Coagulation and fibrinolysis in pregnancies complicated by fetal growth retardation.

Saline extracts were made from portions of 17 normal placentae and from 8 placentae from pregnancies complicated by fetal growth retardation, but not hypertension. The ability of these extracts to inhibit urokinase-induced fibrinolysis was measured using a fibrin plate technique. Placental extracts from pregnancies complicated by fetal growth retardation exhibited greater inhibition of urokinase-induced fibrinolysis. There was no evidence of disseminated intravascular coagulation in these patients, but certain coagulation factors in the peripheral blood were raised.     

Maternal left ventricular dimension in pregnancies complicated by fetal growth retardation

Previous studies using two-dimensional chest radiographs have found a significant correlation between prematurity, fetal growth retardation, and the size of the maternal heart. Accordingly, we evaluated maternal left ventricular size and function by M-mode echocardiography near the end of gestation in 42 women with suspected fetal growth retardation and in 79 women whose pregnancies were normal. No significant differences were found between the two groups, implying that maternal left ventricular size and function is adequate in pregnancies complicated by "idiopathic" fetal growth retardation.     

Changes in platelet function in pregnancies complicated by fetal growth retardation.

Platelet function was investigated in three patients with severely decreased fetal growth rates detected by ultrasound scanning. Only one patient had hypertension, which was mild and developed after decreased fetal growth and altered platelet responses had been detected. Much higher concentrations of platelet-activating factor (PAF) (20-500 nM) were required to stimulate maximal platelet aggregation in all three patients compared with the concentrations of PAF (5-10 nM) required in control pregnancies of similar gestational age. In a fourth patient, platelet desensitisation was observed 5 weeks before the detection of decreased fetal growth. These results are similar to those observed in women with hypertensive disorders of pregnancy, and indicate that there may be a similar change in platelet function in gestational hypertension and in fetal growth retardation, although the clinical manifestations are different.     

Amniotic fluid C-peptide and cortisol in normal and diabetic pregnancies and pregnancies accompanied by fetal growth retardation

The interrelationship between amniotic fluid (AF) concentration and content (AF X conc) of C-peptide and cortisol was studied in four groups of women comprising 10 gestational and 16 type-I diabetics, 11 women with intrauterine growth retarded fetuses (IUGR), and 17 healthy control women. Mean AF volume was significantly greater (P less than 0.05) in the type-I diabetic group than in the control group. Both concentration and content of AF C-peptide was significantly higher in the type-I diabetic group than in the control group (P less than 0.05 and P less than 0.01, respectively). The corresponding values were significantly lower in mothers with IUGR fetuses compared to controls (P less than 0.05). AF cortisol content was significantly higher (P less than 0.05) in the gestational diabetic group compared to the control group; there were no other significant differences between the groups regarding the cortisol concentration or content. Both cortisol and C-peptide contents were significantly interrelated in both control women (r = 0.68, P less than 0.01) and women with gestational (r = 0.68, P less than 0.05) and type-I diabetes (r = 0.63, P less than 0.01). The C-peptide/cortisol ratio was lowest in the IUGR group and highest in the type-I diabetic group. The same ratio was intermediate and almost equal in the control and gestational diabetic group. Both C-peptide and cortisol concentrations were unrelated to AF volume as well as infant birthweight. C-peptide content was significantly correlated to birthweight percentile in type-I diabetic women (r = 0.61, P less than 0.05). No such correlation was found in the three other groups.     

Decreased prostacyclin production by placental cells in culture from pregnancies complicated by fetal growth retardation

Summary. Production of prostacyclin (PGI₂) in vitro by human placental cells from pregnancies complicated by fetal growth retardation was significantly reduced compared with that in placental cells from normal pregnancies of either matched gestation or at term. This appeared to be due to a reduction of synthesis of PGI₂ rather than to any alteration in the rate of its enzymic metabolism. Addition of oestradiol and progesterone increased PGI₂ production by cells from pregnancies with fetal growth retardation in a similar manner to that by cells from first trimester pregnancies, implying that the placental cells are not irreversibly damaged by ischaemia. The decreased PGI₂ production by cells of trophoblastic origin may be an aetiological factor in the thrombotic occlusion of the uteroplacental circulation which impairs fetal growth.     

Doppler assessment of the fetal asphyxia in pregnancies complicated by gestational hypertension and intrauterine growth retardation

OBJECTIVES: Gestational hypertension is associated with a high morbidity for both mother and fetus. Doppler ultrasound has allowed the fetal circulation to be examined. Now it is possible to monitor the response of the fetal circulation to hypoxia. DESIGN: The aim of this study was to determine flow patterns in fetal circulation from pregnancies complicated by gestational hypertension and intrauterine growth restriction. MATERIALS AND METHODS: The investigation included 23 fetuses with signs of the gestational hypertension and intrauterine growth restriction. We evaluated cerebral-placental ratio (CPR) and pulsation index (PI) in the middle cerebral artery (MCA) and the umbilical artery (UA). We also evaluated flows in umbilical vein. RESULTS: We observed abnormal flow pattern in all cases of analyzing fetuses. The most common abnormal flow was vein pulsation (48%). CONCLUSIONS: All analyzing fetuses shown signs of the hypoxia. Present of the umbilical vein pulsation or decompensate of the brain sparing effect is closely related o increased perinatal mortality.     

Flow-velocity profiles of the fetal aorta and umbilical artery in pregnancies complicated by pregnancy-induced hypertension and fetal growth retardation

Sixty-seven women undergoing ultrasonographic evaluation in the high-risk clinic were randomly recruited to be examined by a newly developed computerized method that presents flow-velocity profiles derived from pulsed Doppler-generated flow-velocity waveforms. Each woman had pulsed Doppler flow velocimetry of the fetal aorta and umbilical arteries done. Subjects were either normal controls (N = 20) or had pregnancies complicated by pregnancy-induced hypertension (N = 29), fetal growth retardation (N = 11), or both (N = 7). Distinct patterns of flow-velocity distribution across the fetal aorta and proximal umbilical arteries were identified in the pregnancies characterized by increased placental resistance. At peak systole, normal velocity was maintained only at a narrow area around the center of the vessel, whereas velocity in the rest of the vessel area was markedly reduced. These changes were present in 40 of 47 subjects (85.1%) with complicated pregnancies, whereas 27 of 47 (57.4%) had umbilical artery systolic-diastolic ratios above the 95th percentile. No significant differences between normal and complicated pregnancies were seen during diastole. Our findings suggest that increased placental resistance results in a redistribution of velocities within fetal blood vessels, often before maximal end-diastolic velocity is decreased.     

Management of pregnancies complicated by anti-E alloimmunization

OBJECTIVE: There is limited information published about anti-E alloimmunization. We review our experience at The Ohio State University to determine appropriate management strategies. METHODS: We reviewed records from June 1959 to April 2004 to identify pregnancies managed for anti-E alloimmunization. Information collected included antibody titers, DeltaOD450 values, Liley zones, middle cerebral artery peak systolic velocity, fetal and neonatal hemoglobin (Hb) and antigen typing, fetal and neonatal direct antiglobulin test, and outcomes. Pregnancies affected only by anti-E alloimmunization with a positive direct antiglobulin test or positive E antigen typing in the fetus or newborn were included. RESULTS: A total of 283 pregnancies were identified with anti-E. Of these, 32 pregnancies in 27 women were at risk for hemolytic disease of the fetus or newborn from anti-E only and had complete records. Sixteen of these pregnancies had titers greater than or equal to 1:32, with amniocenteses performed for DeltaOD450 in 15 pregnancies. Values of DeltaOD450 in zone IIB or zone III in combination with serologic titers identified all pregnancies with fetal or neonatal anemia. Five of 32 (15%) fetuses had Hb less than 10 g/dL and 1 fetus had hydrops fetalis due to anti-E alloimmunization. There was 1 perinatal death attributable to anti-E hemolytic disease of the fetus or newborn. Middle cerebral artery peak systolic velocity was measured in 2 cases and corroborated information obtained from amniocentesis. CONCLUSION: Anti-E alloimmunization can cause hemolytic disease of the fetus or newborn requiring prenatal intervention. Based on our population, clinical strategies developed for Rh D alloimmunization using maternal serology, amniotic fluid spectrophotometry, and fetal blood sampling are useful in monitoring E alloimmunization.     

The effect of fetal anemia on fetal cardiac troponin T in pregnancies complicated by RhD alloimmunization

Objective: To study the effect of fetal anemia on fetal cardiac troponin T (cTnT) in pregnancies complicated by RhD alloimmunization. Method: Twenty pregnant women complicated by RhD alloimmunization who underwent intrauterine transfusion (IUT) for treatment of fetal anemia were studied. Immediately before IUT, fetal blood was obtained for hemoglobin and cTnT measurements. Results: Complete measurements of hemoglobin and cTnT before IUT were obtained in 49 procedures, of which 20 were first-time. The regression analysis between hemoglobin z-score and cTnT values in 49 procedures showed significant negative correlation (r = ?0.43, p = 0.002, Regression equation Log(cTnT) = ?1.5057 + ?0.07563 Hb z-score). Cardiac TnT values before first IUT were significantly associated with perinatal death. In the group with elevated cTnT (n = 7), fetal or neonatal death was more frequent (2 IUD and 2 NND) when compared to normal cTnT group (n = 13, 1 IUD) (57.1 vs. 7.7%, p = 0.031, Fisher’s exact test). Conclusion: Fetal blood concentration of cTnT before IUT was negatively correlated to hemoglobin z-score, and levels of cTnT help to manage the pregnancies complicated by RhD alloimmunization.     

The effect of bedrest in hospital on fetal outcome in pregnancies complicated by intra-uterine growth retardation

A prospective study was made to evaluate whether bedrest in hospital is beneficial in pregnancies where intra-uterine growth retardation (IUGR) was suspected. Diagnosis was based on routine fetometry at 32 weeks of gestation, in conjunction with general ultrasound screening. 107 patients with suspected IUGR-pregnancies were divided into two groups, 49 in a hospital bedrest group and 58 in an 'out-patient' group. Fifteen women in the bedrest group refused hospitalization, and 8 women in the out-patient group had to be hospitalized for medical reasons other than suspected growth retardation, leaving 79% of the women in their allocated group. The women in the bedrest group were hospitalized for a mean duration of 29.2 days (range 5-54). The results suggest that bedrest in hospital is not beneficial, either to fetal growth or to pregnancy outcome.     

Fetal blood flow in pregnancies complicated by intrauterine growth retardation

A noninvasive pulsed Doppler ultrasound technique was used to characterize blood flow in the descending thoracic aorta and the intra-abdominal part of the umbilical vein in 159 fetuses suspected of intrauterine growth retardation (IUGR) on the basis of ultrasound fetometry. From this group, 74 infants with IUGR (defined as gestational age-related birth weight of 2 standard deviations [SD] or more below the population mean) were born. The blood flow results were not available to the clinicians managing the pregnancies. Blood flow mean velocity in the fetal aorta was lower, pulsatility index and rising slope higher, and umbilical volume flow and umbilical flow per 100 g placental tissue were lower in the pregnancies with IUGR than in 21 normal pregnancies. The waveform of the maximum aortic velocity envelope was related to operative delivery for fetal distress, Apgar score, and umbilical cord blood pH. The pulsatility index and the configurational assessment of the diastolic part of the waveform were combined to form a new concept, the blood flow class. The blood flow class was abnormal in 57% of the fetuses classified as having IUGR at birth and in 93% of those growth-retarded fetuses who subsequently developed signs of fetal distress requiring operative delivery. Waveform analysis, in terms of blood flow class, seems to be a useful tool in the surveillance of fetuses when IUGR is suspected. Abnormal blood flow class is a marker of fetal distress and probably gives an earlier indication than antenatal nonstressed cardiotocography. The results of this study point to a strong association between IUGR and impaired fetal blood flow. The aortic volume blood flow, unlike waveform analysis, does not seem to be a variable sensitive enough to predict fetal outcome in the individual pregnancy.     

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.     

Essential fatty acids in pregnancies complicated by intrauterine growth retardation.

The relative fatty acid composition of lecithin was measured in maternal and cord blood serum in human pregnancies at risk for intrauterine growth retardation (IUGR) (n = 28) as compared to controls (n = 20). In the IUGR cases (n = 13) linoleic acid was lower in maternal samples but higher in cord blood, oleic acid was elevated in both whereas docosohexaenoic acid was lower. Essential fatty acid composition of lecithin was found to be different in IUGR.     

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.     

Average acceleration and deceleration capacity of fetal heart rate in normal pregnancy and in pregnancies complicated by fetal growth restriction

Objective: To study fetal heart rate (FHR), its short term variability (STV), average acceleration capacity (AAC), and average deceleration capacity (ADC) throughout uncomplicated gestation, and to perform a preliminary comparison of these FHR parameters between small-for dates (SFD) and control fetuses. Methods: Prospective observational study of 7?h FHR-recordings obtained with a fetal-ECG monitor in the second half of uncomplicated pregnancies (n = 90) and pregnancies complicated by fetal SFD (n = 30). FHR and STV were calculated according to established analysis. True beat-to-beat FHR, recorded at 1?ms accuracy, was used to calculate AAC and ADC using Phase Rectified Signal Averaging (PRSA). Mean values of FHR, STV, AAC, and ADC derived from recordings in SFD fetuses were compared with the reference curves. Results: Compared with the control group the mean z-scores for STV, AAC, and ADC in SFD fetuses were lower by 1.0 SD, 1.5 SD, and 1.7 SD, respectively (p < 0.0001 for all comparisons). In SFD fetuses, both the AAC and ADC z-scores were lower than the STV z-scores (p < 0.02 and p < 0.002, respectively). Conclusions: Analysis of the AAC and ADC as recorded with a high resolution fECG recorder may differentiate better between normal and SFD fetuses than STV.     

Differing fetal growth patterns in pregnancies complicated by preterm labor

Previous studies have demonstrated diminished ultrasonic fetal growth parameters in women delivering preterm. In this study, we tested the following hypothesis: In pregnancies complicated by spontaneous preterm labor, 1) unsuccessful tocolysis is likely to be associated with diminished fetal growth, and 2) successful tocolysis is likely to occur when fetal growth is normal. Ultrasound examinations were performed in 78 pregnancies complicated by preterm labor before 35 weeks' gestation. Tocolysis was attempted unless contraindicated or unless cervical dilatation was advanced (4 cm or greater). Pregnancies delivering before 36 weeks' gestation were compared with those delivering after this gestational age. Among the 48 pregnancies delivered before 36 weeks' gestation, a significantly greater proportion had ultrasonic growth parameters lower than normal values at corresponding gestational ages. In contrast, those pregnancies that had successful tocolysis and delivered near term demonstrated a normal distribution of ultrasound growth parameters. In pregnancies complicated by preterm labor, ultrasonic documentation of diminished fetal growth may identify the subgroup at increased risk for preterm delivery.     

Intrauterine growth in twin pregnancies: prediction of fetal growth retardation

In 80 consecutive twin pregnancies, prenatal measurements of fetal biparietal diameter (BPD) and abdominal diameter were made and growth curves were calculated using routine ultrasound examinations. Nineteen percent of the infants were growth retarded. Growth retardation was found in both fetuses in four pregnancies and in one fetus in 22 other pregnancies. Linear regression analysis between birth weight and gestational age showed the standard deviation of birth weight to be proportional to gestational age. A more linear growth curve also was found when the mean fetal weight was calculated by use of the BPD and abdominal diameter measurements in the formula developed for singletons. The estimated weight compared with birth weight in 62 twins who had ultrasound examinations less than seven days before delivery showed a significant correlation (r = 0.89, P less than .001) with a coefficient of variation of 12.4%. The identification of intrauterine growth retardation (IUGR) in twin pregnancies by ultrasound had a sensitivity of 62%, a specificity of 98%, and a predictive value of positive and negative test of 93% and 83%, respectively.