1628 Correspondence
none of these intervention techniques is important? A possible answer to the findings of this most unique "prospective controlled randomized trial" is that during the time of the study the socioeconomic status of their entire clinic population changed to be more like that of the private population. In attempting to reduce the prematurity rate in Denver in pregnant clinic populations, our success has been limited by the noncompliant patient, by the users of street drugs, and by those patients who have no message telephone. In addition, the authors did not mention how gestational age was estimated. We now seem to have more mature small-for-gestational-age newborns (as judged by nursery personnel) than in the past, which improves our rate of premature births. In contrast to this bleak record, Hispanic patients appear to be reducing their rates of premature births. Is it possible that these detrimental factors do not operate in Pittsburgh? What was the outcome in the authors' "refuser" group? Perhaps this group can solve the puzzle of why the controls did so well. Robert C. Goodlin, MD City and County of Denver Department of Health and Hospitals 777 Bannock St. Denver, CO 80204-4507
Reply To the Editors: We appreciate the comments of Goodlin as well as Goldenberg et al. with regard to our article. In response we would like to reemphasize the comment in our article that "we noted that the change in attitude of the medical personnel toward this preterm birth prevention program defeated the controlled randomized design of the study because management of the control group was not the same as it would have been before the onset of the study." For this reason, we titled our article "evaluation" rather than "results" of a prospective controlled randomized trial. As a result of our educational sessions, medical providers on their own began to give more instruction about preterm labor to patients irrespective of their risk assignment. We thought that it would be unethical and probably futile to ask medical providers not to do this, whereas we fully realized that our results would not be those of a prospective controlled randomized trial. Cervical examinations in patients not in the high-risk intervention group may have been more frequent but certainly were not done weekly, and we must conclude that weekly cervical examination did not contribute to the decrease in preterm birth rate. As we have pointed out, the decrease in preterm birth rate over time was a result of fewer patients first seen in preterm labor rather than more patients in preterm labor first seen as candidates for tocolysis. With respect to determination of gestational age we used last menstrual period, size of uterus at early examination, quickening, and other clinical information.
June 1990 Am J Obstet Gyneco1
In cases of uncertainty and discrepancy early ultrasonographic examination was done and gestational age was adjusted when there was a 2::2-week discrepancy. Gestational age estimates were verified after delivery by Dubowitz scoring by the pediatrician. In contrast to Goldenberg et al. we have not changed our ultrasonic measurement techniques of the fetus during our study and thus have been spared the difficulty that they had in their preterm birth prevention study. We agree with Goldenberg et al. that on the basis of our results, screening for high-risk status is of limited value. In turn we suggest education of all pregnant patients about subtle symptoms and signs of preterm labor, uterine palpation and rest, and self-hydration when more than occasional uterine activity is noted. We are aware that others have not observed a decrease in preterm birth rate in preterm birth prevention studies. This may be because of differences in patient population as suggested by Goodlin. Recent analysis of our study population by race revealed a very significant decrease in preterm births (P < 0.00 I) in 2446 white indigent patients in year 2 and 3 of the study with preterm birth rates lower than those in our white private population. In contrast, in 2599 black indigent study patients the pre term birth rate decreased much more modestly, reaching statistical significance (P < 0.01) only in year 3 of the study despite particular efforts to communicate with our black study population. It appears from our results that preterm birth prevention studies that involve predominantly black indigent patient populations and small sample sizes are not likely to show significant changes in preterm birth rate. Eberhard Mueller-Heubach, MD Department of Obstetrics and Gynecology Bowman Gray School of Medicine of Wake Forest University 300 S. Hawthorne Road Winston-Salem, NC 27103
Volume and timing are key to use of intraumbilical oxytocin for management of retained placenta To the Editors: I read with great interest the article by Reddy and Carey (Reddy VV, Carey JC. Effect of umbilical vein oxytocin on puerperal blood loss and length of the third stage of labor. AM J OBSTET GVNECOL 1989; 160: 206-8). As they state in the Comment section, some controversy concerning the value of intraumbilical injection of oxytocin for the management of the third stage of labor or for the retained placenta does indeed exist. As for the routine use of oxytocin in the management of the third stage oflabor, the above study clearly shows in a randomized controlled manner that this maneuver shortens the length of the third stage of labor and diminishes blood loss. This confirms a previous observation, although uncontrolled, by N eri et al.I I definitely agree with their conclusion that this management
Correspondence 1629
Volume 162 Number 6
is a useful alternative to the traditional management of the third stage of labor, especially when fluid intake should be restricted or blood loss minimized. As for the use of intraumbilical oxytocin for the management of the retained placenta, despite few reports that do not claim an advantage of the procedure,2-4 I have no doubt in my mind that the properly timed intraumbilical injection of oxytocin is of great value in the management of the retained placenta. Chestnut et al. 2 injected intraumbilical oxytocin if the placenta was not expelled in 5 minutes, which obviously is too short of an interval. Kristiansen et al. 3 have waited 20 minutes, which might still be too short of a waiting period before intervention. These authors have also used a smaller volume (10 ml) for the intraumbilical injection, which I believe is not enough to overcome the "dead space" in the umbilical cord and the placental vasculature. The hydraulic effect of the injected solution has its merits as it may in itself enhance placental separation by changing placental uterine interrelations. This principle was the basis for the Majon Gabastou maneuver, intraumbilical injection of 200 to 250 ml of physiologic solution, which was popular in the early 1930s in Europe when placental separation was delayed. I Haukson et aJ.4 have waited as long as 60 minutes before intervention. It is possible that by increasing the waiting period some placentas otherwise defined as "retained" would be delivered. The 60-minute wait could have preselected the especially difficult cases (placenta accreta or increta), which could account for the relatively lower success rate (46%) and the reported longer injection-expulsion interval supports this assumption. We all know that it was common practice in earlier days to wait an hour or even longer. However, today it is considered unwise to wait that long, exposing the parturient to the risks of increased third-stage blood loss and subsequent puerperal anemia. The risks of puerperal infections related to anemia and to puerperal blood transfusions should be continuously kept in mind. Even in Kirstiansen's study 40% to 42% of the retained placentas could have avoided manual lysis under general anesthesia, which usually is the traditional management. 5 In our hands the intraumbilical injection of oxytocin seems to be a very effective, quick, and safe method for the separation and delivery of the retained placenta. It has been successful in avoiding manual lysis under general anesthesia in more than 70% of cases. 5- 7 I believe that oxytocin applied in this manner reaches the partially disrupted placental bed in a relatively higher concentration, stimulating uterine contraction and enhancing the cleavage of the placenta at the decidua spongiosa level. The hematoma that forms in this area further accelerates the process, and the placenta eventually separates and is delivered. It seems that the injected solution may also have an hydraulic effect and may in itself contribute to placental
separation by mechanical pressure as with the injection of saline solution alone. Thus the volume of the injected solution is of considerable importance. The timing of intervention is also of critical importance. It should not be too early and should not be unnecessarily delayed. I believe that the recommended waiting interval should be neither more nor less than 30 minutes. No maternal ill effects were reported even by the method's objectors, so why not use it when there is a chance to avoid manual lysis and general anesthesia, even if the success rate is not as high as in our experience? Abraham Golan, MD Department of Obstetrics and Gynecology Assaf Harofhe Medical Center POB Beer Yaakov Zerifin, Israel 70300 REFERENCES I. Neri A, Goldman], Gans B. A new method in the man-
agement of the third stage oflabor. Harefuah 1966; 70:351. 2. Chestnut DH, Wilcox LL. Influence of umbilical vein administration of oxytocin on the third stage of labor: a randomized, double-blind, placebo-controlled study. AM] OBSTET GYNECOL 1987;157:160. 3. Kristiansen FV, Frost L, Kaspersen P, Moller BR. The effect of oxytocin injection into the umbilical vein for the management of the retained placenta. AM] OBSTET GYNECOL 1987;156:979. 4. Hauksson A. Oxytocin injection into the umbilical vein in women with retained placenta. AM ] OBSTET GYNECOL 1986; 155: 1140. 5. Golan A. Intraumbilical oxytocin for the retained placenta. AM] OBSTET GYNECOL 1988;159:1309. 6. Golan A, (Baruch) Lidor AL, Wexler S, David MP. A new method for management of the retained placenta. AM ] OBSTET GYNECOL 1983;146:708. 7. Golan A, (Baruch) Lidor AL, Wexler S, David MP. Reply to Liner. AM] OBSTET GYNECOL 1984;148:232.
Response declined
Effects of selection bias on outcomes at referral centers To the Editors: Lubchenco et al. (Lubchenco LO, Butterfield LJ, Delaney-Black V, Goldson E, Koops BL, Lazotte DC. Outcome of very-low-birth-weight infants: Does antepartum versus neonatal referral have a better impact on mortality, morbidity, or long-term outcome? AM J OBSTET GYNECOL 1989; 160:539-45) concluded that the better place to deliver a newborn weighing 500 to 1499 gm is a tertiary care referral center. They reported fewer fetal deaths, less neonatal morbidity, possibly a lower neonatal mortality, and better long-term outcome, when compared with results at the surrounding level I community hospitals. But their claims have been derived from a selected population at their referral center, not a stochastic one, as they have inferred by calling their study a total population-based one. The authors were well aware of selection biases that distort reports of outcome at referral centers. All new-
none of these intervention techniques is important? A possible answer to the findings of this most unique "prospective controlled randomized trial" is that during the time of the study the socioeconomic status of their entire clinic population changed to be more like that of the private population. In attempting to reduce the prematurity rate in Denver in pregnant clinic populations, our success has been limited by the noncompliant patient, by the users of street drugs, and by those patients who have no message telephone. In addition, the authors did not mention how gestational age was estimated. We now seem to have more mature small-for-gestational-age newborns (as judged by nursery personnel) than in the past, which improves our rate of premature births. In contrast to this bleak record, Hispanic patients appear to be reducing their rates of premature births. Is it possible that these detrimental factors do not operate in Pittsburgh? What was the outcome in the authors' "refuser" group? Perhaps this group can solve the puzzle of why the controls did so well. Robert C. Goodlin, MD City and County of Denver Department of Health and Hospitals 777 Bannock St. Denver, CO 80204-4507
Reply To the Editors: We appreciate the comments of Goodlin as well as Goldenberg et al. with regard to our article. In response we would like to reemphasize the comment in our article that "we noted that the change in attitude of the medical personnel toward this preterm birth prevention program defeated the controlled randomized design of the study because management of the control group was not the same as it would have been before the onset of the study." For this reason, we titled our article "evaluation" rather than "results" of a prospective controlled randomized trial. As a result of our educational sessions, medical providers on their own began to give more instruction about preterm labor to patients irrespective of their risk assignment. We thought that it would be unethical and probably futile to ask medical providers not to do this, whereas we fully realized that our results would not be those of a prospective controlled randomized trial. Cervical examinations in patients not in the high-risk intervention group may have been more frequent but certainly were not done weekly, and we must conclude that weekly cervical examination did not contribute to the decrease in preterm birth rate. As we have pointed out, the decrease in preterm birth rate over time was a result of fewer patients first seen in preterm labor rather than more patients in preterm labor first seen as candidates for tocolysis. With respect to determination of gestational age we used last menstrual period, size of uterus at early examination, quickening, and other clinical information.
June 1990 Am J Obstet Gyneco1
In cases of uncertainty and discrepancy early ultrasonographic examination was done and gestational age was adjusted when there was a 2::2-week discrepancy. Gestational age estimates were verified after delivery by Dubowitz scoring by the pediatrician. In contrast to Goldenberg et al. we have not changed our ultrasonic measurement techniques of the fetus during our study and thus have been spared the difficulty that they had in their preterm birth prevention study. We agree with Goldenberg et al. that on the basis of our results, screening for high-risk status is of limited value. In turn we suggest education of all pregnant patients about subtle symptoms and signs of preterm labor, uterine palpation and rest, and self-hydration when more than occasional uterine activity is noted. We are aware that others have not observed a decrease in preterm birth rate in preterm birth prevention studies. This may be because of differences in patient population as suggested by Goodlin. Recent analysis of our study population by race revealed a very significant decrease in preterm births (P < 0.00 I) in 2446 white indigent patients in year 2 and 3 of the study with preterm birth rates lower than those in our white private population. In contrast, in 2599 black indigent study patients the pre term birth rate decreased much more modestly, reaching statistical significance (P < 0.01) only in year 3 of the study despite particular efforts to communicate with our black study population. It appears from our results that preterm birth prevention studies that involve predominantly black indigent patient populations and small sample sizes are not likely to show significant changes in preterm birth rate. Eberhard Mueller-Heubach, MD Department of Obstetrics and Gynecology Bowman Gray School of Medicine of Wake Forest University 300 S. Hawthorne Road Winston-Salem, NC 27103
Volume and timing are key to use of intraumbilical oxytocin for management of retained placenta To the Editors: I read with great interest the article by Reddy and Carey (Reddy VV, Carey JC. Effect of umbilical vein oxytocin on puerperal blood loss and length of the third stage of labor. AM J OBSTET GVNECOL 1989; 160: 206-8). As they state in the Comment section, some controversy concerning the value of intraumbilical injection of oxytocin for the management of the third stage of labor or for the retained placenta does indeed exist. As for the routine use of oxytocin in the management of the third stage oflabor, the above study clearly shows in a randomized controlled manner that this maneuver shortens the length of the third stage of labor and diminishes blood loss. This confirms a previous observation, although uncontrolled, by N eri et al.I I definitely agree with their conclusion that this management
Correspondence 1629
Volume 162 Number 6
is a useful alternative to the traditional management of the third stage of labor, especially when fluid intake should be restricted or blood loss minimized. As for the use of intraumbilical oxytocin for the management of the retained placenta, despite few reports that do not claim an advantage of the procedure,2-4 I have no doubt in my mind that the properly timed intraumbilical injection of oxytocin is of great value in the management of the retained placenta. Chestnut et al. 2 injected intraumbilical oxytocin if the placenta was not expelled in 5 minutes, which obviously is too short of an interval. Kristiansen et al. 3 have waited 20 minutes, which might still be too short of a waiting period before intervention. These authors have also used a smaller volume (10 ml) for the intraumbilical injection, which I believe is not enough to overcome the "dead space" in the umbilical cord and the placental vasculature. The hydraulic effect of the injected solution has its merits as it may in itself enhance placental separation by changing placental uterine interrelations. This principle was the basis for the Majon Gabastou maneuver, intraumbilical injection of 200 to 250 ml of physiologic solution, which was popular in the early 1930s in Europe when placental separation was delayed. I Haukson et aJ.4 have waited as long as 60 minutes before intervention. It is possible that by increasing the waiting period some placentas otherwise defined as "retained" would be delivered. The 60-minute wait could have preselected the especially difficult cases (placenta accreta or increta), which could account for the relatively lower success rate (46%) and the reported longer injection-expulsion interval supports this assumption. We all know that it was common practice in earlier days to wait an hour or even longer. However, today it is considered unwise to wait that long, exposing the parturient to the risks of increased third-stage blood loss and subsequent puerperal anemia. The risks of puerperal infections related to anemia and to puerperal blood transfusions should be continuously kept in mind. Even in Kirstiansen's study 40% to 42% of the retained placentas could have avoided manual lysis under general anesthesia, which usually is the traditional management. 5 In our hands the intraumbilical injection of oxytocin seems to be a very effective, quick, and safe method for the separation and delivery of the retained placenta. It has been successful in avoiding manual lysis under general anesthesia in more than 70% of cases. 5- 7 I believe that oxytocin applied in this manner reaches the partially disrupted placental bed in a relatively higher concentration, stimulating uterine contraction and enhancing the cleavage of the placenta at the decidua spongiosa level. The hematoma that forms in this area further accelerates the process, and the placenta eventually separates and is delivered. It seems that the injected solution may also have an hydraulic effect and may in itself contribute to placental
separation by mechanical pressure as with the injection of saline solution alone. Thus the volume of the injected solution is of considerable importance. The timing of intervention is also of critical importance. It should not be too early and should not be unnecessarily delayed. I believe that the recommended waiting interval should be neither more nor less than 30 minutes. No maternal ill effects were reported even by the method's objectors, so why not use it when there is a chance to avoid manual lysis and general anesthesia, even if the success rate is not as high as in our experience? Abraham Golan, MD Department of Obstetrics and Gynecology Assaf Harofhe Medical Center POB Beer Yaakov Zerifin, Israel 70300 REFERENCES I. Neri A, Goldman], Gans B. A new method in the man-
agement of the third stage oflabor. Harefuah 1966; 70:351. 2. Chestnut DH, Wilcox LL. Influence of umbilical vein administration of oxytocin on the third stage of labor: a randomized, double-blind, placebo-controlled study. AM] OBSTET GYNECOL 1987;157:160. 3. Kristiansen FV, Frost L, Kaspersen P, Moller BR. The effect of oxytocin injection into the umbilical vein for the management of the retained placenta. AM] OBSTET GYNECOL 1987;156:979. 4. Hauksson A. Oxytocin injection into the umbilical vein in women with retained placenta. AM ] OBSTET GYNECOL 1986; 155: 1140. 5. Golan A. Intraumbilical oxytocin for the retained placenta. AM] OBSTET GYNECOL 1988;159:1309. 6. Golan A, (Baruch) Lidor AL, Wexler S, David MP. A new method for management of the retained placenta. AM ] OBSTET GYNECOL 1983;146:708. 7. Golan A, (Baruch) Lidor AL, Wexler S, David MP. Reply to Liner. AM] OBSTET GYNECOL 1984;148:232.
Response declined
Effects of selection bias on outcomes at referral centers To the Editors: Lubchenco et al. (Lubchenco LO, Butterfield LJ, Delaney-Black V, Goldson E, Koops BL, Lazotte DC. Outcome of very-low-birth-weight infants: Does antepartum versus neonatal referral have a better impact on mortality, morbidity, or long-term outcome? AM J OBSTET GYNECOL 1989; 160:539-45) concluded that the better place to deliver a newborn weighing 500 to 1499 gm is a tertiary care referral center. They reported fewer fetal deaths, less neonatal morbidity, possibly a lower neonatal mortality, and better long-term outcome, when compared with results at the surrounding level I community hospitals. But their claims have been derived from a selected population at their referral center, not a stochastic one, as they have inferred by calling their study a total population-based one. The authors were well aware of selection biases that distort reports of outcome at referral centers. All new-
