Fetal and uteroplacental blood flow in prolonged pregnancies. A clinical study.

In a prospective study during 1 year, 102 women with prolonged pregnancies (more than 294 completed gestational days) were followed with serial pulsed Doppler blood flow examinations every 2nd day, either to spontaneous onset of labor (n = 82) or to induction of labor due to subsequently occurring complications (n = 20). Mean aortic blood velocity did not change significantly with gestational age beyond 294 days either in fetuses with normal outcome or in fetuses that developed asphyxia at birth. The flow velocity waveforms in the descending aorta, the umbilical artery, the common carotid artery and the uterine artery did not change significantly compared to the values at term. Abnormal flow velocity waveforms in the fetal descending aorta, umbilical artery or uterine artery had no significant relationship to fetal asphyxia. Absence of diastolic flow velocities was not found in any of the vessels examined, indicating that the fetuses did not suffer from chronic hypoxia in utero and that aging of the placenta did not alter fetal and uteroplacental blood flow. Notching of the aortic flow velocity waveform was a common finding among prolonged pregnancies. The hemodynamic implications and consequences of this phenomenon are discussed.     

First-trimester uteroplacental and fetal blood flow velocity waveforms in normally developing fetuses: a longitudinal study.

Our objectives were to obtain a complete overview of uteroplacental and fetal hemodynamics early in pregnancy and to record flow velocity waveforms in the vitelline artery using color Doppler equipment. Flow velocity waveforms were recorded in 18 uneventful pregnancies between 6 and 16 weeks of gestation. Doppler recordings were made of the left and right uterine and spiral arteries from 6 weeks of gestation onwards. Recordings of c the umbilical artery, fetal aorta and fetal cerebral arteries started in weeks 7, 8 and 9, respectively. Where possible, the vitelline arteries were also recorded. The resistance and pulsatility indices and 95% confidence intervals for predictions were calculated.For the uterine and spiral arteries, characteristics of the waveforms were assessed. The resistance index of both uterine and spiral arteries gradually decreased with advancing pregnancy. For the umbilical artery, aorta and cerebral artery, the earliest possible Doppler recordings and characteristics of the waveforms were established. The pulsatility index of the umbilical arteries and fetal aorta showed a sharp decrease towards the 16th week. The pulsatility index of the fetal cerebral artery showed only a mild decrease towards week 16. In a longitudinal analysis, there were significant changes of the resistance and pulsatility indices for each patient. In the vitelline artery, recordings were possible in eight out of 18 fetuses, and only in weeks 7 and 8 of gestation. The pulsatility index showed a wide range and was not dependent on menstrual age.Knowledge of the normal flow velocity waveforms in the maternal uteroplacental and fetal circulations early in pregnancy may lead to a better understanding of physiological mechanisms.     

Doppler flow velocity waveforms in fetal surveillance of twins: a prospective longitudinal study.

In 37 consecutive twin pregnancies, monthly Doppler sonographic measurements were made of blood flow velocity waveforms of the internal carotid and umbilical artery of each fetus. A total of 197 Doppler studies were performed. Of the 74 infants, 23 were small for gestational age (SGA). Thirty-five of the SGA Doppler studies were abnormal, giving an overall sensitivity for predicting SGA fetus of 58% and a positive predictive value of 71%. These data are not as sensitive and specific as our earlier data; however, Doppler criteria preceded sonographic diagnosis of SGA by a mean interval of 3.7 weeks and demonstrated better sensitivity and specificity. A combination of these parameters improves sensitivity to 84%. We conclude that Doppler velocimetry complements real-time ultrasonography for the early diagnosis of abnormal growth in twin pregnancies.     

Doppler studies of the uteroplacental circulation in pregnancies complicated by diabetes.

The aim of this study was to evaluate the uteroplacental side of the circulation in pregnancies complicated by diabetes. A total of 54 women with pregnancies complicated by diabetes underwent uterine and umbilical artery Doppler studies. Uterine Doppler velocity waveforms were not obtained in two women. The prevalence of abnormal uterine artery velocity waveforms was much higher than in a non-diabetic population (15.4% vs. 2%, p < 0.001). Those eight women with abnormal uterine Doppler studies had a statistically higher incidence of poor glycemic control, chronic hypertension, polyhydramnios, vasculopathy, pre-eclampsia, Cesarean births for fetal distress and newborns with respiratory distress syndrome. In this group of patients, the umbilical circulation was not considered to be a contributing factor in the development of problems.     

Uteroplacental circulation in growth retardation--experiences with the clinical use of continuous-wave Doppler]

Doppler ultrasound measurement of blood flow velocity represents a non-invasive method of studying uteroplacental and feto-placental haemodynamics. Using a continuous-wave Doppler device, the blood flow velocity was examined in the uterine and arcuate arteries, as well as in the umbilical artery in 81 patients demonstrating fetal growth retardation. An increase in vessel resistance was found in the uterine and arcuate arteries in most of the patients. In addition, patients with fetal retardation showed a significantly higher rate of diastolic notching and incomplete registration of uterine and arcuate wave forms, especially in pregnancies complicated by hypertension. The implementation of the continuous-wave technique as a simple Doppler system allows differential evaluation of placental function and provides information on the nutritional supply to the fetus.     

Splenic artery Doppler in the prediction of the small-for-gestational age infant.

OBJECTIVES: We hypothesized that, as with other areas of the peripheral circulation, fetal splenic artery blood flow undergoes changes in small-for-gestational age (SGA) fetuses due to a redistribution of cardiac output, and that the Doppler peak systolic velocity (PSV) reflects such changes and thus may be used to predict fetuses being SGA. METHODS: Splenic artery Doppler PSV, end-diastolic velocity (EDV), resistance index (RI) and umbilical artery RI were measured prospectively in fetuses at risk for being SGA at birth. Normal reference data were generated from appropriately grown fetuses delivering at > or = 37 weeks without complications, and SGA was defined as birth weight < 10th percentile. The Doppler indices were expressed as multiples of the normal median (MoM) for gestational age. Using receiver operating characteristic curves, optimal Doppler thresholds for the detection of SGA cases were determined and the areas under the curves calculated. The analysis was limited to singleton pregnancies delivered within 2 weeks of the last Doppler examination. RESULTS: There were 88 study patients of which 60 had SGA babies. The mean gestational age at Doppler examination was 31.4 weeks with a mean interval of 5.6 days from Doppler to delivery. The splenic artery PSV was lower in SGA, compared to normal cases: mean PSV (MoM), 0.93 vs. 1.09, respectively (P = 0.0001). The sensitivity, specificity and area under the curve were 70.0%, 72% and 0.734, respectively (P < 0.003), for the PSV in the prediction of delivery of a SGA fetus. For the splenic artery RI, values were 70%, 46% and 0.539, respectively (not significantly different), and for umbilical artery RI these were 70%, 61% and 0.689, respectively (P < 0.01). Splenic artery EDV was significantly reduced in SGA vs. normally grown fetuses (0.924 MoM vs. 1.145 MoM, P = 0.007). CONCLUSIONS: Fetal splenic artery PSV decreases in SGA infants, and is a strong predictor of the delivery of a SGA infant. It appears to be superior to the standard Doppler index, the RI, in predicting this outcome.     

Assessment of fetal heart rate variability and velocity variability by Doppler velocimetry of the descending aorta at 10-20 weeks of gestation.

OBJECTIVES: Determination of gestational age-related modulations in fetal heart rate and descending aorta blood flow velocity in the early human fetus and comparison of aortic variability data with data obtained from the umbilical artery. It is hypothesized that these modulations present in the umbilical artery also occur in the descending aorta. METHODS: Doppler studies of descending aorta velocity waveforms were performed at 10-20 weeks in 55 normal pregnant women. In 24 of the 55 women, Doppler recordings from both the descending aorta and the umbilical artery were collected. Absolute values and variability of fetal heart rate, peak systolic and time-averaged velocities were determined from flow velocity waveforms of at least 18 s in duration. RESULTS: From 10 to 20 weeks of gestation, the descending aorta peak systolic and time-averaged velocities increased, whereas the fetal heart rate decreased. The descending aorta peak systolic variability also increased. However, the time-averaged velocity variability and fetal heart rate variability remained constant during the study period. In the subset of 24 women, the fetal heart rate variability and velocity variability data from the descending aorta and umbilical artery were not significantly different. CONCLUSIONS: Reproducible fetal heart rate and velocity variability data can be derived from the descending aorta and umbilical artery. The increase in heart rate variability observed in the umbilical artery was not seen in recordings obtained from the descending aorta. Different fetal activity states may be the underlying mechanism for these heart rate variability discrepancies.     

Uterine and fetal cerebral Doppler predict the outcome of third-trimester small-for-gestational age fetuses with normal umbilical artery Doppler.

OBJECTIVE: To assess the value of different admission tests in predicting the outcome of small-for-gestational age (SGA) fetuses with normal Doppler waveforms in the umbilical artery. METHODS: Criteria for admission into this retrospective study included: singleton pregnancy with a birth weight < 10th centile; absence of severe maternal complications; no evidence of fetal anomalies on the sonogram; normal umbilical artery Doppler; and availability of complete follow-up. At the first antenatal sonogram classifying the fetus as SGA, Doppler analysis of the uterine and middle cerebral arteries was performed and amniotic fluid volume was assessed. Outcome variables included adverse perinatal outcome (perinatal death, severe morbidity) and emergency Cesarean section for fetal distress. RESULTS: Two hundred and thirty-one pregnancies were included in the study. The mean +/- standard deviation birth weight and gestational age at delivery were 2222 +/- 502 g and 37.3 +/- 2.9 weeks, respectively. In 37 cases (16%), an emergency Cesarean section was performed. There was one intrauterine death and three fetuses delivered by emergency Cesarean section developed severe morbidity. Logistic regression demonstrated that abnormal velocimetry of the uterine arteries and fetal middle cerebral artery were independently correlated with the occurrence of Cesarean section. CONCLUSIONS: SGA fetuses with normal umbilical artery Doppler waveforms and abnormal uterine arteries and fetal middle cerebral artery waveforms have an increased risk of developing distress and being delivered by emergency Cesarean section. Particularly when both uterine and fetal cerebral waveforms are altered at the same time, the risk is exceedingly high (86%) and delivery as soon as fetal maturity is achieved seems advisable. On the other hand, when both vessels have normal waveforms, the chances of fetal distress are small (4%) and expectant management is the most reasonable choice.     

Customized fetal weight limits for antenatal detection of fetal growth restriction.

OBJECTIVE: To define cut-off limits for individually adjustable fetal weight standards for the detection of intrauterine growth restriction. DESIGN: Retrospective study, with the outcome measures small-for-gestational age (SGA) birth weight, operative delivery for fetal distress, umbilical artery pH < 7.15, and admission to the neonatal intensive care unit. SUBJECTS AND METHODS: Two hundred and fifteen women considered to be at increased risk of uteroplacental insufficiency were recruited to a study of serial ultrasound scans. Fetal weights were derived using standard formulae and, retrospectively, weight percentiles were calculated after individual adjustment for maternal height, weight in early pregnancy, ethnic group, parity and fetal sex. INTRODUCTION: One or more antenatal scans indicative of fetal weight below the 10th customized percentile were predictive for a SGA neonate at birth (P < 0.001), operative delivery for fetal distress (P < 0.01) and admission to neonatal intensive care (P < 0.01) but not for a low umbilical artery pH (P = 0.6). Receiver-operator curves showed the optimal customized fetal weight percentile limit for predicting an SGA neonate to be the 18th percentile (sensitivity 83%, specificity 79%, positive predictive value 63% and negative predictive value 92%). For the prediction of operative delivery for fetal distress and admission to neonatal intensive care, the optional customized cut-off value was the 8th percentile. CONCLUSIONS: The assessment of fetal weight using ultrasound and an individually-adjusted standard is predictive of growth restriction and perinatal events associated with hypoxia or diminished reserve. The optimal cut-off value for predicting operative delivery for fetal distress or admission to the neonatal intensive care unit suggests that the 10th customized percentile is a good limit for clinical use.     

Systemic assessment of fetal hemodynamics by Doppler ultrasound

The aim of our study was to investigate the parameters of fetal circulation of normal pregnancies and their relationship to fetal cardiac output. We performed a cross-sectional study of 315 normal singleton pregnancies between 20 and 40 weeks' gestation without fetal chromosomal or structural malformations. After follow-up to delivery, 212 patients who fit all the criteria were enrolled for final analysis. Blood flow velocity waveforms were obtained from the tricuspid and mitral ventricular inflow, ascending aorta (AAO), pulmonary artery (PA), middle cerebral artery (MCA), renal artery (RA), umbilical artery (UA), descending aorta (DAO), inferior vena cava (IVC) and ductus venosus (DV) using duplex (real-time Doppler) ultrasound (US) scanner. The peak velocity of DV, AAO, PA and MCA were also obtained. At the intracardiac level, the ratio of peak flow velocity of E wave to peak flow velocity of A wave (E:A ratio) of mitral valve (MV) increased more rapidly than tricuspid valve (TV) E:A ratio. For the great vessels, aortic peak velocity remained higher than the pulmonary peak velocity with advancing gestation. The cardiac output closely correlated to the cardiac compliance and flow resistance indices at arterial and venous level. The acceleration time in the fetal arteries increased with advancing gestation in AAO, PA, MCA and DAO, but it decreased in RA and kept constant in UA. In addition, the acceleration time of UA was unrelated to cardiac output. The changes of the fetal intracardiac, arterial and venous impedances were remarkable through the gestation and related to cardiac output. Fetal cardiac output correlated well with the changes of arterial resistance, except with the DAO. The ventricular compliance increased with advancing gestation, especially in the left side, and was highly related to the change of cardiac output. The acceleration time in major arteries positively correlated with the gestational age and cardiac output, except in UA and RA; this indicates the difference of the changes of mean arterial pressure in uteroplacental circulation, fetal organs and great vessels. In conclusion, the fetal cardiac output correlated well with the ventricular compliance and was influenced by both hemodynamic changes in peripheral resistance and mean arterial pressure.     

Hemodynamic changes in growth retarded fetuses during maternal oxygen administration as predictors of fetal outcome

The changes in fetal hemodynamics during maternal administration of 60% humidified oxygen were assessed by Doppler ultrasonography in 15 growth retarded fetuses characterized by abnormal blood flow velocity waveforms. During oxygen treatment, nine fetuses exhibited temporary hemodynamic modifications as expressed by a recovery toward the normal range of vascular impedance in the descending aorta and internal carotid artery, whereas no changes were found in the remaining six fetuses. In this latter group, a rapid deterioration of fetal condition occurred and all the fetuses were delivered by emergency cesarean section within 9 days from the Doppler examination. The absence of recovery of vascular resistance during acute maternal oxygen administration seems therefore to be a useful marker of imminent acute distress in fetuses with growth retardation secondary to chronic hypoxia.     

Fetal arterial Doppler studies in twin-twin transfusion syndrome.

This cross-sectional study investigates the circulatory profile of the donor and recipient fetuses in pregnancies with twin-twin transfusion syndrome manifested by acute polyhydramnios during the second trimester of pregnancy. Doppler investigations of the umbilical arteries and of the fetal descending thoracic aortas and middle cerebral arteries were performed in both fetuses of 27 pregnancies with twin-twin transfusion syndrome at 18 to 25 (mean, 21.7) weeks' gestation. Significant differences from normal values were increased umbilical artery pulsatility index and decreased aortic mean velocity in both donor and recipient fetuses, decreased middle cerebral artery pulsatility index in recipients and decreased middle cerebral artery mean velocity in donors. Increased umbilical artery pulsatility index in some donor and recipient fetuses may be the consequence of abnormal placental development and polyhydramnios-related compression, respectively. Doppler findings in the fetal circulation are compatible with hypovolemia in the donor and hypervolemia with congestive heart failure in the recipient.     

Ultrasonic measurement of fetal blood velocity wave form as a secondary diagnostic test in screening for intrauterine growth retardation

Based on routine fetometry screening at 32 weeks of gestation, 80 out of 3226 singleton pregnancies were suspected of intrauterine growth retardation (IUGR) and 72 of them were subjected to repeated fetal blood flow measurements by Doppler ultrasound for evaluation of the fetal condition. The maximum blood velocity wave form recorded from the fetal descending aorta and umbilical artery was classified as normal or abnormal depending on the presence or absence of positive end-diastolic blood flow. Compared to the pregnancies with normal fetal blood flow, the group of 30 pregnancies with abnormal blood flow patterns had significantly more pregnancy complications and more operative deliveries for fetal distress. In the latter group, all newborns but one were small-for-gestational age and had low 1-min Apgar scores more frequently. Fetal blood flow measurements have a good capacity for predicting unfavorable fetal outcomes and can be recommended for clinical use. The combination of ultrasound screening and Doppler blood flow measurement has reduced the number of pregnancies requiring intensive surveillance.     

Uterine artery score and perinatal outcome.

OBJECTIVE: To evaluate a modified uterine artery score based on the pulsatility index and presence or absence of notching in the Doppler velocity waveform recorded from both uterine arteries in relation to the perinatal outcome. METHODS: A retrospective analysis was performed in 741 third-trimester high-risk pregnancies. The uterine artery score was constructed assigning one point to each abnormal parameter-high pulsatility index and presence of notch-thus ranging from 0 (normal findings in both uterine arteries) to 4 (notch and high pulsatility index in both uterine arteries). In a subgroup with lateral placenta (n = 359), two definitions of abnormal pulsatility index were compared. In the uniform uterine artery score, a pulsatility index > 1.20 in both uterine arteries was considered abnormal, disregarding the placental location; in the subgroup with lateral placenta, the high pulsatility index was defined as > 1.00 on the placental side and > 1.40 on the non-placental side. RESULTS: Receiver-operating characteristic curves did not reveal any difference in the diagnostic capacity between the group with a uniform uterine artery score and the subgroup with lateral placenta (P = 0.54). In the total material, the odds ratios and linear regression analysis showed an increased risk for an adverse perinatal outcome with increasing uterine artery score (P < 0.01). At a uterine artery score > 2, there was a significantly increased risk for operative delivery for fetal distress, neonatal intensive care unit admission, 5-min Apgar score < 7, preterm delivery and delivery of a small-for-gestational age fetus. CONCLUSION: In high-risk third-trimester pregnancies, Doppler velocity waveforms of the uterine arteries can be evaluated using the uterine artery score disregarding the placental location. The uterine artery score possesses a high predictive value regarding adverse perinatal outcome.     

Screening for pre-eclampsia and fetal growth restriction in twin pregnancies at 23 weeks of gestation by transvaginal uterine artery Doppler.

OBJECTIVE: To assess the value of transvaginal uterine artery Doppler at 23 weeks of gestation in predicting the development of adverse perinatal outcomes in twin pregnancies. PATIENTS AND METHODS: Women with twin pregnancies attending for routine ultrasound examination at 23 weeks in any one of seven hospitals underwent Doppler assessment of the uterine arteries. The right and left uterine arteries were identified using color flow mapping and velocity waveforms were obtained using pulsed Doppler. The mean pulsatility index (PI) of the two arteries was determined and the presence of uterine artery notching noted. Results were compared between monochorionic and dichorionic twins, and with our previously reported data from singleton pregnancies. Screening characteristics in the prediction of pre-eclampsia, fetal growth restriction (FGR), placental abruption, fetal death and early preterm delivery were calculated. RESULTS: Uterine artery Doppler at 22-24 weeks of gestation was performed in 360 twin pregnancies, including 324 dichorionic and 36 monochorionic diamniotic twins. Complete outcome data were available in 351 (97.5%). The mean uterine artery PI did not change significantly with gestation and there was no significant difference in mean PI between the dichorionic and monochorionic groups. However, the mean PI was significantly lower in twin pregnancies than in singletons. The pregnancy was complicated by pre-eclampsia in 6.0% of cases, FGR below the 5th centile of both twins in 8.8%, abruption in 0.9%, intrauterine fetal death in 1.7% and early preterm delivery at less than 32 completed weeks of gestation in 5.7% of cases. The respective sensitivities of uterine artery mean PI above the 95th centile for these complications were 33.3%, 9.7%, 66.6%, 33.3% and 18.6%. CONCLUSIONS: In twin pregnancies PI in the uterine arteries is lower than that in singleton pregnancies, but there is no significant difference between dichorionic and monochorionic twins. Doppler assessment of the uterine arteries at 23 weeks identifies a large proportion of twin pregnancies destined to develop adverse outcomes related to uteroplacental insufficiency.     

Second-trimester uterine artery Doppler and spontaneous preterm delivery.

OBJECTIVE: To assess the relationship between second-trimester uterine artery (UtA) Doppler measurements and spontaneous preterm delivery. METHODS: This was a retrospective analysis of UtA Doppler findings at 18-23 weeks' gestation in 234 singleton pregnancies with spontaneous preterm labor and 5472 pregnancies delivered at term. Cases with fetal chromosomal or structural abnormalities, pre-eclampsia, small-for-gestational-age (SGA) fetuses, concurrent maternal disease, cervical cerclage or history of cone biopsy were excluded. RESULTS: UtA mean resistance index (RI) and number of protodiastolic notches were not significantly different in the spontaneous preterm labor group compared to the normal group. The 62 preterm deliveries not preceded by spontaneous preterm premature rupture of membranes (PPROM) showed a significantly higher RI and prevalence of bilateral notches than cases of preterm deliveries preceded by PPROM (n = 172). However, this difference was not confirmed in a logistic regression model. CONCLUSION: Despite pathological evidence suggesting that defective placentation is associated with spontaneous preterm delivery, second-trimester UtA resistance, as assessed by Doppler ultrasound investigation, is not different in pregnancies subsequently complicated by preterm labor compared to pregnancies delivered at term.     

Changes in fetal hemodynamics with ritodrine tocolysis.

OBJECTIVE: To evaluate the effect of ritodrine on the fetal cardiovascular system. METHODS: Cardiac and extracardiac Doppler waveforms were recorded in 12 fetuses prior to and during ritodrine therapy used for preterm labor. Maternal and fetal heart rates, the Doppler pulsatility indices of the umbilical artery, middle cerebral artery, descending thoracic aorta and renal artery, and time velocity integrals of the atrioventricular valves and the ductus arteriosus, were measured. RESULTS: Ritodrine infusion caused an increase in maternal and fetal heart rates, the left cardiac output as measured by the product of time velocity integral and heart rate, and the pulsatility index of the middle cerebral artery, and a decrease in the pulsatility index of the umbilical artery. CONCLUSIONS: Ritodrine infusion may alter placental and cerebral blood flow and may have a selective effect on the left side of the heart.     

Screening for pre-eclampsia and fetal growth restriction by uterine artery Doppler at 11-14 weeks of gestation.

OBJECTIVE: To examine the value of uterine artery Doppler at 11-14 weeks of gestation in the identification of women at risk of developing pre-eclampsia and fetal growth restriction. METHODS: Uterine artery Doppler was carried out at 11-14 weeks in 3324 consecutive singleton pregnancies attending for routine care in three London hospitals. The right and left uterine arteries were identified using color flow mapping and velocity waveforms were obtained using pulsed Doppler. The mean pulsatility index of the two arteries was determined and the predictive value of a mean pulsatility index > the 95th centile in the prediction of pre-eclampsia and/or fetal growth restriction was calculated. RESULTS: Satisfactory flow velocity waveforms were obtained from both uterine arteries in 3195 (96.1%) of the 3324 pregnancies examined and complete outcome information was obtained for 3045 (95.3%) of these women. The 95th centile of the uterine artery mean pulsatility index was 2.35 and did not change significantly with gestational age. The pregnancy was complicated by pre-eclampsia in 63 (2.1%) cases and by fetal growth restriction in 290 (9.5%) cases. The sensitivity of a mean pulsatility index > 2.35 for pre-eclampsia (with or without fetal growth restriction) was 27.0% but for fetal growth restriction alone it was 11.7%. The respective sensitivities for these complications requiring delivery before 32 weeks of gestation were 60.0% and 27.8%, respectively. CONCLUSION: Uterine artery Doppler at 11-14 weeks of gestation identifies a high proportion of women who develop severe pre-eclampsia and/or fetal growth restriction.     

Fetal brain/liver volume ratio and umbilical volume flow parameters relative to normal and abnormal human development.

OBJECTIVES: To estimate fetal brain volume from head circumference and published postmortem data; to determine normal values for the fetal brain/liver volume ratio relative to gestational age; to establish the relationship between the brain/liver volume ratio and fetal circulatory parameters during normal and restricted (SGA) fetal growth. PATIENTS AND METHOD: This was a cross-sectional study involving a total of 47 uncomplicated pregnancies appropriate-for-gestational age (AGA) and 23 pregnancies resulting in the delivery of a SGA fetus. At enrollment gestational age ranged between 20 and 36 weeks in both groups. Umbilical venous cross-sectional area and time-averaged velocity for calculation of volume flow as well as velocity waveforms from the umbilical artery, middle cerebral artery and ductus venosus, were recorded. Fetal liver volume measurements were obtained using three-dimensional ultrasound. Fetal brain volume was estimated from fetal head volume following comparison with published postmortem data on fetal brain weight. RESULTS: A significant correlation was observed between prenatally estimated fetal head volume and postmortem fetal brain volume. Fetal brain volume was approximately half that of fetal head volume. The normal fetal brain/liver volume ratio demonstrated a significant reduction with gestational age (R = -0.54; P < 0.001). The normal mean +/- standard deviation (SD) fetal brain/liver volume ratio (3.4 +/- 0.7) was significantly different (P < 0.001) from the mean fetal brain/liver volume ratio in the SGA group (n = 23) (5.9 +/- 1.9). A significant difference existed for mean umbilical venous volume flow between AGA (104.7 +/- 26.9 mL/min/kg) and SGA (59.6 +/- 22.7 mL/min/kg) fetuses. In the SGA fetus, there was a significant inverse relationship (P < 0.001) between fetal weight-related umbilical venous volume flow and fetal brain/liver volume ratio. In a subset of 16 SGA and 16 AGA fetuses matched for gestational age, a significant difference existed for umbilical artery pulsatility index (2.30 +/- 1.52 vs. 0.99 +/- 0.19), fetal middle cerebral artery pulsatility index (1.3 +/- 0.4 vs. 2.1 +/- 0.3) and late diastolic flow velocity in the fetal ductus venosus (6.9 +/- 14.2 cm/s vs. 23.9 +/- 8.8 cm/s), but not for peak systolic, early diastolic and time-averaged velocity in the ductus venosus. CONCLUSION: Sonographic estimates of fetal brain volume can be obtained. The fetal brain/liver volume ratio is a predictor of fetal outcome in the growth-restricted fetus. An inverse relationship exists in SGA fetuses between brain/liver volume ratio and fetal weight-related umbilical venous blood flow.