Neonatology Flashcards
What are thd steps of embryo logical development of cardiac system ❓
🔺The heart develops initially as a tube from yolk sac mesoderm.
🔺It begins to beat from about 3 weeks’ gestation
🔺In the fourth week the primitive heart loops to form four chambers.
🔺Septation between the four chambers and the aorta and pulmonary trunk occurs in the fifth week.
®️How embryo logical heart septum developed ❓❓
🔹The septum primum grows down from the upper part of the primitive atrium and then fuses with the endocardial cushions (septum intermedium) in the atrioventricular canal
🔹Bulbotruncal septation divides the common arterial trunk into the aorta and pulmonary trunk as spiral ridges develop in the caudal end of the heart.
🔹Completion of ventricular septation occurs as these fuse with the septum intermedium
How the heart pump the blood and how the main arteries form ❓❓
• Blood is pumped caudally from the embryonic heart by six pairs of pharyngeal arch arteries to the paired dorsal aortas.
®️Some of this system regresses and
✔️ the third arch arteries form the carotid vessels.
✔️The right fourth arch artery forms the right subclavian artery with that of the left, forming the aortic arch.
✔️The left sixth arch artery forms the ductus arteriosus with branch pulmonary arteries forming from the right
What is the Embryology of the central nervous system ❓❓
3rd week🔺 The neural plate develops from ectoderm and forms the neural tube by 3 weeks’ gestation.
4th week🔺The neural groove closes in a cranial-to-caudal direction by the end of the fourth week
🔺 Three swellings evolve from the caudal end of the neural tube – the prosencephalon (forebrain) forms the cerebral hemispheres, the mesencephalon forms the midbrain, and the rhombencephalon (hind brain) forms the pons, medulla and cerebellum
🔺Neuroblasts migrate from the centre of the brain to further develop the cerebral hemispheres
12th week 🔺Myelination from Schwann cells occurs from 12 weeks’ gestation.
Myelination accelerates from about 24 weeks but is not complete until around 2 years of age. This has important implications for the interpretation of brain MR (magnetic resonance) scans in neonates and early childhood
What are the cells that Neural crest cells differentiate into ❓❓
🔹meninges
🔹peripheral nerves
🔹chromaffin cells
🔹melanocytes
🔹adrenal medulla
How much is the risk of congenital malformations in diabetic mother ❓❓ and what are the common malformation ❓❓
🔺Threefold increased risk of congenital malformations
🔹congenital heart disease
🔹sacral agenesis
🔹microcolon
🔹neural tube defects)
What other abnormalities associated with maternal diabetes ❓❓
• Small for gestational age (SGA) three times the normal rate because of small-vessel disease
• Macrosomia as a result of increased fetal insulin
• Hypoglycaemia
• Hypocalcaemia
• Hypomagnesaemia
• Surfactant deficiency
• Transient hypertrophic cardiomyopathy (septal)
• Polycythaemia and jaundice
What abnormalities associated with maternal Hypertension and pre-eclampsia❓❓
▪️SGA
▪️polycythaemia
▪️neutropenia
▪️thrombocytopenia
▪️hypoglycaemia
What is the effect of Maternal thyroid disease on the neonate ❓❓
💛• Neonatal thyrotoxicosis can be caused by transplacental thyroid-stimulating antibodies (i.e. longacting thyroid stimulator [LATS]) with maternal Graves disease • Rare – only 1:70 mothers with thyrotoxicosis
💛Neonatal hypothyroidism may be caused by maternal antithyroid drugs taken during pregnancy, so check TFTs between 4 and 7 days after birth.
What is the Clinical presentation of neonatal hypothyroidism❓❓ and when should we test TFT if the mother have gravis disease ❓❓
🔺May present with fetal tachycardia or within 1–2 days of birth, but sometimes delayed if mother is taking antithyroid drugs
🔺Usually causes goitre
• Thyroid function tests (TFTs) should be assessed between 7 and 10 days in all babies of motherswith Graves disease (or sooner if the baby is symptomatic)
📴What is treatment of neonatal hyperthyroidism ❓❓
• Only severe cases require treatment with β blockers and antithyroid drugs because it resolves spontaneously as antibody levels fall over the first few months
What is Maternal systemic lupus erythematosus (SLE) associated with❓
• Increased risk of miscarriage; recurrent miscarriage is associated with antiphospholipid antibody
• Increased risk of SGA babies. Risk is higher with maternal hypertension and renal disease
• Congenital complete heart block – associated with presence of anti-Ro and anti-La antibodies
• Butterfly rash – transient because of transplacental passage of SLE antibodies
What is the cause of Thrombocytopenia in neonates ❓❓
Transplacental passage of maternal antiplatelet antibodies causes neonatal thrombocytopenia. If the mother is also thrombocytopenic, the cause is likely to be maternal idiopathic thrombocytopenia (also associated with maternal SLE)
What is the cause of Alloimmune thrombocytopenia❓❓and what is the treatment ❓❓
occurs following maternal sensitization if mother is PLA1 antigen negative:
• Approximately 3% of white people are PLA1 antigen negative
• First pregnancies may be affected; severity is usually greater in subsequent pregnancies
• Antenatal intracranial haemorrhage is common (20–50%)
• Treatment – washed irradiated maternal platelets or intravenous IgG and random donor platelets
Myasthenia gravis Babies of mothers with myasthenia gravis have a 10% risk of a transient neonatal form of the disease:
• Usually the result of transplacental passage of anti-acetylcholinesterase receptor antibodies but baby may produce own antibodies
• Risk is increased if a previous baby was affected • Maternal disease severity does not correlate with that of baby; a range of symptoms from mild hypotonia to ventilator-dependent respiratory failure may occur• Diagnosis – antibody assay, electromyography and edrophonium or neostigmine test (also used as treatment)
• Babies of mothers with myasthenia gravis should be monitored for several days after birth • Usually presents soon after birth and resolves by 2 months. Physiotherapy may be required to prevent/relieve contractures
• Congenital myasthenia gravis should be considered if antibodies are absent or if symptoms persist or recur
What are the Clinical features of Fetal alcohol syndrome ❓❓
> 3-4 units /day ➡️fetal alcohol syndrome, even moderate alcohol intake may reduce birthweight.
Features of fetal alcohol syndrome include:
📍Small for gestational age
📍Dysmorphic face with mid-face hypoplasia
🔹 short palpebral fissures, 🔹epicanthic folds,🔹 flat nasal bridge (resulting in small upturned nose),🔹 long philtrum,🔹 thin upper lip, 🔹micrognathia and🔹 ear abnormalities
📍Microcephaly with subsequent intellectual impairment
📍Congenital heart disease
📍 Postnatal growth failure
Maternal smoking
• Reduces birth weight by 10% on average • Increases risk of sudden infant death syndrome
What is the effect of maternal phenytoin ❓❓
• Phenytoin (fetal hydantoin syndrome) – dysmorphic face (broad nasal bridge, hypertelorism, ptosis, ear abnormalities)
What is the effect of maternal valproate ❓❓
• Valproate – neural tube defects, fused metopic suture, mid-face hypoplasia, congenital heart disease, hypospadias, talipes, global developmental delay
What is the effect of maternal retinoids ❓❓
• Retinoids (isotretinoin) and large doses of vitamin A – dysmorphic face (including cleft palate), hydrocephalus, congenital heart disease
What is the effect of maternal cocaine use ❓❓
• Cocaine – SGA, prune belly and renal tract abnormalities, gut, cardiac, skeletal and eye malformations
• Other teratogenic drugs include thalidomide (limb defects), lithium, carbamazepine, chloramphenicol and warfarin
What are the complications associated with Maternal opiate abuse❓❓
• Associated with intrauterine growth retardation (IUGR)
• Results in withdrawal symptoms or neonatal abstinence syndrome
What is Embryological origin of the genitourinary system❓❓
• The genitourinary systems develop from mesoderm on the posterior abdominal wall and drain into the urogenital sinus of the cloaca
What are the Embryological development stages of the urinary system ❓❓
📍the mesonephros ➡️ pronephrose is the primitive kidney .
📍The ureteric bud appears at the start of week 5 of embryogenesis as a small branch of the mesonephric duct. The mesonephric (wolffian) ducts drain urine from primitive tubules into the urogenital sinus.
📍Repeated branching from week 6 onwards gives rise to the calyces, papillary ducts and collecting tubules by week 12
📍 Differentiation of the metanephros into nephrons – glomeruli, tubules and loop of Henle occurs from 4 weeks. These structures then join with the lower wolffian ducts to form the collecting systems. Branching and new nephron induction continues until week 36
📍The metanephros develops from the most caudal part of the mesodermal ridge, but the kidney eventually becomes extrapelvic because of the growth of surrounding areas
How gonads differentiation occurs ❓❓
• The Y chromosome (SRY gene) influences development of primitive gonads to form testes after 6 weeks. Testes ‘secrete’ müllerian inhibition factor (MIF) which results in regression of müllerian structures (uterus, fallopian tubes and vagina)
• Testosterone influences the development of wolffian structures (prostate, seminiferous tubules and vas deferens) as well as later masculinization
When withdrawal symptoms of opiates occur after birth ❓❓
– onset usually within 1–2 days of birth but may be delayed until 7–10 days and continue for several months; onset is later and symptoms persist for longer with methadone
What are Symptoms of opiate withdrawal syndrome ❓❓
• Wakefulness
• Irritability
• Tremors, temperature instability, tachypnoea
• High-pitched cry, hyperactivity, hypertonia
• Diarrhoea, disorganized suck
• Respiratory distress, rhinorrhoea • Apnoea
• Weight loss • Autonomic dysfunction • Lacrimation
Also seizures, myoclonic jerks, hiccups, sneezing, yawning
• Surfactant deficiency is less common
• Sudden infant death syndrome is more common
What is the management of opiate withdrawal syndrome ❓❓
• Management – monitor using withdrawal score chart.
Less than 50% require pharmacological intervention.
Indications for this are severe withdrawal symptoms or seizures. ✔️Oral morphine is the usual treatment of choice.
✔️Methadone, phenobarbital, benzodiazepines and chlorpromazine have also been used
What are the stages of embryogenesis till the implantation ❓❓
🔺The fertilized ovum divides to form➡️ a blastocyst which attaches itself to the inside wall of the uterus.
🔺The outer cells of the blastocyst, the trophoblasts, eat their way into the endometrium and these and surrounding endometrial cells form the placenta and membranes.
What is the source of nutrition of the embryo ❓❓
💛The trophoblasts are therefore the source of nutrition for the early embryo in the first 12 weeks.
💛In the second and third trimesters, maternal blood flows into the placental sinuses which surround the placental villi.
💛 Oxygen and nutrients diffuse into the fetal blood supply via the villi. Diffusion of oxygen occurs because maternal PO2 is approximately 7 kPa, compared with 4 kPa in the fetus
Where Is the Oestrogen produced and what it is function ❓❓
➡️ Initially produced by the corpus luteum and then in increasing amounts by the placenta as pregnancy progresses
• Causes the uterine smooth muscle to proliferate
• Enhances development of the uterine blood supply
• Changes pelvic musculature and ligaments to facilitate birth
• Causes breast development by increasing proliferation of glandular and fatty tissue
Where is Progesterone produced and what it is function ❓❓
➡️Limited amounts produced by the corpus luteum in the early part of pregnancy – much larger amounts produced by the placenta after the first trimester
• Causes endometrial cells to store nutrients in first trimester • Relaxes uterine smooth muscle; decrease in secretion of progesterone in the final few weeks of pregnancy coincides with onset of labour
• Facilitates glandular development of breasts
Where is Human chorionic gonadotrophin produced and what it is function ❓❓
• Secreted by trophoblasts
• Prevents degeneration of corpus luteum
• Peak concentration at around 10 weeks; falls rapidly to low levels by 20 weeks’ gestation
Where is Human placental lactogen produced and what it is function ❓❓
• Secreted by placenta in increasing amounts throughout pregnancy • Has growth hormone-like effect on fetus
• Has prolactin-like effect on breasts, facilitating milk production
What is the function of Oxytocin ❓
• Release is stimulated by irritation of the cervix ➡️ Oxytocin causes contraction of uterine smooth muscle
• Causes milk secretion – stimulation via the hypothalamus
Amniotic fluid is produced by the
amnion, fetal urine and fetal lung secretions
The amniotic fluid index (AFI)
is the sum of the depth of the deepest pool in each quadrant
Deepest pool of amniotic fluid normally 3–8 cm
Oligohydramnios (decreased AFI) may be caused by
: • Placental insufficiency (IUGR is usually also present) • Fetal urinary tract abnormalities • Prolonged rupture of membranes (PROM)
Polyhydramnios (increased AFI) may be the result of:
• Maternal diabetes
• Karyotype abnormalities
• Twin-to-twin transfusion syndrome (sometimes called polyhydramnios–oligohydramnios sequence)
• Neuromuscular disorders such as: • Congenital myotonic dystrophy • Spinal muscular atrophy (types 1 or 0 – type 0 is antenatal presentation of the disease) • Congenital myopathies • Möbius syndrome
• Oesophageal atresia
• Congenital diaphragmatic hernia
• Idiopathic/unexplained (a cause is more likely to be found in severe cases)
10% of the weight loss
Early postnatal diuresis occurs within 1–2 days because of further loss of extracellular (interstitial) fluid and partly accounts for up to 10% of the weight loss – this may be delayed in babies with respiratory failure
Why newborns loss heat and what are the mechanism of heat production ❓❓
Surface area to weight ratio is high in newborn babies (more so in preterm infant) so that the heat loss to heat production ratio is also high
✔️ generate heat as a response to cold stress using brown adipose tissue (non-shivering thermogenesis).
✔️ Peripheral vasoconstriction may also help maintain body temperature.
These mechanisms may be impaired in preterm or sick babies and are also limited during the first few hours of postnatal life
Hydrops fetalis
Definition: subcutaneous oedema and fluid in at least two of: pleural effusions, ascites, pericardial effusion.
What are the Causes of hydrops fetalis ❓❓
♀️Immune cause is usually rhesus disease.
♀️Non-immune causes include:
✔️ Anaemia:
• Twin-to-twin transfusion • Fetomaternal haemorrhage
• Homozygous α-thalassaemia
✔️Heart failure:
• Arrhythmias (supraventricular tachycardia, complete heart block)
• Structural (cardiomyopathy, hypoplastic left and right heart, etc.)
• High output (arteriovenous malformations, angiomas)
• Chromosomal abnormalities (Turner syndrome, trisomy 21 and other trisomies)
✔️✔️Congenital malformations:
• Congenital cystic adenomatoid malformation
• Diaphragmatic hernia
• Cystic hygroma
• Chylothorax and pulmonary lymphangiectasia
• Osteogenesis imperfecta
• Asphyxiating thoracic dystrophy
✔️ Infection:
• Parvovirus B19 • Cytomegalovirus (CMV) • Toxoplasmosis • Syphilis
• Chagas disease (a South American parasite infection)
✔️✔️Congenital nephrotic syndrome
✔️ Idiopathic – 15–20% cases
What is HbF and what it is characteristics ❓❓
Four globin chains are α2γ2
♂️ The γ chains have reduced binding to 2,3-diphosphoglycerate (2,3-DPG)
♂️The reduced 2,3-DPG in HbF causes the oxyhaemoglobin dissociation curve to be shifted to the left, i.e. there is a higher saturation for a given PO2 or P50 decreases (the PO2) at which half the haemoglobin is saturated.
💙 Fetal red blood cells therefore have a higher affinity for oxygen, making it easier to unload from the maternal circulation.
💙 leads to a decreased rate of unloading to tissues.
What HbF percent at birth ❓❓
Approximately 80% of haemoglobin is HbF at term. This falls to <10% by 1 year •
The following also shift the oxyhaemoglobin dissociation curve to the left
• Alkalosis
• Hypocapnia
• Hypothermia
When is closure of the ductus venosus and ductus arteriosus occur after birth ❓❓
♀️Functional closure of the ductus venosus occurs within hours of birth, with anatomical closure completed within 3 weeks
♀️Ductus arteriosus patency is maintained in fetal life by prostaglandin E2 and prostaglandin I2 (prostacyclin).
Functional closure of the ductus arteriosus usually occurs within 15 hours of birth
Functional closure of the ductus arteriosus usually occurs within 15 hours of birth and is facilitated by ❓❓
♀️ Reduced sensitivity of the ductus to prostaglandins and
♀️increased breakdown of prostaglandin E2 occurring in the lungs towards the end of pregnancy
♀️Increased PO2 after the onset of breathing
♀️Reduced pulmonary vascular resistance
How much blood goes to the fetal lung and why ❓❓
Before birth only about 10% of cardiac output goes to the lungs because pulmonary vascular resistance is higher than systemic vascular resistance
What changes that lead to drop in pulmonary vascular resistance after birth ❓❓
✔️Chemosensitivity of the pulmonary arteriolar bed increases with advancing gestation
✔️ Increased PO2 and lung expansion immediately after birth,
✔️along with increased release of vasodilator substances (prostaglandins, bradykinin and nitric oxide), lead to a fall in pulmonary vascular resistance after birth
♀️Pulmonary artery pressure falls to half the prebirth levels within 24 hours and pulmonary blood flow doubles as a result
What are the Causes of Persistent pulmonary hypertension of the newborn and how it is treated ❓❓
• Normal circulatory changes after birth are delayed either because of increased muscularization of the pulmonary arterioles or as a response to hypoxia
• Treatment includes
💲💲 ventilation with hyperoxia,
💲💲 induced metabolic alkalosis
💲💲 the use of pulmonary vasodilators such as nitric oxide
How foramen ovale closes ❓❓
After birth, the left atrial pressure increases as a result of increased pulmonary blood flow and right atrial pressure falls because of the absence of placental blood from the umbilical vein.
This causes a functional closure of the foramen ovale within a few minutes of birth. Anatomical closure may take weeks
What is Nitric oxide ❓❓
• Free radical
• Synthesized in endothelial cells from L-arginine by the enzyme nitric oxide synthase – also known as endothelium-derived relaxing factor
What is the mechanism of action of nitric oxide ❓❓
➿In vascular smooth muscle – nitric oxide activates guanylyl cyclase to increase intracellular guanosine cyclic 3’:5’-monophosphate (cGMP)
➿This leads to smooth muscle relaxation and vasodilatation by stimulating cGMP-dependent protein kinase which reduces intracellular calcium
Stillbirth
in utero death after 24 weeks’ gestation (28 weeks in most other European countries, 20 weeks in USA, 12 weeks in Japan).
Perinatal mortality rate –
stillbirths and deaths within 6 days of birth per 1000 live- and stillbirths.
Neonatal mortality rate –
deaths of liveborn infants < 28 days old per 1000 live births
What are the neonate Weight categories ❓❓
Low birthweight (<2500 g)
Very low birthweight (<1500 g)
Extremely low birthweight (<1000 g)
following are associated with an increased risk for spontaneous preterm birth:
• Social/demographic factors:
• Maternal country of birth Africa or Caribbean
• Low socioeconomic class
• Age <20 or >40 years
• Past obstetric or medical history:
• Previous preterm birth
• Uterine abnormalities
• Cervical abnormalities
• Current pregnancy:
• Multiple pregnancy
• Poor nutrition
• Low pre-pregnancy weight
• Poor pre- and antenatal care
• Anaemia
• Smoking
• Bacteriuria
• Genital tract colonization (particularly group B streptococci)
• Cervical dilatation >1 cm Z
• Pre-term PROM
t seems reasonable to actively resuscitate
most appropriately grown (i.e. more than approximately 500 g) infants greater than 23 weeks’ gestation who have reasonable signs of life after birth.
The definition of SGA
varies between birthweight <3rd centile and a birthweight <10th centile. Over 50% of babies with birthweight <10th centile are constitutionally small; the rest have IUGR
Fetal/neonatal complications of IUGR
• In utero death/stillbirth
• Fetal hypoxia/acidosis (associated with neonatal encephalopathy/birth depression)
• Polycythaemia, neutropenia (and increased infection risk), thrombocytopenia
• Hypothermia
• Hypoglycaemia
• Necrotizing enterocolitis
What are are the causes of SGA infants ❓❓
▪️ maternal (hypertension, diabetes, lupus, smoking, altitude), ▪️placental and fetal (multiple gestations, malformations, infections)
Long-term complications of IUGR
• Increased risk of neurodevelopmental problems
• Hypertension
• Diabetes
• Hyperlipidaemias
What is the features of Thrombocytopenia due to maternal ITP and what is the Management ❓❓
• Platelet count proportional to that of mother
• Rarely causes very low neonatal platelet counts or symptoms
• Risk of intracranial haemorrhage if platelet count <50 × 109/l (may occur antenatally, so caesarean section not always protective)
• Treatment: intravenous immunoglobulin G (IgG) and platelet transfusion
What type of pneumocytes and what are there function ❓❓
▪️type 2 pneumocytes which line 5–10% ➡️Endogenous surfactant
▪️type 1 pneumocytes ➡️responsible for gas exchange.
What is constituents of endogenous surfactant ❓
▪️Phospholipids – 80-85%
Dipalmitoylphosphatidylcholine (DPPC) – 45-70%
Other phospholipids include:
• Phosphatidylcholine
• Phosphatidylglycerol
• Phosphatidylinositol •
▪️Other phospholipids =sphingomylines
▪️Surfactant proteins
What are the types of Surfactant proteins ❓
• Surfactant protein A:
• Mainly immune function but also has a role in spreading and recycling of surfactant
• Has been shown to increase microbial killing by alveolar macrophages
• Increases resistance to inhibitors of surface activity which occurs in sepsis
• Surfactant protein B:
• Major role in adsorption, spreading and recycling of surfactant
• Case reports suggest that congenital deficiency of surfactant protein B is a lethal, autosomal recessive condition
• Surfactant protein C:• Similar function to surfactant protein B
• Surfactant protein D: • Immune function
Increased incidence of surfactant deficiency in❓❓
Prematurity
• Male sex
• Sepsis
• Maternal diabetes
• Second twin
• Elective caesarean section
• Strong family history
Surfactant deficiency is decreased in:
• Female sex
• PROM
• Maternal opiate use
• IUGR
• Antenatal glucocorticoids
• Prophylactic surfactant
What is Amniotic fluid (or gastric aspirate) lecithin:sphingomyelin (L:S) ratios indicate ❓❓
• <1.5 = immature – 70% risk of surfactant deficiency
• 1.5–1.9 = borderline – 40% risk of surfactant deficiency
• 2.0–2.5 = mature – very small risk unless mother has diabetes
• >2.5 = safe
Maternal antenatal corticosteroids (betamethasone or dexamethasone) before preterm birth reduce the effects of surfactant deficiency and have been shown to:
• Reduce neonatal mortality by approximately 31%
• Decrease intraventricular haemorrhage by approximately 46% • Reduce the risk of necrotizing enterocolitis (NEC)
• Decrease the need for respiratory support for respiratory distress syndrome (RDS)
• Decrease the need for neonatal intensive care unit (NICU) admission
• Reduce the risk of infection in the first 48 hours
guidelines suggest giving maternal corticosteroids to women
likely pre-term birth between week 24 and 34+6 of gestation, and also to consider in those from 23+0 weeks.
any elective caesarean section up to 38+6 weeks.
Exogenous surfactant considerably
reduces mortality and incidence of pneumothoraces and chronic lung disease. Early treatment with surfactant and use of animal rather than synthetic surfactants enhance these outcomes.
Synthetic vs animal surfactant ❓❓
Synthetic = DPPC +hexadecanol
ANIMAL = DPPC +surfactant protein B / C
Synthetic action within hours
ANIMAL action within minutes
✔️Early treatment with surfactant and use of animal rather than synthetic surfactants enhance these outcomes.
What are the function and regulation of Prolactin ❓❓
• Produced by the hypothalamic–anterior pituitary axis
⬇️• Production is inhibited during pregnancy by high levels of oestrogen and progesterone produced by the placenta; the sudden decrease in these after delivery of the placenta increases prolactin release
• Prolactin causes secretion of milk from the breasts
⬇️• Hypothalamic production of a prolactin inhibitory factor increases if the breasts are engorged with milk and decreases as the baby breast-feeds
• Prolactin inhibits follicle-stimulating hormone immediately postpartum, thereby preventing ovulation
What is the function of surfactant phospholipids ❓
• The main surface-active components, which lower surface tension at the air–alveolar interface preventing alveolar collapse
Chronic lung disease – bronchopulmonary dysplasia
Definition – respiratory support with supplementary oxygen ± mechanical ventilation for >28 days with typical chest radiograph changes (see below).
In very-low-birthweight (VLBW) infants = requiring oxygen ± mechanical ventilation >36 weeks corrected gestational age and typical changes on a chest radiograph.
Risk factors for chronic lung disease
• Prematurity
• Prolonged mechanical ventilation with high pressures and high fractional inspired oxygen (FiO2)
• Lung over-inflation (volutrama or barotrauma) or under-inflation (‘atelectotrauma’)
• Oxygen toxicity (free radical mediated)
• Pulmonary air leak (pneumothoraces or pulmonary interstitial emphysema)
• Gastro-oesophageal reflux
• Patent ductus arteriosus (PDA)
• Chorioamnionitis
• Postnatal infection (particularly with Ureaplasma urealyticum and cytomegalovirus)
Radiological stages of Chronic lung disease ❓❓
• Stage 1: first few days =indistinguishable from surfactant deficiency
• Stage 2: 2nd week =generalized opacity of lung fields
• Stage 3: 2–4 weeks= streaky infiltrates
• Stage 4: >4 weeks=hyperinflation, cysts, areas of collapse/consolidation, cardiomegaly
Management of chronic lung disease ❓❓
• Ventilatory support as required
• no benefit of a high oxygen saturation target (i.e. 95-98%) compared with a lower level (91–94%)
• Good nutrition is of paramount importance; increased alveolar growth accompanies general growth – particularly in the first 1–2 years
• Treatment of underlying exacerbating factors – infection, gastro-oesophageal reflux, fits, cardiac problems, etc.
• Dexamethasone – facilitate weaning off mechanical ventilation butconcern has been raised over short-term side effects and long-term side effects (adverse neurodevelopmental outcome, particularly cerebral palsy)
• Inhaled steroids – only proven benefit is to reduce the need for systemic steroids
• Bronchodilators – used only if there is evidence of reversible airway obstruction
• Diuretics – likely to be of benefit only in the presence of PDA, cor pulmonale or excessive weight gain
• Respiratory syncytial virus (RSV) prophylaxis with monoclonal antibodies (e.g. palivizumab)
Respiratory syncytial virus (RSV) prophylaxis and it’s benefits and the recommendation for use ❓❓
monoclonal antibodies (e.g. palivizumab) has been shown to reduce hospitalization in high-risk cases, but use is controversial because of the high cost of the drug and the need for monthly intramuscular injections throughout the RSV season
Outcome of babies with chronic lung disease
• Most are weaned off supplementary oxygen before discharge home
• Few require home oxygen
• Most babies discharged on home oxygen are weaned off before 1–2 years
• High risk of readmission to hospital with viral respiratory infections in the first 1–2 years of life
• Increased risk of recurrent cough and wheeze in pre-school age group but most outgrow this tendency and have normal exercise tolerance in childhood
Meconium aspiration syndrome (MAS) Risk factors
• Term or post-term (incidence much higher in births after 42 weeks) • Small for gestational age
• Perinatal asphyxia
Major effects of MAS on lung function
💛 Airway blockage:
• Increased airway resistance with ball–valve mechanism and gas trapping
• High risk of pneumothorax
💛Chemical pneumonitis
💛 Increased risk of infection:
• Even though meconium is sterile
• Escherichia coli is the most common infective agent
💛Surfactant deficiency:
• Lipid content of meconium displaces surfactant from alveolar surface
• Persistent pulmonary hypertension of the newborn
MAS changes on chest radiographs include .
▪️initial patchy infiltration and hyperinflation. Pneumothoraces are common at this stage.
▪️A more homogeneous opacification of the lung fields may develop over the next 48 hours, as chemical pneumonitis becomes more of a problem.
▪️ In severe cases, changes similar to chronic lung disease may develop over the following weeks
What are the mode of transmission of Pneumonia in neonates ❓❓
congenital
intrapartum
nosocomial
What are the most common organisms acquired during Intrapartum infection ❓❓
• Bacterial:
• Group B streptococci
• Coliforms (as above)
• Haemophilus sp.
• Staphylococci
• Pneumococci
• Listeria sp.
• Viral:
• Herpes simplex virus • Varicella-zoster virus
What are the most common Nosocomial infection
(Onset is after 48 hours) :
• Bacterial:
• Staphylococci
• Streptococci
• Pseudomonas sp.
• Klebsiella sp.
• Pertussis
• Viral: • RSV • Adenovirus • Influenza viruses • Parainfluenza viruses • Common cold viruses
• Other: • Pneumocystis jiroveci
Respiratory problems in neonates ❓❓
▪️Surfactant deficiency
▪️Chronic lung disease
▪️Meconium aspiration
▪️Air leak
▪️▪️▪️
Rare in preterm but said to occur with congenital listeriosis (more likely to be pus than meconium).
What is the cause of The passage of meconium in fetal distress❓❓ .
may be the result of increased secretion of motilin
What are the Causes of Congenital pneumonia ❓❓
®️®️ Bacterial:
• Streptococci (group B streptococci)
• Coliforms (E. coli, Klebsiella, Serratia, Shigella, Pseudomonas spp., etc.)
• Pneumococci
• Listeria sp.
®️®️ Viral
• CMV • Rubella virus • Herpes simplex virus • Coxsackievirus
®️®️Other
• Toxoplasmosis
• Chlamydia sp.
• Ureaplasma urealyticum
• Candida sp
What are the Causes and mechanisms of pneumothoraces in neonates❓❓
♀️♀️Occurs in up to 1% of otherwise healthy term infants (it is usually asymptomatic)
♀️♀️Overdistension of alveoli is more likely to occur in immature lungs because of a decreased number of pores of Kohn, which redistribute pressure between alveoli
What are the most common causes of pneumothorace ❓❓
More common in surfactant deficiency, MAS, pneumonia and pulmonary hypoplasia
How pneumothorax Risk is reduced ❓❓
®️volume target ventilation or lower ventilator pressures to avoid overdistension
®️faster rate ventilation with shorter inspiratory times,
®️paralysis of infants fighting the ventilator
®️surfactant replacement therapy
What are characteristics of Pulmonary interstitial emphysema ❓❓
• May occur in up to 25% of VLBW infants, usually confined to those with the worst surfactant deficiency
• May be more common in chorioamnionitis
• Alveolar rupture results in small cysts in the pulmonary interstitium
Pneumomediastinum
• May complicate surfactant deficiency or other forms of neonatal lung disease, when it may coexist with pneumothorax or may be iatrogenic following tracheal rupture secondary to intubation
Pulmonary hypoplasia
Primary pulmonary hypoplasia is rare but may present with persistent tachypnoea which resolves with lung growth several months after birth. Secondary pulmonary hypoplasia may be the result of:
• Reduced amniotic fluid volume – Potter syndrome (renal agenesis) or other severe congenital renal abnormalities resulting in markedly decreased urine volume (infantile [autosomal recessive] polycystic kidney disease, severe bilateral renal dysplasia, posterior urethral valves)
• Preterm rupture of membranes – occurs only if membranes ruptured before 26 weeks; 23% of pregnancies with rupture of membranes before 20 weeks are unaffected; outcome with rupture of membranes before 24 weeks is usually poor
• Amniocentesis – mild-to-moderate respiratory symptoms are more likely to occur in the neonatal period and incidence of respiratory symptoms in the first year of life is increased
• Lung compression – pulmonary hypoplasia is common in small-chest syndromes including asphyxiating thoracic dystrophy and thanatophoric dwarfism, diaphragmatic hernia, congenital cystic adenomatoid malformation and pleural effusions
• Reduced fetal movements – pulmonary hypoplasia occurs in congenital myotonic dystrophy, spinal muscular atrophy and other congenital myopathies
Congenital diaphragmatic hernia• Most common congenital abnormality of the respiratory system – incidence is 1 in 2500–3500 births
• Twice as common in males
90% are Bochdalek or posterolateral hernias • 85–90% are left sided
Less severe cases may not present initially but develop increasing respiratory distress over the first 24 hours as the gut becomes more air filled.
Bag-and-mask positive-pressure ventilation should be avoided • Wide-bore nasogastric tube should be placed as soon as possible to deflate gut and to confirm diagnosis, and therefore distinguish between differential diagnoses of congenital cystic adenomatoid malformation or pneumothorax on subsequent chest radiograph
• Consider paralysing baby to avoid air swallowing and to reduce the risk of pneumothorax Surgical management
• There is some evidence to suggest that stabilizing the baby before surgery improves outcome • Malrotation is corrected if present; the diaphragmatic defect is usually closed with a synthetic
Mortality rate overall is approximately 40%
Rare, abnormal proliferation of bronchial epithelium, containing cystic and adenomatoid portions • Lower lobes affected more frequently
Diagnosis by antenatal ultrasound scan allows antenatal drainage by insertion of intercostal drains, which may reduce the risk of pulmonary hypoplasia and facilitate resuscitation after birth
• Ventilatory support may be required postnatally, along with intermittent intercostal drainage • Volume of chyle can be reduced by using a medium-chain triglyceride milk formula or avoidingenteral feeds for up to several weeks as the underlying abnormality resolves with time; protein and lymphocyte depletion may complicate this
• Surgical treatment is needed for the small number of cases that do not resolve spontaneously
There are three types.
Type 1 CCAM • Single or small number of large cysts • Most common type (50% cases) • May cause symptoms by compression or may be asymptomatic initially • Good prognosis after surgery
Type 2 CCAM • Multiple small cysts • Usually cause symptoms by compression of surrounding normal lung • Prognosis variable
Type 3 CCAM • Airless mass of very small cysts giving the appearance of a solid mass • Worst prognosis
Congenital lobar emphysema
• Affected lobe is overinflated • Left upper lobe is most commonly affected (also right middle and upper lobes); rare in lower lobes • More common in boys
Associated with congenital heart disease in approximately one in six cases (usually as a result of compression of airways by aberrant vessels)
• Unaffected lobes in affected lung are compressed • Mediastinal shift and compression of the contralateral lung may also occur
Chest radiograph shows hyperlucent affected lobe ± compression of other lobes • Reduced ventilation and perfusion of the affected lobe is seen on a ventilation–perfusion scan in more severe cases
Presents with signs of respiratory distress, wheezing, chest asymmetry and hyperresonance
Effusion of lymph into the pleural space as a result of either: • Underlying congenital abnormality of the pulmonary lymphatics • Iatrogenic abnormality after cardiothoracic surgery
What are Chest wall abnormalities in neonates ❓❓
Asphyxiating thoracic dystrophy
Ellis–van Creveld syndrome
Short-rib polydactyly syndromes
Thanatophoric dysplasia
Camptomelic dysplasia
What are characteristics of Asphyxiating thoracic dystrophy ❓❓❓
• Autosomal recessive • Variable severity • Short ribs with bell-shaped chest • May have polydactyly and other skeletal abnormalities also • Long-term prognosis good in infants who survive >1 year
What are the abnormalities in Ellis–van Creveld syndrome ❓❓
• Autosomal recessive
• Short ribs, polydactyly, congenital heart disease, cleft lip and palate • Pulmonary hypoplasia is usually not severe and symptoms improve later
Short-rib polydactyly syndromes
• Four variants – all autosomal recessive • Death from severe respiratory insufficiency occurs in the neonatal period
Thanatophoric dysplasia
• Usually sporadic • Very short limbs – femur radiograph described as ‘telephone handle’ shape • Very small, pear-shaped chest • Death from lung/chest hypoplasia occurs in the neonatal period
Camptomelic dysplasia
• Autosomal recessive • Very bowed, shortened long bones • Death from respiratory insufficiency usually occurs in childhood
What is the incidence of Choanal atresia❓❓
• Incidence approximately 1:8000
• More common in girls
Pierre Robin sequence
• Consists of protruding tongue, small mouth and jaw, and cleft palate • Incidence approximately 1:2000 • Problems include obstructive apnoea, difficulty with intubation and aspiration
Laryngomalacia
• Most common cause of stridor in the first year of life • Inspiratory stridor increases with supine position, activity, crying and upper respiratory tract infections
• Usually resolves during the second year of life • Upper airway endoscopy is merited if persistent accessory muscle use occurs, with recurrent apnoea or faltering growth
Risk factors for acquired subglottic stenosis
• Prematurity • Recurrent reintubation • Prolonged intubation • Traumatic intubation• Inappropriately large or small endotracheal tube • Black babies (keloid scar formation) • Oral as opposed to nasal intubation (this is a theoretical but unproven factor) • Gastro-oesophageal reflux • Infection
Subglottic stenosis
• May be congenital but usually acquired
Staging of subglottic stenosis ❓❓
Severity is categorized by the Myer–Cotton staging:
• Grade 1 – <50% obstruction • Grade 2 – 51–70% obstruction • Grade 3 – 71–99% obstruction • Grade 4 – total obstruction
Systemic steroids may facilitate extubation in mild to moderately severe subglottic stenosis. Laser or cryotherapy to granulomatous tissue seen on upper airway endoscopy may also be of benefit in these cases. Severely affected babies require surgery – anterior cricoid split (laryngotracheal reconstruction) or tracheostomy.
Tracheomalacia
• Causes expiratory stridor • Usually caused by extrinsic compression – most commonly as a result of vascular rings • Also associated with tracheo-oesophageal fistula • Surgical treatment of underlying pathology usually leads to resolution, but tracheostomy and positive-pressure ventilation or CPAP (continuous positive airway pressure) may be required
Principles of mechanical ventilation in neonates
• Aims are to: • ensure adequate oxygenation • adequately remove carbon dioxide to prevent respiratory acidosis • minimize the risk of lung injury (VILI or ventilator-induced lung injury)
Pressure-limited, time-cycled ventilation (PLV) is used most commonly via either an oral or a nasal endotracheal tube. Patient-trigger modes may improve synchronization with the baby’s own respiratory efforts, thus improving oxygenation, reducing the risk of air leak and facilitating weaning from the ventilator
Volume-targeted ventilation (VTV) is now being used more commonly because of advances in ventilator technology, along with recent evidence from RCTs suggesting a reduction in several important clinical outcomes with VTV compared with PLV, including: • Combined death or bronchopulmonary dysplasia (BPD) • Pneumothorax • Hypocapnia • Combined periventricular leukomalacia (PVL) or severe intraventricular haemorrhage (IVH)• Time on ventilator
High-frequency oscillation may be used initially for any cause of neonatal respiratory failure, but is most often used as ‘rescue’ in severe cases where conventional ventilation has failed
Nasal CPAP is often used in preterm babies once extubated. This maintains functional residual capacity and reduces the work of breathing
What is the pathophysiology of choanal atresia ❓❓
• Occurs as a result of a failure of breakdown of bucconasal membrane
• May be unilateral or bilateral, bony or membranous
What are the associations of choanal ❓❓
• 60% associated with other congenital abnormalities including the CHARGE association: C = colobomas, H = heart defects, A = atresia of choanae, R = retarded growth and development, G = genital hypoplasia in males, E = ear deformities
What is diagnostic investigation and management of choanal atresia ❓❓
• Oral airway insertion relieves respiratory difficulties. Diagnosis confirmed by contrast study or CT scan
• Surgical correction by perforating or drilling the atresia requires postoperative nasal stents
What is management of perry Robin
• To maintain airway patency and prevent obstructive apnoea, prone position should be used initially; if this fails an oral airway should be inserted. Intubation may be needed in severe cases who may eventually require tracheostomy
• Glossopexy and other surgical procedures have been attempted with some degree of success • Gradual resolution of airway problems occurs as partial mandibular catch-up growth progresses during the first few years of life
What type of Extracorporeal membrane oxygenation (ECMO) ❓❓
• Venoarterial (VA) – blood removed from right atrium (usually via right internal jugular vein) and returned via a common carotid artery
• Venovenous (VV) – a double-lumen, right atrial cannula is used
ECMO should be considered in severe neonatal respiratory failure if ❓
• Lung disease is reversible • Infant is >35 weeks’ gestation • Weight > 2 kg • Cranial ultrasound scan shows no intraventricular haemorrhage > grade 1 • No clotting abnormality • Oxygenation index >40
What is Oxygenation index (OI) and why it is measured ❓❓
is used to quantify the degree of respiratory failure.
It is measured as: OI = (Mean airway pressure × FiO2 × 100) ÷ PO2
where mean airway pressure is in cmH2O, FiO2 (fractional inspired oxygen) is a fraction and PO2 is in mmHg (
What OI indicates?
OI >25 indicates severe respiratory failure
OI >40 indicates very severe respiratory failure with a predicted mortality rate of >80% with conventional treatment – therefore consideration to refer for ECMO is appropriate
Alveolar–arterial oxygen difference (A–aDO2)
• A–aDO2 = (716 × FiO2) – PCO2/0.8) – PO2 • A normal A–aDO2 is <50 mmHg. • If >600 mmHg for successive blood gases over 6 hours, then there is severe respiratory failure with predicted mortality rate >80% with conventional treatment
Ventilation index (VI) =
PCO2 × RR × PIP/1000, where RR is the respiratory rate and PIP is thepeak inspiratory pressure: • VI > 70 indicates severe respiratory failure • VI > 90 indicates very severe respiratory failure – suitable for consideration of ECMO
Patent ductus arteriosus (PDA) when it present ❓❓
• Often presents around third day of life in VLBW infants because left-to-right shunt increases as pulmonary vascular resistance falls; approximately 40% of VLBW infants with surfactant deficiency have clinically significant PDA on day 3 of life
clinically significant PDA in VLBW infants is associated with an increased risk of:
• Pulmonary haemorrhage • Chronic lung disease • IVH • Necrotizing enterocolitis • Mortality
Causes of hypotension in neonates
💛 Hypovolaemia:
▪️Antenatal acute blood loss: • Placental abruption • Placenta praevia • Maternofetal haemorrhage • Twin-to-twin transfusion (usually not acute) • Vasa praevia
▪️Postnatal acute blood loss:
= Internal
• Intracranial haemorrhage • Intra-abdominal haemorrhage • Intrathoracic/pulmonary haemorrhage • Severe bruising
= External:• Dislodged vascular lines
💛Excessive water loss: • High urine output • High insensible losses – common in extreme prematurity
💛 Third spacing: • Hydrops • Pleural effusions • Ascites • Postoperative
•💛Vasodilatation: • Common in preterm infants • Sepsis • Drug induced (tolazoline, prostaglandins, prostacyclin)
💛 Cardiogenic:
▪️Myocardial dysfunction: • Perinatal asphyxia • Metabolic acidosis
▪️Congenital heart disease: • Hypoplastic left heart • Other single-ventricle physiological conditions
▪️ Arrhythmias: • Supraventricular tachycardia • Complete heart block
💛Reduced venous return: • Pulmonary air leak • Pericardial effusion/tamponade • Lung hyperinflation (more common in high-frequency oscillation or with high positive endexpiratory pressure [PEEP])
Causes of hypertension in neonates
• Vascular:
• Renal artery thrombosis (associated with umbilical artery catheterization) • Aortic thrombosis (associated with umbilical artery catheterization) • Renal vein thrombosis (more common in infants of mothers with diabetes) • Coarctation of aorta • Middle aortic syndrome
• Renal:
• Obstructive uropathy • Dysplastic kidneys • Polycystic kidney disease• Renal tumours
• Intracranial hypertension
• Endocrine: • Congenital adrenal hyperplasia • Hyperthyroidism • Neuroblastoma • Phaeochromocytoma
• Drug induced: • Systemic steroids
• Inotropes
• Maternal cocaine
note that to convert kPa to mmHg, multiply by 7.6).
note that to convert kPa to mmHg, multiply by 7.6).
What are the causes of cyanosis ❓❓
Congenital cyanotic heart disease: • Transposition of the great arteries • Pulmonary atresia • Critical pulmonary stenosis • Severe tetralogy of Fallot • Tricuspid atresia • Ebstein anomaly • Truncus arteriosus • Total anomalous pulmonary venous drainage • Hypoplastic left heart syndrome
• Persistent pulmonary hypertension of the newborn • Respiratory disease • Methaemoglobinaemia: • Arterial PO2 is normal • Can be congenital: • NADH-methaemoglobin reductase deficiency (autosomal recessive) • Haemoglobin M (autosomal dominant)
• Can be iatrogenic: • Secondary to nitric oxide therapy • Nitrate or nitrite ingestion
• Treat with intravenous methylene blue • Acrocyanosis and facial bruising also give the appearance of cyanosis
What is the causes of Methaemoglobinaemia:
• Arterial PO2 is normal
✔️Can be congenital:
• NADH-methaemoglobin reductase deficiency (autosomal recessive)
• Haemoglobin M (autosomal dominant)
✔️ Can be iatrogenic:
• Secondary to nitric oxide therapy
• Nitrate or nitrite ingestion
What is the incidence of Necrotizing enterocolitis ❓❓
Incidence varies – occurs in about 10% of VLBW infants.
Risk factors
• Prematurity • Antepartum haemorrhage • Perinatal asphyxia • Polycythaemia • PDA • PROM
The incidence of NEC in preterm infants is
6–10 times higher in those fed formula milk compared with those given breast milk
severity of NEC can be classified using the
Bell staging: Stage1 – suspected NEC
• General signs – temperature instability, lethargy, apnoea • Increased gastric aspirates, vomiting, abdominal distension Stage 2 – confirmed NEC
• Stage 1 signs, plus • Upper or lower gastrointestinal bleeding • Intramural gas (pneumatosis intestinalis) or portal vessel gas on abdominal radiograph
Stage 3 – severe NEC
• Stage 1 and 2 signs, plus • Signs of shock, severe sepsis and/or severe gastrointestinal haemorrhage • Bowel perforation
Complications of NEC ❓❓
• Perforation occurs in 20–30% of confirmed NEC cases
• Overwhelming sepsis
• Disseminated intravascular coagulation (DIC)
• Strictures – occur in approximately 20% cases of confirmed NEC • Recurrent NEC – occurs in <5% cases (consider Hirschsprung disease)
• Short-bowel syndrome after extensive resection
• Lactose intolerance
Medical management of NEC ❓❓
• Cardiorespiratory support as required • Stop enteral feeds for 7–14 days (depending on the severity of illness) • Nasogastric tube on free drainage • Give intravenous fluids/total parenteral nutrition (TPN) • Give intravenous antibiotics • Treatment of thrombocytopenia, anaemia, DIC • Serial abdominal radiographs (to exclude perforation
Surgical management of NEC ❓❓
• Placement of peritoneal drain • Early laparotomy – with resection of bowel ± ileostomy/colostomy; indications for early surgery include perforation or failing medical management
• Late laparotomy ± bowel resection; most common indication is stricture formation confirmed with contrast radiographs
Breast-feeding Physiology
• A surge in maternal prolactin (from the anterior pituitary) occurs immediately postpartum, which stimulates milk production
• Suckling stimulates prolactin receptors in the breast and oxytocin release (from the posterior pituitary). Oxytocin facilitates the ‘let-down’ reflex by contraction of breast myoepithelial cells
• Colostrum is produced over the first 2–4 days. Subsequent milk production is controlled mainly by the amount of suckling or expression
What is the content of protein in breast milk, term formula and preterm formula ❓❓
B 1.1g T 1.5 g. PT 2 g
What is the content of carbohydrates in breast milk, term formula and preterm formula ❓❓
B 7.4 T 7.2 PT 8.6
What is the content of fats in breast milk, term formula and preterm formula ❓❓
B 4.2 T 3.6. PT 4.4
What is the content of calories in breast milk, term formula and preterm formula ❓❓
B 70. T 65. PT 80
Maternal drugs that should be used with caution/monitoring if breast-feeding ❓❓
• Some antidepressants
• Some antihistamines
• Carbamazepine
• Carbimazole
• Clonidine
• Co-trimoxazole
• Ethambutol
• Histamine antagonists
• Isoniazid
• Gentamicin
• Metronidazole (makes milk taste bitter)
• Oral contraceptives
• Phenytoin
• Primidone
• Theophylline
• Thiouracil
is an average fluid intake of approximately
150 ml/kg per 24 hours but this may vary considerabl
Important notes of fluid balance ❓❓
and initial fluid and electrolyte provision should facilitate postnatal weight loss with negative water and sodium balance. Failure to do this is likely to increase the risk of complications such as PDA, pulmonary haemorrhage, NEC and chronic lung disease.
Daily nutritional requirements per kilogram for stable, growing, preterm babies are approximately as follows:
•
Protein – 3.0–3.8 g
• Energy – 110–120 kcal
• Carbohydrates – 3.8–11.8 g
• Fat – 5–20% of calories
• Sodium – 2–3 mmol
• Potassium – 2–3 mmol
• Calcium – 2–3 mmol
• Phosphate – 1.94–4.52 mmol
• + other minerals (iron, zinc, copper etc.), trace elements (selenium, manganese etc.) and vitamins
Indications for TPN
milk intolerance, poor gut motility (common in extreme prematurity), NEC, postoperativ
Parenteral nutrition consists of:
• Protein – up to 3.5 g/kg per day of amino acids (mainly essential amino acids) • Carbohydrates – up to 18 g/kg per day. Parenteral nutrition should be given via a central venous line if dextrose concentration >12.5%• Lipids – soya bean oil emulsions (e.g. Intralipid) provide essential fatty acids, a concentrated source of calories and a vehicle for delivering fat-soluble vitamins; 20% Intralipid is tolerated better than 10%. Regular monitoring of plasma lipid levels is recommended. SMOF lipid is a newer preparation which contains soya oil, medium-chain triglycerides, olive oil and fish oils and has been shown to improve liver function compared with a pure soya-bean oil preparation
• Water • Minerals – sodium, potassium, calcium, phosphate, magnesium • Trace elements – zinc, copper, manganese, selenium, etc. • Water-soluble vitamins • Fat-soluble vitamins
Complications of parenteral nutrition in neonates include:
• Sepsis – mainly intravenous line related (bacterial/fungal) • Intravenous line extravasation • Venous thrombosis (line related) • Fluid/electrolyte imbalance • Hyperlipidaemia • Nutritional deficiencies • Cholestatic jaundice
Oesophageal atresia and tracheo-oesophageal fistula
• Occurs as a result of the failure of development of the primitive foregut • Incidence is approximately 1:3000: • 85% – blind proximal oesophageal pouch with a distal oesophageal to tracheal fistula • 10% – oesophageal atresia without fistula • 5% – proximal ± distal fistula
Management of oesophageal atresia
• Respiratory support as needed • Riplogle tube (large-bore, double-lumen suction catheter) on continuous suction is placed in the proximal oesophageal pouch
• Surgical management includes early division of the fistula and early or delayed oesophageal anastomosis. This depends on the distance between the two ends of atretic oesophagus – for wide gaps, delayed anastomosis to allow growth may improve outcome. Cervical oesophagostomy or colonic transposition may also be used in this situation.
H-type tracheo-oesophageal fistula (tracheo-oesophageal fistula without oesophageal atresia) association and presentation
s much less common and is usually not associated with preterm birth or other severe anomalies. It may present in the neonatal period or later with respiratory distress associated with feeding, or recurrent lower respiratory infections.
Duodenal atresia association
• Approximately 70% are associated with other congenital anomalies (trisomy 21, congenital heart disease, malrotation, etc.)
Often diagnosed antenatally with ultrasound ‘double-bubble’ or polyhydramnios • Usually presents postnatally with bilious vomiting
Malrotation
• Occurs as a result of incomplete rotation of the midgut in fetal life resulting in intermittent and incomplete duodenal obstruction by Ladd bands
• Associated with diaphragmatic hernia, duodenal and other bowel atresias and situs inversus
How malrotation present ❓
Presents with bilious vomiting and some abdominal distension with sudden deterioration in the event of midgut volvulus
How can you diagnose malrotation
Upper gastrointestinal contrast studies show the duodenal–jejunal flexure on the right of the abdomen with a high caecum
Meconium ileus
•
Most common presentation of cystic fibrosis in neonates (10–15% cases) • >90% of babies with meconium ileus have cystic fibrosis,
Water-soluble contrast enemas may lead to resolution of meconium ileus
Important to distinguish between meconium ileus and meconium plug – with meconium plug, symptoms usually resolve after passage of plug and the problem is not associated with cysticfibrosis
Anorectal atresia
• May have other features of VACTERL association • May be high or low with the puborectalis sling differentiating – more likely to be a low lesion in girls
Clinical presentation
• Polyhydramnios • Excessive salivation • Early respiratory distress • Abdominal distension • Vomiting/choking on feeds • Inability to pass nasogastric tube • Absence of gas in gut on radiograph if no tracheo-oesophageal fistula • Other anomalies in 30–50% – VACTERL (
What are the functions of surfactant proteins ❓❓
• Facilitate adsorption, spreading and recycling of surfactant and have immunoregulatory properties
Colostomy is needed for all high atresias
Renal tract ultrasound scan, micturating cystogram ± cystoscopy are needed to exclude rectovaginal, rectourethral or rectovesical fistula or other urinary tract anomaly
Hirschsprung disease
• Occurs as a result of an absence of ganglion cells in either a short or long segment of the bowel; the rectum and sigmoid colon are most often affected but cases extending to the upper GI tract have been described
Exomphalos (omphalocele)
• Results from failure of the gut to return into the abdominal cavity in the first trimester
Approximately 75% cases have other congenital anomalies – trisomies, congenital heart disease, Beckwith–Wiedemann syndrome
Results from failure of the gut to return into the abdominal cavity in the first trimester • The defect is covered by peritoneum which may be ruptured at birth
Topical application of silver sulfadiazine (Flamazine) to promote granulation and epithelialization of the peritoneal covering of the exomphalos before delayed surgical closure has been shown to produce good outcomes
Gastroschisis
• Incidence in the UK is rising (approximately 1 in 2000 live births) and is now nearly five times as common as exomphalos
• Aetiology unknown but strong association with teenage pregnancy and possibly smoking and recreational drugs
Bowel is not covered by peritoneum and therefore becomes stuck together with adhesions; this leads to functional atresias and severe intestinal motility problems after surgical repair of theabdominal wall defect
• Prognosis is mostly good
germinal matrix or layer occurs in the caudothalamic notch of the floor of the lateral ventricles. It is the site of origin of migrating neuroblasts from the end of the first trimester onwards. By 24–26 weeks’ gestation this area has become highly cellular and richly vascularized. This remains so until approximately 34 weeks’ gestation, by which time it has rapidly involuted. The delicate network of capillaries in the germinal matrix is susceptible to haemorrhage, which is likely to occur with changes in cerebral blood flow. Preterm infants have decreased autoregulation of the cerebral blood flow, which contributes to the pathogenesis. In term infants peri-IVH (PIVH) may originate from the choroid plexus.
Risk factors for PIVH
• Prematurity (28% at 25 weeks; <5% after 30 weeks) • Lack of antenatal maternal steroids • Sick and needing artificial ventilation • Hypercapnia • Metabolic acidosis • Pneumothoraces (as a result of increased venous pressure or possibly related to surge in blood pressure when drained)
• Abnormal clotting • Rapid volume infusions (particularly with hypertonic solutions) or increases in blood pressure with inotropes
• Perinatal asphyxia • Hypotension • PDA
Timing of PIVH
• ≥50% in first 24 hours • Approximately 10–20% days 2–3 • Approximately 20–30% days 4–7 • Approximately 10% after the first week
Classification of PIVH
• Grade 1 – germinal matrix haemorrhage • Grade 2 – IVH without ventricular dilatation• Grade 3 – IVH with blood distending the lateral ventricle • Grade 4 – echogenic intraparenchymal lesion associated with PIVH; previously this was thought to be an extension of bleeding from the lateral ventricles into the surrounding periventricular white matter but it is likely to be venous infarction
Several classification systems have been described. The most widely accepted is that of Papile
Prevention of PIVH The following have been shown to reduce the incidence of PIVH
• Antenatal steroids
• Maternal vitamin K
• Indomethacin (but long-term neurodisability is not reduced)
What are the Clinical presentation of PIVH ❓❓
• Grades 1 and 2 PIVH ➡️ silently and are detected by routine ultrasonography
• Grade 3 PIVH ➡️ presents with shock from blood volume depletion
• Grade 4 PIVH ➡️may present similarly and occasionally with neurological signs (seizures, hypotonia, bulging fontanelle)
What Is the Management of hydrocephalus post PIVH
Early, aggressive intervention with repeated lumbar puncture and/or ventricular taps has not been shown to be of benefit; drainage should probably be considered if the baby is symptomatic, cerebrospinal fluid (CSF) pressure is very high (>12 mmHg or 15.6 cmCSF; normal CSF pressure is 5.25 mmHg or 6.8 cmCSF) or head circumference and/or ventricular measurement on ultrasound scan is increasing rapidly
• Timing of surgical intervention with CSF reservoir or ventriculoperitoneal shunt insertion is controversial
• Drug treatment with acetazolamide with or without diuretics has been shown to be ineffective
What is Post-haemorrhagic ventricular dilatation (PHVD)
Defined as lateral ventricle measurement >4 mm above 97th centile following PIVH • A minority of PIVH cases develop PHVD – risk is higher with more severe lesions • Spontaneous resolution occurs in approximately 50% of cases of PHVD; the rest develop hydrocephalus (i.e. PHVD that requires drainage)
Which type of hydrocephalus is common after PIVH
As a sequel to PIVH, communicating hydrocephalus (as a result of malfunction of the arachnoidvilli) is more commcommon than non-communicating hydrocephalus (as a result of blockage of the cerebral aqueduct)
What is Normal CSF pressure in neonates
normal CSF pressure is 5.25 mmHg or 6.8 cmCsf
Periventricular leukomalacia
• PVL is haemorrhagic necrosis in the periventricular white matter that progresses to cystic degeneration and subsequent cerebral atrophy. It is often associated with infection (chorioamnionitis) and may be cytokine mediated. Hypoxia and ischaemia may also play a role
On ultrasound scan,
the initial necrosis appears as echogenicity (often described as ‘flare’) within a few days of the causative insult. This sometimes resolves but it may become a multicystic area after 1–4 weeks. The long-term neurological effects are usually bilateral, although initial ultrasound appearances are sometimes unilateral
Long-term neurodevelopmental effects of cystic PVL are:
• Spastic diplegia or tetraplegia (>90%) • Learning difficulties • Seizures (including infantile spasms) • Blindness
• Worse outcomes are associated with subcortical PVL.
Neonatal Encephalopathy
also known as hypoxic–ischaemic encephalopathy. The underlying cause is often unclear but it may originate antenatally, peripartum or postnatally. Placental insufficiency is a factor in the vast majority of cases.
Clinical presentation This can be staged according to the scheme suggested by Sarnat and Sarnat:
• Stage 1 – hyperalert, irritable; normal tone and reflexes; signs of sympathetic overactivity; poor suck; no seizures; symptoms usually resolve <24 hours; good outcome in approximately 99%
• Stage 2 – lethargic, obtunded, decreased tone and weak suck and Moro reflexes; seizures are common; approximately 75–80% have good outcomes; this is less likely if symptoms persist for >5 days
• Stage 3 – comatose with respiratory failure; severe hypotonia and absent suck and Moro reflexes; seizures less common but EEG abnormalities common – flat background or burst suppression; over 50% die and majority of survivors have major handicap
Management of HIE
is largely supportive but recent evidence supports the use of therapeutic hypothermia in babies >35 weeks’ gestations
What is therapeutic hypothermia
Baby cooled to between 33°C and 35°C by either total body or head-only cooling device • Maximum benefit likely if cooling starts within 6 hours of birth and is continued for 72 hours, followed by slow warming to normal temperature
Pathophysiology of neonatal encephalopathy Primary and secondary neuronal injuries have been described:
• Primary neuronal injury results from energy failure because of the inefficiency of anaerobic respiration to produce high-energy phosphocreatine and ATP. Glucose utilization increases and lactic acid accumulates. Energy failure and myocardial dysfunction further exacerbate this, leading to ion pump failure (Na+/K+-ATPase) and neuronal death as a result of cerebral oedema
• Secondary or delayed neuronal injury occurs because there are marked changes in cerebral blood flow with initial hypoperfusion and then reperfusion after resuscitation. This is associated with neutrophil activation and is exacerbated by prostaglandins, free radicals and other vasoactive substances. Excitatory amino acid neurotransmitters such as glutamate and N-methyl D-aspartate (NMDA) lead to excessive calcium influx and delayed neuronal death. The cellular mechanism for this may be necrosis or apoptosis (programmed cell death)
What is the benefits of Therapeutic hypothermia:
• RCTs show that the risk of death or severe neurological problems is significantly reduced
Causes of seizures in the newborn
• Neonatal encephalopathy
• Cerebral infarction: • Usually presents on day 1 or 2 • Often presents with focal seizures • Aetiology uncertain but thrombosis secondary to hypercoagulation tendency is a possibility • Outcome good in approximately 50%; the other 50% may develop mono- or hemiplegia or longterm seizure disorder
• Intracranial haemorrhage (massive PIVH, subarachnoid or subdural haemorrhage)
• Birth trauma (head injury equivalent)
• Meningitis
• Other sepsis
• Congenital infection
• Neonatal drug withdrawal
• Fifth-day fits (onset day 3–5, unknown cause, resolve spontaneously)
• Hypoglycaemia
• Hypocalcaemia
• Hypo- or hypermagnesaemia
• Inborn errors of metabolism: • Non-ketotic hyperglycinaemia • Sulphite oxidase deficiency • Biotinidase deficiency • Maple-syrup urine disease • Pyridoxine dependence • Urea cycle defect • Organic acidaemias (e.g. methylmalonic acidaemia)
• Structural brain abnormalities (migration disorders, etc.)
• Hydrocephalus
• Polycythaemia
• Neonatal myoclonus – not a true seizure, benign and common in preterm infants
Management of neonatal seizures
• Investigate for, and treat, underlying condition
• Initial treatment with phenobarbital, followed by midazolam, other benzodiazepines and paraldehyde
• Currently no evidence that suppression of clinical or electrographic seizures improves outcome
Causes of hypotonia in the newborn
Central causes
• Neonatal encephalopathy
• Intracranial haemorrhage
• Infection – generalized sepsis, meningitis, encephalitis
• Chromosomal abnormalities – trisomy 21, 18 or 13 • Structural brain abnormalities – neuronal migration disorders, etc.
• Metabolic disease – amino and organic acidaemias, urea cycle defects, galactosaemia, non-ketotic hyperglycinaemia, peroxisomal disorders, mitochondrial disorders, congenital disorders of glycosylation, Menkes syndrome
• Drugs – opiates, barbiturates, benzodiazepines, etc. • Prader–Willi syndrome
• Hypothyroidism
• Early kernicterus
Spinal cord lesions
• Trauma to the cervical spinal cord during delivery – usually involves traction and rotation with forceps
• Tumours, cysts and vascular malformations of spinal cord Neuromuscular disease
• Spinal muscular atrophy
• Congenital myotonic dystrophy
• Congenital myopathies
• Myasthenia gravis
Retinopathy of prematurity
• Retinopathy of prematurity (ROP) consists of vascular proliferation secondary to retinal vasoconstriction. This may progress and lead to fibrosis and scarring
• Prematurity and hyperoxia are known associations,
ROP stages
• Stage 1 – demarcation line• Stage 2 – ridge • Stage 3 – ridge with extraretinal fibrovascular proliferation • Stage 4 – subtotal retinal detachment • Stage 5 – total retinal detachment • Stages 1 and 2 disease resolves without risk of visual impairment if there is no progression • Stage 3 disease increases the risk of visual impairment • Stages 4 and 5 always lead to visual impairment
Zone 1, 2 or 3 (where zone 1 is the most central [i.e. posterior] around the optic disc) • The risk is greatest if zone 1 is affected ROP extent is described in terms of the number of clock hours. Plus disease includes tortuosity of the retinal vessels, pupil rigidity and vitreous haze.
Usually stage 3 plus disease should be treated with either cryotherapy or laser therapy, but location and extent of ROP also determine the need for treatment
More than 90% of neonates pass urine within 24 hours of birth. The collecting ducts have increased sensitivity to antidiuretic hormone (ADH) after birth and urine-concentrating ability increases rapidly.
Babies <32 weeks’ gestation at birth and <1500 g birthweight should be
screened by ophthalmological examination from 30 weeks’ corrected gestational age
What are the Causes of Obstructive uropathy in newborn ❓❓
**Posterior urethral valves
*Pelviureteric junction (PUJ) obstruction
**Mild renal pelvis dilatation
*Prune-belly syndrome (megacystis–megaureter)
**Ureterocele
* Urethral stricture
**Tumours (neuroblastoma, Wilms tumour)
Posterior urethral valves
• Mucosal folds in posterior urethra of male infants leading to dilatation of renal tract proximal to obstruction
• Bladder is often hypertrophied
• Diagnosed by micturating cystourogram • Suprapubic catheter is inserted initially, followed by surgical resection by cystoscopy or vesicostomy, followed by later resection
Pelviureteric junction (PUJ) obstruction
• Usually unilateral
• Diagnosed on antenatal ultrasound scan or presents with abdominal mass
• Gross hydronephrosis is associated with decreased renal function (confirmed with 99mTc-labelled MAG-3 (mertiatide) renogram); nephrectomy is usually required. Ureteroplasty is carried out for milder cases
Mild renal pelvis dilatation
Should be confirmed on postnatal ultrasound scan and investigated with a micturating cystourogram to exclude reflux nephropathy, which is a risk for recurrent urinary tract infection and subsequent scarring
Prune-belly syndrome (megacystis–megaureter)
• Lax abdominal musculature,
dilated bladder and ureters, and
undescended testes
• Neurogenic bladder
• Usually as a result of abnormalities of lumbosacral spine
Ureterocele •
Dilatation of distal ureter leading to obstruction
Haematuria in the newborn
• Urinary tract infection
• Obstructive uropathy
• Acute tubular necrosis
• Renal artery or vein thrombosis
• Renal stones
• Trauma
• Tumours
• Cystic dysplasia and other malformations
• Abnormal clotting
Causes of acute renal failure in neonates
Prerenal
• Hypotension • Dehydration • Indomethacin
Renal
• Cystic dysplasia and infant polycystic kidney disease • Renal artery/vein thrombosis • Congenital nephrotic syndrome • DIC • Nephrotoxins, e.g. gentamicin
Postrenal • Obstructive nephropathy
Ambiguous genitaliaSee Section On examination, note the following:
• If gonads are palpable they are nearly always testes • Length of phallus – if <2.5 cm stretched length in a term baby it is unlikely that the baby can function as a male
• Severity of hypospadias and fusion of labia • Other dysmorphic features/congenital abnormalities
Prompt diagnosis and appropriate management are
essential to resolve this and to exclude or treat congenital adrenal hyperplasia before electrolyte imbalances occur
Differential diagnosis
🧡True hermaphroditism:
Testes and ovaries both present (rare)
🧡Male pseudohermaphroditism – underdevelopment (↓ virilization) of male features:
• Androgen insensitivity (= testicular feminization) – most common
• Defects in testosterone synthesis
• Some forms of congenital adrenal hyperplasia
• Panhypopituitarism (should be suspected if hypoglycaemia is also present)
• Defects in testosterone metabolism (5α-reductase most common)
• Defects in testicular differentiation (rare)
🧡 Female pseudohermaphroditism – virilization of female:
• Congenital adrenal hyperplasia – most common enzyme deficiency is 21-hydroxylase deficiency (↑ 17α-hydroxyprogesterone)
🧡 Chromosomal abnormalities: • 45X/46XY mosaicism (rare)
Investigations
• Karyotype
• Daily electrolytes until diagnosis is established
• Blood pressure monitoring
• Blood sugar monitoring
• Abdominal ultrasound scan
• Serum hormone assay – 17α-hydroxyprogesterone, 11-deoxycortisol, testosterone, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone
• Urine steroid profile
• Genitogram/micturating cystourogram
What is the percentage of Group B streptococcus (GBS) colonization in pregnant women ❓❓
• Up to 20% of pregnant women have genital tract colonization with GBS
How many serotypes of GBS and what are the serious one ❓❓
• Three serotypes have been identified
• Serotype 3 is more common in late-onset GBS disease or meningitis if this is part of early onset disease
What are the Clinical presentation of Gas infection ❓
• Neonatal GBS infection may be early (within first few days, usually presenting by 24 hours) or late (after first week, usually at 3–4 weeks)
• Early disease often presents with septicaemia and respiratory distress (pneumonia or persistent pulmonary hypertension of the newborn)
• Late disease is usually septicaemia or meningitis – may be vertical or nosocomial transmission; antibiotics given intrapartum or in first few days do not always prevent late GBS disease
Escherichia coli
• Usually causes vertical infections in neonates and is often associated with preterm birth; can also cause nosocomial infection
• K1 capsular antigen is the most common serotype
What is the presentation of E Coli infection in neonates ❓❓
Septicaemia and meningitis are the most common presentations if vertically transmitted; urinary tract infections and NEC have been noted in nosocomial E. coli sepsis in neonates
Coagulase-negative staphylococci
• Most common nosocomial pathogen in neonatal intensive care units • VLBW infants with indwelling catheters are most at risk • Often resistant to flucloxacillin
Listeria monocytogenes
• May present with a flu-like illness in pregnant women and then lead to stillbirth or severe neonatal septicaemia and meningitis
• Gram-positive rod • Outbreaks have been caused by dairy products, coleslaw, pâté and undercooked meat
Listeria monocytogenes
• May present with a flu-like illness in pregnant women and then lead to stillbirth or severe neonatal septicaemia and meningitis
What is the presentation of Listeria monocytogenes infection in neonates ❓❓
Early and late-onset disease have been noted, similar to GBS • Early onset disease is associated with preterm birth and ‘meconium’-stained amniotic fluid (which is in fact often pus rather than meconium)
maculopapular or pustular rash is typical
Risk factors for vertically acquired bacterial sepsis
• Preterm rupture of membranes
• Prolonged rupture of membranes (>12–24 h)
• Maternal fever (>38°C or other signs of chorioamnionitis, e.g. white cell count > 15 × 109/l)
• Maternal colonization with GBS
• Fetal tachycardia
• Lack of intrapartum antibiotics in the presence of above risk factors • Foul-smelling amniotic fluid
• Preterm birth/low birthweight
• Twin pregnancy
• Low Apgar scores
Amoxicillin and gentamicin are the antibiotic combination of choice
Risk factors for nosocomial sepsis
• Prematurity/low birthweight
• SGA infants • Neutropenia • Indwelling catheters • TPN • Surgery
Cytomegalovirus
• Member of the Herpesviridae family (DNA virus) • Transmitted by close personal contact, blood products or breast-feeding. May also be sexually transmitted
• Prematurity/low birthweight
• SGA infants
• Neutropenia
• Indwelling catheters
• TPN
• Surgery
What are the long term complication of CMV neonatal infection ❓❓
Long-term neurodevelopmental sequelae are common and include cerebral palsy, learning disability, epilepsy, blindness and deafness
How is CMV diagnosed ❓❓
• Rising specific IgG antibodies in mother or baby
• Specific IgM may be raised for up to 16 weeks after primary infection
• Virus can be isolated from urine or throat swab
• Detection of early antigen fluorescent foci (DEAFF) is a newer technique used to detect viral antigen from urine and other body fluids
Aciclovir has been used with some success in immunosuppressed adults but may be toxic in neonates and is not of proven efficacy
Parvovirus
Fetal blood can be used to confirm the diagnosis by viral antigen detection with polymerase chain reactions.Parvovirus is a DNA virus.
Aciclovir has been used with some success in immunosuppressed adults but may be toxic in neonates and is not of proven efficacy
Neonatal hypoglycaemia Definition – blood glucose ≤S2.6 mmol/l
Normal term babies commonly have blood sugars <2.6 mmol/l, particularly in the first 24 hours (especially if the baby is breast-fed), but are not at risk of any long-term sequelae because they can utilize alternative fuels (e.g. ketones, lactate). It is therefore unnecessary to perform blood glucose analysis on healthy term babies.
Infants at risk of clinically relevant hypoglycaemia include:
• Those with increased demand/decreased supply, i.e. • Preterm • IUGR • Hypothermia • Infection • Asphyxia• Polycythaemia
• Hyperinsulinism: • Infant of a mother with diabetes • Haemolytic disease of the newborn • Transient neonatal hyperinsulinism • Beckwith–Wiedemann syndrome • Persistent hyperinsulinaemic hypoglycaemia of infancy (previously called nesidioblastosis) • Islet cell adenoma
• Endocrinopathies: • Pituitary (e.g. growth hormone deficiency, septo-optic dysplasia) • Adrenal (e.g. congenital adrenal hyperplasia)
• Carbohydrate metabolism disorders: • Glycogen storage disease • Galactosaemia
• Amino acidopathies • Organic acidaemias • Fat oxidation defects:
Babies at risk of clinically significant hypoglycaemia should be treated immediately with intravenous dextrose (2 ml/kg 10% dextrose followed by intravenous infusion) if blood glucose is <1.5 mmol/l.
Fat oxidation defects: • Deficiencies of medium-chain and very-long-chain acyl-coenzyme A dehydrogenases (MCADD and VLCAD), long-chain hydroxyacyl-coenzyme A dehydrogenase (LCHAD)
Panhypopituitarism Presents with:
• Persistent hypoglycaemia • Poor feeding • Micropenis • Hyperbilirubinaemia (conjugated) • Midline facial defects (cleft palate etc.) • Optic atrophy • Low growth hormone, cortisol (may cause hyponatraemia) and thyroid-stimulating hormone
Physiological jaundice occurs as a result of:
• Increased haemolysis: • Bruising • Antibody induced • Relative polycythaemia • Lifespan of red blood cells (in term infants – 70 days, in preterm infants – 40 days)
• Immature hepatic enzyme systems • ‘Shunt’ bilirubin from breakdown of non-red blood cell haem pigments • Enterohepatic circulation
Adrenal insufficiency Causes include:
• Congenital adrenal hyperplasia: • Most common cause is 21 α-hydroxylase deficiency (may or may not involve salt loss) • May be X-linked or autosomal recessive inheritance • Smith–Lemli–Opitz syndrome• Wolman syndrome (liposomal acid lipase deficiency) • Adrenal haemorrhage • Secondary causes: • Panhypopituitarism • Withdrawal from steroid treatment
Jaundice is considered non-physiological if any of the following are present:
• Onset before 24 hours of age • Serum bilirubin >270 μmol/l • Lasting >14 days (>21 days in preterm infants) • Associated pathological conditions that are known to cause jaundice
Note that levels of conjugated bilirubin >25 μmol/l should be investigated.
Prevention of haemolytic disease is by the following:
• Intramuscular anti-D is given after any possible event leading to sensitization in RhD-negative women
• Maternal serum screening for antibodies at booking with re-testing between 28 and 36 weeks for RhD-negative women with no antibodies
• Referral to a specialist fetal medicine centre for all those with antibodies.
ultrasound scanning to detect signs of hydrops, amniocentesis and spectrophotometric estimation of bilirubin in the amniotic fluid or fetal blood sampling to detect anaemia
• Serial fetal blood transfusions in severe cases
• Preterm delivery
Measurement of bilirubin
• Use of a transcutaneous bilirubinometer is recommended in babies >35 weeks’ gestation and >24 hours’ old
• Serum bilirubin should be measured if <35 weeks’ gestation, <24 hours’ old or if transcutaneous level >250 μmol/l
Treatment thresholds are lower for babies who are
sick, preterm, have evidence of haemolysis or rapidly rising serum bilirubin (>200 μmol/l per 24 h
What is the mechanism of Phototherapy ❓❓
photooxidizes and isomerizes bilirubin, facilitating increased excretion via urine and bile.
Complications of phototherapy are mainly minor and include:
• Diarrhoea • Transcutaneous fluid loss • Rashes
Complications of exchange transfusion include:
• Infection and other line-related complications• Fluid and electrolyte disturbance • Thrombocytopenia and coagulopathy • Transfusion reaction
What is the type of Exchange transfusion for neonatal jaundice and what it is effect ❓❓
Usually a double-volume exchange transfusion is performed via arterial and central venous lines over 1–2 hours, replacing the baby’s blood volume twice with donor blood.
🔺Dilute bilirubin
🔺Remove sensetized RBCs
🔺Correct anemia
When is Intravenous immunoglobulin for neonatal jaundice recommended ❓❓
Intravenous immunoglobulin (IVIG) (500 mg/kg over 4 h) is recommended as an adjunct to intensive phototherapy and exchange transfusion in haemolytic disease or ABO incompatibility if ➡️the serum bilirubin continues to rise rapidly (i.e. >200 μmol per 24 h).
What are NICE guidelines that recommend in preterm and term babies with prolonged jaundice ❓❓
• Look for pale, chalky stools and/or dark urine that stains the nappy • Measure the conjugated bilirubin
• Carry out a full blood count, blood group determination, DAT and urine culture
• Ensure that routine metabolic screening has been performed • Follow expert advice about care for babies with a conjugated bilirubin level >25 μmol
What are the causes of Polycythaemia ❓❓
haematocrit >65%.
• IUGR
• Maternal diabetes
• Delayed cord clamping
• Twin-to-twin transfusion
• Maternofetal transfusion
• Trisomies (13, 18, 21)
• Endocrine disorders (congenital adrenal hyperplasia, thyrotoxicosis, Beckwith syndrome)
Complications of Polycythaemia ❓❓
• Hypoglycaemia
• Jaundice
• NEC
• Persistent pulmonary hypertension of the newborn
• Venous thromboses
• Stroke
Haemorrhagic disease of the newborn, How can be prevented ❓❓
either a single intramuscular injection of vitamin K at birth or an oral dose at birth followed by two further oral doses at 1–2 weeks and 6 weeks in those who are predominantly breast-fed
When hemorrhagic disease of newborn can be presented ❓❓
📍Early
between days 2 and 6 with gastrointestinal haemorrhage, umbilical stump bleeding, nose bleeds or intracranial haemorrhage
📍Late
Late haemorrhagic disease may occur between 8 days and 6 months; intracranial haemorrhage is more common in these cases
What can exacerbate hemorrhagic disease of newborn ❓❓
perinatal asphyxia
liver dysfunction
maternal phenytoin or phenobarbital
Disseminated intravascular coagulation
This may occur in any sick neonate, e.g. those with:
• Sepsis
• Placental abruption or other perinatal events
• NEC
• Meconium aspiration syndrome
What precautions during Hemophilia baby birth ❓❓
Antenatal diagnosis is possible by chorionic villous biopsy, if there is a family history
• Vaginal birth is safe if uncomplicated but Ventouse delivery should be avoided
• Oral vitamin K (rather than intramuscular) should be given
Haemophilia A presentation ❓❓
• Almost 40% of cases present in the neonatal period with IVH, cephalohaematoma or excessive bleeding elsewhere
Bleeding should be treated with recombinant factor VIII,
Von Willebrand disease
• Two forms of von Willebrand disease may present in neonates • Type 2b is autosomal dominant, presents with thrombocytopenia but rarely presents with bleeding • Type 3 is autosomal recessive; presentation is similar to haemophilia A, but girls can be affected
Embryology of the gastrointestinal system
• The endodermal lining of the yolk sac forms the primitive gut • The midgut lengthens and protrudes into the yolk sac via the vitelline duct. Meckel’s diverticulum is the remnant of this
• The extra-abdominal gut rotates 270º anticlockwise around the mesentery which contains the superior mesenteric artery. Failure to complete this results in malrotation
• The gut returns to the abdominal cavity by the end of week 12
What is the difference between exomphalos and gastroschisis from Embryological point of view ❓❓
▪️The gut returns to the abdominal cavity by the end of week 12. Exomphalos is the result of this not occurring
▪️Gastroschisis is a failure of closure of the anterior abdominal wall
What changes in 2,3-DPG level after birth ❓❓
➿➿Levels of 2,3-DPG rise rapidly in the first few days to meet the increased metabolic requirements that occur after birth.
➿➿ Preterm infants have lower 2,3-DPG levels and therefore have a limited ability for oxygen to be unloaded from red blood cells
How to Identify fetal compromise ❓❓
• Kick charts
• Symphysis–fundus height – to estimate fetal size/growth
• Ultrasound scan measurement – to estimate fetal size/growth
• Amniotic fluid volume (see below)
• Umbilical artery Doppler studies – reflect placental blood flow
• Fetal Doppler scans – reflect hypoxia if abnormal
• Biophysical profile – fetal movement, posture and tone, breathing, amniotic fluid volume and cardiotachograph assessed
