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.     

Evaluation of the maternal and umbilical vein serum sFas/sFasL system in pregnancies complicated by preeclampsia with intrauterine growth retardation

OBJECTIVE: The aim of this study was to determine the maternal and umbilical vein soluble Fas and its ligand (sFasL) serum levels in pregnancies complicated by preeclampsia with intrauterine growth retardation (IUGR). PATIENTS AND METHODS: The study was carried out on 11 preeclamptic delivering patients in the third trimester of pregnancy with severe preeclampsia complicated by intrauterine growth retardation. The control group consisted of 12 healthy normotensive delivering patients with singleton uncomplicated pregnancies, without any renal, heart and vascular diseases and with normal laboratory tests. Maternal and umbilical serum soluble Fas and FasL concentrations were estimated using a sandwich ELISA assay. RESULTS AND CONCLUSIONS: Increased maternal and umbilical vein serum sFas and increased umbilical vein serum sFasL levels were found in the study group in comparison with the control group. In our study in both groups of patient higher maternal sFas values were observed in comparison with the umbilical cord blood. Further studies are necessary to evaluate the role of Fas/FasL pathway in pregnancies complicated by preeclampsia and intrauterine growth retardation.     

The effect of a maternal infusion of amino acids on umbilical uptake in pregnancies complicated by intrauterine growth restriction

OBJECTIVE: To establish whether, in human pregnancies complicated by intrauterine growth restriction (IUGR), the maternal intravenous infusion of amino acids can increase fetal amino acid concentrations and umbilical uptake. STUDY DESIGN: Before elective cesarean delivery, a solution of amino acids was infused into a maternal vein in 8 patients with pregnancies complicated by IUGR (experimental group). At cesarean delivery, maternal, umbilical venous, and arterial blood samples were obtained. Ten comparable IUGR pregnancies were compared with those in the experimental group. RESULTS: In the experimental group, all maternal amino acid concentrations were increased significantly. In the umbilical vein, valine, methionine, isoleucine, leucine, phenylalanine, arginine, serine, glycine, and proline concentrations were elevated. Umbilical venoarterial differences of amino acid per mole of oxygen for leucine, isoleucine, methionine, arginine, glycine, serine, and proline were elevated but not for lysine, histidine, threonine, valine, and phenylalanine. CONCLUSION: In pregnancies complicated by IUGR, increasing the maternal concentration of amino acids leads to an increased umbilical uptake of some of the amino acids to the fetus. There was no evidence of a change in the uptake of 3 essential amino acids: lysine, histidine, and threonine.     

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.     

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 TNFalpha and sTNFR1 play a crucial role in pathogenesis and sequelae of preeclampsia with and without intrauterine growth retardation.     

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.     

Correlation of fetal DNA levels in maternal plasma with Doppler status in pathological pregnancies

OBJECTIVES: To evaluate whether intrauterine growth restriction (IUGR) as seen in preeclampsia is associated with high levels of fetal DNA in maternal circulation, and whether fetal DNA is related to altered uterine and/or umbilical artery Doppler velocimetry. METHODS: Fetal DNA quantification was performed by real-time PCR on SRY sequences in 64 male-bearing pregnant women with IUGR and/or preeclampsia and 89 controls. RESULTS: Fetal DNA content was significantly elevated in IUGR pregnancies similar to preeclampsia and correlated with altered umbilical Doppler velocimetry, while no correlation was found with uterine Doppler status. CONCLUSION: Increased fetal DNA levels in maternal plasma may be a sign of placental or fetal pathology even in the presence of normal uterine Doppler velocimetry, allowing a more precise diagnostic evaluation. The finding that elevated fetal DNA in IUGR pregnancies correlates with abnormal umbilical Doppler velocimetry suggests that fetal DNA release is associated more with fetal chronic hypoxia than with fetal size.     

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.     

Endothelin 1 and leptin in the pathophysiology of intrauterine growth restriction.

OBJECTIVES: To evaluate the relationship of endothelin 1 (ET-1) and leptin concentrations in women and newborns following a pregnancy complicated with intrauterine growth restriction (IUGR). METHODS: Twenty-five women with a pregnancy complicated with IUGR at 19 different gestational ages were matched with women with uncomplicated pregnancies. Blood samples from the umbilical artery and maternal peripheral venous circulation were collected at delivery, and ET-1 and leptin levels were determined from the blood samples. Data relating to obstetric complications (e.g., pregnancy-induced hypertension), delivery (e.g. mode, birth weight, signs of intrapartum fetal distress, and Apgar scores) were also recorded. RESULTS: Mean maternal ET-1 (13.4+/-6.2-9.9+/-2.9 pmol/l) and mean fetal ET-1 (14.5+/-4.2-11.7+/-3.1 pmol/l) concentrations were significantly higher when women had experienced pregnancies complicated with IUGR than when they had had normal pregnancies. Mean fetal leptin concentration was significantly lower in the study group (6.8+/-2.2 ng/ml) than in the control group (10.6+/-3.6 ng/ml (P<0.05). However, fetal leptin per kilogram of fetal weight was not significantly different in the study group (3.16+/-1.18 ng/ml) than in the control group (3.23+/-0.96 ng/ml) (P>0.05, paired t-test). However, a statistically significant correlation was observed between fetal leptin concentrations per kilogram of fetal weight and fetal endothelin concentrations in pregnancies complicated with IUGR (r=0.546; P<0.05). CONCLUSIONS: These results suggest the intertwined roles of ET-1 and leptin in the pathophysiology of IUGR. Further studies concerning interaction between these peptides in different pregnancy conditions may provide important information about the actions of ET-1 and leptin on fetal growth.     

Maternal and fetal plasma endothelin levels in intrauterine growth restriction: relation to umbilical artery Doppler flow velocimetry

The objective of this study was to examine maternal and fetal endothelin-1 (ET-1) in pregnancies complicated with intrauterine growth restriction (IUGR) and to correlate these data with umbilical artery Doppler flow velocity waveforms (FVW). Higher mean maternal (13.8 +/- 6.4 vs 9.2 +/- 3.4 pmol/L, p < 0.05) and fetal (18.5 +/- 9.6 vs 11.7 +/- 6.9 pmol/L, p < 0.05) ET-1 levels were found in pregnancies complicated with IUGR than in controls. Fetal ET-1 level was related to birth weight percentile for gestational week. Maternal and fetal ET-1 concentrations were not related to umbilical artery Doppler flow S/D ratio, PI and RI. Maternal or fetal ET-1 concentrations were also not related to umbilical artery pH, PO2 and PCO2. Pregnancy-induced hypertension was significantly associated with an elevated fetal and maternal ET-1 concentration. In conclusion, increased production and secretion of ET-1 may play a role in the pathophysiology of idiopathic IUGR. Over-production of ET-1 in IUGR is not associated with increased placental resistance as reflected in abnormal umbilical artery Doppler FVW.     

Discordant clinical presentations of preeclampsia and intrauterine fetal growth restriction with similar pro- and anti-angiogenic profiles

Abstract

Objective: To evaluate the plasma levels of angiogenic factors in preeclampsia (PE) and intrauterine fetal growth restriction (IUGR) and their potential as biomarkers to distinguish normal from pathologic pregnancies.

Methods: Case control study included singleton pregnancies in four categories: (i) normal (n?=?29), (ii) PE (n?=?15), (iii) PE and IUGR (n?=?16) and (iv) IUGR (n?=?24). The classification of IUGR included umbilical artery Doppler resistance. Maternal plasma placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble kinase domain receptor (sKDR) and soluble endoglin (sEng) as well as fetal umbilical artery sFlt-1 levels were determined. Each individual marker and their ratios were assessed for their potential to distinguish normal pregnancy from pregnancies affected by PE and/or IUGR.

Results: We found (i) elevated plasma sFlt-1, sEng and reduced PlGF, sKDR in PE and IUGR; (ii) similar angiogenic profiles in PE and IUGR and (iii) sEng and sFlt-1*sEng/PlGF performed best as biomarkers in identifying pathologic pregnancies.

Conclusions: PE and IUGR have similar angiogenic profiles, suggesting that angiogenic marker profiles lack specificity in identifying PE and that other factors are required for the development of PE instead of IUGR. sEng should be included in a biomarker profile for predicting PE or IUGR.     

Sonographic Measurement of Umbilical Vein and Umbilical Cord Diameters in Normal and Diabetic Pregnancies

Sonographic visualization of umbilical cord components is becoming increasingly important in evaluating fetal well-being. Standard graphs of umbilical vein and cord measurements during the last two trimesters of 219 normal singleton pregnancies showed a linear increase in transverse dimensions with advancing gestational age. Preliminary data on 38 pregnancies complicated by maternal diabetes mellitus, showed significant deviations from normal umbilical measurements.     

Interaction between risk factors for fetal growth retardation associated with abnormal umbilical artery Doppler studies

BACKGROUND: The role of antenatal risk factors associated with the occurrence of fetal growth restriction complicated by abnormal umbilical artery Doppler studies has not yet been studied extensively. We evaluated the role and the interactions of antenatal antecedents of fetal growth restriction complicated by abnormal umbilical artery end-diastolic velocities. METHODS: We compared antenatal variables in 183 pregnancies complicated by fetal growth retardation and abnormal umbilical artery Doppler studies and 549 appropriately grown fetuses with normal end-diastolic velocity waveform in the umbilical artery. Logistic regression was used to evaluate the association between antenatal variables and fetal growth retardation and to test for interaction. RESULTS: In logistic models, increasing maternal age [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.01-1.11], nulliparity (OR 2.2, 95% CI 1.37-3.5), smoking during pregnancy (OR 2.56, 95% CI 1.56-4.22), preeclampsia (OR 27.5, 95% CI 15.1-49.9), first-trimester hemorrhage (OR 2.25, 95% CI 1.32-3.82) and low (< 0.2 kg/week) weight gain in pregnancy (OR 3.48, 95% CI 1.71-3.05) were significantly associated with an increased risk of fetal growth restriction complicated by abnormal Doppler studies. These risk factors were also significantly correlated with the occurrence of absent/reversed end-diastolic blood flow in the umbilical artery. Maternal smoking during pregnancy interacted negatively with preeclampsia but positively with a low weight gain in pregnancy. CONCLUSIONS: The results of this study have shown that antenatal risk factors for intrauterine growth retardation (IUGR) complicated by abnormal Doppler studies are similar to those associated with the birth of a small-for-gestational-age infant. Preeclampsia, maternal smoking and low weight gain in pregnancy play a significant causal role in the origin of fetal growth restriction associated with abnormal uteroplacental blood flow.     

Endothelial cell apoptosis is induced by fetal plasma from pregnancy with umbilical placental vascular disease

OBJECTIVE: Vascular disease in the umbilical placental circulation that is detected by umbilical artery Doppler study is associated with adverse fetal outcome. Endothelial cell activation and platelet consumption are features of this pathologic condition. We postulated that this was due to the local release of factors that cause endothelial cell injury and that these would spill into the fetal circulation. To test this hypothesis, we examined for the presence in fetal plasma of factors that induced endothelial cell apoptosis in pregnancies that were complicated by umbilical placental vascular disease. STUDY DESIGN: Isolated and cultured human umbilical vein endothelial cells were exposed to fetal plasma from the 3 fetal groups: normal pregnancy (n = 32 patients), pregnancy with umbilical placental vascular disease that was identified by an abnormal umbilical artery Doppler study (n = 38 patients), and pregnancy with maternal preeclampsia and normal umbilical artery Doppler study (n = 16 patients). Early apoptosis can be recognized by a loss of plasma membrane asymmetry with membrane uptake of annexin V. This was measured with annexin V and propidium iodide staining by fluorescent-activated cell scanning. Cells that underwent early apoptosis stained positive for annexin V and negative for propidium iodide (in contrast with cells that underwent necrosis). Cytosolic proteolytic activity was also measured. The lysates from endothelial cells that were stimulated by fetal plasma from umbilical placental vascular disease were tested for caspase-3 and caspase-8 activities by a fluorescent assay with spectrofluorophotometry. RESULTS: The percentage of endothelial cells that underwent apoptosis was significantly higher (P <.05) when stimulated with fetal plasma from pregnancies with umbilical placental vascular disease (17.71% +/- 1.31%) than with fetal plasma from normal pregnancies (9.76% +/- 0.87%). In the presence of maternal preeclampsia with normal umbilical artery Doppler study, the percent of apoptotic cells (11.31% +/- 1.59%) was similar to that of the normal group. In the group with abnormal umbilical artery Doppler study, there was no difference between pregnancies with preeclampsia (n = 17 pregnancies) and without preeclampsia (n = 21 pregnancies). The protease activity of caspase-3 was significantly enhanced in the group with umbilical placental vascular disease compared with normal pregnancy (0.79 +/- 0.06 vs 0.45 +/- 0.08 microMol/L). However, no difference in caspase-8 activity was detected (0.66 +/- 0.05 vs 0.56 +/- 0.05 microMol/L). CONCLUSION: Endothelial cell apoptosis is a feature of umbilical placental vascular disease. Our study demonstrates the presence of factors in the fetal plasma that caused endothelial cells to undergo early apoptosis. This increased apoptosis was only seen in the presence of placental vascular disease and was independent of the presence or absence of maternal preeclampsia. Our results indicate that programmed endothelial cell death occurs in the fetal circulation as a part of the injury that is associated with the development of umbilical placental vascular disease. The caspase-3, rather than caspase-8, signal transduction pathway appears to be involved in the mediation of endothelial cell apoptosis that was detected in our study.     

Umbilical artery N-terminal peptide of proatrial natriuretic peptide in hypertensive pregnancies and fetal acidemia during labor

OBJECTIVE: To assess the activity of the human fetal atrial natriuretic peptide system in hypertensive pregnancies with and without signs of increased fetal systemic venous pressure and in pregnancies complicated by fetal acidemia during labor. METHODS: Umbilical artery plasma N-terminal peptide of proatrial natriuretic peptide concentrations were measured in neonates by radioimmunoassay. The control group consisted of 50 neonates with uncomplicated gestation and labor. In group 1, there were 22 newborns of hypertensive pregnancies. Doppler ultrasonography showed abnormal umbilical artery blood velocity waveform in five cases and normal nonpulsatile umbilical vein blood velocity profile in every case. Group 2 consisted of five newborns of pregnancies complicated by maternal hypertensive disorder. Atrial pulsations in the umbilical vein and retrograde diastolic blood velocity pattern in the umbilical artery were detected in every case. Group 3 was composed of 27 newborns of uncomplicated pregnancies with fetal acidemia (pH 7.10 or less) during labor. RESULTS: In groups 1-3, N-terminal peptide of proatrial natriuretic peptide concentrations were higher (P <.001) than in the control group. In group 1, neonates with abnormal umbilical artery blood velocity pattern had higher N-terminal peptide of proatrial natriuretic peptide concentrations than neonates with normal umbilical artery Doppler findings (P <.006). N-terminal peptide of proatrial natriuretic peptide concentrations were higher in group 2 (P <.002) than in groups 1 and 3. CONCLUSIONS Maternal hypertensive disorder and fetal acidemia during labor stimulate fetal atrial natriuretic peptide production, which was greatest in fetuses with severe placental insufficiency and signs of congestive heart failure.     

Betamethasone associated changes in umbilical artery flow velocity waveforms in multiple pregnancies with umbilical artery absent end diastolic flow

OBJECTIVES: It has been previously shown that glucocorticoids alter umbilical artery flow velocity waveforms in singleton pregnancies complicated by umbilical artery absent end diastolic flow. Whether similar effects are evident in multiple pregnancies where one fetus has umbilical artery absent end diastolic flow is not known. METHODS: Women with a twin or triplet pregnancy complicated by umbilical artery absent end diastolic flow in one fetus were admitted to hospital for intensive fetal surveillance including daily umbilical artery flow velocity waveform studies, as per hospital protocol. All women received prophylactic betamethasone (11.4 mg x 2, 24 h apart) in anticipation of preterm delivery. RESULTS: Between October 1996 and February 2002, 24 women with a multiple pregnancy complicated by umbilical artery absent end diastolic flow were cared for. Of these, six had a pregnancy with feto-fetal transfusion and excluded from further analysis. Of the remaining 18 women, eight had monochorionic diamniotic twins, eight had dichorionic twins, and two had trichorionic, triamniotic triplets. The median (range) gestation at diagnosis of umbilical artery absent end diastolic flow was 210.5 days (173-241). In nine (50%) of the 18 pregnancies the administration of betamethasone was associated with return of umbilical artery end diastolic flow for a median of 5 days. There was no association between this effect and chorionicity. The median (range) interval from diagnosis of umbilical artery absent end diastolic flow to delivery was 11 days (1-46). CONCLUSIONS: As previously reported in singleton pregnancies, the maternal administration of betamethasone in multiple pregnancies with umbilical artery absent end diastolic flow is associated with a transient return of end diastolic flow.     

Biochemical changes in the mother and the fetus during labor and its significance for the management of the second stage

In 69 patients with uneventful pregnancies, term labor was studied prospectively with respect to length of second stage, number of bearing down efforts, maternal and fetal levels of lactate, epinephrine and norepinephrine. Maternal venous blood concentrations were measured in early labor and at the time of delivery while samples from umbilical artery and vein provided fetal blood. There was a significant rise of lactate and catecholamines in maternal blood during labor and at delivery fetal lactate concentration was lower than the maternal level while for epinephrine and norepinephrine fetal levels were higher. For all three compounds umbilical artery concentrations were higher than umbilical venous levels. While there was no correlation between the biochemical parameters in maternal blood and length of second stage maternal lactate and norepinephrine concentration at the time of delivery significantly correlated with the number of bearing down efforts. Umbilical artery lactate correlated with both, length of second stage and number of bearing down efforts.     

Phase-rectified signal averaging as a new method for surveillance of growth restricted fetuses

Objective: This study aims to compare average acceleration capacity (AAC), a new parameter to assess the dynamic capacity of the fetal autonomous nervous system, and short term variation (STV) in fetuses affected by intrauterine growth restriction (IUGR) and healthy fetuses. Methods: A prospective observational study was performed, including 39 women with IUGR singleton pregnancies (estimated fetal weight <10th percentile and umbilical artery resistance index >95th percentile) and 43 healthy control pregnancies matched according to gestational age at recording. Ultrasound biometries and Doppler examination were performed for identification of IUGR and control fetuses, with subsequent analysis of fetal heart rate, resulting in STV and AAC. Follow-up for IUGR and control pregnancies was done, with perinatal outcome variables recorded. Results: AAC [IUGR mean value 2.0 bpm (interquartile range = 1.6–2.1), control 2.7 bpm (2.6–3.0)] differentiates better than STV [IUGR 7.4?ms (5.3–8.9), control 10.9?ms (9.2–12.7)] between IUGR and control. The area under the curve for AAC is 97 % [95% CI = (0.95–1.0)], for STV 85 % (CI = 0.76–0.93; p < 0.01). Positive predictive value for STV is 77% and negative predictive value is 81%. For AAC both positive and negative predictive values are 90%. Conclusions: AAC shows an improvement to discriminate between normal and compromised fetuses at a single moment in time, in comparison with STV.     

Doppler examinations of fetal and uteroplacental blood flow in AGA and IUGR fetuses before and after maternal physical exercise with the bicycle ergometer

OBJECTIVE: To study changes in uteroplacental and fetal circulation after maternal exercise in appropriate-for-gestational-age fetuses (AGA) and intrauterine-growth-retarded fetuses (IUGR). MATERIALS AND METHOD: 33 women with an uncomplicated course of pregnancy and ten women with IUGR were examined. Physical stress was caused through a bicycle ergometer with 1.25 W/kg maternal weight. Doppler examinations were performed in the umbilical artery, fetal aorta, middle cerebral and in the uterine artery. Fetal heart rate was documented by monitoring. Maternal lactate and glucose levels as well as maternal blood pressure and heart rate were recorded. RESULTS: No significant changes after cycling could be observed in umbilical and uterine vessels either in the normal pregnancies or in pregnancies with IUGR. In contrast, in the fetal aorta an increase of the RI was recorded in both groups (an increase of 16% [P<0.01] and 18% [P<0.05], respectively for AGA and IUGR cases). In cerebral arteries a decrease of the RI was observed after cycling in both groups (a decrease of 24% [P<0.01] and 13% [P<0.05], respectively for AGA and IUGR cases). In AGA fetuses the RI of the aorta and middle cerebral artery returned to pre-test level by the 18th minute of examination. In IUGR fetuses the RI of the aorta and middle cerebral artery did not return to pre-test levels at the end of the test. Fetal heart rate remained unchanged in both groups. Maternal blood pressure and heart rate increased during the exertion phase but returned to initial values at the end of the test. A 21% and 24% (for AGA and IUGR groups respectively) reduction of maternal glucose values after exercise was observed (P<0.001). Lactate values doubled in both groups after exercise (P<0.001). CONCLUSION: From the results obtained we conclude that maternal exercise does not significantly alter uterine and umbilical perfusion in AGA and IUGR pregnancies, suggesting an absence of change in the uterine vascular bed resistance. However, submaximal maternal exercise was followed by fetal cerebral vasodilatation and an increase of resistance in the fetal aorta that was more evident in IUGR fetuses. This might be due to slight fetal hemoglobin desaturation in those cases.     

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.