Dr K Flo, Department of Obstetrics and Gynaecology, University Hospital of Northern Norway, Sykehusveien 38, PO Box 24, N-9038 Tromsø, Norway. Email firstname.lastname@example.org
Please cite this paper as: Flo K, Wilsgaard T, Vårtun Å, Acharya G. A longitudinal study of the relationship between maternal cardiac output measured by impedance cardiography and uterine artery blood flow in the second half of pregnancy. BJOG 2010;117:837–844.
Objective To study serial changes in maternal systemic and uterine artery haemodynamics and establish reference ranges for the second half of pregnancy.
Methods Fifty-three low-risk pregnancies were evaluated at approximately 4-weekly intervals. Maternal systemic haemodynamics was assessed with impedance cardiography. Uterine artery blood velocity and diameter were measured using Doppler ultrasonography and uterine artery volume blood flow (Quta) was calculated as the product of mean velocity and cross-sectional area of the uterine artery. The fraction of cardiac output (CO) distributed to the uterine circulation was calculated as: Quta/CO × 100.
Main outcome measures CO, Quta, uterine vascular resistance (Ruta) and the fraction of CO distributed to the uterine circulation.
Results The CO increased (P = 0.0063) until 34 weeks and remained stable until term. Total Quta increased from 299 to 673 ml/minute and Ruta halved from 0.26 to 0.13 mmHg/ml/minute (P < 0.0001). The fraction of CO distributed to the uterine circulation increased from 5.6% to 11.7% (P < 0.0001).
Conclusion During the second half of pregnancy, Quta and the fraction of maternal CO distributed to the uterine circulation increase approximately two-fold, mainly as a result of decrease in Ruta.
Some of the most striking physiological changes in pregnancy are the increase in cardiac output (CO)1,2 and uterine artery volume blood flow (Quta).3–5 However, there are no published studies that have measured maternal CO and Quta longitudinally in the same women to explore their inter-relationship. The fraction of maternal CO distributed to the uterine arteries in humans is not known.
It is possible to measure the CO and Quta noninvasively using impedance cardiography (ICG) and Doppler ultrasonography, respectively. The accuracy of ICG has been validated in pregnancy using thermodilution.6,7 Noninvasively measured Quta has been shown to correlate with and be approximately equal to Quta measured directly using ultrasonic transit-time flow probes in animal experiments.8
The aim of this study was to study serial changes in maternal systemic and uterine artery haemodynamics and establish reference ranges for the second half of normal pregnancy.
The study protocol was approved by the Regional Committee for Medical Research Ethics and all participants gave informed written consent. The study participants were women aged >18 years attending the antenatal clinic for routine ultrasonography at 17–20 weeks of gestation with a viable singleton pregnancy without any obvious fetal abnormality. From a population of 177 consecutive women who consented to participate in an ongoing study of maternal and fetal haemodynamics and endothelial function, 53 with low-risk pregnancies were randomly selected for the longitudinal arm of the study. Previous history of pre-eclampsia, intrauterine fetal growth restriction, diabetes or any other significant medical illness excluded participation in the longitudinal study. Examinations were performed at approximately 4-weekly intervals from 22+0 to 39+6 weeks of gestation.
Height and weight at booking were taken from the medical records. Weight was measured at each visit and the body mass index was calculated as weight/height². Body surface area (BSA) was calculated using the Du Bois formula: BSA (m²) = 0.007184 × [Height (cm)]0.725 × [Weight (kg)]0.425, which has been validated in pregnancy.9
Maternal cardiac function, systemic haemodynamics and thoracic fluid content were investigated using ICG (Philips, Böblingen, Germany). Technical details have been previously described.6,10 In brief, the women were studied in the morning after a minimum of 8 hours of fasting. Room temperature was maintained at approximately 22°C, and the participants were instructed not to move or speak during the examination.
After 15 minutes of rest, they were examined in a supine semi-recumbent (half-sitting) position to avoid possible compression of the inferior vena cava by the gravid uterus. Some investigators have used a left lateral position for this purpose1,2,11 but ICG measurements are cumbersome to perform in this position. To investigate possible differences in haemodyamics between the supine semi-recumbent and the left lateral positions we performed ICG in both positions in 20 randomly selected women at 32–35 weeks and 36–39 weeks of gestation.
Four sensors were used to obtain ICG signals, two placed vertically on each side of the neck and the other two on each side of the thorax at the anterior axillary line.
A sphygmomanometer cuff connected to the equipment recorded systolic, diastolic and mean arterial (MAP) blood pressures. Central venous pressure (CVP) and pulmonary arterial occlusion pressure (PAOP) were preset to 4 and 8 mmHg, respectively. The following parameters were automatically calculated and recorded: heart rate, stroke volume, CO, systemic vascular resistance (SVR) and left ventricular work index (LCWI).
An ultrasound system with a 6-MHz curvilinear transducer (Acuson Sequoia 512, Mountain View, CA, USA) was used for Doppler ultrasonography. Women were in the supine semi-recumbent position during examinations. One single operator (K.F.) performed all examinations, hence eliminating interobserver variability. The biparietal diameter, abdominal circumference and femur length of the fetus were measured and fetal weight was estimated at each visit according to the Hadlock formula.12
Blood velocity waveforms were obtained from each uterine artery immediately proximal to the cross-over of the external iliac artery using colour-directed pulsed-wave Doppler and the time-averaged intensity-weighted mean velocity (TAV) was measured. The velocity measurements were performed at the lowest possible angle of insonation (kept at <30°) and angle correction was used if necessary. The measurements were performed online and the recorded values were an average of three consecutive cardiac cycles. The colour Doppler mode was then switched to power Doppler angiography mode and the uterine artery diameter was measured as described previously.13 The scale of intensity was set at maximum and the gain was optimised to reduce artefacts and overestimation of the vessel diameter. Volume blood flow (Q) of each uterine artery was calculated as the product of TAV and the cross-sectional area (CSA) of the vessel, where CSA = 3.14 × (diameter/2)². For the purpose of this study we calculated total Quta as the sum of the right and left uterine artery volume blood flows. Uterine vascular resistance (Ruta) was calculated as: MAP/Quta. The course and outcome of pregnancy, including any maternal or fetal complications, gestational age at delivery, mode of delivery, neonatal weight, sex, Apgar scores, placental weight and umbilical cord blood acid–base status, were recorded prospectively.
Agreement between ICG measurements performed in left lateral and supine semi-recumbent positions were assessed using Bland–Altman analysis14 in 20 women at 32–35 and 36–39 weeks of gestation when one would expect the maximal effect of posture on haemodynamic parameters because of the possible compression of the inferior vena cava. Reproducibility of uterine artery diameter, TAV and Quta measurements was assessed in 25 women using intra-observer coefficient of variation (CV) and intra-class correlation coefficient (ICC).
Data were analysed using Statistical Analysis Software version 9.2 (SAS Institute Inc., Cary, NC, USA). Assumption of normality was checked for each variable. Logarithmic or power transformations were performed as appropriate to achieve normal distribution. The best transformation was determined using the Box–Cox regression. Fractional polynomials were used to obtain best-fitting curves in relation to gestational age for each variable analysed. Multilevel modelling was used to estimate the reference percentiles.15
Baseline characteristics of the study population are given in Table 1. All 53 women completed the study. The outcome data were available for each participant and none were excluded from final analysis. None of the participants developed any significant pregnancy complications. Three (5.6%) women underwent a caesarean section; two as a result of dystocia and one because of breech presentation. There were six (11.2%) vacuum extractions; four because of failure to progress and two for fetal distress in the second stage of labour. None of the neonates had a 5-minute Apgar score <7.
Table 1. Baseline characteristics of the study population (n = 53)
Data are presented as median (range), mean ± SD or n (%) as appropriate.
Body mass index at booking (kg/m²)
23.5 (± 3.1)
Mean arterial pressure at booking (mmHg)
83 ± 8
Gestational age at birth (weeks)
Birth weight (g)
3562 ± 470
Placental weight (g)
591 ± 117
5-minute Apgar score
Umbilical artery pH
7.24 ± 0
Agreement results for the ICG measurements obtained in supine semi-recumbent and left lateral positions are given in Table 2. Intra-observer reproducibility of the uterine artery diameter and blood flow measurements is presented in Table 3.
Table 2. Agreement between maternal haemodynamic parameters measured by impedance cardiography in supine semi-recumbent (S) and left lateral (L) positions in 20 low-risk pregnancies at 32–35 weeks (I) and 36–39 weeks (II)
Limits of agreement
Limits of agreement
Table 3. Intra-observer reproducibility of uterine artery diameter, blood velocity and flow measurements
Reference intervals for the parameters of maternal systemic haemodynamics are presented in Figure 1. Figure 2 shows the relative distributions of CO to the uterine arteries and the rest of the maternal circulation. Reference tables with gestational-age-specific percentiles for the parameters of maternal systemic haemodyamics measured by ICG are available as supplementary material online (Tables S1–S12). Maternal heart rate increased steadily and reached a maximum at 34 weeks, then decreased slightly until term (P < 0.0001). Stroke volume decreased from 22 weeks of gestation until the end of pregnancy (P = 0.018). The CO increased from 5.5 l/minute at 22 weeks to 5.8 l/minute at 34 weeks (P = 0.006), and remained stable until term. The MAP (P < 0.0001), SVR (P < 0.001) and LCWI (P = 0.0002) increased from 22 weeks of gestation to term.
Gestational-age-specific reference intervals for uterine artery diameter, TAV, Quta, Quta normalised for estimated fetal weight, Ruta and the fraction of maternal CO distributed to the uterine circulation are presented in Figure 3. The mean diameter of the uterine arteries increased from 0.33 to 0.37 cm (P < 0.0001) and the TAV from 29 to 43 cm/second (P < 0.0001) resulting in an increase in total Quta from 299 ml/minute at 22 weeks of gestation to 673 ml/minute at 39 weeks of gestation (P < 0.0001). There were no significant differences between the right and left uterine arteries (data not shown). The Ruta decreased from 0.26 to 0.13 mmHg/ml/minute (P < 0.0001). Both Quta and Ruta normalised for estimated fetal weight decreased (P < 0.0001). The fraction of the maternal CO distributed to the uterus increased almost linearly from 5.6% at 22 weeks to 11.7% at 39 weeks (P < 0.0001). However, the uterine fraction of maternal CO did not correlate significantly with the birthweight (R = 0.01; P = 0.94). The Quta did not correlate significantly with estimated fetal weight (P = 0.16). The Quta measured close to term (last measurement) did not correlate significantly with the neonatal birth weight (R = 0.15; P < 0.31) or the placental weight (R =−0.014; P = 0.92).
To our knowledge, this is the first study investigating maternal CO and Quta in the same women allowing calculation of serial changes in the fraction of maternal CO distributed to the uterine circulation during the second half of pregnancy. The Quta and the fraction of CO distributed to the uterine circulation doubled during 22+0 to 39+6 weeks of gestation.
The most significant increase in CO occurs during the first half of pregnancy mainly as the result of an increase in stroke volume.2 The increase of CO in the second half of pregnancy was smaller and was mostly because of an increase in heart rate. The SVR increased and there was a significant increase in LCWI, suggesting increased left ventricular work possibly because of increased myocardial oxygen consumption.
Whether the CO increases steadily until term or there is a decrease in late pregnancy remains controversial. Some studies report a steady increase until term,1,11,16 whereas others report a plateau or decrease in the third trimester.2,17–20 Diverging results can be explained by differences in study design and methodology, including maternal position during the examination.
The importance of adequate maternal uteroplacental blood flow for fetal growth and development cannot be overemphasised. Using electromagnetic flow probes in women undergoing termination of pregnancy, Assali et al.4 measured Quta of 50–60 ml/minute in the late first trimester increasing to 185 ml/minute at 28 weeks. Two small studies that report on noninvasively measured Quta in early pregnancy report higher values but a similar trend.21,22 At term most of the studies report a value between 450 and 750 ml/minute.4,5,23–25 Our result of 647–673 ml/minute at 37–39 weeks is comparable with those studies. Quta normalised for estimated fetal weight has been shown to decrease,4,13, which is in accordance with our findings. The decrease in normalised Quta with advancing gestation is most likely a result of relatively faster fetal growth compared with the growth of the uteroplacental unit in the second half of pregnancy.
We found uterine artery diameter to increase with gestation and the diameters were similar on both sides. Inaccurate measurement of vessel diameter can lead to significant errors in volume blood flow calculation.26 We used colour power angiography to measure uterine artery diameter, a method that has been validated in an animal model.8 Furthermore, our findings agree with uterine artery diameter measurements obtained in late pregnancy using contrast angiography.27
Uterine artery pulsatility and resistance indices have been used as surrogate measures of Ruta in clinical practice. Our study describes a noninvasive method for measuring Ruta that may prove to be clinically valuable. Invasively measured mean Ruta in seven pregnant women undergoing caesarean section at 38–40 weeks was reported to be 0.12 (range 0.09–0.14) mmHg/ml/minute3, which is close to our noninavsively measured Ruta value of 0.13 mmHg/ml/minute near term.
The uterine fraction of maternal CO in humans has been reported to vary between 3.5% and 12% from early pregnancy to term using assumed CO from other studies.23 We found this to increase from 5.6% at 22 weeks of gestation to 11.7% at term. In sheep, this fraction has been reported to be 24% at term.28 Several of the ewes in that study had multiple pregnancies, which may explain this discrepancy.
It remains unsolved whether the increase in uteroplacental blood flow is solely caused by an increase in CO or there is a redistribution of blood flow. Two studies have previously compared the blood flow in the iliac arteries and the uterine arteries indicating flow redistribution in favour of uterus and placenta, as the flow increased in the uterine arteries but not in the external iliac arteries.24,29 Our study supports some degree of redistribution, as the increase in maternal CO was only modest and reached a maximum at 34 weeks, whereas Quta continued to increase until the end of pregnancy. The SVR increased and the Ruta decreased, hence directing relatively more blood volume towards the uterus. Increasing differences in the SVR and the Ruta could possibly be one of the mechanisms involved in maintaining high uterine blood flow rate during pregnancy.
Our study has some limitations. It only assesses the systemic haemodynamics and the uterine artery blood flow in the second half of pregnancy. The prepregnancy, early pregnancy and postpartum values were not investigated. The accuracy of ICG has been questioned,30 but in recent years the ICG technology has improved and its accuracy has been validated.10 Its simplicity, user friendliness and noninvasiveness make it suitable for defining trends over time. During the ICG measurements, the values for the CVP and PAOP were preset at 4 and 8 mmHg, respectively, and any significant changes in their values could overestimate or underestimate the stroke volume and SVR measurements. However, these parameters have been shown to be similar among pregnant and nonpregnant women and to not change significantly during the course of healthy pregnancy.17,31
Measurement of maternal CO using echocardiography is usually performed in the left lateral position to avoid inferior vena cava compression. However, this position is inconvenient for ICG because it requires simultaneous measurement of blood pressure. Therefore, we chose a supine semi-recumbent position to reduce the risk of maternal haemodynamic instability. Furthermore, comparison of ICG measurements performed in the left lateral and supine semi-recumbent positions in 20 women in late gestation showed good agreement.
The uterine artery Doppler indices have been used to identify women at risk for developing pregnancy complications such as pre-eclampsia and intrauterine fetal growth restriction. In low-risk populations it is not an efficient screening tool because the positive predictive value is low.32 There is now growing evidence that insufficient maternal cardiovascular adaptation to pregnancy is a contributing factor to these complications.33 Although Quta and the uterine fraction of maternal CO did not correlate significantly with birthweight or placental weight in our population of low-risk pregnancies, reduced Quta and increased Ruta might be associated with adverse outcomes. Whether assessing maternal systemic haemodynamics and measuring the actual Quta and Ruta rather than the surrogate Doppler indices would have a clinical benefit merits further investigation.
We have established longitudinal reference intervals for noninvasive evaluation of maternal systemic haemodynamics and uterine circulation. During the second half of pregnancy, Quta and the fraction of maternal CO distributed to the uterine circulation increase approximately two-fold mainly as a result of decrease in the Ruta.
Disclosure of interest
No conflicts of interest.
Contribution to authorship
K.F. recruited the participants, collected data and performed ultrasound examinations.T.W. performed the statistical analysis and helped in the interpretation of the results, Å.V. performed ICG examinations and G.A. conceived and designed the study. G.A. and K.F. interpreted the results and wrote the manuscript. All authors approved the final version.
Details of ethics approval
The study protocol was approved by the Regional Committee for Medical Research Ethics in Northern Norway (Ref.nr. 5.2005.1386).
This study was funded by the Regional Health Authority of Northern Norway.
We would like to thank Gun Jensen, Annbjørg Tretten, Tove Johnsen and Karen Andersen for their help in recruiting the participants to this study.