Early
Human
Development,
29 (1992)
259
259-267
Elsevier Scientific Publishers Ireland Ltd. EHD 01286
The role of Doppler technology in the evaluation of fetal hypoxia G.C. Di Renzo, G. Luzi, G.C. Cucchia, G. Caserta, P. Fusaro, A. Perdikaris and E.V. Cosmi Institute
of
Gynecology
University of Perugia and and Obstefrics, Gynecology, University ‘La Sapien--a ‘, Roma
2nd Institute (Italy)
of
Obstetrics
and
Summary Failing intrauterine support to the fetus can lead to intrauterine growth retardation (IUGR) and hypoxia and it is associated with a high risk of perinatal morbidity and mortality. The main effects of moderate to severe hypoxia on the fetus are different degrees of blood flow redistribution and reduction of oxygen consumption to maintain oxygen delivery to the central organs at the expenses of peripheral organs. The redistribution results in a ‘brain sparing’ effect. Recently, a Doppler ultrasonic technology (continuous wave, pulsed wave and colour flow imaging) has been developed for the non invasive measurement of flow. Doppler velocimetry detects the flow velocity waveform (FVW) which reflects the cardiac output, the vascular compliance and the resistance to the flow in a defined point of the vessel. Velocity waveform indices or even simpler criteria, such as the presence or absence of diastolic flow or flow reverse during diastole, have been applied to a number of fetal vessels. A significant relationship exists between blood oxygen, systemic lactic acidosis (determined by cordocentesis) and increase PI values in umbilical artery (UA), thoracic aorta (TA) and renal artery (RA). Moreover, in experimental animals during steady state hypoxia, several cardiovascular parameters are affected (heart rate/cardiac output decreases and blood pressure increases) while placental flow don’t show a significant variation thus suggesting a raise in placental vascular resistance. Redistribution of the flow may be reliably evaluated by the cerebroplacental ratio (i.e. ratio between PI of MCA and PI of UA, c/p). The phenomenon of absent or reverse end diastolic flow (ARED) has been related to severe fetal hypoxia and this abnormal finding is suggested to occur before FHR monitoring shows evidence of fetal distress. Doppler ultrasound, in combination with ultrasonic Correspondence 10: G.C. Di Renzo, Institute of Gynecology and Obstetrics, University of Perugia Policlinico Monteluce, 06122 Perugia, Italy.
0378-3782/92/$05.00 0 1992 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland
260
imaging, offers the possibility of assessing fetal hypoxia in some detail, without significant discomfort for the patient and without any known risk. This functional assessment of the fetus offers the possibility of furthering our knowledge of mechanisms involved and the consequences of the low oxygen level in the fetus and of the effects of various therapeutic measures. Key words: Doppler; fetal hypoxia; umbilical artery; placental blood flow
Introduction The intrauterine support of fundamental nutritional substances to the fetus is mediated through their transit from placental blood to umbilical blood by a variety of complex mechanisms. The most important sign of alterated support is the failing of oxygen level in the fetal blood, which, consequently, compromises the fetal homeostasis and behaviour [l]. The definition of fetal hypoxia is controversial and rather difficult. In a strict sense all fetuses are born ‘asphyxiated’, because there is a mixed respiratory and metabolic acidosis and hypoxemia in newborns with a normal intrapartum course and outcome [2]. ‘Fetal hypoxia’ is usually referred to a decrease in level of fetal oxygenation below a normal limit [3]. However, the question arises on what is the normal oxygen level. The fetus, infact, maintains an adequate uptake of oxygen in the presence of very low oxygen tension in the umbilical circulation in contrast to the adult; it is known that this phenomenon is related to the particular properties of fetal hemoglobin [4]. On the other hand asphyxia has the pathologic meaning of insufficiency or absence of exchange of respiratory gases although etimologically it is derived from the Greek word meaning ‘pulseless’ [2-31; its severity is described in terms of acidosis, hypoxemia and hypercarbia; with prolonged hypoxia, anaerobic metabolism within the organism results in lactic acidemia, which aggravates the acidosis and creates the so called ‘fetal distress’ [2-31. Fetal distress, therefore, is a progressive fetal asphyxia that, if not corrected or circumvented, will result in decompensation of physiologic responses, primarily redistribution of blood flow to preserve oxygenation of vital organs [2]. Whatever definition is accepted, it is doubtless that severe fetal asphyxia can cause cerebral palsy and lesser degrees of neurologic damages although it is now clear that the portion of cerebral palsy caused by birth asphyxia is relatively small, confined to less than 10% [5]. There are basically three common means by which the human fetus can became asphyxiated or, as said more commonly, hypoxic: (1) insufficiency of uterine blood flow; (2) insufficiency of umbilical blood flow; (3) a decrease in maternal arterial oxygen content (61. Other mechanisms, such as fetal anemia or increased fetal oxygen needs (i.e. in pyrexia) are relatively rarely seen clinically [2]. When such a case occurs, the fetus adapts progressively to chronic low PO, through some mechanisms, the most prominent of which is the decrease of activity and the reduction of growth. In this period, the fetus shows a redistribution of blood supply to
261
vital organs (brain, heart, adrenals); when the hypoxia continues to be unbalanced, the fetus increases his circulatory red blood cells and then activates anaerobic metabolism with consequent metabolic acidosis [l-6]. This cascade of events is regulated by endocrine and paracrine mechanisms; in particular, the hemodynamic alterations are controlled by oxygen levels, CO2 tension, alpha-adrenergic and betaadrenergic activity, renin-angiotensin system, endogenous opioids, prostaglandins and others unidentified regulators [6]. Cerebral and myocardial oxygen consumption can be maintained during moderate hypoxia by the increase in blood flow to the respective organs that exactly balances a decrease in arterovenous oxygen content difference. At moderate degrees of hypoxia the overall cardiac output remain fairly stable but at more severe degrees of hypoxia or asphyxia cardiac output decreases [7]. In the brain the asphyxia result in oxygen debt to brain cells and impaired autoregulation of cerebral blood flow with intracellular swelling; subsequently focal ischemia occurs and then generalized brain swelling with increased intracranial pressure and cerebral necrosis and, at the end, atrophic cortical sclerosis [8]. In summary, fetal distress is ‘a progressive fetal hypoxia or asphyxia that not corrected or circumvented, will result in decompensation of the physiologic responses (primarily redistribution of blood flow to preserve oxygenation of vital organs) and cause permanent central nervous system and or the damage or death’ [2]. It is therefore of outmost importance to monitor the fetal state in order to detect as early as possible impending risk of hypoxia. Doppler velocimetry studies There are several pathologic conditions in pregnancy which dictate a careful monitoring of fetal conditions, the most common being: chronic hypertension, pregnancy induced hypertension, gestational diabetes, previous stillbirth, suspected IUGR, prolonged pregnancy, decrease fetal movements, premature rupture of membranes, advanced maternal age, sickle cells disease [9]. In recent year the perinatal armamentarium has gained several instruments for fetal surveillance: fetal movement survey, non stress test, oxytocin challenge test, test of fetal stimulation, biophysical profile, amniotic fluid index, placental grading, cordocentesis and Doppler velocimetry; all this tests are complementary to each other and necessitate of, at least, two instrumentations: the cardiotocographic equipment and the ultrasound imaging system coupled with a Doppler system. The recent development in Doppler technique has made three Doppler systems available for clinical application: pulsed, continuous and colour flow mapping. The three systems are complementary to each other for obtaining information on blood flow velocity within the cardiovascular system in the fetus and newborn [lo]. The Doppler technique can be used to study almost all fetal and maternal vascular districts in pregnancy; every vessel has a characteristic flow velocity waveform (FVW) which can be modified by gestational age and pathological pregnancy development. The FVW reflects the phase of the cardiac cycle: the ascending part and the initial descending part reflect the force of systolic input and depend from the distance of the heart from the vessel; the remaining descending part and the
262
diastolic waveform reflect the vasal compliance (due to the type of arterial vessel) and the resistance to flow [ll]. Therefore the uterine artery (UA) FVW shows a diminished resistance to blood flow during normal pregnancy [12], while the fetal aorta maintains an unalterated profile during pregnancy [13], as expression of the sum of different alterations of resistance into the various vascular districts of the fetus. In the cerebral circulation [12] a slight fall of resistance to flow is reported, compared to the umbilical circulation. For the objective evaluation of the FVW variations, several indices have been introduced, the most common being the
Fig. 1. Femoral artery FVW in normal (a) and IUGR fetuses (b). PI index: a = 1.8, b = 2.9
263 TABLE
1
Pulsatility Fetal
index
(PI)
variation
during
hypoxia
in the third
Method
vessels
Umbilical artery Middle cerebral artery Internal carotid artery Common carotid artery Thoracic aorta Abdominal aorta Renal artery External iliac artery Femoral artery PWD,
in the fetal vessels
pulsed
wave
PWD PWD PWD PWD PWD PWD
6’4 WC& WA) (CC.4 PA) (AA) WA) WA) CF.4
Doppler;
CFI,
PWD PWD colour
flow
trimester
of pregnancy.
PI I I I 1 I= I= f t I
CFI CFI CFI CFI CFI CFI CFI
imaging.
systolic-diastolic ratio (S/D or A/B), the resistance index (RI) and the pulsatility index (PI) [lo]. The FVW of the fetal vessels may also reflect the variation of vascular resistance of the fetal circulation due to the hypoxia: the FVW of the umbilical artery reflects the increase of placental resistance: as the diastolic flow diminishes, the PI index increases. Other important vessels, like the renal artery or the femoral artery [14- 151 (Fig. 1) show increased resistance during gestation; theoretically these vessels should be more sensitive to the vasoconstriction due to hypoxia than the umbilical artery but for many reasons (i.e. difficulty in vessel detection, at least without colour flow mapping, the small diameter of the vessel, the
TABLE
II
Indices of blood flow last half of pregnancy;
velocity waveform cumulative data
Population
Index
(N)
Umbilical artery 1303 759 227 Fetal aorta 134 Fetal cerebral circulation 36 105 112 PI, pulsatility
index;
in umbilical artery, fetal aorta years 1984-1989 (data modified
and cerebral circulation from Ref. 27)
during
Gestational
age (weeks)
20
24
28
32
36
40
3.9 0.75 1.7
3.5 0.72 1.5
3.2 0.7 1.1
2.8 0.65 0.9
2.5 0.59 0.8
2.1 0.54 0.75
PI
1.9
1.8
2.0
1.8
1.9
S/D RI PI
6.4
8.4 0.85 2.7
0.82 2.6
2.3
3.8 0.72 1.8
S/D RI PI
S/D,
systolic-diastolic
ratio;
RI,
resistance
index.
264
movements of the fetus and so on) are detected only sometimes. In the cerebral circulation the vessel’s resistance diminishes: during hypoxia the FVW increases in diastole and PI decreases in most cerebral vessels [16] (Tables I and II). A correlation between flow indexes of umbilical artery and PO* tension and/or lactate concentration in fetal blood obtained by cordocentesis has been demonstrated: low PO, tension and high lactate concentration are related to high PI values [17-181. On the other hand the hyperoxygenation obtained by maternal oxygen therapy in cases of IUGR does not seem to change significantly the UA flow’s indices [19-201. Probably this fact is due to the particular characteristics of fetal hemoglobin. In our hands, the best index of fetal hypoxia is the cerebra-placental ratio (C/P) which is the ratio between the PI of the middle cerebral artery and the PI of the umbilical artery; this index is mainly the expression of the balance in the redistribution of fetal circulation. We reported that, when this ratio is less than one, there is a significant reduction of growth centile at birth, a high percentage of abnormal intrapartum CTG and a high percentage of low-Apgar score at first minute [21-221 (Table III). Sensitivity and specificity of this index are fairly good (Table IV).
TABLE
III
Cerebro-placental fetuses (means
ratio f SD.).
(C/P)
and
Normal of UA
No. of cases Gestational age (weeks) Mean Range Pathological pregnancies PIH IUGR Birth weight (g) Mean Centile Pathological intrapartum CTG Apgar score 1st min Mean No. I
Pathologic PI of UA C/P < I
22
I8
39.4 f 35-41
I.9
38.3 zt I.8 35-41
8 (17.7%) 7 (15.5%)
5 (22.7%) 6 (27.2%)
8 (44.4”h,) 10 (55.5’%)
3.268 + 429* 46.2 f 25.9
3.006 f 409 35.6 + 22.5
2.271 zt 622’ 22.2 f 22.0
9 (20%)
4 (18.2%)
13 (72.5”%)
8.35 zt 1.3* 6 (13.1%)
8.64 f 2 (9%)
0.9*
7.08 zt 1.2* 10 (55.5%)
and healthy
265 TABLE IV C/P value as diagnostic test of fetal hypoxia in the third trimester of pregnancy. Sensitivity (%)
Specificity (%)
NPV (%)
PPV (%)
65
95
88
83
Numbers: 56 IUGR, 27 controls. NPV, negative predictive value; PPV, positive predictive value.
Fig. 2. ARED flow and fetal hypoxia.
266 TABLE Ability
V of the Doppler
velocimetry
to predict
Sensitivity A/B of UA Mean Range C/P < 1 ARED of UA Mean Range
fetal
distress
(%)
Specificity
(data
modified
Refs
21-26).
NPV
85.5
30.5
89.5
65
72-95 95
18-50 83
78-92 88
87.5 82-92
95 90- 100
83 66-100
97.5 96-99
ratio; PPV, positive umbilical artery.
predictive
value;
(‘XI)
from
PPV (1%)
34.1 15-57
A/B, sistolic-diastolic predictive value; UA,
in labour
C/P, cerebra-placental
ratio;
NPV,
(“AI)
negative
Another important signal of hypoxia is claimed to be the absent or reverse diastolic flow (ARED) in the umbilical artery [23]; although the etiology of the phenomenon is still unknown, the possible mechanisms connected with ARED flow are: (1) abnormalities of the maternal uterine arterioles; (2) a decrease in the number of small arterial vessels in the tertiary stem villi due to the obliteration and embolization of the placental arteries; (3) placental weight too low for gestational age; and (4) the reduction in blood flow within the aorta and umbilical artery secondary to a compensatory redistribution of fetal blood flow, which occurs in response to hypoxia [24]. The appearance of ARED is now commonly considered a sign of poor perinatal outcome [25] (Fig. 2). It should however be pointed out that ARED in UA after 20 weeks gestational age is an infrequent finding associated with an adverse assortment of maternal and fetal pathology [26,27]. This heterogeneity precludes the formulation of a specific management plan appropriate for all cases with such Doppler abnormality. Table V summarises the ability of Doppler technique in the detection of fetal hypoxia. The evaluation of umbilical artery FVW is very poor by itself alone to serve as a screening test for fetal surveillance. ARED flow seems to be the most ominous sign and anticipate a negative outcome [25-281. The predictive value of the Doppler parameters seems to be equal, if not better, than those of cardiotocographic monitoring [29].
TABLE Ability
VI of the Doppler
velocimetry
and CTG
Specificity A/B
of UA
CTG Reactive Fisher score PPV,
positive
>7 predictive
to detect
(%)
fetal distress Sensivity
(%)
(data
modified
from
Ref.
27)
PPV (%)
NPV
85
60
64
83
97 88
17 36
69 58
72 75
value;
NPV,
negative
predictive
value.
(%)
261
In conclusion, Doppler velocimetry is a safe and reliable method for fetal surveillance: abnormal Doppler recordings in fetal vessels indicate the need for a very intensive clinical observation and should be matched with other clinical and/or instrumental tests before taking any action. Acknowledgements This work was supported in part by CNR, P.F. ‘FATMA’ and MURST (40%), Italy. The authors would also like to thank MS Karin Fridehn for preparing the manuscript. References 1 Chin-Chu, Lin. (1986): Recent Advances in Perinatology, pp. 55-62. Editors: K. Maeda, K. Okuyama and Y. Takeda. Elsevier, Amsterdam. 2 Parer, J.T. and Livingston, E.G. (1990): Am. J. Obstet. Gynecol., 162, 1421-1427. 3 Eskes, T.K.A.B., Ingemarsson, I., Pardi, G., Nijhus, J.G. and Ruth, V.J. (1991): Perinatal Med., 19, (suppl. l), 126-133. Brace, R.A. (1986): Am. J. Obstet. Gynecol., 155, 889-893. Low, J.A., Robertson, D.M. and Simpson, L.L. (1989): Am. J. Obstet. Gynecol., 160, 608-614. Cosmi, E.V. (1981): Obstetrics anaesthesia and perinatology. Appleton Century Crofts pp. 113-215. Yaffe, H., Parer, J.T., Block, B.S. and Ranos, A.J. (1987): J. Dev. Physiol., 9, 325-336. Brann, A.W. and Dykes, F.D. (1977): Clin. Perinat., 4, 149-165. Ambrose, SE. and Petrie, R.R. (1989): Fetal Med. Rew., 1, 27-41. Regulation for the use of Doppler technology in perinatal medicine (1989): Report of the European Committee on Doppler technology in Perinatal Medicine. Institut Universitari Dexeus, Barcelona, Spain. 11 Mires, G.J., Patel, N.B. and Dempster, J. (1990): J. Obstet. Gynecol., 10, 261-270. 12 Mulders, L.G.M., Jongsma, H.W., Wijn, P.F.F. and Heinz, P.R. (1988): The uterine artery blood flow velocity waveform in pathological pregnancy. Early Hum. Dev., 18, 45-47. 13 Trudinger, B.J., Cook, CM. and Giles, W.B. et al. (1991): Br. J. Obstet. Gynaecol., 98, 378-384. 14 Tonge, H.M., Struijk, P.C. and Wladimiroff, J.W. (1984): Clin. Cardiol., 7, 323-329. 15 Mari, G.C. (1991): Am. J. Obstet. Gynecol., 165, 143-151. 16 Hari, C.C., Floise, K.J. and Deter, R.L. et al. (1989): Am. J. Obstet. Gynecol., 160, 689-703. 17 Vyas, S., Nicolaides, K.H. and Campbell, S. (1989): Am. J. Obstet. Gynecol. 161, 168-172. 18 Nicolaides, K.H., Economidies, D.L. and Soothill, P.W. (1989): Am. J. Obstet. Gynecol., 161, 996-1001. 19 Bilardo, C.M., Snijders, S., Campbell, S. and Nicolaides, K.H. (1991): Ultrasound Obstet. Gynecol., 1, 250-257. 20 Meyenburg, M., Bartnicki, J., Saling, E. (1991): J. Perinat. Med., 19, 185-190. 21 Guidetti, R., Luzi, G., Simonazzi. E., Di Renzo, G.C. and Cosmi, E.V. (1989): Perinatal Medicine, pp. 670-677. Editors: E.V. Cosmi and G.C. Di Renzo. Harwood, London. 22 Luzi, G., Gori, F., Chiodi, A., Di Renzo, G.C. and Cosmi, E.V. (1990): New Trends Gest. Perinat. Hypertension, 3, 207-2 15. 23 Rochelson, B, Schulman, H. and Farmakides, G. et al. (1987): Am. J. Obstet. Gynecol., 156, 1213-1218. 24 Fouron, J.C., Teyssier, G. and Maroto, E. et al. (1991) Am. J. Obstet. Gynecol., 164: 195-203. 25 Al-Ghazali, W.H., Chapman, M.G., Rissik, J.M., Allan L.D. (1990): J. Obstet. Gynaecol., 10, 271-275. 26 Malcus, P., van Beek, E. and Marsal K. (1991): Ultrasound Obstet. Gynecol., 1, 95-101. 27 Wenstrom, M.D., Weiner, C.P. and Williamson, R.K. (1991): Obstet. Gynecol., 77, 374-378. 28 Low, J.A. (1991): Am. J. Obstet. Gynecol., 164, 1049-1063. 29 Trudinger, B.J., Cook, C.M., Jones, L. and Giles W.B. (1986): Br. J. Obstet. Gynaecol., 93, 171- 175.
Human
Development,
29 (1992)
259
259-267
Elsevier Scientific Publishers Ireland Ltd. EHD 01286
The role of Doppler technology in the evaluation of fetal hypoxia G.C. Di Renzo, G. Luzi, G.C. Cucchia, G. Caserta, P. Fusaro, A. Perdikaris and E.V. Cosmi Institute
of
Gynecology
University of Perugia and and Obstefrics, Gynecology, University ‘La Sapien--a ‘, Roma
2nd Institute (Italy)
of
Obstetrics
and
Summary Failing intrauterine support to the fetus can lead to intrauterine growth retardation (IUGR) and hypoxia and it is associated with a high risk of perinatal morbidity and mortality. The main effects of moderate to severe hypoxia on the fetus are different degrees of blood flow redistribution and reduction of oxygen consumption to maintain oxygen delivery to the central organs at the expenses of peripheral organs. The redistribution results in a ‘brain sparing’ effect. Recently, a Doppler ultrasonic technology (continuous wave, pulsed wave and colour flow imaging) has been developed for the non invasive measurement of flow. Doppler velocimetry detects the flow velocity waveform (FVW) which reflects the cardiac output, the vascular compliance and the resistance to the flow in a defined point of the vessel. Velocity waveform indices or even simpler criteria, such as the presence or absence of diastolic flow or flow reverse during diastole, have been applied to a number of fetal vessels. A significant relationship exists between blood oxygen, systemic lactic acidosis (determined by cordocentesis) and increase PI values in umbilical artery (UA), thoracic aorta (TA) and renal artery (RA). Moreover, in experimental animals during steady state hypoxia, several cardiovascular parameters are affected (heart rate/cardiac output decreases and blood pressure increases) while placental flow don’t show a significant variation thus suggesting a raise in placental vascular resistance. Redistribution of the flow may be reliably evaluated by the cerebroplacental ratio (i.e. ratio between PI of MCA and PI of UA, c/p). The phenomenon of absent or reverse end diastolic flow (ARED) has been related to severe fetal hypoxia and this abnormal finding is suggested to occur before FHR monitoring shows evidence of fetal distress. Doppler ultrasound, in combination with ultrasonic Correspondence 10: G.C. Di Renzo, Institute of Gynecology and Obstetrics, University of Perugia Policlinico Monteluce, 06122 Perugia, Italy.
0378-3782/92/$05.00 0 1992 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland
260
imaging, offers the possibility of assessing fetal hypoxia in some detail, without significant discomfort for the patient and without any known risk. This functional assessment of the fetus offers the possibility of furthering our knowledge of mechanisms involved and the consequences of the low oxygen level in the fetus and of the effects of various therapeutic measures. Key words: Doppler; fetal hypoxia; umbilical artery; placental blood flow
Introduction The intrauterine support of fundamental nutritional substances to the fetus is mediated through their transit from placental blood to umbilical blood by a variety of complex mechanisms. The most important sign of alterated support is the failing of oxygen level in the fetal blood, which, consequently, compromises the fetal homeostasis and behaviour [l]. The definition of fetal hypoxia is controversial and rather difficult. In a strict sense all fetuses are born ‘asphyxiated’, because there is a mixed respiratory and metabolic acidosis and hypoxemia in newborns with a normal intrapartum course and outcome [2]. ‘Fetal hypoxia’ is usually referred to a decrease in level of fetal oxygenation below a normal limit [3]. However, the question arises on what is the normal oxygen level. The fetus, infact, maintains an adequate uptake of oxygen in the presence of very low oxygen tension in the umbilical circulation in contrast to the adult; it is known that this phenomenon is related to the particular properties of fetal hemoglobin [4]. On the other hand asphyxia has the pathologic meaning of insufficiency or absence of exchange of respiratory gases although etimologically it is derived from the Greek word meaning ‘pulseless’ [2-31; its severity is described in terms of acidosis, hypoxemia and hypercarbia; with prolonged hypoxia, anaerobic metabolism within the organism results in lactic acidemia, which aggravates the acidosis and creates the so called ‘fetal distress’ [2-31. Fetal distress, therefore, is a progressive fetal asphyxia that, if not corrected or circumvented, will result in decompensation of physiologic responses, primarily redistribution of blood flow to preserve oxygenation of vital organs [2]. Whatever definition is accepted, it is doubtless that severe fetal asphyxia can cause cerebral palsy and lesser degrees of neurologic damages although it is now clear that the portion of cerebral palsy caused by birth asphyxia is relatively small, confined to less than 10% [5]. There are basically three common means by which the human fetus can became asphyxiated or, as said more commonly, hypoxic: (1) insufficiency of uterine blood flow; (2) insufficiency of umbilical blood flow; (3) a decrease in maternal arterial oxygen content (61. Other mechanisms, such as fetal anemia or increased fetal oxygen needs (i.e. in pyrexia) are relatively rarely seen clinically [2]. When such a case occurs, the fetus adapts progressively to chronic low PO, through some mechanisms, the most prominent of which is the decrease of activity and the reduction of growth. In this period, the fetus shows a redistribution of blood supply to
261
vital organs (brain, heart, adrenals); when the hypoxia continues to be unbalanced, the fetus increases his circulatory red blood cells and then activates anaerobic metabolism with consequent metabolic acidosis [l-6]. This cascade of events is regulated by endocrine and paracrine mechanisms; in particular, the hemodynamic alterations are controlled by oxygen levels, CO2 tension, alpha-adrenergic and betaadrenergic activity, renin-angiotensin system, endogenous opioids, prostaglandins and others unidentified regulators [6]. Cerebral and myocardial oxygen consumption can be maintained during moderate hypoxia by the increase in blood flow to the respective organs that exactly balances a decrease in arterovenous oxygen content difference. At moderate degrees of hypoxia the overall cardiac output remain fairly stable but at more severe degrees of hypoxia or asphyxia cardiac output decreases [7]. In the brain the asphyxia result in oxygen debt to brain cells and impaired autoregulation of cerebral blood flow with intracellular swelling; subsequently focal ischemia occurs and then generalized brain swelling with increased intracranial pressure and cerebral necrosis and, at the end, atrophic cortical sclerosis [8]. In summary, fetal distress is ‘a progressive fetal hypoxia or asphyxia that not corrected or circumvented, will result in decompensation of the physiologic responses (primarily redistribution of blood flow to preserve oxygenation of vital organs) and cause permanent central nervous system and or the damage or death’ [2]. It is therefore of outmost importance to monitor the fetal state in order to detect as early as possible impending risk of hypoxia. Doppler velocimetry studies There are several pathologic conditions in pregnancy which dictate a careful monitoring of fetal conditions, the most common being: chronic hypertension, pregnancy induced hypertension, gestational diabetes, previous stillbirth, suspected IUGR, prolonged pregnancy, decrease fetal movements, premature rupture of membranes, advanced maternal age, sickle cells disease [9]. In recent year the perinatal armamentarium has gained several instruments for fetal surveillance: fetal movement survey, non stress test, oxytocin challenge test, test of fetal stimulation, biophysical profile, amniotic fluid index, placental grading, cordocentesis and Doppler velocimetry; all this tests are complementary to each other and necessitate of, at least, two instrumentations: the cardiotocographic equipment and the ultrasound imaging system coupled with a Doppler system. The recent development in Doppler technique has made three Doppler systems available for clinical application: pulsed, continuous and colour flow mapping. The three systems are complementary to each other for obtaining information on blood flow velocity within the cardiovascular system in the fetus and newborn [lo]. The Doppler technique can be used to study almost all fetal and maternal vascular districts in pregnancy; every vessel has a characteristic flow velocity waveform (FVW) which can be modified by gestational age and pathological pregnancy development. The FVW reflects the phase of the cardiac cycle: the ascending part and the initial descending part reflect the force of systolic input and depend from the distance of the heart from the vessel; the remaining descending part and the
262
diastolic waveform reflect the vasal compliance (due to the type of arterial vessel) and the resistance to flow [ll]. Therefore the uterine artery (UA) FVW shows a diminished resistance to blood flow during normal pregnancy [12], while the fetal aorta maintains an unalterated profile during pregnancy [13], as expression of the sum of different alterations of resistance into the various vascular districts of the fetus. In the cerebral circulation [12] a slight fall of resistance to flow is reported, compared to the umbilical circulation. For the objective evaluation of the FVW variations, several indices have been introduced, the most common being the
Fig. 1. Femoral artery FVW in normal (a) and IUGR fetuses (b). PI index: a = 1.8, b = 2.9
263 TABLE
1
Pulsatility Fetal
index
(PI)
variation
during
hypoxia
in the third
Method
vessels
Umbilical artery Middle cerebral artery Internal carotid artery Common carotid artery Thoracic aorta Abdominal aorta Renal artery External iliac artery Femoral artery PWD,
in the fetal vessels
pulsed
wave
PWD PWD PWD PWD PWD PWD
6’4 WC& WA) (CC.4 PA) (AA) WA) WA) CF.4
Doppler;
CFI,
PWD PWD colour
flow
trimester
of pregnancy.
PI I I I 1 I= I= f t I
CFI CFI CFI CFI CFI CFI CFI
imaging.
systolic-diastolic ratio (S/D or A/B), the resistance index (RI) and the pulsatility index (PI) [lo]. The FVW of the fetal vessels may also reflect the variation of vascular resistance of the fetal circulation due to the hypoxia: the FVW of the umbilical artery reflects the increase of placental resistance: as the diastolic flow diminishes, the PI index increases. Other important vessels, like the renal artery or the femoral artery [14- 151 (Fig. 1) show increased resistance during gestation; theoretically these vessels should be more sensitive to the vasoconstriction due to hypoxia than the umbilical artery but for many reasons (i.e. difficulty in vessel detection, at least without colour flow mapping, the small diameter of the vessel, the
TABLE
II
Indices of blood flow last half of pregnancy;
velocity waveform cumulative data
Population
Index
(N)
Umbilical artery 1303 759 227 Fetal aorta 134 Fetal cerebral circulation 36 105 112 PI, pulsatility
index;
in umbilical artery, fetal aorta years 1984-1989 (data modified
and cerebral circulation from Ref. 27)
during
Gestational
age (weeks)
20
24
28
32
36
40
3.9 0.75 1.7
3.5 0.72 1.5
3.2 0.7 1.1
2.8 0.65 0.9
2.5 0.59 0.8
2.1 0.54 0.75
PI
1.9
1.8
2.0
1.8
1.9
S/D RI PI
6.4
8.4 0.85 2.7
0.82 2.6
2.3
3.8 0.72 1.8
S/D RI PI
S/D,
systolic-diastolic
ratio;
RI,
resistance
index.
264
movements of the fetus and so on) are detected only sometimes. In the cerebral circulation the vessel’s resistance diminishes: during hypoxia the FVW increases in diastole and PI decreases in most cerebral vessels [16] (Tables I and II). A correlation between flow indexes of umbilical artery and PO* tension and/or lactate concentration in fetal blood obtained by cordocentesis has been demonstrated: low PO, tension and high lactate concentration are related to high PI values [17-181. On the other hand the hyperoxygenation obtained by maternal oxygen therapy in cases of IUGR does not seem to change significantly the UA flow’s indices [19-201. Probably this fact is due to the particular characteristics of fetal hemoglobin. In our hands, the best index of fetal hypoxia is the cerebra-placental ratio (C/P) which is the ratio between the PI of the middle cerebral artery and the PI of the umbilical artery; this index is mainly the expression of the balance in the redistribution of fetal circulation. We reported that, when this ratio is less than one, there is a significant reduction of growth centile at birth, a high percentage of abnormal intrapartum CTG and a high percentage of low-Apgar score at first minute [21-221 (Table III). Sensitivity and specificity of this index are fairly good (Table IV).
TABLE
III
Cerebro-placental fetuses (means
ratio f SD.).
(C/P)
and
Normal of UA
No. of cases Gestational age (weeks) Mean Range Pathological pregnancies PIH IUGR Birth weight (g) Mean Centile Pathological intrapartum CTG Apgar score 1st min Mean No. I
Pathologic PI of UA C/P < I
22
I8
39.4 f 35-41
I.9
38.3 zt I.8 35-41
8 (17.7%) 7 (15.5%)
5 (22.7%) 6 (27.2%)
8 (44.4”h,) 10 (55.5’%)
3.268 + 429* 46.2 f 25.9
3.006 f 409 35.6 + 22.5
2.271 zt 622’ 22.2 f 22.0
9 (20%)
4 (18.2%)
13 (72.5”%)
8.35 zt 1.3* 6 (13.1%)
8.64 f 2 (9%)
0.9*
7.08 zt 1.2* 10 (55.5%)
and healthy
265 TABLE IV C/P value as diagnostic test of fetal hypoxia in the third trimester of pregnancy. Sensitivity (%)
Specificity (%)
NPV (%)
PPV (%)
65
95
88
83
Numbers: 56 IUGR, 27 controls. NPV, negative predictive value; PPV, positive predictive value.
Fig. 2. ARED flow and fetal hypoxia.
266 TABLE Ability
V of the Doppler
velocimetry
to predict
Sensitivity A/B of UA Mean Range C/P < 1 ARED of UA Mean Range
fetal
distress
(%)
Specificity
(data
modified
Refs
21-26).
NPV
85.5
30.5
89.5
65
72-95 95
18-50 83
78-92 88
87.5 82-92
95 90- 100
83 66-100
97.5 96-99
ratio; PPV, positive umbilical artery.
predictive
value;
(‘XI)
from
PPV (1%)
34.1 15-57
A/B, sistolic-diastolic predictive value; UA,
in labour
C/P, cerebra-placental
ratio;
NPV,
(“AI)
negative
Another important signal of hypoxia is claimed to be the absent or reverse diastolic flow (ARED) in the umbilical artery [23]; although the etiology of the phenomenon is still unknown, the possible mechanisms connected with ARED flow are: (1) abnormalities of the maternal uterine arterioles; (2) a decrease in the number of small arterial vessels in the tertiary stem villi due to the obliteration and embolization of the placental arteries; (3) placental weight too low for gestational age; and (4) the reduction in blood flow within the aorta and umbilical artery secondary to a compensatory redistribution of fetal blood flow, which occurs in response to hypoxia [24]. The appearance of ARED is now commonly considered a sign of poor perinatal outcome [25] (Fig. 2). It should however be pointed out that ARED in UA after 20 weeks gestational age is an infrequent finding associated with an adverse assortment of maternal and fetal pathology [26,27]. This heterogeneity precludes the formulation of a specific management plan appropriate for all cases with such Doppler abnormality. Table V summarises the ability of Doppler technique in the detection of fetal hypoxia. The evaluation of umbilical artery FVW is very poor by itself alone to serve as a screening test for fetal surveillance. ARED flow seems to be the most ominous sign and anticipate a negative outcome [25-281. The predictive value of the Doppler parameters seems to be equal, if not better, than those of cardiotocographic monitoring [29].
TABLE Ability
VI of the Doppler
velocimetry
and CTG
Specificity A/B
of UA
CTG Reactive Fisher score PPV,
positive
>7 predictive
to detect
(%)
fetal distress Sensivity
(%)
(data
modified
from
Ref.
27)
PPV (%)
NPV
85
60
64
83
97 88
17 36
69 58
72 75
value;
NPV,
negative
predictive
value.
(%)
261
In conclusion, Doppler velocimetry is a safe and reliable method for fetal surveillance: abnormal Doppler recordings in fetal vessels indicate the need for a very intensive clinical observation and should be matched with other clinical and/or instrumental tests before taking any action. Acknowledgements This work was supported in part by CNR, P.F. ‘FATMA’ and MURST (40%), Italy. The authors would also like to thank MS Karin Fridehn for preparing the manuscript. References 1 Chin-Chu, Lin. (1986): Recent Advances in Perinatology, pp. 55-62. Editors: K. Maeda, K. Okuyama and Y. Takeda. Elsevier, Amsterdam. 2 Parer, J.T. and Livingston, E.G. (1990): Am. J. Obstet. Gynecol., 162, 1421-1427. 3 Eskes, T.K.A.B., Ingemarsson, I., Pardi, G., Nijhus, J.G. and Ruth, V.J. (1991): Perinatal Med., 19, (suppl. l), 126-133. Brace, R.A. (1986): Am. J. Obstet. Gynecol., 155, 889-893. Low, J.A., Robertson, D.M. and Simpson, L.L. (1989): Am. J. Obstet. Gynecol., 160, 608-614. Cosmi, E.V. (1981): Obstetrics anaesthesia and perinatology. Appleton Century Crofts pp. 113-215. Yaffe, H., Parer, J.T., Block, B.S. and Ranos, A.J. (1987): J. Dev. Physiol., 9, 325-336. Brann, A.W. and Dykes, F.D. (1977): Clin. Perinat., 4, 149-165. Ambrose, SE. and Petrie, R.R. (1989): Fetal Med. Rew., 1, 27-41. Regulation for the use of Doppler technology in perinatal medicine (1989): Report of the European Committee on Doppler technology in Perinatal Medicine. Institut Universitari Dexeus, Barcelona, Spain. 11 Mires, G.J., Patel, N.B. and Dempster, J. (1990): J. Obstet. Gynecol., 10, 261-270. 12 Mulders, L.G.M., Jongsma, H.W., Wijn, P.F.F. and Heinz, P.R. (1988): The uterine artery blood flow velocity waveform in pathological pregnancy. Early Hum. Dev., 18, 45-47. 13 Trudinger, B.J., Cook, CM. and Giles, W.B. et al. (1991): Br. J. Obstet. Gynaecol., 98, 378-384. 14 Tonge, H.M., Struijk, P.C. and Wladimiroff, J.W. (1984): Clin. Cardiol., 7, 323-329. 15 Mari, G.C. (1991): Am. J. Obstet. Gynecol., 165, 143-151. 16 Hari, C.C., Floise, K.J. and Deter, R.L. et al. (1989): Am. J. Obstet. Gynecol., 160, 689-703. 17 Vyas, S., Nicolaides, K.H. and Campbell, S. (1989): Am. J. Obstet. Gynecol. 161, 168-172. 18 Nicolaides, K.H., Economidies, D.L. and Soothill, P.W. (1989): Am. J. Obstet. Gynecol., 161, 996-1001. 19 Bilardo, C.M., Snijders, S., Campbell, S. and Nicolaides, K.H. (1991): Ultrasound Obstet. Gynecol., 1, 250-257. 20 Meyenburg, M., Bartnicki, J., Saling, E. (1991): J. Perinat. Med., 19, 185-190. 21 Guidetti, R., Luzi, G., Simonazzi. E., Di Renzo, G.C. and Cosmi, E.V. (1989): Perinatal Medicine, pp. 670-677. Editors: E.V. Cosmi and G.C. Di Renzo. Harwood, London. 22 Luzi, G., Gori, F., Chiodi, A., Di Renzo, G.C. and Cosmi, E.V. (1990): New Trends Gest. Perinat. Hypertension, 3, 207-2 15. 23 Rochelson, B, Schulman, H. and Farmakides, G. et al. (1987): Am. J. Obstet. Gynecol., 156, 1213-1218. 24 Fouron, J.C., Teyssier, G. and Maroto, E. et al. (1991) Am. J. Obstet. Gynecol., 164: 195-203. 25 Al-Ghazali, W.H., Chapman, M.G., Rissik, J.M., Allan L.D. (1990): J. Obstet. Gynaecol., 10, 271-275. 26 Malcus, P., van Beek, E. and Marsal K. (1991): Ultrasound Obstet. Gynecol., 1, 95-101. 27 Wenstrom, M.D., Weiner, C.P. and Williamson, R.K. (1991): Obstet. Gynecol., 77, 374-378. 28 Low, J.A. (1991): Am. J. Obstet. Gynecol., 164, 1049-1063. 29 Trudinger, B.J., Cook, C.M., Jones, L. and Giles W.B. (1986): Br. J. Obstet. Gynaecol., 93, 171- 175.
