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The focus in this chapter is the assessment of fetal well-being, particularly as a means for the recognition of the infant that may be at risk of hypoxic-ischemic cerebral injury. The identification of an intrauterine disturbance in gas exchange between the human fetus and mother (i.e., asphyxia) or the likelihood that such a disturbance will occur during labor or delivery is critical, in view of the large body of data indicating that intrauterine asphyxia occurs in a large proportion of infants with hypoxic-ischemic encephalopathy. Moreover, attempts at prevention of the brain injury caused by intrapartum asphyxia demand an awareness of when a risk for such injury is present. This chapter reviews the major current means of antepartum assessment of the fetus as it relates to decisions regarding the timing and mode of delivery, followed by the approach to intrapartum assessment of fetal well-being. Issues that are reviewed in other sections of the book include those related to evaluation of the placenta and to conditions that may influence fetal well-being ( Chapters 9 to 11 ), genetic disorders, cerebral dysgenesis ( Chapters 5 to 8 ), and fetal cerebral metabolic disorders ( Chapters 31 to 33 ).
Although the nature, timing, and frequency are not entirely established, it is clear that some hypoxic-ischemic insults affect the brain before labor and delivery (i.e., during the antepartum period). The search for means of assessing such disturbances, acute or chronic, has been the subject of a vast amount of obstetrical research. Antepartum surveillance regimens were developed principally to prevent stillbirth, particularly in the setting of a high-risk pregnancy, such as intrauterine growth restriction (IUGR). Thus the evaluation of antepartum techniques of monitoring for a reduction in hypoxic-ischemic injury has not been specifically studied. However, with the expansion of monitoring, the impact of monitoring on Apgar scores and neonatal intensive care unit (NICU) admission has allowed some insights (see later). In this section, a brief review of the current means of evaluating the fetus during the antepartum period is provided. The techniques are best divided into those based on measurement of fetal movement, fetal heart rate (FHR), a combination of factors that include fetal movement and heart rate (biophysical profile), fetal growth, and blood flow velocity in uterine and fetal blood vessels ( Table 21.1 ). All of these techniques are usually applied with greater frequency to women who are deemed to be at greater risk for pregnancy and neonatal complications. Thus identifying the fetus at risk for cerebral injury may allow timely detection of impending fetal jeopardy allowing intervention or delivery to reduce the risk of possible cerebral injury.
Fetal movement |
Detection by maternal perception or by real-time ultrasonography |
Fetal heart rate |
Nonstress test: response of fetal heart rate to movement |
Contraction stress test: response of fetal heart rate to stimulated (oxytocin and nipple stimulation) or spontaneous uterine contraction |
Fetal biophysical profile |
Combination of fetal breathing, movement, tone, heart rate reactivity, and amniotic fluid volume |
Fetal growth |
Detection of intrauterine growth retardation |
Fetal blood flow velocity |
Detection by the Doppler technique of flow velocity in umbilical and fetal systemic and cerebral vessels |
A common theme found in relation to all the techniques outlined later is that the presence of normal results is associated with good fetal and neonatal outcomes. Thus the absence of any abnormality can be reassuring . However, abnormal tests have low positive predictive values for abnormal outcomes, making their utility as diagnostic tests for fetal vulnerability poor. Finally, many studies have not included outcomes of greatest relevance, including neonatal morbidity and neurodevelopmental outcomes.
Fetal movement is a useful indicator of fetal health. Techniques for monitoring fetal movement have included systematic maternal recording of perceived activity, electromechanical devices (tocodynamometry), and real-time ultrasonography (see Table 21.1 ). The first of these methods is the most convenient and widely used, the second is primarily an investigative tool, and the third has received increasingly wide clinical and investigational use because of the diversity of information that it can provide.
Fetal movements are one aspect of the determination of fetal behavioral states. Most commonly, fetal behavioral states are defined according to the quantitative and qualitative aspects of fetal body movements, eye movements, and FHR. Distinct fetal states are definable by 36 to 38 weeks of gestation. Recognizable behavioral states at that time are summarized in Table 21.2 . These states approximate neonatal behavioral states, that is, quiet sleep, rapid eye movement sleep, quiet waking, and active waking. Active sleep is the most frequently observed, followed by quiet sleep. The waking states are either infrequent or rare.
STATE b | BODY MOVEMENTS | EYE MOVEMENTS | FETAL HEART RATE PATTERN |
---|---|---|---|
1F | Absent (occasional startle) | Absent | Narrow variability, isolated acceleration |
2 F | Present (frequent bursts) | Present | Wide variability, acceleration with movement |
3 F | Absent | Present | Wide variability, no accelerations |
4 F | Present (almost continuous) | Present (continuous) | Long accelerations or sustained tachycardia |
b These fetal states approximate neonatal behavioral states: quiet sleep (1F), active sleep (2F), quiet waking (3F), and active waking (4F).
Distinct maturational changes in fetal movement can be identified ( Fig. 21.1 ). Although with ultrasonography it is possible to detect movement as early as the second month of gestation, maternal perception of movement (“quickening”) occurs at approximately 16 weeks. Thereafter, the movements increase in strength and reach a plateau from 26 to 32 weeks of gestation, when an abrupt fall to a second plateau occurs between 32 and 36 weeks. No appreciable change occurs thereafter until delivery. A recent cross-sectional study examining maternal perception of fetal movement in pregnancies with normal outcome found that the strength of fetal movements in the last trimester is accretive, with frequent presence of fetal hiccup, and that a diurnal pattern of fetal movements is much more commonly appreciated in the evening and at nighttime, including bedtime. These investigators emphasized that a more sensitive marker of fetal well-being is a change in the quality of fetal movements compared with arithmetic counting.
Prechtl and others emphasized the quality of fetal movements and the striking maturational changes in the variety and complexity of these movements. Certain fetal movements increase in incidence gradually with advancing gestation (e.g., breathing, sucking, and swallowing); other movements increase in incidence to a plateau (e.g., general movements, isolated arm movements); and still others increase in incidence and then decrease (e.g., startles, hiccups).
The relation of quantity and quality of fetal movement to fetal well-being is illustrated by the study summarized in Fig. 21.2 . Most investigations examining fetal movements and perinatal outcomes have done so through two fundamentally different but related ways . The first series of studies has examined the association of altered fetal movements in retrospective case-control studies of women who experienced a stillbirth infant compared with controls. The second series of studies have prospectively studied the effect of maternal monitoring of fetal movements on perinatal outcomes, focused on reduction in stillbirths.
Concerning the retrospective association of reduced fetal movements with women who experienced stillbirth, it has been estimated approximately 30% to 55% of women who have a late stillbirth will have experienced an episode of reduced fetal movement within a week of their stillbirth. With specific regard to the observation that reduced fetal movements are a risk indicator for stillbirth, there have been six large cohort case-control studies published since 2015 that have assessed the relationship between women’s reporting reduced fetal movements and stillbirth, with all of them documenting a positive correlation between reduced fetal movements and stillbirth ( Table 21.3 ).
RETROSPECTIVE STUDIES OF FETAL MOVEMENTS AND STILLBIRTH | PROSPECTIVE MONITORING OF FETAL MOVEMENTS TO REDUCE STILLBIRTH | CLINICAL PRACTICE RECOMMENDATIONS FOR MONITORING FETAL MOVEMENTS |
---|---|---|
Strong association of report of altered fetal movements in the week before stillbirth | Monitoring for number of movements (count to 10) shows trend toward reduced stillbirth | WHO recommends monitoring fetal movements |
Reduced frequency of movements | Unproven benefit in monitoring fetal movements prospectively to reduce stillbirth | 10%–15% of all women report reduced movement in late gestation (low specificity) |
Reduced quality of movements in evening, reduced bursts of high activity, and reduced hiccups | Monitoring quality may increase sensitivity and specificity of monitoring |
With more specific regard to the nature of the fetal movements, in one large study it was noted that not only decreased frequency of fetal movements (adjusted odds ratio [aOR] 2.29, 95% confidence interval [CI] 1.31 to 4.0) but also the perception of “quiet or light” fetal movement in the evening (aOR 3.82, 95% CI 1.57 to 9.31) was associated with an increased risk for late stillbirth. Conversely, the investigators also noted that more instances of “more vigorous than usual” fetal movement (aOR 0.52, 95% CI 0.32 to 0.82), daily perception of fetal hiccups (aOR 0.28, 95% CI 0.15 to 0.52), and increased length of fetal movement clusters or “busy times” (aOR 0.23, 95% CI 0.11 to 0.47) were all associated with reduced risk of stillbirth. In conclusion, in these retrospective studies women with stillbirth were more likely than controls to have experienced alterations in fetal movement, including decreased strength, frequency, and in particular a fetus that was “quiet” in the evening .
However, although this association is reported retrospectively by women who have experienced a stillbirth, the effect of the prospective maternal monitoring for reduced fetal movements on perinatal outcomes has been of less clear association with stillbirth ( Table 21.3 ). Two recent large studies examined the effect of training interventions to increase women’s awareness of fetal movements to reduce the incidence of stillbirths and other adverse perinatal outcomes. Both studies found that increasing women’s awareness toward fetal movements was not associated with reduced stillbirth incidence or improved perinatal outcome. The AFFIRM study was the larger of these studies and included 33 hospitals with data collected from 409,175 pregnancies (157,692 deliveries during the control period, 23,623 deliveries in the washout period, and 227,860 deliveries in the intervention period). The incidence of stillbirth was 4.40 per 1000 births during the control period and 4.06 per 1000 births in the intervention period (aOR 0.90, 95% CI 0.75 to 1.07; P = .23). The authors concluded that the reduced fetal movements care package did not lead to a reduction in the risk of stillbirths and that the benefits of a policy that promotes awareness of reduced fetal movements remain unproven.
These findings are consistent with a Cochrane review from 2015 on the efficacy of fetal movement counting for the assessment of fetal well-being, which included five studies with 71,458 women. All included women with uncomplicated pregnancies, except one study that included high-risk women as participants. Two studies compared fetal movement counting with standard care, as defined by trial author. Two studies compared two types of fetal movement counting comparing once-a-day (Cardiff Count to Ten) with more than once-a-day fetal movement counting methods. One study compared fetal movement counting with hormone assessment evaluated with an average of five determinations of serum total estriol and human placental lactogen. The first comparison of fetal movement monitoring compared with standard care showed no difference in mean stillbirth rates (standard mean difference 0.23, 95% CI 0.61 to 1.07) or fetal deaths. There was no difference in cesarean section rate between groups within any of these three comparisons of fetal movement monitoring. There were no data on perinatal mortality or severe morbidities. The conclusions of the Cochrane review were that sufficient evidence did not exist to influence clinical practice.
In a more recent systematic review, women who used fetal movement counting once or more per week had fewer stillbirths by 21% than did control women, a difference with a strong trend that was not statistically significant. However, in the studies that included women who undertook systematic counting of fetal movements ( n = 11,069), a significant reduction in the rate of stillbirth was found.
Despite the evidence demonstrating a strong association between reduced fetal movements and stillbirth, the majority of women reporting reduced fetal movements will have a healthy baby. Approximately 10% to 15% of women of late pregnancy will experience symptoms of reduced fetal movements but the percentage of fetal death is much lower than 10% to 15%.
It remains a common obstetrical practice to educate women about the normal range and duration of fetal movements to count 10 fetal movements typically within 30 minutes ( Table 21.3 ). Others have suggested that rather than the counting-to-10 alarm limits, every woman should be familiarized with her own baby’s characteristics of movements to detect deviations in the personal pattern. Currently, the World Health Organization continues to recommend the daily surveillance of fetal movements, using any kind of method, as an effort to make pregnant women and health care professionals aware of the importance of fetal movements as an indicator of fetal well-being, especially in late pregnancy.
The observations described in the preceding paragraphs are reminiscent of many of those made during the neonatal neurological examination. The use of fetal movements as part of a detailed analysis of fetal behavior by real-time ultrasonography led to the identification of distinct behavioral states , as noted earlier. These analyses include assessment of a large variety of specific body movements (e.g., yawning, stretching, and startle), as well as fetal eye movements, posture, breathing, and heart rate. The analogy of these phenomena to those observed after birth in the premature infant (see Chapter 12 ) is obvious, and, indeed, to a major extent, one can consider these observations a kind of fetal neurological examination . When amplified by such assessments as habituation of the fetus to vibrotactile stimuli or response to acoustical stimuli, the analogy to neurological assessment becomes even more impressive. Finally, detailed analysis of the quantity and quality of fetal breathing can provide still further information about the fetal nervous system. A recent review noted the major factors that can affect the behaviors of fetal body movements, breathing, and fetal behavioral states ( Table 21.4 ). With the wide use of real-time ultrasonography, the standardization of the neurological phenomena observable, and—most important and still most difficult—the correlation of aberrations with the topography of neuropathology, highly valuable evaluation of the fetal central nervous system (CNS) and dysfunction thereof should be possible. The design of appropriate interventions for disturbances then would be an appropriate next step.
EXPOSURE | BODY MOVEMENTS | BREATHING MOVEMENTS | BEHAVIORAL STATE |
---|---|---|---|
Oligohydramnios | Smaller amplitude, slow | Decreased | |
IUGR | Decreased, smaller amplitude | Decreased | Delayed, disorganized |
Maternal nicotine | Temporarily reduced | Decreased | Prolonged state 1 F |
Maternal cocaine | Increased/excessive | Altered | Delayed/disorganized |
Maternal steroids | Decreased 1–3 days | Decreased 1–3 days | Loss of diurnal rhythm |
Maternal diabetes | Abnormal, poor repertoire | Increased | Longer activity cycles |
The evaluation of fetal well-being by antepartum FHR testing is a standard obstetrical practice in high-risk pregnancies. The two commonly used techniques determine FHR changes with either stimulated (or spontaneous) uterine contractions (contraction stress test) or spontaneous fetal events (e.g., fetal movement test, or nonstress test) (see Table 21.1 ).
Of the two techniques, the nonstress test is the approach often used as an initial evaluation. In general, the particular value of the technique is the determination of a healthy fetus, based on the demonstration of at least two accelerations of FHR during the period of observation (usually ≈40 minutes), generally in association with fetal movement or vibroacoustical stimulation. The accelerations must exceed 15 beats/min and last at least 15 seconds, and the normal result is called a reactive nonstress test. A nonreactive test is characterized by the failure to note such accelerations over the observation period. The demonstration of accelerations of FHR with acoustical stimulation and the correlation of a reactive acoustical stimulation test with the conventional nonstress test have led to use of such stimulation as part of the nonstress test in many centers.
Concerning the predictive value of nonstress testing, the incidence of fetal distress leading to cesarean delivery increases from about 1% to 20% when antepartum reactive and nonreactive patterns are compared. It is clear, however, that most “abnormal” or nonreactive tests are not followed by difficulties with labor and delivery. A normal, reactive nonstress test is highly predictive of fetal well-being. Thus, as with most other modes of fetal evaluation, both antepartum and intrapartum, the prediction of a normal fetus and the relative lack of need for intervention are the greatest values of the test .
Nonstress tests appear to have less value in noncompromised fetuses before 32 weeks of gestation. Between 24 and 28 weeks gestational age, up to 50% of nonstress tests have been documented as nonreactive, decreasing to 15% being nonreactive from 28 to 32 weeks. In general, 15% of all nonstress tests will be nonreactive. In the largest series of nonstress tests, the stillbirth rate (corrected) was 1.9 per 1000. Thus, the negative predictive value is 99.8%, with a high false-positive rate (75% to 90%) associated with nonreactive nonstress tests. In addition, the test does not detect such important maternal-fetal problems as oligohydramnios, umbilical cord or placental abnormalities, growth disorders, and twin demise. When suspicion or concern for such problems exists, another approach, using ultrasonography, as in fetal biophysical profile, is essential. Despite the rational approach to these measures of fetal behavior and well-being, several randomized prospective trials that have used weekly surveillance with nonstress tests have shown no benefit to the fetus or infant.
The contraction stress test in the past was most commonly used as a follow-up evaluation after a nonreactive stress test. Experimental data suggest that the occurrence of late decelerations with contractions, the basis for a positive (abnormal) stress test , is an early warning sign of uteroplacental insufficiency. The established clinical and experimental premise of the stress test is that chronic uteroplacental insufficiency results in late decelerations of the FHR, a sign of fetal hypoxia (see following discussion), in response to uterine contractions, which can be stimulated by breast stimulation or oxytocin infusion. In approximately 10% of women, spontaneous uterine contractions obviate the need to stimulate uterine contractions. A positive (abnormal) result is indicated by persistent late decelerations over several or more contractions; these positive tests can be subdivided further as reactive , when accompanied by accelerations at some time during the test, or nonreactive , when not accompanied by accelerations. An equivocal result refers to the occurrence of nonpersistent late decelerations . A negative stress test is defined as absence of any late decelerations with the contractions.
As with nonstress testing and other fetal assessments, a negative stress test is a reliable indicator of fetal well-being. Concerning the predictive value of a positive stress test, in one multiinstitutional study of high-risk pregnancies, a negative test was followed by perinatal death in less than 1% of cases versus 5% to 20% of infants with positive contraction tests (the lower value was for infants with reactive positive tests, and the higher value was for those with nonreactive positive tests). Similarly, an Australian study showed that among 72 patients with nonreactive positive spontaneous contraction stress test results, there was a 28% perinatal mortality rate and of the 42 infants that survived the neonatal period and were assessed, 27% had neurological handicap.
Currently, the contraction stress test is no longer the principal method for follow-up in most centers. This change relates to logistical and interpretive difficulties and relatively low positive predictive values. The fetal biophysical profile is now favored as the primary means of fetal surveillance for high-risk pregnancies, identified by a nonreactive nonstress test or other evidence.
In view of the relatively high incidence of false-positive assessments with the tests of FHR just described, a series of fetal measures , termed a composite biophysical profile , has been used to refine antepartum evaluation ( Table 21.5 ). These measures include quantitation not only of FHR reactivity (see the earlier discussion of the nonstress test) but also of fetal breathing movements, gross body movements, fetal tone (as assessed by posture and flexor-extensor movements), and amniotic fluid volume (see Table 21.1 ). Each item is graded, usually on a score of 0 to 2. The use of real-time ultrasonography has made such an assessment possible, and the relative ease of this methodology in modern obstetrical centers has led to widespread use. The rationale of using such a profile is entirely reasonable (i.e., the various measures reflect activity of several levels of the CNS, including cerebrum, diencephalon, and brainstem). However, the threshold level of hypoxemia or acidemia necessary to alter the output of these CNS centers is unknown. The centers that regulate the coupling of fetal movement with heart rate accelerations (reactivity) and fetal breathing movements are most sensitive, followed by those regulating fetal movements, and finally by those controlling fetal tone.
BIOPHYSICAL PROFILE SCORE a | INTERPRETATION | PREDICTED PERINATAL MORTALITY | RECOMMENDED MANAGEMENT |
---|---|---|---|
0/10 | Severe acute asphyxia | 60/100 | Immediate delivery by cesarean section |
2/10 | Acute fetal asphyxia, most likely with chronic decompensation | 125/100 | Delivery for fetal indications (usually cesarean section) |
4/10 | Acute fetal asphyxia likely; if oligohydramnios present, chronic asphyxia also very likely | 9.1/100 | Delivery by obstetrically appropriate method with continuous monitoring |
10/10 | No evidence of fetal asphyxia | <0.1/100 | No acute intervention |
The predictive value of the score for fetal acidemia is demonstrated by the data in Fig. 21.3 , which illustrate the relation of the fetal biophysical score to umbilical venous pH determined by cordocentesis. Similar correlations are available regarding incidence of meconium passage during labor, signs of intrapartum fetal distress, and perinatal mortality. Of particular importance, the degree of abnormality of the fetal biophysical score has been shown to correlate with the later occurrence of cerebral palsy (CP) ( Fig. 21.4 ) and predicted perinatal mortality ( Table 21.4 ). Data from a single center suggested that alterations in obstetrical management provoked by the results of the score could lead to a three- to fourfold decline in CP rates. Despite these positive results, a recent Cochrane review found no significant difference in outcomes between those high-risk pregnancies monitored with biophysical profile compared with other forms of fetal assessment, mainly FHR monitoring. This finding supports the challenge in the widespread implementation of these evaluative tools of fetal well-being in randomized controlled trials, despite strong and rational observational data. The apparent lack of benefit may relate to subject selection, application of the testing, and/or limitations in the outcome measures. The modified biophysical profile consists of the nonstress test and amniotic fluid index to assess for fetal well-being. This profile combines a short-term marker with the chronic marker of amniotic fluid. Amniotic fluid index is measured by summing the measurements of deepest cord-free amniotic fluid pocket in each of the abdominal quadrants. A sum of 5 or greater is considered reassuring. The negative predictive value for this test is similar to that for the full biophysical profile.
As with other antepartum assessments, advances in ultrasound technology have provided the capability of accurate quantitative assessment of fetal growth (see Chapter 9 ). The particular value of this assessment is in the detection of intrauterine growth retardation (see Table 21.1 ), although other aberrations of growth (e.g., large body size and large head) have important implications for management of labor and delivery and the neonatal period, as discussed elsewhere in this book. Detection of intrauterine growth retardation is important, principally because significant management decisions follow. Most such fetuses are “constitutionally small,” are not at increased perinatal risk, and do not require aggressive intervention. However, some such infants (≈5% to 10%) exhibit a major developmental anomaly, including chromosomal aberration, that may require further intrauterine assessment (e.g., amniocentesis and chromosomal or other genetic analyses). Moreover, of greatest importance, particularly in this context, is that approximately 10% to 15% of infants with intrauterine growth retardation are growth retarded because of uteroplacental failure and are at risk for intrapartum asphyxia . In one series from a single high-risk service, 35% of growth-retarded fetuses exhibited intrapartum FHR abnormalities indicative of fetal distress. A significant increase in fetal asphyxia, as judged by cord acid-base studies, was apparent even when growth-retarded infants were compared with other high-risk groups. Moreover, growth-retarded infants with intrapartum fetal heart decelerations demonstrate considerably higher umbilical artery (UA) lactate levels than do normally grown infants with similar decelerations. Thus growth-retarded infants tolerate labor less well than do normally grown infants, perhaps in part because of deficient stores of glycogen in liver, heart, and, possibly, brain. Therefore antepartum detection of such infants is important in formulating rational decisions concerning further assessment of the fetus (e.g., fetal biophysical profile, Doppler blood flow velocity studies) and optimal management of labor and delivery (see next section). A recent review for the American College of Obstetrics and Gynecology by experts in the field showed that the biophysical profile correlated with acidemia on cordocentesis in surveillance of IUGR ( Fig. 21.5 ).
Doppler velocimetry is a now well-described technique used to assess fetal status ( Table 21.6 ). Several vessels have been interrogated, including the (maternal) uterine artery, fetal middle cerebral artery (MCA), UA, umbilical vein, and ductus venosus (DV). The most commonly examined and clinically useful vessel is the fetal UA. The waveform in normally growing fetuses is characterized by high-velocity diastolic flow, and the commonly measured indices include systolic/diastolic ratio, resistance index, and pulsatility index (PI) (see Chapter 13 ). Marked abnormality in the waveform is characterized by absent or reversed diastolic flow. These waveforms correlate histopathologically with small artery obliteration in placental tertiary villi, and functionally with fetal hypoxia, acidosis, and prenatal morbidity and mortality. These studies have been predominantly undertaken in women who have a fetal diagnosis of intrauterine growth retardation.
METHOD | MEASURES | INDICATIONS | VALUE |
---|---|---|---|
Umbilical cord artery |
|
High-risk fetus, particularly IUGR | Reduction in fetal mortality and in obstetrical interventions |
Fetal MCA |
|
High-risk fetus, particularly IUGR | Abnormal MCA PI was associated with greater perinatal morbidity |
Fetal DV |
|
IUGR—particularly useful between 20 and 32 weeks’ gestation | Determination of delivery by DV measures resulted in slight increase in mortality but reduction in morbidity |
Most studies based on the use of Doppler in pregnancy have focused on the UA. The principal quantitative parameters of the Doppler waveform used have been the PI of Gosling (peak systolic velocity [PSV] – end diastolic velocity [EDV]/mean velocity), the resistance index of Pourcelot (PSV-EDV/PSV) and the PSV/EDV ratio . The values of these ratios, in general, are not affected by the angle of insonation, clearly difficult to maintain constant in the clinical situation. The PI and the resistance index reflect, in largest part, vascular resistance. The principal change in UA blood flow velocity with progression of normal pregnancy is a decline in the resistance parameters. Although the decline is gradual, a more pronounced decrease occurs after 30 weeks of gestation. This decrease is considered secondary to a decrease in placental vascular resistance, related particularly to increased numbers of small vessels. A similar phenomenon was documented in the fetal lamb. The decrease in placental vascular resistance with advancing pregnancy is accompanied by an increase in volemic placental blood flow, calculated in human fetuses by simultaneous measurements of the blood flow velocity in the umbilical vein and the cross-sectional area of that vessel by combined Doppler and imaging ultrasonography ( Fig. 21.6 ).
The major application of Doppler studies of blood flow velocity in the UA has been in the investigation of the high-risk fetus. In intrauterine growth retardation, the principal finding is an increase in the resistance measures. With progression of this disturbance in resistance measures in the UA, marked impairment of the end diastolic flow (EDF) or even loss or reversal of diastolic flow (an ominous sign) may occur ( Fig. 21.7 ).
In one study, the changes in resistance indices preceded antepartum late heart rate decelerations in more than 90% of fetuses who developed such decelerations, and the median duration of the interval between the severe abnormality of resistance measure and decelerations was 17 days. The importance of the rising placental vascular resistance to the fetus is shown by the striking curvilinear relationship between the PI in the UA and the lactate concentration in fetal blood, a measure of fetal hypoxia ( Fig. 21.8 ). The clinical predictive value of the diastolic flow in the UA was apparent in a study of 459 high-risk pregnancies. Thus, the rate of fetal or neonatal death in the presence of EDF was 4% and increased to 41% with absence of flow and to 75% with reversal of flow. With prompt and detailed further fetal assessments and appropriate interventions, the unfavorable outlook with absence of diastolic flow has not been so marked. However, reversal of flow is associated with a considerable risk of fetal compromise, perinatal mortality, neonatal neurological disturbances, and subsequent neurodevelopmental disability, with the magnitude of risk varying considerably with the selection of the population studied.
The use of Doppler assessment of the UA flow in fetuses with growth restriction or those at risk, such as hypertensive pregnancies, has been shown to lead to a reduction in perinatal mortality and reduced unnecessary obstetrical intervention. Further meta-analyses, comparing the use of umbilical Doppler in high-risk groups, has confirmed this conclusion. A recent Cochrane review with 18 studies and more than 10,000 pregnancies, demonstrated that women with Doppler assessment had a significantly lower perinatal mortality (1.2%) compared with those without Doppler studies (1.7%) (risk ratio [RR] 0.67, 95% CI 0.46 to 0.96). Although the data for secondary outcomes showed that there were fewer adverse outcomes in the Doppler group, this finding did not reach statistical significance. Interestingly, there was a reduction in interventions, such as induction of labor and cesarean delivery in the Doppler group. Importantly, though, there is a lack of data on long-term neurological development on the infants in either group.
The central abnormality in the growth-retarded fetus leading to the increase in placental vascular resistance is a disturbance in placental vessels. The major features include loss of small blood vessels, decreased vascular diameter because of media and intima thickening, and thrombosis. Placental vascular obstruction produced by a variety of experimental techniques in pregnant sheep reproduced the changes in the resistance measures observed in the human fetus. Indeed, elevated UA resistance measures have been observed in a variety of pathological conditions of the placenta, including partial abruption, placental scarring from intervillous thrombosis, and inflammatory villitis secondary to bacterial or viral infection. Thus, the value of this technique in the evaluation of a wide variety of high-risk pregnancies is very high.
The most recent Cochrane review of fetal and umbilical Doppler ultrasound in high-risk pregnancies found that the use of Doppler ultrasound of the UA was associated with fewer perinatal deaths (RR 0.71, 95% CI 0.52 to 0.98; 16 studies, 10,225 babies, 1.2% vs. 1.7%). The results for stillbirths were consistent with the overall rate of perinatal deaths, although there was no difference between groups for this outcome (RR 0.65, 95% CI 0.41 to 1.04; 15 studies, 9560 babies). When Doppler ultrasound was used, there were fewer inductions of labor (average RR 0.89, 95% CI 0.80 to 0.99; 10 studies, 5633 women) and fewer cesarean sections (RR 0.90, 95section Rsection 0.90section 95% CI 0.84 to 0.97; 14 studies, 7918 women). No difference was found in operative vaginal births (RR 0.95, 95% CI 0.80 to 1.14; four studies, 2813 women), or in Apgar scores lower than 7 at 5 minutes (RR 0.92, 95% CI 0.69 to 1.24, seven studies, 6321 babies). Data for serious neonatal morbidity were not pooled because of high heterogeneity between the three studies that reported this outcome (1098 babies).
In a recent review of the international guidelines for the surveillance and timing of birth in infants with IUGR, Doppler evaluations of the UA were considered a key mode of surveillance and mode for determination of the timing and mode of delivery ( Table 21.7 ).
UNITED STATES | UNITED KINGDOM | CANADA | |
---|---|---|---|
UA Doppler frequency | From GA where delivery considered every 1–2 weeks | Every 2 weeks if UA normal and twice weekly if abnormal | Every 2 weeks |
Cerebral Doppler studies | Insufficient evidence to recommend | MCA Doppler > 32 weeks with normal UA Doppler | MCA and DV recommended with Doppler studies |
CTG | If abnormal Doppler, twice weekly | Not as only surveillance | Consider if BPP abnormal |
BPP | If abnormal Doppler, twice weekly | Do not use | Not discussed |
Timing of birth with abnormal Doppler | Consider delivery >37 weeks when decreased diastolic flow in UA | Deliver by 37 weeks if MCA PI < 5th centile or abnormal UA Doppler | Consider delivery >34 weeks if any Doppler abnormal |
Timing of birth with normal Doppler | Deliver between 38 and 39 + 6 weeks | >34 weeks if static growth or by 37 weeks | >37 weeks or earlier if BPP or amniotic fluid decreased |
Mode of birth | IUGR alone not indication of cesarean delivery | Induction with continuous CTG | Not specified |
In contrast, Doppler measurement of UA flow has been shown repeatedly not to be useful in a low-risk or unselected population . A Cochrane review, including more than 14,000 women from 20 studies, compared the outcomes of low-risk pregnancies with either routine ultrasound or no Doppler ultrasound. This comparison failed to demonstrate a reduction in perinatal death or serious neonatal morbidity in the Doppler group, nor were there differences in the secondary outcomes, including prematurity, mode of delivery, neonatal resuscitation, or a 5-minute Apgar score lower than 7.
Fetal MCA Doppler has been proposed as an additional test to UA Doppler. The changes in the fetal MCA may better reflect fetal cardiovascular adaptations to hypoxia or blood flow redistribution that may have neurological effects. There are multiple measures from the fetal MCA, including EDV, PSV, and time-averaged (mean) velocity (TAV). The fetal MCA PI has become a key parameter used in fetal middle cerebral arterial Doppler assessment being calculated by subtracting the EDV from the PSV and then dividing by the TAV. A decrease in the PI has been considered a compensatory phenomenon to protect the fetal brain in the context of IUGR. During normal pregnancy , in contrast to the decreasing values for resistance measures defined in the umbilical circulation, values in the cerebral circulation change little until approximately the last 5 weeks, when a distinct decline is apparent ( Fig. 21.9 ).
As with Doppler studies of the umbilical vessels, study of cerebral blood flow velocity has been directed most commonly at the growth-retarded fetus. The dominant abnormality has been a diminished value of cerebral resistance indices, in contrast to the elevated value in the UA ( Fig. 21.10 ). This apparent vasodilation in the cerebrum at a time of decreasing umbilical flow has been interpreted as an adaptive response, perhaps mediated by hypoxia, and has been termed fetal brain sparing . It seems reasonable to suggest that, with severe impairment of umbilical flow and hypoxia, such an adaptive response could become insufficient. Indeed, the decline in cerebral resistance indices and the increase in umbilical resistance indices have been quantitatively combined as a cerebral-to-umbilical ratio.
An adaptation of MCA Doppler study is the cerebroplacental ratio (CPR), which is calculated as the ratio of MCA PI to UA PI Doppler and has been hypothesized to be more accurate than its individual components. An association with adverse perinatal outcome has been the focus of several literature reviews. A recent review comparing CPR and UA Doppler measures was undertaken in 30 studies (5046 patients); MCA Doppler and UA Doppler were compared in 38 studies (18,999 patients); and CPR and MCA Doppler were compared in 23 studies (4262 patients). The data showed that sensitivity of CPR outperformed that of UA Doppler, and sensitivity of MCA Doppler performed less well than did those of UA Doppler and CPR. A metaregression analysis was performed to compare the prognostic accuracy of the three tests. The CPR was significantly better than UA Doppler in predicting composite adverse outcome ( P < .001) and emergency delivery for fetal distress ( P = .003) but comparable with UA Doppler in predicting perinatal death ( P = .686), low Apgar score ( P = .595) and NICU admission ( P = .107). MCA Doppler was significantly worse than UA Doppler in predicting low Apgar score ( P = .017) and emergency delivery for fetal distress ( P = .034) and significantly worse than CPR in predicting composite adverse outcome ( P < .001) and emergency delivery for fetal distress ( P = .013) ( Table 21.8 ). Thus it appears that CPR measures, combining information from both the UA and MCA Doppler PIs may have great value in fetal assessment.
RATIO a < 1.08 ( N = 18) | RATIO a > 1.08 ( N = 72) | |
---|---|---|
Small for gestational age | 100% | 38% |
Cesarean section (for fetal distress) | 89% | 12% |
Umbilical vein pH (mean) | 7.25 | 7.33 |
Five-minute Apgar score <7 | 17% | 3% |
Neonatal complications b | 33% | 1% |
a Ratio of pulsatility index from cerebral circulation to index from umbilical artery; normal mean value is approximately 2.0.
b Intracerebral hemorrhage, seizures, respiratory distress syndrome.
The value of MCA Doppler in the prediction of adverse fetal outcome and fetal assessment has been inconsistent. Some studies have suggested that the MCA Doppler measures are useful, whereas others have found poor predictive value. A meta-analysis of 35 eligible studies including 4025 fetuses reviewed the predictive value of MCA Doppler for adverse perinatal outcome. The study reported that low MCA PI appeared to be predictive of impaired fetal well-being assessed by either acidosis (pH < 7.20) at birth, higher likelihood of 5-minute Apgar score lower than 7 (positive likelihood ratio [LR] 1.65 [1.07, 2.52]), or reduced admission to a NICU (positive LR 4.00 [2.16, 7.50]; negative LR 0.62 [0.47, 0.82]). Abnormal MCA PI recording was also predictive of an overall composite measure of adverse perinatal outcome (positive LR 2.77 [1.93, 3.96]; negative LR 0.58 [0.44, 0.69]) and perinatal mortality (positive LR 1.36 [1.10, 1.67]; negative LR 0.51 [0.29, 0.89]). Although these findings suggest that there is an association between abnormal MCA recordings and adverse outcomes, the association is weak.
The potential value of Doppler study of the cerebral circulation in other fetal states is suggested by the demonstration of increased values for PI in the presence of hydrocephalus. This observation is identical to that made postnatally with posthemorrhagic hydrocephalus (see Chapter 28 ) and raises the possibility of the use of Doppler in determination of the need for intervention in fetal hydrocephalus. Changes in cerebral blood flow velocity have also been documented with changes in fetal behavioral states and after administration of indomethacin to the mother.
The DV is a fetal vessel connecting the abdominal umbilical vein to the left portion of the inferior vena cava just below the diaphragm. The function of the DV is to shunt the substrate-rich blood coming from the placenta via the umbilical vein to the heart. The DV diverts 25% of the blood, with the remainder being distributed to the liver and joining the circulation via the hepatic portal system.
The DV waveform can be detected by Doppler and is sensitive to cardiac function, which in turn is adversely affected by chronic severe decrease in substrate/oxygen availability. In response to hypoxia, the DV becomes more dilated and there is reduced flow during ventricular diastole, resulting in increased DV PI for veins, followed by increasingly retrograde flow during atrial systole, seen as absent or reversed a-wave ( Fig. 21.11 ).
The utility of the DV waveform is primarily in the very premature fetus with IUGR, or in the preterm fetus with abnormal UA waveforms. Reversal or absence of the DV a-wave ( Fig. 21.11 ), particularly in combination with umbilical vein pulsations, has been shown to be closely associated with an umbilical cord pH less than 7.20 at delivery (65% sensitivity and 95% specificity). Similarly, these DV Doppler changes are associated with an 11-fold increase in major adverse neonatal outcomes and a doubling in neonatal mortality.
A recent study, (the TRUFFLE study), used DV Doppler measures to assist in determining timing of delivery in preterm infants with IUGR. In cases where delivery was determined by increased DV PI or absent DV a-wave, perinatal mortality was elevated at 10% in the DV Doppler measures group compared with 6% in control group. However, neurological outcome at 2 years of age in survivors was improved in the DV Doppler measures group, with 9% having neurological impairment compared with 5% in the control group. Although the outcomes were not significantly different between the groups, the study suggests that delivery based on later DV Doppler changes may provide better long-term outcomes, possibly at the expense of a small increase in perinatal mortality.
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