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One-Stage Screening for Pregnancy Complications by Color Doppler Assessment of the Uterine Arteries at 23 Weeks’ Gestation

From Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, London, United Kingdom.

Address reprint requests to: Christoph Lees, MD Harris Birthright Research Centre for Fetal Medicine King’s College Hospital, Denmark Hill London SE5 9RS United Kingdom E-mail: cclees{at}compuserve.com

	Abstract

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Objective: To estimate the value of screening for preeclampsia and fetal growth restriction by performing color Doppler assessment of uterine arteries at 23 weeks’ gestation in predicting adverse pregnancy outcome.

Methods: Women with singleton pregnancies who attended routine ultrasonography at 23 weeks had color Doppler uterine artery imaging. Bilateral uterine artery notches were noted and left and right uterine artery pulsatility indices (PI) were measured. A mean PI of more than 1.45 was considered increased. Screening characteristics for predicting preeclampsia and delivery of small-for-gestational-age infants were calculated.

Results: Of 1757 pregnancies, increased PI was present in 89 (5.1%) and bilateral notches were noted in 77 (4.4%). Twenty-three of 65 women (35.3%; 95% confidence interval [CI] 23.9, 48.2) had increased PI and later developed preeclampsia, and 8 of 10 (80%; 95% CI 44.4, 97.5) with preeclampsia required delivery before 34 weeks. The respective values for women with bilateral notches were 21 of 65 (32.3%; 95% CI 21.2, 45.1) and 8 of 10 (80%; 95% CI 44.4, 97.5). The sensitivity of increased PI was 30 of 143 (21%; 95% CI 14.6, 28.6) for delivery of an infant with birth weight below the tenth percentile and 7 of 10 (70% 95% CI 34.8,93.3) for birth weight below the tenth percentile delivered before 34 weeks. The respective values for bilateral notches were 19 of 143 (13.3%; 95% CI 8.2, 20) and 5 of 10 (50%; 95% CI 18.7, 81.3).

Conclusion: A one-stage color Doppler screening program at 23 weeks identified most women who subsequently developed serious complications of impaired placentation associated with delivery before 34 weeks. The screening results were similar when the high-risk group was defined as women with increased PI or bilateral notches.

Preeclampsia, fetal growth restriction (FGR), placental abruption, and some cases of fetal death during the latter half of pregnancy are believed to result from impaired placentation in early gestation.¹ Deficient placentation is characterized by inadequate trophoblast invasion into the maternal spiral arteries and failure to develop low-resistance uteroplacental circulation. In the past 20 years, Doppler ultrasonographic studies of uteroplacental circulation have shown that high impedance to flow is associated with subsequent preeclampsia, FGR, and related complications.²

In our hospital, uterine artery Doppler assessment used to be an integral part of 20-week scanning that was offered to all pregnant women. Women with abnormal Doppler results were examined again at 24 weeks, and those with persistently abnormal results were followed in a high-risk clinic. The data from that two-stage approach were reported^3,4 and variations on the design were described.^5,6 Harrington et al⁴ found bilateral early diastolic notches in about 3.9% of the population, a group that contained about 54.5% of women who subsequently developed preeclampsia and 21.8% of those who delivered infants with birth weights below the tenth percentile for gestation.

Our policy on the second-trimester scan changed recently. The scan is done at 23 weeks and color Doppler is used in all cases to examine uterine arteries. This study examined the performance of one-stage color Doppler ultrasonography in predicting adverse pregnancy outcomes.

	Methods

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Women who had routine antenatal care at King’s College Hospital, London, an inner-city teaching hospital, had color Doppler examination of the uterine arteries at 23 weeks’ gestation (Acuson Aspen, Acuson Co., Mountain View, CA or Aloka SSD-1700, Aloka Co., Tokyo, Japan). The right and left uterine arteries were identified at the apparent crossover with the external iliac arteries, and pulsed-wave Doppler was used to obtain waveforms. When three similar consecutive waveforms were obtained, an early diastolic notch was noted, the pulsatility index (PI) was measured, and the mean PI of the two vessels was calculated.

Women with normal uterine artery Doppler received routine antenatal care. Those with bilateral uterine artery notches or those with mean PIs of 1.45 or higher constituted the screen-positive group and were followed in a high-risk clinic starting at 24 weeks’ gestation. A PI of 1.45 was chosen because it corresponds to the 95th percentile of the reference range for our population at that gestation.

Adverse outcomes were defined as preeclampsia, and birth weight less than the tenth and third percentiles for gestation⁷ before 34 weeks. Other adverse outcomes were fetal death and placental abruption (defined as vaginal bleeding leading to emergency delivery and evidence of retroplacental clot at delivery). Preeclampsia was defined by blood pressure of 140/90 mmHg or greater on two occasions more than 2 hours apart, with proteinuria (minimum of 300 mg per 24 hours or dipstick testing of 300 mg/L).

During the study (May through November 1998), 1941 consecutive women with singleton pregnancies who attended the ultrasonography unit had uterine artery Doppler examinations at 22 to 25 (mean, 23) weeks’ gestation. Doppler findings were recorded in a computer patient database, and thermal waveform images were retained. Complete demographic and outcome data were available for 1757 (90.6%) women. No women were subsequently excluded from the analysis. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated by using the Statistical Package for Social Sciences, version 6 (SPSS, Inc., Chicago, IL). Receiver-operating characteristic (ROC) curves for mean PI relating to adverse outcomes were generated by using a logarithmic trendline in the Microsoft Excel 97 software package (Microsoft, Inc., Redmond, WA).

	Results

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Complete demographic and outcome data were available for 1757 women (Tables 1 and 2). Their mean age was 30 years (range, 18 to 44 years). Abnormal Doppler results were present in 128 women (7.3%), including 77 (4.4%) with bilateral notches, 89 (5.1%) with mean PIs above 1.45, and 38 (2.2%) with high PIs and notches. In the group with missing outcomes, the proportion with high PIs or bilateral notches was 9 of 184 (5.1%), which was similar to that in patients with complete follow-up.

View larger version (15K): [in this window] [in a new window]   Figure 1. Receiver-operating curves of mean pulsatility index for preeclampsia. Curves of best fit are shown for the total group (dashed line) and for women who delivered before 34 weeks’ gestation (solid line).

View larger version (19K): [in this window] [in a new window]   Figure 2. Receiver-operating curves of mean pulsatility index for delivery of a small-for-gestational-age infant. Curves of best fit are shown for birth weight less than the tenth percentile (light dashed line) and less than the third percentile (light solid line) for the total group and weight less than the tenth percentile (dark dashed line) and less than the third percentile among women with delivery before 34 weeks’ gestation (dark solid line).

	Discussion

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Sensitivity for preeclampsia and delivery of small infants at the severe end of the spectrum were similar to those achieved in other two-stage programs. Thus, in a study of 1326 women at 19 to 21 weeks’ and 24 weeks’ gestation, Harrington et al⁴ reported that abnormal results on uterine artery Doppler were present in 3.9% of pregnant women, including 81.2% of those who developed preeclampsia before 34 weeks and 57.6% of those who delivered infants with birth weights below the tenth percentile before 34 weeks.

The main features of our study that distinguish it from previous ones are the use of color Doppler as the primary technique and relatively late gestation at screening. Most previous studies used continuous-wave Doppler to obtain waveforms from the uterine arteries without viewing them.^8,9 With color Doppler imaging, the precise location of uterine arteries as they cross the external iliac arteries is first identified and waveforms are obtained under direct vision with pulsed-wave Doppler. Gestation of 23 weeks was selected because previous studies that examined uterine arteries at earlier gestations reported high false-positive rates (the reason that two-stage programs were developed). In those previous studies, patients were examined with routine second-trimester fetal anomaly scans (18 to 20 weeks’ gestation), and those with abnormal uterine artery waveforms underwent second-stage screening, typically at around 24 weeks. For example, in the study of Harrington et al,⁴ the screen-positive rate (defined as bilateral notches or a unilateral notch and resistance index of more than 0.55) at 20 weeks was 17%; this rate decreased to 8.9% at 24 weeks.

One of the major criticisms of uterine artery Doppler screening studies has been the excessive reliance on subjective assessment of uterine artery waveforms for presence or absence of early diastolic notches. Our study used only color Doppler equipment, which might be associated with more reproducible measurements of impedance indices than is continuous-wave Doppler. For the same screen-positive rate, sensitivity of PI for preeclampsia and delivery of infants with birth weights less than the tenth percentile might be better than that of bilateral notches. Although some adverse outcomes occurred in the group with bilateral notches and normal PIs, inclusion of bilateral notches in the definition of screen-positive group introduces an element of subjectivity in the program and nearly doubles the screen-positive rate but only marginally improves sensitivity.

Women at highest risk are those with bilateral notches and a high mean PI. They have a 40% chance of developing preeclampsia and 45% for delivering infants of birth weight less than the tenth percentile. Although they comprise only 2% of the screened population, the relative risks for adverse outcomes before 34 weeks and fetal death in that group range from 50 to 100, a clinical risk that merits close antenatal surveillance.

Another important finding of our study was the negative predictive value, which was more than 99% for adverse outcomes before 34 weeks, placental abruption, and fetal death. This finding suggests that uterine artery screening might be used to determine the appropriate level of antenatal care in specific women. Women with normal uterine artery Doppler results are unlikely to develop preeclampsia, FGR or placental abruption and therefore do not necessarily need antenatal follow-up that is as close as that required in women with abnormal uterine artery Doppler findings. The real value of this method of screening is that using a mean uterine artery PI above 1.45 predicts most women who will experience severe preterm consequences of impaired placentation.

	Footnotes

 
The study was supported by The Fetal Medicine Foundation (Charity number 1037116).

The authors thank Paul Seed, Division of Primary Care and Health Sciences, Guy’s, King’s and St. Thomas’s Hospitals, for valuable statistical input.

PII S0029-7844(00)00946-7

Received September 27, 1999. Received in revised form April 17, 2000. Accepted May 11, 2000.

	References

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