CLINICAL OBSTETRICS AND GYNECOLOGY Volume 45, Number 4, 986992 2002, Lippincott Williams & Wilkins, Inc.

Nonstress Test: Evidence-Based Use in High-Risk Pregnancy

LAWRENCE D. DEVOE, MD, and CHANDRA R. JONES, MD Section of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta, Georgia

For three decades, the nonstress test (NST) has been accepted as a primary fetal surveillance tool for pregnancies at risk for intrauterine death. Subsequently, the NST has been used in combination with ultrasound observations of fetal activity and amniotic fluid volume as the biophysical profile. More recently, this test has been modified by the addition of vibroacoustic stimulation (VAS) or by Doppler recordings of fetal movement (actocardiotocography [ACTG]). The NSTs popularity stems from its ease of application in ambulatory settings, modest technical requirements, and lack of contraindications. Extensive clinical experience has been reported on use of the NST; however, the bulk of the evidence supporting its role in antepartum management is based on level II-3 evidence (multiple time series) rather than level I evidence (randomized controlled trials). In spite of this caveat, the incorporation of the NST into high-risk antepartum protocols has been associated with an apparent reduction in intrauterine feCorrespondence: Lawrence Devoe, MD, Medical College of Georgia, Department of OB/GYN, 1120 15th Street, Suite BA 7300, Augusta, GA 30912-3305. E-mail: ldevoe@mcg.edu
CLINICAL OBSTETRICS AND GYNECOLOGY /

tal death.1 This monograph will address the biologic basis of the NST in antepartum assessment, its application and interpretation, as well as the best evidence to support its continued use in the care of complicated pregnancies.

Developmental and Physiologic Basis

The NST is derived from intrapartum electronic fetal monitoring, in which the observation of fetal heart rate (FHR) accelerations presaged a good perinatal outcome.2 The generation of FHR patterns requires intact electrical conduction pathways, appropriate myocardial neurohormone receptors, sympathetic and parasympathetic reflex arcs, and inherent myocardial contractility. The FHR patterns that signal cellular hypoxia and acidosis include relatively fixed FHR baselines, loss of FHR variation and accelerations, and/or the appearance of spontaneous late FHR decelerations.3 The NST is also affected by constitutional and environmental factors such as fetal state and maturation, maternal state and medications, and diurnal biorhythms. As the
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Nonstress Test in High-Risk Pregnancy fetus approaches term, gross body movements linked with FHR accelerations increase.4 Fetal behavioral states influence the appearance of the NST. Quiet sleep states contain decreased levels of fetal activity and FHR variability; they typically last about 20 minutes but may persist for 2 hours in normal term fetuses. Fetal wakeful states are the periods when reactive FHR accelerations are most likely to be registered.5 In preterm pregnancies (2432 weeks gestational age), maturation of FHR central regulatory centers is incomplete. NSTs in this age group have lower mean amplitude (10 bpm) accelerations and brief spontaneous decelerations associated with movement.6 Quiet sleep states are also more common; longer observation may be needed to register sufficient acceleration counts. Maternal factors, such as fed state and glycemia, have inconsistent effects on NST appearance. Antihypertensive drugs, such as beta-blocking agents, lower mean baseline FHR and reduce acceleration frequency. Central nervous sytem depressants (barbiturates, opiates) may prolong quiet sleep states, while stimulants (cocaine, nicotine) may raise FHR baseline and decrease acceleration amplitude. In both circumstances, the time required to obtain test reactivity may need to be extended.7,8 Acute fetal hypoxemia may exert effects on resting FHR patterns that differ from those seen with milder, more chronic hypoxemia. Acute hypoxemia produces sudden and profound declines in numbers of fetal movements and accelerations, while chronic hypoxemia is associated with more gradual declines in these parameters. Consequently, the latter condition may not be detected by the NST for days to weeks.

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Doppler signals are not exact reproductions of electrocardiographic R-R intervals, as would be obtained from a direct fetal scalp electrode, the recent consensus statement on FHR interpretation suggests that long-term trends in FHR variability can be adequately approximated in such tracings.9
VAS

Fetal VAS with an electronic artificial larynx has been used as a primary method of FHR testing. Typical VAS responses of healthy term fetuses show at least a 10-bpm rise in baseline, occurring within 10 seconds, and lasting from 5 to 10 minutes. VAS-induced responses become more consistent as the fetus matures and during quiet sleep states.10
ACTG

Special Doppler filtering systems have permitted the registration of low-frequency shifts that occur with fetal movements. Besinger and Johnson11 have reported strong correlations of Doppler-detected fetal activity with that observed by concurrent realtime ultrasonography. These systems are now incorporated in many currentgeneration electronic fetal monitors. They enable better discrimination of fetal behavioral states by incorporating FHR reactivity, variability, and movements in the same time frame.

Indications, Interpretation, and Follow-Up

All pregnant women at high risk for intrauterine fetal compromise are candidates for NSTs. Common test indications include prolonged pregnancy; intrauterine growth restriction (IUGR); maternal hypertensive disorders; intrauterine growth restriction; selected fetal anomalies; Rh sensitization; and maternal diabetes mellitus, renal disease, and cardiac disease. No absolute or major relative contraindications exist for the NST.

Test Methods
STANDARD NST

Continuous wave Doppler transducers produce the signal sequences that are processed to generate a baseline rate. Although these

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DEVOE AND JONES

Test reactivity requires a minimum frequency of qualifying FHR accelerations during a specified time period. Recently, the NICHD Workshop on Fetal Heart Rate Monitoring concurred that a minimum threshold for acceleration recognitionthat is, amplitude of 10 bpm (<32 weeks gestational age) versus 15 bpm (>32 weeks gestational age)should reflect gestational age norms.9 In term gestations, a qualifying reactive tracing should contain at least two accelerations of amplitude more than 15 bpm in 20 minutes.1 For the VAS, a single qualifying acceleration must occur after application of the stimulus.1 NST nonreactivity is defined as the absence of or an inadequate number of qualifying accelerations. Additional qualifying features of an abnormal NST include sustained tachycardia (rate >160 bpm) or bradycardia (rate <110 bpm), decreased variability, periodic late or variable decelerations, spontaneous decelerations or bradycardias, or fetal arrhythmia. Sequential studies of NSTs in the same fetus12 suggest that fetal compromise may be signaled by a gradual decrease in acceleration counts, a subsequent decrease in the incidence of fetal movements, decoupling of accelerations with fetal movements, and finally the disappearance of both accelerations and movements. Appropriate use of the NST must consider the gestational age at test initiation, the frequency of test repetition, and the mode of test follow-up. The threshold for neonatal survival should determine the earliest such testing would be practical at a given institution (generally >24 weeks gestation). The interval between tests may vary according to specific medical/obstetric conditions. Since the screening performance of the NST declines with increasing test interval, most protocols recommend at least weekly testing.1 In selected and generally unstable high-risk conditions, such as severe IUGR or brittle diabetes mellitus, testing might be performed daily. The false-positive rate of nonreactive NSTs is sufficiently high to support addi-

tional testing. Immediate antepartum management after a nonreactive NST might include other studies, including ultrasound assessment of fetal anatomy, amniotic fluid volume, or a complete biophysical profile. Adverse perinatal outcomes after normal or reassuring FHR tests are uncommon.1 A cumulative review of available literature shows that a normal test confers a corrected antenatal mortality rate of only 0.3/1,000 and a perinatal death rate of 2.3/1,000.13

Validation and Supportive Evidence

The NST was incorporated into routine obstetric practice without rigorous randomized clinical trials. While the following supportive evidence represents the best that is currently available, no prospective randomized controlled trial containing sufficient numbers of patients adequately matched for gestational age, high-risk conditions, or obstetric management has yet been conducted. Critical reviews of testing standards and diagnostic values have shown a wide range of test sensitivity, specificity, and predictive values.13,14 Most reports on the NST demonstrate relatively high specificity (>90%) but much lower sensitivity, averaging 50%. Predictive values, positive and negative, are typically less than 50% and more than 90%, respectively. This suggests that the NST is better at ruling out than at ruling in fetal compromise. The relatively low prevalence of poor outcomes in most of the older reports (usually 10 15%) accounts for the decreased positive predictive value. Moreover, numerous antepartum, intrapartum, and postnatal outcomes, such as fetal death, neonatal death, intrapartum fetal distress, low Apgar scores, and neonatal intensive care, are often lumped together. Such lumping of outcomes that are not all readily predictable in the antepartum state may confound the assessment of the real value of this modality. Our group reported on the use of the NST in 1,000 consecutive high-risk patients15 categorized by test indications (eg, maternal

Nonstress Test in High-Risk Pregnancy

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FIG. 1.

Screening performance of NST versus test indications. First, not all of these trials used similar methods of randomization, and some discretion was allowed in clinical management. Next, they reflect practices of two decades ago and were applied to rather broadly defined obstetric populations. Finally, the number enrolled, 1,579 subjects, is an order of magnitude smaller than the minimum number required to demonstrate efficacy in reducing perinatal mortality in high-risk populations (approximately 15,000). 2. NST versus VAS. The meta-analysis of the randomized controlled trials comparing the NST with VAS is shown in Table 2.17 Few trials have compared these two testing methods for the major question of interest: can the TABLE 1.
Outcome C-section IP Abnl FHR Low Apgar score Abnl NN CNS NICU admission Perinatal death

hypertension, diabetes mellitus, IUGR, postdatism) (Fig. 1). In this study, screening values varied significantly according to the indication for testing. The best NST screening performances (sensitivities >70%) were associated with tests performed for IUGR or maternal hypertension.
RANDOMIZED CONTROLLED TRIALS

Prospective randomized controlled trials of the effectiveness of the NST have been very limited. These have consisted of NST (study group) versus NST concealed or not performed (control group); NST (control group) versus VAS (study group); and NST (control group) versus biophysical profile (study group). Meta-analyses of these three trial methodologies are discussed below.
1. NST versus non-NST (concealed or not performed).Table 1 summarizes the primary outcomes of interest examined in the metaanalysis.16 The four studies included in this review were performed in the United Kingdom during the mid-1980s. While it would appear that the use of the NST alone did not decrease the rates of adverse outcomes or obstetric interventions, these conclusions must be tempered by a number of considerations.

Effects of NST for Fetal Assessment on Outcomes

Odds Ratio 1.08 1.24 0.94 1.09 1.06 3.01 95% CI 0.851.37 0.981.58 0.691.27 0.631.88 0.791.41 1.197.62

Modified from Pattison N, McCowan L. Cardiotocography for antepartum fetal assessment. Cochrane Review. Cochrane Library, Issue 1, 2002, Oxford: Update Software.

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DEVOE AND JONES VAS: Effects on Perinatal Outcomes

Odds Ratio 0.61 1.40 0.86 0.18 95% CI 0.490.75 0.277.12 0.391.91 0.009.48

TABLE 2.
Outcome

Nonreactive test 5 Apgar <7 IPFD Stillbirth

also the potential irony of comparing a test with itself, as the NST is an important component of the biophysical profile. The cumulative sample size, again, lacks the power to convince clinicians that the more complex biophysical profile scheme is superior to the NST alone in reducing perinatal death or preventing unneeded interventions.

Modified from Tan KH, Smyth R. Fetal vibroacoustic stimulation for facilitation of tests of fetal well-being. Cochrane Review. Cochrane Library, Issue 1, 2002. Oxford: Update Software.

shorter VAS test be substituted for the standard NST without jeopardizing fetal management? Testing time in the trials included was reduced by an average of 5 minutes. The benefit of reducing overall testing time and the number of nonreactive tests (thereby decreasing unnecessary subsequent testing) was achieved without higher risks of fetal compromise. While more than 2,000 subjects were included in the cumulative metaanalysis, this review suggests that conclusions on efficacy in reducing perinatal death would require significantly larger numbers of subjects. 3. NST versus biophysical profile. A metaanalysis has been performed on the randomized controlled trials designed to compare the NST (control) versus the full biophysical profile (study group).18 While the study designs varied in nearly all of these trials, including methods of randomization, criteria for entry, and details of clinical management, the NST was used in the control arm, either alone or with an additional biophysical component (usually the amniotic fluid index). The intent to demonstrate the superiority of the complete biophysical profile over simpler surveillance techniques (eg, NST) was not upheld by the cumulative data shown in Table 3. There is TABLE 3.
Outcome Perinatal death 5 Apgar <7 Intrapartum fetal distress NICU admission

A recent randomized controlled trial has been performed that compares visual analysis versus computer analysis of the NST.19 This type of trial may become more important as automated FHR analytic systems gradually migrate into clinical settings. The computer system used was a commercially available automated FHR analysis system (Oxford Sonicaid System 8000, Chichester, UK) that has been extensively studied over the past two decades. Two groups (visual analysis and computer analysis) were compared for the need for additional testing (eg, full biophysical profile) and selected birth outcomes of interest (Apgar score, neonatal morbidity, perinatal death). The use of automated FHR analysis appeared to reduce the need for subsequent testing without increasing perinatal morbidity or mortality. A major concern for this study was that only 400 patients were enrolled and that sample size was determined a priori by the number needed to show a 50% reduction in neonatal intensive care duration.
NONRANDOMIZED PROSPECTIVE TRIALS

BPP: Effects on Perinatal Outcomes

Odds Ratio 1.30 1.21 0.74 0.14 95% CI 0.582.92 0.751.96 0.391.43 0.012.18

Modified from Alfirevic Z, Neilson JP. Biophysical profile for fetal assessment in high-risk pregnancies. Cochrane Review. Cochrane Library, Issue 1, 2002, Oxford: Update Software.

Few large studies have compared the NST with its predecessor, the contraction stress test (CST), an older testing method that was believed to be a more rigorous assessment of fetal-placental function. Freeman et al,20 reporting on more than 7,000 patients, showed that both tests were effective but noted higher antepartum death rates and perinatal morbidity occurred when the NST rather than the CST was used as the primary surveillance method. This study was biased in patient selection (more patients in the CST arm, more low-birthweight infants in the NST arm) and lacked standardization of test

Nonstress Test in High-Risk Pregnancy interpretation or follow-up. Devoe et al21 reported a prospective study comparing the NST and nipple stimulation CST in 1,200 patients (Table 4). Both arms were similar for gestational age, high-risk conditions, NST interpretation, and test follow-up. Neither testing approach was associated with significant differences in perinatal mortality or morbidity rates. The slightly greater sensitivity of the NST was counterbalanced by its increased mean testing time.

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Conclusions
In contemporary practice, obstetricians are constantly seeking a surveillance scheme that can provide the widest application, greatest ease of use, and highest effectiveness within the real constraints of time and cost. Any fetal well-being test can have significant consequences since it may launch subsequent, potentially risky interventions. The effectiveness of different testing schemes can be objectively measured by comparing their use versus either no testing or alternative tests. The best evidence to date shows that antepartum surveillance may use the NST but should not rely on it as a sole screening tool. Similar conclusions may be drawn for the use of VAS testing. Few clinical, nonrandomized trials of ACTG have been reported. A recent large survey of ACTG found that the predictive values of Doppler movement detection were as reli-

able as those provided by standard NST parameters.22 This review has demonstrated that the best evidence supporting the effectiveness of the NST is based on very limited population surveys, many of which were acquired in a different clinical era. More importantly, the most recent meta-analyses suggest that the sample sizes reported were too small to provide conclusive evidence on the actual effectiveness of the NST or its various modifications, including the VAS and biophysical profile. Further advances in FHR testing methods such as automated analysis and eventually expert systems may improve the technical performance of the NST. In turn, such improved tools may encourage the much larger population trials needed to answer the central question posed in this monograph on NST effectiveness. Finally, it is important to place a proper perspective on the role of FHR testing in the larger picture of clinical management of high-risk pregnancies. It should be clear that the NST can only be intended as a single rather than the sole part of the comprehensive evaluation of such patients. Clinical management, including obstetric interventions, should be based on a composite picture that incorporates as much patient information as possible and that includes adequate determination of fetal age and maturity.

References
TABLE 4. Comparative Data of the NST-CST Prospective Trial
NST Number of patients Adverse outcomes (%) Sensitivity (%) Specificity (%) Pos. pred value (%) Neg. pred value (%) 613 11.3 48 99 92 94 CST 582 11.5 30 99 80 92 P Value 0.91 0.03 0.39 0.30 0.39

Modified from Devoe LD, Morrison J, Martin J, et al. A prospective comparative study of the extended nonstress test and nipple stimulation contraction stress test. Am J Obstet Gynecol. 1987; 157:531.

1. American College of Obstetricians and Gynecologists. Antepartum Fetal Surveillance. Practice Bulletin 9, October 1999, Washington DC. 2. Powell OH, Melville A, MacKenna JL. Fetal heart rate acceleration in labor: Excellent prognostic indicator. Am J Obstet Gynecol. 1979;134:36. 3. Murata Y, Martin CB, Ikenoue T, et al. Fetal heart rate accelerations and late decelerations during the course of intrauterine death in chronically catheterized rhesus monkeys. Am J Obstet Gynecol. 1982;144:218. 4. Natale R, Nasello-Patterson C, Turok R.

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