Effects of chronic hypoxia in vivo on the expression of human placental glucose transporters

Birth weight is reduced and the risk of preeclampsia is increased in human high altitude pregnancies. There has been little work to determine whether hypoxia acts directly to reduce fetal growth (e.g. reduced blood flow and oxygen delivery), or via changes in functional capacities such as nutrient transport. We therefore investigated the expression of a primary nutrient transporter, the GLUT1 glucose transporter and two in vitro markers of hypoxia (erythropoietin receptor, EPO-R, and transferrin receptor, TfR) in the syncytial microvillous (MVM) and basal membrane fractions (BMF) of 13 high (3100 m) and 12 low (1600 m) altitude placentas from normal term pregnancies. Birth weight was lower at 3100 m than at 1600 m despite similar gestational age, but none of the infants were clinically designated as fetal growth restriction. EPO-R, TfR and GLUT1 were examined by immunoblotting and maternal circulating erythropoietin and transferrin by ELISA. EPO-R was greater on the MVM (+75%) and BMF (+25%) at 3100 m. TfR was 32% lower on the MVM at 3100 m. GLUT1 was 40% lower in the BMF at 3100 m. Circulating EPO was greater at high altitude, while transferrin was similar, and neither correlated with their membrane receptors. BMF GLUT1 was positively correlated with birth weight at high, but not low altitude. In this in vivo model of chronic placental hypoxia, syncytial EPO-R increased as expected, while nutrient transporters decreased, opposite to what has been observed in vitro. Therefore, hypoxia acts to reduce fetal growth not simply by reducing oxygen delivery, but also by decreasing the density of nutrient transporters.     

Chronic hypoxia diminishes pregnancy-associated DNA synthesis in guinea pig uteroplacental arteries

Enlargement of the uterine artery (UA) during pregnancy is diminished in women residing at a high altitude. We asked whether chronic hypoxia alters the rise in DNA synthesis in uteroplacental vessels and, if so, whether the reduction is related to the intrauterine growth retardation (IUGR) observed under conditions of chronic hypoxia. We used bromodeoxyuridine (BrdU) labelling to measure DNA synthesis in all vascular layers of the UA, mesometrial arteries (MA), thoracic aorta and mesenteric artery of guinea pigs, residing throughout pregnancy at a low (1600 m) or high (3962 m) altitude. Pregnancy increased DNA synthesis throughout the UA at both altitudes, yet the maximal value was less at high than low altitude (P<0.05). Likewise, pregnancy increased DNA synthesis throughout the MA, yet at high altitude pregnancy elevated levels returned to non-pregnant values after 42 days of gestation, whereas at low altitude DNA synthesis continued to be elevated until near term. Fetal weights were lower (P=0.01) and placental/fetal weight ratios tended to be greater in high than low altitude, near term pups (P = 0.09). We conclude that a diminished growt response by the uteroplacental vasculature to pregnancy may contribute to the previously reported reduced uterine artery blood flow and resulting IUGR at high altitude.     

Relative abundance of placental pro-atrial natriuretic factor mRNA in normal pregnancy and pre-eclampsia

Atrial natriuretic factor (ANF), produced by cytotrophoblast cells of the human placenta, may be involved in the regulation of uteroplacental blood flow. Pre-eclampsia is associated with maternal hypertension and reduced uteroplacental perfusion. The relationship between pre-eclampsia and placental production of ANF is not known. This study measured pro-ANF mRNA levels by Northern blot analysis in placentae delivered by caesarean section at preterm and term gestations from women with normotensive and pre-eclamptic pregnancies and found no significant difference between pre-eclampsia and normal pregnancy at either gestation. This result suggests that placental production of ANF is not altered at the pretranslational level during pre-eclampsia.     

Altered blood pressure course during normal pregnancy and increased preeclampsia at high altitude (3100 meters) in Colorado.

OBJECTIVE: Our purpose was to determine the case incidences of preeclampsia at low and high altitudes and whether maternal blood pressure course during pregnancy differs between low and high altitudes. STUDY DESIGN: This was a retrospective cohort study of pregnancies in sociodemographically matched communities at low and high altitudes in Colorado; each community had a small hospital served by family practitioners and was located >100 miles from major urban areas. Included were consecutive singleton pregnancies of women without chronic disease that resulted in live-born infants at >28 weeks' gestation during an 18-month period (n = 116 at 1260 m, n = 93 at 3100 m). Clinic and hospital medical records were searched and data pertaining to hypertensive complications of pregnancy and serial blood pressure measurements were abstracted. RESULTS: Despite similar maternal risk factors, the case incidences of preeclampsia were 16% at 3100 m and 3% at 1260 m. As in sea-level pregnancies, mean blood pressure fell until week 20 in normotensive pregnancy at 1260 m. Mean pressure rose linearly, however, in normotensive women at 3100 m and in women with preeclampsia at both 1260 m and 3100 m. High altitude acted independently of known risk factors and yielded an odds ratio for preeclampsia of 3.6 (95% confidence interval 1. 1-11.9). Birth weight was 285 g lower at 3100 m despite similar gestational ages. CONCLUSION: The normal pregnancy-associated fall in blood pressure was absent at 3100 m, even in women who remained normotensive. The incidence of preeclampsia was increased at high altitude. Residence at high altitude interferes with the normal vascular adjustments to pregnancy, increasing the incidence of preeclampsia, and is perhaps analogous to other conditions that decrease uteroplacental oxygen delivery.     

Impact of Pregnancy at High Altitude on Placental Morphology in Non-native Women With and Without Preeclampsia

Previous data indicate that placentas from normotensive pregnancies in non-native women at 3100 m (Leadville, CO) are not hypoxic at term, despite lower uterine artery blood flow, than in the same population at sea-level. We hypothesized that placental vascular development is greater at 3100 m in compensation. Further, because the incidence of preeclampsia (PE), which has been linked to placental hypoxia, is 3–4 fold higher in this population, we investigated if preeclamptic placentas have altered vascularity compared to normotensive controls at 3100 m. Placentas from normotensive (NT) pregnancies at sea-level, 1600 and 3100 m, and late-onset preeclamptic placentas were collected at 3100 m. Placental and birth weights were determined, and stereology performed on paraffin- and resin-embedded tissue. Both normal and preeclamptic placentas at high altitude were smaller than those at sea-level, and birth weights trended down with no change in the placental index. Volume fractions of the placental and villous compartments were similar between all conditions, but the absolute volume of each compartment was reduced at 3100 m compared to sea-level. Villous volume was equivalent between sea-level and 1600 m. There were no differences between PE and NT placentas at 3100 m. Placental vascularity was similar at all altitudes, and the gas-exchange area was preserved at 1600 m but not 3100 m. Late-onset preeclampsia was not associated with placental changes at 3100 m.     

Pregnancy of diabetic women with diabetic angiopathy. Clinical results in correlation of morphological findings on the placenta]

In comparison with morphological changes of the placentae 58 pregnancies of class D and F-diabetics (with diabetic angiolopathy) were analysed. The incidence of toxaemia was 55%. Insulin requirement decreased some days before delivery in 8 cases (14%). The perinatal mortality rate amounted to 17%. Birth weights were found between 2500 and 3000 g in 9 cases, below 2500 g in 8 cases with signs of intrauterine growth retardation. The majority of placentae showed medium-sized to severe diabetic disturbances of maturation on an average more severe than in diabetics without angiolopathy. A "modification" or "mascing" of maturation disturbances by severe toxaemia is discussed. The antenatal retardation of fetal growth in some cases was attributed in part to the diabetic maturation disturbances of the placentae. Another cause may be the defective uteroplacental circulation caused by narrowing processes of myometrial and decidual arteries in consequence of long-term diabetes and hypertension.     

Changes in fetal capillaries during preplacental hypoxia: growth,shape remodelling and villous capillarization in placentae from high-altitude pregnancies

Patterns of fetoplacental angiogenesis and villous growth vary in pregnancies complicated by different forms of fetal hypoxia. This study uses stereological estimators to examine absolute and relative dimensions of villi and fetal capillaries in cases of preplacental hypoxia due to pregnancy at high altitude. Placental samples were drawn from well-defined subjects in different ethnic groups born, raised and completing term pregnancies at low (500 m) and high altitude (3600 m above sea level). Volumes, surfaces and lengths were used to monitor the nett growth of villi and capillaries. Indices of villous capillarization comprised volume, surface and length densities and capillary:villus surface and length ratios. Villus/capillary 'calibre' and shape were quantified using cross-sectional areas, perimeters and shape coefficients (perimeter(2)/area). Group comparisons were drawn by two-way analyses of variance with altitude and ethnicity as the main factors. Volumes, surfaces and lengths of villi, and volumes of capillaries, were reduced at high altitude. Capillary volume declined primarily by formation of narrower microvessels which were more irregular in outline. There were no differences in capillary surface area or length. Cross-sectional sizes and shapes of villi were unaltered. Differences in villous capillarization were confined to higher surface and length densities. Ethnic differences in villous length, capillary length and cross-sectional area tended to favour native groups who are pre-adapted to life at high altitude. Results show that high-altitude pregnancy is not accompanied by increased angiogenesis but may involve enhanced villous capillarization and vascular shape remodelling. Comparisons are drawn with changes seen in maternal anaemia. It is concluded that absolute and relative measures of villous and capillary growth are required lest misinterpretations are introduced by equating hypercapillarization with enhanced angiogenesis or the pattern of capillary branching. The importance of controlling for various potential confounders is also emphasized.     

SQUID biomagnetometry of the uterine arteries in normal and pre-eclamptic pregnancies.

AIM: This study was designed to investigate the hemodynamics of the uteroplacental circulation in normal and pre-eclamptic pregnancies using the biomagnetometer SQUID. METHOD: Twenty-two pregnancies complicated by pre-eclampsia and 49 normal pregnancies were included in this study. All were near term. Biomagnetic signals were recorded from the uterine arteries. After statistical Fourier analysis, the findings were designated in terms of spectral amplitudes as high (140-300 fT/square root of Hz), low (50-110 fT/square root of Hz) and borderline (111-139 fT/square root of Hz). RESULTS: The uterine artery waveforms and the corresponding spectral densities were of high amplitudes in most (89.7%) normal pregnancies and of low amplitudes in most (81.8%) pregnancies complicated by pre-eclampsia (p < 0.005). These findings were of statistical significance and were correlated with fetal heart rate (FHR) monitoring, pH, Apgar score at 1 and 5 minutes and birth weight percentiles: high amplitude cases were related with normal FHR patterns, pH > 7.25, Apgar score > 7 and birth weight > 75th percentile, while low amplitude recordings were connected with abnormal FHR patterns, pH < 7.25, Apgar score < 7, and birth weight < 10th percentile (8 cases) and < 50th percentile (10 cases). CONCLUSION: Biomagnetic measurement of the uterine artery flow, is a promising procedure in assessing fetal health, especially in high-risk pregnancies.     

Uteroplacental Blood Flow in Pre-Eclampsia Measurements with Indium-113M and a Computer-Linked Gamma Camera

Uteroplacental blood flow was measured with a computer-linked gamma camera after intravenous injection of 1 mCi indium-113m. Results of the measurements from 32 pre-eclamptic pregnancies and 37 normal controls are compared. The uteroplacental blood flow was measured as an index calculated from the rise time and maximum activity of the isotope accumulation curve. The uteroplacental blood flow was reduced with 50% in pre-eclampsia. In severe pre-eclampsia it was more compromised than in mild pre-eclampsia. A diminished uteroplacental blood flow was found in pre-eclampsia even in the absence of intrauterine growth retardation. The maternal placental circulation in the supine position was reduced with one third compared to that in the left lateral recumbent position.     

The regional expression of insulin-like growth factor II (IGF-II) and insulin-like growth factor binding protein-1 (IGFBP-1) in the placentae of women with pre-eclampsia

Insulin-like growth factors and their binding proteins regulate cellular proliferation, differentiation and function, and play an important role in placental development. IGF-II and IGFBP-1 are abundantly expressed by cells at the maternal-fetal interface and mediate cell-to-cell communication between trophoblasts and decidua. Placentae of pre-eclamptic pregnancies show villous cytotrophoblast proliferation, increased syncytial sprout formation and impaired trophoblast invasion. We hypothesized that the expression of IGF-II and IGFBP-1 by cells at the maternal-fetal interface is altered in pre-eclampsia. We determined the regional abundance and cellular localization of IGF-II mRNA and IGFBP-1 mRNA and protein in placentae from normotensive control and pre-eclamptic pregnancies. IGF-II mRNA was expressed in both the chorionic villi and basal plate decidua regions. Increased IGF-II mRNA abundance was observed in the intermediate trophoblasts of peri-infarct regions. IGFBP-1 expression was present only in the decidua of the basal plate and membranes, and this expression was decreased significantly in pre-eclamptic placentae. The increased IGF-II expression in the intermediate trophoblast surrounding placental infarcts suggests a role for IGF-II in placental repair or remodelling. Decreased IGFBP-1 mRNA expression in the basal plate decidua suggests that the increased concentrations of IGFBP-1 the circulation of pre-eclamptic women is not of decidual origin. The altered IGF-II and IGFBP-1 expression at the fetomaternal interface may be important in the pathophysiology of pre-eclampsia.     

Are placental lakes of any clinical significance?

The aim of this study was to determine prospectively whether an association exists between the finding of placental lakes at the 20 week scan and an increased risk of uteroplacental complications or a poor pregnancy outcome. We studied the placental appearances in 1,198 consecutive second trimester ultrasound scans performed for routine foetal abnormality screening at our institution. The placental thickness was measured at its widest diameter in the sagittal plane and the presence or absence of placental lakes was recorded. The birth weight in each case was plotted against the centile charts in use at the hospital and recorded. Specific outcome measures included foetal growth restriction (IUGR) with a birth weight below the 5th centile, pre-eclampsia, placental abruption, and perinatal deaths. Placental lakes were seen in 17.8 per cent of the scans. There was no significant association with either maternal socio-demographic factors or perinatal mortality (OR 0.94, 95 per cent CI 0.35-2.51). No association was seen with maternal cigarette smoking (OR 1.07, 95 per cent CI 0.75-1.52), a birth weight below the 5th centile (OR 0.68, 95 per cent CI 0.39-1.18), the development of pregnancy induced hypertension (OR 0.68, 95 per cent CI 0.35-1.32), severe pre-eclampsia (OR 0.72, 95 per cent CI 0.21-2.50), or placental abruption (OR 1.79, 95 per cent CI 0.46-6.99). A finding of placental lakes was six times more likely with a thick placenta >3 cm at 20 weeks gestation (OR 6.30, 95 per cent CI 4.39 to 9.05). A finding of placental lakes during the second trimester ultrasound scan does not appear to be associated with uteroplacental complications or an adverse pregnancy outcome. The lesions are more prevalent with increasing placental thickness.     

Potential role for elevated maternal enzymatic antioxidant status in Andean protection against altitude-associated SGA

Oxidative stress has been implicated in the uteroplacental ischemia characteristic of preeclampsia and small-for-gestational-age (SGA) birth, both of which are more common at high (>2500 m) vs low altitude. Since Andeans are protected relative to Europeans from the altitude-associated rise in SGA, we asked whether alterations in maternal antioxidant status or oxidative stress contributed to their protection. Enzymatic antioxidant (erythrocyte catalase and superoxide dismutase [SOD]) activity and a plasma marker of lipid peroxidation (8-iso-PGF2α) were measured during pregnancy and in the non-pregnant state in Andean or European residents of low (400 m) or high altitude (3600–4100 m). Pregnancy and altitude increased catalase and/or SOD activity to a greater extent in Andeans than Europeans. 8-iso-PGF2α levels were independent of altitude and pregnancy. SOD was lower in mothers of SGA infants at weeks 20 and 36. Our findings are consistent with the possibility that elevated enzymatic antioxidant activity contributes to Andean protection against altitude-associated SGA.     

Immunohistochemical localization of pregnancy-associated plasma protein A (PAPP-A) in placentae from normal and pre-eclamptic pregnancies

An immunohistochemical method was used to locate pregnancy-associated plasma protein A (PAPP-A) in the placenta and uterus. In addition to 10 placentae and basal plates from normal pregnancies, ranging in gestational age from 37 to 40 weeks, the following specimens were studied: three uteri obtained by hysterectomy during early pregnancy; and three placentae from patients with severe hypertensive pre-eclampsia. In early gestation, PAPP-A was localized in the villous cytotrophoblastic cell layer and the endometrial glands but was not found in the villous syncytiotrophoblast, the cytotrophoblastic cell columns or the decidual cells. On histochemical examination of placentae from cases of pre-eclampsia with hypertension, an increased number of villous cytotrophoblastic cells and so-called X-cells was observed. The monospecific antiserum to PAPP-A reacted strongly and evenly with the cytoplasm of these cells. The present study strongly suggests that the active production sites of PAPP-A are the villous cytotrophoblastic cells and the X-cells.     

Defective deep placentation

Defective deep placentation is characterised by defective remodelling of the utero-placental arteries. Under certain conditions, it is also characterised by the presence of arterial lesions, such as acute atherosis and the persistence of endovascular trophoblast. The condition has been associated with a spectrum of complications during pregnancy, including pre-eclampsia, intrauterine growth restriction, pre-term birth, pre-term premature rupture of membranes, late sporadic miscarriage and abruptio placentae. Criteria are proposed for the classification of defective deep placentation into three types based on the degree of restriction of remodelling and the presence of obstructive lesions in the myometrial segment of the spiral arteries. Although the underlying mechanisms are not understood, evidence is emerging that the origin of defective deep placentation may not lie in primary defect of the trophoblast, but in abnormalities of the endometrium and inner myometrium before or during the early stages of placentation.     

Uterine artery Doppler flow and uteroplacental vascular pathology in normal pregnancies and pregnancies complicated by pre-eclampsia and small for gestational age fetuses

This study was conducted to investigate the association between uterine artery Doppler flow patterns and uteroplacental vascular pathology in normal and complicated pregnancies in view of the recently described concept of heterogeneous causes of hypertensive pregnancy complications. Forty-three women whose pregnancies were complicated by pre-eclampsia, the HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome and/or small for gestational age (SGA) fetuses and 27 women with normal pregnancies undergoing elective caesarean section were included. We obtained uterine artery Doppler waveforms at a mean of 4 days before delivery. Placental bed biopsies were obtained at caesarean section and analysed for physiological changes and pathological changes. We found that abnormal uterine artery Doppler flow was strongly associated with pregnancy complications. Absence of physiological changes was seen in 58 per cent of complicated pregnancies and 40 per cent of normal pregnancies. Pathological changes were seen in 58 per cent of complicated pregnancies and 53 per cent of normal pregnancies; they occurred in spiral arteries with and without physiological changes, and there was no significant correlation to Doppler results. In conclusion, absence of physiological changes is associated with abnormal uterine artery Doppler flow and pregnancy complications. However, there is a gradient in the severity of uteroplacental vascular pathology and the correlation with pregnancy complications is not as strong as previously thought. There is also a significant degree of uteroplacental vascular pathology in normal pregnancies with normal uterine artery Doppler flow. This variation may be partly due to sampling error, as a typical biopsy contains only one or two spiral arteries. We hypothesize that additional factors might be necessary to induce the clinical syndrome of pre-eclampsia.     

Fetal gender and gestational-age-related incidence of pre-eclampsia

BACKGROUND: Male fetal gender is associated with an overall increased risk of pre-eclampsia. However, it was recently shown that the male: female birth ratio was decreased in pre-eclampsia associated with preterm delivery. The reason for this discrepancy is not known. OBJECTIVE: To investigate whether the fetal and newborn gender is associated with the incidence of antenatal maternal pregnancy complications, and to investigate if gender-associated risk changes with gestational age at delivery. METHODS: Population-based study including 1,158,276 infants born in Sweden 1990-2001. Five maternal diagnosis groups (pre-eclampsia, infection, preterm premature rupture of membranes, abruptio placentae, and polyhydramnios) were explored in relation to newborn infant gender and gestational age at delivery. RESULTS: When all gestational ages were evaluated, male newborn gender was associated with increased odds ratios for all five diagnosis groups, and for preterm birth before 37 weeks gestation, M/F ratio 1.17. In very preterm births (gestational age below 32 weeks), male newborn gender was associated with a significantly lower risk for pre-eclampsia (OR 0.88, 95%CI 0.80-0.97), and a marginally lower risk for polyhydramnios (OR 0.74, 95%CI 0.54-1.01). CONCLUSION: The fetal gender seems to affect the occurrence of pre-eclampsia, and possibly also polyhydramnios. The finding could be due to an increased risk for spontaneous abortions in pregnancies with male fetuses, but could also be associated with the etiology of these conditions. Evaluation of antenatal pregnancy complications from a fetal/newborn gender perspective may contribute to new insights regarding their pathophysiological mechanisms.     

Placental morphogenesis in pregnancies with Down's syndrome might provide a clue to pre-eclampsia

Insufficient perfusion of placenta in pre-eclampsia is commonly associated with oxidative stress leading to increased superoxide formation and reduced invasion of uterine spiral arteries by differentiated migratory cytotrophoblasts. The superoxide dismutase (SOD) level, responsible for eliminating toxic superoxides, drops significantly in pre-eclampsia. On the contrary, the SOD synthesis increases dramatically, compared to that of normal placenta, in pregnancies with trisomy 21 (T21) fetus. However, despite a low level of placental hypoplasia, the overall perfusion of T21 placentae is comparable to that of normal pregnancy. In the light of recent reports on alternative modes of SOD function and factors regulating pathways of cytotrophoblast differentiation, here we have attempted to reconcile the two seemingly disparate pregnancy conditions and suggest that trisomy 21 pregnancies might provide new insight into our understanding of placental morphogenesis in pre-eclampsia.     

Placental growth from the first to the second trimester of pregnancy in SGA-foetuses and pre-eclamptic pregnancies compared to normal foetuses

The aim of this study was to determine placental growth between 12-22 weeks in normal pregnancies compared to pregnancies complicated by foetal SGA and maternal pre-eclampsia (PE). The placentae of 1199 women were measured 3D sonographically at 12, 16 and 22 weeks of gestation. Placental volume growth was then calculated. Neonatal birthweight, birth centile and the occurrence of pre-eclampsia were recorded in every woman and correlated with placental growth (four groups: normals, SGA, PE, SGA+PE). SGA-placentae are already smaller at 12 weeks but then develop in a similar way to normal placentae. PE placentae are slightly, but significantly, larger at 12 weeks, grow rapidly until 16 weeks and then stop growing normally between 16 and 22 weeks. If SGA goes together with PE, both placental volume (PV) at 12 weeks as well as growth is reduced significantly. Nevertheless, placental growth between week 12 and 22 is too heterogeneous to justify using this method as a clinical tool, but it can provide new information on placental physiology underlying unfavourable obstetric outcomes.     

Pre-eclampsia: associated with increased syncytial apoptosis when the infant is small-for-gestational-age

The present investigation was undertaken to study the association between placental apoptosis and pre-eclampsia, discriminating between pre-eclamptic pregnancies with appropriate-, and small-for-gestational-age (SGA), infants. Twenty pregnancies with pre-eclampsia and SGA (birth weight at or below -2 standard deviations) infants were selected in a retrospective study. Subsequently, corresponding numbers of gestational age-matched pre-eclampsia cases with appropriate-gestational-age (AGA) (birth weight at or above the 50% centile) infants and AGA controls without pre-eclampsia were selected. Formalin-fixed placental tissue was obtained from all groups. Apoptosis was assessed by a monoclonal antibody (M30), detecting a neoepitope of cytokeratin that is generated early in the apoptotic cascade. M30-positive cells were counted in villous and decidual/ basal plate tissue fields, and results were given as numbers of M30-positive cells per field. The study was performed blinded. Increased apoptosis was found in the syncytiotrophoblast layer in pre-eclampsia with SGA infants (0.14 apototic incidents per field of villous tissue, with 0.04-0.23 as the corresponding 25-75% inter quartile range (IQR) (P=0.05)). Syncytial apoptosis in the syncytial layer in the pre-eclampsia group with AGA infants was lower (0.09, IQR 0.03-0.15) and corresponded to the level detected among controls (0.06, IQR 0.03-0.17). Apoptosis in other placental cellular compartments did not differ between groups. The increased syncytial apoptosis found in placentas from pregnancies with SGA infants may either be due to specific mechanisms associated with pre-eclampsia complicated with growth restriction, or may simply reflect the presence of syncytiotrophoblast layer damage, regardless of underlying pathological condition.     

Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational age infants

An examination of the maternal vascular response to placentation shows that physiological changes in the placental bed normally extend from the decidua into the inner myometrium. In pre-eclampsia and in a proportion of pregnancies with small-for-gestational age infants (SGA) the physiological changes are restricted to the decidual segments alone. In addition, complete absence of physiological changes throughout the entire length of some spiral arteries is seen in pre-eclampsia and SGA. This new observation is confirmed in a study of basal plates of placentas from abnormal pregnancies. Intraluminal endovascular trophoblast may be seen in the placental bed spiral arteries in the third trimester in pre-eclampsia and SGA, a feature not seen beyond the second trimester in normal pregnancy. These findings point to a defect in the normal interaction between migratory trophoblast and maternal uterine tissues in pre-eclampsia and in SGA.