Fetal and Neonatal Brain Injury: Mechanisms, Management, and the Risks of Practice, 3rd Edition

Half-title......Page 3
Title......Page 5
Copyright......Page 6
Contents......Page 7
Contributors......Page 11
Foreword......Page 17
Preface......Page 19
PART I Epidemiology, Pathophysiology, and Pathogenesis of Fetal and Neonatal Brain Injury......Page 21
1 Perinatal asphyxia: an overview......Page 23
Asphyxia......Page 25
Incidence of asphyxia and correlation with outcome......Page 26
Fetal and neonatal blood gas levels......Page 29
Laboratory correlates......Page 31
Seizures......Page 32
Neonatal neurologic syndrome......Page 34
Multiple organ dysfunction in asphyxiated infants......Page 36
Focal brain infarcts (stroke) in neonates......Page 37
Conditions causing neonatal depression and/or neonatal encephalopathy that mimic perinatal asphyxia......Page 38
Cerebral palsy......Page 39
Epidemiology of mental retardation......Page 41
Conclusion......Page 42
REFERENCES......Page 43
2 Mechanisms of brain damage in animal models of hypoxia–ischemia in newborns......Page 50
Piglet model of HIE......Page 51
Neuronal signal transduction mechanisms important for brain damage in HI......Page 52
Role of excitotoxic mechanisms in HI brain damage in newborns......Page 56
Glutamate transporter defects do not occur early during the emergence of striatal neurodegeneration after HI......Page 57
NMDA receptor phosphorylation is elevated in piglet striatum after HI......Page 61
Na, K-ATPase is defective early after HI in newborn piglets......Page 65
Neuronal cell death in newborn animal models of HI......Page 68
The apoptosis–necrosis cell death continuum......Page 71
REFERENCES......Page 73
Cellular energy transformations......Page 78
Excitatory neurotransmitter neurotoxicity......Page 81
Intracellular calcium overload......Page 85
Reactive oxygen species, iron, and nitric oxide......Page 88
Nitric oxide......Page 90
Necrosis vs apoptosis......Page 92
REFERENCES......Page 97
Causes of pathological asphyxia......Page 103
What initiates neuronal injury?......Page 104
Systemic and cardiovascular adaptation to asphyxia......Page 105
Fetal responses to hypoxia......Page 106
Fetal responses to asphyxia......Page 108
Uterine contractions and brief repeated asphyxia......Page 111
1:2.5 occlusion series......Page 112
Acute-on-chronic asphyxia......Page 113
Acidosis: friend or foe?......Page 116
Hypotension and the “watershed” distribution of neuronal loss......Page 118
The pattern of injury: repeated insults......Page 119
Cortical vs subcortical grey matter......Page 120
White-matter injury......Page 121
Temperature and hypoxia–ischemia......Page 122
Concluding thoughts......Page 123
REFERENCES......Page 125
Anencephaly and neural tube defects......Page 131
Occipital encephalocele......Page 134
Anterior encephalocele......Page 135
Atelencephaly and aprosencephaly......Page 136
Hydrocephalus......Page 137
Chiari II malformation......Page 138
Megalencephaly......Page 139
Vascular malformations......Page 140
Vein of Galen malformation......Page 141
Carotid artery malformations......Page 142
Diagnostic approach to newborn malformations of the brain......Page 143
REFERENCES......Page 144
Factors associated with prematurity......Page 149
Obstetrical factors......Page 150
Management of preterm labor......Page 151
Initial approach......Page 152
Management of labor and delivery in the preterm gestation......Page 153
Malpresentation, multiple gestations......Page 154
Labor and delivery......Page 155
Management of FHR patterns......Page 157
Shoulder dystocia......Page 158
Fetal......Page 159
REFERENCES......Page 160
Introduction......Page 165
Factors affecting fetal growth......Page 166
Incidence of IUGR......Page 167
Fetal factors......Page 168
Maternal factors......Page 169
Environmental factors......Page 171
Other associations with IUGR......Page 172
Detection of the fetus with IUGR......Page 173
Fetal and neonatal asphyxia......Page 174
Hyperglycemia......Page 175
Hematologic problems......Page 176
Delayed ossification and large fontanels......Page 177
Accelerated neurological development......Page 178
Historical perspective......Page 179
Mortality and morbidity......Page 180
Development and intelligence quotient......Page 181
Cerebral palsy......Page 182
Prevention......Page 183
Conclusion......Page 185
REFERENCES......Page 186
Intraventricular hemorrhage in the full-term infant......Page 195
Extracorporeal membrane oxygenation (ECMO)......Page 196
Neonatal intracranial hemorrhage in pretern infants......Page 197
Pathogenesis of ICH......Page 198
Risk and protective factors for ICH......Page 199
Diagnosis of ICH......Page 200
Diagnosis of posthemorrhagic ventriculomegaly......Page 201
Outcome following ICH......Page 202
Phenobarbital......Page 203
Antenatal prevention......Page 204
REFERENCES......Page 205
PART II Pregnancy, Labor, and Delivery Complications Causing Brain Injury......Page 209
Introduction......Page 211
Diabetes mellitus......Page 212
Thyroid disease......Page 214
Congenital adrenal hyperplasia......Page 216
Seizure disorder......Page 217
Psychiatric disorders in pregnancy......Page 218
Reproductive effects of metabolic disorders......Page 220
Genetic disorders......Page 221
Autoimmune disorders, including systemic lupus erythematosus......Page 222
Medications during pregnancy......Page 223
Presence of antiphospholipid antibodies and SS-A (Ro) and SS-B (La) antibodies.......Page 224
Patient in remission with SS-A or SS-B antibodies......Page 225
Summary......Page 226
REFERENCES......Page 227
Perinatal mortality......Page 232
Sensitivity, specificity, positive and negative predictive value......Page 233
Contraction stress test......Page 234
How to interpret the test......Page 235
When to perform the NST......Page 236
How to interpret the test......Page 237
Vibroacoustic stimulation......Page 238
Maternal perception of fetal movement......Page 239
The biophysical profile......Page 240
Doppler......Page 241
REFERENCES......Page 242
The history of EFM......Page 246
Fetal oxygenation......Page 247
Chemoreceptors, baroreceptors, and cardiac output......Page 248
Accelerations......Page 251
Fetal response to hypoxia/asphyxia......Page 252
Periodic patterns: late, early, and variable decelerations......Page 253
Changes in baseline rate: tachycardia and bradycardia......Page 254
Role of EFM in predicting perinatal asphyxia......Page 257
Methods for detecting fetal acidemia......Page 260
REFERENCES......Page 261
Clinical presentation and diagnosis......Page 264
Placental abruption......Page 265
Management......Page 266
Clinical presentation and diagnosis......Page 267
Candidate selection......Page 268
Managing labor in patients undergoing VBAC......Page 269
Summary......Page 270
REFERENCES......Page 271
Epidemiology......Page 276
A genetic basis for preeclampsia?......Page 277
Definition......Page 278
Outcome studies......Page 279
Fetal effect of disorders of ß-oxidation of fatty acids on maternal health......Page 280
Amniotic fluid embolism......Page 281
Risk factors......Page 282
Shoulder dystocia......Page 283
Risk factors......Page 284
Complications of shoulder dystocia......Page 285
Operative intervention......Page 287
REFERENCES......Page 290
Drug distribution in pregnancy......Page 294
Methodologic limitations......Page 295
Ethanol......Page 296
Tobacco......Page 299
Marijuana......Page 301
Cocaine......Page 302
Opioids......Page 306
Sympathomimetics......Page 308
PCP......Page 309
Volatile substances of abuse......Page 310
Adulterants, substitutes, and contaminants......Page 311
Screening......Page 312
Summary......Page 313
REFERENCES......Page 314
Laboratory investigation......Page 323
Incidence......Page 324
Microbiologic pathogens......Page 325
Adverse fetal outcome......Page 326
Chorioamnionitis and cerebral palsy......Page 327
Treatment......Page 329
REFERENCES......Page 330
Risk factors......Page 334
Diagnosis......Page 335
Treatment......Page 338
Specific organisms......Page 339
Epidemiology......Page 340
Clinical presentation......Page 341
Prevention......Page 342
Chemoprophylaxis......Page 344
Escherichia coli......Page 345
Streptococcus pyogenes (group A beta-hemolytic streptococcus)......Page 346
REFERENCES......Page 347
Need for lumbar puncture......Page 353
Etiology......Page 355
Bacteremia and susceptibility......Page 356
Blood-brain barrier......Page 357
Cerebrospinal fluid......Page 358
Other laboratory evaluations......Page 359
Complications......Page 360
Treatment and management......Page 361
Choice of antibiotics......Page 362
Duration of antibiotics......Page 363
Corticosteroids......Page 364
Neurological sequelae......Page 365
Neonatal approach......Page 367
REFERENCES......Page 368
Toxoplasmosis......Page 375
Outcome in infants symptomatic at birth......Page 376
Recommendations......Page 377
Outcome in infants asymptomatic at birth......Page 378
Outcome in infants symptomatic at birth......Page 379
Rubella......Page 380
Clinical manifestations of intrauterine rubella infection and the risk of neurologic sequelae......Page 381
Recommendations......Page 382
Congenital syphilis......Page 383
Recommendations......Page 384
Varicella-zoster virus......Page 386
Herpes simplex virus......Page 388
Clinical manifestations and consequences of perinatal and intrauterine HSV infections......Page 389
Diagnosis and treatment......Page 391
REFERENCES......Page 392
Introduction......Page 397
Perinatal transmission......Page 398
Time to AIDS......Page 402
Neurologic manifestations in the infant......Page 403
Prognostic factors......Page 405
Recommendations......Page 406
REFERENCES......Page 407
Patterns of brain injury in HIE and inborn errors of metabolism......Page 412
Clinical features of HIE and inborn errors of metabolism......Page 416
Isolated seizures......Page 417
Nonketotic hyperglycinemia......Page 418
GABA transaminase deficiency......Page 419
Organic acidemias and urea cycle disorders......Page 420
Fatty acid oxidation defects......Page 421
Mitochondrial disease......Page 422
Maple syrup urine disease......Page 423
HHH syndrome......Page 424
Summary......Page 425
REFERENCES......Page 426
PART III Diagnosis of the Infant with Asphyxia......Page 429
General evaluation......Page 431
Neurologic assessment in hypoxic–ischemic encephalopathy......Page 432
Electroencephalography......Page 433
Management of hypoxic–ischemic encephalopathy......Page 434
Neuroprotection......Page 435
Parasagittal border-zone injury......Page 436
Deep gray nuclei......Page 437
Cerebellum......Page 438
Focal brain injury......Page 439
White-matter injury......Page 440
Conclusion and future prospects......Page 441
REFERENCES......Page 442
Indication for EEG......Page 445
Electrodes and application......Page 446
Duration to obtain sleep states......Page 447
Documenting behavior during recording......Page 448
Report format......Page 449
Ontogeny of sleep stage......Page 450
Theta bursts......Page 451
EEG in diffuse encephalopathy......Page 456
Grading encephalopathy using the EEG......Page 457
Specificity of the “encephalopathic” EEG......Page 458
Prognostic value of the encephalopathic EEG......Page 459
Aicardi syndrome......Page 460
Periventricular leukomalacia......Page 461
REFERENCES......Page 462
Introduction......Page 466
The fundamentals of neurosonographic imaging......Page 467
Fundamentals of Doppler cerebral blood flow velocity studies......Page 468
Germinal matrix and intraventricular hemorrhage......Page 469
Periventricular leukomalacia......Page 475
Profound perinatal asphyxia/hypoxic–ischemic injury......Page 477
Limitations......Page 479
Computed tomography......Page 491
Overview of MR techniques......Page 492
Magnetic resonance spectroscopy......Page 496
Perfusion magnetic resonance imaging and functional MRI......Page 497
CT and MR in neonates with perinatal hypoxic–ischemic injury......Page 499
SPECT/PET neuroimaging of neonatal brain injury......Page 503
REFERENCES......Page 505
NIRS devices......Page 510
Assumptions and potential limitations......Page 514
Measurement and validity of cerebral hemodynamic parameters in the term and preterm infant......Page 515
Measurement and validity of cerebral oxygenation parameters in the term and preterm infant......Page 517
Neonatal cerebral hemodynamics and oxygenation during intensive care......Page 518
Correlating cerebral NIRS measurements with outcome......Page 522
Applications in cardiovascular surgery......Page 523
Antenatal applications......Page 525
Brain imaging......Page 526
Use of exogenous dyes and contrast agents......Page 530
Future challenges......Page 533
REFERENCES......Page 534
Terminology and histopathology......Page 541
Fetal placental thrombi......Page 542
Villitis of unknown etiology......Page 544
The “Collaborative Study”......Page 545
Considerations of reliability studies......Page 546
Differences of opinions......Page 547
The era of cytokines......Page 548
Epidemiology, epiphenomena, and need for placental examinations......Page 549
Meconium and pulmonary pathology......Page 550
Pharmacopathologic concepts of meconium......Page 551
Physiopathologic considerations of meconium......Page 552
History......Page 553
Diagnosis, etiology, and timing of placental NRBCs......Page 554
Brief comments on recent articles on nucleated red blood cells......Page 555
Closing considerations of the chronology of fetal and neonatal brain injury......Page 556
REFERENCES......Page 561
25 Correlations of clinical, laboratory, imaging and placental findings as to the timing of asphyxial events......Page 566
Prepartum evaluation......Page 567
Meconium-stained amniotic fluid......Page 568
Nucleated red blood cell count......Page 569
Biochemical markers of asphyxia......Page 570
Newborn neurological evaluations......Page 571
Imaging studies......Page 572
Conclusion......Page 573
REFERENCES......Page 574
PART IV Specific Conditions Associated with Fetal and Neonatal Brain Injury......Page 577
26 Hypoglycemia in the neonate......Page 579
Definition......Page 580
Management of the neonate at risk......Page 582
Therapy......Page 583
Recurrent or persistent neonatal hypoglycemia......Page 585
Hormone deficiencies......Page 586
Hyperinsulinemic (organic) hypoglycemia......Page 587
Animal data......Page 589
Follow-up studies......Page 590
Pathogenesis and pathophysiology......Page 592
Summary......Page 593
REFERENCES......Page 594
Neonatal jaundice and neurotoxicity......Page 597
Prediction of hyperbilirubinemia......Page 599
Management of neonatal hyperbilirubinemia......Page 600
Reemergence of kernicterus......Page 601
REFERENCES......Page 602
Effects of increased hematocrit on organ blood flow and function......Page 604
Relationship between polycythemia, blood viscosity, and organ oxygenation......Page 605
Problems in the newborn period......Page 606
Long-term sequalae......Page 607
Summary......Page 608
REFERENCES......Page 609
Proposed mechanisms of edema formation in patients with hydrops......Page 612
Neurologic injury associated with hydrops......Page 614
Postnatal management......Page 615
Outcome of hydropic infants......Page 616
REFERENCES......Page 617
Effect of respiratory acidosis/alkalosis on cerebral blood flow......Page 619
Effect of metabolic acidosis/alkalosis on cerebral blood flow......Page 624
Effect of respiratory acidosis/alkalosis on cerebral metabolism......Page 625
Effect of metabolic acidosis/alkalosis on cerebral metabolism......Page 627
Hypoxic–ischemic brain damage and metabolic acidosis......Page 628
Hypoxic–ischemic brain damage and respiratory acidosis/alkalosis......Page 630
Acidosis and perinatal hypoxic–ischemic brain damage......Page 632
Acknowledgments......Page 633
REFERENCES......Page 634
Historical aspects......Page 638
Meconium-stained amniotic fluid and fetal distress......Page 639
Adverse neurologic outcomes......Page 640
Pathophysiology of meconium passage......Page 643
Potential mechanisms of neurologic injury......Page 644
Timing of meconium passage......Page 649
Other elements used to assess timing of injury......Page 652
Thick-versus thin-consistency meconium......Page 655
REFERENCES......Page 656
32 Persistent pulmonary hypertension of the newborn......Page 662
Differential diagnosis of persistent pulmonary hypertension of the newborn......Page 663
Pathogenesis of persistent pulmonary hypertension of the newborn......Page 664
Ventilator management......Page 666
Inhaled nitric oxide......Page 667
Extracorporeal membrane oxygenation......Page 668
Outcome of PPHN survivors treated with conventional medical therapy......Page 669
PPHN follow-up studies......Page 670
Risks associated with ECMO......Page 673
ECMO follow-up studies......Page 674
Outcome studies comparing conventional medical therapy and ECMO......Page 678
NO follow-up studies......Page 681
REFERENCES......Page 682
Preoperative period......Page 689
Circulatory arrest......Page 690
Hypothermia......Page 691
Postoperative (reperfusion injury)......Page 692
REFERENCES......Page 694
PART V Management of the Depressed or Neurologically Dysfunctional Neonate......Page 697
Objectives of neonatal resuscitation......Page 699
Anticipation of the need of resuscitation......Page 700
Personnel......Page 701
Immediate assessment......Page 702
Airway clearing and positioning of the infant......Page 703
Management of the infant with meconium staining of the amniotic fluid......Page 705
Routes of drug administration......Page 706
Glucose......Page 707
Oxygen......Page 708
Bicarbonate......Page 709
Methods of increasing the heart rate......Page 710
Fluid resuscitation......Page 711
Crystalloid and colloid solutions......Page 712
Calcium......Page 713
Delivery room decision making......Page 714
REFERENCES......Page 715
Supporting ventilation......Page 718
Sustaining cardiac output......Page 721
Dopamine......Page 722
Management of anemia......Page 723
Detection of ductal shunting......Page 724
Hyperoxia–hyperventilation test......Page 726
Severe pulmonary parenchymal disease......Page 727
Cyanotic congenital heart disease......Page 729
Hyperventilation......Page 730
Corticosteroids......Page 731
Barbiturates......Page 732
Excitatory amino acids (EAA) receptor inhibitors......Page 733
Oxygen free radical inhibitors......Page 734
Growth factors and hypothermia......Page 735
REFERENCES......Page 736
Biphasic cell death after hypoxic–ischemic injury......Page 741
Mechanisms of delayed cell loss......Page 742
Endogenous neuroprotective responses......Page 743
Cerebrovascular responses in the delayed phase......Page 744
Insulin-like growth factors......Page 745
IGFs in the injured central nervous system......Page 746
Neuronal rescue with IGF-1......Page 747
Derivative molecules......Page 748
Temperature and experimental hypoxia–ischemia......Page 749
Cooling in the secondary phase......Page 750
Conclusions......Page 751
REFERENCES......Page 752
Diagnostic dilemmas: reliance on clinical vs EEG criteria for seizures......Page 761
Subtle seizure activity......Page 762
Clonic seizures......Page 764
Tonic seizures......Page 765
Myoclonic seizures......Page 766
Tremulousness or jitteriness without EEG correlates......Page 769
Neonatal myoclonus without EEG seizures......Page 772
Electrographic seizure criteria......Page 774
Ictal EEG patterns – a more reliable marker for seizure onset, duration, and severity......Page 775
Periodic discharges – prolonged repetitive discharges; ictal or interictal?......Page 776
Subcortical seizures vs nonictal functional decortication......Page 777
Electroclinical dissociation suggesting subcortical seizures......Page 778
Interictal EEG pattern abnormalities......Page 782
Major etiologies for seizures – multiple overlapping conditions along a variable timeline......Page 786
Hypocalcemia......Page 790
Cerebrovascular lesions......Page 791
Central nervous system malformations......Page 794
Inborn errors of metabolism......Page 796
Progressive neonatal epileptic syndromes......Page 798
Seizures in the clinical context of maternal–fetal–placental diseases following a diagnostic algorithm......Page 799
Prognosis......Page 800
Diagnostic dilemmas regarding treatment......Page 801
Discontinuation of drug use......Page 802
Consequences of neonatal seizures on brain development......Page 803
REFERENCES......Page 804
Historical perspective......Page 811
New methodologies......Page 812
The future......Page 814
Conclusion......Page 815
REFERENCES......Page 816
Gastric feeding: intermittent gavage or continuous infusion......Page 817
Transpyloric feeding......Page 819
Parenteral feeding......Page 821
Clinical picture......Page 824
Timing of enteral feeding......Page 826
Osmolality of feeds......Page 828
Benefits of human milk......Page 829
lschemia and hypoxia......Page 830
Role of corticosteroids......Page 831
Newer thoughts on etiology......Page 832
Prevention of NEC......Page 834
REFERENCES......Page 835
PART VI Assessing the Outcome of the Asphyxiated Infant......Page 841
The pilot version of the Neurobehavioral Assessment of the Preterm Infant......Page 843
Subjects......Page 844
The examination......Page 845
The clinical validity of the NAPI......Page 847
Description of the NMI......Page 848
Conditions requiring a classification of III, IV, or V, regardless of length of time on assisted ventilation......Page 849
The predictive validity of the NAPI......Page 850
NAPI training......Page 851
REFERENCES......Page 852
Introduction......Page 855
Overview......Page 858
Outcome measurements......Page 860
Cerebral palsy......Page 861
Cognitive deficit......Page 863
Epilepsy......Page 864
Hearing loss......Page 865
Early childhood disabilities using a current operational definition of intrapartum asphyxia......Page 866
Motor skills......Page 867
Cognitive ability......Page 869
Academic function......Page 870
School-age skills......Page 871
Language skills......Page 873
Memory......Page 874
Case 1......Page 875
Case 2......Page 876
Summary......Page 877
REFERENCES......Page 878
42 Appropriateness of intensive care application......Page 885
Ethical arguments for limiting the application of neonatal intensive care technology......Page 887
The infant has virtually no chance of surviving, even with intensive care......Page 888
The effort to enable the infant to survive is inflicting harms massively disproportional to any hoped-for benefits......Page 889
Should the infant survive, his or her capacities for personal life will be profoundly diminished......Page 891
The cost of providing neonatal intensive care to some infants may be disproportionally large relative to the meager, hoped…......Page 893
Strategies for building consensus......Page 896
REFERENCES......Page 897
Duty......Page 899
Breach of duty......Page 900
Damages......Page 901
Documentation......Page 902
Allegations vs prenatal obstetrician......Page 906
Allegations vs hospital (nursing staff)......Page 907
Discussion......Page 908
Case study – obstetric discharge/pediatric follow-up......Page 909
Allegations vs pediatrician......Page 910
REFERENCES......Page 911
Index......Page 913