子痫前期并发HELLP综合征及微血管病变的诊治

HELLP综合征主要病理生理表现为全身小动脉痉挛、微血管病变,一旦发生会危及母儿生命。加强围生期监护、解痉、糖皮质激素治疗和适时终止妊娠等尤为重要。     

Posttraumatic stress disorder following preeclampsia and HELLP syndrome

Posttraumatic stress disorder (PTSD) in connection with pregnancy was first described in the 1990s - initially in relation to childbirth but later more specifically to the mode of delivery. Instrumental vaginal delivery carries the highest risk of PTSD followed by emergency caesarean section and normal spontaneous delivery. Loss of pregnancy, spontaneous abortion or intrauterine death for example can also lead to PTSD. Little systematic research has been performed regarding the psychological consequences of severe preeclampsia or HELLP syndrome, although it would seem obvious that these conditions may have a great effect. The combination of suffering a serious illness combined with an unexpected caesarean section or delivery, often of a premature child, is a heavy burden to bear both physically and psychologically. We describe here three patients who developed PTSD after pregnancies complicated by severe preeclampsia or HELLP syndrome. PTSD can develop after preeclampsia or HELLP syndrome.     

Maternal and fetal outcome of pregnancy complicated by HELLP syndrome

Objective.?The study evaluated the maternal and fetal outcome in 64 pregnancies complicated by HELLP syndrome.

Methods.?A retrospective analysis of the medical records was performed of patients with HELLP syndrome managed at this tertiary Obstetric unit between January 1996 and December 2005, who were admitted for preeclamsia/eclampsia and had documented evidence of hemolysis, elevated liver enzymes and low platelet count. Maternal and neonatal complications were recorded and analyzed.

Results.?The incidence of HELLP syndrome in the study was 8.3%. Mean gestational age at delivery was 32.4?±?4.2 weeks and mean birth weight was 1851?±?810?g. Forty-two percent of the patients had deliveries <32 weeks and 28% IUGR. Respiratory distress syndrome was the main indication for NICU admissions (33.9%). The PNM rate was 20%. Maternal morbidity rate was 34%. The most common maternal complications were abruptio placentae (36.4%) and DIC (31.8%). There was no maternal death.

Conclusion.?Once the diagnosis of HELLP syndrome is confirmed, the management depends on several obstetric and maternal variables like gestational age, severity of laboratory abnormalities and fetal status. As soon as the maternal condition is stabilized and fetal assessment is obtained, prompt delivery of the fetus is indicated. It is not yet established whether expectant management in preterm pregnancies with HELLP syndrome would improve perinatal outcome.     

Perinatal outcome for pregnancies complicated with thrombocytopenia

Introduction: Thrombocytopenia affects about 10% of all pregnancies. Preeclampsia/HELLP syndrome induced thrombocytopenia may associate perinatal morbidity, preterm delivery, or low-birth-weight newborns. Objective: To assess perinatal outcome and complications of pregnancy in women presenting with thrombocytopenia. Methods: We retrospectively analyzed 936 consecutive pregnant women admitted during a 6-month period. Results: Incidence of thrombocytopenia in pregnancy was 11.11% (104/936). Thrombocytopenia represented a risk factor for premature delivery – highest risk for severe thrombocytopenia (RR?=?8.69, p?<?0.01). Thrombocytopenic preeclampsia or HELLP syndrome associated the highest rates of prematurity (RR?=?7.97, p?=?0.00, respectively 12.32). Thrombocytopenia also represented a risk factor for low-birth-weight newborns, especially severe thrombocytopenia – 2047.50?±?938.98?g (p?=?0.02) versus 3224.86?±?496.00?g in controls. Again, thrombocytopenic preeclampsia was significantly associated with low-birth-weight newborns (RR?=?11.94, p?=?0.00), with medium weight of 2462.05?±?794.54?g versus 2932.37?±?708.91?g in thrombocytopenic pregnancies, respectively 3224.86?±?496.00?g (p?=?0.00) in normal pregnancies. Conclusions: Thrombocytopenia in pregnancy was associated with perinatal morbidity, with the strongest association for preeclampsia and HELLP syndrome – for both prematurity and low-birth-weight: the lower the platelet count, the higher the risks for the fetus/newborn. Therefore, we strongly recommend close surveillance of thrombocytopenic mothers and their babies, in order to establish the etiology and the best moment for intervention.     

The transplacental passage of prednisolone in pregnancies complicated by early-onset HELLP syndrome

During pregnancy the placental 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) enzyme inactivates prednisolone by interconversion into prednisone, protecting the fetus from high levels of prednisolone. Recent reports suggest decreased placental 11beta-HSD2 activity in pregnancies complicated by preeclampsia. The purpose of our investigation was to study the transplacental passage of prednisolone in patients suffering from early preterm HELLP syndrome, a severe complication of preeclampsia. We examined the maternal and umbilical cord plasma concentration of prednisolone in nine women receiving 50 mg of prednisolone twice a day. Samples were obtained during caesarean section at a gestational age between 27 and 31 weeks. Mean fetal concentration was 10-fold lower as compared to maternal prednisolone concentration (mean+/-SD 52.8 nmol/L+/-27.0 vs. 477.5 nmol/L+/-300, p<0.01). A significant correlation was found between the last dose of prednisolone to delivery interval and the fetal prednisone concentration (Spearman's correlation coefficient r=-0.946, p<0.000). Our data demonstrate unimpaired placental 11beta-HSD2 activity in patients suffering from HELLP syndrome at early gestational age as shown by both a 10-fold lower fetal prednisolone concentration as compared to the mother and a strong correlation between the last dose of prednisolone to delivery interval and the fetal prednisone concentration. Prednisolone may therefore have less effect on the fetus than betamethasone or dexamethasone.     

HELLP syndrome in pregnancies below 26th week

Objective: To test the hypothesis that HELLP syndrome may be more likely to develop earlier, if a pregnant woman has aPL antibodies, and to observe clinical and laboratory factors preceding the occurrence of HELLP syndrome. Materials and methods: The study consisted in retrospective analysis, with updated verification, of HELLP syndrome in pregnancies below 26th week in our clinic in the years 1992–2010. Results: HELLP syndrome, if it occurred before the 26th week, occurred only in women with preeclampsia superimposed on chronic hypertension and in women with aPL antibodies. HELLP syndrome with aPL antibodies occurred with low level of platelets (mean 35.5?×?10⁹/L), lower level of AT III (mean 71.3%), lymphopenia, higher CRP (mean 9.1) and pale infarct of placenta (100%). The occurrence of HELLP syndrome was always preceded by surges in blood pressure resistant to antihypertensive drugs. Conclusion: HELLP syndrome in early pregnancy may indicate the presence of aPL antibodies. It may also be a clinical symptom of APS. A surge in blood pressure is a clinical forerunner of the coming HELLP syndrome. HELLP syndrome in women with APS is characterized by low level of platelets.     

Postpartum spontaneous rupture of a liver hematoma associated with preeclampsia and HELLP syndrome

We report the case of a 28-year-old nulliparous woman who presented at 36 weeks’ gestation with preeclampsia: high blood pressure, proteinuria and edema. Serum test results were normal and platelet count was 155 × 10³/mm³. After 30 h the patient initiated severe epigastric pain and vomits, and lab tests presented a slight increase in liver enzymes. The platelet count remained above 150,000/μL. Cesarean section (CS) was performed. Six hours after CS, she developed a hypovolemic shock and lab tests became increasingly abnormal (liver enzymes increased sharply and hemoglobin and platelet count decreased sharply). Abdominal ultrasound showed suggestive signs of hepatic rupture. The patient was stabilized and exploratory laparotomy was performed. Perihepatic packing was applied. The patient was discharged after 25 days of admission (15 days at the ICU) and three explorative laparotomies. This case highlights the unpredictability of this event based on the changes of liver enzyme values, LDH and platelet count. These changes only occurred when the rupture had already occurred and the patient was in hypovolemic shock.     

Conservative versus active management in HELLP syndrome: results from a cohort study

Objective: HELLP syndrome exposes to severe maternal and fetal complications. Prompt delivery is thus recommended after 34 weeks of gestation, or earlier in case of nonreassuring maternofetal conditions. However, no consensus has been raised in the treatment of HELLP syndrome occurring before 34 weeks of gestation, when both maternal and fetal conditions are stable: it remains still unclear whether an active attitude should be prioritized over expectant management. Herein, we aimed to compare mother and child outcomes according to the type of obstetrical management, either active or conservative.

Study design: Retrospective and multicenter study involving two tertiary care units. In Center A, obstetrical attitude consisted in expectant management: all women received full antenatal betamethasone therapy and pregnancy was prolonged until maternal or fetal follow up indicated delivery. In Center B, management was active: all deliveries were initiated within 48?hours following diagnosis.

Results: From 2003 to 2011, 118 patients were included (87 in Center A, 31 in Center B). Both groups of patients were similar regarding maternal and fetal features at baseline. Active management led to increased risks of post-partum hemorrhage (relative risks (RR)?=?5.38, 95%CI: 1.2–24.06) and neonatal morbidity including respiratory distress syndrome (RR?=?3.1, 95%CI: 1.4–7.1), sepsis (RR?=?2.5, 95%CI: 1.1–6.0), necrotizing enterocolitis (RR?=?4.8, 95%CI: 1.1–21.2), intracerebral hemorrhage (RR?=?5.4, 95%CI: 2.1–13.6), and blood transfusion (RR?=?6.1, 95%CI: 1.7–21.7).

Conclusions: Conservative management may be beneficial for both mother and newborn in patients with stable HELLP syndrome. Identification of maternal and fetal specific prognostic factors would allow a better stratification of women with HELLP syndrome according to illness progressive potential, resulting in a more personalized management.     

Expression of clusterin in normal and preeclamptic placentas

Aim:  Clusterin is a multifunctional protein that is up-regulated during many different pathophysiological states. Clusterin may be related to a compensation mechanism involving aggregation of soluble proteins, inhibition of complement-mediated cell damage, adaptive regeneration or apoptosis. Clusterin may increase in response to cell damage that results from hypoxic stress in the preeclamptic placenta. The goal of this study was to measure clusterin expression and localization in normal and preeclamptic placental tissues.
Methods:  Immnunohistochemical and double immunofluorescent staining for clusterin was performed on eight normal and eight preeclamptic placental tissues, and clusterin expression was quantified by Western blotting.
Results:  Immunohistochemical analysis of clusterin in placental tissues obtained from normal pregnancies and those with preeclampsia showed localization of clusterin mainly in the syncytiotrophoblasts and villous endothelial cells. In the double immunofluorescent staining, clusterin was detected in the cytoplasm. The Western blot analysis showed that clusterin expression in the placental tissues of the preeclampsia group was significantly higher than in the normal pregnancy group.
Conclusions:  Increased expression of clusterin in placental tissues might play an important role in the pathogenesis of preeclampsia.     

Expression of EGF,EGFR, and proliferation in placentas from pregnancies complicated with preeclampsia

Objective: To investigate proliferation, EGF and EGFR expression of villous trophoblast (VTB), decidual cells (DC), and extravillous trophoblast (EVTB) in the placentas from pregnancies complicated with preeclampsia (PE) and to compare them with placentas from normal pregnancies. Methods: Twenty-nine PE placentas and 19 control placentas were studied for EGF and EGFR immunohistochemical expression (noted as week, moderate or strong). Proliferation was expressed as the proliferation index. The CK7 antibody was used to distinguish DC from EVTB. Results: DC and EVTB proliferation was significantly higher in PE placentas. EGFR and EGF expression showed no significant difference. Conclusion: Higher DC and EVTB proliferation in PE could contribute to PE development.     

HELLP综合征并发围生儿死亡危险因素分析

目的:探讨HELLP综合征并发围生儿死亡的危险因素。方法:回顾分析1991年1月至2010年12月天津市中心妇产科医院收治的76例HELLP综合征患者临床资料,按是否发生围生儿死亡分为死亡组和对照组,比较两组患者的一般临床资料和各项实验室指标。结果:围生儿死亡率为22.4%(17/76)。卡方检验结果显示:生产次数、早产情况、胎儿窘迫、收缩压、舒张压、血红蛋白、血小板计数、血清胆红素、24h尿蛋白定量为影响HELLP综合征并发围生儿死亡有统计学意义的因素(P<0.05);Logistic回归分析结果显示:舒张压、血红蛋白、血小板计数、血清胆红素、24h尿蛋白定量是影响HELLP综合征中围生儿死亡有统计学意义的因素。结论:血红蛋白和血小板计数降低及血清胆红素、舒张压和24h蛋白尿升高是影响HELLP综合征围生儿死亡的危险因素。     

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. (Am J Obstet Gynecol 1999;180:1373-84.)     

E-钙黏附素和β-连环素在重度子痫前期胎盘中的表达

目的探讨E-钙黏附素（E-cadherin，E-cad）和β-连环素（beta-catenin，β-cat）与子痫前期发生、发展的关系，以及早发型重度子痫前期发病机制的特点。方法采用免疫组织化学染色及图像分析方法检测35例重度子痫前期患者（重度子痫前期组）和20例正常晚期妊娠妇女（对照组）的胎盘组织中E-cad和β-cat的水平，并分析子痫前期组患者胎盘组织中E-cad和β-cat表达的相关性。结果与对照组比较，重度子痫前期患者胎盘组织中E-cad和β-cat的表达显著升高（P〈0．05），且两者呈正相关（r=0．749，P〈0．001），早发型重度子痫前期与晚发型重度子痫前期比较，差异无显著性（P〉0．05）。结论E-cad和β-cat在胎盘组织中的高表达可能与重度子痫前期的发生有关。