Steven A. Friedman

Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome)

OBJECTIVE Our purpose was to describe the incidence and effects of serious obstetric complications on maternal outcome in pregnancies complicated by HELLP syndrome. STUDY DESIGN A prospective cohort study was performed on 442 pregnancies with HELLP syndrome managed at this center from August 1977 through July 1992. RESULTS Of 437 women who had 442 pregnancies with HELLP syndrome; 309 (70%) of the cases occurred ante partum and 133 (30%) post partum; 149 (11%) developed at < 27 weeks and 80 (18%) at term. Maternal mortality was 1.1% (five patients). Serious maternal morbidity included disseminated intravascular coagulation (21%), abruptio placentae (16%), acute renal failure (7.7%), pulmonary edema (6%), subcapsular liver hematoma (0.9%), and retinal detachment (0.9%). Fifty-five percent of patients required transfusions with blood or blood products, and 2% required laparotomies for major intraabdominal bleeding. Abruptio placentae was strongly correlated with the development of disseminated intravascular coagulation (p < 0.0001), acute renal failure (p < 0.001), and pulmonary edema (p < 0.01). Moreover, there was a strong association between pulmonary edema and acute renal failure (p < 0.0001). There were no differences in laboratory findings between HELLP syndrome before and after delivery; however, women with postpartum HELLP syndrome had significantly higher incidences of pulmonary edema and renal failure. CONCLUSION HELLP syndrome is associated with serious maternal morbidity, especially when it arises in the postpartum period.

Trial of calcium to prevent preeclampsia

Background Previous trials have suggested that calcium supplementation during pregnancy may reduce the risk of preeclampsia. However, differences in study design and a low dietary calcium intake in the populations studied limit acceptance of the data. Methods We randomly assigned 4589 healthy nulliparous women who were 13 to 21 weeks pregnant to receive daily treatment with either 2 g of elemental calcium or placebo for the remainder of their pregnancies. Surveillance for preeclampsia was conducted by personnel unaware of treatment-group assignments, using standardized measurements of blood pressure and urinary protein excretion at uniformly scheduled prenatal visits, protocols for monitoring these measurements during the hospitalization for delivery, and reviews of medical records of unscheduled outpatient visits and all hospitalizations. Results Calcium supplementation did not significantly reduce the incidence or severity of preeclampsia or delay its onset. Preeclampsia occurred in 158 of the 2295 wome...

Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial.

OBJECTIVE Our purpose was to determine whether aggressive or expectant management of severe preeclampsia at 28 to 32 weeks is more beneficial to maternal and neonatal outcome. STUDY DESIGN Ninety-five eligible patients were randomly assigned to either aggressive (n = 46) or expectant management (n = 49). Aggressive management patients were prepared for delivery, either by cesarean or induction, 48 hours after glucocorticoids were administered. Expectant management patients were managed with bed rest, oral antihypertensives, and intensive antenatal fetal testing. RESULTS At the time of randomization there were no differences between the two groups in mean systolic blood pressure (170 +/- 9.7 vs 172 +/- 9.4 mm Hg), diastolic blood pressure (110 +/- 5.4 vs 112 +/- 4.2 mm Hg), proteinuria (3.0 +/- 2.3 vs 3.6 +/- 2.3 gm per 24 hours), and gestational age (30.4 +/- 1.6 vs 30.7 +/- 1.5 weeks) for the aggressive and expectant management groups. The average latency period in the expectant management group was 15.4 days (range 4 to 36), and this period was not affected by the amount of proteinuria at randomization. There was no eclampsia or perinatal death in either group. The two groups had similar incidences of abruptio placentae (4.1% vs 4.3%) and similar days of postpartum hospital stay. The expectant management group had a significantly higher gestational age at delivery (32.9 +/- 1.5 vs 30.8 +/- 1.7 weeks, p < 0.0001), higher birth weight, lower incidence of admission to the neonatal intensive care unit (76% vs 100%, p = 0.002), lower mean days of hospitalization in the intensive care unit (20.2 +/- 14 vs 36.6 +/- 17.4, p < 0.0001), and lower incidence of neonatal complications. CONCLUSION Expectant management, with close monitoring of mother and fetus at a perinatal center, reduces neonatal complications and neonatal stay in the newborn intensive care unit.

Clinical utility of strict diagnostic criteria for the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome

OBJECTIVE Our purpose was to compare the maternal outcome of pregnancies complicated by HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, partial HELLP syndrome, or severe preeclampsia. STUDY DESIGN In a retrospective cohort study we reviewed the maternal charts of 316 women with HELLP syndrome or severe preeclampsia managed at our perinatal center between July 1, 1992, and June 30, 1995. HELLP syndrome was strictly defined by previously published laboratory criteria. Women were divided into three groups: HELLP syndrome (n = 67), partial HELLP syndrome (one or two but not all three features of HELLP syndrome, n = 71), and severe preeclampsia (no features of HELLP syndrome, n = 178). Results were compared by chi 2 analysis and one-way analysis of variance. RESULTS Mean gestational ages at delivery in the HELLP, partial HELLP, and severe preeclampsia groups were, respectively, 31.7, 32.7, and 34.5 weeks (p < 0.001 between HELLP and severe preeclampsia). There was one maternal death from intracerebral hemorrhage in the HELLP group. In women with HELLP syndrome there was a higher incidence of cesarean section (p < 0.05), disseminated intravascular coagulation (p < 0.001), and need for transfusion (p < 0.001) than in the other two groups. CONCLUSIONS Higher incidences of maternal complications in women with HELLP syndrome stress the importance of strict criteria for the definition of HELLP syndrome. Women with partial HELLP syndrome should be studied and managed separately from women with complete HELLP syndrome.

High plasma cellular fibronectin levels correlate with biochemical and clinical features of preeclampsia but cannot be attributed to hypertension alone.

Current concepts of the pathogenesis of preeclampsia involve the generalized dysfunction of maternal vascular endothelial cells. We measured the endothelial isoform of fibronectin as a marker of endothelial cell injury throughout pregnancy in a prospective, case-control study. Nineteen women met strict criteria for the diagnosis of preeclampsia. Nineteen normal pregnant women, and 19 women with gestational hypertension but without other stigmata of preeclampsia (transient hypertension) were selected from the same cohort and matched according to race, age, nulliparity, and gestational age at delivery. Plasma levels of cellular fibronectin were significantly elevated in women meeting strict clinical and biochemical criteria for preeclampsia but not in women with normal pregnancies or transient hypertension. Moderate but significant elevations in mean levels were found in the second trimester in women destined to have preeclampsia, as compared with matched normal and transient hypertension groups (p less than 0.05). The results indicate that elevated plasma levels of cellular fibronectin are not simply the result of increased blood pressure but reflect a maternal insult specific to the syndrome of preeclampsia. Elevation of the mean concentration during the midtrimester is consistent with the hypothesis that endothelial cell injury is a specific lesion that occurs early in the course of preeclampsia, before clinical signs and symptoms.

Urinary dipstick protein: A poor predictor of absent or severe proteinuria☆☆☆*

OBJECTIVE Our purpose was to compare urinary protein dipstick values with standard 24-hour urinary protein excretion in women with hypertension in pregnancy. STUDY DESIGN Urinary protein dipstick determinations and concurrent 24-hour urinary protein excretion measurements were compared by review of 300 urine samples obtained from women with hypertension in pregnancy. RESULTS One hundred twenty-three samples had negative to trace protein on dipstick on two occasions at least 6 hours apart. Eight-one (66%) of these patients had significant proteinuria (> or = 300 mg per 24 hours). Seventy-six samples revealed 3+ to 4+ protein on dipstick in at least two samples. Of these, 27 (36%) had heavy proteinuria (> or = 5 gm per 24 hours), and 42 (55%) had nephrotic range proteinuria of > or = 3.5 gm per 24 hours. One hundred one patients had urine dipstick values of 1+ to 2+, of whom 89 (88%) had significant proteinuria. CONCLUSION Urinary protein dipstick values > or = 1+ have a positive predictive value of 92% (162/177) for predicting > or = 300 mg per 24 hours. In contrast, a dipstick of negative to trace should not be used to rule out significant proteinuria because its negative predictive value is only 34% (42/123) in hypertensive patients. Moreover, urine dipstick values of 3+ to 4+ should not be used to diagnose severe preeclampsia because their positive predictive value is only 36% (27/76).

Biochemical corroboration of endothelial involvement in severe preeclampsia

This prospective, nested, case-control study investigated whether elevated plasma cellular fibronectin concentrations previously reported in preeclamptic women likely reflect endothelial dysfunction. In addition to higher maternal plasma concentrations of cellular fibronectin, we found higher levels of von Willebrand factor, tissue plasminogen activator, and plasminogen activator inhibitor-1 in maternal plasma, providing biochemical corroboration of endothelial dysfunction in severe preeclampsia.

Late Postpartum Eclampsia Revisited

Objective: To describe the clinical and neurologic findings in patients with late postpartum eclampsia (convulsions beginning more than 48 hours, but less than 4 weeks, after delivery). Methods: This study evaluated all patients with the diagnosis of late postpartum eclampsia managed at our institution between August 1977 and July 1992. Results: There were 54 cases of late postpartum eclampsia among a total of 334 cases of eclampsia during the study period. Late postpartum eclampsia constituted 56% of total postpartum eclampsia and 16% of all cases of eclampsia. Convulsions began from postpartum days 3‐23 (mean 6). Thirty women (56%) had been identified as preeclamptic before their convulsions. A history of either severe headache or visual disturbances before convulsion was elicited in 83% of the patients. During the study period, eight women not included in the study group had late postpartum seizures attributed to other causes. Conclusions: Severe headache or visual disturbance frequently antedates late postpartum eclampsia. Only eight of 62 patients with late postpartum seizures had identifiable etiologies other than eclampsia. (Obstet Gynecol 1994;83:502‐5)

Neonatal outcome in severe preeclampsia at 24 to 36 weeks' gestation: does the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome matter?

OBJECTIVE Our purpose was to compare neonatal outcome after preterm delivery of infants whose gestation was complicated by the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, partial HELLP syndrome, or severe preeclampsia. STUDY DESIGN We reviewed the maternal and neonatal charts from 269 consecutive pregnancies complicated by the HELLP syndrome or severe preeclampsia managed at our perinatal center. The HELLP syndrome was defined by previously published laboratory criteria. Viable pregnancies were divided into 3 groups: HELLP syndrome, partial HELLP syndrome (at least 1, but not all 3, features of the HELLP syndrome), and severe preeclampsia (no features of the HELLP syndrome). Results were compared by means of chi2 analysis and Student t test where appropriate. Logistic regression was used to evaluate outcome variables at different gestational ages. RESULTS There were no significant differences in complications among the 3 groups at each gestational age. There was, as expected, a significant decrease in morbidity and mortality rates with advanced gestational age. CONCLUSIONS In severe preeclampsia, neonatal morbidity and death are related to gestational age rather than to the presence or absence of the HELLP syndrome. Whether expectant management is safe for women with the HELLP syndrome requires further study.

Cerebrovascular disorders complicating pregnancy - Beyond eclampsia

OBJECTIVE Our purpose was to investigate the problems encountered in the diagnosis and management of cerebrovascular disorders associated with pregnancy and the puerperium. STUDY DESIGN Pregnancies complicated by cerebrovascular disorders were identified by retrospective chart review (1985 to 1995). Events associated with trauma, neoplasm, drug ingestion, and infection were excluded. RESULTS The study population comprised 24 women with a variety of cerebrovascular disorders: 14 with infarction (5 arterial, 9 venous), 6 with intracranial hemorrhage (3 anatomic malformation, 3 unknown etiology), 3 with hypertensive encephalopathy, and 1 with an unruptured aneurysm. Blood pressure reflected physical condition at presentation and did not predict diagnosis or outcome except in the 3 women with hypertensive encephalopathy. Only 4 of 14 women with infarction and 1 of 6 with intracranial hemorrhage had a diastolic blood pressure > or = 110 mm Hg. Presumption of eclampsia delayed the diagnosis in 10 women (41.7%). In addition, patient delay in seeking medical attention complicated 10 cases. After review, none of the adverse maternal outcomes were deemed preventable by earlier physician intervention. Seven maternal deaths occurred (29.2%). Neonatal outcome was related to the gestational age and the maternal condition at presentation. CONCLUSION Cerebrovascular disorders are an uncommon and unpredictable complication of pregnancy that are associated with substantial maternal and fetal mortality. Suspected eclampsia unresponsive to magnesium sulfate therapy warrants an immediate neuroimaging study. Interestingly, in women with intracranial hemorrhage, severe hypertension was not an associated predictive factor.