Cerebro vascular reactivity (CVR) of middle cerebral artery in response to CO25% inhalation in preeclamptic women

Abstract

Objective: To compare the cerebro vascular reactivity (CVR) of middle cerebral artery (MCA) in response to CO2_5% inhalation between preeclamptic and normotensive pregnant women, also, between mild and severe preeclampsia.

Study design: A comparative study was performed on 61 women with preeclampsia and 65 normotensive pregnant women who were in the third trimester of gestation. MCA transcranial Doppler ultrasound was used to measure CVR in response to CO2_5% inhalation. Pulsatility index (PI), resistance index (RI), blood pressure, maternal age, gestational age and gravidity were also recorded.

Results: Baseline PI and RI were lower in the preeclamptic group (p?<?0.05). Inhalation of CO2_5% caused significant increase in CVR among normotensive pregnant women in comparison with preeclamptic group (1.006?±?0.229 versus 0.503?±?0.209, p?=?0.0001). Significantly, more cerebral vasodilatation was found among mild preeclamptic women in comparison with severe preeclamptic women (0.583?±?0.193 versus 0.383?±?0.173, p?=?0.0001). The receiver operating characteristics curve analysis revealed acceptable difference between CO2 stimulation test of preeclamptic and normotensive women (Area under curve?=?0.973, p?=?0.0001).

Conclusion: CVR in response to CO2_5% is less in preeclamptic pregnant women than normotensives, also, in severe preeclampsia, it is less than mild preeclampsia.     

Alteration of vascularization in preeclamptic placentas measured by three-dimensional power Doppler ultrasound

Abstract

Objective: To evaluate the alteration of vascularization in preeclamptic placentas measured by three-dimensional (3D) power Doppler ultrasound.

Methods: We performed a prospective study of placental vascularization and placental volume in 27 singleton pregnancies complicated by preeclampsia and 41 normal pregnancies from 27 to 39 weeks of gestation. The placental volume was analyzed using the VOCAL imaging analysis program and 3D power histogram was used to calculate the placental vascular indices including vascularization index (VI), flow index (FI) and vascularization flow index (VFI).

Results: Of the 27 preeclamptic pregnancies, 9 were complicated by intrauterine growth restriction and 15 were severe preeclampsia. Furthermore, nine of the preeclamptic pregnancies had abnormal end diastolic flow in the umbilical artery. No significant correlation was noted between the placental vascular indices and gestational age in normal pregnancies. The placental vascular indices including VI, FI and VFI were significantly lower in preeclamptic placentas compared with controls (VI, p?<?0.001; FI, p?=?0.022; VFI, p?<?0.001). Preeclamptic placental volume was also decreased compared with that of the controls (p?=?0.002). After adjustment for confounding factors, significant differences were observed in VI and placental volume. However, no correlation was found between 3D power Doppler vascular indices and umbilical artery flow velocities, and neither intrauterine growth restriction nor the severity of preeclampsia could be predicted by the vascular indices.

Conclusion: VI and placental volume are reduced in preeclamptic placenta. Placental vascular indices using 3D power Doppler ultrasound provide insights of placental vascularization in preeclampsia.     

Placental maturity,hypertensive disorders of pregnancy and birth weight

Objectives: To compare maturity of placentas from women with hypertensive disorders with those from normotensive pregnancies and to determine the relationship between placental maturity (PM) and the diagnosis of small-for-gestational-age (SGA) in the newborns. Materials and methods: We examined placental stained specimens from women with normotensive pregnancies (n?=?100), diagnosis of gestational hypertension (n?=?38), mild (n?=?10), or severe preeclampsia (n?=?34) in an optical microscope. Placental Maturity Index (PMI) was calculated as the number of vasculo-syncytial membranes (VSM) in 1?mm² divided by VSM thickness (µm). Hypermaturity was defined as >90th percentile of the PMI from placentas of normotensive pregnancies. Newborns were classified as SGA, adequate-for-gestational-age (AGA) or large-for-gestational-age (<10th, 10–90th, and >90th percentile from weight for gestational age reference tables, respectively). Results: PMI in preeclamptic women (taking together mild and severe preeclampsia, PMI?=?43.4?±?1.6) was significantly higher than in normotensive women (PMI?=?36?±?2, p?=?0.045). Hypermaturity was more frequent (p?p?=?0.41). The frequency of hypermaturity in placentas from women with gestational hypertension was not statistically different than in normotensive women. Hypermaturity was also more frequent in placentas from SGA (OR?=?2.63, p?Conclusion: The PMI was increased in preeclampsia, but not in gestational hypertension. Placental hypermaturity was also associated with the diagnosis of SGA in newborns. PM might have a role in the relationship between maternal factors and SGA.     

Mechanism of increased maternal serum total activin a and inhibin a in preeclampsia

OBJECTIVE: To determine whether increased levels of maternal serum total activin A and inhibin A in preeclampsia are related to total blood volume, urinary clearance, or placental production. STUDY DESIGN: Activin A and inhibin A levels were measured in preeclamptic subjects and matched normotensive gravidas. In a subset of preeclamptic subjects (n = 21) and controls (n = 30), we performed blood volume studies. In an overlapping subset of preeclamptic subjects (n = 56), creatinine clearance results were available. Placental tissue was obtained from six preeclamptics and matched normotensive gravida for analysis of activin A and inhibin A mRNA expression. RESULTS: Maternal serum levels of inhibin A but not activin A were significantly negatively correlated with blood volume in preeclampsia (r(2) =.26, P =.017, and r(2) =.02, P =.44, respectively). Levels of both proteins were negatively correlated to creatinine clearance (r(2) =.29, P <.0001, and r(2) =.15, P =.003, respectively). Placental mRNA expression for both the alpha and betaA subunits was increased in preeclampsia (P =.038 and.049, respectively). CONCLUSION: Although placental mRNA expression of the subunits for both analytes is increased in preeclampsia, the increased levels of activin A appear to be more specifically a reflection of increased placental production than do the increased levels of inhibin A.     

Evaluation of maternal and umbilical serum TNFα levels in preeclamptic pregnancies in the intrauterine normal and growth-restricted fetus

Objective.?The aim of this study was to carry out a comparative analysis of the maternal and umbilical cord TNFα serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth, in preeclamptic pregnancies with intrauterine growth restriction (IUGR), and in normotensive pregnant patients.

Patients and methods.?The study was carried out on eight patients with severe preeclampsia complicated by IUGR and 18 preeclamptic patients with normal intrauterine fetal growth. The control group consisted of 18 healthy normotensive patients with singleton uncomplicated pregnancies. Maternal and umbilical serum TNFα concentrations were estimated using a sandwich ELISA assay.

Results and conclusions.?Pregnant women with severe preeclampsia had significantly higher maternal and umbilical serum TNFα levels than those in the normotensive controls. Our findings and other reports indicate that TNFα may participate in the pathogenesis and sequelae of preeclampsia with and without IUGR. The results of excessive umbilical serum activity of tumor necrosis factor α (TNFα) in preeclamptic pregnancy complicated by intrauterine growth restriction (IUGR) may suggest additional changes and dysfunction of the placental–fetal unit and deterioration of placental function, leading to fetal hypotrophia in the course of preeclampsia.     

The frequency and severity of placental findings in women with preeclampsia are gestational age dependent

OBJECTIVE: The purpose of this study was to evaluate placental lesions found in women with preeclampsia compared with normotensive control subjects and to determine whether the presence of these lesions are related to gestational age at delivery. STUDY DESIGN: Placental disease of women with preeclampsia at 24 to 42 weeks of gestation was compared with the placental disease of normotensive gestational age-matched control subjects. The placental lesions that were studied specifically included decidual arteriolopathy, thrombi in the fetal circulation, central infarction, intervillous thrombi, and hypermaturity of villi. Data analysis involved the chi(2) test, the Student t test, and logistic regression; odds ratios and CIs were estimated. RESULTS: Placentas from women with preeclampsia (n=158) and normotensive control subjects (n=156) were evaluated. Among women with preeclampsia, 67% had severe disease. Placental lesions were studied according to gestational age at delivery: <28, 28 to 32, 33 to 36, and >or=37 weeks of gestation. Of the placental lesions that were studied, decidual arteriolopathy (odds ratio, 23.8, 95% CI 10.0-57.0), hypermaturity of villi (odds ratio, 12.4; 95% CI 5.3-29.2), intervillous thrombi (odds ratio, 1.95;95% CI 1.0-3.7), central infarction (odds ratio, 5.9; 95% CI 3.1-11.1), and thrombi in the fetal circulation (odds ratio, 2.8; 95% CI 1.2-6.6) were found to have significantly higher rates in the preeclamptic group. In contrast, the rate of chorioamnionitis was significantly lower in the preeclamptic group (odds ratio, 0.2; 95% CI 0.1-0.4). The rates of abruptio placentae and meconium staining were not different between the two groups. Within the preeclamptic group, the rates of decidual arteriolopathy (P<.0001), central infarction (P=.0001), and hypermaturity of villi (P<.0001) were higher the earlier the gestational age at delivery. CONCLUSION: Placentas in women with preeclampsia have increased amounts of disease. The rate is increased with lower gestational ages at the time of delivery for women with preeclampsia.     

Placental leptin in HIV-associated preeclampsia

Objective

HIV-associated preeclampsia reflects a combination of opposing influences on the immune status. The adipocyte hormone leptin has been implicated in the pathophysiology of preeclampsia and in enhancing immunity. This study is the first, to our knowledge, to determine whether leptin levels in the placenta differ between HIV-associated normotensive and preeclamptic pregnancies. The study also compares leptin levels between the exchange and conducting areas of the placenta.

Study design

Pregnant women were recruited antenatally and grouped as follows: normotensive HIV uninfected (n = 30), normotensive HIV infected (n = 60), preeclamptic HIV uninfected (n = 30) and preeclamptic HIV infected (n = 60). Anthropometric data were collected and placental leptin was analysed by immunohistochemistry and ELISA.

Results

Leptin levels were similar in the central and peripheral regions of the placenta. Leptin immunoreactivity was observed amongst the different trophoblast cell populations. Both ELISA and immunohistochemistry of the placental exchange villi indicated that leptin levels were higher in preeclampsia compared to normotensive pregnancies (p < 0.001). HIV status had no effect on leptin levels but levels were higher in participants on highly active antiretroviral treatment (HAART) compared to those on prophylaxis for prevention of mother to child transmission (PMTCT) with normotensive (p = 0.006) and preeclamptic (p = 0.002) pregnancies. The area of immunostaining was greater in the exchange compared to the conducting villi in HIV infected and uninfected preeclampsia.

Conclusions

This novel study establishes an elevation of leptin in preeclamptic placentae, irrespective of HIV status. Leptin elevation was not focal in that it occurred in both central and peripheral regions of the preeclamptic placenta. This suggests a role of leptin in the pathophysiology of preeclampsia.     

Angiopoietin-2: A Promising Indicator for the Occurrence of Severe Preeclampsia

Background. The known connection between placental hypoxia and the development of preeclampsia suggests that angiogenic factors in the placenta would be changed and affect the maternal and/or umbilical cord plasma levels in patients with preeclampsia. Objective. The aim of this study was to determine the difference and correlation of placental mRNA expression and maternal/umbilical cord plasma concentrations of vascular endothelial growth factor A (VEGF-A), angiopoietin-1, and angiopoietin-2 between women with severe preeclampsia and normal pregnancies. Methods. Sixteen patients with severe preeclampsia and 29 normotensive pregnant women were studied. The placental mRNA expression was assessed using real-time quantitative RT-PCR analysis. Maternal/umbilical cord plasma levels were measured using an enzyme-linked immunoassay. Nonparametric methods were applied for statistical analysis. Results. Placental mRNA expression of angiopoietin-2 was significantly increased in patients with severe preeclampsia (p < 0.001). The maternal plasma angiopoietin-2 protein level was also significantly increased in women with severe preeclampsia (p < 0.05) and showed a positive correlation with the placental mRNA expression of angiopoietin-2 (r = 0.54, p < 0.005). For VEGF-A and angiopoietin-1, there were no significant differences between the two groups. A maternal plasma angiopoietin-2 concentration of 8.4 ng/mL had a sensitivity of 63% and a specificity of 83% for predicting severe preeclampsia. Conclusion. Placental angiopoietin-2 mRNA expression was increased and correlated with the maternal plasma angiopoietin-2 protein concentration in women with severe preeclampsia. This suggests that the plasma angiopoietin-2 protein level may be a candidate marker for severe preeclampsia.     

The assessment of placental volume and mean gray value in preeclamptic placentas by using three-dimensional ultrasonography

Objectives: We aimed to evaluate the placental volume and placental mean gray value in preeclampsia and healthy placentas by using three-dimensional (3D) ultrasonography and Virtual Organ Computer-aided AnaLysis (VOCAL).

Methods: This case–control prospective study consisted of 27 singleton pregnancies complicated by preeclampsia and 54 healthy singleton pregnancies matched for gestational age, maternal age and parity. Placental volume and placental volumetric mean gray values were evaluated. The placental volume (cm³) was analyzed using the VOCAL imaging program, and 3D histogram was used to calculate the volumetric mean gray value (%).

Results: Preeclamptic and control group consisted of 27 (mean age: 28.90?±?5.95 years, mean gestation: 32.0?±?4.55 weeks) and 54 (mean age: 29.48?±?5.78 years, mean gestation: 32.61?±?4.23 weeks) singleton pregnancies, respectively. Placental volume was significantly smaller in preeclampsia (250.62?±?91.69 versus 370.98?±?167.82?cm³; p?=?0.001). Volumetric mean gray value of the placenta was significantly higher in preeclampsia (38.24?±?8.41 versus 33.50?±?8.90%; p?=?0.043). Placental volume was significantly correlated with the estimated fetal weight (r?=?0.319; p?=?0.003). There was negative significant relation between placental volume and umbilical artery pulsatility index, resistance index and systolic/diastolic ratio (r?=?–0.244, p?=?0.024; r?=?–0.283, p?=?0.005; r?=?–0.241, p?=?0.024, respectively).

Conclusions: Placental volume diminishes significantly in preeclampsia, whereas volumetric mean gray values increases. This may reflect the early alterations in preeclamptic placentas, which may help to understand the pathophysiology better.     

Association of Maternal Serum CRP,IL-6, TNF-α, Homocysteine,Folic Acid and Vitamin B12 Levels with the Severity of Preeclampsia and Fetal Birth Weight

Objective: To assess the levels and clinical significance of high sensitive(hs)-CRP (C‐reactive protein), IL-6(interleukin-6), TNF-α(tumor necrosis factor-α), homocysteine, folic acid and vitamin B12 in normotensive healthy pregnant women, mild and severe preeclamptic patients, and to evaluate the correlations between these markers and the severity of preeclampsia and fetal birth weight. Study design: Using a cross-sectional study design, hs-CRP, IL-6, TNF-α, homocysteine and vitamin B12 were measured in the third trimester of pregnancy from normotensive healthy women with uncomplicated pregnancies (n = 62), mild (n = 61) and severe (n = 60) preeclamptic patients. Results: There were statistically significant differences between three groups for hs-CRP (p = 0.012), TNF- α (p = 0.046), IL-6 (p = 0.015), homocysteine (p < 0.001) and fetal birth weight (p < 0.001). Fetal birth weights in mild (2477 ± 746) and severe (2435 ± 768) preeclamptic patients were significantly lower than controls (3485 ± 365) (p < 0.001). No significant difference was found between the three groups for folic acid (p = 0.066) and vitamin B12 (p = 0.286). Bonferroni adjusted multiple comparison test showed that the statistical differences with respect to TNF-α, IL-6 and homocysteine were mainly created by control and severe preeclampsia groups. Hs-CRP levels still remained higher in severe preeclampsia patients than mild preeclampsia and normotensive patients except for overweight patients in the previous two groups after Bonferroni post hoc adjustment test. Conclusion: Elevated maternal serum levels of hs-CRP, TNF- α, IL-6 and homocysteine in preeclamptic women correlate with fetal birth weight in the early third trimester.     

Increased Placental Telomerase mRNA in Hypertensive Disorders of Pregnancy

Objective.?We assessed hTERT mRNA levels in normal versus preeclamptic placental samples, examining hTERT expression levels in different clinical manifestations of hypertensive disorder of pregnancy.?Methods.?We performed a single-site, prospective case-control study of hTERT mRNA levels in placentas from term and preterm pregnancies with hypertensive disorders compared with unaffected pregnancies. Placental biopsies were collected from 61 patients (preeclamptic: 32; non-preeclamptic (control): 29). Total RNA from placenta was isolated and reversely transcribed to c‐DNA. A probe-specific real-time quantitative PCR assay was employed to determine the relative expressional levels of hTERT mRNA levels in these placentas from both unaffected and affected pregnancies with different categories of hypertensive disorders including preeclampsia, severe preeclampsia, eclampsia and HELLP syndrome (Hemolysis, Elevated Liver function tests, Low Platelet).?Results.?The average ratio of hTERT mRNA levels was 1.73 in the preeclamptic group and 1.02 for control group (p < 0.0001). The hTERT expression levels were elevated for each of the different categories of hypertensive disorders of pregnancy compared with control: HELLP syndrome 1.86, severe preeclampsia 1.81, eclampsia 1.71 and mild preeclampsia 1.63. In addition, hTERT levels were higher in severe than mild preeclampsia (p < 0.01). Conclusions.?Elevated hTERT mRNA expression is observed in placentas from pregnancies with different clinical manifestations of hypertensive disorders of pregnancy. The patho-physiological significance of this finding awaits further studies.     

The effects of placental extracts from normotensive and preeclamptic women on vasoconstriction and oxidative metabolism

OBJECTIVE: A circulating factor derived from the placenta has been implicated in the pathogenesis of preeclampsia. The aim of this study was to determine whether placental extracts from normotensive women and women with preeclampsia increase oxidative metabolism and histamine-induced vasoconstriction in porcine carotid artery. STUDY DESIGN: Placental extracts from normotensive women and women with preeclampsia were applied to porcine carotid artery, and oxidative metabolism was measured. Histamine-induced isometric force responses were also determined in the absence and presence of placental extracts. RESULTS: Application of placental extracts to porcine carotid artery caused a fall in oxygen tension, which reflects increased consumption. Extracts from placentas taken from women with preeclampsia caused a greater fall than those from normotensive women (0.117 +/- 0.026 vs 0.018 +/- 0.0024 micromol oxygen per milligram; P < or =.01). Histamine-induced contractions were potentiated by extracts from preeclampsia but not from those of women without hypertension. The maximal steady-state force values were 13,137 +/- 3647, 12,921 +/- 3684, and 21,673 +/- 7189 N/m(-2) for control, normotensive, and preeclamptic samples at 10-micromol/L histamine (P < or =.05, compared with control placental extracts). CONCLUSIONS: Placental extracts from women with preeclampsia cause a greater stimulation of porcine artery oxygen consumption and exacerbation of histamine-induced vasoconstriction than extracts from normotensive women.     

Is there any role of prolidase enzyme activity in the etiology of preeclampsia?

Objective: To evaluate a relationship between preeclampsia and prolidase enzyme activity.

Methods: A prospective cohort study of 41 pregnant women diagnosed with preeclampsia and 31 healthy pregnant women as control group was selected at Harran University Hospital Department of Obstetrics and Gynecology. The prolidase enzyme activity was analyzed in maternal and umbilical cord plasma, amniotic fluid and placental and umbilical cord tissues by Chinard method in addition to maternal serum levels of lactate dehydrogenase (LDH), serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT).

Results: A significant relationship was found between plasma prolidase activity (635?±?83?U/L) (p =?0.007), umbilical cord plasma prolidase activity (610?±?90?U/L) (p?=?0.013), amniotic fluid prolidase activity (558?±?100?U/L) (p =?0.001), umbilical cord tissue prolidase activity (4248?±?1675?U/gr protein) (p =?0.013) and placental tissue prolidase activity (2116?±?601?U/gr protein) (p =?0.001) in preeclamptic group when compared to healthy pregnant women.

Conclusion: There is a strong correlation between prolidase enzyme activity and preeclampsia. Prolidase enzyme activity may play a role in preeclampsia.     

Urinary clusterin and glutathione-s-transferase levels in HIV positive normotensive and preeclamptic pregnancies

Objective: To determine the level and effect of urinary clusterin (CLU) and glutathione-s-transferase (GST) proteins in normotensive and preeclamptic pregnant women with HIV infection. Methods: The urine concentration of CLU and GST in normotensive (n = 38) and preeclamptic pregnant (n = 38) women stratified by HIV status were estimated using the Bio-Plex® Pro^TM immunoassay. Results: Across the group, a significant down-regulation of CLU (p = 0.039) with a reduced trend in GST was shown in HIV positive preeclampsia. Conclusion: HIV infection affects the activity of urinary CLU protein in HIV positive preeclampsia. However, the cytoprotective role of these proteins neutralizes the oxidative radicals associated with preeclampsia development through complement response in HIV infection.     

Anti-Hypertensive Drugs Alter Cytokine Production from Preeclamptic Placentas and Peripheral Blood Mononuclear Cells

Objective: Antihypertensive drugs are administered to women with preeclampsia to control blood pressure and fluid overload. Whether they modulate placental or circulating cytokine production in women with preeclampsia is unknown. This study examines the effect of pharmacological doses of antihypertensive drugs on the production of IL-10, tumor necrosis factor α (TNF-α), and IL-6 in placental tissue and peripheral blood mononuclear cells (PBMCs) from women with preeclampsia. Methods: Term placenta samples (n = 6) and PBMCs from whole blood (n = 6) were obtained from women with preeclampsia. Both villous explants and PBMCs were cultured with increasing concentrations of antihypertensive drugs (clonidine, diazoxide, hydralazine, and furosemide). The dose effect of drugs on the production of placental and circulating cytokines IL-10, TNF-α, and IL-6 was examined by enzyme-linked immunosorbent assay (ELISA). Results: Our data suggest that clonidine can stimulate anti-inflammatory IL-10 production from PBMC while decreasing pro-inflammatory TNF-α, whereas low doses of hydralazine increased the production of IL-10, TNF-α, and IL-6 from preeclamptic PBMCs. There was a reduction in IL-10, TNF-α, and IL-6 production with increasing doses of clonidine and hydralazine by placentas in preeclampsia. IL-10, TNF-α, and IL-6 production from preeclamptic placenta and PBMCs were inhibited by diazoxide and furosemide. Conclusions: Antihypertensive drugs may alter Th1/Th2 cytokine balance in preeclamptic tissues in vitro.     

D2-40/podoplanin expression in the human placenta

Placental tissue expresses many lymphatic markers. The current study was undertaken to examine if D2-40/podoplanin, a lymphatic endothelial marker, was expressed in the human placenta, and how it is altered developmentally and pathologically. We examined D2-40/podoplanin and VEGFR-3 expressions in placentas from normotensive pregnancies at different gestational ages and in placentas from women with clinically defined preeclampsia. D2-40 expression in systemic lymphatic vessel endothelium served as a positive control. Protein expression for D2-40, VEGFR-3, and β-actin was determined by Western blot in placentas from normotensive (n = 6) and preeclamptic (n = 5) pregnancies. Our results show that D2-40/podoplanin was strongly expressed in the placenta, mainly as a network plexus pattern in the villous stroma throughout gestation. CD31 was limited to villous core fetal vessel endothelium and VEGFR-3 was found in both villous core fetal vessel endothelium and trophoblasts. D2-40/podoplanin expression was significantly decreased, and VEGFR-3 significantly increased in preeclamptic placental tissues compared to normotensive placental controls. Placental villous stroma is a reticular-like structure, and the localization of D2-40 to the stroma suggests that a lymphatic-like conductive network may exist in the human placenta. D2-40/podoplanin is an O-linked sialoglycoprotein. Although little is known regarding biological functions of sialylated glycoproteins within the placenta, placental D2-40/podoplanin may support fetal vessel angiogenesis during placenta development and reduced D2-40/podoplanin expression in preeclamptic placenta may contribute to altered interstitial fluid homeostasis and impaired angiogenesis in this pregnancy disorder.     

Placental expression of insulin-like growth factor-I,fibroblast growth factor-basic,and neural cell adhesion molecule in preeclampsia

Objective. To investigate placental expression of insulin-like growth factor-I (IGF-I), fibroblast growth factor-basic (FGF-b), and neural cell adhesion molecule (N-CAM) in preeclampsia.

Study design. An immunohistochemical analysis using IGF-I, FGF-b, and N-CAM antibodies was conducted on 4% paraformaldehyde-fixed placental tissues of preeclamptic patients (N = 14) and normotensive pregnant subjects (N = 10). Immunostaining patterns of chorionic villi and amniochorionic membranes were assessed.

Results. Significantly increased FGF-b and N-CAM immunoreactivities in cytotrophoblasts and increased FGF-b immunoreactivity in capillary endothelium of chorionic villi of preeclamptic subjects were noted. Significantly increased FGF-b and decreased N-CAM immunoreactivities in extravillous trophoblasts and decidual cells of amniochorionic membranes obtained from preeclamptic subjects were demonstrated. Additionally, a significantly increased IGF-I immunoreactivity was shown in decidual cells of preeclamptic cases.

Conclusion. Investigation of the regional distribution of IGF-I, FGF-b, and N-CAM at the maternal–fetal interface establishes a better understanding of cell-specific altered growth processes, which may be associated with the pathogenesis of preeclampsia.     

Placental growth hormone is increased in the maternal and fetal serum of patients with preeclampsia

Objectives. Placental growth hormone (PGH) is a pregnancy-specific protein produced by syncytiotrophoblast and extravillous cytotrophoblast. No other cells have been reported to synthesize PGH Maternal. PGH Serum concentration increases with advancing gestational age, while quickly decreasing after delivery of the placenta. The biological properties of PGH include somatogenic, lactogenic, and lipolytic functions. The purpose of this study was to determine whether the maternal serum concentrations of PGH change in women with preeclampsia (PE), women with PE who deliver a small for gestational age neonate (PE + SGA), and those with SGA alone.

Study design. This cross-sectional study included maternal serum from normal pregnant women (n = 61), patients with severe PE (n = 48), PE + SGA (n = 30), and SGA alone (n = 41). Fetal cord blood from uncomplicated pregnancies (n = 16) and PE (n = 16) was also analyzed. PGH concentrations were measured by ELISA. Non-parametric statistics were used for analysis.

Results. (1) Women with severe PE had a median serum concentration of PGH higher than normal pregnant women (PE: median 23,076 pg/mL (3473–94 256) vs. normal pregnancy: median 12 157 pg/mL (2617–34 016); p < 0.05), pregnant women who delivered an SGA neonate (SGA: median 10 206 pg/mL (1816–34 705); p < 0.05), as well as pregnant patients with PE and SGA (PE + SGA: median 11 027 pg/mL (1232–61 702); p < 0.05). (2) No significant differences were observed in the median maternal serum concentration of PGH among pregnant women with PE and SGA, SGA alone, and normal pregnancy (p > 0.05). (3) Compared to those of the control group, the median umbilical serum concentration of PGH was significantly higher in newborns of preeclamptic women (PE: median 356.1 pg/mL (72.6–20 946), normal pregnancy: median 128.5 pg/mL (21.6–255.9); p < 0.01). (4) PGH was detected in all samples of cord blood.

Conclusions. (1) PE is associated with higher median concentrations of PGH in both the maternal and fetal circulation compared to normal pregnancy. (2) Patients with PE + SGA had lower maternal serum concentrations of PGH than preeclamptic patients without SGA. (3) Contrary to previous findings, PGH was detectable in the fetal circulation. The observations reported herein are novel and suggest that PGH may play a role in the mechanisms of disease in preeclampsia and fetal growth restriction.