index...

Index

3-phosphoglyceratedehydrogenase (3-PGD)deficiency 395

22q11.2 deletion 443, 448

abdominal decompressiontherapy for IUGR 88–89

absence of septum pellucidum268, 269

academic outcomes afterprematurity 566–568

educational resource andsupport utilization rate 567

long-term outcomes567–568

reading and related skills566–567

reading in children withneural injuries 567

acidemia, definition 64acidosis, definition 64, 402acidosis and neonatal brain

injury 402–404hypoxic–ischemic events403–404

metabolic acidosis 403–404respiratory acidosis 402–403

acute bilirubin encephalopathy(ABE)

clinical features 311, 312definition 311toxic level of bilirubin 311see also bilirubin toxicity

acute events, timing ofneonatal brain injury 256

acute near-total asphyxia, HIEpatterns of injury191, 192

adaptive hypometabolism afterHI 492–493

adaptive responses of cells toinjury 40–42

erythropoietin (EPO) 41hypoxia-inducible factor 1(HIF-1) 40–41

vascular endothelial growthfactor (VEGF) 41–42

ADHDand language and speechdevelopmental disorders569

neonatal encephalopathyoutcome 579

adjuncts to management ofHIE 478–481

adverse intrapartum events,relationship to CP 8–9

agenesis of the corpuscallosum 271

agyria 269–270Aicardi-Goutieres syndrome

281–282Aicardi syndrome 271

EEG diagnosis 204AIDS see perinatal HIV

infectionalcohol consumption and

IUGR risk 80see also ethanol abuse inpregnancy; fetal alcoholsyndrome

alcohol-related birth defects(ARBD) 112, 113

alcohol-relatedneurodevelopmentaldisorder (ARND)112, 113

alkalosis, definition 402alkalosis and neonatal brain

injury 404metabolic alkalosis 405respiratory alkalosis404–405

alpha-2 adrenergic agonists,use in CP management560

amnioinfusion in PROM 63amnionitis 137amniotic fluid embolism

136–137amniotic fluid infection

248–249amphetamine abuse in

pregnancy 119amplitude-integrated EEG

(aEEG) 203–204, 258anemia

IUGR complication 84management followingresuscitation 473

anencephaly 266angiogenesis

association withneurogenesis 42


antenatal prevention ofGMH-IVH 290

antenatal risk factors forneurodevelopmentalsequelae 551

antenatal steroidadministration

for fetal lung maturity 62GMH-IVH prevention 290

antepartum asphyxia events,indicative findings 262

antepartum events,relationship to neonatalencephalopathy 1–2, 8–9

antepartum fetal evaluationbiochemical tests 164–165biophysical profile (BPP)169

biophysical techniques164–170

Cardiff Count-to-Tenprotocol 168

choice of test 163contraction stress test(CST) 165

Doppler ultrasound 169–170false-positive results fromtests 164

fetal mortality rate (FMR)163–164

limitations of tests 165maternal perception of fetalmovement 168–169

non-stress test (NST)165–167

perinatal mortality rate(PMR) 163

perinatal mortality risk163–164

predictive value of tests 164racial differences in PMRand FMR 163

sensitivity of tests 164specificity of tests 164variability of the fetalneurologic state 164

vibroacoustic stimulation(VAS) 167–168

antepartum period, risk factorsfor neonatalencephalopathy 3–4

antibody-related fetal disease98–100

antiepileptic medications,effects on fetaldevelopment 100–101

antihypertensive medicationsfetal effects 131–132for chronic hypertension

128for pre-eclampsia 130

Apgar scorecorrelation with neonatal

encephalopathy 4preterm neonates 64

APOE (apolipoprotein E)gene polymorphisms447–448

apoptosis 14–15, 16, 17–18activation in the immature

brain 40attenuation of mitochondrial

response 40consequences of failure to

complete 40continuum with autophagy

15, 18continuum with necrosis

14–15non-classical variants 17–18structural appearance of

classical form 15, 17see also cell death

continuum conceptapoptosis-inducing factor

(AIF) 21–22apoptosis regulation

(molecular and cellular)16, 17, 18–23

apoptosis-inducing factor(AIF) 21–22

Bcl-2 family of survival anddeath proteins 16, 17, 18,19–20

caspase family of celldemolition proteases17, 18, 20–21

caspase-independentapoptosis 21

cell surface death receptors22

DNA damage as cell deathtrigger 22

endoplasmic reticulum (ER)stress-induced apoptosis19, 20

608

© Cambridge University Press www.cambridge.org

Cambridge University Press978-0-521-88859-2 - Fetal and Neonatal Brain Injury, Fourth EditionEdited by David K. Stevenson, William E. Benitz, Philip Sunshine, Susan R. Hintz and Maurice L. DruzinIndexMore information

http://www.cambridge.org/9780521888592

http://www.cambridge.org


excitotoxic cell death 22–23Fas mediation of celldeath 22

genetic control of celldeath 18–19

inhibitor of apoptosisprotein (IAP) family 21

mitochondrial regulation16, 17, 18, 19–20, 21

p53/p63/p73 family oftumor suppressors 22

p75NTR mediation ofapoptosis 22

role of cytochrome c 16,19–20, 21

Arnold–Chiari malformation267

asphyxia (fetal and neonatal)and cerebral palsy 143and neonatalencephalopathy 143

causes of pathologicalasphyxia 143

definition 2, 64development of metabolicacidosis 2

factors affecting fetal braininjury 143, 144

factors affecting fetalresponse 143, 144

indirect indicators 2initiators of neuronal injury144–145

intrauterine acute totalevents 2–3

intrauterine prolongedpartial asphyxia 3

IUGR complications 82pathogenesis of cell death144–145

preterm fetus 63–64sentinel events 2–3umbilical cord prolapse2–3

uterine rupture 2–3see also timing of asphyxialevents

asphyxial brain injurydeterminants 143, 144, 153

chorioamnionitis andhyperthermia 155

chronic hypoxia 154–155hyperthermia andhypoxia–ischemia 155

hypotension 147, 148, 151,153–154

hypothermia andhypoxia–ischemia 155

identification of the fetusat risk 155–157

pattern of repeated insults154, 155

pre-existing metabolic status154–155

pyrexia in labor 155temperature and hypoxia–ischemia 155

watershed distribution ofneuronal loss 147, 148,151, 153–154

see also fetal adaptations toasphyxia, fetal responsesto asphyxia

asphyxiated premature infant,nutritional support531–532

assisted reproductivetechnologies (ART), riskof preterm birth 60

astrocytes, activation in HIbrain injury 39

attention problems, andlanguage and speechdevelopmentaldisorders 569

auscultation, fetalmonitoring 63

autonomic nervous system,influence on fetal heartrate 176

autophagy 14, 15, 18continuum with apoptosis15, 18

baclofenintrathecal use in CPmanagement 560–561

oral use in CP management560

bacterial meningitis in theneonate

anatomical pathology349–350

anti-inflammatory therapy354

antibiotic therapy 352–354antibody to commonbacteria 352

association with neonatalsepsis 347

bacteremia andsusceptibility 349

bacterial meningo-encephalitis 347

case-fatality rate (mortality)348, 355

cerebrospinal fluid changes351

clinical features 350complications 352corticosteroids 354definition 347diagnosis 350–352etiology 348–349imaging studies 351–352incidence 347, 348laboratory evaluations 351lumbar puncture 347–348major causative organisms348–349

management 352neurological sequelae355–356

outcome 348, 355–356

pathophysiology andpathology 349–350

permeability of theblood-brain barrier 350

prevention 356role of cytokines andchemokines 350

treatment 352see also specific bacterialorganisms

bacterial resistance andneonatal sepsis 340,341, 342

bacterial sepsis in the neonateassociation with neonatalmeningitis 347

bacterial resistance 340,341, 342

clinical presentation 333diagnosis 333early-onset disease (EOD)331

enterococcal groupD streptococci(enterococcus) 342

epidemiology 331–332etiology 332–333group A beta-hemolyticstreptococcus (GAS)341–342

incidence 331–332intrapartum antibioticprophylaxis 331

late-onset disease (LOD)331

major bacterial organisms331, 332–333, 336–342

outcome 335–336pathogenesis 332prevention 336risk factors 332Streptococcus pyogenes(group A beta-hemolyticstreptococcus) 341–342

treatment 335vancomycin-resistantenterococcus (VRE) 342

see also specific bacterialorganisms

balloon atrial septostomy(BAS) 444–445

barbituratesabuse in pregnancy 118use in HIE management478–479

Barker hypothesis 127baroreceptors, influence on

fetal heart rate 176basal nuclei-predominant

pattern of brain injury576, 580

Bcl-2 family of survival anddeath proteins 16, 17,18, 19–20

bed rest in hospital for IUGR 89behavioral abnormalities and

IUGR 84

behavioral problems, neonatalencephalopathy outcomes579

benzodiazepinesabuse in pregnancy 118use in CP management

560bilirubin-induced neurologic

function (BIND) 311bilirubin toxicityclinical features 311, 312diagnosis of kernicterus

311, 312effects of early hospital

discharge after birth 314exchange transfusion

313–314genetic influences 311–312management of

hyperbilirubinemia313–314

mechanism of bilirubintoxicity 311

neonatal jaundice 311–312phototherapy 313–314prediction of

hyperbilirubinemia312–313

re-emergence of reportedkernicterus 314

risk factors 312terminology 311toxic level of bilirubin 311

biochemical markers ofasphyxia 258–259

biophysical profile (BPP)antepartum fetal evaluation

169evaluation of fetal growth

and well-being 81birth asphyxiaand cerebral palsy 59definition 1, 2see also asphyxia

birth location, and risk ofGMH-IVH 286

bleeding, preterm birth riskfactor 60

bleeding in the newborn,neurogenetic causes 282

blindness, neonatalencephalopathy outcome578

blood-brain barrierpermeability in HI braininjury 38

blood gas evaluations,correlation with neonatalencephalopathy 5

blood pressure changes, fetalresponse 176

botulinum toxin A (BTX-A),use in CP management560

brachial plexus injury duringlabor and delivery 136

bradycardia (fetal) 177, 180–181

Index

609






brain development (normaldevelopment) 265, 266

cell migration 265cell process formation 265cell proliferation andneuronal generation 265

induction phase 265neuronal differentiation 265neuronal migration 265neurulation (neural tubeformation) 265

synapse formation 265vesicle development 265

brain disorderssee neurogeneticdisorders of the brain

brain injurieseffects on language andspeech development 566

neurogenetic disorders withsimilar features 277

brain malformation diagnosis274–275

EEG diagnosis 204fetal imaging 274–275genetic evaluation 275neuroimaging after birth275

patient history 275brain malformation prognosis

275brain malformationsabsence of septumpellucidum 268, 269

agenesis of the corpuscallosum 271

agyria 269–270Aicardi syndrome 271anencephaly 266Arnold–Chiarimalformation 267

cell proliferation disorders269

cerebellar vermis hypoplasia273

Chiari II malformation 267combined and overlappingmalformations 271

cortical dysplasia 270cortical organizationabnormalities 270

Dandy–Walkermalformation 273

Dandy-Walker variant 273encephalocele 266encephaloclastic lesions272–273

etiologies 265hemimegalencephaly 269heterotopias 269, 270hind-brain organizationand patterning defects273

holoprosencephaly 267–268hydranencephaly 272hydrocephalus 274Joubert syndrome 273

lissencephaly 266, 269–270macrencephaly 269megalencephaly 269meningocele 266microcephaly 269microdysgenesis 270microencephaly 269mid-brain organization andpatterning defects 273

‘molar tooth’ malformation273

myelomeningocele 267neural tube defects 266neuronal generationdisorders 269

neuronal migrationdisorders 269–270

neurulation (neural tubeformation) disorders266–267

pachygyria 269–270polymicrogyria 270porencephaly 272–273schizencephaly 270, 272septo-optic dysplasia 268termination period concept265

timing 265tuberous sclerosis complex270

vascular malformations 274vein of Galen malformations274

ventral patterning(prosencephalic cleavage)disorders 267–268

brainstem injury inHIE 191, 192brainstem release phenomena

510–511breech presentation 138–139

preterm delivery 63bronchopulmonary dysplasia

(BPD) 551

Caenorhabditis elegans(nematode), geneticcontrol of cell death 18

caffeine consumption andIUGR risk 80

calcium-channel blockers, usein HIE management 480

cardiac output (fetus), factorsinfluencing 176

cardiac output supportfollowing resuscitation472–473

cardiac surgery see pediatriccardiac surgery

Cardiff Count-to-Tenprotocol, antepartum fetalevaluation 168

cardiogenic shock 6cardiopulmonary bypass

(CPB) 445–446cardiopulmonary resuscitation

of the newborn 7–8,453–459

airway 455anticipation 453–454appropriately trainedpersonnel 454

breathing (ventilation)455–457

cardiac output 458crystalloid and colloidsolutions 459

epinephrine 458equipment 454, 455glucose administration 459hypoglycemia management459

infant with meconiumstained amniotic fluid 457

information required by theneonatal resuscitationteam 454

meconium staining of theamniotic fluid 457

metabolic acidosis 459naloxone administration460

planning 453–454rapid cardiopulmonaryassessment in the deliveryroom 454–455

sodium bicarbonateadministration 459

stabilization aftercardiopulmonaryresuscitation 459

use of oxygen 457–458ventilation 455–457volume resuscitation458–459

cardiovascular and respiratoryproblems, risk of GMH-IVH 286

cardiovascular system, signsof asphyxia injury 6

caspase family of celldemolition proteases17, 18, 20–21

caspase-independent apoptosis21

CDH (congenitaldiaphragmatic hernia),outcome of ECMO forPPHN 434–435

cell death continuum concept14–15, 23–24, 24–25

cell death matrix 24–25cell death mechanisms

14–15, 40apoptosis 14–15, 16, 17–18,18–23, 40

autophagy 14, 15, 18cell death continuumconcept 14–15, 23–24,24–25

hybrid forms of cell death 40hybrid forms ofdegeneration 14–15

necrosis 14–15, 15–17,267

programmed cell death(PCD) 14see also apoptosis

cell death pathogenesis inasphyxia 144–145

cell proliferation disorders 269cell surface death receptors 22cellular responses to injury

41central hypoventilation,

neurogenetic causes 283cerclage, use in cervical

incompetence 61, 70cerebellar injuryin HIE 191–192language and speech

developmental disorders571

cerebellar vermis hypoplasia273

cerebral edema associated withHIE

corticosteroids 478hyperventilation 477–478management issues 476–477mannitol 478methods of decreasing

cerebral edema 477–478cerebral oximetry see NIRS-

based cerebral oximetrycerebral palsy (CP)and birth asphyxia 8–9, 59,

143and cesarean births 10–11and prenatal and perinatal

asphyxial events 143and preterm birth 10, 59and preterm infection/

inflammation 51classification system 557–558clinical features 556definition 556–557description 556direct and indirect costs 556Gross Motor Function

Classification System(GMFCS) 561

Gross Motor FunctionMeasure (GMFM) 561

incidence 10, 174–175, 556link with intrapartum

events 64neonatal encephalopathy

outcome 578outcome 558, 561outcome of IUGR 87, 88relationship to MR 11relationship to neonatal

encephalopathy 10–11risk factors 10–11risk with multiple gestations

69timing of injury 10use of EFM 174–175,

182–183cerebral palsy (CP)

management 558–561

Index

610






alpha-2 adrenergic agonists560

baclofen (intrathecal)560–561

baclofen (oral) 560benzodiazepines 560botulinum toxin A (BTX-A)560

clonidine 560constraint-inducedmovement therapy 559

dantrolene 560electrical stimulation559–560

general principles 558locally injected medications560–561

occupational therapy 559oral medications 560pharmacologic treatments560–561

physical therapy 559selective dorsal rhizotomy560

tizanidine 560treatments to reducespasticity 558, 559

cerebral resuscitation of thenewborn 460

cerebral sinovenousthrombosis (CSVT)296–297

cervical incompetencein multiple gestations 70risk of preterm birth 60–61use of cerclage 61, 70

cesarean delivery rate,influence of EFM 174

cesarean section (operativeabdominal delivery)65, 134

and cerebral palsy 10–11and risk of GMH-IVH285

preterm 63vaginal birth after cesarean(VBAC) 2, 65, 72,134–135

chemokines, role in HI braininjury 40

chemoreceptors, influence onfetal heart rate 176

Chiari II malformation 267childhood assessments,

neurodevelopmentaloutcomes of pretermbirth 544–548, 552

chlamydia infection 61chorioamnionitis 9, 51, 137and hyperthermia 155risk factor for neonatalencephalopathy 4

chromosomal abnormalities,and IUGR 78

chronic hypertension 127–128antihypertensivemedications 128

definition 127effects on maternalphysiology 127

effects on the fetus 128fetal monitoring 128risk of IUGR 128risk of placental abruption128

risk of pre-eclampsia 128secondary causes 127treatment in pregnancy 128

chronic twin-to-twintransfusion 244see also twin-to-twintransfusion syndrome

Citrobacter diversus, causeof neonatal meningitis349

cleft lip/palate, associationwith tobacco use inpregnancy 115

clinical manifestations ofneonatal encephalopathy7–8

clonic seizures 500–504clonidine, use in CP

management 560cobalamin disorders 282cobblestone lissencephaly

266, 270, 280cocaine use in pregnancy

116–117effects on labor and delivery117

effects on the fetus 116–117excretion in breast milk 117forms of cocaine 116long-term effects on thechild 117

mechanisms of fetalexposure 116

neonatal effects 117neonatal exposure throughbreast milk 117

neonatal signs of withdrawal117

risk of fetal demise 117risk of IUGR 80risk of placentalabnormalities 117

risk of sudden infant deathsyndrome (SIDS) 117

teratogenic mechanisms 116withdrawal signs inneonates 117

cognitive deficits, neonatalencephalopathy outcomes578–579

cognitive impairment,association with languageand speech disorders568–569

computed tomography (CT)209–210

HIE features 189timing of neonatal braininjury 260

congenital adrenal hyperplasia(CAH), effects on fetaldevelopment 97

congenital centralhypoventilationsyndrome 283

congenital cytomegalovirus(CMV) infection 9,363–365

association with IUGR77–78

incidence 363outcome in asymptomaticneonates 363–364

outcome in symptomaticneonates 364–365

recommendations 365sources of infection 363

congenital disorders ofglycosylation (CDG) 399

congenital heart disease22q11.2 deletion 443association with congenitalmalformation of thebrain 444

association with IUGR 78association with structuralbrain abnormality 444

balloon atrial septostomy(BAS) 444–445

DiGeorge syndrome 443Down syndrome (trisomy21) 443

genetic associations 443–444potential for neurologicalmorbidity 443

preoperative neurologicalinjury 444–445

velocardiofacial syndrome(VCFS) 443

see also pediatric cardiacsurgery

congenital hypomyelinatingneuropathy 281

congenital infections 9and IUGR 77–78

congenital malformation,association with IUGR 78

congenital malformations ofthe brain see brainmalformations

congenital musculardystrophies 280–281

congenital myasthenias 281congenital myopathies 280congenital neuropathies 281congenital perinatal infection

361 see also specificcongenital infections

congenital rubella syndrome365, 366, 367see also rubella

congenital syphilis(Treponema palliduminfection) 367–369

association with IUGR 77–78diagnosis 367

early congenital syphilis367–368

incidence 367neurologic manifestations

367–368recommendations 368–369transmission of infection to

the fetus 367Treponema pallidum 332

congenital toxoplasmosis(Toxoplasma gondiiinfection) 9, 361–363


clinical features 361incidence 361outcome in asymptomatic

neonates 362outcome in symptomatic

neonates 362prenatal diagnosis 362–363prenatal treatment 361prevention 363recommendations 363screening 362–363transmission of the infection

to the fetus 361congenital varicella syndrome

369–370see also varicella-zostervirus (VZV) infection

constraint-induced movementtherapy, CP management559

continuous NG feeding,premature infant 527

contraction stress test (CST)81, 165

contraindications 165interpretation of the test 165

cordocentesis 81–82Cornelia de Lange syndrome 78cortical dysplasia 270cortical organization

abnormalities 270corticosteroidsfor fetal lung maturity 130management of cerebral

edema 478role in necrotizing

enterocolitis pathogenesis537

Coumadin, fetal warfarinsyndrome 80

CP see cerebral palsycranial ultrasonographyHIE features 189imaging of preterm infant

brain injury 549–550CSF flow and brain/cord

motion MRI imaging 211CT angiography and

venography 209–210cyanotic congenital heart

disease 476, 477cytochrome c, role in apoptosis

16, 19–20, 21

Index

611






cytokineserythropoietin (EPO)actions in brain injury 41

role in HI brain injury 39–40role in preterm brain injury52

cytomegalovirus see congenitalcytomegalovirus infection

Dandy–Walker malformation273

Dandy-Walker variant 273dantrolene, use in CP

management 560decision making see delivery

room decision making,medical ethics inintensive care

deep gray-matter nuclei(thalamus and basalganglia) lesions 191, 192

Dejerine–Sottas syndrome 281delayed cord clamping,

and risk of GMH-IVH285–286

delivery room decision making460–461 see also laborand deliverycomplications

delivery room performancesee patient safety

delivery room resuscitation,IUGR complications 82

demographic risk factors forpreterm birth 60

depressed neonate,determination of causeand timing 255–256

developmental abnormalitiesclassification by gestationaltiming 214–216

neuroimaging diagnosis210, 211, 213, 214–216

DHCA (deep hypothermiccirculatory arrest) 446

diabetes mellitus 96–97childhood/adulthoodeffects 97

embryonic effects 96–97fetal effects 97gestational diabetes 96IUGR 97macrosomia 97management of diabetes inpregnancy 96

neonatal effects 97pregestational diabetes 96teratogenic effects ofhyperglycemia 96

transient neonatal diabetesmellitus 78, 83

dietary supplements,neuroprotectivepotential 42

diffuse brain injury in HIE 192diffuse encephalopathy, use of

EEG 201

DiGeorge syndrome 443see also 22q11.2 deletion

dihydropyrimidinedehydrogenase (DPD)deficiency 395

diplegia development, andGMH-IVH 289–290

diving reflex 2, 7, 8DNA damage as cell death

trigger 22dobutamine use in newborn

intensive care 473dopamine use in newborn

intensive care 472–473Doppler flow velocity

waveforms of fetalcirculation 81

Doppler ultrasonographyantepartum fetal evaluation169–170

techniques 209, 210Down syndrome (trisomy 21),

congenital heart disease443

drugs taken in pregnancy,IUGR risk 80see also substance abusein pregnancy

DTI (diffusion tensor imaging)211, 213

ductal shunting, detection of474–475

DWI (diffusion-weightedimaging) 211, 213

dysmaturity syndrome137–138

dysmorphic syndromes,association with IUGR 78

dystonia without EEG seizuresin neonates 507–508

E. coli see Escherichia coliearly gastrointestinal priming

529–530eclampsia 130ECMO (extracorporeal

membrane oxygenation)incidence of intracranialhemorrhage 292

treatment for PPHN424–425

use of EEG 203ECMO outcome for PPHN

428–435comparison withconventional medicaltherapy 432–434

follow-up studies429–432

infants with CDH(congenital diaphragmatichernia) 434–435

risks associated with ECMO428–429

EEG (electroencephalography)abnormal findings inneonates 7–8

amplitude-integrated EEG(aEEG) 203–204

burst–suppression pattern201, 202, 203

HIE features 189indications for 196information about neonatalbrain function 196

interpretation of EEGrecordings 198

low-voltage undifferentiatedpattern 201, 202, 203

prognostic significanceof EEG patterns 201,202, 203

prognostic value inencephalopathy 201–204

specificity of theencephalopathic EEG 201

timing of a brain insult 203timing of the EEG 196timing of neonatal braininjury 257–258

use in diffuseencephalopathy 201

use in ECMO (extracorporealmembrane oxygenation)203

use ingradingencephalopathy201, 202, 203

value in assessment ofneonatal brain function196

video-EEG/polygraphicmonitoring 499–500,508–510

EEG correlation with specificdisorders

Aicardi syndrome 204brain malformation 204encephalitis 205holoprosencephaly 204hyperammonemia 204infectious disease 205intraventricular hemorrhage204–205

lissencephaly 204maple syrup urine disease204

maternal drug use 205meningitis 205metabolic encephalopathies204

non-ketotichyperglycinemia 204

periventricular–intraventricularhemorrhage 204–205

periventricular leukomalacia205

pyridoxine dependency 204stroke 205

EEG epileptiform transients493

effects of hypothermiatherapy after HI injury490–492

EEG maturational features198–201

changes in EEG with age198–199

delta brush wave pattern200

discontinuity of thebackground 199–200

frontal sharp transients200–201

midline rhythms 201ontogeny of sleep states

199, 200specific wave patterns

200–201sporadic sharp waves

200–201theta bursts 201time of rapid brain

maturation 198EEG technical considerations

196–198age of the infant 198artifacts in the recording

198challenging environment

of the NICU 198display of recordings 197documenting behaviour

when recording 198duration to obtain sleep

states 197–198EEG technologist 198electrode application 197electrode placement 197general description of EEG

function 196–197international 10–20 system

of placement 197interpretation by the

electroencephalographer198

sedation 197simultaneous recording

of physiologic variables197

EEG technologist 198EFM (electronic fetal

monitoring)and incidence of cerebral

palsy 174–175current ACOG

recommendations foruse 183

detection of metabolicacidemia 182–183

detection of metabolicacidosis 174, 175

diagnosis of pretermlabor 61

during labor and delivery139–140

effects on CP and neonatalseizure rates 182–183

history of EFM 174–175history of FHR monitoring

174–175

Index

612






influence on cesareandelivery rate 174

management of non-reassuring FHR 183

observer variability ininterpretation 182

prediction of fetal hypoxia 64role in predicting perinatalasphyxia 182–183

studies of efficacy 174–175use to identify HIE 175widespread use 174–175

ELBW infants see extremelylow birthweight (ELBW)infants

electrical stimulation, use inCP management 559–560

electroencephalogram see EEGelectroencephalographer,

interpretation of EEGrecordings 198

electroencephalographysee EEG

electronic fetal monitoringsee EFM

en caul vaginal delivery,preterm 63

encephalitis, EEG diagnosis 205encephalocele 266encephaloclastic lesions

272–273encephalopathic period 470encephalopathyHIV encephalopathy ininfants 380–382, 391

see also hypoxic–ischemicencephalopathy (HIE),neonatal encephalopathy

endocrine disorders, role inIUGR etiology 78

endocrine measurements ofmaternal serum or urine,IUGR detection 81

endogenous neuroprotectionpost-insult adaptivehypometabolism 492–493

sympathoinhibition after HI492–493

endoplasmic reticulum (ER),role in apoptosis 19, 20

enteral feeding, prematureinfant 527–530see also necrotizingenterocolitis pathogenesis

Enterobacter cloacae, causeof neonatal sepsis333, 341

enterococcal groupD streptococci(enterococcus), cause ofneonatal sepsis 342

environmental factors, role inIUGR etiology 80

ephedrine use in pregnancysee sympathomimetics

epilepsy, neonatalencephalopathy outcome

578 see also neonatalseizures; seizures; statusepilepticus

epinephrine (adrenaline)use in cardiopulmonaryresuscitation of thenewborn 458

use in newborn intensivecare 473

erythroblasts see nucleated redblood cell count

erythropoietin (EPO), cellularresponse to injury 41

Escherichia colicause of neonatal meningitis348–349

cause of neonatal sepsis 332,333, 341

ESPGN guidelines for feedingthe preterm infant 529

ethanol abuse in pregnancy112–114

adverse effects on fetus andneonate 112, 113

alcohol-related birth defects(ARBD) 112, 113

alcohol-relatedneurodevelopmentaldisorder (ARND) 112, 113

effects on the developingfetal brain 112

ethanol in breast milk 114ethanol withdrawal inneonates 114

fetal alcohol spectrumdisorders (FASD) 112, 113

fetal and postnatal growthdeficiency 114

fetal cardiovascularabnormalities 114

fetal functionalabnormalities 113–114

fetal genitourinaryabnormalities 114

fetal visual and hearingdefects 114

incidence 112incidence of fetal alcoholsyndrome 112

long-term effects on thechild 114

neonatal exposure throughbreast milk 114

partial fetal alcohol syndrome(PFAS) 112, 113

recommendations onalcohol use in pregnancy114

teratogenic mechanism112–113

ethchlorvynol use inpregnancy 118

ethical decision makingsee medical ethics inintensive care

ethnicity, and risk of pretermbirth 59, 60

excitatory amino acids (EAAs)receptor inhibitors479–480

excitotoxic cell death 22–23excitotoxicity after HI, effects

of hypothermia therapy490–492

executive function deficitsand language and speechdisorders 569

neonatal encephalopathyoutcomes 579

extended managementfollowing resuscitation

adjuncts to management ofHIE 478–481

afterload reduction 473barbiturates 478–479calcium-channel blockers480

cerebral edemamanagement 476–478

cyanotic congenital heartdisease 476, 477

detection of ductal shunting474–475

dobutamine administration473

dopamine administration472–473

encephalopathic period 470epinephrine (adrenaline)administration 473

excitatory amino acids(EAAs) receptorinhibitors 479–480

fluid management 470growth factors 481hyperoxia test 474hypothermia 481hypoxemia evaluationand management473–481

identification of infantswho require intensivecare 470

iNO (inhaled nitric oxide)therapy 472

inotropic drugs 472–473lazaroids (21-aminosteroids) 480–481

management of anemia 473monosialgangliosides 480oxygen-free radicalinhibitors 480–481

pulmonary arterialdisease 476

refractory hypoxemiaevaluation andmanagement 473–481

severe pulmonaryparenchymal disease475–476

supporting ventilation470–472

surfactant replacementtherapy 471–472

sustaining cardiac output472–473

window of opportunity forintervention 470

external cephalic version 139extracorporeal membrane

oxygenation see ECMOextremely low birthweight

(ELBW) infantscosts of medical support 544potential

neurodevelopmentaloutcomes 544

survival rates 544see also neurodevelopmental

outcomes of pretermbirth; preterm birth

face presentation for birth 138family history, risk of neonatal

encephalopathy 3, 4Fas mediation of cell death 22fast and ultrafast MRI

techniques 211fatty acid oxygenation defects

396–397feeding see nutritional supportfetal acidosis see metabolic

acidosisfetal adaptations to asphyxia

145adaptations to intrauterine

conditions 145defense mechanisms 145

fetal alcohol spectrumdisorders (FASD) 112, 113

fetal alcohol syndrome (FAS)11, 80, 112–114

adverse effects of maternalethanol consumption112, 113

cardiovascularabnormalities 114

effects in adulthood 114effects on the developing

brain 112ethanol withdrawal in

neonates 114fetal and postnatal growth

deficiency 114functional abnormalities

113–114genitourinary abnormalities

114incidence 112incidence of ethanol abuse

in pregnancy 112long-term consequences

for the child 114teratogenic mechanism

112–113visual and hearing defects 114

fetal anemia 243fetal anomalies, risk of preterm

birth 60fetal demise, and cocaine use

in pregnancy 117

Index

613






fetal distress 64fetal effects of antihypertensive

medications 131–132fetal effects of chronic

hypertension 128fetal effects of hypertensive

disease in pregnancy127, 131

fetal effects of maternalmedications 131–132

fetal effects of pre-eclampsia 129fetal factors in IUGR etiology

77–78fetal growth 76–77fetal growth factors 76–77maternal influences 76placental growth factors76, 77

fetal growth and well-being,evaluation 81–82

fetal growth classification75–76see also intrauterinegrowth restriction(IUGR)

fetal growth factors 76–77fetal growth hormone(GH) 77

insulin 76–77insulin-like growth factors(IGF-1, IGF-2) 77

leptin 77fetal growth hormone (GH) 77fetal heart rateabsent or minimalvariability 181–182

accelerations 177–178baseline features 177–179baseline rate 177bradycardia 177, 180–181changes in baseline rate180–181

early deceleration 179episodic decelerations 179,180

fetal response to hypoxia/asphyxia 178–179

late deceleration 179management of non-reassuring FHR 183

normal characteristics177–179

observer variability in EFMinterpretation 182

periodic patterns 179–181prolonged decelerations179, 180

sinusoidal patterns 181, 182tachycardia 177, 181variability 177variability absent orminimal 181–182

variable decelerations179–180

variant patterns 179–182fetal heart-rate abnormalities,

IUGR complications 82

fetal heart-rate (FHR)monitoring 5, 64

current ACOGrecommendations foruse 183

during labor and delivery139–140

evaluation of FHRpatterns 64

history of 174–175see also EFM

management of FHRpatterns 64–65

measures to improve fetalstatus 64–65

timing of neonatal braininjury 256–257

fetal heart-rate physiologycharacteristics of normalfetal heart rate 177–179

effect of gestational age onFHR 176

factors influencing cardiacoutput 176

fetal oxygenation 175–176fetal response to hypoxia176

parasympathetic NSinfluences 176

response to blood pressurechanges 176

role of baroreceptors 176role of chemoreceptors 176role of the autonomicnervous system 176

sympathetic NS influences176

fetal hemolytic anemia, andhydrops fetalis 325

fetal hemorrhage 243fetal hydantoin syndrome

80, 100fetal hypoxemia, effects of

tobacco use inpregnancy 114

fetal indications for operativevaginal delivery 65

fetal injury during labor anddelivery, incidence 134

fetal ischemic strokeclinical manifestations 296definition 296see also perinatal stroke

fetal lung maturityadministration ofcorticosteroids 130

administration ofglucocorticoids 130

antenatal steroids forpreterm birth 62

fetal malnutrition and diseasein adult life 87–88

fetal monitoring 63–64Apgar scores 64auscultation 63chronic hypertension 128continuous EFM 64

evaluation of FHR patterns64

fetal heart-rate (FHR)patterns 64

management of FHRpatterns 64–65

measures to improve fetalstatus 64–65

prediction of fetal hypoxia 64umbilical cord bloodgases 64

see also fetal heart-rate(FHR) monitoring

fetal mortality rate 163–164fetal oxygenation 175–176fetal predisposition to adult

diseases (Barkerhypothesis) 127

fetal pulse oximetry 184fetal responses to asphyxia

147–153, 178–179acute on chronic hypoxia/asphyxia 151, 152

brief repeated asphyxiaexperimental studies150–151

brief repeated asphyxiawith uterine contractions149–150

clinical implications 148–149decompensation 147, 148, 149factors affecting 143, 144gender differences inresponses 152–153

initial rapid responses147–148

maturational changes inresponses 147, 148,151–152

slow onset asphyxia 149uterine contractions andbrief repeated asphyxia149–150

fetal responses to bloodpressure changes 176

fetal responses to hypoxia145–146, 176, 178–179

effects of prolonged hypoxia146

maturational changes inresponse 146–147

fetal stress see intrauterinestress

fetal trimethadionesyndrome 80

fetal vascular thrombosis247, 248

fetal warfarin syndrome 80fetomaternal hemorrhage

320–322clinical presentation 321diagnosis 321etiology 321incidence 320–321Kleihauer–Betke test 321outcomes 321–322treatment 321

FHR monitoring see fetalheart-rate (FHR)monitoring

FLAIR (fluid attenuationrecovery technique)211, 212

fluid management followingresuscitation 470

FMRI (functional MRI) 211,212–213

focal brain injury in HIE 192folinic acid-responsive seizures

394–395forceps delivery 135–136Foresight monitor 233fractional anisotropy 211, 213Frank–Starling mechanism in

the fetus 176Fukuyama congenital

muscular dystrophy 280funisitis 137

GABA transaminasedeficiency 395

gastric feeding, prematureinfant 527

gastroesophageal reflux,premature infant 527

gastrointestinal priming529–530

gastrointestinal tractdevelopment 527, 528, 529

gender differenceseffects of brain injury and

therapeutics 40fetal responses to asphyxia

152–153language and speech

development afterprematurity 568

response to therapies 40risk for neurodevelopmental

sequelae 551genetic control of cell death

18–19genetic disease and fetal

development 101genetic disorders

see neurogeneticdisorders of the brain

germinal matrix hemorrhage–intraventricularhemorrhage (GMH–IVH)285

classification system 286diagnosis 286–288diplegia development

289–290effects of birth location 286effects of cardiovascular and

respiratory problems 286effects of cesarean section

285effects of delayed cord

clamping 285–286effects of maternal

pre-eclampsia 286

Index

614






hemiplegia development289–290

incidence 286intracerebellar hemorrhage288

management 288–289neuropathology 285outcome 289–290pathogenesis 285PHVD 287, 288–289risk factors in the pre- andperinatal periods 285–286

ventriculomegaly 289germinal matrix hemorrhage–

intraventricularhemorrhage (GMH–IVH)prevention 290

antenatal prevention 290antenatal steroids 290effects of NICUcharacteristics 290

general care and handling290

ibuprofen 290indomethacin 290magnesium sulphate 290phenobarbital 290postnatal prevention 290vitamin K 290

gestational age, effects onFHR 176

gestational hypertension 128absence of proteinuria128–129

course of the disease 128definition 128diagnosis 128

gestational timing,classification ofdevelopmentalabnormalities 214–216

glucocorticoids for fetal lungmaturity 130

gluconeogenesis disorders399

glucose administration afterneonatalcardiopulmonaryresuscitation 459

glucose metabolism disorders82–83

GLUT-1 deficiency syndrome395

glutamate excitotoxicity, rolein preterm brain injury50–51

glycine encephalopathy (non-ketotic hyperglycinemia)394

glycogen storage disorders398–399

gonococcus infection 61grading (staging) of

encephalopathy, use ofEEG 201, 202, 203

Grave's disease, effects on fetaldevelopment 98

Gross Motor FunctionClassification System(GMFCS) 561

Gross Motor FunctionMeasure (GMFM) 561

group A beta-hemolyticstreptococcus (GAS),cause of neonatal sepsis332, 341–342

group B beta-hemolyticStreptococcus (GBS) 61

group B streptococcus (GBS)336–341

cause of neonatal meningitis347, 348–349

cause of neonatal sepsis332–333

chemoprophylaxis 340clinical presentation 337–338diagnosis 338epidemiology 337IAP 339–340immunoprophylaxis 340–341nature of the organism336–337

outcome 338pathogenesis 337prevention 338–341risk factors 332, 337treatment 338

growth factor therapies 10use in HIE management 481

growth restriction, definition 59guanidinoacetate

methyltransferase(GAMT) deficiency 395

HAART (highly activeantiretroviral therapy)382–383

hearing loss, neonatalencephalopathy outcome578

heart disease see congenitalheart disease

heart surgery see pediatriccardiac surgery

hematologic problems,IUGR complications82, 83–84

hematological abnormalities,timing of neonatal braininjury 258, 259

hemimegalencephaly 269hemiplegia development, and

GMH-IVH 289–290Hemophilus influenzae, cause

of neonatal meningitis 349hemorrhagic perinatal stroke

296clinical manifestations 297see also perinatal stroke

hereditary hemorrhagictelangiectasia 282

heroin use in pregnancysee opioid abuse inpregnancy

herpes, congenital infection 9herpes simplex virus (HSV)

infection 371–373clinical manifestations371–372

consequences of perinataland intrauterineinfections 371–372

diagnosis 373incidence of neonatalinfection 371

neonatal diseasemanifestations 371

prevention 372–373recommendations 372–373transmission to the fetusand newborn 371

treatment 373herpes zoster 369, 370heterotopias 269, 270HHH syndrome 398HI see hypoxia–ischemiaHIE see hypoxic–ischemic

encephalopathyhigh altitude hypoxia and

IUGR 80–81high-frequency ventilation

(HFV) techniques 471treatment for PPHN 422

high hematocrit, IUGRcomplication 83–84

history of poor outcome inpregnancy, and IUGRrisk 79–80

HIV (humanimmunodeficiency virus)


see also perinatal HIVinfection

holoprosencephaly 267–268EEG diagnosis 204

human error see patient safetyhuman milk, benefits for

premature infants535–536, 539

hydantoin, fetal hydantoinsyndrome 80, 100

hydranencephaly 272hydrocephalus 274communicatinghydrocephalus 274

genetic forms 274neurogenetic causes 282–283non-communicatinghydrocephalus 274

hydrocephalus with stenosis ofthe aqueduct of Sylvius(HSAS) 282–283

hydrops fetalisantenatal management 327definition 325diagnosis 325fetal hemolytic anemia 325immune hydrops 325management (antenatal) 327management (perinatal) 327

management (postnatal)327–328

mechanisms of edemaformation 325–326

neurologic injury 326–327non-immune hydrops

325, 326outcome of hydropic

infants 328perinatal management 327postnatal diagnostic

studies 327postnatal management

327–328prognosis 325

hyperammonemia, EEGdiagnosis 204

hyperbilirubinemiaclinical features 311, 312effects of early hospital

discharge after birth 314exchange transfusion

313–314management 313–314phototherapy 313–314prediction 312–313reemergence of reported

kernicterus 314risk factors 312toxic level of bilirubin 311see also bilirubin toxicity

hypercapnia see respiratoryacidosis

hyperekplexia 507hyperglycemia, IUGR

complication 83hyperinsulinemic (organic)

hypoglycemia 308–309hyperoxia test 474hypertensive disease in

pregnancyacute management 132antihypertensive

medications 131–132Barker hypothesis 127chronic hypertension

127–128chronic management 131classification 127fetal effects 127, 131fetal effects of maternal

medications 131–132fetal predisposition to adult

diseases 127gestational hypertension 128iatrogenic prematurity 131incidence 127magnesium sulfate tocolysis

131neonatal effects 127, 131normal hypertension in

pregnancy 127placental insufficiency 131pre-eclampsia 128, 129–130risk of IUGR 131superimposed pre-eclampsia

128, 129

Index

615






hypertensive disease inpregnancy (cont.)

see also pre-eclampsiahyperthermia and hypoxic–

ischemic injury 155hyperventilation treatmentuse in management ofcerebral edema 477–478

use in PPHN 471hyperviscosity syndrome,

IUGR complication83–84

hypocalcemia, IUGRcomplication 83

hypocapnia see respiratoryalkalosis

hypoglycemia, IUGRcomplication 82–83

hypoglycemia and the brain305–306

cerebral glucose and oxygenuptake 305

neurodevelopmentaloutcome 306

studies in animals 305–306studies in human neonates306

hypoglycemia in the neonatecauses 307clinical presentations306–307

definition 304–305hyperinsulinemic (organic)hypoglycemia 308–309

initiation of systemicglucose production 304

management after neonatalcardiopulmonaryresuscitation 459

management of the neonateat risk 307, 308

neurodevelopmentaloutcome 306

operational thresholds forintervention 304–305

persistent or recurrenthypoglycemia 307, 308

routine monitoring of theneonate at risk 307, 308

studies 306therapy 307–308transient hyperinsulinemia308

transient hypoglycemia 307transition to extrauterinelife 304

hypophosphatasia 78hypotensionand asphyxial injury 147,148, 151, 153–154

HIE patterns of injurycaused by 190–191, 192

hypothermiaIUGR complication 83, 84neuroprotective potential 42

hypothermia therapy after HIinjury 155

clinical evidence fortherapeutic effect 487

depth of cooling 487duration of cooling 486–487effects on EEG epileptiformtransients 490–492

effects on excitotoxicity afterHI 490–492

effects on inflammatorysecond messengers489–490

effects on programmed celldeath 488–489

effects on spreadingdepression 492

interventions for neonatalHIE 14

long-term neuroprotection487

neuroprotective effects486–487

therapeutic targets 488–492timing of initiation 486treatment techniques 9, 10use in HIE management 481

hypothyroidism, effects onfetal development 98

hypotonia, caused byneurogenetic disorders277–281

hypoxemiadefinition 64evaluation and managementfollowing resuscitation473–481

hypoxiadefinition 64tolerance of the pretermbrain 59

see also fetal responses tohypoxia

hypoxia-inducible factor 1(HIF-1), cellular responseto injury 40–41

hypoxia–ischemia (HI)and language and speechdevelopmental disorders570

necrotizing enterocolitispathogenesis 536

neuroimaging diagnosis216–219

pathogenesis of cell death144–145

sensitization to 53hypoxia–ischemia (HI) brain

injuryadaptive responses of cells40–42

astrocyte activation 39blood–brain barrierpermeability 38

effects of mast cells 39failure of mitochondrialATP production 38, 39

functioning of theneurovascular unit 38

gender differences inischemic injury 40

influential factors 38mechanisms of neuronaldeath 40

microglial activation 38–39neuroinflammation 38–40preterm brain injury 49–51role of chemokines 40role of cytokines 39–40SVZ neurogenerativeresponse 42

time course of injuriousevents 38, 39

see also neuroprotectionafter HI injury

hypoxia–ischemia (HI)therapeutic targets 488–492

excitotoxicity after HI490–492

inflammatory secondmessengers 489–490

insulin-like growth factors(IGFs) 489

programmed cell death488–489

spreading depression 492hypoxic–ischemic

encephalopathy (HIE)and metabolic acidosis403–404

cell death continuumconcept 15, 23–24, 24–25

consequences of HI injury187

definition 1, 2factors affectingneurodegeneration 14

hypothermia interventions 14metabolism-connectivityconcept 14

neonatal animal modelsof neurodegeneration26–29

neurodegeneration innewborn human 25–26

selective vulnerability ofneural systems 14

therapies for HIEsee hypothermia therapy,stem cell therapy

use of EFM foridentification 175

see also neonatalencephalopathy

hypoxic–ischemicencephalopathy (HIE)clinical features

computed tomography(CT) 189

cranial ultrasonography 189electroencephalography(EEG) 189

general evaluation 187grading (staging) systems187–188

laboratory evaluations 189

magnetic resonance imaging(MRI) 189

mild encephalopathy(Stage I) 188

moderate encephalopathy(Stage II) 188

neuroimaging studies 189neurologic assessment

187–188severe encephalopathy

(Stage III) 188hypoxic–ischemic

encephalopathy (HIE)differential diagnosis


clinical features 392–399congenital disorders of

glycosylation (CDG) 399dihydropyrimidine

dehydrogenase (DPD)deficiency 395

fatty acid oxygenationdefects 396–397

folinic acid-responsiveseizures 394–395


gluconeogenesis disorders399

GLUT-1 deficiencysyndrome 395

glycine encephalopathy(non-ketotichyperglycinemia) 394


guanidinoacetatemethyltransferase(GAMT) deficiency 395

HHH syndrome 398inherited encephalopathies

399inherited myopathies 399isolated seizures 393–396lactic acidosis, hypotonia

and systemic involvement396–397

lethargy withhyperammonemia 398

lethargy withoutmetabolic acidosisor hyperammonemia397–398

lysinuric protein intolerance398

maple syrup urine disease(MSUD) 397–398

mevalonic aciduria 398mitochondrial disease 397mitochondrial disorders 395organic acidemias 395–396,

397patterns of brain injury

389–392peroxisomal disorders 395

Index

616






pyridoxal-dependentseizures 394

pyridoxine-dependentseizures 394

pyruvate metabolismdisorders 396

Rett syndrome 399severe ketoacidosis 397sulfite oxidase deficiency 394tricarboxylic acid cycledefects 396

urea cycle disorders395–396, 398

see also inborn errors ofmetabolism

hypoxic–ischemicencephalopathy (HIE)management adjuncts478–481

barbiturates 478–479calcium-channel blockers480

excitatory amino acids(EAAs) receptorinhibitors 479–480

growth factors 481hypothermia 481lazaroids (21-aminosteroids) 480–481

monosialgangliosides 480oxygen-free radicalinhibitors 480–481

hypoxic–ischemicencephalopathy (HIE)patterns of injury189–193

brainstem injury 191, 192cerebellar injury 191–192deep gray-matter nuclei(thalamus and basalganglia) lesions 191, 192

diffuse brain injury 192effects of acute near-totalasphyxia 191, 192

effects of hypotension190–191, 192

focal brain injury 192parasagittal border-zoneinjury 190–191, 192

partial hypoxic–ischemicinjury 190

periventricular/intraventricularhemorrhages 193

periventricular leukomalacia192–193

premature infant 189–190relation to mechanisms ofinjury 189

selective injury 191–192status marmoratus lesion191

term infant 189–190ulegyria 190–191watershed infarction190–191

white-matter injury 192–193

I-cell disease 78iatrogenic prematurity,

hypertensive disease inpregnancy 131

ibuprofen, GMH-IVHprevention 290

ICD-9 criteria for neonatalencephalopathy 1, 2

imaging studies, timing ofneonatal brain injury260–261

immune hydrops 325immune maladaptation in

pre-eclampsia 129–130immunological deficiency,

IUGR complication 84inborn errors of metabolism


clinical features comparedwith HIE 392–399

congenital disorders ofglycosylation (CDG) 399

dihydropyrimidinedehydrogenase (DPD)deficiency 395

fatty acid oxygenationdefects 396–397

folinic acid-responsiveseizures 394–395


gluconeogenesis disorders 399GLUT-1 deficiencysyndrome 395

glycine encephalopathy(non-ketotichyperglycinemia) 394


guanidinoacetatemethyltransferase(GAMT) deficiency 395

HHH syndrome 398isolated seizures 393–396lactic acidosis, hypotoniaand systemic involvement396–397

lethargy withhyperammonemia 398

lethargy withoutmetabolic acidosisor hyperammonemia397–398


maple syrup urine disease(MSUD) 397–398

mevalonic aciduria 398mitochondrial disease 397mitochondrial disorders 395organic acidemias 395–396,397

patterns of brain injurycompared with HIE389–392

peroxisomal disorders 395pyridoxal-dependentseizures 394

pyridoxine-dependentseizures 394

pyruvate metabolismdisorders 396

severe ketoacidosis 397sulfite oxidase deficiency394

tricarboxylic acid cycledefects 396

urea cycle disorders395–396, 398

indomethacin, GMH-IVHprevention 290

infant mortality rate 163–164infectionEEG diagnosis 205intra-amniotic 137neurogenetic disorders withsimilar features 281–282

neuroimaging diagnosis 223,224

role in preterm brain injury51–53

susceptibility in IUGR 84infectious agentsassociation with IUGR77–78

necrotizing enterocolitispathogenesis 536

see also specific infectiousagents

inflammation, role in pretermbrain injury 51–53

inflammatory processes,neuroimaging diagnosis223, 224

inflammatory secondmessengers, effects ofhypothermia therapy489–490

inhibitor of apoptosis protein(IAP) family 21

inhaled nitric oxide (iNO)therapy 423, 426–428,472

inotropic drugs 472–473insulin, fetal growth factor

76–77insulin-like growth factors

(IGF-1, IGF-2) 77insulin-like growth factors

(IGFs), HI therapeutictargets 489

intelligence quotient (IQ),outcomes of IUGR86–87, 88

intensive care decision makingsee medical ethics inintensive care

intermittent gavage, prematureinfant 527

intra-amniotic infection 137intracerebellar hemorrhage 288intracranial hemorrhage

in preterm infants 285neurogenetic causes 282neuroimaging diagnosis

219–220, 221see also germinal matrix

hemorrhage–intraventricularhemorrhage (GMH–IVH)

intracranial hemorrhage in theterm infant

ECMO-treated infants 292intraventricular hemorrhage

(IVH) 290–291neonatal alloimmune

thrombocytopenia 292subarachnoid hemorrhage

291subdural hemorrhage 291subgaleal hemorrhage

291–292intrapartum asphyxiaconditions which mimic

effects of 9indicators of 184

intrapartum causes of neonatalencephalopathy 1–2, 8–9

risk factors for neonatalencephalopathy 2, 4

see also labor and deliverycomplications

intrapartum fetal evaluationcurrent recommendations

184current recommendations

for FHR monitoring 183fetal pulse oximetry 184indicators of intrapartum

asphyxia 184management of non-

reassuring FHR 183ST waveform analysis

(STAN) 184see also EFM (electronic fetal

monitoring); fetal heart-rate (FHR) monitoring

intrapartum fetal resuscitation453 see also neonatalresuscitation

intrapartum hypoxia andacidosis, preterm fetus63–64

intrauterine asphyxiaacute total events 2–3prolonged partial asphyxia 3

intrauterine growth restriction(IUGR)

classification of fetal growth75–76

definitions 75–76evaluation of fetal growth

and well-being 81–82factors affecting fetal growth

76–77fetal growth factors 76–77incidence 77management of the fetus

and newborn 82

Index

617






intrauterine growth restriction(IUGR) (cont.)

maternal influences 76placental growth factors76, 77

ponderal index 75proportional anddisproportional growth75–76

symmetrical andasymmetrical growth75–76

terminology 75–76intrauterine growth restriction

(IUGR) complications82–85

accelerated neurologicaldevelopment 84

altered behavior 84anemia 84asphyxia (fetal andneonatal) 82

fetal and neonatalasphyxia 82

fetal heart-rateabnormalities 82

glucose metabolismdisorders 82–83

hematologic problems 82,83–84

high hematocrit 83–84hyperglycemia 83hyperviscosity syndrome83–84

hypocalcemia 83hypoglycemia 82–83hypothermia 83, 84immunological deficiency84

increased nucleated redblood cells (erythroblasts)83–84

metabolic acidosis 83metabolic disturbances82–83

necrotizing enterocolitis 84neurological abnormalities84–85

neutropenia 83–84parent–infant interactiondifficulties 85

persistent pulmonaryhypertension 82

resuscitation required in thedelivery room 82

susceptibility to infection 84thrombocytopenia 83–84transient diabetes mellitus ofthe newborn 83

intrauterine growth restriction(IUGR) diagnosis 81–82

biophysical profile 81contraction and non-contraction stress tests 81

cordocentesis 81–82Doppler waveforms of fetalcirculation 81

maternal endocrinemeasurements 81

symphysis-to-fundusheight 81

ultrasound evaluation 81vibroacoustic stimulation 81

intrauterine growth restriction(IUGR) etiology 77–81

alcohol effects 80caffeine consumption 80chronic hypertension 128cocaine use 80congenital malformation 78drugs taken by mothers 80dysmorphic syndromes 78endocrine disorders 78environmental factors 80fetal alcohol syndrome 80fetal chromosomalabnormalities 78

fetal factors 77–78fetal hydantoin syndrome 80fetal trimethadionesyndrome 80

fetal warfarin syndrome 80high altitude hypoxia 80–81history of poor outcome inpregnancy 79–80


infectious agents 77–78marijuana use 80maternal diabetes mellitus 97maternal drug-taking 80maternal factors 79–80maternal hypoxia 80–81maternal illness 79, 80maternal malnutrition 79maternal stress 81mercury toxicity 81metabolic disorders 78monochorionic twins 78monozygotic twins 78multiple gestations 78nutritional status of themother 79

placental factors 78poverty 78pre-eclampsia 78, 79, 80role of race 78smoking 80tobacco use in pregnancy 115twin-to-twin transfusionsyndrome (TTTS) 78

intrauterine growth restriction(IUGR) interventions88–89

abdominal decompression88–89

bed rest in hospital 89identification of previouscause of IUGR 89

low-dose aspirin 89maternal oxygen therapy82, 89

nutrient supplementation 89plasma volume expansion 89

intrauterine growth restriction(IUGR) outcomes 85–88

cerebral palsy 87, 88fetal malnutrition anddisease in adult life87–88

historical perspective 85intelligence quotient86–87, 88

learning deficits 87, 88morbidity 85–86mortality 85–86neonatal encephalopathy 2neurodevelopmental andcognitive outcomes86–87, 88

physical growth 86VLBW infants born SGA86–87, 88

intrauterine growth restriction(IUGR) prevention 88–89

abdominal decompression88–89

bed rest in hospital 89identification of previouscause of IUGR 89

low-dose aspirin 89maternal oxygen therapy 89nutrient supplementation 89plasma volume expansion 89

intrauterine stressmeconium release 240–242placental pathologiccorrelates 240–243

release of nucleated redblood cells (NRBCs)242–243

timing of 240–243intrauterine stroke 9intraventricular hemorrhage

(IVH)EEG diagnosis 204–205effects on language andspeech development 566

in the term infant 290–291INVOS cerebral oximeter 233iron-overload disease and

IUGR 78ischemic perinatal strokeclassification 296clinical manifestations296–297

definition 296see also perinatal stroke

IVF, risk factor for neonatalencephalopathy 3

jitteriness with EEG correlatesin neonates 506

Joubert syndrome 273

kernicterusclinical features 311, 312definition 311diagnosis 311, 312effects of early hospitaldischarge after birth 314

re-emergence of reportedkernicterus 314

toxic level of bilirubin 311see also bilirubin toxicity

Klebsiella pneumoniae, cause ofneonatal sepsis 333, 341

Klebsiella spp., cause ofneonatal meningitis348, 349

L1 syndrome 282–283labor and delivery

complicationsamnionitis 137amniotic fluid embolism

136–137as cause of neonatal

encephalopathy 134brachial plexus injury 136breech presentation

138–139cesarean section 134chorioamnionitis 137dysmaturity syndrome

137–138electronic fetal heart-rate

monitoring (EFM)139–140

external cephalic version 139face presentation 138fetal heart-rate monitoring

139–140forceps delivery 135–136funisitis 137incidence of fetal injury 134infection (intra-amniotic)

137intra-amniotic infection 137malpresentation 138–139meconium aspiration

syndrome 137–138meconium staining 137–138non-vertex presentation

138–139operative vaginal delivery

135–136post-termpregnancy 137–138prolonged second stage 139shoulder dystocia 136uterine rupture

(spontaneous) 135uterine rupture (with

VBAC) 134–135vacuum delivery 135–136vaginal births after cesarean

(VBAC) 134–135villitis 137see also intrapartum events

laboratory findingscorrelation with neonatal

encephalopathy 7evaluation of HIE 189timing of neonatal brain

injury 258–259lactic acidosis, hypotonia and

systemic involvement396–397

Index

618






language and speechdevelopment

assessment in youngchildren 565

disorders in the generalpopulation 565

typical childhood stages564–565

language and speechdevelopment afterprematurity 565–566

academic outcomes 566–568conflicting results fromstudies 565–566

effects of brain injuries 566effects of intraventricularhemorrhage (IVH) 566

effects of periventricularhemorrhage (PVH) 566

effects of periventricularleukomalacia (PVL) 566

effects of socioeconomicstatus 568

gender differences 568moderators of outcomes 568Peabody Picture VocabularyTest-Revised (PPVT-R)568

language and speechdevelopmental disorders

and ADHD 569association with cognitiveand motor impairment568–569

attention problems 569cerebellar injury 571clinical implications 571effects of hypoxia andischemia 570

functional neuralorganization patterns 571

future research 571neural basis 570–571outcome of neonatalencephalopathy 579

plasticity of the youngbrain 570

problems of executivefunctioning 569

relation to otherdevelopmental domains568–570

Specific Learning Disorder(SLI) 569

white-matter injury 570lazaroids (21-aminosteroids),

use in HIE management480–481

learning deficits, outcomesof IUGR 87, 88

legal issues see medicalmalpractice, medicolegalissues

leprechaunism 78leptin 77lethargy with

hyperammonemia 398

lethargy without metabolicacidosis orhyperammonemia397–398

leukoencephalopathies 226–227lissencephaly 266, 269–270

EEG diagnosis 204Type 1 270Type 2 (cobblestonelissencephaly) 266, 270, 280

Listeria monocytogenes 332cause of neonatal meningitis349

low birthweight, definition 59see also preterm birth

low-dose aspirin therapy forIUGR 89

LSD use in pregnancy 119lymphocyte counts, timing

of neonatal braininjury 258

lymphoid interstitialpneumonia (LIP) 380


macrencephaly 269macrosomia, and maternal

diabetes mellitus 97magnesium sulfate

administration beforepreterm delivery 65

fetal effects 131GMH-IVH prevention 290tocolytic agent 64

magnetic resonance imagingsee MRI

malaria, association withIUGR 77–78

malpresentation 138–139malpresentations for preterm

delivery 63mannitol, use in management

of cerebral edema 478maple syrup urine disease

(MSUD)EEG diagnosis 204HIE differential diagnosis397–398

marginal cord insertion 107marijuana use in pregnancy

116IUGR risk 80

massive perivillous fibrindeposition (MPFD)251, 252

mast cells, actions in HI braininjury 39

maternal ageand risk of neonatalencephalopathy 3, 4

and risk of preterm birth 60maternal alloimmunization

99–100maternal cocaine use,

necrotizing enterocolitisrisk 536–537

maternal disease affectingfetal development

antibody-related fetaldisease 98–100

antiepileptic medications100–101

congenital adrenalhyperplasia (CAH) 97

diabetes mellitus 96–97fetal hydantoin syndrome100

genetic disease 101Grave's disease 98hypothyroidism 98maternal alloimmunization99–100

mechanisms of teratogenesis96

medications and toxins100–101

neonatal alloimmunethrombocytopenia(NAIT) 100

neonatal lupus syndrome98–99

phenylketonuria (PKU)97–98

placental insufficiency 100pre-conception counseling101

Rhesus (Rh)alloimmunization 99–100

systemic lupus erythematosus(SLE) 98–99

toxic metabolic endproducts 96–98

underproduction ofessential metabolicproduct 98

maternal drug useEEG diagnosis 205IUGR risk 80see also substance abuse inpregnancy

maternal education level andrisk of neurodevelopmentalsequelae 551

maternal factors in IUGRetiology 79–80

maternal–fetal transportationfor preterm delivery61–62

maternal floor infarction(MFI) 251, 252

maternal history of fetalactivity, timing ofneonatal brain injury256

maternal hypoxia and IUGR80–81

maternal illness and IUGR79, 80

maternal indications foroperative vaginaldelivery 65

maternal influences on fetalgrowth 76

maternal malnutrition andIUGR risk 79

maternal medications, fetaleffects 131–132

maternal oxygen therapy forIUGR 82, 89

maternal perception of fetalmovement 168–169

maternal pre-eclampsia, andrisk of GMH-IVH 286

maternal risk factors forneonatal encephalopathy3–4

maternal stress and IUGR 81maternal vascular

underperfusion249–250, 251

meconiumnature of 411origin of the name 409

meconium aspirationsyndrome (MAS)137–138

adverse neurologicoutcomes 410–411

historical studies 409–410pathophysiology of

meconium passage411–412

potential mechanismsof neurologic injury412–413

respiratory distress 410thick versus thin consistency

meconium 415meconium-induced umbilical

vascular necrosis240–241

meconium-stained amnioticfluid (MSAF) 4–5,137–138

adverse neurologicoutcomes 410–411

adverse non-neurologicoutcomes 410

and development ofrespiratory distress 410

and fetal distress 410and fetal heart-rate

abnormalities 410cardiopulmonary

resuscitation of thenewborn 457

historical studies 409–410incidence 409meconium aspiration

syndrome (MAS) 410pathophysiology of

meconium passage411–412

potential mechanismsof neurologic injury412–413

thick versus thin consistencymeconium 415

timing of meconium passage413–415

Index

619






meconium-stained amnioticfluid (MSAF) (cont.)

timing of neonatal braininjury 257

MECP2-related congenitalencephalopathy 279

medical conditions, and risk ofneonatal encephalopathy3, 4

medical error see patient safetymedical ethics in intensive carebasis for ethical decisionmaking 588–593

decision to treat or not totreat 588–593

methods to be appliedto achieve the objective585–588

objective of medicalintervention 585–588

what needs to be decided585–588

who makes the decision593–596

medical malpracticebreach of duty 598–599case study (obstetrics/laborand delivery) 603–605

case study (obstetricdischarge/prenatalfollow-up) 605–606

causation 599–600damages 600, 601–602definition of malpractice 598documentation 600duty 598, 599terminologymatters 600–603

medical training and educationfuture enhancements467–468

historical perspective464–465

Institute of MedicineReports (1999 and2001) 464

JCAHO recommendations(2004) 464

limitations of the traditionalmodel 464–465

meeting the challengesof the delivery room465–467

new methodologies 465–467patient safety reportsand recommendations464

safety in the delivery room467–468

medications and toxins, effectson fetal development100–101

medicolegal issues, neonatalresuscitation 453,460–461, 461–462see also medicalmalpractice

megalencephaly 269

membrane rupture, pretermpremature rupture ofamniotic membranes(PPROM) 61

memory problems, neonatalencephalopathy outcomes579

meningitis, EEG diagnosis 205see also bacterialmeningitis in the neonate

meningocele 266Menkes syndrome 78mental retardation (MR)

and preterm birth 59definition 11epidemiology 11fetal alcohol syndrome 11link with intrapartumevents 64

relationship to CP 11meprobamate use in

pregnancy 118mercury toxicity and

IUGR 81metabolic acidemia, detection

using EFM 182–183metabolic acidosis

and HIE 403–404correlation with neonatalencephalopathy 5

detection using EFM174, 175

development in asphyxia 2IUGR complication 83management after neonatalcardiopulmonaryresuscitation 459

metabolic alkalosis 405metabolic disorders 9

classification 225IUGR complications82–83

neuroimaging diagnosis210, 211, 213, 223–228

role in IUGR etiology 78see also inborn errors ofmetabolism

metabolic disorders differentialdiagnosis 225

disorders affecting corticalgray matter 226

disorders affecting deep graymatter 226

disorders affecting whitematter 226–227

disorders affecting whitematter and cortical graymatter 227

disorders affecting whitematter and deep graymatter 227–228

use of MR spectroscopy(MRS) 213, 219, 228

metabolic encephalopathies,EEG diagnosis 204

metabolism-connectivityconcept 14

methamphetamine abuse inpregnancy 119

methaqualone use inpregnancy 118

methodone use in pregnancysee also opioid abuse inpregnancy

methyl mercury toxicity andIUGR 81

methylphenidate abuse inpregnancy 119

mevalonic aciduria 398microcephaly 269microdysgenesis 270microencephaly 269microgliaactivation in HI braininjury 38–39

role in preterm braininjury 52

mid-brain and hind-brainorganization andpatterning defects 273

mild encephalopathy (Stage I)188

mitochondriafailure of ATP productionin HI brain injury 38, 39

regulation of apoptosis 16,17, 18, 19–20, 21

role in apoptosis after HI 40mitochondrial disease, HIE

differential diagnosis 397mitochondrial disorders, HIE

differential diagnosis 395mitochondrial permeability

transition, necrosispathway 16–17

moderate encephalopathy(Stage II) 188

‘molar tooth’ malformationof the brain 273

monochorionic twins, andIUGR 78

monosialgangliosides, use inHIE management 480

monozygotic twins, associationwith IUGR 78

mortality ratesIUGR 85–86neonatal encephalopathy9–10

motor impairment, associationwith language and speechdevelopmental disorders568–569

motor problems in the absenceof cerebral palsy 578

mouse, neonatalneurodegeneration inHIE 16, 19, 26–27

MR (magnetic resonance)vascular imaging 211

MRA (MR angiography andvenography) 211, 212

MRI (magnetic resonanceimaging) 210, 211–213

HIE features 189preterm infant brain injury

550–551timing of neonatal brain

injury 260–261MRI techniquesdiffusion-weighted imaging

(DWI) 211, 213fast and ultrafast techniques

211fat suppression short

TI inversion recoveryimaging (STIR)211, 212

fluid attenuation recoverytechnique (FLAIR)211, 212

magnetization transferimaging (MTI) 211, 212

motion-sensitive techniques213

MR angiography andvenography (MRA)211, 212

MR vascular imaging 211perfusion MRI (PMRI)

211, 212MRS (MR spectroscopy) 211,

212, 213use in metabolic disorder

diagnosis 213, 219, 228MRSA (methicillin-resistant

S. aureus), cause ofneonatal sepsis 332

MTHFR (methylenetetrahydrofolatereductase) deficiency 282

MTI (magnetizationtransfer imaging) 211,212

multidetector CT (MDCT)209–210

multifocal (fragmentary)clonic seizures 502–504

multiple gestationsabnormal growth 71amnionicity 69–70and IUGR 78chorionicity 69–70conjoined twins 69diagnosis 69–70dizygotic twins 69embryology 69incidence 69incidence of prematurity

69, 70monoamnionic twins 69, 72monochorionic twins 69, 70,

71–72monozygotic twins 69

see also monochorionictwins

peripartum management 72prematurity 69, 70preterm delivery route 63preterm labor 70risk of cerebral palsy 69

Index

620






risk of preterm birth 60twin-to-twin transfusionsyndrome (TTTS) 70

ultrasound evaluation 69–70vaginal birth after cesarean(VBAC) 72

zygosity 69–70multiple organ damage,

correlation with neonatalencephalopathy 6–7

muscle-eye-brain disease 280muscular dystrophies,

congenital conditions280–281

myasthenia, congenitalmyasthenias 281

myelomeningocele 267myoclonic movements without

EEG seizures in neonates506–507

myoclonic seizures 505–506myopathies, congenital

conditions 280myotonic disease 9myotonic dystrophy type 1, 279

naloxone (Narcan), neonataladministration 118, 460

nasogastric feeding, prematureinfant 527

necrosiscauses 15continuum with apoptosis14–15

signaling pathways 16–17structural appearance 15–16see also cell deathcontinuum concept

necrotizing enterocolitis(NEC) 532–539

clinical picture 532–533endemic rate 532epidemics 532epidemiology 532IUGR complication 84outcome 538pathogenesis 533–538prevention 538–539risk of neurodevelopmentalsequelae 551–552

treatment 533necrotizing enterocolitis

(NEC) pathogenesis533–538

benefits of human milk535–536, 539

enteral feeding 534immunologic considerations535

infectious agents 536ischemia and hypoxia 536maternal cocaine use 536–537new thoughts on etiology537–538

osmolality of feeds 535rate and volume of enteralfeeds 534–535

role of corticosteroids 537role of vitamin E 536timing of enteral feeding 534

negligence see medicalmalpractice

Neisseria meningitidis, cause ofneonatal meningitis 349

neonatal alloimmunethrombocytopenia(NAIT) 100, 292

neonatal arterial stroke 296neonatal brain injury

see neonatalencephalopathy

neonatal care see patient safetyneonatal depression,

conditions which mimicintrapartum asphyxia 9

neonatal effects ofhypertensive disease inpregnancy 127, 131

neonatal encephalopathyand asphyxial events 2–3,143 see also asphyxia

antepartum (in utero)events 1–2

conditions which mimicintrapartum asphyxia 9

definition 1, 2diagnostic criteria 3early identification ofpatients 1

factors affecting incidenceand mortality 3

ICD-9 criteria 1, 2incidence 3intrapartum events 1–2, 8–9intrauterine growthrestriction (IUGR) 2

labor and deliverycomplications as cause 134

preterm infants 2range of studies 1risk factors 2, 3–4timing of causal events 1–2see also hypoxic–ischemicencephalopathy (HIE)

neonatal encephalopathycorrelative findings 4–8

abnormalelectroencephalography7–8

blood gas evaluations 5clinical signs 7–8fetal heart-rate monitoring 5laboratory studies 7low Apgar score 4meconium in the amnioticfluid 4–5

metabolic acidosis 5multiple organ damage 6–7need for cardiopulmonaryresuscitation 7–8

neuroimaging 8pH of umbilical arterialblood 5

seizures 5–6

neonatal encephalopathy inthe term newborn

association with adverseneurocognitiveoutcomes 575

basal nuclei predominantpattern of injury 576, 580

brain injuries leading toneurocognitive deficits575–576

clinical syndrome 575etiologies 575incidence 575patterns of brain injury576, 580

selective vulnerability in theneonatal brain 576

timing of brain injury575–576

watershed predominantpattern of injury 576, 580

neonatal encephalopathyoutcomes 9–11

ADHD 579behavioral problems 579blindness 578case study of follow-up580–582

cerebral palsy (CP) 10–11,578

cognitive deficits 578–579development of newtherapies 10

epilepsy 578executive function deficits579

hearing loss 578language developmentdisorders 579

memory problems 579mental retardation (MR) 11mortality rates 9–10motor problems in theabsence of cerebralpalsy 578

neuromotor problems 578neurosensory problems 578quality of life 579–580relation to extent of injury9–10

relation to patterns of braininjury 580

relation to severity ofencephalopathy 580

sensorineural hearing loss578

specific neurologicaloutcomes 577–580

spectrum of neurocognitiveabnormalities 576–577

visual impairment 578neonatal intensive careNICU characteristics andGMH-IVH prevention290

see also extendedmanagement following

resuscitation; medicalethics in intensive care

neonatal ischemic strokeclinical manifestations

296–297definition 296in the preterm infant 297see also perinatal stroke

neonatal jaundice andneurotoxicity 311–312see also bilirubin toxicity

neonatal lupus syndrome98–99

neonatal resuscitationdelivery room decision

making 460–461evidence-based principles

453evidence-based resuscitation

medicine 460importance of good

communication 453,460–461

information required by theneonatal resuscitationteam 453, 454

intrapartum fetalresuscitation 453

medicolegal issues 453,460–461, 461–462

Neonatal ResuscitationProgram of the AAP 453

see also cardiopulmonaryresuscitation of thenewborn; cerebralresuscitation; extendedmanagement followingresuscitation

Neonatal ResuscitationProgram of the AmericanAcademy of Pediatrics 453

neonatal seizure rates, effectsof using EFM 182–183

neonatal seizuresantiepileptic drug treatment

519–520, 520–521,521–522

brainstem releasephenomena 510–511

classification 500–506, 516clinical seizure criteria

500–506, 516clonic seizures 500–502,

502–504electroclinical dissociation

512–513electroclinical uncoupling

510, 512–513electrographic seizure

criteria 508–510etiologies 513–517ictal EEG patterns

classification 510incidence rates with clinical

vs. EEG criteria 513issues regarding who and

how to treat 499, 501

Index

621






neonatal seizures (cont.)multifocal (fragmentary)clonic seizures 502–504

myoclonic seizures 505–506non-epileptic behaviors ofneonates 506–508

non-ictal functionaldecortication 510–511

novel antiepileptic drugapproaches 521–522

pathogenesis and timingof the disease process517–518

principles of therapy519–522

prognosis 518–519recognition of seizures499–500

seizure duration andtopography 510

status epilepticus 510subcortical seizures510–511, 512–513

subtle seizure activity 500tonic seizures 504–505video-EEG/polygraphicmonitoring 499–500,508–510

see also epilepsy; seizures;status epilepticus

neonatal sepsis 9risk of neurodevelopmentalsequelae 551–552

see also bacterial sepsis inthe neonate

neonatal stroke 5–6see also perinatal stroke

neonatal thyrotoxicosis 78neural tube defects 266neurodegeneration in HIEneonatal animal models26–29

neonatal rat and mouse16, 19, 26–27

neuroprotection andneuroregenerativestrategies in the pigletmodel 28–29

newborn human HIE25–26

newborn piglet 28–29relevance of animal modelsof HIE 26

neurodegenerationmechanisms see cell deathmechanisms

neurodegenerative disorders,neuroimaging diagnosis210, 211, 213, 223–228

neurodevelopmental andcognitive outcomes ofIUGR 86–87, 88

neurodevelopmental disability,correlation with pretermbrain injury 48

neurodevelopmental outcomesof preterm birth 544

early childhood assessments544–548

EPIcure study 545–547Finnish National ELBWCohort 546, 547

later childhood and beyond552

NICHD Neonatal ResearchNetwork Follow-up StudyGroup 546, 547–548

Rainbow Babies ELBWcohorts 546, 547

Victoria InfantCollaborative StudyGroup reports 545, 546

neurodevelopmental sequelaerisk factors 548–552

antenatal factors 551bronchopulmonarydysplasia (BPD) 551

cranial ultrasound (CUS)abnormalities 549–550

gender-specific vulnerability551

level of maternal education551

magnetic resonance imaging(MRI) findings 550–551

necrotizing enterocolitis(NEC) 551–552

neonatal sepsis 551–552preterm infant brain injury549–551

racial factors 551scoring systems for multiplemorbidities 552

social factors 551neurogenesis

response of the subventricularzone (SVZ) 42

self-repair response toinjury 42

neurogenetic disorders of thebrain

Aicardi-Goutieres syndrome281–282

apparent TORCH infection281–282

bleeding in the newborn 282central hypoventilation 283clinical genetics evaluation277

cobalamin disorders 282conditions presenting withhypotonia 277–281

congenital centralhypoventilationsyndrome 283

congenital musculardystrophies 280–281

congenital myasthenias 281congenital myopathies 280congenital neuropathies281

diagnostic approach tohypotonic conditions277–278

hereditary hemorrhagictelangiectasia 282

hydrocephalus 282–283intracranial hemorrhage 282L1 syndrome 282–283MECP2 related congenitalencephalopathy 279

MTHFR deficiency 282myotonic dystrophy type 1279

Pompe disease (infantiletype) 280

Prader–Willi syndrome278–279

resemblance to fetaland neonatal braininjury 277

spinal muscular atrophy(SMA I type) 279

ventriculomegaly 282–283X-linked hydrocephaluswith stenosis of theaqueduct of Sylvius(HSAS) 282–283

neuroimagingHIE features 189neonatal encephalopathy 8

neuroimaging diagnosis214–228

developmentalabnormalities 210, 211,213, 214–216

hypoxia–ischemia 216–219infections 223, 224inflammatory processes223, 224

intracranial hemorrhage219–220, 221

metabolic disorders 210,211, 213, 223–228

neurodegenerativedisorders 210, 211, 213,223–228

neurovascular disease216–222

occlusive neurovasculardisease and sequelae220–222

toxic disorders 210, 211,213, 223–228

trauma 220, 222–223neuroimaging technologies

209–213computed tomography (CT)209–210

functional imaging 209magnetic resonanceimaging (MR, MRI)210, 211–213

nuclear medicine (NM)210–211

positron emissiontomography (PET)210–211

single photon emissioncomputed tomography(SPECT) 210–211

structural imaging 209ultrasonography (US)

209, 210neuroinflammation, in HI

brain injury 38–40neurological abnormalities,

IUGR complications84–85

neurological development andIUGR 84

neuromotor problems,neonatal encephalopathyoutcomes 578

neuronal death mechanisms 40see also cell deathmechanisms

neuronal generation disorders269

neuronal injury initiators inasphyxia 144–145

neuronal migration disorders9, 269–270

neuropathies, congenitalconditions 281

neuropathological evaluations,timing of neonatal braininjury 261

neuroprotection after HIinjury

biphasic cell death after HIinjury 485–486

conditions which causeHIE 485

effects on EEG epileptiformtransients 490–492

effects on excitotoxicity afterHI 490–492

endogenousneuroprotection 492–493

hypothesis and implications493–494

induced hypothermia486–487

insulin-like growth factors(IGFs) 489

‘latent’ phase in earlyrecovery 486–487, 493

therapeutic targets ofhypothermia therapy488–492

timing of interventiontherapies 486–487,493–494

window of opportunity forinterventions 486–487,493–494

neuroprotection withhypothermia 486–487

clinical evidence fortherapeutic effect 487

depth of cooling 487duration of cooling 486–487effects on inflammatory

second messengers489–490

effects on programmed celldeath 488–489

Index

622






long-term neuroprotection487

therapeutic targets 488–492timing of initiation 486

neuroprotective endogenousresponses

post-insult adaptivehypometabolism 492–493


neurosensory problems,neonatal encephalopathyoutcomes 578

neurovascular disease,neuroimaging diagnosis216–222

neurovascular unit,functioning in HI braininjury 38

neurulation (neural tubeformation) disorders266–267

neutropenia, IUGRcomplication 83–84

newborn neurologicalevaluations, timing ofneonatal brain injury 259

NICU characteristics andGMH-IVH prevention290

NIRO 500 monitor 233NIROS-SCOPE 232NIRS (near-infrared

spectroscopy),development of cerebraloximeters 232

NIRS-based cerebral oximetersin current use 233–234

Foresight monitor 233INVOS cerebral oximeter233

NIRO 500 monitor 233NIRS-based cerebral oximetryaccuracy compared to a goldstandard 234

cytochrome absorption ofnear-infrared light 232

defining the ischemicthreshold 234

hemoglobin absorption ofnear-infrared light 232

interpreting abnormalcerebral oximetry 235–236

lack of randomizedcontrolled clinical trials232

NIROS-SCOPE 232relevance to clinicaloutcome 234–235

theory 232–233validation 234–235

NIRS future possibilitiesautoregulation analysis 237measures of cerebral bloodflow 236

measures of cerebral bloodvolume 236

somatic regional oximetry236

visible light spectroscopy(VLS) 236–237

nitric oxide, inhaled nitricoxide (iNO) therapy 423,426–428, 472

nitroglycerin (tocolyticagent) 64

NOMO-VAD postoperativesupport 447

non-contraction stress test 81non-epileptic behaviors of

neonates 506–508dystonia without EEGseizures 507–508

jitteriness with EEGcorrelates 506

myoclonic movementswithout EEG seizures506–507

tremulousness with EEGcorrelates 506

non-ictal functionaldecortication 510–511

non-immune hydrops 325, 326non-ketotic hyperglycinemia,

EEG diagnosis 204non-reassuring FHR,

management 183non-specific chronic villitus

250, 251non-stress test (NST) 165–167

basis for the NST 166efficacy 167how to perform the test 166interpretation of the test166–167

when to perform 166non-vertex presentation

138–139NSC (neural stem cell)/NPS

(neural progenitor cell)transplantation after HI29–30

nuchal cord 246nuclearmedicine (NM) 210–211nucleated red blood cell

(NRBC, erythroblast)count

and intrauterine stress242–243

increase in IUGR 83–84timing of neonatal braininjury 258, 259

nutrient supplementation forIUGR 89

nutritional status and risk ofpreterm birth 60

nutritional status of themother and IUGR risk 79

nutritional support(asphyxiated infant)531–532

necrotizing enterocolitis532–539

recommendations 539

nutritional support (prematureinfant)

complications due toimmature gastrointestinaltract 527, 528, 529

continuous NG feeding 527development of thegastrointestinal tract 527,528, 529

early gastrointestinalpriming 529–530

enteral feeding 527–530ESPGN guidelines forfeeding 529

gastric feeding 527gastroesophageal reflux 527gastrointestinal priming529–530

intermittent gavage 527nasogastric feeding 527necrotizing enterocolitis532–539

parenteral feeding 530–531recommendations forasphyxiated infants 539

routine support 527, 528,529

transpyloric feeding 527–529trophic feeding 529–530

observer variability in EFMinterpretation 182

obstetric abnormalitiesmarginal cord insertion 107placenta accreta 106–107placenta increta see placentaaccreta

placenta percretasee placenta accreta

placenta previa 103–104placental abruption104–105

short umbilical cord 107vasa previa 105–106velamentous cord insertion107, 247 see also vasaprevia

obstetrical risk factors forpreterm birth 60–61

occlusive neurovasculardisease and sequelae,neuroimaging diagnosis220–222

occupational therapy, use inCP management 559

olfactory bulb, source of NSCs/NPCs for transplantationafter HI 29–30

oncosis see necrosisoperative abdominal delivery

see cesarean sectionoperative vaginal delivery 65,

135–136fetal indications for 65maternal indications for 65

opioid abuse in pregnancy117–118

contraindications forbreastfeeding 118

neonatal administration ofnaloxone (Narcan) 118


neonatal health risks 118neonatal respiratory

depression 118risk of sudden infant death

syndrome (SIDS) 118withdrawal in neonates 118withdrawal in pregnancy 118

organ damage, indicationsof asphyxia 6–7

organic acidemias, HIEdifferential diagnosis395–396, 397

oxygen, use incardiopulmonaryresuscitation of thenewborn 457–458

oxygen free radical inhibitors10, 480–481

oxygen free radicals, role inpreterm brain injury 51

p53/p63/p73 family of tumorsuppressors 22

p75NTR mediation ofapoptosis 22

pachygyria 269–270pain relief in preterm

labor 62pancuronium bromide 471parasagittal border-zone injury

190–191, 192parasympathetic NS, influence

on fetal heart rate 176parent–infant interaction

difficulties and IUGR 85parenteral feeding 530–531partial fetal alcohol syndrome

(PFAS) 112, 113partial hypoxic–ischemic

injury 190parvovirus, congenital

infection 9patient safetycomponents of a safe

delivery room 467–468future enhancements of

medical training 467–468history of medical training

464–465Institute of Medicine Reports

(1999 and 2001) 464JCAHO recommendations

(2004) 464limitations of traditional

medical training model464–465

new training andperformancemethodologies 465–467

reports andrecommendations 464

Index

623






patient safety (cont.)training for the challengesof the delivery room465–467

PCP (drug) use in pregnancy119

PCP (Pneumocystis jirovecii(carinii) pneumonia) 380

Peabody Picture VocabularyTest-Revised (PPVT-R)568

pediatric cardiac surgeryanesthesia 445balloon atrial septostomy(BAS) 444–445

cardiopulmonary bypass(CPB) 445–446

CO2 flooding 446cooling (perioperative) 446cooling (postoperative) 447corticosteroids 447DHCA (deep hypothermiccirculatory arrest) 446

glycemic control followingsurgery 447

head perfusion 446limitation of peri-operativeneurological injury445–447

low-flow CPB 446modified ultra-filtration(MUF) 447

NIRS-intraoperativemonitoring of cerebraloxygen delivery 446

NOMO-VAD postoperativesupport 447

postoperative management447

preoperative neurologicalinjury 444–445

timing of surgery 445pediatric cardiac surgery

neurodevelopmentaloutcomes 447–449

congenital heart lesiontype 448

correlation with length ofhospital stay 449

effects of intrinsic geneticvariables 447–448

effects of APOE(apolipoprotein E) genepolymorphisms 447–448

effects of 22q11.2 deletion448

effects of socioeconomicstatus 448

intraoperative factors448–449

perinatal asphyxia, role ofEFM in prediction182–183 see also asphyxia

perinatal care see medicalmalpractice, patient safety

perinatal death, and pretermbirth 59

perinatal HIV infectionAIDS-defining illnessesfor children 380

antiretroviral drug therapy382–383

antiretroviral prophylaxis383

classification of HIVinfection in children 380

clinical manifestations 380early diagnosis 380early treatment 382–383epidemiology 378HAART (highly activeantiretroviral therapy)382–383

HIV encephalopathy ininfants 380–382, 391

lymphoid interstitialpneumonia (LIP) 380

mechanisms of transmission379

neurologic manifestationsin the infant 380–382

PCP (Pneumocystisjirovecii (carinii)pneumonia) 380

prevention 383–384prognosis 383rates of transmission378–379

risk factors 379timing of transmission 379

perinatal hypoxia, incidence 49perinatal mortality rate

(PMR) 163perinatal mortality risk

163–164perinatal stroke

classification systems 296clinical manifestations296–297

development of therapies300–301

disorders caused by 296epidemiology 296incidence 296modeling stroke 300–301terminology 296

perinatal stroke evaluation 298electroencephalography298–299

history 298laboratory studies 299neuroimaging 298physical examination 298

perinatal stroke management299

perinatal stroke outcome299–300

epilepsy 300neonatal seizures 300neurobehavioral outcome300

neuromotor outcome 300stroke recurrence 300visual function 300

perinatal stroke risk factors297–298

antepartum factors 298infant factors 298intrapartum factors 298maternal factors 297–298

periventricular hemorrhage(PVH) 566

periventricular leukomalacia(PVL) 48, 192–193

effects on language andspeech development 566

EEG diagnosis 205periventricular–

intraventricularhemorrhage

EEG diagnosis 204–205in HIE 193

peroxisomal disorders, HIEdifferential diagnosis 395

persistent pulmonaryhypertension of thenewborn (PPHN)

characteristics 419complication of IUGR 82definitions 419differential diagnosis419–420

pathogenesis 338, 420–421terminology 419

persistent pulmonaryhypertension of thenewborn (PPHN)comorbidities

growth and nutritionaldifficulties 436–437

hearing loss (sensorineuralhearing loss) 435–436

respiratory morbidities436

persistent pulmonaryhypertension of thenewborn (PPHN)outcome 425–435

conventional medicaltherapy (CMT) 425–426,432–434

ECMO treatment 428–435,430–431

inhaled nitric oxide (iNO)therapy 426–428

persistent pulmonaryhypertension of thenewborn (PPHN)treatment 421

alkalosis induced byventilation 422

exogenous surfactant422–423

extracorporeal membraneoxygenation (ECMO)424–425

gentle ventilation 422high-frequency ventilation(HFV) 422

hyperventilation andhypocapnia 422

inhaled nitric oxide (NO)423

liquid ventilation 422magnesium sulfate 424non-specific, physiologic

interventions 421–422pharmacologic approaches

422–424phosphodiesterase (PDE)

inhibitors 423–424vasodilation pharmacologic

therapies 423–424ventilator management 422

pH of umbilical arterialblood 5

pharmacologic treatments,use in CP management560–561

phenobarbital, GMH-IVHprevention 290

phenylephrine use in pregnancysee sympathomimetics

phenylketonuria (PKU),effects on fetaldevelopment 97–98

phenylpropanolamine use inpregnancysee sympathomimetics

phenytoin, fetal hydantoinsyndrome 100


physical growth, outcomesof IUGR 86

physical therapy, use in CPmanagement 559

piglet, neonatalneurodegeneration inHIE 28–29

placenta accreta 106–107association with tobacco

use in pregnancy 115clinical presentation

106–107complications 107description 106diagnosis 106–107etiology 106incidence 106management 107risk factors 106

placenta increta see placentaaccreta

placenta percreta see placentaaccreta

placenta previa 103–104association with tobacco use

in pregnancy 115clinical presentation 103complications 103–104description 103diagnosis 103etiology 103incidence 103management 103risk factors 103

Index

624






placental abnormalitiesand cocaine use inpregnancy 117

and IUGR etiology 78placental abruption 104–105association with tobacco usein pregnancy 115

clinical presentation 104complications 105description 104diagnosis 104etiology 104incidence 104management 104–105risk factors 104risk with chronichypertension 128

placental insufficiencyeffects on fetal development100


placental pathologyacute blood flow disruption243–244

amniotic fluid infection248–249

chronic twin-to-twintransfusion 244

correlates of intrauterinestress 240–243

fetal anemia 243fetal hemorrhage 243massive perivillous fibrindeposition (MPFD)251, 252

maternal floor infarction(MFI) 251, 252

maternal vascularunderperfusion 249–250,251

mechanisms of diminishedplacental reserves 249–251

mechanisms of umbilicalcord blood flowcompromise 244–248

meconium-inducedumbilical vascularnecrosis 240–241

meconium release and fetalstress 240–242

non-specific chronic villitus250, 251

pre-eclampsia 129–130purpose of investigations240

release of nucleated redblood cells (NRBCs)242–243

timing of intrauterine stress240–243


twin-to-twin transfusionsyndrome 244

villitus of unknown etiology(VUE) 250, 251

plasma volume expansiontherapy for IUGR 89

platelet counts, timingof neonatal braininjury 258

PMRI (perfusion MRI) 211,212

polycythemia 317–320asymptomatic infants 320blood flow and functionalchanges in organs318–319

blood viscosity 317–318blood viscosity and organoxygenation 318

brain uptake of oxygen 318causes 317, 318definition 317effects of increasedhematocrit on organs 317

effects on neurologicfunction 319

effects on organ blood flowand function 317

incidence 317long-term sequelae 319–320organ oxygenation andblood viscosity 318

problems in the newbornperiod 318, 319

recommendations fortherapy 320

signs and symptoms318–319

small-for-gestational-ageinfants 319

symptomatic infants 318,319–320

polyhydramnios, risk ofpreterm birth 60

polymicrogyria 270pomegranate juice,

neuroprotectivepotential 42

Pompe disease (infantile type)280

ponderal index 75porencephaly 272–273positron emission tomography

(PET) 210–211post-term pregnancy 137–138posthemorrhagic ventricular

dilation (PHVD) 287,288–289

postnatal hypotension/hypoperfusion, andbrain injury 50

postnatal prevention ofGMH-IVH 290

Potter's syndrome 78poverty, role in IUGR

etiology 78PPROM (preterm premature

rupture of the amnioticmembranes) 61

Prader–Willi syndrome278–279

pre-conception counseling,maternal disease and fetaldevelopment 101

pre-eclampsia 128, 129–130antihypertensivemedications 130

clinical features 129corticosteroids for fetal lungmaturity 130

definition 128, 129diagnosis 128, 129eclampsia 130effects on the fetus 129glucocorticoids for fetal lungmaturity 130

immune maladaptation129–130

incidence 129pathogenesis 129–130placental pathology 129–130risk factors 129risk with chronichypertension 128

role in IUGR 78, 79, 80seizure prophylaxis 130timing of delivery 130treatment 130

pregnancy complications,risk of preterm birth 61

premature birth see pretermbirth

prematurity in multiplegestations 70

causes of premature birth 70incidence 69, 70pathophysiology of pretermlabor 70

prediction of pretermlabor 70

prevention of pretermlabor 70

treatment of preterm labor 70prepartum evaluation, timing

of neonatal brain injury256

presentation, non-vertexpresentation 138–139

presumed perinatal ischemicstroke (PPIS)

clinical manifestations 297definition 296

preterm birthassociation with tobacco usein pregnancy 115

causes 59–60costs of medical support 544definition 59effects on academicoutcomes 566–568

effects on language andspeech development565–566

ethnic differences inincidence 59

etiology 59–60hypoxia tolerance of thepreterm brain 59

incidence 59neurological morbidity 59pathogenesis of spontaneous

preterm labor 60risk of cerebral palsy 10, 59risk of mental retardation 59risk of neurodevelopmental

sequelae 544, 549–551risk of perinatal death 59risk of vision impairment 59survival rates 59, 544see also neurodevelopmental

outcomes of pretermbirth, prematurity inmultiple gestations

preterm birth risk factorsassisted reproductive

technologies (ART) 60bleeding 60cervical incompetence

60–61complications of

pregnancy 61demographic factors 60ethnicity 60fetal anomalies 60history of preterm birth 60maternal age 60medical or surgical

complications 61multiple gestations 60obstetrical risk factors

60–61polyhydramnios 60poor nutrition 60preterm premature rupture

of the amnioticmembranes (PPROM) 61

socioeconomic status 60substance abuse 60uterine abnormalities 60

preterm brain injurycorrelation with

neurodevelopmentaldisability 48

effects of loss of input fromother cells 49

etiology 49HIE patterns of injury

189–190incidence of perinatal

hypoxia 49long-term

neurodevelopmentalhandicap 48

neonatal encephalopathy 2neuropathology 48–49periventricular leukomalacia

(PVL) 48reduced grey matter

volume 48role of acute neural injury

48–49timing 49white-matter injury 48

preterm brain injurymechanisms

Index

625






preterm brain injurymechanisms (cont.)

glutamate excitotoxicity50–51

hypoxic/ischemic injury49–51

infection/inflammation51–53

oxygen free radicals 51postnatal hypotension/hypoperfusion 50

pyrexia 52–53role of cytokines 52role of microglia 52secondary tissue hypoxia52–53

sensitization to hypoxia–ischemia 53

vulnerable populations ofcells 50

preterm deliveryantenatal steroids for fetallung maturity 62

breech presentation 63cesarean section (operativeabdominal delivery)63, 65

delayed cord clamping 65delivery route 63en caul vaginal delivery 63fetal indications foroperative vaginaldelivery 65

magnesium sulfateadministration before 65

malpresentations 63management of 61–62maternal–fetaltransportation 61–62

maternal indications foroperative vaginaldelivery 65

multiple gestations 63operative vaginal delivery 65pain relief in pretermlabor 62

prophylactic forceps-assistedvaginal delivery 63

use of tocolytic agents 64vertex presentation 63very-low-birth-weightbreech fetus 63

preterm fetuseffects of asphyxia 63–64fetal monitoring 63–64intrapartum hypoxia andacidosis 63–64

preterm labordiagnosis 61multiple gestations 70pathogenesis 60

preterm neonateApgar scores 64umbilical cord blood gases 64

preterm premature rupture ofthe amniotic membranes(PPROM) 61

progesterone supplementationto prevent pretermlabor 70

programmed cell death(PCD) 14

autophagy 14, 15, 18effects of hypothermiatherapy 488–489

non-apoptotic forms 18see also apoptosis

prolapse of the umbilical cord,risk of asphyxia 2–3

PROM, amnioinfusion 63prophylactic forceps-assisted

vaginal delivery 63pseudoephedrine use in

pregnancysee sympathomimetics

pulmonary arterial disease 476pulmonary manifestations of

asphyxia 6pulmonary parenchymal

disease 475–476pyrexia

and preterm brain injury52–53

in labor 155pyridoxal-dependent seizures

394pyridoxine dependency,

EEG diagnosis 204pyridoxine-dependent

seizures 394pyruvate metabolism

disorders 396

quality of life, neonatalencephalopathy outcomes579–580

racial factorsdifferences in PMR andFMR 163

risk of neurodevelopmentalsequelae 551

role in IUGR etiology 78rat, neonatal

neurodegeneration inHIE 16, 19, 26–27

reading and related skillsacademic outcomes afterprematurity 566–567

assessment in children 565definition of readingdisability 565

outcomes in children withneural injuries 567

reading disorders in thegeneral population 565

see also language and speechdevelopment

refractory hypoxemiafollowing resuscitation,evaluation andmanagement 473–481

renal system, signs of asphyxiainjury 6

respiratory acidosis 402–403respiratory alkalosis 404–405resuscitation see neonatal

resuscitationRett syndrome, HIE

differential diagnosis 399Rhesus (Rh) alloimmunization

99–100risk factors for neonatal

encephalopathy 2, 3–4antepartum period 3–4intrapartum period 2, 4prior to conception 3, 4

rubella 365–367association with IUGR 77–78clinical signs of congenitalrubella syndrome 366

congenital rubellasyndrome 365

nature of the rubellavirus 365

neurologic manifestationsof congenital rubellasyndrome 367

recommendations 367transmission of rubella tothe fetus 365

vaccination programs365, 367

schizencephaly 270, 272Seckel syndrome 78secondary tissue hypoxia,

and preterm brain injury52–53

sedative-hypnotics, abuse inpregnancy 118

seizure prophylaxis,pre-eclampsia 130

seizurescorrelation with neonatalencephalopathy 5–6

HIE differential diagnosis393–396


see also epilepsy; neonatalseizures; status epilepticus

selective dorsal rhizotomy, usein CP management 560

sensitization to hypoxia–ischemia 53

sensorineural hearing loss,neonatal encephalopathyoutcome 578

sentinel events (acute totalasphyxia) 2–3

septicemia see bacterial sepsisin the neonate

septo-optic dysplasia 268severe encephalopathy

(stage III) 188severe ketoacidosis, HIE

differential diagnosis 397severe pulmonary

parenchymal disease475–476

short umbilical cord 107shoulder dystocia 136Silver syndrome 78single photon emission

computed tomography(SPECT) 210–211

small-for-gestational-age(SGA), definition 75–76see also intrauterinegrowth restriction (IUGR)

Smith-Lemli-Opitz syndrome 78smoking in pregnancy

see tobacco use inpregnancy

social risk factors forneurodevelopmentalsequelae 551

socioeconomic risk factorsfor language and speech

development afterprematurity 568

for neonatal encephalopathy3, 4

for preterm birth 60sodium bicarbonate

administration 459specific language impairment

(SLI) 569spina bifida 267spinal cord, signs of asphyxia

damage 6–7spinal muscular atrophy

(SMA I type) 279spreading depression, effects

of hypothermia therapyafter HI injury 492

ST waveform analysis(STAN) 184

stabilization aftercardiopulmonaryresuscitation 459

glucose administration 459hypoglycemia management

459metabolic acidosis 459naloxone administration 460sodium bicarbonate

administration 459Staphylococcus aureus, cause

of neonatal sepsis 332Staphylococcus epidermidis,

cause of neonatalmeningitis 349

status epilepticus 510see also epilepsy; neonatalseizures; seizures

status marmoratus 191, 507–508stem cell therapy for pediatric

HIE 29source of NSC/NPSs for

transplantation 29–30stillbirth, association with

tobacco use inpregnancy 115

STIR (fat suppression short TIinversion recoveryimaging) 211, 212

Index

626






Streptococcus agalactiae, causeof neonatal meningitis348–349 see also groupB streptococcus (GBS)

Streptococcus pnemoniae(pneumococcus), cause ofneonatal meningitis 349

Streptococcus pyogenes(group A b-hemolyticstreptococcus), causeof neonatal sepsis 332,341–342

strokeEEG diagnosis 205intrauterine stroke 9neonatal stroke 5–6see also perinatal stroke

subarachnoid hemorrhage inthe term infant 291

subcortical seizures 510–511,512–513

subdural hemorrhage in theterm infant 291

subgaleal hemorrhage in theterm infant 291–292

substance abuse in pregnancyadulterants in illicitdrugs 120

alcohol see ethanolamphetamine 119barbiturates 118benzodiazepines 118cocaine 116–117contaminants in illicitdrugs 120

drug distribution inpregnancy 110

ethanol 112–114general effects on the fetus110–111

heroin see opioidsincidence 110LSD 119marijuana 116methadone see opioidsmethamphetamine 119methodological limitationsin studies 111–112

methylphenidate 119opioids 117–118parental care of thenewborn 121

PCP 119risk of preterm birth 60routes of fetal exposure 110screening for substanceabuse 120–121

sedative-hypnotics 118smoking see tobaccosocial support for motherand newborn 121

substitutes in illicitdrugs 120

sympathomimetics 119tobacco 114–116toluene embryopathy 120volatile substances 120

subtle seizure activity 500subventricular zone (SVZ),

neurogenerative responseto injury 42

sudden infant death syndrome(SIDS)

and cocaine use inpregnancy 117

and opioid abuse inpregnancy 118

and tobacco use inpregnancy 115, 116

percentage of overall infantmortality 163–164

sulfite oxidase deficiency 394superimposed pre-eclampsia

128, 129see also pre-eclampsia

surfactant replacement therapy471–472

sympathetic NS, influence onfetal heart rate 176


sympathomimetics, abuse inpregnancy 119

symphysis-to-fundus height,evaluation of fetalgrowth 81

syphilis see congenital syphilissystemic lupus erythematosus

(SLE), effects on fetaldevelopment 98–99

tachycardia (fetal) 177, 181temperature and hypoxic–

ischemic injury 155terbutaline (tocolytic agent) 64term infant, HIE patterns of

injury 189–190termination period concept

265thanatophoric dwarfing 78thrombocytopenia, IUGR

complication 83–84thrombophilia, and IUGR 89timing of asphyxial events

biochemical markers ofasphyxia 258–259

computed tomography (CT)scan 260

electroencephalogram(EEG) evaluation257–258

fetal heart-rate monitoring256–257

findings which suggestantepartum events 262

hematological abnormalities258, 259

identification of etiology255–256

imaging studies 260–261laboratory findings 258–259lymphocyte counts 258maternal history of fetalactivity 256

meconium-stained amnioticfluid 257

MRI studies 260–261neuropathologicalevaluations 261

newborn neurologicalevaluations 259

nucleated red blood cell(NRBC) count 258, 259

placental pathology 261platelet counts 258prepartum evaluation 256process of determination255–256

reasons for determination255

recognition of an acuteevent 256

seizures 257ultrasound examination 260

timing of intrauterine stress,placental pathologiccorrelates 240–243

tizanidine, use in CPmanagement 560

tobacco use in pregnancy114–116

association with cleft lip/palate 115

association with IUGR 80association with placentaaccreta 115

association with placentaprevia 115

association with placentalabruption 115

association with pretermbirth 115

association with stillbirth115

consumption of smokelesstobacco 115

environmental tobaccosmoke exposure 115–116

fetal effects of carbonmonoxide 114

fetal effects of cyanide 114fetal exposure to nicotine115

health risks for the infant115

incidence of smoking inpregnancy 114

maternal passive smokeexposure 115–116

mechanisms causing fetalhypoxemia 114


nicotine in breast milk 115tobacco products secreted inbreast milk 115

toxic substances in tobacco114

tocolytic agents 64tocolytic therapy (for preterm

labor) 61

toluene embryopathy 120tonic seizures 504–505TORCH agents of infection

361neurogenetic disorders with

similar features 281–282toxic disorders, neuroimaging

diagnosis 210, 211, 213,223–228

Toxoplasma gondii infectionsee congenitaltoxoplasmosis

toxoplasmosis see congenitaltoxoplasmosis

transient neonatal diabetesmellitus 78, 83

transpyloric feeding,premature infant 527–529

trauma, neuroimagingdiagnosis 220, 222–223

tremulousness with EEGcorrelates in neonates 506

Treponema pallidum 332see also congenitalsyphilis

tricarboxylic acid cycledefects 396

trichomonas infection 61trimethadone, fetal

trimethadione syndrome80

trophic feeding 529–530Trypanosoma cruzi infection,


tuberous sclerosis complex 270tumor necrosis factor (TNF)

family, mediation ofapoptosis 22

twin-to-twin transfusionsyndrome (TTTS) 70, 244

amnioreduction 71association with IUGR 78clinical presentation 70–71description 70diagnosis 70–71endoscopic laser

photocoagulation 71incidence 70management 71neonatal outcomes 71

twins see multiple gestations

ulegyria 190–191ultrasonography (US) 209, 210ultrasound evaluationfetal growth and well-being

81multiple gestations 69–70timing of neonatal brain

injury 260umbilical arterial blood pH 5umbilical corddelayed clamping in

premature infants 65marginal cord insertion 107short umbilical cord 107

Index

627






umbilical cord (cont.)velamentous cord insertion107, 247 see also vasaprevia

umbilical cord blood flowcompromise

coiling 245compression 244–245constriction (stricture,torsion, coarctation) 245

cord entanglement 246cord prolapse 2–3, 247excessively long or shortcord 245–246

fetal vascular thrombosis247, 248

nuchal cord 246obstruction 244–245true knots 246–247velamentous vessels 247

umbilical cord blood gases,fetal monitoring 64

urea cycle disorders, HIEdifferential diagnosis395–396, 398

uterine abnormalities, pretermbirth risk factors 60

uterine rupturerisk of asphyxia 2–3spontaneous 135with VBAC 134–135

VACTERL association 78vacuum delivery 135–136

vaginal birth after cesarean(VBAC) 2, 65, 72,134–135

vancomycin-resistantenterococcus (VRE) 342

varicella-zoster virus (VZV)infection 369–371


congenital varicellasyndrome 369–370

herpes zoster 369, 370recommendations 371vaccination 370

vasa previa 105–106clinical presentation 105complications 106description 105diagnosis 105etiology 105incidence 105management 105–106risk factors 105


vascular malformations of thebrain 274

VATER association 78vecuronium iodide 471vein of Galen malformations

274velamentous cord insertion

107, 247 see also vasaprevia

velocardiofacial syndrome(VCFS) 443see also 22q11.2 deletion

ventilationcardiopulmonaryresuscitation of thenewborn 455–457

support followingresuscitation 470–472

ventral patterning(prosencephalic cleavage)disorders 267–268

ventriculomegaly 282–283, 289vertex presentation, preterm

delivery 63vibroacoustic stimulation

(VAS) 81, 167–168video-EEG/polygraphic

monitoring 499–500,508–510

villitis 137villitis of unknown etiology

(VUE) 250, 251visible light spectroscopy

(VLS) 236–237vision impairmentand preterm birth 59neonatal encephalopathyoutcome 578

vitamin E, role in necrotizingenterocolitis pathogenesis536

vitamin K, GMH-IVHprevention 290

VLBW (very-low-birth-weight) breech fetus,preterm delivery 63

VLBW infants born SGA,outcomes of IUGR86–87, 88

volatile substance abuse inpregnancy 120

Walker-Warburg syndrome280

warfarin, fetal warfarinsyndrome 80

watershed distributionof neuronal loss inasphyxia 147, 148, 151,153–154

watershed infarction 190–191watershed-predominant

pattern of brain injury576, 580

white-matter injury in HIE192–193

language and speechdevelopmentaldisorders 570

see also metabolic disordersdifferential diagnosis

Williams syndrome 78

X-linked hydrocephaluswith stenosis of theaqueduct of Sylvius(HSAS) 282–283

Index

628






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