---

📚 Growth & Development - University Exam Notes

Based on OP Ghai's Essential Pediatrics & Nelson Textbook of Pediatrics

---

1. DEFINITIONS

Growth and development always occur together - the child grows and develops as a whole unit.

---

2. PRINCIPLES OF GROWTH & DEVELOPMENT

1. Growth is continuous but not uniform - fastest in fetal life, first year, and puberty
2. Development proceeds in a cephalocaudal direction (head to foot)
3. Development proceeds in a proximodistal direction (center to periphery)
4. Development proceeds from mass to specific movements
5. Sequence is constant but rate varies among children
6. Development is integrated - all domains (physical, mental, social, emotional) are interrelated
7. Primitive reflexes are replaced by voluntary activity

---

3. DETERMINANTS OF GROWTH & DEVELOPMENT

Genetic Factors

• Influence height, weight, mental & social development, personality
• Account for ~60-80% of height variation

Environmental Factors

1. Nutrition - most important modifiable factor; malnutrition causes growth retardation (catch-up growth possible)
2. Infections - intrauterine (TORCH, rubella, syphilis) and postnatal infections slow growth
3. Hormones - GH, thyroid, insulin, sex hormones, cortisol
4. Psychological factors - love, care, parent-child relationship
5. Socioeconomic status - higher income = better nutrition, healthcare access
6. Physical surroundings - sunshine, housing, ventilation
7. Birth order & spacing - later-born children may have nutritional disadvantage
8. Parasitosis - roundworms compete for nutrients

---

4. PHYSICAL GROWTH

4a. Weight

4b. Height / Length

• 0-1 year: 25 cm/year
• 1-2 years: 12 cm/year
• 2-3 years: 8 cm/year
• Pre-pubertal: 5-6 cm/year
• Pubertal growth spurt: 8-10 cm/year

4c. Head Circumference (HC)

• HC reflects brain growth - most important growth parameter in early life
• Microcephaly: HC < 3rd percentile
• Macrocephaly: HC > 97th percentile

4d. Chest Circumference (CC)

4e. Fontanelles

• Bulging AF = raised ICP (meningitis, hydrocephalus)
• Sunken AF = dehydration
• Large AF = hypothyroidism, rickets, hydrocephalus
• Third fontanelle between anterior and posterior = Down syndrome

4f. Teeth

---

5. DEVELOPMENT - DOMAINS

Four Domains (GHAI / Denver System):

1. Gross Motor (GM) - large muscle groups, posture, locomotion
2. Fine Motor & Adaptive (FM/A) - hand-eye coordination, manipulation
3. Language (L) - communication, hearing, understanding
4. Personal-Social (PS) - self-care, interaction with others

---

6. DEVELOPMENTAL MILESTONES (Key Exam Table)

Gross Motor

Fine Motor & Adaptive

Language

Personal-Social

---

7. PRIMITIVE REFLEXES (Nelson + Ghai)

---

8. DEVELOPMENTAL ASSESSMENT TOOLS

1. Denver Developmental Screening Test (DDST / Denver II) - most widely used; screens 0-6 years across 4 domains
2. Vineland Social Maturity Scale (VSMS) - measures social age (SA) and Social Quotient (SQ)
3. Gesell's Developmental Schedule - 4 weeks to 5 years
4. Bayley Scales of Infant Development - 1-42 months

---

9. GROWTH CHARTS & MONITORING

• WHO Child Growth Standards (2006): 0-5 years; based on breastfed children in 6 countries
• IAP (Indian Academy of Pediatrics) Growth Charts: recommended for Indian children
• Road to Health Chart (RHC) / Growth Monitoring Card: used in community/PHC settings
• Plotted parameters: weight-for-age, height-for-age, weight-for-height, BMI-for-age
• Grades of Malnutrition (Gomez): based on % of median weight-for-age
  • Grade I: 75-90%
  • Grade II: 60-75%
  • Grade III: <60%

---

10. PUBERTY

Girls (earlier by ~2 years than boys)

Boys

Tanner Stages (both sexes): Stages I-V

• Stage I = prepubertal
• Stage V = adult

Precocious Puberty:

• Girls: puberty before 8 years
• Boys: puberty before 9 years

---

11. GROWTH VELOCITY & TYPES OF GROWTH

Scammon's Curves (4 growth patterns):

1. General (somatic) - body size, muscles, lungs, kidneys - S-shaped curve
2. Neural - brain, spinal cord - rapid in first 2 years; 90% adult size by age 6
3. Genital - lymphoid/reproductive - dormant until puberty, then rapid
4. Lymphoid - thymus, lymph nodes - peaks at age 12 (200% adult size), then involutes

---

12. BONE AGE & SKELETAL MATURITY

• Bone age (Radiological age) assessed by wrist X-ray (typically left hand and wrist)
• Reference: Greulich and Pyle atlas
• Number of ossification centers (wrist rule for children):
  • No. of wrist carpal bones = age (years) + 1 (up to 8 years)
• Bone age delayed in: hypothyroidism, GH deficiency, malnutrition
• Bone age advanced in: precocious puberty, congenital adrenal hyperplasia

---

13. DEVELOPMENTAL RED FLAGS (when to refer)

Regression is always abnormal and requires urgent evaluation.

---

14. COGNITIVE & PSYCHOSOCIAL DEVELOPMENT

Piaget's Cognitive Development

Erikson's Psychosocial Development

---

15. KEY HIGH-YIELD EXAM FACTS

• First social smile: 6-8 weeks (2 months)
• Object permanence: 9 months
• First meaningful word: 10 months
• 2-word phrases: 2 years
• Walks alone: 15 months
• Pincer grasp: 10 months (crude), 12 months (fine)
• Age of ambiguity (walks, runs, climbs): 18 months
• Social smile absent = always red flag
• Birth weight doubles at 5 months, triples at 1 year, quadruples at 2 years
• Length doubles at 4 years
• Head circumference equals chest circumference at 1 year
• Anterior fontanelle closes by 18 months; posterior by 6-8 weeks
• Moro reflex disappears at 4-6 months (persistence = cerebral palsy)

---

---

PEDIATRICS - FINAL YEAR EXAMINATION NOTES

Based on OP Ghai's Essential Pediatrics & Nelson's Textbook of Pediatrics

---

---

1. BACTERIAL MENINGITIS

Definition

---

Etiology (Age-based - HIGH YIELD)

Mnemonic for neonates: "GEL K" - GBS, E. coli, Listeria, Klebsiella

---

Pathogenesis

1. Colonization of nasopharynx by pathogen
2. Bacteremia - spread via bloodstream
3. Invasion of blood-brain barrier (BBB) via choroid plexus or cerebral capillaries
4. Multiplication in subarachnoid space (CSF - poor immune environment: low complement, low immunoglobulin, low leukocytes)
5. Inflammatory response - cytokines (TNF-alpha, IL-1, IL-6) released
6. Cerebral edema - vasogenic + cytotoxic + interstitial
7. Raised ICP -> brain herniation -> death

---

Clinical Features

In Older Children (Classic Triad - 85% cases):

1. Fever (high grade)
2. Headache (severe, throbbing)
3. Neck stiffness (meningismus)

Additional Features:

• Nausea, vomiting (35%)
• Photophobia, phonophobia
• Seizures (30%) - especially in pneumococcal meningitis
• Altered consciousness, confusion, lethargy
• Cranial nerve palsies (III, VI, VII, VIII) - 10-20%
• Papilledema (uncommon early - if present early, think brain abscess)
• Petechial/purpuric rash on trunk and extremities - pathognomonic of meningococcal meningitis ("fulminant purpura")

In Neonates (atypical - RED FLAGS):

• Bulging anterior fontanelle (late sign)
• High-pitched cry / irritability
• Poor feeding, weak sucking
• Temperature instability (fever OR hypothermia)
• Vomiting, diarrhea
• Apnea
• Seizures (40%)
• Note: Neck stiffness is ABSENT/unreliable in infants <1 year

Signs:

• Kernig's sign: Patient supine; hip flexed 90°; inability to extend knee to 135° due to pain = positive
• Brudzinski's sign: Passive flexion of neck causes involuntary flexion of knees and hips = positive
• Jolt accentuation: Horizontal head rotation worsens headache (sensitive for meningism)

---

Risk Factors / Predisposing Conditions

• Otitis media (most common)
• Sinusitis, mastoiditis
• CSF leak (from closed head trauma, fractures)
• Immunocompromised state (HIV, asplenia, complement deficiency)
• Non-immunized children (Hib, PCV, MCV vaccines)
• Crowded conditions (meningococcal outbreaks)
• Alcoholism (adults)

---

Investigations

1. Lumbar Puncture (LP) - DEFINITIVE TEST

• Papilledema
• Focal neurological signs
• Depressed consciousness
• Coagulopathy, thrombocytopenia

CSF Analysis (KEY TABLE)

2. Blood Investigations:

• CBC: leukocytosis with left shift (neutrophilia)
• Blood culture (positive in 50-70%)
• CRP, ESR, Procalcitonin (elevated)
• Blood glucose (for CSF:blood glucose ratio)
• Coagulation profile (DIC in meningococcemia)
• Electrolytes (SIADH - hyponatremia)

3. Imaging:

• CT brain: before LP if signs of raised ICP; may show meningeal enhancement, hydrocephalus
• MRI with gadolinium: superior - shows leptomeningeal enhancement

---

Treatment

Emergency Management (Do NOT delay antibiotics for LP):

• Dose: 0.15 mg/kg IV 6-hourly x 4 days
• Reduces inflammation, decreases hearing loss (especially for H. influenzae and pneumococcal meningitis)

• S. pneumoniae: Penicillin G / Ceftriaxone (if resistant: Vancomycin + Ceftriaxone)
• N. meningitidis: Benzyl Penicillin / Ceftriaxone
• H. influenzae: Ceftriaxone
• L. monocytogenes: Ampicillin + Gentamicin

• N. meningitidis: 5-7 days
• H. influenzae: 7-10 days
• S. pneumoniae: 10-14 days
• Neonatal/gram-negative: 21 days

Supportive Care:

• Maintain hydration (restrict fluids to 2/3 maintenance if SIADH suspected)
• Anticonvulsants for seizures (Lorazepam, Phenobarbital)
• Treat raised ICP: head elevation 30°, mannitol 0.5-1 g/kg
• Monitor glucose, electrolytes, neurological status

---

Complications

Acute:

• Brain herniation (tonsillar or uncal) - most feared
• Hydrocephalus (communicating or obstructive)
• Subdural effusion (especially in H. influenzae)
• Waterhouse-Friderichsen syndrome - bilateral adrenal hemorrhage in meningococcemia -> adrenal insufficiency -> shock
• DIC (meningococcemia)
• SIADH
• Cerebral venous sinus thrombosis

Long-term:

• Sensorineural hearing loss (most common sequela - 10-30%)
• Cognitive impairment, intellectual disability
• Seizure disorder
• Motor deficits, hemiplegia
• Visual impairment
• Hydrocephalus
• Behavioral problems
• Mortality: 5-10% in developed world; higher in developing countries

---

Prevention / Prophylaxis

1. Vaccines: Hib vaccine, PCV13/PCV10, Meningococcal vaccine (MenACWY), BCG
2. Rifampicin prophylaxis for close contacts of meningococcal meningitis:
   • Adults: 600 mg BD x 2 days
   • Children: 10 mg/kg BD x 2 days
   • Infants <1 month: 5 mg/kg BD x 2 days
3. Ceftriaxone single IM dose - alternative prophylaxis

---

---

2. NEURAL TUBE DEFECTS (NTDs)

Definition

---

Embryology

• Neural plate forms at week 3
• Begins to fold -> neural folds -> neural tube (by day 22-28)
• Anterior neuropore closes: day 25 (failure = anencephaly)
• Posterior neuropore closes: day 27-28 (failure = spina bifida)
• Failure of closure = NTD

---

Etiology / Risk Factors

Environmental:

• Folic acid deficiency (most important and preventable cause)
• Valproate / carbamazepine use in pregnancy (increase risk 10-fold)
• Maternal diabetes mellitus
• Maternal hyperthermia (fever, hot tubs in early pregnancy)
• Maternal obesity
• Nutritional deficiencies (B12, zinc)

Genetic:

• Multifactorial inheritance (polygenic + environmental)
• Specific gene mutations: MTHFR C677T polymorphism
• Chromosomal anomalies: Trisomy 18

• General population: 0.1-0.2%
• 1 affected sibling: 3-5%
• 2 affected siblings: 10%

---

Classification of NTDs

A. Open NTDs (Neural tissue exposed):

1. Anencephaly - most severe; no cranial vault or cerebral hemispheres; incompatible with life
2. Craniorachischisis - total NTD: anencephaly + spina bifida
3. Myelomeningocele (spina bifida aperta) - most common clinically significant NTD

B. Closed NTDs (skin-covered):

1. Meningocele - meninges herniate, cord is normal
2. Spina bifida occulta - failure of vertebral arch fusion, no herniation; asymptomatic usually
3. Lipomyelomeningocele, tethered cord, dermal sinus - occult forms

---

Types in Detail

1. Anencephaly

• Absence of brain, skull vault, and scalp above the orbits
• Pituitary may be absent -> prolonged pregnancy (no ACTH -> adrenal hypoplasia -> no cortisol -> no prostaglandin E production to initiate labor)
• AFP markedly elevated in maternal serum and amniotic fluid
• Uniformly lethal (stillborn or die within hours/days of birth)

2. Spina Bifida Occulta

• Posterior arch of vertebra (usually L5/S1) fails to fuse - vertebra not completely closed
• No herniation of meninges or cord
• Covered by skin; may have surface marker:
  • Dimple, tuft of hair, lipoma, hemangioma, skin tag over spine
• Usually asymptomatic but may present with:
  • Tethered cord syndrome: progressive neurological deficit with growth
  • Foot deformities, bladder dysfunction
• Diagnosis: X-ray spine / MRI

3. Meningocele

• Meninges herniate through vertebral defect as a CSF-filled sac
• Spinal cord is normal (remains in spinal canal)
• Covered by thin membrane/skin
• Neurological function usually normal
• Treatment: surgical repair

4. Myelomeningocele (MMC) - MOST IMPORTANT

Features:

• Meninges + spinal cord/nerve roots herniate through vertebral defect
• Open neural placode (neural tissue exposed)
• Most common at lumbosacral region (L3-S1)
• Most severe form compatible with life

Clinical Features (depend on level of lesion):

Associations:

• Arnold-Chiari type II malformation (almost universal) - cerebellar tonsils + brainstem herniate through foramen magnum -> obstructive hydrocephalus
• Hydrocephalus (80-90% of cases with Arnold-Chiari II)
• Club foot (talipes equinovarus)
• Scoliosis/kyphosis
• Hip dislocation
• Latex allergy (50-70% develop sensitivity)
• Tethered cord post-repair

---

Investigations

Prenatal:

• MSAFP (Maternal Serum Alpha-Fetoprotein): elevated in open NTDs at 15-20 weeks
• Amniocentesis: elevated AFP + acetylcholinesterase (AChE) - specific for open NTDs
• Level II ultrasound (18-20 weeks): gold standard - shows defect, lemon sign (frontal scalloping), banana sign (curved cerebellum = Arnold-Chiari II)
• Fetal MRI

Postnatal:

• MRI spine (best): shows extent of defect, level, tethering
• MRI brain: Arnold-Chiari II, hydrocephalus
• X-ray spine: vertebral defects
• Urodynamic studies: bladder function
• Urinalysis, renal US: urological complications
• Neuropsychological assessment

---

Management

Preventive (Most Important):

• Folic acid supplementation:
  • Low risk: 0.4 mg/day from 1 month before conception to end of first trimester
  • High risk (previous NTD child, on anticonvulsants): 4-5 mg/day
• Diet rich in folate (green leafy vegetables, legumes, fortified cereals)

Surgical:

• Myelomeningocele repair: within 24-72 hours of birth (prevents infection, progressive deficit)
• Fetal surgery (in-utero MMC repair at 19-25 weeks): reduces need for VP shunt, improves leg function (MOMS trial)
• VP shunt for hydrocephalus (placed at time of MMC repair or shortly after)
• Orthopedic procedures: clubfoot correction, hip reduction

Ongoing Management (Multidisciplinary):

• Neurological: monitor for tethered cord, shunt function
• Urological: clean intermittent catheterization (CIC), anticholinergics (oxybutynin) for neurogenic bladder; renal US every 1-2 years
• Orthopedic: AFOs (ankle-foot orthoses), crutches, wheelchair; treatment of scoliosis
• Bowel program: dietary fiber, laxatives, bowel training
• Rehabilitation: physiotherapy, occupational therapy, speech therapy
• Psychological/Social support

---

Prognosis

• Anencephaly: uniformly fatal
• Isolated meningocele: excellent
• Myelomeningocele (with modern management):
  • 85% survive to adulthood

  • 75% have normal intelligence

  • Most require mobility aids
  • Frequent UTIs, renal damage if bladder not managed

---

---

3. DUCHENNE MUSCULAR DYSTROPHY (DMD)

Definition

---

Genetics

• Inheritance: X-linked recessive
• Gene: Dystrophin gene (DMD gene) on chromosome Xp21
• Largest gene known: spans 2.4 million base pairs, 79 exons
• Mutation types:
  • Large deletions: 65-70% (usually exons 44-52 or 2-20) - detected by multiplex PCR
  • Duplications: 10-15%
  • Point mutations/small insertions: ~25%
• Frameshift rule: deletions that disrupt reading frame = DMD (severe); in-frame deletions = Becker MD (milder)
• ~1/3 cases arise from de novo mutations (no family history)
• Carrier females: usually asymptomatic; may have elevated CK; 10% manifest some weakness ("manifesting carriers")

---

Pathophysiology

• Dystrophin protein: subsarcolemmal structural protein that links actin cytoskeleton to the extracellular matrix via dystrophin-associated glycoprotein complex (DGC)
• In DMD: absent dystrophin -> membrane instability during muscle contraction -> repeated sarcolemmal tears -> calcium influx -> muscle fiber necrosis -> replaced by fat and fibrous tissue -> pseudohypertrophy
• Progressive loss of muscle cells -> weakness

---

Clinical Features

Onset and Progression:

• Onset: typically 2-3 years of age (may be noted as late walking, toe-walking, or falls)
• Rarely symptomatic in first year of life

Motor Features:

• Proximal muscle weakness - lower limbs before upper limbs
• Difficulty: climbing stairs, running, rising from floor, raising arms
• Gowers' sign (PATHOGNOMONIC):
  • Child rises from floor by "walking up" own legs with hands due to proximal hip/thigh weakness
• Waddling gait (Trendelenburg gait) - due to gluteus medius weakness
• Toe-walking (to compensate for ankle dorsiflexor weakness)
• Pseudohypertrophy of calves (firm, rubbery on palpation - fat + fibrosis)
• Lumbar lordosis (compensation for weak hip extensors)
• Loss of ambulation by 9-12 years (without corticosteroids); up to 13-14 years with steroids
• Wheelchair-bound by age 12 on average
• Upper limb weakness: later (neck flexors, shoulder girdle)
• Beevor's sign: umbilicus moves upward with neck flexion (upper abdominals weaker than lower)

Respiratory:

• Progressive diaphragm and intercostal weakness
• FVC declines; restrictive pattern on PFTs
• Nocturnal hypoventilation (first sign - morning headaches, poor sleep)
• Death usually from respiratory failure (most common cause of death, average age 20s)

Cardiac (present in ALL patients by adolescence):

• Dilated cardiomyopathy (due to posterior basal cardiac fibrosis)
• Arrhythmias (particularly sinus tachycardia, AF, right bundle branch block)
• ECG: tall R in V1, deep Q in left leads (specific for DMD)
• Echocardiography: dilated cardiomyopathy
• Cardiac complications: 2nd most common cause of death

Cognitive/Behavioral:

• Average IQ ~85 (one SD below mean) - not progressive
• Intellectual disability in 30% (full scale IQ <70)
• ADHD, autism spectrum features in some
• Dystrophin isoforms (Dp71, Dp140) in brain - correlate with cognitive function

---

Investigations

1. Serum Creatine Kinase (CK):

• Markedly elevated: 50-100 times normal (up to 10,000-50,000 IU/L)
• Elevated from birth (even before symptoms)
• Decreases as muscle mass is lost (late disease)

2. Genetic Testing (diagnostic):

• Multiplex PCR / MLPA (Multiplex Ligation-dependent Probe Amplification): detects deletions/duplications - positive in 70-80%
• Next-Generation Sequencing (NGS) of entire DMD gene: detects point mutations
• If genetic testing inconclusive -> muscle biopsy

3. Muscle Biopsy:

• Histology: variation in fiber size, necrosis and regeneration, fibrosis, fat replacement
• Immunohistochemistry: absent dystrophin staining (vs. reduced/abnormal in Becker)
• Western blot: absent dystrophin band

4. EMG: myopathic pattern (short-duration, low-amplitude polyphasic motor unit potentials)

5. Cardiac investigations:

• ECG: annually from diagnosis
• Echocardiography: every 2 years until age 10, annually after

6. Pulmonary function tests (PFTs):

• FVC: every 6-12 months when cooperative (~age 5-6)

---

Diagnosis Criteria

1. Progressive proximal muscle weakness
2. Markedly elevated CK (>10,000)
3. Characteristic muscle biopsy
4. Absent dystrophin on immunohistochemistry
5. Dystrophin gene mutation on molecular testing

---

Management

1. Corticosteroids (MAINSTAY of treatment):

• Deflazacort (preferred) or Prednisolone
  • Prednisolone: 0.75 mg/kg/day (daily) - start at age 4-5 years, when plateau in motor function
  • Deflazacort: 0.9 mg/kg/day
• Benefits: prolongs ambulation by 2-3 years; improves respiratory and cardiac function; reduces scoliosis
• Side effects: weight gain, behavioral changes, cataracts, osteoporosis, growth delay

2. Gene-based Therapies (newer):

• Exon skipping: antisense oligonucleotides (Eteplirsen, Golodirsen) - restore reading frame for specific exon deletions; approved for exon 51, 53, 45 skipping
• Gene therapy: dystrophin micro-gene delivery via AAV vector - clinical trials
• Stop codon read-through: Ataluren (Translarna) - for nonsense mutations; approved in Europe

3. Respiratory Management:

• Cough-assist device / mechanically assisted cough
• Non-invasive ventilation (BiPAP) when FVC <50% or symptomatic nocturnal hypoventilation
• Tracheostomy and ventilation in advanced disease (family decision)

4. Cardiac Management:

• ACE inhibitors (lisinopril/enalapril): when cardiomyopathy detected or by age 10 prophylactically
• Beta-blockers (carvedilol): added with cardiac dysfunction
• No competitive sports

5. Orthopedic:

• Ankle-foot orthoses (AFOs): prevent equinus contractures
• Serial casting, Achilles tendon release
• Spinal fusion for progressive scoliosis (>20-25° when FVC >30%)

6. Physiotherapy:

• Passive stretching daily
• Swimming, gentle exercise (avoid overexertion)
• Wheelchair positioning

7. Nutritional:

• High protein, controlled calorie diet
• Calcium and vitamin D supplementation (especially on steroids)
• Bisphosphonates for corticosteroid-induced osteoporosis

8. Psychological/Multidisciplinary:

• Psychological support for child and family
• Educational support / IEP (Individualized Education Program)
• Palliative care planning in advanced disease

---

Differential Diagnosis

• Becker Muscular Dystrophy (BMD): same gene, in-frame deletion, milder, later onset (5-15 yrs), ambulation preserved into 20s+
• Limb-girdle muscular dystrophy (LGMD)
• Spinal muscular atrophy (SMA) - CK normal/mildly elevated
• Polymyositis/dermatomyositis (elevated CK, rash, inflammatory)
• Emery-Dreifuss MD

---

Prognosis

• Without steroids: loss of ambulation by 9-12 years; death 2nd-3rd decade
• With steroids + modern respiratory care: many survive into 30s-40s
• Cause of death: respiratory failure (most common), cardiomyopathy

---

---

4. CYSTIC FIBROSIS

Definition

---

Genetics

• Inheritance: Autosomal recessive
• Gene: CFTR gene on chromosome 7q31.2 (27 exons, ~190 kb)
• CFTR protein: Chloride channel (ABC transporter family) - regulates Cl⁻ transport across epithelial membranes
• Most common mutation: ΔF508 (deletion of phenylalanine at position 508) - present in ~70% of CF alleles in Caucasians
• Over 2000 mutations identified in CFTR
• Incidence: 1/2500 Caucasian births; 1/15,000 in Blacks; 1/31,000 in Asians
• Carrier frequency: 1/25 (Caucasians)

---

CFTR Mutation Classes (Pharmacologically important):

---

Pathophysiology

• Defective CFTR -> decreased chloride secretion + increased sodium absorption across airway epithelium
• Net effect: dehydrated, thickened mucus (in airway, pancreatic duct, bile duct, intestine, sweat gland)
• Sweat glands: Cl⁻ not reabsorbed -> sweat has high [Cl⁻] and [Na⁺]
• Airways: mucus plugging -> bacterial colonization -> chronic infection -> bronchiectasis
• Pancreas: mucus obstructs ducts -> autodigestion -> fibrosis -> exocrine insufficiency + eventually endocrine (CFRD)
• Liver: inspissated bile -> focal biliary cirrhosis

---

Clinical Features

1. Pulmonary (Most important - cause of 85-95% mortality):

• Recurrent bacterial respiratory infections
  • Infancy/childhood: Staphylococcus aureus, H. influenzae
  • Older children/adults: Pseudomonas aeruginosa (mucoid form - biofilm - nearly impossible to eradicate; marker of worse prognosis)
  • Burkholderia cepacia (particularly virulent; accelerates decline)
• Chronic productive cough (purulent sputum)
• Wheeze, airflow obstruction
• Bronchiectasis (permanent cylindrical/saccular dilation of bronchi)
• Cor pulmonale (late)
• Pneumothorax (5-8% of adults)
• Hemoptysis (massive in advanced disease)
• Nasal polyps (25-30%)
• Chronic sinusitis

2. Pancreatic:

• Pancreatic exocrine insufficiency (85-90%):
  • Steatorrhea (bulky, greasy, foul-smelling stools)
  • Fat malabsorption -> fat-soluble vitamin deficiency (A, D, E, K)
  • Failure to thrive, poor weight gain
• Meconium ileus (10-15% of neonates with CF) - first presentation; pathognomonic if seen on X-ray as "soap bubble" appearance in RLQ
• DIOS (Distal Intestinal Obstruction Syndrome) - older children
• Rectal prolapse (often presenting feature in young children)
• Cystic fibrosis related diabetes (CFRD) - 30-40% of adults; type 3c diabetes
• Pancreatitis (in pancreatic-sufficient patients)

3. Hepatobiliary:

• Focal biliary cirrhosis -> multilobular cirrhosis in 5-10%
• Portal hypertension, varices, splenomegaly
• Cholestasis, gallstones

4. Reproductive:

• Males: Congenital bilateral absence of vas deferens (CBAVD) -> azoospermia -> infertility (>98% infertile)
• Females: thick cervical mucus -> reduced fertility; can become pregnant with assisted reproduction

5. Sweat Glands (diagnostic):

• Elevated sweat Cl⁻ and Na⁺
• "Tastes salty" - history given by parents
• Salt depletion in hot weather / fever -> hyponatremic dehydration, metabolic alkalosis

6. Other:

• Finger clubbing (universal in established disease)
• Hypertrophic pulmonary osteoarthropathy (HPOA)
• Vitamin K deficiency -> bleeding tendency
• Vitamin D deficiency -> rickets/osteoporosis
• Vitamin E deficiency -> hemolytic anemia, neuropathy

---

Investigations

Diagnostic:

• Immunoreactive trypsinogen (IRT) on Guthrie card (heel prick at day 5)
• Elevated IRT -> repeat IRT or genetic testing

• Pilocarpine iontophoresis -> collect sweat -> measure [Cl⁻]
• Positive: Cl⁻ ≥60 mmol/L (diagnostic)
• Borderline: 30-59 mmol/L (repeat or proceed to genetics)
• Normal: <30 mmol/L
• Requires minimum 75 mg sweat; unreliable in neonates <2 weeks

• Panel for common CFTR mutations (confirms diagnosis)
• Full gene sequencing if common panel negative but high suspicion

Other Investigations:

• Spirometry: obstructive pattern (reduced FEV1/FVC); FEV1 best prognostic marker
• CXR/CT chest: hyperinflation, bronchiectasis, mucus plugging
• Sputum culture (for organisms, sensitivities)
• Fecal elastase-1 (low = pancreatic insufficiency)
• Fecal fat estimation
• 72-hour fecal fat (steatorrhea > 7g/day)
• LFTs, abdominal USS (liver fibrosis)
• HbA1c, OGTT (CFRD screening annually >10 yrs)
• Bone densitometry (DEXA scan)
• Semen analysis (males)

---

Management

Multidisciplinary team: Pediatric pulmonologist, gastroenterologist, physiotherapist, dietitian, psychologist, nurse specialist, geneticist

1. Airway Clearance:

• Chest physiotherapy (CPT): multiple sessions/day; postural drainage + percussion; Active Cycle of Breathing Technique (ACBT)
• Flutter device / Acapella (oscillating PEP)
• High-frequency chest wall oscillation (HFCWO) - ThAIRapy/The Vest
• Exercise: as part of airway clearance regime

2. Mucolytics:

• Dornase alfa (DNase / Pulmozyme): inhaled; cleaves extracellular DNA in mucus -> reduces viscosity; first-line in moderate-severe disease
• Hypertonic saline (7%): inhaled; osmotic agent, hydrates airway surface liquid

3. Bronchodilators:

• Inhaled SABA (salbutamol) before physiotherapy and CFTR modulators

4. Anti-infectives:

• Chronic Pseudomonas colonization:
  • Inhaled tobramycin (TOBI) or colistin: alternating monthly
  • IV aminoglycoside + anti-pseudomonal beta-lactam for exacerbations
• Chronic S. aureus: anti-staphylococcal agents
• Azithromycin: long-term anti-inflammatory, anti-bacterial (3x/week); improves FEV1

5. CFTR Modulators (disease-modifying - target the protein defect):

• Ivacaftor (Kalydeco): G551D mutation (gating defect - class III); potentiator - opens CFTR channel; >6 months
• Lumacaftor + Ivacaftor (Orkambi): ΔF508 homozygous; corrector + potentiator
• Tezacaftor + Ivacaftor (Symdeko): ΔF508 + selected mutations
• Elexacaftor + Tezacaftor + Ivacaftor (Trikafta/Kaftrio): ΔF508 (one copy); triple combination - most effective; >6 years; reduces sweat Cl⁻, improves FEV1, reduces exacerbations

6. Pancreatic:

• Pancreatic enzyme replacement therapy (PERT): Creon (pancrelipase) with every meal and snack; titrate to stool consistency
• Fat-soluble vitamins (A, D, E, K) daily
• High-calorie, high-protein, high-salt diet
• Gastrostomy for severe FTT

7. CFRD:

• Insulin (preferred); oral hypoglycemics not recommended

8. Liver:

• Ursodeoxycholic acid (UDCA): reduces bile viscosity; liver protection
• Liver transplant if end-stage cirrhosis

9. Lung Transplant:

• Bilateral sequential lung transplant for end-stage lung disease (FEV1 <30% predicted)
• 5-year survival: ~50-60% post-transplant

---

Prognosis

• Median survival: ~50 years in developed countries (improving rapidly with CFTR modulators)
• FEV1 is the best predictor of mortality
• Lung disease accounts for 85-95% of deaths
• CFTR modulators (especially Trikafta) have revolutionized outcomes

---

---

5. FEBRILE SEIZURES

Definition

---

Epidemiology

• Most common seizure disorder in childhood
• Prevalence: 2-5% of children
• Peak age: 14-18 months
• Male > Female (slightly)
• Family history positive in 25-40% (autosomal dominant tendency in some families)

---

Classification

Simple Febrile Seizures (80-85%):

• Duration: <15 minutes
• Type: generalized (tonic-clonic)
• No focal features
• Single episode within 24 hours
• Returns to normal within 1 hour (post-ictal period may be brief)

Complex Febrile Seizures (15-20%):

• Duration: >15 minutes (febrile status epilepticus if >30 min)
• OR focal (hemi-convulsion, Todd's paresis)
• OR recurs within 24 hours (serial)
• Higher risk of epilepsy and underlying structural lesion

---

Etiology of Fever

• Viral URTI (most common) - HHV-6 (Roseola infantum), influenza, RSV
• Otitis media
• Tonsillitis, pharyngitis
• UTI
• Post-immunization fever (DPT, MMR - febrile seizure risk: MMR at day 8-14 post; not a contraindication)
• Rarely: pneumonia, meningitis (must be excluded)

---

Pathophysiology

• Fever lowers seizure threshold by increasing neuronal excitability
• Rapid rise in temperature is more important than absolute temperature level
• Immature neurons in young children are more susceptible to temperature-induced depolarization
• Na+ channel mutations (SCN1A, SCN1B) in familial febrile seizures (GEFS+)

---

Clinical Features

• Usually occurs within first 24 hours of fever onset (often the first sign of illness)
• Often occurs at beginning of febrile illness (not necessarily high temperature)
• Generalized tonic-clonic seizure most common
• Lasts typically 1-5 minutes (simple)
• Child is well after seizure except for post-ictal drowsiness (recovers fully)
• No signs of meningism or CNS infection

---

Investigations

For Seizure Itself (simple FS - minimal workup needed):

• Lumbar puncture: MANDATORY if:
  • Age <12 months (strongly consider)
  • Age 12-18 months (consider)
  • Signs of meningism / bulging fontanelle / photophobia / altered sensorium
  • Complex febrile seizure
  • Prolonged post-ictal state
  • Child appears ill / toxic
  • Fully immunized child >18 months: LP not routinely required
• EEG: NOT routinely recommended after simple febrile seizure (does NOT predict recurrence or epilepsy)
• Neuroimaging (MRI/CT): NOT routine; indicated for:
  • Complex FS (especially focal)
  • Focal neurological deficit
  • Raised ICP signs
• Serum electrolytes, glucose, Ca²⁺, Mg²⁺: only if clinically indicated (prolonged seizure, malnutrition)

For Fever Source:

• FBC, CRP, urine analysis (if UTI suspected)
• Throat swab, viral PCR if needed

---

Management

Acute Management:

• IV/IO/Rectal Diazepam: 0.3 mg/kg IV or 0.5 mg/kg rectal
• Intranasal Midazolam: 0.2 mg/kg (preferred if no IV access) - increasingly first-line
• Buccal Midazolam: 0.3 mg/kg - effective and easy to administer
• If no response after 10 min: repeat benzodiazepine OR give IV Phenobarbital 20 mg/kg slowly
• If still seizing: IV Phenytoin/Fosphenytoin 20 mg/kg (or IV Levetiracetam)
• Febrile status epilepticus: treat as per status epilepticus protocol

• Paracetamol (15 mg/kg q4-6h) or Ibuprofen (10 mg/kg q8h)
• Tepid sponging
• Note: antipyretics do NOT prevent recurrence of febrile seizures

• Reassure: most febrile seizures are benign and self-limiting
• Seizure first aid instruction
• When to call emergency services
• When to seek medical attention

---

Risk of Recurrence

1. Young age at first FS (<18 months) - strongest predictor
2. Lower temperature at time of seizure (<40°C)
3. Brief duration of fever before seizure (<1 hour)
4. Family history of febrile seizures (first-degree relative)
5. Developmental delay

---

Risk of Subsequent Epilepsy

1. Complex febrile seizure
2. Neurodevelopmental abnormality
3. Family history of epilepsy (not febrile seizures)
4. Multiple recurrent febrile seizures (especially complex)

---

Prophylaxis - Anticonvulsants

NOT recommended routinely (risk vs. benefit unfavorable)

Intermittent oral diazepam:

• 0.3 mg/kg q8h during febrile illness (for 48h)
• Reduces recurrence but causes sedation; may mask signs of meningitis
• Used selectively in: multiple recurrences + very anxious family

Continuous prophylaxis (valproate/phenobarbital):

• Not recommended for simple FS
• Rarely used for complex FS with high recurrence risk and parental distress
• Side effects outweigh benefits for most children

---

Prognosis - Excellent

• No increased risk of death in simple FS
• No cognitive impairment or developmental delay
• Normal school performance
• Mesial temporal sclerosis (hippocampal sclerosis) - rare; may follow prolonged/complex FS -> temporal lobe epilepsy later; debated causal relationship

---

---

6. CEREBRAL PALSY

Definition

---

Epidemiology

• Incidence: 2-3 per 1000 live births
• Most common cause of physical disability in childhood
• Prevalence is higher in premature and low birth weight infants

---

Etiology / Risk Factors

Prenatal (80-90% of cases - most common):

• Periventricular leukomalacia (PVL) - prematurity (most common overall cause)
• Congenital brain malformations (cortical dysplasia, pachygyria)
• Intrauterine infections (TORCH - CMV most important)
• Maternal thyroid disorders
• Placental insufficiency (chronic hypoxia)
• Multiple gestation

Perinatal:

• Hypoxic-ischemic encephalopathy (HIE) (historically overemphasized - accounts for only 10-15%)
• Birth trauma, intracranial hemorrhage
• Neonatal stroke
• Neonatal hypoglycemia, hyperbilirubinemia (kernicterus -> dyskinetic CP)

Postnatal (acquired CP - up to age 2-3 years):

• Meningitis / encephalitis
• Head trauma (including non-accidental injury)
• Near-drowning
• Severe hypoglycemia

---

Classification

By Motor Type (most clinically important):

• Upper motor neuron lesion -> spasticity (velocity-dependent increase in muscle tone)
• Clasp-knife rigidity on examination
• Exaggerated deep tendon reflexes, clonus, extensor plantar (Babinski)
• Sub-types:
  • Spastic hemiplegia (30-40%): one side of body; arm > leg
  • Spastic diplegia (30-40%): both legs > arms; classic in premature infants (PVL)
  • Spastic quadriplegia (10-15%): all four limbs; most severe; often with intellectual disability and seizures

• Basal ganglia/thalamus lesion (often from kernicterus or HIE)
• Involuntary movements:
  • Athetosis: slow, writhing, worm-like movements (distal)
  • Dystonia: sustained muscle contractions -> twisting postures
  • Chorea: quick, random, dance-like movements
• Intelligence often preserved (vs. spastic quadriplegia)
• Kernicterus -> choreoathetoid CP + sensorineural deafness + upward gaze palsy

• Cerebellar lesion
• Wide-based gait, intention tremor, incoordination
• Hypotonia
• May have cognitive delay

• Combination of types; usually spastic + dyskinetic

By Topography:

• Hemiplegia, diplegia, quadriplegia/tetraplegia, triplegia, monoplegia

---

Associated Conditions (co-morbidities - very important in exam)

• Intellectual disability: 50-70% overall (especially in spastic quadriplegia ~100%)
• Epilepsy: 25-35% (more common in spastic hemiplegias and quadriplegias)
• Visual impairment: squint (strabismus) in 50%; amblyopia, cortical visual impairment
• Hearing loss: 10-15% (sensorineural); risk in kernicterus
• Speech and communication: 50-60% have speech/language difficulties (dysarthria, aphasia)
• Feeding difficulties / dysphagia: oromotor dysfunction; risk of aspiration pneumonia
• Drooling (sialorrhea): oromotor dysfunction
• Gastroesophageal reflux (GERD): common
• Constipation: due to spasticity, immobility, dietary issues
• Orthopaedic complications: hip subluxation/dislocation, scoliosis, contractures, pes equinus (toe-walking)
• Pain: often under-recognized
• Behavioral and psychiatric: ADHD, autism, anxiety

---

Clinical Presentation

Early Warning Signs (Red Flags for CP):

• Abnormal tone (hypotonia early, then spasticity)
• Persistence of primitive reflexes beyond expected age
• Delayed motor milestones
• Asymmetric hand use before 12 months (suggests hemiplegia)
• Abnormal posture - fisting, scissoring legs
• Feeding difficulties

Examination:

• Increased tone, clasp-knife rigidity
• Exaggerated DTRs, clonus
• Extensor plantar response (up to 18 months is normal)
• Characteristic postures:
  • Hemiplegic: arm flexed/pronated, wrist flexed; leg extended, circumduction gait
  • Diplegic: scissors gait (hip adduction, knee flexion, toe-walking)
  • Quadriplegic: all limbs involved, may have opisthotonus

• Moro reflex: normally absent by 6 months
• ATNR: absent by 6 months
• Palmar grasp: absent by 3-4 months
• Persistence suggests cerebral pathology

---

Investigations

Brain Imaging (most important):

• MRI brain: investigation of choice
  • Shows PVL (periventricular white matter injury - hyperintensities, volume loss)
  • Cortical malformations
  • Basal ganglia lesions (HIE, kernicterus)
  • Can be normal in 10-15% of CP
• CT brain: if MRI unavailable; less sensitive for white matter changes

To Establish Diagnosis and Etiology:

• TORCH serology, CMV PCR (if congenital infection suspected)
• Metabolic screen: thyroid function, amino acids, organic acids (if no clear etiology)
• Genetic testing (chromosomal microarray): if malformation present or no clear etiology
• EEG (if seizures)
• Coagulation screen (if neonatal stroke)

Assessment of Associated Conditions:

• Formal cognitive/developmental assessment (Griffiths, BSID, WISC)
• Vision assessment (ophthalmology)
• Hearing assessment (BERA)
• Speech and language assessment
• Gait analysis (in older children for orthopedic planning)

---

Management (Multidisciplinary - LIFELONG)

1. Physiotherapy:

• Inhibition of abnormal movement patterns
• Facilitation of normal movement (Bobath/neurodevelopmental therapy)
• Stretching, range of motion exercises
• Strengthening exercises
• Postural management (seating, standing frames)

2. Occupational Therapy:

• Upper limb function, fine motor skills
• ADL training, adaptive equipment
• Splints, orthoses

3. Speech Therapy:

• Feeding therapy, safe swallowing
• Communication (AAC - Augmentative and Alternative Communication if non-verbal)

4. Spasticity Management:

• Baclofen (GABA-B agonist): reduces spasticity; oral or intrathecal
• Diazepam: short-term; sedating
• Tizanidine: alpha-2 agonist; reduces spasticity
• Dantrolene: acts on muscle directly; reduces calcium release

• Botulinum toxin A (BoNT-A / Botox) injections: most effective; into spastic muscles (gastrocnemius, hip adductors, hamstrings); lasts 3-6 months; combined with physiotherapy
• Phenol/alcohol nerve blocks

• Selective Dorsal Rhizotomy (SDR): surgical cutting of sensory nerve rootlets in lumbar spinal cord; permanently reduces lower limb spasticity in ambulatory diplegic CP; best in 3-8 year olds
• Intrathecal Baclofen pump (ITB): continuous intrathecal baclofen for severe spasticity/dystonia in non-ambulatory children

5. Orthopedic Surgery:

• Tendon lengthening (Achilles, hamstrings, hip adductors)
• Hip surveillance protocol: regular hip X-rays (migration percentage); if >40%, soft tissue surgery; if >60%, hip reconstruction
• Scoliosis surgery (posterior spinal fusion)

6. Seizure Management:

• As per epilepsy guidelines (valproate, levetiracetam, carbamazepine)

7. Nutritional Support:

• High calorie feeds
• Gastrostomy tube feeding if significant dysphagia

8. Drooling:

• Anticholinergics (glycopyrrolate, hyoscine patch)
• BoNT-A into parotid/submandibular glands
• Salivary gland relocation surgery

9. Educational and Psychological:

• Mainstream school with support vs. special school (based on cognitive level)
• IEP (Individualized Education Program)
• Psychological support

---

Prognosis

• CP is non-progressive - does NOT get worse with time (brain lesion stable)
• Functional outcomes depend on type and severity
• GMFCS (Gross Motor Function Classification System): Level I-V
  • Level I-II: walk without aids
  • Level III: walk with aids
  • Level IV-V: limited or no walking; wheelchair-dependent
• Independent ambulation possible in: hemiplegia (100%), diplegia (70-80%), quadriplegia (<50%)
• Most survive into adulthood with appropriate management

---

---

7. ACUTE BRONCHIOLITIS

Definition

---

Epidemiology

• Most common cause of hospitalization in infants worldwide
• Peak age: 2-6 months
• Peak season: winter/cold months (November to March in northern hemisphere)
• More severe in: premature infants, infants <6 weeks, congenital heart disease, immunodeficiency, chronic lung disease

---

Etiology

---

Pathophysiology

1. RSV infects bronchiolar epithelium -> ciliated cell necrosis
2. Peribronchiolar lymphocytic infiltration and edema
3. Mucus secretion increases
4. Plugging of small airways with cellular debris + mucus
5. Air trapping (check-valve mechanism) -> hyperinflation
6. Atelectasis (complete obstruction) -> V/Q mismatch
7. Hypoxemia (most important physiological effect)
8. Respiratory fatigue (in severe cases) -> hypercapnia -> respiratory failure

---

Clinical Features

Prodromal Phase (1-3 days):

• URTI symptoms: rhinorrhea, nasal congestion, sneezing
• Low-grade fever
• Poor feeding

Lower Respiratory Phase (days 3-7):

• Progressive cough
• Wheeze (first episode; expiratory predominantly)
• Tachypnea (respiratory rate >50/min in infants)
• Subcostal, intercostal, and suprasternal retractions (signs of respiratory distress)
• Nasal flaring, grunting (in severe cases)
• Hyperinflation: barrel-shaped chest, depressed liver/spleen
• Auscultation: fine crackles + wheeze bilaterally; reduced air entry (if very severe)
• Apnea (particularly in premature infants, infants <2 months - can be presenting feature)
• Cyanosis (severe)
• Poor feeding (inability to coordinate suck-swallow-breathe)

Peak Severity: Days 3-5

Recovery: 7-10 days (cough may persist 2-4 weeks)

---

Assessment of Severity

---

Investigations

Clinical diagnosis - investigations NOT routinely required for typical cases

• SpO₂ monitoring (continuous): most important
• Nasopharyngeal aspirate (NPA) + RSV antigen test/PCR: confirms RSV; useful for cohorting in hospitals
• CXR: NOT routine; indicated if:
  • Diagnostic uncertainty
  • Severe disease
  • Failure to improve
  • Findings: hyperinflation (flattened diaphragms, horizontal ribs), peribronchial thickening, segmental/lobar atelectasis (mimics consolidation)
• Blood gas (capillary/arterial): if SpO₂ <92% or severe respiratory distress
• FBC, CRP: not routine; if bacterial superinfection suspected
• Blood culture: only if suspected bacterial sepsis

---

Management

Principle: Supportive care - no specific treatment is of proven benefit

1. Oxygen:

• Mainstay of treatment
• Supplemental O₂ if SpO₂ <90-92% (varies by guideline)
• High-flow nasal cannula (HFNC) oxygen: e.g., Optiflow - reduces work of breathing, improves oxygenation; increasingly first-line for moderate-severe disease
• Conventional low-flow O₂ via nasal prongs or face mask

2. Fluid Management:

• Poor feeding -> risk of dehydration
• Small frequent feeds or nasogastric tube feeding (if tachypnea >60/min or SpO₂ drops with feeding)
• IV fluids: if too unwell to feed via NG (severe respiratory distress)
• Restrict fluids to 2/3 maintenance (risk of SIADH + pulmonary edema)

3. Nasal suctioning:

• Gentle nasal saline drops + bulb syringe suction before feeds

4. NOT RECOMMENDED (evidence does NOT support):

• Bronchodilators (nebulized salbutamol/ipratropium): do NOT improve oxygenation or shorten hospital stay - routine use not recommended (occasional trial, discontinue if no response)
• Corticosteroids (systemic or inhaled): no benefit in bronchiolitis
• Antibiotics: unless bacterial co-infection suspected
• Ribavirin: not used routinely
• Nebulized epinephrine: some evidence for short-term improvement in SpO₂ in ED; not recommended for routine inpatient use

5. Nebulized Hypertonic Saline (3%):

• Some evidence for modest reduction in hospital stay; recommended by some guidelines (AAP uncertain; NICE UK - consider in hospitalized infants)

6. Caffeine: for apneas in very young infants (<34 weeks corrected gestational age)

7. Invasive Ventilation:

• Indications: apnea, exhaustion, progressive hypercapnia (PaCO₂ >55-60), SpO₂ <90% despite HFNC
• CPAP or BiPAP before intubation

---

Indications for Hospital Admission:

• SpO₂ <92-94% on room air
• Significant respiratory distress (RR >60, retractions, grunting)
• Apnea
• Poor feeding (<50-75% normal intake)
• Age <3 months or prematurity
• Social concerns / parental inability to cope
• Underlying heart/lung disease

---

Prevention:

• Palivizumab (Synagis): Monthly IM injection of RSV monoclonal antibody
  • Prophylaxis for high-risk infants: premature (<29 weeks), congenital heart disease, chronic lung disease
  • During RSV season (5 doses)
  • Does NOT treat RSV; reduces hospitalization by ~55%
• Nirsevimab (Beyfortus): newer long-acting RSV monoclonal antibody; single dose; broader protection; WHO recommended for all infants
• Breastfeeding: protective
• Hand hygiene: prevents nosocomial RSV spread
• No vaccine available currently (RSV vaccine trials ongoing)

---

Prognosis

• Most recover fully within 2-4 weeks
• Mortality: <1% in healthy term infants; up to 1-3% in high-risk groups
• Recurrent wheeze and asthma: RSV bronchiolitis in infancy is associated with increased risk of recurrent wheezing and asthma in later childhood (causal vs. genetic predisposition debated)

---

---

8. PNEUMONIA IN CHILDREN

Definition

---

Classification

By Cause:

• Bacterial, viral, fungal, parasitic, chemical/aspiration

By Radiological Pattern:

• Lobar/segmental pneumonia (bacterial)
• Bronchopneumonia (patchy, bilateral - viral/bacterial)
• Interstitial pneumonia (viral, atypical)

By Setting:

• Community-acquired pneumonia (CAP)
• Hospital-acquired pneumonia (HAP) - >48 hours after admission
• Aspiration pneumonia
• Pneumonia in immunocompromised

By Age:

---

Etiology (Age-Based - HIGH YIELD)

Most common cause of bacterial pneumonia at ALL ages in children: Streptococcus pneumoniae Most common cause overall (including viral): RSV in infants/young children; Mycoplasma in older children

---

Pathogenesis

1. Aspiration of pathogen-containing secretions from nasopharynx (most common route)
2. Pathogen reaches alveoli -> evades mucociliary clearance
3. Alveolar macrophages activated -> cytokine cascade
4. PMN infiltration -> alveolar exudate (consolidation)
5. Stages of lobar pneumonia (classic but mainly pneumococcal):
   • Stage 1: Congestion (vascular engorgement, edema)
   • Stage 2: Red hepatization (RBCs + PMNs fill alveoli; liver-like consistency)
   • Stage 3: Grey hepatization (RBCs lyse; PMNs + fibrin remain)
   • Stage 4: Resolution (macrophage clearance; normal aeration restored)

---

Clinical Features

General:

• Fever (high-grade; especially bacterial)
• Cough (dry initially, may become productive)
• Tachypnea (most sensitive and specific sign of pneumonia in children)
• Respiratory distress: nasal flaring, subcostal/intercostal retractions, grunting
• Hypoxemia (SpO₂ <95%)
• Chest pain (older children; pleuritic)
• Abdominal pain (lower lobe pneumonia irritates diaphragm)
• Lethargy, poor feeding in infants

Examination Findings (lobar bacterial pneumonia):

• Tachypnea, tachycardia
• Decreased breath sounds over affected lobe
• Dullness to percussion (consolidation)
• Bronchial breathing (harsh, tubular sound)
• Aegophony (bleating quality to voice transmission)
• Crackles (particularly on inspiration; end-inspiratory crackles in consolidation)
• Increased tactile vocal fremitus

Atypical (Mycoplasma) Features:

• Gradual onset, low-grade fever, prominent dry/non-productive cough
• Systemic features: headache, myalgia, sore throat
• CXR: more extensive than clinical signs suggest ("walking pneumonia")
• Extrapulmonary: hemolytic anemia, rash (erythema multiforme/Stevens-Johnson), arthralgia, bullous myringitis

---

WHO ARI (Acute Respiratory Infection) Classification

Fast breathing (tachypnea thresholds - WHO):

• <2 months: ≥60 breaths/min
• 2-12 months: ≥50 breaths/min
• 1-5 years: ≥40 breaths/min

---

Investigations

1. Chest X-Ray (standard investigation):

• Lobar/segmental consolidation (homogeneous opacity, air bronchograms) - bacterial (especially pneumococcal)
• Patchy bilateral infiltrates (bronchopneumonia) - bacterial or viral
• Interstitial pattern (peribronchial thickening, hazy infiltrates) - viral, Mycoplasma
• Pleural effusion (parapneumonic) - S. pneumoniae, S. aureus, H. influenzae
• Pneumatocele (thin-walled air cysts) - S. aureus
• Abscess formation - S. aureus, anaerobes, Klebsiella

2. Blood Tests:

• CBC: leukocytosis + neutrophilia (bacterial); lymphocytosis (viral)
• CRP, procalcitonin (elevated in bacterial; PCT most specific)
• Blood culture (positive in only 10-20% of bacterial CAP; mandatory in hospitalized children)
• LFTs, electrolytes (if ill)
• Cold agglutinins (Mycoplasma - positive >1:32)

3. Sputum:

• Difficult to obtain in children <5 years
• If obtained: Gram stain + culture

4. Other:

• Nasopharyngeal aspirate: viral PCR (RSV, influenza, rhinovirus panel)
• Mycoplasma IgM serology (positive from day 7)
• Urine pneumococcal antigen test (adults; less validated in children)
• Thoracentesis + pleural fluid analysis (if effusion)
• Bronchoalveolar lavage (BAL) in immunocompromised

---

Management

WHO Approach (outpatient for mild/moderate):

• Oral Amoxicillin 40-90 mg/kg/day in 2-3 divided doses x 5-7 days (first-line)
• Alternative: Co-amoxiclav, azithromycin (if Mycoplasma suspected)

• IV Benzylpenicillin or Ampicillin 100-200 mg/kg/day 6-hourly
• Add IV Gentamicin if ill-appearing / neonatal age

• IV Ceftriaxone 100 mg/kg/day (covers pneumococcus and H. influenzae)
• Add IV Cloxacillin/Flucloxacillin if S. aureus suspected (pneumatoceles, abscess, rapid deterioration)
• Add Azithromycin/Clarithromycin if atypical organisms suspected

Specific Antimicrobials:

Supportive Care:

• Oxygen (target SpO₂ >92-94%)
• IV/NG fluids if unable to feed
• Antipyretics (paracetamol/ibuprofen)
• Chest physiotherapy: NOT indicated in acute phase (can worsen hypoxemia); useful during resolution for airway clearance
• Monitor for complications

---

Complications

• Parapneumonic effusion (most common) - 40% of hospitalized S. pneumoniae
• Empyema (pleural pus) - drainage required (intercostal tube drain / VATS)
• Lung abscess - prolonged antibiotics (4-6 weeks)
• Pneumatocele (S. aureus) - usually resolves spontaneously
• Pneumothorax / Bronchopleural fistula
• Septicemia, meningitis (hematogenous spread)
• Respiratory failure -> ARDS
• Organizing pneumonia (post-inflammatory fibrosis)
• Bronchiectasis (post-adenoviral or recurrent)

---

Prevention

• PCV13/PCV10: in immunization schedule (reduces pneumococcal pneumonia by 70-80%)
• Hib vaccine: reduces H. influenzae type b pneumonia
• Influenza vaccine: annually in high-risk children
• Breastfeeding, good nutrition, hand hygiene
• Reducing indoor air pollution (biomass fuel)

---

---

9. BRONCHIAL ASTHMA IN CHILDREN

Definition

1. Airway inflammation (eosinophilic predominantly)
2. Airway hyperresponsiveness (AHR) - exaggerated response to triggers
3. Reversible airway obstruction - spontaneously or with treatment

---

Epidemiology

• Most common chronic disease of childhood
• Prevalence: 5-15% in children globally; ~6-8% in Indian children
• Peak onset: childhood; 80% of asthma begins before age 6
• Boys > Girls in childhood; reverses after puberty

---

Etiology / Risk Factors

Host Factors:

• Atopy (genetic predisposition to IgE-mediated sensitization) - strongest risk factor
• Family history of asthma/eczema/allergic rhinitis (atopic march)
• Male sex (in childhood)
• Obesity
• Prematurity, low birth weight

Environmental Factors:

• Indoor: house dust mite (HDM - Dermatophagoides), cockroach, pet dander (cats, dogs), molds
• Outdoor: pollens (grass, trees, weeds), fungi

• Viral URTIs (rhinovirus - most common trigger)
• Exercise (exercise-induced bronchoconstriction)
• Cold air / changes in weather
• Allergen exposure
• Cigarette smoke (active + passive)
• Air pollution (particulate matter, ozone, SO₂)
• NSAID/aspirin (aspirin-exacerbated respiratory disease - AERD)
• Beta-blockers (contraindicated in asthma)
• Emotional stress, crying, laughing
• GERD

---

Pathophysiology

Phase 1 - Sensitization:

• Allergen exposure -> antigen presentation by dendritic cells -> Th2 polarization
• B cells produce IgE -> binds to mast cells and basophils

Phase 2 - Early Asthmatic Response (EAR) - within minutes:

• Re-exposure to allergen -> IgE cross-linking -> mast cell degranulation
• Release of: histamine, leukotrienes (LTC4, LTD4, LTE4 = Cys-LTs), prostaglandins, tryptase
• Immediate bronchoconstriction, mucus secretion, vasodilation

Phase 3 - Late Asthmatic Response (LAR) - 4-8 hours later:

• Eosinophil and T-cell infiltration (recruited by IL-5, eotaxin)
• Eosinophilic inflammation: eosinophils release major basic protein (MBP), eosinophilic cationic protein (ECP) -> epithelial damage
• Airway hyperresponsiveness established

Phase 4 - Airway Remodeling (chronic uncontrolled asthma):

• Goblet cell hyperplasia -> excess mucus
• Sub-epithelial fibrosis (thickened basement membrane)
• Smooth muscle hypertrophy/hyperplasia
• Angiogenesis
• Irreversible airflow obstruction (fixed component)

---

Classification

By Frequency (GINA / NAEPP):

By Phenotype (GINA approach):

• Allergic asthma (most common in children): atopic, eosinophilic, responds well to ICS
• Non-allergic asthma: no atopy, mixed inflammatory cells
• Exercise-induced bronchoconstriction (EIB)
• Occupational asthma
• Aspirin-exacerbated

---

Clinical Features

Typical Symptoms:

• Episodic wheeze (high-pitched, expiratory)
• Recurrent cough (particularly nocturnal and early morning; dry/non-productive)
• Breathlessness
• Chest tightness
• Symptoms often worse: at night, early morning, with exercise, with viral infections
• Symptoms vary in frequency and intensity

Signs (Between Episodes):

• Often completely normal examination
• May have eczema, allergic rhinitis (atopic triad)

Signs During Acute Episode:

• Tachypnea, tachycardia
• Expiratory wheeze (prolonged expiration) - "musical" wheeze
• Use of accessory muscles (sternocleidomastoid, scalenes)
• Hyperinflation (barrel chest, depressed diaphragm)
• Subcostal/intercostal retractions
• Reduced air entry (silent chest = SEVERE - airflow too poor to wheeze)
• Pulsus paradoxus >10 mmHg (severe)
• Cyanosis (very severe)
• Altered consciousness (life-threatening)

---

Assessment of Acute Severity

---

Investigations

1. Spirometry (Gold standard - >5 years):

• Obstructive pattern: FEV1 reduced, FVC normal, FEV1/FVC <0.75 (or <0.8 in children)
• Reversibility test (POSITIVE): FEV1 improves by ≥12% AND ≥200 mL after salbutamol (or ≥12% in children; some use ≥12% predicted)
• Normal spirometry does NOT exclude asthma

2. Bronchial Provocation Tests (if spirometry normal):

• Methacholine challenge test (PC20 <8 mg/mL = positive)
• Exercise challenge test
• Exhaled NO (FeNO): elevated (>25 ppb) suggests eosinophilic airway inflammation; predicts steroid responsiveness

3. Peak Expiratory Flow Rate (PEFR):

• Inexpensive, portable
• Diurnal variation >20% (morning dip) = highly characteristic of asthma
• PEFR <50% = severe; <33% = life-threatening

4. Allergy Testing:

• Skin prick test (SPT): gold standard for allergen sensitization
• Specific IgE (RAST): serum allergen-specific IgE; useful if SPT not feasible
• Total serum IgE (elevated in atopy)
• Blood eosinophil count: elevated (>300 cells/µL) suggests eosinophilic/allergic asthma; guides biologics

5. CXR:

• Normal between attacks
• During acute attack: hyperinflation (flattened diaphragm, horizontal ribs, >6 anterior ribs)
• To exclude: pneumothorax, pneumonia, foreign body

6. Other:

• CBC (eosinophilia)
• Sputum eosinophils (if obtainable)
• Sweat chloride test (if CF suspected)
• Bronchoscopy (if foreign body or structural airway abnormality suspected)

---

Management

A. Chronic Management (Step-up therapy - GINA Steps 1-5):

1. Inhaled Corticosteroids (ICS) - CORNERSTONE of controller therapy
   • Budesonide, Beclomethasone, Fluticasone
   • Low dose: ≤200 mcg/day budesonide equivalent
   • Medium: 200-400 mcg/day; High: >400 mcg/day
   • Mechanism: reduce inflammation, decrease AHR, prevent remodeling
   • Side effects: oral candidiasis (rinse mouth), growth suppression with high doses (minimal at low dose)
2. Long-Acting Beta-2 Agonists (LABAs) (add to ICS if uncontrolled on ICS alone)
   • Salmeterol, Formoterol
   • NEVER use LABA without ICS (increased risk of asthma death if used alone)
3. Leukotriene Receptor Antagonists (LTRAs)
   • Montelukast (oral, once daily)
   • Used as add-on or ICS alternative in mild persistent asthma
   • Useful: exercise-induced bronchoconstriction, aspirin-sensitive asthma, concomitant allergic rhinitis
   • FDA warning (2020): neuropsychiatric events (depression, nightmares, suicidal ideation)
4. Long-Acting Muscarinic Antagonists (LAMAs)
   • Tiotropium (Spiriva Respimat): add-on therapy for severe asthma (≥6 years)
5. Theophylline (now rarely used)
   • Oral bronchodilator/anti-inflammatory
   • Narrow therapeutic index; drug interactions; monitor levels

GINA Step-wise Approach:

Biologics (Step 5 - severe uncontrolled):

• Omalizumab (anti-IgE): for allergic asthma; monthly SC; reduces exacerbations by 50%
• Mepolizumab, Reslizumab (anti-IL-5): for eosinophilic asthma; reduces eosinophils
• Benralizumab (anti-IL-5Rα): depletes eosinophils
• Dupilumab (anti-IL-4Rα): blocks IL-4 and IL-13 signalling; type 2 inflammation; also treats eczema

Reliever medications:

• SABA (Short-Acting Beta-2 Agonists): salbutamol (albuterol) - first-line reliever
  • Inhaled: 2-4 puffs via MDI+spacer; or 2.5 mg nebulized
  • Onset: 5-15 min; Duration: 4-6 hours
• ICS-formoterol (MART): now preferred as reliever in Steps 3-5 (reduces exacerbations vs. SABA-only)
• SAMA (Short-acting muscarinic antagonist): Ipratropium - add-on in severe acute exacerbation

B. Management of Acute Exacerbation:

1. Salbutamol MDI + spacer: 4-8 puffs, every 20 min for 3 doses, then reassess
2. Prednisolone 1-2 mg/kg/day (max 40 mg) oral, for 3-5 days
3. Supplemental O₂ to maintain SpO₂ >94%

1. Continuous nebulized salbutamol (0.15 mg/kg/dose, max 5 mg) every 20 min or continuous
2. Ipratropium bromide nebulized (added to salbutamol in first hour) - reduces hospitalization
3. IV/oral Prednisolone or IV hydrocortisone (4 mg/kg q6h)
4. IV Magnesium sulphate 50 mg/kg (max 2g) over 20 min - bronchodilator; for severe/life-threatening; IV or nebulized
5. IV Salbutamol: 15 mcg/kg bolus -> infusion for life-threatening
6. IV Aminophylline (loading + infusion): for refractory severe asthma (declining use due to side effects)
7. Heliox (Helium-Oxygen mixture): reduces airway resistance; used in near-fatal asthma
8. Intubation and mechanical ventilation: last resort; permissive hypercapnia strategy

• As above + intubation if needed
• Ketamine (bronchodilator properties; induction agent)
• Inhalation anesthetics (isoflurane): for refractory bronchospasm

---

Differential Diagnosis ("Not all that wheezes is asthma")

• Bronchiolitis (infants)
• Viral-induced wheeze
• Cystic fibrosis
• Foreign body aspiration (unilateral wheeze)
• Tracheomalacia / bronchomalacia
• Vascular rings
• Cardiac failure (cardiac asthma)
• Vocal cord dysfunction (paradoxical vocal cord movement)
• Endobronchial tuberculosis
• Allergic bronchopulmonary aspergillosis (ABPA)

---

Monitoring Asthma Control

• Well-controlled: ≤1 day/week symptoms; no nocturnal waking; PEFR >80%; no limitation of activity
• Partly controlled: >2 days/week symptoms; or nighttime symptoms; or PEFR 60-80%
• Uncontrolled: ≥3 features of partial control

---

Prevention

Primary:

• Avoid allergen sensitization (breastfeeding, avoid smoking in pregnancy/early life)
• Vitamin D supplementation in infancy
• Diverse microbial exposure (farm exposure, microbiome)

Secondary:

• Regular ICS prevents progression and remodeling
• Allergen immunotherapy (specific desensitization):
  • Subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT)
  • HDM SLIT particularly useful in children ≥5 years with HDM-sensitive asthma
  • Reduces symptoms, medication use, may prevent new sensitizations

Tertiary:

• Avoid known triggers
• Written Asthma Action Plan
• Regular review and step-down when controlled

---

Prognosis

• 50-60% of childhood asthma remits by adulthood (especially mild intermittent)
• Persistent asthma: early-onset, severe, continued allergen exposure, female sex, atopy
• Airway remodeling with long-standing uncontrolled disease -> fixed obstruction
• Asthma deaths: rare in children with modern management; associated with under-treatment, overuse of SABA, inadequate ICS

---

Quick Reference: What to Emphasize in 25-mark Answers