Neonatology

Question 1

Overview

Answer 1

-Jaundice
-Prematurity
-Bilious vomiting
-Feeding problems
-Low blood sugar
-Common genetic disorders (Downs’, Fragile X, CF)
-Failure to thrive
-Hypospadias

Question 2

General issues of neonates

Answer 2

-Increased requirement for support at delivery
-Poor temp regulation
-Poor barrier defence thin skin)
-Increased water losses
-Poor respiratory drive (apnoea and brady)

Warm, sweet, pink

Question 3

Describe the Apgar score

Answer 3

The Apgar score is used to assess the health of a newborn baby. NICE recommend that it is assessed at 1, and 5 minutes of age. If the score is low then it is again repeated at 10 minutes.

Pulse, Respiratory effort, colour, muscle tone, reflex irritability

A score of 0-3 is very low score, between 4-6 is moderate low and between 7 - 10 means the baby is in a good state

Question 4

Neonatal blood spot screening

Answer 4

Neonatal blood spot screening (previously called the Guthrie test or ‘heel-prick test’) is performed at 5-9 days of life

The following conditions are currently screened for:
congenital hypothyroidism
cystic fibrosis
sickle cell disease
phenylketonuria
medium chain acyl-CoA dehydrogenase deficiency (MCADD)
maple syrup urine disease (MSUD)
isovaleric acidaemia (IVA)
glutaric aciduria type 1 (GA1)
homocystinuria (pyridoxine unresponsive) (HCU)

Question 5

Red flags in history for neonatal jaundice

Answer 5

-Timing of jaundice (sudden/gradual)
-Precipitating factors (e.g. drugs, recent infections)
-Progression (e.g. persistent/intermittent)
-Stool/urine colour: babies in first 3 months of life cannot concentrate urine, putty coloured stools are acholic (no bilirubin or pigmented metabolites)
-Any bleeding, bruising
-Unwell or not
-Family history (e.g. liver disease)

Question 6

Red flags in exam for neonatal jaundice

Answer 6

-Growth; dysmorphic features (metabolic)
-Unwell or not
-Hepatosplenomegaly, ascites; spider naevi, venous shunting(chronicity)
-Bleeding or bruising
-Check urine and stool colour
-Not just unwell! - Could this be a life-threatening situation?

Question 7

Causes of neonatal jaundice in first 24 hours

Answer 7

-Jaundice in first 24 hours ALWAYS pathological
=Rhesus haemolytic disease
=ABO haemolytic disease
=Hereditary spherocytosis
=Glucose-6-phosphodehydrogenase

Question 8

Causes of jaundice in the neonate from 2-14 days

Answer 8

Jaundice in the neonate from 2-14 days is common (up to 40%) and usually physiological. It is due to a combination of factors, including more red blood cells, more fragile red blood cells and less developed liver function.

Break down feto haemoglobin release unconjugated bilirubin (conjugated in liver)

It is more commonly seen in breastfed babies

Question 9

Causes of jaundice after 14 days (prolonged)

Answer 9

-Biliary atresia
-Hypothyroidism
-Galactosaemia
-UTI
-Breast milk jaundice
=jaundice is more common in breastfed babies
=mechanism is not fully understood but thought to be due to high concentrations of beta-glucuronidase → increase in intestinal absorption of unconjugated bilirubin
-Prematurity
=due to immature liver function
=increased risk of kernicterus
-Congenital infections e.g. CMV, toxoplasmosis

Question 10

Overview of biliary atresia

Question 11

What is in a prolonged jaundice screen?

Answer 11

-Conjugated and unconjugated bilirubin: the most important test as a raised conjugated bilirubin could indicate biliary atresia which requires urgent surgical intervention
-Direct antiglobulin test (Coombs’ test)
-TFTs
-FBC and blood film
-Urine for MC&S and reducing sugars
-U&Es and LFTs

UV light to treat
Unconjugated bilirubin passes BBB and causes brain damage

Question 12

Inherited causes of jaundice

Answer 12

Conjugated hyperbilirubinemia
-Dubin-Johnson syndrome
=Autosomal recessive, defective hepatic excretion of bilirubin, grossly black liver, benign
-Rotor syndrome
=Autosomal recessive defect in hepatic uptake and storage of bilirubin, benign

Unconjugated
-Gilbert’s syndrome
=Autosomal recessive, mild deficiency of UDP-glucuronyl transferase, benign
-Crigler-Najjar syndrome
=Autosomal recessive, absolute deficiency, do not survive to adulthood (type 1), type 2 less severe, more common and may improve with phenobarbital

Question 13

What are the likely causes of death in acute or chronic liver disease?

Answer 13

-Bleeding – coagulopathy
-Infection
-Encephalopathy (sleepy, unarousable, irritable)

Question 14

Risks of prematurity

Answer 14

-Increased mortality depends on the gestation
-Respiratory distress syndrome
-Intraventricular haemorrhage
-Necrotizing enterocolitis
-Chronic lung disease, hypothermia, feeding problems, infection, jaundice
-Retinopathy of prematurity
=Important cause of visual impairment in babies born before 32 weeks gestation
=The cause is not fully understood and multivariate. One of the contributing factors is thought to be over oxygenation (e.g. during ventilation) resulting in a proliferation of retinal blood vessels (neovascularization)
=Screening is done in at-risk groups
-Hearing problems

Question 15

Preterm resp disease

Answer 15

-Surfactant-deficient lung disease (RDS)
-Air leaks (leads to tension pneumothorax)
-Infection
-Haemorrhage
-Bronchopulmonary dysplasia (BPD/CLD)

Question 16

Overview of Respiratory Distress Syndrome

Answer 16

1-3% all births
-Surfactant deficiency phospholipids and proteins, 22/40 weeks, reduces surface tension and improved compliance by prevention lung collapse)
-Common if preterm, male, cold, asphyxiated
-Treatment: prevention steroids), supportive (O2, fluids, nCPAP), specific (surfactant, animal-derived, prophylaxis or rescue, decreases mortality)

Question 17

Overview of bronchopulmonary dysplasia

Answer 17

-Chronic lung disease in ex-prem babies
-Oxygen requirement @3640 CGA
=Type 2 resp failure
=Disordered/ delayed development
-Oxygen + pressure + time + inflammation
-Increased resp admissions

-Grow out of it, smaller lungs

Question 18

Congenital Cardiac Conditions

Answer 18

-Acyanotic: L to R
=VSD
-Cyanotic: R to L
=Tetralogy of Fallot

Preterm association:
1. Patent Ductus Arteriosus
2. Hypotension ((immature myocardium)

Question 19

Overview of Intraventricular Haemorrhage (IVH)

Answer 19

-Pre-term brains are vulnerable
=Germinal matrix is unstable, may rupture
=Immature autoregulation so cannot control blood flow
=<32/40
-Diagnose on USS
-Complications
=Post haemorrhagic hydrocephalus, blood in ventricles, blocks up sponge that reabsorbs CF so big head
=Neurodisability
=Death

Question 20

Examples of neurodisability

Answer 20

-Cerebral palsy
-Learning difficulties
-Behavioural problems

=Periventricular Leucomalacia: cytokines stunts neuron growth
=Cortical Visual Impairment: optic radiation damaged

Question 21

Overview of retinopathy of prematurity

Answer 21

-Potentially blinding, preventable, curable
-Screen all <32/40, <1500g
=25% survivors (10% laser)
-Retina vascularised from 16/40-36/40
=Becomes disordered, as VEFG in hypoxia causes vascularisation (womb hypoxic)
=Oxygen implicated: now 90-95%
-Treatment: laser or anti VEFG antibodies

Question 22

Overview of necrotising enterocolitis

Answer 22

-Haemorrhagic pancolitis
=5% of VLBW
-Presentation
=Feed intolerance, abdominal distension, bloody stools, collapse
-M: resus/ supportive, NBM/NGT/ABtx +/- surgery
-Complications
=Short gut: long-term parenteral nutrition
=Death

Question 23

Iatrogenesis

Answer 23

-Sepsis/ infection: x2 cerebral palsy risk
-Ischaemia
-Extravasation
-Burns (alcohol)
-Scars/ trauma

Question 24

Causes of bilious vomiting in neonates

Answer 24

-Duodenal atresia
=1/5000 (higher in Down’s)
=Few hours after birth
=AXR shows double bubble sign, contrast study may confirm
=Duodenoduodenostomy

-Malrotation with volvulus
=Usually caused by incomplete rotation
=Usually 3-7 days after birth, volvulus with compromised circulation may result in peritoneal signs and haemodynamic instability
=Upper GI contrast: DJ flexure medial, USS abnormal orientation

-Jejunal/ ileal atresia
=Vascular insufficiency in utero, 1/3000
=Within 24 hours
=AXR: air-fluid levels

-Meconium ileus
=15-20% CF babies/ 1/5000 normal
=First 24-48 hours with abdominal distention
=AXR: air-fluid levels, sweat test

-Necrotising enterocolitis
=2.4/1000, premature and intercurrent illness
=Second week of life
=AXR: dilated bowel loops, pneumatosis and portal venous air

Question 25

Feeding problems

Answer 25

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Question 26

Overview of neonatal hypoglycaemia

Answer 26

-Normal term babies often have hypoglycaemia especially in the first 24 hrs of life but without any sequelae, as they can utilise alternate fuels like ketones and lactate.
-There is no agreed definition of neonatal hypoglycaemia but a figure of < 2.6 mmol/L is used in many guidelines.
-Transient hypoglycaemia in the first hours after birth is common.

-Persistent/severe hypoglycaemia may be caused by:
=preterm birth (< 37 weeks)
=maternal diabetes mellitus
=IUGR
=hypothermia
=neonatal sepsis
=inborn errors of metabolism
=nesidioblastosis
=Beckwith-Wiedemann syndrome

-P:
=may be asymptomatic
=autonomic (hypoglycaemia → changes in neural sympathetic discharge)
=’jitteriness’
=irritable
=tachypnoea
=pallor
=neuroglycopenic
=poor feeding/sucking
=weak cry
=drowsy
=hypotonia
=seizures
=other features may include apnoea and hypothermia

-M: depends on the severity of the hypoglycaemia and if the newborn is symptomatic
=asymptomatic: encourage normal feeding (breast or bottle) monitor blood glucose
=symptomatic or very low blood glucose: admit to the neonatal unit, intravenous infusion of 10% dextrose

Question 27

Overview of Down’s features and complications

Answer 27

-Face: upslanting palpebral fissures, epicanthic folds, Brushfield spots in iris, protruding tongue, small low-set ears, round/flat face
flat occiput
-Single palmar crease, pronounced ‘sandal gap’ between big and first toe
-Hypotonia
-Congenital heart defects (40-50%, see below)
-Duodenal atresia
-Hirschsprung’s disease

-Cardiac complications
=multiple cardiac problems may be present
=endocardial cushion defect (most common, 40%, also known as atrioventricular septal canal defects)
=ventricular septal defect (c. 30%)
=secundum atrial septal defect (c. 10%)
=tetralogy of Fallot (c. 5%)
=isolated patent ductus arteriosus (c. 5%)

-Later complications
=subfertility: males are almost always infertile due to impaired spermatogenesis. Females are usually subfertile, and have an increased incidence of problems with pregnancy and labour
=learning difficulties
=short stature
=repeated respiratory infections (+hearing impairment from glue ear)
=acute lymphoblastic leukaemia
=hypothyroidism
=Alzheimer’s disease
=atlantoaxial instability

Question 28

Antenatal testing for Downs’ syndrome

Answer 28

-Combined test is now standard
=Done between 11 - 13+6 weeks
=Nuchal translucency measurement + serum B-HCG + pregnancy-associated plasma protein A (PAPP-A)
=Down’s syndrome is suggested by ↑ HCG, ↓ PAPP-A, thickened nuchal translucency
=Trisomy 18 (Edward syndrome) and 13 (Patau syndrome) give similar results but the hCG tends to lower

-Quadruple test
=If women book later in pregnancy the quadruple test should be offered between 15 - 20 weeks
=Quadruple test: alpha-fetoprotein (decrease), unconjugated oestriol (decrease), human chorionic gonadotrophin (increase) and inhibin A (increase)

-High chance: 1 in 150 or less, low chance: 1 in 150 chance or more

-If a woman has a ‘higher chance’ results she will be offered a second screening test (NIPT) or a diagnostic test (e.g. amniocentesis or chorionic villus sampling (CVS). Given the non-invasive nature of NIPT and extremely high sensitivity and specificity, it is likely this will be the preferred choice for the vast majority of women.

-NIPT
=Analyses small DNA fragments that circulate in the blood of a pregnant woman (cell free fetal DNA, cffDNA)
=cffDNA derives from placental cells and is usually identical to fetal DNA
=Analysis of cffDNA allows for the early detection of certain chromosomal abnormalities
=Sensitivity and specificity are very high for trisomy 21 (>99%) and similarly high for other chromosomal abnormalities
=Private companies (e.g. Harmony) offer NIPT screening from 10 weeks gestation

Question 29

Overview of Fragile X

Answer 29

-Fragile X syndrome is a trinucleotide repeat disorder.

-P in males: learning difficulties, large low set ears, long thin face, high arched palate
macroorchidism, hypotonia, autism is more common, mitral valve prolapse

-P in females (who have one fragile chromosome and one normal X chromosome) range from normal to mild

-D: can be made antenatally by chorionic villus sampling or amniocentesis, analysis of the number of CGG repeats using restriction endonuclease digestion and Southern blot analysis

Question 30

Overview of Cystic Fibrosis

Answer 30

-Cystic fibrosis (CF) is an autosomal recessive disorder causing increased viscosity of secretions (e.g. lungs and pancreas). It is due to a defect in the cystic fibrosis transmembrane regulator gene (CFTR), which codes a cAMP-regulated chloride channel
-In the UK 80% of CF cases are due to delta F508 on the long arm of chromosome 7. Cystic fibrosis affects 1 per 2500 births, and the carrier rate is c. 1 in 25

-Organisms which may colonise CF patients
=Staphylococcus aureus
=H. influenzae
=Pseudomonas aeruginosa
=Burkholderia cepacia
=Non-tuberculous mycobacteria
=Aspergillus

-P: neonatal period (around 20%): meconium ileus, less commonly prolonged jaundice
=recurrent chest infections (40%)
=malabsorption (30%): steatorrhoea, failure to thrive
=other features (10%): liver disease
=Short stature, DM, delayed puberty, rectal prolapse (due to bulky stools), nasal polyps, male infertility and female subfertility

-I: Whilst many patients are picked up during newborn screening programmes or early childhood, it is worth remembering that around 5% of patients are diagnosed after the age of 18 years. Sweat test (abnormally high sweat chloride, CF indicated by >60), Immunoreactive trypsin on bloodspot card, mutation analysis if IRT high

-M: Regular chest physiotherapy and postural drainage, high calorie diet and high fat intake, minimise contact with each other to prevent cross infection with Pseudomonas, vitamins, pancreatic enzyme supplement, lung transplant (chronic infection with Burkholderia cepacia contraindication) immunoglobulin Ivacaftor/Kaftrio/Orkambi/Symkevi, prophylactic antibiotics, mucolytic (DNAse, hypertonic saline)

Question 31

Causes for false readings in Sweat Test

Answer 31

-Causes of false positive sweat test
=malnutrition
=adrenal insufficiency
=glycogen storage diseases
=nephrogenic diabetes insipidus
=hypothyroidism, hypoparathyroidism
=G6PD
=ectodermal dysplasia

-The most common reason for false negative tests is skin oedema, often due to hypoalbuminaemia/ hypoproteinaemia secondary to pancreatic exocrine insufficiency.

Question 32

Complications of CF

Answer 32

-Recurrent infections
-Bronchiectasis
-Resp failure
-Pneumothorax
-Haemoptysis
-Nasal polyps
-Chronic sinusitis
-Allergic bronchopulmonary aspergillosis

-Exocrine pancreatic insufficiency
-Pancreatitis
-CF-related diabetes

-GI
-Liver: cholestasis, cirrhosis, gallstones

-Male infertility: CBAVD, delayed puberty

-Skin: increased sweat losses (secondary hyperaldosteronism, dehydration)

-Arthropathy arthritis
-Osteoporosis

Question 33

Failure to thrive

Answer 33

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Question 34

Hypospadias

Answer 34

-Hypospadias is a congenital abnormality of the penis which occurs in approximately 3/1,000 male infants. There appears to be a significant genetic element, with further male children having a risk of around 5-15%.
-It is usually identified on the newborn baby check. If missed, parents may notice an abnormal urine stream.

-Hypospadias is characterised by
=a ventral urethral meatus
=a hooded prepuce
=chordee (ventral curvature of the penis) in more severe forms
=the urethral meatus may open more proximally in the more severe variants. However, 75% of the openings are distally located.
-Hypospadias most commonly occurs as an isolated disorder. However, associated conditions include cryptorchidism (present in 10%) and inguinal hernia.

-M: once hypospadias has been identified, infants should be referred to specialist services, corrective surgery is typically performed when the child is around 12 months of age, it is essential that the child is not circumcised prior to the surgery as the foreskin may be used in the corrective procedure. In boys with very distal disease, no treatment may be needed.