I1 2
Correspondence
Tests of fetal well-being ro the Editors: In the ‘Communications in Brief’ (THIS JOURNAL 130: 849, 1978) Drs. Salerno and Kay reported the occurrence of a fetal death in utero within one week of I negative oxytocin challenge test (OCT). The authors hereby offered further challenge to the validity of the ceekly interval between OCT’s. I believe that this -ommunication. however unintentional. offers more han just a challenge to the prognostic ability of this test )f fetal well-being. Instead, it clearly demonstrates the ailure to utilize correctly the various parameters of eta1 well-being that we have at our disposal. With this n mind, let us review the management of the case in Joint, as presented by the authors. The patient, with an expected date of confinement of lanuary 15, 1977, was thought to have a small-for-date t‘etus (to be interpreted as intrauterine growth retarda.ion [IUGR]) at the end of December, which would have placed the gestational age at approximately 37 iveeks. Because of the apparent concern for IUGR, plasma fl-ee estriol and human placental lactogen levels :HPL) were determined on December 28, 1976, and reported as 3.0 ng. and 2.3 pg per milliliter, respectively. Both values were significantly less than those regarded as normal for the gestational age in question. The estriol value was below the tenth percentile range for 37 weeks and the HPL value was within the range defined by Spellacy as the “fetal danger zone” (any value below 4 pg per milliliter after 30 weeks’ gestation). The patient was then scheduled for an OCT to be performed nine days later, on January 6. 1977. On the day of the OCT, which was negative for fetal distress, repeat estriol and HPL levels were obtained and reported as 4.8 ng and 2.6 pg per milliliter, respectively, values obviously not reassuring of fetal well-being. The authors were apparently concerned over these values because a pelvic examination was performed and revealed the cervix to be unfavorable for induction of labor. The patient was then rescheduled for an outpatient OCT one week later, on January 13, 1977. at which time the patient would have been two days short of term. The OCT was never performed because on the morning of January 13, 1977, fetal heart tones were no longer present. On January 25. 1977, the patient was delivered of a macerated stillborn infant, weighing 4 pounds, 11 ounces, clearly below the tenth percentile of birth weight for a gestational age of almost 40 weeks. The authors suggest that “decreasing the interval between OCT’s might have saved this baby.” Be that as it may, I feel rather strongly that in this particular case the frequency of OCT’s in determining the outcome is irrelevant. In view of the ominous results of the biological parameters ascertained on two occasions, coupled with the clinical suspicion of IUGR and its association with sudden fetal death in utero, I feel that more appropriate and deliberate action should have been un-
dertaken to save this baby. Plasma estriol andior HPI. levels should have been determined morta frequentIt, ideally every day or a minimum of three times ;I wcel\. OCT or nonstress testing (MT) should have been initiated immediately following the clinic al susl)icion oi’ IUGR and repeated on d more frequt!llt basis. KS’1 . because of its noninvasiveness. could ha\ t’ brc!l performed as often as deemed necessar). An amniocentesis at 37 to 38 weeks was in order, tot. clrte~.~~~inalirtr, of lung maturity and the presence (11 Aencc of meconium. In addition, this patieut would hit\e benefitted from an early and expeditious deliver\, rrgardless of the unfavorableness of the cervix. b\- either serial induction of labor or by cesarean se.c.tion. To base one’s clinical management (JII ;I single parameter of fetal well-being (OCT), despite el-idencc to the contrary, was, to put it mildly, intrepid. Once the, diagnosis of IUGR is established b!, whatever- mear?s. the fetus should be delivered as soon A:, it she\\ s c\ idence of pulmonary maturity or eve11 sooner it thei-e is reason to suspect imminent fetal death. Good management of high-risk pregnant? u~volves the proper utilization, appreciation. and interpretation of the various biological and bioelecttical parameters available for the determination of fetal well-being. .St/qhe,, .!I. I:iah, 5f.D. Fellow in Maternal-Fe& Medictnr Department of Obstetrics rend Gyvecoloq iJniver.sity of Calijornin School qf Medicine The Center for the Health Scienus Los hgeles, California 90024
Reply to Dr. Lieb To tk Editors: Dr. Lieb seems to have missed the point of the article. The purpose of the paper was not to describe a protocol to manage inyrauterine growth retardation nor to commend the management of either case presen.ted but to point out how blind faith in a single parameter of fetal well-being can lead to disastrous results. To quote the last sentence of the article: “Thus, it would seem wise to test at more frequent intervals and/or more frequently use other tests of fetal well-being, even in the presence of a negative OCT.” Nichohu J. Sakrrco, ,W.D. 1916 State Highway 70 East Cher? Hill, New Jersey 08003
Eqcuatkm abortion To the Editors: Some comments are necessary on Dr. Charles E. Flowers’ remarks concerning the paper by Burkman and associates entitled “Hyperosmolar urea for elective midtrimester abortion” (AM. J. OBSTET. GYNECOL. 131: 10, 1978).
Volume Number
132 8
Correspondence
He decried the documentation of safety for evacuation abortions by noting that unskilled operators will have more complications in carrying out a procedure that is new to them. Some suggestions as to how skills might be improved and how preceptorships could be arranged would have been preferable. More startling were the obvious racist remarks that concluded this segment of Dr. Flowers’ observations. Their inclusion in the most prestigious journal of our specialty as well as their origin from one of the best-known societies of obstetrics and gynecology in our country is most unseemly and warrants a public apology. Alan J. Margolis, M.D. Sadja Goldsmith, M.D., M.P.H. Department of Obstetrics, Gynecology and Reproductive Sciences School of Medicine University of California, San Francisco San Francisco, Caljfornia 94143
Reply to Drs. Margolis and Goldsmith To the Editors: This University has had an inordinate number of referrals of patients with complications from evacuation abortions performed after 14 weeks of pregnancy. Retained products of conception, infection, and hemorrhage are complications that are prevalent throughout the country and explain the reason this technique has not achieved the popularity that prostaglandinurea termination is achieving. I think there are inherent risks and problems associated with this procedure that do not warrant the arrangement of preceptorships to extend its use. I appreciate that Drs. Margolis and Goldsmith have contrary opinions. It never occurred to me that the danger of “. . . walking down the streets of Harlem at midnight whistling Dixie” is racist. The statement is true for members of both races. It would also be dangerous to walk down the streets of Tripoli, Libya, at midnight speaking Yiddish. Both statements express facts; this is how it is in the world in which we live. Beauty or ugliness is in the eyes of the beholder. Charles E. Flowers, Jr., M.D. Department of Obstetrics and Gynecology Medical Center University of Alabama in Birmingham University Station Birmingham, Alabama 35294
Plasma oxytocin values To the Editors: The recent paper OBSTET.
GYNECOL.
new data regarding
by Vasicka and associates (AM. J. 130: 263, 1978) contains important regulation of oxytocin secretion in
913
pregnancy. As pointed out by the authors, their plasma oxytocin values are substantially higher than those reported by several other laboratories in which specific extraction techniques had been utilized. Vasicka and associates proposed to reconcile these differences on the basis of differing immunopotency of the oxytocin preparations used as standards for the radioimmunoassay. We believe that this is an unlikely explanation. Our own studies of oxytocin immunoreactivity with United States Pharamacopeia posterior pituitary extract used as a standard have shown very consistent results when this natural, bioassayed standard is compared to either Pitocin* or synthetic 0xytocin.t While it is also possible that polymerization of synthetic oxytocin in aqueous solution can diminish both immunoreactivity and bioactivity, such differences are at most of the order of 100 to 200 per cent. Therefore, it is highly unlikely that differences among standards could account for the substantial elevations in plasma oxytocin reported by the authors. Current experience by many investigators suggests that the most likely explanation for the extremely high levels of oxytocin reported by Vasicka and associates is the use of whole plasma for immunoassay. Experience with radioimmunoassays for other small peptides have shown substantial, nonspecific immunoreactivity when unextracted plasma is used. The authors themselves raised these questions in their discussion but unfortunately their answers are inaccessible for critical review since the documentation is included in a paper that has only been submitted for publication. It certainly would seem appropriate for the authors to provide further validation of their assay methodology and, in particular, confirmation of individual immunoassay results with bioassay. Richard E. Weitzman, M.D. Hypertension Section Division of Nephroloa and Hypertension Theodore H. Glatz, M.D. Perinatal Research Laboratory Harbor General Hospital 1000 West Carson Street Torrance, California 90509
*Parke, Davis & Co., Detroit, Michigan. TBachem Chemicals.
Reply to Drs. Weitzman and Glatz To the Editors: Concerning low and high plasma oxytocin (OT) levels, in our paper, “Plasma oxytocin in initiation of labor,” we simple pointed out possible sources of the differences peculiar to the patient, events of pregnancy and labor, and the baby. We also enumerated possible sources of interlaboratory differences with no attempt at definite reconciliation at this stage of OT research; in
Correspondence
Tests of fetal well-being ro the Editors: In the ‘Communications in Brief’ (THIS JOURNAL 130: 849, 1978) Drs. Salerno and Kay reported the occurrence of a fetal death in utero within one week of I negative oxytocin challenge test (OCT). The authors hereby offered further challenge to the validity of the ceekly interval between OCT’s. I believe that this -ommunication. however unintentional. offers more han just a challenge to the prognostic ability of this test )f fetal well-being. Instead, it clearly demonstrates the ailure to utilize correctly the various parameters of eta1 well-being that we have at our disposal. With this n mind, let us review the management of the case in Joint, as presented by the authors. The patient, with an expected date of confinement of lanuary 15, 1977, was thought to have a small-for-date t‘etus (to be interpreted as intrauterine growth retarda.ion [IUGR]) at the end of December, which would have placed the gestational age at approximately 37 iveeks. Because of the apparent concern for IUGR, plasma fl-ee estriol and human placental lactogen levels :HPL) were determined on December 28, 1976, and reported as 3.0 ng. and 2.3 pg per milliliter, respectively. Both values were significantly less than those regarded as normal for the gestational age in question. The estriol value was below the tenth percentile range for 37 weeks and the HPL value was within the range defined by Spellacy as the “fetal danger zone” (any value below 4 pg per milliliter after 30 weeks’ gestation). The patient was then scheduled for an OCT to be performed nine days later, on January 6. 1977. On the day of the OCT, which was negative for fetal distress, repeat estriol and HPL levels were obtained and reported as 4.8 ng and 2.6 pg per milliliter, respectively, values obviously not reassuring of fetal well-being. The authors were apparently concerned over these values because a pelvic examination was performed and revealed the cervix to be unfavorable for induction of labor. The patient was then rescheduled for an outpatient OCT one week later, on January 13, 1977. at which time the patient would have been two days short of term. The OCT was never performed because on the morning of January 13, 1977, fetal heart tones were no longer present. On January 25. 1977, the patient was delivered of a macerated stillborn infant, weighing 4 pounds, 11 ounces, clearly below the tenth percentile of birth weight for a gestational age of almost 40 weeks. The authors suggest that “decreasing the interval between OCT’s might have saved this baby.” Be that as it may, I feel rather strongly that in this particular case the frequency of OCT’s in determining the outcome is irrelevant. In view of the ominous results of the biological parameters ascertained on two occasions, coupled with the clinical suspicion of IUGR and its association with sudden fetal death in utero, I feel that more appropriate and deliberate action should have been un-
dertaken to save this baby. Plasma estriol andior HPI. levels should have been determined morta frequentIt, ideally every day or a minimum of three times ;I wcel\. OCT or nonstress testing (MT) should have been initiated immediately following the clinic al susl)icion oi’ IUGR and repeated on d more frequt!llt basis. KS’1 . because of its noninvasiveness. could ha\ t’ brc!l performed as often as deemed necessar). An amniocentesis at 37 to 38 weeks was in order, tot. clrte~.~~~inalirtr, of lung maturity and the presence (11 Aencc of meconium. In addition, this patieut would hit\e benefitted from an early and expeditious deliver\, rrgardless of the unfavorableness of the cervix. b\- either serial induction of labor or by cesarean se.c.tion. To base one’s clinical management (JII ;I single parameter of fetal well-being (OCT), despite el-idencc to the contrary, was, to put it mildly, intrepid. Once the, diagnosis of IUGR is established b!, whatever- mear?s. the fetus should be delivered as soon A:, it she\\ s c\ idence of pulmonary maturity or eve11 sooner it thei-e is reason to suspect imminent fetal death. Good management of high-risk pregnant? u~volves the proper utilization, appreciation. and interpretation of the various biological and bioelecttical parameters available for the determination of fetal well-being. .St/qhe,, .!I. I:iah, 5f.D. Fellow in Maternal-Fe& Medictnr Department of Obstetrics rend Gyvecoloq iJniver.sity of Calijornin School qf Medicine The Center for the Health Scienus Los hgeles, California 90024
Reply to Dr. Lieb To tk Editors: Dr. Lieb seems to have missed the point of the article. The purpose of the paper was not to describe a protocol to manage inyrauterine growth retardation nor to commend the management of either case presen.ted but to point out how blind faith in a single parameter of fetal well-being can lead to disastrous results. To quote the last sentence of the article: “Thus, it would seem wise to test at more frequent intervals and/or more frequently use other tests of fetal well-being, even in the presence of a negative OCT.” Nichohu J. Sakrrco, ,W.D. 1916 State Highway 70 East Cher? Hill, New Jersey 08003
Eqcuatkm abortion To the Editors: Some comments are necessary on Dr. Charles E. Flowers’ remarks concerning the paper by Burkman and associates entitled “Hyperosmolar urea for elective midtrimester abortion” (AM. J. OBSTET. GYNECOL. 131: 10, 1978).
Volume Number
132 8
Correspondence
He decried the documentation of safety for evacuation abortions by noting that unskilled operators will have more complications in carrying out a procedure that is new to them. Some suggestions as to how skills might be improved and how preceptorships could be arranged would have been preferable. More startling were the obvious racist remarks that concluded this segment of Dr. Flowers’ observations. Their inclusion in the most prestigious journal of our specialty as well as their origin from one of the best-known societies of obstetrics and gynecology in our country is most unseemly and warrants a public apology. Alan J. Margolis, M.D. Sadja Goldsmith, M.D., M.P.H. Department of Obstetrics, Gynecology and Reproductive Sciences School of Medicine University of California, San Francisco San Francisco, Caljfornia 94143
Reply to Drs. Margolis and Goldsmith To the Editors: This University has had an inordinate number of referrals of patients with complications from evacuation abortions performed after 14 weeks of pregnancy. Retained products of conception, infection, and hemorrhage are complications that are prevalent throughout the country and explain the reason this technique has not achieved the popularity that prostaglandinurea termination is achieving. I think there are inherent risks and problems associated with this procedure that do not warrant the arrangement of preceptorships to extend its use. I appreciate that Drs. Margolis and Goldsmith have contrary opinions. It never occurred to me that the danger of “. . . walking down the streets of Harlem at midnight whistling Dixie” is racist. The statement is true for members of both races. It would also be dangerous to walk down the streets of Tripoli, Libya, at midnight speaking Yiddish. Both statements express facts; this is how it is in the world in which we live. Beauty or ugliness is in the eyes of the beholder. Charles E. Flowers, Jr., M.D. Department of Obstetrics and Gynecology Medical Center University of Alabama in Birmingham University Station Birmingham, Alabama 35294
Plasma oxytocin values To the Editors: The recent paper OBSTET.
GYNECOL.
new data regarding
by Vasicka and associates (AM. J. 130: 263, 1978) contains important regulation of oxytocin secretion in
913
pregnancy. As pointed out by the authors, their plasma oxytocin values are substantially higher than those reported by several other laboratories in which specific extraction techniques had been utilized. Vasicka and associates proposed to reconcile these differences on the basis of differing immunopotency of the oxytocin preparations used as standards for the radioimmunoassay. We believe that this is an unlikely explanation. Our own studies of oxytocin immunoreactivity with United States Pharamacopeia posterior pituitary extract used as a standard have shown very consistent results when this natural, bioassayed standard is compared to either Pitocin* or synthetic 0xytocin.t While it is also possible that polymerization of synthetic oxytocin in aqueous solution can diminish both immunoreactivity and bioactivity, such differences are at most of the order of 100 to 200 per cent. Therefore, it is highly unlikely that differences among standards could account for the substantial elevations in plasma oxytocin reported by the authors. Current experience by many investigators suggests that the most likely explanation for the extremely high levels of oxytocin reported by Vasicka and associates is the use of whole plasma for immunoassay. Experience with radioimmunoassays for other small peptides have shown substantial, nonspecific immunoreactivity when unextracted plasma is used. The authors themselves raised these questions in their discussion but unfortunately their answers are inaccessible for critical review since the documentation is included in a paper that has only been submitted for publication. It certainly would seem appropriate for the authors to provide further validation of their assay methodology and, in particular, confirmation of individual immunoassay results with bioassay. Richard E. Weitzman, M.D. Hypertension Section Division of Nephroloa and Hypertension Theodore H. Glatz, M.D. Perinatal Research Laboratory Harbor General Hospital 1000 West Carson Street Torrance, California 90509
*Parke, Davis & Co., Detroit, Michigan. TBachem Chemicals.
Reply to Drs. Weitzman and Glatz To the Editors: Concerning low and high plasma oxytocin (OT) levels, in our paper, “Plasma oxytocin in initiation of labor,” we simple pointed out possible sources of the differences peculiar to the patient, events of pregnancy and labor, and the baby. We also enumerated possible sources of interlaboratory differences with no attempt at definite reconciliation at this stage of OT research; in
