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Assessment of fetal growth, size, and well-being 

Assessment of fetal growth, size, and well-being
Assessment of fetal growth, size, and well-being

Murray Enkin

, Marc J. N. C. Keirse

, James Neilson

, Caroline Crowther

, Lelia Duley

, Ellen Hodnett

, and Justus Hofmeyr

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Subscriber: null; date: 16 October 2017

  1. 1 Introduction

  2. 2 Size and growth

  3. 3 Abdominal examination

  4. 4 Fetal movement counting

  5. 5 Biophysical tests

    1. 5.1 Ultrasound measurements

    2. 5.2 Doppler ultrasound

    3. 5.3 Contraction stress testing

    4. 5.4 Non-stress cardiotocography

    5. 5.5 Fetal biophysical profile

  6. 6 Biochemical tests

  7. 7 Conclusions

1 Introduction

A wide range of tests of fetal well-being have been introduced during the last thirty years, and have enjoyed waves of popularity. Both biochemical tests (which monitor the endocrine function of the placenta or the fetoplacental unit) and biophysical methods of monitoring (which provide different information about fetal growth and physiological function) have the theoretical ability to detect changes in fetal well-being that may occur over hours, days, or weeks. No known method of assessment can predict sudden events, such as cord prolapse or placental abruption, which may also cause fetal damage or death.

Two general assumptions underlie the contention that antenatal monitoring is clinically useful: first, that these methods can detect or predict fetal compromise; and second, that with appropriate interpretation and action, they can reduce the frequency or severity of adverse perinatal events or prevent needless interventions.

Tests of fetal well-being have been used both as screening tests with the purpose of preventing those otherwise unpredictable fetal problems that occur from time to time, and in specific clinical situations with a high estimated fetal risk. ‘High-risk’ circumstances include diabetes or pre-eclampsia, multiple and post-term pregnancy and, most of all, when the fetus is thought to grow poorly. Because of the frequency with which such babies are monitored, and because of the controversy over what constitutes ‘growth restriction’, it is worthwhile to re-examine the definitions and underlying pathophysiological concepts.

2 Size and growth

Fetal size and fetal growth are often confused in clinical practice. It is common to see ‘birthweight-for-gestational age’ standards described as ‘fetal growth charts’, and a weight-for-gestation below some arbitrary centile referred to as ‘intrauterine growth restriction’. There are two main reasons why this may lead to false conclusions. First, the weights of babies born at a given length of gestation are not a good reflection of fetal weights at the same gestation. Second, some authors have made inferences about fetal growth by comparisons with cross-sectionally derived mean or median birthweights at consecutive weeks of gestation. This approach is misleading because it ignores the important distinction between size and growth. Infants below a particular centile are ‘light-for-gestational age’ without necessarily being ‘growth restricted’. Growth cannot be estimated without two or more measurements of size. What the clinician would like to know is whether fetal growth has deviated from its normal progression.

The term ‘intrauterine growth restriction’ should be used only for fetuses with definite evidence that growth has faltered. Such infants may not necessarily be ‘light-for-gestational age’; a fetus whose weight falls from the 90th centile to the 30th in a short period of time is almost certainly in greater peril than a fetus who has maintained a position on the 5th centile.

Genuine fetal growth restriction is attributed to an inadequate supply of nutrition to the fetus by a malfunctioning placenta (or, more accurately, insufficient blood supply to the placenta). The fetus responds to this unfavorable environment by making adjustments that maximize the chances of survival. These include redistribution of blood flow (more to brain and heart, less to liver and kidneys) and limiting unnecessary movements. These adaptive phenomena provide the basis of some tests of fetal well-being.

3 Abdominal examination

The simplest clinical method of estimating fetal size – abdominal palpation – is so inaccurate as to be little better than a blind guess: 20% of such assessments just before birth are not within 450 g of the actual birthweight, and the errors are worse at the extremes of the range, where the information is most needed. A more quantitative approach is to measure the increase in size of the maternal abdomen, which must, to some extent, reflect uterine growth. The two most widely practised techniques are the measurement of fundal height (the distance between the upper border of the pubic symphysis and the uterine fundus) and the measurement of abdominal girth at the level of the umbilicus.

There have been several studies of fundal height as an indicator of fetal size, but little investigation of the potential of this measurement for assessing growth. This is understandable, given the considerable inter- and intra-observer variation in measuring fundal height. Nevertheless, several studies have shown quite good sensitivity and specificity of fundal height for predicting low birthweight for gestation. The ability to predict low birthweight is not the same as the ability to detect growth restriction, but fundal height may be useful as a screening test for further investigation – albeit that only very limited trial information is available. Abdominal girth measurement has not been adequately evaluated at all.

4 Fetal movement counting

Reduction or cessation of fetal movements may precede fetal death by a day or more. In theory, recognition of this reduction, followed by appropriate action to confirm fetal jeopardy and expedite delivery, could prevent fetal death. This is the basis for using counts of fetal movements as a test of fetal well-being. The most commonly used method is to ask the mother to record on a chart each day, the time at which she has noticed 10 kicks.

Not all late fetal deaths are even theoretically preventable in this way. Some are not preceded by a reduction in fetal movements. For others, there may be insufficient time between the reduction and fetal death to allow clinical action. Still others may be preceded by conditions that are recognizable in their own right, such as pre-eclampsia or intrauterine growth restriction. In the latter circumstances, fetal movement counting might still be theoretically useful as a supplement to other tests of fetal well-being.

The cause of most antepartum late fetal deaths, however, is unknown. These deaths are unpredictable and the extent to which they can be prevented by current forms of antenatal care is, therefore, limited. Screening by fetal movement counting, because it can be performed each day, has theoretical advantages over other tests of fetal well-being, all of which are either difficult or impossible to perform daily for practical reasons.

Two randomized, controlled trials have addressed the question of whether clinical actions taken on the basis of fetal movement counting improve fetal outcome, the largest involving over 68 000 women. These trials collectively provide no evidence that routine formal fetal movement counting reduces the incidence of fetal death in late pregnancy. Routine counting results in more frequent reports of diminished fetal activity, greater use of other techniques of fetal assessment, more frequent antepartum admission to hospital, and an increased use of elective delivery for decreased movement, hence an increase in the use of resources without compensating benefit. The practice does not appear to result in either a significant increase or decrease in feelings of anxiety among mothers.

There is a marginal possibility that an occasional late fetal death might be prevented by fetal movement counting. The wider social, psychological, and economic implications of recommending routine fetal movement counting, however, must be taken into account as they affect all women.

5 Biophysical tests

5.1 Ultrasound measurements

Ultrasound imaging has the potential to assist assessment of fetal growth and well-being in a number of ways: by assessing fetal size at a single point in time to confirm or refute the clinical impression that a fetus is small for gestational age; by measuring fetal growth over a period of time by repeated measurements; by assessing amniotic fluid volume (and therefore indirectly fetal urine production); by investigating the appearance of the placenta; and by examining the movement and behavior of the fetus.

The use of fetal measurements to assess whether or not the fetus is growing satisfactorily may be considered in the general framework of diagnostic tests, and appraised from the standpoints of their test properties: sensitivity, specificity, and predictive values. It is not clear, however, precisely what one is trying to predict. There is no absolute postnatal criterion of growth restriction that can be used to assess the validity of the ‘test’. In the absence of an appropriate outcome measure, authors frequently use some measure of ‘relatively low’ birthweight, such as being below the 10th centile for gestational age.

There has been very little research aimed at producing true growth curves based on repeated measurements over time of the same fetus. Such information would provide a far sounder basis for assessing fetal growth, and is arguably the only valid approach for detecting growth restriction. This approach is particularly useful when gestational age is unknown or uncertain. Ultrasonography, rather than ‘birthweight-forgestational-age’, should be considered as the ‘gold standard’ for measuring fetal growth. Despite this, controlled trials show that routine ultrasound measurement of fetal size in late pregnancy results in an increased rate of antenatal hospital admission, and possibly of induction of labor, with no evidence of any substantive benefit to the baby. No adequately controlled trial data are available from specifically high-risk pregnancies.

‘Light-for-dates’ fetuses form a heterogeneous group within which individual risk varies greatly. Attempts have been made to analyze patterns of growth in the hope of uncovering the underlying pathogenesis and of providing an estimate of the risk to the individual fetus. ‘Light-for-dates’ fetuses can be divided into two groups: the first showing arrest of previously normal growth; the second showing early departure from normal limits of growth that continues until delivery. The first of these patterns has been attributed to ‘uteroplacental insufficiency’, and the second to low growth potential. This latter group includes infants that are inherently abnormal (especially chromosomally abnormal), some that have suffered a major insult (e.g. from rubella) during the critical period of organogenesis, and some that are small because of their genetic endowment. Comparative measurements of the fetal head and abdomen have been suggested as a means to further differentiate these two groups. While there is a higher incidence of intrapartum fetal distress and operative delivery in the asymmetrical-growth group, the perinatal mortality and incidence of low Apgar scores are similar and high in both groups.

The significance of ultrasonically detected patterns of fetal growth requires further study, and seeking correlations with the results of Doppler studies would be of interest. Thus far, the evidence indicates that abdominal measurements are superior to head measurements in predicting ‘light-for-dates’ babies, but little is known about serial measurements, and particularly about their relationship to neonatal outcome.

A single trial reported in 1987 has examined the value of ultrasound placental appearances. Reporting placental ‘texture’ to clinicians providing antenatal care resulted in less meconium stained amniotic fluid in labor, fewer babies with low 5-min Apgar scores, and, most importantly, fewer deaths of normally formed babies, than occurred for women whose clinicians were not provided with the report of placental grading. It appears that knowledge of placental grading can lead to appropriate clinical action that can improve pregnancy outcome. This study deserves to be repeated. In the meantime, it seems advisable to report the placental grade following ultrasound examinations for specific clinical indications during the third trimester.

The only information available from randomized trials on the use of amniotic fluid volume estimation by ultrasound is in the clinical context of post-term pregnancy assessment, or as part of the biophysicalprofile test (see below).

5.2 Doppler ultrasound

Doppler ultrasound has been used for a number of years to identify and record fetal heart pulsation, and, in adults, to assess blood flow in compromised vessels. The use of the technique to demonstrate blood velocity wave forms in the fetal umbilical artery was first described in 1977. Alterations in fetal umbilical blood flow may occur as an early event in conditions of fetal compromise. For this reason, Doppler studies could provide important information on the pathophysiology of compromised pregnancies (especially of fetal growth restriction), and be a useful technique for evaluating fetal well-being in high-risk pregnancies.

Information from trials supports this hypothesis. Combined evidence from several trials in high-risk pregnancies (complicated mainly by fetal growth restriction or maternal high blood pressure) shows that there are fewer stillbirths and neonatal deaths among normally formed babies when the results of Doppler velocimetry are made available to the clinicians. A number of the deaths in the control groups in these studies seem to have resulted from uteroplacental insufficiency, and these might well have been avoided by Doppler study and the clinical action prompted by it. The use of Doppler ultrasound in high-risk pregnancies so far appears also to lead to fewer admissions to hospital during pregnancy and fewer elective deliveries. There has been no demonstrated effect on the incidence of cesarean section or on the condition of the newborn baby, other than a greater likelihood of being born alive.

In contrast to its effectiveness in decreasing perinatal mortality among women at identified high risk, Doppler ultrasound appears to have little, if any effect on pregnancy outcome when used as a screening test in unselected pregnancies. This should not be surprising; when used in a low-risk population, the predictive power of any test is low, and the benefits from adequately responding to the few true positive tests can be more than counterbalanced by the harm done in response to the inevitable high proportion of false-positive tests.

5.3 Contraction stress testing

Continuous recording of fetal heart rate and uterine activity was first developed for use in labor, in an attempt to identify the fetus at risk of death or morbidity due to intrapartum asphyxia. Because many fetal deaths occur prior to the onset of labor, the stimulation of contractions with oxytocin for short periods of time was proposed to allow observation of the fetal heart rate under labor-like conditions in pregnancies at risk.

This technique, which subsequently became known as the ‘oxytocinchallenge test’ or ‘contraction stress test’, has no demonstrated benefits and suffers from a number of disadvantages. It is time-consuming, requires an intravenous infusion, and has the potential to harm the fetus. Its use is contra-indicated in some pregnancies at risk, for example, when there is antepartum bleeding, placenta praevia, a history of preterm labor, or preterm rupture of membranes.

The nipple-stimulation stress test is similar in purpose to, and has been directly compared with, the oxytocin-challenge test. The pregnant woman is encouraged to stimulate her nipples with her fingers, palms, a warm, moist face cloth, or a heating pad, either directly or through her clothing. Contractions can be stimulated effectively, but the mechanism, previously assumed to be oxytocin release, remains unknown. The nipple-stimulation stress test has some of the same disadvantages as the oxytocin-challenge test with the additional problem that, while stimulation is easily discontinued, there is a time-lag of more than three minutes between stimulation and peak uterine response. Excessive uterine activity occurs in over half the women who undergo this test, and this will result in fetal bradycardia in 7–14%. Cases of severe uterine tetany associated with fetal heart rate abnormalities have also been reported. Because of these concerns, and because it offers no clear advantages over other techniques, the nipple-stimulation stress test should be relegated to the history books.

5.4 Non-stress cardiotocography

The evaluation of fetal heart rate patterns, without the added stress of induced contractions, was first proposed in 1969. This ‘non-stress test’ has been widely incorporated into antenatal care for both screening and diagnosis.

There is no universally accepted technique for performing non-stress antepartum cardiotocography. Various durations and frequencies of monitoring are used, and these can have a powerful influence on the predictive properties of the test. Additional manoeuvres, such as abdominal stimulation, sound stimulation, glucose infusions, postprandial repeat tests, and follow-up oxytocin-challenge tests for suspected abnormal records, have been suggested or used. None of these have been shown to improve the predictive value of the test.

Many factors may interfere with the interpretation of the non-stress test. Like the contraction stress test, the non-stress test requires sophisticated equipment, which may occasionally malfunction. Fetal and maternal movements may produce artefacts, since ultrasound monitoring detects movement rather than sound. During fetal rest periods, which not uncommonly last for more than thirty minutes, normal physiological reduction in heart rate variability may be confused with pathological change. Medications taken by the mother are often transferred to the fetus, and, particularly in the case of drugs with a sedative effect on the central nervous system, may in themselves produce heart-rate patterns that can be interpreted as abnormal. Likewise, the gestational age of the fetus has a strong influence on the frequency of false-positive non-reactive tests, with ‘abnormal’ patterns being more frequently described in the preterm fetus. When all these factors are taken into consideration, as many as 10–15% of all records may be unsatisfactory for interpretation.

A variety of methods for interpreting non-stress cardiotocograms have been described, all of which include evaluation of some or all of the following characteristics: baseline fetal heart rate; various interpretations of fetal heart-rate variability; accelerations of fetal heart rate associated with spontaneous and/or stimulated movements of the fetus; and decelerations associated with spontaneous uterine contractions. The more complicated systems assign scores to some or all of these parameters, sometimes subsequently grouping the scores. The most commonly used method is to divide traces into reactive (normal) and non-reactive (abnormal), based on the presence or absence of adequate baseline heart-rate variability and heart-rate accelerations with fetal movement. It is now well documented that even when a standardized method is used, interpretation of a trace may vary when an individual observer reads the same trace at different times, or when the same trace is read by different observers.

In addition to the difficulties with test interpretation, there is a danger inherent in any form of screening when the likelihood of the fetus being in difficulty is small. A higher proportion of positive tests will be false-positive when the probability of an adverse outcome is small. Intervention based on the results of a ‘positive’ non-stress test in a low-risk group of women will often do more harm than good.

This risk is real, rather than only theoretical. In each of the four trials of non-stress testing that have been reported, perinatal deaths from causes other than malformations were more common in the groups in which clinicians had access to the test results. Collectively, the increase in perinatal deaths among the women tested was importantly (more than threefold) and statistically significantly higher. There was no demonstrable effect on cesarean section rates, incidence of low Apgar scores, abnormal neonatal neurological signs, or admission to specialcare nurseries. These analyses provide no support at all for the use of antepartum non-stress cardiotocography, as used in these studies, as a supplementary test of fetal well-being in ‘high-risk’ pregnancies. One can only speculate as to why cardiotocography continues to be used in such an extensive way, and why the results from the only four randomized trials that have been published are so widely disregarded by many obstetricians.

Antepartum cardiotocography is essentially an assessment of immediate fetal condition. Unless evidence emerges to the contrary its clinical use would seem best restricted to situations in which acute fetal hypoxemia may be present e.g. sudden reduction of fetal movement, or antepartum hemorrhage.

5.5 Fetal biophysical profile

The ‘biophysical profile’ was derived from a study of serial ultrasound examinations and antenatal cardiotocography (non-stress test) in highrisk pregnancies. Combining five biophysical ‘variables’ considered to be of prognostic significance (fetal movement, tone, reactivity, breathing, and amniotic fluid volume) into a score, reduced the frequency of false-positive and false-negative results compared to the non-stress test alone. An additional advantage of the biophysical profile over the nonstress test is that it permits assessment of the possibility of major congenital anomalies. This may be important, as detection of a serious anomaly may on occasion help to avoid a cesarean section when the baby is clearly abnormal.

Only two controlled trials of biophysical-profile testing have been performed. Both were conducted in women referred to units specializing in fetal biophysical assessment. They compared care based on biophysical score results with that based on non-stress test results, following a management protocol. In both studies, the biophysical profile score was a better predictor of low 5-min Apgar scores than the non-stress test. The biophysical profile was both more sensitive and more specific in predicting overall abnormal outcome than the nonstress test.

Despite the better predictive value of the biophysical score than the non-stress test, its use did not result in any improvements in outcome for the baby. Outcomes measured included perinatal death, fetal distress in labor, low Apgar score, and low birthweight-for-gestationalage. Compared with cardiotocography alone, biophysical-profile testing showed no obvious effect (either beneficial or deleterious) on these outcome measures. The available evidence provides no support at all for the use of biophysical profile as a test of fetal well-being in highrisk pregnancies. However, the number of women included in these studies is so small that any estimates of effect are extremely imprecise.

6 Biochemical tests

Biochemical testing in late pregnancy is now only of historical interest. The enthusiasm for estrogen assays that prevailed in the 1960s and 1970s was based on the observation that perinatal mortality rates were twice as high in women with low estriol excretion than in the general population. However, the usefulness of the tests was marred by the facts that they were not sensitive enough to detect the majority of pregnancies destined to have an adverse outcome, and that a great many women with normal pregnancies falsely appeared to be at risk.

Among the many studies reported, there has been only one randomized, controlled trial. In this trial, knowledge of estriol levels had no detectable effect on either perinatal mortality or the rate of elective delivery. Similar conclusions were reached from comparison of pregnancy outcomes within the same institution in two consecutive periods with and without the use of estriol assays. Thus, there is no evidence to suggest any benefit from estriol assays.

Similarly, there was only one randomized intervention study of human placental lactogen measurement. The results of this trial suggest, on first inspection, that revealing the results of human placental lactogen measurements to a clinician armed with a predetermined intervention program, statistically significantly reduced fetal and perinatal mortality. Although the data of this trial have been cited to indicate that human placental lactogen measurements are beneficial for the surveillance of high-risk pregnancy, they relate only to the 8% (4% in each group) of pregnancies that had abnormal human placental lactogen values. Data on the large majority of pregnancies (92%) that did not belong to that category were not reported, and are no longer available. One cannot exclude the possibility that the apparent benefit in the small minority with abnormal placental lactogen values was offset by negative effects in the majority of pregnancies with normal tests.

7 Conclusions

Tape measurement of symphysis–fundal height is simple, inexpensive, and widely used during antenatal care. Fundal height could be used as a screening device for referral of women to an obstetrician for further assessment, but many small fetuses will be missed, and many perfectly well-grown fetuses will be considered worryingly small. Nevertheless, in our present state of knowledge it would be unwise to abandon the practice.

Ultrasound techniques have the capacity to detect abnormalities of fetal growth, but have not been effectively exploited. There is a need for prospective studies to examine the differential growth of fetal parts, in large populations, to see whether patterns of growth that are associated with fetal compromise and later infant morbidity can be defined. Such studies should be carried out with scheduled repeated measurements. It is particularly crucial that better measures of outcome should be defined. Intervention based on assessments of size or growth should be evaluated in randomized trials before they are accepted into general obstetrical practice. For the present, the evidence provides no support for routine ultrasonography for fetal measurement in late pregnancy.

Biochemical tests of fetal well-being are expensive and have a low predictive value for adverse outcome. While they have added immensely to knowledge of placental and fetal physiology, none of them have been shown to be clinically useful. Their use should be restricted to research, and they should not be employed in clinical practice.

Monitoring of fetal movements by the mother is a simple and inexpensive test of fetal well-being that can be performed daily. There is no evidence, however, that a policy of routine fetal movement counting will have beneficial results. If used at all, it should be used in individual circumstances, for example, where a woman perceives diminished fetal movements. The results should prompt other diagnostic tests rather than more definitive obstetric intervention. The possibility of congenital malformation should be considered before delivery is expedited.

Biophysical tests are employed today with the same enthusiasm that characterized biochemical testing in the past. These tests have greatly increased our understanding of fetal behavior and development, but with the exception of Doppler studies of umbilical artery wave form in high-risk pregnancies, and possibly placental grading, their use has not been demonstrated to confer benefits in the care of an individual woman and her baby. For this reason, and despite their widespread clinical use, most biophysical tests of fetal well-being should be considered of experimental value only, rather than as validated clinical tools. They should be acknowledged as such and, at the very least, further extension of their clinical use should be curtailed until or unless they can be demonstrated to be of benefit in improving the outcome for mother or baby.

The role of non-stress cardiotocography as either a screening or a diagnostic test seems questionable, because of its poor predictive properties. The biophysical profile may have greater potential as a diagnostic test for women in whom there is a high risk of fetal problems, but the usefulness of this approach is still not established.

Doppler ultrasound has been evaluated more rigorously and extensively than any other test of fetal health or fetoplacental function. The encouraging results justify the use of Doppler ultrasound during high-risk pregnancy to guide clinical care, but there is no evidence that any benefit is derived from routine Doppler screening in unselected pregnancies.


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