Fetal Doppler mechanical PR interval: correlation with fetal heart rate, gestational age and fetal sex

Authors

  • A. Wojakowski,

    1. Fetal Medicine Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
    2. Division of Radiology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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  • G. Izbizky,

    1. Fetal Medicine Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
    2. Division of Obstetrics, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
    3. Department Obstetrics & Gynecology, Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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  • M. E. Carcano,

    1. Fetal Medicine Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
    2. Division of Radiology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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  • H. Aiello,

    1. Fetal Medicine Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
    2. Division of Obstetrics, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
    3. Department Obstetrics & Gynecology, Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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  • P. Marantz,

    1. Fetal Medicine Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
    2. Division of Pediatric Cardiology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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  • L. Otaño

    Corresponding author
    1. Fetal Medicine Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
    2. Division of Obstetrics, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
    3. Department Obstetrics & Gynecology, Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
    • Division of Obstetrics, Hospital Italiano de Buenos Aires, Potosí 4135, (1199), Buenos Aires, Argentina
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Abstract

Objectives

To establish normal fetal values for the mechanical PR interval by pulsed-wave Doppler at 16–36 weeks of gestation, and to evaluate the influence of fetal heart rate (FHR), gestational age (GA) and fetal sex.

Methods

Fetal mechanical PR intervals were evaluated prospectively by obstetric ultrasound examination. Healthy mothers with sonographically normal fetuses from singleton pregnancies were included. Mechanical PR intervals were measured from simultaneous mitral and aortic Doppler waveforms, from the onset of left atrial contraction (mitral A-wave) to the onset of left ventricular ejection (aortic pulse wave). Simple and multiple linear regression analyses were performed to examine the correlation between PR interval and GA, FHR and fetal sex.

Results

We evaluated 336 fetuses at 16–36 weeks. The mean ± SD FHR was 143.4 ± 8.3 beats per min (bpm). The PR intervals had a typical Gaussian distribution with a mean ± SD of 122.4 ± 10.3 ms. Robust linear regression showed that the PR increased by about 0.40 ms (95% CI, 0.22–0.58) per gestational week (P < 0.001), and this relationship remained after adjustment for FHR and fetal sex. PR intervals diminished by 1.4 (95% CI, 0.75 to 2.0) ms for each 5 bpm increase in FHR (P < 0.001), independently of GA and fetal sex. No fetal sex differences were observed.

Conclusions

We provide normal fetal values for the mechanical PR interval at 16–36 weeks of gestation. Mechanical PR intervals in normal fetuses are influenced by GA and FHR independently, and both variables should be taken into account when evaluating fetuses at risk for congenital heart block. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.

INTRODUCTION

Isolated congenital heart block (CHB) is a rare condition with an incidence of 1 in 15 000–20 000 liveborns1, 2. However, fetuses from pregnant women with anti-SSA/Ro and anti-SSB/La auto-antibodies are at increased risk for CHB3–7. These antibodies are detected mainly in patients with systemic lupus erythematosis, rheumatoid arthritis, Sjögren syndrome and undifferentiated autoimmune disease, but also in asymptomatic individuals8. The risk of CHB in the presence of these antibodies is around 2%, and the risk is five to 10 times higher if there is a previously affected fetus or child. There is some evidence that this condition could be total or partially prevented by administration of corticosteroids6, 9–12.

Though a third-degree atrioventricular (AV) block may be the first abnormal sign of cardiac dysfunction, there is a subgroup of pregnancies in which the heart block takes place in two stages13, 14. The first stage occurs between 18 and 24 weeks and is characterized by a normal fetal heart rate (FHR) with a prolonged PR interval. In the second stage, the pathological process progresses to a complete block. In pregnancies treated with dexamethasone during the first stage, normalization of the PR interval has been observed13–15. Thus, the key to the prevention of severe forms of CHB lies in the early identification of affected fetuses, during the first stage of the condition, by means of PR interval measurement.

Measurement of the PR interval by fetal electrocardiography has been described16; however, the technique has not been widely adopted into clinical practice. In 2000, Glickstein et al.17 developed a method to measure the fetal mechanical PR interval by echocardiography with pulsed Doppler, which is equivalent to the electric PR interval in surface electrocardiography13, 17–27. The diagnostic accuracy and reproducibility of this methodology were validated among physicians participating in a multicenter prospective fetal echocardiographic study22. However, the influence of gestational age (GA), FHR and fetal sex on the PR interval has not been well established. Some authors found that the PR interval is independent of GA and FHR17, 28, while others observed a positive correlation with GA measured by pulsed Doppler, electrocardiography or magnetocardiography19, 24, 29.

The objective of our study was to establish reference values of the AV conduction time through Doppler assessment of the mechanical PR interval and to evaluate its correlation with GA, FHR and fetal sex.

METHODS

This was an observational study conducted between February 2007 and February 2008 in the Fetal Medicine Unit at the Hospital Italiano de Buenos Aires. Doppler measurement of the fetal mechanical PR interval was performed prospectively in sonographically normal singleton pregnancies between 16 and 36 weeks of gestation. GA was established according to last menstrual period and first-trimester ultrasound; in case of discrepancy, ultrasound dating was used. Fetal sex assignment was performed by ultrasound and confirmed postnatally. All women underwent transabdominal sonography which included color and pulsed Doppler examination of the fetal heart. For the purposes of this study, each fetus was evaluated on a single occasion during the pregnancy.

The mechanical PR interval was measured during basic echocardiography which is part of our routine obstetric ultrasound examination. All evaluations were performed by one of two operators (A.W. and H.A.) using a Toshiba Xario (Toshiba Medical Systems, Tokyo, Japan) ultrasound machine equipped with a 3.5-MHz convex transducer. The mechanical Doppler PR interval was measured using a pulsed wave of the fetal heart to obtain the measurements. The two-dimensional directed pulsed Doppler gate was placed distal to the mitral valve at an angle of 20° with respect to the long axis of the left ventricular outflow tract. By obtaining the pulsed Doppler signal in this location, the mitral valve Doppler flow pattern could be determined (specifically, the E/A ratio), as well as the aortic Doppler pattern simultaneously on the same tracing (Figure 1). The sweep speed of the tracing was 4 cm/s. The image was frozen, and the interval between the onset of the mitral valve A-wave and the upstroke of the aortic valve flow were measured. The time interval in milliseconds (ms) between these two Doppler samples represents the delay between the onset of atrial contraction and the onset of ventricular contraction, which is representative of the mechanical PR interval (Figure 2). Three measurements per subject were taken, over two consecutive cardiac cycles, and averaged. Fetal heart rate, expressed in beats per min (bpm), was assessed in the same time frame (Figure 2).

Figure 1.

Four-chamber view and position of the simple Doppler volume in the mitral-aortic continuity. The flow waves through the mitral valve (E- and A-waves) and the aortic valve (V-wave) are shown on the left.

Figure 2.

Mechanical PR interval measured between the onset of atrial contraction (A-wave) and the onset of ventricular contraction (V-wave).

The distribution of the different variables was evaluated by graphic methods and by the Shapiro–Wilk test. To investigate the relation between mechanical PR interval and GA, FHR and fetal sex, simple and multiple robust (with variance calculated by the sandwich method of Huber/White) linear regression models were used. The 95th and 99th centiles of PR interval measurements were calculated. The study protocol was evaluated and approved by the local institutional review board.

RESULTS

Three hundred and thirty-six low-risk pregnant women with a single sonographically normal fetus between 16 and 36 weeks were included. The median GA was 26 (interquartile interval, 20–31) weeks. The mean ± SD FHR was 143.4 ± 8.3 bpm. The mechanical PR interval showed a typical Gaussian distribution, with a mean ± SD of 122.4 ± 10.3 ms. One hundred and forty-eight fetuses were male and 188 were female.

Mechanical PR increased with increasing GA. The robust linear regression model showed that the mechanical PR interval increased by around 0.40 (95% CI, 0.22–0.58) ms per week of GA (P < 0.001) (Figure 3). This increment remained after adjusting for FHR and fetal sex. In contrast, mechanical PR decreased with increasing FHR, dropping by 1.4 (95% CI, 0.75–2.0) ms for every 5 bpm increment in FHR (P < 0.001), independent of GA and fetal sex (Figure 4). The expected values of mechanical PR according to GA and FHR can be obtained with the following formula: mechanical PR interval (ms) = 143.9 + 0.29 × GA (weeks) − 0.20 × FHR (bpm). The PR intervals were similar in male and female fetuses.

Figure 3.

Linear regression of mechanical PR interval against gestational age (GA). The median (continuous line) and 95% CIs (dashed lines) are shown. Mechanical PR interval (in ms) = 112 + 0.40 × GA (in weeks).

Figure 4.

Linear regression of mechanical PR interval against fetal heart rate (FHR). The median (continuous line) and 95% CIs (dashed lines) are shown. Mechanical PR interval (in ms) = 163.3 − 0.28 × FHR (bpm).

Reference values are given in Tables 1 and 2.

Table 1. Mechanical PR interval (in milliseconds) according to gestational age (GA)
GA (weeks)Percentile
50th95th99th
16–19117.0132.3138.1
20–24121.0136.9143.3
25–29121.0139.9146.8
30–34125.0142.9150.5
35–38121.0145.7153.9
Table 2. Mechanical PR interval (in milliseconds) according to fetal heart rate (FHR)
FHR (bpm)Percentile
50th95th99th
120–124129.0146.8154.6
125–129129.0147.5155.0
130–134125.0145.6152.9
135–139123.0141.4148.5
140–144121.6139.8146.6
145–149117.0135.8142.4
150–154118.5135.1141.4
155–159117.0133.0139.1
160–180121.0139.6145.4

DISCUSSION

Our data suggest that the mechanical PR interval is significantly influenced by GA and FHR. The PR interval increased with increasing GA, and the increment seemed to be constant between 16 and 36 weeks. The PR interval decreased with increasing FHR. Importantly, our data show that these effects are independent of each other.

The literature has shown conflicting results on this issue. Some authors found that the PR interval is independent of GA and FHR17, 28. This was the principle on which the PRIDE trial was based; thus, it used a fixed cut-off of 150 ms (3 SD), above which the PR interval was considered to be prolonged15. Conversely, similar to our results, others described a direct correlation between PR interval and GA, when the former was measured by fetal echocardiography19 or fetal magnetography30 and in electrophysiological studies31, and an inverse correlation between PR interval and FHR was found19. Although it might be assumed that the variation in PR interval with FHR and GA is due to the association between these two variables (decreasing FHR with increasing GA), our data show that GA and FHR in fact have an independent effect on PR interval. The fact that PR interval decreases with increasing FHR might seem intuitive, given that a higher FHR will result in shorter cardiac cycles and consequently a shorter PR interval, which forms part of the cardiac cycle. The observation that PR interval increases with increasing GA independently of FHR could be explained by the increase in cardiac size with progressing GA. The larger the size of the cardiac chambers, the more prolonged is the time required for the depolarization/repolarization wave in the myocardium23.

The natural history of CHB has not been elucidated completely. Some cases of third-degree block would not be preceded by a less severe degree of block. It is not yet known what proportion of affected fetuses shows two-step progression to a complete heart block, nor what proportion of fetuses with a prolonged PR interval shows spontaneous regression15. The presence of a fetal third-degree heart block is associated with a high risk of perinatal morbidity and mortality, and it does not respond to prenatal treatment. Thus, early detection is key in the prevention of severe forms of CHB. However, it is essential to establish appropriate cut-off values in order to identify fetuses at risk. For instance, using the fixed cut-off of 150 ms that was used in the PRIDE study15, some prolonged PR intervals (> 99th centile) would be missed in the second trimester, while some normal values could be interpreted as being abnormal in the third trimester (Tables 1 and 2).

We evaluated fetal sex because it is well known that this variable influences other biometric parameters, including biparietal diameter, head circumference, abdominal circumference, femur length, fetal weight, nuchal translucency thickness and width of brain lateral ventricular atrium32–35. Recent reports have also suggested that early cardiovascular development may differ in male and female fetuses36. However, with respect to mechanical PR, we did not find any difference between male and female fetuses.

In conclusion, our data show that normal values of mechanical PR interval vary independently with GA and FHR, and both variables need to be considered when it is measured in both clinical and research situations. Our study suggests that, with proper training, assessment of PR interval could be performed to screen the at-risk population in the context of an obstetric scan; abnormal results should then trigger the use of a specialized echocardiographic assessment.

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