Modified myocardial performance index for evaluation of fetal cardiac function in pre-eclampsia

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1 Ultrasound Obstet Gynecol 2009; 33: Published online 11 December 2008 in Wiley InterScience ( DOI: /uog.6272 Modified myocardial performance index for evaluation of fetal cardiac function in pre-eclampsia O. API*, M. BALCIN EMEKSIZ*, M. API, V. UǦUREL* and O. UNAL* Departments of Obstetrics & Gynecology, *Dr Lutfi Kirdar Kartal Teaching and Research Hospital and Haseki Teaching and Research Hospital, Istanbul, Turkey KEYWORDS: Doppler; fetal cardiac function; modified myocardial performance index; pre-eclampsia ABSTRACT Objective To assess cardiac function by means of the modified myocardial performance index (Mod-MPI) in fetuses of pre-eclamptic mothers without intrauterine growth restriction and to compare this with values from normal controls. Methods A cross-sectional study was conducted including a total of 72 fetuses at between 26 and 40 weeks gestation. Forty fetuses of healthy mothers were assigned as the control group (Group I) while 15 fetuses of mildly pre-eclamptic mothers constituted Group II and 17 fetuses of severely pre-eclamptic mothers constituted Group III. Two-dimensional gray-scale and Doppler fetal echocardiography was used to exclude cardiac anomalies and calculate the Mod-MPI. Results The mean ± SD Mod-MPI values of Groups I, II and III were 0.43 ± 0.045, 0.44 ± and 0.44 ± 0.064, respectively (P = 0.680). The mean aortic peak systolic velocity (PSV), the mean mitral valve early ventricular filling (E-wave) and active atrial filling (A-wave) peak velocities were significantly lower in fetuses of severely pre-eclamptic mothers than in fetuses of mildly pre-eclamptic mothers and control fetuses. Conclusion The fetal global myocardial function assessed by Mod-MPI does not seem to change in mild or severe pre-eclampsia. The lower mitral E-wave and A-wave peak velocities and the lower aortic PSV seem to reflect the increased cardiac afterload against which the fetal heart has to work, rather than systolic or diastolic cardiac dysfunction, in the fetuses of severely pre-eclamptic mothers. Copyright 2008 ISUOG. Published by John Wiley & Sons, Ltd. INTRODUCTION The myocardial performance index (MPI) was first proposed by Tei et al. 1 for the evaluation of heart function in adults with dilated cardiomyopathy. The non-invasive, Doppler-derived MPI has been reported to be useful as a combined index of global myocardial function. The MPI is defined as the sum of isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) divided by ejection time (ET). Tsutsumi et al. 2 were the first to report using the MPI to assess fetal global myocardial function. Different researchers 3 8 then proposed the MPI as a potentially useful method of estimating fetal cardiac adaptive changes in complicated pregnancies such as growth-restricted fetuses, fetuses of diabetic mothers, fetuses with heart failure including hydropic fetuses, and fetuses with Rh sensitization. However, the reported reference MPI values for left fetal cardiac assessment show a wide variation 2,9,10. The wide variation in the normal reference values has been attributed to the lack of clear landmarks in the Doppler waveforms to calculate the time-periods. In order to overcome this problem, different modifications have been proposed by a number of authors Recently, a modification of myocardial performance index (Mod-MPI) based on Doppler echoes of the mitral valve (MV) and aortic valve (AV) clicks, which is associated with a lower variation and better inter- and intraobserver agreement than the MPI, has been described by Hernandez-Andrade et al. 13,14.Since the Mod-MPI has been very recently introduced to the literature, it has not been included in the evaluation of fetal cardiac function in the presence of pregnancy-associated complications. Pre-eclampsia, which affects about 2% of pregnancies, is a major cause of perinatal and maternal morbidity and mortality 15,16. Although the exact cause of preeclampsia remains unclear, many theories center on the problems of placental implantation and partial or complete failure of trophoblastic invasion Inadequate trophoblastic invasion of the maternal spiral arteries is thought to give rise to vascular resistance in the uteroplacental circulation 20,21. The increased vascular Correspondence to: Dr O. Api, Orhantepe Mah. Acelya Sok. No: 12/2 Postal code: Dragos, Kartal, Istanbul, Turkey ( olusapi506@hotmail.com, olusapi@gmail.com) Accepted: 10 July 2008 Copyright 2008 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER

2 52 Api et al. placental resistance may affect the fetal cardiac function by causing an increase in the fetal cardiac afterload. In a recent study it was reported that the MPI increased under pathological conditions, such as an increase in the cardiac afterload secondary to increased placental vascular resistance 7. Since the contractility of the heart is markedly affected by preload and afterload, we hypothesized that fetal cardiac function might be impaired in pre-eclamptic mothers. Cardiac dysfunction and mild myocardial damage have been reported in a recent paper 22 on the neonates of mildly pre-eclamptic mothers but there has been no study evaluating fetal cardiac function in pre-eclampsia. The MPI is a simple and useful method for evaluating fetal ventricular function. It is well known that fetal circulation is right-ventricle dominant and that fetal cardiac output redistributes in favor of the left ventricle in complicated pregnancies 23. Although the evaluation of fetal right ventricular function by MPI has been reported in the literature, most of the published data 2,7,9 13 have made use of the fetal left ventricular MPI. Furthermore, it has been proposed that left ventricular MPI could become a part of routine assessment of fetal well-being 11. Thus, we surmised that the assessment of left ventricular Mod- MPI could adequately evaluate fetal myocardial function in pre-eclamptic pregnancies. The purpose of the present study was to investigate fetal cardiac function in pre-eclamptic pregnancies and compare it with that in normal controls. METHODS A cross-sectional study was conducted including a total of 72 fetuses (32 fetuses of mothers with pre-eclampsia and 40 fetuses of mothers without pre-eclampsia) whose mothers presented to the high-risk pregnancy unit of the Dr Lutfi Kirdar Kartal Teaching and Research Hospital between July 2007 and January Informed consent was obtained from all the patients and the study was approved by the local ethics committee. Forty healthy pregnant women of gestational age 26 to 40 weeks were assigned as controls (Group I). All the fetuses were found to have growth appropriate for gestational age and had normal heart findings with normal sinus rhythm. A total of 32 fetuses were assigned to the pre-eclampsia group. Pre-eclampsia was defined as a pregnancy-specific syndrome occurring after midgestation and consisting of hypertension (systolic blood pressure 140 mmhg or diastolic blood pressure 90 mmhg in two recordings at least 6 h apart), accompanied by proteinuria of 300 mg in 24 h, or a 2+ reading on dipstick testing of midstream urine or a catheter specimen if no 24- h urine collection was available 24. The pre-eclamptic patients were divided into two subgroups 15 mothers with mild pre-eclampsia (Group II) and 17 mothers with severe pre-eclampsia (Group III) according to the severity of the disease as defined by the American College of Obstetricians and Gynecologists criteria 16. Severe pre-eclampsia was defined as systolic blood pressure 160 mmhg or diastolic blood pressure 110 mmhg on two occasions at least 6 h apart in a woman on bed rest, accompanied by proteinuria 5 g in 24 h or 3+ reading on dipstick testing of two random urine samples collected at least 4 h apart. Other features of severe pre-eclampsia include oliguria (less than 500 ml of urine in 24 h), cerebral or visual disturbances, pulmonary edema or cyanosis, epigastric or right upper quadrant pain, impaired liver function, thrombocytopenia, and intrauterine growth restriction (IUGR). Although IUGR is included in the diagnostic criteria of severe pre-eclampsia, we excluded any fetuses with IUGR from the study. IUGR was defined as an estimated fetal weight less than the 10 th percentile and reduced amniotic fluid volume 25,26. Other exclusion criteria were fetuses of pregestational or gestational diabetic mothers, fetuses with heart failure including hydropic fetuses, fetuses with Rh sensitization, fetuses of mothers treated with a tocolytic agent and multifetal pregnancies. For the ultrasound examinations, a Siemens Acuson Antares (Siemens Medical Solutions, Issaquah, WA, USA) ultrasound machine, equipped with a 5-MHz curvilinear transducer, was used. All the Doppler measurements were performed in each case by a single specially trained examiner (O. A.) in the absence of fetal body and respiratory movements and with the mother in voluntary suspended respiration. The mechanical and thermal indices never exceeded 1. None of the pre-eclamptic mothers was started on any antihypertensive medication or magnesium sulfate therapy before our examination. Initially, all the fetuses were evaluated for fetal growth and amniotic fluid assessment. Fetal biometric measurements included biparietal diameter, abdominal circumference and femur length, and fetal weight was estimated. Doppler measurements were obtained for the uterine arteries (UtA), umbilical artery (UA) and middle cerebral artery (MCA) by previously described methods Atleast three measurements were taken once a clear and consistent Doppler trace had been obtained, and the measurement taken from the clearest waveform was included in the final analysis. Two-dimensional fetal echocardiography was also used to exclude a structural cardiac anomaly. The Mod-MPI was calculated in the fetal left ventricle as originally described by Hernandez-Andrade et al. 13. A cross-sectional image of the fetal thorax at the level of the four-chamber view with an apical projection of the heart was obtained. By sweeping the ultrasound probe slightly in the apical direction, the origin of the aorta could be observed. The Doppler sample volume was opened to 3 mm and placed in the internal leaflet of the MV. In this location, owing to its closeness to the AV, the opening and closing AV clicks could be registered. The angle of insonation was maintained as close as possible to 0 and was always less than 30. To clearly identify the components of the Mod-MPI, the fastest velocity (15 cm/s) of the Doppler sweep was used, and the E/A waveform was always displayed as positive flow. The Doppler gain was lowered as far as

3 Cardiac function in pre-eclampsia 53 Figure 1 Apical four-chamber view of the fetal heart showing the components (ejection time, isovolumetric contraction time and isovolumetric relaxation time) of the modified myocardial performance index. The Doppler sample gate is positioned in the internal wall of the ascending aorta, close to the internal leaflet of the mitral valve and below the aortic valve. The Doppler waveform shows the opening and closing clicks of both valves. possible to clearly visualize the echoes corresponding to the opening and closing clicks of the two valves at the beginning and at the end of the E/A (mitral valve) and aortic waveforms. A high-pass wall filter was used to avoid slow blood movements. The time cursor was placed at the beginning of each Doppler click. The three time periods were estimated as follows: (1) ICT from the beginning of MV closure to AV opening; (2) ET from AV opening to closure; and (3) IRT from AV closure to MV opening (Figure 1). The Mod-MPI was calculated as: Mod-MPI = (ICT + IRT)/ET. Three consecutive recordings were made and the mean was considered as representative for each fetus. Other Doppler fetal echocardiography measurements included: (1) pulmonary arterial and aortic peak systolic velocities (PSV); (2) time to peak velocity (TPV), which was calculated as the time difference from the onset of the waveform to its peak velocity as an index of ventricular systolic function; and (3) E-wave (early ventricular filling) and A-wave (active atrial filling) peak velocities and the ratio between them (the E : A ratio) at the level of both atrioventricular valves as an index of ventricular diastolic function 31,32. Prior to the main research, we conducted a pilot study to analyze the inter- and intraobserver variability of the Mod-MPI assessments. We recruited 18 subjects with healthy pregnancies at weeks gestation and the first observer (O. A.) assessed ICT, IRT and ET measurements of each subject; then the second observer (M. B.), blinded to the first observer s measurements, assessed the same parameters of the same subject. All Mod-MPI values were calculated using the (ICT + IRT)/ET formula with computer assistance. Statistical reliability analysis was performed. Cronbach s alpha value based on standardized items was found to be The correlation coefficient (r) between measurements of the observers was Intraobserver reliability analysis for the first observer (O. A.), who would be the principal investigator in the main research, was also conducted and Mod-MPI measurements were performed on the same subjects at different times during the same gestational week, with blinding to the first measurements. Cronbach s alpha value based on standardized items was found to be The correlation coefficient (r) between first and second measurements of the same observer was This pilot study not only helped us to assess the reproducibility and validity of our measurements but also gave us the standard deviation and variance of the measurements needed to calculate the required sample size for our main study. The mean Mod-MPI of our pilot study was 0.44 and the standard deviation of all measurements taken together was around Assuming a power of 80% at a type I error of 0.05 and a standard deviation of 0.06, 23 subjects would be required in each arm to detect a difference of at least 0.05 between the Mod-MPI measurements of each group. Because of the nature and technical difficulties encountered in recruiting enough cases in each group, we included a total of 72 fetuses, 32 of which were of pre-eclamptic mothers and 40 of which were controls. As already mentioned, the preeclamptic pregnancies were divided into two subgroups (15 fetuses of mothers with mild pre-eclampsia and 17 fetuses of mothers with severe pre-eclampsia) according to the severity of the disease. With this new sample volume unequally distributed accross the groups, we found that the power of our study was reduced from 80% to 77% at a type I error of For the data analysis, the SPSS 13.0 (SPSS Inc., Chicago, IL, USA) statistical package was used. Normal distribution of the continuous variables was assessed with the Kolmogorov Smirnov test. Comparisons of the variables among the three groups were performed by means of the one-way ANOVA test when the distribution of data was similar to the Gaussian form and by means of the the Kruskal Wallis test when the distribution differed significantly from Gaussian form. The Tukey s HSD posthoc test was used in order to identify the source of difference when a statistically significant difference was found among the three groups. Comparisons between the control and the two study groups were performed using the Mann Whitney U-test. Correlations between Mod-MPI and gestational age were assessed using Pearson s correlation coefficient. P < 0.05 was considered statistically significant. RESULTS The study and control groups were comparable in terms of the demographic parameters of maternal age, gravidity, parity and gestational age (Table 1). Our study groups were not completely comparable in gestational age, although no statistically significant difference was detected (Table 1). Ertan et al. 33 have

4 54 Api et al. Table 1 Demographic characteristics of the study groups Maternal age (years) 26 (18 36) 26 (21 38) 29 (20 38) 0.056* Gravidity 2 (1 6) 2 (1 5) 2 (1 6) 0.856* Parity 0.5 (0 4) 1 (0 3) 1 (0 4) 0.870* Gestational age at time of study (weeks) 34 (28 40) 37 (28 40) 35 (26 40) Data are presented as median (range). Group I, controls; Group II, mild pre-eclampsia group; Group III, severe pre-eclampsia group. *Kruskal Wallis test. One-way ANOVA. Table 2 Comparison of pulsatility indices (PI) of the uterine arteries (UtA), umbilical artery (UA) and middle cerebral artery (MCA) among the study groups Mean UtA-PI 0.89 ± ± ± 0.43* UA-PI 0.97 ± ± ± MCA-PI 1.79 ± ± ± Adjusted MCA-PI 1.70 ± ± ± Data are presented as mean ± SD. All P-values relate to Kruskal Wallis tests. Group I, controls; Group II, mild pre-eclampsia group; Group III, severe pre-eclampsia group. *n = 15. n = 16. Normalized with reference to values at 37 weeks gestation. Table 3 Comparison of heart rate, pulsed Doppler-derived time intervals and modified myocardial performance index (Mod-MPI) among the study groups Heart rate (bpm) ± ± ± * ICT (s) ± ± ± * IRT (s) ± ± ± ET (s) ± ± ± Mod-MPI 0.43 ± ± ± Data are presented as mean ± SD. Group I, controls; Group II, mild pre-eclampsia group; Group III, severe pre-eclampsia group. *Kruskal Wallis test. One-way ANOVA. ET, ejection time; ICT, isovolumetric contraction time; IRT, isovolumetric relaxation time. produced nomograms of Doppler parameters, reporting that MCA pulsatility index (PI) values decline between 34 and 37 weeks of gestation, but that UA-PI and UtA-PI do not change. Therefore, the MCA Doppler data were normalized with reference to the 37 th gestational week for all the groups. Doppler measurements of the UtA were obtained in 97.2% (70/72) of cases. When we compared the mean UtA-PIs among the groups, we detected a statistically significant difference (Table 2). The mean UtA-PI was significantly higher in Group III when compared to Group I and Group II (Table 2). Doppler measurements of UA were obtained in all fetuses. No significant difference was found in the UA-PI among the three groups (Table 2). Doppler measurements of the MCA were obtained in 98.6% (71/72) of fetuses. We found a statistically significant difference in the MCA-PI among the groups (Table 2). Upon posthoc analysis, the mean MCA-PI values were found to be significantly lower in Group III when compared to Group I and Group II. The ICT, IRT and ET were easily obtained in all fetuses, and the Mod-MPI was calculated from the these data (see above). No statistically significant difference was found in ICT, IRT, ET or Mod-MPI measurements between the three groups (Table 3). The mean heart rates were also similar among the groups. No statistically significant correlation was detected between the Mod-MPI measurements and gestational age (Group I: r = 0.059, P = 0.719; Group II: r = 0.142, P = 0.613; Group III: r = 0.049, P = 0.853; overall: r = 0.032, P = 0.788) (Figure 2). Pulmonary arterial PSV and aortic PSV, tricuspid valve E-wave and A-wave peak velocities, the E : A ratio and mitral valve E-wave and A-wave peak velocities were easily obtained in all the fetuses, whereas pulmonary arterial TPV and aortic TPV could be obtained in 97.2% (70/72) of fetuses. The mean aortic PSV of Group III was found to be statistically significantly lower than the mean aortic PSV of Group I and of Group II (Table 4), but no significant difference was found between the other indices of ventricular systolic function (pulmonary arterial PSV and TPV and aortic TPV) among the groups. When we compared the groups in terms of ventricular diastolic function, a statistically significant difference was found in the mean MV E-wave peak velocity and the mean

5 Cardiac function in pre-eclampsia 55 Modified myocardial performance index Gestational age (weeks) Figure 2 Correlation plot of modified myocardial performance index (Mod-MPI) values against completed weeks of gestation in the study population (n = 72), showing the controls ( ) and mild pre-eclamptic ( ) and severe pre-eclamptic ( ) cases. No statistically significant correlation was detected between the Mod-MPI measurements and gestational age (Group I: r = 0.059, P = 0.719; Group II: r = 0.142, P = 0.613; Group III: r = 0.049, P = 0.853; overall: r = 0.032, P = 0.788). Linear regression lines are given for control ( ), mildly pre-eclamptic ( ) and severely pre-eclamptic (...) groups. MV A-wave peak velocity among the groups (Table 5). The mean mitral valve E-wave peak velocity and A-wave velocity were found to be significantly lower in Group III than in Groups I and II; however, there was no difference between Groups I and II. When we compared the groups in terms of other indices of ventricular diastolic function (tricuspid valve E-wave and A-wave peak velocities, the tricuspid valve E : A ratio and mitral valve E : A ratio), no statistically significant difference was found. DISCUSSION Numerous fetal and pregnancy-associated conditions have a considerable impact on fetal cardiac function. In a recent study 7, it was reported that myocardial performance might be impaired in recipient fetuses with twin twin transfusion syndrome, most probably owing to an increase in the cardiac afterload secondary to hypervolemia or increased placental vascular resistance. Pre-eclampsia is a condition that may also lead to increased cardiac afterload owing to placental vascular resistance. If this is confirmed, it would be reasonable to expect that these fetuses may become vulnerable to cardiovascular diseases later in life. Another recent study described cardiac dysfunction detected upon echocardiography and mild myocardial damage in the neonates of mildly preeclamptic mothers 22. Additionally, intrauterine exposure to pre-eclampsia has been shown to be associated with untoward effects on biochemical risk factor markers for cardiovascular disease 34. Therefore, it has been suggested that the cardiovascular risk of newborns of pre-eclamptic mothers may begin in utero. In the present study the Mod-MPI values were 0.43, 0.44 and 0.44 in our control, mild pre-eclampsia and severe pre-eclampsia groups, respectively. The currently available literature contains a wide variation in reported reference MPI values for left fetal cardiac Table 4 Comparison of ventricular systolic function indices among the study groups Ao PSV (cm/s) ± ± ± Ao TPV (s) ± ± ± PA PSV (cm/s) ± ± ± PA TPV (s) ± ± ± Data are presented as mean ± SD. Group I, controls; Group II, mild pre-eclampsia group; Group III, severe pre-eclampsia group. All P-values relate to Kruskal Wallis tests. Ao PSV, aortic peak systolic velocity; Ao TPV, time to aortic peak velocity; PA PSV, pulmonary artery peak systolic velocity; PA TPV, time to pulmonary artery peak velocity. Table 5 Comparison of ventricular diastolic function indices among the study groups MV-E PV (cm/s) ± ± ± * MV-A PV (cm/s) ± ± ± * MV E : A 0.73 ± ± ± * TV-E PV (cm/s) ± ± ± TV-A PV (cm/s) ± ± ± TV E : A 0.74 ± ± ± * Data are presented as mean ± SD. Group I, controls; Group II, mild pre-eclampsia group; Group III, severe pre-eclampsia group. *One-way ANOVA. Kruskal Wallis test. MV-A PV, mitral valve A-wave peak velocity; MV-E PV, mitral valve E-wave peak velocity; MV E : A, mitral valve E : A wave ratio; TV-A PV, tricuspid valve A-wave peak velocity; TV-E PV, tricuspid valve E-wave peak velocity; TV E : A, tricuspid valve E : A wave ratio.

6 56 Api et al. assessment. Falkensammer et al. 9 reported a mean left fetal cardiac MPI of 0.41 that remained constant throughout pregnancy. Eidem et al. 10 reported a normal left MPI value of 0.35 and Friedman et al. 11 reported a mean MPI of 0.53 for normal fetuses with no changes during gestation. Conversely, Tsutsumi et al. 2 described a gradual reduction in the left MPI with advancing gestation, with normal values above 0.6. Hernandez- Andrade et al. 14, whose technique was used in our study, reported that the Mod-MPI slightly increases from 0.35 at 19 weeks to 0.37 at 39 weeks of gestation. The mean ICT, IRT, ET and Mod-MPI values of our study groups were all within the normal ranges (50 th 95 th percentile) as described by Hernandez-Andrade et al. 14, although they were closer to the 95 th percentile. Our reliability analysis prior to the main study showed good results, supporting the accuracy of the values that we obtained. To our knowledge, our study is the first to evaluate the clinical application of Mod-MPI in fetuses of preeclamptic mothers. There seems to be a need for studies evaluating the clinical application of this new method of fetal cardiac assessment, as only a few trials using the Mod-MPI have been published 13,14. Although the MPI has been reported to increase under pathological conditions such as hypervolemia and an increase in the cardiac afterload 7, and pre-eclampsia is a condition in which the fetal circulation is affected by increased cardiac afterload due to placental vascular resistance, we could not demonstrate any increase in the Mod-MPI in fetuses of pre-eclamptic mothers. This may be owing to the fact that none of the fetuses in our study had severe co-existing complications that would have had an additional impact on fetal cardiac function, such as severe placental insufficiency, IUGR or oligohydramnios. It has been shown that fetal global myocardial function and ventricular compliance were not changed even in conditions with significant myocardial cell damage 5,11, and neonatal troponin T levels a marker of myocardial cell damage were found to be significantly increased in pregnancies complicated by maternal hypertensive disorder only in the presence of abnormal umbilical venous return 35. Therefore, it is suggested that preeclampsia without IUGR does not have a major impact on fetal global myocardial performance. However, the neonates of mildly pre-eclamptic mothers were shown to have higher cardiac troponin T levels, lower mitral A values and higher mitral E : A values than the neonates of non-pre-eclamptic mothers 22. This finding was thought to be associated with mild myocardial damage in the neonates of pre-eclamptic mothers. Since we did not investigate any biochemical marker of myocardial damage in our study, it is not possible to comment on the presence of myocardial injury associated with pre-eclampsia. However, we found lower mean mitral E values and A values with lower aortic PSV in the fetuses of severely preeclamptic mothers than the fetuses of mildly pre-eclamptic and healthy mothers, although the E : A ratio never fell below the 5 th percentile in any of the groups. These echocardiographic findings in the fetuses of severely preeclamptic mothers seem to reflect the increased cardiac afterload, rather than any systolic or diastolic cardiac dysfunction. Since the aim of our research was to study the effects of pre-eclampsia on the fetal circulation, we also investigated the blood flow in the uterine, umbilical and middle cerebral arteries. The mean UtA-PI was significantly higher in the severely pre-eclamptic mothers when compared to the mildly pre-eclamptic and healthy mothers. The mean UA Doppler indices were within the normal ranges in all our groups and no difference was detected among the groups. Interestingly, the blood flow in the MCA increased in the fetuses of severely preeclamptic mothers and remained unchanged in fetuses of mildly pre-eclamptic mothers when compared with the fetuses of healthy mothers. It is well known that abnormal UA Doppler indices precede decreases in cerebroplacental ratio and MCA-PI 36. The mean MCA-PI was not more than 2 SD below the mean for gestational age in fetuses of severely pre-eclamptic mothers, meaning that there was no evidence of brain sparing in these fetuses. Previously, it has been shown that in growth-restricted fetuses with more severe placental insufficiency, right ventricular cardiac output was significantly less than in fetuses with relatively mild placental insufficiency 23.Furthermore,in a recent study 5, it has been suggested that fetuses with increased right ventricular afterload shift their cardiac output from the right to the left ventricle. Therefore, it is speculated that this finding of increased cerebral blood flow despite normal UA blood flow in the fetuses of severely pre-eclamptic mothers could be a reflection of the redistribution of fetal cardiac output in favor of the left ventricle due to increased cardiac afterload secondary to increased placental vascular resistance. We conclude that fetal global myocardial function as assessed by Mod-MPI does not seem to change in mild or severe pre-eclampsia. 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