Clinical Management




Keywords

preeclampsia, eclampsia, hypertension, evidence-based management, magnesium sulfate therapy

 


Editors’ comment: Although not an obstetrician or a clinician, Leon Chesley, PhD, was associated through most of his career with academic clinical departments and hospitals. Still, in the single-authored first edition of this text he devoted two entire chapters to management of preeclampsia and eclampsia. His chapters bear rereading, for they display Chesley’s critical assessment of the literature with an acumen that surpassed that of most obstetricians and hypertension experts of his time. The introductory chapter of this edition contains a historical compilation of treatment approaches through the age, and this Management chapter contains Chesley’s pioneering studies concerning infused magnesium sulfate in preeclampsia, as well as prescient analyses of published treatment regimens used in the 1960s and 1970s .


The goal of this chapter differs from most that precede it, which were more specifically aimed at describing and critiquing progress in the field, focusing primarily on possible etiopathogenesis of the preeclampsia syndrome. This chapter is designed to help physicians in the day- to-day management of women with preeclampsia, and to do so we describe some of the management schemes used at Parkland Hospital in Dallas. This tertiary-care center, in which one of the editors has been involved clinically for over 40 years, has been responsible for the obstetrical care of over 450,000 indigent women who had more than 50,000 pregnancies complicated by hypertension. Thus the approach of the chapters authors will stress the practical aspects of treatment, emphasizing those references that have had the most influence on our practice .




Introduction


Management of preeclampsia depends upon its severity as well as the gestational age at which it becomes clinically apparent. While in most cases diagnosis is made by the appearance of new-onset gestational hypertension accompanied by proteinuria, observations over the last two decades – which are discussed in detail in other chapters – have emphasized the importance of endothelial cell injury and multiorgan dysfunction as integral parts of the preeclampsia syndrome .


As emphasized in Chapter 2 , there are instances where it is not possible to make a definitive diagnosis of preeclampsia. For this reason, and given the explosive nature of the disorder, the American College of Obstetricians and Gynecologists ACOG Task Force and the National High Blood Pressure Education Program (NHBPEP) Working Group recommend close surveillance even if preeclampsia is only “suspected.” Increases in systolic and diastolic blood pressure can either be normal physiological changes or signs of developing pathology . With increased surveillance, temporal changes in blood pressure and laboratory values, as well as the development of signs and symptoms are monitored. Thus, increased surveillance permits rapid recognition of ominous changes in blood pressure, critical laboratory findings, and development of clinical signs and symptoms.


The basic management objectives for any pregnancy complicated by preeclampsia are:



  • 1.

    Termination of pregnancy with the least possible trauma to mother and fetus.


  • 2.

    Birth of an infant who subsequently thrives.


  • 3.

    Complete restoration of health to the mother.



In certain women with preeclampsia, especially those at or near term, all three objectives are served equally well by induction of labor. One of the most important clinical questions for successful management is precise knowledge of the age of the fetus.




Preeclampsia


Early Diagnosis and Evaluation


Traditionally, the frequency of prenatal visits is increased during the third trimester and this facilitates early detection of preeclampsia. Women with overt new-onset hypertension – 140/90 mm Hg or greater – are frequently admitted to the hospital for 2 to 3 days primarily to determine whether the rise in pressure is due to preeclampsia, and if so to evaluate its severity. Women with persistent severe disease are observed closely, and many are delivered. Conversely, women with apparently mild disease especially if remote from term may be carefully managed as outpatients.


Hospitalization is considered at least initially for women with new-onset hypertension, especially if there is persistent or worsening hypertension or development of proteinuria. A systematic evaluation is instituted to include the following:



  • 1.

    Detailed examination followed by daily scrutiny for clinical findings such as headache, visual disturbances, epigastric pain, and rapid weight gain.


  • 2.

    Weight on admittance and daily thereafter.


  • 3.

    Analysis for proteinuria on admittance and at least every 2 days thereafter.


  • 4.

    Blood pressure readings in the sitting position with an appropriate-size cuff every 4 hours, except during normal sleeping hours.


  • 5.

    Measurements of plasma or serum creatinine and liver enzymes, and hemogram to include platelet quantification. The frequency of testing is determined by the severity of hypertension. Some recommend measurement of serum uric acid and lactic acid dehydrogenase levels as well as coagulation studies, but some investigations have called into question the value of these tests.


  • 6.

    Frequent evaluation of fetal size and well-being and amniotic fluid volume either clinically or using sonography.



Goals of such management include early identification of worsening preeclampsia and the development of a management plan for obstetrical care which includes a plan for timely delivery. If any of these observations leads to a diagnosis of severe preeclampsia, further management is the same as described subsequently for eclampsia.


Hospitalization Versus Outpatient Management


For women with non-severe stable hypertension – whether or not preeclampsia has been confirmed – continued surveillance either in hospital, or at home for reliable patients, or through a day-care unit is carried out. At least intuitively, reduced physical activity throughout much of the day seems beneficial, but absolute bed rest is unnecessary and it may predispose to venous thromboembolism. A number of observational studies as well as randomized trials have addressed the benefits of inpatient care as well as outpatient management to include day-care unit observation and these are subsequently discussed. Somewhat related, Abenhaim et al. conducted a retrospective cohort study of 677 women hospitalized for bed rest because of threatened preterm delivery. When outcomes of these women were compared with their general obstetrical population, bed rest was associated with a significantly reduced risk of developing preeclampsia – RR 0.27 (0.16–0.48). In a review of two small randomized trials totaling 106 women, prophylactic bed rest 4–6 hours daily at home in women at high risk of preeclampsia was successful in lowering the incidence of preeclampsia, but not gestational hypertension. These and other observations support the claim that restricted activity alters the underlying pathophysiology of the preeclampsia syndrome.


Many cases of new-onset hypertension, either with or without proteinuria, prove to be sufficiently mild and have an onset near enough to term that they can be managed conservatively until labor commences spontaneously or until the cervix becomes favorable for labor induction. Complete abatement of all signs and symptoms, however, is uncommon until after delivery. Almost certainly, the underlying disease persists until after delivery .


High-Risk Pregnancy Unit


An inpatient antepartum unit was established in 1973 by Dr Peggy Whalley at Parkland Hospital in large part to provide care for women with hypertensive disorders. Initial results from this unit were reported by Hauth et al. and Gilstrap et al. The majority of women hospitalized have a beneficial response characterized by disappearance or improvement of hypertension. These women are not “cured,” because nearly 90% have recurrent hypertension before or during labor . By the end of 2013, more than 10,000 nulliparous women with mild to moderate early-onset hypertension during pregnancy had been managed successfully in this unit. Provider costs ( not charges) for this relatively simple physical facility, modest nursing care, no drugs other than iron and folate supplements, and the very few laboratory tests that are essential are minimal when compared with the cost of neonatal intensive care for a preterm infant.


Home Health Care


Many clinicians believe that further hospitalization is not warranted if hypertension abates within a few days, and this has unfortunately legitimized third-party payers to refuse hospital reimbursement. Consequently, most women with mild to moderate hypertension are managed at home. Outpatient management may continue as long as the disease does not worsen and if fetal jeopardy is not suspected. Sedentary activity throughout the greater part of the day is recommended. These women are instructed in detail about reporting symptoms. Home blood pressure and urine protein monitoring or frequent evaluations by a visiting nurse may be necessary. Lo et al. and more recently Ostchega et al. cautioned about the use of certain automated home blood pressure monitors that may fail to detect severe hypertension.


In an observational study by Barton et al. 1182 women with mild “gestational hypertension” – 20% had proteinuria – were managed with home health care. These nulliparous women were a mean of 32–33 weeks pregnant at enrollment and 36–37 weeks at delivery. Pregnancy outcomes are shown in Table 20.1 . Severe preeclampsia developed in about 20%, and although some developed HELLP syndrome, eclampsia, or abruptio placentae, perinatal outcomes were generally acceptable.



Table 20.1

Pregnancy Outcomes for 1182 Women Hospitalized for Mild Gestational Hypertension or Preeclampsia


































































Group No. Maternal Characteristics and Outcomes
Admission Delivery Perinatal Outcomes
EGA (wks) Prot (%) EGA (wks) Prot (%) CD (%) HELLP (%) SP (%) ECL (%) Mean BW (g) SGA (%) PMR (%)
Hispanic 92 33.2 22 36.8 65 38 4.3 26 1.1 2710 30 0
African-American 476 33.2 23 36.5 53 48 2.1 21 0 2735 22 1.1
White 614 33.5 19 36.9 54 45 2.9 16 0.2 2845 18 0

EGA=estimated gestational age; Prot=proteinuria≤1+; CD=cesarean delivery; SP=severe preeclampsia; ECL=eclampsia; BW=birth weight; SGA=small-for-gestational-age; PMR=perinatal mortality rate.

Data from Barton and colleagues.


Several prospective studies have been designed to compare continued hospitalization with either home health care or a day-care unit. In a pilot study from Parkland Hospital, Horsager et al. randomly assigned 72 nulliparas with new-onset hypertension from 27 to 37 weeks to continued hospitalization versus outpatient care. In all of these women, proteinuria had receded to<500 mg per day when randomized. Outpatient management included daily blood pressure monitoring by the patient or her family, and weight and spot urine protein were determined three times weekly. A home health nurse visited twice weekly and the women were seen weekly in the obstetrical complications clinic. Perinatal outcomes were similar in each group. The only significant difference was that women in the home-care group developed severe preeclampsia more frequently than hospitalized women – 42% versus 25% ( p <0.05).


A larger randomized trial reported by Crowther et al. included 218 women with mild gestational (nonproteinuric) hypertension, half of whom remained hospitalized after evaluation and the remainder were managed as outpatients. As shown in Table 20.2 , the mean duration of hospitalization was 22.1 days for women with inpatient management compared with only 6.5 days in the home-care group, otherwise all other outcomes were similar.



Table 20.2

Randomized Clinical Trials Comparing Hospitalization Versus Routine Care for Women with Mild Gestational Hypertension or Preeclampsia




























































































































































































Study Groups No. Maternal Characteristics – Admission Maternal Outcomes – Delivery Perinatal Outcomes
Para0 (%) Chronic Htn (%) EGA (wks) Prot. (%) EGA (wks) <37 wks (%) <34 wks (%) CD (%) Mean Hosp (d) HELLP (%) SP (%) ECL (%) Mean BW (g) SGA (%) PMR (%)
Crowther et al. 218 a
Hospitalization 110 13 14 35.3 0 38.3 12 1.8 21 22.2 3080 14 0
Outpatient 108 13 17 34.6 0 38.2 22 3.7 15 6.5 3060 14 0
Turnbull et al. 374 b
Hospitalization 125 63 0 35.9 22 39 8.5 0 20.8 0.8 3330 3.8 0
Day unit 249 62 0 36.2 22 39.7 7.2 0 14.9 0 3300 2.3 0
Tuffnell et al. 54 a
Day unit 24 57 23 36 0 39.8 1.1 3320 0
Usual care 30 54 21 36.5 21 39 5.1 3340 0

Para0=never delivered a viable pregnancy before; Htn=Hypertension; EGA=estimated gestational age; Prot=proteinuria≤1+; CD=cesarean delivery; SP=severe preeclampsia; ECL=eclampsia; BW=birth weight; SGA=small-for-gestational-age; PMR=perinatal mortality rate.

a Excluded women with proteinuria at entry.


b Included women with≤1+proteinuria.



Day-Care Unit


Another approach, now quite common in European countries, is day care. This approach has been evaluated by several investigators. In the study designed by Tufnell et al., 54 women developing hypertension after 26 weeks were assigned to either day care or routine management ( Table 20.2 ). Hospitalizations, progression to overt preeclampsia, and labor inductions were significantly increased in the routine management group. In another study performed in Australia, Turnbull et al. enrolled 395 women who were randomly assigned to either day care or inpatient management ( Table 20.2 ). Almost 95% had mild to moderate hypertension – 288 without proteinuria and 86 with≥1+proteinuria at baseline. Fetal outcomes overall were good and none of the women developed eclampsia or HELLP syndrome, and there were no neonatal deaths. Routes of delivery and neonatal complications were similar. Surprisingly, the costs of the two schemes were not significantly different. Perhaps not surprisingly, general satisfaction favored day care.


Antepartum Hospitalization Versus Outpatient Care


From the above, it appears that either inpatient or close outpatient management is appropriate for the woman with mild de novo hypertension, with or without non-severe preeclampsia. The key to success is close follow-up and a conscientious patient.


Antihypertensive Therapy for Mild to Moderate Hypertension


The use of antihypertensive drugs in attempts to prolong pregnancy or modify perinatal outcomes in pregnancies complicated by various types and severities of hypertensive disorders has been of considerable interest. Treatment for women with chronic hypertension complicating pregnancy is discussed in detail in Chapter 18 while the pharmacology and use during pregnancy of specific antihypertensive drugs are discussed in Chapter 19 .


Drug treatment for early mild preeclampsia has been disappointing, as shown in representative studies listed in Table 20.3 . Sibai et al. performed a randomized study to evaluate the effectiveness of labetalol and hospitalization compared with hospitalization alone. They evaluated 200 nulliparous women with preeclampsia diagnosed between 26 and 35 weeks. Although women given labetalol had significantly lower mean blood pressures, there were no differences between the groups in terms of mean pregnancy prolongation, gestational age at delivery, or birth weight. The cesarean delivery rates were similar, as were the numbers of infants admitted to special-care nurseries. It was problematic that growth-restricted infants were twice as frequent in women given labetalol compared with those treated by hospitalization alone 19 versus 9% .



Table 20.3

Randomized Placebo-Controlled Trials of Antihypertensive Therapy for Early Mild Hypertension Due to Pregnancy






























































































Study Study Drug (No.) Prolongation Pregnancy (Days) Severe Hyper- tension a (%) Cesarean Delivery (%) Abruptio Placentae (%) Mean Birth Weight (g) Growth Restriction (%) Neonatal Deaths
Sibai et al. Labetalol (100) 21.3 5 36 2 2205 19 1
200 inpatients Placebo (100) 20.1 15 b 32 0 2260 9 b 0
Sibai et al. Nifedipine (100) 22.3 9 43 3 2405 8 0
200 outpatients Placebo (100) 22.5 18 b 35 2 2510 4 0
Pickles et al. Labetalol (70) 26.6 9 24 NS c NS NS NS
144 outpatients Placebo (74) 23.1 10 26 NS NS NS NS
Wide-Swensson et al. Isradipine (54) 23.1 22 26 NS NS NS 0
111 outpatients Placebo (57) 29.8 29 19 NS NS NS 0

a Includes postpartum hypertension.


b Significant ( p <0.05) when study drug compared with placebo.


c NS=not stated.



The three other studies listed in Table 20.3 were performed to compare the beta-blocking agent, labetalol, or calcium-channel blockers, nifedipine and isradipine, with placebo. In none of these studies were any benefits of antihypertensive treatment shown. Von Dadelszen et al. performed a meta-analysis that included the aforementioned trials for the purpose of determining the relation between fetal growth and antihypertensive therapy, and this is further analyzed in the systematic review undertaken in Chapter 19 . Von Dadelszen et al. concluded that treatment-induced decreases in maternal blood pressure may adversely affect fetal growth.


Abalos et al. performed a literature search for randomized trials of active antihypertensive therapy compared with either no treatment or placebo given to women with mild to moderate gestational hypertension. They included a total of 46 trials (4282 women) in their analysis, which is summarized in Table 20.4 . As seen, except for a halving of the risk of developing severe hypertension, active antihypertensive therapy had no beneficial effects. Importantly, fetal-growth restriction was not increased in the treated women. These issues are further discussed in Chapter 19 .



Table 20.4

Summary of Randomized Trials Comparing Antihypertensive Therapy Versus no Drug or Placebo for Women with Mild to Moderate Gestational Hypertension




































Factor Trials (No.) Antihypertensive Versus None
RR 95% CI
Developed severe hypertension 19 0.50 (0.41–0.61) *
Developed preeclampsia 22 0.97 (0.83–1.13)
Stillborn infant 26 0.73 (0.50–1.08)
Preterm birth 14 1.02 (0.89–1.16)
Fetal growth restriction 19 1.04 (0.84–1.27)

Data from Abalos et al.

* p <0.05, all other comparisons nonsignificant.



Indications for Delivery


Delivery is the only current cure known for preeclampsia. Headache, visual disturbances, or epigastric pain are indicative that convulsions may be imminent, and oliguria is another ominous sign. Most clinicians manage severe preeclampsia with prophylactic anticonvulsant magnesium sulfate infusion. Antihypertensive therapy is given to lower dangerously elevated blood pressure. Treatment is identical to that described subsequently for eclampsia. The prime objectives are to forestall convulsions, to prevent intracranial hemorrhage and serious damage to other vital organs, and to deliver a healthy infant.


At term, delivery is typically indicated as opposed to the preterm gestation where temporizing measures are often employed. Exactly when to temporize versus facilitate delivery is not agreed upon, however, and this has not been well studied. The HYPITAT trial demonstrated improved maternal outcome with induction of women with mild preeclampsia beyond 37 weeks in a randomized controlled trial. Tavik et al. later published a secondary analysis from the same trial showing that this improvement in maternal outcome occurred with induction even if the cervix was unfavorable. For women with a late preterm gestation, the decision to deliver is not clear. Barton et al. reported excessive neonatal morbidity in women delivered before 38 weeks despite having stable, mild nonproteinuric hypertension. The Netherlands study of 4316 infants delivered between 34 0/7 and 36 6/7 weeks also described substantive neonatal morbidity. When the decision has been made to delay delivery because of prematurity, the hope is that a few more weeks in utero will reduce the risk of neonatal death or serious morbidity. Such a policy certainly is justified with non-severe hypertension. Assessments of fetal well-being and placental function are carried out, especially when there is hesitation to deliver the fetus preterm. Most investigators recommend frequent performance of various tests currently used to assess fetal well-being as described by the American College of Obstetricians and Gynecologists. These include the nonstress test or the biophysical profile . Measurement of the lecithin:sphingomyelin ratio in amniotic fluid will provide evidence of lung maturity in cases with unsure gestational dating.


With moderate or severe preeclampsia that does not improve after hospitalization, delivery is usually advisable for the welfare of both mother and fetus. Often labor is induced with intravenous oxytocin, usually along with cervical ripening techniques such as a prostaglandin or osmotic dilator. Whenever it appears that labor induction almost certainly will not succeed, or attempts at induction have failed, cesarean delivery is indicated. There is no evidence that failed efforts at induction followed by cesarean delivery are harmful to low-birthweight infants.


Delayed Delivery with Early-Onset Preeclampsia


In the past, all women with severe preeclampsia were usually delivered without delay. Over the past 25 years, a different approach for women with severe preeclampsia remote from term has been advocated. This calls for conservative or “expectant” management in a selected group of women with the aim of improving neonatal outcome without compromising the safety of the mother. Aspects of such conservative management always include careful daily – and usually more frequent – monitoring of the pregnancy in the hospital, with or without use of drugs to control hypertension.


Theoretically, antihypertensive therapy has potential application when preeclampsia severe enough to warrant termination of pregnancy develops before neonatal survival is likely. The caveat is that such management is controversial, and it may be catastrophic. In an early study, the Memphis group attempted to prolong pregnancy because of fetal immaturity in 60 women with severe preeclampsia diagnosed between 18 and 27 weeks. The total perinatal mortality rate was 87%, and although no mother died, 13 suffered placental abruption, 10 had eclampsia, three developed renal failure, two had hypertensive encephalopathy, and one each had an intracerebral hemorrhage and a ruptured hepatic hematoma .


Later, the Memphis group redefined their study criteria and performed a randomized trial of expectant versus aggressive management of 95 women who had severe preeclampsia but with more advanced gestations of 28 to 32 weeks. Women with HELLP syndrome were excluded from this trial. Aggressive management included glucocorticoid administration for fetal lung maturation followed by delivery in 48 hours. Expectantly managed women were observed at bed rest and given either labetalol or nifedipine orally to control severe hypertension. Pregnancy was prolonged for a mean of 15.4 days in the expectant management group with an overall improvement in neonatal outcomes.


Following these experiences, expectant management became more commonly practiced but women with HELLP syndrome or growth-restricted fetuses were usually excluded. In a follow-up observational study, the Memphis group compared outcomes for 133 women with HELLP syndrome and infants delivered between 24 and 36 weeks with 136 women with severe preeclampsia but no HELLP criteria. Women with HELLP syndrome were subdivided into three study groups. The first group included those with hemolysis, elevated liver enzymes, and low platelets. The second included those with partial HELLP syndrome – this was defined as either one or two, but not three, of these laboratory findings. The third group included women who had severe preeclampsia without any of the accoutrements of the HELLP syndrome. Perinatal outcomes were similar in each group and this led the investigators to conclude that women with partial HELLP syndrome, as well as those with severe preeclampsia alone, could be managed expectantly. They also concluded that infant outcomes were related to gestational age rather than the hypertensive disorder per se.


Women in the Abramovici study were indeed severely hypertensive and had mean diastolic blood pressures of 110 mm Hg. The distinguishing feature between those with complete and those with partial HELLP syndrome appears to be the platelet count – the mean value was 52,000/μL in women with complete HELLP syndrome compared with 113,000/μL in those with partial HELLP syndrome. Gestational ages at delivery were about 2 weeks more advanced in women with severe preeclampsia alone compared with those with some degree of HELLP syndrome. Accordingly, neonatal outcomes, in terms of need for mechanical ventilation and neonatal death, were better in women with severe preeclampsia alone. Fetal-growth restriction was not related to the severity of maternal disease and was prevalent in all three groups. Maternal morbidity was not described. A most important observation was that the median elapsed time from admission to delivery was 0, 1, and 2 days for women with HELLP syndrome, partial HELLP syndrome, or severe preeclampsia, respectively. Later reports describing this cohort indicated that growth restriction adversely affected survival in infants from that institution.


Sibai and Barton reviewed most reports since the early 1990s of expectant management of women with severe preeclampsia with early onset from 24 to 34 weeks gestation. Some of these studies, as well as those published since 2005, are shown in Table 20.5 . While the average time gained ranged from 5 to 10 days, maternal morbidity was formidable and included placental abruption, HELLP syndrome, pulmonary edema, renal failure, and eclampsia. Moreover, perinatal mortality averaged from 15 to 480 per 1000. Fetal-growth restriction was common, and in the study from the Netherlands it was an astounding 94%. Perinatal mortality is disproportionately high in these growth-restricted infants, but maternal outcomes are not appreciably different from those in women without growth-restricted fetuses. Barber et al. provided a 10-year review of 3408 women with severe preeclampsia from 24 to 28 weeks who had been entered into the California vital statistics database. They found correlation between increased lengths of stay and increased rates of both maternal and neonatal morbidity.



Table 20.5

Maternal and Perinatal Outcomes Reported Since 2005 with Expectant Management of Severe Preeclampsia from 24 to 34 Weeks







































































































Study EGA at Enrollment wks No. Days Gained Maternal Outcomes (Percent) Perinatal Outcomes (Percent)
Placental Abruption HELLP Syndrome Pulmonary Edema ARF Eclampsia FGR PMR
Oettle (2005) 24–34 131 a 11.6 23 4.6 0.8 2.3 2.3 NS 13.8
Shear (2005) 24–34 155 5.3 5.8 27 3.9 NS 1.9 62 3.9
Ganzevoort (2005a,b) 24–34 216 11 1.8 18 3.6 NS 1.8 94 18
Sarsam (2008) 24–34 35 9.2 5.7 11 2.9 2.9 18 31 2.8
Bombrys (2009) 27–34 66 5 11 8 9 3 0 27 1.5
Abdel-Hady (2010) 24–34 211 12 3.3 7.6 0.9 6.6 0.9 NS 48
Range 814 5–12 1.8–23 4.6–27 0.9–3.9 2.3–6.6 0.9–18 27–94 1.5–48

ARF=acute renal failure; EGA=estimated gestational age; FGR=fetal-growth restriction; HELLP=hemolysis, elevated liver enzymes, low platelet count; NS=not stated; PMR=perinatal mortality rate.

a Includes one maternal death.



Expectant Management of Midtrimester Severe Preeclampsia


A number of small studies have focused on expectant management of the severe preeclampsia syndrome before 28 weeks. In their review, Bombrys et al. found eight such studies, which included a total of nearly 200 women with severe preeclampsia from less than 24 to 26 completed weeks. Maternal complications were common and there were no infant survivors in those less than 23 weeks, and the authors recommend pregnancy termination for these. For those at 23 weeks, perinatal survival was 18% but morbidity was unknown. For those at 24–26 weeks, perinatal survival approaches 60%, and it averaged almost 90% for those at 26 weeks. Results from five studies published since 2005 are shown in Table 20.6 . Again, there are extraordinarily high maternal and perinatal morbidity and mortality rates in these extremely preterm pregnancies. At this time, there are inadequate contemporaneous comparative studies attesting to the perinatal benefits of such expectant treatment versus early delivery in the face of serious maternal complications that approach 50%. Thus, the caveat for detailed maternal counseling is repeated here. The 2013 Task Force supports these findings and recommended that a fetus that is<23 weeks gestation be considered previable and that women with severe preeclampsia be delivered.



Table 20.6

Maternal and Perinatal Outcomes with Expectant Management in Women with Midtrimester Severe Preeclampsia







































Study No. Maternal Complications (%) Perinatal Mortality (%)
Hall et al. 8 36 88
Gaugler-Senden et al. 26 65 * 82
Budden et al. 31 71 71
Bombrys et al. 46 38–64 43
Belghiti et al. 51 43 58
Weighted average 152 55 61

* One maternal death.



Glucocorticoids


In attempts to enhance fetal lung maturation, glucocorticoids have been administered to women with severe hypertension who are remote from term. Treatment does not seem to worsen maternal hypertension and a decrease in the incidence of respiratory distress and improved fetal survival have been cited. That said, we are aware of only one randomized trial of corticosteroids given to hypertensive women for fetal lung maturation. This trial included 218 women with severe preeclampsia between 26 and 34 weeks who were randomly assigned to be given betamethasone or placebo. Neonatal complications, including respiratory distress, intraventricular hemorrhage, and death, were decreased significantly when betamethasone was given compared with placebo. But there were two maternal deaths and 18 stillbirths . We add these findings to buttress our unenthusiastic acceptance of attempts to prolong gestation in many of these women.


Corticosteroids to Ameliorate HELLP Syndrome


Over 20 years ago, Thiagarajah et al. suggested that glucocorticoids might also play a role in treatment of the laboratory abnormalities associated with the HELLP syndrome. Subsequent investigators, however, reported less than salutary effects. Investigators at the University of Mississippi have been the staunchest advocates of corticosteroids to treat HELLP syndrome. Martin et al. reviewed outcomes of almost 500 such women. From 1994 to 2000, 90% were treated, and their outcomes considered more favorable than the cohort from 1985 to 1991, during which time only 16% were treated with steroids. Their randomized trial, while comparing two corticosteroid compounds, did not include a nontreated group. There have since been at least two prospective randomized studies designed to address this and they are summarized in Table 20.7 . Fonseca et al. from Cali, Columbia, randomized 132 women with HELLP syndrome to blinded treatment with either dexamethasone or placebo. Outcomes assessed included duration of hospitalization, time to recovery for abnormal laboratory tests, recovery of clinical parameters, and complications. None of these was statistically different between the two groups. In a similar blinded study Katz et al. randomized 105 postpartum women with HELLP syndrome to dexamethasone versus placebo. They analyzed outcomes similar to the Cali study and found no advantage to dexamethasone to hasten recovery ( Table 20.7 ). Shown in Fig. 20.1 are recovery times for platelet counts and serum AST and LDH levels in the Katz study. The responses are almost identical in women receiving the corticosteroid compared with those receiving placebo. The 2013 Task Force does not recommend use of corticosteroids to treat women with HELLP syndrome.



Table 20.7

Randomized Clinical Trials of Intravenous Dexamethasone Versus Placebo for Women with Severe Preeclampsia with HELLP Syndrome













































































Study No. Before Treatment a Maternal Outcomes (%) a
Platelets (10 /μL) AST (U/L) LDH (U/L) ARF Pulmonary Edema Eclampsia Death
Fonseca et al. 132 b
Dexamethasone 66 61±19 573±621 2124±1849 10 4.6 14 4.6
Placebo 66 58±21 492±579 2242±1671 13 1.5 15 1.5
Katz et al. 105 c
Dexamethasone 56 91±45 155±241 1103±1500 16.1 3.6 14 3.6
Placebo 49 95±57 240±371 1020±1282 24.5 10.2 25 4.1

HELLP=Hemolysis, Elevated Liver enzymes, Low Platelets; AST=aspartate transferase; LDH=lactate dehydrogenase; ARF=acute renal failure.

a All comparisons p >0.05.


b Includes 60 antepartum, 72 postpartum.


c All postpartum.




Figure 20.1


Serial laboratory values from initiation of therapy – dexamethasone versus placebo – in women with HELLP syndrome.

(From Katz et al. , with permission.)


Risks Versus Benefits – Recommendations


Taken in toto , these studies do not show overwhelming evidence of favorable risk-versus-benefits of expectant management of severe preeclampsia from 24 to 32 weeks. The Society of Maternal Fetal Medicine as well as the 2013 Task Force have determined that such management is a reasonable alternative in selected women with severe preeclampsia before 34 weeks. As shown in Table 20.8 , this type of management calls for in-hospital maternal and fetal surveillance with delivery prompted by evidence of worsening severe preeclampsia or maternal or fetal compromise. While attempts are made for vaginal delivery in most cases, the likelihood of cesarean delivery increases with decreasing gestational age.



Table 20.8

Indications for Delivery in Women with Severe Preeclampsia *





























Maternal
Persistent severe headache or visual changes; eclampsia
Shortness of breath; chest tightness with rales and/or SaO 2 <94% breathing room air; pulmonary edema
Uncontrolled severe hypertension despite treatment
Oliguria<500 mL/24 hr or serum creatinine≥1.5 mg/dL
Persistent platelet counts<100,000/μL
Suspected abruption, progressive labor, and/or ruptured membranes
Fetal
Severe growth restriction –<5th percentile for EGA
Persistent severe oligohydramnios – AFI<5 cm
Biophysical profile≤4 done 6 hours apart
Reversed end-diastolic umbilical artery flow
Fetal death

AFI=amniotic fluid index.

From Sibai and Barton.

* Indications represent recommendations of the article’s authors and are not society guidelines.



Undoubtedly, the overriding reason to terminate pregnancies with severe preeclampsia is maternal safety. There are no data to suggest that expectant management is beneficial for the mother. Indeed, it seems obvious that a delay to prolong gestation in women with severe preeclampsia may have serious maternal consequences such as those shown in Table 20.8 . Notably, placental abruption develops in up to 20% and pulmonary edema in up to 4%. Moreover, there are substantive risks for eclampsia, cerebrovascular hemorrhage, and maternal death. These observations are especially pertinent when considered along with the absence of convincing evidence that perinatal outcomes are markedly improved by the average prolongation of pregnancy of about 1 week. If expectant management is undertaken, the caveats from the Society for Maternal Fetal Medicine and those shown in Table 20.8 should be strictly heeded. Thus, indications for delivery include worsening symptoms or hypertension; eclampsia, abruption, or pulmonary edema; renal dysfunction or oliguria; HELLP syndrome; fetal growth restriction, oligohydramnios, or other evidence of fetal compromise; and a gestational age of 34 weeks.

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Sep 20, 2018 | Posted by in GYNECOLOGY | Comments Off on Clinical Management
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