From the Departments of 1Obstetrics and Gynecology and 2Hematology, Faculté de Médecine, Université de Montréal, Centre Hospitalier Universitaire, Sainte-Justine, Montréal, Quebec, Canada; 3Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada; and 4Department of Obstetrics and Gynecology, Faculté de Médecine, Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Quebéc (Centre Hospitalier de l’Université Laval), Québec, Quebec, Canada.
Corresponding author: Dr. Marc Boucher, Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire, Sainte-Justine, 3175 Côte Sainte-Catherine Road, Montréal, Quebec, Canada, H3T 1C5; e-mail: firstname.lastname@example.org.
Financial Disclosure The authors have no potential conflicts of interest to disclose.
OBJECTIVE: To estimate the frequency and volume of fetomaternal hemorrhage during external cephalic version for term breech singleton fetuses and to identify risk factors involved with this complication.
METHODS: A prospective observational study was performed including all patients undergoing a trial of external cephalic version for a breech presentation of at least 36 weeks of gestation between 1987 and 2001 in our center. A search for fetal erythrocytes using the standard Kleihauer-Betke test was obtained before and after each external cephalic version. The frequency and volume of fetomaternal hemorrhage were calculated. Putative risk factors for fetomaternal hemorrhage were evaluated by χ2 test and Mann-Whitney U test.
RESULTS: A Kleihauer-Betke test result was available before and after 1,311 trials of external cephalic version. The Kleihauer-Betke test was positive in 67 (5.1%) before the procedure. Of the 1,244 women with a negative Kleihauer-Betke test before external cephalic version, 30 (2.4%) had a positive Kleihauer-Betke test after the procedure. Ten (0.8%) had an estimated fetomaternal hemorrhage greater than 1 mL, and one (0.08%) had an estimated fetomaternal hemorrhage greater than 30 mL. The risk of fetomaternal hemorrhage was not influenced by parity, gestational age, body mass index, number of attempts at version, placental location, or amniotic fluid index.
CONCLUSION: The risk of detectable fetomaternal hemorrhage during external cephalic version was 2.4%, with fetomaternal hemorrhage more than 30 mL in less than 0.1% of cases. These data suggest that the performance of a Kleihauer-Betke test is unwarranted in uneventful external cephalic version and that in Rh-negative women, no further Rh immune globulin is necessary other than the routine 300-microgram dose at 28 weeks of gestation and postpartum.
LEVEL OF EVIDENCE: II
Publication of the Term Breech Trial1 has brought major changes in the management of term breech fetuses. For the vast majority of patients with a breech presenting fetus at term, an elective prelabor cesarean delivery is now offered as the standard of care.2
Since the 1980s, external cephalic version has moved to the forefront of the management of term fetuses with a breech presentation. It is now considered to be a safe method to convert breech fetuses to a vertex presentation.3 The American College of Obstetricians and Gynecologists recommends that external cephalic version be offered to every woman with a breech presentation at term to reduce the number of elective cesareans done for that indication.4
All medical procedures require that informed consent be obtained. This consent should be based on firm and valid evidence, giving the patient the most precise picture of the risks to her and her fetus. Obstetric invasive procedures as well as abdominal trauma are factors held responsible for fetomaternal hemorrhage. Previous studies have reported fetomaternal hemorrhage rates after external cephalic version varying from 2% to 28%, but most did not consider the normal occurrence of fetal erythrocytes in the maternal circulation.5–9
The main objective of the current study was to estimate the frequency and volume of fetomaternal hemorrhage during external cephalic version for term breech singleton fetuses and, secondarily, to identify the risk factors involved with this complication. Our aim was to provide the medical community with solid evidence on which to base counseling of potential candidates for this procedure.
MATERIALS AND METHODS
This was a prospective observational study performed at a single institution, Centre Hospitalier Universitaire Sainte-Justine in Montréal, Québec, Canada (nearly 4,000 deliveries yearly) after approval by our Research Ethics Review Board. In 1987, a program of external cephalic version was implemented with two weekly clinics staffed by the same two Maternal–Fetal Medicine subspecialists (M.B. and G.P.M.). Pregnant women whose fetuses were found to be in breech presentation were referred to those special clinics on an outpatient basis and were sent by physicians or midwives practicing in our own institution or from the greater Montréal metropolitan area.
Every pregnant woman who was referred for external cephalic version and met the inclusion criteria had a separate research data sheet filled out recording demographic, clinical, and ultrasonographic variables obtained at the time of preliminary evaluation before and after the attempted external cephalic version. Labor and delivery data were obtained by chart review when patients were delivered in our hospital or through a questionnaire sent back by the referring physician when the patient came from an outlying location.
Our protocol has been previously published.10–11 Briefly, inclusion criteria were a singleton live pregnancy with breech presentation at 36 weeks or more of gestational age with no major anomalies, normal growth measurements, and no history of abruptio placentae or abnormal placental implantation. Patients with severe oligohydramnios (amniotic fluid index less than 5 cm) were excluded from the procedure. They had to have a normal reactive fetal heart rate and a mobile breech. Breech mobility was defined as the possibility to elevate the fetal presentation from the maternal pelvis through suprapubic pressure but not by vaginal manipulation. Women in active labor or with any contraindication to vaginal delivery were excluded from the external cephalic version program. Patients referred to our center for external cephalic version who met inclusion criteria and who had complete demographic, ultrasonographic, and hematologic data recorded are included in this study. Patients were managed according to the following scheme: a medical and obstetric history was obtained, then a physical evaluation including breech mobility assessment was performed, followed by a complete ultrasound evaluation including fetal biometry, placental position and grade, amniotic fluid index, and type of breech presentation. After informed consent, fetal well-being was assessed by nonstress test or biophysical profile in cases of nonreactive fetal heart rate. An intravenous line was initiated, and a sample of blood was obtained for a Kleihauer-Betke test.12 A uterine activity inhibiting agent (either ritodrine or magnesium sulfate) was initially used for all patients. Since 1996, it has been used only for nulliparous patients after the publication of our study showing the ineffectiveness of ritodrine in parous women.10 External cephalic version was attempted for a maximum of three times. After abdominal manipulations, a nonstress test was repeated. Upon the end of the nonstress test, another blood sample for Kleihauer-Betke test was obtained. No women received any type of analgesia or anesthesia during the procedure.
The Kleihauer-Betke tests were performed by the hematology laboratory of our institution and processed according to the following standardized procedure12–15: a thin smear of maternal oxalated venous blood was prepared on a clean glass slide and air dried for 10 minutes. Slides were then fixed by covering them with 80% ethanol for 5 minutes, rinsed thoroughly in tap water and then air dried. Slides were immersed in citrate-phosphate buffer in a 37°C incubator for 5 minutes with agitation at 1 and 3 minutes. Slides were rinsed again in tap water and dried. Staining was performed for 3 minutes with acid hematoxylin, followed by a step of water rinse and then staining again for 4 minutes in eosin. After the final rinse, slides were dried and covered with cover glasses. The resulting slides were then reviewed under high magnification (400x) and adult F cells and fetal cells were distinguished by intensity and intracellular distribution of the pink staining. The pale, eluted adult erythrocytes and slightly pink adult F cells were classified as negative. Positive, negative, and a mixed sample of 50% cord blood and 50% adult blood controls were run with each test to assess the accuracy of the technique. The estimation of fetal blood volume was initially calculated by the equation: “Number of fetal erythrocytes per 15 high power fields divided by two” as suggested by Mollison as a screening procedure.15 When the estimated blood volume was more than 4 mL, the modified Kleihauer-Betke equation was used: “1,800 (volume of maternal erythrocytes) x ratio fetal/adult erythrocytes x 4/3 (correction factor).” This correction factor was proposed by Mollison to allow for the fact that not all fetal cells retain their hemoglobin during the preparation of the smear. In our laboratory, the limit of quantifiable detectability was reported to be 1.0 mL of fetal blood, and a Kleihauer-Betke test result less than 1.0 mL of fetal blood was reported as “rare fetal erythrocytes.” For the purpose of the study, we considered significant any increase greater than 50% or greater than 5 mL of the estimated fetal blood volume for women with fetomaternal hemorrhage detectable before the procedure.13
No sample size was originally calculated. The original goal of this study was to ensure adequate quality assessment of the external cephalic version program established in our center. The SPSS 13.0 software (SPSS Inc., Chicago, IL) was used for statistical analysis. Dichotomous data were evaluated by χ2 test, and continuous data were analyzed by Mann-Whitney U test. Significance was set at a P<.05.
Between 1987 and 2001, external cephalic version was attempted on 1,426 pregnant women at 36 weeks of gestation or more. A Kleihauer-Betke test result was available for both samples collected before and after external cephalic version on 1,311 patients. The remaining 115 patients did not significantly differ in terms of maternal age, maternal body mass index, gestational age, placental location, number of external cephalic version attempts, and in the rate of successful external cephalic version. None had an emergency cesarean or reported complication secondary to the procedure. The main reason for the unavailability of data were an inadequate sampling or laboratory procedure. Data for women who refused the procedure or for those who did not meet inclusion criteria was not collected.
As depicted in Figure 1, of the 1,311 women included in our cohort, 1,244 (94.9%, 95% confidence interval [CI] 93.7–96.1%) had no fetal erythrocytes detected from the peripheral blood before the procedure (negative Kleihauer-Betke test). Of them, 30 (2.4%, 95% CI 1.6–3.3%) converted to a positive Kleihauer-Betke test after external cephalic version, including 20 (1.6%, 95% CI 0.9–2.3%) with a Kleihauer-Betke test reported as “rare fetal erythrocytes”; 10 (0.8%, 95% CI 0.3–1.3%) with an estimated fetomaternal hemorrhage volume greater than 1 mL and only one (0.08%, 95% CI 0–0.24%) with an estimated fetomaternal hemorrhage volume greater than 30 mL (the patient had an estimated fetomaternal hemorrhage of 80 mL). From the 67 (5.1%, 95% CI 3.9–6.3%) women with identified fetal erythrocytes from peripheral blood before the procedure (positive Kleihauer-Betke test), 42 (3.2%, 95% CI 2.3–4.2%) had an estimated fetomaternal hemorrhage volume more than 1 mL and 2 (0.2%, 95% CI 0–0.37%) had an estimated fetomaternal hemorrhage volume larger than 30 mL before the procedure. However, none of those 67 women had a fetomaternal hemorrhage related to the procedure (fetomaternal hemorrhage after external cephalic version minus fetomaternal hemorrhage before external cephalic version) greater than 30 mL, and 15 of them who had a Kleihauer-Betke test reported as “rare fetal erythrocytes” before the procedure had a negative Kleihauer-Betke test after the procedure.. Overall, there was an absolute increase in the rate of positive Kleihauer-Betke test from 5.1% (67 cases) to 6.3% (82 cases).
Women who converted from negative to positive Kleihauer-Betke test were compared with those with a preprocedure and postprocedure negative Kleihauer-Betke test for factors that could be associated with the transfusion of fetal blood to the maternal circulation (Table 1). No factors were found to be significant. However, despite the small number of patients positive for fetomaternal hemorrhage, an anterior placenta approached the level of significant difference with a P=.11. The same comparisons were applied for the selected group of women demonstrating a fetomaternal hemorrhage greater than 1 mL to those with a preprocedure and postprocedure negative Kleihauer-Betke test, but no significant difference was found. The only patient with an estimated fetomaternal hemorrhage volume greater than 30 mL (estimated fetomaternal hemorrhage of 80 mL) had a successful external cephalic version at 37 weeks gestation after a single attempt. She had a posterior grade 2 placenta, and her amniotic fluid index was 7.5 cm. The procedure was described as uneventful.
We conducted a univariable analysis of factors that could be thought of as related to a positive Kleihauer-Betke test before the external cephalic version procedure. We found that women with a positive Kleihauer-Betke test before the procedure were not different in term of maternal age, parity, gestational age, anterior placentation, and amniotic fluid index.
From this large cohort study of women who underwent an external cephalic version with collection of blood for Kleihauer-Betke test before and after the procedure, we found the following: 1) approximately 3% of women between 36 and 41 weeks of gestation with breech fetuses had a positive Kleihauer-Betke test with an estimated fetomaternal hemorrhage volume greater than or equal to 1.0 mL regardless of the performance of external cephalic version, 2) approximately 0.8% of women with a negative Kleihauer-Betke test before external cephalic version showed evidence of fetomaternal hemorrhage greater than or equal to 1.0 mL after the procedure, 3) approximately 0.1% of women undergoing external cephalic version had an estimated fetomaternal hemorrhage larger than 30 mL of fetal blood that could be directly related to external cephalic version, 4) no clinical or ultrasonographic parameters seemed to be a predictor of significant fetomaternal hemorrhage.
Our results are in agreement with several studies with reported rates of fetomaternal hemorrhage from 1% to 28% and fetomaternal hemorrhage greater than 1 mL from 0% to 2% of external cephalic version procedures.5–9 Among them was Marcus et al,5 who, from 100 attempted external cephalic version cases, reported six instances (6%) of increased volume of fetal erythrocytes detected before and after the external cephalic version. Of note, only one (1%) was diagnosed with a fetomaternal hemorrhage greater than 1 mL (6 mL), and the average fetomaternal hemorrhage was estimated at 0.4 mL of fetal blood for the five others. Kleihauer-Betke test results were not reported for the 94 women with no significant increase in the amount of fetal erythrocytes. Of 100 women who underwent external cephalic version, Nord et al7 reported one (1%) case of positive Kleihauer-Betke test before the procedure, followed by two negative Kleihauer-Betke tests after the procedure; three cases of positive Kleihauer-Betke test before and after the procedure without increase in the amount of fetal erythrocytes; and finally two cases of negative Kleihauer-Betke test followed by positive Kleihauer-Betke test after the procedure, including one case with an estimated fetomaternal hemorrhage less than 0.1 mL and one case with an estimated fetomaternal hemorrhage of 0.2 mL. They did not report any case of fetomaternal hemorrhage greater than 0.2 mL. Gjøde et al6 reported 14 (28%) cases of fetomaternal hemorrhage in 50 women who underwent external cephalic version. In all cases the estimated fetomaternal hemorrhage volume related to the procedure was between 0.1 mL and 1.5 mL. In a recent literature review, Ghidini and Korker9 reported a rate of 2.4% of positive Kleihauer-Betke tests after external cephalic version from seven studies, including a total of 664 patients. However, in most of these studies, Kleihauer-Betke test was not performed before the procedure and therefore few conclusions can be drawn.
The most important limitation of our study is directly related to the limits of the Kleihauer-Betke test technique during the third trimester of pregnancy. The Kleihauer-Betke test has been shown to have an interobserver and intraobserver variability mainly when the volume of fetal erythrocyte is low.16,17 However, manual Kleihauer-Betke test has been shown to be reasonably accurate and comparable to automated methods for fetal blood volume estimation when it is greater than 0.001% (approximately 5 mL).15 Therefore, we believe that our reported rate of women with a feto-hemorrhage greater than 30 mL of 0.1% is a true estimate of this risk. Finally, it is possible that such factors as ABO incompatibility and/or antepartum immune globulin given at 28 weeks to Rh-negative patients could have modified the results of Kleihauer-Betke test. However, we believe that such effect is minimized by the fact that blood was drawn shortly after the external cephalic version.
In conclusion, we believe that women can be reassured about the risk of fetomaternal hemorrhage during external cephalic version. It remains rare, and it is not related to placental location, fetal estimated weight, or the occurrence of fetal heart deceleration during the procedure. Our results demonstrate that a fetomaternal hemorrhage larger than 30 mL during external cephalic version procedure is a very rare occurrence. Consequently, we believe that the performance of routine testing for fetal erythrocytes in maternal blood is unwarranted after an uneventful external cephalic version. Standard accepted clinical indications for the Kleihauer-Betke test should remain the same. Moreover, we consider that our reported incidence and amount of external cephalic version–related fetomaternal hemorrhage is so low that sensitization should be prevented by the standard 300 micrograms of Rh-immune prophylaxis already routinely given in North America at 28 weeks of gestation and postpartum. Because 300 micrograms of Rh-immune globulin protects against 30 mL of Rh-positive blood and has a half-life of about a month, adding another dose of Rh-immune globulin does not seem to be necessary.
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Figure. No caption available.