Maternal cardiovascular function in pregnancies complicated by intrauterine growth restriction.

OBJECTIVE: To investigate maternal cardiovascular function in pregnancies complicated by intrauterine growth restriction (IUGR). METHODS: Maternal echocardiography and ambulatory blood pressure monitoring were performed in pregnancies complicated by IUGR (n = 12) and controls (n = 12), all of whom were normotensive at enrollment. RESULTS: Compared to controls, maternal blood pressure (P = 0.016) and total vascular resistance (P = 0.008) were higher in IUGR pregnancies. Heart rate was lower (P = 0.003), as was systolic function expressed by midwall fractional shortening (P = 0.04). No significant differences between the two groups were observed for left atrial or left ventricular dimensions, nor for left ventricular geometry. Assessment of diastolic function by means of transmitral Doppler flow measurements revealed a significantly longer isovolumetric relaxation time in pregnancies with IUGR (P = 0.006). CONCLUSIONS: In normotensive pregnancies complicated by IUGR, as compared to controls, there is decreased diastolic and systolic maternal cardiac function, and a higher blood pressure.     

High maternal blood S100B concentrations in pregnancies complicated by intrauterine growth restriction and intraventricular hemorrhage

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with perinatal mortality and with neurologic damage from intraventricular hemorrhage (IVH). We investigated whether S100B, a neural protein found in high concentrations after cell injury in the nervous system, is increased in serum of women whose pregnancies are complicated by IUGR and whose newborns develop IVH. We also explored the prognostic accuracy of maternal serum S100B for IVH in the newborn. METHODS: We conducted a case-control study of 106 pregnancies complicated by IUGR, including a subgroup (n = 26) who developed IVH after birth, and 212 unaffected pregnancies matched for gestational age. Ultrasound examination, Doppler velocimetry patterns (in the utero-placental vessels and middle cerebral artery), and maternal blood collection were performed before birth; cerebral ultrasound and neurologic examinations were performed after birth. RESULTS: S100B was higher (P <0.001) in IUGR pregnancies complicated by IVH than in those that were not and in controls. At a cutoff of 0.72 microg/L, sensitivity was 100% [95% confidence interval (95% CI), 87%-100%] and specificity was 99.3% (97.5%-99.9%) for prediction of IVH (area under the ROC curve, 0.999). The prevalence of IVH was 8.2% in the whole study population, 93% (95% CI, 83.6%-100%) in those with maternal S100B >0.72 microg/L, and 0% (0%-2.5%) in those with maternal S100B <0.72 microg/L. CONCLUSION: For prediction of IVH, measurements of maternal S100B may be useful at times before clinical, laboratory, and ultrasound patterns can identify risk of IVH.     

Angiogenic growth factors in maternal and fetal serum in pregnancies complicated by intrauterine growth restriction

The present study was performed to compare serum concentrations of maternal and fetal angiogenic growth factors in IUGR (intrauterine growth restriction) and normal pregnancy at the time of delivery. VEGF (vascular endothelial growth factor), PlGF (placental growth factor), sFlt-1 (soluble fms-like tyrosine kinase 1), sKDR (soluble kinase domain receptor) and bFGF (basic fibroblast growth factor) were measured by ELISA in serum from a maternal peripheral vein, the umbilical vein and the umbilical arteries in 15 women with pregnancies complicated by IUGR and 16 controls (women with normal pregnancies). In IUGR, sFlt-1 was increased, and PlGF and sKDR were decreased, in both maternal serum and serum from the umbilical vein. Additionally, bFGF was increased in serum from the umbilical vein of women with pregnancies complicated by IUGR. No significant differences in growth factor concentrations between the groups were found in serum from the umbilical artery. In both groups, levels of VEGF were higher and levels of sFlt-1 were lower in serum from the umbilical vein and umbilical artery compared with maternal serum. PlGF levels were found to be lower in serum from the umbilical vein compared with maternal serum in both groups, whereas PlGF levels in serum from the umbilical artery were significantly lower only in the control group. These findings suggest an imbalance of angiogenic and anti-angiogenic factors in IUGR, with formation of an anti-angiogenic state in maternal and, to a lesser extent, umbilical vein blood. The placenta appears to play a central role in the release of sFlt-1 into maternal and umbilical blood. Umbilical artery blood was unaffected in IUGR, indicating that the fetus does not contribute to changes in angiogenic growth factor concentrations.     

Abnormal maternal cardiac function and morphology in pregnancies complicated by intrauterine fetal growth restriction.

OBJECTIVE: To explore maternal cardiac function through an echocardiographic evaluation, in a group of nulliparous patients with intrauterine fetal growth restriction during the third trimester of pregnancy. METHODS: Twenty-one consecutive nulliparous pregnant women who had fetuses with intrauterine growth restriction (IUGR) and abnormal umbilical artery Doppler pulsatility index (PI) underwent maternal echocardiographic examination during the third trimester of gestation. The data were then compared with those obtained from 21 normal nulliparous women who had fetuses with an estimated fetal weight > 10th percentile and a normal umbilical artery Doppler PI who were considered as the control group. RESULTS: Heart rate was slightly lower in the IUGR group, whereas blood pressure and total vascular resistance were higher compared with the control subjects. End-diastolic volume, stroke volume and cardiac output were lower in the IUGR patients compared with normal patients. The IUGR group had smaller left atrial maximal dimensions and greater left atrial minimal areas compared with the control subjects. Left atrial function was depressed in the IUGR group. A smaller left ventricular mass was present in the IUGR patients compared with the control subjects. Isovolumetric relaxation time (IVRT) was prolonged in the IUGR patients compared with the controls. CONCLUSIONS: The absence of a 'correct' maternal cardiovascular compensatory response to abnormal trophoblastic invasion, might be one of the factors that slowly determine the conditions of reduced placental perfusion and eventually of the development of fetal growth restriction.     

Angiogenic growth factor levels in maternal and fetal blood: correlation with Doppler ultrasound parameters in pregnancies complicated by pre-eclampsia and intrauterine growth restriction.

OBJECTIVES: To correlate levels of angiogenic growth factors with Doppler ultrasound parameters in pregnancies complicated by pre-eclampsia and intrauterine growth restriction (IUGR). METHODS: In 16 women with pre-eclampsia and 15 women with isolated IUGR, pulsatility indices (PI) in the umbilical and uterine arteries were measured by Doppler ultrasonography. At delivery, maternal and fetal blood (umbilical vein and artery separately) was sampled and angiogenic growth factors measured by means of enzyme linked immunosorbent assay (ELISA). RESULTS: Umbilical artery PI was significantly higher in women with IUGR than in those with pre-eclampsia, whereas uterine artery PI was not statistically significantly different. Maternal soluble fms-like tyrosine kinase-1 (sFlt-1) levels were higher in women with pre-eclampsia than in those with IUGR (P < 0.0001). Umbilical vein basic fibroblast growth factor (bFGF) levels were lower in women with pre-eclampsia than in those with IUGR (P < 0.05). Placental growth factor (PlGF) levels in the umbilical vein were below the detection limit in nearly all samples of IUGR fetuses and lower than in those with pre-eclampsia (P < 0.001). Maternal PlGF levels were inversely correlated with PI values of both vessels. In the umbilical vein sFlt-1 was positively and soluble kinase insert domain receptor (sKDR) negatively correlated with umbilical artery PI. No correlation could be found in the serum of the umbilical artery for all growth factors and for vascular endothelial growth factor (VEGF) in all compartments. CONCLUSIONS: The correlations between maternal and fetal angiogenic growth factor serum levels and Doppler ultrasound indices of uterine and umbilical arteries in pre-eclampsia and IUGR reflect the severity of the disorders especially for the fetus. A combination of both measurements may be useful in future screening for early prediction of pregnancy complications. Published by John Wiley & Sons, Ltd.     

Upregulation of ENDOU in cytotrophoblasts from placenta complicated with preeclampsia and fetal growth restriction

Placental hypoplasia is associated with the pathophysiology of fetal growth restriction and preeclampsia. The placenta consists of differentiated trophoblasts, including cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts. Cytotrophoblasts are thought to have stem-like characteristics and the ability to differentiate into syncytiotrophoblasts and extravillous trophoblasts. However, it is poorly understood whether isolated cytotrophoblasts derived from hypoplastic placentas have specific features compared with those in normal placentas. This study aimed to determine the features of cytotrophoblasts in hypoplastic placentas. Differentially expressed proteins between isolated cytotrophoblasts from hypoplastic placenta with fetal growth restriction and those from the normal placenta were determined by liquid chromatography-tandem mass spectrometry. Among 6,802 proteins, 1,253 and 2,129 proteins were more than 2-fold upregulated and downregulated, respectively. Among them, ENDOU (endonuclease, poly(U) specific), which has high homology with the coronavirus endoribonuclease nonstructural protein 15 (Nsp15), showed a significantly increased expression in cytotrophoblasts from the placenta with fetal growth restriction related to preeclampsia compared with those in normal control placenta. These results provide insight into the pathological mechanisms of placental hypoplasia and additional information on preeclamptic symptoms in cases of SARS-CoV-2 infected placenta, although further investigation is needed.     

Monitoring of fetuses with intrauterine growth restriction: a longitudinal study.

OBJECTIVE: To describe the time sequence of changes in fetal monitoring variables in intrauterine growth restriction and to correlate these findings with fetal outcome at delivery. METHODS: This was a prospective longitudinal observational multicenter study on 110 singleton pregnancies with growth-restricted fetuses after 24 weeks of gestation. Short-term variation of fetal heart rate, pulsatility indices of fetal arterial and venous Doppler waveforms and amniotic fluid index were assessed at each monitoring session. The study population was divided into two groups: Group 1 comprised pregnancies with severely premature fetuses, which were delivered < or =32 weeks and Group 2 included pregnancies delivered after 32 completed weeks. Logistic regression was used for modeling the probability for abnormality of a variable in relation to the time interval before delivery. Trends over time were analyzed for all variables by multilevel analysis. RESULTS: Ninety-three (60 in Group 1 and 33 in Group 2) fetuses had at least three data sets (median, 4; range, 3-27) and had the last measurements taken within 24 h of delivery or intrauterine death. The percentage of abnormal test results and the degree of abnormality were higher in Group 1 compared to Group 2. Amniotic fluid index and umbilical artery pulsatility index were the first variables to become abnormal, followed by the middle cerebral artery, aorta, short-term variation, ductus venosus and inferior vena cava. In Group 1, short-term variation and ductus venosus pulsatility index showed mirror images of each other in their trend over time. Perinatal mortality was significantly higher if both variables were abnormal compared to only one or neither being abnormal (13/33 (39%) vs. 4/60 (7%); P = 0.0002; Fisher's exact test). CONCLUSION: Ductus venosus pulsatility index and short-term variation of fetal heart rate are important indicators for the optimal timing of delivery before 32 weeks of gestation. Delivery should be considered if one of these parameters becomes persistently abnormal.     

Altered placental development and intrauterine growth restriction in IGF binding protein-1 transgenic mice

IGF binding protein-1 (IGFBP-1) is a secretory product of decidualized endometrium and a major constituent of amniotic fluid. It is thought to modulate the actions of the IGFs on trophoblast cells and is therefore potentially important in regulating placental development and fetal growth. To investigate this hypothesis, we have studied the effects of decidual IGFBP-1 excess on fetoplacental growth in transgenic mice overexpressing human IGFBP-1. Endogenous fetal IGFBP-1 overexpression is associated with a transient impairment of fetal growth in midgestation. Maternal decidual IGFBP-1 excess is also associated with impaired fetal growth in midgestation independent of fetal genotype, indicating placental insufficiency. Our data also demonstrate that amniotic fluid IGFBP-1 is derived almost exclusively from maternal sources. Decidual IGFBP-1 overexpression has a marked effect on placental development. Placental morphology is abnormal in transgenic females due to altered trophoblast invasion and differentiation. These changes result in an increase in placental mass throughout pregnancy. This study provides the first compelling in vivo evidence that IGFBP-1 plays a role in placentation and suggests that IGFBP-1 has a pathological role in preeclampsia, a disorder characterized by shallow uterine invasion and altered placental development.     

The detrimental role of angiotensin receptor agonistic autoantibodies in intrauterine growth restriction seen in preeclampsia

Growth-restricted fetuses are at risk for a variety of lifelong medical conditions. Preeclampsia, a life-threatening hypertensive disorder of pregnancy, is associated with fetuses who suffer from intrauterine growth restriction (IUGR). Recently, emerging evidence indicates that preeclamptic women harbor AT₁ receptor agonistic autoantibodies (AT₁-AAs) that contribute to the disease features. However, the exact role of AT₁-AAs in IUGR and the underlying mechanisms have not been identified. We report that these autoantibodies are present in the cord blood of women with preeclampsia and retain the ability to activate AT₁ receptors. Using an autoantibody-induced animal model of preeclampsia, we show that AT₁-AAs cross the mouse placenta, enter fetal circulation, and lead to small fetuses with organ growth retardation. AT₁-AAs also induce apoptosis in the placentas of pregnant mice, human villous explants, and human trophoblast cells. Finally, autoantibody-induced IUGR and placental apoptosis are diminished by either losartan or an autoantibody-neutralizing peptide. Thus, these studies identify AT₁-AA as a novel causative factor of preeclampsia-associated IUGR and offer two possible underlying mechanisms: a direct detrimental effect on fetal development by crossing the placenta and entering fetal circulation, and indirectly through AT₁-AA–induced placental damage. Our findings highlight AT₁-AAs as important therapeutic targets.Intrauterine growth restriction (IUGR) is generally defined as fetal growth in <10th percentile for gestational age (Cetin et al., 2004) and affects 7–15% of pregnancies (Alexander et al., 2003; Cetin and Alvino, 2009). Growth-restricted fetuses have a higher incidence of mortality and morbidity than fetuses of normal growth, and are at increased risk for future development of metabolic disorders such as hypertension, coronary heart disease, dyslipidemia, obesity, impaired glucose tolerance, type 2 diabetes mellitus, and many other diseases (Barker, 1998; Godfrey and Barker, 2000; Baum et al., 2003; Hales and Ozanne, 2003). Most cases of IUGR, particularly those with significant recurrent risks, are often considered the result of ischemic placental disease (Roberts and Post, 2008; Cetin and Alvino, 2009). However, the factors contributing to placental distress and IUGR remain largely unknown.IUGR and ischemic placentas are frequently associated with a serious hypertensive disorder of pregnancy, preeclampsia (Kaufmann et al., 2003). When IUGR is observed, the preeclamptic mothers often have a poorly developed placenta characterized by shallow trophoblast invasion and inadequate spiral artery remodeling (Zhou et al., 1997a; Zhou et al., 1997b). Therefore, preeclampsia represents an appropriate disease model to investigate the molecular basis of placental damage and IUGR. Alterations in both the immune system and the renin–angiotensin system (RAS) are believed to contribute to the pathophysiology of preeclampsia (Redman and Sargent, 2005; Shah, 2006; Saito et al., 2007, Irani and Xia, 2008). Recently, these two mechanisms have been merged with reports that preeclamptic women harbor autoantibodies that activate the major angiotensin II (Ang II) receptor, AT₁, and are hence termed AT₁ receptor agonistic autoantibodies (AT₁-AAs; Wallukat et al., 1999). Many features of preeclampsia can be explained by the ability of these autoantibodies to activate AT₁ receptor on a variety of cell types (Xia et al., 2003; Thway et al., 2004; Bobst et al., 2005; Zhou et al., 2008a). We have recently shown that the introduction of these autoantibodies into pregnant mice resulted in hypertension, proteinuria, and other key features of preeclampsia (Zhou et al., 2008b). The autoantibody-induced features of preeclampsia were prevented by coinjection with losartan, an AT₁ receptor antagonist, or a 7-aa epitope peptide that blocks autoantibody-induced AT₁ receptor activation. These in vivo studies provide the first direct evidence of the pathophysiological role of AT₁-AAs in the maternal features of preeclampsia, and suggest that this animal model will be an extremely valuable investigative tool to analyze the underlying pathogenic mechanisms of various abnormalities associated with the disease. Thus, we used this animal model of preeclampsia to address the exact contributory role of AT₁-AAs in IUGR and its underlying mechanisms.In this paper, we show that AT₁-AAs exist in the cord blood of women with preeclampsia and in the fetal circulation of autoantibody-injected pregnant mice. We also observed that the autoantibody-induced preeclamptic model results in IUGR with impaired multiple organ development. Our findings indicate that these pathogenic autoantibodies enter the fetal circulation, where they may have a direct detrimental effect on fetal growth and maturation. Additionally, we found that AT₁-AAs impair placental development, resulting in organs characterized by increased apoptosis. These results were corroborated with similar findings in human placental villous explants and in cultured human trophoblast cells exposed to the autoantibody. These studies demonstrate that an abnormal placenta may be another underlying mechanism for AT₁-AA–induced IUGR. Finally, autoantibody-induced fetal growth restriction and placental apoptosis were largely corrected by coinjection with either losartan or an antibody-neutralizing 7-aa epitope peptide, indicating that autoantibody-mediated AT₁ receptor activation was required. Overall, our studies reveal the detrimental role of AT₁-AAs in IUGR and reveal two underlying mechanisms for this process. These novel findings point to possible adverse effects of AT₁-AAs on babies born to mothers with preeclampsia and identify these autoantibodies as potentially important therapeutic targets.     

核因子κB与诱导型一氧化氮合酶在糖尿病肾病大鼠肾组织中的表达

目的:观察抑制核因子κB的活性对糖尿病大鼠肾组织诱导型一氧化氮合酶表达的影响及与肾功能损害的关系。方法:实验于2005-09/2006-07在辽宁医学院生物化学实验室完成。将45只SD大鼠随机分为正常对照组、模型组和PDTC干预组3组,每组15只。模型组和PDTC干预组大鼠腹腔注射链脲佐菌素60mg/kg制备大鼠糖尿病模型,正常对照组注射相应体积的柠檬酸缓冲液。造模成功后PDTC干预组腹腔注射核因子κB活性抑制剂吡咯烷二硫基甲酸酯(PDTC),2次/d,剂量按每周20mg/kg。于注射链脲佐菌素12周末检测血清肌酐、尿素氮和24h尿蛋白定量,然后处死大鼠,留取肾标本,观测肾脏的病理改变并以Western-blot法检测核因子κB的含量,免疫组化法分析核因子κBP65及诱导型一氧化氮合酶的表达,同时应用直线相关法分析这2项指标的表达与生化指标间的关系。结果:30只大鼠进入结果分析。①模型组肾组织中核因子κBP65阳性小管数多于正常对照组和PDTC干预组[(49.35±3.87)%,(1.76±0.82)%,(24.61±3.05)%,P<0.01],PDTC干预组高于正常对照组(P<0.01)。②模型组肾组织中诱导型一氧化氮合酶阳性小管数多于正常对照组和PDTC干预组[(51.63±4.75)%,(2.52±0.93)%,(26.41±2.86)%,P<0.01],PDTC干预组高于正常对照组(P<0.05)。③模型组核因子κB的灰度值明显高于正常对照组和PDTC干预组(0.2995±0.006,0.1375±0.005,0.2045±0.004,P<0.01),PDTC干预组高于正常对照组(P<0.05)。④模型组和PDTC干预组血清肌酐、尿素氮和24h尿蛋白均高于正常对照组(P<0.01,0.05),但PDTC干预组几项指标均低于模型组(P<0.01)。⑤直线相关分析结果显示核因子κB的表达与诱导型一氧化氮合酶的表达、肾功能损害呈显著相关。结论:抑制核因子κB活性能使诱导型一氧化氮合酶的表达减少进而降低肾功能损害,提示大鼠糖尿病肾病的发生可能与肾组织中核因子κB活化介导诱导型一氧化氮合酶表达上调有关。     

细胞外调节蛋白激酶与核因子-κB活化对重症急性胰腺炎大鼠中性粒细胞凋亡延迟的调控作用

目的探讨细胞外调节蛋白激酶和核因子-κB活化对重症急性胰腺炎（severe acute pancreatitis,SAP）大鼠中性粒细胞凋亡延迟的调控作用。方法60只雄性SD大鼠随机分为对照组、SAP组、吡咯烷二硫代氨基甲酸盐（pyrrolidine thiocarbamate,PDTC）组（CPTC组）和细胞外调节蛋白激酶特异性抑制剂PD98059组各15只,对照组大鼠仅作开腹再缝合,SAP组、PDTC组和PD98059组大鼠采用胆胰管逆行注射质量分数4％牛磺胆酸钠建立SAP模型,PDTC组和PD98059组大鼠造模前分别注射PDTC和PD98059,对照组和SAP组仅注射等量生理盐水。24h后于大鼠下腔静脉取血分离中性粒细胞,体外培养16h后采用流式细胞仪检测中性粒细胞凋亡率和Bcl—xl基因表达情况。结果体外培养16h后,SAP组中性粒细胞凋亡率明显低于对照组、PDTC组和PD98059组（P〈0．01）,Bcl—xl基因表达水平明显高于对照组、PDTc组和PD98059组（P〈0．01）;PDTC组和PD98059组中性粒细胞凋亡率低于对照组（P〈0．01）;PD98059组Bcl—xl基因表达水平高于对照组（P〈0．01）,PDTC组与对照组比较差异无统计学意义（P〉0．05）。结论SAP时大鼠中性粒细胞中Bcl-xl表达明显增加,导致其自发凋亡率减低,PD98059或PDTC可明显抑制Bcl-xl表达,恢复其自发凋亡率。     

恒河猴肝移植急性排斥反应中核因子κBp65的表达

背景：核因子κB作为一种重要的核内转录因子,是多种信号转导途径的汇聚点,参与机体免疫细胞的增殖、分化及细胞凋亡等多种反应物质基因的表达调控,在体液和细胞免疫中发挥重要作用。目的：探讨恒河猴移植肝组织内核因子κBP65蛋白表达与急性排斥反应的关系。方法：将恒河猴随机分为2组：急性排斥反应组肝移植后不给予抗排斥处理,对照组肝移植过程中及移植后均给予抗排斥处理。分别在移植后6,12,24和72h4个时间点收集血标本,全自动生化分析仪测定丙氨酸氨基转移酶、总胆红素,取移植肝脏组织行苏木精-伊红染色观察组织形态结构和排斥反应,根据Banff评分系统判断排斥反应程度,采用Western blot法检测肝脏组织中核因子κBp65的表达。结果与结论：肝移植急性排斥反应发生时肝功能变化滞后于肝组织病理学检查。当急性排斥反应发生时,移植肝组织中核因子κBp65表达上调,急性排斥反应程度也随之加剧。并且在急性排斥反应早期,肝功能、病理学仅有轻微改变时,核因子κBp65表达显著升高。因此移植肝组织中核因子κBp65表达水平的检测对移植后急性排斥反应的早期诊断有重要意义,同时核因子κB可能成为控制移植急性排斥反应的新靶点。     

Fetal upper arm volume in predicting intrauterine growth restriction: a three-dimensional ultrasound study

As fetuses with intrauterine growth restriction (IUGR) may have increased risks with perinatal morbidity and mortality, prenatal diagnosis of IUGR is a very important issue in perinatology. To assess the efficacy of fetal upper arm volume in predicting IUGR, we undertook a prospective, cross-sectional study using quantitative three-dimensional (3D) ultrasound (US). In total, 40 fetuses with IUGR and 442 fetuses without IUGR were included for the upper arm volume assessment in utero by 3D US. All the fetuses were singletons and were followed up to delivery to establish whether they were complicated with IUGR or not. Our results showed that fetal upper arm volume assessed by 3D US can differentiate fetuses with IUGR from fetuses without IUGR well. The best predicting threshold for IUGR is at the 10th percentile by upper arm volume. Using the 10th percentile as the cutoff, the sensitivity of fetal upper arm volume in predicting IUGR was 97.5%, with specificity 92.8%, predictive value of positive test 54.9%, predictive value of negative test 99.8% and accuracy 93.1%. Furthermore, upper arm volume is the best parameter for detecting IUGR among the common fetal biometric indices, such as biparietal diameter (BPD), occipitofrontal diameter (OFD), head circumference (HC), abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW). In conclusion, fetal upper arm volume assessed by quantitative 3D US can be used to predict fetuses with IUGR antenatally. We believe fetal upper arm volume assessment by 3D US would be a useful test in detecting fetuses with IUGR.     

核转录因子-κB在不同宫颈组织中的活性及意义

目的:探讨核转录因子-κB(NF-κB)在宫颈癌中的活性及意义.方法:应用电泳迁移率变动分析方法(EMSA)检测宫颈癌、慢性宫颈炎和正常宫颈组织中的NF-κB活性.结果:宫颈癌中NF-κB活性明显高于慢性宫颈炎和正常宫颈组织(P<0.01);肿瘤细胞分化程度越低,其NF-κB活性越高(P<0.05);伴淋巴结转移者亦比不伴转移者显著增高(P<0.01).结论:NF-κB的活性与宫颈癌的发生、发展密切相关.其机制可能为NF-κB能调控肿瘤细胞的分化和转移.     

Correlation of Doppler and placental immunohistochemical features in normal and intrauterine growth-retarded fetuses.

The aim of this study was to correlate and compare Doppler and anatomical placental findings obtained from 48 normal and 35 intrauterine growth-retarded (IUGR) fetuses. The IUGR group consisted of 19 fetuses from pregnancies complicated by pre-eclampsia and 16 from healthy mothers. Color Doppler evaluation of umbilical, spiral and uterine arteries was performed. Placental specimens from both normal and growth-retarded fetuses were obtained at the time of delivery. Placental specimens were evaluated using histochemical and immunohistochemical techniques. A progressive decrease in the pulsatility index was observed in umbilical, spiral and uterine arteries throughout pregnancy in the normal-growth fetuses. High umbilical artery pulsatility index values were obtained in 29 out of the 35 growth-retarded fetuses, six of them showing absent or reversed end-diastolic umbilical artery flow pattern. A total of 13 IUGR fetuses showed high resistance uterine artery flow velocity waveforms. Increased pulsatility index values were obtained from the spiral arteries of 16 growth-retarded fetuses. Abnormal histological and histochemical placental patterns were observed in all the growth-retarded fetuses with umbilical artery Doppler abnormalities. The presence of a peculiar dendritic cell subpopulation, strongly resembling the Langerhans cells, expressing the HLA-DR+/CD1+ phenotype, was detected in all growth-retarded fetuses, whether there was maternal pathology or not. Our data show uterine and spiral artery data as being ineffective in the monitoring of IUGR fetuses. The placental extracellular matrix seems to play an important role in the regulation of the umbilical circulation. The presence of CD1+ cells as a sign of a possible immunological mechanism in the pathogenesis of the intrauterine growth retardation is discussed.     

Prenatal sonographic diagnosis of congenital heart disease and intrauterine growth restriction: a case-control study

PURPOSE: To determine the prevalence of intrauterine growth restriction (IUGR) in cases of congenital heart disease (CHD) and to evaluate whether the prenatal diagnosis of isolated CHD was a significant risk factor for IUGR. METHODS: We conducted a retrospective case-control study of prenatally detected CHD with delivery at >/=20 weeks' gestation between January 1, 1998, and December 31, 2001. Four groups were analyzed: (1) all cases with CHD, (2) after exclusion of abnormal karyotype, (3) after exclusion of abnormal karyotype and prenatally diagnosed extracardiac anomaly, and (4) after exclusion of abnormal karyotype and prenatally and postnatally diagnosed extracardiac anomaly. The prevalence of IUGR was determined in each of the 4 study groups and was compared with controls. RESULTS: There were 13,395 deliveries at >/=20 weeks' gestation. Of the 180 cases of CHD, 22.8% were associated with IUGR compared with 11.6% of controls (p < 0.01). In contrast, there was no statistically significant difference in the prevalence of IUGR in the 140 cases of isolated CHD compared with controls (12.9% versus 10.0%). CONCLUSION: The prenatal detection of isolated CHD does not seem to be associated with IUGR.     

Maternal and fetal hemodynamic effects induced by nitric oxide donors and plasma volume expansion in pregnancies with gestational hypertension complicated by intrauterine growth restriction with absent end-diastolic flow in the umbilical artery.

OBJECTIVE: To evaluate the effect of plasma volume expansion (PVE) and nitric oxide (NO) donors, in addition to antihypertensive therapy for gestational hypertensive pregnancies complicated by intrauterine growth restriction (IUGR) with absent end-diastolic flow (AEDF) in the umbilical artery (UA). METHODS: This was a case-control study into which 32 gestational hypertensive pregnancies with IUGR and AEDF were enrolled. Sixteen of these were treated with antihypertensive drugs, NO donors and PVE (Group A), and 16, matched for maternal age, gestational age and fetal conditions, were treated with antihypertensive drugs only (Group B). All patients underwent fetal and uteroplacental assessment and maternal echocardiography to evaluate total vascular resistance (TVR) and cardiac output before and 5-14 days after initiation of treatment. RESULTS: After 5-14 days of treatment, the maternal TVR in Group A fell from 2170 +/- 248 to 1377 +/- 110 dynes.s.cm(-5) (P < 0.01), and that in Group B fell from 2090 +/- 260 to 1824 +/- 126 dynes.s.cm(-5) (P < 0.01), with the reduction being greater in Group A than in Group B (P < 0.01). There was a significant increase in cardiac output in Group A after 5-14 days of treatment vs. baseline (6.19 +/- 0.77 vs. 4.32 +/- 0.66, P < 0.001), and, after treatment, cardiac output was significantly greater in Group A than it was in Group B (6.19 +/- 0.77 vs. 4.70 +/- 0.44, P < 0.001). Reappearance of end-diastolic flow in the UA occurred in 14/16 patients in Group A but in no patients in Group B (87.5% vs. 0%, P < 0.05). The interval between detection of UA-AEDF and delivery was 28 +/- 16 days in Group A and 11 +/- 6 days in Group B (P < 0.05). CONCLUSION: Administration of NO donors and PVE in gestational hypertensive pregnancies affected by IUGR and UA-AEDF appears to improve both maternal and fetal hemodynamics, inducing prolongation of gestation.     

Physiologic restriction versus genetic weight potential: study in normal fetuses and in fetuses with intrauterine growth retardation.

Physiologic weight restriction is defined as the difference between the genetic and real weight in a normal fetus. The aims of this study were (1) to obtain, in normal pregnancies, reference values of mean weight restriction between 32 and 42 weeks for both male and female fetuses, and (2) to observe how weight restriction may influence intrauterine growth retardation. In the first part of the study, 1004 ultrasonograms of 389 different women were studied and the estimated fetal weights with their regression curves were calculated and drawn for all fetuses by sex. Differences between the 50th percentile of the genetic curves in normal population and the estimated fetal weight values for each of the 1004 examinations were calculated and weight restriction 50th and 90th percentiles were described. In the second part of the study, genetic curves were constructed retrospectively for 20 fetuses with intrauterine weight restriction whose examinations were performed before week 28 and were compared with curves for the normal population. Finally, for the 20 patients with intrauterine weight restriction, differences between genetic and real weight at delivery were plotted and compared with weight restriction 50th and 90th percentiles. Also, fetuses with intrauterine weight restriction were compared according to differing degrees of restriction. Weight restriction began between 31 and 33 weeks of gestation and was earlier and marked in female fetuses. Genetic percentiles were higher in normal fetuses than in fetuses with intrauterine weight restriction. In addition, pregnancies of intrauterine growth restricted fetuses with greater degrees of weight restriction were more abnormal than those of fetuses with a lesser degree of weight restriction. Both facts imply that some of the fetuses included in the classic diagnosis of intrauterine weight restriction may be genetically small fetuses. Concepts of weight restriction and physiologic weight restriction might be applied to discriminate between normal, genetically small fetuses and fetuses affected with intrauterine growth retardation.