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) Predisposed infant Systematic manifestations: temperature instability, lethargy, apnoeas, b radycardias GI manifestations: feed intolerance, vomiting (may be bilious), occult blood in vomit or stool, mild abdominal distension Abdominal radiographs: bowel distension only Stage II (de \201 nite NEC) As above plus mild/moderate acidosis and/or thrombocytopaenia Persistent occult or gross GI bleeding, marked abdominal distension Abdominal radiographs show distension and bowel wall thickening, intramural gas (portal vein or a \201 xed bowel loop) Stage III (advanced NEC) As above plus shock, severe acidosis, electrolyte abnormalities, thrombocytopaenia, DIC Mar ked GI bleeding Abdominal radiographs may show pneumoperitoneum 06_McClure_06.indd 179 11/14/2012 11:22:50 PM CHAPTER 6 Neonatology 180 Neonatal infection Neonatal infection can be acquired transplacentally (congenital, see b p .182), by ascent from the vagina, during birth (intrapartum infection), or postnatally from the environment or contact with others. Infections are categorized as early-onset ( \201 rst 48hr of age) vs. late-onset sepsis (>48hr). Preterm infants are at greater risk for bot h types of infections. Risk factors for early-onset neonatal sepsis \200 \200 \200 \200 \200 Prolonged rupture of membranes >18hr, especially if preterm. Signs of maternal infection, e .g. maternal fever, chorioamnionitis, UTI. Vaginal carriage or previous infant with GBS. Pr eterm labor; fetal distress. Skin and mucosal breaks. Risk factors for late-onset sepsis \200 \200 \200 Central lines and catheters. Congenital malformations, e.g. spina bi \201 da. Severe illne ss, malnutrition, or immunode \201 ciency. Early-onset neonatal infection (2 \200\2235/1000 live births) Infection is caused by organi sms acquired from the mother, usually GBS, E. coli, or Listeria. Other possibilities includ e herpes virus, H. in \202 uenza, anaerobes, Candida, and Chlamydia trachomatis. Presentation (symptomatic) Includes temperature instability, lethargy, poor feeding, respir atory dis- tress, collapse, DIC, and osteomyelitis or septic arthritis. Initial investigations \200 These include blood culture, cerebrospinal \202 uid (glucose, protein, cell count and cul ture), FBC, CXR. (cid:1). The diagnostic value of CRP in early neonatal sepsis is unclear F ailure to respond within 24hr should prompt further investigation. \200 Treatment \200 \200 Supportive (may require ventilation, volume expansion, inotropes). Broad-spectrum antibioti cs, e.g. penicillin and gentamicin (consider ampicillin/amoxicillin if listeria a possibili ty). If meningitis con \201 rmed or strongly suspected then treatment with cefotaxime (+/ \200\223 amp/amoxicillin) should be commenced. Length of antibiotic course and choice of an tibiotics will depend on local sensitivities/policy as well as the age/gestation of baby. I f infant has remained well, and initial index of suspicion was low, then consider stopping antibiotics if culture results are negative (748hr), and observe. Length of treatment in CSF positive meningitis ranges from 14 to 21 days (or greater). A re peat LP demonstrating resolution at the proposed end of treatment may be of value in decidi ng length of course. 06_McClure_06.indd 180 11/14/2012 11:22:50 PM NEONATAL INFECTION 181 Prognosis Up to 15% mortality (up to 30% if VLBW). Late-onset neonatal infection (4 \200\2235/1000 live births) Infection is caused by environ mental organisms such as coagulase \200\223ve staphylococci, Staph. aureus, E. coli, and o ther Gram \200\223ve bacilli, Candida spp., and GBS. Investigation FBC, blood culture, urinalysis (clean catch) and urine culture, CSF glucose, protein, cell count and culture. Treatment \200 \200 \200 Give broad spectrum antibiotics, e.g. \202 ucloxacillin and gentamicin IV. Consider cefot axime if meningitis is likely. Vancomycin if coagulase \200\223ve with indwelling central venous catheter. Decisions on removing/ continuing to use any central catheter should be ma de by a senior doctor. Fungal sepsis is relatively uncommon in the UK (1% of VLBW infants), however, should be considered in any infant who fails to respond to standard therapy or ha s additional risk factors. Staph. sepsis likely, e.g. preterm infant 06_McClure_06.indd 181 11/14/2012 11:22:50 PM CHAPTER 6 Neonatology 182 Transplacental (congenital infection) Causes \200 \200 \200 \200 \200 \200 \200 \200\230TORCH \200\231 infections. Herpes zoster. Parvovirus B19. Syphilis. Enterovirus. H IV; hepatitis B. Rarely bacterial, e.g. GBS, Listeria monocytogenes, N. gonorrhoeae. Presentation \200 TORCH infection: purpura, chorioretinitis, micro-ophthalmos, cerebral calci \201 cation, m icro/macrocephaly, hydrocephalus. Rubella and CMV: disease, osteitis (rubella only). Parvov irus B19: Herpes zoster: defects. Congenital syphilis: mucous membranes, osteochondritis, m eningitis. Bacterial infections present with features that may be non-speci \201 c or even result in multi-organ failure. Gonorrhea causes purulent conjunctivitis (ophthalmia). List eriosis causes preterm labor and meconium-stained liquor. SGA, jaundice, hepatitis, hepatosplenomegaly, also cause deafness, cataracts, congenital heart \200 rubella-like rash, aplastic anemia +/ \200\223 hydrops. cutaneous scarring, limb defects, m ultiple structural SGA, jaundice, hepatomegaly, rash, rhinitis, bleeding Investigation Consider: \200 \200 \200 \200 \200 \200 \200 \200 \200 Blood culture. Pathogen-speci \201 c IgM and IgG (paired for Herpes zoster, Venereal Disea se Research Laboratory (test)(VDRL). Maternal-speci \201 c serology. Urine CMV culture. Th roat swab viral culture. CSF culture and latex particle agglutination (GBS). Stool viral cu lture. Skin vesicle viral culture and electron microscopy. Toxoplasma). Treatment \200 \200 Most congenital infections have no speci \201 c treatment. General treatment is supportive and involves careful follow-up to identify sequelae, e.g. deafness and CMV. Toxoplasma: py rimethamine (3wks 1mg/kg/day) plus sulfadiazine (1yr 50 \200\223100mg/kg/ day). Syphilis: S ymptomatic CMV: spiramycin (4 \200\2236wks 100mg/kg/day) alternating with \200 benzylpenicillin 14 days 30mg/kg 12-hourly IV. consider IV ganciclovir then oral valganciclovir (cid:1). Prognosis Variable and depends on disease severity. 06_McClure_06.indd 182 11/14/2012 11:22:50 PM TRANSPLACENTAL (CONGENITAL INFECTION) 183 06_McClure_06.indd 183 11/14/2012 11:22:51 PM CHAPTER 6 Neonatology 184 Prevention of neonatal infection General measures \200 \200 \200 \200 \200 \200 \200 \200 Good hand washing with antiseptic solutions and use of gloves. Avoidance of overcrowding. L ow nurse to patient ratio. Nurse cohorting. Patient isolation and barrier nursing. Minimal handling. Rational antibiotic use. Minimize indwelling vascular access. Group B streptococcal disease The best approach to minimize early onset sepsis due to Group B strepto- coccal infection is uncertain because there have not been trials that permit th e overall risks and bene \201 ts of intrapartum antibiotic prophylaxis (IAP) to be judged. IAP reduces the number of newborns with positive blood cultures, but with a very low disea se incidence and a very high rate of ma- ternal GBS colonization (around 25%) a very large number of women must be treated to prevent a case if bacteriological screening programs are implemented. Routine bacteriological screening of pregnant women is not presently recommen ded in the UK. Current practice follows a risk factor based approach. The incidence of earl y-onset GBS disease in term infants without antenatal risk factors in the UK is 0.2cases/10 00 births. The Royal College of Obstetrics and Gynecology1 recommend that intrapartum IV penicillin (o r clindamycin) should be offered to women with a previous baby with neonatal GBS disease. O ther risk factors that should prompt consideration of IAP are: \200 \200 \200 \200 C; intrapartum fever >38 preterm (<37/40); PROM >18hr; GBS maternal carriage detected on low v aginal swab culture or GBS bacteriuria. Management of the newborn is not well evidenced. Any ill newborn infants should have cultur es taken and be treated with broad spectrum antibiot- ics that are effective against Group B streptococcus and other common neonatal pathogens. Well infants exposed to the above risk factors should be evaluated clini- cally and observe d. Because more than 90% of cases of early onset GBS disease present in the \201 rst 12 \200\22324hr after birth. Infants who remain well after this time are not at increased risk of disease in comparison with infants without risk factors. There is no need to send inves tigations on infants who are not ill. If there are multiple risk factors, or a previous chi ld has been affected by Group B streptococcal sepsis many would consider blood culture and starting antibiotics appropriate. 06_McClure_06.indd 184 11/14/2012 11:22:51 PM PREVENTION OF NEONATAL INFECTION 185 Hepatitis B Usually contracted at birth. Routine antenatal screening detects maternal carri er state (hepatitis B (HBsAg) +ve). Transmission risk 710% if mother is a low-risk carrier, (i.e. anti-HBe +ve). To reduce vertical transmission give hepatitis B vaccine to infant wi thin 24hr of birth. Also give speci \201 c hepatitis B immunoglobulin 200IU IM if mother i s a high-risk carrier, (i.e. mother HBeAg +ve, or, anti-HBe \200\223ve, or, antibody/antig en status unknown), since the untreated transmission risk is 90%. In both groups, subsequen t hepati- tis B vaccine is required at 1, 2, and 12mths (UK schedule). Human immunode \201 ciency virus (HIV) See b p.726. Vertical transmission rate 715 \200 \22325%. Risk markedly reduced by: \200 Maternal antiretroviral drug therapy to minimize viral load during third trimester and labo r and then postnatal treatment of baby for 6wks. Elective lower segment Cesarean section (L SCS). Avoidance of breastfeeding (in developed world). \200 Infants are usually asymptomatic at birth. Test at birth and 3 and 6mths for: \200 \200 \200 HIV viral PCR; P24 antigen; speci \201 c IgA. Infection is very unlikely if all negative at 6mths and baby well. Herpes simplex 85% of neonatal HSV is contracted at birth from active maternal genital le- sions. Elective LSCS reduces transmission if mother has active genital her- pes. Treat infa nt with prophylactic IV aciclovir if born by vaginal delivery and there is primary maternal herpes (transmission risk of 50% compared with 3% in secondary herpes). To prevent infecti on from carers with cold sores, the lesions should be covered with a mask and the sores tre ated with topical aciclovir. Herpes zoster Perinatal infection can cause severe disseminated disease with high mortal- i ty (30%) if: \200 Maternal rash occurs in the period between 7 days antenatally and 7 days postnatally; A LBW infant (<1mth old) has contact with varicella and whose mother is non-immune (i.e. check m aternal antibody status if unsure). Prevention Oral aciclovir and speci \201 c zoster immunoglobulin (ZIG) 100mg IM given soon after delivery. Reference 1 Royal College of Obstetrics and Gynecology (2003). Prevention of early onset ne onatal group B streptococcal disease, RCOG Guideline No. 36, November 2003. London: RCOG Press. 06_McClure_06.indd 185 11/14/2012 11:22:51 PM CHAPTER 6 Neonatology 186 Neonatal abstinence syndrome A cluster of symptoms caused by withdrawal from a dependency-i nducing substance. In the UK this is commonly related to methadone (+/ \200\223 heroin), or benzodiazepines, however, withdrawal is well documented with a num- ber of other substance s, for example; cocaine, amphetamine, SSRIs (e.g. \202 uoxetine), alcohol, caffeine, and nicotine. Presentation \200 Timing depends on substance: birth, methadone within 24hr, and benzodiazepines later. CNS s ymptoms: seizures. Non-CNS: severe nappy rash), sneezing, tachycardia, sweating, respirator y depression, fever (be cautious \200\224sepsis may co-exist or present with similar sympto ms). heroin and SSRIs often present soon after include irritability, sleepiness, hyperactivity, tremors, poor/disorganized feeding, vomiting, diarrhea (can cause Management \200 Observe \200\230at risk \200\231 infants for signs of withdrawal for several days after bi rth. Several scoring systems exist for quantifying withdrawal. General and supportive measu res: quiet environment, frequent low volume feeding. A pragmatic approach to starting drug treatment (low dose oral morphine) would be to start if signi \201 cantly symptomatic, e.g . sleeping <1hr after feeds, continuous high-pitched cry, unable to feed. Once stable, wean morphine slowly over several days. Start apnoea monitor if preterm or require large doses of morphine. Seizures should be controlled by phenobarbital (also drug of choice to treat b arbiturate withdrawal). swaddling, minimal handling, dark and \200 Other points to consider are: \200 Does baby need a urine screen (remember this will effectively drug- test the mother)? Ensur e Social Services are aware as child protection and family support issues must be considere d. Consider associated pathologies, e.g. HIV or hepatitis B or C infection. Breastfeeding i s not contraindicated unless mother is taking high doses of methadone (>20mg/day), amphetam ines, cocaine, or is HIV +ve. \200 Prognosis It is dif \201 cult to establish whether any adverse outcomes are directly relat - ed to drug exposure as literature is confounded by social and environmen- tal factors. Th ere is an increased risk of: \200 \200 \200 \200 \200 \200 prematurity; IUGR; sudden infant death syndrome (SIDS); congenital HIV/hepatitis B/C infect ion; social problems; neurodevelopmental impairment. 06_McClure_06.indd 186 11/14/2012 11:22:51 PM INBORN ERRORS OF METABOLISM 187 Inborn errors of metabolism See also b pp.102 \200\223105, Chapter 26. The common presentat ions of IEM are as follows: \200 Encephalopathy without metabolic acidosis: seizures, urea cycle enzyme defects (hyperammona emia; see b pp.960, 964); Encephalopathy with metabolic acidosis p.958); Hepatic failure: N on-immune hydrops due to lysosomal storage disorder, e.g. Gaucher disease (see b p.968); Si gni \201 cant dysmorphism: e.g. mucopolysaccharidosis; peroxisomal disorders, e.g. Zellweg er syndrome; mitochondrial disorders; biosynthetic defects, e.g. albinism; receptor defects , e.g. pseudo-hypoparathyroidism; non-speci \201 c illness (see b p.128); severe hypotonia ; resistant Other: hypoglycaemia; cataracts; odors; cardiomyopathy; severe diarrhea. e.g. pyridoxine-dependent : e.g. organic acidurias (see b \200 e.g. galactosaemia (see b pp.342, 960); : can be hematological, e.g. -thalassaemia, or these can be divided into: lysosomal disorders, Investigations \200 blood for U&E, SBR, gas analysis, glucose, Ca2+, Hb, ammonia, Initial: and anion gap (norma l range 12 \200\22316mmol/L). Urine for ketones and reducing substances. \200\230Metabolic screen \200\231 (for amino acid and organic acid analysis): save blood in heparinized (1 \200\2232mL) and EDTA (3 \200\2235mL) tubes and save urine (5 \200\22310mL) in sterile cont ainer with no preservatives. Subsequent investigation after discussion with expert: diagnos is, seek permission to take: \200 \200 \200 \200 take and if child dies prior to further blood for storage (clotted and heparinized); skin biopsy placed in sterile saline; liver and muscle biopsy; send immediately to pathology laboratory for preservation. Acute management \200 \200 Supportive. Stop all protein intake, including milk, and start 10% glucose IV infusion. Cor rect electrolyte/acid-base imbalance. Broad spectrum antibiotics in case crisis was precipi tated by infection. Speci \201 c treatments after expert advice. \200 \200 Prognosis Depends on disease. 06_McClure_06.indd 187 11/14/2012 11:22:51 PM CHAPTER 6 Neonatology 188 Retinopathy of prematurity See also b p.920. Retinopathy of prematurity (ROP) is a leading cause of preventable blindness. Infants born <32/40 and those weighing <1500g at birth are at greatest risk. The incidence is decreasing and recent data sug- gest that around 90% of infants born weighing >1000g will have no ROP, however, this number drops to only 38% for t hose <750g at birth. The cause is multifactorial. In utero, the retinal vasculature develop s in a rela- tively hypoxic environment, with vessels stimulated to grow towards the most h ypoxic regions. This development is disrupted with preterm deliv- ery. ROP is associated wi th retinal arterial hyperoxic vasoconstriction and retinal ischaemia during retinal develop ment before 32wks gestation. It is therefore, essential to monitor and prevent hyperoxia in infants requiring supplemental O2. Minimizing variability in oxygenation may also be impor - tant. Classi \201 cation ROP is a proliferative retinopathy that is classi \201 ed according to interna- tionally accepted guidelines (see Box 6.6).1 Screening criteria (cid:1) \200 27/40: \201 rst screen at 30 \200\22331/40 CGA. \200 \200 27 \200\22332/40: Screen 2wkly thereafter unless: \200 \200 \200 \200 Screening is performed by indirect ophthalmoscopy after pharmacological pupil dilatation or increasingly by wide \201 eld digital retinal imaging. Screening continues until vascularization has progressed into zone 3 (usually >36/40). \201 rst screen at day 28 \200\22335 of life. any stage 3 disease; any plus/pre-plus disease; vessels end in zone 1, or posterior zone 2; weekly screening if present. Treatment Diode laser treatment within 72hr (48hr if aggressive disease) of meeting any of the treatment criteria (see Box 6.6). Babies should be ventilated, adequately sedated, and given a muscle relaxant. Atropine should be available. Side effects of treatment include: Need for re-vent ilation. Bradycardia. Apnoea. Ocular hemorrhage. Eyelid trauma. Laser burns. \200 \200 \200 \200 \200 Infants should be re-examined 5 \200\2237 days following treatment, and if no regression, r e-treatment should be performed at 10 \200\22314 days after initial therapy. Steroid eye dr ops may be useful in decreasing post-operative 06_McClure_06.indd 188 11/14/2012 11:22:51 PM RETINOPATHY OF PREMATURITY 189 swelling. Direct injections of monoclonal antibodies against vascular endothelial growth fa ctor (VEGF) are showing promise as an alternative. Prognosis Almost all cases can be treated effectively so blindness is a rare outcome. There may be reduced visual \201 elds in severe cases. Refractive errors are common. Box 6.6 Classi \201 cation of ROP1 Severity \200 \200 \200 \200 Stage 1: Stage 2: Stage 3: Stage 4: fovea) Stage 5: demarcation line visible ridge evident ridge with extraretinal \201 brovascular prolifera tion subtotal retinal detachment (4A, extrafoveal; 4B involves the total retinal detachment Location \200 \200 from the optic disc Zone 1 extends a radius of 30 Zone 2 extends from the nasal retina periphery in a circle ar ound the anatomical equator Zone 3 involves the anterior residual crescent of temporal reti na Extent Recorded as clock hours in each eye in the appropriate zone. \200\230Plus \200\231 (+) disease Indicates aggressive disease and is used when there is: engorgement and tortuosity of posterior pole retinal vessels; iris rigidity or vessel engor gement; vitreous haze. Treatment criteria \200 \200 \200 \200 Zone 1, any stage if \200\230Plus \200\231 disease present Zone 1, stage 3 (no plus) Zone 2, stage 3 with \200\230Plus \200\231 disease Seriously consider if Zone 2, stage 2 with \200\230Plus \200\231 Reference 1 Royal College of Ophthalmologists/RCPCH Medicine Joint Working Party (2008) Ret inopathy of prematurity: guidelines for screening and treatment. London: Royal College of O phthalmologists and British Association of Perinatal Medicine. 06_McClure_06.indd 189 11/14/2012 11:22:51 PM CHAPTER 6 Neonatology 190 Metabolic bone disease Also known as osteopenia of prematurity, the incidence is 32 \200 \22390% in pre- term infants (mostly ELBW). Cause Chronic substrate de \201 ciency \200\224usually phosphate, rarely calcium or vita- min D. Risk is increased if: \200 \200 \200 prolonged PN; breastfed (low in phosphate); chronic diuretic treatment. Presentation \200 b Investigations); Bone mineral biochemical derangement (see measure serum Ca2+, PO4 infants under 33wks gesta tion. 3- and alkaline phosphatase weekly in all d \200 \200 Linear growth. Rib or distal long bone fractures. Investigations \200 Biochemistry: >1000IU/L. Bone X-ray: Urine Ca PO4 3- <1.2mmol/L; Ca2+ >2.7mmol/L; alkaline phosphatase PO4 \200 osteoporosis, features of rickets, fractures. 3- ratio >1 after 3wks of age (high renal 2+/PO4 3- reabsorption). Treatment \200 3- 1mmol/kg/day supplement if milk fed. Oral PO 4 \200 3- (consult pharm acist). Increase TPN Ca 2+ and PO4 Prevention In infants <2kg or <33wks gestation: \200 3- 1mmol/kg/day (not required if Supplement breast milk with oral PO 4 3- ); fed preterm fo rmula as already contains added PO4 Oral vitamin D 400IU/day; Ensure TPN contains Ca (organ ic phosphate solution avoids mineral precipitation); 10min/day of passive exercise appears bene \201 cial. \200 3- 2.5mmol/kg/day 2+ 2mmol/kg/day and PO4 Prognosis Stature is reduced at age 18mths. Bone mineralization and fracture risk appear to be normal by 2yrs. 06_McClure_06.indd 190 11/14/2012 11:22:51 PM OROFACIAL CLEFTS 191 Orofacial clefts See also b p.846. Orofacial clefts are due to failure of fusion of maxilla ry and pre-maxillary processes. They may be unilateral or bilateral and result in cleft lip and/or cleft palate. The incidence is 71/1000 live births. Causes Multifactorial and includes genetic and environmental factors. 66% of clefts are iso lated. Majority have no obvious cause. \200 maternal folic acid de \201 ciency; maternal exposure Enviromental factors: to alcohol, tobacco, steroids, anticonvulsants, and retinoic acid. 7 \200 30% are syndromic, e.g. Pierre \200\223Robin syndrome (large midline posterior cleft palate, mandible hypoplasia, prone to upper airway obstruction due to a pos teriorly displaced tongue). Treatment \200 \200 Refer to specialized \200\230cleft lip and palate \200\231 multidisciplinary team. Possibl e upper airway obstruction is a recognized complication of a large cleft palate, e.g. Pierr e \200\223Robin syndrome. If it occurs or is likely: \200 \200 \200 nurse prone; nasopharyngeal airway may be helpful; monitor SpO should be taken very serious ly; \200 intubation may be dif \201 cult and require specialist (ENT) support. Feeding p roblems are common. Specialist nursing input, special feed devices and prosthetic plate (ob durator) may all be required if cleft palate is too large to allow adequate suck. Be aware of increased risk of infections (aspiration pneumonia and, later, secretory otitis media wi th conductive hearing loss). Treat as appropriate. Surgical repair of lip is usually at 3mt hs; palate at 6 \200\22312mths. Later speech defects and dental problems can occur requirin g speech therapy and dental input respectively. 2 \200\224a low or worsening SpO2 is an ominous sign and \200 Prognosis Repair of unilateral complete or incomplete lesions usually produces a good resul t. As well as those complications described above later prob- lems may include: \200 \200 Hindered parental bonding. Psychological morbidity. 06_McClure_06.indd 191 11/14/2012 11:22:51 PM CHAPTER 6 Neonatology 192 Neonatal hematology Anemia See also b pp.610 \200\223629. Causes Antenatal \200 \200 \200 \200 \200 Alloimmune haemolytic disease, e.g. Rhesus disease. Twin to twin transfusion syndrome. Parv ovirus B19 infection. Antepartum hemorrhage. Red cell defects or aplasia. Postnatal \200 \200 \200 Nutritional de \201 ciency. Chronic illness. Anemia of prematurity occurs 6 \200\22312wks after preterm delivery and is caused by: \200 \200 \200 d erythropoietin; \200 fast growth rate. repeated and frequent blood sampling; shorter hbf red cell half-life; Presentation \200 i \200 \200 \200 Pallor and tachycardia. O2 requirement or apnoea. (cid:1). Poor feeding Growth failure (cid:1). Treatment \200 \200 Start iron supplement at 4wks old for 12mths if <35wks gestation. Further research is requi red to establish appropriate blood transfusion thresholds for preterm infants. Transfuse if clinically indicated. Volume to transfuse (mL) = desired rise in Hb (g/dL) x weight (kg) x [4 (packed cells) or 6 (whole blood)]. Alternatively, give 20mL/kg over 4hrs. Blood should be CMV \200\223ve and irradiated. Erythropoietin is useful, but not cost-effective for ro utine use and may increase the risk of retinopathy of prematurity. Use is limited to infant s from Jehovah \200\231s witness families. Polycythaemia See also b p.630. De \201 ned as arterial or venous packed cell volume (PCV) >65%. More common if placental insuf \201 ciency, maternal diabetes mellitus, Down \200 \231s syndrome, or after twin to twin transfusion. Risk of complications due to thrombosis and or microvascular sludging. Treatment If \200 symptomatic: (lethargy, seizures, respiratory distress, poor feeding, th rombocytopenia, stroke, renal failure, NEC) perform dilutional exchange transfusion with 20 \200\22330mL/kg of normal saline over 30 \200\22360min. If asymptomatic: it is probably wise to perform dilutional exchange transfusion if PCV >70% to prevent complications. 06_McClure_06.indd 192 11/14/2012 11:22:51 PM NEONATAL hematology 193 Thrombocytopenia See also b p.642. Common neonatal causes include: \200 \200 \200 \200 Sepsis, including congenital infection. NEC. IUGR. Maternal idiopathic thrombocytopenic pur pura (ITP) (due to passive transfer of autoimmune IgG antiplatelet antibodies). Neonatal al loimmune thrombocytopenia (NAIT) resulting from transplacental passage of maternal speci \201 c IgG antiplatelet antibodies sensitized to differing fetal human platelet antigen (HP A). In 85% antibody is to HPA1 antigen. Placental dysfunction. Pre-eclampsia. DIC. \200 \200 Presentation \200 Petechiae. \200 Thrombocytopenia. \200 Intracranial hemorrhage (10 \200\22320%) particularly with NAIT. Treatment Platelet transfusion 10 \200\22315mL/kg if platelet count is <50 and active bleed - ing or <30 plus additional haemorrhagic risk factor or <20 in a well baby. NAIT-speci \201 c treatment \200 \200 fetal platelet transfusion. Maternal IV immunoglobulin. Antenatal: observe if platelets >40 x 109/L. If platelets less or infant Postnatal: symptomatic, give platelet transfusion (HP A1-negative if relevant) and consider corticosteroids, IV immunoglobulin, or even exchange transfusion (liaise with blood transfusion/hematology). Coagulation disorders See also b pp.632 \200\223640. The most common neonatal cause is DIC. Rarely, there is a speci \201 c coagulation defect, e.g. hemophilia, or haemorrhagic dise ase of newborn. Haemorrhagic disease of newborn Bleeding is due to de \201 ciency of vitamin K dependent f actors resulting from: \200 \200 \200 \200 Poor transplacental supply. Lack of enteric bacteria. Maternal anticonvulsants. Low vitamin K levels in breast milk. Typical presentation: is at age 2 \200\2237 days with bruising and spontaneous bleeding, e. g. from umbilicus, GI tract, or intracranial. Investigation: shows i prothrombin time (PT) and partial thromboplastin time (PTT), whilst platelet count is normal. Prevention: vitamin K1 at birth (see b p.140). Treatment: immediate IV vitamin K1 1mg and fresh frozen plasma 10mL/kg. 06_McClure_06.indd 193 11/14/2012 11:22:51 PM CHAPTER 6 Neonatology 194 Rh disease (rhesus haemolytic disease) Hemorrhage of fetal blood of differing rhesus group into the maternal circulation leads to maternal anti-D IgG production (usually fetus RhD +v e, mother RhD \200\223ve). Transplacental passage of this antibody leads to fetal RBC haem olysis. The condition is usually asymptomatic or only mild in the \201 rst affected pregn ancy. Severity usually increases with subsequent pregnancies. Maternal blood group and rhes us antibody status are routine- ly checked in early pregnancy. Elevated or rising titres in dicate that further fetal investigation is warranted, e.g. serial anti-Rh titres, fetal US, fetal blood sampling. The risk of disease is predicted by maternal anti-Rh titre: \200 \200 \200 Unlikely when maternal anti-Rh titre <4u/mL. 10% when titre is 10 \200\223100u/mL. 70% when fetal Hb <7g/dL or titre >100u/mL. Iso-immunization may also occur with other blood group incompatibilities, (e.g. ABO \200 \224usually baby A or B and mother O), other rhesus groups (e.g. c, C, e, E), Kell, Kidd, D uffy. Clinical presentation is usually milder than with RhD (particularly ABO). Presentation \200 fetal anemia, hydrops foetalis. Antenatal: \200 Postnatal: hydrops fo etalis, early jaundice, kernicterus (b p.195), cutaneous haemopoietic lesions ( \200\230blu eberry muf \201 n \200\231), hepatosplenomegaly, coagulopathy, thrombocytopenia, leucopeni a. Late: anemia, inspissated bile syndrome. Investigations \200 \200 group (usually RhD \200\223ve), i anti-Rh titre. Maternal blood for: Initially, cord or neonatal blood for: DCT +ve, group (usually RhD +ve) , i SBR. After diagnosis monitor SBR 4-hourly (until rate of rise known), blood glucose, ra te of Hb fall. Check coagulation screen. d Hb, i reticulocytes, d platelets, Treatment See also hydrops foetalis, b p.138. \200 \200 Close antenatal supervision +/ \200\223 intrauterine blood transfusion. After birth check c ord SBR and Hb, start high risk infants on intensive phototherapy whilst awaiting results. If SBR>100 mol/L then prepare infant for exchange transfusion, consider IVIG (see b pp.130 , 646). Supportive treatment as required, e.g. correct any coagulopathy. If treatment requi red, oral folic acid 250mcg/kg/day for 6mths. Check Hb every 1 \200\2232wks to detect anemi a for up to 12wks. Transfuse if symptomatic or Hb <7g/dL. Perform audiology screening if ex change transfusion required. Prophylaxis: +ve fetus or possible foeto-maternal hemorrhage. \200 \200 \200 Rh anti-D IgG given to RhD \200\223ve mothers after birth of Rh Prognosis Mortality <20% even if hydropic. Risk of late onset anemia. 06_McClure_06.indd 194 11/14/2012 11:22:51 PM BILIRUBIN ENCEPHALOPATHY (KERNICTERUS) 195 Bilirubin encephalopathy (kernicterus) A clinical syndrome resulting from the development o f excessive neuro- toxic unconjugated bilirubin levels. Toxic levels lead to selective dama ge of the cerebellum, basal ganglia, and brainstem auditory pathways. It may occur in the h ealthy neonate if serum bilirubin is >360 mol/L , but usually only occurs at signi \201 c antly higher serum levels (>430 mol/L after 48hr of life) unless: \200 \200 \200 \200 \200 \200 Infant is <24hr old. Infant is preterm. Infant is severely ill (any cause). Infant is acido tic. Caused by iso-immunization haemolytic disease. Reduced albumin binding caused by drugs or hypoalbuminanaemia. Presentation \200 \200 \200 \200 \200 \200 Lethargy progressing to hypertonia then hypotonia. Poor feeding. Fever. High-pitched cry. O pisthotonos. Seizures and coma. Main differential diagnosis is meningoencephalitis/sepsis. Neonatal tetany may also present with opisthotonos. Treatment \200 \200 Supportive (likely to require full intensive care). Urgent reduction of serum bilirubin by intensive phototherapy and exchange transfusion. Give IV immunoglobulin. Treat underlying c ause. \200 Prognosis Majority survives, but there is a high risk of athetoid cerebral palsy, deaf- nes s, and low IQ. 06_McClure_06.indd 195 11/14/2012 11:22:52 PM CHAPTER 6 Neonatology 196