Brian K. Rinehart

The spectrum of severe preeclampsia: Comparative analysis by HELLP (hemolysis, elevated liver enzyme levels, and low platelet count) syndrome classification☆☆☆★

OBJECTIVE This study was undertaken to explore the spectrum of maternal disease with a triple classification system of HELLP (hemolysis, elevated liver enzyme levels, and low platelet count) syndrome and compare these classes with severe preeclampsia without HELLP syndrome. STUDY DESIGN In this retrospective analytic study the pregnancies of 777 patients with class 1, 2, or 3 HELLP syndrome were compared and contrasted with those of 193 women with severe preeclampsia but without HELLP syndrome. RESULTS Eclampsia, epigastric pain, nausea and vomiting, significant proteinuria, major maternal morbidity, and stillbirth increased as HELLP syndrome worsened from class 3 to class 1. In contrast, headache and diastolic hypertension were more common among the significantly heavier patients with severe preeclampsia without HELLP syndrome. Approximately half of pregnancies complicated by class 1 HELLP syndrome exhibited significant maternal morbidity, compared with only 11% of those complicated by severe preeclampsia without HELLP syndrome. Although a significant trend was apparent in increasing levels of lactate dehydrogenase, aspartate aminotransferase, and uric acid as HELLP syndrome worsened, there was considerable variation within groups. CONCLUSION Laboratory and clinical indices of disease severity in patients with severe preeclampsia or eclampsia generally were highest with class 1 HELLP syndrome and were lowest when HELLP syndrome was absent. Class 3 HELLP syndrome is considered a clinically significant transitional group.

Expression of the placental cytokines tumor necrosis factor α, interleukin 1β, and interleukin 10 is increased in preeclampsia ☆ ☆☆ ★

Abstract Objective: We sought to determine whether placental cytokine expression is altered in patients with preeclampsia. Study Design: Whole placental tissue was collected at cesarean delivery, and total ribonucleic acid was extracted. Reverse transcriptase–polymerase chain reaction was performed to determine cytokine expression. Product bands were quantitated by scanning densitometry, and results were expressed as a ratio of cytokine/housekeeping gene (cytokine expression index). Statistical analysis was performed by the Student t test and the Mann-Whitney U test. Results: Placentas from 6 patients with preeclampsia and 4 normotensive patients were analyzed. Placental expression of interleukin 1β and interleukin 10 was greater in preeclamptic women than in normotensive subjects (median interleukin 1β cytokine expression index, 0.675; range, 0.394-0.953; vs 0.106; range, 0.084-0.166; P = .011; median interleukin 10 cytokine expression index, 1.042; range, 0.672-1.192; vs 0.126; range, 0.062-0.398; P Conclusion: Placentas from preeclamptic patients demonstrated increased expression of interleukin 1β, interleukin 10, and tumor necrosis factor α. This may be in association with placental hypoxia and may contribute to the global endothelial dysfunction observed in preeclampsia. (Am J Obstet Gynecol 1999;181:915-20.)

Interleukin-10 administration and bacterial endotoxin-induced preterm birth in a rat model.

OBJECTIVE To determine whether intrauterine infusion of interleukin‐10 prevents preterm delivery in rats treated with endotoxin. METHODS Pregnant rats underwent implantation of uterine catheters and were randomly assigned to receive intrauterine infusion of either normal saline, 50 μg lipopolysaccharide endotoxin, or 50 μg lipopolysaccharide with 500 ng interleukin‐10 administered either concurrently or 24 hours later. The interval from infusion to delivery for each group was recorded, along with the number of live born pups and their birth weight. We calculated that to obtain a power of 80%, assuming a 24‐hour difference in the treatment to delivery times between the test and control subjects, at least six animals would be needed in each group. RESULTS In females receiving lipopolysaccharide (50 μg) alone, the interval to delivery (P < .05), live birth rate (P < .05), and pup weight (P < .001) were reduced compared with the saline‐infused controls. In contrast, females receiving interleukin‐10 at the time of the endotoxin challenge or 24 hours after delivered at term with no difference in litter size or live birth weight compared with the controls. CONCLUSION Animals treated with both lipopolysaccharide and interleukin‐10, administered concurrently or 24 hours after the endotoxin challenge, delivered normal weight pups at term with a similar litter size as the saline‐infused controls. Interleukin‐10 appears to be effective in preventing endotoxin‐induced preterm birth and fetal wastage in pregnant rats.

Early risk assessment of severe preeclampsia: Admission battery of symptoms and laboratory tests to predict likelihood of subsequent significant maternal morbidity

OBJECTIVE This study was undertaken to investigate the utility of an admission battery of findings and laboratory data in the discrimination of patients with severe preeclampsia with or without HELLP (hemolysis, elevated liver enzyme levels, and low platelet count) syndrome at high risk for development of significant maternal morbidity. STUDY DESIGN The clinical and laboratory findings at hospital admission for 970 patients with severe preeclampsia with or without HELLP syndrome were studied retrospectively to develop parameters associated with low, moderate, and high risks for the subsequent development of significant maternal morbidity involving the hematologic and coagulation, cardiopulmonary, and hepatorenal systems. RESULTS Nausea and vomiting and epigastric pain are independent risk factors for complicated severe preeclampsia. Results of a panel of tests with values including lactate dehydrogenase level >1400 IU/L, aspartate aminotransferase level >150 IU/L, alanine aminotransferase level >100 IU/L, uric acid level >7.8 mg/dL, serum creatinine level >1.0 mg/dL, and 4+ urinary protein by dipstick can be used to discriminate the patient at high risk for significant maternal morbidity. Concentrations of lactate dehydrogenase, aspartate aminotransferase, and uric acid above these cut points have the strongest predictive value and are risk additive with worsening thrombocytopenia. CONCLUSION The presence of nausea and vomiting, epigastric pain, or both in association with admission laboratory values that are in excess of the cutoffs for lactate dehydrogenase, aspartate aminotransferase, and uric acid concentrations or for all 6 tests is predictive of high risk of morbidity for the patient with severe preeclampsia. These factors are independent of and additive with the rising maternal risk associated with decreasing platelet count.

Preeclampsia-associated Hepatic Hemorrhage and Rupture: Mode of Management Related to Maternal and Perinatal Outcome

This article is a critical review of the obstetric literature concerning preeclampsia-associated hepatic hemorrhage to develop guidelines conducive to optimal maternal and perinatal outcomes. An English literature search was performed for reports of hepatic hemorrhage or hepatic rupture in pregnancy during 1960 to 1997. Data were analyzed by Statmost packages using ANOVA, Chi-square, and Fishers exact tests. One hundred forty-one patients with hepatic rupture/hemorrhage were reported. The three most common presenting findings were epigastric pain, hypertension, and shock. With rare exception, patients had evidence of preeclampsia. Diagnosis was elusive and most frequently accomplished at laparotomy. When utilized, ultrasound and computed tomography (CT) were helpful diagnostic modalities. Maternal survival was highest in the arterial embolization treatment group. Maternal and perinatal survival improved considerably during the study interval. Route of delivery did not seem to impact survival rates. It was concluded that the application of ultrasound and CT for diagnosis and the use of hepatic artery embolization for treatment of hepatic hemorrhage/rupture seem to be beneficial management options for this rare event.

Dexamethasone compared with betamethasone for glucocorticoid treatment of postpartum HELLP syndrome

Objectives: To compare the efficacy of dexamethasone and betamethasone to ameliorate the course of postpartum hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. Methods: A prospective, mixed randomized/non‐randomized clinical investigation of patients with postpartum HELLP syndrome. Treatment with either dexamethasone or betamethasone was continued until there was evidence of disease recovery. Results: Baseline characteristics of both the dexamethasone (n=18) and betamethasone (n=18) groups were similar. Although the time to discharge from the obstetrical recovery room was not statistically significant between groups, reduction in mean arterial blood pressure was more pronounced in the dexamethasone group as compared with the betamethasone group (−15.3±1.4 mmHg vs. −7.5±1.4 mmHg, respectively, P<0.01). Patients in the dexamethasone group required less antihypertensive treatment than the betamethasone group (6% vs. 50%, P=0.01) and also had a decreased need for readmission to the obstetrical recovery room (0% vs. 22%, P=0.03). Conclusion: This investigation supports the use of dexamethasone as the superior glucocorticoid to use for patients with postpartum HELLP syndrome.

Modern obstetric management and outcome of infants with gastroschisis

OBJECTIVE To determine whether outcomes of infants with gastroschisis differed by mode or site of delivery, diagnostic method, or when maternal-fetal medicine consultation was given. METHODS Charts of 32 infants born at the University of Mississippi Medical Center or admitted to the neonatal intensive care unit between September 1992 and June 1998 were reviewed for maternal demographic characteristics and neonatal outcomes. Statistical analysis was done using Student t test, analysis of variance, chi2, and Kruskal-Wallis test with P<.05 considered statistically significant. RESULTS There were no statistically significant differences in neonatal outcomes by method or site of delivery, diagnostic method, or maternal-fetal medicine consultation before delivery. Infants delivered vaginally had higher Apgar scores at 1 and 5 minutes (9 versus 7 and 9 versus 8, respectively, P<.05). Vaginally delivered infants required more days of antibiotic therapy than those delivered abdominally (10 versus 3 days, P<.05) but had a shorter interval to enteral feedings (15 versus 30 days, P<.05). CONCLUSION Outcomes of infants with isolated gastroschisis were not significantly affected by method or site of delivery, diagnostic method, or maternal-fetal surveillance. Although the findings of this investigation were largely negative and the statistical power limited due to the rarity of this fetal disruption, small series of cases of gastroschisis need to be analyzed to resolve current controversies surrounding optimal treatment of gastroschisis.

A 12-hour urine collection accurately assesses proteinuria in the hospitalized hypertensive gravida.

OBJECTIVE:To determine whether a urine collection of <24 hours duration accurately assesses the level of proteinuria in inpatients being evaluated for preeclampsia.STUDY DESIGN:Patients admitted to the University of Mississippi between January and June of 1998 for evaluation of preeclampsia underwent two consecutive 12-hour urine collections. Each collection was analyzed for total protein, total calcium, total volume, and urine creatinine. A concurrent serum creatinine value was obtained. The protein:creatinine ratio, calcium:creatinine ratio, and creatinine clearance were calculated. Pearson’s correlation, sensitivity, specificity, and positive and negative predictive values were assessed.RESULTS:A total of 25 patients (86%) were preeclamptic. Total protein, the protein:creatinine ratio, and serum creatinine were significantly correlated between the first and second urine collection. The sensitivity and specificity of the 12-hour urine collection was 96% and 100%, respectively.CONCLUSION: A 12-hour urine collection accurately depicts the amount of proteinuria in hospitalized gravidas being evaluated for preeclampsia.

Second-trimester uterine evacuation: A comparison of intra-amniotic (15S)-15-methyl-prostaglandin F2α and intravaginal misoprostol

OBJECTIVE Our purpose was to compare the efficacy, safety, and adverse effects of intra-amniotically administered (15S)-15-methyl-prostaglandin F(2alpha) and intravaginally administered misoprostol for second-trimester uterine evacuation. STUDY DESIGN Fifty-one patients were randomly assigned to receive either a single 2.5-mg intra-amniotic injection of (15S)-15-methyl-prostaglandin F(2)(alpha) (n = 26) or two 200-microg intravaginal doses of misoprostol (n = 25) at 12-hour intervals. The primary outcome measured was evacuation of the uterus within 24 hours. RESULTS The mean time from initiation of termination to uterine evacuation was less in the prostaglandin group than in the misoprostol group (17.5 +/- 8.6 hours vs 22.3 +/- 12.5 hours), but this was not statistically significant (P >.05). The rate of successful fetal evacuation at 24 hours was significantly higher in the prostaglandin group than in the misoprostol group (88% vs 60%, P =.02). The complete-abortion rate and the incidence of adverse effects were similar in both groups. CONCLUSION The use of an intra-amniotic injection of (15S)-15-methyl-prostaglandin F(2alpha) for midtrimester pregnancy termination is safe and is associated with a greater number of successful uterine evacuations within 24 hours, without an increase in adverse effects, than intravaginal administration of misoprostol.

Randomized trial of intermittent or continuous amnioinfusion for variable decelerations.

Objective To determine whether continuous or intermittent bolus amnioinfusion is more effective in relieving variable decelerations. Methods Patients with repetitive variable decelerations were randomized to an intermittent bolus or continuous amnioinfusion. The intermittent bolus infusion group received boluses of 500 mL of normal saline, each over 30 minutes, with boluses repeated if variable decelerations recurred. The continuous infusion group received a bolus infusion of 500 mL of normal saline over 30 minutes and then 3 mL per minute until delivery occurred. The ability of the amnioinfusion to abolish variable decelerations was analyzed, as were maternal demographic and pregnancy outcome variables. Power analysis indicated that 64 patients would be required. Results Thirty-five patients were randomized to intermittent infusion and 30 to continuous infusion. There were no differences between groups in terms of maternal demographics, gestational age, delivery mode, neonatal outcome, median time to resolution of variable decelerations, or the number of times variable decelerations recurred. The median volume infused in the intermittent infusion group (500 mL) was significantly less than that in the continuous infusion group (905 mL, P = .003). Conclusion Intermittent bolus amnioinfusion is as effective as continuous infusion in relieving variable decelerations in labor. Further investigation is necessary to determine whether either of these techniques is associated with increased occurrence of rare complications such as cord prolapse or uterine rupture.