Grzegorz H. Bręborowicz

Evaluation of fetal circulation redistribution in pregnancies with absent or reversed diastolic flow in the umbilical artery

AIM To record blood flow velocimetry in the superior mesenteric, hepatic and middle cerebral arteries for detection of circulation redistribution and prediction of perinatal outcome in fetuses with absent or reversed diastolic flow in the umbilical artery. STUDY DESIGN The fetal superior mesenteric, hepatic and middle cerebral artery blood velocimetry was recorded in 33 pregnancies complicated by pregnancy-induced hypertension and/or intra-uterine growth retardation between 27 and 41 weeks of gestation. Uterine artery and umbilical vein velocimetries were also recorded. RESULTS An abnormal mesenteric artery pulsatility index (PI) was found in four cases; two newborns died due to prematurity, growth retardation and necrotizing enterocolitis. An abnormal fetal hepatic artery PI was found in 17 cases. The brain-sparing effect in the middle cerebral artery was found in 16 cases; three newborns died after delivery. Signs of redistribution in mesenteric, hepatic and middle cerebral artery velocimetry were not related to most of the perinatal outcome variables. Umbilical vein velocimetry correlated with low arterial and venous pH. All perinatal mortalities had umbilical venous pulsations. CONCLUSIONS Signs of visceral circulation redistribution could not predict adverse outcome. Umbilical venous pulsations were, however, seen in nearly all fetuses; this was the only variable suggesting adverse outcome in the present study of severely compromised fetuses.

Fetal and placental power Doppler imaging in normal and high-risk pregnancy

OBJECTIVE Computer analysis of organ power Doppler (PD) imaging has recently become available. The aim of the study was to evaluate gestational trends in placenta-, fetal lung-, liver- and kidney-blood flow in normal pregnancies and relate it to signals in high-risk pregnancies. METHODS PD signals were recorded in normal singleton pregnancies between 26 and 42 weeks of gestation. Signals were also recorded in 63 high-risk pregnancies. Fixed preinstalled PD system installations for each organ were used during examinations. Images from PD scan were recorded on video tape and off-line analysed by computer. Mean flow signal intensity was calculated for each organ. Umbilical and uterine artery Doppler velocimetry were also recorded in high-risk pregnancies. RESULTS PD signals from the four organs indicated increasing organ blood flow until approximately 34 weeks of gestation, from where the organ signals seemed to decrease. High-risk pregnancies seemed to have lower PD signal intensity, which was more pronounced in cases with signs of placental vascular resistance. CONCLUSION The results suggest that a decrease in fetal organ blood flow might indicate a centralisation of fetal circulation in normal pregnancy at term, as a physiological response to a decrease in placental perfusion. In the high-risk pregnancies the placental and fetal organ blood flow seem to be even further reduced, suggesting a more intense centralisation of circulation.

Fetal superior mesenteric artery blood flow velocimetry in normal and high-risk pregnancy.

Abstract The aim: To record blood flow velocimetry in the fetal superior mesenteric artery in normal pregnancy and to evaluate if blood flow recordings in the vessel might predict adverse outcome in high-risk pregnancy. Methods: The fetal superior mesenteric artery blood velocimetry was recorded in a cross sectional manner in 75 normal pregnancies between 27 and 41 weeks of gestation. Reference curves were performed for pulsatility and resistance indices. The superior mesenteric artery was also located in 48 singleton pregnancies complicated by pregnancy-induced hypertension and/or intra-uterine growth retardation. Middle cerebral artery, umbilical artery and vein and uterine artery velocimetry were also recorded. Results: Superior mesenteric artery PI and RI values expressed an increase in resistance to blood flow with gestational age after 32 weeks of gestation. In all except eight high-risk pregnancies the fetal mesenteric artery PI values were within normal range. Among the pregnancies with absent or reversed blood flow in the umbilical artery, all had abnormal mesenteric artery pulsatility index (PI) (>97.5th percentiles), one fetus died intrauterine and two others died after delivery due to prematurity, growth retardation and necrotizing enterocolitis. In the remaining fetuses with increased mesenteric artery PI, necrotizing enterocolitis was diagnosed in three cases. Conclusions: Increased vascular resistance in the mesenteric artery might be a late sign of fetal circulation redistribution and frequently related to necrotizing enterocolitis in the newborn.

1166C mutation of angiotensin II type 1 receptor gene is correlated with umbilical blood flow velocimetry in women with preeclampsia

OBJECTIVE To ascertain the frequency of polymorphic variants of the gene coding for angiotensin II type 1 receptor (AT1) and its correlation with umbilical artery (UA) blood flow velocity in a group of women with preeclampsia (PE). STUDY DESIGN AT1 polymorphism, pulsatility index (PI) in UA, and perinatal outcome in 47 women with PE and in 113 healthy pregnant women were investigated. Investigation of AT1 receptor genotypes was performed by PCR/RFLP assays. PI value has been measured by Doppler velocimetry technique. RESULTS The overrepresentation of CC homozygotic genotype in PE group (6.4% vs. 2.7%) and the overrepresentation of mutated C allele in the PE group were observed (28.7% vs. 23.0%). Analyzing PI index we observed statistically significant differences between PE and control groups. Comparing PI values in PE group between genotypes: AA vs. AC + CC statistically significant differences (p < 0.05) have been observed. CONCLUSIONS Observed overrepresentation of mutated C allele of the AT1 gene was correlated with increased blood flow in umbilical artery in women with preeclampsia. Doppler velocimetry might be a useful tool for indication in the high-risk group with overrepresentation of C alleles.

Fetal and maternal Doppler velocimetry and cytokines in high-risk pregnancy

Abstract Objective: Fetal hypoxia and preterm delivery are reported to be strongly associated with brain damage and neurodevelopmental delay. Doppler signs of fetal brain sparing have been described during chronic hypoxia, but whether they are related to brain damage is unknown. The aim of this study was to evaluate if markers of tissue injury, i.e., tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) are related to signs of increased perinatal vascular impedance and/or fetal brain sparing in high-risk pregnancies. Study design: TNF-α and IL-6 levels were evaluated in maternal blood serum of 67 high-risk pregnancies. Serum samples were taken at the time of umbilical, middle cerebral artery and uterine artery Doppler velocimetry examination. The values for TNF-α and IL-6 were correlated with reference median values obtained with gestational age in the form of a Z-score. Results: TNF-α levels showed values within the normal range in only four cases. IL-6 values were found normal in 14 cases. The Z-score for mean middle cerebral artery pulsatility index (PI) showed a significant correlation to TNF-α and IL-6 levels, P<0.0001 and P<0.003, respectively. This might suggest a strong correlation between signs of fetal brain sparing and increased maternal serum TNF-α and IL-6 levels. Abnormal uterine artery PI and the presence of a “notch” were also highly significantly related to TNF-α and IL-6 levels, which were nearly two-fold higher compared to normal uterine artery blood flow and the absence of a “notch”. Abnormal cerebro/placental ratios showed significant correlations to TNF-α and IL-6 levels. Conclusion: The present results suggest a strong correlation between levels of TNF-α and IL-6 not only for signs of fetal brain sparing, but also for uteroplacental blood flow. This finding supports the role of tissue injury in cases of fetal brain sparing, but whether this is a reflection of brain damage or secondary to placental pathology needs further evaluation.

Glucocorticoid Metabolism in Hypertensive Disorders of Pregnancy: Analysis of Plasma and Urinary Cortisol and Cortisone

Objectives The aim of the study was to analyze the plasma and urinary cortisol (F) and cortisone (E) levels in normotensive and hypertensive pregnant women. The parameters known to reflect the function of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) were calculated to verify the changes in glucocorticoid balance over the course of gestational hypertension (GH) and pre-eclampsia (PE). Materials and Methods This retrospective case-control study included women in the third trimester of pregnancy, diagnosed with: GH (n = 29), PE (n = 26), or chronic hypertension (CH; n = 22). Normotensive women in their third trimester of pregnancy were also included (controls; n = 43). The plasma and urinary F and E levels were measured with the HPLC-FLD method. The 11β-HSD2 function was estimated by calculating the following ratios: plasma F/E and urinary free F to urinary free E (UFF/UFE). A statistical analysis was performed based on case-control structure. Results and Discussion PE was characterized by lower plasma F levels (639.0 nmol/L), UFF/Cr levels (3.80 μg/mmol) and F/E ratio (3.46) compared with that of the controls (811.7 nmol/L, 6.28 μg/mmol and 5.19, respectively) with marked abnormalities observed in the changes of F/E and UFF/UFE ratios with advancing gestation. GH patients showed significant disparities in the urinary steroid profile with lower UFF/UFE ratio (0.330 vs. 0.401) compared with the normotensive controls and abnormal changes in the UFF/UFE throughout pregnancy. The observed tendency towards lower F/E and UFF/UFE ratios in PE and GH patients may reflect more intensive F metabolism over the course of those disorders. In the normal pregnancy group, the plasma F/E and UFF/UFE ratios tended to present inverse correlations with advancing gestation. This trend was much less marked in PE and GH patients, suggesting that the abnormalities in 11β-HSD2 functions progressed with the GA. The birth weights of neonates born from pre-eclamptic pregnancies were lower than those from uncomplicated pregnancies, although only when the babies were born prematurely. Children born at term to normotensive mothers or mothers suffering from PE had comparable birth weights.

Comparison of power Doppler and velocimetry in predicting outcome of high-risk pregnancy

Objective: Prospectively evaluate semi-quantitative computer analysis of power Doppler (PD) signals in the placenta, fetal brain, lung, liver, kidney and spleen in high-risk pregnancies in relationship to perinatal outcome and also to compare tissue blood flow in the fetal brain and placenta with Doppler velocimetry. Methods: PD signals were recorded in 180 high-risk pregnancies between 27 and 41 weeks of gestation. Images from PD angiographic scans were transmitted for computer analysis of pixel intensity. Mean flow signal intensity was recorded for each organ. The PD brain/lung ratio was calculated. The PD results were plotted on reference values and related to perinatal outcome. Middle cerebral (MCA), umbilical (UA) and uterine artery (Ut. A) velocimetry was also performed. Results: High-risk pregnancies displayed lower PD signal intensity from the placenta, fetal lung, liver and kidney as compared to normals. However, the brain and spleen signals showed higher intensities suggesting increased tissue perfusion. PD signals from the fetal brain, lung, placenta and PD brain/lung ratio were correlated with perinatal outcome. The PD signal intensity from the fetal liver, kidney and spleen showed poor correlation with perinatal outcome. Fetal brain tissue blood flow showed better correlation with the outcome than MCA velocimetry. Placental tissue blood flow results were similar in predicting outcome to those obtained by means of UA and Ut. A velocimetry. Conclusion: In comparison with conventional Doppler velocimetry, computer analysis of PD signals, give similar results in the prediction of adverse perinatal outcome.

Blood velocity in the fetal vein of Galen and the outcome of high-risk pregnancy

BACKGROUND Pulsation in the flow velocity waveform in the umbilical vein is related to perinatal mortality but the flow velocity waveform in the fetal vein of Galen is normally even and without fluctuation. OBJECTIVES To establish whether blood flow velocity pulsations in the vein of Galen in high-risk pregnancies are related to outcome. STUDY DESIGN The vein of Galen was located by colour Doppler ultrasound in 102 pregnancies complicated by severe pregnancy-induced hypertension. The blood velocity waveform was recorded by pulsed Doppler within 2 days of delivery and the presence pulsations related to pregnancy outcome, including emergency operative intervention and neonatal distress. Umbilical artery and vein and uterine artery blood flow velocity waveform were also recorded at the same time. The clinicians managing the women were unaware of the venous flow results. RESULTS Pulsation were present in the vein of Galen in 68 cases and in the umbilical vein in 21. Both were significantly related to adverse outcome. Pulsations in the vein of Galen were seen in all seven perinatal deaths. CONCLUSIONS Since umbilical venous pulsation are a late sign of fetal compromise, and pulsations in the vein of Galen seem to appear earlier, thus being an intermediate sign of fetal compromise that might be of great value for fetal surveillance.

Cerebroplacental ratio in prediction of adverse perinatal outcome and fetal heart rate disturbances in uncomplicated pregnancy at 40 weeks and beyond.

Introduction The aim of the study was to determine the usefulness of Doppler velocimetry, based on cerebroplacental ratio (C/U) evaluation, in predicting intrapartum fetal heart rate abnormalities and adverse neonatal outcome in uncomplicated pregnancies at 40 weeks and beyond. Material and methods One hundred and forty-eight women in uncomplicated pregnancies, between 40 and 42 completed weeks, were divided into control and study groups: with the absence (n = 79) and with the presence of a fetal brain-sparing effect (n = 69), respectively. Pulsatility and resistance indices in the middle cerebral, the umbilical artery and the C/U ratio were evaluated daily by Doppler ultrasonography. C/U < 1.1 was reported as suggestive of a brain-sparing effect. Abnormal flow indices were analyzed and compared to adverse pregnancy and neonatal outcome determinants. Results In the abnormal C/U group the abnormal CTG records were significantly more frequently observed (62.3%) than in normal C/U group (19.0%) (p = 0.0001). The comparison of selected Doppler indices revealed that C/U showed the highest sensitivity in prediction of both the intrapartum abnormal FHR (74.1%) and the adverse neonatal outcome (87.8%). Conclusions The C/U index shows the highest sensitivity in prediction of FHR abnormalities and adverse neonatal outcome in uncomplicated pregnancies at 40 weeks and beyond. The C/U index is useful in clinical practice in antenatal monitoring of these women in order to select those at high risk of intra- and postpartum complications.

Effect of Pentoxifylline, administered in Preterm Labour, on the Foetal–Placental Circulation and Neonatal Outcome: A Randomized, Prospective Pilot Study

The aim of the study was to evaluate the pentoxifylline administration on the foetal-placental circulation and neonatal outcome in women with threatened preterm labour. Pentoxifylline was given as a supplement to standard tocolytic therapy in a group of 43 patients (pentoxifylline group) as an intravenous infusion and oral supplementation in a total dosage of 800 mg/day. The drug was administered within 3 weeks after admission. No pentoxifylline was given in the control group (53 patients). Doppler velocimetry of pulsatility indices (PI) of the umbilical (UA) and middle cerebral (MCA) arteries as well as cerebro-placental ratio (CPR) were calculated. Also, the neonatal outcome was estimated in both groups. From the second week of therapy with pentoxifylline, the PI decreased in umbilical artery and increased in the MCA, whereas in the control group, there were no changes. The value of PIUA, evaluated after the third week of pentoxifylline administration, was statistically significantly lower when compared to data obtained on admission (mean: 0.99 ± 0.22 versus 0.82 ± 0.12; p =0.016). Pentoxifylline significantly increased CPR values calculated after third week of drug administration, which were statistically significantly higher in the pentoxifylline group when compared with respective data in the control group (mean: 2.30 versus 1.61; p = 0.001). The risk of severe neonatal complications was significantly lower in the pentoxifylline group (p = 0.026). Pentoxifylline changed foetal-placental blood circulation in patients with threatened preterm labour and improved neonatal outcome.