Plasma homocysteine in early and late pregnancies complicated with preeclampsia and isolated intrauterine growth restriction

BACKGROUND: Elevated circulating homocysteine is an independent risk factor for cardiovascular disease. Increased homocysteine plasma levels have been reported to occur in approximately 20-30% of women with preeclampsia and it has been suggested that they may predict the subsequent development of preeclampsia. METHODS: In a cohort of 1874 pregnant women followed longitudinally, who participated in the Down screening program, 27 developed preeclampsia and 36 intrauterine growth restriction (IUGR). A control group of 63 uneventful pregnancies was selected. Plasma homocysteine was assayed in the early second trimester and at delivery in all groups. Data were compared with Wilcoxon's matched-pair test. RESULTS: No statistically significant difference of plasma homocysteine between controls and preeclamptic or IUGR pregnancies in the early second trimester were found. There was a significant difference, only at delivery, between the preeclamptic subjects and the controls. CONCLUSIONS: We failed to demonstrate a plasma homocysteine predictive value in pregnancies subsequently complicated by preeclampsia and IUGR. As previously stated, we found that an elevated homocysteine plasma level is associated with overt preeclampsia.     

Perinatal outcome of twin pregnancies complicated with preeclampsia.

Twenty-five mild and 19 severe preeclampsia cases in twin pregnancies (12.5%) were compared to 44 matched for gestational age controls. All three groups were similar with respect to maternal age, intertwin birthweight differences, and rates of abdominal deliveries and low (less than 7) 5-minute Apgar scores. The frequency of primiparas in the severe preeclampsia group was significantly higher compared with controls (p less than 0.03). Severe preeclampsia patients delivered at a significantly earlier gestational age (p less than 0.005) and had a significantly lower mean twin birthweight (p less than 0.003) compared with the mild preeclamptic group. The mean twin birthweight of the severe preeclamptic cases was also significantly lower compared with that of controls. All three neonatal deaths occurred in severely discordant second twins born to severe preeclamptic patients. It is concluded that adverse perinatal outcome is associated with severe but not with mild preeclampsia in twin gestations.     

Increased placental apoptosis in pregnancies complicated by preeclampsia

Placentas were obtained at delivery from 34 pregnancies complicated by preeclampsia and from 34 uncomplicated pregnancies. The incidence of apoptotic nuclei was significantly greater (P <.01) in the placentas from the pregnancies complicated by preeclampsia.     

Plasma total homocysteine in uncomplicated pregnancy and in preeclampsia

OBJECTIVES: (a) To establish the reference values for plasma total homocysteine in our pregnant population. (b) To determine the possible association between hyperhomocysteinemia and preeclampsia in our geographical area. STUDY DESIGN: Control-case study with 32 preeclamptic patients and 64 controls without pregnancy complications. Plasma total homocysteine, determined by HPLC (fluorescence detection), was correlated with serum folate and Vitamin B(12) (analyzed by competitive protein binding chemiluminescent assay). Statistical analyses: Mann-Whitney, Wilcoxon and Spearman test (SPSS, 10.0). RESULTS: Homocysteine concentrations in the controls were significantly higher while folate was significantly lower in the third trimester of pregnancy when compared with the second (P<0.0001). Homocysteine and folate values were significantly higher in patients compared with controls in the third trimester (P=0.005 and 0.005, respectively). The OR for preeclampsia in hyperhomocysteinemia was 7.7 (95% CI: 1.7-34.8). CONCLUSION: Pregnant women with hyperhomocysteinemia have a 7.7-fold risk for preeclampsia (CI 95%: 1.7-34.8) compared with normal controls.     

Decreased maternal serum leptin in pregnancies complicated by preeclampsia

OBJECTIVE: To determine whether circulating levels of leptin differed between women with preeclampsia and women who had an uncomplicated pregnancy. METHODS: Maternal and umbilical venous plasma leptin concentrations obtained at delivery were compared in 36 pairs of women with either preeclampsia or normal pregnancy, matched 1:1 for prepregnancy body mass index and fetal gestational age at delivery. RESULTS: Prepregnancy body mass index was 21.1 +/- 2.1 kg/m2 in either study group (range 17.6-25.3 kg/m2 and 17.7-25.3 kg/m2 in the normal and preeclamptic group, respectively). Mean fetal gestational age at delivery was 40.1 +/- 1.3 weeks and 40.1 +/- 1.2 weeks in the normal and preeclamptic group, respectively. Median leptin concentrations were significantly lower (P <.0001) in women with preeclampsia (8.3 ng/mL, range 3.5-20.0 ng/mL) than in normal pregnant women (20.2 ng/mL, range 6.0-63.7 ng/mL). Median umbilical venous leptin was not significantly different between groups (preeclampsia 11.8 ng/mL, range 2.0-37.2 ng/mL; normal 7.6 ng/mL, range 1.6-24.3 ng/mL; P = .377). Umbilical venous leptin levels correlated positively with birth weight in both groups (preeclampsia rho = 0.501, P = .002; normal rho = 0.517, P = .001), whereas no correlations were found between maternal and fetal hormone concentrations. Maternal leptin concentrations did not correlate with birth weight. CONCLUSION: Our data suggest that the correlation between umbilical venous leptin concentration and birth weight is independent of the presence of preeclampsia. Given the inconsistency in literature concerning circulating leptin levels in preeclampsia, further studies should investigate the regulatory systems of leptin in preeclampsia.     

Fathers with PTSD and depression in pregnancies complicated by preterm preeclampsia or PPROM

Purpose

To assess prevalence and risk factors for posttraumatic stress disorder (PTSD) and depression in fathers after early preeclampsia (PE) or preterm premature rupture of membranes (PPROM).

Methods

Partners of patients hospitalized for PE or PPROM and partners of healthy controls completed PTSD (PSS-SR) and depression (BDI-II) questionnaires during pregnancy (t ₁) and 6 weeks postpartum (t ₂). 85 of the 187 eligible men participated (51 partners of patients, 34 partners of control) at t ₁, and 66 men participated both time points.

Results

No significant differences were found between partners of patients and partners of controls in symptoms of PTSD and depression (t ₁: p = 0.28 for PTSD and p = 0.34 for depression; t ₂: p = 0.08 for PTSD and p = 0.31 for depression). For partners of patients, correlation between PTSD and depression sum-scores was 0.48 (p < 0.001) at t ₁ and 0.86 (p < 0.001) at t ₂. Within-couple correlation was low and not significant during pregnancy, but strong at postpartum (PSS-SR: r = 0.62, p < 0.001; BDI-II: r = 0.59, p < 0.001). Higher paternal age was associated with more symptoms of PTSD and depression postpartum in partners of patients. Symptoms of PTSD and depression during pregnancy predicted the occurrence of PTSD symptoms following childbirth in partners of patients.

Conclusions

Symptoms of PTSD and depression occurred at a similar rate in partners of women with PE or PPROM and partners of healthy pregnant controls. Symptoms of PTSD and depression during pregnancy predicted the occurrence of PTSD symptoms following childbirth. Increased paternal age predicted more symptoms of PTSD and depression postpartum. At 6 weeks postpartum, a strong association was found between men and women in symptoms of PTSD and depression.     

Polymorphisms of genes involved in homocysteine metabolism in preeclampsia and in uncomplicated pregnancies

OBJECTIVE: To evaluate the possible relationship between preeclampsia and polymorphisms in the main genes involved in folate-homocysteine metabolism. STUDY DESIGN: Case-control study: 43 patients with preeclampsia and 122 controls without pregnancy complications. Laboratory studies: tHcy and other amino acids, folate and vitamin B(12) and polymorphisms: 677C > T and 1298A > C (MTHFR); 699C > T, 844ins68 and 1080C > T (CBS); 2756A > G (MTR); and 66G > A, IVS1+766G > A and IVS1+754A > C (MTRR). RESULTS: Plasma tHcy and folate values were significantly higher (P = 0.004 and P = 0.019), while Met/tHcy ratios were lower (P < 0.001) in the patients compared with controls. No association was observed between polymorphisms tested and preeclampsia. In the control group, four such associations were found: the 1298A > C polymorphism (MTHFR) with the ratio Met/tHcy (P = 0.014); the 699C > T polymorphism (CBS) with the ratio tHcy/SigmaAA (P = 0.013); the 2756A > G polymorphism (MTR) with tHcy (P = 0.034); and the IVS1+766G > A polymorphism (MTRR) with hyperhomocysteinemia (P = 0.012). CONCLUSION: An association between the polymorphisms analysed and preeclampsia could not be demonstrated.     

血清、脐血中MPO水平变化及胎盘组织MPO mRNA表达与子痫前期发病的关系

目的:研究重度子痫前期(PE)患者血清MPO及胎盘组织中MPO mRNA表达水平变化与PE发病的关系,探讨糖脂代谢异常及氧化应激在PE病理生理机制中的可能作用。方法:选取60例重度PE孕妇,按发病时孕周不同分为早发型PE组(孕周34周)和晚发型PE组(孕周≥34周)各30例。另选取同期健康晚期妊娠孕妇60例,分为对照1组(孕周34周)和对照2组(孕周≥34周)各30例。采用实时荧光定量PCR技术检测胎盘组织中MPO mRNA表达水平;ELISA法检测血清MPO水平。检测患者血压、血脂、血糖、胰岛素水平等指标,进行相关性分析。结果:PE组的血清MPO水平高于对照组(P0.05),且早发型高于晚发型PE组(P0.05);但对照组间比较无差异(P0.05)。PE组的血清TC、TG、LDL、FINS、HOMA-IR分别高于对照组(P0.05),HDL水平低于对照组(P0.05);但PE组间比较及对照组间比较,均无差异(P0.05)。PE组的脐血MPO水平、胎盘组织中MPO mRNA表达水平均高于对照2组(P0.05),且早发型高于晚发型组(P0.05)。PE组的血清MPO水平与TG、HoMA-IR、FINS、胎盘组织MPO mRNA表达水平均呈正相关(r=0.557、0.615;0.694、0.511;0.766、0.717;0.696、0.695),与血HDL呈负相关(r=-0.697,-0.576);对照2组则无相关性。结论:MPO可能参与了PE的病理生理过程。胎盘组织中MPO mRNA表达水平升高可能是血清MPO水平升高的重要原因。PE患者血脂代谢异常及胰岛素抵抗增加与血清MPO水平升高有关,它们可能参与了血清MPO水平升高后促发PE的氧化应激的病理生理过程。     

Expression of inflammatory cytokines in placentas from pregnancies complicated with preeclampsia and HELLP syndrome

Abstract

Objective: To investigate the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in villous trophoblast, syncytial knots and decidua placentas from pregnancies complicated with preeclampsia (PE), Hemolysis, Elevated Liver enzymes and Low Platelet count (HELLP) syndrome and gestational age-matched controls.

Methods: Study group included 35 placentas from pregnancies complicated with PE and 35 placentas from pregnancies with HELLP syndrome. Control group included 35 placentas from idiopathic preterm labor. Placentas were matched according to the gestational age. Expression of TNF-α, IL-6 and IL-10 was determined by immunohistochemistry and semi-quantitative HSCORE method in villous trophoblast, syncytial knots and decidua. Non-parametric statistics were used for analyses.

Results: There was no difference in the expression of TNF-α, IL-6 and IL-10 in all the studied placental segments between PE, HELLP and gestational age-matched control group. TNF-α (F?=?32, 41, p?<?0.001), IL-6 (F?=?58, 53, p?<?0.001) and IL-10 (F?=?17, 62, p?<?0.001) expression was significantly different in different placental cell types, the highest expression of cytokines was in decidua.

Conclusion: There was no difference in cytokine expression in villous trophoblast, syncytial knots and decidua among the studied placental groups. The expression of cytokines was highest in decidua in all the studied placental groups.     

Angiogenin and vascular endothelial growth factor in pregnancies complicated by preeclampsia.

OBJECTIVE: To investigate the role of the angiogenic factors, vascular endothelial growth factor (VEGF) and angiogenin in the pathophysiology of preeclampsia and how their concentrations correlate with the severity of the disease and fetal outcome. PATIENTS AND METHODS: A prospective study was carried out on 71 pregnant patients with preeclampsia and 20 pregnant normotensive controls. Maternal serum levels of VEGF and angiogenin were determined in all cases by enzyme immunoassay. Assessment of fetal well-being using the Biophysical Profile Score (BPS), umbilical and uterine artery Doppler velocimetry, and infant birthweight were carried out. RESULTS: Maternal serum VEGF and angiogenin levels were significantly increased in cases of mild and severe preeclampsia compared to controls. Their increase was positively correlated with elevated systolic and diastolic blood pressure, as well as poor BPS, abnormal Doppler velocimetry, and low birthweight. CONCLUSION: Elevated levels of both VEGF and angiogenin could confirm the existence of vascular reactivity and endothelial disturbance in preeclampsia. Measurement of these angiogenic factors in maternal serum may be a useful as biomarkers for the assessment of the severity of the disease and of fetal outcome.     

Cardiovascular risk markers in pregnancies complicated by diabetes mellitus or preeclampsia

ObjectiveTo explore biomarkers indicating cardiovascular disease in pregnant women with diabetes or preeclampsia, since these women are at increased risk for future cardiovascular disease.Study designEDTA-plasma from 262 women in gestational week 24–42 (healthy pregnancies n = 71, preeclampsia n = 105, type 2 diabetes n = 17, gestational diabetes n = 61, diabetes with preeclampsia n = 8) was analyzed by immunoassay for neopterin, midregional pro-adrenomedullin (MR-proADM) and C-terminal pro-arginine vasopressin (CT-proAVP). The diabetes groups were also analyzed for midregional pro-atrial natriuretic peptide (MR-proANP), and compared to previously reported MR-proANP concentrations for healthy, normotensive and preeclamptic patients.ResultsIn contrast to preeclampsia, median plasma MR-proANP was not increased in pregnancies complicated by diabetes, but in fact lower, compared to healthy pregnancies. Neopterin was increased in diabetic pregnancies and in late onset preeclampsia, compared to healthy pregnancies. Median plasma MR-proADM was increased in pregnancies complicated by gestational diabetes or preeclampsia, compared to healthy pregnancies. Median plasma MR-proANP was increased in diabetic pregnancies complicated by preeclampsia compared to pregnant women with diabetes only.ConclusionWomen with pregnancies complicated by diabetes mellitus or preeclampsia are at risk for future cardiovascular disease, but differ in circulating cardiovascular biomarker profile. A cardiovascular biomarker profiling during pregnancy might prove helpful in identifying women at risk for future cardiovascular disease, thus enabling targeted prophylactic interventions and follow-up.     

慢性高血压并发子痫前期的母儿结局分析

目的 了解慢性高血压并发子痫前期与非慢性高血压并发子痫前期患者的临床特征和母儿结局.方法 回顾分析2009年1月1日至2017年12月31日在广州医科大学附属第三医院住院分娩的妊娠≥20周的单胎妊娠诊断为子痫前期的病例资料.按是否为慢性高血压分为慢性高血压并发子痫前期组及非慢性高血压并发子痫前期组,分析两组的临床特征与...     

Increased plasma soluble fms-like tyrosine kinase 1 and endoglin levels in pregnancies complicated with preeclampsia

Background.?Increased maternal plasma levels of proinflammatory cytokines as well as the anti-angiogenic agents soluble fms-like tyrosine kinase 1 (sFlt-1) and endoglin (sEng) are associated with promoting vascular dysfunction leading to the maternal syndrome of preeclampsia.

Objective and method.?Nulliparous women complicated with preeclampsia (n = 29) and their corresponding controls (n = 29) delivering at the Enrique C. Sotomayor Obstetrics and Gynecology Hospital, Guayaquil-Ecuador were requested to participate in a study evaluating plasma levels of soluble anti-angiogenic factors (sFlt-1 and sEng) and pro-inflammatory cytokines: interleukin 6 (IL-6), interleukin 8 (IL-8), granulocyte colony stimulating factor (G-CSF), and tumor necrosis factor-alpha (TNF-α). Maternal and neonatal data were also assessed and compared among the study groups.

Results.?No significant differences in either maternal baseline or delivery characteristics were observed among the study groups. Compared with controls, preeclamptic women exhibited higher plasma levels of sFlt-1 (19.0 ± 15.1 vs. 12 ± 8.3 ng/mL) and of sEng (20.4 ± 9.9 vs.15.9 ± 9.4 ng/mL); respectively, p < 0.05. Women with severe disease displayed higher sFlt-1 and sEng levels when compared with mild ones (34.5 ± 11.6 vs. 9.5 ± 1.6 ng/mL, and 29.5 ± 9.0 vs. 14.8. ± 5.2 ng/mL, respectively; p < 0.001). In contrast, women with preeclampsia exhibited significant lower IL-8 and G-CSF levels compared with controls. No differences existed between either group in IL-6 levels or TNF-α.

Conclusion.?Consistent with previous reports, increased sFlt-1 and Eng levels in maternal plasma is consistent with vascular dysfunction found in gestations complicated with 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.     

Plasma fibronectin in pregnancy complicated by diabetes mellitus and preeclampsia

OBJECTIVES: The aim of this study was to evaluate concentration of plasma fibronectin (FN) in course of pregnancy complicated by preeclampsia accompanied by diabetes mellitus and to assess whether the concentration of FN depends on the state of carbohydrate metabolism. MATERIAL AND METHODS: The study was carried out in 2 groups: group K--consisting of 35 healthy pregnant women without complications, and group G --consisting of 12 pregnant women, 4 with gestational diabetes mellitus and 8 with pregestational diabetes mellitus, who developed preeclampsia, in course of research, after 37th week of pregnancy. Concentration of FN and Fm--in order to the state of carbohydrate metabolism--was marked in the following: before 33rd week of pregnancy, between 33rd and 37th week of pregnancy and after 37th week of pregnancy. RESULTS: No correlation between concentration of FN and duration of pregnancy in group K was found. Average concentration of FN in the subsequent periods of the pregnancy in group K were similar and have not shown vital, statistical differences. In group G crucial statistical increase in FN concentration along with increase of pregnancy duration was found (r = 0.3860, p < 0.07). No correlation between concentration of FN nor Fm was found in both groups. CONCLUSIONS: The results obtained demonstrate that vascular endothelial damage, as expressed by increase in plasma fibronectin levels, is a condition specific for preeclampsia, preceding its clinical manifestation. Maternal blood concentrations of FN do not depend on the state of carbohydrate metabolism estimated by concentration of Fm.