1626 Correspondence
is included in published data on complications and therapy in twin pregnancies. Geoffrey A. Machin, MD Keith Still, MD Departments of Pathology and Obstetrics W. C. Mackenzie Health Sciences Centre University of Alberta Edmonton, Alberta, Canada T6G 2R7 REFERENCES 1. Chescheir NC, Seeds ]W. Polyhydramnios and oligohy-
dTamnios in twin gestations. Obstet Gynecol 1988;71: 882-4. 2. AchiTOn R, Rosen N, Zakut H. Pathophysiologic mechanism of hydramnios development in twin transfusion syndTOme. A case repOTt. J RepTOd Med 1987;32: 305-8. 3. D'Alton ME, Dudley DKL. Ultrasound in the antenatal management of twin gestation. Semin Perinatol 1986; 10:30-8. 4. Azuma C, Kamiura S, Nobunaga T, NegoTO T, Saji F, Tanizawa O. Zygosity determination of multiple pregnancy by deoxyribonucleic acid fingerprints. AM] OBSTET GVNECOL 1989;160:734-6. A complete list of references is available from the authors on request.
Reply To the Editors: We appreciate the comments on our article and we are happy to address issues that these authors have raised. First, with regard to the zygosity of each twin pair, monozygotic dichorionic placentas were confirmed in two twin sets (twins 1 and 4) and dichorionic, diamniotic placentas were confirmed in the remaining twins. In two twins (1 and 5) no membrane was seen at initial assessment, which did raise the possibility of monoamniotic monozygosity twins. With treatment a membrane subsequently became visible. In case I, the working diagnosis was a twin-to-twin transfusion. In case 5 congenital heart disease in one twin was suspected. In the remaining twins, inasmuch as growth profiles and Doppler ultrasonographic studies were normal, the cause for the gross hydramnios was unexplained. The hematocrit values varied between cases, from 41.3% to 63.1 %, but between twins the mean difference was small, averaging 3.8%. In only one pair did the difference in hematocrit exceed 5% (A = 4l.3%, B = 52.7%). There was no significant discordance in cord pH, blood gas values, or Apgar scores. There was hydramnios in both twins in all cases before treatment. In three cases one twin showed a more marked diminution in fluid with indomethacin treatment than that of the other twin. Subsequent to this report five further cases have been treated in a similar matter. In one case, there was unequivocal oligohydramnios in one sac and hydramnios in the other. Treatment was maintained from 27 to 31 weeks' gestation and labor occurred within 24 hours of discontinuing indomethacin. Transie'nt oliguria was
June 1990 Am J Obstet Gynecol
noted in the twin with oligohydramnios. There was clinical evidence of a twin-to-twin transfusion. I. Lange, MD Department of Obstetrics and Gynecology Foothills Hospital 1403 29th St. NW Calgary, Alberta, Canada T2N 2T9 C. R. Harman, MD Fetal Assessment Unit Women's Hospital 735 Notre Dame Ave. Winnipeg, Manitoba, Canada R3E 0L8
Study of preterm birth draws different interpretation To the Editors: Because we have participated in a multicenter trial of preterm birth prevention similar to that reported by Mueller-Heubach et al. (Mueller-Heubach E, Reddick D, Barnett B, Bente R. Preterm birth prevention: Evaluation of a prospective controlled randomized trial. AM J OBSTET GYNECOL 1989; 160: 1172-8) but achieved little success, we naturally were interested in the results of this study and wanted to make several observations. First, we learned as we were performing our trial that gestational age is a more ephemeral measurement than we initially believed.! We found that whereas the apparent gestational age distribution changed over time predominantly because of changes in the use of ultrasonography, the birth weight distribution and mean birth weight did not change. Because one possible explanation for the reported improvement in the preterm delivery rate over time is a change in the definition of gestational age, we would be interested to know, first, how the gestational age was determined, and second, what happened to the birth weight distribution over the time of their study? It is, of course, encouraging to see a decrease in neonatal mortality over time. However, whereas the results are statistically significant there may be potential for bias in the results. For example, even though the authors admitted patients to the project at 20 weeks' gestation, which is equivalent to about 350 gm fetal weight, they nonetheless defined a neonatal death as those beginning at 500 gm, equivalent to about 23 or 24 weeks gestational age. Therefore the lower tail of potential mortality was excluded. In addition, the authors do not present the neonatal mortality for the entire population studied, but only for those babies that by their definition were preterm. It would be interesting to know the neonatal mortality for the entire population admitted to the study and to see how this changed over time. In any case, neonatal mortality has improved over time in many institutions even when the preterm delivery rate did not. As an example, in the Mueller-Heubach article the neonatal mortality showed as large an improvement in the first year of the study, before any improvement in the preterm delivery rate, as occurred in subsequent years when the reported preterm delivery rate was lower.
Correspondence
Volume 162 "'umber 6
However, even if the preterm delivery rate did change over time and the neonatal mortality improved, it is interesting to speculate what in the program may have led to these results. The authors state that the reason they believe the preterm delivery rate improved over time was that the method to be tested (i.e., risk screening, weekly evaluation, teaching) was adopted widely throughout their system. It is not clear from the methods section, but when the authors state that their entire prenatal system adopted the preterm prevention method, does this mean that the entire system went to a weekly visit with pelvic examinations and that this approach was applied to both high-risk controls and to their low-risk patients? This should be quantifiable and we would be interested in seeing these numbers. However, if that did not happen, the authors' statement about similarity in care between the high-risk treatment and all other groups should not be casually accepted because the difference in care between groups is important. For example, if the high-risk control and lowrisk groups did not have weekly visits with examinations, it seems unlikely that the weekly visits and the weekly pelvic examinations played a significant role in the reduction in preterm delivery. In regard to screening, inasmuch as nearly two thirds of the preterm deliveries came from the low-risk group, our calculations suggest that a substantial part of the improvement in the preterm delivery rate must have come from the low-risk population. If substantial improvement did occur in the low-risk group, then it seems safe to assume that screening for high-risk status was probably not of much value in producing the improvement. Also, because there was no significant difference in outcome between the high-risk treatment and control groups, it also appears that it is of little value to actually classify patients and move them into a high-risk group. Because it seems that neither the screening, nor the classification, nor the weekly visits, nor the weekly pelvic examinations are plausible explanations or even necessary components for the improvement over time, it is not apparent to us which components of the program may have been responsible for its success. Certainly none of these program components is likely to be responsible for the reduction in the diagnosis of preterm labor, especially because the entire program was designed not to reduce the incidence of preterm labor, but to diagnose it early and treat it appropriately.2 Finally, we would like to remind the readers that the primary hypothesis and the study design involved a randomized trial of a specific intervention. This study design failed to show any benefit. In fact, although not statistically significant, the treatment group had a worse outcome (with a preterm delivery rate of 22.1 % in the intervention group and 20.8% in the control group). This was also true in Philadelphia in a study by Main et al. 3 and in our part of the multicenter trial in Alabama! It seems to us that what is important in this study is the result of the randomized trial, and its failure should not be so casually explained. Again, the MuellerHeubach article and the Main' article, the only two randomized trials of this method of prematurity pre-
1627
vention that are now in print, failed to show any difference between the treatment and the control group. Certainly the authors did not prove that "the preterm birth rate ... could be markedly decreased as a result of medical provider and patient education" nor did they show "that an intensive educational program among patients and providers can have a marked impact on the frequency of preterm birth." It is important to reread the title of this paper- "Preterm birth prevention: Evaluation of a prospective controlled, randomized trial." The results were negative. Any other interpretation, we believe, is misleading. Robert L. Goldenberg, MD Richard O. Davis, MD Rachel C. Baker, RN University of Alabama at Birmingham Department of Obstetrics and Gynecology University Station Birmingham, AL 35294 REFERENCES I. Goldenberg RL, Davis RO, Cutter GR, Hoffman Hj,
Brumfield CG. Prematurity, postdates, and growth retardation: the influence of use of ultrasonography on reported gestational age. AM j OBSTET GYNECOL 1989; 160:462-70. 2. Herron MA, Katz M, Creasy RK. Evaluation of a preterm birth prevention program: preliminary report. Obstet Gynecol 1982;59:452-6. 3. Main DM, Gabbe SG, Richardson D, Strong S. Can preterm deliveries be prevented? AM j OBSTET GYNECOL 1985; 151:892-8. 4. Goldenberg RL, Davis RO, Baker RC, Corliss DK, Andrews jB, Carpenter AH. The Alabama Preterm Birth Prevention Project. Obstet Gynecol 1990 [In pressl.
Conclusions lack support To the Editors: After reading E. Mueller-Heubach et al.'s article, (Mueller-Heubach E, Reddick D, Barnett B, Bente R. Pre term birth prevention: evaluation of a prospective controlled randomized trial. AM J OBSTET GVNECOL 1989; 160: 1172-8), my evaluation of their study was very different from theirs. The authors concluded that "we were able to demonstrate that an intensive educational program ... can have a marked impact on the frequency of preterm birth." I found no support in their article for this conclusion. The authors assumed that the general change in attitude of medical personnel explains the lack of difference in preterm births between the intervention and the control groups. Were the controls seen weekly from 22 to 37 weeks' gestation as was the intervention group, and did they have weekly cervical examinations? Did the controls have the same intensive teaching with regard to symptoms and signs of preterm labor as did the intervention group? Were the amounts of rest, cessation of smoking, and use of tocolysis the same in both groups? From the description in the methods section, the answer has to be no! Yet, as noted, the authors did not find a difference in preterm births between the control and intervention groups. Does this mean that
is included in published data on complications and therapy in twin pregnancies. Geoffrey A. Machin, MD Keith Still, MD Departments of Pathology and Obstetrics W. C. Mackenzie Health Sciences Centre University of Alberta Edmonton, Alberta, Canada T6G 2R7 REFERENCES 1. Chescheir NC, Seeds ]W. Polyhydramnios and oligohy-
dTamnios in twin gestations. Obstet Gynecol 1988;71: 882-4. 2. AchiTOn R, Rosen N, Zakut H. Pathophysiologic mechanism of hydramnios development in twin transfusion syndTOme. A case repOTt. J RepTOd Med 1987;32: 305-8. 3. D'Alton ME, Dudley DKL. Ultrasound in the antenatal management of twin gestation. Semin Perinatol 1986; 10:30-8. 4. Azuma C, Kamiura S, Nobunaga T, NegoTO T, Saji F, Tanizawa O. Zygosity determination of multiple pregnancy by deoxyribonucleic acid fingerprints. AM] OBSTET GVNECOL 1989;160:734-6. A complete list of references is available from the authors on request.
Reply To the Editors: We appreciate the comments on our article and we are happy to address issues that these authors have raised. First, with regard to the zygosity of each twin pair, monozygotic dichorionic placentas were confirmed in two twin sets (twins 1 and 4) and dichorionic, diamniotic placentas were confirmed in the remaining twins. In two twins (1 and 5) no membrane was seen at initial assessment, which did raise the possibility of monoamniotic monozygosity twins. With treatment a membrane subsequently became visible. In case I, the working diagnosis was a twin-to-twin transfusion. In case 5 congenital heart disease in one twin was suspected. In the remaining twins, inasmuch as growth profiles and Doppler ultrasonographic studies were normal, the cause for the gross hydramnios was unexplained. The hematocrit values varied between cases, from 41.3% to 63.1 %, but between twins the mean difference was small, averaging 3.8%. In only one pair did the difference in hematocrit exceed 5% (A = 4l.3%, B = 52.7%). There was no significant discordance in cord pH, blood gas values, or Apgar scores. There was hydramnios in both twins in all cases before treatment. In three cases one twin showed a more marked diminution in fluid with indomethacin treatment than that of the other twin. Subsequent to this report five further cases have been treated in a similar matter. In one case, there was unequivocal oligohydramnios in one sac and hydramnios in the other. Treatment was maintained from 27 to 31 weeks' gestation and labor occurred within 24 hours of discontinuing indomethacin. Transie'nt oliguria was
June 1990 Am J Obstet Gynecol
noted in the twin with oligohydramnios. There was clinical evidence of a twin-to-twin transfusion. I. Lange, MD Department of Obstetrics and Gynecology Foothills Hospital 1403 29th St. NW Calgary, Alberta, Canada T2N 2T9 C. R. Harman, MD Fetal Assessment Unit Women's Hospital 735 Notre Dame Ave. Winnipeg, Manitoba, Canada R3E 0L8
Study of preterm birth draws different interpretation To the Editors: Because we have participated in a multicenter trial of preterm birth prevention similar to that reported by Mueller-Heubach et al. (Mueller-Heubach E, Reddick D, Barnett B, Bente R. Preterm birth prevention: Evaluation of a prospective controlled randomized trial. AM J OBSTET GYNECOL 1989; 160: 1172-8) but achieved little success, we naturally were interested in the results of this study and wanted to make several observations. First, we learned as we were performing our trial that gestational age is a more ephemeral measurement than we initially believed.! We found that whereas the apparent gestational age distribution changed over time predominantly because of changes in the use of ultrasonography, the birth weight distribution and mean birth weight did not change. Because one possible explanation for the reported improvement in the preterm delivery rate over time is a change in the definition of gestational age, we would be interested to know, first, how the gestational age was determined, and second, what happened to the birth weight distribution over the time of their study? It is, of course, encouraging to see a decrease in neonatal mortality over time. However, whereas the results are statistically significant there may be potential for bias in the results. For example, even though the authors admitted patients to the project at 20 weeks' gestation, which is equivalent to about 350 gm fetal weight, they nonetheless defined a neonatal death as those beginning at 500 gm, equivalent to about 23 or 24 weeks gestational age. Therefore the lower tail of potential mortality was excluded. In addition, the authors do not present the neonatal mortality for the entire population studied, but only for those babies that by their definition were preterm. It would be interesting to know the neonatal mortality for the entire population admitted to the study and to see how this changed over time. In any case, neonatal mortality has improved over time in many institutions even when the preterm delivery rate did not. As an example, in the Mueller-Heubach article the neonatal mortality showed as large an improvement in the first year of the study, before any improvement in the preterm delivery rate, as occurred in subsequent years when the reported preterm delivery rate was lower.
Correspondence
Volume 162 "'umber 6
However, even if the preterm delivery rate did change over time and the neonatal mortality improved, it is interesting to speculate what in the program may have led to these results. The authors state that the reason they believe the preterm delivery rate improved over time was that the method to be tested (i.e., risk screening, weekly evaluation, teaching) was adopted widely throughout their system. It is not clear from the methods section, but when the authors state that their entire prenatal system adopted the preterm prevention method, does this mean that the entire system went to a weekly visit with pelvic examinations and that this approach was applied to both high-risk controls and to their low-risk patients? This should be quantifiable and we would be interested in seeing these numbers. However, if that did not happen, the authors' statement about similarity in care between the high-risk treatment and all other groups should not be casually accepted because the difference in care between groups is important. For example, if the high-risk control and lowrisk groups did not have weekly visits with examinations, it seems unlikely that the weekly visits and the weekly pelvic examinations played a significant role in the reduction in preterm delivery. In regard to screening, inasmuch as nearly two thirds of the preterm deliveries came from the low-risk group, our calculations suggest that a substantial part of the improvement in the preterm delivery rate must have come from the low-risk population. If substantial improvement did occur in the low-risk group, then it seems safe to assume that screening for high-risk status was probably not of much value in producing the improvement. Also, because there was no significant difference in outcome between the high-risk treatment and control groups, it also appears that it is of little value to actually classify patients and move them into a high-risk group. Because it seems that neither the screening, nor the classification, nor the weekly visits, nor the weekly pelvic examinations are plausible explanations or even necessary components for the improvement over time, it is not apparent to us which components of the program may have been responsible for its success. Certainly none of these program components is likely to be responsible for the reduction in the diagnosis of preterm labor, especially because the entire program was designed not to reduce the incidence of preterm labor, but to diagnose it early and treat it appropriately.2 Finally, we would like to remind the readers that the primary hypothesis and the study design involved a randomized trial of a specific intervention. This study design failed to show any benefit. In fact, although not statistically significant, the treatment group had a worse outcome (with a preterm delivery rate of 22.1 % in the intervention group and 20.8% in the control group). This was also true in Philadelphia in a study by Main et al. 3 and in our part of the multicenter trial in Alabama! It seems to us that what is important in this study is the result of the randomized trial, and its failure should not be so casually explained. Again, the MuellerHeubach article and the Main' article, the only two randomized trials of this method of prematurity pre-
1627
vention that are now in print, failed to show any difference between the treatment and the control group. Certainly the authors did not prove that "the preterm birth rate ... could be markedly decreased as a result of medical provider and patient education" nor did they show "that an intensive educational program among patients and providers can have a marked impact on the frequency of preterm birth." It is important to reread the title of this paper- "Preterm birth prevention: Evaluation of a prospective controlled, randomized trial." The results were negative. Any other interpretation, we believe, is misleading. Robert L. Goldenberg, MD Richard O. Davis, MD Rachel C. Baker, RN University of Alabama at Birmingham Department of Obstetrics and Gynecology University Station Birmingham, AL 35294 REFERENCES I. Goldenberg RL, Davis RO, Cutter GR, Hoffman Hj,
Brumfield CG. Prematurity, postdates, and growth retardation: the influence of use of ultrasonography on reported gestational age. AM j OBSTET GYNECOL 1989; 160:462-70. 2. Herron MA, Katz M, Creasy RK. Evaluation of a preterm birth prevention program: preliminary report. Obstet Gynecol 1982;59:452-6. 3. Main DM, Gabbe SG, Richardson D, Strong S. Can preterm deliveries be prevented? AM j OBSTET GYNECOL 1985; 151:892-8. 4. Goldenberg RL, Davis RO, Baker RC, Corliss DK, Andrews jB, Carpenter AH. The Alabama Preterm Birth Prevention Project. Obstet Gynecol 1990 [In pressl.
Conclusions lack support To the Editors: After reading E. Mueller-Heubach et al.'s article, (Mueller-Heubach E, Reddick D, Barnett B, Bente R. Pre term birth prevention: evaluation of a prospective controlled randomized trial. AM J OBSTET GVNECOL 1989; 160: 1172-8), my evaluation of their study was very different from theirs. The authors concluded that "we were able to demonstrate that an intensive educational program ... can have a marked impact on the frequency of preterm birth." I found no support in their article for this conclusion. The authors assumed that the general change in attitude of medical personnel explains the lack of difference in preterm births between the intervention and the control groups. Were the controls seen weekly from 22 to 37 weeks' gestation as was the intervention group, and did they have weekly cervical examinations? Did the controls have the same intensive teaching with regard to symptoms and signs of preterm labor as did the intervention group? Were the amounts of rest, cessation of smoking, and use of tocolysis the same in both groups? From the description in the methods section, the answer has to be no! Yet, as noted, the authors did not find a difference in preterm births between the control and intervention groups. Does this mean that
