Head box (concentration easily monitored). Nasal cannula <2L/min (cannot monitor effective FiO gas \202 ow rate, FiO2, and tidal volume, can \200\231t humidify effectively). >2L/mi n. Can be effectively humidi \201 ed. High \202 ow nasal cannula Generates CPAP effect. 2 \200\224depends on CPAP Prevents airway collapse and loss of lung volume. Maintenance of functional residual c apacity above closing volume reduces work of breathing. Uses \200 \200 \200 RDS and respiratory support, particularly for preterm infants. Post-extubation. In upper ai rway obstruction. Method \200 \200 Nasal mask or binasal prongs, rarely face mask or via ETT. Usual pressure is 5 \200\2236cmH but i risk of pulmonary air leaks as pressure i. Some equipment can deliver bi-level CPAP with or without synchronization to spontaneous breaths. 2O. Probable safe upper level is 8cmH2O, Complications \200 Pulmonary air leaks, e.g. pneumothorax. (particularly if treating RDS in an infant who has not received surfactant). Nasal trauma. Baby upset leading to hypoxia. i Upper GI distensio n or perforation (insert gastric tube on free drainage to reduce risk, rarely seen with mod ern equipment). \200 \200 Airway resistance and effort of breathing. \200 Positive pressure ventilation Intermittent positive pressure ventilation (IPPV) See b p.162 . High frequency oscillatory ventilation (HFOV) See b p.164. Synchronized ventilation Nomen clature confusing, but includes the following: \200 Synchronized intermittent positive pressure ventilation (SIPPV)/assist control/patient-trig gered ventilation (PTV): every spontaneous patient breath can trigger time-limited positive pressure in \202 ation. 06_McClure_06.indd 160 11/14/2012 11:22:47 PM NEONATAL RESPIRATORY SUPPORT 161 Synchronized intermittent mandatory ventilation (SIMV breaths is pre-set; any other spontan eous patient breaths are unassisted \200\224in case of apnoea the set rate is given. Pressu re support: all spontaneous breaths are supported by positive pressure for as long as inspi ratory \202 ow continues above a de \201 ned threshold. Can be combined with other modes . ): rate of triggered Studies in newborn infants show no particular advantage for SIPPV or SIMV compared to conve ntional IPPV during acute stages of respiratory illnesses such as RDS. May be useful during weaning, or if infant is not synchronizing with ventilator. Smaller infants may not be abl e to trigger breaths (older ventilators). Autocycling can cause over ventilation in PTV. Extracorporeal life support (ECLS) Provided only in a very small number of specialist cente rs in the UK. Also known as extracorporeal membrane oxygenation (ECMO), ECLS reduces mortal ity in severe respiratory disease, e.g. meconium aspiration syn- drome, persistent pulmonar y hypertension of the newborn.1 Early transfer to an ECLS center is important as these infa nts are often critically unwell. Criteria for eligibility: severe, but reversible cardiac or respiratory disease and oxygena tion index persistently >30 \200\22340 where: Oxygenation index = [(mean airway pressure \227 FiO2)/PaO2 (kPa)] \227 100 FiO2 is expressed as a decimal, e.g. 30% O2 = 0.3 Contraindications \200 Weight <1.8kg. \200 Gestation <34wks. \200 Severe congenital malformation. \200 Intracranial hemorrha ge or poor CNS prognosis (e.g. severe HIE). \200 Coagulopathy. Technique Blood taken from a major cannula is passed through a membrane oxy- genator and th en returned to the body. Blood is heparinized (activated clotting time 2 \200\2233 \227 no rmal) and low level conventional ventilation is main- tained. ECMO is maintained until dise ase recovery. May be: \200 double lumen cannula in right jugular vein or right Venous \200\223venous: atrium; Venous \200\223arterial: right carotid artery. blood drawn from right jugular vein and returned to Outcome Survival rates are high for reversible lung pathologies. Up to 10% of ECMO survivor s suffer major long-term problems. Complications include brain injury (secondary to neck ve ssel trauma, thromboembo- lism, CNS hemorrhage, complication of pre-ECMO disease/therapy) a nd peripheral thromboembolic phenomenon, e.g. may cause renal failure. Reference 1 UK Collaborative Trial Group (1996). UK collaborative randomized trial of neona tal extracor- poreal membrane oxygenation. Lancet 348: 75 \200\22382. 06_McClure_06.indd 161 11/14/2012 11:22:47 PM CHAPTER 6 Neonatology 162 Conventional positive pressure ventilation IPPV via ETT with continuous \202 ow of heated and humidi \201 ed gas allows the non-paralyzed baby to breathe spontaneously. The ventil ator is time- cycled, pressure limited (TCPL) where the user sets the positive inspira- tor y pressure (PIP), inspiration time (Ti) and ventilator rate. In this mode the tidal volume is determined by the lung compliance. Some ventilators can adjust PIP within a set range to deliver a set tidal volume (volume guarantee). Some ventilators can terminate inspiration when a set volume is reached or when inspiratory \202 ow is declining below a threshold l evel. Whichever method is chosen the user must be familiar with the operation and limitatio ns of the ventilator. Indications \200 \200 \200 \200 \200 \200 \200 \200 \200 Worsening respiratory failure, e.g. RDS. Impending or actual respiratory arrest from any ca use. Recurrent apnoeas. Massive pulmonary hemorrhage. Severe cardiac failure. Persistent pu lmonary hypertension of the newborn. Severe congenital lung malformation, e.g. diaphragmati c hernia. Severe HIE. Anesthesia. Ventilation parameters \200 \200 \200 \200 \200 Peak inspiratory pressure (PIP). PEEP. TI and expiratory (TE) time (often expressed as I:E ratio). Inspired O Gas \202 ow (L/min) through ventilator circuit (may not be adjustable) . 2% or fraction inspired O2 (FiO2). Monitoring ventilation \200 Review and adjust ventilation settings soon after commencement (see Box 6.4 for care princi ples). Monitor blood gasses and adjust ventilation as appropriate. Acceptable limits will d epend on the clinical situation, however, as a guide in preterm infants; pH 7.2 \200\2237.3 5, PCO2 5 \200\2238kPa, PO2 6 \200\22310kPa, saturation 90 \200\22395%, expired tidal volum e around 5mL/kg. \200 2 is too low \200\224i FiO2, or i mean airway pressure (the latter by If PaO either i PIP, i PEEP, or d TE which will i rate as TI stays constant). Do the opposite if PaO2 is too hig h. If PaCO PIP, or d PEEP, or i rate. Do the opposite if PaCO2 is too low. 2 is too high \200\224i alveolar ventilation, i.e. minute volume, by i 06_McClure_06.indd 162 11/14/2012 11:22:47 PM CONVENTIONAL POSITIVE PRESSURE VENTILATION 163 Box 6.4 Care principles in assisted ventilation in newborns Endotracheal tube (ETT) Use correct size and secure appropriately. Elective intubation Give prior sedation with opiate, e.g. morphine or fen- tanyl, and muscl e relaxant, e.g. suxamethonium (ONLY if staff experi- enced in airway management are presen t). Minimal handling Reduces episodes of deterioration. Sedation/analgesia Evidence does not support routine use of morphine infusion for ventilate d preterm infants. (cid:1) Prolonged neuromuscular relaxation (e.g. Vecuronium) \200 \200 Consider in speci \201 c circumstances, e.g. severe meconium aspiration Give sedation/anal gesia to paralyzed infants, e.g. morphine infusion Feeding Once stable, ventilation is not a contraindication to careful gas- tric feeding. Ve ry ill babies may not tolerate feeding as gastric distension can cause diaphragmatic splint ing. Humidify and warm inspired gas Minimal routine suctioning Continue monitoring \200 SpO \200 \200 \200 Pulse, BP, respiratory rate 2, TcO2, TcCO2 Tidal volume Intermittent blood gas analysis (capillary or arterial) Acute deterioration during ventilation May present as systemic collapse, dd PaO2, or ii PaC O2. Ventilate with manual system, e.g. T-Piece (preferably with PEEP), and O2 as required. Rapid improvement suggests ventilator problem. Otherwise consider ob- structed ETT, displac ed ETT, pneumothorax, or non-respiratory disease, e.g. intraventricular hemorrhage (IVH), g ut perforation. Slow deterioration during ventilation May present as slow deterioration in overall clinical condition, i PaCO2, or d PaO2. Consider: worsening respiratory disease; partial ETT obstru c- tion; airway circuit leak; non-respiratory disease. Ventilation weaning As condition starts to improve aim to wean ventilation. Wean O2 to low- est needed to maintain adequate PaO2 (d retinopathy risk). As lung com- pliance improves w ean PIP to maintain appropriate expired tidal volume (d risk of pulmonary air leak) in 2cmH 2O steps until 12 \200\22314cmH2O (moni- tor blood gasses). Then wean rate by 5 or 10 incre ments until 10 \200\22320breaths/ min. Following extubation it is often helpful in preterm infants to start nasal CPAP 5cmH2O (see b p.160). Extubation without CPAP may be appropriat e after short-term ventilation. 06_McClure_06.indd 163 11/14/2012 11:22:47 PM CHAPTER 6 Neonatology 164 High frequency oscillatory ventilation A continuous positive distending pressure (mean airw ay pressure) is ap- plied and, around this pressure amplitude (or \210\206p) is oscillated by a dia- phragm or an interrupter device in the ventilator circuit. High frequency oscill atory ventilation (HFOV) has an ef \201 cacy equivalent to IPPV in the primary treatment o f RDS. It may be indicated for: \200 \200 \200 \200 \200 \200 Rescue treatment when IPPV has failed. Pulmonary air leaks. Meconium aspiration syndrome. P PHN. Pulmonary hypoplasia. Congenital diaphragmatic hernia (see Fig. 6.7). Ventilation parameters \200 Mean airway pressure (P FiO \200 2. \200 \200 \200 Oxy genation (PaO2) is dependent on both Paw and FiO2. As Paw i, PaO2 will improve as functiona l residual capacity (FRC) i. At some point, how- ever, further Paw i will d PaO2 because of over distension. aw). aw (amplitude or \210\206p). Airway pressure difference generated around P Oscillation frequency per second. Circuit gas \202 ow. CO2 removal (PaCO2) is dependent on alveolar ventilation and, so, on both the frequency and amplitude. Unlike IPPV, ventilator constraints make tidal volume inversely proportional to the frequency. It is normal for generated tidal volumes to be less than that physiological ly required, yet adequate ventilation occurs \200\224this apparent paradox is explained by com- plicated air \202 ow physics of HFOV that augment CO2 diffusion. Once the frequency is set, CO2 removal is increased by i amplitude and vise versa. Commencing ventilation If v entilating for the \201 rst time, appropriate initial settings at term are: P \200 \200 \200 FiO \200 If transferring from IPPV: \200 Set initial HFOV P \200 Start on the same FiO aw 8cmH2O. Amplitude 20cmH Frequency 10Hz. 2O. 2 0.5, i.e. 50% inspired O2 concentration. aw 2cmH2O higher then Paw used in IPPV. 2, and set frequency at 10Hz. 06_McClure_06.indd 164 11/14/2012 11:22:47 PM HIGH FREQUENCY OSCILLATORY VENTILATION 165 Monitoring ventilation \200 Once ventilated, observe the infant \200\231s chest expansion and oscillation, and alter se ttings as required. Perform a CXR after 1hr to assess chest expansion: 8 posterior ribs vis ible above the diaphragm is appropriate until the baby is stable. Monitoring ventilation is otherwise as for IPPV (see b p.162). Be aware that rapid eliminat ion of CO2 can occur leading to over-ventilation. Anticipate and monitor blood gas/transcut aneous readings closely. \200 2 is too low: i either the FiO2 or mean airway pressure (MAP) If PaO by 1 \200\2232cmH2O ev ery 30 \200\22360min (avoid chest overexpansion), and vise versa. If CO Optimal CO does not usually need to be changed. \200 2 is too high: i amplitude by 2cmH2O increments and vise versa. 2 elimination occurs at 10H z, and, hence, the frequency Weaning ventilation As clinical status improves: d FiO2 to 0.5 and then d Paw by 2cmH2O ste ps until 6 \200\2237cmH2O is tolerated. Also progressively d amplitude to the mini- mum req uired to maintain normal CO2. Some babies will tolerate weaning to what is essentially CPAP, whilst others, below a certain Paw, do better if changed to slow rate IPPV. 06_McClure_06.indd 165 11/14/2012 11:22:47 PM CHAPTER 6 Neonatology 166 Bronchopulmonary dysplasia See also b p.276. Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that affects infants who have been born preterm. Over the last decade advances in neonatal care, including the increasing use of antenatal steroids, and early su rfactant therapy, have modi \201 ed a change in the underlying pathology in many cases. \200\230Old \200\231 BPD was described as a disease of scarring, and repair. This condition was associated with long periods of mechanical ventilation, often with high PIP, and high FiO2. \200\230New \200\231 BPD is a condition of impaired alveolar development, with less destruction and scarring. Mechanical, oxidative and in \202 ammatory factors all contrib- ute to lung injury. The radiographic appearances of more recent cases are less dramatic (se e Fig. 6.6), however, the impairment in lung function continues through childhood, and is a ssociated with a number of other impairments. De \201 nition The de \201 nition of BPD has evolved with time. The most commonly used de \201 nition is \200\230Oxygen requirement at 36/40 corrected gestational age (CGA) \200 \231. This de \201 nition does not have any grading of severity, and encom- passes a wide spectrum of disease. NICHD/NHLBI De \201 nitions (2001) \200 \200 Mild: Moderate: 36/40 CGA Severe: need for supplemental O2 at age 28 days, but not at 36/40 CGA need for supplemental O2 <30% at age 28 days and at mechanical ventilation or requiring >30% O2 at (cid:2) 36/40 CGA \200\230Walsh \200\231 test (2003) \200 \200 \200 Test at 36 1/40 CGA. Aim to maintain S BPD if need If <30% O inability to maintain SpO2 >8 8% for 1hr pO2 > 88% (cid:2) 30% O2 to maintain SpO2 >88% (or ventilated) 2, then FiO2 is gradually decreased to air. BPD is de \201 ned as Incidence and risk-factors Incidence is dependent on de \201 nition used. Wide variations between cen- tres with a range of 4 \200\22358% (mean 23%) of at-risk babies. BPD more like ly with: \200 \200 \200 \200 \200 \200 \200 Gestational immaturity. Low birth weight. Males. Caucasian heritage. IUGR. Family history o f asthma. History of chorioamnionitis. 06_McClure_06.indd 166 11/14/2012 11:22:47 PM BRONCHOPULMONARY DYSPLASIA 167 Prevention of BPD No evidence of effect \200 Surfactant and ANC steroids (effect may be off-set by increased survival?) Closure of PDA D iuretics Inhaled steroids Inhaled nitric oxide HFOV compared to conventional ventilation Tr eating \200 \200 \200 \200 \200 Ureaplasma urealyticum (more research needed) May be of bene \201 t in certain infants \200 (cid:1) (clinical trials needed as increased risk Systemic corticosteroids of CP) nCPAP vs. intubation (cid:1) (need for surfactant, risk of pneumothorax) Evidence of effect \200 \200 Caffeine citrate for apnoea of prematurity in infants <1250g Vitamin A supplementation for infants <1000g Treatment of established BPD (cid:1) No speci \201 c treatment has been demonstrated to sh ow an improve- ment in outcome of BPD. Oxygen is the most commonly used therapeutic agent, although the \200\230correct \200\231 dose and what SpO2 is acceptable has not been establ ished. A number of large trials are ongoing and their results are awaited (Ref: NeOPrOM Col laboration). Other treatments include; diuretics, corticosteroids, sildena \201 l, optimiz- ing nutrition. Immunization for at-risk infants with monoclonal respiratory syncytial virus (RSV) antibody has recently been recommended by the UK depart- ment of health. (cid:1) This involves mont hly injections during the RSV season. Outcome Increased survival of preterm infants has led to an increase in the number survivin g with BPD. Mortality has improved (previously 10 \200\22320% would die from cor-pulmonale or respiratory infection). Other problems include: \200 \200 \200 \200 Increased risk of CP. Poorer cognitive functioning and academic performance. High risk of r e-hospitalization with respiratory illness. Poorer lung function. Respiratory problems seem to lessen as children get older, perhaps re \202 ecting the lung \200\231s continued growth and development. 06_McClure_06.indd 167 11/14/2012 11:22:47 PM CHAPTER 6 Neonatology 168 Circulatory adaptation at birth Fetal circulation Oxygenated placental blood (PaO2 75kPa) r eturns to the fetus via the umbilical vein. Blood bypasses the liver via the ductus venosus and \202 ows into the inferior vena cava, and then the right atrium. This blood is then channeled to the left atrium and so to the left ventricle (via the foramen ovale). Oxygenat ed blood is then pumped to the cerebral and coronary vessels. The right ventricle mostly re ceives deoxygenated blood from the superior vena cava. About 15% is pumped to the lungs and the rest is diverted, via the ductus arteriosus, to the descending aorta so that it can go to the placenta via the umbilical arteries. Postnatal circulation At birth, oxygen inhalation leads to pulmonary arterial vasodilatatio n, lead- ing to d arterial resistance and i pulmonary blood \202 ow. At the same time sys temic vascular resistance i due to loss of the low resistance placental circulation. The du ctus arteriosus constricts as PaO2 i. The foramen ovale closes as pulmonary venous return t o left atrium i and right atrial pres- sure d. Although initially rapid, these changes cons olidate over 2 \200\2233wks. Persistent pulmonary hypertension of the newborn (PPHN) Failure of pulmonary vascular resis tance to fall after birth causes decreased pulmonary blood \202 ow; incidence 1/1000 \200 \2231500 live births. Causes Rarely primary/idiopathic due to disease of pulmonary vasculature. More commonly, it is a secondary complication of severe illness. Presentation \200 \200 Hypoxia disproportionate to any dif \201 culty with CO Discrepancy between pre- and post-d uctal arterial oxygen saturations >10%. Mild breathlessness (as PaCO determinant of respira tory rate), acidosis, hypotension. Loud single second heart sound. 2 elimination. 2, not PaO2, is the main physiological Echocardiography shows i pulmonary arterial pressure, large right to left shunt at the leve l of the foramen ovale and ductus arteriosus. Management \200 \200 \200 Treat cause; minimal handling. Optimize BP, pH (aim high-normal), Hb, U&E, blood glucose. V entilate (aim for high PaO helpful. Inhaled nitric oxide (results in selective pulmonary va sodilatation): dose 20ppm for 6hr initially and monitor for toxic levels of NO2 and methaem oglobin. ECMO, if severe. 2 and normal PaCO2). HFOV may be Prognosis 10 \200\22330% mortality. Risk of neurodevelopmental impairment in survivors. 06_McClure_06.indd 168 11/14/2012 11:22:47 PM PATENT DUCTUS ARTERIOSUS 169 Patent ductus arteriosus De \201 ned as failure of ductus arteriosus to close normally aft er birth. The ductus is normally functionally closed within 1 \200\2233 days of birth in te rm infants. Common in preterms (>50% if VLBW). Presentation \200 \200 Small: Large: \200 asymptomatic. poor growth, dif \201 culty feeding, respiratory dif \201 culty, systolic or continuous \200\230machinery \200\231 murmur at the upper left sternal edge radiating to back, heart f ailure; CXR. Cardiomegaly, pulmonary plethora; echocardiography con \201 rms PDA and degre e of shunt. \200 Complications Poor growth, heart failure, pulmonary hemorrhage, i risk of BPD. Management (cid:1) There is considerable uncertainty about whether preterm infants ben- e \201 t from treatment for PDA and, if so, what is the optimal treatment. There is wide vari ation in practice with some units treating many cases and others almost none. An approach c onsidered sensible by many is: If asymptomatic Observe because most close spontaneously. If symptomatic In a preterm infant consider the following: \200 \200 \200 \200 Restrict \202 uids, e.g. 100 \200\223120mL/kg/day. Optimize blood oxygenation, e.g. blood transfusion if anemic. Treat heart failure, e.g. furosemide 1mg/kg 12-hourly PO or IV. Con sider pharmacological closure (e.g. indomethacin or ibuprofen). If duct fails to close a re peat course may be given. Side effects: d renal blood \202 ow leading to oliguria, \202 uid retention, +/ \200\223 hyponatraemia; d cerebral blood \202 ow; GI complications (bl eeding, ulceration); bleeding (d platelet function); displaces protein bonding of bilirubin . Consequently, indomethacin is contraindicated if severe jaundice, necrotizing enterocolit is (NEC), thrombocytopenia, or renal failure. Pharmacological closure is also contraindicat ed when the PDA is necessary for pulmonary blood \202 ow (e.g. some forms of congenital h eart disease). Surgery may be necessary if medical management fails to control symptoms or if there is signi \201 cant heart failure, ventilator dependence, or prolonged failure to close. Prognosis Generally good, but infants who require PDA treatment often have other morbiditie s that affect prognosis, including severe BPD. Surgery after failed medical treatment carri es a signi \201 cant risk of mortality. PDA is much less likely to close when present in t erm infants. Medical treatment in term infants is not likely to be effective. 06_McClure_06.indd 169 11/14/2012 11:22:48 PM CHAPTER 6 Neonatology 170 CNS malformations Overall incidence 74 \200\2235/10 000 births. There has been a dramatic f all in last 50yrs. Neural tube defects \200 \200 Failure of primary neural tube closure during 4th week of gestation. Prevalence decreasing due to: \200 \200 iAFP, USS) leading to termination; prenatal diagnosis ( maternal periconceptual folate therapy Anencephaly Lethal condition comprising absence of skull bones, fore- brain and upper brain -stem. Encephalocele Midline skull defect with brain tissue herniation. The lesion is covered with skin and requires surgical excision and closure. Associated brain abnormality usually lead s to poor neurodevelopment. Spina bi \201 da Several types, all secondary to failure of midline fusion of dorsal verte bral bodies. All forms require specialist advice and treatment. \200 Spina bi \201 da occulta: no herniation of neural tissue. Often overlying dermal sinus, di mple, lipoma, or hairy naevus is present (perform spinal US or MRI). Associated with diaste matomyelia or cord tethering. Meningocele: Requires surgical closure. Excellent prognosis. Myelomeningocele: covered by meninges/skin or be open. Adjacent spinal cord is always abnor mal. Usually thoraco-lumbar, lumbar, or lumbo-sacral. \200 herniation of meninges and \202 uid only with skin covering. herniation of spinal neural tissue, which may be problems fecal incontinence; urinary tract dilatation; hydrocephalus; bulbar paresis second ary to Chiari malformation; and vertebral anomalies (e.g. kyphosis); treatment prognosis wo rst if lesion very large or high. Palliative care may be appropriate. include \200\224 \202 accid paralysis below the lesion; urinary and \200 \200\224surgical closure and hydrocephalus drainage; \200\224related to severity of assoc iated problems. Prognosis Congenital hydrocephalus Excessive head growth caused by CSF accumulation (see also b p.535 ). \200 : congenital (aqueduct stenosis, Dandy \200\223Walker malformation, Causes congenital infection, e.g. CMV, cerebral tumor); acquired (IVH, subarachnoid hemorrh age, CNS infection, e.g. meningitis). Features bulging fontanelle, \200\230sun-setting \200\231 sign of eyes. Con \201 rmed by cranial US or MRI. Treatment: ventriculo-peritonea l shunt. : OFC above the 97th centile with wide cranial sutures and \200 surgical insertion of indwelling drainage device, e.g. Dandy \200\223Walker malformation \200 Cerebellar vermis hypoplasia associated with: \200 \200 hydrocephalus; posterior fossa CSF collection ( \200\230cyst \200\231) expanding into 4th v entricle. 06_McClure_06.indd 170 11/14/2012 11:22:48 PM CNS MALFORMATIONS 171 \200 Associated with variety of syndromes: Prognosis: fetal alcohol, trisomy 13 + 18. depends on associated abnormalities/underlying condition. Agenesis of the corpus callosum \200 Non-speci \201 c feature of numerous conditions and is associated with a wide variety of c onditions. May be total or partial. May be incidental \201 nding. Prognosis depends on as sociated syndromes/features. \200 \200 Hydrancephalus \200 Absence of cerebral hemispheres with cavity \201 lled with CSF. Brainstem and midbrain ar e usually spared. Cause: necrosis. Prognosis: impairment. severe (vascular) cerebral insult leading to extensive cortical usually lethal. Survivors have severe neurodevelopmental Microcephaly See also b p.534. OFC progressively falls below 3rd centile. \200 \200 Primary defect is reduction in brain size. Causes: syndromes, maternal drug/alcohol abuse, brain injury. Prognosis: intrauterine infection, chromosomal defects, various generally poor neurodevelopmental outcome. Holoprosencephaly Severe developmental defect of the forebrain. There is a single central c erebral ventricular cavity with varying degrees of development and sepa- ration of the hemi spheres. Midline facial defects are common. May be isolated or associated with chromosomal defects, particularly trisomy 13. Poor prognosis. Neuronal migration defects Includes lissencephaly (smooth brain), pachygyria (very few gyri ), poly- microgyria (numerous underdeveloped gyri), schizencephaly (deep cere- bral cleft), neuronal heterotopia (foci of neurones in abnormal locations within the brain). All are as sociated with poor neurodevelopmental out- come and seizures, but eventual outcome is depen dent on severity of malformation. 06_McClure_06.indd 171 11/14/2012 11:22:48 PM CHAPTER 6 Neonatology 172 Hypoxic \200\223ischaemic encephalopathy Clinical syndrome of brain injury secondary to a h ypoxic-ischaemic insult. In developed countries the incidence is 72 \200\2235/1000 live bir ths (moderate to severe incidence is 1 \200\2232/1000 live births). Causes d \200 d \200 d \200 \200 \200 Umbilical blood \202 ow, e.g. cord prolapse. Placental gas exchange, e.g. placental abrup tion. Maternal placental perfusion. Maternal hypoxia from whatever cause. Inadequate postnatal cardiopulmonary circulation. Presentation Varies depending on severity of cerebral hypoxia. An infant may have a range o f symptoms and signs affecting: level of consciousness, muscle tone, posture, tendon re \202 exes, suck, heart rate and central nervous system ho- meostasis.1 Before concluding that an infant may have HIE secondary to an intra- partum hypoxic-ischaem ic event, assess for evidence of an intrapartum problem (e.g. CTG abnormality, sentinel eve nt such as abruption or cord prolapse). There should be respiratory depression at birth and a need for resuscitation, including IPPV (Apgar score at 5min < 5). There should be modera te to severe acidosis soon after birth (pH<7.0, base excess worse than \200\22312). The ba by should develop encephalopathy within 24hr of birth. Other causes of encephalopathy shoul d be excluded. Management \200 \200 \200 \200 \200 \200 Resuscitate at birth; insert IV arterial lines. Avoid hyperthermia. Assess eligibility f or therapeutic hypothermia (TH) (see Box 6.5). Start cerebral function analysis monitoring (CFAM). Assess for features of dysmorphism and birth trauma. Assess neurological features. Exclude other causes of encephalopathy, e.g. meningitis, metabolic disturbances, maternal d rugs, CNS malformation, and hemorrhage. Expect and manage associated multi-organ failure, e .g. cardiac or renal. 2+, Mg2+ blood glucose, Monitor and maintain homeostasis, e.g. U&E, C a Hb, blood gasses, coagulation. Support BP. Mild \202 uid restriction initially (e.g. 40 mL/kg/day 10% dextrose) as there may be oliguria. Omit milk feeds for 1 \200\2232 days if H IE severe and then feed slowly. Treat seizures \200 (cid:1). Therapeutic hypothermia This is now the standard of care for term infants with moderate/sev ere hy- poxic ischaemic encephalopathy.2 Cooling is achieved using a temperature controlled mattress or wrap, and eligible infants have their temperature lowered to 33 \200\22334 C within 6hr of insult. Hypothermia is maintained for 72hr before gradual re-warming. 06_McClure_06.indd 172 11/14/2012 11:22:48 PM HYPOXIC \200\223ISCHAEMIC ENCEPHALOPATHY 173 Box 6.5 Criteria for therapeutic hypothermia: (A) Infants >36/40 and >1800g and <6hr old with one of (cid:1) 5 or continued need for resu scitation at 10min \200 cord pH (or any blood gas in \201 rst hour) <7/BE(cid:1) \200 \22316 \200 Apgar Acidosis: (B) Moderate or severe encephalopathy Altered level of consciousness (lethargy/stupor/coma) and one of: \200 \200 \200 Hypotonia Abnormal re \202 exes, e.g. moro, suck, gag, papillary, oculovestibular Clinical seizures If criteria A and B both met then assess for criterion C (CFAM) (C) At least 30min of CFAM recording which shows either abnormal background activity or sei zures (clinical or electrical). If CFAM not available and criteria A&B are met, cooling can be started after senior doctor discussion (e.g. before or during transportation). Cerebral function analysis monitoring (CFAM) Single or 2 channel machines available (2 chan nel = left and right hemi- spheres). Displays \200\230raw \200\231 EEG and a compressed \200\230amplitude integrated \200\231 re- cording. Pattern of a EEG is used for classi \201 cation of background activity (see Figs 6.9 \200\2236.12). Normal CFAM (aEEG) recordin g (term infants): \200 \200 (cid:1)5 V (when awake), upper margin (cid:2)10 V. Lower margin Evidence of sleep-wake cycling, no seizures. Prognosis Without cooling, risk of later disability or death is: grade I <2%; grade II 24%; grade III 78%. Disabilities are likely to be one or more of the follow- ing: spastic quadr iplegia, dyskinetic cerebral palsy, severely reduced IQ, cortical blindness, hearing loss, and epilepsy. References 1 Sarnat HB, Sarnat MS (1976) Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 33: 696 \200\223705. 2 Edwards AD, Brocklehurst P, Gunn AJ, et al. (2010) Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis an d meta-analysis of trial data. Br Med J 340: c363. 06_McClure_06.indd 173 11/14/2012 11:22:48 PM CHAPTER 6 Neonatology 174 Fig. 6.9 Normal CFAM trace. Note sleep-wake cycling (narrowing and widening of trace). Fig. 6.10 Moderately abnormal CFAM trace. Note the widened aEEG trace (baseline <5) and sup pressed raw EEG with periodic high-voltage complexes. 06_McClure_06.indd 174 11/14/2012 11:22:48 PM HYPOXIC \200\223ISCHAEMIC ENCEPHALOPATHY 175 Fig. 6.11 Severely abnormal CFAM trace \200\224burst suppression. Note the very low baselin e voltage (<5) with high voltage discharges (as seen on raw trace below) giving a spiked pa ttern to the aEEG. Fig. 6.12 Severely abnormal CFAM trace \200\223 continuous low voltage. Note that there is almost no electrical activity. 06_McClure_06.indd 175 11/14/2012 11:22:49 PM CHAPTER 6 Neonatology 176 Cerebral hemorrhage and ischaemia Periventricular hemorrhage (PVH) and intraventricular hem orrhage (IVH) Rare >32wks gestation. Hemorrhage starts in the vascular germinal ma- trix (s ubependymal). Bleeding may then extend into, and may dilate, the lateral ventricles (IVH). Haemorrhagic periventricular infarction may then occur secondary to impairment of cerebral venous drainage by intraven- tricular hemorrhage. Incidence: 710 \200\22315% of infants bor n <32wks. Risk i with i prematurity. Causes: related to rapid alteration in cerebral blood \202 ow, e.g. severe RDS, pneumothorax, hypotension, hypoxia, i/d PaCO2. Presentation: mo st occur within 72hr of birth. Seldom occur before birth unless there is alloimmune thrombo cytopenia. Up to 50% are asympto- matic. Larger bleeds may present as sudden catastrophic s ystemic col- lapse, bulging fontanelle, neurological dysfunction (e.g. seizures or paucity/ abnormal movements), anemia, and jaundice. \200 \200 Diagnosis con \201 rmed using cranial US. At risk groups or preterm infants <32wks should be screened by cranial US (at 1wk, and at 1mth, or after sudden deterioration). Several gra ding systems exist, but it is better to describe the location and extent of hemorrhage as o ne of: \200 \200 \200 subependymal only; or IVH IVH ventricular dilatation; or parenchymal involvement. Prevention Antenatal steroids reduce incidence. Prophylactic neonatal indometacin treatment reduces incidence, but does not improve long term neurodevelopmental outcome. Treatment Supportive. Irrigation of lateral ventricles following surgical drain insertion i s experimental. Complications \200 ventricular dilatation (PHVD): s to obstruction of Post-haemorrhagic CSF \202 ow or absorption. Clinical features include: increasing OFC; w ide cranial sutures; apnoea; seizures; feed intolerance; \200\230sun setting \200\231 eyes . Diagnosis con \201 rmed and monitored by measuring ventricular index on cranial US. 50% resolve spontaneously. Progressive symptomatic PHVD requires CSF drainage either by serial LP or intracranial reservoir and then by insertion of ventriculo-peritoneal shunt. Haemorrh agic periventricular infarction: occurs in 15%. Blood in the lateral ventricles impairs adj acent venous drainage, which results in adjacent cerebral infarction. Cranial US: cystic pa renchymal area(s) adjacent and communicating with lateral ventricle (porencephalic cyst). Prognosis Sub-ependymal or uncomplicated IVH does not affect neurode- velopment. Cerebral p alsy is common if either PHVD present and treat- ment is required (50%), or there is parenc hymal extension (80%). 06_McClure_06.indd 176 11/14/2012 11:22:50 PM CEREBRAL hemorrhage AND ISCHAEMIA 177 Term intracranial hemorrhage \200 \200 Subdural: Subgaleal swelling all over scalp, not limited by sutures. Subarachnoid: Parenchy mal or intraventricular: seizures possible. Cephalohaematoma: take weeks to resolve, and ma y partially calcify. increased risk with dif \201 cult extraction. : potential massive blood loss with systemic collapse. Boggy \200 asymptomatic, or may present with seizures/irritability. is usually haemorrhagic infarction \200\224 subperiosteal bleed, limited by suture lines, may Periventricular leucomalacia (PVL) Severe HIE can lead to cortical neuronal necrosis, basal ganglia injuries, focal cerebral infarctions or subcortical leukomalacia. PVL is character ized by periventricular white matter lesions: i echogenicity; cysts. \200 poor cerebral p erfusion or ischemia, in \202 ammation. \200 Cause: Risk factors: hypocarbia. May not be apparent for several weeks after birth. Diagnos is: Prognosis: particularly if there is cyst formation. extreme prematurity; hypotension; severe illness; \200 \200 periventricular echodensities or cysts seen on cranial US. higher risk of cerebral palsy (e specially spastic diplegia), Cerebral infarction (perinatal stroke) \200 1:1600 to 1:5000 births. \200 Incidence: Neurological signs and symptoms caused by a vascular event around the time of de livery. Presentation depends on timing and nature of event; focal seizures, encephalopathy, apnoea, poor feeding, asymmetrical re \202 exes/ movement/tone. May be associated with ma ternal/neonatal coagulation disorders (e.g. Factor V Leiden, Protein C or S de \201 ciency ). Management: supportive, cover infection, correct any metabolic (e.g. hypoglycaemia) or h ematological (e.g. polycythemia) abnormalities. Start CFAM and treat any seizures. Investig ation: EEG. depends on site and nature of lesion. 750% of affected Prognosis: children will carry some neurological impairment into childhood. FBC/Coag/U&E(Ca2+, Mg2+)/LFTs/Glucose/CFAM/ MRI/ 06_McClure_06.indd 177 11/14/2012 11:22:50 PM CHAPTER 6 Neonatology 178 Necrotizing enterocolitis Incidence The most common neonatal surgical emergency. Incidence 1 \200\2233/1000 live births (5 \200\22310% in VLBW infants). Incidence is reduced 6-fold i n preterm infants fed breast milk. Typically a sporadic condition affecting preterm infants (790% of cases), but can be epidemic or occur in term infants. The disease may just involv e an isolated area of gut, or be extensive. Distal ter- minal ileum and proximal colon are most frequently affected. Multi-organ failure is associated with diffuse disease. Cause Multifactorial. Severe intestinal necrosis is end result of an exaggerated immune res ponse within the immature bowel leading to in \202 ammation and tissue injury. NEC rarely occurs before milk feeding commences, but tim- ing of \201 rst feed appears not to be rel evant. Predisposing factors: \200 \200 \200 \200 \200 \200 Prematurity. IUGR (causes chronic bowel ischaemia). Hypoxia. Polycythaemia. Exchange transf usion. Hyperosmolar milk feeds. Presentation Most common in the second week after birth. Early \200 \200 \200 \200 Non-speci \201 c illness. Vomiting/bilious aspirate from gastric tube. Poor feed toleratio n (increasing gastric aspirates). Abdominal distension. Late \200 \200 \200 \200 \200 \200 \200 \200 Additional abdominal tenderness. Blood, mucus, or tissue in stools. Bowel perforation. Shoc k. DIC; multi-organ failure. AXR shows intestinal distension (see Fig. 6.8). Pneumatosis in testinalis. Hepatic portal venous gas. Signs of intestinal perforation, e.g. free peritonea l gas or gas outlining of falciform ligament ( \200\230football \200\231 sign). Management \200 Prophylaxis: evidence for prevention by administration of probiotic bacte ria. Investigations: gas; blood culture; AXR; Group and cross match. Stop milk feeds for 10 \200\22314 days \200\230Bell staging \200\231 (see Table 6.2) may be useful in grading se verity. antenatal steroids and breast milk are protective. Emerging FBC; U&E; creatinine; coagulation screen; albumin; blood \200 (cid:1). Insert gastric tube on free drainage. 06_McClure_06.indd 178 11/14/2012 11:22:50 PM NECROTIZING ENTEROCOLITIS 179 IV antibiotics for 10 \200\22314 days, e.g. benzylpenicillin, gentamicin, and metronidazole . Systemic support: parenteral nutrition (PN). Surgical deterioration despite above medical treatment (necrotic bowel likely), GI obstruction secondary to stricture formation (late). If localized disease, surgical resection of involved bowel with primary repair. If more ex tensive, two stage repair with bowel resection(s) and enterostomy, followed later by intest inal re-anastomosis. e.g. assisted ventilation, correct BP and DIC, opinion: indications for surgery are GI perforation, Prognosis Overall mortality is 722%. Increased mortality is associated with: \200 \200 \200 \200 VLBW. Extensive intestine involvement. Multi-organ failure. Intrahepatic portal gas. Extensive bowel resection may result in short bowel syndrome. Excellent prognosis is seen i n those who respond to medical treatment, but subse- quent stricture may develop. Table 6.2 Bell staging of NEC Stage I (suspected NEC)