Pediatrics

Definition and Mechanism

A hypercyanotic or ""Tet"" spell is a paroxysmal, potentially life-threatening episode of acute worsening of cyanosis occurring characteristically in infants with Tetralogy of Fallot (and other forms of right ventricular outflow tract obstruction with a VSD), caused by a sudden, dynamic increase in right ventricular outflow tract (infundibular) obstruction and/or a fall in systemic vascular resistance. Either mechanism increases right-to-left shunting across the VSD, acutely reducing pulmonary blood flow and causing profound hypoxaemia.

Precipitating Factors

• Crying, feeding, defecation (Valsalva-like straining), fever, dehydration, waking from sleep, and any event causing a fall in systemic vascular resistance or an increase in myocardial contractility/heart rate
• Typically occurs in infants 2–6 months to 2 years of age, often peaking in frequency/severity in the morning after waking

Clinical Features

• Sudden onset of increasing cyanosis/blue discolouration, deep and rapid (hyperpnoeic) breathing without significant respiratory distress signs (a distinguishing feature from primary respiratory causes of cyanosis), irritability/inconsolable crying progressing to limpness/lethargy
• Softening or disappearance of the previously audible systolic ejection murmur (reflects markedly reduced flow across the obstructed RVOT as the obstruction worsens — a paradoxical but classic sign)
• Severe spells may progress to syncope, seizures (from cerebral hypoxia), or death if not promptly treated

Management – Stepwise Approach

Longer-Term/Preventive Management

• Oral propranolol may be started for prevention of recurrent spells while awaiting definitive/corrective surgery
• Correction of anaemia and adequate hydration (avoiding fasting periods) reduce spell frequency, since anaemia increases the tendency to hypoxaemia and viscosity changes with dehydration worsen shunting
• Definitive treatment is early complete surgical repair — recurrent or severe spells are themselves an indication to expedite surgery (or a palliative BT shunt if the infant is not yet a candidate for complete repair)

Principles of Catch-Up Immunization

• A vaccine series is never restarted regardless of the interval since the last (or only) dose — the child simply continues from where doses are missing, respecting minimum age and minimum interval requirements between doses
• Live vaccines not given together on the same day should be separated by at least 4 weeks unless given simultaneously
• Vaccines are prioritised by the child's current risk of exposure and disease severity — in a 5-year-old, this means completing protection against measles/rubella, polio, diphtheria-pertussis-tetanus, and age-appropriate additions (typhoid, hepatitis A/B, varicella) become relevant, while some purely infancy-specific vaccines (e.g., Hib, PCV, Rotavirus) have reduced or no benefit if not started in the appropriate early window, per IAP recommendations
• This particular child has received ONLY BCG at birth and nothing subsequently — essentially every other vaccine on the schedule needs catch-up planning at age 5 years

Suggested Catch-Up Plan for This 5-Year-Old (as per IAP schedule principles)

Specific Points for This Age Group (5 years)

• Hib conjugate vaccine is generally NOT recommended for catch-up beyond 5 years of age in an otherwise healthy child, as the risk of invasive Hib disease falls sharply after this age due to acquired natural immunity
• Rotavirus vaccine has a strict upper age cut-off (first dose not after 14–15 weeks; last dose by 8 months) and is therefore NOT given at all in a 5-year-old catch-up schedule — the window has permanently passed
• PCV (pneumococcal conjugate vaccine) catch-up beyond 2 years in a healthy child is of reduced benefit and generally not routinely pursued unless the child has a specific risk factor (immunocompromise, asplenia, chronic illness), in which case it is still recommended
• OPV vs IPV: as per current recommendations, at least one dose of IPV should be included in the catch-up schedule alongside OPV doses to ensure adequate humoral (IPV) immunity, particularly relevant in the polio-endgame context
• The exact number and spacing of remaining doses should be individualised and confirmed against the current IAP-ACVIP schedule/product inserts at the time of administration, and the family counselled that catch-up requires multiple visits over several months to complete, with each visit an opportunity to reinforce compliance

Classification of Congenital Heart Disease (CHD)

CHD occurs in approximately 8–10 per 1000 live births and is the most common group of major congenital malformations. The most clinically useful classification, followed in Nelson Textbook of Pediatrics and Ghai Essential Pediatrics, is based on the presence or absence of cyanosis, further sub-divided by pulmonary vascularity and shunt physiology.

A. Clinical (Physiological) Classification

B. Mnemonic-Based Cyanotic CHD List (5 T's + others)

• Tetralogy of Fallot (commonest cyanotic CHD overall after infancy)
• Transposition of great arteries (commonest cyanotic CHD presenting in the newborn period)
• Tricuspid atresia
• Truncus arteriosus
• Total anomalous pulmonary venous connection
• Others: Pulmonary atresia with intact septum, Ebstein anomaly, Hypoplastic left heart syndrome, Double outlet right ventricle

C. Anatomical/Segmental (Van Praagh) Classification

Used chiefly by paediatric cardiologists/surgeons for precise surgical planning — describes cardiac anatomy in three segments: (1) Atrial situs (solitus/inversus/ambiguus), (2) Ventricular looping (D-loop/L-loop), and (3) Relationship of the great arteries (normally related/D-TGA/L-TGA), summarised as {S,D,S} for the normal heart. This systematic segmental approach is essential in complex CHD such as single ventricle physiology and heterotaxy syndromes.

D. Epidemiological Classification (by frequency)

VSD (largest single group, ≈25–30%) > ASD > PDA > Pulmonary stenosis > Tetralogy of Fallot > Coarctation of aorta > Aortic stenosis > TGA > others.

Surgical Management of Congenital Heart Disease

Surgical strategy in CHD is broadly divided into palliative procedures (improve physiology without correcting the underlying defect, used as a bridge to definitive repair or in single-ventricle pathways) and corrective/reparative procedures (restore normal or near-normal anatomy and physiology). The timing of surgery is individualised based on lesion type, symptoms, growth failure, pulmonary vascular resistance, and risk of Eisenmenger physiology.

1. Palliative Procedures

2. Corrective/Reparative Procedures (Lesion-wise)

3. General Principles Guiding Surgical Timing

• Duct-dependent lesions (critical pulmonary/aortic stenosis, HLHS, TGA, pulmonary/tricuspid atresia) require prostaglandin E1 infusion to maintain ductal patency and urgent surgical/catheter intervention in the neonatal period
• Repair of large left-to-right shunts is timed before irreversible pulmonary vascular disease (Eisenmenger syndrome) sets in — generally before 1 year of age for large VSD/AVSD
• Down syndrome patients with AV canal defects need EARLIER repair (by 3–4 months) as they develop pulmonary vascular obstructive disease faster than the general population
• Cardiopulmonary bypass, deep hypothermic circulatory arrest, and improved myocardial protection have allowed increasingly complex neonatal repairs with markedly improved survival over the last two decades
• Minimally invasive/transcatheter techniques (device closure of ASD/VSD/PDA, balloon valvuloplasty for pulmonary/aortic stenosis, stenting of coarctation) have progressively reduced the need for open surgery in selected anatomically suitable lesions
• Hybrid procedures (combined surgical + catheter-based approach, e.g., hybrid Norwood with PA banding + ductal stenting) are increasingly used in high-risk neonates as a bridge to later definitive surgery

Background

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder caused by biallelic deletion/mutation of the SMN1 gene (5q13), leading to progressive loss of anterior horn cells. Disease severity is modified by the copy number of the near-identical paralogue SMN2, which produces mostly non-functional, truncated protein due to exon-7 skipping, but each extra SMN2 copy provides a small amount of functional protein and correlates with milder phenotype. Until 2016, management was purely supportive (respiratory, nutritional, orthopaedic); three disease-modifying therapies (DMTs) approved since then have transformed the natural history of the disease.

The Three Approved Disease-Modifying Therapies

Key Clinical Points

• Newborn screening for SMA is now recommended in many national programmes — presymptomatic treatment (started before onset of motor neuron loss) gives dramatically superior motor outcomes compared to treatment after symptom onset, making early diagnosis the single biggest determinant of outcome
• Onasemnogene abeparvovec is a one-time gene therapy but carries risk of hepatotoxicity (needs prednisolone cover and LFT monitoring), thrombotic microangiopathy, and requires anti-AAV9 antibody titres to be low (pre-existing immunity precludes use)
• Nusinersen requires repeated intrathecal administration (lumbar puncture) — challenging in patients with scoliosis/spinal instrumentation, where CT/fluoroscopy-guided or intraoperative administration may be needed
• Risdiplam crosses the blood-brain barrier and distributes systemically, with theoretical benefit for extra-CNS manifestations of SMA (cardiac, GI); long-term safety data (including on male fertility, seen in animal studies) are still being accumulated
• Combination/sequential therapy (e.g., gene therapy followed by risdiplam) is being studied where a single agent gives suboptimal SMN protein levels, though robust comparative trial data remain limited
• None of the current therapies reverse already-lost motor neurons — hence the overwhelming emphasis on newborn screening and presymptomatic initiation

Standard of Care Beyond DMTs

Multidisciplinary care per the 2017/2024-updated International SMA Standards of Care: respiratory (non-invasive ventilation, airway clearance/cough-assist), nutritional (early gastrostomy where needed), orthopaedic (scoliosis surveillance and bracing/surgery), and rehabilitation support remain essential even in DMT-treated children.

Principles of Paediatric ART

Current WHO/NACO and IAP guidance recommends immediate ART for ALL children diagnosed with HIV, regardless of CD4 count or WHO clinical stage (""treat all"" strategy) — a major shift from earlier CD4-threshold-based initiation. Goals are durable viral suppression, immune reconstitution, prevention of transmission, and normal growth/neurodevelopment.

Preferred First-Line Regimens by Age (WHO 2021 onward)

Why Dolutegravir (DTG) Represents the Major Recent Advance

• Integrase strand transfer inhibitor (INSTI) — blocks HIV integration into host genome
• Superior virological suppression and a markedly higher genetic barrier to resistance compared with efavirenz- or nevirapine-based regimens historically used in children
• Available as child-friendly dispersible, taste-masked tablets that can be dosed by weight band, improving palatability and adherence versus older syrups
• Early concern about neural tube defects with periconceptional DTG exposure in women of childbearing potential has been substantially reassured by subsequent large surveillance data (Tsepamo study), and DTG remains preferred even in this group with appropriate counselling

Other Key Advances

• Point-of-care early infant diagnosis (POC-EID) using HIV DNA/RNA PCR platforms allows same-day results and rapid ART initiation in HIV-exposed infants, drastically cutting loss-to-follow-up compared with centralised laboratory testing
• Long-acting formulations (e.g., long-acting cabotegravir + rilpivirine injections) are being extended into adolescent populations to address adherence challenges, though paediatric approval for younger children is still evolving
• Fixed-dose combinations (FDCs) and once-daily regimens reduce pill burden and improve caregiver-reported adherence, a major determinant of long-term virological success in children
• Universal ART initiation (""treat all"") plus optimised regimens has shifted the focus of paediatric HIV care toward long-term issues: growth, neurocognitive outcomes, cardiometabolic risk, and transition of adolescents to adult care

Definition

Operational (working) definition: a continuous seizure lasting ≥5 minutes, OR two or more discrete seizures without full recovery of consciousness in between. ""Established"" status epilepticus is seizure activity persisting despite two adequate doses of anti-seizure medication; ""refractory"" status epilepticus continues despite first- and second-line therapy, requiring anaesthetic/coma-inducing agents; ""super-refractory"" status persists ≥24 hours despite anaesthetic therapy or recurs on weaning.

Time-Bound Management Protocol

Simultaneous Steps Throughout

• Search for and correct precipitating causes in parallel with treatment: hypoglycaemia, hyponatraemia, hypocalcaemia, CNS infection (meningitis/encephalitis), trauma, toxin ingestion, non-compliance with existing AEDs in a known epileptic, febrile illness
• Investigations: blood glucose, electrolytes (Na, Ca, Mg), ABG, AED levels (if applicable), septic screen/CSF study if infection suspected, neuroimaging if focal signs or raised ICP concern
• Continuous cardiorespiratory monitoring is mandatory once benzodiazepines/second-line AEDs are given, given the risk of respiratory depression, hypotension, and arrhythmia (especially with IV phenytoin)

Rationale

Young children (especially <5 years) in household contact with a sputum smear-positive (""open""/infectious) pulmonary TB case are at very high risk of infection and rapid progression to disseminated/severe disease (miliary TB, TB meningitis) because of immature cell-mediated immunity. TB preventive treatment (TPT) in exposed, asymptomatic, disease-free contacts reduces the risk of progression from infection to active disease by 60–90%.

Step 1: Screen Before Prophylaxis

Who Receives TB Preventive Treatment

• All children <5 years in household contact with a smear-positive (or clinically diagnosed) pulmonary TB case, regardless of tuberculin skin test (TST)/IGRA status
• Children ≥5 years and adolescents with a positive TST/IGRA in household contact with an infectious case
• All HIV-infected children who are household contacts of a TB case, and all HIV-infected children with a positive TST, irrespective of contact history
• Neonates born to mothers with active TB (special approach – see below)

Preventive Regimens (National TB Elimination Programme / WHO)

Special Situations

• Pyridoxine (Vitamin B6) supplementation is added with isoniazid-based regimens in malnourished children, adolescents, and those with HIV to prevent peripheral neuropathy
• Neonate born to a mother with active TB: if mother is smear-positive/infectious at delivery, the infant should NOT be given BCG immediately; give isoniazid prophylaxis for 6 months, then perform TST – if negative, give BCG; if the infant develops disease at any point, switch to full treatment
• Contact tracing (""reverse"" and ""forward"") should be done for every index case as per NTEP protocol, and TPT should be documented and monitored for completion — poor adherence remains the biggest programmatic challenge
• Multidrug-resistant (MDR)-TB contact: preventive regimens differ (e.g., fluoroquinolone-based) and should be managed at a specialist centre — standard isoniazid/rifampicin prophylaxis is not appropriate

Overview

Acute lymphoblastic leukaemia (ALL) is the commonest childhood malignancy. Contemporary risk-stratified, multi-agent chemotherapy protocols (e.g., BFM-based, UKALL, ICiCLe/MCP-841 in India) have raised long-term event-free survival to 85–90% in standard-risk disease. Treatment is organised into sequential phases, with intensity and drug choice tailored by risk stratification.

Risk Stratification (Key Determinants)

• Age at diagnosis (1–9 years = most favourable; <1 year or ≥10 years = higher risk)
• Initial WBC count at diagnosis (≥50,000/µL = higher risk)
• Immunophenotype (B-lineage generally better prognosis than T-lineage in most protocols, though treatment is intensified accordingly rather than implying worse overall outcome with modern therapy)
• Cytogenetics/molecular markers: favourable – hyperdiploidy >50 chromosomes, ETV6-RUNX1 (TEL-AML1); unfavourable – BCR-ABL1 (Philadelphia chromosome), KMT2A (MLL) rearrangement, hypodiploidy
• Minimal residual disease (MRD) by flow cytometry/PCR at end of induction (day 29) and later time-points — now the single most powerful independent predictor of relapse and the backbone of modern risk-adapted therapy

Phases of Treatment

Recent Advances

• MRD-directed risk stratification – treatment intensity is escalated or de-escalated based on MRD clearance kinetics rather than presenting features alone, improving cure rates while minimising overtreatment toxicity in truly low-risk patients
• Targeted therapy for Philadelphia-chromosome-positive ALL: addition of tyrosine kinase inhibitors (imatinib/dasatinib) to chemotherapy backbone has transformed outcomes in this previously very high-risk subgroup, now approaching outcomes of Ph-negative ALL
• Immunotherapy for relapsed/refractory B-ALL: Blinatumomab (bispecific CD19-CD3 T-cell engager) and Inotuzumab ozogamicin (anti-CD22 antibody-drug conjugate) provide effective bridge-to-transplant options
• CAR-T cell therapy (tisagenlecleucel, anti-CD19 chimeric antigen receptor T-cells) is approved for relapsed/refractory B-ALL in children and young adults, achieving high remission rates even in heavily pre-treated disease, though with risk of cytokine release syndrome and neurotoxicity requiring specialised centre management
• Reduction in use of cranial radiotherapy (reserved for very select high-risk/CNS-relapse cases) due to recognised late effects (neurocognitive decline, secondary malignancy, endocrinopathy), replaced by intensified intrathecal and systemic CNS-penetrant chemotherapy
• Pharmacogenomic testing (e.g., TPMT/NUDT15 genotyping) individualises 6-mercaptopurine dosing to reduce severe myelosuppression in genetically susceptible children

Concept

Point-of-care ultrasound (POCUS) refers to a focused, goal-directed ultrasound examination performed and interpreted by the treating clinician at the bedside in real time to answer a specific clinical question, integrated directly into the physical examination — distinct from a comprehensive radiologist-performed study. Its portability, absence of ionising radiation, repeatability, and increasing availability of compact handheld devices have made it a rapidly growing extension of clinical assessment in paediatric emergency and critical care.

Key Clinical Applications in Sick Children

Advantages Specific to the Paediatric Setting

• No ionising radiation — particularly valuable given children's higher lifetime radiosensitivity and the frequent need for repeated imaging in critically ill children
• Can be performed at the bedside without transporting a haemodynamically unstable child to the radiology suite, reducing risk during transport
• Real-time integration with clinical decision-making (""visual stethoscope"") shortens time to diagnosis in time-critical situations (tamponade, pneumothorax, intussusception)
• Increasing evidence supports its incorporation into paediatric early warning/shock protocols and resuscitation algorithms (e.g., extended FAST in trauma, lung ultrasound in bronchiolitis/pneumonia)

Limitations

• Operator-dependent; requires structured training and credentialing for reliable, reproducible interpretation
• Focused/binary answers to specific questions — NOT a substitute for a comprehensive formal radiology-performed ultrasound when a broader differential needs evaluation
• Technically more challenging in a struggling, uncooperative young child, though generally easier than in adults due to thinner chest wall and less lung aeration artifact overall

Definition

Polyarticular JIA (ILAR classification) is defined as arthritis affecting ≥5 joints during the first 6 months of illness, sub-classified as Rheumatoid Factor (RF)-positive (resembles adult rheumatoid arthritis, generally more severe/erosive course) or RF-negative (more heterogeneous group). Treatment goals under the modern ""Treat-to-Target"" paradigm are inactive disease or clinically minimal disease activity, achieved as early as possible to prevent joint damage, growth disturbance, and long-term disability.

Treatment Ladder — Evolution to Modern Practice

Key Recent Advances

• Treat-to-target / early aggressive therapy: shift from a slow ""step-up"" ladder to early initiation of methotrexate ± early biologic in patients with poor prognostic features (RF/anti-CCP positivity, polyarticular RF+ disease, early erosions), aiming for inactive disease within months rather than years
• Expanding biologic choices with different mechanisms — allows switching within class (e.g., between TNF inhibitors) or to a different mechanism (IL-6, abatacept, JAK inhibitor) in partial responders, individualising therapy
• Withdrawal/de-escalation strategies – growing evidence base guiding when and how to safely taper biologics/methotrexate after sustained remission, balancing flare risk against drug toxicity/burden
• Treat-to-target clinical tools: standardised composite disease activity scores (JADAS – Juvenile Arthritis Disease Activity Score) are used to objectively guide escalation/de-escalation decisions in clinical practice and trials
• Growing recognition of the need for monitoring for uveitis (particularly ANA-positive, young-onset disease) with regular ophthalmological screening regardless of joint disease activity, as ocular inflammation can be asymptomatic and sight-threatening