379 CLASSIFICATION The hypertensive disorders of pregnancy have been variously clas- sified without consensus being achieved as to a lasting classifica- tion. A practical classification may be achieved by modification of the system proposed by the American Committee on Maternal Wel- fare (1985). I. Pregnancy Induced Hypertension (Preeclampsia-eclampsia, toxemia, EPH, and gestosis) ● Gestational hypertension * ● Preeclampsia 1. Mild * 2. Severe * ● HELLP Syndrome * ● Eclampsia * II. Chronic hypertension ● Primary (essential, idiopathic) ● Secondary (to some known cause) 1. Renal: e.g., parenchymal (glomerulonephritis, chronic pyelonephritis, interstitial nephritis, and polycystic kid- ney disease), renovascular nephritis 2. Adrenal: cortical-Cushing’s disease, hyperaldosteronism, medullary-pheochromocytoma 3. Other: coarctation of the aorta, thyrotoxicosis, etc. III. Chronic hypertension with superimposed preeclampsia IV.Transient (atypical, undiagnosed) hypertension (a nebulous group of patients who develop hypertension in labor or immediately postpartum) 13 HYPERTENSIVE DISORDERS DURING PREGNANCY CHAPTER * Modifications Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use. BENSON & PERNOLL’S 380 HANDBOOK OF OBSTETRICS AND GYNECOLOGY PREGNANCY-INDUCED HYPERTENSION DEFINITIONS, INCIDENCE, ETIOLOGY, AND IMPORTANCE Preeclampsia-eclampsia, a multisystem disorder of unknown etiol- ogy peculiar to pregnant women, remains a major contributor to maternal and perinatal morbidity and mortality both in developing as well as industrialized nations. Currently, it is not possible to pre- dict who will acquire the processes. There are no strategies for pre- vention. This group of conditions are progressive, but with variable presentations and rates of progression. Moreover, after clinical symptoms have occurred, there are only symptomatic therapeutic options. One or another of the hypertensive disorders will compli- cate approximately 10% of pregnancies. The mildest form of the process is gestational hypertension, which consists of systolic blood pressure .140 with a rise of .30 mmHg and/or diastolic blood pressure of .90 mmHg with a rise of .15 mmHg. Only 15%–25% of women having gestational hyper- tension will develop preeclampsia. This progression is more likely with earlier presentation or if the woman has had a prior sponta- neous abortion. Women with gestational hypertension Ͼ36 weeks have ϳ10% risk of developing preeclampsia. Preeclampsia is characterized by hypertension (as previously de- fined), plus generalized edema, and/or proteinuria occurring after the 20th week of pregnancy (usually in the last trimester or early puer- perium). Any two of the three signs are diagnostic. The only excep- tion to the 20th week for onset is when pregnancy-induced hyper- tension (PIH) is associated with trophoblastic disease. Preeclampsia is divided into mild and severe, based on blood pressure and labora- tory abnormalities (see below). Although up to 40% of patients with preeclampsia will have some hemostatic abnormalities, for reasons yet unknown, some preeclamptic patients will develop the HELLP syndrome. This includes the signs of preeclampsia (as above) plus hemolysis (H), elevated liver enzymes (EL), and low platelets (LP, see below). These gravidas deserve even more special consideration because of the potential for poor perinatal and maternal prognosis with- out early diagnosis and proper therapy, including expeditious delivery. Eclampsia, the most fulminating degree of PIH, is character- ized by convulsions or coma, in addition to the other signs and symptoms of preeclampsia. Uncontrolled preeclampsia may progress to eclampsia, with resultant permanent disability or death. Chronic hypertension (CH) alone or with superimposed pre- eclampsia (SIPE) must be differentiated from PIH. The risks of chronic hypertension in pregnancy (abruptio placenta, fetal growth restriction and prematurity) are worsened by the superimposition of preeclampsia. Additionally, the maternal and perinatal risk increase in relation to the severity of the preexisting chronic hypertension. About 8% (recent reports range from 5%–10%) of all pregnant women in the United States develop preeclampsia; however, there is great geographic variation in incidence. Approximately 5% of these cases progress to eclampsia, and about 5% of women with eclampsia die of the disease or its complications. At least 95% of cases of PIH occur after the 32nd week, and about 75% of these patients are primigravidas. The incidence is at least doubled with multiple pregnancy, hydatidiform mole, and polyhydramnios. Prim- igravidas of all ages are affected. PIH is more prevalent among blacks and Native Americans than whites. Other factors predisposing to PIH include age Ͻ20 and Ͼ35, vascular or renal disease, diabetes mellitus, gestational diabetes mel- litus, obesity, chronic hypertension, pheochromocytoma, systemic lupus erythematosus, nonimmune fetal hydrops, malnutrition, and low socioeconomic status. Interestingly, if a multigravida remarries, her chance of having PIH with her next pregnancy is similar to what it would be as a nul- lipara. Pregnancies achieved through assisted reproductive tech- nology with a male donor to whom the gravida has not previously been exposed have the same risk as a primigravida, even if they are a multipara. In preliminary data, donated gametes further increase the risk of preeclampsia (to Ͼ18%). All of these conditions con- tribute to maternal and perinatal morbidity and mortality; however, given the spectrum of the processes, the amount and type of risk is variable. This information is summarized as follows. Although many associations have been detailed (see previous discussion), the cause of preeclampsia-eclampsia remains unknown and speculation has been so rife that this disorder has been called a disease of theories. Currently there are four popular hypotheses: ● Placental ischemia. Increased trophoblast deportation, as a consequence of ischemia, may inflict endothelial cell dys- function. Certainly evidence for endothelial involvement in this condition abounds. ● Preeclampsia is the manifestation of a toxic reaction. At least two areas are being investigated: Very low density lipopro- tein toxicity prevention. In pregnancy, nonesterified fatty CHAPTER 13 HYPERTENSIVE DISORDERS DURING PREGNANCY 381 BENSON & PERNOLL’S 382 HANDBOOK OF OBSTETRICS AND GYNECOLOGY acids are mobilized to compensate for increased energy de- mands. Albumin, which has a specific antitoxic activity, also transports the nonesterified fatty acids from adipose tissues to the liver. Low albumin concentrations may allow an ex- pression of very low density lipoprotein toxicity. Impaired antioxidant activity and the reduction of antioxidant levels, which increase the level of lipid peroxidation products, may cause peroxidative damage of vascular endothelium. ● Immune maladaptation. The immune interaction between mother and invading cytotrophoblast may be aberrant, lead- ing to shallower endovascular cytotrophoblastic cell inva- sion of spiral arteries. This dysfunction may lead to in- creased decidual release of cytokines, proteolytic enzymes, and free radial species. Preeclampsia is associated with widespread apoptosis of placental cytotrophoblasts with the uterine wall. ● Genetic imprinting. Genetic imprinting for pregnancy in- duced hypertension could be based on a single recessive gene or a dominant gene with incomplete penetrance (depending on fetal genotype). Preeclampsia during the pregnancy of a mother is a risk factor for development of preeclampsia dur- ing the pregnancy of her daughters. PATHOLOGIC PHYSIOLOGY VASOSPASM Arteriolar spasm, consistently observed in the retinas, kidneys, brain, and splanchnic region, promotes hypertension. Furthermore, the nor- mal refractoriness to angiotensin II (A-II) is lost weeks before the onset of preeclampsia. In contrast, normal pregnant women lose their refractoriness to A-II after receiving prostaglandin synthetase in- hibitors (e.g., aspirin, which implicates prostaglandin as a mediator of vascular reactivity to A-II during pregnancy). Moreover, A-II re- fractoriness can be restored to preeclamptic individuals by drugs that increase levels of cyclic AMP (cAMP) (e.g., theophylline). An im- balance between prostacyclin (PGI 2 ), a vasodilator and inhibitor of platelet aggregation, and thromboxane (TXA 2 ), a vasoconstrictor and platelet aggregator in preeclampsia, also occurs because PGI 2 pro- duction is decreased months before the clinical onset of preeclamp- sia. Mild preeclampsia is associated with lower systemic daytime production of prostacycline, elevated plasma norepinephrine levels, and blunting of the normal diurnal variations of brain natriuretic pep- tide, atrial natriuretic peptide, norepinephrine, and aldosterone. SODIUM AND WATER RETENTION Sodium retention is an adjunct of growth and is normal during preg- nancy, but sodium retention, particularly intracellular, is exagger- ated in PIH. Nonetheless, sodium retention does not cause this dis- order. However, an alteration at the cellular membrane level may inhibit the usual exchange of sodium. Reduced serum levels of al- bumin and globulin resulting from proteinuria account for the di- minished oncotic pressure of the blood despite hemoconcentration. Increased excretion of corticosteroids (including aldosterone) and vasopressin in certain patients suggests increased tissue concentra- tions of these substances. This results in enhanced sodium and wa- ter retention. PROTEINURIA Degenerative changes in the glomeruli permit loss of protein via the urine. The albumin–globulin ratio in the urine of patients with preeclampsia-eclampsia is approximately 3:1 (vs. 6:7 in patients with glomerulonephritis). In this case, renal tubular disease con- tributes only slightly to the leakage of protein. HEMATOLOGIC ALTERATIONS The Hgb and Hct are elevated due to hemoconcentration. Preeclamp- sia is a hypercoagulative status that may be explained by a de- rangement of the platelet L-arginine-nitric oxide pathway. Severe preeclampsia-eclampsia shares similarities with the disorders of coagulation because disseminated intravascular coagulation (DIC) of varying degrees so frequently occurs. The magnitude of the coagulation defect does not always correlate with the severity of preeclampsia-eclampsia. The alterations may include thrombocy- topenia, decreased coagulation factors (especially reduced fibrino- gen), and the presence of fibrin split products. Microfibrin emboli may occur in the lungs, liver, or kidneys. Occasionally, hemolysis (e.g., microangiopathic hemolytic anemia, deformed red blood cells), elevated liver enzymes, and thrombocytopenia occur in pa- tients with preeclampsia-eclampsia. This combination is termed the HELLP syndrome. BLOOD CHEMISTRY ABNORMALITIES Uric acid levels are generally .6 mg/dL. Serum creatinine is most often normal but may be elevated in severe cases. Some serum CHAPTER 13 HYPERTENSIVE DISORDERS DURING PREGNANCY 383 BENSON & PERNOLL’S 384 HANDBOOK OF OBSTETRICS AND GYNECOLOGY albumin and globulin are lost via the urine, but blood proteins must also be lost or destroyed in other ways, since proteinuria alone is not sufficient to explain the abnormally low protein levels in severe cases. Acidosis occurs after convulsions. Elevated levels of hepatic enzymes indicate hepatic dysfunction. Placental clearance of dehy- droepiandosterone sulfate (DHEAS), as a measure of placental per- fusion, decreases before the onset of preeclampsia. In summary, PIH is marked by vasospasm. Whereas normal pregnancy is marked by sodium and water retention, together with increased blood volume, in preeclampsia, there is enhanced sodium and water retention with a contracted plasma volume. Swan-Ganz catheter studies in preeclampsia reveal normal wedge pressures and normal or elevated cardiac output. PATHOLOGY KIDNEY In severe preeclampsia and eclampsia, the only typical lesion is glomerular capillary endotheliosis (i.e., swelling of the glomerular capillary endothelium, narrowing of the capillary lumen, and suben- dothelial fibrinoid deposition). These abnormalities are totally re- versible and disappear by 6 weeks postpartum. In patients with the clinical diagnosis of preeclampsia, renal biopsy reveals glomeru- lar capillary endotheliosis in ϳ70% of primigravidas Ͻ25 years, and ϳ25% have unsuspected renal disease. Other electron micro- scopic abnormalities include massive subendothelial and mesan- gial deposits of lipids and fibrillar fibrins, monocyte invasion in the mesangium, and rupture and duplication of the glomerular cap- illary wall. CARDIOPULMONARY Pulmonary edema may occur with severe preeclampsia or eclampsia from cardiogenic or noncardiogenic causes. It is most common post- partum and also may be related to fluid overload and decreased plasma colloid oncotic pressure. Preeclampsia is usually character- ized as a hyperdynamic state, with increased cardiac output, normal wedge pressure, and normal or slightly elevated systemic vascular re- sistance. Aspiration of gastric contents may occur as a complication of eclamptic seizures. Death may result from particulate matter obstructing airways or from chemical pneumonitis, leading to the adult respiratory distress syndrome. GASTROINTESTINAL In the liver, chronic passive congestion and subcapsular hemor- rhages may develop. FETUS As a result of the poor intervillous blood flow, intrauterine growth retardation may be marked. Fetal death may follow hypoxia or aci- dosis. This is further compounded by both severe hypertension and maternal multiple organ involvement, which may necessitate early delivery. PLACENTA Grossly, no specific placental lesions are typical of preeclampsia- eclampsia, although the placenta is often smaller than normal, and intervillous fibrin deposits (red infarcts) are common. Increased and more severe endarteritis and periarteritis, a thinned and broken syn- cytium, and calcium and intervillous fibrin deposition may appear (grossly, microscopically, and sonographically) as premature aging. There are two very serious microscopic placental alterations in pa- tients with preeclampsia: the spiral arteries in the myometrium fail to lose their musculoelastic structure, and acute atherosis develops in the myometrial segment of the spiral arteries. This leads to in- creased vascular resistance and a compromise of the vessel lumen. Thus, the fetus receives less intervillous blood flow. SYMPTOMS AND SIGNS Except for an abnormal blood pressure, patients with gestational hypertension are usually asymptomatic. Preeclampsia-eclampsia is characterized by hypertension, generalized edema, and proteinuria in the absence of vascular or renal disease. The manifestations de- velop from the 20th week of pregnancy through the 6th week after delivery. HYPERTENSION Hypertension is the key sign in the diagnosis of PIH. Gestational hypertension is a rise in systolic blood pressure of Ն30 mm Hg, a rise in diastolic pressure of Ն15 mm Hg, or a blood pressure of Ն140/90. Some (Canadian Hypertension Society Consensus Conference) consider only the diastolic blood pressure. Except for CHAPTER 13 HYPERTENSIVE DISORDERS DURING PREGNANCY 385 BENSON & PERNOLL’S 386 HANDBOOK OF OBSTETRICS AND GYNECOLOGY very high diastolic readings (.110), it is recommended that all diastolic readings be confirmed after 4 hours. Hypertension also exists with a mean arterial pressure rise of 20 mm Hg. The levels described must occur at least twice, 6 h or more apart, and be based on previously recorded blood pressures. Occasional patients with hypertension during pregnancy must remain unclassified until stud- ies can be evaluated after the puerperium. EDEMA Edema is the least precise sign of PIH because dependent edema is normal in pregnancy and up to 40% of patients with PIH do not have edema. However, the following criteria may facilitate the diagnosis. ● Generalized accumulation of fluid in tissues (i.e., Ͼ2ϩ pit- ting edema after 1 h bedrest). ● A weight gain of Ն2 pounds/wk because of the influence of pregnancy. ● Nondependent edema of the hands and face present on aris- ing in the morning. PROTEINURIA Gestational proteinuria is often the last sign to develop and is de- fined as $0.3 g/liter in a 24-h specimen or .1 g/liter (1ϩ to 2ϩ by dipstick methods) with urinalysis on random midstream or catheter specimens. Up to 30% of patients with eclampsia will not have pro- teinuria, but when present, proteinuria signals increased fetal risk (more SGA infants and enhanced perinatal mortality). If only the noted criteria for preeclampsia are present, it is classified as mild preeclampsia. The criteria for severe preeclampsia follow. ● Blood pressure Ͼ160 systolic or Ͼ110 diastolic (at bedrest, on two occasions at least 6 h apart) ● Proteinuria Ͼ5 g/24 h (3ϩ to 4ϩ on dipstick) ● Oliguria (Յ500 mL/24 h) ● Cerebral or visual disturbances ● Epigastric pain ● Pulmonary edema or cyanosis OTHER Severe, persistent, generalized headache, vertigo, malaise, and nervous irritability are prominent symptoms in cases of severe preeclampsia. Scintillating scotomas and partial or complete blind- ness are due to edema of the retina, retinal hemorrhage, or retinal detachment. Epigastric pain, nausea, and liver tenderness are the result of congestion or thrombosis of the periportal system and sub- capsular hepatic hemorrhages. There are no consistent symptoms of the HELLP syndrome. This nonspecificity is problematic for early diagnosis. Similarly, eclamp- sia may occur with little or no warning. COMPLICATIONS Maternal complications are related directly to progression from gestational hypertension to preeclampsia, the HELLP syndrome or eclampsia. The fetal complications are related to acute and chronic uteroplacental insufficiency (e.g., asymmetric or symmetric SGA fetus, stillbirth, or intrapartum fetal compromise) and early deliv- ery (complications of prematurity). LABORATORY STUDIES All patients with PIH may need the following studies (additional studies or repetition may also be necessary): Hct, or Hgb, WBC; urinalysis, urine culture and sensitivity; serum protein and albu- min/globulin ratio; and serum uric acid and creatinine. Also, de- pending on the gestational age and seriousness of the situation, it may be useful to determine fetal physiologic maturity by amnio- centesis and appropriate tests. A 24-h urine collection is collected for total protein, creatinine clearance, and vanillylmandelic acid (if BP varies greatly). Baseline coagulation studies usually include a platelet count, total fibrinogen, prothrombin, partial thrombo- plastin time, and split fibrin products (if DIC is suspected). A liver function profile is usually added to rule out HEELP syndrome. This includes bilirubin and liver enzymes (lactate dehydrogenase, as- partate aminotransferase, alanine amniotransferase). Recently, some have recommended that the laboratory evalua- tion of patients suspected of preeclampsia may be abbreviated in certain circumstances. Specifically, if there is no evidence of bleed- ing or of a condition that could produce coagulopathy and if the platelet count and lactate dehydrogenase level are both normal, a PT, a PTT, or fibrinogen test is not necessary. IMAGING Sonography is useful in detailing the fetal size and position and in estimation of well-being. Additionally, Doppler evaluation of the uterine artery velocimetry may be useful in predicting adverse preg- nancy outcomes from compromised fetuses. CHAPTER 13 HYPERTENSIVE DISORDERS DURING PREGNANCY 387 BENSON & PERNOLL’S 388 HANDBOOK OF OBSTETRICS AND GYNECOLOGY MANAGEMENT The objectives of treatment of all hypertensive states complicating pregnancy are to prevent or control convulsions, ensure survival of the mother without (or with minimal) morbidity, and deliver a sur- viving infant without serious sequelae. GENERAL MEASURES If the patient is stable and not severely preeclamptic or eclamptic, general diet without sodium restriction may be appropriate, as is unrestricted fluid intake (but with recorded intake and output). The lateral recumbent position increases renal blood flow, which assists in resolving edema. Therefore, the patient is encouraged to assume right or left lateral recumbency as much as possible. High-risk ob- stetric care and treatment of complications is required to optimize outcomes. The keys to treatment are bedrest and delivery at a time of fetal maturity. Those who have gestational hypertension may be followed un- der close supervision as outpatients. Such supervision usually in- volves bedrest (lateral recumbent position as much as possible), blood pressure evaluation (while awake) every 4 h, a daily urine dipstick evaluation for proteinuria, a minimum of twice weekly physician visits, weekly nonstress testing (or other evaluation of fe- tal well-being), and maternal fetal motion counting. Careful patient education is necessary concerning signs that would require immediate hospitalization: proteinuria, increasing blood pressure, severe headache, and epigastric pain. In some circumstances, for gestational hypertension and in all preeclamptic women, maternal hospitalization may help prevent premature delivery and thus be less expensive (compared to pre- mature neonatal care). An example of hospital care includes bedrest (again, in the lateral recumbent position), daily weights, blood pres- sures every 4 h (because the highest pressures of the day occur at 3–5 AM, it is worthwhile to screen these occasionally); daily urine dipstick for proteinuria, and 24-h urine once or twice weekly (for creatinine clearance and total protein). On admission and weekly thereafter, the following laboratory studies may be employed: hemogram, liver function studies, uric acid and creatinine, elec- trolytes, serum albumin, and a coagulation profile. Sonography for gestational age is usually obtained on admis- sion and every 2 weeks thereafter. Weekly testing for fetal well-being may be performed by serial BPPs, or NSTs. Should an abnormal- ity arise, a CST may be necessary. Glucose tolerance testing is [...]... Diagnosis & Treatment, 4th ed Lange, 1982 CHAPTER 13 HYPERTENSIVE DISORDERS DURING PREGNANCY 399 hypertension The use of antihypertensive therapy during pregnancy in all of preceding high-risk chronic hypertensive patients has been demonstrated to improve both maternal and perinatal outcomes However, in lower risk chronic hypertensive states, the data for antihypertensive therapy to improve maternal or perinatal... DIFFERENTIAL DIAGNOSIS Although convulsions may be due to hypertensive encephalopathy, epilepsy, thromboembolism, drug intoxication or withdrawal, trauma, CHAPTER 13 HYPERTENSIVE DISORDERS DURING PREGNANCY 393 hypoglycemia, hypocalcemia (of parathyroid or renal origin), hemolytic crisis of sickle cell anemia, or the tetany of alkalosis, during pregnancy, eclampsia is the first consideration A brief coma... premature separation of the placenta have one of the hypertensive disorders Approximately half of such patients will be found to have hypertensive disease and about one quarter will have preeclampsia-eclampsia 396 BENSON & PERNOLL’S HANDBOOK OF OBSTETRICS AND GYNECOLOGY Postpartum hemorrhage is common in patients with hypertensive syndromes during pregnancy Toxic delirium in patients with eclampsia,... well as target organ damage from TABLE 13-1 DIFFERENTIAL DIAGNOSIS OF CHRONIC HYPERTENSIVE CARDIOVASCULAR DISEASE AND PREECLAMPSIA Features Hypertensive Disease Preeclampsia Onset of hypertension Before pregnancy; during first 20 weeks of pregnancy Permanent; hypertension persists beyond 3 months postpartum After 20th week of pregnancy (exception: trophoblastic tumors) Hypertension usually absent at 6... Prompt delivery must be considered for the indications noted previously CHAPTER 13 HYPERTENSIVE DISORDERS DURING PREGNANCY 391 PREVENTION Since there are no known specific causes of preeclampsia-eclampsia, prevention can be achieved only in a general way by providing the highest-quality prenatal care The diet during pregnancy should be high in protein and contain adequate vitamins and minerals The... eclampsia Although platelet counts are significantly increased postpartum after normotensive pregnancy, there is a further 2- to 3-fold rise in preeclamptic patients Peak values occur 6–14 d after delivery Most authorities recommend a complete evaluation 6 weeks to 6 months CHAPTER 13 HYPERTENSIVE DISORDERS DURING PREGNANCY 397 postpartum for the women who have had eclampsia or severe preeclampsia FOR... plus insensible fluid loss (approximately 500 mL/day) is usually replaced with salt-free fluids (including parenteral fluids) This may include CHAPTER 13 HYPERTENSIVE DISORDERS DURING PREGNANCY 395 200–300 mL of 20% dextrose in water 2–3 times daily during the acute phase to protect the liver, to replace fluids, and to aid in nutrition Do not give 50% glucose, since it scleroses the veins The use of...CHAPTER 13 HYPERTENSIVE DISORDERS DURING PREGNANCY 389 indicated after 20 weeks gestation if the patient has hyperglycemia or multiple pregnancy A vanillylmandelic acid study is effective in ruling out pheochromocytoma if wide blood pressure fluctuations occur Criteria to allow... one third of all chronic hypertensives in pregnancy) on hospitalization may seem to stabilize but then deteriorate rapidly One of the complications is premature separation of the placenta, noted in Ͼ10% of patients with chronic hypertension (Ͼ10 times the incidence in normal pregnancy) Other problems include thrombocytopenia, oliguria, and retinal detachment Even if chronic hypertensive patients have... insufficiency, almost all these patients will develop preeclampsia-eclampsia Intrauterine growth retardation is a major fetal hazard if preeclampsia is superimposed on chronic CHAPTER 13 HYPERTENSIVE DISORDERS DURING PREGNANCY 401 hypertension Prematurity is often another problem because preterm delivery may occur spontaneously or by necessity The seriousness of the preeclampsia-eclampsia is directly . 13 HYPERTENSIVE DISORDERS DURING PREGNANCY 387 BENSON & PERNOLL’S 388 HANDBOOK OF OBSTETRICS AND GYNECOLOGY MANAGEMENT The objectives of treatment of all hypertensive states complicating pregnancy. investigated: Very low density lipopro- tein toxicity prevention. In pregnancy, nonesterified fatty CHAPTER 13 HYPERTENSIVE DISORDERS DURING PREGNANCY 381 BENSON & PERNOLL’S 382 HANDBOOK OF OBSTETRICS. (abrup- CHAPTER 13 HYPERTENSIVE DISORDERS DURING PREGNANCY 389 BENSON & PERNOLL’S 390 HANDBOOK OF OBSTETRICS AND GYNECOLOGY tio placenta, eclampsia, coagulopathy, renal failure, hypertensive encephalopathy,