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Advanced ultrasonic placental maturation in twin pregnancies
Pittaway and Fayez
unit of human chorionic gonadotropin (Clinetics Corporation, Tustin, California) was performed on each sample to exclude an occult pregnancy. The data were evaluated by paired and unpaired t tests.
Results As shown in Fig. 1, the mean CA-125 levels were significantly higher during menses in both the group without endometriosis (p < 0.02) and the group with endometriosis (p < 0.05). In both groups, all CA-125 levels before menses were less than 65 U/ml. In the group without endometriosis one of nine women ( 11%) and in the group with endometriosis four of 11 women (36%) had CA-125levels >65 U/ml during the menses.
Comment In 988 nonpregnant patients attending a gynecologic clinic, 11 (l.l %) had elevated CA-125 levels (>65 U/ml). 3 Since a large proportion of these patients (n = 652) were presenting for an annual checkup and since women nearly always arrange a gynecologic visit while not menstruating unless vaginal bleeding has been a problem, most of the women in that series would not be expected to be menstruating.
January 1987 Am J Obstet Gynecol
In the present study of a selected group of infertile women, a higher CA-125 level was observed during menses, and five of 20 women (25%) had elevated levels (>65 U/ml) during but not before menses. An increase in CA-125levels during menses has also been observed in rhesus monkeys with and without endometriosis! We conclude that CA-125 determinations performed during the menses, particularly in women with endometriosis, represent a source of higher values and false positive results.
REFERENCES I. Bast RCJr, Klug TL, Stjohn E, eta!. A radioimmunoassay
using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Eng! J Med 1983;309:883. 2: Barbieri RL, Bast RC, Niloff JM, Kistner RW, Knapp RC. Elevated serum concentrations ofCA-125 in patients with advanced endometriosis. Fertil Steril 1986;45:630. 3. Nil off JM, Knapp RC, Schaetzl E, Reynolds C, Bast RC Jr. CA-125 antigen levels in obstetrics and gynecologic patients. Obstet Gynecol 1984;64:703. 4. Pittaway DE, Klimek M, Koritnik DR. CA-126 antigen in rhesus monkeys with spontaneous endometriosis. Fertil Steril (in press).
Advanced ultrasonic placental maturation in twin pregnancies G. Ohel, M.D., M. Granat, M.D., D. Zeevi, M.D., A. Golan, M.D., Sh. Wexler, M.D., M. P. David, M.D., and J. G. Schenker, M.D. Jerusalem and Tel Aviv, Israel The mean length of twin pregnancies is shorter than that of singleton pregnancies. The possibility that the shorter gestation of twins is associated with advanced fetal maturational changes was studied in relation to placental maturation. For this purpose, the sonographically determined placental gradings of 158 twin pregnancies and 474 singleton pregnancies were compared at different gestational ages. The percent distributions of placental grades, from I to Ill, were significantly different throughout the third trimester, with a preponderance of Grade Ill placentas in the twin group (p < 0.001 ). Considering the reported association of Grade Ill placentas with advanced gestation as well as fetal lung maturity, the present study suggests earlier maturational changes in twin fetuses compared with singleton fetuses. (AM J OBSTET GYNECOL 1987;156:76-8.)
Key words: Sonographic placental maturation, twin pregnancies Advances in ultrasonic imaging have enabled the characterization of placental restructuring throughout
From the Department of Obstetrics and Gynecology, Hadassah University Hospital, Jerusalem, and the Department of Obstetrics and Gynecology "B," Serlin (Hakirya) Maternity Hospital, Tel Aviv. Received for publication April1, 1986; accepted july 30, 1986. Reprint requests: G. Ohel, M.D., Department of Obstetrics and Gynecology, Hadassah University Hospital, P. 0. B. 12000, Jerusalem 91120, Israel.
76
gestation. A grading system, from 0 to 3, has been proposed to describe placental maturational changes/ and these have been correlated to fetal pulmonary maturity.1·4 Since normal twin gestations are commonly shorter than singleton pregnancies, 5 it may be anticipated that maturational processes, including those involved in fetal lung development, occur at an earlier gestational age in twins than in singleton fetuses. The present study has attempted to investigate this possibility by compar-
Ultrasonic placental maturation in twin pregnancies
Volume 156 Number I
~
zw
77
~TWINS
100
D
u
~ 80
SINGLETONS
D..
I= I w 0
60
<
0
40
....
0
20
26-28
29-31 WEEKS
32-34 OF
38-40
35-37
PREGNANCY
Fig. 1. The percentage of Grade III placentas in twin and singleton pregnancies, compared at different gestational ages (p < 0.001 for all age groups).
Table I. The percent distribution of placental grades in twin and singleton pregnancies Twins
Singletons
Placental Grade (%) Weeks' gestation
38-40 35-37 32-34 29-31 26-28 23-25
No. of patients
I
21 44 37 3,5 13 8
0 9.1 32.4 42.9 61.5 87.5
I :\.
II
23.8 31.8 40.6 42.9 38.5 12.5
I
Placental Grade(%) Ill
76.2 59.1 27 14.2 0 0
ing the sonographic placental grading at different gestational ages in both twin and singleton pregnancies. Material and methods
A retrospective analysis was carried out on records of routine real-time ultrasonic examinations of twin and singleton pregnancies. In all studied cases, the gestational ages were known through the "last menstrual period" or early ultrasound examinations. Cases were omitted when discrepancies of more than 2 weeks were noted between the clinical and sonographically determined gestational ages. Also not considered were cases with medical or obstetric complications. A total of 158 twins were studied, each with one ultrasonic examination, at gestational ages that ranged from 23 weeks to term. For each twin pregnancy, three consecutively performed ultrasound examinations of singleton pregnancies, matched for gestational age, served as c~ntrols. Ultrasound examinations were performed with the use of linear array real-time scanners with 3.5 MHz transducers. Placental maturation was evaluated with the use of the grading classification of Grannum et a!.'
No. of patients
63 132 Ill
105 39 24
I
0 15.2 42.3 66.7 74.4 100
I
[[
63.5 58.3 53.2 33.3 25.6 0
I
Ill
p Value
36.5 26.5 4.5 0 0 0
<0.01 <0.001 <0.001 <0.001
NS NS
Where an equivocal grading was given, the more advanced grade was assigned to that case. The X2 test was used to analyze the difference in the distribution of placental Grades I to III at the different gestational ages in the two study groups. A logistic regression analysis, with the Bio Medical Program Logistic Regression (BMDPLR) computer program, was used to demonstrate the difference between singleton and twin pregnancies with regard to the proportion of cases with Grade III placentas at the different gestational ages. Results
The percent distribution of placental gradings, from I to III, in the twin and singleton pregnancies is shown in Table I. From 29 weeks to term the percent distribution of placental gradings showed a statistically significant difference when the two groups were compared, with a preponderance of Grade III placentas in the twin group. No differences were apparent at the earlier gestational ages of 23 to 28 weeks. The proportion of Grade III placentas in the twin and singleton groups is shown in Fig. I.
78
Ohel et al.
While the proportion of Grade III placentas was increased with advancing gestation in both groups, it was significantly greater in the twins at each gestational age group from 29 weeks to term (p < 0.001).
Comment The key finding of this study is the demonstration of an advanced sonographic maturation of twin placentas as compared with singleton placentas. Grade III placentas were first noted in twins of 29 to 31 weeks' gestation, while this grade was absent in singleton pregnancies of comparable gestational ages. Thereafter, at each 3-week interval to term, Grade III placentas were significantly more common in twins compared with singletons (p < 0.001). Previous studies have demonstrated that the placenta undergoes a series of progressive morphologic changes, observed by ultrasonography, and these are related to gestational age and fetal lung maturation. 11 That gestational age is not the only determinant of placental grading is well illustrated by our finding of a more advanced placental maturation in twins compared with singletons of similar gestational ages. This' may point to a difference in the rate of maturation dynamics of twins and singletons. In this respect our findings are in accord with, and complementary to, a recent study of the amniotic fluid lecithin/sphingomyelin ratio, which demonstrated fetal lung maturation to occur several weeks earlier in twins compared with singletons. 6 A possible explanation of the observed differences in placental maturation may be related to the different intrauterine growth pattern of singleton and twin fetuses.7 The altered growth potential of twins may parallel the situation of growth retardation in singleton fetuses. It has been suggested that intrauterine growth is an important determinant of sonographically diagnosed placental maturity and that for the small fetus a mature (Grade III) placeta is significantly associated with growth retardation." In the case of singleton pregnancies, it is very unlikely for a neonate to develop hyaline membrane disease in the presence of a Grade III placenta near term_ I-I Nevertheless, this view is not shared by all, and one report has concluded that placental grading is not accurate
January 1987 Am J Obstet Gynecol
enough to replace amniocentesis as the standard test of fetal pulmonary maturity. 9 As the presence of a Grade III placenta is affected by both gestational age and pregnancy complications,"- 10 at least in a subgroup of preterm complicated pregnancies, sonographic grading of the placenta as Grade III may still be associated with hyaline membrane disease. 10 With this in mind and until data that correlate placental grading of twins with hyaline membrane disease become available, it would seem unjustified in twin pregnancies to rely solely on placental grading as an indicator of fetal pulmonary maturity. We thank Mr. Israel Einot of the statistical consultation service at the Hebrew University, Mount Scopus, Jerusalem, Israel. REFERENCES 1, Grannum PAT, Berkowitz RL, Hobbins JC. The ultrasonic
2. 3. 4.
5. 6. 7. 8.
9.
10.
changes in the maturing placenta and their relation to fetal pulmonic maturity, AM J 0BSTET GY:-IECOL 1979; 133:915, Hobbins JC Use of ultrasound in complicated pregnancies, Clin Perinatal 1980;7:397. Petrucha RA, Golde SH, Platt LD. Real-time ultrasound of the placenta in assessment of fetal pulmonic maturity. A\1 J 0BSTET GYNECOL 1982; 142:463. Kazzi GM, Gross TL, Sokol RJ, Kazzi SNJ. Noninvasive prediction of hyaline membrane disease: an optimized classification of sonographit placental maturation. AM J 0BSTF.T GYI'\ECOL 1985;152:213. Ho SK, Wu PYK. Perinatal factors and neonatal morbidity in twin pregnancy. AMJ 0BSTET GYNECOL 1975; 122:979. Leveno KJ, Quirk JG, Whalley PJ, Herbert WNP, Trubey R. Fetal lung maturation in twin gestation. A:\1 J OBSTET GYI'\ECOL 1984; 148:405. Gruenwald P. Environmental influences on twins apparent at birth. A preliminary study. Bioi Neonate 1970; 15:79. Kazzi GM, Gross TL, Sokol RJ, Kazzi N.J. Detection of intrauterine growth retardation: a new use for sonographic placental grading. AM J 0BSTET GYI'\ECOL 1983; 145:733. Harman CR, Manning FA, Stearns E, Morrison I. The correlation of ultrasonic placental grading and fetal pulmonary maturation in five hundred sixty-three pregnancies. AM J 0BSTET GYNECOL 1982; 143:941. Kazzi GM, Gross TL, Rosen MG, Kazzi NYJ. The relationship of placental grade, fetal lung m·aturity, and neonatal outcome in normal and complicated pregnancies. AMJ 0BSTET GYNECOL 1984;148:54.
unit of human chorionic gonadotropin (Clinetics Corporation, Tustin, California) was performed on each sample to exclude an occult pregnancy. The data were evaluated by paired and unpaired t tests.
Results As shown in Fig. 1, the mean CA-125 levels were significantly higher during menses in both the group without endometriosis (p < 0.02) and the group with endometriosis (p < 0.05). In both groups, all CA-125 levels before menses were less than 65 U/ml. In the group without endometriosis one of nine women ( 11%) and in the group with endometriosis four of 11 women (36%) had CA-125levels >65 U/ml during the menses.
Comment In 988 nonpregnant patients attending a gynecologic clinic, 11 (l.l %) had elevated CA-125 levels (>65 U/ml). 3 Since a large proportion of these patients (n = 652) were presenting for an annual checkup and since women nearly always arrange a gynecologic visit while not menstruating unless vaginal bleeding has been a problem, most of the women in that series would not be expected to be menstruating.
January 1987 Am J Obstet Gynecol
In the present study of a selected group of infertile women, a higher CA-125 level was observed during menses, and five of 20 women (25%) had elevated levels (>65 U/ml) during but not before menses. An increase in CA-125levels during menses has also been observed in rhesus monkeys with and without endometriosis! We conclude that CA-125 determinations performed during the menses, particularly in women with endometriosis, represent a source of higher values and false positive results.
REFERENCES I. Bast RCJr, Klug TL, Stjohn E, eta!. A radioimmunoassay
using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Eng! J Med 1983;309:883. 2: Barbieri RL, Bast RC, Niloff JM, Kistner RW, Knapp RC. Elevated serum concentrations ofCA-125 in patients with advanced endometriosis. Fertil Steril 1986;45:630. 3. Nil off JM, Knapp RC, Schaetzl E, Reynolds C, Bast RC Jr. CA-125 antigen levels in obstetrics and gynecologic patients. Obstet Gynecol 1984;64:703. 4. Pittaway DE, Klimek M, Koritnik DR. CA-126 antigen in rhesus monkeys with spontaneous endometriosis. Fertil Steril (in press).
Advanced ultrasonic placental maturation in twin pregnancies G. Ohel, M.D., M. Granat, M.D., D. Zeevi, M.D., A. Golan, M.D., Sh. Wexler, M.D., M. P. David, M.D., and J. G. Schenker, M.D. Jerusalem and Tel Aviv, Israel The mean length of twin pregnancies is shorter than that of singleton pregnancies. The possibility that the shorter gestation of twins is associated with advanced fetal maturational changes was studied in relation to placental maturation. For this purpose, the sonographically determined placental gradings of 158 twin pregnancies and 474 singleton pregnancies were compared at different gestational ages. The percent distributions of placental grades, from I to Ill, were significantly different throughout the third trimester, with a preponderance of Grade Ill placentas in the twin group (p < 0.001 ). Considering the reported association of Grade Ill placentas with advanced gestation as well as fetal lung maturity, the present study suggests earlier maturational changes in twin fetuses compared with singleton fetuses. (AM J OBSTET GYNECOL 1987;156:76-8.)
Key words: Sonographic placental maturation, twin pregnancies Advances in ultrasonic imaging have enabled the characterization of placental restructuring throughout
From the Department of Obstetrics and Gynecology, Hadassah University Hospital, Jerusalem, and the Department of Obstetrics and Gynecology "B," Serlin (Hakirya) Maternity Hospital, Tel Aviv. Received for publication April1, 1986; accepted july 30, 1986. Reprint requests: G. Ohel, M.D., Department of Obstetrics and Gynecology, Hadassah University Hospital, P. 0. B. 12000, Jerusalem 91120, Israel.
76
gestation. A grading system, from 0 to 3, has been proposed to describe placental maturational changes/ and these have been correlated to fetal pulmonary maturity.1·4 Since normal twin gestations are commonly shorter than singleton pregnancies, 5 it may be anticipated that maturational processes, including those involved in fetal lung development, occur at an earlier gestational age in twins than in singleton fetuses. The present study has attempted to investigate this possibility by compar-
Ultrasonic placental maturation in twin pregnancies
Volume 156 Number I
~
zw
77
~TWINS
100
D
u
~ 80
SINGLETONS
D..
I= I w 0
60
<
0
40
....
0
20
26-28
29-31 WEEKS
32-34 OF
38-40
35-37
PREGNANCY
Fig. 1. The percentage of Grade III placentas in twin and singleton pregnancies, compared at different gestational ages (p < 0.001 for all age groups).
Table I. The percent distribution of placental grades in twin and singleton pregnancies Twins
Singletons
Placental Grade (%) Weeks' gestation
38-40 35-37 32-34 29-31 26-28 23-25
No. of patients
I
21 44 37 3,5 13 8
0 9.1 32.4 42.9 61.5 87.5
I :\.
II
23.8 31.8 40.6 42.9 38.5 12.5
I
Placental Grade(%) Ill
76.2 59.1 27 14.2 0 0
ing the sonographic placental grading at different gestational ages in both twin and singleton pregnancies. Material and methods
A retrospective analysis was carried out on records of routine real-time ultrasonic examinations of twin and singleton pregnancies. In all studied cases, the gestational ages were known through the "last menstrual period" or early ultrasound examinations. Cases were omitted when discrepancies of more than 2 weeks were noted between the clinical and sonographically determined gestational ages. Also not considered were cases with medical or obstetric complications. A total of 158 twins were studied, each with one ultrasonic examination, at gestational ages that ranged from 23 weeks to term. For each twin pregnancy, three consecutively performed ultrasound examinations of singleton pregnancies, matched for gestational age, served as c~ntrols. Ultrasound examinations were performed with the use of linear array real-time scanners with 3.5 MHz transducers. Placental maturation was evaluated with the use of the grading classification of Grannum et a!.'
No. of patients
63 132 Ill
105 39 24
I
0 15.2 42.3 66.7 74.4 100
I
[[
63.5 58.3 53.2 33.3 25.6 0
I
Ill
p Value
36.5 26.5 4.5 0 0 0
<0.01 <0.001 <0.001 <0.001
NS NS
Where an equivocal grading was given, the more advanced grade was assigned to that case. The X2 test was used to analyze the difference in the distribution of placental Grades I to III at the different gestational ages in the two study groups. A logistic regression analysis, with the Bio Medical Program Logistic Regression (BMDPLR) computer program, was used to demonstrate the difference between singleton and twin pregnancies with regard to the proportion of cases with Grade III placentas at the different gestational ages. Results
The percent distribution of placental gradings, from I to III, in the twin and singleton pregnancies is shown in Table I. From 29 weeks to term the percent distribution of placental gradings showed a statistically significant difference when the two groups were compared, with a preponderance of Grade III placentas in the twin group. No differences were apparent at the earlier gestational ages of 23 to 28 weeks. The proportion of Grade III placentas in the twin and singleton groups is shown in Fig. I.
78
Ohel et al.
While the proportion of Grade III placentas was increased with advancing gestation in both groups, it was significantly greater in the twins at each gestational age group from 29 weeks to term (p < 0.001).
Comment The key finding of this study is the demonstration of an advanced sonographic maturation of twin placentas as compared with singleton placentas. Grade III placentas were first noted in twins of 29 to 31 weeks' gestation, while this grade was absent in singleton pregnancies of comparable gestational ages. Thereafter, at each 3-week interval to term, Grade III placentas were significantly more common in twins compared with singletons (p < 0.001). Previous studies have demonstrated that the placenta undergoes a series of progressive morphologic changes, observed by ultrasonography, and these are related to gestational age and fetal lung maturation. 11 That gestational age is not the only determinant of placental grading is well illustrated by our finding of a more advanced placental maturation in twins compared with singletons of similar gestational ages. This' may point to a difference in the rate of maturation dynamics of twins and singletons. In this respect our findings are in accord with, and complementary to, a recent study of the amniotic fluid lecithin/sphingomyelin ratio, which demonstrated fetal lung maturation to occur several weeks earlier in twins compared with singletons. 6 A possible explanation of the observed differences in placental maturation may be related to the different intrauterine growth pattern of singleton and twin fetuses.7 The altered growth potential of twins may parallel the situation of growth retardation in singleton fetuses. It has been suggested that intrauterine growth is an important determinant of sonographically diagnosed placental maturity and that for the small fetus a mature (Grade III) placeta is significantly associated with growth retardation." In the case of singleton pregnancies, it is very unlikely for a neonate to develop hyaline membrane disease in the presence of a Grade III placenta near term_ I-I Nevertheless, this view is not shared by all, and one report has concluded that placental grading is not accurate
January 1987 Am J Obstet Gynecol
enough to replace amniocentesis as the standard test of fetal pulmonary maturity. 9 As the presence of a Grade III placenta is affected by both gestational age and pregnancy complications,"- 10 at least in a subgroup of preterm complicated pregnancies, sonographic grading of the placenta as Grade III may still be associated with hyaline membrane disease. 10 With this in mind and until data that correlate placental grading of twins with hyaline membrane disease become available, it would seem unjustified in twin pregnancies to rely solely on placental grading as an indicator of fetal pulmonary maturity. We thank Mr. Israel Einot of the statistical consultation service at the Hebrew University, Mount Scopus, Jerusalem, Israel. REFERENCES 1, Grannum PAT, Berkowitz RL, Hobbins JC. The ultrasonic
2. 3. 4.
5. 6. 7. 8.
9.
10.
changes in the maturing placenta and their relation to fetal pulmonic maturity, AM J 0BSTET GY:-IECOL 1979; 133:915, Hobbins JC Use of ultrasound in complicated pregnancies, Clin Perinatal 1980;7:397. Petrucha RA, Golde SH, Platt LD. Real-time ultrasound of the placenta in assessment of fetal pulmonic maturity. A\1 J 0BSTET GYNECOL 1982; 142:463. Kazzi GM, Gross TL, Sokol RJ, Kazzi SNJ. Noninvasive prediction of hyaline membrane disease: an optimized classification of sonographit placental maturation. AM J 0BSTF.T GYI'\ECOL 1985;152:213. Ho SK, Wu PYK. Perinatal factors and neonatal morbidity in twin pregnancy. AMJ 0BSTET GYNECOL 1975; 122:979. Leveno KJ, Quirk JG, Whalley PJ, Herbert WNP, Trubey R. Fetal lung maturation in twin gestation. A:\1 J OBSTET GYI'\ECOL 1984; 148:405. Gruenwald P. Environmental influences on twins apparent at birth. A preliminary study. Bioi Neonate 1970; 15:79. Kazzi GM, Gross TL, Sokol RJ, Kazzi N.J. Detection of intrauterine growth retardation: a new use for sonographic placental grading. AM J 0BSTET GYI'\ECOL 1983; 145:733. Harman CR, Manning FA, Stearns E, Morrison I. The correlation of ultrasonic placental grading and fetal pulmonary maturation in five hundred sixty-three pregnancies. AM J 0BSTET GYNECOL 1982; 143:941. Kazzi GM, Gross TL, Rosen MG, Kazzi NYJ. The relationship of placental grade, fetal lung m·aturity, and neonatal outcome in normal and complicated pregnancies. AMJ 0BSTET GYNECOL 1984;148:54.