- Email: [email protected]
Intrapartum fetal surveillance: Monitoring fetal oxygenation with fetal blood sampling and umbilical cord blood analysis
International Congress Series 1279 (2005) 338 – 345
www.ics-elsevier.com
Intrapartum fetal surveillance: Monitoring fetal oxygenation with fetal blood sampling and umbilical cord blood analysis Paul van den Berg University Medical Centre, Groningen, The Netherlands
Abstract. Although electronic fetal heart rate monitoring remains the most popular technique for fetal surveillance during labour, there is much concern about the ever rising Caesarean section rate, probably partly due to this practice. Fetal blood sampling is still the gold standard when it comes to measuring fetal oxygenation. There is enough evidence that the combination of EFM and FBS is more efficient in detecting fetal hypoxia and prevents an unnecessary high intervention rate. Another tool to assess the efficacy of intrapartum fetal monitoring is the measurement of pH and blood gases in the umbilical cord blood. This method can also rule out fetal hypoxia in cases with unreassuring fetal heart rate patterns, meconium and low Apgar scores. Continuing inadequate fetal oxygenation during labour may lead to pathological fetal acidaemia. This means that there is a mixed acidosis in the fetal blood with hypercarbia and a substantial base deficit. A pH b7.00 may lead to later sequelae but the base deficit, indicating the duration of the insult, is a better predictor of neonatal morbidity. D 2005 Elsevier B.V. All rights reserved. Keywords: Electronic fetal heart rate monitoring; Fetal blood sampling; Umbilical cord blood analysis; Fetal oxygenation; Fetal acid-base balance; Hypoxia
The aim of fetal surveillance is simple and straightforward, to identify fetal compromise and prevent morbidity and mortality by timely interventions. Various methods of intrapartum fetal monitoring, such as intermittent auscultation of the fetal heart rate, electronic fetal heart rate monitoring (EFM) and fetal scalp blood sampling, have been developed to identify signs of fetal compromise during labour. When EFM was introduced in the early sixties, hopes were high that with this technique, which supplies continuous information about the fetal heart rate pattern, early E-mail address: [email protected]. 0531-5131/ D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2005.01.014
P. van den Berg / International Congress Series 1279 (2005) 338–345
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signs of hypoxia would be detected, so that timely interventions could decrease mortality or later sequelae [19]. Probably based on this great enthusiasm, EFM was introduced into clinical practice without proper validation. During the mid-seventies there were many reports indicating that electronically monitored fetuses were much better off than those undergoing intermittent auscultation during birth. Fewer intrapartum deaths and better outcomes were observed [4,9,17,18]. Most of these reports were based on retrospective investigations, with data for controls being drawn from women in the pre-monitoring years. That means that many improvements in antenatal and intensive care of the newborn, unrelated to EFM, had been taking place over the same period. The first randomized trial by Haverkamp et al. [6] failed to show any benefit from EFM, compared to auscultation. Furthermore, there was an increase in Caesarean births in the group monitored with EFM as compared to the other group. A subsequent study of the long-term outcome [11] did not reveal any difference between the two groups. Further studies were performed in high as well as in low risk populations without showing a clear difference in the direct neonatal course or long-term follow-up [7,10,13–15,20,28,30]. However, an increase in obstetric interventions in the EFM group was observed. 1. Fetal blood sampling Fetal blood sampling (FBS) to monitor fetal oxygenation during labour was introduced by Saling in 1962 [21]. Adamson validated this method in fetal monkeys [1]. Normal values for pH in uncomplicated labour and delivery ranged from 7.36 to 7.14. Based on this research fetal acidosis was defined as a pH below 7.20 [22]. The use of EFM as the single diagnostic tool to assess the fetal condition became very popular. This is probably one of the reasons for this era of intervention obstetrics. The preoccupation with the fetal heart rate patterns as well as difficulties in performing and measuring a fetal scalp blood sample (FBS) has led away from this technique in some countries. However, the combination of EFM and FBS to verify fetal oxygenation showed less interventions compared to EFM alone in 6 randomized studies [10,13–15,20,27]. Combined fetal supervision with EFM and FBS results in adequate detection of fetal hypoxia and prevents an unnecessarily high Caesarean section rate [25]. The fetal acid–base status is the most reliable index of fetal oxygenation and leaves no room for interpretation. But the degree of academia which leads to a significant increase of neonatal morbidity is still controversially discussed. This may be another motive of a not more widespread use. Nevertheless, obstetricians using EFM as a screening method but basing treatment decisions on FBS as well, were convinced of the intrinsic value of EFM [28]. Other authors have objected to FBS being invasive, cumbersome and disliked by the patients [2]. It is a disadvantage that information about fetal oxygenation is only available at the time of sampling. Over the last three decades, many different approaches have been investigated with the goal to develop a continuous, easy to apply, noninvasive tool which measures fetal oxygenation, to improve the efficacy of fetal surveillance [16].
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P. van den Berg / International Congress Series 1279 (2005) 338–345
2. Umbilical cord blood analysis In 1958 James [8] showed a correlation between umbilical cord pH and depression of the neonate. The umbilical artery offers an easily accessible pathway to investigate fetal oxygenation during labour. The acid–base balance in the cord blood represents an objective parameter of the neonatal condition. Most investigators agree that the umbilical artery pH and blood gas parameters should be used as an indicator of the fetal oxygenation. pH values in the umbilical vein, which comes from the placenta, represent the placental perfusion and should be used as a reference value. Standardized sampling, storing and measurement are essential to be able to compare the results in different populations and clinics. Normal values of a university clinic population have been published by Eskes et al. [3]. They found that maternal factors, intrapartum characteristics and fetal parameters can influence the fetal acid–base balance. Others have also calculated mean values ranging from 7.20 to 7.30 in populations that were defined differently. In numerous studies the correlation between the acid–base balance in the umbilical cord blood and other measures of neonatal condition and outcome were investigated. However, there is no consensus on the definition of fetal acidosis. The relation between Apgar score and umbilical artery pH is problematic as well. Sykes at al. [24] observed that only 21% of infants with a 1 min Apgar score of less than 7 and 19% with a 5 min Apgar score of less than 7 had severe acidosis at birth. On the other hand, 73% of the infants with severe acidosis (umbilical artery pHb7.10 and base deficit N13 mmol/L) at birth had an Apgar score of 7 or more. Other authors also found a weak association between umbilical artery pH and the Apgar score after 1 or 5 min. Silverman et al. [23] found a relation between severe acidosis (umbilical artery pHb7.05) with a metabolic component and a 5 min Apgar score b7. Sampling of the umbilical cord will provide objective documentation about the fetal oxygenation, which can be used as an objective measure to assess intrapartum care. This method can rule out perinatal asphyxia in cases with pathological fetal heart rate patterns, meconium and low Apgar scores. Routine sampling has therefore been proposed. The absence of fetal acidosis, however, does not exclude the possibility that hypoxic episodes have preceded labour and delivery. 3. Fetal oxygenation To maintain aerobic metabolism, oxygen is of vital importance to the fetus. In utero oxygen tensions are low compared to the outside world, and therefore the comparison was made with an environment of high altitude (8000–9000 m) like on Mount Everest, where oxygen tensions are correspondingly low. Although oxygen tension in the umbilical vein is only one-third of that of the human breathing air at sea level, evolution has made some adaptations that guarantee an adequate oxygen supply to the fetus. The first adaptation is found in the fetal circulation, already described by Harvey in 1628 [5], which comprises bypasses (foramen ovale and ductus arteriosus) that close after birth. In 1939 Barclay et al. reported the existence of parallel blood streams in the fetus: well-oxygenated blood coming from the placenta, flows via the inferior caval vein, through the foramen ovale into the left auricle and ventricle, into the aorta to the myocard and the brain. Less-oxygenated blood enters the heart from the superior caval into the right
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Table 1 Maternal and fetal blood gas values
pO2 (mm Hg) SO2 (%) pH pCO2 (mm Hg) Hb (g/l)
Maternal Arterial (ut.)
Maternal venous (ut.)
Fetal venous (umb)
Fetal arterial (umb)
95 98 7.40 32 120
38 72 7.35 40 120
30 85 7.38 43 160
22 60 7.34 48 160
7.5 mm Hg=1 kPa.
ventricle and flows through the pulmonary valve into the pulmonary arteries or via the ductus arteriosus into the aorta. Because of this parallel circulation, the heart and brain are given preferential treatment with respect to the supply of well-oxygenated blood. Further adaptations are the relatively high haemoglobin concentration in the fetal blood and the higher oxygen affinity of fetal haemoglobin compared to adult haemoglobin. Therefore, despite the lower oxygen tension, the oxygen content (99% of oxygen is bound to haemoglobin) equals that of human blood after birth (Table 1). Fetal oxygenation has been well taken care of by nature. 4. The fetal acid–base balance A well-oxygenated fetus mainly metabolizes glucose. The only product of the aerobic metabolism which affects the hydrogen ion concentration is CO2 as CO2 þ H2 O X H2 CO3 X Hþ þ HCO 3 As a result of these acidotic waste products, without adequate precautions, the intraand extra cellular environment would rapidly become acidotic. For optimal cell function, however, stable pH and CO2 levels are mandatory. This means that CO2 must be eliminated via the placenta to the maternal circulation. During transport CO2 is buffered by haemoglobin and HCO3 is formed. This buffer diffuses into plasma and is of vital importance to maintain a steady acid–base balance. The pH or log [H+] of blood plasma depends on the pCO2 and HCO3 concentration. The pH can be calculated according to the formula of Henderson and Hasselbalch: 4 pH ¼ pKV þ log HCO 3 =s pCO2 pKV=6.1 (log ionisation constant of CO2), s*=solubility coefficient of CO2 in plasma. The [HCO3] is influenced by kidney secretion, which is a slow process and the efficacy is related to fetal age. The pCO2 in the fetal blood plasma is a result of (normally rapid) placental diffusion from the fetal to the maternal circulation. pH and blood gases can be measured. HCO3 is calculated as buffer base and base excess or deficit. 5. Fetal CO2 transport Apart from its own metabolism the fetal acid–base balance is influenced by placental factors and the fetal–maternal pCO2 gradient.
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In the steady state, the total cellular CO2 production equals the transplacental CO2 elimination, and thus no changes occur in the fetal pH (see Fig. 1). In the placenta oxygen diffuses to the fetal side where it is bonded to haemoglobin. H+ is formed which binds with HCO3 to form CO2. This diffuses through the syncitio-capillary membrane of the placenta to the maternal side. CO2 binds better to desoxyhaemoglobin than oxyhaemoglobin. The difference in binding capacity between haemoglobin and CO2 depending on the degree of oxygenation is called the Haldane effect. The transplacental diffusion CO2 is apart from the pCO2 gradient and the Haldane effect, also determined by the placental diffusion capacity. Diffusion capacity of the placenta is dependent upon fetal and maternal perfusion and the area of diaplacental gas exchange. Changes in maternal (hypo perfusion in preeclampsia) or fetal (bradycardia) circulation, or placental infarction may influence fetal homeostasis. 6. Maternal factors Early in pregnancy, a physiological decrease of maternal pCO2 from the nonpregnant level of 5.1 kPa (38 mm Hg) to 4.3 kPa (32 mm Hg) occurs due to hyperventilation as a consequence of hormonal changes. Progesterone lowers the threshold of the chemoreceptor for pCO2 and leads to hyperventilation. Because of a larger gradient between fetus and mother, the diffusion is facilitated. Under physiological circumstances this gradient is 2.4 kPa. Changes in maternal pCO2 are paralleled by changes in fetal pCO2. The fetal venous pH is under normal conditions approximately 0.1 units lower than the maternal arterial pH. Lactate concentration in mother and fetus are, however, the same. This difference is thus probably caused by a lower pCO2 gradient in the placenta compared to the lung. During labour the maternal pCO2 is further lowered to values of 2.7 to 3.3 kPa, as a consequence of hyperventilation due to painful contractions. The fetal acid–base balance may also be influenced by metabolic acidosis of the mother due to long labour and exhaustion. In this case lactate slowly diffuses to the fetal circulation causing a fetal metabolic acidosis, although fetal oxygenation has been adequate.
Fig. 1. Transplacental diffusion of CO2 and HCO 3.
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7. Hypoxia Oxygen is essential to ensure adequate energy supply in the cell. Glucose is metabolized to pyruvate and 2 mol of adenosine tri phosphate (ATP)(Emden– Meyerhof cycle). Free ATP is the source of energy for the synthesis of proteins, the sodium–potassium pump, muscle contractions, etc. ATP is being reduced to ADP and metabolized by the mitochondria. Pyruvate metabolizes in aerobic conditions to CO2 and H2O and 36 mol ATP per mol glucose (Krebs cycle). Adequate oxygenation depends on maternal, placental and fetal factors. Inadequate oxygen supply leads to fetal acidosis. During labour contractions may lead to insufficient placental perfusion. On the fetal side the O2 level will drop, CO2 will accumulate and pH will consequently start to drop. If hypoxic conditions persist the fetal circulation will be directed to the vital organs which will minimize oxygen consumption. Anaerobic glycolysis will supply the necessary energy. Pyruvate will be metabolized to lactate. The extra H+ ions are buffered by HCO3. This will lead to a lowering of the buffer capacity or a higher base deficit. Cellular energy supply will drop from 38 mol ATP to 2 mol ATP per mol glucose. The fetus develops a metabolic acidosis due to a pyruvate overload. 8. Pathologic fetal acidaemia Classically an umbilical artery pH of 7.20 was used to define fetal acidosis, but no strong correlations have been found using this limit. Other studies, using an umbilical artery pH between 7.00 and 7.20 as definition of acidosis, did not show good 160 pH=7.00
6.90
6.80
6.70
140
pCO2 (mmHg)
120 100 80 60 40 20 0 0
5
10
15
20
25
30
base deficit (mmol/l)
Fig. 2. Acid–base balance in the umbilical artery in neonates with a pH b7.00. Almost all neonates have a mixed acidosis with hypercarbia N65 mm Hg and a base deficit N12 mmol/L. 5: preterm neonates without neurological complications; n: preterm neonates with neurological complications; D: term neonates without neurological complications; E: term neonates with neurological complications [26].
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correlations either. Winkler et al. [29] proposed a value of pH b7.00 in the umbilical artery to be a clinically more useful cut-off value for diagnosing fetal acidosis. This was based on the significant increase of neonatal neurological dysfunction (seizures) below this level. Others have confirmed these findings, showing also an increase in respiratory, cardiovascular and renal morbidity. It is further argued that there should be a considerable metabolic component (base deficit) to cause multi-organ injury, indicating the duration of insufficient oxygen supply [12]. Van den Berg et al. [26] showed that most fetuses with an umbilical artery pH b7.00 have a mixed acidosis (hypercarbia with large base deficit) (see Fig. 2). Neurological complications were predominantly seen in neonates with a base deficit N15 mmol/L. Other authors also report newborn complications in neonates with severe acidaemia combined with low Apgar scores [23]. Only a small percentage of neonates born with severe acidaemia showed long-term neurological morbidity, however. Probably only 10% of cerebral palsy can be attributed to hypoxic perinatal events. Based on these findings, good clinical practice is probable, whenever in doubt about the fetal condition during labour perform a FBS. When the fetal pH is lower than 7.20 and the base deficit is more than 8 to 9 mmol/L, an operative delivery should be considered. A pH higher than 7.10 in the umbilical artery with a base deficit smaller than 12 mmol/L should be considered as normal. A pH lower than 7.00 with a base deficit greater than 16 mmol/L poses a threat to the neonate’s health [26,27]. References [1] K. Adamsons, R.W. Beard, R.E. Myers, Comparison of the composition of arterial, venous, and capillary blood of the fetal monkey during labor, Am. J. Obstet. Gynecol. 107 (1970) 435 – 440. [2] S.L. Clark, R.H. Paul, Intrapartum fetal surveillance: the role of fetal scalp blood sampling, Am. J. Obstet. Gynecol. 153 (1985) 717 – 720. [3] T.K.A.B. Eskes, H.W. Jongsma, P.C.W. Houx, Percentiles for gas values in human umbilical cord blood, Eur. J. Obstet. Gynecol. Reprod. Biol. 14 (1983) 341 – 346. [4] H.A. Gabert, M.A. Stenchever, Continuous fetal monitoring of fetal heart rate during labor, Am. J. Obstet. Gynecol. 115 (1973) 919 – 923. [5] W. Harvey, Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus. Sumptibus Gulielmi Fitzeri, Frankfurt. 1628. [6] A.D. Haverkamp, et al., The evaluation of continuous fetal heart rate monitoring in high-risk pregnancy, Am. J. Obstet. Gynecol. 125 (1976) 310 – 317. [7] A.D. Haverkamp, et al., A controlled trial of the differential effects of intrapartum fetal monitoring, Am. J. Obstet. Gynecol. 134 (1979) 399 – 412. [8] L.S. James, et al., The acid–base status of human infants in relation to birth asphyxia and onset of respiration, J. Pediatr. 52 (1958) 379 – 394. [9] V.C. Kelly, D. Kulkarni, Experiences with fetal monitoring in a community hospital, Obstet. Gynecol. 41 (1978) 526 – 532. [10] I.M. Kelso, et al., An assessment of continuous fetal heart rate monitoring in labor—a randomized trial, Am. J. Obstet. Gynecol. 131 (1978) 526 – 532. [11] S. Langendoerfer, et al., Pediatric follow-up of a randomized controlled trial of intrapartum fetal monitoring techniques, J. Pediatr. 97 (1980) 103 – 107. [12] J.A. Low, B.G. Lindsay, E.J. Derrick, Threshold of metabolic acidosis associated with newborn complications, Am. J. Obstet. Gynecol. 177 (1997) 1391 – 1394.
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[13] D.A. Luthy, et al., A randomized trial of electronic fetal monitoring in preterm labor, Obstet. Gynecol. 69 (1987) 687 – 695. [14] D. MacDonald, et al., The Dublin randomized controlled trial of intrapartum fetal heart rate monitoring, Am. J. Obstet. Gynecol. 152 (1985) 524 – 539. [15] S. Neldam, et al., Intrapartum fetal heart rate monitoring in a combined low- and high-risk population: a controlled clinical trial, Eur. J. Obstet. Gynecol. Reprod. Biol. 23 (1986) 1 – 11. [16] C. Nickelsen, S.G. Thomsen, T. Weber, Continuous acid–base assessment of the human fetus during labour by tissue-pH and transcutaneous carbon dioxide monitoring, Br. J. Obstet. Gynaecol. 92 (1985) 220 – 225. [17] R.H. Paul, Clinical fetal monitoring: experience on a large clinical service, Am. J. Obstet. Gynecol. 113 (1972) 573 – 577. [18] R.H. Paul, E.H. Hon, Clinical fetal monitoring V. Effect on perinatal outcome, Am. J. Obstet. Gynecol. 118 (1974) 529 – 533. [19] E.J. Quilligan, R.H. Paul, Fetal monitoring: is it worth it? Obstet. Gynecol. 45 (1975) 96 – 100. [20] P. Renou, et al., Controlled trial of fetal intensive care, Am. J. Obstet. Gynecol. 126 (1976) 470 – 476. [21] E. Saling, Erstmalige Blutgasenalysen und pH Messungen an Feten unter der Geburt und die klinische Bedeutung dieses neuen Verfahrens, Arch. Gynakol. 198 (1962) 82. [22] E. Saling, Fetal scalp blood analysis, J. Perinat. Med. 9 (1981) 165 – 177. [23] F. Silverman, et al., The Apgar score: is it enough? Obstet. Gynecol. 66 (1985) 331 – 336. [24] G.S. Sykes, et al., Do Apgar scores indicate asphyxia, Lancet i (1982) 494 – 495. [25] P.P. van den Berg, et al., Fetal distress and the condition of the newborn using cardiotocography and fetal blood analysis during labour, Br. J. Obstet. Gynaecol. 94 (1987) 72 – 75. [26] P.P. van den Berg, et al., Neonatal complications in newborns with an umbilical artery pHb7.00, Am. J. Obstet. Gynecol. 175 (1996) 1152 – 1157. [27] R. Victory, et al., Umbilical cord pH and base excess values in relation to adverse outcome events for infants delivering at term, Am. J. Obstet. Gynecol. 191 (2004) 2021 – 2028. [28] A.M. Vintzeleos, et al., A randomized trial of intrapartum electronic fetal heart rate monitoring versus intermittent auscultation, Obstet. Gynecol. 81 (1993) 899 – 907. [29] C.L. Winkler, et al., Neonatal complications at term as related to the degree of umbilical artery academia, Am. J. Obstet. Gynecol. 164 (1991) 637 – 641. [30] C. Wood, et al., A controlled trial of fetal heart rate monitoring in a low-risk obstetric population, Am. J. Obstet. Gynecol. 141 (1981) 527 – 534.
www.ics-elsevier.com
Intrapartum fetal surveillance: Monitoring fetal oxygenation with fetal blood sampling and umbilical cord blood analysis Paul van den Berg University Medical Centre, Groningen, The Netherlands
Abstract. Although electronic fetal heart rate monitoring remains the most popular technique for fetal surveillance during labour, there is much concern about the ever rising Caesarean section rate, probably partly due to this practice. Fetal blood sampling is still the gold standard when it comes to measuring fetal oxygenation. There is enough evidence that the combination of EFM and FBS is more efficient in detecting fetal hypoxia and prevents an unnecessary high intervention rate. Another tool to assess the efficacy of intrapartum fetal monitoring is the measurement of pH and blood gases in the umbilical cord blood. This method can also rule out fetal hypoxia in cases with unreassuring fetal heart rate patterns, meconium and low Apgar scores. Continuing inadequate fetal oxygenation during labour may lead to pathological fetal acidaemia. This means that there is a mixed acidosis in the fetal blood with hypercarbia and a substantial base deficit. A pH b7.00 may lead to later sequelae but the base deficit, indicating the duration of the insult, is a better predictor of neonatal morbidity. D 2005 Elsevier B.V. All rights reserved. Keywords: Electronic fetal heart rate monitoring; Fetal blood sampling; Umbilical cord blood analysis; Fetal oxygenation; Fetal acid-base balance; Hypoxia
The aim of fetal surveillance is simple and straightforward, to identify fetal compromise and prevent morbidity and mortality by timely interventions. Various methods of intrapartum fetal monitoring, such as intermittent auscultation of the fetal heart rate, electronic fetal heart rate monitoring (EFM) and fetal scalp blood sampling, have been developed to identify signs of fetal compromise during labour. When EFM was introduced in the early sixties, hopes were high that with this technique, which supplies continuous information about the fetal heart rate pattern, early E-mail address: [email protected]. 0531-5131/ D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2005.01.014
P. van den Berg / International Congress Series 1279 (2005) 338–345
339
signs of hypoxia would be detected, so that timely interventions could decrease mortality or later sequelae [19]. Probably based on this great enthusiasm, EFM was introduced into clinical practice without proper validation. During the mid-seventies there were many reports indicating that electronically monitored fetuses were much better off than those undergoing intermittent auscultation during birth. Fewer intrapartum deaths and better outcomes were observed [4,9,17,18]. Most of these reports were based on retrospective investigations, with data for controls being drawn from women in the pre-monitoring years. That means that many improvements in antenatal and intensive care of the newborn, unrelated to EFM, had been taking place over the same period. The first randomized trial by Haverkamp et al. [6] failed to show any benefit from EFM, compared to auscultation. Furthermore, there was an increase in Caesarean births in the group monitored with EFM as compared to the other group. A subsequent study of the long-term outcome [11] did not reveal any difference between the two groups. Further studies were performed in high as well as in low risk populations without showing a clear difference in the direct neonatal course or long-term follow-up [7,10,13–15,20,28,30]. However, an increase in obstetric interventions in the EFM group was observed. 1. Fetal blood sampling Fetal blood sampling (FBS) to monitor fetal oxygenation during labour was introduced by Saling in 1962 [21]. Adamson validated this method in fetal monkeys [1]. Normal values for pH in uncomplicated labour and delivery ranged from 7.36 to 7.14. Based on this research fetal acidosis was defined as a pH below 7.20 [22]. The use of EFM as the single diagnostic tool to assess the fetal condition became very popular. This is probably one of the reasons for this era of intervention obstetrics. The preoccupation with the fetal heart rate patterns as well as difficulties in performing and measuring a fetal scalp blood sample (FBS) has led away from this technique in some countries. However, the combination of EFM and FBS to verify fetal oxygenation showed less interventions compared to EFM alone in 6 randomized studies [10,13–15,20,27]. Combined fetal supervision with EFM and FBS results in adequate detection of fetal hypoxia and prevents an unnecessarily high Caesarean section rate [25]. The fetal acid–base status is the most reliable index of fetal oxygenation and leaves no room for interpretation. But the degree of academia which leads to a significant increase of neonatal morbidity is still controversially discussed. This may be another motive of a not more widespread use. Nevertheless, obstetricians using EFM as a screening method but basing treatment decisions on FBS as well, were convinced of the intrinsic value of EFM [28]. Other authors have objected to FBS being invasive, cumbersome and disliked by the patients [2]. It is a disadvantage that information about fetal oxygenation is only available at the time of sampling. Over the last three decades, many different approaches have been investigated with the goal to develop a continuous, easy to apply, noninvasive tool which measures fetal oxygenation, to improve the efficacy of fetal surveillance [16].
340
P. van den Berg / International Congress Series 1279 (2005) 338–345
2. Umbilical cord blood analysis In 1958 James [8] showed a correlation between umbilical cord pH and depression of the neonate. The umbilical artery offers an easily accessible pathway to investigate fetal oxygenation during labour. The acid–base balance in the cord blood represents an objective parameter of the neonatal condition. Most investigators agree that the umbilical artery pH and blood gas parameters should be used as an indicator of the fetal oxygenation. pH values in the umbilical vein, which comes from the placenta, represent the placental perfusion and should be used as a reference value. Standardized sampling, storing and measurement are essential to be able to compare the results in different populations and clinics. Normal values of a university clinic population have been published by Eskes et al. [3]. They found that maternal factors, intrapartum characteristics and fetal parameters can influence the fetal acid–base balance. Others have also calculated mean values ranging from 7.20 to 7.30 in populations that were defined differently. In numerous studies the correlation between the acid–base balance in the umbilical cord blood and other measures of neonatal condition and outcome were investigated. However, there is no consensus on the definition of fetal acidosis. The relation between Apgar score and umbilical artery pH is problematic as well. Sykes at al. [24] observed that only 21% of infants with a 1 min Apgar score of less than 7 and 19% with a 5 min Apgar score of less than 7 had severe acidosis at birth. On the other hand, 73% of the infants with severe acidosis (umbilical artery pHb7.10 and base deficit N13 mmol/L) at birth had an Apgar score of 7 or more. Other authors also found a weak association between umbilical artery pH and the Apgar score after 1 or 5 min. Silverman et al. [23] found a relation between severe acidosis (umbilical artery pHb7.05) with a metabolic component and a 5 min Apgar score b7. Sampling of the umbilical cord will provide objective documentation about the fetal oxygenation, which can be used as an objective measure to assess intrapartum care. This method can rule out perinatal asphyxia in cases with pathological fetal heart rate patterns, meconium and low Apgar scores. Routine sampling has therefore been proposed. The absence of fetal acidosis, however, does not exclude the possibility that hypoxic episodes have preceded labour and delivery. 3. Fetal oxygenation To maintain aerobic metabolism, oxygen is of vital importance to the fetus. In utero oxygen tensions are low compared to the outside world, and therefore the comparison was made with an environment of high altitude (8000–9000 m) like on Mount Everest, where oxygen tensions are correspondingly low. Although oxygen tension in the umbilical vein is only one-third of that of the human breathing air at sea level, evolution has made some adaptations that guarantee an adequate oxygen supply to the fetus. The first adaptation is found in the fetal circulation, already described by Harvey in 1628 [5], which comprises bypasses (foramen ovale and ductus arteriosus) that close after birth. In 1939 Barclay et al. reported the existence of parallel blood streams in the fetus: well-oxygenated blood coming from the placenta, flows via the inferior caval vein, through the foramen ovale into the left auricle and ventricle, into the aorta to the myocard and the brain. Less-oxygenated blood enters the heart from the superior caval into the right
P. van den Berg / International Congress Series 1279 (2005) 338–345
341
Table 1 Maternal and fetal blood gas values
pO2 (mm Hg) SO2 (%) pH pCO2 (mm Hg) Hb (g/l)
Maternal Arterial (ut.)
Maternal venous (ut.)
Fetal venous (umb)
Fetal arterial (umb)
95 98 7.40 32 120
38 72 7.35 40 120
30 85 7.38 43 160
22 60 7.34 48 160
7.5 mm Hg=1 kPa.
ventricle and flows through the pulmonary valve into the pulmonary arteries or via the ductus arteriosus into the aorta. Because of this parallel circulation, the heart and brain are given preferential treatment with respect to the supply of well-oxygenated blood. Further adaptations are the relatively high haemoglobin concentration in the fetal blood and the higher oxygen affinity of fetal haemoglobin compared to adult haemoglobin. Therefore, despite the lower oxygen tension, the oxygen content (99% of oxygen is bound to haemoglobin) equals that of human blood after birth (Table 1). Fetal oxygenation has been well taken care of by nature. 4. The fetal acid–base balance A well-oxygenated fetus mainly metabolizes glucose. The only product of the aerobic metabolism which affects the hydrogen ion concentration is CO2 as CO2 þ H2 O X H2 CO3 X Hþ þ HCO 3 As a result of these acidotic waste products, without adequate precautions, the intraand extra cellular environment would rapidly become acidotic. For optimal cell function, however, stable pH and CO2 levels are mandatory. This means that CO2 must be eliminated via the placenta to the maternal circulation. During transport CO2 is buffered by haemoglobin and HCO3 is formed. This buffer diffuses into plasma and is of vital importance to maintain a steady acid–base balance. The pH or log [H+] of blood plasma depends on the pCO2 and HCO3 concentration. The pH can be calculated according to the formula of Henderson and Hasselbalch: 4 pH ¼ pKV þ log HCO 3 =s pCO2 pKV=6.1 (log ionisation constant of CO2), s*=solubility coefficient of CO2 in plasma. The [HCO3] is influenced by kidney secretion, which is a slow process and the efficacy is related to fetal age. The pCO2 in the fetal blood plasma is a result of (normally rapid) placental diffusion from the fetal to the maternal circulation. pH and blood gases can be measured. HCO3 is calculated as buffer base and base excess or deficit. 5. Fetal CO2 transport Apart from its own metabolism the fetal acid–base balance is influenced by placental factors and the fetal–maternal pCO2 gradient.
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In the steady state, the total cellular CO2 production equals the transplacental CO2 elimination, and thus no changes occur in the fetal pH (see Fig. 1). In the placenta oxygen diffuses to the fetal side where it is bonded to haemoglobin. H+ is formed which binds with HCO3 to form CO2. This diffuses through the syncitio-capillary membrane of the placenta to the maternal side. CO2 binds better to desoxyhaemoglobin than oxyhaemoglobin. The difference in binding capacity between haemoglobin and CO2 depending on the degree of oxygenation is called the Haldane effect. The transplacental diffusion CO2 is apart from the pCO2 gradient and the Haldane effect, also determined by the placental diffusion capacity. Diffusion capacity of the placenta is dependent upon fetal and maternal perfusion and the area of diaplacental gas exchange. Changes in maternal (hypo perfusion in preeclampsia) or fetal (bradycardia) circulation, or placental infarction may influence fetal homeostasis. 6. Maternal factors Early in pregnancy, a physiological decrease of maternal pCO2 from the nonpregnant level of 5.1 kPa (38 mm Hg) to 4.3 kPa (32 mm Hg) occurs due to hyperventilation as a consequence of hormonal changes. Progesterone lowers the threshold of the chemoreceptor for pCO2 and leads to hyperventilation. Because of a larger gradient between fetus and mother, the diffusion is facilitated. Under physiological circumstances this gradient is 2.4 kPa. Changes in maternal pCO2 are paralleled by changes in fetal pCO2. The fetal venous pH is under normal conditions approximately 0.1 units lower than the maternal arterial pH. Lactate concentration in mother and fetus are, however, the same. This difference is thus probably caused by a lower pCO2 gradient in the placenta compared to the lung. During labour the maternal pCO2 is further lowered to values of 2.7 to 3.3 kPa, as a consequence of hyperventilation due to painful contractions. The fetal acid–base balance may also be influenced by metabolic acidosis of the mother due to long labour and exhaustion. In this case lactate slowly diffuses to the fetal circulation causing a fetal metabolic acidosis, although fetal oxygenation has been adequate.
Fig. 1. Transplacental diffusion of CO2 and HCO 3.
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7. Hypoxia Oxygen is essential to ensure adequate energy supply in the cell. Glucose is metabolized to pyruvate and 2 mol of adenosine tri phosphate (ATP)(Emden– Meyerhof cycle). Free ATP is the source of energy for the synthesis of proteins, the sodium–potassium pump, muscle contractions, etc. ATP is being reduced to ADP and metabolized by the mitochondria. Pyruvate metabolizes in aerobic conditions to CO2 and H2O and 36 mol ATP per mol glucose (Krebs cycle). Adequate oxygenation depends on maternal, placental and fetal factors. Inadequate oxygen supply leads to fetal acidosis. During labour contractions may lead to insufficient placental perfusion. On the fetal side the O2 level will drop, CO2 will accumulate and pH will consequently start to drop. If hypoxic conditions persist the fetal circulation will be directed to the vital organs which will minimize oxygen consumption. Anaerobic glycolysis will supply the necessary energy. Pyruvate will be metabolized to lactate. The extra H+ ions are buffered by HCO3. This will lead to a lowering of the buffer capacity or a higher base deficit. Cellular energy supply will drop from 38 mol ATP to 2 mol ATP per mol glucose. The fetus develops a metabolic acidosis due to a pyruvate overload. 8. Pathologic fetal acidaemia Classically an umbilical artery pH of 7.20 was used to define fetal acidosis, but no strong correlations have been found using this limit. Other studies, using an umbilical artery pH between 7.00 and 7.20 as definition of acidosis, did not show good 160 pH=7.00
6.90
6.80
6.70
140
pCO2 (mmHg)
120 100 80 60 40 20 0 0
5
10
15
20
25
30
base deficit (mmol/l)
Fig. 2. Acid–base balance in the umbilical artery in neonates with a pH b7.00. Almost all neonates have a mixed acidosis with hypercarbia N65 mm Hg and a base deficit N12 mmol/L. 5: preterm neonates without neurological complications; n: preterm neonates with neurological complications; D: term neonates without neurological complications; E: term neonates with neurological complications [26].
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correlations either. Winkler et al. [29] proposed a value of pH b7.00 in the umbilical artery to be a clinically more useful cut-off value for diagnosing fetal acidosis. This was based on the significant increase of neonatal neurological dysfunction (seizures) below this level. Others have confirmed these findings, showing also an increase in respiratory, cardiovascular and renal morbidity. It is further argued that there should be a considerable metabolic component (base deficit) to cause multi-organ injury, indicating the duration of insufficient oxygen supply [12]. Van den Berg et al. [26] showed that most fetuses with an umbilical artery pH b7.00 have a mixed acidosis (hypercarbia with large base deficit) (see Fig. 2). Neurological complications were predominantly seen in neonates with a base deficit N15 mmol/L. Other authors also report newborn complications in neonates with severe acidaemia combined with low Apgar scores [23]. Only a small percentage of neonates born with severe acidaemia showed long-term neurological morbidity, however. Probably only 10% of cerebral palsy can be attributed to hypoxic perinatal events. Based on these findings, good clinical practice is probable, whenever in doubt about the fetal condition during labour perform a FBS. When the fetal pH is lower than 7.20 and the base deficit is more than 8 to 9 mmol/L, an operative delivery should be considered. A pH higher than 7.10 in the umbilical artery with a base deficit smaller than 12 mmol/L should be considered as normal. A pH lower than 7.00 with a base deficit greater than 16 mmol/L poses a threat to the neonate’s health [26,27]. References [1] K. Adamsons, R.W. Beard, R.E. Myers, Comparison of the composition of arterial, venous, and capillary blood of the fetal monkey during labor, Am. J. Obstet. Gynecol. 107 (1970) 435 – 440. [2] S.L. Clark, R.H. Paul, Intrapartum fetal surveillance: the role of fetal scalp blood sampling, Am. J. Obstet. Gynecol. 153 (1985) 717 – 720. [3] T.K.A.B. Eskes, H.W. Jongsma, P.C.W. Houx, Percentiles for gas values in human umbilical cord blood, Eur. J. Obstet. Gynecol. Reprod. Biol. 14 (1983) 341 – 346. [4] H.A. Gabert, M.A. Stenchever, Continuous fetal monitoring of fetal heart rate during labor, Am. J. Obstet. Gynecol. 115 (1973) 919 – 923. [5] W. Harvey, Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus. Sumptibus Gulielmi Fitzeri, Frankfurt. 1628. [6] A.D. Haverkamp, et al., The evaluation of continuous fetal heart rate monitoring in high-risk pregnancy, Am. J. Obstet. Gynecol. 125 (1976) 310 – 317. [7] A.D. Haverkamp, et al., A controlled trial of the differential effects of intrapartum fetal monitoring, Am. J. Obstet. Gynecol. 134 (1979) 399 – 412. [8] L.S. James, et al., The acid–base status of human infants in relation to birth asphyxia and onset of respiration, J. Pediatr. 52 (1958) 379 – 394. [9] V.C. Kelly, D. Kulkarni, Experiences with fetal monitoring in a community hospital, Obstet. Gynecol. 41 (1978) 526 – 532. [10] I.M. Kelso, et al., An assessment of continuous fetal heart rate monitoring in labor—a randomized trial, Am. J. Obstet. Gynecol. 131 (1978) 526 – 532. [11] S. Langendoerfer, et al., Pediatric follow-up of a randomized controlled trial of intrapartum fetal monitoring techniques, J. Pediatr. 97 (1980) 103 – 107. [12] J.A. Low, B.G. Lindsay, E.J. Derrick, Threshold of metabolic acidosis associated with newborn complications, Am. J. Obstet. Gynecol. 177 (1997) 1391 – 1394.
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[13] D.A. Luthy, et al., A randomized trial of electronic fetal monitoring in preterm labor, Obstet. Gynecol. 69 (1987) 687 – 695. [14] D. MacDonald, et al., The Dublin randomized controlled trial of intrapartum fetal heart rate monitoring, Am. J. Obstet. Gynecol. 152 (1985) 524 – 539. [15] S. Neldam, et al., Intrapartum fetal heart rate monitoring in a combined low- and high-risk population: a controlled clinical trial, Eur. J. Obstet. Gynecol. Reprod. Biol. 23 (1986) 1 – 11. [16] C. Nickelsen, S.G. Thomsen, T. Weber, Continuous acid–base assessment of the human fetus during labour by tissue-pH and transcutaneous carbon dioxide monitoring, Br. J. Obstet. Gynaecol. 92 (1985) 220 – 225. [17] R.H. Paul, Clinical fetal monitoring: experience on a large clinical service, Am. J. Obstet. Gynecol. 113 (1972) 573 – 577. [18] R.H. Paul, E.H. Hon, Clinical fetal monitoring V. Effect on perinatal outcome, Am. J. Obstet. Gynecol. 118 (1974) 529 – 533. [19] E.J. Quilligan, R.H. Paul, Fetal monitoring: is it worth it? Obstet. Gynecol. 45 (1975) 96 – 100. [20] P. Renou, et al., Controlled trial of fetal intensive care, Am. J. Obstet. Gynecol. 126 (1976) 470 – 476. [21] E. Saling, Erstmalige Blutgasenalysen und pH Messungen an Feten unter der Geburt und die klinische Bedeutung dieses neuen Verfahrens, Arch. Gynakol. 198 (1962) 82. [22] E. Saling, Fetal scalp blood analysis, J. Perinat. Med. 9 (1981) 165 – 177. [23] F. Silverman, et al., The Apgar score: is it enough? Obstet. Gynecol. 66 (1985) 331 – 336. [24] G.S. Sykes, et al., Do Apgar scores indicate asphyxia, Lancet i (1982) 494 – 495. [25] P.P. van den Berg, et al., Fetal distress and the condition of the newborn using cardiotocography and fetal blood analysis during labour, Br. J. Obstet. Gynaecol. 94 (1987) 72 – 75. [26] P.P. van den Berg, et al., Neonatal complications in newborns with an umbilical artery pHb7.00, Am. J. Obstet. Gynecol. 175 (1996) 1152 – 1157. [27] R. Victory, et al., Umbilical cord pH and base excess values in relation to adverse outcome events for infants delivering at term, Am. J. Obstet. Gynecol. 191 (2004) 2021 – 2028. [28] A.M. Vintzeleos, et al., A randomized trial of intrapartum electronic fetal heart rate monitoring versus intermittent auscultation, Obstet. Gynecol. 81 (1993) 899 – 907. [29] C.L. Winkler, et al., Neonatal complications at term as related to the degree of umbilical artery academia, Am. J. Obstet. Gynecol. 164 (1991) 637 – 641. [30] C. Wood, et al., A controlled trial of fetal heart rate monitoring in a low-risk obstetric population, Am. J. Obstet. Gynecol. 141 (1981) 527 – 534.