Volume
125
Number
4
Correspondence
carcinoma,‘, 6 suggest that the “estriol hypothesis” advanced by Lemon,’ MacMahon and associates,8 and others regarding the etiology of breast carcinoma may be relevant to the problem of endometrial carcinoma. Lemon has suggested that 25 per cent of Caucasian women may be homozygous for estrogen 16ahydroxylase deficiency and another 25 per cent may be heterozygous.7 Perhaps the leukocyte estrogen 16ahydroxylase assay developed by Lemon’ should be utilized in future studies of endometrial carcinoma. If the “estriol hypothesis” is correct, women with estrogen 1Ga-hydroxylase deficiency might be better served if estriol were used for postmenopausal estrogen replacement therapy, rather than the equine preparations which are currently predominant. Bruce V. Stadel, M.D., M.P.H. Medical Ofjcer Contraceptive Evaluation Branch Center for Population Research National Institute of Child Health and Human Development Department of Health, Education, and Welfare Bethesda, ilfaryland 20014 REFERENCES 1. Quint,
patterns in endometrial carcinoma, 122: 498, 1975. Stadel, B. V., and Weiss, N.: Characteristics of menopausal women: A survey of King and Pierce Counties in Washington. 1973-1974. Am. I. Euidemiol. In mess. Siiteri, P. K:, and McDonald, %. d.: In Creep, k. O., and Astwood, E., editors: Handbook of Physiological Endocrinology, Washington, D. C., 1973, Vol. 2, part 1, American Physiological Society, p. 615. Hausknecht, R. U., and Gusberg, S. B.: Estrogen metabolism in patients at high risk for endometrial carcinoma, AM. j. OBSTET. GYN~OL. 116: 981, 1973. Vonetama. V.. Kurohora. S. S.. Badie. A. 0.. et al.: Second prim&-y cancers of endbmetrial carcinoma, Cancer 26: 842, 1970. MacMahon, B., and Austin, J. H.: Association of carcinomas of the breast and corpus uteri, Lancet 1: 275, 1969. Lemon, H. M.: Genetic predisposition to carcinoma of the breast: multiple human genotypes for estrogen 16 alpha hydroxylase activity in Caucasians, J. Surg. Oncol. 4: 255, 1972. MacMahon, B., Cek, P., and Brown, J.: Etiology of human breast cancer: a review, J. Natl. Cancer Inst. 50: 21, 1973. Lemon, H. M.: Presentation to the American Association for Cancer Research, March, 1974. AM.
2. 3.
4. 5. 6.
B. C.: Changing
J. OBSTET.
GYNECOL.
cinoma” (N. Engl. J. Med. 1975), which was not published at the time my manuscript was prepared. The comment regarding estriol is particularly appropriate. The sentence, “These data appear to have been inappropriately analyzed, and their full import is missed,” seems somewhat harsh, and I question the author’s claim that his reshuffling of the figures adds clarity. However, this may be no more than vanity and nit
picking
Reply to Dr. Stadel
Donald C. Smith tion of exogenous
and
Walter estrogen
L. Herrmann, “Associaand endometrial car-
on my
part.
Boyd C. Quint, M.D. 801 Broadway Seattle, Washington
98122
Routine fetal monitoring in normal labor and delivery To the Editors: I enjoyed reading the excellent article by Drs. Tutera and Newman, “Fetal monitoring: Its effect on the perinatal mortality and cesarean section rates and its complications,” (AM. J. OBSTET. GYNECOL. 122: 750, 1975), but believe I must add a complication which we physicians frequently do not consider when we speak of “routine” fetal monitoring. Many patients in today’s world are desirous of labor and delivery without interference. They believe, and I agree with them in most situations, that pregnancy is a normal condition which only infrequently results in complications. The failure of our specialty to recognize this fact has helped further the proliferation of midwifery and home deliveries where people are seeking an alternative to the rigidly controlled hospital programs. To subject a patient with an otherwise normal labor and a negative prenatal history to either internal or external monitoring frequently results in a complication of interfering with the patient’s ability to manage contractions and thus to proceed “naturally” through labor and delivery without anxiety or unnecessary analgesia. It has been my experience that, in more cases than not, the attachment of an external fetal monitor requires the patient to maintain a supine or semisupine position in order to obtain an adequate tracing. In addition, as the labor progresses, one must frequently readjust the position of the abdominal leads as the fetus changes position and descends through the pelvic canal. More frequently than not, if an adequate tracing is not obtained after all these maneuvers are performed, instead normal
To the Editors: I believe the comments of Dr. Stadel are imminently acceptable. He cited several references not included in my paper which help to support the hypothesis presented. An additional reference is the article by
573
of abandoning the procedure in an otherwise labor, we rupture the membranes and insert
a fetal scalp electrode. We now have a patient with a strap on the leg and a lead on the abdomen, and all of this
is attached
to a machine
beeping
and
“bleeping”
away and definitely not contributing to the decor of the labor suite and the relaxation of the patient and her husband. Please do not fetal monitoring
misinterpret in residency.
me. I was trained I use fetal monitoring.
with I
574
Correspondence
use scalp sampling, but I do believe that we have reached a point where the procedure is beginning to be overutilized. I believe that the procedure should be discussed with obstetric patients. and, if they desire, it should be used on a routine basis: however, I do not feel it is fair to subject all of our patients to the routine use of fetal monitoring. Pud 7‘. H&r, M.D. San Rafael i%dical Gmcp 1540 Fifth kmue San Rafuul, Calfornia 94901
Dexamethasone in prevention of respiratory distress syndrome To the Editors: I was intrigued by the excellent results obtained by Caspi and associates’ in their paper, “Changes in amniotic fluid lecithin-sphingomyelin ratio following maternal dexamethasone administration” (AM. J. OBSTET. GYNECOL. 122: 327, 1975). Their results, if reproduced by other research centers. will certain]) point the way to prevention of the respiratory distress syndrome (RDS) in the premature infant. However, there are a few facts that must be discussed and clarified. In Liggins and Howie’s series,2 6 mg. of betamethasone was given intramuscularly to each mother at least 24 hours prior to delivery, and, if delivery had not occurred within 24 hours, a similar second dose was given. These researchers were able to obtain satisfactory results in infants only up to 32 weeks’ gestation but not beyond, and the lecithin/ sphingomyelin (L/S) ratios were not consistently changed by treatment. However, Caspi and his associates we;e able to reduce the incidence of RDS to 9 per cent in live-born infants from 27 to 34 weeks’ gestation, and they obtained consistent changes in the L/S ratios by giving mothers 12 mg. of dexamethasone intramuscularly or orally for seven consecutive dail) doses prior to delivery (if the pregnancy lasted that long). After reviewing the paper of Caspi and his associates, I had the feeling that the expected incidence of RDS in this group of infants (27 to 34 weeks) was much too high. If these authors believed that every infant with an L/S ratio of less than 2 would develop RDS, then 12 of the 13 infants (92 per cent) in which pretreatment L/S ratios were done (Table I) should have developed RDS if nothing were done. However. the mothers in this series were given dexamethasone, and only one infant developed RDS; this infant had no pretreatment L/S estimation done. Furthermore, it was a second twin. and these infants are usually more susceptible to RDS. If we limit the analysis to those infants deZiuel-ed between 27 and 34 weeks, the results will be slightly different. It will be found that only eight of 11 infants had both pretreatment and posttreatment analysis of the L/S ratio. One infant was anencephalic (stillborn);
one showed little change in the L/S ratio, and the remainder showed a significant change. However, if we consider those 11 infants with and without pretreatment L/S ratios. one was anencephalic (stillborn), onr had RDS, one had little change. and the remainder showed a significant change. On this basis, it is noted that one of 11 in the whole group delivered between 27 and 34 weeks’ gestation developed RDS (9 per cent). My curiosity and belief that a 91 per cent incidence of RDS in this group of infants was too high led mc to review the records of all live-born infants betweet 27 and 34 weeks delivered in two different hospitals during the past two years. In one hospital there were 12 cases of RDS of 42 live-born infants (2P.j per cent) rind in the other hospital there were 14 cases of RDS of .46 infants (30.4 per cent). None of the infants had surfactant measurements. and none had dexamethasone treatmenl. Had Caspi and his associates let their mothers deliver Fvithout dexamethasone treatment, do they sincere13 believe that 91 per cent of the infants Fvould have developed RI%? Do they feel that surfactant deficiency is the o~lr factor in RDS, or are there other factors as well? If they believe that surf&rant deticienq is the onl) factor. how do they explain the following: (I) the higher incidence of RDS in infants delivered b\ cesarean section than in those delivered vaginally”; (i) the higher incidence of RDS in infants delivered vaginally in mothers with placenta previa and abruptio placentae: (3) the pathologic findings in the lungs of infants dying from hyaline membrane disease (HMD)-the presence of amniotic fluid contents in the membrane, the red cells in the alveolar ducts. the origin of the fibrin, and the hemoglobin-like hemochromogen in the membrane. Is the fibrin a transudatc from the infant or an aspirate of the mother’s blood at the time of delivery? This fact has not yet been proved. I have previously suggested that aspiration of amniotic fluid and its contents play a significant role in this condition. Aspiration of uncontaminated amniotic Huid may result in transient RDS. whereas aspiration of’ unclotted maternal blood in atnniotic fluid results in HMD, hyaline membrane-like disease without mcmbranes, some cases of intra-alveolar pulmonary hemol-rhage, cases of lobar opacification, and some cases of‘ atelectasis in the lungs of newborn infants. Aspiration c~f meconiuni results in the meconium aspiration syndrome. Each condition results in its own typical pathologic condition.” There is no doubt that the L/S ratio and otllct measurements of surfactant levels are excellent measures of pulmonarv maturity, but are they really accurate indicators of RDS? One needs on]), to reviert a large number of’ published series to see that man) infants with immature surfactant patterns do tlot develop RDS.
125
Number
4
Correspondence
carcinoma,‘, 6 suggest that the “estriol hypothesis” advanced by Lemon,’ MacMahon and associates,8 and others regarding the etiology of breast carcinoma may be relevant to the problem of endometrial carcinoma. Lemon has suggested that 25 per cent of Caucasian women may be homozygous for estrogen 16ahydroxylase deficiency and another 25 per cent may be heterozygous.7 Perhaps the leukocyte estrogen 16ahydroxylase assay developed by Lemon’ should be utilized in future studies of endometrial carcinoma. If the “estriol hypothesis” is correct, women with estrogen 1Ga-hydroxylase deficiency might be better served if estriol were used for postmenopausal estrogen replacement therapy, rather than the equine preparations which are currently predominant. Bruce V. Stadel, M.D., M.P.H. Medical Ofjcer Contraceptive Evaluation Branch Center for Population Research National Institute of Child Health and Human Development Department of Health, Education, and Welfare Bethesda, ilfaryland 20014 REFERENCES 1. Quint,
patterns in endometrial carcinoma, 122: 498, 1975. Stadel, B. V., and Weiss, N.: Characteristics of menopausal women: A survey of King and Pierce Counties in Washington. 1973-1974. Am. I. Euidemiol. In mess. Siiteri, P. K:, and McDonald, %. d.: In Creep, k. O., and Astwood, E., editors: Handbook of Physiological Endocrinology, Washington, D. C., 1973, Vol. 2, part 1, American Physiological Society, p. 615. Hausknecht, R. U., and Gusberg, S. B.: Estrogen metabolism in patients at high risk for endometrial carcinoma, AM. j. OBSTET. GYN~OL. 116: 981, 1973. Vonetama. V.. Kurohora. S. S.. Badie. A. 0.. et al.: Second prim&-y cancers of endbmetrial carcinoma, Cancer 26: 842, 1970. MacMahon, B., and Austin, J. H.: Association of carcinomas of the breast and corpus uteri, Lancet 1: 275, 1969. Lemon, H. M.: Genetic predisposition to carcinoma of the breast: multiple human genotypes for estrogen 16 alpha hydroxylase activity in Caucasians, J. Surg. Oncol. 4: 255, 1972. MacMahon, B., Cek, P., and Brown, J.: Etiology of human breast cancer: a review, J. Natl. Cancer Inst. 50: 21, 1973. Lemon, H. M.: Presentation to the American Association for Cancer Research, March, 1974. AM.
2. 3.
4. 5. 6.
B. C.: Changing
J. OBSTET.
GYNECOL.
cinoma” (N. Engl. J. Med. 1975), which was not published at the time my manuscript was prepared. The comment regarding estriol is particularly appropriate. The sentence, “These data appear to have been inappropriately analyzed, and their full import is missed,” seems somewhat harsh, and I question the author’s claim that his reshuffling of the figures adds clarity. However, this may be no more than vanity and nit
picking
Reply to Dr. Stadel
Donald C. Smith tion of exogenous
and
Walter estrogen
L. Herrmann, “Associaand endometrial car-
on my
part.
Boyd C. Quint, M.D. 801 Broadway Seattle, Washington
98122
Routine fetal monitoring in normal labor and delivery To the Editors: I enjoyed reading the excellent article by Drs. Tutera and Newman, “Fetal monitoring: Its effect on the perinatal mortality and cesarean section rates and its complications,” (AM. J. OBSTET. GYNECOL. 122: 750, 1975), but believe I must add a complication which we physicians frequently do not consider when we speak of “routine” fetal monitoring. Many patients in today’s world are desirous of labor and delivery without interference. They believe, and I agree with them in most situations, that pregnancy is a normal condition which only infrequently results in complications. The failure of our specialty to recognize this fact has helped further the proliferation of midwifery and home deliveries where people are seeking an alternative to the rigidly controlled hospital programs. To subject a patient with an otherwise normal labor and a negative prenatal history to either internal or external monitoring frequently results in a complication of interfering with the patient’s ability to manage contractions and thus to proceed “naturally” through labor and delivery without anxiety or unnecessary analgesia. It has been my experience that, in more cases than not, the attachment of an external fetal monitor requires the patient to maintain a supine or semisupine position in order to obtain an adequate tracing. In addition, as the labor progresses, one must frequently readjust the position of the abdominal leads as the fetus changes position and descends through the pelvic canal. More frequently than not, if an adequate tracing is not obtained after all these maneuvers are performed, instead normal
To the Editors: I believe the comments of Dr. Stadel are imminently acceptable. He cited several references not included in my paper which help to support the hypothesis presented. An additional reference is the article by
573
of abandoning the procedure in an otherwise labor, we rupture the membranes and insert
a fetal scalp electrode. We now have a patient with a strap on the leg and a lead on the abdomen, and all of this
is attached
to a machine
beeping
and
“bleeping”
away and definitely not contributing to the decor of the labor suite and the relaxation of the patient and her husband. Please do not fetal monitoring
misinterpret in residency.
me. I was trained I use fetal monitoring.
with I
574
Correspondence
use scalp sampling, but I do believe that we have reached a point where the procedure is beginning to be overutilized. I believe that the procedure should be discussed with obstetric patients. and, if they desire, it should be used on a routine basis: however, I do not feel it is fair to subject all of our patients to the routine use of fetal monitoring. Pud 7‘. H&r, M.D. San Rafael i%dical Gmcp 1540 Fifth kmue San Rafuul, Calfornia 94901
Dexamethasone in prevention of respiratory distress syndrome To the Editors: I was intrigued by the excellent results obtained by Caspi and associates’ in their paper, “Changes in amniotic fluid lecithin-sphingomyelin ratio following maternal dexamethasone administration” (AM. J. OBSTET. GYNECOL. 122: 327, 1975). Their results, if reproduced by other research centers. will certain]) point the way to prevention of the respiratory distress syndrome (RDS) in the premature infant. However, there are a few facts that must be discussed and clarified. In Liggins and Howie’s series,2 6 mg. of betamethasone was given intramuscularly to each mother at least 24 hours prior to delivery, and, if delivery had not occurred within 24 hours, a similar second dose was given. These researchers were able to obtain satisfactory results in infants only up to 32 weeks’ gestation but not beyond, and the lecithin/ sphingomyelin (L/S) ratios were not consistently changed by treatment. However, Caspi and his associates we;e able to reduce the incidence of RDS to 9 per cent in live-born infants from 27 to 34 weeks’ gestation, and they obtained consistent changes in the L/S ratios by giving mothers 12 mg. of dexamethasone intramuscularly or orally for seven consecutive dail) doses prior to delivery (if the pregnancy lasted that long). After reviewing the paper of Caspi and his associates, I had the feeling that the expected incidence of RDS in this group of infants (27 to 34 weeks) was much too high. If these authors believed that every infant with an L/S ratio of less than 2 would develop RDS, then 12 of the 13 infants (92 per cent) in which pretreatment L/S ratios were done (Table I) should have developed RDS if nothing were done. However. the mothers in this series were given dexamethasone, and only one infant developed RDS; this infant had no pretreatment L/S estimation done. Furthermore, it was a second twin. and these infants are usually more susceptible to RDS. If we limit the analysis to those infants deZiuel-ed between 27 and 34 weeks, the results will be slightly different. It will be found that only eight of 11 infants had both pretreatment and posttreatment analysis of the L/S ratio. One infant was anencephalic (stillborn);
one showed little change in the L/S ratio, and the remainder showed a significant change. However, if we consider those 11 infants with and without pretreatment L/S ratios. one was anencephalic (stillborn), onr had RDS, one had little change. and the remainder showed a significant change. On this basis, it is noted that one of 11 in the whole group delivered between 27 and 34 weeks’ gestation developed RDS (9 per cent). My curiosity and belief that a 91 per cent incidence of RDS in this group of infants was too high led mc to review the records of all live-born infants betweet 27 and 34 weeks delivered in two different hospitals during the past two years. In one hospital there were 12 cases of RDS of 42 live-born infants (2P.j per cent) rind in the other hospital there were 14 cases of RDS of .46 infants (30.4 per cent). None of the infants had surfactant measurements. and none had dexamethasone treatmenl. Had Caspi and his associates let their mothers deliver Fvithout dexamethasone treatment, do they sincere13 believe that 91 per cent of the infants Fvould have developed RI%? Do they feel that surfactant deficiency is the o~lr factor in RDS, or are there other factors as well? If they believe that surf&rant deticienq is the onl) factor. how do they explain the following: (I) the higher incidence of RDS in infants delivered b\ cesarean section than in those delivered vaginally”; (i) the higher incidence of RDS in infants delivered vaginally in mothers with placenta previa and abruptio placentae: (3) the pathologic findings in the lungs of infants dying from hyaline membrane disease (HMD)-the presence of amniotic fluid contents in the membrane, the red cells in the alveolar ducts. the origin of the fibrin, and the hemoglobin-like hemochromogen in the membrane. Is the fibrin a transudatc from the infant or an aspirate of the mother’s blood at the time of delivery? This fact has not yet been proved. I have previously suggested that aspiration of amniotic fluid and its contents play a significant role in this condition. Aspiration of uncontaminated amniotic Huid may result in transient RDS. whereas aspiration of’ unclotted maternal blood in atnniotic fluid results in HMD, hyaline membrane-like disease without mcmbranes, some cases of intra-alveolar pulmonary hemol-rhage, cases of lobar opacification, and some cases of‘ atelectasis in the lungs of newborn infants. Aspiration c~f meconiuni results in the meconium aspiration syndrome. Each condition results in its own typical pathologic condition.” There is no doubt that the L/S ratio and otllct measurements of surfactant levels are excellent measures of pulmonarv maturity, but are they really accurate indicators of RDS? One needs on]), to reviert a large number of’ published series to see that man) infants with immature surfactant patterns do tlot develop RDS.
