Fetal asphyxia during the intrapartum period in intrauterine growth-retarded infants

Fetal asphyxia during the intrapartum in intrauterine growth-retarded J. A. R.

W.

LOW,

period

infants

M.D.

BOSTON,

S. R.

PANCHAM,

Kingston,

Ontario,

M.D. M.D. Canada

A study of the acid-base data obtained during labor and at delivery has demonstrated fetal asfihyxia with moderate or severe metabolic acidosis at delivery in 50 per cent of the intrauterine growth-retarded infants, a significantly greater frequency and severity of fetal asphyxia than in newborn infants above the tenth weight-gestational age percentile. The increasing metabolic acidosis is associated with an increasing lactate concentration and calculated excess lactate and with a significant decrease of oxygen content. Fetal asphyxia with moderate or severe metabolic acidosis in the intrauterine growth-retarded infant occurred more frequently in the primiparous obstetric patient with a premature delivery complicated by severe toxemia. The intrauterine growth-retarded infants at delivery with evidence of fetal asphyxia with moderate or severe metabolic acidosis demonstrated a significant decrease in I and 5 minute Apgar scores.

fined to include those newborn infants below the tenth percentile on the weight-gestational age scale and are referred to as the intrauterine growth retardation (IUGR) group in this report. The significance in respect to the perinatal mortality rate of intrauterine growth retardation was demonstrated in the British Perinatal Mortality Study2 in which a perinatal mortality rate 8 times, or 6 times if congenital anomalies and macerated stillbirths were excluded, that of all infants of the same gestational age was recorded. The particular significance of the intrapartum period is suggested by the fivefold increase of intrapartum stillbirths for the comparable gestational age. Intrapartum fetal asphyxia, and ,its associated metabolic acidosis, has been defined by the umbilical artery buffer base (UABB) measured at delivery. Four categories were defined: no fetal asphyxia, UABB > 40 mEq. per liter; fetal asphyxia with mild metabolic acidosis, UABB 37.0 to 39.9 mEq. per liter; fetal asphyxia with moderate meta-

THE 0 B J EC TIVE of the present study was to demonstrate the frequency and extent of fetal asphyxia during the intrapartum period in the fetus compromised by intrauIntrauterine growth retardation. terine growth retardation leading to a small-fordates infant is widely recognized, although the criteria defining the extent of this entity have not been finally established. The problem is complicated by the variable weightgestational age scales and different indices utilized in studies to date. The standard used in this study was the weight-gestational age scale described by Gruenwa1d.l Significant intrauterine growth retardation has been deFrom the Department of Obstetrics Gynaecology and the Department Paediatrics, Queen’s University. Received 1971.

for

publication

September

f;;;pted

for

publication

February

Repint requests: Dr. J. A. Low, of Ob./Gyn., Queen’s University, Kingston, Ontario, Canada.

and of 27, 10, Dept.

351

352

low,

Boston,

Table I. Incidence metabolic

bolic liter; bolic

acidosis

and

June 1, 1972 Am. J. Obstet. Ggnccol.

Pancham

of fetal asphyxia in the 4 quartiles

with

1

67

44

65

23

35

; 4

66 50 68

55 44 53

84 88 78

116 15

16 1” 22

acidosis, UABB 34.0 to 36.9 mEq. per and fetal asphyxia with severe metaacidosis, UABB’ < 34.0 mEq. per liter.

Method Uterine activity and fetal heart rate characteristics were monitored during the intrapartum period in 251 obstetric patients selected because of concern for ti potentially compromised fetus in respect to fetal asphyxia. Clinical documentation included the characteristics of the mother, the antenatal course, labor and delivery, the Apgar score, and the immediate neonatal course. Uterine work was recorded with an intra-amniotic fluid-filled catheter; fetal assessment was provided by continuous recording of fetal heart rate patterns, periodic acid-base assessment of fetal capillary blood during labor, and umbilical vein and artery blood at delivery. The gestational age assigned was in completed weeks, and this maturity was corroborated by the clinical appearance of the newborn infant.3 The weight percentile for gestational age of each newborn infant was defined on the basis of this gestational age and weight at delivery according to the weight-gestational age scale of Gruenwald. For the purposes of the present analysis, the patients have been divided into 4 quartiles based on their assigned percentile. The first quartile includes the IUGR group and those infants between the tenth and twenty-fourth percentiles, which in this report will be referred to as the borderline group; the second quartile, the twenty-fifth to forty-ninth percentiles; the third quartile, the fiftieth to seventy-fourth percentiles, and the fourth quartile, the > seventy-fifth percentile.

Acid-base assessment in capillary and cord blood included measurements of pH made with the Astrup micro electrode (AME-1) pH meter. Oxygen tension and carbon dioxide tension were measured with an IL 113-Sl system with a Clark type 0, electrode and a Severinghaus CO, electrode. Buffer base was calculated from the Singer-Hastings nomogram with the pH and Pco, and corrected for the degree of oxygen unsaturation. Protein precipitation with 10 per cent trichloroacetic acid was carried out within 3 minutes of delivery of the samples of umbilical artery and vein blood for the measurement of lactate and pyruvate, and the filtrates were stored in an ice-water bath. Lactate determinations were carried out in duplicate by the method of Barker and Summersom4 Pyruvate determinations were carried out by the partial extraction method of Friedman and Haughen5 as modified by Huckabee,6 with washed pure 0-xylene and a filtrate to solvent ratio of 12 to 4 ml. with the final solution alkalinized with 1 ml. of l,ON sodium hydroxide added slowly with vigorous mixing. The blood-water content was determined, and the results of lactate and pyruvate concentration were additionally expressed as millimoles per liter of blood-water. Fetal excess lactate (XL) expressed in millimoles per liter of blood-water was calculated from the equation: XL = (Lua - Luv) - (Pua - Puv)

(Luv) -. Puv

Results The number of patients in each quartile demonstrating either no fetal asphyxia or fetal asphyxia wi,th either moderate or severe metabolic acidosis is outlined in Table I. The twenty-three, or 35 per cent, of patients in the first quartile demonstrating fetal asphyxia with moderate or severe metabolic acidosis was a significantly higher proportion (p < 0.001) than the 6, or 12 per cent, of patients in the second quartile, the 11, or 16 per cent, of patients in the third quartile, and the 15, or 22 per cent, of patients in the fourth quartile.

Volume Number

113 3

Asphyxia

2450

in IUGR

infants

353

-

50th.% 3300315030002850-

IOth.%

270025502400.

; CI, l5 iii s I k m

.

2250-

I

21001950-

.

I cooEOO1650-

.

ISOOl3501350-, l2001200lO501050900750600-

I

I ‘28

I 29

I 30

I 31

I 32

I 33

I 34

GESTATIONAL Fig.

1. The

gestational

age and

I 35

I 36

AGE weight

The principal concern of this study is the 31 infants in the IUGR group. The gestational age and weight of each of these infants are recorded in -Fig. 1. The patients of the first quartile are subdivided into the IUGR and borderline groups in respect to fetal asphyxia with metabolic acidosis in Table II. It is evident that the significantly higher proportion of patients with fetal asphyxia with moderate or severe metabolic acidosis in the first quartile is principally due to those patients in the IUGR group with 15, or 48 per cent, demonstrating fetal asphyxia with moderate dr severe metabolic acidosis at delivery. The degree of the metabolic acidosis was also greater in the IUGR group in comparison with the borderline group or the second, third, or fourth quartile groups. The mean

I 37

I 36

I 39

I1

I 40

41

42

(Weeks)

of the infants

in the IUGR

group.

Table II. Incidence of fetal asphyxia with metabolic acidosis in the IUGR and borderline groups of the first quartile

IUGR Borderline

31 36

16 28

52 78

15 8

48 22

UABB of those cases with moderate or severe metabolic acidosis in each group (Table III) provides an indication of this trend. The mean UABB was in the IUGR group, 30.9 mEq. per liter; the borderline group, 33.3 mEq. per liter; the second quartile, 36.4 mEq. per liter; the third quartile, 35.1 mEq.

354

Low,

Boston,

and

10 -

June 1, 1972

Pancham

Am. J.

Ohatrt.Gynecol.

1.U.G.R GROUP BORDERLINE

A

17 -

i”. .

16 -I . w” E

a14 13 I2

p

Il-

Q z

IO9-

a -I

A

5 A

a76-

l

A

5-

A

Q b

4-

0

3-

A. 0 90,.

08 A

2-

I.. :@

I I0

I II I I I1 I9 20 21 22 23 24 25

BUFFER

I II I 26 27 28 29

BASE

I I I I I I I I I I I I I 30 ?.I 32 33 34 35 36 37 36 39 40 41 42

-

l

A

I II 43 44

mEq/L

Fig. 2. Scattergram demonstrating a significant relationship between UABB and umbilical lactate concentration in the IUGR and borderline groups.

Table III.

Severity of metabolic acidosis in those patients with fetal asphyxia with moderate or severe metabolic acidosis in the IUGR group, borderline group, and the second, third, and fourth quartiles Moderate or severe metabolic acidosis, mean UABB (mEq./L.)

IUGR

group

Borderlinegroup Second quartile Third quartile Fourth quartile

30.9 33.3 36.4 35.1 34.6

per liter, and the fourth quartile, 34.6 mEq. per liter. A measureof the duration of fetal asphyxia with metabolic acidosis may be obtained by serial sampling and acid-base assessmentof fetal capillary blood. Table IV includes those patients

in the IUGR

and borderline

groups

in which serial capillary blood studies had been carried out prior to and at delivery. Metabolic acidosis has been defined on the basis of a capillary blood buffer base of less than 40 mEq. per liter. Fetal asphyxia of short duration is defined as metabolic acidosis present for less than 30 minutes. These preliminary observations would indicate that

45

artery

Table IV. Duration of fetal asphyxia metabolic acidosis in the IUGR and borderline groups Metabolic acidosis

Mild Moderate Severe

Duration

< 30 Min. 8 5

1

prior

with

to delivery 1

> 30 Min. 7 3 7

duration tends to be related to severity. In only 1 of the 8 patients with severe metabolic acidosis at delivery would these observations suggestthat the metabolic acidosis had been present for less than 30 minutes, whereas in 13 of the 23 patients with mild or moderate metabolic acidosis at delivery fetal asphyxia with metabolic acidosiswas not evident 30 minutes prior to delivery. The relationships between UABB and umbilical artery lactate concentration and between UABB and calculated excesslactate in the IUGR and borderline groups are demonstrated in Figs. 2 and 3, respectively. There is a very significant inverse relationship between buffer base and lactate concentration (p < O.OOl), demonstrating that the decreasing buffer base identifying the increasing severity of metabolic acidosisis associated

Volume Number

Asphyxia

113 3

2.4

I.U.G.R. GROUP BORDERLINE

-

2.2-

A

2.0

-

J .

I.8

-

w”

I.6 I.4

in IUGR infants

355

* .

-

E

I.2

-

W t-a

I.0

-

5

0.6 0,6

-

-1

0.4

-

2

0.2

-

W

0

-

x” W

-0.2

-

-0.4

-

-0.6 -0.6

-

-1.0

A

-

A A

0

A A@ 0

A

d

0

0

l

A0

A

A

A

’ A

A 00 a

IIll I.9 I9 20

21 22

l 23

I I I I I 24 25 26 27 26

BUFFER

I 29

I I I I 30 31 32 33

BASE

Fig. 3. Scattergram excess lactate

A

demonstrating a significant in the IUGR and borderline groups.

with an increasing lactate concentration. There is a similar significant relationship between decreasing buffer base and increasing calculated excesslactate (p < 0.001) . The umbilical artery blood oxygen and carbon dioxide tensions in those patients with no, mild, moderate, or severe metabolic acidosisin the newborn infant at delivery in the IUGR group are outlined in Table V. There is a small decrease of the umbilical artery oxygen tension between those patients with no metabolic acidosis and severe metabolic acidosis. The oxygen tension in the IUGR group was 14.0 mm. Hg with no metabolic acidosis and 9.8 mm. Hg with severe metabolic acidosis. This small change in oxygen tension is of greater significance in respect to oxygen saturation and content due to the changing pH related to the increasing metabolic and respiratory acidosis. Oxygen saturation with an oxygen tension of 14.0 mm. Hg and no metabolic acidosis is of the order of 20 per cent and with an oxygen tension of 9.8 mm. Hg and severe metabolic acidosis is of the order of 1 to 5 per cent. Significant changes in respect to carbon dioxide tension are not apparent until severe metabolic acidosis has developed.

-

I I 34 35

I I 36 37

I 36

I I 39 40

I I l 11 41 42 43 44 45

mEq/L

relationship

between

UABB

and

calculated

Table V. The mean levels of oxygen and carbon dioxide tension in the umbilical artery in those patients with no, mild, moderate, or severe metabolic acidosis in the IUGR group IUGR

group

No metabolic acidosis Mild metabolic acidosis Moderate metabolic acidosis Severe metabolic acidosis

UABB

LJA Pot UA Pcot

41.5 38.6 35.7

14.0 10.9 12.1

53.6 55.8 54.2

28.7

9.8

71.7

The mean maternal venous blood buffer base in those patients with no, mild, moderate, or severe metabolic acidosisin the newborn infant at delivery in the IUGR group is outlined in Table VI. The maternal venous blood buffer base is essentially the same in all groups, indicating that although maternal metabolic acidosis may contribute to fetal metabolic acidosis in the occasional patient it has not been a significant factor in the present study. A number of relevant maternal and obstetric characteristics of the patients in the IUGR group are outhned in Table VII. Fetal asphyxia with moderate or severe

356

Low,

B&ton,

and

Table VI. Relationship and fetal

June 1, 1972 ,\rn. J. Ohtet. Gynecot.

Pancham

between maternal acidosis in the IUGR

metabolic

group IUGR

group

UABB

No metabolic acidosis Mild metabolic acidosis Moderate or severe metabolic acidosis

Maternal buffer

venous base

41.5

41.0

38.6

41.4

31.0

41.0

Table VII.

Relevant maternal characteristics of the patients

and obstetric in the IUGR

group No or mild metabolic acidosis Gestational age < 37 weeks 37-44 weeks

Moderate or severe metabolic acidosis

1 15

7 8

7 9

12 3

Parity Prirniparas MuItiparas Toxemia

Mild

or moderate

Severe

,

8 2

2 9

Uterine work < 200 M.U. > 200 M.U.

9 4

7 7

M.U.

= Montevideo

units.

metabolic acidosis at ‘delivery occurred in 7 of the 8 obstetric patients (87 per cent) at less ‘than 37 weeks of gestation and ‘in 8 of the 23 patients (35 per cent) at between 37 and 44 weeks of gestation. Fetal asphyxia with moderate or severe metabolic acidosis at delivery occurred in 12 of the 19 primiparous obstetric patients (63 per cent) and 3 of the 12 multiparous obstetric patients (25 per cent). Acute toxemia was, the principal obstetric complication and occurred in 21 of the 31 patients in the IUGR group. This is not an accurate reflection of the incidence of acute toxemia in pregnancies complicated. by intrauterine growth retardation due to the selective nature of the patients’ studied; however, the relevance of severe toxemia (i.e., eclampsia or pre-eclampsia with blood pressure > 160/100 and/or albuminuria 5 Gm. per 24 hours) to the occurrence of fetal

Table VIII.

The Apgar minutes in the newborn IUGR group IUGR

score at 1, 3, and 5 infants of the

group

No metabolic acidosis Mild metabolic acidosis Moderate metabolic acidosis Severe metabolic acidosis

I Min.

3 Min.

5 Min.

10

8

9

7

8

6.5 4

9 6.5

9.5

10 7.5

asphyxia with moderate or severe metabolic acidosis is apparent. Fetal asphyxia with moderate or severe metabolic acidosis at delivery occurred in 9 of the 11 patients (82 per cent) with severe toxemia and 2 of the 10 patients (20 per cent) with mild or moderate toxemia. The average intensity of uterine work during the last two hours of labor was expressed in Montevideo units. Fetal asphyxia with moderate or severe metabolic acidosis at delivery occurred in 7 of the 16 patients (44 per cent) in whom the average intensity of uterine work was less than 200 Montevideo units and 7 of the 11 patients (64 per cent) in whom the average intensity of uterine work was more than 200 Montevideo units. The Apgar score at 1, 3, and 5 minutes is outlined in Table VIII. The Apgar score at 1 minute was 7 in those infants with fetal asphyxia with mild metabolic acidosis, 6.5 in those infants with fetal asphyxia with moderate metabolic acidosis, and 4 in those infants with fetal asphyxia with severe metabolic acidosis. The 5 minute Apgar score was 10 except in those infants with severe metabolic acidosis with an average of 7.5. Comment Intrauterine growth retardation was identified in this study on the basis of an infant weighing less than the tenth percentile for the gestational age at the time of delivery. The standard used was the weight-gestational age scale described by Gruenwald. The 31 infants of the ‘IUGR group ranged from 30 to 1,100 Gm. below the tenth percentile for gestational age at delivery. These infants are all considered to be of low weight because of a chronic nutritional deficiency of the intrauterine environment; we did not

Volume Number

113 3

Asphyxia

include congenital abnormalities or obviously constitutionally small infants. Fetal asphyxia with metabolic acidosis has been identified by a decrease of UABB. The significant relationships between umbilical artery lactate concentration and calculated excess lactate would suggest that this metabolic acidosis is due to tissue oxygen debt leading to anaerobic metabolism with increasing lactate concentrations. The decrease in umbilical artery oxygen tension is small but represents a very significant decrease in oxygen content and saturation in the infants with metabolic acidosis due to the changing pH related to the respiratory and metabolic acidosis. Intrauterine growth retardation would appear to be associated with a significantly greater frequency and severity of intrapartum fetal asphyxia with its resultant metabolic acidosis at delivery than in the case of newborn infants in the borderline group and in the second, third, and fourth weight-gestational age quartiles. Fetal asphyxia with moderate or severe metabolic acidosis at delivery was observed in approximately 50 per cent of newborn infants in the IUGR group with a mean UABB of 30.9 mEq. per liter in those cases with moderate or severe metabolic acidosis. The preliminary data derived from serial sampling and assessment of fetal capillary blood suggest a relationship between the duration and severity of fetal asphyxia. Metabolic acidosis exceeded 30 minutes in duration in 7 of the 8 cases with severe metabolic acidosis but in only 10 of the 23 cases with mild or moderate metabolic acidosis at delivery.

2.

3.

Gruenwald, P. : AM. 1112, 1966. The Second Report Mortality Survey, in man, E. D., editors: burgh, 1969, E & S Usher, R., McLean,

J. OBSTET.

94:

4.

of the British Perinatal Butler, N. R., and AlberPerinatal Problems, EdinLivingstone, Ltd. F., and Scott, K. E.:

5.

GYNECOL.

infants

357

The occurrence of fetal asphyxia with moderate or severe metabolic acidosis in the IUGR group is associated with several maternal obstetric characteristics. Fetal asphyxia occurred more frequently in the primiparous patient, 60 per cent in relation to 25 per cent in the multiparous patient, and more frequently in the premature gestation, 87 per cent in relation to the 35 per cent in mature gestations. The frequent occurrence of intrapartum fetal asphyxia in the obstetric patient with severe toxemia in relation to mild or moderate toxemia is striking. However, fetal asphyxia with moderate or severe metabolic acidosis may occur in the intrauterine growth retardation infant in obstetric patients with no maternal medical or obstetric complications and was observed in 3 patients in this series. Although it has been proposed that maternal metabolic acidosis may lead to fetal metabolic acidosis, this was not a significant factor in this study. Moderate or severe intensity uterine work with its impact on intervillous space blood flow is associated with an increased tendency to fetal asphyxia in the IUGR group. The Apgar score as a measure of immediate neonatal behavior is a result of an interplay of several factors including maturity, trauma, analgesia and anesthesia, and asphyxia. Fetal asphyxia with moderate or severe metabolic acidosis is associated with a significant decrease of the 1 minute Apgar score which is still evident at 5 minutes in those infants with fetal asphyxia with severe metabolic acidosis.

REFERENCES

1.

in IUGR

6.

Pediatr. Clin. North Am. 13: 835, 1966. Barker, F. B., and Summerson, W. H.: J. Biol. Chem. 138: 535, 1941. Friedman, T. E., and Haughen, G. E.: J. Biol. Chem. 147: 415, 1943. Huckabee, W. E.: J. Appl. Physiol. 9: 147, 1956.