Umbilical cord acid base changes associated with perinatal cardiac failure

Umbilical cord acid base changes associated with perinatal cardiac failure Harhinder S. Brar, MD, Martin K. Wong, MD, Thomas H. Kirschbaum, MD, and Richard H. Paul, MD Los Angeles, California Two infants delivered by emergency cesarean section because of fetal distress are described, and the umbilical blood acid-base findings are discussed. One fetus was stillborn, the other died in the immediate neonatal period, and both showed signs of cardiac dilation and failure on postmortem examination. Umbilical cord blood gas determination at the time of delivery showed almost normal values of pH, Pco2. and Po2 in the umbilical vein but acidotic pH with high Pco2 and low Po 2 values in the umbilical artery samples. These findings are probably the result of a prolonged umbilical blood circulation time because of fetal cardiac failure. This sluggish perfusion allows the equilibration of fetal blood with maternal intervillous blood, and the findings in the fetal umbilical vein approximate maternal uterine venous values. Umbilical cord acid-base determinations in perinatal surveillance are commonly recommended without specific details. Umbilical artery samples must be obtained to properly assess the metabolic status of the fetus at the time of birth. (AM J 0BSTET GYNECOL 1988;158:511-8.)

Key words: Cardiac failure, acid-base changes For almost three decades, the well-being of the fetus and neonate, particularly with respect to acid-base status, has been of special interest to perinatologists and neonatologists. Bowe et al. 1 introduced human fetal acid-base evaluation in North America and investigated the relationship of the acid-base status of maternal and fetal cord blood. Umbilical blood acid-base determinations are usually performed in an effort to evaluate fetal condition before birth and to provide insight into the neonatal cardiorespiratory status. Sample collection is simple, and determinations are readily available and relatively inexpensive. Umbilical samples often have defined etiologic factors, enhanced diagnoses, and directed the management and resolution of perinatal problems. A thorough understanding of umbilical cord acid-base evaluations is essential to the obstetrician, obstetric anesthesiologist, and neonatologist. The purpose of this article is to describe the analysis of cord blood gases and fetal heart rate tracings in two fetuses with findings of perinatal cardiac failure.

Case reports Case 1. M. J., a 24-year-old primigravid woman, presented in labor at Women's Hospital, Los Angeles

From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Southern California, School of Medicine, and Women's Hospital, Los Angeles County/University of Southern California Medical Center. Received for publication December 9, 1986; revised August 21, 1987; accepted September 16, 1987. Reprint requests: Richard H. Paul, MD, Women's Hospital, Room 5K40, 1240 North Mission Road, Los Angeles, CA 90033.

County/University of Southern California Medical Center, with a 40-week intrauterine pregnancy. She reported uterine contractions every I 0 minutes, fetal movements, and no vaginal bleeding. Spontaneous rupture of the membranes occurred on admission with evidence of meconium-stained amniotic fluid. Prenatal care had begun in the seventeenth week of pregnancy with no antepartum obstetric problems. Midtrimester ultrasonography documented the fetal gestational age to be consistent with the date of last menstrual period. No other complaints or symptoms were noted. Physical examination on admission revealed normal vital signs and pertinent findings confined to the abdomen and pelvis. The fundal height was 33 cm, estimated fetal weight was 3200 gm, and the fetal heart rate was 140 beats/min. The cervix was completely effaced and I cm dilated, the fetus was in a breech position, presenting at the - I station. The patient was admitted to the labor and delivery service for further intrapartum management. External monitoring documented a baseline fetal heart rate of 140 to 145 beats/min with average variability and uterine contractions every 3 to 6 minutes (Fig. I, A). The breech presentation and estimated fetal weight were substantiated by real-time ultrasonography. Radiographic pelvimetry revealed normal pelvic dimensions. The fetal head was flexed with a frank breech presentation. A trial of labor with informed consent was begun. The fetal heart rate tracing demonstrated occasional accelerations over the baseline heart rate. No spontaneous or periodic decelerations were noted (Fig. I, B and C). Augmentation for inadequate uterine contractions with a graduated oxytocin infusion was initiated 4 hours after admission. Seven hours after admission, the cervix was completely effaced and was I to 2 cm 511

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dilated. The frank breech was at the - l station. A direct fetal electrocardiogram electrode was not placed because of the presenting scrotum. As noted in Fig. l, D to F, the fetal heart rate remained unchanged with periodic accelerations. Peri-

odic uterine activity was apparent but poorly demonstrated with the external tocodynamometer. Ten hours after admission, a variable deceleration of fetal heart rate to approximately 95 beats/min was noted. Immediate vaginal examination revealed progress of labor to

Perinatal cardiac failure and acid-base changes

Volume 158 Number 3, Part l

513

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9 cm dilatation at the 0 station. Umbilical cord prolapse was not evident. A direct fetal electrocardiogram electrode was then placed that revealed a momentary fetal heart rate of 140 to ·145 beats/min followed by an abrupt drop in rate to 30 to 40 beats/min (Fig. 1, G to/). The fetal bradycardia did not resolve with oxygen

administration, position changes, or elevation of the breech from the pelvis. A primary cesarean section with the patient under general anesthesia resulted in an uncomplicated delivery of a 2500 gm male infant within 13 minutes from the onset of the bradycardia. Neonatal resuscitation in

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the delivery room was initiated by neonatologists. Immediate cardiopulmonary resuscitation with full pharmacologic measures, umbilical artery catheterization, and endotracheal intubation-ventilation was performed. However, the infant failed to respond to all resuscitative efforts and was pronounced dead 20 min-

utes after birth. Apgar scores o.f 0, 0, and 0 were assigned at I, 5, and I 0 minutes, respectively. At the time of delivery, the umbilical cord appeared normal with no compromise in utero. The amniotic Huid was clear and the placenta, weighing 400 gm, appeared without anomalies or evidence of abruptio pla-

Perinatal cardiac failure and acid-base changes

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Table I. Umbilical cord blood gas analysis in Case I

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Pco,

pH

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Pco2

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centae. L'mbilical cord blood gas analysis is shown in Table I. The mother's postoperative recovery was uncomplicated and she was discharged on the fourth postoperative day. Postmortem examination of the neonate revealed normal external morphologic features for a term, small for gestational age infant. lntracranial hemorrh<;1ge was not present. Additionally, congestive heart failure was suggested by findings that included cardiomegaly with biventricular enlargement, myocardial edema, and endocardial fibroelastosis, as well as a pericardia! effusion. Coronary artery disease was not evident. Small bilateral pleural effusions (35 ml on the right and 15 ml on the left), mild ascites ( 15 ml), and focal ischemia of the small bowel were also noted. The pathologist felt these findings were consistent with moderate to severe chronic cardiac failure. The possibility of viral myocarditis leading to fibroelastosis and chronic cardiac failure was also raised by the pathologist. Case 2. M. G., a 25-year-old primigravid woman, presented to LAC/USC Medical Center at 421/2 weeks' gestation with a history of leaking amniotic Huid for 2 days and a temperature of I 01.2° F. The patient had five prenatal visits with possible growth retardation of the fetus noted on the last two visits. She had received a consultative referral to LAC/USC Medical Center but failed to keep her appointment. On admission, the cervix of the patient was 4 cm dilated and completely effaced. The vertex was presenting at the 0 station with thick meconium. The baseline fetal heart rate was 110 to 120 beats/min with decreased to absent variability and repetitive late decelerations (Fig. 2, A and B). A scalp pH determined at 9:35 PM revealed a pH of 6.7. An emergency cesarean section was performed at 9:45 PM and a 3280 gm male fetus with meconium below the vocal cords was delivered. Apgar scores were I, 3, and 5 at I, 5, and 10 minutes, respectively. The neonate died at 16 hours of age. Neonatal echocardiography revealed large dilated left and right ventricles. Postmortem findings included cardiac dilatation and hypertrophy and a small amount of pleural and pericardia! effusion, consistent with cardiac failure. Umbilical cord values are shown in Table II.

Bicarbonate

Base excess

Ox)'gen saturation

II 15

-19 -8

8 93

Comment

Electronic fetal heart rate monitoring is a widely used adjunct that guides the management of obstetric practice. Various patterns have been associated with the fetal condition.'·; Acceleration during labor, as seen in Case I, is most commonly associated with fetal wellbeing. In this case, the intrapartum fetal heart rate monitoring failed to provide adequate insight into what was to become a catastrophic outcome. When the intrapartum fetal heart rate is judged to be suspicious for fetal jeopardy, as in Case 2, determination of fetal acidbase status by scalp sampling, as described by Saling and Schneider" may help to clarify the situation. In this case a diagnosis of severe fetal acidosis was made, and an emergency cesarean section was performed. The correlation of intermittently obtained fetal acid-base status with continuous intrapartum fetal heart rate tracings has been reported by various investigators."· 11 Umbilical cord acid-base determinations are increasingly recommended to relate these values to fetal heart rate data, fetal acid-base data, and the subsequent condition of the infant. In the two cases reported here, the pathophysiologic characteristics of the catastrophic outcome would probably have been less clear if cord gas values had not been obtained. The cord gas values in Case I represent a predominantly metabolic acidosis of a moderate degree, whereas in Case 2 a mixed metabolic and respiratory acidosis is seen. Respiratory acidosis results from the failure of the fetus to excrete carbon dioxide, a condition leading to an increase in Pco 2 " (normal arterial Pco 2 , 35 to 55 mm Hg; venous Pco 2 , 30 to 50 mm Hg). In the fetus, carbon dioxide is transferred by diffusion across the placenta to maternal blood. As in Case 2, umbilical cord compression, as evidenced by deep variable decelerations 12 with reduced placental perfusion, is a common cause of carbon dioxide retention and respiratory acidosis. The increase in Pco 2 leads to hydrolysis and dissociation of carbonic acid with a fall in pH.1' On the other hand, the genesis of fetal metabolic

Volume 158 Number 3, Part I

acidosis is a reflection of chronic dysfunction of the uteroplacental unit, which results in activation of the anaerobic glycolytic pathway and increased production of lactate." The lactic acid is buffered in the fetus by sodium bicarbonate on a mole equivalent basis, yielding increased carbon dioxide. Some of the excess lactic acid is also buffered by hemoglobin. The reduction of total buffer base is expressed by a decrease in base excess." This buffer shift leads to an increase in Pco, and a decrease in bicarbonate and adds a metabolic component to the acidosis, which started as pure respiratory acidosis. Most fetal acidotic states have mixed metabolic and respiratory components as in Case 2. Generally, metabolic acidosis exhibits an increase in base deficit with a slightly elevated Pco 2 (Case I) and respiratory acidosis exhibits a near-normal base deficit with a marked increase in Pco 2 • Usually, the fetal capillary blood pH correlates best with umbilical arterial pH (Case 2) and helps in assessing the fetal condition when the tracing is questionable.'" The umbilical arterial values are more indicative of the metabolic state of the fetus, whereas the umbilical venous values reflect the respiratory exchange functions of the placenta in addition to the metabolic state of the fetus. In view of the rapid death of the infant in Case I (13 minutes after the onset of catastrophic bradycardia), it is remarkable that the umbilical blood gas values are only moderately abnormal. This suggests that the tissue oxygen deprivation was far more serious than was reflected in the umbilical arterial blood sample, which can lag behind the tissue acid-base status. It is difficult to ascertain whether cardiac failure preceded the bradycardia or was a result ofit. In both of these cases, augmented anaerobic fetal metabolism seems to have occurred with the reduction of oxygen availability and augmented concentrations of carbon dioxide and lactate. Since cardiac failure was evident in postmortem examinations of both infants, it is probable that the sluggish blood flow in the umbilical circulation allowed the fetal blood to equilibrate with the maternal blood and resulted in near-normal values of the umbilical venous blood gas analysis. Additionally, bradycardia and partial cord compression could have contributed to the sluggish blood flow in the placenta. Thus, the wide difference in values between the umbilical arterial and venous blood, with the umbilical venous blood values approaching the values of maternal uterine venous blood, appears to be associated with perinatal cardiac failure, as exemplified by these two cases. Finally, one should remember that sheep experiments have shown that when fetal cardiac output is low, the difference in oxygenation and acid-base status between fetal cerebral and umbilical arteries increases in

Perinatal cardiac failure and acid-base changes

517

such a way that umbilical arterial blood analysis overestimates the degree of acidosis and hypoxia present in the brain." This difference may not be significant biologically when the asphyxia is severe enough to cause fetal death as in these two cases. Clearly, in the same way, umbilical vein blood analysis can vastly underestimate fetal brain hypoxia. In addition, umbilical venous samples showing near-normal pH values but an increased base deficit should make one suspect that umbilical arterial samples (which are more reflective of the metabolic state) could be very abnormal, showing acidosis, hypoxia, hypercarbia, and increased base def~ icit. These discordant but abnormal umbilical venous and arterial values appear to be associated with perinatal fetal cardiac failure. From the foregoing discussion, it seems imperative that ideally one should obtain both umbilical venous and arterial samples for the assessment of fetal acidbase status. This is further underscored by the litigious medicolegal climate currently in existence. To obtain meaningful information, one should have the samples analyzed for pH, Pco 2 , Po,, and base deficit. Mixed arterial and venous samples could be misleading. If a single umbilical sample is to be obtained for e\'aluation of fetal acid-base status, it must be arterial because this sample is more reflective of metabolic state than the venous sample, although on occasion, as in these two cases, additional information is provided if umbilical vein samples are also analyzed. REFERENCES I. Bowe ET, Beard RW, Finster M, et al. Reliabilitv of fetal blood samples. A\I .J 0BSTET Gy:-;u:ot. 1970; I 07:297. 2. Everston LR, Paul RH. Antepartum fetal heart rate testing: the nonstress test. A\t .J 0BSTET (;y:-;u:o1. 1978; 132:895. 3. Schifrin BS, Foye G, Amato J, Kates R, l\facKenna.J. Routine fetal heart rate monitoring in the antepartum period. Obstet Gynecol 1979;54:2 l. 4. Lee CY, Diloreto PC, O'Lane .JYI. A study of fetal heart rate acceleration patterns. Obstet (;ynecol 1975;45: 142. 5. Leveno K.J, Williams ML, DePalma RT, Whalley PJ. Perinatal outcome in the absence of antepartum fetal heart rate acceleration. Obstet Gynecol 1983;61:347. 6. Gilstrap LC III, Hauth.JC, Toussaint S. Second stage fetal heart rate abnormalities and neonatal acidosis. Obstet (;ynecol I 984;63:209. 7. Bourgeois F.J, Thiagarajah S, Harbert c;M Jr. The significance of fetal heart rate abnormalities and neonatal acidosis. Obstet Gynecol I 984;63:209. 8. Saling E, Schneider D. Biochemical supervision of the fetus during labor. Br .J Obstet Gynaecol I 967;74:799. 9. Starks GC. Correlation of meconium-stained amniotic fluid, early intrapartum fetal pH and Apgar scores as predictors of perinatal outcome. Obstet Gynecol 1980; 56:604. 10. Tejani MN, Mann LI, Bhakthavathsalan A, et al. Correlation of fetal heart-rate-uterine contraction patterns with fetal scalp blood pH. Obstet Gynecol 1975;46:392. 11. Wood C, Fertusen R, Leeton J, et al. Fetal heart rate and acid-base status in the assessment of fetal hypoxia. A\t .J 0BSTET GY:-;ECOI. 1967;98:62.

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12. Goodlin RC. Fetal cardiovascular responses to distress: a review. Obstet Gynecol 1977;49:37 l. 13. Kaiser IH. The significance offetal acidosis. AM J OBSTET GY:\ECOI. l 959;77:573. 14. Paul WM, Gare DJ, Wheatham JC, et al. Assessment of fetal scalp sampling in labor. A~1 J OBSTET GY:\ECOL I 967;99:745. 15. Hon EH, Khazin A. Observations on fetal heart rate and

March 1988 Am J Obstet Gynecol

fetal biochemistry. I. Base deficit. AM J 0BSTET GY:\ECOL 1969; 105:721. 16. Wible JL, Petrie RH, Koons A, et al. The clinical use of umbilical cord acid-base determinations in perinatal surveillance and management. Clin Perinatol 1982;9{2):387. 17. Dawes GS, Mott SC. Changes in 0 2 distribution and consumption in the fetal lamb with variations in umbilical blood flow. J Physiol 1964; 170:524.

Placental-type plasminogen activator inhibitor in preeclampsia Karin de Boer, MD, Ingegerd Lecander, MD, Jan W. ten Cate, MD, Judocus J. J. Bonn, MD, and Pieter E. Treffers, MD Amsterdam, The Netherlands, and Lund, Sweden The present cross-sectional study in patients with preeclampsia and gestational hypertension and in gestational age-matched controls was undertaken to investigate further the fibrinolytic system in these conditions. In preeclampsia we observed increased levels of total plasminogen activator inhibitor (p < 0.001) but low levels of placental-type plasminogen activator inhibitor (p < 0.05) compared with controls. The levels of placental-type plasminogen acti'lator inhibitor were even more reduced (p < 0.002) in pregnancies with a poor fetal outcome. It is concluded that placental-type plasminogen activator inhibitor does not contribute to the increased levels of total plasminogen activator inhibitor activity in preeclampsia. Placental-type plasminogen activator inhibitor levels correlated significantly with birth weight and placenta weight and may therefore reflect placental function. (AM J OBSTET GYNECOL 1988;158:518-22.)

Key words: Preeclampsia, fibrinolysis, plasminogen activator inhibitor, placental-type plasminogen activator inhibitor, fetal outcome Preeclampsia is associated with activation of blood coagulation and, in severe cases, with fibrin deposits in various organs resulting in low plasma levels of the coagulation inhibitor antithrombin III.'·' Previous work from our laboratory has shown that antithrombin III levels in preeclampsia correlate with the degree of maternal and fetal morbidity.' However, the permanent deposition of fibrin (for example, in the placenta) may also be due to defects of the fibrinolytic system. The precise role of the fibrinolytic system in the pathophysiology of preeclampsia is uncertain. Tissue-type plasminogen activator, which converts plasminogen to plasmin, is one of the key enzymes in the fibrinolytic system. The activity of tissue-type plasminogen activator, which is released from the vessel wall and cleared From the Division of Haemostasis and Thrombosis and Department of Obstetrics and Gynecology, Academic Medical Center and the Research Laboratory of the Department of Obstetrics and Gynecology, University Hospital Lund. Supported by a grant from the foundation De Drie Lichten and the Swedish Medical Research Council (No. 04523). Received for publication March 27, 1987; revised October 14, 1987; accepted November 6, 1987. Reprint requests: Karin de Boer, MD, Division of Haemostasis and Thrombosis, Academisch Medisch Centrum F4-209, Meibergdreef 9, 1105 AZ Amsterdam.

518

by the liver, is regulated by its interaction with fibrin, which enhances its activity, and by the fast-acting tissuetype plasminogen activator inhibitor present in plasma. 3 Increased plasminogen activator inhibitor levels in plasma are associated with decreased in vitro fibrinolytic activity and have been observed in patients with thromboembolic complications. In normal pregnancy the levels of plasminogen activator inhibitor increase progressively, while in preeclampsia higher levels have been observed.'· 5 These high levels of plasminogen activator inhibitor may be of pathophysiologic significance by contributing to the process of intra vascular fibrin deposition. Interestingly, two immunologically different plasminogen activator inhibitors in plasma have been described, one isolated from placental tissue and one similar to that produced in cultured endothelial cells. The latter has been detected in plasma and platelets, while placental-type plasminogen activator inhibitor is present only in plasma obtained from pregnant women. 6 We undertook the present cross-sectional study in selected patient groups to investigate the plasma levels of total and placental-type plasminogen activator inhibitor, antithrombin III, platelets, and fibrin degra-