Pregnancy Flow Research Articles

Impairment of IKCa channels contributes to uteroplacental endothelial dysfunction in rat diabetic pregnancy.

Diabetes in rat pregnancy is associated with impaired vasodilation of the maternal uteroplacental vasculature. In the present study, we explored the role of endothelial cell (EC) Ca(2+)-activated K(+) channels of small conductance (SKCa channels) and intermediate conductance (IKCa channels) in diabetes-induced uterine vascular dysfunction. Diabetes was induced by injection of streptozotocin to second-day pregnant rats and confirmed by the development of maternal hyperglycemia. Control rats were injected with citrate buffer. Changes in smooth muscle cell intracellular Ca(2+) concentration, membrane potential, and vasodilation induced by SKCa/IKCa channel activators were studied in uteroplacental arteries of control and diabetic rats. The impact of diabetes on SKCa- and IKCa-mediated currents was explored in freshly dissociated ECs. NS309 evoked a potent vasodilation that was effectively inhibited by TRAM-34 but not by apamin. NS309-induced smooth muscle cell intracellular Ca(2+) concentration, membrane potential, and dilator responses were significantly diminished by diabetes; N-cyclohexyl-N-2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4-pyrimidinamine (CyPPA)-evoked responses were not affected. Ca(2+)-activated ion currents in ECs were insensitive to paxilline, markedly inhibited by charybdotoxin (ChTX), and diminished by apamin. NS309-induced EC currents were generated mostly due to activation of ChTX-sensitive channels. Maternal diabetes resulted in a significant reduction in ChTX-sensitive currents with no effect on apamin-sensitive or CyPPA-induced currents. We concluded that IKCa channels play a prevalent role over SKCa channels in the generation of endothelial K(+) currents and vasodilation of uteroplacental arteries. Impaired function of IKCa channels importantly contributes to diabetes-induced uterine endothelial dysfunction. Therapeutic restoration of IKCa channel function may be a novel strategy for improvement of maternal uteroplacental blood flow in pregnancies complicated by diabetes.

Cerebrovascular haemodynamics in preeclamptic patients

The goal of the study was to analyse cerebral blood flow in pregnancy complicated by preeclampsia.

725: Does corticosteroid therapy impact fetal pulmonary artery blood flow in women at risk for preterm birth?

Maternal corticosteroid administration in pregnancy is known to enhance fetal lung maturity in at risk fetuses. The aim of this study was to test the hypothesis that corticosteroid therapy alters fetal pulmonary blood flow in pregnancies at risk for preterm birth (PTB).

Doppler parameters of the maternal hepatic artery blood flow in normal pregnancy: maternal hepatic artery blood flow in normal pregnancy

ObjectiveObjective of our study was to evaluate changes in Doppler resistance indices in the common hepatic artery during normal pregnancy. Study designCross-sectional study included 210 healthy pregnant women gestational age 6–40 weeks, 40 healthy non-pregnant women and 30 women after delivery. We divided all pregnant women by pregnancy trimester. We registered pulsatility index (PI) and resistive index (RI) in the common hepatic artery and compared the evaluated values among non-pregnant women and women in first, second and third trimester and post partum and tested correlation of both parameters with gestational age. Statistical analysis was done by Chi square test, one-way ANOVA followed by post-hoc test and two-tailed Pearson and Spearman correlation. The difference was considered to be significant if p<0.05. ResultsWe found lower values of PI and RI in the third trimester compared to control group and first and second trimester (p<0.01). There is negative correlation between the values of PI and RI with the gestation (p<0.01). ConclusionHepatic artery resistance indices decrease during the third trimester of pregnancy. This decrease may be the result of systemic arterial vasodilatation in normal pregnancy. The arterial resistance indices may be more useful for the evaluation of liver blood flow over the total blood flow as they are more reliable, being angle independent, easier to obtain, reflect vascular changes and might help in quick orientation about liver blood flow in pregnancies complicated by preeclampsia and HELLP syndrome. Our study is a pilot one, and further studies are needed to establish nomograms for the PI and RI during the gestation.

Elevated testosterone levels during rat pregnancy cause hypersensitivity to angiotensin II and attenuation of endothelium-dependent vasodilation in uterine arteries.

Elevated testosterone levels increase maternal blood pressure and decrease uterine blood flow in pregnancy, resulting in abnormal perinatal outcomes. We tested whether elevated testosterone alters uterine artery adaptations during pregnancy, and whether these alterations depend on endothelium-derived factors such as nitric oxide, endothelium-derived hyperpolarizing factor, and prostacyclin, or endothelium-independent mechanisms such as angiotensin II (Ang-II). Pregnant Sprague-Dawley rats were injected with vehicle (n=20) or testosterone propionate (0.5 mg/kg per day from gestation day 15 to 19; n=20). Plasma testosterone levels increased 2-fold in testosterone-injected rats compared with controls. Elevated testosterone significantly decreased placental and pup weights compared with controls. In endothelium-intact uterine arteries, contractile responses to thromboxane, phenylephrine, and Ang-II were greater in testosterone-treated rats compared with controls. In endothelium-denuded arteries, contractile responses to Ang-II (pD2=9.1±0.04 versus 8.7±0.04 in controls; P<0.05), but not thromboxane and phenylephrine, were greater in testosterone-treated rats. Ang-II type 1b receptor expression was increased, whereas Ang-II type 2 receptor was decreased in testosterone-exposed arteries. In endothelium-denuded arteries, relaxations to sodium nitroprusside were unaffected. Endothelium-dependent relaxation to acetylcholine was significantly lower in arteries from testosterone-treated dams (Emax=51.80±6.9% versus 91.98±1.4% in controls; P<0.05). The assessment of endothelial factors showed that nitric oxide-, endothelium-derived hyperpolarizing factor-, and prostacyclin-mediated relaxations were blunted in testosterone-treated dams. Endothelial nitric oxide synthase, small conductance calcium-activated potassium channel-3, and prostacyclin receptor expressions were significantly decreased in arteries from testosterone-treated dams. Hypoxia-inducible factor-1α, Ankrd37, and Egln were significantly increased in testosterone-exposed placentas. These results suggest that elevated maternal testosterone impairs uterine vascular function, which may lead to an increased vascular resistance and a decrease in uterine blood flow.

Editorial (Thematic Issue: Uteroplacental Circulation and Fetal Vascular Development and Function)

The striking increase of uterine blood flow in pregnancy is essential both for optimal growth and survival of the fetus, as well as for cardiovascular well-being of the mother. Maladaptation of the uteroplacental circulation during pregnancy is associated with high incidence of clinical complications including preeclampsia and fetal intrauterine growth restriction. Thus, a comprehensive understanding of regulatory mechanisms of uteroplacental vascular adaptation in pregnancy has long been sought, but has not been achieved. Interactions between the mother and fetus via the placenta during gestation are sophisticated and complex, which determine the optimal growth and health of the fetus. Pregnancy complications and fetal growth restriction occur when things go wrong in the uteroplacental circulation. One of the most provocative recent findings in modern medicine is that uteroplacental insufficiency and perinatal stress not only significantly increase maternal and infant mortality and morbidity rates, but also have long-term adverse effects on adult health, predisposing to cardiovascular and metabolic diseases later in life. Multiple factors may be involved in determining maternal/fetal health and developmental programming of health and disease but the function of uteroplacental circulation is the center of all. This hot-topic issue provides broad and up-to-date information and recent advancement of our knowledge in physiology and pathophysiology of the uteroplacental circulation and the development of fetal cerebral, coronary and pulmonary vasculatures. Each Chapter is written by leading experts in the field, providing the highest academic level for readers including basic, clinical, and translational scientists, pediatricians, maternal-fetal medicine specialists, and physiologists.

Pattern of fetal arterial blood flow in selected vessels in patients with pregnancy induced hypertension in Aminu Kano Teaching Hospital Kano, Nigeria

Background: Doppler velocimetry of fetal arterial blood flow in pregnancy induced hypertension (PIH) determines fetal hemodynamic adjustment. Objective: This study was aimed to determine the pattern of fetal arterial blood flow of selected vessels in patients with PIH. Materials and Methods: A total of 34 pregnant women with PIH at a gestational age of 24-37 weeks were prospectively examined with Doppler ultrasound of the fetal middle cerebral artery (MCA), umbilical artery and placental blood flow (uterine artery). Results: The mean peak systolic velocity (PSV) of the fetal MCA was 8.23±3.96, resistance index (RI) was 0.763±0.07 and systolic diastolic (S/D) ratio was 4.558±1.36. The mean PSV of umbilical artery was 72.28±26.585, RI was 0.62±0.19 and S/D was 2.63±0.75. The mean placental blood flow (uterine artery) PSV was 141.34±70.58, RI was 0.59 and S/D was 2.42±1.07. Uterine artery PSV was normal in only six patients. Uterine artery was also not sonographically demonstrated in two patients. Conclusion: Doppler velocimetry of arterial blood vessels in pregnancy complicated with PIH reveals abnormal pattern; its application in PIH would be useful for further management.

Chronic Hypoxia During Gestation Causes Epigenetic Repression of the Estrogen Receptor-α Gene in Ovine Uterine Arteries via Heightened Promoter Methylation

Estrogen receptor-α (ERα) plays a key role in the adaptation of increased uterine blood flow in pregnancy. Chronic hypoxia is a common stress to maternal cardiovascular homeostasis and causes increased risk of preeclampsia. Studies in pregnant sheep demonstrated that hypoxia during gestation downregulated ERα gene expression in uterine arteries. The present study tested the hypothesis that hypoxia causes epigenetic repression of the ERα gene in uterine arteries via heightened promoter methylation. Ovine ERα promoter of 2035 bp spanning from −2000 to +35 of the transcription start site was cloned. No estrogen or hypoxia-inducible factor response elements were found at the promoter. Two transcription factor binding sites, USF −15 and Sp1 −520 , containing CpG dinucleotides were identified, which had significant effects on the promoter activity. The USF element binds transcription factors USF1 and USF2, and the Sp1 element binds Sp1, as well as ERα through Sp1. Deletion of the Sp1 site abrogated 17β-estradiol–induced increase in the promoter activity. In normoxic control sheep, CpG methylation at the Sp1 but not the USF site was significantly decreased in uterine arteries of pregnant as compared with nonpregnant animals. In pregnant sheep exposed to long-term high-altitude hypoxia, CpG methylation at both Sp1 and USF sites in uterine arteries was significantly increased. Methylation inhibited transcription factor binding and the promoter activity. The results provide evidence of hypoxia causing heightened promoter methylation and resultant ERα gene repression in uterine arteries and suggest new insights of molecular mechanisms linking gestational hypoxia to aberrant uteroplacental circulation and increased risk of preeclampsia.

Hypoxia modulates pregnancy‐mediated transcriptional regulation of BKca β1 subunit expression in ovine uterine arteries

BKca channels play a key role in the increased uterine artery blood flow in pregnancy, which is attenuated by chronic hypoxia during gestation. We examined transcriptional mechanisms of BKca β1 subunit promoter in ovine uterine arteries. We cloned a 2‐kb promoter of β1 gene in sheep, which contains several transcription factor binding sites with CpG dinucleotides in their core binding sequences, including ERα/SP1, SP1, and AP1. ERα/SP1, but not SP1 or AP1, sites were hypomethylated in uterine arteries of pregnant as compared with nonpregnant animals, which was reversed by chronic hypoxia. The binding of ERα and SP1 to the site was confirmed by EMSA with super shift and ERα and SP1 bind simultaneously to the site. CpG methylation inhibited the binding. Deletion of the ERα/SP1 binding site significantly attenuated reporter gene activity of β1 promoter. ChIP assay showed an increase in ERα and SP1 binding to β1 promoter in pregnant uterine arteries, which was abrogated by chronic hypoxia. In accordance, β1 protein expression was increased in pregnant uterine arteries, which was blocked by hypoxia. The results demonstrate a novel mechanism of promoter methylation in transcriptional regulation of BKca β1 subunit gene expression patterns in uterine arteries in response to pregnancy and hypoxia. (Supported in part by NIH grants HL89012 and HL110125).

Role of BKCa channels in regulating uterine vascular contractility: effect of high altitude hypoxia

BKCa channels play a key role in the increased uterine artery blood flow in pregnancy. The present study tested whether chronic hypoxia attenuates pregnancy‐mediated enhanced BKCa channel activities and increases PKC‐mediated uterine vascular tone. Uterine arteries were isolated from nonpregnant (NPUA) and nearterm pregnant (PUA) sheep maintained at sea level (~300 m) or high altitude (3801 m) for 110 days. In contrast to previous studies in normoxic sheep, PKC activator PDBu‐induced contractions were increased in PUA, which was not significantly different from that of NPUA in hypoxic sheep. BKCa channel blocker TEA increased PDBu‐induced contractions in NPUA but not PUA. However, TEA increased norpinephrine (NE)‐induced contractions in both NPUA and PUA. Both BKCa channel opener, NS1619 and SKCa channel opener, NS309 caused minimal relaxations (~20%) of NPUA and PUA pre‐contracted by NE in the present or absence of endothelial cells. In addition, Western blot showed a decrease in the β1, but not α, subunit of BKCa channels in hypoxic PUA as compared with normaxic PUA. The results suggest that chronic hypoxia selectively attenuates basal uterine vascular BKCa channel activity, but not BKCa channel activation in pregnant animals, which may contribute to enhanced uterine vascular tone observed in sheep during pregnancy at high altitude hypoxia. (Supported in part by NIH grant HD31226)

Gestational vasoconstriction of the brachial artery at low-flow; a novel observation that suggests shear stress has a primary role in the vasodilatation of healthy pregnancy

IntroductionDuring healthy pregnancy there is marked and progressive vasodilatation leading to increased blood flow to maternal organs, in particular the utero-placental circulation. While using a measure of flow-mediated dilatation (FMD)...

The Importance of Venous Doppler Velocimetry for Evaluation of Intrauterine Growth Restriction

The management of growth-restricted fetuses requires accurate diagnosis to optimize the timing of delivery. Doppler velocimetry is the only noninvasive method for assessing the fetoplacental hemodynamic status. This review will give a critical overview of the current knowledge on fetal venous blood flow in pregnancies complicated by in-trauterine growth-restricted fetuses. Adaptation of the circulation in intrauterine growth-restricted fetuses is described. Normal and abnormal venous Doppler waveforms are presented. Correlations of abnormal waveforms with the presence of acidemia and perinatal outcomes are emphasized. Limitations of venous Doppler velocimetry for optimizing the time for delivery and the perinatal outcome are also presented.

First‐trimester umbilical vein blood flow in pregnancies with low serum pregnancy‐associated plasma protein‐A levels: an early predictor of fetal growth restriction

To investigate umbilical vein blood flow (UVBF) during the first trimester in pregnancies with low serum pregnancy-associated plasma protein-A (PAPP-A) levels and to relate umbilical vein (UV) diameter, time-averaged maximum velocity (TAMXV) and UVBF values to the subsequent development of fetal intrauterine growth restriction (IUGR). UVBF assessment was performed at 11 + 0 to 13 + 6 weeks' gestation in 102 singleton pregnancies with PAPP-A concentrations of < 0.3 multiples of the median. UV diameter, UV-TAMXV and UVBF were calculated and analyzed in relation to pregnancy outcome. Pregnancy outcomes were: 51 pregnancies with birth weight ≥ 10(th) centile (Group A), 30 pregnancies with birth weight < 10(th) centile with normal Doppler in the umbilical artery throughout gestation (Group B) and 21 pregnancies with birth weight < 10(th) centile and abnormal umbilical artery Doppler later in gestation (Group C). No differences were found in PAPP-A levels between groups. Group C fetuses exhibited significantly lower values of UV-TAMXV (z-score - 1.99 SDs, t = 8.527, P ≤ 0.0001) and UVBF (z-score - 0.97 SDs, t = 7.420, P ≤ 0.0001) in comparison with normal reference ranges, while no differences were found in Groups A or B. Decreased UV-TAMXV and UVBF at 11 + 0 to 13 + 6 weeks' gestation identify fetuses at risk of developing IUGR among pregnancies with low levels of PAPP-A.

Determining uterine blood flow in pregnancy with magnetic resonance imaging

The purpose of this study is to determine the feasibility of measuring total uterine blood flow in pregnancy using magnetic resonance imaging (MRI) technique. Uterine blood flow was determined in pregnant women in whom MRI was being carried out to assess a fetal anomaly. A two-dimensional time-of-flight magnetic resonance (MR) angiogram sequence was performed. Scout images and a peripherally gated phase contrast MR sequence were planned to study simultaneous blood flow in the uterine and ovarian arteries. The MR pelvic angiogram sequence was completed in 13 women. The uterine arteries were visualized and their cross-sectional area determined. The complexity of the pelvic blood supply prevented the calculation of blood flow velocity and, thus, total uterine blood flow. The measurement of total uterine blood flow during pregnancy was not possible using our MR technique. The ovarian vessels were not consistently visualized. Doppler ultrasonography remains the best modality by which to estimate total uterine blood flow in pregnancy.

Vena caval blood flow affects the quality of CTPA during pregnancy

Sir,We thank Dr. Karabulut for his insightful comments regarding the effects of breathing on caval blood flow in pregnancy and its potential effects on enhancement during CTA of the pulmonary arteries. We all have seen unexplained failure of contrast-enhancement in CT angiography of the pulmonary arteries. In our practice we can sometimes identify breathing-related effects, especially deep inspiration and Valsalva manoeuvres as the culprit [1]. The precise mechanisms, however, have not yet sufficiently been studied. The work by Kuzo et al. is a starting point [2]. The authors used MR to measure blood flow in the superior vena cava (SVC) and inferior vena cava (IVC) during various respiratory manoeuvres in a small number of volunteers. Kuzo et al. found that deep continuous inspiration, such as performed immediately prior to data acquisition in a typical pulmonary CTA (“take a deep breath”), will increase total venous return and increase the relative contribution of the IVC to venous return. This should lead to dilution of the injected contrast material. Pulmonary CTA in breath-hold, however, will be started exactly by the time this diluted contrast material reaches the lung. This effect could explain the modest enhancement in those patients that are especially compliant with the breathing command and take a very deep breath. The Valsalva manoeuvre, on the contrary, should be good for enhancement because it reduces venous return and therefore should reduce dilution. Clinical practice, however, teaches that enhancement during a Valsalva manoeuvre is often not optimal, which suggests that there are more influencing factors. When looking at the data published by Kuzo et al., one sees that a potential explanation lies in the substantial interindividual variation of the relative contribution of the SVC and IVC: the ratio of blood flow in the SVC and IVC varies between approximately 1 and 3 for the Valsalva manoeuvre and between 1.1 and 3.6 for the inspiration manoeuvre. The variability in end-inspiration is much less, between 1.2 and 2.2. This suggests that patients react differently to the inspiratory commands (as is known from the ultrasound literature [3]), which in turn may cause substantial variations in contrast enhancement. While the work of Kuzo provides better understanding of the influence of breathing on caval blood flow, it did not study the effect of injecting fluid during these breathing manoeuvres. It is, for example, not clear whether the increased intrathoracic pressure during the Valsalva manoeuvre also influences the inflow of the injected contrast agent or not. The loss of hepatic venous pulsatility towards the end of pregnancy indeed suggests continuous forward flow of unopacified blood via the IVC. How this effect interacts with the effects studied by Kuzo et al. will have to be the subject of future studies. Avoiding deep inspiration before the pulmonary CTA data acquisition appears a good suggestion. Holding the breath during the course of normal respiration may be the answer to this problem. Knowledge about the physiological changes during breathing and their relation to pregnancy is important for further optimization of image quality in pulmonary CTA. However, reducing interindividual variations and improving patient compliance are probably equally important issues.

OP11.07: Changes of uterine and umbilical flow in pregnancy complicated by Diabetes Mellitus in relation to the perinatal outcome

Objectives: To explore the association of uterine arteries (UA) waveform analysis with brachial artery flow-mediated dilation (BAFMD) in the prediction of preeclampsia in high-risk pregnancies. Methods: UA waveforms were recorded using Pulsed Doppler ultrasonography in 33 women at 22–24 weeks of gestation with high risk factors for preeclampsia (PE). Mean Pulsatility Index (PI) of both UA were registered. At the same time, brachial artery diameter was evaluated in basal and after stress conditions using Color Doppler; BAFMD was expressed as percent change in diameter from baseline. The onset of PE was divided in early (before 34 weeks of gestation) or late (after 34 weeks). Logistic regression models were developed, and their predictive ability assessed using ROC curves. Results: The prevalence of PE in the studied group was 24% (8/33), 5 early and 3 late-onset. Mean UA-PI and BAFMD values of cases without PE were lower, but not significant, than those developing PE (mean difference (MD): −0.39 (95% CI: −0.90–0.13) and −4.41% (95% CI: −16.1–7.3) respectively). Area under ROC curve for mean UA-PI was of 0.70 (95% CI: 0.41–0.99%), and for BAFMD of 0.59 (95% CI: 0.37–0.80). Logistic regression analysis was only significant for mean UA-PI (P = 0.034), and adding BAFMD did not improve the prediction. For early-onset PE, there were significant higher values in mean UA-PI (MD: 0.56 (95% CI: 0.19–0.94)), and higher BAFMD results but not significant (MD: 8.8% (95% CI: −4.6–22.2%)). Area under ROC curve for mean UA-PI was of 0.79 (95% CI: 0.44–1), and for BAFMD of 0.69 (95% CI: 0.46–0.91). Logistic regression analysis was only significant for mean UA-PI (P = 0.02), multivariate regression analysis combining UA-PI and BAFMD did not get better the prediction of early-onset PE. Conclusions: Although there is a trend of higher BAFMD in pregnancies with PE, the test in the second trimester did not improve the capacity for prediction of PE that provides the UA by itself.

P46.08: Blood flow in pregnancies complicated with IUGR

P46.08: Blood flow in pregnancies complicated with IUGR

Direct Effects of Nicotine on Contractility of the Uterine Artery in Pregnancy

Recent studies indicate that smoking/nicotine increases maternal blood pressure and decrease in uterine blood flow in pregnancy. However, the mechanisms are not fully understood. The present study was designed to test the hypothesis that nicotine exposure decreases endothelium-dependent relaxation and increases vascular contractility of the uterine artery in pregnancy. Uterine arteries were isolated from near-term ( approximately 140 days gestation) pregnant ewes. Arteries were subjected to acute (20 min) or chronic (48 h) nicotine treatment, and agonist-induced contractions and relaxations were measured in tissue bath. Endothelial eNOS was detected by immunohistochemistry in situ in arteries and by Western blotting in isolated endothelial cells. Chronic nicotine treatment produced a concentration-dependent increase in alpha(1)-adrenoceptor agonist phenylephrine-induced contractions. In contrast, the acute treatment showed no effect. Inhibition of eNOS with N(G)-nitro-L-arginine (L-NNA) significantly increased phenylephrine-induced contractions, which was abolished in uterine arteries after chronic nicotine treatment. In the presence of L-NNA, there was no significant difference in phenylephrine-induced contractions between control and nicotine-treated vessels. Chronic, but not acute, nicotine treatment significantly attenuated the calcium ionophore A23187-induced relaxations. Unlike A23187, the endothelium-independent relaxation mediated by sodium nitroprusside was not affected by nicotine. Endothelial eNOS protein levels and the phosphorylation levels of eNOS(Ser1179) were significantly decreased in nicotine-treated uterine arteries. The results suggest that nicotine impairs uterine vascular function in pregnancy, which may lead to an increased vascular resistance and a decrease in uterine blood flow.

P09.14: In search of a novel methodology to measure uterine arteries blood flow in pregnancy

P09.14: In search of a novel methodology to measure uterine arteries blood flow in pregnancy

Assessment of fetal liver volume and umbilical venous volume flow in pregnancies complicated by insulin‐dependent diabetes mellitus

To determine fetal liver volume and its relation with umbilical venous volume flow and maternal glycosylated haemoglobin (HbA1c) in pregnancies complicated by diabetes mellitus type I. A cross sectional matched control study. Obstetric out patient clinic, Erasmus MC-University Medical Centre, Rotterdam. Data from fetuses of diabetic women (n = 32; 18-36 weeks) were compared with data from normal controls (n = 32) matched for gestational age. Umbilical venous cross sectional area (mm(2)) and time-averaged velocity (mm/s Doppler) were determined for calculation of volume flow (mL/min) and flow per kilogram fetal weight (mL/min/kg). Umbilical artery pulsatility index was determined. Fetal liver volume measurements were obtained using a Voluson 530-D. Fetal liver volume, umbilical venous volume flow and downstream impedance. A statistically significant difference between fetuses of diabetic women and normal controls was found for liver volume (mean [SD]: 45.9 [34.0] vs 38.3 [28.7] mL), abdominal circumference (22.2 [6.6] vs 21.3 [5.6] cm), estimated fetal weight (1162 [898] vs 1049 [765] g) and fetoplacental weight ratio (0.22 vs 0.19) and liver volume/estimated fetal weight ratio (4.13% [0.007] vs 3.62% [0.009]). Umbilical venous volume flow (mL/min) and umbilical artery pulsatility index were not essentially different between the two study groups, but umbilical venous volume flow per kilogram fetal weight was lower (P < 0.05) in the diabetes group (94.3 [26.1] mL/min kg) compared with normal controls (109.5 [28.0] mL/min/kg). A positive correlation existed between fetal liver volume and maternal HbA1c (P = 0.002). Measurement of fetal liver volume by three-dimensional ultrasound may play a role in identifying fetal growth acceleration in diabetic pregnancies. Fetal liver volume increase is positively related to maternal HbA1c levels reflecting degree of maternal glycemic control. Fetal liver volume normalised for estimated fetal weight is significantly higher in the fetuses of diabetic women. In the present study, umbilical venous volume flow and fetoplacental downstream impedance are not different between diabetic and normal pregnancies.