Paediatrics Flashcards

Question

How common is neonatal polycythemia

Answer 1

1-5% of newborns

Answer 2

``` Small for gestational age Large for gestational age Infants of diabetic mothers Twin to twin transfusion syndrome (recipient) Maternal tobacco use Chromosomal abnormalities Delayed umbilical cord clamping ```

Answer 3

Delayed umbilical cord clamping → erythrocyte transfusion → ↑ circulating red blood mass (HCT) Placental insufficiency or chronic intrauterine hypoxia → increased intrauterine erythropoiesis → ↑ circulating red blood mass (HCT)

Answer 4

``` Respiratory distress, cyanosis, apnea Poor feeding, vomiting Hypoglycemia Plethora Lethargy and irritability Tremors or seizures ```

Answer 5

Venous HCT > 65% | Hemoglobin > 22 g/dL

Answer 6

Monitoring IV hydration Partial exchange transfusion: a procedure in which part of the blood is replaced with an isotonic fluid to lower the hematocrit -Indicated in asymptomatic patients with high hematocrit (> 75%) or symptomatic patients with hematocrit > 65% -Increased risk of necrotising enterocolitis

Answer 7

Hypoglycaemia Hyperbilirubinaemia Necrotising enterocolitis

Answer 8

A benign self limiting rash that appears within the first week of life

Answer 9

Small red macules and papules that progress to pustules with surrounding erythema Located on trunk and proximal extremities Spares the palms of hands and soles of feet

Answer 10

Based on clinical appearance of rash | Biopsy or smear of pustual (rarely necessary) but would show high eosinophils

Answer 11

Observation only

Answer 12

Typically resolves without complications within 7-14 days

Answer 13

AKA Mongolian spot | A benign blue-ray pigmented lesion of newborns

Answer 14

Asian and Native American: 85–100% African American: > 60% Hispanic: 46–70% White: < 10%

Answer 15

Melanocytes migrating from the neural crest to the epidermis during development become entrapped in the dermis

Answer 16

Blue-gray pigmented macule (may also be green or brown) Diameter: typically < 5 cm, may be > 10 cm Location: most common on the back, also seen on the buttocks, flanks, and shoulders

Answer 17

Based on clinical appearance It is important to document the diagnosis of Mongolian spots, as they may resemble bruises and lead to false suspicions of child abuse.

Answer 18

Usually resolves spontaneously during childhood (typically by the age of 10 years)

Answer 19

``` Vary in size: < 1.5 cm to > 20 cm A nevus larger than 20 cm in size is referred to as a giant congenital melanocytic nevus Light to darkly pigmented lesion Often with increased hair growth 1/20,000 births ```

Answer 20

Surgical excision or laser ablation (depending on type and size of lesion)

Answer 21

Large nevi are at risk of degeneration for need frequent follow up

Answer 22

AKA strawberry hemangioma Occurs in 3-10% of infants Mostly affects girls Manifests during the first few days to months of life Progressive presentation: blanching of skin → fine telangiectasias → red painless papule or macule (strawberry appearance) Most commonly on head and neck Usually solitary lesions

Answer 23

Abnormal development of vascular endothelial cells | Rapid proliferation followed by subsequent spontaneous slow involution (occurring at the age of 5–8 years)

Answer 24

Based on clinical findings | The differential diagnosis of a cherry angioma is found mostly in adults

Answer 25

Active nonintervention: (monitoring, parental education) Systemic therapy with propranolol in complicated cases: - Rapidly growing cutaneous hemangiomas - Periorbital hemangioma: vascular anomaly in the periorbital region, most commonly the upper eyelid - Hemangiomas in the airways, gastrointestinal tract, or liver - Hemangiomas with high risk of complications If unresponsive to medication: - Cryotherapy - Laser therapy - Resection if necessary

Answer 26

Ulceration | Disfigurement

Answer 27

Usually good prognosis Spontaneous resolution is common Visual impairment if periorbital hemangioma is left untreated

Answer 28

Definition: tiny epidermal papules caused by the buildup of keratin and sebaceous secretions Clinical features: pinhead-sized lesions located on the face/trunk Treatment: not necessary Prognosis: benign skin lesion, spontaneous resolution without scarring

Answer 29

Naevus flammeus, port-wine stain, firemark Definition: congenital, benign vascular malformations of the small vessels in the dermis Epidemiology: may occur in association with a neurocutaneous disorder such as Sturge-Weber syndrome Clinical features: typically unilateral, blanchable, pink-red patches that grow and become thicker and darker with age Treatment: cosmetic laser treatment if desired (not necessary) Prognosis: benign skin lesion

Answer 30

AKA TNPM Definition: a benign, transient, idiopathic neonatal skin condition Epidemiology: - Incidence: ∼ 2% - Most commonly occurs in African American infants (5 %) Clinical features: - Solitary or clustered pustules and vesicles on a nonerythematous base - Hyperpigmented, erythematous macules and collarettes of fine scale - Most commonly affects the forehead, anterior neck, and lower back Treatment: reassurance Prognosis: benign, self-limiting skin lesion

Answer 31

Definition: a pale patch of skin that does not create erythema in response to trauma, heat, or cold Etiology: caused by a vascular anomaly (increased sensitivity of cutaneous blood vessels to naturally occurring catecholamines) Treatment: not required

Answer 32

AKA Noonan syndrom with multiple lentigines Lentigines: lenticular hyperpigmentation (dark macules) Electrocardiographic conduction abnormalities Ocular hypertelorism Pulmonary stenosis Abnormalities of genitalia Retardation of growth Deafness

Answer 33

A descriptive term for neonates born with multiple bluish, purple marks in the skin, which can be due to extramedullary erythropoiesis, purpura, or metastases. The differential includes various cancers (e.g., rhabdomyoscarcoma), blood disorders (e.g., hemolytic disease of the new born), and congenital viral infections (e.g., rubella)

Answer 34

``` Macrosomia or anatomical abnormalities Extremely premature infants; low birth weight Abnormal fetal presentation Breech presentation Shoulder dystocia Forceps-assisted delivery or vacuum delivery Prolonged or rapid labor Small maternal stature ```

Answer 35

Soft tissue injuries of the scalp in infants are mostly caused by shearing forces during vacuum or forceps delivery. Head molding: - Transient deformation of the head into an elongated shape due to external compression of the fetal head as it passes through the birth canal during labor - Typically resolves within a few days after the birth Caput succedaneum: - Benign oedema of the scalp tissue that extends across the cranial suture lines - Firm swelling; pits if gentle pressure is applied - No treatment required; resolves within hours or days Cephalohematoma: - Subperiosteal hematoma that is limited to cranial suture lines - Complications: calcification of the hematoma, secondary infection - No treatment required; resolves within several weeks or months Subgaleal hemorrhage: - Rupture of the emissary veins and bleeding between the periosteum of the skull and the aponeurosis that may extend across the suture lines - Associated with a high risk of significant hemorrhage and hemorrhagic shock

Answer 36

Epidemiology: most common fracture during birth (∼ 2% of deliveries) ``` Clinical features: Usually asymptomatic Possible pseudoparalysis Bone irregularities, crepitus, and tenderness over the clavicle possible on palpation Possible brachial plexus palsy ```

Answer 37

Clinical diagnosis | X-ray only indicated in cases of gross bone deformation

Answer 38

Reassurance and promote gentle handling of the arm (e.g., while dressing) To avoid discomfort, pin shirt sleeve to the front of the shirt with the arm flexed at 90 degrees Consider analgesics Follow-up 2 weeks later to confirm proper healing: via clinical findings of a callus formation, and possibly an x-ray Usually self-resolves within 2–3 weeks without surgical intervention or long-term complications

Answer 39

Twisted or rotated neck caused by contraction of the sternocleidomastoid muscle It can be acquired or congenital

Answer 40

Acquired torticollis: - Sternocleidomastoid or trapezius muscle injury - Cervical muscle spasm - Cervical nerve irritation Congenital torticollis: - Not fully understood; likely from muscular or skeletal injury during delivery with subsequent fibrosis and contracture of the sternocleidomastoid muscle - Associated with: - - Intrauterine constraint, which causes unilateral shortening of the sternocleidomastoid muscle - -- Oligohydramnios - -- Multiple gestation - -- Macrosomia - - Decreased fetal movement - - Breech presentation - - Assisted vaginal delivery

Answer 41

Head noticeably tilted to one side with the chin rotated towards the opposite side Muscular tightness; limited passive range of motion Potentially palpable thickening of the SCM Conditions associated with congenital torticollis: - Developmental dysplasia of the hips - Brachial plexus palsy - Clubfoot - Craniofacial asymmetry

Answer 42

``` Postural preference Vertebral anomalies Absence of cervical musculature Ocular anomalies Underlying conditions (e.g. spina bifida) ```

Answer 43

Early initiation of physiotherapy, passive positioning | Surgery at 12 months of age if conservative management is insufficient: myotomy or bipolar release of the affected SCM

Answer 44

Craniofacial asymmetry | Scoliosis of the cervical spine

Answer 45

Epidemiology: most common cranial nerve injury during birth Pathomechanism: - Injury occurs during forceps-assisted delivery (most common) - Prolonged birth in which the head is pressed against the maternal sacral promontory Clinical features Peripheral facial nerve palsy: difficulty feeding, incomplete eye closure, absent nasolabial fold Treatment: eye care with artificial tears and ointment Prognosis: spontaneous recovery in 90% of cases within several weeks

Answer 46

Excessive lateral traction on the neck during delivery → injury to the upper trunk of the brachial plexus → Erb palsy (most common iatrogenic brachial plexus injury during delivery) Excessive traction on the arm during delivery → injury to the lower trunk of the brachial plexus → Klumpke palsy Prognosis: approx. 25% of affected infants experience persistent functional impairment

Answer 47

An obstetric emergency in which the anterior shoulder of the fetus becomes impacted behind the maternal pubic symphysis during vaginal delivery Occurs in ~0.2-3% of births

Answer 48

``` History of shoulder dystocia Fetal macrosomia Prolonged second stage of labor Maternal diabetes mellitus Maternal obesity ```

Answer 49

Features of arrested active phase of labor Turtle sign: the fetal head is partially delivered but retracts against the perineum Failed restitution of the head

Answer 50

Clinical diagnosis

Answer 51

The patient should stop bearing down and lie supine with the buttocks on the edge of the bed. Perform shoulder dystocia maneuvers: - First-line: McRoberts maneuver - Any of the other internal maneuvers may be attempted to next (Rubin maneuver, Woods maneuver, Delivery of posterior arm) - Move to another maneuver if delivery is not accomplished within 20–30 seconds. - If all above maneuvers fail, attempt the all fours position. Last-resort options: - Fracture of fetal clavicle - Zavanelli maneuver - Symphysiotomy

Answer 52

Fetal: - Brachial plexus injury (Erb palsy is more common than Klumpke palsy) - Clavicle or humerus fracture - Hypoxia over an extended period of time as a result of umbilical cord compression Maternal: - Perineal lacerations - Postpartum hemorrhage

Answer 53

An intrauterine infection of the foetal membranes, placenta and amniotic fluid most commonly caused by bacteria ascending from the vagina

Answer 54

Common bacteria: - Ureaplasma urealyticum (up to 50% of cases) - Mycoplasma hominis (up to 30% of cases) - Gardnerella vaginalis - Bacteroides - Group B streptococcus - E. coli

Answer 55

Prolonged labor or premature rupture of membranes (PROM) Pathological bacterial colonization of vaginal tract (e.g., STDs, frequent UTIs) Iatrogenic: multiple digital vaginal exams, invasive procedures (e.g., amniocentesis)

Answer 56

Maternal: - Fever (> 38 °C or > 100°F) - Tachycardia > 120/min - Uterine tenderness, pelvic pain - Malodorous and purulent amniotic fluid, vaginal discharge - Premature contractions, PROM Fetal tachycardia > 160/min in cardiotocography

Answer 57

Chorioamnionitis is a clinical diagnosis (fever plus ≥ 1 additional symptom). Tests support or confirm diagnosis if the clinical presentation is ambiguous (e.g., in subclinical chorioamnionitis). Maternal blood tests: - Leukocytosis > 15,000 cells/μL (∼ 70–90% of cases) - ↑ CRP Bacterial cultures: - Urogenital secretions - Amniotic fluid (most reliable, but rarely conducted) - Group B Streptococcus screening: cervicovaginal and rectal swabs

Answer 58

Maternal antibiotic therapy: - Vaginal delivery: IV ampicillin plus gentamicin (broad coverage) - Cesarean delivery: IV ampicillin and gentamicin, plus clindamycin (anaerobe coverage to minimize postcesarean complications, e.g., endometritis) Delivery: - Swift delivery is generally indicated to minimize both maternal and fetal complications. - Cesarean delivery is not generally indicated, but is often necessary because of obstetrical complications (e.g., insufficient contractions).

Answer 59

Maternal: - Uterine atony - Postpartum hemorrhage - Endometritis - Septic shock - DIC - Venous thrombosis - Pulmonary embolism - Death Fetal/neonatal: - Fetal deat - Premature birth - Asphyxia - Intraventricular hemorrhage - Cerebral palsy - Neonatal infection

Answer 60

Early-onset infection/sepsis: - ≤ 6 days after delivery - Common causes: - -chorioamnionitis - -bacterial colonization of the maternal genital tract (pathogen transfer to the infant) - Common pathogens: - -group B Streptococcus (GBS, Streptococcus agalactiae) and E. coli; - -less common are Listeria monocytogenes, Staphylococcus aureus, Enterococcus, and Haemophilus influenzae. Late-onset infection/sepsis: - 7–89 days after delivery - Common causes: hospital acquired infection - Common pathogens: group B Streptococcus (GBS, Streptococcus agalactiae) and E. coli; less common are coagulase-negative Staphylococcus, Staphylococcus aureus, Klebsiella, Pseudomonas

Answer 61

Maternal: - Fever - PROM, premature labor - Infections (e.g., UTI) Fetal: - Premature birth, low birth weight, low Apgar score - Difficult delivery - Asphyxia - Intravascular catheter or nasal cannula (in late-onset sepsis)

Answer 62

General presentation: - Nonspecific - Irritability, lethargy, poor feeding - Temperature changes (fever and hypothermia both possible) - Cardiocirculatory: tachycardia, hypotension, poor perfusion, and delayed capillary refill > 3 sec - Respiratory: tachypnea, dyspnea (e.g., expiratory grunting), apnea (more common in preterm infants) - Skin tone: jaundiced and/or bluish-gray (indicates poor perfusion) Specific symptoms: - Neonatal meningitis - - Often no signs of meningism - - Early phase: general symptoms, vomiting - - Late phase: bulging fontanelles, shrill crying, seizures, stupor - Neonatal pneumonia - - Tachypnea with intercostal/sternal retractions and nasal flaring - - Reduced oxygen saturation with cyanosis

Answer 63

Blood cultures or urine culture for suspected UTI -In GBS sepsis: blood agar plate reveals β-hemolytic, gram-positive cocci that enlarge the area of hemolysis formed by S. aureus Blood tests: - Leukocytopenia or leukocytosis, thrombocytopenia - ↑ CRP Lumbar puncture: -Test cerebrospinal fluid for possible meningitis Chest x-ray: -May reveal clear signs of pneumonia (e.g., segmental infiltrates) but more often nonspecific with diffuse opacities

Answer 64

Supportive care (cardiopulmonary monitoring and support) Broad-spectrum antibiotics: IV ampicillin and gentamicin -Indications: clinical suspicion, confirmed or suspected maternal infection (e.g., chorioamnionitis) Adapt therapy according to antibiogram results

Answer 65

Indication: - Maternal GBS colonization - - Determined via culture of vaginal and rectal swabs - - Indicated between 36 0/7 – 37 6/7 weeks' gestation - Anytime GBS bacteriuria occurs during pregnancy or if a previous newborn had a GBS infection - The presence of risk factors (e.g., chorioamnionitis, fever, ↑ CRP, premature contractions, PROM) Medication: - Intrapartum IV penicillin G or ampicillin (readminister every 4 hours until delivery) - If previous mild penicillin reaction: IV cefazolin - If severe penicillin allergy: clindamycin

Answer 66

May cause septic shock within hours if treatment is inadequate (mortality rate up to 50%) The longer symptoms are present, the higher the risk of developing meningitis.

Answer 67

Bacterial infection of the umbilical stump occurring 3–9 days after delivery

Answer 68

Staphylococcus aureus Group A Streptococcus E. coli Klebsiella pneumoniae Clostridium tetani: common cause of omphalitis and neonatal tetanus in developing countries

Answer 69

Periumbilical redness, tenderness, swelling, and hardening Purulent discharge Signs of systemic infection

Answer 70

Generally a clinical diagnosis, although cultures should be conducted Bacterial cultures: pathogen identification and antibiogram (sample of discharge) In systemic infection: blood and cerebrospinal fluid cultures (detection of sepsis and meningitis)

Answer 71

Broad-spectrum IV antibiotics: antistaphylococcal penicillin (e.g., oxacillin) PLUS aminoglycoside (e.g., gentamicin) Surgery: complete debridement if complications arise

Answer 72

Sepsis | Necrotizing fasciitis and myonecrosis (infectious muscle involvement): rare; associated with high mortality rates

Answer 73

Keep the navel dry (frequent diaper change) | Observe general hygiene measures

Answer 74

AKA surfactant deficiency disorder A lung disorder in infants that is caused by a deficiency of pulmonary surfactant

Answer 75

It is caused by impaired synthesis and secretion of surfactant

Answer 76

- Premature birth - Maternal diabetes (leading to increased fetal insulin, which inhibits surfactant synthesis) - Hereditary - C section delivery (results in lower levels of fetal glucocorticoids than in vaginal delivery, in whiich higher levels are released as a response to stress from uterine contractions) - Hydrops fettles - Multiple pregnancies - Male sex

Answer 77

Incidence: - 1% of all newborns - 10% of all preterm babies The risk of developing NRDS depends on gestational age: - < 28 weeks of gestation: > 50% - > 37 weeks of gestation: < 5%

Answer 78

Pulmonary surfactant is a mixture of phospholipids and proteins produced by lamellar bodies of type II alveolar cells. These phospholipids reduce alveolar surface tension, preventing the alveoli from collapsing. Surfactant deficiency is most likely to occur in preterm infants, because: - Surfactant production begins at approximately 20 weeks gestation. - Distribution throughout the lungs begins at 28-32 weeks' gestation and does not reach sufficient concentration until 35 weeks gestation. Surfactant deficiency → little or no reduction of alveolar surface tension → increased alveolar collapse → atelectasis → decreased lung compliance and functional residual capacity → hypoxemia and hypercapnia Hypoxemia and hypercapnia → vasoconstriction of the pulmonary vessels (hypoxic vasoconstriction) and respiratory acidosis → intrapulmonary right-to-left shunt → increased permeability due to alveolar epithelial damage → fibrinous exudation within the alveoli → development of hyaline membranes in the lungs (hyaline membrane disease)

Answer 79

- Maternal history of premature birth - Onset of symptoms is usually immediately after birth but can occur up to 72 hours postpartum - Signs of increased respiratory effort: - - Tachypnea - - Nasal flaring - - moderate to severe subcostal/intercostal and jugular retractions - Characteristic expiratory grunting - Decreased breath sounds on auscultation - Cyanosis due to pulmonary hypoxic vasoconstriction

Answer 80

Physical exam Maternal history X ray chest: - Interstitial pulmonary oedema with perihilar streaking - Diffuse, fine, reticulogranular (ground-glass) densities with low lung volumes and air bronchograms - Atelectasis Blood gas analysis: - Hypoxia with respiratory acidosis may lead to increased lactate levels - Evaluate for partial respiratory failure or global respiratory failure Amniocentesis for prenatal testing of NRDS: - screening for markers of fetal lung immaturity - Lecithin-sphingomyelin ratio <1.5 (≥ 2 is considered mature) - Foam stability index <0.48 - Low surfactant-albumin ratio Histological findings: - Hyaline membranes lining the alveoli - - Composed of fibrin, cellular debris and red blood cells - - Eosinophilic appearance, amorphous material lining the alveolar surface - Engorged and congested capillary vessels in the interstitium

Answer 81

Pulmonary hypoplasia Congenital diaphragmatic hernia Pneumothorax Neonatal pneumonia

Answer 82

Underdevelopment of the lungs characterised by a decreased number of alveoli and small airways and reduced lung volumes in on eor both lobes Results in impaired gas exchange and severe respiratory distress that may require intubation Associated with congenital diaphragmatic hernia (usually left-sided), oligohydramnios, and Potter sequence

Answer 83

Ventilation: - Nasal CPAP with a PEEP of 3–8 cm H2O - If respiratory insufficiency persists, start intubation with mechanical ventilation and O2 inhalation. Endotracheal administration of artificial surfactant within 2 hours postpartum Supportive measures: IV fluid replacement; stabilization of blood sugar levels and electrolytes

Answer 84

Around 90% | A saturation 100% is considered toxic for neonates

Answer 85

- Bronchopulmonary dysplasia - Pneumothorax - Hypoxia - Patent ductus arteriosus (the persistently low partial pressure of oxygen in the blood contributes to PDA) - Cardiovascular arrest - Neonatal sepsis ``` Complications of O2 inhalation: -Retinopathy of prematurity -Bronchopulmonary dysplasia -Intraventricular hemorrhage (Baby Oxen have RIBs) ```

Answer 86

Mortality rate <10% | Most cases resolve within 3-5 days if treated promptly

Answer 87

Prevent premature birth where possible (use of tocolysis to slow down) Antenatal corticosteroid therapy administered to the mother to stimulate infant lung maturation: -48 hours before delivery -2 doses of IM betamethasone 24 hours apart or 4 doses of IM dexamethasone 12 hours apart

Answer 88

An environmental factor that causes a permanent structual or functional abnormality, growth restriction or death of the embryo or foetus

Answer 89

``` VACTERL association: Vertebral, Anal, Cardiac, Tracheoesophageal fistula, Renal, and Limb abnormalities - All due to a defect during the development of embryonic mesoderm ```

Answer 90

Syndactyly: fusion of two or more fingers or toes (most common congenital malformation of the limbs) Polymelia/polydactyly: supernumerary limbs, fingers, or toes Oligodactyly, adactyly: absence of one or more of the fingers or toes Ectromelia: collective term for hypoplasia and/or aplasia of one or more long bones, resulting in limb deformity Peromelia/perodactyly: amputation-like stump of a limb, finger, or toe

Answer 91

In first trimester Hyperglycemia → inhibition of myoinositol uptake → abnormalities in the arachidonic acid-prostaglandin pathway → birth defects and spontaneous abortion

Answer 92

Congenital heart disease: - transposition of the great vessels, - ventricular septal defect, - truncus arteriosus, - tricuspid atresia, - patent ductus arteriosus, - dextrocardia Neural tube defects Caudal regression syndrome: - Definition: rare structural anomaly of the caudal region - Clinical features: - - Mild to severe motor function impairment, paralysis, and/or bladder incontinence - - Anorectal malformations and sacral agenesis (aplasia or hypoplasia of the sacrum and/or lumbosacral spine) - - Lower limb or foot deformities are common. - Prognosis: severe disease in the neonatal period that often results in infant death secondary to cardiac and renal complications Duodenal atresia Small left colon syndrome: self-limiting inability to pass meconium Vertebral anomalies Cleft palate Flexion contracture of the limbs Renal agenesis

Answer 93

In the second and third trimester Chronic fetal hyperglycemia → fetal hyperinsulinemia, islet cell hyperplasia, ↑ insulin-like growth factor, and ↑ growth hormones → ↑ metabolic effects and oxygen demand → fetal hypoxemia

Answer 94

Macrosomia (increased risk of birth injuries) Polycythemia (associated with an increased risk of hyperviscosity syndrome and hyperbilirubinemia) Neonatal hypoglycemia Electrolyte imbalances (hypocalcemia, hypomagnesemia) Respiratory distress (due to insufficient production of pulmonary surfactant) Hypertrophic cardiomyopathy (polycythemia → redistribution of iron → iron deficiency in cardiac tissue and hypoxemia → impaired cardiac remodeling) Polyhydramnios (fetal hyperglycemia → fetal polyuria)

Answer 95

``` Neonatal thyrotoxicosis Microcephaly Frontal bossing and triangular facies Craniosynostosis Developmental and behavioral problems ```

Answer 96

Congenital hypothyroidism with a possible congenital iodine deficiency syndrome

Answer 97

Neural tube defects Cleft lip and cleft palate Congenital heart disease Limb reduction abnormalities

Answer 98

IUGR Microcephaly Intellectual disability Congenital heart disease

Answer 99

Most common cause of teratogenic damage in children (0.2–1.5 per 1,000 live births) [10] Most common preventable cause of intellectual disability in the US

Answer 100

Failed neuronal and glial cell migration

Answer 101

Dysmorphic features: - Thin upper lip - Smooth hypoplastic philtrum (the vertical groove between the middle of the upper lip and the nose) - Down-slanting, short palpebral fissures (the opening between the upper and lower eyelid, defined as the elliptical space between the medial and lateral canthi of the open eye) - Hypertelorism - Microcephaly - Epicanthal folds - Receding chin Features of specific systemic defects: - Heart defects (mainly ventricular septal defect) - Heart-lung fistulas - Skeletal anomalies (limb dislocations, joint contractures, pectus excavatum/pectus carinatum) - Renal anomalies (aplastic/dysplastic kidneys) leading to hypertension - Prenatal or postnatal growth retardation → short stature - Holoprosencephaly: a developmental field defect, in which the forebrain fails to divide into two hemispheres resulting in fusion of ventricles (leading to the formation of monoventricle) and other bilateral cerebral structures, e.g., basal ganglia - - Typically occurring during the 3rd–4th week of pregnancy - - Potential genetic causes include: - -- Mutations in SHH gene coding for sonic hedgehog protein - -- Trisomy 13 - - Associated clinical features: - -- Craniofacial abnormalities (cyclopia and/or cleft lip/palate) - -- Endocrine disorders related to pituitary dysfunction (e.g., diabetes insipidus) - -- Seizures and epilepsy Hyperactivity, intellectual disability (e.g., impaired language development, learning disabilities, memory deficits), and subsequent problems in social interactions and school performance

Answer 102

Down syndrome Fragile-X syndrome Williams syndrome

Answer 103

Nicotine: ↑ catecholamine release → vasoconstriction of uteroplacental blood vessels → compromised blood flow and oxygen delivery to the fetus Carbon monoxide: ↑ COHb causes tissue hypoxia

Answer 104

Intrauterine growth restriction and low birth weight Increased risk of preterm labor and miscarriage (e.g., due to placental abnormalities such as placental abruption) Attention deficit hyperactivity disorder (ADHD) and conduct disorder Sudden infant death syndrome (SIDS) Cleft lip and palate

Answer 105

Fetal dysgenesis Placental abruption Respiratory depression Neonatal abstinence syndrome

Answer 106

Causes vasoconstriction in the placental vessels Intrauterine growth retardation and low birth weight Increased risk of preterm labor and placental abruption

Answer 107

A synthetic estrogen that is primarily used to prevent miscarriages in expectant mothers

Answer 108

Vaginal clear cell adenocarcinoma Congenital anomalies of the Müllerian duct

Answer 109

A sedative that was used to treat nausea or vomiting in pregnant women (now administered in limited indications, e.g., multiple myeloma)

Answer 110

Thalidomide embryopathy: - Symmetrical amelia (complete absence of limbs) - Micromelia (“flipper limbs”) - Anotia (absence of the external ear) - Phocomelia: a teratogenic limb defect that is characterized by the absence of the proximal portion of a limb (hand or foot are directly attached to the shoulder or hip)

Answer 111

Chromosomal damage or cell death leading to: - Microcephaly - Intellectual disability - Growth restriction - Malignancy

Answer 112

Spontaneous abortion Stillbirth Hemangiomas, lymphangiomas, hydroceles, skin tags, undescended testes VACTERL

Answer 113

Cerebellar atrophy Atrophy of the visual brain cortex Polyneuritis

Answer 114

SIDS The abrupt and unexplained death of an infant Diagnosis requires that a forensic examination reveals no other cause of death

Answer 115

Peak incidence at 2-6 months In rare cases during the first days of life Male>female Over 90% of SIDS occur during sleep

Answer 116

Unclear but suggests that caused by a combination of both extrinsic and intrinsic factors which ultimately lead to acute or chronic hypoxia Extrinsic factors (triggers): - Sleeping in the prone position - Exposure to nicotine during pregnancy and after birth (including 2nd-hand smoking) - Overheating - Unsafe sleeping environment or CO2 rebreathing: e.g., a shared blanket, stuffed animals in the crib (because of the grasping reflex, newborns tend to drag items to their faces) - Many more correlations: - - SIDS in siblings, - - babies born prematurely, - - young mothers (< 20 years), - - low socioeconomic status, etc. Intrinsic factors: -Brainstem disorder that includes morphologic/ biochemical abnormalities of serotonin (known as 5-hydroxytryptamine or 5-HT), which impacts the respiratory drive, the ability to wake up, blood pressure, upper respiratory reflexes , and body temperature.

Answer 117

Diagnosis of exclusion. If there is an unexplained death of an apparently healthy infant, an autopsy is required by law to rule out other causes of death. Differentials: - Congenital anomalies that could lead to infant death (e.g., cardiac anomalies) - Intentional suffocation; evidence of battered child syndrome

Answer 118

A sudden and unexpected event occurring in an infant that is considered life-threatening by the observer and is characterized by some combination of the following: - Apnea - Changes in skin color (usually cyanosis or pallor) and/or muscle tone (e.g., rigidity, floppiness) - Choking/gasping May occur when the infant is awake or asleep Not associated with SIDS

Answer 119

Reported incidence is 0.05-6%

Answer 120

Most common causes: - seizure, - respiratory tract infection, - gastroesophageal reflux, - cardiac conditions (e.g., arrhythmia) Associated risk factors: - age < 10 weeks, - prematurity, - prior ALTE, - feeding difficulties, - and/or symptoms of upper respiratory infection

Answer 121

Recurrence is high but overall mortality is low (<1%)

Answer 122

Parents should receive information on how to prevent SIDS during prenatal care and in pediatric check-ups after birth. During pregnancy: - No smoking, alcohol, or recreational drugs - Prenatal care Protective factors after birth: - The infant should be placed to sleep in the supine position - Safe sleep environment: - - firm mattress; - - no: - -- pillows, - -- blankets, - -- stuffed animals, - -- bumper pads in the crib. - In the first 6 months, co-sleeping in the same room without bed-sharing - Second-hand smoke and overheating should be avoided - Use of pacifier during sleep - Breastfeeding until the 4th–6th month - "Tummy time" - Immunization in line with the official schedule

Answer 123

Pathogens transmitted from mother to child during pregnancy (transplacentally) or delivery (permpartum)

Answer 124

Toxoplasmosis Others: - Syphilis (Treponema pallidum) - Listeriosis - Varicella zoster virus - Parovirus B19 infection Rubella virus Cytomegalovirus (CMV) Herpes simplex virus (HSV)

Answer 125

Vertically transmitted infections (acquired directly from the mother and transmitted to the embryo, fetus or newborn through the placenta or birth canal) that are capable of significantly influencing fetal and neonatal morbidity and mortality

Answer 126

Live vaccines: measles, mumps, rubella and varicella Conception should be avoided for 1 months after immunisation with live vaccines

Answer 127

~0.5-1 : 10,000 live births per year

Answer 128

Toxoplasma gondii

Answer 129

Mother: - Cat feces - Raw or insufficiently cooked meat - Unpasteurized milk (especially goat milk) Fetus: - Transplacental transmission - - First trimester: ∼ 15% - - Third trimester: ∼ 70%

Answer 130

First trimester: - Increased risk of premature birth and spontaneous abortion - Classic triad of toxoplasmosis - - Chorioretinitis (a form of posterior uveitis) - - Diffuse intracranial calcifications - - Hydrocephalus - Possible other nonspecific clinical features: - - Petechiae and purpura (blueberry muffin rash) - - Fever - - Jaundice - - Hepatosplenomegaly - - Lymphadenopathy - - Pneumonitis - - Seizures - - Macrocephaly or microcephaly - - Thrombocytopenia Second or third trimester: -Subclinical or mild toxoplasmosis Sequelae of congenital toxoplasmosis: - Epilepsy - Intellectual disability - Visual disabilities (chorioretinitis → increased risk of retinal lesions , cataracts, and glaucoma) - Sensorineural hearing loss

Answer 131

Fetus: -PCR for T.gondii in amniotic fluid Newborn: -CT/MRI: intracranial calcifications, hydrocephalus, ring-enhancing lesions -T. gondii-specific IgM antibodies (CSF, serum) PCR forT. gondii DNA (CSF, serum) -Ophthalmological evaluation: chorioretinitis

Answer 132

Mother: immediate administration of spiramycin to prevent fetal toxoplasmosis Fetus: When confirmed or highly suspected, switch to pyrimethamine, sulfadiazine, and folinic acid. Newborn: pyrimethamine, sulfadiazine, and folinic acid

Answer 133

Cerbral calcifications Chorioretinitis hydroCephalus Convulsions

Answer 134

Avoid raw, undercooked, and cured meats. Wash hands frequently, especially after touching soil (e.g., during gardening). Avoid contact with cat litter.

Answer 135

~23:100,000 live births per year in US

Answer 136

Treponema pallidum

Answer 137

Mother: -Sexual contact (contact with infectious lesion) Fetus: - Transplacental transmission from infected mother - Increased risk of transmission with recent syphilis infection - Risk of transmission increases with gestational age Neonate: -Perinatal transmission during birth

Answer 138

In utero syphilis: - Miscarriage - Stillbirth - Hydrops fetalis Early congenital syphilis (onset < 2 years of age): - Hepatomegaly and jaundice - Rhinorrhea with white or bloody nasal discharge (also called “snuffles”) - Maculopapular rash on palms and soles; a bullous form of the rash called pemphigus syphiliticus may be present at birth. - Skeletal abnormalities (e.g., metaphyseal dystrophy, periostitis) - Generalized lymphadenopathy (nontender) Late congenital syphilis (onset > 2 years of age): -Typical facial features: -- saddle nose, -- frontal bossing, -- short maxilla -Dental findings: -- Hutchinson's teeth (notched, widely spaced teeth); -- mulberry molars (poorly developed first molars) -Eyes and ears -- Syphilitic keratitis: nonulcerative, interstitial keratitis that develops as a late complication of syphilis (More common in patients with congenital syphilis than acquired syphilis. Causes stromal inflammation) -- Sensorineural hearing loss -Skin: rhagades (perioral fissures, cracks, and/or scars, particularly near the corners of the mouth and nose) -Skeletal -- Saber shins: An anterior bowing of the tibia, causing it to resemble a saber (Other causes include rickets and Paget disease of bone.) -- Painless arthritis in knees and other joints -Neurological: -- cranial nerve palsies (e.g., CN VIII defect causing deafness), -- intellectual disability, -- hydrocephalus

Answer 139

Newborn and mother: - Initial test: Rapid Plasma Reagin (RPR) or Venereal Disease Research Laboratory (VDRL) (serum) - Confirmatory test: dark-field microscopy or PCR of lesions or bodily fluids Fetus: -repeated ultrasound examinations (looking for placentomegaly, hepatomegaly, ascites, and/or hydrops fetalis)

Answer 140

10 days IV penicillin G for both pregnant women and newborns

Answer 141

Maternal screening and, if positive, antibiotic treatment: should take place in early pregnancy because placental transmission is most likely to occur after the first trimester. Nationally notifiable condition: Congenital syphilis and syphilitic childbirth must be reported

Answer 142

Triad of common symptoms of congenital syphilis Interstitial keratitis Sensorineural hearing loss Hutchinson teeth

Answer 143

~3:100,000 live births per year in the US

Answer 144

Listeria monocytogenes

Answer 145

Mother: - Contaminated food: especially raw milk products - - Other possible sources: fish, meat, and industrially processed vegetables (e.g., ready-made salads) Fetus: - Transplacental transmission from an infected mother - Direct contact with infected vaginal secretions and/or blood during delivery

Answer 146

Listeriosis of pregnancy: - Increased risk of premature birth and spontaneous abortion - Early-onset syndrome: granulomatosis infantiseptica - - Severe systemic infection characterized by disseminated abscesses (may develop in any organ system) - - Most common findings: respiratory distress and skin lesions - - Signs of meningitis may already develop. Neonatal listeriosis: -Late-onset syndrome (5 days to 3 weeks after birth): Listeria meningitis/encephalitis

Answer 147

Culture from blood or CSF samples (pleocytosis)

Answer 148

IV ampicillin and gentamicin for both mother and newborn

Answer 149

Avoidance of soft cheese Avoidance of potentially contaminated water and food Notifiable condition so report to public health

Answer 150

Seroprevalence in the general population is ∼ 95%. Most mothers have been vaccinated, so congenital infection is rare (< 2%).

Answer 151

Varicella zoster virus

Answer 152

Mother: - Primary infection - - Airborne droplets - - Direct skin contact with vesicle fluid - Reactivation: usually in immunocompromised individuals - Chickenpox and Shingles Fetus: -Transplacental transmission from an infected mother

Answer 153

Congenital varicella syndrome (infection during first and second trimester): - Hypertrophic scars (cicatricial skin lesions) - Limb defects (e.g., hypoplasia) - Ocular defects (e.g., chorioretinitis, cataracts, microphthalmia) - CNS defects (e.g., cortical atrophy, seizures, intellectual disability) - Hydrocephalus Neonatal varicella: - Mild infection (maternal exanthem (rash) > 5 days before birth) - Severe infection (maternal exanthem (rash) < 5 days before birth): - - hemorrhagic exanthem, - - encephalitis, pneumonia, or - - congenital varicella syndrome (mortality rate of up to 30%)

Answer 154

Newborn and mother: - Usually clinical diagnosis is confirmed by appearance of skin lesions - DFA or PCR of fluid collected from blisters or cerebrospinal fluid (CSF) - Serology Fetus: -PCR for VZV DNA (in fetal blood, amniotic fluid) and ultrasound to detect fetal abnormalities

Answer 155

For pregnant women or newborns with (severe) infection: acyclovir Administer postexposure prophylaxis in newborns if mother displays symptoms of varicella < 5 days before delivery: -IgG antibodies (varicella-zoster immune globulin, VZIG) Cesarean delivery if lesions are present at the delivery Breastfeeding is encouraged because of the possible protective effect of antibodies in breast milk.

Answer 156

Immunization of seronegative women before pregnancy VZIG in pregnant women without immunity within 10 days of exposure Nationally notifiable condition

Answer 157

∼ 5% incidence in pregnant women per year in the US Higher prevalence in daycare workers and primary school teachers

Answer 158

Pathogen: parvovirus B19 Mechanism of action: infection of erythrocyte progenitor cells in bone marrow and endothelial cells by attaching to their P antigen → cell destruction → hydrops fetalis in neonates and pure RBC aplasia in adults

Answer 159

Mother - Mainly via aerosols - Rarely hematogenous transmission - See “Fifth disease.” Fetus: transplacental transmission from infected mother

Answer 160

Severe anemia and possibly fetal hydrops Fetal demise and miscarriage/stillbirth in approximately 10% of cases (Risk is highest in the first and second trimesters.) Most intrauterine infections do not result in fetal developmental defects.

Answer 161

A fetal condition characterized by generalized edema and accumulation of fluid in serous cavities (e.g., pleural effusion, pericardial effusion, ascites). Diagnosed via ultrasound. Aetiologies include severe fetal anemia (e.g., hemolytic disease of the newborn, hemorrhage), congenital infections (e.g., parvovirus B19), chromosomal abnormalities, and congenital heart defects. Associated with a high rate of perinatal mortality.

Answer 162

Mother: Serologic assays for IgG and IgM against parvovirus B19 Fetus: - PCR for parvovirus B19 DNA (amniotic fluid or blood) - Doppler ultrasound of fetal vessels in suspected hydrops fetalis (every 1–2 weeks) - In cases of suspected anemia according to Doppler ultrasound, fetal hemoglobin levels are determined via the umbilical vein.

Answer 163

Intrauterine fetal blood transfusion in cases of severe fetal anemia Additional platelet transfusion if thrombocytopenia is also present

Answer 164

Hand hygiene (frequent hand washing) Pregnant women with risk factors for TORCH infection should avoid potentially contaminated workplaces (e.g., schools, pediatric clinics).

Answer 165

Most mothers have been vaccinated so congenital infection is very rare

Answer 166

Rubella virus

Answer 167

Mother: Mainly via airborne droplets Fetus: - Transplacental from infected mother - Risk of fetal infection is high in the first trimester, decreased in the second trimester and then increased again in the third trimester. - Risk of congenital rubella syndrome: - - 1–12 weeks gestation (period of organogenesis): highest risk - - 12–20 weeks gestation: very low - - > 20 weeks gestation: no documented cases

Answer 168

Intrauterine rubella infection: - miscarriage, - preterm birth, - fetal growth restriction (especially likely if infection occurs during the first trimester) Congenital rubella syndrome: - Triad of symptoms: - - Cardiac defect: most common defect (e.g., patent ductus arteriosus, pulmonary artery stenosis) - - Cataracts: Other eye manifestations may also occur later in life, including glaucoma and salt and pepper retinopathy (abnormal retinal pigmentation) - - Cochlear defect: bilateral sensorineural hearing loss - Early features: - - Hepatosplenomegaly, jaundice - - Hemolytic anemia, thrombocytopenia - - Petechiae and purpura, i.e., blueberry muffin rash (due to extramedullary hematopoiesis in the skin) - - Transient meningitis and/or encephalitis - - Pneumonia - Late features - - CNS defects: microcephaly, intellectual disability, panencephalitis - - Skeletal abnormalities - - Endocrine disorders (e.g., diabetes, thyroid dysfunction) - - Vascular disease - - Immune defects

Answer 169

Newborn and mother: - PCR for rubella RNA (throat swab, CSF) - Serology (abnormally high or persistent concentrations of IgM and/or IgG antibodies) - Viral culture (nasopharynx, blood) Fetus: - IgM antibody serology (chorionic villi, amniotic fluid) - PCR for rubella RNA (chorionic villi, amniotic fluid)

Answer 170

Intrauterine rubella infection: - < 16 weeks: Counsel about potential maternal-fetal transmission and the possibility of terminating the pregnancy. - > 16 weeks: reassurance and symptomatic therapy (e.g., acetaminophen) Congenital rubella syndrome: -supportive care (based on individual disease manifestations) and surveillance (including monitoring for late-term complications)

Answer 171

Immunization of seronegative women before pregnancy Nationally notifiable condition

Answer 172

Cataracts Cochlear defects Cardiac abnormality

Answer 173

~0.5%-1% of live births per year in the US

Answer 174

Cytomegalovirus

Answer 175

Mother: via CMV-contaminated blood, urine, saliva, and genital secretions: - Blood transfusions - Sexual transmission - Droplet transmission - Transplant-transmitted infection (e.g., bone marrow, lungs, kidneys) Fetus: transplacental transmission from an infected mother Newborn: during birth or postnatal via breastmilk from infected mother

Answer 176

Fetal infection: - Increased risk of fetal demise - IUGR - Oligohydramnios or polyhydramnios, placental abnormalities Newborn infection: - Severity - - Subclinical infection (∼ 90%): ∼ 10% go on to develop a late complication (most commonly hearing loss) - - Symptomatic infection at birth (∼ 10%): ∼ 70–80% go on to develop a late complication. - CNS findings - - Hydrocephalus - - Microcephaly . - Sensorineural hearing loss (∼ 30%) - Chorioretinitis (∼ 10%) - Nonspecific findings (similar to other TORCH infections) - - Petechiae, purpura (blueberry muffin rash) - - Hepatosplenomegaly, jaundice - - Small for gestational age (SGA) - - Seizures, lethargy, poor suck - - Hemolytic anemia, thrombocytopenia - - Pneumonia - Late complications - - Hearing loss, vision impairment - - Psychomotor retardation, intellectual disability - - Dental abnormalities

Answer 177

Fetus and newborn - CNS imaging: - - hydrocephalus, - - periventricular calcifications, - - intraventricular hemorrhage - Ultrasound: - - periventricular calcifications, - - hyperechogenic foci (bowel and liver, ascites) - - hydrops fetalis Newborn and mother: - CMV IgM antibodies (blood) - Viral culture or PCR for CMV DNA (urine, saliva) Fetus - Viral culture or PCR for CMV DNA (amniotic fluid) - CMV IgM antibodies (fetal blood)

Answer 178

Congenital toxoplasmosis: - Causes chorioretinitis, hydrocephalus, and intracranial calcifications - Intracranial calcifications in congenital toxoplasmosis typically show ring-enhancement.

Answer 179

Fetus: - Severe anemia: intrauterine blood transfusions - Thrombocytopenia: platelet transfusions Newborn: - Supportive therapy of symptoms (e.g., fluid and electrolyte imbalances, anemia, thrombocytopenia, seizures, secondary infections) - Ganciclovir, valganciclovir, or foscarnet Mother: -Valacyclovir is the only therapy approved during pregnancy

Answer 180

Frequent hand washing, especially after contact with bodily secretions of small children (e.g., diaper changing) Avoidance of food sharing with children Avoidance of kissing small children on the mouth

Answer 181

~1:3,000-10,000 live births per year

Answer 182

Mainly HSV-2; in rare cases HSV-1

Answer 183

Mother: - Primary infection: contact with contaminated oral secretions via small skin lesions - Reactivation: usually in immunocompromised individuals Fetus: -transplacental transmission from an infected mother (rare) Newborn: perinatal transmission during birth (∼ 30% transmission rate if mother has not yet undergone seroconversion at time of delivery)

Answer 184

Intrauterine HSV infection (∼ 5% of cases): - Fetal demise, preterm birth, very low birth weight - Microcephaly, hydrocephalus, and other CNS defects - Microphthalmia and chorioretinitis - Vesicular skin lesions Perinatal and postnatal transmission: - Skin, eye, and mouth disease - - Vesicular skin lesions - - Keratoconjunctivitis leading to cataracts, chorioretinitis - - Vesicular lesions of oropharynx - CNS disease - - Meningoencephalitis (manifesting with fever, lethargy, irritability, poor feeding, seizures, bulging fontanelle) - - Possibly vesicular skin lesions - Disseminated disease - - Features similar to those of sepsis, with organ involvement (e.g., liver, CNS, lungs, heart, adrenal glands, kidneys, GI tract) - - Vesicular skin lesions (may not appear until late in disease course)

Answer 185

Mother: typically a clinical diagnosis Fetus: The ultrasound may show CNS abnormalities. Newborn (and mother) - Standard: viral culture of HSV from skin lesions, conjunctiva, oro/nasopharynx, or rectum - Alternative: PCR for HSV DNA (CSF, blood)

Answer 186

Newborn and mother: IV acyclovir or valacyclovir Additionally in newborns: supportive therapy of fluid/electrolyte imbalances, SIRS, septic shock, seizures, secondary infections, etc.

Answer 187

Antiviral therapy (acyclovir) beginning at 36 weeks of gestation for individuals with a known history of HSV lesions Cesarean delivery in women with active genital lesions or prodromal symptoms (e.g., burning pain)

Answer 188

Phototherapy: - Primary treatment in those with unconjucated hyperbilirubinaemia - Procedure: - - Exposure to blue light (non-UV, wavelength: 420–480 nm) → photoisomerization (major mechanism) and photooxidation (minor mechanism) of unconjugated (hydrophobic) bilirubin in skin to water-soluble forms → excretion of water-soluble form in urine and/or bile - - Continued until total bilirubin levels < 15 mg/dL - - Adequate fluid supplementation to prevent dehydration - - Eye protection to prevent retinal damage - Contraindications: - - Concomitant use of photosensitizing medications - - Congenital erythropoietic porphyria - - Family history of porphyria Exchange transfusion: - Most rapid method for lowering serum bilirubin concentrations - Indications - - Threshold in a 24-hour-old term baby is a total serum bilirubin value > 20 mg/dL - - Inadequate response to phototherapy, or a rapid rise in the total serum bilirubin level (> 1 mg/dL/hour in less than 6 hours) - - Acute bilirubin encephalopathy - - Hemolytic disease, severe anemia - Procedure - - Use ABO-matched and Rh-negative erythrocyte concentrate. - - Exchange blood in quantities of 5–20 mL via an umbilical venous catheter until total serum bilirubin is < 95thpercentile on nomogram. - Side effects - - Higher mortality and morbidity from infections - - Acidosis - - Thrombosis - - Hypotension - - Electrolyte imbalances IV immunoglobulin: - Indications: used in cases with immunologically mediated conditions, or in the presence of Rh, ABO, or other blood group incompatibilities that cause significant neonatal jaundice - Dose range for IVIG: 500–1000 mg/kg

Answer 189

Diarrhea, dehydration Changes in skin hue (bronzing) and skin rashes Separation of the neonate from the mother ↑ Risk of AML Bronze baby syndrome (rare): - Occurs in infants with elevated direct bilirubin (conjugated bilirubin > 2mg/dL) following phototherapy - Thought to be caused by abnormal accumulation of bronze-colored pigments (photoisomers of bilirubin) within the skin - Presents with a reversible grayish-brown discoloration of the skin, urine, and serum - Usually resolves slowly after cessation of phototherapy without complications

Answer 190

Acute bilirubin encephalopathy: - Onset within first days of life - Lethargy, hypotonia (floppy infant syndrome), poor feeding - Fever, shrill cry - Stupor, apnea, seizures - Possibly fatal if neurotoxicity is severe Kernicterus (chronic bilirubin encephalopathy): - Develops over first years of life - Pathophysiology: deposition of unconjugated bilirubin (liposoluble) in the basal ganglia and/or brain stem nuclei - Clinical features: - - Cerebral paresis, hearing impairment, vertical gaze palsy - - Movement disorder (athetosis) - - Apparent intellectual and developmental disabilities - - Dental enamel hypoplasia

Answer 191

Favorable in most cases In rare cases, kernicterus may occur, resulting in permanent neurological sequelae.

Answer 192

Interruption of enterohepatic circulation with adequate enteral nutrition Frequent feeds with breast milk Protein-rich nutrition in the form of breast milk or special formula feeds In the case of dehydration, protein-rich feeding solutions are preferred over glucose or water.

Answer 193

A condition characterised by blood group incompatibility between mother and fetus that leads to the destruction of foetal erythrocytes by maternal antibodies

Answer 194

ABO incompatibility: - Present in ∼ 20% of all pregnancies - However, only 5–10% of newborns from these pregnancies are symptomatic. Rh incompatibility: -Rare following routine anti-D prophylaxis Kell blood group system incompatibility: -Second most common cause of severe HDFN after Rh disease Risk factors: - Maternal exposure to fetal blood during pregnancy - Antenatal procedures (e.g., amniocentesis, cesarean delivery, termination of pregnancy) - Pregnancy-related complications (e.g., ectopic pregnancy, placental abruption) - Trauma

Answer 195

ABO incompatibility: - Highest risk: mother with blood group O; newborn with blood group A or B - Maternal antibodies (anti-A and/or anti-B) against nonself antigens of the ABO system are present even if sensitization has not occurred, so fetal hemolysis may occur during the first pregnancy. Rh incompatibility: - In an Rh-negative mother and Rh-positive newborn: maternal exposure to fetal blood (fetomaternal hemorrhage) → production of maternal IgM antibodies against the Rh antigen → over time, seroconversion to Rh-IgG (able to cross the placenta) - In a subsequent pregnancy with an Rh-positive newborn: rapid production of maternal IgG anti-D antibodies to fetal RhD antigens → Rh-IgG agglutination of fetal RBCs with hemolytic anemia → risk of HDFN with possible hydrops fetalis

Answer 196

A subgroup of haemolytic diseases of the fetus and newborn not caused by red cell alloimmunisation

Answer 197

Incidence: ∼ 1 in 4,000 pregnancies Accounts for over 90% of all hydrops fetalis cases

Answer 198

Congenital heart defects and arrhythmias Chromosomal aberrations (e.g., Turner syndrome, Down syndrome, trisomy 18) Severe fetal anemia (e.g., thalassemia, twin-to-twin transfusion syndrome, fetomaternal hemorrhage) Congenital TORCH infections (especially parvovirus B19 infection)

Answer 199

Severe fetal anemia → hypoxia → ↓ hepatic and renal blood flow → activation of RAAS → ↑ central venous pressure and ↓ lymphatic flow → fetal edema

Answer 200

Prenatal: -Hydrops fetalis (expected in cases of Rh incompatibility and in nonimmune hydrops fetalis) Postnatal: - Neonatal anemia - Hepatosplenomegaly - Neonatal jaundice - - Usually present at birth or manifests within the first 24 hours of life - - In Rh incompatibility, unconjugated bilirubin levels may be dangerously high, causing kernicterus. - Hypoxia - Prematurity - Scattered petechiae (rare but associated with poor prognosis) ABO incompatibility usually has a significantly milder course of disease than Rh incompatibility Anaemia may conceal cyanosis

Answer 201

The diagnosis of HDFN requires evidence of hemolysis in the presence of fetomaternal blood incompatibility. Prenatal diagnosis: Imaging -Ultrasound: to determine hydrops fetalis -- Fetal pleural or pericardial effusions -- Fetal ascites -- Fetal subcutaneous or nuchal edema -- Placental edema -Doppler sonography of fetal blood vessels: -- Increased flow rate indicates fetal anemia. Postnatal diagnosis: - If the newborn has signs of hemolysis, conduct a Coombs test (either direct or indirect). - - Rh incompatibility: positive - - ABO incompatibility: weak positive or negative

Answer 202

An agglutination test that is used either to detect haemolytic antibodies and/or complement proteins that are already bound to erythrocytes (direct Coombs test) or unbound anti-erythrocyte antibodies in serum (indirect Coombs test).

Answer 203

A rare condition in newborns characterised by maternal-fetal platelet incompatibility resulting in fetal thrombocytopenia The leading cause of severe thrombocytopenia in the newborn

Answer 204

Formation of maternal antibodies against fetal platelets (most commonly targeting platelet antigen 1a) → maternal IgG cross the placenta and result in the destruction of fetal platelets → fetal and neonatal thrombocytopenia

Answer 205

Mild: asymptomatic thrombocytopenia Moderate: petechia and/or ecchymoses within a few hours after birth Severe: spontaneous intracranial hemorrhage

Answer 206

Prenatal: - Intrauterine blood transfusion via the umbilical vein, umbilical artery, peritoneal cavity, or heart (should only be performed in centers with experience in fetal transfusions.) - Possible IV immunoglobulin (IVIG) in severe cases Postnatal: -Anemia: iron supplementation and, if necessary, RBC transfusion. -Hyperbilirubinemia: phototherapy; if necessary, exchange transfusion with red blood cells See “Treatment” in neonatal jaundice. -In severe cases, IV immunoglobulin (IVIG) may be administered.

Answer 207

SCREENING: ABO and Rh typing of the mother - Rh-positive mothers do not need further screening. - Rh-negative mothers: screening for anti-D antibodies - - No anti-D antibodies (unsensitized mothers): antibody screening repeated at 28 weeks' gestation and at delivery. - - Anti-D antibodies manifest with an anti-D antibody titer > 1:8, which indicates maternal sensitization to fetal Rh antigens (sensitized mothers). - - Further monitoring with amniocentesis and imaging is required for evidence of hemolysis. Fetomaternal hemorrhage in Rh-negative mother - Conduct a rosette test (initial test of choice). - - This is a qualitative test that assesses whether fetomaternal hemorrhage has occurred. - - The apt test is an alternative to the rosette test, but it only differentiates whether the origin of blood is fetal/newborn or from the mother, e.g., from: - -- Newborn gastrointestinal (stool, vomiting) or pulmonary bleeding - -- Antepartum hemorrhage (e.g., vasa previa) - If the rosette test is positive, conduct a Kleihauer-Betke test. - - Quantitative testing to evaluate fetomaternal hemorrhage - - The amount of fetal hemoglobin determines the amount of Anti-D immunoglobulin necessary. - - Flow cytometry is an alternative, but its use is limited by equipment and costs. Fetal Rh genotyping ANTI-D IMMUNOGLOBULIN: Anti-D prophylaxis protects newborns in subsequent pregnancies Only indicated in unsensitised mothers ``` Anti-D should be adminstered during the 28th week of gestation and within 72 hours following the birth of an Rh-positive baby Anti-D should also be given in any sensitising events: -miscarriage -ectopic pregnancy -termination of pregnancy -bleeding during pregnancy -invasive procedures: -- amniocentesis -- chorionic villus sampling ``` Dose: - Standard dose: 300μg (1500 IU) IV/IM - If whole fetal blood is >30 mL (i.e., fetal RBCs > 15 mL): 300 μg (1500 IU) IM should be given for every 30 mL of fetal blood volume.

Answer 208

Spontaneous bleeding in a newborn caused by a deficiency of vitamin K dependent coagulation factors.

Answer 209

Without prophylaxis it affects ~0.25-1.7% of newborns

Answer 210

The underlying cause is always a deficiency of vitamin K, which can be due to various factors: - Exclusive breastfeeding: low vitamin K levels in breast milk (most important in late-onset VKDB) - Low liver storage capacity - Poor placental passage of vitamin K - Vitamin K deficiency in the mother (e.g., because of anticonvulsant therapy; most important in early-onset VKDB; maternal malnutrition) - Underdeveloped intestinal flora (which produces vitamin K), e.g., due to premature birth - Chronic diarrhea of the newborn - Long-term antibiotic treatment in newborns - Cholestatic diseases (e.g., biliary atresia)

Answer 211

Early onset: within 24 hours after birth; intracranial bleeding common Classic: within 4 weeks after birth; intracranial bleeding rare Late onset: between 2–8 months after birth; intracranial bleeding common

Answer 212

Coagulation studies: - ↑ Prothrombin time (PT) - Normal or ↑ activated partial thromboplastin time (PTT) - Normal bleeding time - ↓ Factors II, VII, IX, and X

Answer 213

Transfusions as necessary Administration of vitamin K

Answer 214

Newborns can recieve intramuscular vitamin K (0.5-1mg) at birth

Answer 215

Characterised by serum bilirubin levels of ≥ 1.1 mg/dL (11mg/L)

Answer 216

Most common inherited hyperbilirubinemia: The prevalence is 3–7% in the US ♂ > ♀ Age of onset: adolescence

Answer 217

Mutation in the promoter region of UGT1A1 gene → mild reduction of UDP-glucuronosyltransferase activity → ↓ conjugation of bilirubin → ↑ indirect bilirubin Alternative: missense mutation in UGT1A1 gene Impaired hepatic bilirubin uptake Autocomal recessive or autosomal dominant inheritance pattern

Answer 218

Asymptomatic or unspecific symptoms such as fatigue and loss of appetite Transient, usually mild jaundice (varying from mild scleral jaundice to general jaundice) Triggering factors of transient jaundice: - Stress (e.g., trauma, illness, exhaustion) - Fasting periods - Alcohol consumption

Answer 219

Slightly ↑ indirect bilirubin but < 3 mg/dL (higher levels are possible during episodes of increased bilirubin breakdown) Normal liver function No evidence of hemolysis Detection of mutation using PCR

Answer 220

No treatment required as this is a benign condition

Answer 221

UDP-glucuronosyltransferase is (almost completely) absent. Autocomal recessive inheritance

Answer 222

Excessive, persistent neonatal jaundice Kernicterus: neurological symptoms (onset during infancy or later in childhood)

Answer 223

- ↑ Indirect bilirubin (20–50 mg/dL) - Normal liver function tests - No evidence of hemolysis

Answer 224

Phototherapy: conversion of unconjugated bilirubin (hydrophobic bilirubin) to more polar, water-soluble form → ↑ excretion via urine and/or bile Plasmapheresis during acute rises in serum bilirubin levels Tin protoporphyrin Calcium carbonate Liver transplantation is the only curative treatment.

Answer 225

Without treatment, Crigler-Najjar syndrome type I is incompatible with life because it causes kernicterus. If treated, patients may survive past puberty, but most will eventually develop kernicterus.

Answer 226

Reduced levels of UDP-glucuronosyltransferase Autosomal recessive or autosomal dominant inheritance pattern

Answer 227

Arias syndrome

Answer 228

Often asymptomatic No neonatal jaundice, although jaundice may occur during the patient's first year of life No neurological symptoms

Answer 229

↑ Indirect bilirubin (< 20 mg/dL) Normal liver function tests No evidence of hemolysis Responds to phenobarbital → ↓ serum bilirubin levels

Answer 230

Patients are less likely to develop kernicterus. Specific treatment may therefore not be required. The following treatment options are, however, available if patients become icteric. Phenobarbital: leads to induction of UDP-glucuronosyltransferase Phototherapy (as in type I) Avoid hormonal contraception and hepatic enzyme inhibitors

Answer 231

Usually favourable | Management of jaundice allows for normal quality of life

Answer 232

Defective multidrug resistance-associated protein 2 (MRP2) → impaired excretion of conjugated bilirubin from the hepatocytes into the bile canaliculi Autosomal recessive inheritance

Answer 233

Mild to moderate jaundice - Onset often occurs during adolescence - May worsen because of medication (particularly contraceptives) or pregnancy Splenomegaly may occur in rare cases.

Answer 234

Direct hyperbilirubinemia (direct bilirubin/total bilirubin up to 50%) Liver biopsy: dark, granular pigmentation (due to accumulation of epinephrine metabolites)

Answer 235

Not required (benign condition) Be careful when administering a drug that is toxic to hte liver as it may worsen jaundice Contraindication for oral contraception

Answer 236

Defective organic anion transport proteins (OATP) 1B1 and 1B3 in hepatocytes → impaired transport and reduced storage capacity of conjugated bilirubin (direct bilirubin) Autosomal recessive inheritance

Answer 237

Usually asymptomatic but mild jaundice may occur (milder presentation compared to Dubin-Johnson syndrome)

Answer 238

Moderate, direct hyperbilirubinemia and mild, indirect hyperbilirubinemia Normal liver function test ↑ Urinary coproporphyrins I and III (fraction of isomer I < 70% of total) Liver biopsy: normal, no pigmentation

Answer 239

Not required Be careful when administering a drug that is toxic to hte liver as it may worsen jaundice Contraindication for oral contraception

Answer 240

In Rotor syndrome, the liver appears Regular In Dubin-johnson syndrome, the liver appears Dark

Answer 241

Hereditary metabolic disorders characterised by defects in the enzymes responsible for glycogenolysis or glycolysis 13 different types have been found All types cause abnormal accumulation of glycogen due to impaired glycogen metabolism

Answer 242

Incidence: up to 1:20,000 live births Age of onset: presentation during infancy or childhood Sex: ♂ = ♀ Mode of inheritance: mostly autosomal recessive (types I, II, III, and V)

Answer 243

Defective enzymes responsible for glycolysis or glycogenolysis → impaired glycogen metabolization → ↑ storage of either normal or abnormal glycogen Liver, heart, and muscle are the most common sites of glycogen storage and are, therefore, predominantly affected.

Answer 244

Glycogen storage disorders can be classified as muscle and/or liver GSD according to the presenting symptoms. Muscle involvement: - Seen in types II, III, IV, V - Two groups of skeletal muscle symptoms are seen: - - Defects of muscle glycogenolysis and muscle glycolysis: - -- Easy fatiguability, exercise intolerance - -- Cramps - -- Rhabdomyolysis → myoglobinuria (burgundy-colored urine) - - Defects of muscle glycogenesis (type IV) and lysosomal glycogenolysis (type II): - -- progressive weakness of extremities and trunk (proximal myopathy) - Cardiac involvement - - Seen in several types (e.g., type II, type III) - - Hypertrophic cardiomyopathy and/or conduction defects are most common in type II. Liver involvement - Seen in types I, III, IV - Hypoglycemia (typically fasting hypoglycemia) and ketosis - Symptoms of hypoglycemia in infancy: seizures, hypotonia, poor feeding, cyanosis, irritability - Hepatomegaly → distended abdomen Additional clinical manifestations: - Growth delay/growth retardation/failure to thrive: types I, II, III, IV - Anemia: type I - Hyperlipidemia: types I, III - Macroglossia: type II - Lactic acidosis: type I - Hyperuricemia: type I

Answer 245

Initial tests: - Muscle and/or liver biopsy (depending on the enzyme deficiency): glycogen storage appears as PAS-positive granules . - Enzyme assays in RBCs, leukocytes, liver tissue, muscle tissue, or fibroblasts (depending on the enzyme deficiency) Confirmatory test: DNA testing for the gene defects Additional tests: - Muscle GSD - - Ischemic forearm test: an important test to evaluate if a patient has a metabolic disorder of muscle function - -- A sphygmomanometer cuff is tied around the arm and inflated to beyond systolic blood pressure. The patient is then asked to repeatedly form a fist. The cuff is then deflated and multiple blood samples are taken to measure serum lactate levels. - -- The normal response to an ischemic exercise test is an increase in the levels of lactate as a result of anaerobic metabolism of glucose. - -- In the case of GSD type III and type V, not enough glucose is produced from glycogen. As a result, lactate levels do not rise. - - ↑ Creatine kinase - - Electroneuromyography: to identify proximal myopathy - - ECG and/or echocardiography: to identify cardiac hypertrophy and conduction blocks - Liver GSD - - ↑ Serum biotinidase serves as diagnostic biomarkers in type I and type III - - Liver function tests and abdominal ultrasonography: to detect liver cirrhosis and/or hepatic failure

Answer 246

General: - Most forms of GSD can be managed effectively with dietary therapy (e.g., uncooked corn starch, glucose preparations) with the aim of preventing hypoglycemia and/or muscle symptoms - Foods rich in fructose and galactose should be avoided in patients with GSD type I Definitive therapy: - Enzyme replacement therapy is available for some forms of GSD - A liver transplant may be required in the case of liver GSD that progress to liver cirrhosis and/or result in poor metabolic control. - Cardiac involvement - - Severe conduction defects: pacemaker implantation

Answer 247

Hereditary defects in enzymes that are responsible for the metabolism of galactose

Answer 248

A component of the disaccharide lactose, which is present in breast milk

Answer 249

``` Poor feeding Failure to thrive Vomiting, diarrhea Jaundice, hepatomegaly Cataracts Cognitive impairment ↑ Risk of E. coli sepsis (esp. in neonates) Hypoglycemia ```

Answer 250

Newborn screening test: ↑ galactose/galactose-1-phosphate in blood Urine galactose levels: galactosuria Total serum bilirubin: hyperbilirubinemia

Answer 251

Complete cessation of lactose-containing feeds and lifelong adherence to galactose-free and lactose-free diet

Answer 252

Food allergies

Answer 253

Hypersensitivity reaction against select ingredients in food

Answer 254

``` Cow's milk Eggs Nuts Peanuts Seafood (shellfish, fish) Soy Wheat Fruits (eg kiwi) ```

Answer 255

Commonly IgE-mediated: Type I hypersensitivity reaction (immediate onset; within minutes to 2 hours of ingestion) Mixed IgE/non-IgE-mediated and non-IgE-mediated reactions are also possible (delayed onset; hours to days after ingestion)

Answer 256

Skin (most common): pruritus, urticaria, exanthem, angioedema, atopic dermatitis Respiratory: rhinitis (often with sneezing), nasal congestion, dyspnea, wheezing, laryngeal edema Gastrointestinal tract: oral allergy syndrome (oral pruritus, tingling numbness, and swelling of the lips, tongue, palate, and throat) , nausea, vomiting, abdominal pain, diarrhea Cardiovascular: hypotension, tachycardia, dysrhythmias CNS: headache Non-IgE or mixed reactions are typically limited to the ckin and GI tract Respiratory manifestations can be fatal

Answer 257

Patient history: determine type of food, time and amount of ingestion, and the type of reaction Suspected IgE-mediated reaction: - IgE skin prick test - RAST (radioallergosorbent test) - - An immunoassay that detects specific compounds using antibodies coupled to radioactive tags. - - Previously used to detect allergen-specific IgE but is no longer widely used. - - IgE serum levels are measured in response to predetermined food allergens. - Total IgE-antibody serum test - N-methylhistamine (urine) If above tests are inconclusive or suspected food is not a common allergen: - Elimination diet: The suspected allergens are eliminated from the patient diet, while being observed for an improvement in symptoms without the need for medication. - Oral food challenge: the effect of potential allergens on the mucous membranes is tested (the patient is given different foods that contain potential allergens to chew but not swallow in increasing doses over a fixed period of time). May be implemented after a positive elimination diet.

Answer 258

Otherwise healthy infant with appropriate weight gain Paroxysmal episodes of loud and high pitched crying that often occur at the same time each day (usually in the late afternoon or evening) Hypertonia (e.g., clenched fists, stretched legs) during episodes Infant is not easily consoled

Answer 259

crying that lasts ≥ 3 hours per day, ≥ 3 days per week, for ≥ 3 weeks in an otherwise healthy infant <3 months old

Answer 260

Reassurance Soothing techniques Trial of various feeding techniques

Answer 261

Infantile colic Lactose and fructose intolerance Coeliac disease

Answer 262

Avoid allergens and in case of emergency treat anaphylactic reactions Oral immunotherapy is a novel approach being studies and not yet widely available

Answer 263

The majority of children with milk and egg allergies will outgrow them by 5 years of age. A lot of children with food allergies will develop asthma and allergic rhinitis. Adult-onset food allergies usually remain for life.

Answer 264

Stabilize the patient (ABCDE approach). - Airway assessment and management - Rapid sequence intubation (RSI) for airway compromise - Oxygen: Provide FiO2 of 100% (e.g., high-flow O2 by nonrebreather mask). - Aggressive IV fluid resuscitation if hypotension present - Position the patient supine. If anaphylaxis is likely, start initial treatment immediately: - Remove inciting allergen - Administer adrenalin IM 1:1,000 (1 mg/mL) into the anterolateral thigh Once stabilized, consider adjunctive therapy with antihistamines, corticosteroids (e.g., methylprednisolone) Continuous reassessment and subsequent management

Answer 265

Reflexes that are normally present during infancy and disappear with the development of inhibitory pathways to the subcortical motor areas (usually within the 1st year of life

Answer 266

In children: indicates impaired brain development In adults: suggests frontal lobe lasions (frontal release signs)

Answer 267

``` Moro reflex Rooting reflex Sucking reflex Palmar grasp Plantar grasp Plantar reflex Stepping reflex Galant reflex Asymmetrical tonic neck reflex (ATNR) Glabellar tap sign Landau reflex Snout reflex Parachute reflex ```

Answer 268

Holding an infant in the supine position while supporting the head, then allowing the head to suddenly fall back elicits abduction and extension of the infant's arms and elbows, followed by their flexion. Age of resolution: 3-6 months

Answer 269

Unilateral absence: - Ipsilateral brachial plexus injury - Ipsilateral fractured clavicle Bilateral absence indicates brain injury (e.g., due to birth asphyxia, intracranial hemorrhage) or bilateral brachial plexus injury

Answer 270

Stroking the cheek elicits turning of the head towards the stimulus and opening of the mouth Age of resolution: 4 months

Answer 271

Touching the roof of the mouthe elicits a sucking motion Age of resolution: 4 months

Answer 272

Unilateral absence indicates peripheral nerve injury Bilateral absence or premature resolution: - Perinatal asphyxia - Intracranial hemorrhage

Answer 273

Stimulation of the palm elicits a grasping motion Resolves around 3-6 months

Answer 274

Unilateral absence: - Brachial plexus injury - Peripheral nerve injury Bilateral absence of the reflex at birth may indicate cerebral palsy.

Answer 275

Stimulation of the sole elicits curling of the toes (plantar flexion). Resolves at 3 months

Answer 276

Bilateral absence: suggestive of cerebral palsy.

Answer 277

Stroking the sole of the foot from heel to toe elicits dorsiflexion of the foot with concomitant extension of the big toe and fanning of the other toes. Resolves at 12-24 months

Answer 278

Persistence or reappearance after 24 months indicates an upper motor neuron lesion (Babinski sign).

Answer 279

Holding the infant upright with feet on the examination table elicits a stepping motion with alternating flexion and extension of the legs. Resolves at 2 months

Answer 280

Infants born at term step from heel to toe. Preterm infants tiptoe.

Answer 281

Holding the infant in the prone position and stroking it on one side of the paravertebral region elicits flexion of the lower back and hip towards the stimulus. Resolves at 2-6 months

Answer 282

Persistent galant reflex may be associated with bed wetting

Answer 283

Turning the head to one side elicits extension of the arm and leg on the side the head is facing and flexion of the contralateral arm and leg (fencing posture). Resolves at 3-4 months

Answer 284

The ATNR aids in the development of hand eye coordination

Answer 285

Tapping the glabella elicits blinking Resolves 4-6 months

Answer 286

The region of the face above the root of the nose and between the eyebrows.

Answer 287

Persistent glabellar tap sign is a frontal release sign called Myerson sign

Answer 288

Placing the infant in a prone position elicits arching of the back and raising of the head Resolves by 24 months

Answer 289

Tapping or applying light pressure to closed lips elicits puckering Resolves at 4 months

Answer 290

Holding the infant in an upright position, followed by sudden lowering towards the examination table elicits extension of the infant's arms. This reflex appears at 6–9 months of age and persists

Answer 291

Infants suffering from neonatal encephalopathy may show an asymmetric or absent parachute reflex

Answer 292

Should be suspected when the child's age is >25% of the mena age at which a particular milestone is attained or >1.5 standard deviations on a standardised developmetnal screening tests

Answer 293

Term neonates lose up to 7% of their birth weight in the first few days after delivery and normally regain it within 2 weeks. Birth weight should double by 4 months, triple by 1 year and quadruple by 2 years of age.

Answer 294

An infant's height/length increases by approx. 30% within the first 6 months and by approx. 50% within the first year. Midparental height (target height): ♀ height = [mother's height in cm + (father's height in cm - 13)]/2 ♂ height = [father's height in cm + (mother's height in cm + 13)]/2 From birth to 6 months: 2.5 cm (1 in) per month From 6 months to 1 year: 1.3 cm (0.5 in) per month

Answer 295

Useful in detecting malnutrition in children <5 years of age Heigh/length at 1 year of age should be ~50% more than birth height/length

Answer 296

Used for microcephaly and macrocephaly screening, especially during the first 3 years of life

Answer 297

In a healthy infant, head circumference increases by: - 5 cm during first 3 months. - 4 cm between 3–6 months. - 2 cm between 6–9 months. - 1 cm between 9–12 months.

Answer 298

A head circumference that is > 2 standard deviations below the mean size for a given age and sex (usually < 3rdpercentile) Seen in: - chromosomal trisomies, - fetal alcohol syndrome, - congenital TORCH infections, - cranial anatomic abnormalities, - neural tube defects

Answer 299

A head circumference that is ≥ 2 standard deviations above the mean size for a given age and sex (usually ≥ 97thpercentile) Seen in: - hydrocephalus, - neurofibromatosis, - tuberous sclerosis, - skeletal dysplasia, - acromegaly, - intracranial hemorrhage, - cerebral metabolic diseases (e.g., Tay-Sachs disease, maple syrup urine disease)

Answer 300

Normal growth rates in children can be approximated by multiples of five: birth–1 year (50–75 cm, 25 cm/year), 1–4 years (75–100 cm, 10 cm/year), 4–8 years (100–125 cm, 5 cm/year), 8–12 years (125–150 cm, 5 cm/year).

Answer 301

Inadequate growth of a child for their age Seen in up to 10% of children in the United States (most <18 months of age) Anthropometric criteria of FTT: - Weight-for-age: <5th percentile - Length-for-age: <5th percentile - Body mass index-for-age: <5th percentile - Deceleration of weight velocity that crosses 2 major lines on the growth chart

Answer 302

Nonorganic FTT (∼ 90% of cases): - No underlying disorder - Usually associated with: - - Wrong feeding practices - - Wrong preparation of formula feeds - - Child neglect - - Poor socioeconomic status - - Intrauterine growth restriction - - Prematurity and low birth weight Organic FTT (∼ 10% of cases) is associated with disorders that: - Prevent nutrient intake - - Cleft palate and/or lip - - Gastroesophageal reflux disease - Prevent nutrient absorption - - Hypertrophic pyloric stenosis - - Food intolerance - - Celiac disease - - Inflammatory bowel disease - - Inborn errors of metabolism - Cause excessive calorie loss - - Cystic fibrosis - - Congenital heart defects (CHDs) - - Malignancies - - Other chronic diseases

Answer 303

Developmental delay Failure to gain weight despite adequate feeds Recurrent vomiting and diarrhea Recurrent infections General signs of malnutrition (e.g., lymphadenopathy, oedema, organomegaly)

Answer 304

History of feeding habits (e.g., number and frequency of feeds, food refusal) Laboratory studies - Complete blood count and ESR - Urinalysis - Hepatic and renal function tests - Thyroid function tests - Immunoglobulin levels assessment: to evaluate for underlying immunodeficiencies (e.g., HIV, tuberculosis) Imaging - Hand and wrist x-ray - Echocardiogram - Upper gastrointestinal series with small bowel follow-through

Answer 305

Treatment of the underlying cause Counseling parents on appropriate child nutrition Formula supplementation for infants and nutritional supplementation for toddlers Close follow-up and monitoring of the child's growth

Answer 306

Charting of growth and recording of developmental milestones Evaluation of resolution of primitive reflexes BP measured after 3 y/o Abdo: palpate for masses (Wilms tumor, neuroblastoma) Heart: New murmurs, rate/rhythm disturbances Spine: Assess for scoliosis once able to stand Evaluate for developmetnal dysplasia of the hip in neonates and tibial torsion, femoral torsion, and metatarsus adductus in the first 2-4 years of life Genital: For testicular descen and congenital hydrocele in all male infants; imperforate hymen in all female infants; and inguinal hernias in all infants; pubescent genital development (Tanner stages)

Answer 307

Ocular motility and visual acuity assessment Photoscreening: Paaediatric vision test used to detect errors of refraction, screen for amblyogenic risk factors and test visual acuity in preverbal or non-cooperative children Physiological red reflex evaluation (in newborns): absence or leukocoria should prompt further investigation Strabismus and amblyopis screening: Strabismus is a normal finding in children <3months old

Answer 308

Recommended in newborns and then at ages 4,5,6,8, and 10; or if there are >1 risk factor for hearing loss which include: - FH of childhood hearing loss - TORCH infections - History of meningitis/ head trauma - Recurrent or persistent otitis media - Neonatal ICU stay for >5 days - Behavioural abnormalities Screening tests included: - Electric response audiometry - Tympanometry - Otoacoustic emission Undetected hearing loss in children: - Can cause speech, language or social delay - May be mistake for neurodevelopmental disorder, especially communication disorders

Answer 309

Raises head and chest when prone Follows objects past midline Coos ``` Smiles back (social smile) Recognises parents ```

Answer 310

Holds head straight Roles over front to back Props self up on wrists in prone position Holds and shakes rattle Laughs Makes constant sounds Localises sounds

Answer 311

Sits without support Rolls over back to the front Grabs and transfers objects from one hand to the other Raking grasp Babbles Develops stranger anxiety (6-9months) Develops object permanence (6-9months)

Answer 312

Crawls Stands when holding on to something Pincer grasp (9-12months) Says mama or dada Orients to name Imitates actions Has separation anxiety

Answer 313

Starts to walk Can throw objects Points at objects Knows 1-5 words Follows commands

Answer 314

Starts to run Learns to walk backwards with help Stacks up 4 blocks Uses spoon and cup Knows 10-50 words Play pretend

Answer 315

Walks up and downstairs, stepping with both feet on each step Kicks ball Jumps Stacks up to 6 blocks (number of blocks = years x 3) Draws a line Knows >50 words Uses sentences of up to 2 words Engages in parallel play (2-3 years) Moves away and comes back to parent Follows 2 step commands Removes clothes

Answer 316

Alternates feet when walking up and down the stairs Pedals a tricycle Stacks up to 9 blocks Copies a circle Mostly intelligible speech Knows >300 words and understnads >1000 words Uses sentences of up to 3 words Understands gender difference Brushes teeth and grooms self Has bladder and bowel control (however, bed wetting until 5 years of age is considered normal) Plays away from parents

Answer 317

Hops on one foot Catches and throws ball overhand Copies a square Tells complex stories Can identify some colours and numbers Plays cooperatively May have imaginary friends

Answer 318

Skips Copies a triangle Can tie shoelaces Can write some letters Speak fluently Counts 10 or more things Uses sentences of up to 5 words Learns how to read Understands directions (left and right) Plays dress up

Answer 319

Children: height of > 2 SDs below the mean for children of the same age, sex, and similar genetic background Adults: height of ≤ 4 ft 10 in (147 cm) for women and ≤ 5 ft 1 in (155 cm) for men

Answer 320

Limbs proportionate to trunk | Seen in most cases of familial short stature

Answer 321

Limbs disproportionately short compared to trunk | Seen in most cases of skeletal dysplasia

Answer 322

Growth rate below the rate considered appropriate for sex and age

Answer 323

Short stature can have a variety of genetic, systemic, and psychosocial causes. Genetic causes include: - Familial short stature - Constitutional growth delay - Laron syndrome - Turner syndrome Systemic causes include: - Congenital hypothyroidism - GH deficiencies - Glucocorticoid excess Psychosocial causes include: - Maternal substance use (e.g., alcohol) - Psychosocial short stature - Psychiatric conditions (e.g., anorexia nervosa)

Answer 324

Patient history: -Physical examination findings -Growth rate -Family history of short stature -Midparental height (estimated adult height of a child calculated on the basis of parental height), calculated via the following formula: ♀ = [mother's height in cm + (father's height in cm - 13)]/2 ♂ = [father's height in cm + (mother's height in cm + 13)]/2 Laboratory tests: - FBC, differential blood count, ESR - Thyroid function tests (Hypothyroidism) - Renal function tests and urinalysis (in case of CKD and associated renal osteodystrophy) - Screening for GH deficiency (Hypopituitarism) - Hormone profile (LH, FSH, estrogen/testosterone) for puberty status assessment - Karyotyping Imaging tests - X-ray: used to determine an individual's bone age and height by comparing their x-ray images of the left hand and wrist to those displayed in the standard bone development atlas - Cranial MRI: in suspicion of hypothalamic or pituitary tumors

Answer 325

Management depends on the underlying cause: - Reassurance that low height is a normal variant (e.g., familial short stature) that does not require treatment - Discontinuation of growth-inhibiting medication (e.g., glucocorticoids) - Sex hormone substitution in children with delayed puberty and growth - GH supplementation (e.g., somatropin) in cases of GH deficiency, idiopathic short stature, and Turner syndrome - In case of primary severe IGF-1 deficiency: mecasermin (recombinant insulin-like growth factor) - Treatment of underlying conditions

Answer 326

A height of more than 2 standard deviations above the population mean or exceeding the 97th percentile on the normal growth curve for age and sex Most tall children do not have a pathological cause

Answer 327

History: - Assess milestones (exclude developmental delay) - Determine midparental height Physical examination - Accurate serial measurements of individual body areas - - Proportional vs disproportional growth (e.g., disproportionately long extremities usually indicate Marfan syndrome) - - Length or height - - Growth velocity - Exclude the following: - - Secondary sexual characteristics - - Neurological lesions - - Dysmorphisms Further diagnostic measures (if a pathological cause is suspected) - Bone age - Karyotyping - Endocrine laboratory tests (depends on which pathology is suspected e.g., insulin-like growth factor for excess growth hormone, or TSH and T4 hormone for hyperthyroidism)

Answer 328

A rare disorder characterised by abnormal linear growth during childhood due to growth hormone excess while the epiphyseal growth plates are still open

Answer 329

Most common: ↑ growth hormone (GH) secretion from the anterior pituitary (i.e., adenoma ) → ↑ IGF-1 synthesis → ↑ cell growth and proliferation ↑ GHRH secretion from the hypothalamus (i.e., tumors) ↑ Production of IGF-binding protein → ↑ half-life of IGF-1

Answer 330

Associated with an ↑ incidence of pituitary tumors Multiple endocrine neoplasia type 1 (MEN 1) McCune-Albright syndrome Carney complex Neurofibromatosis Tuberous sclerosis

Answer 331

Tall stature ↑ Growth of distal limbs (i.e., hands, feet, fingers, toes) Tumor mass symptoms: headaches, visual changes , features of hypopituitarism Progressive macroencephaly Coarse facial features, frontal bossing, prognathism Obesity

Answer 332

↑ Serum IGF-1 ↑ GH after oral glucose tolerance test confirms pituitary gigantism. After a biochemical diagnosis is established: - MRI: pituitary mass - CT if MRI is negative: exclude other GH-secreting tumors (e.g., pancreas, adrenal glands, ovarian, bronchial)

Answer 333

Transsphenoidal surgery: pituitary adenoma excision Medical therapy - Somatostatin analogs (e.g., octreotide ) - GH receptor antagonists (e.g., pegvisomant)

Answer 334

Carpal tunnel syndrome Cardiovascular disease - Heart failure (the most common cause of death) - Hypertension Osteoarthritis Endocrine disorders (i.e., hypogonadism, diabetes, hyperprolactinemia) Benign tumors (i.e., uterine leiomyomas, prostatic hypertrophy, colonic polyps)

Answer 335

Gigantism Precocious puberty Hyperthyroidism

Answer 336

Congenital disorder of growth with a predisposition to tumour development

Answer 337

∼ 1/15,000 newborns in the US Increased risk of Wilms tumor, hepatoblastoma, neuroblastoma, adrenal tumors

Answer 338

WT2 gene mutation on chromosome 11 (~80% of cases)

Answer 339

Macrosomia, omphalocele (i.e., exomphalos) Macroglossia, organ enlargement (heart, liver, kidney, etc.) Hemihypertrophy (hemihyperplasia): One side or a part of one side of the body is larger than the other. Features of neonatal hypoglycemia: irritability, intellectual disability Genitourinary abnormalities Facies: midface hypoplasia, infraorbital and earlobe creases Cleft palate (rare)

Answer 340

↓ Blood glucose, ↑ serum insulin, IGF-2 (hypoglycemia) Screening options for embryonal tumors: - Abdominal ultrasound every 3 months until 8 years of age - Alpha-fetoprotein levels every 3 months until 4 years of age

Answer 341

Frequent feedings to maintain sufficient blood glucose levels Resection of embryonal tumors

Answer 342

Cerebral gigantism

Answer 343

1/10,000–14,000 newborns

Answer 344

Autosomal dominant mutation in the NSD1 gene on chromosome 5

Answer 345

Tall stature Macrocephalus Facies - High forehead - Elongated face - Hypertelorism - Pointed chin - Receding hairline Psychomotor retardation Hypotonia Delays in achieving milestones (e.g., walking, talking, clumsiness)

Answer 346

Clinically DNA studies (5q35 microdeletions and partial NSD1 deletions in 10–15% of cases) Prenatal diagnosis possible

Answer 347

Only symptomatic treatment is possible | Multiprofessional approach

Answer 348

Normal growth rate from 3–5 years of age (only moderately increased adult height) Permanent cognitive-developmental impairments are common.

Answer 349

``` Sotos syndrome Marfan syndrome Homocystinuria Fragile X syndrome Neurofibromatosis type 1 Klinefelter syndrome (47, XXY) Weaver syndrome ```

Answer 350

A phase of development between childhood and complete, functional maturation of the reproductive glands and external genitalia (adulthood)

Answer 351

The age of pubertal onset may vary, but the order of changes that occur in each person is consistent. Adrenarche: activation of adrenal androgen production (axillary and pubic hair, body odor, and acne) Gonadarche: activation of reproductive glands by the pituitary hormones FSH and LH Thelarche: onset of breast development Pubarche: onset of pubic hair growth Menarche: onset of menstrual bleeding: - Anovulatory cycle: The menstrual cycle may be irregular in adolescents during the first few months/years after menarche. - - Immaturity of the hypothalamic-pituitary-gonadal axis → irregular secretion of gonadotropins → short luteal phase, and lack of progesterone → endometrium remains in the proliferative phase → irregular menses and heavy menstrual bleeding - - Does not require treatment because menses become regular as hypothalamic-pituitary-gonadal axis matures

Answer 352

Unknown initial trigger → ↑ activators and/or ↓ inhibitors of GnRH secretion → pulsatile GnRH secretion→ ↑ FSH and ↑ LH secreted by the anterior pituitary gland → stimulation of the Leydig cells and Sertoli cells in the testicles, and the theca and granulosa cells in the ovary. The hypothalamic-pituitary-gonadal axis is tightly regulated by a negative feedback mechanism. Testosterone inhibits further GnRH secretion from the hypothalamus. FSH-stimulated Sertoli cells also secrete inhibin, which further inhibits FSH secretion from the pituitary.

Answer 353

``` General health (nutritional state, bodyweight) Genetics Social environment (e.g., family stress) ```

Answer 354

Normal age of onset: 8–13 years (average 11 years) Normal order of changes: adrenarche → gonadarche → thelarche (age of onset 8–11 years) → growth spurt (age of onset 11.5–16.5 years) → pubarche (mean age of onset 12 years) → menarche (age of onset 10–16 years, mean age: 13 years) The first sign of puberty is breast development

Answer 355

Normal age of onset: 9–14 years (average 13 years) Normal order of changes: adrenarche → gonadarche (age of onset 9–14 years) → pubarche (mean age of onset 13.5 years)→ growth spurt (mean age of onset 13.5 years)→ androgenic hair growth The first visible sign of puberty in males is testicular enlargement

Answer 356

The appearance of secondary sexual characteristics before the age of 8y in girls and 9y in boys

Answer 357

Incidence: 1:5,000 to 1:10,000 children | Ten times more common in girls than boys.

Answer 358

Central precocious puberty (gonadotropin-dependent precocious puberty, true precocious puberty) Peripheral precocious puberty (gonadotropin-independent precocious puberty, peripheral pseudopuberty, peripheral precocity) Isosexual precocious puberty: premature development of secondary sexual characteristics appropriate for gender (can be complete or incomplete) Heterosexual precocious puberty: masculinization of girls or feminization of boys Benign pubertal variants - Precocious thelarche - Idiopathic premature pubarche - Premature adrenarche - Precocious menarche Obesity-related precocious sexual development

Answer 359

Precocious puberty with elevated GnRH levels

Answer 360

Idiopathic (most common cause) CNS lesions - Intracranial tumors (e.g., hamartoma, glioma, craniopharyngioma) - Trauma - Infections (e.g., encephalitis, meningitis) - Hydrocephalus Obesity-related precocious sexual development Systemic conditions: tuberous sclerosis, neurofibromatosis Radiation

Answer 361

Early activation of the hypothalamo-hypophyseal axis → abnormally early initiation of pubertal changes → early development of secondary sexual characteristics

Answer 362

Premature sexual development typically follows the normal pattern of puberty, except that it is early. Symmetric development of secondary sexual characteristics or, occasionally, as isolated premature thelarche, adrenarche, or menarche. Increased growth velocity: Children tend to be taller than their peers during adolescence, but are of shorter stature by the time they reach adulthood (due to early closure of the epiphyseal plate).

Answer 363

Laboratory tests: - Serum LH and FSH: increased - GnRH stimulation test (gold standard): evaluates the reactivity of the hypothalamic-pituitary-axis to GnRH stimulation - - Indications: suspicion of precocious puberty or delayed puberty - - Method: base LH and FSH values → administer GnRH → blood is drawn after a certain time for reevaluation of LH and FSH levels - - Gonadotropin (LH and FSH) levels increase after intravenous administration of GnRH. - Serum testosterone/estradiol: increased Imaging: -X-ray of the left hand and wrist: allows comparison between skeletal maturation and chronological age -- Assess and confirm accelerated bone growth. Bone age is within 1 year of a child's age: Puberty likely has not started. -- Bone age is > 2 years of the child's age: Puberty has been present for a year or longer. -MRI/CT of the brain with contrast: when ↑ LH is confirmed -- Perform in girls ≤ 6 years of age, all boys, and children with neurologic symptoms. -- Rule out intracranial causative pathology.

Answer 364

GnRH agonist (e.g., leuprolide, buserelin, goserelin): to prevent premature fusion of growth plates Close monitoring of therapy Follow-up is recommended every 4–6 months to assess progression. Manage underlying cause.

Answer 365

Precocious puberty without elevated GnRH levels (due to ↑ peripheral synthesis of or exogenous exposure to sex hormones)

Answer 366

↑ Androgen production - Congenital adrenal hyperplasia - Virilizing ovarian and adrenocortical tumors (e.g., Sertoli-Leydig cell tumor, Leydig-cell tumor) ↑ Estrogen production - McCune-Albright syndrome - HCG-secreting germ cell tumors (e.g., dysgerminomas) ↑ β-hCG production - Dysgerminoma - Malignant embryonal cell carcinoma - Choriocarcinoma Primary hypothyroidism Exogenous steroid use Obesity-related precocious sexual development

Answer 367

May not follow the normal developmental pattern (signs of estrogen or androgen excess) May exhibit possible features of an underlying condition (e.g., cafe-au-lait spots in McCune-Albright syndrome, testicular mass in Leydig-cell tumor)

Answer 368

Laboratory tests: - Serum basal FSH and LH: decreased - GnRH stimulation test - - No increase in LH levels after GnRH administration. - - Precocious pseudopuberty is associated with low basal LH levels (prepubertal values). - Serum testosterone/estradiol levels: increased (depending on the tumor) - TSH, T3 hormone: suspicion of hypothyroidism - Serum DHEA-S and 17-hydroxyprogesterone: in cases of hyperandrogenism - Corticotropin stimulation test: suspicion of congenital adrenal hyperplasia or an adrenal tumor Imaging: - X-ray of left wrist and hand: accelerated bone growth - Ultrasound of the ovaries, testicles, and abdomen (cases of increased ovarian and/or uterine volume than expected for age, diagnostic uncertainty)

Answer 369

Precocious puberty caused by excessive hormonal production from a tumor in the body: surgical removal Precocious puberty caused by Congenital Adrenal Hyperplasia: cortisol replacement Ovarian cysts: no intervention is necessary (spontaneous resolution is common)

Answer 370

Obesity is associated with early pubertal development, mainly due to obesity-related insulin resistance. This resistance leads to increased insulin and leptin levels.

Answer 371

Central mechanism: Obesity causes increased secretion of leptin, which leads to increased GnRH pulsatility → ↑ production of gonadotropins and sex hormones → early development of secondary sexual characteristics and early gonadarche. Peripheral mechanism: Obesity causes insulin resistance and compensatory hyperinsulinemia → premature adrenarche, thelarche, and pubarche. - Adrenals and ovaries: ↑ androgens - Liver: ↓ SHBG - Adipocytes: ↑ aromatase → ↑ bioavailability of sex steroids

Answer 372

A genetic syndrome caused by a G-protein activating mutation and subsequent continupus stimulation of endocrine functions

Answer 373

Accounts for 5% of cases of precocious puberty (more common in females) Affects 1 in 100,000 to 1 in 1,000,000 individuals in the general population Peak incidence: early childhood

Answer 374

Mosaic mutation in the GNAS1 gene on chromosome 20 (autosomal recessive inheritance) Some cells have a normal version of the GNAS1 gene, while other cells have the mutated version. Embryos only survive if mosaicism occurs. If the mutation occurs before fertilization, it affects all cells so is incompatible with life.

Answer 375

Activating mutation in GNAS gene → impaired Gs-protein signaling → constitutively activated adenylate cyclase → excess production of cAMP

Answer 376

Unilateral café-au-lait spots with unilateral, ragged edges Polyostotic fibrous dysplasia Endocrinopathies: - Peripheral precocious puberty (most common) - Cushing syndrome - Acromegaly - Hyperthyroidism

Answer 377

Clinical features Laboratory tests: - Increased hormone levels (e.g., estradiol, testosterone, cortisol, thyroid hormone, growth hormone, prolactin, somatomedin C) - Increased alkaline phosphatase - Molecular testing: GNAS1 analysis Imaging: - X-rays of long bones: well-defined, lobulated lesions with a thin cortex and a radiolucent, ground-glass appearance - CT/MRI: identify fibrodysplastic lesions - Bone scan: determine the extent of bone disease

Answer 378

Symptomatic: treat underlying endocrinopathies Estrogen synthesis inhibitors - Ketoconazole - Testolactone: an aromatase inhibitor that prevents the conversion of androstenedione to estrone and testosterone to estrogen Selective estrogen receptor modulators (e.g., tamoxifen)

Answer 379

Neurofibromatosis type 1 | Fibrous dysplasia

Answer 380

The condition is lethal when the mutation affects all cells (i.e., occurs before fertilization), but survivable in patients affected by mosaicism.

Answer 381

Polyostotic fibrous dysplasia Pigmentation (cafe au lait spots) Precocious puberty

Answer 382

Absent or incomplete development of secondary sex characteristics by the age of 14 years in boys or 13 years in girls

Answer 383

Physiological causes: constitutional growth delay Pathologic causes: - Hypergonadotropic hypogonadism - - Primary gonadal insufficiency (e.g., Klinefelter syndrome, Turner syndrome, androgen insensitivity syndrome) - - Secondary gonadal insufficiency (e.g., chemotherapy, pelvic irradiation, infections, trauma/surgery, autoimmune disease) - Hypogonadotropic hypogonadism (e.g., CNS lesions, Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, Prader-Willi syndrome, Gaucher disease) - Malnutrition (e.g., anorexia nervosa) - Chronic diseases (e.g., inflammatory bowel disease, hypothyroidism, cystic fibrosis)

Answer 384

Clinical features: depend on the underlying condition Physical examination - Tanner staging (testes ≤ 3 ml, absent breast buds, pubic/axillary hair or menarche) - Assessment of height (short stature) - Assessment of weight - Neurological exam (anosmia)

Answer 385

Medical history (e.g., positive family history of delayed onset of puberty, tanner staging, BMI) Routine tests: - Serum LH, FSH, and testosterone/estradiol - - Low or normal with low testosterone/estradiol: constitutional growth delay, isolated GnRH deficiency, functional hypogonadotropic hypogonadism (e.g., medical illness, malnutrition), or hypothalamic-pituitary disorders (e.g., malformations, hemochromatosis, injury, tumors) - - Elevated: primary hypogonadism - X-ray of the left hand and wrist - - First imaging study - - Shows delayed bone age (less than the individual's chronological age) Additional tests: based on suspected etiology - Serum prolactin level (elevated in prolactinoma) - IGF-1 levels (exclude growth hormone deficiency) - TSH and T4 hormone: evaluate amenorrhea and hypothyroidism - Karyotype (Turner syndrome in girls, Klinefelter syndrome in boys) - Complete blood and biochemical tests (e.g., FBC, ESR, LFT, U and Es, creatinine): suspected systemic disorder in children - Antiendomysial antibody: screen for celiac disease in patients with signs of malabsorption - Abdominal ultrasound (streak ovaries in Turner syndrome, testicular mass) - Head MRI: suspected prolactinoma (e.g., headaches, bitemporal hemianopia)

Answer 386

Constitutional growth delay: - expectant management - No treatment is needed as catch-up growth eventually occurs and the individual reaches a normal adult height. - Serial growth measurements at frequent intervals (∼ every 6 months) - Reassuring the child and parents is sufficient. Other pathologies: Treatment of the underlying disease Hormonal therapy -Testosterone: used in boys to achieve secondary sex characteristics (e.g., virilization, growth spurt) -- Boys with constitutional growth delay usually respond well after one or two courses of testosterone therapy. -- If little or no response is seen, isolated GnRH deficiency should be suspected in boys over the age of 18 years. -Estradiol: used in girls with primary gonadal insufficiency (e.g., Turner syndrome) -- Initially: low-dose estradiol that is gradually increased -- After 2 years: Add cyclic progestin therapy to induce menstruation.

Answer 387

AKA X linked agammaglobulinaemia X-linked recessive disease that causes a complete deficiency of mature B lymphocytes

Answer 388

Occurs mainly in boys

Answer 389

Defect of Bruton tyrosine kinase expressed in B cells leading to a complete deficiency of mature B cell

Answer 390

Symptoms develop between 3 and 6 months of age when maternal IgG levels in fetal serum start to decrease. Hypoplasia of lymphoid tissue (e.g., tonsils, lymph nodes) Recurrent, severe, pyogenic infections (e.g., pneumonia, otitis media), especially with encapsulated bacteria (S. pneumoniae, N. meningitidis, and H. influenzae) Hepatitis virus and enterovirus (e.g., Coxsackie virus) infections

Answer 391

Flow cytometry: - Absent or low levels of B cells (marked by CD19, CD20, and CD21) - Normal or high T cells Low immunoglobulins of all classes Absent lymphoid tissue, i.e., no germinal centers and primary follicles

Answer 392

IV immunoglobulins Prophylactic antibiotics Live vaccines are contraindicated in patients with Bruton agammaglobinaemia

Answer 393

Brutal defects in a B cell make little Boys feel unwell

Answer 394

Most common primary immunodeficiency that is characterized by a near or total absence of serum and secretory IgA

Answer 395

~1:220 to 1:1000 | Unknown aetiology

Answer 396

Often asymptomatic May manifest with sinusitis or respiratory infections (S. pneumoniae, H. influenzae) Chronic diarrhea, partially due to elevated susceptibility to parasitic infection (e.g. by Giardia lamblia) Associated with autoimmune diseases (e.g., gluten-sensitive enteropathy, inflammatory bowel disease, immune thrombocytopenia) and atopy Anaphylactic reaction to products containing IgA (e.g., intravenous immunoglobulin)

Answer 397

Decreased serum IgA levels (< 7 mg/dL) Normal IgG and IgM levels False-positive pregnancy tests

Answer 398

Treatment of infections Prophylactic antibiotics Intravenous infusion of IgA is not recommended because of the risk of anaphylactic reactions (caused by the production of anti-IgA antibodies). To prevent transfusion reactions, IgA-deficient patients must be given washed blood products without IgA or obtain blood from an IgA-deficient donor

Answer 399

``` Asymptomatic Airway infections Anaphylaxis to IgA containing products Autoimmune diseases Atopy ```

Answer 400

Primary immunodeficiency with low serum levels of all immunoglobulins despite phenotypically normal B cells

Answer 401

F=M | Onset: later than other B-cell defects (typically at 20-40 y/o)

Answer 402

Most cases are sporadic with no known family hisotry

Answer 403

B cells are phenotypically normal but are unable to differentiate into Ig-producing cells, resulting in low immunoglubulins of all classes

Answer 404

Recurrent pyogenic respiratory infections, e.g., sinopulmonary infections (in rare cases, enteroviral meningitis) Associated with a high risk of lymphoma, gastric cancer, bronchiectasis, and autoimmune disorders (e.g., rheumatoid arthritis, autoimmune hemolytic anemia, immune thrombocytopenia, vitiligo)

Answer 405

Quantitative immunoglobulin levels: low levels of IgG, IgA, and IgM Decreased number of plasma cells Flow cytometry shows subsets of normal B and T cells Poor response to immunizations

Answer 406

Treatment of infections Prophylactic antibiotics IV immunoglobulins

Answer 407

A malignant embryonal neuroendocrine neoplasm of the sympathetic nervous system that originates from neural crest cells, potentially secretes catecholamines and is usually found in the adrenal glands or sympathetic ganglia

Answer 408

Most common malignancy of the adrenal medulla in infants and third most common childhood cancer overall following leukaemia and brain tumours Mean age of diagnosis is 1-2 y/o The majority of children have progressed to advanced stage disease by the time of diagnosis

Answer 409

Cause: unclear Genetic associations: - chromosomal abnormalities, especially deletions (found in ∼ 50% of neuroblastomas) - - Deletions of 1p, 11q, and 14q chromosomosomal regions - - Amplification and overexpression of oncogene MYCN (N-myc) Risk factors: - Maternal: gestational diabetes, opiates, folate deficiency - Congenital syndromes: Turner syndrome, neurofibromatosis, Hirschsprung's disease, Beckwith-Wiedemann syndrome - Familial

Answer 410

General: - Failure to thrive or weight loss - Fever - Nausea, vomiting, loss of appetite - Hypertension Localised symptoms: - Abdomen (>60% of cases): - - Palpable, firm, irregular abdominal mass that may cross the midline (in contrast to Wilms tumor, which is smooth and usually does not cross the midline) - - Abdominal distension and pain - - Hepatomegaly - - Constipation - Chest (~20% of cases): - - Spinal cord compression → back pain, weakness, numbness, ataxia, loss of bowel or bladder control - - Scoliosis - - Dyspnea, cough - - Inspiratory stridor - Neck: - - Horner syndrome - - Symptoms due to spinal cord compressions Mets locations: - Orbit of the eye: - - periorbital ecchymoses (raccoon eyes) - - Proptosis - Bones: - - Bone pain - - Anaemia (bone marrow suppression) - Skin: - - Subcutaneous nodules Paraneoplastic syndromes: - Chronic diarrhea → electrolyte imbalances - Opsoclonus-myoclonus-ataxia: a paraneoplastic syndrome of unclear etiology characterized by rapid and multi-directional eye movements, rhythmic jerks of the limbs, and ataxia (dancing eyes dancing feet syndrome) - Possibly hypertension, tachycardia, palpitations, sweating, flushing (hypertension is more commonly seen in pheochromocytoma)

Answer 411

International Neuroblastoma Staging System 1. Localized tumor Complete gross excision with or without microscopic residuals Negative ipsilateral lymph nodes 2A. Localized tumor Incomplete gross excision Negative ipsilateral lymph nodes 2B. Localized tumor Complete or incomplete gross excision Positive ipsilateral lymph nodes 3. Unresectable unilateral tumor that crosses the midline with or without lymph node involvement Any tumor with positive contralateral lymph nodes Midline tumor with bilateral tumor or lymph node involvement 4. Any tumor with dissemination to distant lymph nodes or other organs (e.g., bone, liver, skin), with the exception of Stage 4S disease 4S. Localized primary tumor with dissemination to skin, liver, or bone marrow, occurring in infants < 12 months

Answer 412

Laboratory tests: Urine - ↑ Catecholamine metabolites homovanillic acid (HVA) and vanillylmandelic acid (VMA) in 24-hour urine - Urinalysis Blood - ↑ Catecholamine metabolites (HVA/VMA) - ↑ Lactate dehydrogenase (LDH), ferritin, neuron-specific enolase (NSE) - FBC with differential - Serum chemistry profile - Liver and kidney function tests Other procedures: Imaging: - To identify the primary site - Abdominal ultrasound - CT or MRI (depending on the presumable site of the lesion) Scintigraphy: - MIBG scan: Uptake scan of metaiodobenzylguanidine (MIBG) combined with a radioactive iodine tracer. - In MIBG non-avid tumors: technetium bone scan and plain radiographs Biopsy: - Image-guided needle aspiration of the tumor or biopsy at the time of surgical tumor resection - - Evaluation for MYCN gene amplification - - Evaluation for DNA ploidy - Bilateral bone marrow biopsy of iliac crests

Answer 413

Homer Wright rosettes: Halo-like clusters of neuroblast cells surrounding a central pale area containing neuropil (associated with tumors of neuronal origin such as neuroblastoma, medulloblastoma, primitive neuroectodermal tumors, and pineoblastoma) Small round blue cells with hyperchromatic nuclei Bombesin and NSE positive

Answer 414

``` Wilms tumor Pheochromocytoma Lymphoma Sarcomas Osteomyelitis or transient synovitis ```

Answer 415

Neuroblastoma patients are treated based on their risk category (low, intermediate, or high), which is based on the stage of their neuroblastoma (extent of disease), age at diagnosis, and the presence/absence of MYCN amplification. Low risk: generally children with early-stage disease (Stages 1–2) and no MYCN amplification - Observe - Preoperative chemo - Surgery Intermediate risk: generally children with intermediate and late-stage disease (Stages 3–4) and no MYCN amplification - Preoperative chemo - Surgery - Post op chemo - Radiation High risk: generally children with late-stage disease and/or MYCN amplification - Pre op chemo - Surgery - Post op chemo - Radiation - GD2 antibody, dinutuximab, GM-CSF, IL-2 and cis-retinoic acid - MIBG therapy post op Stage 4S (an exception): disseminated disease in infants (< 12 months) - Better prognosis than other stage 4 neuroblastoma and spontaneous regression is very common - Children with Stage 4S belong to the low-risk or intermediate-risk groups unless they have a MYCN amplification, in which case they are high-risk patients

Answer 416

Doxorubicin Cyclophosphamide Etoposide Platinum drug

Answer 417

Prognosis depends on the risk group. Important factors include: -Age -Children with MYCN amplification are classified as high risk -Histopathology, disease dissemination and biochemical markers

Answer 418

Nephroblastoma | Most common renal malignancy in children

Answer 419

Peak incidence between 2 and 5 years | Most common malignant neoplasm of the kidney in children

Answer 420

The exact aetiology of Wilms tumor remains unknown, but it is associated with several genetic mutations and syndromes. Genetic predisposition: - Gene mutations have been found in children both with and without genetic syndromes who have Wilms tumor. - Associated with loss of function mutations of tumor supressor genes on chromosome 11 - - The WT1 (Wilms tumor 1) gene is the most important Wilms tumor gene (mutated in ∼ 10–20% of cases). - - WT2 (Wilms tumor 2) gene Associated syndromes: - WAGR syndrome: Deletion of the 11p13 band leads to the deletion of the WT1 gene and other genes, such as PAX6 - - Wilms tumor - - Aniridia - - Genitourinary anomalies - -- Pseudohermaphroditism, undescended testes in males (due to gonadal dysgenesis) - -- Early-onset nephrotic syndrome - - Range of intellectual disability - Denys-Drash syndrome: point mutation in WT1 gene, which encodes a zinc finger transcription factor - - Wilms tumor - - Pseudohermaphroditism, undescended testes in males (due to gonadal dysgenesis) - - Early-onset nephrotic syndrome caused by diffuse mesangial sclerosis - Beckwith-Wiedemann syndrome: mutations of the WT2 gene

Answer 421

Wilms tumor, Aniridia, Genitourinary anomalies and Range of intellectual disability