Pre-eclampsia: Etiology and Clinical Practice

Cover......Page 1
Half-title......Page 3
Title......Page 5
Copyright......Page 6
Dedication......Page 7
Contents......Page 9
Contributors......Page 13
Preface......Page 19
PART I Basic Science......Page 21
Impaired physiological change in spiral arteries......Page 23
Evidence for impaired trophoblast invasion in pre-eclampsia......Page 27
Histopathology of the spiral arteries in pre-eclampsia......Page 29
Vascular defects in different disorders of pregnancy......Page 33
REFERENCES......Page 35
Introduction: the placental bed......Page 40
Trophoblast invasion: the extracellular matrix and cell adhesion molecules......Page 41
In vivo studies suggest cytotrophoblast invasion is associated with switching of integrins and altered extracellular matrix expression......Page 42
In vitro studies also suggest that invasion is associated with switching of integrin repertoires......Page 43
Cytotrophoblast invasion, CAMs and pre-eclampsia......Page 44
The nitric oxide synthase/nitric oxide pathway and trophoblast invasion......Page 45
Matrix metalloproteinases and their tissue inhibitors......Page 46
MMPs and TIMPs in normal pregnancy......Page 47
Transforming growth factor-Betas and trophoblast invasion in normal pregnancy and pre-eclampsia......Page 48
Oxygen tension and trophoblast invasion in normal pregnancy and pre-eclampsia......Page 49
Apoptosis......Page 50
REFERENCES......Page 51
Cytotrophoblast and syncytiotrophoblast in primary culture......Page 57
Explant models of the villous pathway......Page 59
Placental macrophages......Page 60
Extravillous trophoblast......Page 61
Primary extravillous cytotrophoblast cultures......Page 62
Co-culture models......Page 63
Explant models......Page 64
REFERENCES......Page 65
Endothelium-derived relaxing factors......Page 70
The role of estrogen in stimulating NOS activity......Page 72
Inhibitors of nitric oxide synthase......Page 73
Prostacyclin......Page 74
Endothelins......Page 75
Adhesion molecules......Page 76
Adaptive cardiovascular changes of healthy pregnancy......Page 77
Cyclic guanosine monophosphate (cGMP)......Page 78
Stimulated nitric oxide synthase activity in vitro......Page 79
Nitric oxide synthase activity in vivo......Page 80
Endothelial dysfunction and thrombosis......Page 81
Pre-eclampsia......Page 82
Stimulated NO synthesis in vitro......Page 83
Endothelin in the maternal circulation in pre-eclampsia......Page 84
Prostanoids in the maternal circulation in pre-eclampsia......Page 85
Circulating angiogenic factors in pre-eclampsia......Page 86
The sympathetic nervous system in pre-eclampsia......Page 87
Conclusion......Page 88
REFERENCES......Page 89
Receptors......Page 98
Angiotensinases in normal and pre-eclamptic pregnancy......Page 100
Angiotensin IV (AngIV)......Page 101
The circulating RAS in pre-eclampsia - early and late roles?......Page 102
The utero-placental RAS......Page 103
AngII, vascular permeability and angiogenesis......Page 104
The genetics of the RAS in pre-eclampsia......Page 105
Conclusion......Page 106
REFERENCES......Page 107
Epidemiology......Page 112
Pathogenesis of pre-eclampsia......Page 113
NK cells and killer immunoglobulin-like receptors (KIR)......Page 114
NK allorecognition and pregnancy......Page 116
T cell responses in pregnancy and pre-eclampsia......Page 117
REFERENCES......Page 119
The inflammatory network......Page 123
Systemic inflammation and the acute phase response......Page 124
Metabolism and the systemic inflammatory response......Page 125
Normal pregnancy evokes a systemic inflammatory response......Page 126
The systemic inflammatory response in normal pregnancy is not a form of immune rejection......Page 127
Pre-eclampsia is associated with a more extreme systemic inflammatory response than occurs in normal pregnancy......Page 128
The role of the placenta......Page 130
Maternal predisposing factors......Page 132
The two-stage model of pre-eclampsia (Figure 7.2)......Page 133
Conclusions......Page 134
REFERENCES......Page 135
The generation of free radicals......Page 141
Enzymatic antioxidants......Page 142
Water-soluble antioxidants......Page 143
Assessment of oxidative stress......Page 144
Evidence for increased placental free radical synthesis in pre-eclampsia......Page 145
Placental oxidative damage in pre-eclampsia......Page 146
Evidence of increased systemic free radical generation in pre-eclampsia......Page 147
Maternal antioxidant status in pre-eclampsia......Page 148
Evidence of maternal oxidative damage in pre-eclampsia......Page 150
Prophylaxis of pre-eclampsia using antioxidants......Page 151
REFERENCES......Page 152
The maternal circulation to the placenta......Page 158
Consequences of the changes seen in pre-eclampsia......Page 159
Placental hyperoxia and pre-eclampsia......Page 160
Placental ischemia-eperfusion and pre-eclampsia......Page 161
The effect of intermittent perfusion on intraplacental oxygen concentration......Page 162
The pathophysiology of hypoxia, hyperoxia and ischemia-reperfusion......Page 163
Comparison of the effects of hypoxia and ischemia-reperfusion on placental tissues in vitro......Page 166
Overview......Page 167
REFERENCES......Page 168
The histological features of syncytial knotting have different origins......Page 172
True syncytial sprouting......Page 174
Trophoblastic flat-sectioning, syncytial knotting, Tenney-Parker changes......Page 175
Shedding of aged or degenerative nuclei......Page 176
Conclusions......Page 180
REFERENCES......Page 182
Pregnancy-induced changes in lipid metabolism......Page 184
Changes in circulating lipids with pre-eclampsia......Page 186
Mechanisms of altered lipid metabolism in pre-eclampsia......Page 189
Free fatty acids, oxidative stress and vascular dysfunction......Page 190
Triglycerides, oxidative stress and vascular dysfunction......Page 191
Can dyslipidemia during pregnancy flag later-life cardiovascular risk?......Page 192
Pre-eclampsia, later-life dyslipidemia and cardiovascular risk......Page 194
Concluding remarks......Page 196
REFERENCES......Page 197
Stage 1......Page 203
Stage 2......Page 204
Maternal fetal interactions in pre-eclampsia......Page 205
Linkage of stage 1 and stage 2......Page 206
Directed fetal placental signals and fetal/placental maternal interactions......Page 208
Clinical and research implications of the two-stage model......Page 210
REFERENCES......Page 211
High altitude and hypertension during pregnancy......Page 215
Maternal physiology in high-altitude pregnancy......Page 216
Placental factors......Page 221
REFERENCES......Page 223
Comparison of pregnancy in rodents and humans......Page 229
Hypertension as a predisposing factor for pre-eclampsia......Page 230
Placental contribution to maternal hypertension......Page 231
Systemic endothelial dysfunction......Page 232
REFERENCES......Page 233
Introduction......Page 235
Etiology of pre-eclampsia......Page 237
Consequences of pre-eclampsia......Page 238
Genetic factors......Page 239
Coagulation and fibrinolytic systems in pre-eclampsia......Page 240
Insulin resistance/glucose intolerance......Page 241
The immunology of pre-eclampsia......Page 242
Proteins associated with trophoblast invasion and angiogenesis......Page 243
AT1 receptor autoantibodies......Page 245
Conclusion......Page 246
REFERENCES......Page 247
Case control studies......Page 252
Definition of exposure, maternal characteristics and events......Page 253
Hypertensive disorders in pregnancy and hypertension in later life......Page 254
Hypertensive disorders in pregnancy and cerebrovascular disease in later life......Page 256
Possible mechanisms of association between pre-eclampsia and later disease......Page 257
REFERENCES......Page 258
PART II Clinical Practice......Page 261
Gestational hypertension......Page 263
Pre-eclampsia......Page 264
Clinician's perspective......Page 265
Research perspective......Page 267
Inherent difficulties and pitfalls when measuring blood pressure......Page 269
Dipstick urinalysis to determine proteinuria......Page 270
Protein:creatinine ratio......Page 272
Diagnosis of superimposed pre-eclampsia in chronic hypertension, renal disease and diabetes......Page 273
REFERENCES......Page 274
The importance of blood pressure in pregnancy......Page 278
Pre-eclampsia......Page 279
Blood pressure and defining pre-eclampsia......Page 280
Incremental rise from baseline......Page 281
History of blood pressure measurement......Page 282
White coat hypertension......Page 283
Korotkoff sounds......Page 284
Mercury sphygmomanometry......Page 285
Aneroid and random-zero sphygmomanometers......Page 286
Self-initiated and ambulatory monitoring......Page 287
Validated devices in pre-eclampsia......Page 288
Summary and recommendations......Page 289
REFERENCES......Page 290
Primipaternity versus the birth interval hypothesis......Page 296
Sperm exposure......Page 302
Where is the critical paternal antigen and how is the female organism exposed to the paternal HLA message?......Page 304
Donor insemination and oocyte donation......Page 306
Perspectives......Page 308
Conclusion......Page 310
REFERENCES......Page 311
Introduction......Page 315
Family reports......Page 316
Genetic association studies......Page 318
Linkage analyses......Page 320
Counseling the woman who has pre-eclampsia......Page 321
Conclusions......Page 322
REFERENCES......Page 323
Normal hemostasis......Page 325
Hemostasis in normal pregnancy......Page 326
Thrombophilia......Page 327
Gain of function defects......Page 328
Antiphospholipids......Page 329
Thrombophilia and pre-eclampsia: the evidence......Page 330
APC resistance and factor V Leiden......Page 331
Other heritable abnormalities......Page 334
Acquired APC resistance......Page 338
REFERENCES......Page 339
Age......Page 345
Obesity......Page 346
Management......Page 347
Parity......Page 348
Assisted reproduction......Page 349
Management......Page 350
Diabetes......Page 352
Systemic lupus erythematosus and antiphospholipid syndrome......Page 353
Renal disease......Page 354
REFERENCES......Page 355
The pathological renal characteristics of pre-eclampsia......Page 359
Renal hemodynamics in normal pregnancy and pre-eclampsia......Page 361
Renal handling of protein......Page 363
Early pregnancy assessment......Page 364
Methods of assessing proteinuria......Page 365
Serum urea......Page 366
Proteinuria......Page 367
Hydralazine......Page 368
Calcium channel antagonists......Page 369
Fluid management......Page 370
Control of blood pressure......Page 371
Postnatal management......Page 372
REFERENCES......Page 373
Prediction of disease......Page 377
Pregnancy hypertension......Page 378
Stepwise management......Page 379
Antenatal daycare units......Page 380
Home monitoring programs......Page 381
Assessment of mother......Page 382
Use of antihypertensive therapy......Page 383
Assessment of the fetus......Page 384
Planning of delivery......Page 385
REFERENCES......Page 386
Defining severe pre-eclampsia......Page 389
Severe pre-eclampsia - immediate delivery vs. expectant management......Page 390
Initial evaluation/management......Page 393
Prevention of convulsions......Page 395
Control of severe hypertension......Page 396
Summary......Page 397
REFERENCES......Page 398
Chest pain......Page 400
Hypertension......Page 401
Pulmonary edema......Page 402
Catecholamines......Page 403
Echocardiography......Page 404
Tachypnea......Page 405
Gastrointestinal symptoms......Page 406
Abdominal pain......Page 407
Ascites......Page 409
Elevated liver function tests (LFTs)......Page 411
Renal signs......Page 412
Hyperuricemia......Page 413
Elevated creatinine/decreased creatinine clearance......Page 414
Petechiae......Page 415
Thrombocytopenia......Page 416
Headache......Page 417
Blurred vision......Page 418
Seizure......Page 419
Magnetic resonance imaging......Page 421
Hyperglycemia......Page 423
REFERENCES......Page 424
Eclampsia......Page 426
Magnesium toxicity......Page 427
Malignant hypertension......Page 428
Hypertensive cardiomyopathy......Page 430
Malignant ventricular arrhythmias......Page 431
Pulmonary edema......Page 432
Laryngeal and glottic edema......Page 433
HELLP syndrome......Page 434
Liver rupture......Page 435
Acute renal failure......Page 437
REFERENCES......Page 438
Central nervous system hemodynamics......Page 444
Cerebral blood flow in pregnancy......Page 445
Central nervous system findings in severe pre-eclampsia and eclampsia......Page 448
Therapeutic agents and central nervous system effects......Page 452
REFERENCES......Page 453
Scope of the problem......Page 457
Can we predict an eclamptic seizure?......Page 458
Immediate management of eclampsia......Page 459
Confirming the diagnosis......Page 460
Prevention of recurrent convulsions......Page 461
Control of blood pressure......Page 463
Can initial eclamptic seizures be prevented?......Page 464
Long-term outcome of women with eclampsia......Page 465
Conclusions......Page 466
REFERENCES......Page 467
Criteria for diagnosis......Page 471
Airway and respiratory system......Page 472
Hemodynamic profile......Page 473
Renal function......Page 474
Platelet aggregation, platelet activation and platelet thrombi formation......Page 475
Platelet function......Page 477
Hypercoagulability......Page 478
Uteroplacental perfusion......Page 479
Control of hypertension......Page 480
Sodium nitroprusside (SNP)......Page 481
Stabilization of cardiovascular status and optimization of intravascular volume......Page 482
Pre-anesthetic evaluation......Page 483
Analgesia for labor and delivery......Page 484
Regional anesthesia......Page 486
Postoperative care......Page 488
REFERENCES......Page 489
Neuropathology......Page 496
Cardiorespiratory pathology and pathophysiology......Page 497
Critical care and critical care monitoring......Page 498
Severe and resistant hypertension......Page 499
Eclampsia......Page 500
Seizure prophylaxis......Page 501
The oliguric pre-eclamptic......Page 502
HELLP syndrome......Page 503
Anaphylactoid syndrome of pregnancy ("Amniotic Fluid Embolism")......Page 504
Thrombotic thrombocytopenic purpura (TTP)......Page 505
REFERENCES......Page 506
Uterine artery......Page 509
Ductus venosus......Page 510
Relationship of fetal Doppler indices to hypoxemia and acidemia......Page 512
Ductus venosus......Page 514
Relationship between fetal Doppler indices and long-term outcome......Page 515
High-risk pregnancies......Page 517
Clinical studies of umbilical and fetal Doppler in pre-eclampsia......Page 518
Toward a rational fetal monitoring strategy in pre-eclampsia......Page 519
REFERENCES......Page 521
33 Pregnancy-induced hypertension - the effects on the newborn......Page 526
Intra-uterine growth restriction......Page 527
Polycythemia......Page 528
Feeding......Page 529
Respiratory distress syndrome......Page 531
Infection......Page 533
Respiratory problems......Page 534
Periventricular hemorrhage......Page 536
Follow-up of high-risk infants and long-term outcome......Page 537
Visual problems......Page 538
Learning problems......Page 539
REFERENCES......Page 540
34 Medico-legal implications of the diagnosis of pre-eclampsia......Page 542
Foreseeability of harm......Page 543
Pre-eclampsia litigation......Page 545
Induction of labor and intrapartum "fetal distress"......Page 547
Outpatient vs. inpatient care......Page 550
Telephone liability......Page 551
Timing of delivery......Page 552
REFERENCES......Page 553
Subject Index......Page 555