sphingomyelin ratio

sphingomyelin ratio

Correlation of real-time ultrasonic placental grading with amniotic fluid lecithin/sphingomyelin ratio KHALIL M. A. Los Angeles, California TABSH...

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Correlation of real-time ultrasonic placental grading with amniotic fluid lecithin/sphingomyelin ratio KHALIL

M.

A.

Los Angeles,

California

TABSH,

M.D.

Placental grading with real-time ultrasound was performed on 235 patients who underwent amniocentesis for determination of the lecithin/sphingomyelin (L/S) ratio between 31 and 44 weeks’ gestation. Grades I, II, and Ill placentas were encountered in 88, 72, and 75 patients, respectively. Forty-eight percent of Grade I, 89% of Grade II, and 92% of Grade Ill placentas had mature L/S ratios (L/S z 2.0). All of the 52 patients with a Grade Ill placenta who underwent repeat cesarean section at term gestation had mature L/S ratios. However, 37% of the pregnancies complicated by maternal or fetal disease, with Grade Ill placentas, had immature L/S ratios. The gestational age of these six patients ranged from 34 to 37 weeks. These results suggest that a Grade Ill placenta in normal term gestation has a good correlation with fetal pulmonary maturity as predicted by the amniotic fluid L/S ratio. (AM. J. OBSTET. GYNECOL. 145:504, 1983.)

PREMATURITY has been well established as being responsible for most of the neonatal morbidity and mortality encountered by the obstetrician and pediatrician.’ This poor outcome is related to the respiratory distress syndrome and its sequelae. The incidence of prematurity with elective induction of labor or elective cesarean section without assessment of fetal maturity remains high.2p 3 The advent of antenatal detection of fetal pulmonary maturity by measurement of the lecithin/sphingomyelin (L/S) ratio in amniotic fluid has resulted in a significant decrease in both perinatal morbidity and mortality associated with pulmonary immaturity.4 Unfortunately, this test requires the invasive procedure of amniocentesis with its small but significant morbidity rate.‘-’ Ultrasonography provides a noninvasive technique for the evaluation of fetal gestational maturity.g* lo In 1979, Grannum and associates” described a method for classifying and grading placental maturity based on ultrasound evaluations of placental textural changes in the in vivo placenta (Fig. 1). The authors demonstrated a good correlation between maturational changes in the placenta as seen by ultrasound and the

From

the University

of California

Los Angeles

School of

Table

I. Indications

for amniocentesis

Indicatia

No.

Elective cesarean section Diabetes mellitus Rh sensitization Postdate pregnancy Hypertensive disease or preeclampsia Intrauterine growth retardation Systemic lupus erythematosus Cardiac disease Miscellaneous Total

143

27 23 8 7” 5 6

8 235

fetal pulmonary maturity as determined by the L/S ratio. The value of placental grading in predicting pulmonary maturity prior to elective delivery remains controversial. Petrucha and associates** confirmed Grannum and associates’ findings and reported 100% correlation between the L/S ratio and a Grade III placenta in 15 term pregnancies, whereas Quinlan and Cruz13 reported three cases of Grade III placentas with immature L/S ratios (~2.0). The present study was undertaken to compare and correlate gestational and placental maturity as determined through ultrasonic measurements of the biparietal diameter and placental grading, with the predictor of pulmonary maturity as assessed by the amniotic fluid L/S ratio.

Medicine. Presented in pati at the Twenty-ninth Annual Meeting of the Society for Gynecologic Investigation, Dallas, Texas, March 24-27, 1982. Reprint requests: Khalil Tabsh, M.D., Department of Obstetrics and Gynecology, UCLA School of Medicine, Los Angeles, California 90024.

504

Material and methods From June 1, 1980, to August 30, 1981, 235 amniocenteses that yielded clear amniotic fluid were performed at the University of California Los Angeles. All patients were between 31 and 44 weeks’ gestation. Ges0002-9378/83/040504+05$00.50/0

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1983

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Volume

145

Number

2

Placental

GRADE

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Fig. 1. Schematic diagram illustrating the ultrasonic appearance of the four placental grades. (Reproduced with permission from Grannum, P. A. T., Berkowitz, R. L., and Hobbins. J,: AM. J, OBSTET. GYNECOL. 133:915, 1979.) tational age was established by the clinical correlation of: (1) last menstrual period, (2) ultrasonic measurement of crown-rump or biparietal diameter early in pregnancy, and (3) clinical and neurological assessment of the infant after birth by a neonatologist. The indications for the amniocentesis are shown in Table I. Diabetes mellitus was ruled out in the group of repeat cesarean sections by the obtaining of a 2-hour postGlucola serum glucose reading in the third trimester. All patients had an ultrasound scan performed with a linear-array real-time scanner with the use of a 3.5 MHz transducer (Toshiba), and the biparietal diameter of each fetus was measured at the level of the thalamus. The entire placenta was examined and graded according to the criteria developed by Grannum and associates.” Each placenta was assigned a grade that corresponded to the most mature portion of the placenta. All scans were performed under my personal direction. After the placenta had been graded, amniotic fluid was obtained by transabdominal amniocentesis. All patients signed an informed consent, and all had ultrasound localization of an optimal amniocentesis site before the procedure. Amniotic fluid contaminated with blood or meconium was not included in this study, since these substances are known to affect the L/S ratio.14’ I5 Determination of the L/S ratio was performed according to the methods of Gluck as modified by Borer and included the cold acetone precipitation step.16 The lecithin and sphingomyelin spots were read by pla-

Table II. Correlation gestational age

of placental

grade with

1 I II III TOtill

E 75 235

37 14 _2. 58

42 19 2 25

51 58 68 n7

58 81 91 75

nimetry. I4 Statistical analysis of the data was performed by means of the unpaired t test.

Results Of the 235 patients included in this study, the placentas in 88 were found to be Grade I, T2 were Grade II, and 75 were Grade III. Grade 0 placentas were not encountered in any of these patients (Table II). Of the 88 Grade I placentas, 51 (58%) were in term pregnancies (gestational age ~37 weeks); a Grade I placenta was found in 51 of 177 (29%) term pregnancies (Table II). The mean gestational age f 1 SD for Grade I placentas was 36.5 * 2.85 weeks (range, 31 to 42 weeks) (Fig. 2). In this group, the mean biparietal diameter -C 1 SD was 8.70 & 0.57 cm (range, 7.5 to 10.0 cm) (Fig. 3). Of the total 88 patients with Grade I placentas, 42 (48%) had mature L/S ratios (~2.0)

506

Tabsh

February Am. J. Obstet.

44

.

1

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42 t

.

-

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I 2

1 Placental

I 3

Grade

Fig. 4. Distribution of gestational age in Grades I, II, and III placentas. Horizontal the means. The difference between the means was significant (P < 0.01).

Table III. Correlation

of placental

grade

lines represent

Table IV. Correlation

with L/S ratio

gestational

of placental age and L/S ratio

I

I

I

grade with

I

I

LIS ratio

I

I

22.0

1.5-1.9

jm

Gestational age (4

I II III Total

88 72 75 235

15, 1983 Gynecol.

46 22 3 74

52 31 jj 31

42 50 69 161

48 69 22 69

(Table III). The mean L/S ratio f 1 SD for this group was 1.98 +- 0.46, with a range of 1.3 to 3.2 (Fig. 4). Of the 72 patients with Grade II placentas, 58 (81%) were at term gestation (Table I). The mean gestational age + 1 SD was 37.7 + 1.61 (range, 34 to 42 weeks) (Fig. 2). The mean biparietal diameter ? 1 SD with a Grade II placenta was 8.96 + 0.40 cm (range, 8.0 to 9.8 cm) (Fig. 3). In this group, 50 (69%) had a mature L/S ratio (Table III). The mean L/S ratio was 2.37 f 1 SD (range, 1.4 to to 3.8) (Fig. 4). Of the 75 patients with Grade III placentas, 68 (91%) were at term (Table I). The mean gestational age f 1 SD in this group was 38.6 ? 2.05 weeks (range, 34 to 44 weeks) (Fig. 2). The mean biparietal diameter -t 1 SD for Grade III placentas was 9.09 + 0.33 cm (range, 8.2 to 9.6 cm) (Fig. 3). In this group, 69 (92%) of the patients had a mature L/S ratio. The mean L/S ratio 2 1 SD was 2.65 & 0.60 (range, 1.6 to 4.0) (Fig. 4). A Grade III placenta was found in 68 patients at term gestation and in seven preterm pregnancies. Of

237

Placental grade

Total

No.

%

No.

%

I II III

51 58 68 177

19 16 4 39

37 28 .-!2 22

32 42 64 138

63 72 94 78

I II III

37 14 _1 58

27 6 2 35

73 43 22 60

10 8 2 23

27 57 z! 40

Total 31-36

NO.

the 75 pregnancies with Grade III placentas, four (6%) of those at term had immature L/S ratios, whereas two (29%) of the preterm pregnancies had immature L/S ratios (Table IV). Grade III placentas with biparietal diameters 29.0 cm were present in 56 patients; three (9%) had immature L/S ratios. (Biparietal diameter of 29.0 cm in our population corresponds to a mean gestational age of ~37 weeks.) Of 19 patients with Grade III placentas and a biparietal diameter C9.0 cm, three (16%) had immature L/S ratios (Table V). In 143 patients, the indication for amniocentesis was elective cesarean section. In this group, 52 (36%) patients had a Grade III placenta and a mature L/S ratio. A Grade III placenta was encountered in seven of eight uncomplicated postdate pregnancies: each of these seven patients had a mature L/S ratio. However, in the

Volume Number

145 +

Placental

.

10.0

8.0

7.5

. . . . . . .

I

7.8

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l MO.0

.

0-w

.”

.. ..

onoonn -*-.

3.0

“” ” . .

z tn 1; 2.0

.. .. I

L

1

I

2 Grade

3

Table V. Correlation of placental grade biparietal diameter and L/S ratio

II

I

III Total

41 30 2 22

19 30 53 102

59 70 95 78

56 29 19

33 9 3 45

59 31 Is 43

23 20 Is 59

41 69 84 57

iii

I

0.c

1

1

--l_i__

2 Placental Grade

3

of the L/S ratio in Grades 1, II, and III

placentas. Horizontal lines represent the means. The ence between the means was significant (P < 0.0 1).

13 13 2 29

1 II

1.c

Fig. 4. Distribution

with

32 43 56 131

III

Total

. ..

.-0

. . . .

Fig. S. Distribution of biparietal diameter (BPD) in Grades I, II, and III placentas. Horizontal lines represent the means. The difference between the means was significant (P < 0.01).

<9.0

l *

. .. no

o-0 . . . . . .

Placental

29.0

507

l .

..o...n”. roo.0.a 0.M l ...6GhO . . .n.” .”

0a.n. e0ba.n l OMOl we . ..-. mm “W... HO.9 . . .*.O. W.” . . . . . . “.

-2 go Y n a- 8.5 a

and L/S ratio

4.0

. . . . . . . . .

9.5

grading

16 pregnancies complicated by maternal or fetal disease, six (37%) with a Grade III placenta had immature L/S ratios (Table VI). The gestational age of these six patients ranged from 34 to 37 weeks.

differ-

Table VI. Indications for amniocentesis in all Grade III placentas and in Grade III placentas with an immature L/S ratio

Elective cesarean section Diabetes mellitus Rh sensitization Hypertensive

disease

preeclampsia Intrauterine growth retardation Postdate pregnancy Systemic lupus erythematosus Cardiac disease Miscellaneous Total

or

143 27 23 8

52 4 3 4

0 2 2 1

0 50 66 25

7

1

50

8 5

(J 0

0 0

Comment Iatrogenic prematurity and the respiratory distress syndrome are the leading factors responsible for fetal morbidity and mortality associated with elective delivery. ‘. 3 Neonatal morbidity and mortality associated with premature delivery can be reduced through proper utilization of fetal maturity tests before elective delivery.4 The most widely used tests for antenatal

evaluation of fetal maturity are: (1) amniotic fluid L/S ratio for assessment of pulmonary maturity, (2) the determination of somatic maturity by ultrasound through measurement of the biparietal diameter, and (3) the ultrasonic determination of placental maturity by grading the placenta in vivo.4, *I3 Although it has long been

508

Tabsh

well established that determination of the amniotic fluid L/S ratio by the method of Gluck and co-workers is a reliable and accurate method for the prediction of pulmonary maturity, 4, l6 this procedure has some disadvantages. The L/S ratio test requires an amniocentesis, an invasive method which has potential maternal and fetal complications. 5-8 In cases in which pulmonary maturity can be predicted indirectly by ultrasonography, which is a noninvasive method, the perinatologist has the advantage of gaining the same valuable information with only minimal risk to the mother and fetus.g* *O Fetal maturity is a complex state that involves many organ systems. In normal patients, fetal gestational maturity, somatic maturity, and placental maturity seem to proceed at a rate similar to that of pulmonary maturity. However, in pathologic cases, the time at which fetal pulmonary maturity is reached deviates from that at which it occurs in normal pregnancy. Pulmonary maturity might occur earlier or later in these cases.16 Likewise, comparison of normal pregnancies with high-risk pregnancies reveals that, in pathologic pregnancies, there is a deviation from normal in placental and pulmonary maturity. In pathologic conditions that lead to decreased uteroplacental blood flow and fetal stress, precocious placental maturation is seen, as determined by ultrasound. The placental and decidual pathologic factors lead to further fetal stress and enhancement of pulmonary maturity. In an examination

February

15. 1983

Am. J. Obstet. Gynecol.

of the results of the present study and those reported by Quinlan and Cruz,13 it is not surprising to find placental maturity preceding pulmonary maturity in these patients. Because of hyperinsulinemia in patients with diabetes mellitus, precocious somatic maturity occurs along with a delay in pulmonary maturity, when a comparison is made with normal cases.16 Since placental maturation may continue to proceed at a normal rate in diabetic patients, pulmonary maturity may lag behind placental maturity. The discrepancy between the 32% incidence of Grade III placenta in our population and the 15% and 20% incidences of Grade III placentas reported in two prior major studies”* I2 could be related to gestational age. The mean gestational age of Grade III placentas in this study was 38.6 weeks. The previous two studies did not report the mean gestational age of Grade III placentas. The relationship between gestational age and placental grading has been observed by other investigators.17 In conclusion, placental grading is a reliable method for judging fetal maturity in term pregnancies uncomplicated by medical or obstetric conditions. I wish to thank Ms. Cheri Buonaguidi, Ms. Debbie Timmons, and Mrs. Carol Nelson for their help with this study, and Dr. Charles R. Brinkman III for his advice and encouragement.

REFERENCES

1. Cavanaugh, D., and Talisman, M. R.: Prematurity and the Obstetrician, New York, 1969, Appleton-CenturyCrofts, pp. l-3. 2. Keettel, W. C., Randall, J. H., and Donnelly, M. M.: The hazards of elective induction of labor, AM. J. OBSTET. GYNECOL. 75:496, 1958. 3. Goldenberg, R. L., and Nelson, K.: latrogenic respiratory distress syndrome, AM J. OBSTET. GYNECOL. 143:617, 1975. 4. Gluck, L., Kulovich, M. V., and Borer, R. D.: Diagnosis of the respiratory distress syndrome by amniocentesis, AM. J. OBSTET. GYNECOL. 109:440, 1971. 5. Schwartz, R. H.: Amniocentesis, Clin. Obstet. Gynecol. l&l, 1975. 6. Kirshen, E. T., and Bernirschke, K.: Fetal examination after amniocentesis, Obstet. Gynecol. 44:615, 1973. 7. Sabbagha, R., and Salvino, C.: Report on third trimester amniocentesis at Prentice Women’s Hospital of Northwestern University Medical School, Chicago, Illinois, in Antenatal Diagnosis: Report of a Consensus Development Conference, Bethesda, Maryland, March 5-7, 1979, National Institutes of Health, pp. 1 l-61. 8. Young, B. K.: Report on third trimester amniocentesis at Bellevue Hospital of New York University Medical Center, New York, New York, in Antenatal Diagnosis: Report of a Consensus Development Conference, Bethesda, Maryland, March 5-7, 1979, National Institutes of Health, pp. 1 l-65.

9. Campbell, S.: The prediction of fetal maturity by ultrasonic measurement of the biparietal diameter, J. Obstet. Gynaecol. Br. Commonw. 76~603, 1969. 10. Sabbagha, R. E., Turner, J., Rockehe, H., et al.: Sonar biparietal diameter and fetal age, Obstet. Gynecol. 43:7, 1974. 11. Grannum, P. A. T., Berkowitz, R. L., and Hobbins, J. C.: The ultrasonic changes in the maturing placenta and their relation to fetal pulmonic maturity, AM. J. OBSTET. GYNECOL.

133:915,

1979.

Petrucha, R. A., Golde, S. H., and Plan, L. D.: Real-time ultrasound of the placenta in assessment of fetal pulmanic maturity, AM. J. OBSTET. GYNECOL. 142:463, 1982. 13. Quinian, R. W., and Cruz, A. C.: Ultrasonic placental grading and fetal pulmonic maturity, AM. J. OBSTET. 12.

GYNECOL.

142:

110,

1982.

Tabsh, K. T., Brinkman, C. R., 111, and Bashore, R.: Effect of meconium contamination on the amniotic fluid L/S ratio, Obstet. Gynecol. 58~605, 1981. 15. Buhi, W. C., and Spellacy, W. N.: Effects of blood or meconium on the determination of the amniotic fluid lecithinlsphingomyelin ratio, AM. J. OBSTET. GYNECOL. 14.

141:321,

1975.

Gluck, L., Kulovich, M., Borer, R. C., et al.: The interpretation and significance of the lecithin-sphingomyelin ratio in amniotic fluid, AM. J. OBSTET. GYNECOL. 120:142, 1974. 17. Platt, L. D.: Personal communication. 16.