Risk factors for cardiovascular disease in women with a history of pregnancy complicated by preeclampsia or intrauterine growth restriction.

OBJECTIVE: Women with a history of preeclampsia or intrauterine growth restriction (IUGR) have an increased risk for cardiovascular disease in later life. We determined the presence of traditional and novel risk factors for cardiovascular disease in these women. METHODS: We studied 256 women with a history of preeclampsia and 59 women with a history of intrauterine growth restriction. Fifty-three women with a history of uncomplicated pregnancy served as controls. We determined values for blood pressure, body mass index, concentrations of cholesterol, high-density lipoprotein cholesterol, triglycerides and lipoprotein (a), and insulin resistance. RESULTS: Women with a history of preeclampsia exhibited more risk factors for future cardiovascular disease such as dyslipidemia, hypertension, obesity, and increased insulin resistance compared with women with a history of uncomplicated pregnancy. Women with a history of IUGR have higher concentrations of cholesterol and show a tendency to higher BMI, higher triglyceride concentrations, and increased insulin resistance as compared with women with a history of normal pregnancy. CONCLUSIONS: Preeclampsia or IUGR may represent an early marker for increased risk for early cardiovascular disease.     

Meeting Abstracts

Objective. Preeclampsia is associated with increased risk of cardiovascular disease. The aim of this pilot study was to assess whether the presence of thrombophilia results in a greater tendency to develop endothelial dysfunction and cardiovascular diseases. Methods. Ten women with thrombophilia were matched with 10 women without thrombophilia for a history of hypertensive disorders during pregnancy. Laboratory measurements: blood pressure, insulin sensitivity, and micro- and macrovascular function were determined. Results. Women with thrombophilia had significant lower total- and low-density cholesterol, were more insulin sensitive, and had better microvascular function. Conclusion. This study suggests that thrombophilia “mediates” in lowering of cardiovascular risk factors in women with a history of preeclampsia.     

The prevalence of non-classic adrenal hyperplasia among Turkish women with hyperandrogenism

Insulin resistance in late pregnancy increases nutrition availability in maternal circulation. Moreover, it is the leading cause of oxidative stress in pregnant women. Herein, we aimed to define the correlation between insulin resistance, serum inducible nitric oxide (iNOS) and serum lipid levels in patients with intrauterine growth retardation (IUGR) pregnancies and controls. We performed a cross sectional study of IUGR pregnancies uncomplicated with preeclampsia as cases and age, body mass index, parity and gestational age matched pregnant women as controls. We quantified serum insulin, fasting blood sugar (FBS), iNOS and lipid profile of the cases and controls. Serum total cholesterol and LDL-C were significantly lower when serum iNOS, FBS, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) levels were significantly higher in patients with IUGR pregnancies. There was not any significant difference in serum iNOS levels between patients and controls (12.4?±?2.1 vs. 11.1?±?1.9; p?=?0.52) after multiple adjustment for HOMA-IR. Serum iNOS levels were significantly correlated with maternal serum insulin, triglyceride and HOMA-IR levels in patients with IUGR pregnancies when there was not such a correlation in controls. We showed a positive correlation between insulin resistance and markers of oxidative stress like iNOS in IUGR pregnancies.     

Endoglin in pregnancy complicated by fetal intrauterine growth restriction in normotensive and preeclamptic pregnant women: a comparison between preeclamptic patients with appropriate-for-gestational-age weight infants and healthy pregnant women

Objective: The aim of this study was to determine the maternal serum endoglin concentration in pregnancies with intrauterine growth restriction (IUGR) in the presence or absence of preeclampsia and to compare the results with preeclamptic pregnant women with appropriate-for-gestational-age weight infants and with healthy pregnant controls. Patients and methods: The study was performed on 52 normotensive pregnant patients with pregnancy complicated by isolated IUGR, 33 patients with preeclampsia complicated by IUGR and 33 preeclamptic patients with appropriate-for-gestational-age weight infants. The control group consisted of 54 healthy normotensive pregnant patients with singleton uncomplicated pregnancies. The maternal serum endoglin concentrations were determined using a sandwich enzyme-linked immunosorbent assay assay. Results: Our study revealed increased levels of endoglin in the serum of women with normotensive pregnancy complicated by isolated IUGR, and in both groups of preeclamptic patients with and without IUGR. The levels of endoglin were the highest in pregnancy complicated by fetal intrauterine growth restriction (IUGR) in the course of preeclampsia. The mean values were 12.2?±?4.3 ng/ml in the IUGR group, 14.1?±?3.6 ng/ml in preeclamptic patients with normal intrauterine fetal growth, 15.1?±?3.2 ng/ml in preeclamptic pregnant women with IUGR and 10.6?±?3.7 ng/ml in the healthy controls. We also found positive correlations between serum endoglin levels and systolic and diastolic blood pressure and inverse correlations between maternal endoglin and infant birth weight. Conclusions: Our results suggest that increased endoglin concentration may be at least responsible for the pathogenesis of preeclampsia and/or intrauterine fetal growth restriction. It seems that the pathomechanism underlying the development of preeclampsia and isolated IUGR is similar, but that their beginning or intensity may be different in these two pregnancy complications. The positive correlation between endoglin and blood pressure and inverse correlation between endoglin and infant birth weight and additionally higher levels of ENG in patients with pregnancy complicated by HELLP syndrome (hemolysis, increased liver enzymes, low platelet count) or eclampsia suggest that endoglin may be a marker of severity of these pregnancy disorders.     

REDUCED RED BLOOD CELL DEFORMABILITY,AN INDICATOR FOR HIGH FETAL OR MATERNAL RISK,IS FOUND IN PREECLAMPSIA AND IUGR

Objective: Red blood cell (RBC) deformability is one of the factors determining microcirculation. In preeclampsia (PE) and some cases of intrauterine growth restriction (IUGR), microcirculation appears to be reduced. The aim of the study is to examine whether there are differences in RBC deformability in uncomplicated pregnancy when compared to pregnancies complicated by PE and/or IUGR. Material and methods: RBC deformability of 87 pregnant women with initially normal pregnancies was evaluated with the laser diffractoscope. RBC deformability was measured beginning in week 16 of gestation up to 5 days after delivery. Thirty-seven women had an uncomplicated pregnancy. In addition, RBC deformability of 10 nonpregnant women was measured on days 5 and 22 of their menstrual cycle. RBC deformability of women with preeclampsia (PE, N=15), intrauterine growth restriction (IUGR, N=17), or PE plus IUGR (N=17) was measured weekly, beginning with the onset of clinical symptoms, up to 5 days after delivery. Results: In early uncomplicated pregnancies, RBC deformability does not differ from the nonpregnant state. At week 30 of gestation, there is a slight decrease in RBC deformability followed by a return back to the values of nonpregnant women after delivery. Women with PE and/or IUGR show reduced RBC deformability. This is most pronounced in cases with severe fetal or maternal complications. After delivery, RBC deformability also returns to nonpregnancy values within 5 days. Conclusion: Reduced RBC deformability may contribute to a reduced microcirculation in PE and IUGR. Increasing RBC deformability therapeutically in these cases could offer new options for the treatment of decreased uterine and fetal perfusion and their sequelae.     

Shared and disparate components of the pathophysiologies of fetal growth restriction and preeclampsia

Intrauterine growth restriction (IUGR) and preeclampsia differ in their association with maternal disease but share a similar placental pathology. Moreover, mothers who have had pregnancies complicated by preeclampsia or IUGR are at elevated later-life cardiovascular risk. Why, then, do some women develop IUGR and others develop preeclampsia? In this clinical opinion, based on a review of the literature, we hypothesize that both women experiencing preeclampsia and IUGR enter pregnancy with some degree of endothelial dysfunction, a lesion that predisposes to shallow placentation. In our opinion, preeclampsia develops when abnormal placentation, through the mediator of elevated circulating cytokines, interacts with maternal metabolic syndrome, comprised of adiposity, insulin resistance/hyperglycemia, hyperlipidemia, and coagulopathy. IUGR develops in the absence of antenatal metabolic syndrome. Among these women, the baby is affected by shallow placentation but the mother does not develop clinically apparent disease. This conceptualization provides a testable framework for future etiologic studies of preeclampsia and IUGR.     

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.     

Altered metabolic profiles among older mothers with a history of preeclampsia

Preeclampsia has been linked to increased risk for cardiovascular disease and, more recently, to reduced risk for breast cancer later in life. The altered chronic disease risk associated with prior preeclampsia may reflect underlying metabolic differences. In this case-control study, we examined the metabolic profiles of older mothers with and without a history of preeclampsia in their first pregnancies. At the time of the study, subjects were non-pregnant, non-smoking women who completed their first pregnancies at age 30 or older, were pre-menopausal, and were free of serious chronic disease. Cases were 13 women who experienced preeclampsia in their first pregnancies; controls were 13 women with uncomplicated first pregnancies, frequency matched to cases on race/ethnicity, current age, and age at delivery. A fasting blood sample was collected from each subject during the luteal phase (day 19-22) of the menstrual cycle and assayed for specific factors thought to be linked to hypertensive disease or breast cancer. Compared to women with uncomplicated pregnancies, those with a history of preeclampsia had significantly elevated levels of fasting serum triglycerides, insulin and glucose, and a higher fasting insulin resistance index, suggesting that women with prior preeclampsia were relatively insulin resistant. In addition, cases had higher levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) and a higher molar ratio of IGFBP-3 to IGF-1 than did controls. Adjustment for obesity and other potential confounders did not appreciably alter the magnitude of these associations. This preliminary study suggests that women with a history of preeclampsia have persistent metabolic abnormalities consistent with their observed excess risk for cardiovascular morbidity and mortality, and their apparent reduced risk for breast cancer later in life.     

Evaluation of maternal and umbilical serum TNFalpha 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 TNFalpha 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 TNFalpha concentrations were estimated using a sandwich ELISA assay. RESULTS AND CONCLUSIONS: Pregnant women with severe preeclampsia had significantly higher maternal and umbilical serum TNFalpha levels than those in the normotensive controls. Our findings and other reports indicate that TNFalpha may participate in the pathogenesis and sequelae of preeclampsia with and without IUGR. The results of excessive umbilical serum activity of tumor necrosis factor alpha (TNFalpha) 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.     

Cardiovascular risk after preeclampsia: The effect of communicating risk factors on intended healthy behavior

Objective: We studied the effect of communicating cardiovascular risk factors on intended healthy behavior in women with a history of preeclampsia or uncomplicated pregnancy. Methods: Intention for healthy behavior was assessed before and after cardiovascular risk assessment. Changes were calculated for women with and without cardiovascular risk factors. Results: In women with cardiovascular risk factors, the intention to quit smoking increased; whereas, intended healthy diet and sufficient exercise did not change. In participants without risk factors, none of the healthy behaviors changed. Conclusion: Communicating risk factors alone does not seem to be effective as an intervention to achieve lifestyle changes.     

Women’s Perception of Future Risk Following Pregnancies Complicated by Preeclampsia

Objective. To elicit women’s personal understanding of future cardiovascular risk, following a pregnancy complicated by preeclampsia, and to identify the postnatal needs of these women. Methods. Semi-structured interviews with 12 women with a recent history of preeclampsia who had attended a postnatal follow-up clinic. Results. The interviews were held at a median of 47 weeks postpartum (range 24–62 weeks). Family history of cardiovascular disease was associated with a greater awareness of future cardiovascular risk. Women without traditional risk factors found it hard to envisage themselves as being at risk and may not see the relevance of such information. It may take several months after delivery for a woman to be able to fully consider her own health as well as the baby’s; a reminder of risk and health information is needed. Conclusions. Although receptive to follow-up, the situational factors of being a new mother need to be taken into account to engage successfully with this patient group. Further research is needed to help clarify the extent to which a history of preeclampsia is an independent factor for future cardiovascular disease to provide a solid foundation for effective risk communication.     

Umbilical sP-selectin levels are different in preeclamptic pregnancies with intrauterine normal growth and growth restricted fetus

Objective.?The aim of this study was the analysis of the umbilical cord serum sP-selectin levels in pregnancies complicated by severe preeclampsia with and without intrauterine growth restriction and in normotensive pregnancies.

Patients and methods. The study was carried out on 18 patients with singleton pregnancies complicated by severe preeclampsia with appropriate-for-gestational-age weight infants (group P) and 18 pregnant patients with severe preeclampsia complicated by intrauterine fetal growth restriction (IUGR) (group PI). The control group consisted of 34 patients with singleton uncomplicated pregnancies (group C). Umbilical serum sP-selectin concentrations were estimated using a sandwich ELISA assay according to the manufacturer's instruction (ELISA kit Bender MedSystems Vienna, Austria).

Results.?Our study revealed different concentrations of soluble P-selectin in the umbilical cord in our both studied groups of preeclamptic women with and without IUGR. The umbilical cord levels of sP-selectin were decreased in the group with preeclampsia complicated by IUGR and increased in the preeclamptic women with the normal intrauterine fetal growth. The mean values of umbilical sP-selectin were 839.008?±?625.703?ng/ml in group P, 275.873?±?174.339?ng/ml in group PI, and 288.719?±?199.039?ng/ml in the control group, respectively.

Conclusions.?Higher levels of the umbilical sP-selectin may confirm the presence of platelet and endothelial cell activation and confirm a hypercoagulant state in preeclamptic disorder, especially in preeclampsia without IUGR.     

Serum levels of placental alkaline phosphatase in high-risk pregnancies

A recently developed radioimmunoassay (RIA) for placental alkaline phosphatase (paf) was used to estimate the maternal serum levels of the enzyme in 51 women with various complications of pregnancy. The results were compared with a reference group of 242 women with apparently normal pregnancies. Women with intrauterine growth retardation (IUGR) or severe or mild preeclampsia had significantly low weight of the fetoplacental unit. Simultaneous determinations of PAF in maternal serum and the urinary total estrogen/24 hr gave a clear differentiation of the IUGR group from the other pregnancies at risk. All PAF values from risk pregnancies were below the mean values of normal pregnancy.     

The relation of maternal serum eNOS,NOSTRIN and ADMA levels with aetiopathogenesis of preeclampsia and/or intrauterine fetal growth restriction

Objective: The aim of present study was to assess the maternal serum endothelial nitric oxide synthase (eNOS), NOSTRIN (eNOS-trafficking inducer) and asymmetric dimethylarginine (ADMA) levels in pregnancies with intrauterine growth restriction (IUGR) in the presence or absence of preeclampsia and to compare the results with preeclamptic pregnant women with appropriate-for-gestational-age weight infants.

Patients and methods: The study was performed on 65 normotensive pregnant women with isolated IUGR, 64 preeclamptic women with IUGR, 51 preeclamptic women with normal intrauterine fetal growth and 65 healthy normotensive pregnant women with singleton uncomplicated pregnancies. Severe preeclampsia was defined as blood pressure >?160/110?mmHg with proteinuria >?5?g in a 24-h urinary protein excretion. IUGR were classified when the weight of the fetus was below the 10th centiles with disturbed placental function and abnormal ultrasonographic examination. The diagnosis was confirmed by the infant's weight at birth. The maternal serum eNOS, NOSTRIN and ADMA concentrations were determined using a sandwich enzyme-linked immunosorbent assays.

Results: There were no statistically significant differences in the eNOS and NOSTRIN levels between studied groups of women. Increased levels of ADMA in both preeclamptic groups and in women with pregnancies complicated by isolated IUGR were observed.

Conclusions: Our results allow the conclusion that impaired NO bioavailability in pregnancies complicated by severe preeclampsia and/or IUGR result not from a reduced level or activity of eNOS or from its disturbed intracellular transport, but from increased ADMA levels, an endogenous inhibitor of the enzyme eNOS.     

Birth weight percentile and perinatal outcome: recurrence of intrauterine growth retardation

In 9596 patients followed throughout two pregnancies, recurrence of intrauterine growth retardation (IUGR) was evaluated as a function of previous birth weight percentile and attendant complications of pregnancy. Among 4623 patients with two uncomplicated pregnancies, the prevalence of recurrent IUGR was significantly related to the severity of growth retardation in the first pregnancy (P less than .0001). Those patients with both medical complications and IUGR in the first pregnancy remained at significantly increased risk for recurrent IUGR, even when the second pregnancy was uncomplicated. In second pregnancies, the combination of a previous history of an IUGR neonate and an additional current complication of pregnancy acted synergistically to increase the risk of recurrent IUGR to a level higher than that attributable to either risk factor alone.     

Doppler sonography of the uterine and the cubital arteries in normal pregnancies, preeclampsia and intrauterine growth restriction: evidence for a systemic vessel involvement

AIMS: The decrease in uterine resistance during normal pregnancy is known to be related to invading trophoblast cells which derive from placental tissue. Uterine and peripheral resistance is elevated in preeclampsia. The aim of the present study was to prospectively examine uterine and peripheral resistance in pregnancies complicated by preeclampsia (PE), fetal intrauterine growth restriction (IUGR) and pregnancy induced hypertension (PIH). METHODS: Sixty-seven women with normal pregnancies, 17 with PE, 12 with IUGR underwent Doppler sonographic investigation of the uterine and the cubital arteries. The Pulsatility Index (PI) was calculated for each vessel. Statistical analysis was performed and a P-value <0.05 was considered significant. RESULTS: Patients with preeclampsia and IUGR showed a significant higher resistance at the placental (mean PI 1.267 and 1.063), nonplacental (mean PI 1.631 and 1.124) and cubital artery (mean PI 3,777 and 3.995) compared to the normal pregnancy group (mean PI 0.678; 0.859 and 2.95 respectively). Mean birth weight in the PE group was 1409 g, in the IUGR group 1649 g and 3419 g in the normal pregnancy group. CONCLUSIONS: Pregnancies with IUGR are associated with elevated peripheral resistance in the maternal arterial system as seen in pregnancies with preeclampsia. Our findings encourage to further investigate the maternal vascular system in high risk pregnancies.     

Comparative analysis of the maternal and umbilical interleukin-8 levels in normal pregnancies and in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation

Objectives.?The aim of this study was to determine the maternal and umbilical cord serum levels of interleukin-8 (IL-8) in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation (IUGR), and in normotensive pregnancies.

Patients and methods.?The study was carried out on 15 patients with singleton pregnancies complicated by preeclampsia with appropriate for gestational age weight infants and 12 pregnant patients with preeclampsia complicated by IUGR. The control group consisted of 10 healthy normotensive delivering patients with singleton uncomplicated pregnancies. Maternal and umbilical serum IL-8 concentrations were estimated using the ELISA method.

Results.?There were no statistically significant differences in patient profiles between the groups. Systolic and diastolic blood pressure and mean arterial blood pressure were higher in the study groups in comparison with the control group. Lower birth weight and lower gestational age at birth were observed in the group of patients with preeclampsia complicated by IUGR. Increased maternal and umbilical serum levels of IL-8 were found in both preeclamptic patient groups in comparison with the control group. The umbilical cord blood concentrations of IL-8 in all groups of patients tended to be higher in comparison with the maternal blood.

Conclusions.?It seems that these higher IL-8 concentrations may be associated with apoptosis, inflammation, neutrophil activation, endothelial cell damage and dysfunction, and increased endothelial permeability. They may also participate in an attempt to compensate for the imbalanced apoptosis and vascular resistance. Our findings suggest a possible significant role of IL-8 in the pathogenesis and sequelae of preeclampsia, especially in preeclamptic pregnancies complicated by IUGR.     

Preeclampsia: exposing future cardiovascular risk in mothers and their children

There is an increased risk for future cardiovascular disease in women who have had preeclampsia. In infants born to mothers with preeclampsia, there is growing evidence of increased risk for both cardiovascular disease and preeclampsia. Epidemiologic and experimental data provide a strong link between intrauterine exposure to preeclampsia and subsequent risk for the development of cardiovascular disease in women.     

Pregnancy outcomes in systemic sclerosis, primary pulmonary hypertension, and sickle cell disease

OBJECTIVE: Systemic sclerosis, primary pulmonary hypertension, and sickle cell disease are uncommon vasculopathic diseases affecting women. We estimated the nationwide occurrence of pregnancies in women with these conditions and compared pregnancy outcomes to the general obstetric population. METHODS: We studied the 2002-2004 Nationwide Inpatient Sample, of the Healthcare Cost and Utilization Project to estimate the number of obstetric hospitalizations and deliveries among women with systemic sclerosis, primary pulmonary hypertension, sickle cell disease, and women in the general population. Pregnancy outcomes included length of hospital stay, hypertensive disorders including preeclampsia, intrauterine growth restriction (IUGR), and cesarean delivery. Multivariable regression analyses were performed using maternal age, race or ethnicity, antiphospholipid antibody syndrome, diabetes mellitus, and renal failure as covariates. RESULTS: Of an estimated 11.2 million deliveries, 504 occurred in women with systemic sclerosis, 182 with primary pulmonary hypertension, and 4,352 with sickle cell disease. Systemic sclerosis, was associated with an increased risk of hypertensive disorders including preeclampsia (odds ratio [OR] 3.71, 95% confidence interval [CI] 2.25-6.15), IUGR (OR 3.74, 95% CI 1.51-9.28), and increased length of hospital stay. Primary pulmonary hypertension was associated with an increase in the odds of antenatal hospitalization (OR 4.67, 95% CI 2.88-7.57), hypertensive disorders including preeclampsia (OR 5.62, 95% CI 2.60-12.15) and a substantial increase in length of hospital stay. Sickle cell disease was associated with an increased odds of antenatal hospitalization (OR 5.56 95% CI 5.08-6.09), hypertensive disorders including preeclampsia (OR 1.78, 95% CI 1.48-2.14), and IUGR (OR 2.91, 95% CI 2.16-3.93), with a modest increase in length of hospital stay. CONCLUSION: Women with systemic sclerosis, primary pulmonary hypertension, and sickle cell disease have significantly increased rates of adverse pregnancy outcomes, requiring extensive preconceptional counseling about the risks of pregnancy.     

Maternal and Umbilical sTNF-R1 in Preeclamptic Pregnancies with Intrauterine Normal and Growth Retarded Fetus

Objective: The aim of this study was to determine the maternal and umbilical cord sTNF R1 serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth and in preeclamptic pregnancies with intrauterine growth retardation (IUGR). Patients and Methods: The study was carried out on 8 patients with preeclampsia complicated by intrauterine growth retardation (group PI) and 18 preeclamptic patients with appropriate-for-gestational-age weight infants (group P). The control group consisted of 18 healthy normotensive delivering patients with singleton uncomplicated pregnancies (group C). Maternal and umbilical serum sTNF-R1 concentrations were estimated using a sandwich enzyme-linked immunosorbent assay (ELISA). Results and Conclusions: Pregnant women with severe preeclampsia had higher maternal and umbilical serum sTNF-R1 levels than did normotensive controls. Furthermore significantly higher umbilical levels of sTNF-R1 were observed in the group of patients with preeclampisa complicated by IUGR, compared with preeclamptic patients with appropriate-for-gestational-age weight infants. The umbilical sTNF-R1 levels in preeclamptic groups tended to be higher in comparison with the maternal levels. Our results and those of other reports seem to suggest that TNFα and sTNFR1 play a crucial role in pathogenesis and sequelae of preeclampsia with and without intrauterine growth retardation.