Fetal Umbilical Artery Research Articles

Hotelling's test, multiple t‐tests, and uterine artery Doppler evaluation

I read with interest the paper by Lima et al. in the September 2009 edition of Ultrasound in Obstetrics and Gynecology1. The authors assessed pregnant women showing evidence of premature labor who were given oral nifedipine as a tocolytic agent, performing Doppler ultrasound evaluation before drug administration and after 5 and 24 h. Two Doppler ultrasound parameters, resistance index (RI) and peak systolic velocity (PSV), were recorded from three vessels: maternal uterine, fetal middle cerebral (MCA) and umbilical arteries. Significant changes were observed only in the fetal MCA; a reduction in PSV was observed 5 h after nifedipine (but not after 24 h) and a reduction in RI was observed after 24 h (but not after 5 h). The objective of this paper was to evaluate drug safety. Several issues in this paper arouse concern. Firstly the statistical analysis: the authors compared the ultrasound parameters among the three different times using Hotelling's test and performed pair-wise comparisons using multiple paired t-tests. Hotelling's test is usually used in multivariate analyses, but the authors evaluated Doppler parameters by a univariate approach where repeated measures ANOVA would usually be used. Additionally, two problems are expected when using multiple t-tests: the interpretation becomes cognitively more difficult as multiple results are obtained, and the probability of at least one type I error occurring somewhere in the analysis greatly increases. This increase in type I error resulted in findings of additional significant differences in the PSV of the umbilical and right uterine arteries in the pair-wise comparison that were not observed when the sets of measurements were assessed using Hotelling's test. These problems could be avoided by performing repeated measures ANOVA and a post-hoc test, such as Tukey's test. When describing how they determined their sample size, the authors made a small mistake. They reported an SD for MCA-RI of 0.005 without any reference, but the SD values for this parameter reported for their study population were 0.04 (evaluation before drug and after 5 h) and 0.06 (after 24 h) so I presume that the SD used by the authors to estimate sample size was 0.05 instead of 0.005. However, considering SD = 0.05, the estimated sample size to determine a difference of 0.03 would be 44 and not 33, as reported. Regarding Doppler evaluation, the authors reported use of the triplex system in all scans. When using triplex, spectral Doppler waves are interleaved with color Doppler and B-mode ultrasound waves, which results in noisy signals and limitation of the pulse repetition frequency that can be used. This should be avoided, especially when evaluating uterine arteries, when high velocities are expected. Moreover, the reported measurements of uterine artery PSV are far below the values expected; when evaluating these vessels I usually notice PSV between 100 cm/s and 200 cm/s, sometimes reaching 300 cm/s, whilst the reported means were below 70 cm/s in this paper. This difference was probably due to use of triplex or improper angle correction. Finally, in the discussion section the authors explained that the reduction in MCA-RI could be related to a decrease in PSV, which is a component of the numerator in the RI formula. However, this explanation does not fit with the observed results as the decrease in PSV was observed only 5 h after drug administration, when RI remained unchanged, and the decrease in MCA-RI was observed only 24 h after drug administration, when PSV had already increased. W. P. Martins*, * Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Departamento de Ginecologia e Obstetrícia and Escola de Ultra-sonografia e Reciclagem Médica de Ribeirão Preto (EURP), Rua Casemiro de Abreu, 660, Ribeirão Preto, São Paulo, Brasil CEP: 14020-060

The Changes in Doppler Indices of Fetal Ductus Venosus and Umbilical Artery After Amnioinfusion for Women With Preterm Premature Rupture of Membranes Before 26 Weeks' Gestation

To investigate the changes in Doppler indices of the fetal ductus venosus (DV) and umbilical artery (UMA) after amnioinfusion in pregnant women with preterm premature rupture of membranes (pPROM). Pregnancies with pPROM and severe oligohydramnios cause sequelae in newborns and mothers. This cross-sectional study included a group of 25 patients with pPROM before 26 weeks' gestation. Color Doppler imaging was used to measure the impedance index and quantitative blood flow in the DV and systolic/diastolic ratio (S/D) of the UMA before and 30 minutes after the end of amnioinfusion. The following velocity parameters were measured: (1) DV peak systolic velocity; (2) DV time-averaged velocity; (3) DV maximum forward velocity during atrial contraction; (4) DV S/D; (5) DV pulsatility index (PI); (6) DV Pourcelots resistance index (RI); (7) fetal heart rate; and (8) UMA S/D. Twenty-one of the 25 patients underwent a total of 27 amnioinfusions. The mean PI and RI of the DV, and S/D of the DV and UMA decreased significantly after amnioinfusion (PI, 0.75 +/- 0.24 vs. 0.60 +/- 0.18, p = 0.009; RI, 0.60 +/- 0.15 vs. 0.50 +/- 0.13; DV S/D, 3.07 +/- 1.81 vs. 2.13 +/- 0.66, p = 0.008; UMA S/D, 3.58 +/- 0.87 vs. 2.88 +/- 0.62, p = 0.001). Amnioinfusion increases the space for the fetuses and reduces the impedance of the fetoplacental circulation. Improvements in DV and UMA flow may benefit fetuses suffering severe oligohydramnios in mid-pregnancy.

P20.08: Hypertensive disorders in pregnancy and Doppler fluximetry of the umbilical artery

Doppler-Color sonography is a non-invasive method for the investigation of the in-utero fetal well being. Umbilical cord contains blood, the flow of which might correlate to the fetal well being. To study of the correlation between Doppler sonography and fetal distress in pregnancies with hypertensive disorders and IUGR. At the Department of Gynaecology and Obstetrics, during the years 2004 to 2006, in prospective manner, 115 pregnant women of gestational age 22 + 3 to 40 + 5 with hypertensive disorders were studied. Fetal umbilical artery was examined by Color Doppler sonography. Out of 115 patients with hypertensive disorders, in 85 cases (73.9%) normal fluximetry of the umbilical artery was observed, while in 30 (26.0%) fluximetry was pathological. The following unfavourable perinatal outcomes, in patients with normal umbilical artery fluximetry were recorded: fetal deaths 2 (2.3%), 21 (24.7%) births with Apgar score below 7. In cases with pathological fluximetry, 14 (46.6%) fetal deaths occurred while number of births with Apgar score below 7 was 14 (46.6%). Out of 30 pregnant women with hypertensive disorders and IUGR, where fluximetry of the umbilical artery was pathologic, in 28 cases (93.2%) this method has signalled an unfavourable perinatal outcome. Based on the data from this form of investigation, we can concluded that in pregnant women with hypertensive disorders and IUGR, Doppler sonography correlates with fetal distress and is the earliest alarm sign in comparison with other tests. Application of this type of examination is recommended for all pregnant women with hypertensive disorders.

Effect of short-term maternal fasting in the third trimester on uterine, umbilical, and fetal middle cerebral artery Doppler indices

Objective To assess the effect of short-term maternal fasting on uterine, umbilical, and middle cerebral artery Doppler indices, and on maternal serum glucose levels and fetal behavior. Methods Maternal serum glucose levels, fetal biophysical profiles, and uterine, umbilical, and middle cerebral artery Doppler indices were assessed in 110 healthy women in the third trimester of pregnancy after fasting for 10–12 hours and 2 hours after a balanced meal. Results Maternal serum glucose levels, nonstress test results, fetal breathing movements, and biophysical profile improved after a meal compared with after fasting for 10–12 hours. Uterine, umbilical, and middle cerebral artery Doppler indices were not significantly different after fasting and after a meal. Conclusion Short-term maternal fasting during the third trimester of pregnancy has no effect on uterine, umbilical, or fetal cerebral artery Doppler indices, and has a transient but significant effect on maternal serum glucose levels and fetal behavior.

What Is Spared By Fetal Brain-Sparing? Fetal Circulatory Redistribution and Behavioral Problems in the General Population

Several population-based studies have shown that intrauterine growth restriction is associated with childhood disabilities involving motor skills, cognitive function, concentration, attention, and mood. The most common cause of intrauterine growth restriction is placental insufficiency. Animal studies have shown that when there is growth restriction due to placental insufficiency, fetal circulatory redistribution occurs so that the is preferentially perfused, a fetal adaptive response known as the brain-sparing effect. The investigators tested the hypothesis that the brain effect could protect against behavioral problems in a cohort of 1232 women who were part of the Generation R Study, a population-based prospective study conducted in the Netherlands between 2003 and 2007. During late pregnancy, circulation in the fetal umbilical artery and the middle and anterior cerebral arteries was assessed with Doppler ultrasound. At age 17.5 to 22 months, 935 children resulting from these pregnancies were evaluated with the Child Behavior Checklist, a questionnaire designed to identify behavior problems. The investigators then evaluated the relationship between the umbilical/anterior cerebral ratio and The Total Problems summary score. Logistic regression analysis showed a higher risk of behavioral problems among children with fetal circulatory redistribution to the anterior cerebral artery. Specifically, there was a statistically significant association between a high umbilical artery/anterior cerebral artery ratio and total problems, as well as a higher risk of internalizing problems (emotional reactivity, somatic complaints) and externalizing problems (attention problems). The association between problem behavior and preferential perfusion of the middle cerebral artery was less evident; a high umbilical/middle cerebral ratio was related with problem behavior for only two categories: internalizing and somatic complaints (P <.05). The investigators conclude from these findings that brain sparing does not completely protect the from the consequences of intrauterine growth restriction. Infants who experience preferential perfusion of the during gestation are more likely to have behavioral problems in young childhood.

Effets de l’électrostimulation par Veinoplus ® sur les troubles circulatoires des membres inférieurs chez la femme enceinte. Étude préliminaire

Objective To assess if electrostimulation of lower limbs relieves lower limbs venous insufficiency-related symptoms during pregnancy. Patients and methods A two-step study was conducted. First, a monocentric prospective preliminary study including 30 pregnant women was conducted to assess the effects of electrostimulation on fetal monitoring and uterine contractions. Then, a multicentric prospective non-randomised study including 58 pregnant women with a gestational age between 23 and 33 weeks of amenorrhoea was conducted to evaluate the electrostimulation treatment. This evaluation was based on a clinical examination performed pre- and post-treatment, a CIVIQ questionnaire filled out pre- and post-treatment and a daily diary filled out by the patient during treatment duration. Treatment duration was 21 days including two daily treatment sequences of 20 min. Three groups of patients were identified based on initial intensity of venous insufficiency-related symptoms (group 1 minor symptoms, group 2 moderate symptoms, group 3 severe symptoms). Results Preliminary study showed no interferences between electrostimulation and fetal cardiac rhythm, uterine contractions and maternal uterine and fetal umbilical arteries Doppler. Concerning the evaluation of the electrostimulation: in group 1, electrostimulation significantly reduced heavy legs sensation ( p < 0,001) and calves pain ( p = 0,02) between the beginning and the end of the treatment. The four scores calculated with the CIVIQ questionnaire decreased after treatment and a significant reduction was noted for generalised pain feeling ( p = 0,04) and psychological impact ( p = 0,03). In group 2, a significant decrease was noted for tiredness ( p < 0,001), heavy legs sensation ( p < 0,001), calves pain ( p < 0,001) and edema ( p = 0,02) between the beginning and the end of the treatment. The four scores calculated with the CIVIQ questionnaire significantly decrease after 21 days of treatment. In group 3, a significant decrease of heavy legs sensation ( p = 0,03) and calves and malleoli perimeters ( p < 0,05) was noted. After 21 days of treatment, the four scores calculated with the CIVIQ questionnaire significantly decrease ( p < 0,05). When comparing the three groups, beneficial effects of the treatment are most marked in group 2 regarding subjective symptoms, CIVIQ questionnaire scores and leg pain. According to the patients, effectiveness and tolerance of the treatment ranged from good to excellent in the three groups. Discussion and conclusion Electrostimulation is an effective and well-tolerated treatment of lower limbs venous insufficiency-related symptoms in pregnant women. Its use during pregnancy did not show any effects on fetus and pregnancy.

Reply

We thank Drs Salomon and Bernard for their interest in our paper. In fetuses with a short femur, the outcome was primarily dependent on the coexistence of other abnormalities. So, while the risk of an underlying skeletal dysplasia, genetic syndrome or chromosomal abnormality was high in fetuses with non-isolated short femur, no such outcomes were found in fetuses in which the short femur was isolated (defined as bilateral and symmetrical shortening of the femur in the absence of associated fetal abnormalities). We would therefore like to qualify their statement that ‘One should not fear such a high incidence of abnormalities when finding an isolated short femur in a first-trimester screened woman.’ In such cases with isolated short femur we showed that in about half the cases this will remain unexplained (defined as cases in which intrauterine growth restriction (IUGR) did not develop, or no postnatal diagnosis of skeletal dysplasia or genetic abnormality was made), in about 10% of the cases subsequent re-measurement will find the femur length to be within the normal range, while in the remainder (about 40%) severe IUGR will develop (defined in our study as fetal abdominal circumference below the 5th centile with abnormal fetal umbilical artery Doppler requiring delivery before 37 weeks). Uterine artery Doppler was a useful tool in predicting which pregnancies were at particular risk of subsequent severe IUGR and associated pre-eclampsia and abruption. We agree that the referral population was likely to be biased to some degree, and in the discussion we highlight this: ‘One of the limitations of this study is that there may have been a degree of referral bias. This, in combination with the policy of first-trimester screening for chromosomal abnormalities, may change the relative proportions of pregnancy outcomes. However, the outcomes in each group will be similar…’. In other words, the proportion of isolated to non-isolated short femur may be higher, but the relative proportions of outcomes within these two groups should be similar to those that we report; this is of particular relevance in the isolated group. On the issue of normal ranges, we regret that Salomon and Bernard felt that these were discussed inadequately, and the reference for these is given (reference 7). Some light research would have shown that the population from which these normal ranges were constructed was from the same geographical area as that of our hospital (the two main hospitals are fewer than 10 km apart and have overlapping catchment areas2). We therefore believe that the reference charts used do fit our practice. We accept the importance of providing locally relevant normal ranges. However, one could question from how narrow a geographical area such ranges need to come to be sufficiently accurate, and whether using ranges derived from a very narrow segment of the population can be generalized sufficiently for use. Regarding identification of cases, as we explain in the methods (Page 508): ‘we performed a search of our computerized database in order to identify all cases of short femur diagnosed between 18 and 24 weeks of gestation during the study period’, and this is what was done. Given the likely appropriate charts, it is difficult for us to hypothesize why the number of pregnancies with a femur length < 5th centile was lower than expected. One possible explanation is that sonographers with ‘real time’ charts (i.e. when measurements are plotted on a chart at the time of the scan, as is the case in the referring units) may be more likely to re-measure and ‘normalize’ values that are borderline, when the finding is isolated. As our population was screened previously by first-trimester nuchal translucency measurement it is also likely that the most severe cases associated with chromosomal abnormalities or multiple abnormalities had undergone pregnancy termination before the time of the anomaly scan. Finally, we were impressed with the ability of the authors to back-calculate the number of scans needed, and were amused to find that we may be doing fractions of scans! A. T. Papageorghiou*, N. Fratelli*, A. Bhide*, B. Thilaganathan*, * St George's Hospital, Fetal Medicine Unit, Lanesborough Wing, Blackshaw Road, London SW17 0QT, UK

Resistance-Indices und Arterienflächen bei normalen Feten mit singulärer Nabelschnurarterie

In this study we examined the arterial-adaptive dilatation and Doppler velocimetry, especially RI values, in normal fetuses with a single umbilical artery (SUA). We studied 195 fetuses from 18 to 39 weeks of gestational age with a prenatally identified SUA retrospectively. They were enrolled in this study if the following information applied: > 18 weeks of gestational age, no structural or chromosomal abnormalities, and histopathological confirmation of SUA. Sonographic examination included evaluation of the umbilical artery resistance and the cross-sectional area of the umbilical cord, and its vessels were measured in all cases. Small for gestational age (SGA) was diagnosed when the birth weight was below the 10th percentile for gestational age. Fetuses with intrauterine growth restriction were defined as those with biometric data below the 5th percentile. There were 119 cases of prenatally identified SUA which met the inclusion criteria. RI values were below the 10th percentile in 33/119 (27.33) and below the 50th percentile in 73/119 (61.33). RI values below the 10th percentile were significantly more likely to be in the normal collective than in the growth restricted collective [31/87 (35.63%) vs. 2/32 (6.25%); p = 0.001]. Even more significant differences became apparent when comparing the RI values below the 50th percentile of both groups. An umbilical artery diameter over the 90th percentile was found in 49 (41.9%) of cases and was significantly more likely to be present in normal growing fetuses than in the growth restricted group. Normal fetuses with SUA are at higher risk to be born as SGA. With our study results we can confirm the hypothesis that Doppler flow measurements and arterial diameter in SUA are different from those found in normal fetal umbilical arteries. RI values over the 50th percentile or a cross-sectional area of the artery below 95th percentile after 26th week of gestation significantly increases the risk of SGA.

Left ventricular isovolumic relaxation and renin-angiotensin system in the growth restricted fetus

Objective To determine left ventricular isovolumic relaxation time (LV IRT) in normally developing and growth restricted fetuses (FGR) as an indicator of fetal cardiac afterload and neonatal systolic blood pressure. Study design A prospective longitudinal study in 124 normally developing and 47 growth restricted fetuses (FGR). LV IRT, fetal heart rate (FHR) and umbilical artery pulsatility index (PI) were determined at 2–3 week intervals starting at 22–26 weeks of gestation until delivery. Renin and angiotensin I levels were measured by radioimmunoassay in umbilical venous blood after delivery. Systolic blood pressure was measured at day 1 and day 5 of postnatal life. To evaluate the association between LV IRT, gestational age and FHR, bivariate regression analyses were performed. Results Mean LV IRT (62 ± 8 ms) was 29 percent longer in FGR as compared to the normal subset (47 ± 6 ms) at all gestational ages ( p < 0.001). Mean postnatal active plasma renin level (7.78 ± S.D. 1.03 ng/ml) and postnatal angiotensin I level (4.21 ± 0.70 ng/ml) in the FGR subset were significantly higher ( p < 0.001) than in the normal subset (4.81 ± 1.04 ng/ml, renin and 2.69 ± 0.44 ng/ml, angiotensin I). There was a significant difference ( p < 0.01) in systolic blood pressure between the two subsets on postnatal day 1 (FGR 52 ± 6 mmHg vs. normal 46 ± 4 mmHg) and day 5 (FGR 76 ± 5 mmHg vs. normal 60 ± 6 mmHg). Conclusion Left ventricular isovolumic relaxation time may act as a sensitive index of increased arterial afterload in the growth retarded fetus and may herald raised systolic blood pressure in the early neonatal period.

Impact of maternal psychological distress on fetal weight, prematurity and intrauterine growth retardation

Background There are conflicting results regarding the association of maternal antenatal distress with preterm birth and low birth weight. This study investigated the association between maternal distress and intrauterine growth abnormality, low birth weight and preterm birth. Methods Three mutually exclusive and homogeneous groups of pregnant women (with actual psychiatric disorder, with maternal psychological distress, and healthy comparisons) underwent fetal ultrasound examinations, uterine and umbilical artery Doppler velocimetry. Infant weight was measured and information collected on obstetrical features and sociodemographic factors. Results No differences emerged among the three groups of pregnant women in any ultrasound variables. Antenatal maternal psychiatric disorders and antenatal distress were not associated with an increased risk of preterm birth. Infants of women with psychiatric disorders had lower birth weight and higher percentage of birth weight below the 10th centile for gestational age (30%) than infants of healthy mothers (5%). Limitations These findings are preliminary and warrant further investigation in larger-scale study; they are limited by the heterogeneity of psychiatric diagnoses. Conclusions Maternal psychiatric disorders are associated with a lower birth weight, but the effect is unlikely to be due to abnormal utero-placental or feto-placental vascularisation. Further studies should investigate other possible causes of lower birth weight associated with maternal psychiatric disorders.

Regulation of Maternal and Fetal Hemodynamics by Heme Oxygenase in Mice1

Heme oxygenase (HMOX) regulates vascular tone and blood pressure through the production of carbon monoxide (CO), a vasodilator derived from the heme degradation pathway. During pregnancy, the maternal circulation undergoes significant adaptations to accommodate the hemodynamic demands of the developing fetus. Our objective was to investigate the role of HMOX on maternal and fetal hemodynamics during pregnancy in a mouse model. We measured and compared maternal tissue and placental HMOX activity and endogenous CO production, represented by excreted CO and carboxyhemoglobin levels, during pregnancy (Embryonic Days 12.5-15.5) to nonpregnant controls. Micro-ultrasound was used to monitor maternal abdominal aorta diameters as well as blood flow velocities and diameters of fetal umbilical arteries. Tin mesoporphyrin, a potent HMOX inhibitor, was used to inhibit HMOX activity. Changes in maternal vascular tone were monitored by tail cuff blood pressure measurements. Effects of HMOX inhibition on placental structures were assessed by histology. We showed that maternal tissue and placental HMOX activity and CO production were significantly elevated during pregnancy. When HMOX in the placenta was inhibited, maternal and fetal hemodynamics underwent significant changes, with maternal blood pressures increasing. We concluded that increases in maternal tissue and placental HMOX activity contribute to the regulation of peripheral vascular resistance and therefore are important for the maintenance of normal maternal vascular tone and fetal hemodynamic functions during pregnancy.

Umbilical artery half peak systolic velocity deceleration time throughout pregnancy and its role in fetuses with bradycardia

To describe a new technique for Doppler waveform quantification of the fetal umbilical artery, the half peak systolic velocity (h-PSV) deceleration time, which measures the time that it takes a single flow velocity waveform to halve its maximum systolic velocity. As this measurement is independent of fetal heart rate, its role in the evaluation of placental vascular resistance in fetuses with bradycardia was also explored. The umbilical artery impedance indices and the h-PSV deceleration time were measured in 532 normal singleton fetuses from 17 to 41 weeks of gestation. A nomogram was established and its usefulness in assessing fetuses with bradycardia was evaluated. The relationship between umbilical artery h-PSV deceleration time and gestational age was best described by a linear formula (y = 6.5523x + 12.41; R(2) = 0.6346), h-PSV deceleration time increasing by 6.6 ms per week. The correlation coefficients for the 95(th), 50(th) and 5(th) centiles were 0.97, 0.98 and 0.98, respectively. Measurement of h-PSV deceleration time was reproducible, with interobserver and intraobserver variabilities of 10.7% and 7.4%, respectively. Among fetuses with bradycardia (n = 7), the h-PSV deceleration time was above the 5(th) centile in all cases, suggesting normal placental function in spite of abnormally increased impedance indices obtained with traditional Doppler indices in six. The h-PSV deceleration time increases linearly during the second and third trimesters of pregnancy. As its measurement is reproducible and independent of heart rate, it may be useful in the assessment of well-being in fetuses with bradycardia.

OP25.01: First trimester combined screening: prospective evaluation of performance in an OSCAR setting

Objectives: The study was performed to assess whether hemodynamic effects on the fetus occur in late-pregnancy mice when ultrasound contrast agent (UCA) (SonoVue TM ) is used for clinical applications in obstetrical ultrasonography. Methods: Sixty late-pregnancy mice (Wister mice, median weight, 300 (range, 260–330) g; median gestational age, 19 (range, 16–21) days) were selected and divided into three experimental groups – Group A, the control group, were injected with physiologic saline solution, Group B were injected with a diagnostic dose of UCA − 0.06 mg/kg body weight – and Group C were injected with a high dose of UCA − 12 mg/kg. From each group a random selection of one mouse was made and it was examined by ACUSON Sequoia 512 with contrast pulse sequencing (CPS) technology. Maternal and fetal heart rate, pulsatility index (PI), resistance index (RI), and systolic: diastolic ratios (S/D) were measured in the fetal middle cerebral artery, umbilical artery, and uterine artery before and after administration of UCA or physiologic saline solution. Results: There were no significant differences in maternal and fetal heart rate, PI, RI, and S/D ratios in the fetal middle cerebral artery, umbilical artery and uterine artery between the different dosage groups of UCA or physiologic saline solution (ANOVA, P > 0.05). A significant decrease in the maternal and fetal heart rate, measured in the uterine artery and in the fetal middle cerebral artery, before and after injection of UCA or physiologic saline solution was found (t-test, P 0.05). Conclusions: The SonoVue TM UCA did not produce any harmful fetal or placental effects in late pregnancy and was shown to be safe in this study. The decreases in maternal and fetal heart rates was probably caused by the stress of the procedure.

Middle cerebral artery blood flow velocities and pulsatility index and the cerebroplacental pulsatility ratio: longitudinal reference ranges and terms for serial measurements

To establish reference ranges suitable for serial assessments of the fetal middle cerebral (MCA) and umbilical (UA) artery blood flow velocities, pulsatility index (PI) and cerebroplacental pulsatility ratio and to provide terms for calculating conditional reference intervals suitable for individual serial measurements. This was a longitudinal study of 161 singleton pregnancies. Using Doppler ultrasound, MCA and UA blood velocities and PI were determined three to five times at 3-5-week intervals over a gestational age range of 19-41 weeks. Polynomial regression lines for the 95th, 50th and 5th percentiles were calculated for the peak systolic velocity (PSV), time-averaged maximum velocity (TAMXV), PI and cerebroplacental ratio. Terms for calculating conditional reference intervals were established. Based on 566 observations our new longitudinal reference ranges for fetal middle cerebral PSV, TAMXV and PI provided terms for calculating conditional reference intervals (i.e. predicting expected 95% confidence limits based on a previous measurement), and correspondingly for the cerebroplacental ratio (n = 550). The reference ranges were at some variance with those of previous cross-sectional studies. The narrow 95% confidence limits for the 5(th) and 95(th) percentiles ensured reliable ranges. We have established longitudinal reference ranges appropriate for the serial assessment of MCA blood velocities and PI and cerebroplacental ratio. Particularly the terms for calculating conditional ranges based on a previous observation make this system more appropriate for longitudinal monitoring than are cross-sectional data.

Application of high‐intensity focused ultrasound for umbilical artery occlusion in a rabbit model

To investigate the application of high-intensity focused ultrasound (HIFU) for fetal umbilical artery blood flow occlusion in a rabbit model. A prototype HIFU transducer in combination with an imaging probe with Doppler capability was constructed. Using this transducer, HIFU was applied at 1.4, 2.75 or 5.5 kW/cm(2) through the maternal abdominal skin to the fetal intra-abdominal umbilical arteries of four time-mated Japanese White rabbits (11 fetuses) on gestational day 25. Courses of 5-s HIFU exposure were performed until cessation of umbilical blood flow and cardiac arrest were confirmed by Doppler ultrasonography. Fetal necropsy was performed and exposed lesions were assessed by microscopic histological analysis. The mean diameter of the fetal umbilical artery was 0.6 +/- 0.2 mm and the mean peak systolic velocity of arterial blood flow was 44.7 +/- 18.5 cm/s. When HIFU was applied at 5.5 kW/cm(2), blood flow was completely occluded within 15 courses. HIFU exposure brought about vacuolar degeneration and destruction of elastic fibers in the tunica media of the artery. HIFU can be used to occlude umbilical artery blood flow in fetal rabbits.

L'anesthésie comme cause de souffrance fœtale ?

Objective To describe the effects of anaesthetic techniques and agents on the risk of foetal distress during labour pain relief and anaesthesia for caesarean section. Study design Data on obstetric anaesthesia- and analgesia-induced fœtal distress were searched in Medline database using Mesh terms: foetal distress, anaesthesia, analgesia, labour, caesarean section, and umbilical artery pH. Trials published in English or French language were selected. Results Because of their haemodynamic effects, regional anaesthesia and analgesia, especially spinal anaesthesia for Caesarean section, could induce a decrease in umbilical artery pH (UApH). Moreover, intravenous ephedrine, especially when used in large doses can worsen the acidosis. Labour epidural analgesia is associated with a better acid-base balance than systemic analgesia. Experimental studies have demonstrated harmful effects of systemic opioids and hypnotic drugs on UApH and the foetal brain respectively. Clinical implications of these potentially detrimental effects remain to be determined. Conclusion All obstetric anaesthesia and analgesia techniques are associated with a theoretical risk of fetal distress, but given the fact that regional anaesthesia techniques are also associated with well-demonstrated benefits for the mother and the newborn, the latter remain the preferred choice in obstetric practice.

Normograms of resistance of fetal umbilical artery and middle cerebral artery

目的 了解本地区低危人群胎儿脐动脉(umbilical artery,UA)及大脑中动脉(middle cerebral artery,MCA)搏动指数(pulsatility index,PI)、阻力指数(resistance index,RI)、收缩期峰值流速与舒张末期流速比值(S/D)的正常参考值范围.方法 随机选取2218例孕20～40周的无合并症单胎孕妇,检测脐动脉(近胎儿侧)及大脑中动脉(中段)血流,记录PI、RI、S/D进行分析.结果 脐动脉的血流阻力随着胎龄的增加而降低,大脑中动脉的血流阻力在孕20～26周随孕周的增加而增高,孕26～28周时达高峰,28周以后随着孕周的增加而降低.结论 了解胎儿脐动脉及大脑中动脉血流阻力在不同孕周的变化规律,对判断及随访胎儿宫内缺氧状况, 协助临床做出正确的产科处理具有重要意义。

REGULATION OF MURINE MATERNAL AND FETAL HEMODYNAMIC FUNCTION BY HEME OXYGENASE.

Heme oxygenase (HO) regulates vascular tone and blood pressure through the production of the vasodilator carbon monoxide (CO), derived from the heme degradation pathway. During pregnancy, the maternal circulation undergoes significant adaptations to accommodate for the hemodynamic demands of the developing fetus. Our objective was to investigate the role of HO and its bioactive product, CO, on maternal and fetal hemodynamics during pregnancy. In this study, we hypothesized that CO regulates maternal vascular tone, affecting uteroplacental artery dilation and placental perfusion and subsequently influencing fetal hemodynamic function. Compared with age-matched nonpregnant (control) levels, baseline total body CO excretion (VeCO) rates and blood carboxyhemoglobin (COHb) levels in pregnant mice were significantly elevated as well as HO activity in maternal livers, spleens, and placentas. Placental HO activity was the highest at embryonic ages E12.5 through E15.5. The maternal abdominal aorta (AA) was significantly dilated in pregnant mice compared with nonpregnant controls (0.88 vs 0.68 mm, respectively). To elucidate the function of HO and the production of CO during pregnancy, mice at ≈E12.5 to E14.5 were administered tin mesoporphyrin (SnMP), a potent HO inhibitor, at a dose of 30 μmol/kg, IV. Maternal heart rate and AA diameter, as well as fetal heart rate and umbilical artery blood flow and diameter, were measured using microultrasonography. Two hours post-SnMP administration, VeCO levels were reduced by 20%, and HO activity was significantly inhibited in maternal livers and placentas (80% and 90%, respectively) but only slightly (10%) in the fetal liver. In addition, AA was significantly constricted by 33% (0.88-0.59 mm); this effect was not observed in SnMP-treated nonpregnant mice. Furthermore, maternal heart and respiratory rates were elevated. Umbilical artery blood flow and fetal heart rate increased 44% and 38%, respectively, but umbilical artery diameter did not change. We conclude that during pregnancy, elevated levels of CO are produced by increases in HO activity in the maternal liver and placenta and play an important role in maintaining maternal vascular tone and fetal hemodynamic function. This work was study was supported in part by the Mary L. Johnson and Christopher Hess Research Funds.

Anhydramnios associated with administration of trastuzumab and paclitaxel for metastatic breast cancer during pregnancy

A 38-year-old women in her second pregnancy presented with symptomatic metastatic spinal-cord compression 7 years after undergoing lumpectomy and axillary dissection for stage I primary breast cancer. Immunohistochemistry analysis of the tumour had shown that it was oestrogen-receptor negative, progesterone-receptor positive, and overexpressed ERBB2. The patient had received six cycles of cyclophosphamide, methotrexate, and fl uorouracil followed by radiotherapy and then tamoxifen, which she had taken for 5 years. 86 months after primary diagnosis the patient developed paresthesia and hypoesthesia of the left arm and pain in the cervical vertebrae. MRI showed diff use metastatic infi ltration of the corpus of the second cervical vertebra (fi gure 1) with spinal-cord compression. Additional lesions in the fourth thoracic vertebra and the left femur were also seen with bone scintigraphy, but no other signs of metastatic disease were identifi ed by clinical examination, chest radiograph, or abdominal ultrasound. At this time the patient was 17 weeks pregnant with normal fetal development. After counselling the patient decided to continue pregnancy and was started on hydromorphone hydrochloride. Palliative radiotherapy of 46 Gy given in 23 fractions was administered to the cervical vertebra, which resulted in clinically improved neurological symptoms and pain. Cervical radiotherapy was undertaken with lead shielding of the uterus to protect the fetus. At 25+6 weeks’ gestation the patient received trastuzumab (8 mg/kg loading dose) combined with 175 mg/m of paclitaxel, followed by another cycle at 28+5 weeks with the dose of trastuzumab reduced to 6 mg/kg and the dose of paclitaxel kept the same. Close fetal surveillance was undertaken. Between 26 weeks’ gestation and 32 weeks’ gestation, during two cycles of trastuzumab and paclitaxel, fetal abdominal circumference stopped increasing and the volume of amniotic fl uid decreased to almost anhydramnios (fi gure 2). The mother was of normal constitutional size with normal weight gain of 11 kg during pregnancy and no other risk factors for restriction of intrauterine growth. Tests for premature rupture of the membranes were negative. At 31+6 weeks the volume of both fetal kidneys was decreased below the fi fth percentile. Additionally, the urinary bladder was barely visible, suggesting reduced renal function, and doppler sonography showed increased resistance indices of both the renal arteries (fi gure 3). Doppler sonography of the fetal umbilical and maternal uterine arteries was normal, which suggested healthy placental function. Serial ultrasound measurements of femur length, biparietal diameter, and head circumference were all within normal limits. As a result of the evidence of fetal renal failure and cessation of abdominal growth, fetal lung maturation was induced with corticosteroids after two cycles of trastuzumab and paclitaxel, and a caesarean section was done at 32+1 weeks’ gestation. The male newborn infant weighed 1460 g (tenth percentile), had a body length of 39 cm, and had a head circumference of 29.5 cm. The pH value of the umbilical artery was 7.31. The placenta weighed 290 g and placental histology was normal. The newborn infant showed signs of bacterial sepsis with hypotension, transient renal failure, respiratory failure necessitating mechanical ventilation, and positive laboratory fi ndings (C-reactive protein 30 mg/dL). With antibiotic treatment blood pressure normalised after 2 days and mechanical ventilation was ended on day 6. Diuresis was adequate with serum creatinine slightly increased (1.6 mg/dL) until day 14. Ultrasonography of the fetal kidneys showed transient hyperechodensities in the renal parenchyma that resolved by day 28. These transient hyperechodensities are often noted in newborn infants with transient renal failure as a result of decreased renal perfusion. Echocardiography and cranial ultrasound examinations were normal. The infant was discharged at age 6 weeks weighing 2335 g and in healthy condition. Development at 12 weeks was normal. Lancet Oncol 2007; 8: 79–81

P13.20: Real time velocity profile of fetal umbilical arteries (FUA) by global acquisition and signal processing (GASP) software for multigate spectral Doppler analysis (MSDA)

P13.20: Real time velocity profile of fetal umbilical arteries (FUA) by global acquisition and signal processing (GASP) software for multigate spectral Doppler analysis (MSDA)