Perinatal asphyxia: A Bayesian analysis of prediction and prevention

Journal of Obstetrics and Gynaecology (1 991 ) 11, 3 4 4 0

Perinatal asphyxia: a Bayesian analysis of prediction and prevention

M. S. Rogers and A. M. Z. Chang Prince of Wales Hospital, The Chinese University of Hong Kong

Summary The value of routine intrapartum cardiotocography has yet to be proved despite widespread use. The confounding effects of treatment paradox and relative risk assessment are possible reasons for this.

The pattern of management within 10 000 consecutive deliveries was examined, using an ‘independence Bayes’ probability model to demonstrate changing relationships between test results, obstetric intervention and neonatal outcome.

The incidence of birth asphyxia in the Prince of Wales hospital decreased by 33 per cent between 1985 and 1986. This is shown to have been associated with improvements in the selection of patients for intrapartum cardiotocography and for elective caesarean section, and with an increased rate of intervention for fetal distress. The incidence of fetal distress also decreased, suggesting that factors other than intervention in response to fetal distress were partly responsible for improved perinatal outcome. A higher than expected incidence of asphyxia where delivery was by emergency caesarean section in the absence of fetal distress suggests cardiotocography can also have a detrimental effect on perinatal outcome.

INTRODUCTION INTRAPARTUM cardiotocography has achieved widespread use as a screening test for fetal hypoxia since its introduction in the 1960s. In North Amer- ica its use now represents the standard of practice, raising the malpractice issue where the technology is withheld (Dilts, 1976).

In common with other tests, cardiotocography is unable to achieve absolute discrimination between hypoxia and normality, producing a significant number of both false positive and false negative results (Beard et al., 1971; Van den Berg er af., 1987). Several prospectivc random clinical trials of intrapartum cardiotocography have failed to demonstrate any improvement in obstetric outcome as measured by the incidence of intrapartum death, low Apgar score or fetal acidosis (Banta and Thacker, 1979; Freeman, 1990; Shy et al., 1990). Even in the high risk situation of very preterm labour there appears to be no benefit in

terms of long term neurological sequelae: there may even be an associated increase in cerebral palsy (Shy et al., 1990). Thacker, in a 1987 review, concluded that intrapartum cardiotocography is not useful as a screening procedure for all labouring women, and also warned that such use would result in an unacceptable rise in obstetric intervention rates. Despite this, many doctors continue to treat cardiotocographic patterns as absolute deter- minants of fetal wellbeing; perhaps because they are more comfortable dealing with certainty than uncertainty: “many people flatly refuse to consider uncertainty explicitly in their analyses. Instead they make padded or ‘conservative’ estimates of the unknown quantities that will affect the success or failure of the venture being analysed. They then pretend that the world will be like their estimates and, in essence make their decision under assumed certainty” (Hammond, 1967).

Unfortunately, evaluation of intrapartum cardiotocographic monitoring is confounded both by treatment paradox (Lilford and Chard, 1983) and by the failure to account for prior probability of perinatal asphyxia. The extent of this confounding has not previously been analysed. In this paper we attempt to separate the influence of cardiotocography from these confounding factors by using Bayesian probability estimates of birth asphyxia (Warner et al., 1961; Rogers and Chang, 1989) to examine relationships between obstetric risk assessment, selection of patients for intrapartum monitoring, the results of cardiotocographic monitoring, obstetric intervention and perinatal outcome.

( 1 ) Changes in asphyxia rate over a period of time may reflect improved selection of cases for intrapartum cardiotocographic monitoring and for elective caesarean section. (2) As better selection and management develops over time, an increase in appropriate obstetric intervention reduces the incidence and severity of

@ Institute of Obstetrics and Gynaecology Trust, 1991

Two specific hypotheses were examined:-

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Rogers and Chang: Perinatal asphyxia 35

asphyxia, so that the association between predic- tors and outcome diminishes: in other words, treatment paradox exists.

METHODS The Prince of Wales Hospital was opened in May of 1984. Initially the rate of birth asphyxia was high, reflecting the inexperience of junior medical staff, a higher than expected delivery rate and understaffing at all levels. With improvements in staff-patient ratio, rapidly increasing experience and a greater emphasis being placed on neonatal outcome than on maintaining low intervention rates, a significant reduction in the rate of birth asphyxia was achieved.

In order to examine how obstetric practice changed with time a data base of 10 000 singleton births was constructed. The structure of this data base has been reported earlier (Rogers and Chang, 1989). The cases were entered sequentially over a period of approximately two and a half years. The neonatal outcome used in this paper, as in pre- vious communications (Rogers and Chang, 1987, 1989), is ‘asphyxia’, which is based on the 5 minute Apgar score and modified according to paediatric assessment and requirement for continued physio- logical support beyond 24 hours of life.

The data base was divided into three parts; (a) cases 1-2000 (delivered in 1984); (b) cases 2001- 6000 (delivered in 1985); (c) cases 6001-10000 (delivered in 1986). These divisions are only ap- proximate as the number of cases delivered each year was not exactly 2000 or 4000. For conve- nience they will be referred to as 1984, 1985 or 1986 deliveries in the text.

Conditional probabilities for asphyxia were calculated from I984 deliveries for each of the variable categories listed in Table I. Using an ‘independence Bayes’ programme (Warner et al., 1961; Rogers and Chang 1989) probability estimates for asphyxia were calculated before and after the test (intrapartum cardiotocography) for each of the remaining 8000 cases. The probability of asphyxia before the test is a Bayesian estimate derived from data which are available at the onset of labour and assumes mutual independence of predictor variables (Warner et al., 1961). Probability after the test combines the probability before testing with conditional probabilities associated with intrapartum cardiotocographic monitoring, but excludes other variables associated with labour and delivery. Suspected fetal distress refers to a clinical diagnosis based on fetal heart rate abnor- malities only (fetal scalp pH measurement was not routinely available at the Prince of Wales Hospital during the period studied).

Table I. Variables used for independence Bayes model

Social variables Patient’s occupation: housewife; employed. Husband’s occupation: unemployed or manual;

Education: primary or none; secondary or above. Family income: <2000 HK$/month; 2000 HKS/

semi-skilled, skilled or professional.

month or above.

Physical variables Age: <20; 20-35; >35. Height: < 1 5 3 cm; 1 5 3 cm or greater

Past obstetric history Early pregnancy loss ( < 20 weeks): no; yes. Parity: nulliparous; multiparous; multiparous with

morbid fetal outcome.

Antenatal complications Bleeding: none; in first trimester; after first trimester;

Hypertension: no, yes. Intra-uterine growth retardation: not suspected;

both.

suspected.

Labour variables Intervention: none; induction; augmentation; elec-

tive caesarean. Dystocia: none; in 1 st stage; in 2nd stage; in 1 st and

2nd stages. lntrapartum monitoring: none; normal fetal heart

tracing; fetal distress suspected. Delivery mode: caesarean section before labour;

caesarean section in 1 st stage; caesarean section in 2nd stage; operative vaginal; normal vaginal.

Gestational age at delivery: <37 weeks; 3 7 4 1 weeks; >41 weeks.

Receiver operating characteristic (ROC) curves were generated by using different cut-off values of probability before and after testing for prediction of asphyxia in both 1985 and 1986 deliveries and calculating sensitivity and specificity for the predictions by comparing with the actual diagnosis. ROC curves were compared statistically using the Wilcoxon statistic (Hanky and McNeil, 1982; 1983).

Summation of the individual probabilities of asphyxia before testing was performed to give an expected incidence for each year and provide an estimate of the overall antenatal risk status of the two population samples.

Patients were subdivided into five ranges of probability for asphyxia before testing: 0-0.049, 0.054.099, 0.14.149, 0.154.199 and 0 , 2 4 3 . Further subdivision was performed into the fol- lowing three categories:- (a) elective caesarean section delivery, (b) labour without electronic fetal

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36 Journal of Obstetrics and Gynaecology (1 991) Vol. 11 /No. 1

heart monitoring, (c) labour with electronic fetal heart monitoring.

The distribution of probability ranges amongst patients delivered by elective caesarean section were compared between 1985 and 1986 to evaluate any change in selection of patients for this mode of delivery. The same exercise was then performed for patients who were allowed to labour, to assess the selection of patients for continuous electronic fetal heart monitoring.

In order to examine the impact of intrapartum monitoring on the management of patients and on neonatal outcome, those undergoing labour were further subdivided:- (a) According to presence or absence of fetal distress. (b) According to their mode of delivery (vaginal or emergency caesarean).

Observed and expected frequencies of birth asphyxia were compared using the binomial test (Siegel, 1956). For this exercise the expected values for the incidence of asphyxia represent a summation of probability estimates made after the test rather than before.

RESULTS Four ROC curves representing the prediction of asphyxia using before and after testing probabilities for 1985 and 1986 deliveries respectively are shown in Figures la and b. The statistical comparison of these curves is in Table 11.

There was a significant deterioration in the

Table 11. Statistical comparison of ROC curves in Figure 1

Cases ROC Area*s.e. * ’z’ P curve

4.27 <0.0001 1 0.674*0.020

1985 2 0.735*0.022

0.73t n.s 1 0.665*0.021

1986 2 0.6781t0.024

0.69t n.s. 1985 1 0.674*0.020

1986 1 0.665*0.021

1985 1986 2 0.678*0.024

* Wilcoxon statistic t Unpaired comparison (Hanley and McNeil, 1982). t Paired comparison (Hanley and McNeil, 1983). z=critical ratio. n.s.=not significant.

0 1 -specificity

b 1

1986

> > u) C G)

c ._ .- 4- .-

v)

0 1 -specificity

Figure 1 a. ‘Independence Bayes’ predictions for birth asphyxia in 1985 deliveries. Conditional probabilities derived from 1984 deliveries. ROC curve:- (1) Prediction of asphyxia in 1985 deliveries without intraparturn fetal monitoring. (2) Prediction of asphyxia in 1985 deliveries with intrapartum fetal monitoring.

Figure 1 b. ‘Independence Bayes’ predictions for birth asphyxia in 1986 deliveries. Conditional probabilities derived from 1984 deliveries. ROC curve: (1) Prediction of asphyxia in 1986 deliveries without intrapartum fetal monitoring. (2) Prediction of asphyxia in 1986 deliveries with intrapartum fetal monitoring.

predictive performance of the independence Bayes model between 1985 and 1986. This was almost entirely due to a decrease in the contribution of intrapartum monitoring to prediction in 1986 deliveries; monitoring produced a significant improvement in the prediction of asphyxia in 1985 but not in 1986.

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Both the range of probability before testing and the overall risk status were similar; the estimated incidence of asphyxia being 231.2 in 1985 and 240.9 in 1986. The corresponding estimates for patients who were allowed to labour were 225.7 and 226.8 respectively.

The proportions of labouring patients who received intrapartum cardiotocographic monitoring in 1985 and 1986, is shown for each probability range in Figure 2. The proportions of all patients delivered by elective caesarean section in 1985 and 1986, is shown for each probability range in Figure 3.

Intrapart um cardiotocographic monitoring was used in 1348 cases in 1986 compared to only 1048 in 1985, representing a 28.6 per cent increase. This increased use of monitoring was not evenly distri- buted; the increase amongst patients with a high estimated probability of asphyxia was greater than that amongst those with low estimates. A similar

pattern was observed amongst those undergoing elective caesarean section delivery. There were twice as many elective caesarean sections in 1986 as in 1985; the additional cases occurring predomi- nantly amongst patients whose estimated before testing probability of asphyxia exceeded 0.05.

The changes in the incidence of asphyxia in unmonitored patients, and in patients subjected to monitoring, with and without detection of fetal distress are shown in Figure 4.

Between 1985 and 1986 there was a decrease in the incidence of asphyxia in unmonitored patients and in patients were fetal distress was detected, but not amongst monitored patients where no fetal distress was observed.

The expected and observed incidence of asphyxia in monitored and unmonitored patients according to the mode of delivery are compared in Table 111.

Amongst unmonitored patients there was no

Table 111. Expected and observed incidence of asphyxia according to the results of intraparturn cardiotocography and mode of delivery

Number of Incidence of asphyxia cases Expected Observed Difference

No monitoring

1985 Vaginal delivery 2743 Caesarean section 100 (3.5%) Total 2843

Vaginal delivery 2372 Caesarean section 79 (3.2%) Total 2451

1986

No fetal distress 1985



1986

Fetal distress 1985



1986

101 5

105

88 4

92

40 1 1 51

60 23 83

55 49 104

13 32 45

1 00 13

113

63 5

68

39 17 56

58 32 90

49 38 87

6 9

15

-

P< 0.001 -

P i 0.01

P< 0.01 -

-

P< 0.05 -

-

P< 0.05 -

-

P< 0.05 P< 0.05

P< 0.05 P< 0.00001 P< 0.00001

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38 Journal of Obstetrics and Gynaecology (1 991 ) Vol. 11 /No. 1

0.3 ' ._ 0.25.

6::

s m C'E 0.2 0s '== 0.15 n m 0.1-

difference between the observed and expected inci- 0.3~

.

dence of asphyxia in 1985 deliveries, whereas in 1986 there were fewer cases than expected. On 'z --- subdividing cases according to mode of delivery, there were more cases of asphyxia than expected amongst emergency caesarean sections in 1985, whilst this difference disappeared in 1986. There were also fewer cases of asphyxia amongst vaginal deliveries than predicted in 1986.

In monitored patients where no fetal distress was observed, no difference was demonstrated between the observed and expected incidence of asphyxia in either year. There were more cases of asphyxia than expected amongst those delivered by emergency caesarean section in both years.

Where fetal distress was suspected, there were fewer cases of asphyxia than expected, the difference being greater in 1986 than in 1985. In 1985 the difference was only significant amongst caesarean section deliveries, whereas it was significant in both vaginal and caesarean section deliveries in 1986, being larger with caesarean sections.

DISCUSSION The basic tenet of modem obstetric management is that timely intervention reduces the incidence and severity of poor perinatal outcome. This causes considerable problems in the evaluation of fetal surveillance tests. The sensitivity and specificity of a test (and its ROC curve) are independent of disease prevalence (Fink and Galen, 1982). Where outcome is measured after intervention both parameters may be altered. This phenome- non is known as 'treatment paradox' (Lilford and Chard, 1983).

The positive and negative predictive values of a test are usually of more interest to the clinician than its sensitivity or specificity. Unfortunately predictive value is not only subject to treatment paradox but also to selection bias. Patients may be pre-selected for delivery in a particular unit, affect- ing the overall risk of the population sample, or may not be exposed to the test, either because of elective caesarean delivery or because higher risk patients are given priority. Predictive values also tend to overestimate the amount of useful information a test contributes to decision making (Chang and Rogers, 1989). The clinician has nor- mally estimated the likelihood (risk) of asphyxia from information available to him before performance of the test @robability before testing). It is the difference between probability before and after testing which measures the true contribution of the test to prediction (Fink and Galen 1982; Chang and Rogers, 1989).

Probability estimates can be obtained using

r" 0.151-l

E u,'-

E F E 0.05 = I e a

'0-2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Proportion with intrapartum CTG monitoring

Figure 2. Changes in distribution of risk amongst patients selected for intrapartum cardiotocographic monitoring. ., delivered in 1985; 0, delivered in 1986.

.% 0.31 I ;F :: 0.2

u) 0.15

F 0.1

0) [J,

g j 2 0.05 f W , , , , a '0 0.05 0.1 0.15 0.2 0 . 2 5 3

Proportion delivered by elective caesarean section

Figure 3. Changes in distribution of risk amongst patients selected for delivery by elective caesarean section. ., delivered in 1985; 0, delivered in 1986.

0.351

No CTG Monitoring: Monitoring: Monitoring No fetal Fetal

distress distress

Figure 4. Incidence of birth asphyxia in patients with and without intrapartum cardiotocographic monitoring. ., delivered in 1985; 0, delivered in 1986.

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various statistical techniques, of which Bayesian methods are the most frequently encountered in the field of medical decision making (Chang and Rogers, 1989). The use of these techniques cannot replace the random controlled trial for assessing the full contribution of cardiotocography as there is no true control group (Thacker, l987j. A controlled trial of fetal monitoring would be difficult to stage in the current medicolegal environment and would require approximately 360 000 patients to produce a definitive conclusion (Thompson, 198 1). Using Bayesian methods probability values before and after testing are only relative, reflecting the characteristics of the predictor population (deliveries in 1984 in this study).

A significant reduction in the incidence of birth asphyxia was achieved in the Prince of Wales Hospital over the study period. Only changes in practice could have led to this improvement in neonatal outcome as the overall risk status of the population remained static. Our data demonstrate that the increased use of elective caesarean section and fetal monitoring was not random but was directed towards patients whose risk of birth asphyxia could be objectively assessed as higher. In an established obstetric unit the evidence of treatment paradox demonstrated by this study would probably not have been revealed: perinatal morbidity in the predictor population and in the two test populations (deliveries in 1985 and 1986) would have been similarly low and changes in management would be unlikely to produce significant changes.

In 1985, where fetal distress was suspected, 48.5 per cent of patients were delivered by emergency caesarean section. There were fewer cases of asphyxia than expected amongst these, but not amongst the vaginal deliveries. This can be explained by treatment paradox, neonatal morbidity being reduced by timely caesarean section but affected less where no intervention follows its detection. In 1986 the caesarean delivery rate in cases of fetal distress increased to 68.5 per cent. There was a further improvement in neonatal outcome with both caesarean and vaginal deliveries. There were no changes in diagnostic criteria for fetal distress during the study. We postulate that increasing experience led to an improvement in recognition of abnormal fetal heart rate patterns and that this may have led to earlier intervention.

Amongst monitored patients without evidence of fetal distress the caesarean section rate increased marginally from 20.5 per cent in 1985 to 23.8 per cent in 1986. This reflects the higher overall risk of monitored patients in 1986. There

were more cases of asphyxia than expected in both years. This could be explained by inclusion of patients with unobserved cardiotocographic ab- normalities in this category. As the excess of asphyxiated infants was only amongst caesarean section deliveries. A more likely explanation is that healthy fetal heart tracings gave false reassurance in some cases, leading to delayed intervention. A similar situation was reported by Shy el a/. (1990) who noted that the rate of cerebral palsy amongst babies monitored electronically was higher than that amongst those monitored by intermittent auscultation: the rate was directly proportional to the duration of fetal heart rate abnormality, suggesting that in some cases intervention was delayed due to false reassurance from a ‘not too bad’ cardiotocogram.

Thacker (1987), in a review of seven random controlled trials, concluded that monitoring led to an increase in obstetric intervention. Our data confirms a strong association between monitoring and obstetric intervention, but demonstrates clearly that this is not a causal relationship. The overall caesarean section rate rose from 12.2 per cent in 1985 to 16.4 per cent in 1986, but the proportion of labouring patients delivered by emergency caesarean section decreased from 13.7 per cent to 12 per cent. This was associated with an increase in the proportion monitored electonically from 26.9 to 35.5 per cent. The caesarean section rate amongst monitored patients was 27.7 per cent in 1985 and 27.9 per cent in 1986, compared to 3.5 per cent (1985) and 3.2 per cent (1986) amongst unmonitored patients. The incidence of suspected fetal distress actually fell by over 50 per cent between 1985 and 1986. This suggests that the reverse of Thacker’s argument is true; that modern obstetric management, including elective caesarean section, induction and active management of labour, leads not only to an increase in operative delivery but also to a reduction in the contribution of electronic fetal heart monitoring by reducing fetal distress. This is further confounded by treatment paradox where earlier detection of fetal distress leads to earlier intervention and a reduction in associated morbidity.

These improvements in perinatal outcome, their association with better selection of patients for monitoring and elective delivery and with more appropriate intrapartum intervention, represent the early stages of a learning curve for our department as a whole. Further improvements in perinatal outcome have since been achieved without resort to any further increase in operative intervention.

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40 Journal of Obstetrics and Gynaecology (1 991 ) Vol. 11 /No. 1

REFERENCES Banta H. D. and Thacker S. B. (1979) Costs and Bencfiis

of Electronic Fetal Heart Monitorinp: a Review of The Literature. Washington DC, USDHEW Publication (PHS) 79-3245.

Beard R. W., Filshie G. M., Knight C. A. and Roberts G. M. (1971) The significance of the changes in the continuous fetal heart rate in the first stage of labour. Journal of Obstetrics and G.vnaecoloLqj of [he British Commonwealth 78, 865-88 I .

Chang A. M. 2. and Rogers M. S. (1989) Decision making in obstetrics. Fetal Medicine Review 1. 1-1 1.

Dilts P. V. (1976) Current practices in antepartum and intrapartum fetal monitoring. American Journal o/ Obstetrics and Gynecology 125, 491 494 .

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Hammond J . S. (1967) Better decisions with preference theory. Harvard Business Review November- December: 123-141.

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Hanky J. A. and McNeil B. J. (1983) A method comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology 148,

Lilford R. and Chard T. (1983) Computers in obstetrics: 839-843,

a review. Obstetrics and Gynecological Survey 38, 125- 137.

Rogers M. S. and Chang A. M. Z. (1987) Perinatal asphyxia: the use of path analysis in its explanation. Journal of Obstetrics and Gynaecology 8, 29-35.

Rogers M. S. and Chang A. M. Z. (1989) Perinatal asphyxia: development of an ‘Independence Bayes‘ computer prediction model. Journal Sf Obstetrics and Gynaecology 10. 26- 3 1.

Shy K. K., Luthy D. A., Bennett F. C. et al. (1990) Effects of electronic fetal-heart-rate monitoring, as compared with periodic auscultation, on the neurological development of premature infants. New. Eng- land Journal of’ Medicine 322. 588-593.

Siege1 S. ( 1956) Nonparametric Statistics for the Beha- vioral Sciences. pp. 3642. New York, McGraw Hill.

Thacker S. B. (1987) The efficacy of intrapartum electronic fetal monitoring. American Journal of Obstetrics and G.vneco1og.v 156, 2430.

Thompson M. S. ( I98 1) Decision-analytic determination of study size: the case of electronic fetal monitoring. Medical Decision Making 1, 165-177.

Van den Berg P., Schmidt S., Gesche J. and Saling E. (1987) Fetal distress and the condition of the newborn using cardiotocography and fetal blood analysis during labour. British Journal of Obstetrics and Gynae-

Warner H. R., Toronto A. F., Veasey L. G. and Stephen- son R. (1961) A mathematical approach to medical diagnosis: application to congenital heart disease. Journal ofihe American Medical Association 177, 177- 183.

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Correspondence should be addressed to: Dr M. S. Rogers, Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.

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Perinatal asphyxia: A Bayesian analysis of prediction and prevention