18 Recognition of Chronic Hypoxia and the Preterminal Cardiotocograph. Handbook CTG

 18

Recognition of Chronic Hypoxia and

the Preterminal Cardiotocograph

◈

Austin Ugwumadu

Handbook of CTG Interpretation: From Patterns to Physiology, ed. Edwin Chandraharan.

Published by Cambridge University Press. © Cambridge University Press 2017.

The Fetal Neurologic State

A normal developing fetus exhibits a range of often coordinated and rhythmical

behavioural states including gross movements, eye movements and fetal heart

rate (FHR). An underlying assumption in studying these variables is that they

may reflect fetal brain development and that factors that impair brain

development or function may lead to abnormalities in the clustering of these

variables, their occurrence and/or their qualitative appearance. One such factor

is chronic hypoxia, and its effect on the general characteristics of FHR, in

particular FHR variability, forms the basis of recognition of fetuses with an

antecedent injury.

Although there are marked interfetal variations in the normal neurologic state,

the term and near-term fetus may spend up to 25 per cent of its time in quiet

(non–rapid eye movement [REM] sleep) during which FHR, fetal heart

variability and movements are reduced.1 Near term, quiet sleep lasts for

approximately 20 minutes and active sleep approximately 40 minutes.2 ThePhysiology of FHR Regulation and Variability

mechanisms that control these cycles of rest and activity in the fetus are yet to be

fully elucidated.

Baseline FHR is the summation of moment-by-moment autonomic modulation

from the medullary cardiorespiratory centre in response to an array of inputs

from (a) chemoreceptors, (b) baroreceptors, (c) hormonal regulation, (d) central

nervous system activities such as sleep and arousal states and (e) blood volume

control. The parasympathetic innervation of the heart originates from the medulla

oblongata through the vagus nerve to supply the sinoatrial (SA) and

atrioventricular (AV) nodal pacemaker tissues where on stimulation it exerts two

main effects, namely, reduction in the rate of firing of the SA nodal tissue

resulting in a fall in FHR, and an oscillatory effect which alters the R-wave

intervals resulting in FHR variability.

There is no regulatory vagal innervation to the myocardium. Vagotomy or

administration of atropine will block the release of acetylcholine from the vagus

nerve endings at the SA node with a resultant increase in FHR. Sympathetic

nervous system fibres, on the other hand, are widely distributed throughout the

myocardium of the term fetus. Stimulation releases noradrenaline at the nerve

endings resulting in an increase in FHR, contractility and cardiac output. The

administration of sympathoplegics or lesions of sympathetic pathway results in a

fall in baseline FHR and blunt FHR accelerations.

FHR variability represents slight differences in time intervals between each

heartbeat and the next (aka short-term variability) as counted and recorded by

the heart rate monitor. If these intervals were identical, the FHR trace would be

straight, smooth and regular. Although this beat-to-beat variability is frequently

and loosely attributed to the interactions between sympathetic and

parasympathetic reflexes, the facts are much more complex than that.Fetal Response to Hypoxia-Ischaemia

The source of FHR variability includes input from cerebral cortex, midbrain,

vagus nerve and specialized cardiac pacemaker tissues. That final FHR

variability is due to beat-to-beat adjustments from baroreceptor influence, or

from rapidly oscillating vagal impulses, which vary irregularly in frequency and

amplitude and involve short- and long-term changes.3,4 The magnitude of FHR

variability may be affected by fetal breathing, fetal movements and fetal sleep

state.

In practice, FHR variability is observed as irregular fluctuations in amplitude

and frequency of baseline FHR on a CTG paper and quantified as the amplitude

of peak-to-trough in beats per minute. To exhibit a normal FHR variability, the

fetus requires an intact cerebral cortex, midbrain, vagus nerve and cardiac

conductive tissues.

FHR variability has emerged as a critical determinant of adequate perfusion,

oxygenation and function of the central nervous system and the FHR

characteristic most consistently associated with new-born acidosis and

morbidity. Even in the presence of decelerations or bradycardia, a fetus that

displays a normal variability has a very low risk of acidaemia, immediate death

or asphyxial brain injury,5–7 while absent or reduced variability was associated

with significant new-born acidaemia in both term7,8 and preterm infants.9 In a

recent systematic review, minimal or undetectable FHR variability was the most

consistent predictor of new-born acidaemia.5 In contrast, increased FHR

variation was observed in association with severe acidosis and hypotension in a

hypoxia-ischaemia model using term-equivalent fetal sheep.10 Furthermore,

absent FHR variability may be idiopathic, but usually the other features of FHR

are normal, including cycling activity and absence of FHR decelerations.

Under normal conditions, a large number of control mechanisms are activated in

response to acute hypoxia including chemoreceptor, baroreceptor, sympathetic

and parasympathetic influences. Therefore, fetal response to hypoxia-ischaemiaFHR Characteristics of a Chronically Hypoxic

Fetus

is complex. For the purposes of this chapter, it suffices to state the following

well-established observations: fetal response to maternal hypoxia, reduced

uterine blood flow, or to an umbilical cord occlusion is a prompt FHR

deceleration. This deceleration has a drop of approximately 30 bpm from the

original baseline. This deceleration (or bradycardia) depending on the duration

of insult is variably associated with hypertension and, therefore, can occur with

baroreceptor as well as chemoreceptor activation.

In the absence of progressive acidaemia, the fetal sheep may restore its FHR and

variability to normal after approximately 12–16 hours of exposure to acute

hypoxia. In addition to FHR deceleration outlined above, initial response to

hypoxia includes a rise in fetal blood pressure, a rapid and up to 60 per cent

reduction in oxygen consumption, which can be sustained for up to 45 minutes

depending on the degree of hypoxia and rapidly reversible if the insult is

removed and oxygenation restored. A further response is adrenergic activation.

The resultant β-adrenergic activity leads to increased inotropic effect to maintain

or increase cardiac output and umbilical blood flow, while the α-adrenergic

activity is important in determining regional blood flow in the hypoxic fetus by

selective vasoconstriction. The 60 per cent reduction in oxygen consumption,

FHR deceleration/bradycardia, anaerobic glycolysis and selective

vasoconstriction enable the fetus to survive a relatively long period of limited

oxygen supply currently estimated to be approximately 30–60 minutes without

damage to vital organs. If hypoxia persists, metabolic acidosis would develop

due to lactic acid accumulation in those organs where there has been

vasoconstriction and inadequate oxygen supply for metabolic needs, and in

severe or sustained cases, the above responses fail and are followed by a

decline in cardiac output, blood pressure and blood flow to the brain.The admission CTG may be controversial; however, a prompt recognition of the

fetus with a preexisting brain injury in early labour is one of the strongest

arguments in its favour. Such a key finding permits the obstetrician and/or the

midwife to assign or reassign the patient to her appropriate risk category. A

normal CTG is the hallmark of fetal well-being,11 suggests normoxia,12 normal

acid–base status,13,14 absence of asphyxia13,14 and, in the absence of

unpredictable obstetric catastrophe, a low probability of intrapartum fetal

asphyxia.15

A normal CTG also suggests that the fetal neurological and cardiovascular

systems are intact and able to react and defend the fetus against intrapartum

insults. In contrast, the fetus with an abnormal CTG in early labour may already

be injured and is likely to exhibit maladaptive or no compensatory responses if

exposed to asphyxiating insults during labour. Such a fetus is at risk of adverse

outcome,15 including intrapartum death and long-term neurological deficits.16–18

Fetuses with antecedent brain injury from hypoxic-ischaemic insults do not

exhibit a uniform set of FHR patterns during labour. However, they do display

distinct FHR patterns, which allow the clinician to profile their risk and

management on the basis of initial FHR on admission and subsequent changes in

baseline FHR. The characteristic, but by no means exclusive, FHR pattern of

antenatally injured fetus is nonreactive CTG with a fixed and invariable baseline

from admission to delivery, associated with reduced or average FHR

variability16,17,19 (Figure 18.1). This pattern does not suggest an ongoing

asphyxial insult but represents a post–brain injury compensatory response by the

fetus, a sort of static intrauterine encephalopathy.Figure 18.1 Parous woman, with uneventful antenatal course, admitted with spontaneous

early labour at 38 + 5 weeks of gestation. She was started on CTG because FHR

decelerations were heard on intermittent auscultation. The CTG showed typical nonreactive

FHR pattern with reduced variability of antenatal fetal injury. She delivered spontaneously

many hours later with FHR collapse in the second stage of labour. Apgar score 1 and 1 at

1 and 5 minutes, arterial pH 6.9, venous pH 7.0, HIE grade 3. This outcome is inconsistent

with the gases. MRI showed symmetrical signal abnormality in the thalami and to a lesser

extent in basal ganglia and hippocampi. (A) CTG trace on admission shows absence of

baseline variability. (B) Continuation of the CTG trace shows absence of cycling. (C) CTG

continues to show a higher-than-expected baseline FHR for a posttermfetus. (D) CTG

trace shows the appearance of ‘shallow decelerations’ with advancing labour. (E) CTG

trace shows the onset of a terminal bradycardia which is the end stage of chronic hypoxia

le

ading to an acute on chronic insult.

In a study of 300 brain-damaged babies who were monitored on admission in

labour, a persistently nonreactive FHR pattern was found in 45 per cent.17

Phelan and Kim categorized these nonreactive admission CTGs into three groups

on the basis of baseline FHR and FHR variability in order to correlate the FHR

patterns to the duration of time from injury.20 They concluded that fetuses

admitted with FHR tachycardia >160 bpm and reduced or absent variability

were likely to be closer to the time of insult compared to their peers with normal

baseline FHR and reduced or even average FHR variability who are likely to be

further remote from the time of brain injury.Other Markers of Chronic Hypoxia in the Fetus

Tachycardia associated with a ‘gradually evolving hypoxia’ may still be in

evolution when a woman presents in labour, and this pattern may mimic the

chronically hypoxic fetus. The clinician may be confused because he or she did

not observe the previously normal FHR pattern. However, this pattern is, by

definition, almost always accompanied by repetitive complex variable

decelerations. Once tachycardia begins in response to repetitive decelerations,

the natural history of this pattern may lead to one of a number of outcomes,

namely, FHR tachycardia persists or continues to rise until delivery, or a

prolonged and persistent FHR deceleration or bradycardia until delivery, or

slow but progressive decline of FHR from tachycardia as the fetus approaches

death. In this specific subset of fetuses, the value of FHR variability as a reliable

indicator of fetal well-being has been challenged.21 A proportion of braindamaged children exhibited average FHR variability at the time of their delivery

and manifested cerebral oedema in the neonatal period suggesting that brain

injury in this context may precede loss of FHR variability.

One relevant question is how FHR variability was defined in that study. In

practice, increased FHR variation associated with severe acidosis may be

abrupt, erratic, high amplitude, and lack the natural wavelike characteristic of

normal FHR variability and are oftentimes still classified as increased FHR

variability or saltatory patterns. This is incorrect as it implies exaggerated but

normal wavelike variability.

Other markers of chronic hypoxia and fetal compromise may be observed in

these cases, including reduced fetal movement prior to admission,

oligohydramnios, presence of old meconium staining of amniotic fluid,

meconium aspiration syndrome and subsequent pulmonary hypertension.

Meconium is known to induce vasoconstriction of fetoplacental and chorionic

vessels and in high concentrations may cause ulcerations of these vessels.22,23 InThe Preterminal CTG

Conclusions

addition, meconium degrades the bacteriostatic activity of the amniotic fluid,

thereby increasing the risk of ascending infection and chorioamnionitis.24,25

Therefore, it is conceivable that at least a proportion of the fetuses with

meconium contamination of the amniotic fluid are possibly in a state of systemic

vasoconstriction and may be vulnerable to decompensation and brain injury

during labour. Furthermore, fetuses with a fixed nonreactive FHR pattern have

raised nucleated red blood cells (NRBCs),26,27 prolonged NRBC clearance

times,26 low platelet counts,28 delayed onset of seizures from birth,29 multiorgan

system dysfunction30 and cortical brain injuries.17

The definition of preterminal CTG in classic textbooks and teaching modules,

involving FHR tachycardia, reduced or absent variability and shallow FHR

decelerations, may be misleading in clinical practice. First, the reason such endstage FHR patterns are classified as ‘preterminal’ is because the fetus is at risk

of death if it is not delivered expeditiously. However, there are several other

FHR patterns, which, if left to run their natural courses, would also result in fetal

demise without necessarily operating via the widely recognized and reported

preterminal CTG pattern.

These other patterns include prolonged and persistent FHR deceleration or

bradycardia, particularly if associated with a loss of FHR variability,

tachycardia associated with FHR deceleration and loss of variability, and severe

subacute hypoxia pattern in which there are high amplitude and long-standing

FHR decelerations and short interdeceleration intervals. Clinicians should

rethink their definition and approach to FHR patterns, which carry the risk of

intrapartum fetal death.References

1. Manning FA. Assessment of fetal condition and risk: analysis of single and combined

biophysical variable monitoring. Semin Perinatol. 1985;9:168–83.

2. Van Woerdeen EE, VanGeijn HP. Heart rate patterns and FMs. In J. Nijhuis (ed.) Fetal

Behaviour. New York, NY: Oxford University Press; 1992:41.

3. Parer JT. Fetal heart rate. In R.K. Creasy, R. Resnik, JD Iams (eds.) Maternal Fetal

Medicine: Principles and Practice (5th ed). Philadelphia: Saunders; 2004.

4. Parer JTP, King TL. Whither fetal heart rate monitoring? Obstet Gynecol Fertil.

1999;22:149.

5. Parer JT, King T, Flanders S, Fox M, Kilpatrick SJ. Fetal acidaemia and electronic fetal

heart rate patterns: is there evidence of an association? J Matern Fetal Neonatal Med.

2006;19:289–94.

6. Young BK, Katz M, Klein SA, Silverman F. Fetal blood and tissue pH with moderate

bradycardia. Am J Obstet Gynecol. 1979;135:45–7.

7. Williams KP, Galerneau F. Fetal heart rate parameters predictive of neonatal outcome in the

presence of a prolonged deceleration. Obstet Gynecol. 2002;100:951–4.

A prompt recognition of the FHR pattern of chronically hypoxic fetus and

preterminal CTG is essential to initiating appropriate and timely intervention to

achieve a good outcome. Typically, the fetus with antecedent brain injury

exhibits a nonreactive CTG with a fixed and nonvariable baseline associated

with reduced or average variability, which should not be confused with ongoing

asphyxial insult but represents a postinjury static encephalopathy.

Fetuses admitted with FHR tachycardia >160 bpm and reduced or absent

variability are likely to have suffered a recent injury, in contrast to their peers

with normal baseline FHR and reduced or average FHR variability who are

likely to be remote from the time of brain injury.8. Williams KP, Galerneau F. Intrapartum fetal heart rate patterns in the prediction of neonatal

acidemia. Am J Obstet Gynecol. 2003;188:820–3.

9. Matsuda Y, Maeda T, Kouno S. The critical period of non-reassuring fetal heart rate

patterns in preterm gestation. Eur J Obstet Gynecol Reprod Biol. 2003;106:36–9.

10. Westgate JA, Bennet L, Gunn AJ. Fetal heart rate variability changes during brief repeated

umbilical cord occlusion in near term fetal sheep. Br J Obstet Gynaecol. 1999;106:664–71.

11. Phelan JP. Labour admission test. Clin Perinatol. 1994;21:879–85.

12. Carbonne B, Langer B, Goffinet F, Audibert F, Tardif D, Le Goueff F. et al. Multicenter

study on the clinical value of fetal pulse oximetry. II. Compared predictive values of pulse

oximetry and fetal blood analysis. The French Study Group on Fetal Pulse Oximetry. Am J

Obstet Gynecol. 1997;177:593–8.

13. Clark SL, Gimovsky ML, Miller FC. The scalp stimulation test: a clinical alternative to

fetal scalp blood sampling. Am J Obstet Gynecol. 1984;148:274–7.

14. Shaw K, Clark SL. Reliability of intrapartum fetal heart rate monitoring in the postterm

fetus with meconium passage. Obstet Gynecol. 1988;72:886–9.

15. Ingemarsson I, Arulkumaran S, Ingemarsson E, Tambyraja RL, Ratnam SS. Admission

test: a screening test for fetal distress in labor. Obstet Gynecol. 1986;68:800–6.

16. Phelan JP, Ahn MO. Perinatal observations in forty-eight neurologically impaired term

in

fants. Am J Obstet Gynecol. 1994;171:424–31.

17. Phelan JP, Ahn MO. Fetal heart rate observations in 300 term brain- damaged infants. J

Matern Fetal Inv. 1998;8:1–5.

18. Devoe LD, McKenzie J, Searle NS, Sherline DM. Clinical sequelae of the extended

nonstress test. Am J Obstet Gynecol. 1985;151:1074–8.

19. Leveno KJ, Williams ML, DePalma RT, Whalley PJ. Perinatal outcome in the absence of

antepartum fetal heart rate acceleration. Obstet Gynecol. 1983;61:347–55.

20. Phelan JP, Kim JO. Fetal heart rate observations in the brain-damaged infant. SeminPerinatol. 2000;24:221–9.

21. Takahashi Y, Ukita M, Nakada E. Intrapartum FHR monitoring and neonatal CT brain

scan. Nihon Sanka Fujinka Gakkai Zasshi. 1982;34:2133–42.

22. Altshuler G, Arizawa M, Molnar-Nadasdy G. Meconium-induced umbilical cord vascular

necrosis and ulceration: a potential link between the placenta and poor pregnancy outcome.

Obstet Gynecol. 1992;79:760–6.

23. Pickens J, Toubas PL, Hyde S, Altshuler G. In vitro model of human umbilical venous

perfusion to study the effects of meconium staining of the umbilical cord. Biol Neonate.

1995;67:100–8.

24. Perlman JM, Risser R, Broyles RS. Bilateral cystic periventricular leukomalacia in the

premature infant: associated risk factors. Pediatrics. 1996;97:822–7.

25. Yoon BH, Romero R, Kim CJ, Jun JK, Gomez R, Choi JH, Syn HC. Amniotic fluid

int

erleukin-6: a sensitive test for antenatal diagnosis of acute inflammatory lesions of preterm

placenta and prediction of perinatal morbidity. Am J Obstet Gynecol. 1995;172:960–70.

26. Phelan JP, Ahn MO, Korst LM, Martin GI. Nucleated red blood cells: a marker for fetal

asphyxia? Am J Obstet Gynecol. 1995;173:1380–4.

27. Buonocore G, Perrone S, Gioia D, Gatti MG, Massafra C, Agosta R. et al. Nucleated red

blood cell count at birth as an index of perinatal brain damage. Am J Obstet Gynecol.

1999;181:1500–5.

28. Korst LM, Phelan JP, Wang YM, Ahn MO. Neonatal platelet counts in fetal brain injury.

Am J Perinatol. 1999;16:79–83.

29. Ahn MO, Korst LM, Phelan JP, Martin GI. Does the onset of neonatal seizures correlate

with the timing of fetal neurologic injury? Clin Pediatr (Phila). 1998;37:673–6.

30. Korst LM, Phelan JP, Wang YM, Martin GI, Ahn MO. Acute fetal asphyxia and

permanent brain injury: a retrospective analysis of current indicators. J Matern Fetal Med.

1999;8:101–6.