SEARCH

SEARCH BY CITATION

Keywords:

  • Echocardiography;
  • maternal cardiac output;
  • pre-eclampsia;
  • pregnancy

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Objective  To assess maternal cardiac function in nulliparous women in the first trimester of pregnancy and evaluate its potential role for predicting pre-eclampsia and small for gestational age (SGA).

Design  Prospective, observational, cross-sectional study.

Setting  Maternity unit of a teaching hospital.

Population  Nulliparous women with singleton pregnancies presenting consecutively for routine antenatal care (n= 534).

Methods  Two-dimensional and M-mode echocardiography and uterine artery Dopplers were carried out at 11-14 weeks.

Main outcome measures  Cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), total vascular resistance and uterine artery pulsatility index (UAPI) were compared in four outcome groups according to the development of pre-eclampsia and/or SGA.

Results  Compared with the normal outcome group (n= 457), in those with pre-eclampsia but not SGA (n = 8), CO and MAP were increased; in the group with pre-eclampsia and SGA (n= 19) MAP, TRP and UAPI were increased and in the group with SGA but no pre-eclampsia (n= 50) total peripheral resistance and UAPI were increased. Independent predictors of pre-eclampsia were MAP, SV and UAPI and of SGA SV and UAPI.

Conclusions  Alterations in maternal cardiac function and UAPI are observed in the first trimester of pregnancy in nulliparous women that subsequently develop pre-eclampsia and/or SGA.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Pre-eclampsia is not a uniformly high-resistance, volume-contracted state as previously thought.1 Earlier studies, using direct haemodynamic measurements in women with severe pre-eclampsia requiring invasive monitoring, have described variations in haemodynamic characteristics ranging from a hyperdynamic state with a higher-than-normal cardiac output (CO) and increased left ventricular function to a vasoconstrictive state with decreased CO and diminished left ventricular function. These studies also document variable systemic resistance profiles, ranging from normal- to high-resistance states.2–4 However, since the introduction and evaluation of the Doppler technique for maternal cardiac function in pregnancy,5,6 a series of echocardiographic studies have confirmed the existence of apparent haemodynamic subgroups in women with overt or preclinical pre-eclampsia.7–9 These studies have advocated a maternal hyperdynamic circulation7,9 that is preceding the clinically overt disease9 and may also be present to a variable degree during the more severe stages.7 Furthermore, in one study the effect of maternal haemodynamics on fetal growth in hypertensive pregnancies have been investigated.10 Easterling et al. observed that high-resistance hypertension was associated with lower percentile weights for gestational age, while high CO and low-resistance hypertension were associated with normal fetal growth.10 However, the cardiac investigations in their study were performed in women who were clinically hypertensive.

In previous studies on pre-eclampsia, the influence of the variable characteristics in the maternal central and peripheral haemodynamics on the sensitivity of screening tests or the efficacy of treatment has been masked by the analysis of all pre-eclampsia cases as a single disease entity. However, there is emerging epidemiological evidence to suggest that preterm pre-eclampsia (before 37 weeks) and term pre-eclampsia associated with low-birthweight infants (between 37 and 42 weeks) are likely to share similar disease origins, while term pre-eclampsia may also be associated with large or normal for gestational age fetuses and may thus represent a different subgroup of women.11 Additionally, there is evidence of disparity in screening for pre-eclampsia with uterine artery Dopplers either in the first12 or in the second trimester13 since it has been shown that there is a remarkably higher sensitivity in women with pre-eclampsia complicated by small-for-gestational-age (SGA) babies compared with uncomplicated pre-eclampsia or SGA alone. Furthermore, nondistinction of these varied haemodynamic states may, in part, be why studies utilising volume-loading in severe pre-eclampsia have shown no clear maternal nor fetal benefit.14,15 However, although maternal cardiac function might play an important role in screening and treatment for pre-eclampsia, there is no information to date regarding the degree of changes in the first trimester of pregnancy, presumably because previous investigators were concentrating at the later stages of the disease when it would be more applicable for screening and treatment. Furthermore, in most of the studies so far, hypertensive women have been examined collectively without addressing separately the issue of fetal growth and its interaction on maternal cardiovascular physiology.

The objective of this study was to prospectively investigate maternal cardiac function and peripheral haemodynamics in the first trimester of pregnancy to study the cohort according to eventual pregnancy outcome and assess its impact on screening for pre-eclampsia and SGA.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Patient selection

This was an observational, cross-sectional study performed in the maternity unit of King’s College Hospital, London. Women attending for routine antenatal care are offered a transabdominal ultrasound scan at 11–14 weeks as a method of screening for chromosomal defects, by the measurement of nuchal translucency thickness.16 During a 13-month period (June 2003 to July 2004) women attending for this scan were invited to participate in this study, which was approved by the local ethics committee. Written informed consent was obtained from the women.

Gestational age was calculated from the last menstrual period and was confirmed by the fetal crown-rump length. Only healthy women, with no previous adverse medical history and no prescription medications were included in the study.

In total, 1192 consecutive women had a first trimester scan during this period. Of these women 665 (55.8%) were nulliparous and 527 (44%) multiparous. Of the nulliparous women, 42 women were excluded from the study because of unavailable outcomes, 31 because of fetal loss and 58 because of maternal disease. Therefore, 534 nulliparous women were finally enrolled into the study.

Outcomes

Outcome measures were pre-eclampsia and SGA. Pre-eclampsia was defined according to the guidelines of the International Society for the Study of Hypertension in Pregnancy.17 According to this definition, a woman is classified as pre-eclamptic when the diastolic blood pressure (DBP) is more than 90 mmHg on at least two occasions 4 hours apart in previously normotensive women and there is proteinuria of 300 mg or more in 24 hours or two readings of at least ++ on dipstick analysis of midstream or catheter urine specimens if no 24-hour collection is available. SGA was defined as birthweight below the tenth centile.18

Pregnancy outcomes were obtained from the hospital records and the study cohort was divided into four groups: normal outcome, pre-eclampsia without SGA, pre-eclampsia with SGA and SGA without pre-eclampsia.

Echocardiographic evaluation

M-mode and two-dimensional echocardiography were performed with the woman in left-lateral recumbent position using a 2.5-MHz transducer that was interfaced with an echocardiography-ready ultrasound system (Toshiba Aplio; Toshiba Corporation, Tokyo, Japan).

Systolic function of the left ventricle

Stroke volume (SV) was computed as the product of the cross-sectional area of the left ventricular outflow tract, measured from the parasternal long-axis view, and the velocity time integral of the pulsed Doppler subaortic waveform measured in the five-chamber view. CO was calculated as the product of heart rate and SV. In order to control for the impact of maternal height and weight, the CO was divided by the body surface area and a ‘cardiac index’ was calculated.

The long-axis function of left ventricle was further evaluated by measuring the mitral valve annulus shortening. Two-dimensionally guided M-mode recordings were made through the mitral valve annulus, using the apical four-chamber view for the lateral and septal sides.19 Values were obtained for each of the two sides and the mean value was calculated.

Diastolic function of the left ventricle

Transmitral flow was assessed with pulsed wave Doppler from the apical four-chamber view. The sample volume was placed at the tip of the mitral valve leaflets during diastole, and the peak flow velocities during early diastole (E-wave) and during atrial contraction (A-wave) were measured.20

Mean arterial pressure and total peripheral resistance

Systolic blood pressure (SBP) and DBP were manually measured at rest with a mercury sphygmomanometer. Determination of DBP was with Korotkoff sound. Mean arterial pressure (MAP) was calculated as: MAP = DBP + (SBP − DBP)/3. Total peripheral resistance [dynes/sec/cm5] was calculated as follows: (MAP[mmHg]/CO[L/min]) × 80.

Uterine artery Doppler

Uterine artery Doppler studies were carried out as previously described.12 In brief, women were placed in the semi-recumbent position and transabdominal ultrasound was used to obtain a sagittal section of the uterus and cervical canal. The internal cervical os was first identified. Subsequently, the transducer was gently tilted from side to side and colour flow mapping was used to identify the uterine arteries as aliasing vessels coursing along the side of the cervix and uterus. Pulsed wave Doppler was used to obtain flow velocity waveforms from the ascending branch of the uterine artery at the point closest to the internal os. When three similar consecutive waveforms were obtained the pulsatility index (PI) was measured and the mean PI of the left and right arteries was calculated.

Statistical analysis

The Kolmogorov–Smirnov test was used to assess normality of the distribution of the numerical data. The one-way analysis of variance (ANOVA) was used to assess the differences between the four groups for normally distributed numerical data or for non-normally distributed data that became normally distributed after logarithmic transformation. The Kruskal–Wallis test was used to assess the differences between the four groups for non-normally distributed numerical data. Similarly, the One-Way ANOVA, the Kruskal–Wallis test or the chi-square test, where appropriate, were performed in order to examine the differences in the demographic characteristics between the examined populations. The Tukey–Kramer and Dwass–Steel–Critchlow–Fligner were used as post hoc tests for the ANOVA and Krukal–Wallis tests, respectively. Normally distributed data are presented as mean and standard deviation, while non-normally distributed data are presented as median and interquartile ranges.

Multiple logistic regression analysis was used to determine the significant independent predictors of pre-eclampsia and SGA. In the initial model we included the variables that in a univariate model appeared to be statistically significant predictors of pre-eclampsia or SGA. These variables were maternal height, weight, race, smoking history and SV, MAP and uterine artery mean pulsatility index (UAPI). In this analysis, maternal race and smoking history were used as categorical variables, while all the rest were used as continuous numerical variables. The final logistic regression model was used to calculate the probability score for pre-eclampsia or SGA for each pregnancy. For different probability cutoffs, the sensitivity, specificity, positive and negative predictive values were calculated. The receiver operator characteristic (ROC) curve was calculated for the final model for each of the two outcome variables.

Statistical analyses were performed using MedCalc for Windows, version 8.1.0.0 (MedCalc Software, Mariakerke, Belgium).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

The pre-eclampsia rate for nulliparous women was 5%. From the total of 534 nulliparous women recruited in the study, 457 had normal outcome, 8 developed pre-eclampsia without SGA, 19 developed pre-eclampsia with SGA and 50 had SGA without pre-eclampsia.

The demographic characteristics of the four groups of women are summarised in Table 1. There were no differences between the groups in terms of maternal age, height and gestation at entry into the study. Women with pre-eclampsia and SGA compared with the other groups had a higher proportion of women of black race and an earlier gestation at delivery compared with all other groups. Birthweight was significantly different between all four groups but birthweight centile was significantly lower in the two groups (pre-eclamptic and normotensive) that delivered babies with SGA.

Table 1.  Demographic characteristics of the study populations
 Normal (n= 457)Pre-eclampsia (n= 8)Pre-eclampsia and Bwt < tenth centile (n= 19)Bwt < tenth centile (n= 50)P-value
  • Bwt, birthweight. For categorical data: number (n) and percentage (%); for numerical normally distributed data: mean and standard deviation; for numerical non-normally distributed data: median and interquartile range.

  • *

    Statistically significant differences between these groups and the uncomplicated pregnancies.

  • **

    Statistically significant differences between pregnancies complicated by pre-eclampsia with Bwt < tenth centile and pregnancies complicated by Bwt < tenth centile and uncomplicated pregnancies.

  • ***

    Statistically significant differences between pregnancies complicated by pre-eclampsia with Bwt < tenth centile and all other groups.

  • ****

    Statistically significant differences between all pairwise comparisons.

  • *****

    Statistically significant differences between these pregnancies and those complicated by pre-eclampsia with Bwt < tenth centile and those complicated by Bwt < tenth centile alone.

Maternal age (years)30.2 (25.4–33.3)31.2 (21.6–33.2)30.6 (24.2–34.5)29.0 (21.6–32.3)0.34
Height (cm)165.0 (160.0–168.0)166.5 (157.0–174.0)168.0 (160.7–168.7)163.0 (155.0–165.0)0.60
Weight (kg)62.0 (57.0–70)72.5 (61.7–91.7)*71.0 (57.0–81.0)*60.0 (53.0–72.2)0.03
Ethnicity, n (%)
White278 (61)6 (75)8 (42)21 (42)0.02
Black**128 (28)2 (25)10 (53)18 (36)
Other51 (11) 1 (5)11 (22)
Gestation at entry (days)88.0 (87.0–90.0)87.5 (87.0–91.5)89.0 (87.0–93.5)88.0 (87.0–90.0)0.68
Gestation at delivery (days)282.0 (274.0–286.0)275.0 (262.0–280.0)244.0 (231.0–258.7)***278.0 (270.0–286.0)<0.0001
Birthweight (kg)****3.4 (0.4)3.1 (0.4)1.7 (0.5)2.5 (0.3)<0.001
Birthweight centile47.2 (28.8–69.8)*****28.5 (15.0–72.4)*****2.8 (0.8–6.7)4.5 (1.5–7.9)<0.0001

Tables 2 and 3 summarise the differences in cardiac function and UAPI between the four groups.

Table 2.  Comparison between the groups (normally distributed data: mean and standard deviation; non-normally distributed data: median and interquartile range)
VariableNormal (n= 457)Pre-eclampsia (n= 8)Pre-eclampsia and Bwt < tenth centile (n= 19)Bwt < tenth centile (n= 50)P-value
  • Bwt, birthweight.

  • *

    Statistically significant differences between the pre-eclampsia and all other groups.

  • **

    Statistically significant differences between pregnancies complicated by Bwt < tenth centile and uncomplicated pregnancies.

  • ***

    Statistically significant differences between uncomplicated pregnancies and those with pre-eclampsia and pre-eclampsia with Bwt < tenth centile.

  • ****

    Statistically significant differences between pregnancies complicated by bwt <tenth centile and those pre-eclampsia with Bwt < tenth centile.

  • *****

    Statistically significant differences between pregnancies complicated by pre-eclampsia and those with pre-eclampsia with Bwt < tenth centile and solely Bwt < tenth centile.

  • ******

    Statistically significant differences between pregnancies complicated by pre-eclampsia with Bwt < tenth centile and uncomplicated pregnancies and those with pre-eclampsia.

  • *******

    Statistically significant differences between uncomplicated pregnancies and those with pre-eclampsia with Bwt < tenth centile and solely Bwt < tenth centile.

Cardiac output (l/min)4.9 (4.3–5.5)6.2 (5.4–7.1)*4.9 (4.1–5.6)4.6 (3.9–5.3)<0.001
Cardiac index (l/min/m2)2.9 (2.6–3.3)3.3 (3.0–4.0)*2.8 (2.4–3.0)2.7 (2.4–3.3)0.004
SV (ml)67.0 (11.7)87.9 (15.2)*66.3 (10.9)61.9 (11.5)**<0.001
Heart rate (bpm)75.2 (10.4)73.6 (11.5)74.4 (11.2)76.5 (8.7)0.7
MAP (mmHg)77.3 (72.7–83.3)***90.0 (82.0–91.0)92.0 (81.3–95.3)78.0 (68.0–86.0) ****<0.0001
SBP pressure (mmHg)104 (100–118.5)***116 (111–127.5)114 (110–130)104 (100–110)<0.0001
DBP pressure (mmHg)60 (54–70)***72 (66–77.5)76 (66–80)64 (60–70)<0.0001
Total vascular resistance (dynes/sec/cm5)1260 (1110–1460)1105 (920–1280)*****1410 (1300–1530)******1345 (1120–1590)<0.001
Mitral valve annulus shortening (mm)15.5 (2.0)17.8 (1.7)*14.8 (1.7)15.0 (1.9)0.001
Transmitral E-wave velocity (mm/sec)82.4 (13.6)95.7 (14.6)*79.9 (18.6)82.6 (13.4)0.04
Transmitral A-wave velocity (mm/sec)48.9 (8.4)51.5 (13.9)51.8 (13.9)51.7 (10.8)0.1
UAPI1.72 (0.5)1.87 (0.5)2.43 (0.6)*******2.07 (0.6)*******<0.001
Table 3.  Differences in maternal central and peripheral haemodynamics between the uncomplicated pregnancies and those complicated by pre-eclampsia without SGA, pre-eclampsia with SGA and SGA alone
VariablePre-eclampsia no-SGAPre-eclampsia with SGASGA
MAP (mmHg)[UPWARDS ARROW][UPWARDS ARROW][LEFT RIGHT ARROW]
Total vascular resistance (dynes/sec/cm5)[LEFT RIGHT ARROW][UPWARDS ARROW][UPWARDS ARROW]
UAPI[LEFT RIGHT ARROW][UPWARDS ARROW][UPWARDS ARROW]
Left ventricular systolic function
Stroke volume (ml)[UPWARDS ARROW][LEFT RIGHT ARROW][DOWNWARDS ARROW]
Cardiac output (L/min)[UPWARDS ARROW][LEFT RIGHT ARROW][LEFT RIGHT ARROW]
Cardiac index (L/min/m2)[UPWARDS ARROW][LEFT RIGHT ARROW][LEFT RIGHT ARROW]
Mitral valve annulus shortening (mm)[UPWARDS ARROW][LEFT RIGHT ARROW][LEFT RIGHT ARROW]
Left ventricular diastolic function
Transmitral E-wave velocity (mm/sec)[UPWARDS ARROW][LEFT RIGHT ARROW][LEFT RIGHT ARROW]
Transmitral A-wave velocity (mm/sec)[LEFT RIGHT ARROW][LEFT RIGHT ARROW][LEFT RIGHT ARROW]

Echocardiographic evaluation

Systolic function of the left ventricle

Women with eventual pre-eclampsia without SGA compared with all other groups had a similar heart rate but a greater SV, CO and cardiac index. This group of women also showed greater mitral annulus displacement compared with all other groups.

Women with eventual pre-eclampsia and SGA showed no differences in heart rate, SV and CO when compared with those with normal outcome. They were also similar to the normal outcome group in terms of mitral valve annulus displacement.

The group of women that subsequently delivered babies with SGA without pre-eclampsia had the lowest SV of all the groups.

Diastolic function of the left ventricle

Women with eventual pre-eclampsia without SGA had higher transmitral diastolic E-wave velocities than all other groups. However, there were no differences in the A-wave maximum velocities between the four groups.

MAP and total vascular resistance

While none of the women was clinically hypertensive when undergoing echocardiographic assessment at the end of first trimester, those who would ultimately go on to develop pre-eclampsia without SGA or pre-eclampsia with SGA already demonstrated significantly higher MAPs compared with those with eventual normal outcome. The group with eventual pre-eclampsia with SGA also showed higher MAPs when contrasted with those with SGA without pre-eclampsia. SBP and DBP demonstrated similar differences between groups as those observed for MAP.

In women with eventual pre-eclampsia without SGA total vascular resistance was maintained at levels similar to the normal outcome group, despite higher MAPs, but lower than the two groups that subsequently delivered babies with SGA. The group of women that subsequently developed pre-eclampsia with SGA had the highest total vascular resistance compared with any other group.

Uterine artery Dopplers

Women that delivered babies with SGA, with and without pre-eclampsia, had higher mean UAPI compared with the normal and the uncomplicated pre-eclamptic groups.

Multiple logistic regression

Multiple logistic regression demonstrated that significant independent contribution in the prediction of pre-eclampsia was provided by MAP, UAPI and SV (Table 4). The ROC curve for the final model is presented in Figure 1. The best point on the ROC curve for prediction of pre-eclampsia was at the probability of more than 5.4% with a sensitivity of 77.8%, specificity of 79.1% and a screen-positive rate of 20%.

Table 4.  Logistic regression models for prediction of pre-eclampsia and birthweight below the tenth centile
VariableCoefficientOdds ratio (95% CI)P-value
Pre-eclampsia
MAP0.141.15 (1.09–1.22)<0.0001
Stroke volume0.031.03 (1.0–1.07)0.04
UAPI1.454.26 (2.03–8.95)<0.0001
Birthweight below tenth centile
Stroke volume−0.040.95 (0.92–0.98)0.001
UAPI1.263.52 (2.0–6.19)<0.0001
image

Figure 1. ROC curves for the prediction of pre-eclampsia (A) and SGA (B).

Download figure to PowerPoint

Similarly, multiple logistic regression demonstrated that significant independent contribution in the prediction of SGA was provided by UAPI and SV (Table 4). The ROC curve for the final model is presented on Figure 1. The best point on the ROC curve for prediction of SGA was at the probability of more than 11.8% with a sensitivity of 66%, specificity of 77.5% and a screen-positive rate of 22% (Figure 1).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

The results of this study demonstrate that in nulliparous women who develop pre-eclampsia and/or SGA there are alterations in maternal cardiac function and UAPI from the first trimester of pregnancy.

Pre-eclampsia without SGA

At 11–14 weeks, women who subsequently develop pre-eclampsia without SGA have increased SV, CO and cardiac index. These findings suggest enhanced left ventricular systolic function and are further corroborated by the significantly higher mitral valve annulus shortening. In addition, while these women remain clinically normotensive at this stage in pregnancy, their MAP is increased due to higher CO rather than an increase in peripheral resistance. It is not surprising therefore that the mean UAPI was not different in this group compared with the normal pregnancies.

Similar to the systolic function, assessment of the diastolic function by the transmitral flow velocities has demonstrated higher maximum velocity of the E-wave in these women compared with women from any other group. This increase in E-wave maximum velocity reflects an increase in venous return in the left atrium21 and suggests that the increase in CO is probably the result of an increase in preload rather than an increase in myocardial contractility. Furthermore, the fact that the mitral valve A-wave maximum velocity is not different between groups suggests that the increase in MAP has not yet resulted in impairing left ventricular diastolic function.

SGA without pre-eclampsia

In women who subsequently delivered SGA babies without pre-eclampsia, at 11–14 weeks, MAP was normal, but there was a decrease in SV and an increase in total vascular resistance and mean UAPI. Furthermore, in these women, compared with the women who subsequently developed pre-eclampsia without SGA, the SV, CO and cardiac index were lower, but total vascular resistance and mean UAPI were higher. Further studies are needed to establish whether the increased peripheral resistance, on the background of normal MAP, is the result of reduced intravascular volume expansion and hence increased blood viscosity and/or it is the outcome of primary vascular dysfunction with normal plasma volume expansion.

Pre-eclampsia with SGA

The findings at 11–14 weeks in the pregnancies that had pre-eclampsia with SGA babies were more similar to those that developed SGA without pre-eclampsia than those that developed pre-eclampsia without SGA. However, although they were clinically normotensive, they had higher MAPs and the highest mean UAPI of all the groups. On this occasion, the increased MAP appears to be the result of increased peripheral resistance rather than a hyperdynamic circulation.

During the 1990s there was little consensus regarding the maternal haemodynamic changes in pre-eclampsia. The traditional view was that pre-eclampsia is a condition of a contracted intravascular space, reduced CO and increased peripheral resistance and blood viscosity.1,8,22–24 This was challenged by an alternative view that pre-eclamptic women are actually in a state of high CO and low peripheral resistance.2,7 Although this discrepancy was initially attributed to differences in technique, Bosio et al. in the late 1990s9 demonstrated that maternal central haemodynamics in pre-eclampsia may actually be a combination of these two states, depending on the stage of the disease. They used Doppler echocardiography to examine longitudinally 400 pregnant women and confirmed that those who subsequently developed pre-eclampsia had a more hyperdynamic circulation compared with women with uncomplicated pregnancies. Moreover, they demonstrated that in women developing pre-eclampsia there was a haemodynamic crossover to low CO and high-resistance circulation coinciding with the onset of the clinical syndrome.

However, these studies have not provided data on maternal cardiovascular physiology in the first trimester, presumably because they were concentrating at the later stages of the disease when it would be more applicable for screening and treatment. Additionally, both Bosio’s and Easterling’s data concentrated in late onset pre-eclampsia as evidenced by the fact that the mean gestation at delivery in their reports ranges between 369 and 39 weeks.7 Furthermore, in most of the studies carried out so far hypertensive women have been examined collectively without addressing separately the issue of fetal growth restriction and its interaction on maternal cardiovascular physiology. In one study by Easterling et al. the effect of maternal haemodynamics on fetal growth in hypertensive pregnancies has been investigated.10 They observed that high-resistance hypertension in women was associated with lower percentile weights for gestational age, while high CO and low-resistance hypertension were associated with normal fetal growth. However, the cardiac investigations in their study were performed in women who were clinically hypertensive.

Similarly to pre-eclampsia, the literature regarding maternal cardiovascular adaptation in fetal growth restriction is scanty and mainly concentrated in the second the third trimesters. The results of our work25 and previous reports in the literature26,27 have demonstrated reduced preload, CO and increased peripheral resistance in pregnancies complicated by growth restriction in the third trimester compared with uncomplicated gestations. Maternal cardiovascular function in fetal growth restriction in the first trimester of pregnancy, as evidenced by this study, is consistent with that of late second and third trimesters.

Implications

Our data are in agreement with the second and third-trimester observations of Bosio and Easterling associating pre-eclampsia at term with high maternal CO and low peripheral resistance. It appears that these haemodynamic characteristics are present from as early as the first trimester of pregnancy. However, we have additionally shown that this haemodynamic profile is not homogeneous and that, at least in the first trimester, there are potentially two separate maternal cardiovascular pathophysiological pathways in pre-eclampsia. They both demonstrate increased MAP from the first trimester of pregnancy. However, the first, which is characterised by high maternal CO and low peripheral resistance with normal mean UAPI, is associated with the development of pre-eclampsia without SGA. The second, characterised by low CO and high peripheral resistance and mean UAPI, is associated with pre-eclampsia with SGA. This observed difference between the two subgroups of pre-eclamptic women in peripheral resistance and UAPIs is compatible with the results of studies on uterine artery Doppler screening for pre-eclampsia in the second trimester, which reported that for a 5% screen-positive rate, the sensitivity for late pre-eclampsia (after 34 weeks) is about 25% and for early pre-eclampsia with SGA (before 34 weeks) is 70%.13

In our data, the factors that independently predict pre-eclampsia in the first trimester, even after controlling for maternal race and somatometric characteristics, are MAP, SV and mean UAPI. Similarly, the factors that independently predict SGA are SV and mean UAPI. The level of acceptable screen-positive rate is dependent on the impact on the women and the system of the intended intervention following the screening test. If our results are confirmed by larger observational studies then these may have marked influence on the treatment of pre-eclampsia. Early determination of haemodynamic subgroups may help obstetricians make a more informed selection of anti-hypertensives. Thus, in the group with a hyperdynamic circulation the administration of beta-blockers may be a more efficacious choice than methyldopa, which is a vasodilator. Conversely, in the high-resistance group the administration of an anti-hypertensive, such as a calcium-channel blocker, with the capacity for afterload reduction and improving cardiac function, should perhaps be considered as first-line therapy to prevent deterioration in left ventricular diastolic function.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

We have observed differences in maternal cardiac function and uterine artery resistance between pregnancies with normal outcome, pre-eclampsia without SGA, pre-eclampsia with SGA and those with SGA without pre-eclampsia. This heterogeneity between groups was evident by 11–14 weeks gestation in an apparently healthy, low-risk nulliparous population, well before the onset of clinical disease. These findings need confirmation in larger scale studies and their impact on screening and treatment of pre-eclampsia requires further assessment.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References
  • 1
    Visser W, Wallenburg HC. Central hemodynamic observations in untreated preeclamptic patients. Hypertension 1991;17:10727.
  • 2
    Benedetti TJ, Cotton DB, Read JC, Miller FC. Hemodynamic observations in severe pre-eclampsia with a flow-directed pulmonary artery catheter. Am J Obstet Gynecol 1980;136:46570.
  • 3
    Mabie WC, Ratts TE, Sibai BM. The central hemodynamics of severe preeclampsia. Am J Obstet Gynecol 1989;161:14438.
  • 4
    Phelan JP, Yurth DA. Severe preeclampsia. I. Peripartum hemodynamic observations. Am J Obstet Gynecol 1982;144:1722.
  • 5
    Robson SC, Boys RJ, Hunter S. Doppler echocardiographic estimation of cardiac output: analysis of temporal variability. Eur Heart J 1988;9:31318.
  • 6
    Easterling TR, Watts DH, Schmucker BC, Benedetti TJ. Measurement of cardiac output during pregnancy: validation of Doppler technique and clinical observations in preeclampsia. Obstet Gynecol 1987;69:84550.
  • 7
    Easterling TR, Benedetti TJ, Schmucker BC, Millard SP. Maternal hemodynamics in normal and preeclamptic pregnancies: a longitudinal study. Obstet Gynecol 1990;76:10619.
  • 8
    Kuzniar J, Piela A, Skret A, Szmigiel Z, Zaczek T. Echocardiographic estimation of hemodynamics in hypertensive pregnancy. Am J Obstet Gynecol 1982;144:4307.
  • 9
    Bosio PM, McKenna PJ, Conroy R, O’Herlihy C. Maternal central hemodynamics in hypertensive disorders of pregnancy. Obstet Gynecol 1999;94:97884.
  • 10
    Easterling TR, Benedetti TJ, Carlson KC, Brateng DA, Wilson J, Schmucker BS. The effect of maternal hemodynamics on fetal growth in hypertensive pregnancies. Am J Obstet Gynecol 1991;165:9026.
  • 11
    Vatten LJ, Skjaerven R. Is pre-eclampsia more than one disease? BJOG 2004;111:298302.
  • 12
    Martin AM, Bindra R, Curcio P, Cicero S, Nicolaides KH. Screening for pre-eclampsia and fetal growth restriction by uterine artery Doppler at 11–14 weeks of gestation. Ultrasound Obstet Gynecol 2001;18:5836.
  • 13
    Papageorghiou AT, Yu CK, Bindra R, Pandis G, Nicolaides KH; Fetal Medicine Foundation Second Trimester Screening Group. Multicenter screening for pre-eclampsia and fetal growth restriction by transvaginal uterine artery Doppler at 23 weeks of gestation. Ultrasound Obstet Gynecol 2001;18:4419.
  • 14
    Ganzevoort W, Rep A, Bonsel GJ, Fetter WP, Van Sonderen L, De Vries JI, et al. A randomised controlled trial comparing two temporising management strategies, one with and one without plasma volume expansion, for severe and early onset pre-eclampsia. BJOG 2005;112:135868.
  • 15
    Duley L, Williams J, Henderson-Smart DJ. Plasma volume expansion for treatment of women with pre-eclampsia. Cochrane Database Syst Rev 2000;2:CD001805.
  • 16
    Snijders RJ, Noble P, Sebire N, Souka A, Nicolaides KH. UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10–14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group. Lancet 1998;352:3436.
  • 17
    Davey DA, MacGillivray I. The classification and definition of the hypertensive disorders of pregnancy. Am J Obstet Gynecol 1988;158:8928.
  • 18
    Yudkin PL, Aboualfa M, Eyre JA, Redman CW, Wilkinson AR. New birthweight and head circumference centiles for gestational ages 24 to 42 weeks. Early Hum Dev 1987;15:4552.
  • 19
    Simpson IA. Echocardiographic assessment of long axis function: a simple solution to a complex problem? Heart 1997;78:21112.
  • 20
    Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol 1988;12:42640.
  • 21
    Nishimura R. Diastolic function by Doppler echocardiography. In: ChambersJ, MonaghanMJ, editors. Echocardiography, an International Review. Oxford: Oxford University Press; 1993. pp. 1122.
  • 22
    Groenendijk R, Trimbos JB, Wallenburg HC. Hemodynamic measurements in preeclampsia: preliminary observations. Am J Obstet Gynecol 1984;150:2326.
  • 23
    Hankins GD, Harvey CJ, Clark SL, Uckan EM, Van Hook JW. The effects of maternal position and cardiac output on intrapulmonary shunt in normal third-trimester pregnancy. Obstet Gynecol 1996;88:32730.
  • 24
    Heilmann L, Schmid-Schonbein H. [Hemodynamic and hemorheologic findings in patients with pregnancy-induced hypertension: comparison of pre-eclampsia and chronic hypertension]. Klin Wochenschr 1990;68:55964.
  • 25
    Bamfo JE, Kametas NA, Turan O, Khaw A, Nicolaides KH. Maternal cardiac function in fetal growth restriction. BJOG 2006;113:78491.
  • 26
    Vasapollo B, Valensise H, Novelli GP, Altomare F, Galante A, Arduini D. Abnormal maternal cardiac function precedes the clinical manifestation of fetal growth restriction. Ultrasound Obstet Gynecol 2004;24:239.
  • 27
    Vasapollo B, Valensise H, Novelli GP, Larciprete G, Di Pierro G, Altomare F, et al. Abnormal maternal cardiac function and morphology in pregnancies complicated by intrauterine fetal growth restriction. Ultrasound Obstet Gynecol 2002;20:4527.