The histology and histomorphometry of umbilical cord cross section in preeclampsia and normal pregnancies: a comparative study

ABSTRACT

The umbilical cord is the connecting link between the mother and the fetus and its morphology is an indicator of fetal well-being. Preeclampsia is a disorder of pregnancy associated with new-onset hypertension, which occurs most often after 20 weeks of gestation. There are structural differences in the umbilical cord of normotensive and hypertensive pregnant women. This research aimed to study the histology and histomorphometry of umbilical cord areas in preeclampsia and compare the parameters with normal uncomplicated pregnancies of gestational age 37–40 weeks. A total of 70 umbilical cords were studied from preeclampsia (n = 35) and normal (n = 35) pregnancies. The parameters studied included cross-sectional areas (CSA) of umbilical cord, umbilical vein lumen, umbilical vein wall, umbilical artery lumen, umbilical artery wall, and Wharton’s jelly, including the presence of edema in the vessel walls and Wharton’s jelly and basement membrane thickening. The mean umbilical cord CSA was significantly higher in preeclampsia (p = 0.014). The mean umbilical artery lumen CSA was significantly lower than the normal pregnancy cords (p = 0.006). The mean Wharton’s jelly CSA in preeclampsia was significantly higher than the normal pregnancy cords (p = 0.004). The parameters for umbilical vein lumen CSA, umbilical vein wall CSA, and umbilical artery wall CSA did not show any significant difference. Histological findings were edema (p < 0.001) and thickened basement membranes (p < 0.0001) were considered significant.     

Different Etio-Pathogenesis in Intrauterine Growth Retardation in Developing Country: Histomorphometric Evidence

The present study was conducted to compare histomorphometric parameters of umbilical cord and its vessels in intrauterine growth retarded fetuses and normally grown fetuses. The study was conducted on umbilical cords taken from thirty intrauterine growth retarded (IUGR) fetuses and thirty normally grown fetuses (NGA). Histomorphometric parameters were measured with the help of planimeter. In the present study it was found that in cross section the total umbilical cord area in IUGR group is 59.00+3.67 mm² and in the control group is 75.91+4.77mm² (p<0.05). Jelly area in IUGR group is 47.90+3.11 mm² and in control group is 60.26+4.55 mm2 (p<0.05). Total vessel area in control group is 15.45+1.73 mm² and in IUGR group is 10.95±1.20mm² (p <0.05). Total umbilical cord area, umbilical cord jelly area and total vessel area are significantly lower in the IUGR group but no significant difference was observed in total luminal area, total area of blood vessels and wall thickness of umbilical blood vessels. So in the study it was found that histomorphometric parameters of umbilical cord of IUGR fetuses are significantly lower than that of normally grown fetuses of similar gestational age.     

Fetal endothelial cells express vascular cell adhesion molecule in the setting of chorioamnionitis

PROBLEM: In intrauterine infection, inflammatory mediators may be released into the fetal circulation prior to fetal infection. We hypothesize that, in chorioamnionitis, inflammation alters fetal blood vessels. To test this, fetal endothelial cells were examined for vascular cell adhesion molecule (VCAM). METHOD OF STUDY: Umbilical cords (n = 9) from placentas with chorioamnionitis were immunostained for VCAM. Controls from preterm preeclamptic pregnancies (n = 7) without histologic inflammation were selected, and matched for gestational age and method of delivery. VCAM sections were reviewed by a pathologist blinded to clinical diagnoses. RESULTS: All endothelial cells from each of the nine cords from placentas with chorioamnionitis had strong VCAM staining. Two of nine samples also had acute cord vasculitis. No cord endothelial cells from preeclamptic placentas demonstrated similar VCAM staining (p < 0.01). CONCLUSION: Histologic chorioamnionitis was associated with VCAM expression of the umbilical cord vessels. In chorioamnionitis, inflammatory mediators may have entered the fetal circulation to activate endothelial cells. Intrauterine inflammation was not restricted to the chorioamnion, but also involved the fetal circulation.     

A comparative analysis of glycosaminoglycans from human umbilical arteries in normal subjects and in pathological conditions affecting pregnancy.

BACKGROUND: Vascular cells express different phenotypes in adult and fetal vessels, and the extracellular matrix they synthesize should reflect these differences. Alterations of vascular proteoglycan/glycosaminoglycan is verified in disorders such as hypertension and diabetes, and when occurring during pregnancy, they bring about structural changes to fetal vessels that often lead to impaired fetus growth. Yet there is little data about the extracellular matrix of an important human fetal vessel, the umbilical artery. EXPERIMENTAL DESIGN: This study involved the biochemical characterization of the extracellular matrix of normal umbilical arteries, umbilical arteries from complicated pregnancies (maternal hypertension and diabetes and intrauterine growth retardation syndrome), and, for purpose of comparison, normal adult arteries (aorta and iliac and pulmonary arteries). Although the collagen types I:III ratio was determined in some cases, emphasis was placed on analysis of glycosaminoglycans. RESULTS: Normal umbilical arteries differ from normal adult arteries in that they contain greater concentrations of hyaluronic acid and lesser concentrations of heparan sulfate and chondroitin 4- and 6-sulfate. The umbilical artery also differs from adult arteries in the disaccharide composition of its chondroitin and heparan sulfates and in the molecular weight of this latter glycosaminoglycan. The glycosaminoglycan distribution in umbilical arteries derived from complicated pregnancies is roughly similar to that of controls. However, total glycosaminoglycan and collagen were significantly reduced, and the collagen I:III ratio was increased in the umbilical arteries from hypertension-complicated pregnancies. CONCLUSIONS: The glycosaminoglycan composition of the normal umbilical artery, a fully differentiated tissue, differs in many aspects from that of normal adult arteries. Of the cases of complicated pregnancies studied, the extracellular matrix of umbilical arteries was altered only in maternal hypertension. The changes, notably a mild fibrosis, were not very pronounced and should not impair hemodynamic properties of the vessel.     

胎儿宫内生长迟缓脐血5—羟色胺变化及临床意义

目的：探讨胎儿宫内生长迟缓（ＩＵＧＲ）与５－羟色胺含量关系,方法：采用ＲＦ－５０００型荧光分光乐度计测量法测量正常体重组与ＩＵＧＲ组脐静脉、脐动脉血浆中５０ＨＴ含量。结果：正常新生儿体重及ＩＵＧＲ,脉静脉、脐动脉之间血浆中５－ＨＴ含量无明显差异（Ｐ〉０．０５）ＩＵＧＲ组脐静脉、脐动脉血浆中５－ＨＴ含量明显高于正常体重组,而且差异非常显著（Ｐ〈０．０１）,结论：ＩＵＧＲ脐血管痉挛与５－ＨＴ含量有密切     

'Cor placentale': placental intervillus/intravillus blood flow mismatch is the pathophysiological mechanism in severe intrauterine growth restriction due to uteroplacental disease

The underlying pathophysiology in most cases of severe intrauterine growth restriction and pre-eclampsia is thought to be abnormal and inadequate conversion of the branches of the uterine arteries into low resistance uteroplacental vessels, due to poor extravillous trophoblastic invasion, leading to reduced intervillous blood flow. Since, in most vascular beds the main site of flow resistance is at the level of the small arteries/arterioles rather than the capillary bed itself it is likely that in cases of intrauterine growth restriction due to uteroplacental dysfunction with abnormal fetal umbilical artery flow velocity waveforms, the underlying pathological mechanism is primarily an initial reduction in intervillus flow leading to relative local hypoxia of some villus territories. This results initially in autocrine/paracrine mediated localized stem artery vasoconstriction to minimize intervillus/intravillus flow mismatch which, when widespread, will result in abnormal umbilical artery Doppler waveforms due to the globally increased resistance to fetoplacental flow. Since, a small reduction in vessel radius will result in an exponential increase in flow resistance and reduction in flow, the magnitude of stem vessel constriction need only be small to result in large changes in fetoplacental vascular haemodynamics. Thus, the underlying progressive pathology in this condition may be cardiac failure, secondary to chronic stem vessel vasoconstriction caused by abnormalities in oxygenation of the fetal respiratory system hence the term 'cor placentale' is proposed.     

Umbilical and uterine artery flow velocity waveforms in pregnant women with systemic lupus erythematosus treated with aspirin and glucocorticosteroids.

Pregnancy in systemic lupus erythematosus (SLE) is at high risk to the mother and fetus. Impaired utero-placental perfusion may increase fetal loss and intrauterine growth retardation. We assessed the changes in impedance to blood flow in the umbilical and uterine arteries in five patients with SLE treated with low dose aspirin and corticosteroids, using Doppler ultrasound longitudinally throughout pregnancy. Blood flow velocity waveforms of the umbilical and uterine arteries were studied by transabdominal and transvaginal Doppler ultrasound, respectively. Resistance index (RI) was measured every two to four weeks from week 10 to term, and the values obtained were compared to those of normal pregnancies. All five patients delivered uneventfully. One neonate was delivered at 36 weeks (2550 g) and one neonate was growth retarded (1900 g at 38 weeks). Three women delivered at 39 weeks (3585 g, 2850 g, and 2800 g). Most umbilical artery RI values obtained throughout pregnancy were above the 95th percentile of normal pregnancies. The highest values of RI of the umbilical artery were assessed in the case of fetal growth retardation. However, most measurements of RI of the uterine artery were under the 95th percentile of normal. The improved pregnancy outcome in patients with SLE treated with aspirin and corticosteroids seems to correlate with their normal uterine artery flow velocity wave forms.     

Subchorionic placental cyst: a cause of fetal growth retardation--ultrasound and color-flow Doppler diagnosis and follow-up.

Subchorionic placental cysts are ominous findings. When attached near the umbilical cord insertion, the risk of umbilical cord constriction is increased. This may cause fetal growth retardation and intrauterine asphyxia. This article reports a case of subchorionic placental cyst diagnosed in the first trimester by transvaginal ultrasound. Color Doppler ultrasound demonstrated a reduction of the umbilical cord bloodstream as the cyst increased in size. Fetal growth retardation was evident in the third trimester.     

Pregnancy‐Induced Hypertension is Associated With Altered Anatomical Patterns of Hyrtl's Anastomosis

Umbilical arteries carry the blood from the fetus to the placenta and are typically connected by Hyrtl's anastomosis, a connection that is located near where the umbilical cord meets the placenta. The investigation of the anastomosis in pathological conditions, including pregnancy‐induced hypertension is limited. Hence, 200 placenta and umbilical cords, 100 from normotensive and 100 from pregnancy‐induced hypertensive subjects, were dissected and measurements were recorded. A single anastomosis between the umbilical arteries was observed in167 specimens. In 16 cases, the two umbilical arteries were fused, in 15 cases there was no anastomosis, and in two cases there was a single umbilical artery. In one specimen from a normotensive case, a double anastomosis was observed. To our knowledge this is only the second report of this rare anatomical variant. When an anastomosis is present, the connecting vessel can be transverse to or form an oblique angle with the umbilical arteries. We observed a striking increase in the number of artery pairs connected by a transverse vessel in specimens from hypertensive subjects relative to those from normotensive subjects. Moreover, placentas from hypertensive donors were small if the umbilical arteries were connected by an oblique anastomosis. In addition, the length of the anastomosis and its distance from the cord insertion was shorter in specimens from hypertensive compared to normotensive subjects. We conclude that pregnancy‐induced hypertension alters the anatomy of Hyrtl's anastomosis, and in some circumstances, the placenta. Anat Rec, 297:819–825, 2014. © 2014 Wiley Periodicals, Inc.     

Intrauterine fetal death due to umbilical cord torsion

We report a case of intrauterine fetal death due to torsion of the umbilical cord. Umbilical cord torsion has usually been regarded as secondary to fetal death or cord constriction or due to a lack or abnormality of Wharton's jelly. A postmortem examination showed torsion of the umbilical cord at the placental end in a cord without constriction and with normal Wharton's jelly. We therefore suggest that umbilical cord torsion in the absence of predisposing constriction or abnormality of Wharton's jelly can obstruct the umbilical blood vessels and cause intrauterine death.     

脐动脉血流测定与胎儿脐带绕颈

目的 :研究脐血流测定对脐带绕颈的预后评估。方法 :对 2 8例B超诊断为脐带绕颈的胎儿产前进行了脐动脉血流S/D值的测定 ,追踪观察围产儿出生时羊水性状、Apgar评分、脐带绕颈情况。 结果 :2 8例B超诊断为脐带绕颈的胎儿产时有 5例未发现脐带绕颈 ;而且S/D值 <3 .0的 2 4例 ,围产结局良好 ;S/D值 >3 .0的 4例 ,娩出时均是脐带绕颈很紧 ,其中 3例羊水粪染 ,Apgar评分均 <7分。结论 :S/D值可作为衡量脐带绕颈对胎儿危害程度的一种方法 ,结合B超为临床决定分娩方式提供依据     

子痫前期胎盘、脐血管中神经激肽B表达及组织病理变化的研究

目的研究子痫前期患者胎盘、脐血管中神经激肽B（neurok in in B,NKB）的表达及组织的病理变化情况。方法采用SP法对轻、重度子痫前期组共40例和正常妊娠组20例的胎盘和脐血管组织进行NKB的免疫组化染色,观察各组NKB的定位、分布和表达量的差异。同时常规HE染色观察各组胎盘、脐血管的病理变化。结果NKB在各组胎盘合体滋养细胞、毛细血管内皮细胞、脐静脉内皮细胞中均有不同程度的表达。轻、重度子痫前期胎盘组织中,其NKB含量明显高于正常组（P〈0.05,P〈0.01）,HE染色可见子痫前期组细胞滋养细胞增生,合体细胞结节、纤维素样坏死显著增多等病理变化,与正常组相比有显著性差异。结论胎盘可能是NKB的重要产生释放部位。且NKB可能通过某些直接或间接的途径,参与了子痫前期损伤和代偿并存的复杂变化,在子痫前期的发生发展中起着重要作用。     

Calcification of umbilical artery: two distinct lesions.

The clinical and pathological features of five cases of calcification of umbilical cord vessels were reviewed. Two distinct lesions were identified: calcification could produce either sclerosis of the wall or obliteration of the lumen. In three cases there was calcification within the media and adventitia of the umbilical arteries, with extension into Wharton's jelly in one case. The pathogenesis of this pattern of calcification--the sclerotic variant--is unclear but the findings of inflammation in the umbilical cord and its vessels, membranes, and decidua suggest intrauterine infection. In two cases there was complete calcification of umbilical arterial lumina resulting in total obliteration. The findings of fetal vessels in the chorionic plate with medial calcification in one of these two cases raises the possibility of thrombosis within the umbilical cord vessels as a cause, but the latter was not found. One infant from each group was liveborn. Both had shown signs of fetal distress in utero and delivered prematurely. The other three pregnancies resulted in macerated stillbirth preterm.     

15号环状染色体综合征的产前诊断

目的探讨15号环状染色体综合征产前诊断的进展。方法对1例15号环状染色体综合征胎儿超声检查,脐带血染色体G带分析。结果胎儿脐带血染色体G显带分析为15号环状染色体,伴有单脐动脉,膈疝等。胎儿双亲染色体未见异常。结论本例支持15号环状染色体综合征胎儿伴随膈疝,宫内发育迟缓等症状。     

The nerves of the umbilical cord in man and the rat

A thiocholine technique was used to visualize nerves in human and rat umbilical cords. The allantoic part of the rat umbilical cord was found to be separate from the vitelline part of the cord and its vessels were not innervated. However, acetylcholinesterase-positive nerves formed a plexus around the vessels of the vitelline part of the 21-day rat umbilical cord. These nerves displayed fusiform swellings and terminated as simple endings close to the yolk sac wall. The findings suggest that the vitelline circulation in the rat may function under neural control. An investigation of full-term human umbilical cords revealed extrafetal acetylcholinesterase-positive nerves. Nerve bundles passed from the fetus into the cord and split into a plexus. Beaded nerve terminals were found about 15–20 cm from the fetus. Some of these endings touched the media of the vein; others ended freely in the cord substance between the arteries and the vein. There were no periarterial terminals and no nerves were found in the maternal half of the cord. The free nerve endings in the human cord may have been sensory, since they made no terminal effector contact. However, it should be noted that similar terminals touched the media of the umbilical vein. The endings described could be sensory receptors for the sphincter of the ductus venosus that controls venous return from the fetus.     

肾综合征出血热病毒宫内感染的临床研究

目的 研究肾综合征出血热(HFRS)病毒宫内感染情况及其对婴儿的影响。方法 对妊娠期感染HFRS病毒者，于其分娩时留取母血和脐带血进行抗—HFRS IgG检测，同时对顺产新生儿采取静脉血进行抗—HFRS IgM检测，并应用血凝抑制试验(HI)对HFRS病毒进行分型，另外对顺产的新生儿进行全面查体和定期随访观察。结果 母血抗—HFRS IgG均阳性，死胎的27例脐带血抗—HFRS IgG阳性23例，孕妇痊愈后自然分娩的12例中脐带血和静脉血有2例抗—HFRS IgG阳性，而抗—HFRS IgM阴性。并发现14例顺产新生儿生长发育全部正常。结论 HFRS病毒存在宫内感染，并易致死胎，但对顺产婴儿未发现致畸作用。     

B超引导下游离脐静脉穿刺术用于产前诊断的分析

目的：探讨B超引导下游离脐带穿刺术成功率和安全性。方法：对153例因各种原因行产前诊断的孕妇进行B超引导下游离脐静脉穿刺术。结果：1．43例18w－21w孕妇穿刺成功率为87．3％，60例22w-28w孕妇成功率97．5％，50例28w以上的成功率为100％，总成功率95．5％。2．并发症：96例穿刺经过胎盘，胎盘渗血32．3％（31／96），脐带穿刺后渗血16．3％（25／153）。胎儿心动过缓者占5．9％（9／153）。术后未出现晚期流产、胎死宫内、早产、宫内感染等并发症。结论：B超引导下游离脐带穿刺术用于产前诊断是一项成功率高而且安全的方法。     

Expression of insulin-like growth factor in the placenta of intrauterine growth-retarded human fetuses

Many cases of intrauterine growth retardation (IUGR) are the result of placental and fetal tissue insufficiency. Insulin-like growth factor-I (IGF-I) is known to play a role in placental and fetal growth. An immunocytochemical study was performed to localize IGF-I peptides in human placenta and umbilical cords of normal (n = 3) and IUGR (n = 3) fetuses. The peripartum fetal conditions were evaluated as well. Immunoreactive IGF-I was detected in the cytotrophoblast, syncytiotrophoblast, amnion, endothelial cells of fetal capillaries and in the decidua in both normal and IUGR placental tissue. A more robust immunostaining and increased numbers of positively stained cells were found in the decidua of IUGR placenta (p < 0.001). Intense immunostaining was also found in endothelial cells, smooth muscle cells and fibroblasts of the umbilical vein. IGF-I immunoreactivity was also present in stroma (Hofbauer cells and/or fibroblasts) of IUGR villi. Our results indicate that expression of IGF-I is high in specific sites in placenta and umbilical cords, which indicates a paracrine and/or endocrine function. The increased expression of IGF-I in placenta of IUGR fetuses indicates its involvement in restoring normal growth by means of a positive feed-back mechanism.     

Endomysial antibody detection using human umbilical cord tissue as substrate: reactivity of cells in Wharton's jelly

The measurement of immunoglobulin A (IgA) endomysial antibodies is now established as an important diagnostic test in gluten-sensitive disease. Monkey oesophagus is the commonly used tissue substrate, but it has been proposed that human umbilical cord tissue may be a suitable alternative for antibody detection. In this study, we report a modified method of examining endomysial antibody reactivity with cord tissue. This involves examination of antibody reactivity with cells in Wharton's jelly, and with umbilical cord blood vessel. A total of 370 patients being investigated for coeliac disease were studied and this diagnosis was established in 42. Endomysial antibodies were found in all 42 using umbilical cord tissue, and the test results were confirmed with monkey oesophagus substrate. In three of the remaining 328 non-coeliacs, a false-positive endomysial antibody test was noted and small intestine histology was normal in these patients. All positive sera were found to react with cells in Wharton's jelly, and reticular staining of blood vessels was also present. Examination for immunofluorescence in both Wharton's jelly and blood vessel components of cord tissue greatly simplified test interpretation.     

Pre-eclampsia associated alterations of the elastic fibre system in umbilical cord vessels

Although pre-eclampsia (PE) is often associated with fetal hypoxia, hypertension and/or disturbed function of the fetal circulation, the effect of these altered hemodynamic parameters on the structure and composition of umbilical vessels has not been systematically investigated before. Therefore, this study focuses on PE-associated changes of the elastic fibre system in umbilical cord vessels investigated by light and electron microscopy, immunocytochemistry and biochemistry. In umbilical cord veins, no changes in thickness of the vessel wall or of any sublayer were observed. However, the internal elastic lamina of the veins was split in 80% of the PE-group in contrast to 20% in uncomplicated pregnancies. This effect was significant (α <0.01) from 36 weeks of gestation onwards. In umbilical cord arteries, the entire arterial vessel wall was found to be 15% thicker in PE than in uncomplicated pregnancies. The enlargement was caused by an increase of both the tunica intima and tunica media. The thickening of the tunica intima was attributed to a migration of smooth muscle cells towards the endothelium, accompanied by a splitting of the internal elastic lamina. Compared to uncomplicated pregnancies, smooth muscle cells of arteries and veins in PE showed a metabolic activation demonstrated by highly dilated endoplasmic reticulum. A semiquantitative score method as well as a quantitative dot blot assay indicated a PE-associated reduction of elastin expression in the arterial vessel walls. In summary, PE obviously induces a decrease of the elastin content accompanied by a thickening of the vessel wall in umbilical cord arteries. This remodeling of the elastic fibre system, together with an increased migration of smooth muscle cells, might represent part of the functional adaptation system of the umbilical cord arteries on the altered hemodynamic conditions in PE. Accepted: 29 November 1999