Physiologic Basis for Antenatal Surveillance

The application and interpretation of antepartum fetal monitoring necessitates an understanding of the progressive fetal changes that can occur secondary to increasing placental insufficiency progressing to intrauterine demise. In experiments involving animal and human fetuses, hypoxemia and acidosis have been shown consistently to alter fetal biophysical parameters such as heart rate, movement, breathing, and tone.4,19,21 The fetal heart rate (FHR) is normally controlled by the fetal central nervous system (CNS) and mediated by sympathetic or parasympathetic nerve impulses originating in the fetal brainstem. The presence of intermittent FHR accelerations associated with fetal movement is believed to be an indicator of an intact fetal autonomic nervous system. In a study of fetal blood sampling of pregnancies resulting in healthy neonates, Weiner and colleagues established a range of normal fetal venous pH measurements.²⁷ In this population, the lower 2.5 percentile of fetal venous pH was 7.37. Manning and colleagues. showed that fetuses without heart rate accelerations had a mean umbilical vein pH of 7.28 (± 0.11), and fetuses with abnormal movement had a mean pH of 7.16 (± 0.08).¹⁷ These and similar observations were the basis for the development of antenatal fetal testing modalities that are currently in use.

Patient Assessment of Fetal Movement

The patient’s own subjective assessment of the activity of her fetus is perhaps the simplest and most universal of antepartum surveillance methods, although its subjective nature leads to difficulty in quantification and empiric evaluation. As described above, fetal movement decreases with increasing hypoxia, which serves as the physiologic basis of the biophysical profile as well as subjective fetal movement monitoring. As a result, a perceived decrease in subjective fetal movement should generally be evaluated. Beyond this generalized recommendation, various formalized strategies of fetal monitoring (colloquially referred to as “kick counts”) have been proposed. One of the more common is to determine the time it takes for the perception of 10 movements during a period of specific, restful evaluation and to contact one’s provider if the duration is 2 hours or more. However, systematic reviews have identified neither an optimal strategy nor clear evidence that routine, quantified fetal movement assessment can prevent stillbirth.¹⁵

Nonstress Test

In most institutions, the first-line assessment tool for fetal surveillance is the nonstress test (NST). In the outpatient setting the patient typically rests in a reclining chair with a lateral tilt. Ideally she should have not recently smoked. Although commonly provided in antepartum testing units, the maternal ingestion of juice or food has not been demonstrated to increase the probability of a reactive nonstress test.⁷ The FHR is monitored with an external transducer for up to 40 minutes and observed for the presence of accelerations above the baseline. A reactive test is one in which there are at least two accelerations that peak 15 beats/min above the baseline and last (not at the peak) for at least 15 seconds before returning to baseline (Figure 13-1), colloquially referred to as “15 × 15.” Most NSTs are reactive within the first 20 minutes. For tests that are not, possibly because of a fetal sleep cycle, an additional 20 minutes of monitoring may be needed. A nonreactive NST is one in which two such accelerations do not occur within 40 minutes.

The optimal gestational age at which to begin antenatal surveillance depends on the clinical condition. In making this decision, the physician must weigh the risk of intervention at a premature gestational age against the risk of intrauterine fetal death. The American College of Obstetricians and Gynecologists recommends initiating testing at 32 to 34 weeks’ gestation for most at-risk patients, with the acknowledgment that some situations may warrant testing earlier at 26 to 28 weeks of gestation.¹ FHR variability and reactivity vary with gestational age. Before 28 weeks of gestation, 50% of all NSTs may not be reactive. From 28 to 32 weeks of gestation, approximately 15% of normal fetuses have nonreactive NSTs. Thus prior to 32 weeks nonstress tests are often considered reactive if there are two accelerations that peak 10 beats/min above baseline and last for at least 10 seconds (“10 × 10”) rather than the traditional cutoff (“15 × 15”). Of note, the magnitude of accelerations in fetuses less than 32 weeks can vary normally over time, thus a fetus at less than 32 weeks is reactive by 10 × 10 criteria even if it had previously demonstrated 15 × 15 accelerations.⁹

Although the NST is noninvasive and easy to perform, it is limited by a high false-positive rate. Normal fetuses often have periods of nonreactivity because of benign variations such as sleep cycles. Vibroacoustic stimulation may be used safely in the setting of a nonreactive NST to elicit FHR accelerations without compromising the sensitivity of the NST.²⁹ In this situation the operator places an artificial larynx on the maternal abdomen and activates the device for 1 to 3 seconds. This technique is often useful in situations in which the FHR has normal beat-to-beat variability and no decelerations, but does not show any accelerations. If the test remains nonreactive, further evaluation with a biophysical profile or contraction stress test (CST) is warranted as long as the FHR is otherwise reassuring. However, if the tracing is overtly concerning (see Category III later in this chapter), additional testing may need to be deferred in favor of delivery depending upon the exact gestational age and clinical circumstance.

Contraction Stress Test

The CST is designed to evaluate FHR response to maternal uterine contractions. The principles that are applied to the evaluation of intrapartum FHR monitoring (see FHR Monitoring) are used here. In response to the stress of the contraction, a hypoxemic fetus shows FHR patterns of concern, such as late decelerations.

Similar to the NST, for the CST the patient is placed in a recumbent tilted position, and FHR is monitored with an external fetal monitor. The FHR pattern is evaluated while the patient experiences at least three contractions lasting 40 seconds within a 10-minute period. If the patient is not contracting spontaneously, contractions may be induced with nipple stimulation or intravenous oxytocin. Nipple stimulation can be self-administered by the patient or a breast pump can be used. If no late or significant variable decelerations are noted on FHR tracing, CST is considered to be negative. If there are late decelerations after at least 50% of the contractions, CST is positive. If late decelerations are present less than 50% of the time, or if significant variable decelerations are present, the test is considered to be equivocal. Contraindications to the performance of CST include clinical situations in which labor would be undesirable (e.g., placenta previa or previous classic cesarean section).

Biophysical Profile

The biophysical profile was developed by Manning and associates as an alternative tool to other methods of antenatal surveillance to evaluate fetal well-being.¹⁸ As originally described, it combines NST with four components evaluated by ultrasound (Box 13-1). In a 30-minute period either 2 or 0 points are assigned depending upon if the criteria are fulfilled or unfulfilled. The final score will thus range from 0 to 10 with no odd numbers (either 0 or 2; 1 point is never awarded for each criteria). A combined score of 8 or 10 indicates fetal well-being. A score of 6 is considered to be equivocal; it usually merits delivery if the pregnancy is at term or additional or repeat testing if the pregnancy is preterm. A score of 4 or less is considered to be abnormal, and in the absence of reversible causes consideration would need to be given to delivery except in the setting of extreme prematurity or other unusual extenuating circumstances.

Of note, fetal breathing is not usually present during active labor, to the extent that the absence of fetal breathing on ultrasound has actually been evaluated as an assessment tool for the presence of “true” preterm labor.⁶ Thus there should be precaution in the interpretation of a biophysical profile (BPP) in a patient who is or may be in active labor.

Amniotic Fluid Volume Assessment

Amniotic fluid volume is commonly estimated by ultrasound via one of two primary methods (see Chapter 25). The amniotic fluid index (AFI) is calculated by measuring and adding the maximal vertical pockets of fluid (without loops of umbilical cord) in each of the four quadrants of the maternal abdomen (Figure 13-2). Alternatively, the single deepest vertical pocket of fluid alone can be measured. Decreased amniotic fluid volume, or oligohydramnios, is typically defined as either an AFI of 5 cm or less or no single measurable vertical pocket of fluid greater than 2 cm, although gestational age–specific normograms can be used as well. Neither method is perfectly sensitive or specific for the detection of oligohydramnios.¹⁴ Oligohydramnios can occur secondary to a range of causes including rupture of the fetal membranes and congenital fetal anomalies of the urinary tract. In the absence of membrane rupture or congenital anomalies, however, the most concerning etiology would be decreased fetal urine production secondary to the shunting of blood flow away from the fetal kidneys in the context of uteroplacental insufficiency.

When oligohydramnios is diagnosed, the first step is to rule out membrane rupture and congenital anomalies and, if not present, assess the fetus for other evidence of uteroplacental insufficiency, including fetal biometric measurements to assess growth restriction. Delivery is usually performed for oligohydramnios at term, although at preterm gestations delivery decisions will involve multiple factors including the exact gestational age and presumed etiology of the decreased fluid, with conservative management being reasonable in many circumstances.

Doppler Flow Velocimetry

Qualitative and quantitative evaluation of maternal and fetal blood vessels by Doppler sonography has been the focus of intense research over the last several years and is continuing to evolve rapidly. The list of clinical scenarios in which it has been utilized includes the evaluation of the fetal middle cerebral artery in cases of red blood cell isoimmunization,²⁰ monochorionic twins with twin-twin transfusion syndrome,²⁸ the screening and diagnosis of congenital cardiac anomalies, and the diagnosis of congenital vascular anomalies. These indications will likely continue to expand. However, the primary utility of Doppler sonography is in the evaluation of a fetus with possible intrauterine growth restriction. In normal pregnancies or when the fetus has demonstrated normal growth, there is no current role for Doppler sonography of fetal vessels because they have not been found to convey benefit in a low-risk population.²³

For the fetus in which measurements demonstrate potential growth restriction, Doppler sonography has both diagnostic and predictive benefit. Although more extreme biometric deviations are usually pathologic, many fetuses with ultrasound weight estimations at the fifth to tenth percentile will be small but healthy. In these cases, either the ultrasound weight estimation is incorrect or the true birth weight is less than 10% but the fetus is just an otherwise healthy outlier of the normal weight distribution. Doppler sonography of fetal vessels in these circumstances can potentially identify the fetuses that are healthy, thus avoiding iatrogenic prematurity and additional antenatal testing. Abnormal results, however, can identify a fetus that is at true risk. In cases of suspected growth restriction, abnormal blood flow in the umbilical artery is associated with increased risk of perinatal morbidity and mortality. A Cochrane review of 11 randomized trials showed a trend toward decreased perinatal mortality with the use of Doppler assessment of the umbilical artery in high-risk pregnancies.²² The use of umbilical artery Doppler flow velocimetry as a primary testing method results in fewer antenatal tests and less intervention with similar neonatal outcome compared with pregnancies monitored by NST alone.¹¹

Although there are many potential causes of intrauterine growth restriction, most cases that are not secondary to intrinsic fetal etiology (e.g., TORCH, skeletal dysplasias, genetic anomalies) arise from uteroplacental insufficiency, which itself can be detected through the Doppler evaluation of the umbilical artery carrying blood from the fetus to the placenta. Pathologic placental processes such as thrombosis and infarction decrease the relative size of the placental vascular bed and increase placental vascular resistance. As placental vascular resistance increases, there is a progressive diminution of blood flow during diastole, resulting in an altered ratio of systolic (S) and diastolic (D) blood flow that can be detected with Doppler sonography (Figure 13-3). Numerically, this can be quantified as either the systolic/diastolic (S/D) ratio, resistance index ([S-D]/S), or pulsatility index ([S-D]/average blood flow). In more extreme circumstances, blood flow during diastole may be absent (absent end diastolic flow or AEDF) or even reversed (REDF), as demonstrated in Figure 13-3. Of note, the placental vascular bed normally evolves and increases during the course of pregnancy, and thus S/D ratios are evaluated according to gestational age–specific normograms.

Abnormal umbilical artery Doppler S/D ratios imply placental vascular pathology, although the test does not otherwise specifically address the immediate state of fetal oxygenation or health. Many individuals with mild elevations of the S/D ratio will deliver healthy babies at term, which is why Doppler sonography is discouraged in low-risk patients or those with normal fetal biometric evaluations. For a fetus with both concerning biometric measures and abnormal umbilical artery Doppler results, the immediate fetal health can be assessed by the NST, CST, or BPP as described previously. Additionally, the fetal status can be evaluated through Doppler sonography of additional fetal vessels beyond the umbilical artery. Turan and colleagues serially evaluated 104 fetuses with uteroplacental insufficiency and growth restriction and performed sonography on the middle cerebral artery, umbilical artery and vein, and ductus venosus until the patient was delivered.²⁶ A sequential pattern of worsening and multivessel Doppler anomalies can often be identified prior to a decompensation of fetal health necessitating delivery (Figure 13-4). In response to increasing hypoxia, blood flow is diverted away from nonvital organs such as the kidney (resulting in oligohydramnios) and preferentially toward vital organs such as the brain, a process referred to as cephalization. The increased cerebral blood flow can be reflected in a decreasing pulsatility index in the fetal middle cerebral artery (Figure 13-5). The absence of cephalization can be reassuring, although it should be noted that it can sometimes be absent in critically ill fetuses that have lost the ability to preferentially direct their blood flow. More severe degrees of hypoxia eventually generate myocardial decompensation, which can be evaluated through the Doppler evaluation of the ductus venosus and umbilical artery. Just as jugular venous pulsations can be a sign of heart failure in an older adult with heart disease, myocardial decompensation in the fetus can generate venous pulsations that are then reflected back through the ductus venosus and umbilical vein. When present these can be an ominous finding, with delivery often being necessitated within a few days.

While normal Doppler results in a fetus with concerning biometric measurements signal that a pregnancy can safely continue, the optimal management of a fetus with abnormal Doppler studies is far from clear. If other tests of fetal well-being (nonstress test, biophysical profile) are not reassuring, then delivery is usually indicated. Likewise, abnormal Doppler results can be used to guide the frequency of antepartum testing. Other than additional monitoring, however, few actual treatment options exist to improve the fetal health while in utero, and thus the question often becomes whether or not to deliver prematurely. For a fetus with growth restriction and abnormal multivessel Doppler evaluations but a reassuring NST, CST, or BPP, further decompensation at some point in the future is probable, and ideally one would want to deliver prior to an irreversible injury. Thus one might consider iatrogenic premature delivery despite the reassuring NST or BPP. On the other hand, many fetuses with absent or reverse umbilical artery diastolic flow can safely remain in utero for even several weeks.³ The Growth Restriction Intervention Trial (GRIT) attempted to provide guidance in this regard by randomizing 548 women with “compromise” in a premature fetus to either immediate or delayed delivery.¹⁰ No significant differences in overall mortality were identified between the two groups, since the increase in stillbirth in the expectant management group was balanced by neonatal losses secondary to prematurity in the group that underwent immediate delivery. The subjects included in GRIT were very heterogeneous with regard to growth and Doppler parameters, making more exact clinical recommendations difficult.