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Umbilical cord blood acid-base state: What is normal?
Umbilical cord blood acid-base state: What is normal? Jane I'. Helwig, MD, Julian T. Parer, MD, Phi), Sarah J. Kilpatrick, MD, PhD, and Russell IC Laros, Jr., MD San Francisco, California OBJECTIVE: Umbilical cord blood gases and acid-base data from vigorous neonates were examined to determine normal values and ranges. STUDY DESI6N: The University of California, San Francisco, Perinatal Data Base was used to retrieve information from deliveries between 1977 and 1993. Newborns with 5-minute Apgar scores >7 were selected because it is generally accepted that a vigorous newborn has not had substantial intrapartum asphyxia lasting until delivery. RI=SULTS" Full blood gas and obstetric data were available for 16,060 newborns. Of these, 15,073 (94%) had a 5-minute Apgar score >7. The median umbilical artery values, with 2.5th percentile values in parentheses, were pH 7.26 (7.10), Pco2 52 mm Hg (74), base excess -4 mEq. L-1 (-11), and Po2 17 mm Hg (6). Although the distributions were skewed, the mean _+2 SDs were similar to these values. Data for these babies were further analyzed by method of delivery, gestational age, presentation, and presence of thick meconium. Although the means were significantly different in all groups, the differences between groups were relatively small. CONCLUSION" A wide range of acid-base values were found in babies with normal Apgar scores, defining the "physiologic acidemia" of the normal vigorous newborn. (Am J Obstet Gynecol 1996;174:1807-14.)
Key words: Fetal asphyxia, base excess, Pc%, P%
Asphyxia may be defined as insufficient exchange of respiratory gases. This insufficiency is almost always caused by inadequate unabilical or uterine blood flow, which results in a reduction of oxygen content and elevation of carbon dioxide in fetal blood. Eventually, this gives rise to physiologic compensatory mechanisms, the most important of which is redistribution of blood flow within the fetus. Blood flow to the heart, brain, and adrenal gland increases; blood flow to the placenta is maintained; and blood flow to all other areas decreases. 1Where blood flow is reduced, oxygen delivery is not enough to maintain aerobic metabolism. Anaerobic metabolism occurs, leading to local lactate production and then systemic lat,~,~ acidemia. As the oxygen supply continues to drop, the physiologic compensatory mechanisms themselves fail, with consequent myocardial performance loss and reduced cardiac output. 2' 3 Umbilical blood flow decreases, and the asphyxia worsens. Eventually, the fetus
From the Department of Obstetrics, Gynecology, and Reproductive Sciences and the Cardiovascular Research Institute, University of California, San Francisco. Presented at the Sixty-second Annual Meeting of the Pacific Coast Obstetrical and GynecologicalSodety, Squaw Valley, California, September 16-21, 1995. Reprint requests:Julian T. Parer, MD, PM), Department of Obstetrics, Gynecology, and Reproductive Sciences, Box 0550, University of California, San Francisco, 513Parnassus, Rm. HSE-1462, San Francisco, CA 94143-0550. Copyright © 1996 by Mosby-YearBook, Inc. 0002-9378/96 ~5.00 + 0 6/6/72182
has regional hypoxia to the extent that there is cellular damage. 4 Umbilical cord blood gas analysis allows assessment of the status of the respiratory gases and acid-base values in the newborn immediately before birth. Various authors have suggested normal ranges of values. Ideally, normal blood gas ranges would be derived from a sample reflecting patients having normal labor, normal delivery, and normal neonatal outcome. Examination of the selection used to arrive at several of the reported ranges suggests that the authors define ideal ranges rather than normal ones. The values were generally derived from samples representing only a small, n o n r a n d o m fraction of t h e neonates in their populations. We chose to define the normal neonate as one that is vigorous at birth, and we used the Apgar score as an index of this. There is a great deal of evidence in the literature to suggest that a high Apgar score effectively rules out intrapartum asphyxial brain damage. Gilstrap et al. ~ suggested that newborns are at low risk for immediate complications resulting from intrapartum asphyxia unless the umbilical artery pH is <7.00 and Apgar scores are <3 at both 1 minute and 5 minutes. Of the 358 term infants with a pH <7.20 analyzed by Winkler et al., 6 the only two infants with significant asphyxial complications had both severe acidemia and low Apgar scores at 1 minute (2 and 1) and 5 minutes (4 and 1). Goodwin e t a l 7 analyzed 126 term newborns with a pH <7.00. Of the 29 infants with no comorbidity who had 1807
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1!00 1000 900
/
800
/
700
/
/
600 n
500 400
/
300
/
/
/
200 100 0
. . . . . . . . .
I ....
6.9
.....
I .........
7.0
I .........
7.1
I ....
7.2
'''~'I~'''+'~
7.3
''l+''Lh~'h'l
7.4
b I ~ ' ' ~w-r'T" ]
7.5
7.6
pH Fig. 1. Frequency distribution of umbilical arterial blood pH in babies with Apgar scores ->7at 5 minutes (n = 15,073).
seizures within 48 hours, 24 had 5-minute Apgar scores <7 and 12 had scores <3. Additionally, 76% of newborns with 5-minute Apgar scores of 4 to 7 and pH <7 did not have seizures. Towbin,+in emphasizing the need to correlate obstetric factors with neuropathologic effects, states that "it is implausible to believe that cerebral palsy developing in an infant can be attributed to massive acute cerebral damage incurred intranatally in an infant who was in good clinical condition soon after delivery." Freeman and Nelson, 9 in their review of intrapartum asphyxia and cerebral palsy, agree: " . . . an infant who has little or no evidence of hypoxia in the delivery room, i.e., an Apgar score of greater than 6 at five minutes, has not suffered substantial asphyxia during the preceding several hours of labor." We therefore believe that selecting neonates on the basis of Apgar score <7 at 5 minutes is an acceptable clinical means of ruling out severe intrapartum asphyxia lasting until delivery. The primary aim of this study was to define the mean and range of blood gases and acid-base values in a group of babies selected on the basis of newborn vigor, defined as an Apgar score >7 at 5 minutes. A secondary aim was to determine the association of the umbilical cord values with method of delivery, gestational age, presentation, and the presence of thick meconium. Methods
The University of California, San Francisco, Department of Obstetrics, Gynecology, and Reproductive Sci-
ences has maintained a computerized perinatal database since 1977. The database contains 300 items of information about each mother and infant pair delivered at the institution. Intrapartum data are acquired at delivery, and other maternal and neonatal data are extracted from the medical record at discharge from the hospital. Gestational age is adjudicated by reference to menstrual dating, uhrasonographic examination, and neonatal maturity examination. Only those newborns with an Apgar score of _>7 or at 5 minutes were used in the analysis. Apgar scores were assigned by pediatric house staff or by experienced labor and delivery nurses in conjunction with obstetric house staff u n d e r the guidance of obstetric attending staff. The cord blood samples were collected anaerobically in heparinized syringes from doubly clamped segments of. umbilical cord within 20 minutes of delivery by the anesthesia or obstetric attending staff and analyzed within 30 minutes of birth by the Neonatal Intensive Care Unit Blood Gas Laboratory. This laboratory has maintained strict quality control of analysis and calibration techniques since the early 1970s. Equipment upgrading is regularly carried out, and over the years of observations this has improved speed and convenience of analysis while continuing to provide accurate results. Data analysis began with evaluation of the distribution of the sample. Univariate analysis of umbilical arterial and venous pH, PCO2, Po2, and base excess was then performed. Finally, the data were broken down by four variables: method of delivery, gestational age, presenta-
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1700 1000 000 800 700 n
600 500 400 300 200 100" 0"
I
1.61E-07 1,41E-07
J
I
I
I
I
t
21E-07 1,O1E-07 8.09C-08 6,09E-08 4.09E-08 2.09E-08 H + concentration
- M. ].-i
Fig. 2. Frequency distribution of umbilical arterial blood H÷ ion concentration in babies with Apgar scores >7 at 5 minutes (n= 15,073).
tion (for vaginal deliveries), and presence of heavy meconium. Again, univariate analysis was performed for each grouping, with comparisons of the means.
Results The perinatal database contained information on 26,249 newborns delivered from 1977 through 1993. Multiple births were included. Full blood gas and obstetric data were available for 16,060 newborns. Of these, 15,073 (94%) had a 5-minute Apgar score _>7. The umbilical artery pH values were evaluated for norreality of distribution with the Kolmogorov D statistic. The data were not normally distributed but were skewed. This distribution is shown in Fig. 1. The pH values were converted to hydrogen ion concentration with the expectation that this might affect the skewness. However, the distribution of the hydrogen ion concentration was similarly skewed (Fig. 2). We have presented the results as both mean with SD and median with selected percentiles. Results for all of these newborns with Apgar scores _>7 at 5 minutes are shown in Table I. The mean and median values for pH, Pco2, Po2, and base excess were similar. Also, there were quantitatively similar values for the 2.5th and 97.5th percentiles and +2 SDs. Of the babies included in this analysis 51 (0.34%) had umbilical artery pH values <7.00. Umbilical artery values for the vigorous babies were further analyzed by method of delivery: vaginal, operative vaginal, and cesarean section. By multiple comparisons of the mean, the pH means were significantly different,
although the greatest difference was only 0.03 units (Table II). Similarly, the umbilical artery pH values were analyzed by gestational age: premature babies (<37 weeks' gestation, including 129 babies weighing <1000 gin), term babies (37 to 42 weeks), and postterm babies (>42 weeks). Again the means were significantly different by multiple comparisons (Table III). Omitting babies who were intubated by 5 minutes (and thus might be expected to have artificially elevated Apgar scores) did not change the mean umbilical artery pH value for the premature group. The umbilical artery pH values for infants delivered vaginally were then analyzed by presentation: vertex versus breech. The means were significantly different (Table W). Finally, the umbilical artery pH values were analyzed by the presence of thick meconium. Again the means were significantly different (Table V). The trends in the other blood gas and acid-base factors with the various subgroups were similar to those for pH, and the data are not shown.
Comment This large series of umbilical cord blood gases, selected only on the basis of an Apgar score _>7at 5 minutes, shows a mean umbilical artery pH of 7.26, with the contribution to the acidemia being mild respiratory (Pco 2 53 mm Hg) and mild metabolic (base excess - 4 mEq - L-1) components. The range of normality expressed as either +2 SDs or 2.5 and 97.5th percentiles is similar, reflecting the fact
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T a b l e I. M e a n a n d m e d i a n values o f acid-base a n d b l o o d gas values in u m b i l i c a l arterial a n d v e n o u s c o r d b l o o d in fetuses with A p g a r score _>7 at 5 m i n u t e s
UA pH UA Pc% (ram Hg) UA Po 2 (mm Hg) UA base excess (mEq. L-1) UV pH UV PCO 2 (mm Hg) UV P% (mm Hg) UV base excess (mEq. L-1) n = 15,073.
I
]
2.5th Percentile
5th Percentile
95th Percentile
97.5th Percentile
SD
7.26 53 17 -4
0.07 10 6 3
7.10 35 6 -11
7.13 37 8 -10
7.27 52 17 -4
7.36 69 27 1
7.38 74 30 1
7.34 41 29 -3
0.06 7 7 3
7.20 28 16 -8
7.23 30 18 -8
7.35 41 29 -3
7.44 53 40 1
7.46 57 43 2
UA, Umbilical artery;
Median
]
Mean
UV,,umbilical vein.
T a b l e II. M e a n a n d m e d i a n values of p H in u m b i l i c a l arterial b l o o d in fetuses with A p g a r scores >7 at 5 m i n u t e s by m e t h o d of delivery
Spontaneous vaginal delivery Operative vaginal delivery Cesarean section
No.
Mean
SD
8756 2364 3953
7.27 7.24 7.25
0.07 0.07 0.07
2.5th 5th I 95th I 97.5th Percentile Percentile Median Percentile .Percentile 7.12 7.08 7.07
7.15 7.12 7.11
7.28 7.25 7.26
7.37 7.34 7.34
7.39 7.35 7.35
Operative delivery means are significantly different from vaginal delivery mean, p < 0.05. T a b l e III. M e a n a n d m e d i a n values of p H i n umbilical arterial b l o o d in fetuses with A p g a r scores >7 at 5 m i n u t e s by g e s t a t i o n a l age
Preterm (<37 wk) Term (37-42 wk) Postterm (>42 wk)
No.
Mean
SD
2,018 12,802 253
7.28 7.26 7.24
0.08 0.07 0.08
2.5th Percentile
5th Pementile
7.09 7.10 7.04
7.14 7.14 7.08
Median 7.29 7.27 7.25
[
95th ] 97.5th Percentile Percentile 7.38 7.35 7.34
7.40 7.37 7.35
All means are significantly different from each other, p < 0.05. T a b l e IV. M e a n a n d m e d i a n values of p H in u m b i l i c a l arterial b l o o d in fetuses with A p g a r scores >_7 at 5 m i n u t e s by p r e s e n t a t i o n at delivery (vaginal delivery only)
I Breech Vertex
No. 161 10,959
]
Mean
SD
7.22 7.26
0.09 0.07
2.5th Percentile 6.99 7.11
5th Percentile 7.05 7.14
Median 7.24 7.27
95th i Percentile 7.33 7.36
97.5th Percentile 7.35 7.38
The means are significantly different, p < 0.05. t h a t t h e r e was only m o d e r a t e skewness o f t h e p o p u l a t i o n data. T h e o u t e r limits o f a c i d e m i a , e x p r e s s e d as the 2.5th p e r c e n t i l e , are p H 7.10, P c % 74 m m Hg, a n d base excess - 1 1 m E q • L-1. T h e s e figures are r e a s o n a b l y similar to those r e p o r t e d by o t h e r s in specific series with e i t h e r n o selection criteria or with selection criteria of v a r y i n g rigidity. I n a n u n s e l e c t e d series Sykes et al. x° prospectively coll e c t e d c o r d b l o o d f r o m 1039 o f 1210 deliveries in a 2 - m o n t h p e r i o d a n d analyzed t h e values by A p g a r scores. T h e m e a n u m b i l i c a l a r t e r y p H was 7.20 _+ 0.08. W i b l e et al. .1 analyzed d a t a for 29 infants, for w h o m n o selection criteria were d e f i n e d e x c e p t " n o r m a l A p g a r scores." T h e m e a n u m b i l i c a l a r t e r y p H was 7.24. No SD was given.
U m b i l i c a l c o r d b l o o d gases were o b t a i n e d o n >2000 consecutive deliveries by Westgate et al., 12 a n d 75% of t h e s p e c i m e n s were c o n s i d e r e d valid. No o t h e r selection was applied, T h e m e a n p H was 7.26, a n d 2.5th p e r c e n t i l e was 7.05. T h e m e a n base excess was - 2 . 4 a n d the m e a n 97.5th p e r c e n t i l e - 9 . 7 m E q - L 1. O t h e r a u t h o r s have o f f e r e d selection criteria to d e f i n e " n o r m a l " values. O f t h e s e studies, B r e t s c h e r a n d Saling la b e g a n with a p o p u l a t i o n o f 1500 babies, all in t h e vertex p o s i t i o n a n d all clinically vigorous. A total o f 306 b a b i e s m e t t h e criteria o f " n o fetal distress', (suspected if the p H was <7.20) a n d also s c o r e d well o n Saling's o w n system of n e w b o r n evaluation. C o r d b l o o d was analyzed for 100 of these infants, b u t it was n o t clear h o w t h e 100 were
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Table V. Mean and median values of pH in umbilical arterial blood in fetuses delivered vaginally with Apgar scores _>7 at 5 minutes by presence of thick meconium in amniotic fluid
No. No thick meconium Thick meconium
14,82 271
[ ] M e a SD n 7.26 7.24
0.07 0.07
Percentile 7.10 7.07
Percentile 7.14 7.10
Median 7.27 7.24
Percentile 7.36 7.35
Percentile 7.38 7.38
Means are significantly different, p < 0.05. chosen from the 306. The mean umbilical artery pH was 7.26 + 0.07 (SD); any pH <1 SD below the mean was labeled "pathologic." Yeomans et al. I4 selected for analysis infants from term pregnancies without diabetes, preeclampsia, multiple gestation, Rh incompatibility, or other complications. Fetal indications for exclusion included growth retardation, meconium passage, anomalies, significant fetal heart rate abnormalities, and weight <2500 gin. One hundred forty six infants met these criteria; there is no mention of the population size from which these infants were selected. The mean umbilical artery pH was 7.28 + 0.05. Ruth and Raivio ~5 studied all the deliveries in their institution over a 2-month period, during which 982 infants were born. Applying certain criteria (no maternal chronic disease, no pregnancy or delivery complications, no "neonatal disturbances," and normal infant development at 1 year), they selected 127 infants. Incidentally, all these infant s had Apgar scores of 9 or 10 at 5 minutes, although this was not a selection criterion. They further broke these down into 106 vaginal deliveries and 21 elective cesarean sections. The mean values were vaginal delivery umbilical artery pH 7.29-+ 0.07 and elective cesarean section umbilical artery pH 7.31 + 0.03. Thorp et al. 16 analyzed data from 1924 term nulliparous patients with spontaneous onset of labor, vertex presentations, and singleton gestations. There is no mention of the population size from which this sample was chosen. The mean umbilical artery pH was 7.24 + 0.07. Riley and Johnson ~7 selected 3522 vaginally delivered term and preterm infants born during a 2-month period at their hospital, where cord blood is routinely analyzed. The mean umbilical artery values were preterm pH 7.28 _+0.08 and term pH 7.27 + 0.07. In the studies cited above the mean values for pH span the range Of 7.20 to 7.3l. In general, the other components of the acid-base state (Pco 2, base excess, and Po2) are relatively similar to our values. In our study there were small but statistically significant differences in mean pH when other variables were examined. Thus babies born by cesarean section or operative vaginal delivery were more acidemic than those born by normal spontaneous vaginal delivery, although by only 0.02 or 0.03 pH units. Term and postterm fetuses were slightly more acidemic than preterm fetuses. This was not explained by resuscitation activities but may have been due to the shorter labors seen in the premature group. Breech fetuses born vaginally were more acidemic than vertex fetuses born vaginally. Babies born in the presence
of thick meconium were slightly more acidemic than those without thick meconium. However, in all of the above comparisons the differences in mean values are small and unlikely to be of great clinical significance in this vigorous group of babies. This study does not address the question of whether the values presented define "normality" in terms of later neurologic function. Retrieval of infant data on these babies is not practicable. Other investigators have approached this question by appropriate studies. For example, Low et al. is found that metabolic acidemia of the order of buffer base 25 m E q . L-1, approximately equivalent to a base excess o f - 2 0 mEq • L-~, and a pH of 7.0, were followed by motor and cognitive defects in approximately 50% of children at 1 year of age. Goodwin et al.7 reviewed the course of 129 term nonanomalous singleton infants with umbilical arterial pH <7.00. They concluded that a pH <6.8 with marked hypercarbia (Pco 2 usually >100 mm Hg) and metabolic acidosis (base excess usually <-15 m E q . L-~) relates best to neonatal death or major neurologic dysfunction. Goldaber et al. 19 defined a "pathologic fetal acidemia" as <7.00 in umbilical arterial blood in their review of 3506 term newborns with an umbilical arterial pH <7.20. In conclusion, from a consideration of the published literature regarding fetal asphyxia, it seems clear that setting the outer limits of normal pH at the 2.5th percentile is extremely conservative in defining the likelihood of neurologic sequelae. REFERENCES
1. Court DJ, Parer JT. Experimental studies of fetal asphyxia and fetal heart rate interpretation. In: Nathanielsz PW, Parer JT, editors. Research in perinatal medicine. New York (NY): Perinatology Press, 1984;1:113-69. 2. Yaffe H, Parer JT, Block BS, Llanos AJ. Cardiorespiratory responses to graded reductions of uterine blood flow in the sheep fetus. J Dev Physiol 1987;9:325-36. 3. Block BS, Schlafer DH, Wentworth RA, Kreitzer LA, Nathanielsz PW. Intrauterine asphyxia and the breakdown of physiologic circulatory compensation in fetal sheep. AmJ Obstet Gynecol 1990;162:1325-31. 4. Gunn AJ, ParerJT, Mallard EC, Williams CE, Gluckman PD. Cerebral histological and electrocorticographic changes after asphyxia in fetal sheep. Pediatr Res 1992;31:486-91. 5. Gilstrap LC, Leveno JK, Burns J, Williams ML, Little BB. Diagnosis of birth asphyxia on the basis of fetal pH, Apgar score, and newborn cerebral dysfunction. Am J Obstet Gynecol 1989;161:825-30. 6. Winkler CL, Hauth JT, Tucker JM, Owen J, Brumfield CG. Neonatal complications at term as related to the degree of umbilical artery acidemia. Am J Obstet Gynecol 1991;164: 637-41.
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7. Goodwin TM, Belai I, Hernandez P, Durand M, Paul RH. Asphyxial complications in the term newborn with severe umbilical acidemia. AmJ Obstet Gynecol 1992;167:1506-12. 8. Towbin A. Obstetric malpractice litigation: the pathologist's view. AmJ Obstet Gynecol 1986;155:927-35. 9. FreemanJM, Nelson KB. Intrapartum asphyxia and cerebral palsy. Pediatrics 1988;82:240-9. 10. Sykes GS, Johnson P, Ashworth F, Molloy PM, Gu W, Stirrat GM, et al. Do Apgar scores indicate asphyxia? Lancet 1982; 1:494-6. 11. Wible JL, Petrie RH, Koons A, Perez A. The clinical use of umbilical cord acid-base determinations in perinatal surveillance and management. Clin Perinatol 1982;9:387-97. 12. WestgateJ, GaribaldiJM, Greene Fall Umbilical cord blood gas analysis at delivery: a time for quality data. Br J Obstet GynaecoI 1994;101:1054-63. 13. Bretscher J, Saling E. pH values in the human fetus during labor. AmJ Obstet Gynecol 1967;97:906-11. 14. Yeomans ER, HauthJC, Gilstrap LC, Strickland DM. Umbilical cord pH, Pco2, and bicarbonate following uncomplicated term vaginal deliveries. A m J Obstet Gynecol 1985;151:798800. 15. Ruth VJ, Raivio KO. Perinatal brain damage: predictive value of metabolic and the Apgar score. BMJ 1988;297:24-7. 16. Thorp JA, Sampson JE, Parisi VM, Creasy RK. Routine umbilical cord blood gas determinations? AmJ Obstet Gynecol 1989;161:600-5. 17. Riley RJ,JohnsonJWC. Collecting and analyzing cord blood gases. Clin Obstet Gynecol 1993;36:13-23. 18. LowJA, Galbraith RS, Muir DW, Killen HL, Pater EA, Karchmar EJ. Factors associated with motor and cognitive deficits in children after intrapartum fetal hypoxia. Am J Obstet Gynecol 1984;148:533-9. 19. Goldaber KG, Gilstrap LC, Leveno KJ, DaxJS, McIntire DD. Pathologic fetal acidemia. Obstet Gynecol 1991;78:1103-8.
Editors' note: This m a n u s c r i p t was revised after these discussions were presented. Discussion D~. RAYMONDJ. JENNETT, Phoenix, Arizona. I am certain that I a m n o t alone in admitting confusion over the wide range of definitions of the terms birth asphyxia, acidemia, acidosis, and that most elusive o n e of all, "normal." A n o t h e r word that has b e c o m e increasingly comm o n in the obstetric literature to characterize newborns is "vigorous." Dr. Parer and his associates u n d e r t o o k to address these in their stated objective: "Umbilical c o r d b l o o d gases and acid-base data f r o m vigorous n e o n a t e s were e x a m i n e d to d e t e r m i n e n o r m a l values." T h e authors b e g a n by reviewing o t h e r studies that addressed n o r m a l ranges of acid-base values and t h e n contrasted t h e m to their own approach. They state: "Ideally, n o r m a l b l o o d gas ranges would be derived f r o m a sample reflecting the r e a l m of n o r m a l labor, n o r m a l delivery and n o r m a l neonates. E x a m i n a t i o n of the m e t h o d used to arrive at several of the c u r r e n t r e p o r t e d ranges suggest that they define ideal ranges rather than the n o r m a l ones." Immediately, I e x p e r i e n c e d a b e g i n n i n g resurg e n c e of my confusion. Are n o t " i d e a l " and " n o r m a l " at least related concepts? T h e authors go on to state, "We chose to define the n o r m a l n e o n a t e as o n e that is vigorous at birth and we used the A p g a r score as an i n d e x of this." If the goal is to define the " n o r m a l " acid-base status of the neonate, their study is still n o t entirely objective, a l t h o u g h it is less arbitrary than the s~udies that used the criteria they cited.
All infants with a 5-minute Apgar score of 27 are not necessarily equal. An infant with a 1-minute Apgar score of 1 is hardly a "vigorous" infant at birth, although with adequate resuscitation it may have r e a c h e d a 5 minute score of ->7. In a study published by our g r o u p an index was suggested that took into account both the 1- and 5-minute scores and short-term p r o b l e m s were related significantly m o r e to b o t h our i n d e x and the 1-minute Apgar score than the 5-ininute score) Apgar 2 r e m a r k e d that, a l t h o u g h the 5-minute score m i g h t correlate with brain damage, the 1-minute score was a reflection of the acid-base status o f the fetus. However, given the large sample size (15,073) in Dr. Parer's study, the effect on the m e a n values by depressed infants at 1 m i n u t e would be minimal. O f the studies cited by the a u t h o r for comparison, that of T h o r p et a l ) was the most c o m p a r a b l e and serves as additional validation for the c u r r e n t study. These authors studied 1924 n e o n a t e s whose Apgar scores were >7 at both 1 and 5 minutes. T h e m e a n p H for this group was 7.24 with an SD of +0.07, c o m p a r e d with the c u r r e n t study p H of 7.26. T h e Pco2, Po2, bicarbonate, and base deficit were marginally better in the study of T h o r p et al. I must also confess to an uneasiness with the authors' use of the terms "acidosis" and "acidotic" rather than " a c i d e m i a . " T h e latter t e r m lends itself to quantification in terms of the pH. Acidosis, on the o t h e r hand, has a c o n n o t a t i o n of a pathologic disorder and is i n d e e d so defined in Dorland's Illustrated Medical Dictionary. To define the range of pH, bicarbonate, and base deficit as being within the n o r m a l and then using a t e r m with a pathologic c o n n o t a t i o n seems to be a contradiction. Regardless of my reservations about the use of the terms " n o r m a l values" and "acidosis," the authors have m a d e a valuable contribution to tile range of acid-base values f o r n e o n a t e s who have b e e n stabilized within 5 minutes after birth and to the ranges within which cerebral palsy is n o t a factor. Dr. Parer, please c o m m e n t on one i m m e d i a t e and practical application. Some authors r e c o m m e n d a cord blood acid-base assessment on all neonates, whereas others limit it to selected neonates. W h a t is your r e c o m m e n d a tion? A n d if it is selective, would the findings of your study indicate which neonates to test? O n a subject n o t directly addressed in your p a p e r and given the fact that studies such as the c u r r e n t one are helpful in a retrospective analysis but n o t for a specific clinical situation, what is your o p i n i o n as to the c u r r e n t role of fetal b l o o d sampling as an adjunct to fetal heart rate monitoring? REFERENCES
1. Jennett RJ, Warford HS, Kreinick CK, Waterkotte GW. Apgar index: a statistical tool. AmJ Obstet Gyneco11981;140:206-12. 2. Apgar V. The newborn (Apgar) scoring system: reflections and advice. Pediatr Clin North Am 1966;13:645. 3. ThorpJA, SampsonJE, Parisi VM, Creasy RIC Routine umbilical cord blood gas determinations. Am J Obstet Gynecol 1989;161:600-5. Dm Mm~IAEL P. NAG~OTrE, L o n g Beach, California. At best, using Apgar scores as a triage p o i n t is difficult. In
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some of the historic studies, such as the Collaborative Perinatal Project, an assigned nurse was responsible for determining the Apgar score, which was an improvement over multiple individuals assigning Apgar scores. In the data presented, there appeared to be 30 to 50 babies who met the criteria of vigor and had low pHs at or <2.5th percentile. Did any of those babies exhibit any neurologic sequelae, either immediately or later in the neonatal period? DR, CazvlN HOB~, Los Angeles, California. Dr. Parer's group has added pH to help defin e a normal Apgar score at 5 minutes. Together, the two are very important. In the absence of very important risk factors such as meconium, gestational age, delivery method, and presentation a pH between 7.10 and 7.38 along with Apgar score at 5 minutes defines a normal population of newbborns. DR.JACKIa~mY, Seattle, Washington. In today's scientific research, statistical analysis seems mandatory. However, I would like to commend Dr. Parer for reminding us that, although statistical significance is important in the research and the application of scientific data, many times this clinical significance is not clinically relevant. DR. ROBERT C. GOODUN, Placerville, California. Dr. Parer, I am confused about your statement that you have far more neonatal acid-base values than anyone else. In 1991 I reported to this society nearly 12,000 consecutive umbilical artery pH values from Denver General Hospital. 1 Other departments now have in excess of 30,000 cases. I described cases of umbilical artery pH values >3 SDs below the mean (<6.90 pH), who did well. You should emphasize that your values are from your institution, which is at sea level. Other institutions will have different normal acid-base values. In my 1994 presentation I noted my correspondence with Dr. Low, who agreed that no study excluded the possibility of intraparturn recovery from severe fetal metabolic acidemia. 2 In addition, I believe that maternal acid base values should be considered along with the evaluation of umbilical cord values. REFERENCES
1. Goodlin RC, Freedman WL, McFeeJG, Winter SW. The neonate with unexpected acidemia. J Reprod Med 1994;39:97100. 2. Goodlin RC. Do concepts of causes and prevention of cerebral palsy need revision? Am J Obstet Gynecol 1995; 172:1830-6. D~. PARER(Closing). Dr. J e n n e t t stated that in a review of the literature other authors have presented series of ideal births and ours were relatively unselected. However, whatever term is used is going to be arbitrary. We admit that using the 5-minute Apgar score may be just as arbitrary as picking normal Friedman curves, normal second stages, absence of forceps, and so on. A dialog needs to go on until we have ultimate agreement about what is "ideal" or "normal." Both Dr. J e n n e t t and Dr. Goodlin suggested that some of the babies with a borderline pH of 7.1 might or might not have had some degree of brain damage. One of the problems with intermediate pH values is whether there is
Helwig et al.
1813
a dose response. The all-or-nothing response to asphyxia is well known: a baby is either born dead, or more rarely, with severe brain damage or else recovers essentially intact. With intermediate degrees 0 f p H it has been difficult to show that there is a dose-response in terms of severity of brain damage. I lean toward the theory that there is a pH cliffwhere the baby, once it passes over the edge, falls into the abyss of brain damage. However, before it reaches that cliff, it is unlikely to have p e r m a n e n t brain damage. We have talked in this society before about the breakdown of the physiologic responses occurring at some specific point, depending on the severity and duration of the asphyxia. Although the details are unknown, pH is not the only determinant; blood flow redistribution and oxygen consumption of various organs play major roles as well. The semantic concerns about the differences between acidosis and acidemia seems to confuse everybody. Whenever these terms are used, they have to be redefined. The more we talk about it, the more likely we are to get some agreement about what it all means. Because we were measuring the acidosis in blood, I should have used their term, acidemia. Who should have umbilical cord blood gases analyzed? At the ivory tower of the University of California, San Francisco, data are collected for research. This should not occur at all hospitals. With respect to this question, there is a recent large survey by Johnson and Riley~ in which all the respondents said that they do get cord blood gases, at least in selected cases. Usually this meant that blood gases were obtained on depressed babies, premature babies, babies that were born by cesarean section, babies that had heart rate tracings that were less than "normal," and so forth. Within this group umbilical arterial blood gases were obtained, but umbilical venous specimens were not always sent. Most groups surveyed were not interested in pH alone, but wanted a full panel of blood gases, including the pH, Pco2, and calculation of the metabolic component. What is the current role of fetal blood sampling? Historically it is very interesting, and that is about it. Of the 4 million babies born in the United States today, single digit percentages are born in institutions where it is practically possible to do intrapartum fetal blood sampling, analyze the data, and use it effectively for evaluation and management of labor. Everyone is using either tactile or vibrioacoustic stimulation testing. If you get an acceleration in response to stimulation, this essentially guarantees a pH >7.2, which eliminates "acidosis." Dr. Nageotte asked about the follow-up of babies t h a t were at the tail, the 2.5th percentile. Although we do not have that data, it probably could be pulled from the literature database. At a future meeting we hope to present data on these babies who had Apgar scores <7 at 5 minutes. Unfortunately, we do not always have specific postdischarge follow-up data on these babies to know which of the "acidotic" ones did worse than those above 7.2. Dr. Hobel, thank you for your comment about the interaction between pH and Apgar score. I had not
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Helwiget al.
thought of it that way; it is a nice way to jusfify the Apgar score. Dr. Lame}; thank you for your c o m m e n t about the important difference between statistical and clinical significance. I apologize to Dr. Goodlin for omitting his work, but
June I996 .4anJ Obstet G)~ecol
our literature search was confined to series with a full panel of blood gases. REFERENCE
1. JohnsonJWC, Riley W. Cord blood gas studies: a survey. Clin Obstet Gynecol 1993;36:99-101.
Availability of Journal back issues As a service to our subscribers, copies of back issues of the American Journal of Obstetrics and Gynecology for the preceding 5 years are maintained and are available for purchase from the publisher, Mosby-Year Book, Inc., at a cost of $14.00 per issue. The following quantity discounts are available: one fourth off on quantifies of 12 to 23 and one third off on quantities of 24 or more. Please write to Mosby-Year Book, Inc., Subscription Services, 11830 Wesdine Industrial Drive, St. Louis, MO 63146-3318 or call (800)453-4351 or (314)453-4351 for information on availability of particular issues. If back issues are unavailable from the publisher, photocopies of complete issues are available from UMI, 300 N. Zeeb Road, Ann Arbor, MI 48106-1346. Tel.: (313)7614700.
Key words: Fetal asphyxia, base excess, Pc%, P%
Asphyxia may be defined as insufficient exchange of respiratory gases. This insufficiency is almost always caused by inadequate unabilical or uterine blood flow, which results in a reduction of oxygen content and elevation of carbon dioxide in fetal blood. Eventually, this gives rise to physiologic compensatory mechanisms, the most important of which is redistribution of blood flow within the fetus. Blood flow to the heart, brain, and adrenal gland increases; blood flow to the placenta is maintained; and blood flow to all other areas decreases. 1Where blood flow is reduced, oxygen delivery is not enough to maintain aerobic metabolism. Anaerobic metabolism occurs, leading to local lactate production and then systemic lat,~,~ acidemia. As the oxygen supply continues to drop, the physiologic compensatory mechanisms themselves fail, with consequent myocardial performance loss and reduced cardiac output. 2' 3 Umbilical blood flow decreases, and the asphyxia worsens. Eventually, the fetus
From the Department of Obstetrics, Gynecology, and Reproductive Sciences and the Cardiovascular Research Institute, University of California, San Francisco. Presented at the Sixty-second Annual Meeting of the Pacific Coast Obstetrical and GynecologicalSodety, Squaw Valley, California, September 16-21, 1995. Reprint requests:Julian T. Parer, MD, PM), Department of Obstetrics, Gynecology, and Reproductive Sciences, Box 0550, University of California, San Francisco, 513Parnassus, Rm. HSE-1462, San Francisco, CA 94143-0550. Copyright © 1996 by Mosby-YearBook, Inc. 0002-9378/96 ~5.00 + 0 6/6/72182
has regional hypoxia to the extent that there is cellular damage. 4 Umbilical cord blood gas analysis allows assessment of the status of the respiratory gases and acid-base values in the newborn immediately before birth. Various authors have suggested normal ranges of values. Ideally, normal blood gas ranges would be derived from a sample reflecting patients having normal labor, normal delivery, and normal neonatal outcome. Examination of the selection used to arrive at several of the reported ranges suggests that the authors define ideal ranges rather than normal ones. The values were generally derived from samples representing only a small, n o n r a n d o m fraction of t h e neonates in their populations. We chose to define the normal neonate as one that is vigorous at birth, and we used the Apgar score as an index of this. There is a great deal of evidence in the literature to suggest that a high Apgar score effectively rules out intrapartum asphyxial brain damage. Gilstrap et al. ~ suggested that newborns are at low risk for immediate complications resulting from intrapartum asphyxia unless the umbilical artery pH is <7.00 and Apgar scores are <3 at both 1 minute and 5 minutes. Of the 358 term infants with a pH <7.20 analyzed by Winkler et al., 6 the only two infants with significant asphyxial complications had both severe acidemia and low Apgar scores at 1 minute (2 and 1) and 5 minutes (4 and 1). Goodwin e t a l 7 analyzed 126 term newborns with a pH <7.00. Of the 29 infants with no comorbidity who had 1807
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Helwig et al.
June !996 A m J
Obstet
Gynecol
1!00 1000 900
/
800
/
700
/
/
600 n
500 400
/
300
/
/
/
200 100 0
. . . . . . . . .
I ....
6.9
.....
I .........
7.0
I .........
7.1
I ....
7.2
'''~'I~'''+'~
7.3
''l+''Lh~'h'l
7.4
b I ~ ' ' ~w-r'T" ]
7.5
7.6
pH Fig. 1. Frequency distribution of umbilical arterial blood pH in babies with Apgar scores ->7at 5 minutes (n = 15,073).
seizures within 48 hours, 24 had 5-minute Apgar scores <7 and 12 had scores <3. Additionally, 76% of newborns with 5-minute Apgar scores of 4 to 7 and pH <7 did not have seizures. Towbin,+in emphasizing the need to correlate obstetric factors with neuropathologic effects, states that "it is implausible to believe that cerebral palsy developing in an infant can be attributed to massive acute cerebral damage incurred intranatally in an infant who was in good clinical condition soon after delivery." Freeman and Nelson, 9 in their review of intrapartum asphyxia and cerebral palsy, agree: " . . . an infant who has little or no evidence of hypoxia in the delivery room, i.e., an Apgar score of greater than 6 at five minutes, has not suffered substantial asphyxia during the preceding several hours of labor." We therefore believe that selecting neonates on the basis of Apgar score <7 at 5 minutes is an acceptable clinical means of ruling out severe intrapartum asphyxia lasting until delivery. The primary aim of this study was to define the mean and range of blood gases and acid-base values in a group of babies selected on the basis of newborn vigor, defined as an Apgar score >7 at 5 minutes. A secondary aim was to determine the association of the umbilical cord values with method of delivery, gestational age, presentation, and the presence of thick meconium. Methods
The University of California, San Francisco, Department of Obstetrics, Gynecology, and Reproductive Sci-
ences has maintained a computerized perinatal database since 1977. The database contains 300 items of information about each mother and infant pair delivered at the institution. Intrapartum data are acquired at delivery, and other maternal and neonatal data are extracted from the medical record at discharge from the hospital. Gestational age is adjudicated by reference to menstrual dating, uhrasonographic examination, and neonatal maturity examination. Only those newborns with an Apgar score of _>7 or at 5 minutes were used in the analysis. Apgar scores were assigned by pediatric house staff or by experienced labor and delivery nurses in conjunction with obstetric house staff u n d e r the guidance of obstetric attending staff. The cord blood samples were collected anaerobically in heparinized syringes from doubly clamped segments of. umbilical cord within 20 minutes of delivery by the anesthesia or obstetric attending staff and analyzed within 30 minutes of birth by the Neonatal Intensive Care Unit Blood Gas Laboratory. This laboratory has maintained strict quality control of analysis and calibration techniques since the early 1970s. Equipment upgrading is regularly carried out, and over the years of observations this has improved speed and convenience of analysis while continuing to provide accurate results. Data analysis began with evaluation of the distribution of the sample. Univariate analysis of umbilical arterial and venous pH, PCO2, Po2, and base excess was then performed. Finally, the data were broken down by four variables: method of delivery, gestational age, presenta-
Volume 174, Number 6 AmJ Obstet O)aaecol
Helwig et al. 1809
1700 1000 000 800 700 n
600 500 400 300 200 100" 0"
I
1.61E-07 1,41E-07
J
I
I
I
I
t
21E-07 1,O1E-07 8.09C-08 6,09E-08 4.09E-08 2.09E-08 H + concentration
- M. ].-i
Fig. 2. Frequency distribution of umbilical arterial blood H÷ ion concentration in babies with Apgar scores >7 at 5 minutes (n= 15,073).
tion (for vaginal deliveries), and presence of heavy meconium. Again, univariate analysis was performed for each grouping, with comparisons of the means.
Results The perinatal database contained information on 26,249 newborns delivered from 1977 through 1993. Multiple births were included. Full blood gas and obstetric data were available for 16,060 newborns. Of these, 15,073 (94%) had a 5-minute Apgar score _>7. The umbilical artery pH values were evaluated for norreality of distribution with the Kolmogorov D statistic. The data were not normally distributed but were skewed. This distribution is shown in Fig. 1. The pH values were converted to hydrogen ion concentration with the expectation that this might affect the skewness. However, the distribution of the hydrogen ion concentration was similarly skewed (Fig. 2). We have presented the results as both mean with SD and median with selected percentiles. Results for all of these newborns with Apgar scores _>7 at 5 minutes are shown in Table I. The mean and median values for pH, Pco2, Po2, and base excess were similar. Also, there were quantitatively similar values for the 2.5th and 97.5th percentiles and +2 SDs. Of the babies included in this analysis 51 (0.34%) had umbilical artery pH values <7.00. Umbilical artery values for the vigorous babies were further analyzed by method of delivery: vaginal, operative vaginal, and cesarean section. By multiple comparisons of the mean, the pH means were significantly different,
although the greatest difference was only 0.03 units (Table II). Similarly, the umbilical artery pH values were analyzed by gestational age: premature babies (<37 weeks' gestation, including 129 babies weighing <1000 gin), term babies (37 to 42 weeks), and postterm babies (>42 weeks). Again the means were significantly different by multiple comparisons (Table III). Omitting babies who were intubated by 5 minutes (and thus might be expected to have artificially elevated Apgar scores) did not change the mean umbilical artery pH value for the premature group. The umbilical artery pH values for infants delivered vaginally were then analyzed by presentation: vertex versus breech. The means were significantly different (Table W). Finally, the umbilical artery pH values were analyzed by the presence of thick meconium. Again the means were significantly different (Table V). The trends in the other blood gas and acid-base factors with the various subgroups were similar to those for pH, and the data are not shown.
Comment This large series of umbilical cord blood gases, selected only on the basis of an Apgar score _>7at 5 minutes, shows a mean umbilical artery pH of 7.26, with the contribution to the acidemia being mild respiratory (Pco 2 53 mm Hg) and mild metabolic (base excess - 4 mEq - L-1) components. The range of normality expressed as either +2 SDs or 2.5 and 97.5th percentiles is similar, reflecting the fact
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june 1996 .am~J Obstet Gynecol
T a b l e I. M e a n a n d m e d i a n values o f acid-base a n d b l o o d gas values in u m b i l i c a l arterial a n d v e n o u s c o r d b l o o d in fetuses with A p g a r score _>7 at 5 m i n u t e s
UA pH UA Pc% (ram Hg) UA Po 2 (mm Hg) UA base excess (mEq. L-1) UV pH UV PCO 2 (mm Hg) UV P% (mm Hg) UV base excess (mEq. L-1) n = 15,073.
I
]
2.5th Percentile
5th Percentile
95th Percentile
97.5th Percentile
SD
7.26 53 17 -4
0.07 10 6 3
7.10 35 6 -11
7.13 37 8 -10
7.27 52 17 -4
7.36 69 27 1
7.38 74 30 1
7.34 41 29 -3
0.06 7 7 3
7.20 28 16 -8
7.23 30 18 -8
7.35 41 29 -3
7.44 53 40 1
7.46 57 43 2
UA, Umbilical artery;
Median
]
Mean
UV,,umbilical vein.
T a b l e II. M e a n a n d m e d i a n values of p H in u m b i l i c a l arterial b l o o d in fetuses with A p g a r scores >7 at 5 m i n u t e s by m e t h o d of delivery
Spontaneous vaginal delivery Operative vaginal delivery Cesarean section
No.
Mean
SD
8756 2364 3953
7.27 7.24 7.25
0.07 0.07 0.07
2.5th 5th I 95th I 97.5th Percentile Percentile Median Percentile .Percentile 7.12 7.08 7.07
7.15 7.12 7.11
7.28 7.25 7.26
7.37 7.34 7.34
7.39 7.35 7.35
Operative delivery means are significantly different from vaginal delivery mean, p < 0.05. T a b l e III. M e a n a n d m e d i a n values of p H i n umbilical arterial b l o o d in fetuses with A p g a r scores >7 at 5 m i n u t e s by g e s t a t i o n a l age
Preterm (<37 wk) Term (37-42 wk) Postterm (>42 wk)
No.
Mean
SD
2,018 12,802 253
7.28 7.26 7.24
0.08 0.07 0.08
2.5th Percentile
5th Pementile
7.09 7.10 7.04
7.14 7.14 7.08
Median 7.29 7.27 7.25
[
95th ] 97.5th Percentile Percentile 7.38 7.35 7.34
7.40 7.37 7.35
All means are significantly different from each other, p < 0.05. T a b l e IV. M e a n a n d m e d i a n values of p H in u m b i l i c a l arterial b l o o d in fetuses with A p g a r scores >_7 at 5 m i n u t e s by p r e s e n t a t i o n at delivery (vaginal delivery only)
I Breech Vertex
No. 161 10,959
]
Mean
SD
7.22 7.26
0.09 0.07
2.5th Percentile 6.99 7.11
5th Percentile 7.05 7.14
Median 7.24 7.27
95th i Percentile 7.33 7.36
97.5th Percentile 7.35 7.38
The means are significantly different, p < 0.05. t h a t t h e r e was only m o d e r a t e skewness o f t h e p o p u l a t i o n data. T h e o u t e r limits o f a c i d e m i a , e x p r e s s e d as the 2.5th p e r c e n t i l e , are p H 7.10, P c % 74 m m Hg, a n d base excess - 1 1 m E q • L-1. T h e s e figures are r e a s o n a b l y similar to those r e p o r t e d by o t h e r s in specific series with e i t h e r n o selection criteria or with selection criteria of v a r y i n g rigidity. I n a n u n s e l e c t e d series Sykes et al. x° prospectively coll e c t e d c o r d b l o o d f r o m 1039 o f 1210 deliveries in a 2 - m o n t h p e r i o d a n d analyzed t h e values by A p g a r scores. T h e m e a n u m b i l i c a l a r t e r y p H was 7.20 _+ 0.08. W i b l e et al. .1 analyzed d a t a for 29 infants, for w h o m n o selection criteria were d e f i n e d e x c e p t " n o r m a l A p g a r scores." T h e m e a n u m b i l i c a l a r t e r y p H was 7.24. No SD was given.
U m b i l i c a l c o r d b l o o d gases were o b t a i n e d o n >2000 consecutive deliveries by Westgate et al., 12 a n d 75% of t h e s p e c i m e n s were c o n s i d e r e d valid. No o t h e r selection was applied, T h e m e a n p H was 7.26, a n d 2.5th p e r c e n t i l e was 7.05. T h e m e a n base excess was - 2 . 4 a n d the m e a n 97.5th p e r c e n t i l e - 9 . 7 m E q - L 1. O t h e r a u t h o r s have o f f e r e d selection criteria to d e f i n e " n o r m a l " values. O f t h e s e studies, B r e t s c h e r a n d Saling la b e g a n with a p o p u l a t i o n o f 1500 babies, all in t h e vertex p o s i t i o n a n d all clinically vigorous. A total o f 306 b a b i e s m e t t h e criteria o f " n o fetal distress', (suspected if the p H was <7.20) a n d also s c o r e d well o n Saling's o w n system of n e w b o r n evaluation. C o r d b l o o d was analyzed for 100 of these infants, b u t it was n o t clear h o w t h e 100 were
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Table V. Mean and median values of pH in umbilical arterial blood in fetuses delivered vaginally with Apgar scores _>7 at 5 minutes by presence of thick meconium in amniotic fluid
No. No thick meconium Thick meconium
14,82 271
[ ] M e a SD n 7.26 7.24
0.07 0.07
Percentile 7.10 7.07
Percentile 7.14 7.10
Median 7.27 7.24
Percentile 7.36 7.35
Percentile 7.38 7.38
Means are significantly different, p < 0.05. chosen from the 306. The mean umbilical artery pH was 7.26 + 0.07 (SD); any pH <1 SD below the mean was labeled "pathologic." Yeomans et al. I4 selected for analysis infants from term pregnancies without diabetes, preeclampsia, multiple gestation, Rh incompatibility, or other complications. Fetal indications for exclusion included growth retardation, meconium passage, anomalies, significant fetal heart rate abnormalities, and weight <2500 gin. One hundred forty six infants met these criteria; there is no mention of the population size from which these infants were selected. The mean umbilical artery pH was 7.28 + 0.05. Ruth and Raivio ~5 studied all the deliveries in their institution over a 2-month period, during which 982 infants were born. Applying certain criteria (no maternal chronic disease, no pregnancy or delivery complications, no "neonatal disturbances," and normal infant development at 1 year), they selected 127 infants. Incidentally, all these infant s had Apgar scores of 9 or 10 at 5 minutes, although this was not a selection criterion. They further broke these down into 106 vaginal deliveries and 21 elective cesarean sections. The mean values were vaginal delivery umbilical artery pH 7.29-+ 0.07 and elective cesarean section umbilical artery pH 7.31 + 0.03. Thorp et al. 16 analyzed data from 1924 term nulliparous patients with spontaneous onset of labor, vertex presentations, and singleton gestations. There is no mention of the population size from which this sample was chosen. The mean umbilical artery pH was 7.24 + 0.07. Riley and Johnson ~7 selected 3522 vaginally delivered term and preterm infants born during a 2-month period at their hospital, where cord blood is routinely analyzed. The mean umbilical artery values were preterm pH 7.28 _+0.08 and term pH 7.27 + 0.07. In the studies cited above the mean values for pH span the range Of 7.20 to 7.3l. In general, the other components of the acid-base state (Pco 2, base excess, and Po2) are relatively similar to our values. In our study there were small but statistically significant differences in mean pH when other variables were examined. Thus babies born by cesarean section or operative vaginal delivery were more acidemic than those born by normal spontaneous vaginal delivery, although by only 0.02 or 0.03 pH units. Term and postterm fetuses were slightly more acidemic than preterm fetuses. This was not explained by resuscitation activities but may have been due to the shorter labors seen in the premature group. Breech fetuses born vaginally were more acidemic than vertex fetuses born vaginally. Babies born in the presence
of thick meconium were slightly more acidemic than those without thick meconium. However, in all of the above comparisons the differences in mean values are small and unlikely to be of great clinical significance in this vigorous group of babies. This study does not address the question of whether the values presented define "normality" in terms of later neurologic function. Retrieval of infant data on these babies is not practicable. Other investigators have approached this question by appropriate studies. For example, Low et al. is found that metabolic acidemia of the order of buffer base 25 m E q . L-1, approximately equivalent to a base excess o f - 2 0 mEq • L-~, and a pH of 7.0, were followed by motor and cognitive defects in approximately 50% of children at 1 year of age. Goodwin et al.7 reviewed the course of 129 term nonanomalous singleton infants with umbilical arterial pH <7.00. They concluded that a pH <6.8 with marked hypercarbia (Pco 2 usually >100 mm Hg) and metabolic acidosis (base excess usually <-15 m E q . L-~) relates best to neonatal death or major neurologic dysfunction. Goldaber et al. 19 defined a "pathologic fetal acidemia" as <7.00 in umbilical arterial blood in their review of 3506 term newborns with an umbilical arterial pH <7.20. In conclusion, from a consideration of the published literature regarding fetal asphyxia, it seems clear that setting the outer limits of normal pH at the 2.5th percentile is extremely conservative in defining the likelihood of neurologic sequelae. REFERENCES
1. Court DJ, Parer JT. Experimental studies of fetal asphyxia and fetal heart rate interpretation. In: Nathanielsz PW, Parer JT, editors. Research in perinatal medicine. New York (NY): Perinatology Press, 1984;1:113-69. 2. Yaffe H, Parer JT, Block BS, Llanos AJ. Cardiorespiratory responses to graded reductions of uterine blood flow in the sheep fetus. J Dev Physiol 1987;9:325-36. 3. Block BS, Schlafer DH, Wentworth RA, Kreitzer LA, Nathanielsz PW. Intrauterine asphyxia and the breakdown of physiologic circulatory compensation in fetal sheep. AmJ Obstet Gynecol 1990;162:1325-31. 4. Gunn AJ, ParerJT, Mallard EC, Williams CE, Gluckman PD. Cerebral histological and electrocorticographic changes after asphyxia in fetal sheep. Pediatr Res 1992;31:486-91. 5. Gilstrap LC, Leveno JK, Burns J, Williams ML, Little BB. Diagnosis of birth asphyxia on the basis of fetal pH, Apgar score, and newborn cerebral dysfunction. Am J Obstet Gynecol 1989;161:825-30. 6. Winkler CL, Hauth JT, Tucker JM, Owen J, Brumfield CG. Neonatal complications at term as related to the degree of umbilical artery acidemia. Am J Obstet Gynecol 1991;164: 637-41.
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7. Goodwin TM, Belai I, Hernandez P, Durand M, Paul RH. Asphyxial complications in the term newborn with severe umbilical acidemia. AmJ Obstet Gynecol 1992;167:1506-12. 8. Towbin A. Obstetric malpractice litigation: the pathologist's view. AmJ Obstet Gynecol 1986;155:927-35. 9. FreemanJM, Nelson KB. Intrapartum asphyxia and cerebral palsy. Pediatrics 1988;82:240-9. 10. Sykes GS, Johnson P, Ashworth F, Molloy PM, Gu W, Stirrat GM, et al. Do Apgar scores indicate asphyxia? Lancet 1982; 1:494-6. 11. Wible JL, Petrie RH, Koons A, Perez A. The clinical use of umbilical cord acid-base determinations in perinatal surveillance and management. Clin Perinatol 1982;9:387-97. 12. WestgateJ, GaribaldiJM, Greene Fall Umbilical cord blood gas analysis at delivery: a time for quality data. Br J Obstet GynaecoI 1994;101:1054-63. 13. Bretscher J, Saling E. pH values in the human fetus during labor. AmJ Obstet Gynecol 1967;97:906-11. 14. Yeomans ER, HauthJC, Gilstrap LC, Strickland DM. Umbilical cord pH, Pco2, and bicarbonate following uncomplicated term vaginal deliveries. A m J Obstet Gynecol 1985;151:798800. 15. Ruth VJ, Raivio KO. Perinatal brain damage: predictive value of metabolic and the Apgar score. BMJ 1988;297:24-7. 16. Thorp JA, Sampson JE, Parisi VM, Creasy RK. Routine umbilical cord blood gas determinations? AmJ Obstet Gynecol 1989;161:600-5. 17. Riley RJ,JohnsonJWC. Collecting and analyzing cord blood gases. Clin Obstet Gynecol 1993;36:13-23. 18. LowJA, Galbraith RS, Muir DW, Killen HL, Pater EA, Karchmar EJ. Factors associated with motor and cognitive deficits in children after intrapartum fetal hypoxia. Am J Obstet Gynecol 1984;148:533-9. 19. Goldaber KG, Gilstrap LC, Leveno KJ, DaxJS, McIntire DD. Pathologic fetal acidemia. Obstet Gynecol 1991;78:1103-8.
Editors' note: This m a n u s c r i p t was revised after these discussions were presented. Discussion D~. RAYMONDJ. JENNETT, Phoenix, Arizona. I am certain that I a m n o t alone in admitting confusion over the wide range of definitions of the terms birth asphyxia, acidemia, acidosis, and that most elusive o n e of all, "normal." A n o t h e r word that has b e c o m e increasingly comm o n in the obstetric literature to characterize newborns is "vigorous." Dr. Parer and his associates u n d e r t o o k to address these in their stated objective: "Umbilical c o r d b l o o d gases and acid-base data f r o m vigorous n e o n a t e s were e x a m i n e d to d e t e r m i n e n o r m a l values." T h e authors b e g a n by reviewing o t h e r studies that addressed n o r m a l ranges of acid-base values and t h e n contrasted t h e m to their own approach. They state: "Ideally, n o r m a l b l o o d gas ranges would be derived f r o m a sample reflecting the r e a l m of n o r m a l labor, n o r m a l delivery and n o r m a l neonates. E x a m i n a t i o n of the m e t h o d used to arrive at several of the c u r r e n t r e p o r t e d ranges suggest that they define ideal ranges rather than the n o r m a l ones." Immediately, I e x p e r i e n c e d a b e g i n n i n g resurg e n c e of my confusion. Are n o t " i d e a l " and " n o r m a l " at least related concepts? T h e authors go on to state, "We chose to define the n o r m a l n e o n a t e as o n e that is vigorous at birth and we used the A p g a r score as an i n d e x of this." If the goal is to define the " n o r m a l " acid-base status of the neonate, their study is still n o t entirely objective, a l t h o u g h it is less arbitrary than the s~udies that used the criteria they cited.
All infants with a 5-minute Apgar score of 27 are not necessarily equal. An infant with a 1-minute Apgar score of 1 is hardly a "vigorous" infant at birth, although with adequate resuscitation it may have r e a c h e d a 5 minute score of ->7. In a study published by our g r o u p an index was suggested that took into account both the 1- and 5-minute scores and short-term p r o b l e m s were related significantly m o r e to b o t h our i n d e x and the 1-minute Apgar score than the 5-ininute score) Apgar 2 r e m a r k e d that, a l t h o u g h the 5-minute score m i g h t correlate with brain damage, the 1-minute score was a reflection of the acid-base status o f the fetus. However, given the large sample size (15,073) in Dr. Parer's study, the effect on the m e a n values by depressed infants at 1 m i n u t e would be minimal. O f the studies cited by the a u t h o r for comparison, that of T h o r p et a l ) was the most c o m p a r a b l e and serves as additional validation for the c u r r e n t study. These authors studied 1924 n e o n a t e s whose Apgar scores were >7 at both 1 and 5 minutes. T h e m e a n p H for this group was 7.24 with an SD of +0.07, c o m p a r e d with the c u r r e n t study p H of 7.26. T h e Pco2, Po2, bicarbonate, and base deficit were marginally better in the study of T h o r p et al. I must also confess to an uneasiness with the authors' use of the terms "acidosis" and "acidotic" rather than " a c i d e m i a . " T h e latter t e r m lends itself to quantification in terms of the pH. Acidosis, on the o t h e r hand, has a c o n n o t a t i o n of a pathologic disorder and is i n d e e d so defined in Dorland's Illustrated Medical Dictionary. To define the range of pH, bicarbonate, and base deficit as being within the n o r m a l and then using a t e r m with a pathologic c o n n o t a t i o n seems to be a contradiction. Regardless of my reservations about the use of the terms " n o r m a l values" and "acidosis," the authors have m a d e a valuable contribution to tile range of acid-base values f o r n e o n a t e s who have b e e n stabilized within 5 minutes after birth and to the ranges within which cerebral palsy is n o t a factor. Dr. Parer, please c o m m e n t on one i m m e d i a t e and practical application. Some authors r e c o m m e n d a cord blood acid-base assessment on all neonates, whereas others limit it to selected neonates. W h a t is your r e c o m m e n d a tion? A n d if it is selective, would the findings of your study indicate which neonates to test? O n a subject n o t directly addressed in your p a p e r and given the fact that studies such as the c u r r e n t one are helpful in a retrospective analysis but n o t for a specific clinical situation, what is your o p i n i o n as to the c u r r e n t role of fetal b l o o d sampling as an adjunct to fetal heart rate monitoring? REFERENCES
1. Jennett RJ, Warford HS, Kreinick CK, Waterkotte GW. Apgar index: a statistical tool. AmJ Obstet Gyneco11981;140:206-12. 2. Apgar V. The newborn (Apgar) scoring system: reflections and advice. Pediatr Clin North Am 1966;13:645. 3. ThorpJA, SampsonJE, Parisi VM, Creasy RIC Routine umbilical cord blood gas determinations. Am J Obstet Gynecol 1989;161:600-5. Dm Mm~IAEL P. NAG~OTrE, L o n g Beach, California. At best, using Apgar scores as a triage p o i n t is difficult. In
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some of the historic studies, such as the Collaborative Perinatal Project, an assigned nurse was responsible for determining the Apgar score, which was an improvement over multiple individuals assigning Apgar scores. In the data presented, there appeared to be 30 to 50 babies who met the criteria of vigor and had low pHs at or <2.5th percentile. Did any of those babies exhibit any neurologic sequelae, either immediately or later in the neonatal period? DR, CazvlN HOB~, Los Angeles, California. Dr. Parer's group has added pH to help defin e a normal Apgar score at 5 minutes. Together, the two are very important. In the absence of very important risk factors such as meconium, gestational age, delivery method, and presentation a pH between 7.10 and 7.38 along with Apgar score at 5 minutes defines a normal population of newbborns. DR.JACKIa~mY, Seattle, Washington. In today's scientific research, statistical analysis seems mandatory. However, I would like to commend Dr. Parer for reminding us that, although statistical significance is important in the research and the application of scientific data, many times this clinical significance is not clinically relevant. DR. ROBERT C. GOODUN, Placerville, California. Dr. Parer, I am confused about your statement that you have far more neonatal acid-base values than anyone else. In 1991 I reported to this society nearly 12,000 consecutive umbilical artery pH values from Denver General Hospital. 1 Other departments now have in excess of 30,000 cases. I described cases of umbilical artery pH values >3 SDs below the mean (<6.90 pH), who did well. You should emphasize that your values are from your institution, which is at sea level. Other institutions will have different normal acid-base values. In my 1994 presentation I noted my correspondence with Dr. Low, who agreed that no study excluded the possibility of intraparturn recovery from severe fetal metabolic acidemia. 2 In addition, I believe that maternal acid base values should be considered along with the evaluation of umbilical cord values. REFERENCES
1. Goodlin RC, Freedman WL, McFeeJG, Winter SW. The neonate with unexpected acidemia. J Reprod Med 1994;39:97100. 2. Goodlin RC. Do concepts of causes and prevention of cerebral palsy need revision? Am J Obstet Gynecol 1995; 172:1830-6. D~. PARER(Closing). Dr. J e n n e t t stated that in a review of the literature other authors have presented series of ideal births and ours were relatively unselected. However, whatever term is used is going to be arbitrary. We admit that using the 5-minute Apgar score may be just as arbitrary as picking normal Friedman curves, normal second stages, absence of forceps, and so on. A dialog needs to go on until we have ultimate agreement about what is "ideal" or "normal." Both Dr. J e n n e t t and Dr. Goodlin suggested that some of the babies with a borderline pH of 7.1 might or might not have had some degree of brain damage. One of the problems with intermediate pH values is whether there is
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a dose response. The all-or-nothing response to asphyxia is well known: a baby is either born dead, or more rarely, with severe brain damage or else recovers essentially intact. With intermediate degrees 0 f p H it has been difficult to show that there is a dose-response in terms of severity of brain damage. I lean toward the theory that there is a pH cliffwhere the baby, once it passes over the edge, falls into the abyss of brain damage. However, before it reaches that cliff, it is unlikely to have p e r m a n e n t brain damage. We have talked in this society before about the breakdown of the physiologic responses occurring at some specific point, depending on the severity and duration of the asphyxia. Although the details are unknown, pH is not the only determinant; blood flow redistribution and oxygen consumption of various organs play major roles as well. The semantic concerns about the differences between acidosis and acidemia seems to confuse everybody. Whenever these terms are used, they have to be redefined. The more we talk about it, the more likely we are to get some agreement about what it all means. Because we were measuring the acidosis in blood, I should have used their term, acidemia. Who should have umbilical cord blood gases analyzed? At the ivory tower of the University of California, San Francisco, data are collected for research. This should not occur at all hospitals. With respect to this question, there is a recent large survey by Johnson and Riley~ in which all the respondents said that they do get cord blood gases, at least in selected cases. Usually this meant that blood gases were obtained on depressed babies, premature babies, babies that were born by cesarean section, babies that had heart rate tracings that were less than "normal," and so forth. Within this group umbilical arterial blood gases were obtained, but umbilical venous specimens were not always sent. Most groups surveyed were not interested in pH alone, but wanted a full panel of blood gases, including the pH, Pco2, and calculation of the metabolic component. What is the current role of fetal blood sampling? Historically it is very interesting, and that is about it. Of the 4 million babies born in the United States today, single digit percentages are born in institutions where it is practically possible to do intrapartum fetal blood sampling, analyze the data, and use it effectively for evaluation and management of labor. Everyone is using either tactile or vibrioacoustic stimulation testing. If you get an acceleration in response to stimulation, this essentially guarantees a pH >7.2, which eliminates "acidosis." Dr. Nageotte asked about the follow-up of babies t h a t were at the tail, the 2.5th percentile. Although we do not have that data, it probably could be pulled from the literature database. At a future meeting we hope to present data on these babies who had Apgar scores <7 at 5 minutes. Unfortunately, we do not always have specific postdischarge follow-up data on these babies to know which of the "acidotic" ones did worse than those above 7.2. Dr. Hobel, thank you for your comment about the interaction between pH and Apgar score. I had not
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thought of it that way; it is a nice way to jusfify the Apgar score. Dr. Lame}; thank you for your c o m m e n t about the important difference between statistical and clinical significance. I apologize to Dr. Goodlin for omitting his work, but
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our literature search was confined to series with a full panel of blood gases. REFERENCE
1. JohnsonJWC, Riley W. Cord blood gas studies: a survey. Clin Obstet Gynecol 1993;36:99-101.
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