A streptococcus (GAS)
    • Clinical features
      • Abrupt onset of symptoms
      • Sore throat
      • Nausea, vomiting
      • Fever (moderate to high)
      • Cervical lymphadenomegaly
    • Scarlet fever
      • 10% of streptococcal pharyngitis cases
      • A delayed-type hypersensitivity reaction to streptococcus pyogenes toxin
      • Streptococcal pharyngitis with additional skin symptoms
        • Diffuse erythematous maculopapular rash which gives a “sandpaper” quality to the skin
        • Strawberry red tongue with white coating
        • Pharyngeal erythema
        • Perioral pallor
    • Diagnosis
      • Based on result of RSAT
      • Rapid streptococcal antigen test (RSAT)
        • POC test
        • All children with typical clinical symptoms and findings on visualization should be tested
        • Throat culture can be an alternative
      • Direct visualization
        • Red pharynx
        • Tonsillitis: Enlarged tonsils covered with yellow exudate
    • Treatment
      • Oral amoxicillin or penicillin
        • For 10 days
        • Most cases are self-limiting, but AB accelerates recovery and prevents complications
    • Complications
      • Parapharyngeal abscess
      • Acute rheumatic fever
      • Poststreptococcal glomerulonephritis
  • Tonsillitis
    • Tonsilitis occurs together with pharyngitis, most commonly bacterial pharyngitis
    • There is no tonsillitis without pharyngitis

6. The seriously ill child (recognition, evaluation, monitoring)

  • Ensure your own safety and the safety of the child
  • Check the child’s responsiveness
    • If responsive
      • Leave child in current position
      • Call for help
      • Reassess regularly
    • If unresponsive
      • Open airways by tilting the head and lifting the chin
  • Evaluate breathing
    • While keeping airway open
    • Look for chest movements
    • Listen for breathing sounds
    • Feel for air movement on your cheek
    • If child is breathing
      • Turn child into recovery position
      • Call for help
      • Reassess regularly
    • If child isn’t breathing
      • Remove any obvious airway obstruction
      • Give five initial “rescue” breaths
  • Evaluate circulation
    • Feel for pulse
    • Look for movements or other signs of life
    • If signs of life are detected
      • Continue giving rescue breaths until the child starts breathing on its own
      • Turn child into recovery position
      • Call for help
      • Reassess regularly
    • If no signs of life are detected
      • Give chest compressions at a ratio of 15:2
  • Repeat chest compressions until either of the following apply
    • Child shows signs of life
    • Anyone else can take over
  • Symptoms of seriously ill child
    • Fever/hypothermia
    • Hypotension
    • Dyspnoea
    • Respiratory distress
    • Decreased urine output

7. Assessment of nutritional status (percentile, BMI, skin fold, laboratory tests). Forms of malnutrition

  • Assessment of nutritional status
    • Percentile
      • = comparing parameters to that of other children of the same sex, age, height
      • For example, a child in the 95th percentile for weight is heavier than 95% of children with same sex, age, and height
      • Weight percentile
      • BMI percentile
      • Waist circumference percentile
      • Hip circumference percentile
    • BMI
      • = weight/height2
      • Must be assessed as a percentile
      • Overweight – BMI in the 85th – 95th percentile
      • Obesity – BMI > 95th percentile
    • Ponderal index (PI)
      • = weight/height3
      • Used to detect asymmetric intrauterine growth restriction (in which the PI is low)
    • Skin fold
      • Uses skinfold calliper
      • Cheap
      • Good for assessing distribution of fat
    • Laboratory tests
      • CBC
        • Microcytic anaemia -> iron deficiency
        • Macrocytic anaemia -> folate, B12 deficiency
      • Prealbumin = marker of short-term dietary adequacy
      • Albumin = marker of long-term dietary adequacy
      • Serum vitamin D = marker of vitamin D intake
      • Ferritin, transferrin, serum iron = markers of iron intake
  • Malnutrition
    • Degree
      • Weight is > 90% of the expected weight = no malnutrition
      • Weight is 80 – 90% of the expected weight = mild malnutrition
      • Weight is 70 – 80% of expected weight = moderate malnutrition
      • Weight is < 70% of expected weight = severe malnutrition
    • Feeding of malnourished infant
      • A long-term process (months)
      • Refeeding should start slowly to prevent refeeding syndrome
      • Initially 2x as much energy, protein, and lipid per day
      • Simultaneous psychotherapy
      • Increases weight gain back to baseline over time
  • Failure to thrive
    • = inadequate growth of a child for their age
    • Distinction between slow physiological growth and failure to thrive
Slow growth Failure to thrive
Weight gain Continuous Not continuous
Feeding Normal frequency Less frequent
Muscle tone Good Hypotonic
Skin turgor Good Decreased
Behaviour Normal Abnormal
Urination Normal Less frequent
Defecation Normal Less frequent

8. Vitamin deficiencies (fat- and water-soluble vitamins), trace elements and their deficiencies

  • Iron deficiency
    • Term infants don’t need iron supplement until 4 months of age
    • Preterm infants need iron supplement with breast milk, or iron-fortified formula
    • Iron requirements in infancy
      • Term infants: 1 mg/kg of body weight/day
      • Preterm infants: 2 mg/kg of body weight/day
    • Clinical features
      • Microcytic, hypochromic anaemia
      • Failure to thrive
      • Stomatitis, glossitis
      • GI symptoms
      • Irritability, mild mental problems
      • Depressed immune functions
  • Vitamin C deficiency
    • Etiology
      • Infants fed unsupplemented cow’s milk
      • Diet without fruit and vegetables
    • Scurvy
      • Bleeding gums
      • Irritability
      • Pseudoparalysis because of painful extremities
      • Failure to thrive
  • Vitamin B1 (thiamine) deficiency
    • Etiology
      • Breast fed infants of alcoholic mothers
      • Infants fed unsupplemented cow’s milk
      • Infants fed boiled milk
    • Beriberi
      • Characteristic aphonic cry (appear to be crying but no sound)
      • Heart failure -> dyspnoea, cyanosis
  • Vitamin B3 (niacin) deficiency
    • Tryptophan can be converted to niacin, so deficiency only occurs if both tryptophan and niacin in the diet are deficient
    • Pellagra (4 D’s)
      • Dermatitis
      • Diarrhoea
      • Dysphagia
      • Dementia
  • Vitamin B9 (folate) deficiency
    • Rare in children
    • Newborns have 10x the folate requirement as adults (relative to body weight), but they have no stores of folate
    • Folate is heat labile
    • Etiology
      • Heated milk
    • Causes megaloblastic anaemia
  • Vitamin B12 deficiency
    • Rare in children
    • Etiology
      • Congenital pernicious anaemia
      • Juvenile pernicious anaemia
    • Clinical features
      • Megaloblastic anaemia
      • Peripheral neuropathy
  • Vitamin A deficiency
    • Etiology
      • Poor diet
    • Clinical features
      • Xerophthalmia
        • Night blindness
        • Dry eyes
      • Immunodeficiency
  • Vitamin D deficiency
    • Etiology
      • Poor diet
      • Inadequate sunlight
    • Clinical features
      • Hypocalcaemia
      • Hypophosphataemia
      • Rickets
        • Craniotabes – Thinning of the skull
        • Rachitic rosary – enlargement of costochondral junction
        • Thickening of wrists and ankles
        • Bowlegs
  • Vitamin K deficiency
    • Usually prevented by giving prophylactic vitamin K to all infants
    • Etiology
      • Common in breastfed infants
      • Due to no intestinal flora in infants
    • Clinical features (haemorrhagic disease of the newborn)
      • Generalized ecchymoses
      • GI bleeding
      • Intracranial haemorrhage

9. Congenital and acquired immunodeficiencies

  • Congenital (primary) immunodeficiency
    • Primary immunodeficiency = PID
    • Group of 150 congenital defects of immune system
    • Most are due to single gene defect
    • Epidemiology
      • 1 in 10 000 births
    • Common clinical features
      • Recurrent infections
      • Atypical infections
        • Unusual pathogens
        • Unusual response to therapy
        • Unusual localisation
        • Unusual infections for that age
      • Increased risk of autoimmune disorders
      • Increased risk of lymphoproliferative disease
      • Increased risk of atopic disease
    • Defect according to age of onset
      • Newborn, early infancy
        • Complement deficiency
        • Phagocyte deficiency
      • From 2 – 3 months
        • T-cell deficiency
        • Combined immunodeficiency
      • From 4 – 6 months
        • Antibody (B-cell) deficiency
    • Antibody (B-cell) deficiencies
      • 65% of PID
      • Increased risk of
        • Respiratory infections
        • Infection by encapsulated bacteria
        • Bronchiectasis
        • Autoimmune disease
        • Cancer
      • Laboratory investigations
        • Number of lymphocytes
        • Serum immunoglobulin isotypes
        • B-cell markers
      • Agammaglobulinaemia
        • = severely decreased immunoglobulin levels due to absent or defective B-cells
        • X-linked or autosomal recessive
        • Clinical features
          • Begins in 4 – 6 months
          • Recurrent infections by encapsulated bacteria, enteroviruses, and giardia
          • Mostly sinopulmonary infections
          • Absence of lymphoid tissue (No tonsils, adenoids, lymph nodes)
        • Common variable immunodeficiency
          • = normal number but decreased function of B-cells later in life, causing hypogammaglobulinaemia
          • Clinical features
            • Begins in second/third decade of life
            • Hyperplasia of tonsils and lymph nodes
            • Recurrent respiratory and gastrointestinal infections
            • Autoimmune diseases
      • Selective IgA deficiency
        • = IgA levels < 0,05 g/L
        • Very common (1:500)
        • Clinical features
          • Most are asymptomatic
          • Recurrent respiratory infections
          • Autoimmune diseases
      • Transient hypogammaglobulinaemia of infancy
        • Some degree of hypogammaglobulinaemia in infancy is normal, but in this disorder the IgG levels are lower than normal, > 200 mg/dL
        • IgG levels usually return to normal by 2 – 4 years
      • Treatment of antibody immunodeficiency
        • Lifelong immunoglobulin substitution (IVIG)
          • IV or SC
        • Killed vaccines
    • T-cell and combined immunodeficiencies
      • T-cell deficiency often causes deficiency of B-cells due to how T-cells activate B-cells, so the distinction between T-cell deficiency and combined deficiency is not sharp
      • 20% of PID
      • Increased risk of
        • Candida
        • Viral infections
        • Systemic reactions to live vaccines
      • Laboratory investigations
        • Number of lymphocytes
        • T-cell markers
      • Wiskott-Aldrich syndrome
        • X-linked
        • Clinical features
          • Eczema
          • Recurrent infections
          • Thrombocytopaenia -> bleeding diathesis
      • DiGeorge syndrome
        • Microdeletion at chromosome 22 causes defective development of third and fourth pharyngeal pouches, causing abnormal thymus, parathyroid, and face
        • Clinical features (CATCH-22)
          • Cardiac abnormalities
          • Abnormal face
          • Thymus hypoplasia -> T-cell deficiency
          • Cleft palate
          • Hypoparathyroidism -> hypocalcaemia -> tetany
        • FISH shows 22q11 deletion, labs show decreased number of T-cells
      • Ataxia telangiectasia
        • Defect in a gene for DNA repair -> accumulation of mutations
        • Clinical features
          • Cerebellar ataxia
          • Telangiectasias
          • Chronic respiratory infections
          • Increased risk for cancer
      • Severe combined immunodeficiency (SCID)
        • Defective development of both T and B cells
        • Normal at birth, symptoms begin after 1 month
        • Clinical features
          • Candidiasis
          • Recurrent infections anywhere
          • Chronic diarrhoea
          • Failure to thrive
      • Hyper IgM syndrome
        • Defect in isotype switching from IgM to other isotypes -> increased IgM, decreased IgG, IgA, IgE
        • Clinical features
          • Opportunistic respiratory infections
      • Treatment of T-cell and combined immunodeficiencies
        • Bone marrow transplantation
        • Intravenous immunoglobulin (IVIG)
    • Phagocyte (neutrophil) deficiencies
      • 9% of PID
      • Increased risk of
        • Pyogenic bacteria
        • Fungi
        • Intracellular pathogens
        • Abscesses
        • Chronic osteomyelitis
        • Aphthous stomatitis
      • Types
        • Myeloperoxidase deficiency
        • Chronic granulomatous disease
        • Leukocyte adhesion deficiency
        • Chediak-Higashi syndrome
      • Treatment
        • G-CSF
        • INF-γ
        • Prophylactic antibiotics
    • Complement deficiencies
      • 2% of PID
      • Increased risk of
        • Encapsulated bacteria, especially meningococcus
        • Immune complex disease (SLE, RA, GN)
      • Types
        • Hereditary angioedema (C1 inhibitor deficiency)
        • Terminal complement deficiency (C5 – C9 deficiency)
        • Early complement deficiency (C1 – C4 deficiency)
  • Acquired (secondary) immunodeficiency
    • Epidemiology
      • More common than primary immunodeficiency
    • Etiology
      • HIV/AIDS
      • Diabetes mellitus
      • Cancer
      • Immunosuppressive drugs

10. Juvenile idiopathic arthritis (JIA)

  • Definition
    • Onset < 16 years
    • Arthritis for more than 6 weeks
    • Other etiologies excluded
  • Epidemiology
    • The most common rheumatological disease of childhood
    • 1:1000 children
    • Peak incidence in 2 – 4 years
    • Females > males
  • Clinical features
    • Gradual onset
    • Morning stiffness and joint pain
    • Joint swelling and erythema
    • Limited range of motion
    • Ends of bones surrounding affected joints are longer and wider
    • Painless uveitis -> vision loss
  • Types
    • Oligoarticular JIA
      • Most common type (50% of JIA)
      • Asymmetric involvement of up to four joints
      • Usually affects knee and ankle joint
    • Polyarticular JIA
      • Involvement of five joints or more
      • Asymmetric or symmetric
      • Spine can be affected
      • Mostly affects small joints
    • Psoriatic JIA
      • Psoriasis
      • Dactylitis
      • Arthritis of small joints
      • Arthritis of spine and sacroiliac joints
      • Enthesitis
    • Systemic JIA (Still disease)
      • 10% of JIA
      • Polyarticular arthritis
      • Fever spike once or twice daily
      • Rash
      • Serositis
      • Hepatosplenomegaly
  • Diagnosis
    • Diagnosis of exclusion
      • Exclude early-onset rheumatoid arthritis, infectious arthritis, reactive arthritis, etc.
    • Leukocytosis, elevated ESR, CRP
    • Elevated antinuclear antibodies (ANA) -> increased risk for chronic uveitis
  • Treatment
    • Regular ophthalmological screening with slit lamp
    • NSAIDs
    • Intraarticular steroids
    • Methotrexate
    • Biologic therapy
  • Complications
    • Blindness
      • Due to chronic uveitis
      • Regular screenings obligatory
    • Macrophage activation syndrome
      • A rare but life-threatening complication of systemic JIA
      • 8% mortality even with treatment
      • Occurs in the first days or weeks of systemic JIA
      • Causes spontaneous bleeding, hepatic dysfunction, DIC, shock, coma
      • Treated with high dose steroids

11. Systemic autoimmune diseases (SLE, antiphospholipid syndrome)

  • Systemic lupus erythematosus
    • Epidemiology
      • 10 – 25 : 100 000 children
      • Mostly around puberty
      • Equally common in male and female children
    • Clinical features
      • Nonspecific symptoms
        • Fatigue
        • Malaise
        • Low fever
        • Weight loss
      • Skin symptoms
        • Butterfly rash
        • Photosensitivity
        • Alopecia
        • Ulcers in mouth and nose
      • Lymphadenopathy
      • Splenomegaly
      • Serositis
        • Pleuritis
        • Pericarditis
      • Renal disease
        • Haematuria
        • Proteinuria
        • Nephrotic syndrome
      • Arthralgia, arthritis
      • CNS symptoms
        • Seizures
        • Psychosis
    • Diagnosis
      • Based on criteria by American college of Rheumatology
        • 4 out of 11 typical symptoms must be present for diagnosis
      • Leukopaenia, thrombocytopaenia
      • Positive ANA
        • In almost all cases
        • Sensitive but not specific
      • Anti-dsDNA antibodies
        • Specific and relatively sensitive
      • Anti-Sm antibodies
        • Specific, not sensitive
    • Treatment
      • Hydroxychloroquine
      • Steroids
      • Azathioprine
      • Methotrexate
      • Mycophenolate mofetil
      • Cyclophosphamide
  • Antiphospholipid syndrome
    • Etiology
      • Primary (idiopathic)
      • Secondary
        • SLE
        • Other autoimmune diseases
    • Clinical features
      • DVT
      • Cerebral venous sinus thrombosis
      • Portal vein thrombosis
      • Stroke
    • Diagnosis
      • No widely accepted diagnostic criteria
      • Antiphospholipid antibodies
        • Positive in 50%
    • Treatment
      • Anticoagulation

12. Juvenile dermatomyositis

  • Epidemiology
    • Rare, only 2 – 4 per million children
    • Peaks at around 7 and 12 years
    • Female > male
  • Clinical features
    • Symmetrical, proximal muscle weakness
    • Heliotrope rash
      • Reddish-purple rash on upper eyelids
    • Gottron papules
      • Papulosquamous eruptions on dorsal surface of knuckles
    • Non-specific symptoms
      • Fever
      • Weight loss
      • Fatigue
  • Diagnosis
    • Clinical diagnosis based on typical symptoms
    • Elevated muscle enzymes
      • Creatine kinase
      • LDH
      • Aldolase
    • MRI or EMG
      • Shows myositis
    • Muscle biopsy
      • Rarely necessary
  • Treatment
    • High-dose steroid
    • DMARDs
    • IVIG
    • Cyclophosphamide
  • Complications
    • Calcinosis (dystrophic calcification of skin and soft tissue)

13. Kawasaki disease, Henoch-Schönlein purpura

  • Kawasaki disease
    • Epidemiology
      • Mostly affect children < 5 years
      • Children of Asian descent
    • Etiology unknown
      • It’s a vasculitis
    • Clinical features
      • Fever > 5 days
      • Bilateral nonexudative conjunctivitis
      • Changes of the oral mucosa
        • Fissured lips
        • Inflamed mucosa
        • Strawberry tongue
      • Changes of extremities
        • Erythema of palms or soles
        • Oedema of hands or feet
        • Periungual desquamation
      • Polymorphous rash
      • Cervical lymphadenopathy
    • Diagnosis
      • Clinical diagnosis
        • Fever > 5 days + four other symptoms
      • Other diagnoses should be excluded
        • Scarlet fever
        • Toxic shock syndrome
        • Stevens-Johnson syndrome
      • Echocardiography
        • To screen for complications
        • At diagnosis, then on days 10 and 30 after diagnosis
    • Treatment
      • Self-limiting, but treatment decreases risk for complications
      • IVIG
      • Aspirin
    • Complications
      • Coronary artery aneurysm
      • Occurs in < 5% of treated patients but 25% in untreated patients
  • Henoch-Schönlein purpura (HSP)
    • Also called IgA vasculitis
    • Epidemiology
      • Peak incidence at 6 years
      • Most common vasculitis in childhood
      • Most common in winter
    • Etiology
      • Idiopathic small vessel vasculitis
      • Usually occurs 1-3 weeks after upper respiratory infection
    • Clinical features
      • Palpable purpuras
        • Primarily on butt and lower extremities
      • Arthritis/arthralgia
      • GI symptoms
        • Colicky abdominal pain
      • Renal symptoms
        • Nephritic syndrome
    • Diagnosis
      • Clinical diagnosis based on typical symptoms
      • Thrombocytosis
        • One of the few conditions where there is purpura without thrombocytopaenia
        • Thrombocytopaenia suggests another diagnosis
      • Biopsy for difficult cases
    • Treatment
      • Self-limiting disease
        • < 1% of patients develop chronic complications, mainly renal disease
      • Most are mild and need only supportive outpatient treatment
        • NSAIDs
      • Severe cases should be treated inpatients
        • Systemic steroids

14. The milestones of the normal psychomotor development

  • Most important developmental milestones
    • In the lecture prof. Hollódy said we shouldn’t know the specific milestones at specific ages, but rather the biggest milestones like:
      • At 4 months they should be able to turn themselves
      • At 6 months they should be able to sit
      • At 12 months they should be able to walk

Age

Gross motor milestone Fine motor milestone Personal-social milestone Language milestone
2 weeks Move head side to side Regards (looks at or interacts with) faces

Is alert to sound of bell

2 months

Lift shoulder while prone Can track movement across midline Smiles responsively Cooing

Uses eyes to search for sounds

4 months Lift up on hands while prone

Roll front to back

Reaches for object

Raking grasp

Looks at hand

Begins to work toward toy

Laughs, squeals

6 months

Sits alone Transfers objects from hand to hand Feeds self

Holds bottle

Babbles
9 months Pulls to stand

Gets into sitting position

Crawling

Starting to pincer grasp

Banging things together

Waves bye-bye

Says short words like “dada”, “mama”

12 months

Walks Puts block in cup Drinks from cup Says one to two words
15 months Walks backward Scribbles

Stacks two blocks

Uses spoon and fork

Says three to six words

Follows commands

18 months

Runs Stacks four blocks Removes garments Says at > six words
2 years Walks in stairs Stacks six blocks Puts on clothes

Brushes teeth with help

Puts two words together

Knows body parts

3 years

Stacks eight blocks Uses spoon Names pictures

Says short sentences

4 years Balances on one foot Can copy a circle Brushes teeth without help

Names colours

5 years

Skips Can copy a square Counts
6 years Balance on one foot for 6 secs Can copy a triangle

Defines words

15. Evaluation of the child with developmental delay

  • Evaluation of the child’s psychomotor development
    • Percentile curves, which show how the percentage of children who have reached a specific milestone at a specific age, are used
    • An example:
      • 10% of children have said their first word by month 9
      • The average age at which a child says their first word is around month 12
      • 90% of children have said their first word by month 14
      • If a child hasn’t said their first word by month 14, its language development is in the 10th percentile
  • Bayley II and III
    • Standard scoring system for infant development
    • Gives a developmental quotient (DQ), the normal value of which is 100
  • Indications for further examination
Age Finding
Birth and at any age Lack of response to sound

Lack of interest in interacting with people

4 months Lack of any drive to communicate

Child does not socially smile

6 – 9 months Child does not coo or babble

Child not interested in peek-a-boo

Child does not laugh in playful situation

Poor sound localization

Lack of responsiveness to sound

12 months No verbal routines

Failure to say mama or dada

Child does not search for dropped objects

15 – 18 months No single words

Poor understanding of language

2 years Knows < 50 words

No phrases with two words

Less than 50% of speech is intelligible to strangers

Child avoids eye contact

Child kicks, bites, screams without provocation

3 years Frequent repetition of others’ speech

Flat or stilted intonation

Less than 25% of speech is intelligible to strangers

  • Indications for audiologic evaluation
    • Family history of deafness
    • Prematurity
    • Congenital anomalies
    • Intrauterine infection
    • Delayed language development
    • Parental concern about hearing loss
  • Indications for eye evaluation
    • Intrauterine infection
    • Prematurity
    • Cerebral palsy
    • Strabismus
    • Nystagmus
    • Cataract
  • Clinical features of autism in children
    • Delayed developmental milestones in language
    • Unusual speech
      • Echolalia (repeating others’ speech)
      • Grunting, squealing
      • Speaks only about specific topics of interest
      • Prefers to use single words rather than longer sentences
    • Reduced or absent nonverbal communication
    • Reduced or absent response to others’ gestures or facial expression
    • Reduced or absent response when called by name
    • Lack of social smile or eye contact
    • Lack of interest in other children
    • Lack of awareness of other people; appearing to be in their own world
    • Prefers to play alone
    • Repetitive motor mannerisms
    • Resistance to change, insisting on following same routines
    • Atypical play
      • Likes to line up objects, etc.
      • Becoming upset if others interfere with their games

16. Diabetes mellitus

  • Diabetes mellitus type 1
    • Epidemiology
      • Most common type in childhood
      • 20 : 100 000 (in USA)
      • Higher in Scandinavia
    • Etiology
      • Unknown environmental factor triggers autoimmunity
        • Cow’s milk
        • Viral infections
        • Vitamin D deficiency
      • Associated with other autoimmune diseases
      • Associated with HLA DR3 and DR4
    • Pathomechanism
      • Multiple antibodies against β-cells can be present
        • Islet cell antibody
        • Insulin autoantibody
        • Anti-tyrosine phosphatase antibody
        • Anti-glutamic acid decarboxylase antibody
      • Antibodies and β-cell destruction may’ve been present for years before overt diabetes develops
      • When 80 – 90% of the β-cell mass is destroyed hyperglycaemia and the clinical features of diabetes occur
    • Clinical features
      • Polyuria
      • Polydipsia
      • Polyphagia
      • Weight loss
      • Lipodystrophy (due to insulin injection)
      • Honeymoon period
        • In patients with recently diagnosed T1D who just started treatment, β-cell function can temporarily recover slightly, reducing the need for insulin
        • Begins in the first weeks of therapy, often lasts for a few months but can last up to a year
        • After honeymoon period the insulin need increases
    • Diagnosis
      • One of these:
      • Fasting glucose > 7 mM
      • Random glucose > 11,1 mM
      • OGTT > 11,1 mM
      • HbA1c > 6,5% (48 mmol/mol)
    • Treatment
      • Goals
        • HbA1c < 7,5% (59 mmol/mol)
        • Lowest risk of hypoglycaemia possible
      • Most commonly used insulin regimen
        • Fast-acting insulin injections with meals
        • Long-acting “basal” insulin injection at bedtime
      • Nutrition
        • Diet must be balanced and consistent to prevent hypo and hyperglycaemia
        • Total carbohydrate of daily foods should be held constant
      • Regular HbA1c monitoring (4x a year)
      • Regular blood glucose monitoring
        • Before each meal and at bedtime
      • Screen for complications
        • Annual ophthalmological screening
        • Screening for microalbuminuria
        • Annual measurement of blood pressure and cholesterol
    • Complications
      • Retinopathy
      • Renal disease
      • Cardiovascular disease
      • Hypoglycaemia
        • Common
          • Occurs 1 or 2x a week even in well-controlled T1D
          • Severe episodes in 10% of patients every year
        • Due to inappropriate insulin dose compared to carbohydrate intake or activity
        • Neuroglycopaenic symptoms include headache, confusion, irritability, seizures
        • Sympathetic symptoms include tremor, tachycardia, sweating
        • Treated with oral foods with rapidly absorbed glucose
  • Diabetic ketoacidosis
    • Acute complication of T1D
    • Etiology
      • Undiagnosed T1D
      • Undertreated T1D
      • Periods of stress in patients with T1D where insulin is not increased
        • Infection
        • Surgery
        • Trauma
    • Clinical features
      • May be the presenting feature of new-onset T1D
      • Abdominal pain
      • Polyuria -> dehydration
      • Kussmaul breathing with fruity odour
    • Diagnosis
      • Extreme hyperglycaemia (15 – 50 mM)
      • pH < 7,3
      • HCO3 < 15 mM
    • Treatment
      • IV isotonic fluids with potassium
      • Fast-acting insulin infusion
        • Insulin treats the acidosis, bicarbonate should not be used
    • Complication: cerebral oedema
      • Due to too rapid shift in serum osmolarity and fluid balance
      • Usually occurs 6 – 12 hours after treatment has begun
      • Causes sudden severe headache, vomiting, abnormal vital signs, seizure, etc
      • Treated with IV mannitol and ventilation
  • Diabetes mellitus type 2
    • Epidemiology
      • Becoming more and more prevalent due to obesity epidemic
    • Etiology
      • Metabolic syndrome
      • Family history
      • Obesity
    • Clinical features
      • Many are asymptomatic at time of diagnosis (only detected because of routine physical examination)
      • Polyuria
      • Polydipsia
      • Acanthosis nigricans
    • Diagnosis
      • Same as for T1D
      • To differentiate from T1D, in uncertain cases
        • Autoantibody testing
        • Monitor insulin or C-peptide response to oral carbohydrates
    • Treatment
      • Lifestyle modifications
      • Metformin

17. Obesity and metabolic syndrome

  • Definition
    • Overweight – BMI in the 85th – 95th percentile for age and sex
    • Obesity – BMI > 95th percentile for age and sex
  • Epidemiology
    • Overweight and obesity epidemic in the Western world
    • 1/3 of children in US
    • The epidemic worsened with time, but has recently stalled or receded
  • Types according to etiology
    • Simple obesity (exogenous obesity)
      • 95% of childhood obesity cases
      • Due to multiple factors:
        • Socioeconomic factors
        • Lifestyle factors
        • Genetic factors
    • Secondary obesity (endogenous obesity)
      • < 5% of cases
      • Neuroendocrine
        • Hypothalamic lesions
        • Hypothyroidism
        • PCOS
        • Hypogonadism
        • Cushing disease
      • Immobility
        • Muscular dystrophy
        • Spina bifida
        • Cerebral paresis
      • Psychiatric disease
        • Depression
        • Eating disorder
      • Iatrogenic
        • Steroid treatment
      • Chromosomal abnormalities
        • Down syndrome
        • Klinefelter syndrome
      • Genetic syndromes
        • Prader-Willi syndrome
        • Bardet-Biedl syndrome
      • Monogenic obesity
        • (Only approx. 200 patients are known worldwide)
        • Leptin receptor mutation
        • Melanocortin receptor mutation
        • POMC mutation
  • Clinical features
    • Most frequent skin lesions
      • Acanthosis nigricans (neck, axilla)
      • Striae
      • Mycosis
      • Intertrigo
      • Acne
    • Hirsutism
  • Algorithm for evaluation of obesity
    • Beginning early in life (< 6 years), delayed psychomotor development, extreme obesity
      • -> suspect genetic disease
    • Decreased linear (height) growth, decreased bone age
      • -> suspect endocrine disease
    • Beginning early in life (< 6 years), normal psychomotor development, extreme obesity
      • -> suspect monogenic disease
    • Later onset, normal or increased linear growth, normal psychomotor development, non-extreme obesity
      • -> exogenous obesity most likely
  • Complications of childhood obesity
    • Cardiovascular
      • Dyslipidaemia
      • Hypertension
      • Atherosclerosis
    • Endocrine
      • Type 2 diabetes
    • Pulmonary
      • Sleep apnoea
      • Asthma
    • Gastrointestinal
      • Gallbladder disease
      • Non-alcoholic fatty liver disease
    • Musculoskeletal
      • Slipped capital femoral epiphysis
    • Psychosocial consequences
      • Poor self-esteem
      • Anxiety
      • Depression
  • Prader-Willi syndrome
    • Due to deletion of paternal genes at 15q11-q13
    • Clinical features
      • Hypotonia during infancy
      • Hypogonadism
      • Short stature
      • Morbid obesity (due to hyperphagia)
      • Poor feeding in the first year of life
      • Developmental delay
    • Diagnostics
      • According to certain diagnostic criteria, based on typical clinical features and genetic testing
  • Congenital hypothyroidism
    • Most commonly due to thyroid hypoplasia or abnormal descent
    • Nowadays rare due to neonatal screening
    • Screening
      • At day 5
      • TSH level from blood test
    • Clinical features
      • Constipation
      • Prolonged jaundice
      • Feeding difficulties
      • Lethargy
      • Lack of interest
  • Metabolic syndrome
    • Definition: three out of four features present
      • Obesity
        • As determined by increased waist circumference or BMI
      • Hypertension
      • Dyslipidaemia
      • Impaired glucose metabolism (diabetes or prediabetes)
    • International standards for normal cut-off values don’t exist for lipid levels, insulin resistance, and waist circumference in children

18. Microcytic anaemias

  • Definition of anaemia in childhood
    • Hb < 2 standard deviations below the mean for the same age
    • Children 6 months to 5 years – 11 g/dL
    • Children 5 – 12 years – 11,5 g/dL
    • Children 12 – 15 years – 12 g/dL
  • Iron deficiency anaemia
    • Definition
      • Hb equals to anaemia
      • Ferritin < 15 µg/L
    • Epidemiology
      • Most common anaemia in the world
      • Most common nutritional deficiency in children
      • 9% of toddlers
      • 10% of adolescent females
      • < 1% of adolescent males
    • Etiology
      • Consumption of cow’s milk
        • Cow’s milk increases intestinal blood loss and contains iron with poor bioavailability
        • It decreases the appetite for other iron-containing foods
      • Using infant formula which is not iron-fortified
      • Menstruation
      • Poor dietary intake
    • Clinical features
      • Apathy, irritability, poor concentration
      • Lethargy
      • GI symptoms
    • Diagnosis
      • Laboratory diagnosis not always necessary
        • Diagnosis can be made based on the results of an empiric trial of iron
      • Empiric trial of oral iron
        • Causes rapid improvement in symptoms
        • Neurological symptoms improve within 48 hours
        • Hb levels increase within a few weeks
        • Follow-up after a few weeks to determine whether the anaemia is gone
        • If symptoms don’t improve, look for other causes of microcytic anaemia
      • Microcytic anaemia
      • Serum iron-binding capacity low
      • Serum ferritin low
    • Treatment
      • Dietary changes, see prevention
    • Prevention
      • Exclusive breastfeeding for 6 months, with iron supplementation from month 4
      • Iron supplement after 4 months for term infants who don’t consume iron-fortified formula
      • Iron supplement after 2 weeks for preterm infants who don’t consume iron-fortified formula
      • All infant formula used should be iron-fortified
      • Menstruating adolescent women should have iron-rich diet or iron supplements
  • Thalassaemia
    • Epidemiology
      • More common in populations around the Mediterranean
      • Alpha thalassaemia most common in Asian and black populations
      • Beta thalassaemia most common in Mediterranean and South-East Asian populations
    • Pathomechanism
      • Decreased or absent synthesis of one or more globin chains -> abnormal Hb
      • Four genes code for the alpha globin chain
        • One gene deleted -> silent carrier of thalassaemia, no symptoms
        • Two genes deleted -> Alpha thalassaemia minor
        • Three genes deleted -> Haemoglobin H disease / Alpha thalassaemia intermedia
        • Four genes deleted -> Hb Barts / hydrops foetalis
      • Two genes code for beta globin chain
        • One defective gene -> Beta thalassaemia minor
        • Two defective genes -> Beta thalassaemia major
    • Clinical features
      • Alpha thalassaemia minor
        • Mild anaemia
      • Haemoglobin H disease
        • Severe anaemia
      • Hb Barts
        • Hydrops foetalis
        • Is incompatible with life
      • Beta thalassaemia minor
        • Mild anaemia
      • Beta thalassaemia major
        • Severe anaemia
    • Diagnosis
      • Microcytic anaemia
      • Haemolysis
      • Ferritin normal (unlike iron deficiency anaemia)
      • Hb electrophoresis
        • Shows abnormal Hb
      • Genetic studies
    • Treatment
      • Mild anaemia -> no treatment necessary
      • Severe anaemia
        • Lifelong transfusion therapy
        • Chelating agents for iron overload
        • Splenectomy (if severe splenomegaly)
        • Haematopoietic stem cell transplantation could be curative
  • Anaemia of chronic disease
  • Lead poisoning

19. Normocytic anaemias (haemolytic anaemias)

  • Sickle cell anaemia
    • Epidemiology
      • Most common in African and Mediterranean populations
      • Most common intrinsic haemolytic anaemia
    • Pathomechanism
      • Point mutation in beta globin gene causes haemoglobin to precipitate into a sickle-shape when deoxygenized -> microvascular occlusion and haemolysis
    • Clinical features
      • Splenic dysfunction -> severe infections by encapsulated bacteria
        • Osteomyelitis, sepsis, etc.
      • Severe anaemia
      • Acute splenic sequestration crisis
        • Sudden drop in blood volume as RBCs pool in the spleen
      • Acute aplastic crisis
        • Parvovirus B19 induces transient RBC aplasia in bone marrow
      • Vaso-occlusive events
        • Sudden painful events anywhere
        • Infarction of any organ
      • Dactylitis
    • Diagnosis
      • Normocytic anaemia
      • Haemolysis
      • Sickle cells on blood smear
      • Confirmatory test: Hb electrophoresis
    • Treatment
      • Pain control
        • NSAIDs
        • Opiates
      • Sufficient hydration
      • Transfusion
      • Hydroxyurea
        • Increases amount of haemoglobin F, circumventing the beta globin mutation
      • Haematopoietic stem cell transplantation could be curative
    • Screening
      • At birth for populations at risk
  • G6PD deficiency
    • Epidemiology
      • Most common human enzyme deficiency
      • Most common in African and Mediterranean populations
    • Pathomechanism
      • Deficiency of glucose 6-phosphate dehydrogenase, an enzyme in the pentose phosphate pathway -> decreased glutathione in RBCs -> decreased defence against oxidative stress
    • Clinical features
      • Most are asymptomatic but develop recurrent haemolytic crises when exposed to oxidative triggers
        • Fava beans
        • Antimalarial drugs
        • Sulpha drugs
        • Infections
      • During crisis
        • Sudden onset back or abdominal pain
        • Jaundice
        • Dark urine
        • Transient splenomegaly
    • Diagnosis
      • Normocytic anaemia
      • Haemolysis
      • Bite cells and Heinz bodies on blood smear
      • Confirmatory test: G6PD enzyme analysis
    • Treatment
      • Avoid triggers
  • Hereditary spherocytosis
    • Epidemiology
      • 1 : 5000 in USA
      • More common in Northern Europe
    • Pathomechanism
      • Genetic mutation in RBC membrane protein causes RBC membrane to be less stable -> RBCs destroyed by spleen
    • Clinical features
      • Variable severity, from asymptomatic to severe
      • Haemolytic anaemia
    • Diagnosis
      • Normocytic anaemia
      • Haemolysis
      • Spherocytes on blood smear
      • Confirmatory test: EMA or osmotic fragility test
    • Treatment
      • Transfusion in severe cases
      • Splenectomy in severe cases
        • Should be performed after age 6 to reduce risk for infections by encapsulated bacteria
        • Vaccinations against encapsulated bacteria before splenectomy!

20. Macrocytic anaemias (congenital aplastic and hypoplastic anaemias, megaloblastic anaemia)

  • Congenital aplastic anaemias
    • Congenital syndromes causing bone marrow insufficiency with resulting pancytopaenia
    • Fanconi anaemia
      • Epidemiology
        • Most common congenital aplastic anaemia
        • 1 : 100 000 – 250 000 births
      • Pathomechanism
        • Genetic defect in DNA repair -> bone marrow failure, increased risk for cancer
        • Progression from cytopaenia to pancytopaenia always occurs, but at different ages
      • Clinical features
        • Congenital malformations
          • Thumb and forearm malformations
          • Short stature
        • Hyper or hypopigmentation
        • Cancers
          • 50% of patients develop MDS or AML
          • Myelodysplastic syndrome
          • Leukaemia
          • Squamous cell carcinomas
      • Diagnosis
        • Thrombocytopaenia, macrocytic anaemia, or pancytopaenia
        • Confirmatory test: chromosomal breakage occurs in lymphocytes when exposed to DNA crosslinking agents
      • Treatment
        • Androgen therapy
        • Transfusion
        • Haematopoietic stem cell transplant
          • Only curative treatment
  • Diamond-Blackfan syndrome (also called congenital hypoplastic anaemia)
    • Epidemiology
      • 5 : 1 000 000 live births
      • 50% of cases are familial
    • Pathomechanism
      • Genetic defect in ribosome synthesis -> activation of p53 -> impaired erythropoiesis, increased risk for cancer
      • Only the RBC cell line is affected (pure red cell aplasia)
    • Clinical features
      • Symptoms begin < 1 year
      • Congenital malformations of face, eye, neck, thumb, etc.
      • Cancers
        • Acute myelogenous leukaemia
        • Myelodysplastic syndrome
        • Solid tumours
    • Diagnosis
      • Macrocytic anaemia + reticulocytopaenia
      • Hb electrophoresis shows increased Hb F
      • Genetic testing
    • Treatment
      • Steroids
      • Blood transfusion
      • Haematopoietic stem cell transplant
        • Only curative treatment
  • Megaloblastic anaemia
    • = a subtype of macrocytic anaemia characterised by decreased DNA synthesis in RBC precursors, causing them to be larger and have characteristic “megaloblastic” features
    • Epidemiology
      • Dietary folate and B12 deficiency are very rare in children
    • Etiology
      • Malnutrition
      • Pernicious anaemia
      • Coeliac disease
      • Intestinal resection
      • Maternal B12/folate deficiency (for breastfed infants)
      • Inflammatory bowel disease
      • Anti-folic acid drugs
    • Diagnosis
      • Macrocytic anaemia
      • Hypersegmented neutrophils
      • B12 deficiency -> low serum B12 or elevated serum homocysteine and MMA
      • Folate deficiency -> low RBC folate level or elevated serum homocysteine
      • Pernicious anaemia -> anti-IF antibodies
    • Treatment
      • Treat underlying condition
      • Oral or IM supplement

21. Leukocyte diseases (neutropaenias, neutrophils, eosinophils, monocytosis, lymphocytosis)

  • Neutropaenia
    • = absolute neutrophil count (ANC) < 1500/µL
    • The lower the ANC, the higher the risk for infection
      • At ANC < 1000/µL there is a significant increase in risk
      • Most patients do well with ANC > 500/µL
      • Serious infections occur < 200/µL
    • Congenital neutropaenias
      • Neonatal alloimmune neutropaenia
        • Transient neutropaenia of newborn due to maternal anti-neutrophil antibodies
      • Severe congenital neutropaenia (Kostmann syndrome)
        • Genetic mutation causes promyelocytes to fail to mature
      • Cyclic neutropaenia
      • Shwachman-Diamond syndrome
        • Pancreatic insufficiency + panmyeloid dysfunction
    • Acquired neutropaenias
      • Post-infectious
        • Especially viral
      • Drug-induced
        • Idiosyncratic or cytotoxic (chemo)
      • Hypersplenism
      • Radiation
      • Leukaemia
      • Copper deficiency
    • Clinical features
      • Recurrent infections by bacteria and certain fungi
        • Mostly endogenous bacteria
        • S. aureus
        • E. coli
        • Candida spp.
      • Oral cavity ulcers
    • Treatment
      • Treat underlying condition
      • G-CSF
      • Haematopoietic stem cell transplant
  • Neutrophilia
    • = neutrophils > 8000/µL
    • Infectious
      • Bacteria
      • Virus
    • Inflammatory diseases
      • IBD
      • Juvenile RA
    • Leukaemia
    • Myeloproliferative neoplasms
    • Exercise
    • Congenital disorders
      • Leukocyte adhesion deficiency
      • Chronic neutrophilic leukaemia
  • Eosinophilia
    • = eosinophils > 810/µL
    • Allergy
      • Atopic dermatitis
      • Asthma
      • Allergic rhinitis
      • Food allergy
    • Helminth infection
    • Leukaemia
    • Hodgkin lymphoma
    • Idiopathic hypereosinophilia
  • Monocytosis
    • = monocytes > 1000/µL
    • Can’t find any common reasons for monocytosis
  • Lymphocytosis
    • = lymphocytes > 4500/µL
    • Infectious mononucleosis
    • Toxoplasmosis
    • Viral infections
    • Pertussis
  • Disorders of leukocyte function – see topic 9

22. Immune thrombocytopaenias

  • Immune thrombocytopaenia (ITP)
    • = idiopathic thrombocytopaenia = immune thrombocytopaenic purpura
    • Epidemiology
      • One of the most common symptomatic thrombocytopaenias in children
      • 1 – 6 : 100 000
      • Incidence peak at around 4 years
    • Etiology
      • Idiopathic, but usually follows 1 – 4 weeks after a viral infection
      • Secondary
        • SLE
        • Drugs
        • Lymphoma, leukaemia
    • Pathomechanism
      • IgG antibodies against glycoprotein IIb/IIIa on platelets -> splenic removal of platelets
    • Clinical features
      • Abrupt onset
      • Petechiae, purpura
      • Epistaxis
      • Bruising
      • Mucosal bleeding
      • Can rarely be severe
        • Intracranial haemorrhage
        • GI bleeding
    • Diagnosis
      • Based on clinical features
      • Significant but isolated thrombocytopaenia
      • Bone marrow biopsy in ambiguous cases
    • Treatment
      • Steroids
      • IVIG
      • Transfusion
      • Splenectomy
        • In severe cases
    • Prognosis
      • Most children recover within 3 – 6 months with or without treatment
      • 10 – 20% develop chronic ITP
  • Neonatal immune-mediated thrombocytopaenia
    • Epidemiology
      • 1 : 1000 – 10 000
    • Pathomechanism
      • Neonatal alloimmune thrombocytopaenia
        • Foetus inherits platelet antigens from father, which the mother has antibodies against
        • Maternal antibodies can be transferred to foetus through placenta, causing thrombocytopaenia in newborn
      • Neonatal autoimmune thrombocytopaenia
        • Foetus inherits platelet antigens from a mother with ITP, which the mother has antibodies against (because she has ITP)
        • Maternal antibodies can be transferred to foetus through placenta, causing thrombocytopaenia in newborn
    • Clinical features
      • Range from asymptomatic to severe bleeding
      • Symptoms begin within the first days of life
    • Treatment
      • IVIG or steroid
      • Transfusion if necessary

23. Haemorrhagic diseases (von Willebrand disease, haemophilias)

  • Von Willebrand disease
    • Epidemiology
      • Most common congenital bleeding disorder
      • 0,1 – 1% of the population
    • Pathomechanism
      • Deficiency of von Willebrand Factor (VWF)
      • Some deficiency of factor VIII can also occur
      • Varying degree of deficiency causes varying degree of symptoms
    • Clinical features
      • Mucous membrane bleedings
      • Cutaneous bleedings
      • Epistaxis
      • Bruising
      • Menorrhagia
    • Diagnosis
      • Definitive diagnosis: VWF factor assay
    • Treatment
      • Desmopressin
      • Recombinant factor replacement
  • Haemophilia
    • Epidemiology
      • Almost exclusively affects boys (X-linked recessive)
    • Pathomechanism
      • X-linked inheritance
      • Haemophilia A = factor VIII deficiency
      • Haemophilia B = factor IX deficiency
      • Varying degree of deficiency causes varying degree of symptoms
    • Clinical features
      • Spontaneous bleedings or bleeding with minor trauma
      • Most commonly bleeding into muscles or joints
    • Diagnosis
      • Prolonged aPTT
      • Definitive diagnosis: specific factor assay
    • Treatment
      • Recombinant factor replacement
      • Desmopressin (only for haemophilia A)

24. Leukaemias (ALL, AML, CML)

  • Acute lymphoblastic leukaemia (ALL)
    • Epidemiology
      • Most common childhood cancer
      • 75% of childhood leukaemia
      • B-ALL > T-ALL
      • B-ALL peaks at 2 – 5 years
      • T-ALL peaks in older children
      • 10 – 20x more common in Down syndrome
    • Clinical features
      • Fever without infection
      • Malaise
      • Weight loss
      • Symptoms of bone marrow failure
        • Fatigue, pallor
        • Bleeding disorder
        • Frequent infections
      • Lymphadenopathy
      • Hepatosplenomegaly
      • Infiltration of the CNS -> neurological symptoms
      • Infiltration of the testes -> painless enlargement
    • Diagnosis
      • Anaemia, thrombocytopaenia
      • Immature blasts on blood smear
      • Definitive diagnosis: immunophenotyping of bone marrow biopsy
      • Genetic analysis
      • Lumbar puncture – to look for CNS involvement
    • Treatment
      • Chemotherapy
        • (for 2 – 3 years!)
      • AB prophylaxis for pneumocystis pneumonia
        • Trimethoprim-sulphamethoxazole
    • Prognosis
      • 90% of B-ALL are cured
  • Acute myelogenous leukaemia (AML)
    • Epidemiology
      • 20% of childhood leukaemia
    • Clinical features
      • Fever
      • Malaise
      • Musculoskeletal pain
      • Lymphadenopathy
      • Hepatosplenomegaly
      • DIC
    • Diagnosis
      • Anaemia, thrombocytopaenia, leukocytosis
      • Immature blasts on blood smear
      • Definitive diagnosis: immunophenotyping of bone marrow biopsy
    • Treatment
      • Chemotherapy
    • Prognosis
      • 65% of AML are cured
  • Chronic myelogenous leukaemia (CML)
    • Only 5% of childhood leukaemia
    • Chronic symptoms
    • Non-specific symptoms
    • Splenomegaly

25. Lymphomas (Hodgkin, non-Hodgkin)

  • Epidemiology
    • Lymphomas virtually never occurs in infancy
    • Both are most frequent in adolescence
    • Hodgkin lymphoma (HL) > Non-Hodgkin lymphoma (NHL)
  • Etiology
    • Congenital immunodeficiency
    • Acquired immunodeficiency
  • Types of NHL
    • Burkitt lymphoma
    • Diffuse large B cell lymphoma
    • Lymphoblastic T or B cell lymphoma
    • Anaplastic large cell lymphoma
  • Clinical features
    • Painless, firm lymphadenopathy in a lymph node area
      • Mostly in sites above diaphragm
    • Mediastinal lymphadenopathy -> cough, dyspnoea
    • B symptoms
      • Fever
      • Drenching night sweat
      • Weight loss
  • Diagnosis
    • X-ray to look for mediastinal mass
    • Confirmatory: lymph node biopsy
  • Treatment
    • Chemotherapy
  • Prognosis
    • Survival for HL -> over 90%
    • Survival for NHL -> 70 – 90%

26. Brain tumors in childhood

  • Epidemiology
    • CNS tumours are the most common solid tumours in children
    • CNS tumours are the second most common cancer in children (after leukaemia)
    • CNS tumours in childhood are most frequently primary (in contrast to in adults)
  • Etiology
    • Neurofibromatosis
    • Tuberous sclerosis
    • von Hippel-Lindau syndrome
  • Most common types
    • Glioma
    • Astrocytoma
    • Medulloblastoma
    • CNS neuroectodermal tumours
  • Clinical features
    • Symptoms of mass effect -> increased ICP
      • Vomiting (especially right after waking up in the morning)
      • Headache
      • Seizures
    • Symptoms of cranial nerve impingement
      • Visual defects
      • Abducent palsy
    • Symptoms of CSF obstruction -> hydrocephalus
      • In young children with open sutures -> enlarged head
    • Symptoms of pituitary involvement
      • Precocious puberty
      • Diabetes insipidus
    • Symptoms of cerebellar involvement
      • Ataxia
      • Nystagmus
  • Diagnosis
    • MRI
    • Histology from biopsy or surgical debulking
  • Treatment
    • Dexamethasone (decreases brain oedema)
    • Surgical debulking
    • Radiochemotherapy
  • Prognosis
    • 50 – 60% for all CNS tumours
    • Astrocytomas, craniopharyngioma have highest survival

27. Neuroblastoma and Wilms tumor

  • Neuroblastoma
    • Epidemiology
      • Most common extracranial solid tumour in children
      • Most common cancer in infants
      • Mean age at diagnosis 17 months
    • Pathology
      • Tumour of sympathetic ganglion cells
      • Most common sites
        • Adrenal gland
        • Abdomen
        • Thorax
      • Broad spectrum of clinical behaviour
        • Anywhere from spontaneous regression to rapid spread and death
    • Clinical features
      • Abdominal mass
      • Abdominal pain
      • GI symptoms
      • Exophthalmos
      • Horner syndrome
      • Periorbital ecchymoses (due to orbital bone metastasis)
      • Paraneoplastic syndromes
        • Secretory diarrhoea
        • Profuse sweating
        • Opsomyoclonus
          • Rapid involuntary eye movements (opsoclonus)
          • Myoclonus
    • Diagnosis
      • X-ray (shows calcified tumour)
      • Urinary catecholamines
      • Definite diagnosis: biopsy
    • Treatment
      • Surgery and chemo
  • Wilms tumour (= nephroblastoma)
    • Epidemiology
      • Most common malignant renal tumour in childhood
      • Median age of diagnosis 3 years
      • 5% of cases are bilateral
    • Etiology
      • WAGR syndrome
        • Wilms tumor, aniridia, genitourinary anomalies, retardation
      • Denys-Drash syndrome
    • Pathology
      • Tumour of metanephric blastema
    • Clinical features
      • Most commonly presents as an asymptomatic abdominal mass
      • Abdominal pain
      • Haematuria
      • Hypertension
    • Diagnosis
      • Abdominal ultrasound
      • Definite diagnosis: histology (from biopsy or surgical excision)
    • Treatment
      • Nephrectomy -> adjuvant radiochemotherapy

28. The types of dehydration and their treatment

  • Physiology
    • The younger the person, the larger percentage of the body weight is water
    • Extremely preterm infants are 90% water
    • Term infants are 75% water
    • Adults are 60% water
  • Maintenance fluid requirement
    • For first week of life:

    • Children 3,5 – 10 kg
      • 100 mL/kg/day
      • 4 mL/kg/hour
    • Children 10 – 20 kg
      • 1000 mL + 50 mL/kg/day for every kg over 10 kg
      • 2 mL/kg/hour
    • Children > 20 kg
      • 1500 mL + 20 mL/kg/day for every kg over 20 kg
      • 1 mL/kg/hour
  • Dehydration
    • Etiology
      • Increased fluid loss
        • Vomiting
        • Diarrhoea
        • Diuretics
        • Renal disease
        • Diabetes insipidus
        • Burns
        • Fever
      • Decreased fluid intake
        • Anorexia
        • Coma
        • Abuse
    • Pathophysiology
      • Young infants are prone to dehydration because
        • They have high surface area compared to weight -> allows greater water loss through skin
        • Kidneys are not fully mature -> decreased ability to concentrate urine -> water loss in urine
        • Gastroenteritis is more common in children
    • Types of dehydration
      • Hypotonic (Na+ < 130 mM)
      • Isotonic (Na+ 130 – 150 mM)
      • Hypertonic (Na+ > 150 mM)
    • Severity of dehydration
Signs Mild Moderate Severe
Fluid loss 3 – 5% 6 – 9% > 10%
General status and behaviour Thirsty, alert Thirsty, restless, irritable Drowsy, limp, shock
Pulse Normal Weak Decreased
Tachycardia Absent Present Present
Blood pressure Normal Normal or orthostatic hypotension Decreased
Turgor Normal Slightly decreased Markedly decreased
Eyes Normal Sunken Markedly sunken
Anterior fontanelle Normal Sunken Markedly sunken
Buccal mucosa Normal or slightly dry Dry Very dry, parched
Capillary refill Normal Normal Prolonged (> 3 s)
Urine output Normal Oliguria Anuria or severe oliguria
  • Treatment of dehydration
    • Fluid requirement = maintenance fluid requirement + fluid loss
      • For example, for a 30 kg child with severe (10%) fluid loss:
      • Maintenance fluid requirement = 1500 mL + 20 mL * 10 kg = 1700 mL
      • Fluid loss = 10% of 30 kg = 10% of 30 L = 3000 mL
      • Total fluid requirement = 4700 mL
    • Oral rehydration
      • For mild dehydration
      • 50 mL/kg oral rehydration salts (ORS)
        • WHO ORS
        • ESPGHAN ORS
        • Hipp ORS 200 apple
      • Contraindicated in
        • Persistent vomiting
        • Acute abdomen
        • Low compliance
    • IV rehydration
      • For moderate or severe dehydration
      • Crystalloid solutions which can be given as infusion or bolus
        • Normal (physiologic) saline (NS)
        • Balanced solutions (have similar composition as plasma)
          • Ringer lactate
          • Ringer acetate
          • Isolyte S
    • Timing of rehydration
      • In presence of shock:
        • 20 mL/kg physiological saline or Ringer-lactate in bolus or infusion
        • Repeat until no longer in shock
      • The fluid loss (without the maintenance fluid requirement) should be given like this:
        • First half of the lost volume is administered in the first 8 hours,
        • Second half of the lost volume in the next 16 hours
      • The maintenance fluid requirement should be given like this:
        • Distributed evenly in the first 24 hours
    • Correction of sodium imbalance
      • Correction of moderate to severe dehydration takes precedence over correction of sodium imbalance
      • See topic 29

29. Hyponatremia/hypernatremia and hypokalaemia/hyperkalaemia

  • Hyponatraemia
    • Definition
      • Mild: Na+ 130 – 135 mM
      • Moderate: Na+ 120 – 130 mM
      • Severe: Na+ < 120 mM
      • Acute hyponatraemia: developing within 48 hours
      • Chronic hyponatraemia: developing over > 48 hours
    • Can be hypovolaemic, euvolaemic, or hypervolaemic
    • Etiology
      • Hypovolaemic hyponatraemia
        • Dehydration which is compensated by drinking hypotonic fluid
        • Cystic fibrosis
        • Salt-wasting nephropathy
      • Euvolaemic hyponatraemia
        • Syndrome of inappropriate ADH
        • Water intoxication
        • Hypothyroidism
      • Hypervolaemic hyponatraemia
        • Nephrotic syndrome
        • Cirrhosis
        • Renal failure
        • Heart failure
    • Clinical features
      • Most symptoms are due to brain oedema
      • More symptoms in acutely developing hyponatraemia
      • Anorexia
      • Nausea, vomiting
      • Malaise
      • Headache
      • Altered mental state
    • Treatment
      • Correction of hyponatraemia
        • Too rapid correction -> central myelinolysis
        • IV hypertonic saline
          • 3% NaCl
          • In acute symptomatic hyponatraemia
          • In chronic hyponatraemia with severe symptoms
        • IV physiologic saline
          • Isotonic (0,9% NaCl)
          • In acute asymptomatic hyponatraemia
          • In chronic hyponatraemia with moderate to no symptoms
      • Correction of volume status
        • Hypervolaemia -> fluid restriction
        • Hypovolaemia -> see topic 28
      • Treatment of underlying cause
  • Hypernatraemia
    • Definition
      • Na+ > 150 mM
    • Etiology
      • Iatrogenic excess sodium administration
      • Nephrogenic diabetes insipidus
      • Central diabetes insipidus
      • Vomiting or diarrhoea without fluid replacement
      • Hyperaldosteronism
    • Clinical features
      • Most also have dehydration and symptoms of it
      • More symptoms in acutely developing hypernatraemia
      • Irritability
      • Restlessness
      • Lethargy
      • High-pitched crying (in infants)
    • Treatment
      • Serum Na+ should not decrease more than 12 mM/L every 24 hours
        • To prevent brain oedema
      • IV physiologic saline or Ringer-lactate
      • Treatment of underlying cause
  • Hypokalaemia
    • Definition
      • K+ < 3,5 mM
    • Etiology
      • Drugs
        • Insulin
        • β agonists (salbutamol)
        • Diuretics
      • Diarrhoea
      • Metabolic alkalosis
        • Vomiting
      • Bartter and Gitelman syndromes
      • Hyperaldosteronism
    • Clinical features
      • More symptoms in acutely developing hypokalaemia
      • Muscle weakness
      • ECG changes
      • Cardiac arrhythmias
      • Polyuria
    • Treatment
      • Oral K+ supplementation
        • In mild or chronic hypokalaemia
      • IV potassium chloride
        • In severe hypokalaemia
  • Hyperkalaemia
    • Definition
      • K+ > 5,5 mM
    • Etiology
      • Iatrogenic excess potassium administration
      • Rhabdomyolysis
      • Tumor lysis syndrome
      • Metabolic acidosis
      • Renal disease
      • Beta blockers
      • Aldosterone deficiency
    • Clinical features
      • Often asymptomatic
      • ECG changes
      • Cardiac arrhythmias
    • Treatment
      • Emergent treatment by intracellular shift of K+
        • Temporary treatment of severe or symptomatic hyperkalaemia
        • IV calcium gluconate
        • IV insulin + glucose
        • IV salbutamol
      • Non-emergent treatment to remove K+ from body
        • Permanent treatment of asymptomatic and non-severe hyperkalaemia
        • K+-losing diuretics (loop or thiazides)
        • K+-binding resins
        • Dialysis

30. Vomiting in infancy and childhood

  • Vomiting = forceful expulsion of gastric contents
    • Preceded by nausea
    • Accompanied by gagging and retching
  • Differential diagnosis per age group
    • Neonate
      • Physiologic gastroesophageal reflux
      • GERD
      • Dietary protein intolerance or allergy
      • Pyloric stenosis
      • Inborn errors of metabolism
      • Neonatal necrotizing enterocolitis
    • Infancy
      • Physiologic gastroesophageal reflux
      • GERD
      • Dietary protein intolerance or allergy
      • Gastroenteritis
      • Inborn errors of metabolism
    • Childhood
      • Gastroenteritis
      • Streptococcal pharyngitis
      • Heavy coughing
      • GERD
      • Cyclic vomiting syndrome
    • Adolescence
      • Gastroenteritis
      • Heavy coughing
      • GERD
      • Cyclic vomiting syndrome
    • All ages
      • Increased intracranial pressure
      • UTI
      • Otitis media
      • Hepatitis
  • Red flags of vomit
    • Bilious vomit -> Intestinal obstruction
    • Abdominal pain -> peptic ulcer, appendicitis
    • Haematemesis -> peptic ulcer, Mallory-Weiss tear
    • Early morning vomiting -> pregnancy, increased ICP
    • Haematochezia -> intussusception
    • Fever -> viral gastroenteritis, appendicitis, streptococcal pharyngitis
    • Headache -> migraine
    • Marked abdominal distension -> intestinal obstruction
  • Examination of child with vomiting
    • Physical examination
      • Dehydration status
        • Skin turgor
        • Capillary refill
        • Moistness of mucous membranes
      • Abdominal examination
        • Abdominal distension
        • Organomegaly
        • Bowel sounds
        • Tenderness
        • Guarding
    • Laboratory examination
      • Electrolytes
      • Renal function
      • Liver function
      • CBC
      • Amylase, lipase
  • Physiologic gastroesophageal reflux
    • Epidemiology
      • Extremely common in infants, virtually everyone
      • Decreases with age, usually stops by 1 year
    • Physiology
      • Gastric contents reflux into oesophagus 30 or more times daily
      • Many episodes are accompanied by regurgitation into oral cavity, causing the characteristic “spitting up” almost every infant does
      • Regurgitate “spills” out of the mouth, in contrast to real vomiting
    • Prevention
      • Avoid overfeeding
      • Breast milk instead of formula
      • Avoid tobacco smoke
  • Gastroesophageal reflux disease
    • Reflux with pathological consequences, like oesophagitis, weight loss, respiratory complications, etc.
    • Child is irritable, refuses food, etc.
  • Pyloric stenosis
    • Epidemiology
      • Most common in males
      • Occurs in the first months of life
    • Clinical features
      • Forceful projectile vomiting
      • Vomiting after eating
      • Visibly distended stomach
    • Diagnosis
      • Ultrasound
    • Treatment
      • Surgery

31. Acid-base balance

  • Review
    • Normal values
      • Blood pH = 7,35 – 7,45
      • HCO3 = 20 – 28 mEq/L
      • pCO2 = 35 – 45 mmHg
      • Base excess = -5 – +5
    • Survival range = 6,8 – 8,0
    • Arterial blood generally has higher pH than venous blood
    • Compensatory mechanisms for pH changes
      • Bicarbonate buffer
      • Phosphate buffer
      • Protein buffer
      • Respiratory compensation (CO2 excretion)
      • Renal compensation (H+ excretion)
    • If the compensatory mechanisms return pH into normal range, there is complete compensation. If still outside normal range, there is partial compensation
    • Acidosis = process which decreases pH
    • Alkalosis = process which increases pH
    • Acidaemia = pH < 7,35
      • Decreases synaptic transmission -> CNS depression, arrhythmias, cardiac depression
    • Alkalaemia = pH > 7,35
      • Causes over-excitability of the nervous systems
    • Anion gap = [Na+] – ([Cl] + [HCO3])
      • Normally 10 – 14 mEq/L
  • Metabolic acidosis
    • HCO3 < 22 mEq/L
    • Etiology
      • Normal anion gap metabolic acidosis
        • Diarrhoea
        • Renal tubular acidosis
      • Increased anion gap metabolic acidosis
        • Lactic acidosis
          • Shock
        • Ketoacidosis
          • Diabetes
          • Starvation
          • Alcohol
        • Kidney failure
        • Poisoning
          • Ethylene glycol
          • Methanol
          • Salicylates
        • Inborn errors of metabolism
    • Pathophysiology
      • Increased anion gap = due to elevated levels of acids like lactic acid, ketone bodies, ethylene glycol, etc.
        • The extra acids increase the “gap”
      • Normal anion gap metabolic acidosis = due to increased loss of bicarbonate or decreased loss of H+
        • No extra acids -> no increased “gap”
    • Clinical features
      • Symptoms of underlying condition
      • Acute metabolic acidosis
        • Tachypnoea and hyperpnoea (respiratory compensation)
        • Altered mental state
        • Lethargy
      • Chronic metabolic acidosis
        • Failure to thrive
    • Treatment
      • Treat underlying disease
      • IV bicarbonate
        • In severe acidosis
  • Metabolic alkalosis
    • HCO3 > 26 mEq/L
    • Etiology
      • Vomiting
      • Diuretics
      • Hyperaldosteronism
      • Severe dehydration
      • Excessive administration of base
    • Clinical features
      • Symptoms of underlying condition
      • Symptoms of electrolyte abnormalities
        • Arrhythmias
    • Treatment
      • Correct electrolyte abnormalities
      • Treat underlying disease
      • Administration of acid rarely necessary
  • Respiratory acidosis
    • pCO2 > 45 mmHg (hypercapnia)
    • Etiology
      • Depression of respiratory centre in brainstem
        • Drugs
        • Head trauma
        • Encephalitis
      • Paralysis of respiratory or chest muscles
        • Botulism
        • Guillain-Barré syndrome
        • Muscular dystrophy
      • Pulmonary disease
        • Pneumonia
        • Asthma
      • Upper airway disease
        • Laryngospasm
    • Clinical features
      • Generalized weakness
      • Lethargy, disorientation
      • Coma, death in worst case
    • Treatment
      • Treat underlying disease
      • Artificial ventilation
      • IV bicarbonate
        • Rarely used: Only used if pH is severely decreased
  • Respiratory alkalosis
    • pCO2 < 35 mmHg
    • Etiology
      • Hypoxaemia or hypoxia
        • Carbon monoxide poisoning
        • Cyanotic heart disease
      • Pulmonary disease
        • Pneumonia
        • Pulmonary embolism
      • Stimulation of respiratory centre in brainstem
        • Anxiety
        • Brain tumour
      • Mechanical ventilation
      • Hyperammonaemia
    • Clinical features
      • Numbness
      • Muscle spasms
      • Tetany
      • Seizures
      • Coma, death in worst case
    • Treatment
      • Treat underlying disease
      • Breathe into a paper bag

32. Antibiotic therapy in the infancy and childhood

  • Contraindicated antibiotics
    • Fluoroquinolones
    • Tetracyclines
    • Chloramphenicol (for infants)
  • Most common paediatric conditions in which antibiotics are prescribed
    • Acute otitis media
      • Amoxicillin is antibiotic of choice
      • For children < 2 years
      • For children > 2 years if any of the following are present:
        • Persistent symptoms
        • High fever
        • Otorrhoea
        • Bilateral
    • Coughing (bronchiolitis)
      • Usually viral (RSV, adeno), so doesn’t require antibiotics
      • Only if pertussis or mycoplasma infection is proven
    • Neonatal sepsis
      • Ampicillin + gentamycin
    • Neonatal bacterial meningitis
      • Given even before diagnosis, if suspicion is strong
      • Ampicillin + gentamicin + cefotaxime
    • Rhinosinusitis
      • No antibiotic for viral rhinosinusitis
      • Antibiotic for acute bacterial rhinosinusitis
      • Amoxicillin or amox/clav is antibiotic of choice
    • Pharyngitis
      • Only give if streptococcus is confirmed
      • Penicillin or amoxicillin are antibiotics of choice
    • Urinary tract infection
      • Antibiotics for all diagnosed UTIs
      • Antibiotic choice depends
        • 2nd or 3rd gen cephalosporin
        • Aminoglycoside
  • Fever in childhood is usually due to viral infection, so no antibiotics are usually needed
    • However, fever for more than 3 days is suspicious for bacterial infection and should be investigated as one and treated with empirical antibiotics

33. Fever in childhood (causes, measurement, antipyretics)

  • Causes of fever in childhood
    • Infections
      • Infections characterized by fever and rash
        • Measles
        • Rubella
        • Roseola (HHV-6)
        • Parvovirus B19
        • Varicella
      • Pneumonia
      • UTI
      • Bacteraemia
    • Connective tissue diseases
      • SLE
      • Juvenile idiopathic arthritis
    • Neoplasms
      • Leukaemia
      • Lymphoma
    • Inflammatory bowel disease
  • Measurement of temperature in childhood
    • Rectal thermometry
      • Gold standard for temperature evaluation
      • Generally used for infants and children too young to take oral temperature
      • > 38,0°C is considered fever
      • Contraindications
        • Neutropaenia
        • Bleeding disorder
        • Necrotizing enterocolitis
    • Oral thermometry
      • Typically ~0,6°C lower than rectal
      • > 37,8°C is generally considered fever
      • Good second choice
      • Generally used for children > ~4 years
    • Axillary thermometry
      • Generally lower than rectal temperature, but not by a fixed amount
      • Used for patients who can’t do rectal or oral
  • Antipyretics in paediatrics
    • Aspirin is contraindicated due to risk of Reye syndrome
      • Acute hepatic encephalopathy due to accumulation of salicylate metabolites
      • High mortality
    • Most commonly used antipyretics
      • Paracetamol
        • (10 – 15 mg/kg every 4 – 6 hours, max 75 mg/kg/day)
        • 250 mg every 6 hours for children 3 – 7 years
        • 500 mg every 6 hours for children 7 – 12 years
        • 500 – 1000 mg every 6 hours for children > 12 years (and adults)
        • Not to infants < 3 months
      • Ibuprofen
        • (10 mg/kg/dose every 6 hours, max 40 mg/kg/day)
        • 200 mg every 6 hours for children 7 – 9 years
        • 300 mg every 6 hours for children 10 – 11 years
        • 400 mg every 6 hours for children 12 – 17 years
        • Not to infants < 6 months
    • External cooling
      • Generally not recommended
      • Used in heat stroke, malignant hyperthermia and other heat illnesses

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