Is tocolysis safe in the management of third-trimester bleeding?

OBJECTIVE: Expectant management is among the current treatment options for pregnancies complicated by third-trimester bleeding at <36 weeks' gestation. The use of tocolytic agents to stop associated contractions is still somewhat controversial, however, and the number of cases reported to date is small. The purpose of our study was to find a large number of cases of preterm third-trimester bleeding that was treated with tocolytic agents and evaluate them for any evidence of potential harm related to the use of these agents. STUDY DESIGN: Every case of third-trimester bleeding for a 6-year period was obtained from a perinatal database that was created as patients were hospitalized. Only cases of patients with onset of bleeding between 23 and 36 weeks' gestation were analyzed. Data collected included the gestational age at the time of first bleeding, the gestational age at delivery, whether tocolytic agents were used, the need for transfusion, maternal morbidity, and neonatal outcome. RESULTS: A total of 236 cases, consisting of 131 cases of abruptio placentae and 105 cases of placenta previa, met the study criteria. In the abruptio placentae group 95 women (73%) were treated with tocolytic agents. In this group the mean gestational age at the time of first bleeding was 28.9 weeks, the mean time from bleeding until delivery was 18.9 days, the median time from bleeding until delivery was 7 days, and the neonatal mortality rate was 51 deaths/1000 live births. In the placenta previa group 76 patients (72%) were treated with tocolytic agents. In this group the mean gestational age at first bleeding was 29.5 weeks, the mean time from bleeding until delivery was 29.3 days, the median time from bleeding until delivery was 22 days, and the neonatal mortality rate was 39 deaths/1000 live births. In both groups the need for transfusion and the incidence of fetal distress were not increased by the use of tocolytic agents. Among the 171 combined patients who underwent tocolysis, no maternal morbidity related to the tocolytic agents was found and no stillbirths occurred after admission. The neonatal deaths were all related to complications of prematurity. CONCLUSIONS: This is the largest series to date evaluating the use of tocolytic agents in preterm patients with third-trimester bleeding. From these data there does not appear to be any increased morbidity or mortality associated with tocolytic agent use in a controlled tertiary setting. A prospective randomized trial would be necessary to determine whether tocolytic use carries any benefits.

Prenatal genotyping of the Duffy blood group system by allele-specific polymerase chain reaction.

Maternal allo-immunization to antigens of the Duffy blood group system can result in haemolytic disease of the newborn (HDN), therefore, the application of allele-specific polymerase chain reaction (ASPCR) for prenatal genotyping of the Duffy antigen system to identify pregnancies at risk for HDN was evaluated. Oligonucleotide primers were designed for ASPCR of FYA, FYB and nullFY alleles. A validation study was performed using DNA isolated from 94 serotyped whole blood samples and 8 amniocentesis samples. A concordance rate of 100 per cent was observed between serotyping and ASPCR detection of the FYA, FYB and nullFY alleles. This assay is particularly useful for rapid genotyping of fetal amniotic cells to identify pregnancies at risk for HDN due to maternal fetal incompatibilities within the Duffy blood group system.

Prenatal genotyping of Jk(a) and Jk(b) of the human Kidd blood group system by allele-specific polymerase chain reaction.

An allele-specific polymerase chain reaction (ASPCR) assay for prenatal genotyping of the Kidd antigen system in order to identify pregnancies at risk for haemolytic disease of the newborn (HDN) was developed. Oligonucleotide primers were designed for ASPCR of JKA and JKB. A validation study was performed using DNA isolated from 54 serotyped whole blood samples and 8 amniocentesis samples. A concordance rate of 100 per cent was observed between serotyping and ASPCR detection of the JKA and JKB alleles. Experiments were conducted to quantify the maternal contamination that could be tolerated in Kidd ASPCR assays. The sensitivity of this assay ranged from 0.2 per cent when detecting the presence of JKB and JKA background, to 2 per cent for detecting the presence of JKA in a JKB background. This sensitive assay is particularly useful for rapid genotyping of fetal amniotic cells to identify pregnancies at risk for HDN due to incompatibilities within the Kidd blood group system.

Prolonged bedrest during pregnancy: does the risk of deep vein thrombosis warrant the use of routine heparin prophylaxis?

This is the first study to assess the risk of clinically apparent DVT in pregnant women placed in the hospital at prolonged bedrest. The outcome is discussed with reference to the risks associated with heparin. Information, including delivery data, length of hospital stay, and discharge diagnoses were extracted from a prospectively collected computerized data bank of all deliveries that occurred over a 5.5-year period at Long Beach Memorial Women's Hospital in Long Beach, California, and at St. Joseph's Hospital in Milwaukee, Wisconsin. One group consisted of all pregnant women who had been hospitalized at prolonged antepartum bedrest, as defined by 3 weeks or more. The other group consisted of the remaining population of women whose deliveries occurred during the same time period. There were 48,525 deliveries during the study period, and 266 (0.5%) women were hospitalized at prolonged antepartum bedrest. The mean number of days in the hospital for these women was 34.6 +/- 14 (range 21-82 days). Of these women, one received prophylactic heparin for a prior history of DVT. There were no cases of DVT in the 265 women who did not receive heparin, risk = 0.0 (CI = 0.00-0.99). Of these 265 women, 234 were hospitalized up to the day of delivery. Of these 234 women, 154 (65.8%) underwent cesarean section and no case of DVT occurred in the postoperative period, risk = 0.0 (CI = 0.0-1.7). Out of the remaining 48,259 women who were not hospitalized at prolonged bedrest, there were 18 cases of clinically apparent DVT, and the longest antepartum hospitalization was 4 days. A conservative risk of complications with prophylactic heparin therapy is 1.0% or greater. Although the risk of DVT in pregnant women hospitalized at prolonged bedrest is not zero, our study indicates that it is very low (< 1.0%). Whereas a risk of DVT of at least 1.0% could warrant heparin prophylaxis, even with 265 patients at prolonged bedrest and 48,525 controls, this risk could not be demonstrated. Using a power analysis with an alpha of 0.05 and a power of 80% to demonstrate this risk, one would need 247 cases and approximately 49,000 controls, which were clearly achieved in this study. In view of the risks associated with heparin, routine antenatal prophylaxis is not recommended unless other risk factors for DVT are present.

The sensitivity of allele-specific polymerase chain reaction can obviate concern of maternal contamination when fetal samples are genotyped for immune cytopenic disorders.

OBJECTIVE: Fetuses at risk for immune cytopenic disorders can be identified by molecular genotyping assays. To better understand the impact of maternal contamination on genotyping results, the levels of contamination that are routinely encountered during prenatal testing of fetal samples and the sensitivity of allele-specific polymerase chain reaction in detecting paternal alloalleles were examined. STUDY DESIGN: Reconstitution experiments were performed to define the sensitivity of allele-specific polymerase chain reaction assays. The sensitivities of allele-specific polymerase chain reactions and polymerase chain reaction-restriction fragment length polymorphism were compared for detection of the factor V Leiden mutation. RESULTS: A quantitative analysis of variable-number tandem repeat loci revealed maternal contamination in 4 of 56 fetal samples. Contaminating deoxyribonucleic acid compromised genotyping results when it comprised between 94% and 99% of the total deoxyribonucleic acid. Allele-specific polymerase chain reaction was found to be the more sensitive technique (0.8% sensitivity vs 13% sensitivity). CONCLUSION: These results illustrate that allele-specific polymerase chain reaction is well suited for reliable prenatal identification of fetuses at risk of immune cytopenic disorders.

Antepartum fetal surveillance in patients with diabetes: when to start?

OBJECTIVE: Although antepartum fetal well-being testing is an accepted practice in the management of diabetic patients, there are few data suggesting when to start. Our goal was to examine when testing should be started in the pregnant diabetic woman. STUDY DESIGN: Antepartum test results and patient histories were prospectively collected on all diabetic pregnancies from January 1981 through December 1991. The data were retrospectively analyzed for when fetal compromise became evident. Fetal compromise was defined as stillbirth, first positive contraction stress test, or intervention because of an abnormal antepartum fetal test result. RESULTS: Six hundred fourteen patients were enrolled in the study. There were three stillbirths, 45 (7.4%) patients had at least one positive contraction stress test, and 71 (11.6%) patients were delivered because of an abnormal fetal test result. Those with early compromise (< or = 34 weeks' gestation) could not be identified solely by diabetic class. The majority of patients (73%) requiring early intervention because of an abnormal test were class R or F diabetic patients with a growth-retarded fetus or were patients who had a concomitant diagnosis of hypertension. CONCLUSIONS: Class R or F diabetic patients or diabetic patients with a growth-retarded fetus or a concomitant diagnosis of hypertension may require testing to be started as early as 26 weeks' gestation. Otherwise, testing may be safely delayed until 32 weeks' gestation.

Cocaine intoxication presenting as preeclampsia and eclampsia.

OBJECTIVE: To relate the clinical presentation of acute cocaine intoxication in the third trimester to preeclampsia and eclampsia. METHODS: Eleven women presented to Long Beach Memorial Women's Hospital and the University of California, Irvine Medical Center with hypertension and clinical symptoms of headache, blurred vision, abdominal pain, or seizures in the third trimester of pregnancy. Each had a positive urine drug screen for cocaine. The laboratory evaluation for preeclampsia included a complete blood count, platelet count, uric acid, aspartate aminotransferase, alanine aminotransferase, creatinine, and urine for protein content. RESULTS: All women had a diastolic blood pressure of at least 90 mmHg, which returned to the normal range 45-90 minutes after admission. Each presented with one or more symptoms associated with preeclampsia, which ultimately improved as the drug wore off. In addition, all laboratory evaluations for preeclampsia were negative. CONCLUSION: If a patient presents in the third trimester with hypertension and clinical symptoms of preeclampsia that rapidly improve shortly after admission, cocaine intoxication should be considered as the possible source.

How frequently should the amniotic fluid index be repeated?

OBJECTIVE: Our objective was to determine the most appropriate interval for assessing amniotic fluid volume with amniotic fluid index. STUDY DESIGN: In a retrospective analysis amniotic fluid indexes performed every 3 to 4 days in antepartum testing patients were compared with their follow-up values. Of 10,742 amniotic fluid indexes there were 7393 with follow-up values within 4 days. The results were stratified by current amniotic fluid index, gestational age, and concurrent nonstress test results. The groups were compared with chi 2 analysis. RESULTS: Patients with normal amniotic fluid index (> or = 8 cm) had a 0.54% chance of oligohydramnios developing in the next 4 days. Those patients with low normal amniotic fluid indexes (5 to 8 cm) had a 5% chance of oligohydramnios developing within the next 4 days, and patients with low amniotic fluid indexes (< or = 5 cm) had a 59% chance of persistent oligohydramnios 4 days after the index examination. Subdividing by gestational age demonstrated that patients > or = 41 weeks' gestation had a 2.6% chance of oligohydramnios developing within 4 days if current amniotic fluid index was between 8 and 15 cm. Results of concurrent fetal heart rate findings did not appear to change the risk for development of oligohydramnios. CONCLUSION: In patients < 41 weeks' gestation with normal amniotic fluid indexes, a repeat amniotic fluid index is not necessary for 7 days.

Antepartum testing in the hypertensive patient: when to begin.

Antepartum testing has been recommended for patients whose pregnancies are complicated by hypertension. Although this is considered accepted practice, there are little data available to help the clinician know when to start testing. To help answer this question in patients with chronic hypertension and nonproteinuric pregnancy-induced hypertension, we reviewed the results of all antepartum tests between 1976 and 1987 in patients with these diagnoses. The primary mode of surveillance in the majority of our patients was the contraction stress test. We determined when patients first had positive contraction stress test results and when intervention occurred because of an abnormal antepartum test result. There were a total of 917 patients tested with these diagnoses. Fifty-three (5.8%) of these patients had at least one positive contraction stress test result. Twenty-two patients were delivered of infants before 35 weeks' gestation because of abnormal antepartum test results. Those with early intervention (less than 35 weeks' gestation) could not be differentiated from those with later intervention (greater than or equal to 35 weeks' gestation) by maternal age, diastolic blood pressure, or systolic blood pressure at the time of testing. The majority of patients who were delivered of infants before 35 weeks' gestation had a concomitant diagnosis of systemic lupus erythematosus, intrauterine growth retardation, diabetes mellitus, or superimposed preeclampsia. On the basis of when compromise was evident, patients with these diagnoses may require testing to be started as early as the fetus is considered viable. However, in those without these diagnoses, the clinician may delay the beginning of testing until 33 weeks' gestation without significant risk of pregnancy loss before testing.

Comparison of a rapid enzyme-linked immunosorbent assay test and the Gram stain for detection of group B streptococcus in high-risk antepartum patients.

Early-onset neonatal sepsis with group B streptococci is a major problem in the management of high-risk obstetrics. Intrapartum treatment of the colonized mother reduces neonatal acquisition; however, many high-risk patients are delivered before culture results are available. This study prospectively evaluated a new enzyme-linked immunosorbent assay and the Gram stain for their accuracy in rapid detection of group B streptococci in 131 high-risk patients. Twenty positive cultures for group B streptococci were identified in the study population and were used as the control for test comparisons. The enzyme-linked immunosorbent assay test was 60% sensitive, whereas the Gram stain was 45% sensitive. The enzyme-linked immunosorbent assay showed an increase in sensitivity as the colony count increased; however, two cases of severe neonatal sepsis occurred in patients with low colony counts and both had enzyme-linked immunosorbent assay negative results. In conclusion, the need for a rapid sensitive test for group B streptococci detection still exists.

The contraction stress test.

The contraction stress test has long been used to assess fetal wellbeing in the antepartum period. The CST continues to be a valuable tool for practicing obstetricians when interpreted and managed according to previously published guidelines. More recent data have further defined the level of compromise at which the CST becomes abnormal. When compared to similar reports using the NST or biophysical profile, we are better able to define the capabilities of these various antepartum testing methods. Consequently, we were able to align antepartum testing schemes for the specific clinical situation as opposed to using one method for all patients.

Maternal serum alpha-fetoprotein and fetal triploidy.

Fetal triploidy is commonly found in early pregnancy. The majority of these pregnancies spontaneously abort in the first trimester. Occasionally, the pregnancy progresses to the second and third trimesters. We reviewed the maternal serum alpha-fetoprotein (MSAFP), amniotic fluid alpha-fetoprotein (AFP), amniotic fluid acetylcholinesterase (ACHE), fetal pathology, and placental pathology in sex second-trimester pregnancies complicated by fetal triploidy. Four of these patients had MSAFP values greater than 7.5 multiples of the median (MoM). Five of six pregnancies had MSAFP values greater than 2.25 MoM. All five of these patients had a partial mole. Four patients had amniotic fluid AFP values greater than 2.0 MoM. Two fetuses had associated neural tube defects. These were the only patients with positive amniotic fluid ACHE. None of the other patients had fetuses with anomalies that are known to be associated with an elevated MSAFP. The elevated MSAFP appeared to be related to the presence of a partial mole. Two of the five cases with an MSAFP greater than 2.25 MoM did not have sonographic evidence of a significant anomaly. Therefore, karyotyping can be of benefit in evaluating patients with elevated MSAFP.

Ultrasound findings in pregnancies complicated by fetal triploidy.

Antepartum ultrasound scans of seven pregnancies complicated by fetal triploidy were reviewed. Estimated gestational age (EGA) by ultrasound lagged EGA by last menstrual period in six of seven patients. Normal interval growth of biparietal diameter in the second trimester was demonstrated in all fetuses that had serial scans. Sonographic features commonly associated with fetal triploidy; such as oligohydramnios and cephalocorporal disproportion, were seen in only two cases. Fetal anomalies were evident by ultrasound in five of seven patients. Six of seven patients had partial moles. All of these patients had placentas that appeared abnormal. The ultrasound appearance of the placenta, however, was not the same with each case. Therefore, sonographic features of pregnancies complicated by fetal triploidy are not uniform and the diagnosis cannot be made by ultrasound alone.

Controlled trial of hydration and bed rest versus bed rest alone in the evaluation of preterm uterine contractions.

Patients who are seen with uterine contractions but without documented change in cervical dilation or effacement are often treated with intravenous hydration before the initiation of intravenous tocolytic therapy. This is done with the intention of stopping uterine activity in patients with false preterm labor. A prospective randomized study was conducted to evaluate the effect of hydration on preterm uterine contractions in patients without proved preterm labor. A total of 28 patients were treated with bed rest and an intravenous bolus and subsequent continuous infusion of 5% dextrose in lactated Ringer's solution. A control group of 20 patients were treated with bed rest alone. Uterine activity and arrest of uterine contractions were compared between the two groups. Contractions stopped in 54% of the patients treated with hydration, whereas contractions stopped in 40% of the patients in the control group. This difference was not statistically significant. As a crossover study, those in the control group with contractions that continued after the initial observation period were subsequently treated with intravenous fluids. Only one patient in this group stopped contracting. Of all patients whose contractions with either therapy, 18% eventually were delivered of preterm infants. This included 20% of the hydration group and 14% of the control group. The use of hydration as a pretherapy indicator to differentiate true preterm labor from false preterm labor could not be supported by this study. In addition, patients whose contractions stopped with either hydration or bed rest are at increased risk of subsequent preterm delivery.