Delayed-interval delivery: extended series from a single maternal-fetal medicine practice.

OBJECTIVE: Our purpose was to review the extended experience of a single maternal-fetal medicine practice with delayed-interval delivery. STUDY DESIGN: We completed a retrospective review of our maternal-fetal medicine practice database from January 1991 through March 1999. Patients were derived from both primary and consultative practices. All patients were managed with tocolysis, antibiotics, and cerclage after delivery of the first fetus(es). Retained siblings were investigated by amniocentesis to exclude intra-amniotic infection. RESULTS: Twenty-four consecutive patients had attempted delayed-interval delivery. Exclusion criteria for delayed-interval delivery included monochorionicity, abruptio placentae, severe preeclampsia, and the need for hysterotomy. The mean latency interval was 36 days, with a range of 3 to 123 days. Additionally, patients with previous cerclage(s) had significantly shorter mean latency intervals than patients without previous cerclage(s). Patients with long latency intervals (> or =49 days) had earlier births of the first fetus. CONCLUSION: Selected multichorionic pregnancies may benefit from delayed-interval delivery. Patients with previous cervical cerclage(s) during the index pregnancy are less likely to achieve significant latency intervals. Even modest intervals between births of siblings at critical gestational ages can improve neonatal survival and decrease neonatal morbidity.

A multicenter controlled trial of fetal pulse oximetry in the intrapartum management of nonreassuring fetal heart rate patterns.

OBJECTIVE: Recent developments permit the use of pulse oximetry to evaluate fetal oxygenation in labor. We tested the hypothesis that the addition of fetal pulse oximetry in the evaluation of abnormal fetal heart rate patterns in labor improves the accuracy of fetal assessment and allows safe reduction of cesarean deliveries performed because of nonreassuring fetal status. STUDY DESIGN: A randomized, controlled trial was conducted concurrently in 9 centers. The patients had term pregnancies and were in active labor when abnormal fetal heart rate patterns developed. The patients were randomized to electronic fetal heart rate monitoring alone (control group) or to the combination of electronic fetal monitoring and continuous fetal pulse oximetry (study group). The primary outcome was a reduction in cesarean deliveries for nonreassuring fetal status as a measure of improved accuracy of assessment of fetal oxygenation. RESULTS: A total of 1010 patients were randomized, 502 to the control group and 508 to the study group. There was a reduction of >50% in the number of cesarean deliveries performed because of nonreassuring fetal status in the study group (study, 4. 5%; vs. control, 10.2%; P =.007). However, there was no net difference in overall cesarean delivery rates (study, n = 147 [29%]; vs. control, 130 [26%]; P = .49) because of an increase in cesarean deliveries performed because of dystocia in the study group. In a blinded partogram analysis 89% of the study patients and 91% of the control patients who had a cesarean delivery because of dystocia met defined criteria for actual dystocia. There was no difference between the 2 groups in adverse maternal or neonatal outcomes. In terms of the operative intervention for nonreassuring fetal status, there was an improvement in both the sensitivity and the specificity for the study group compared with the control group for the end points of metabolic acidosis and need for resuscitation. CONCLUSION: The study confirmed its primary hypothesis of a safe reduction in cesarean deliveries performed because of nonreassuring fetal status. However, the addition of fetal pulse oximetry did not result in an overall reduction in cesarean deliveries. The increase in cesarean deliveries because of dystocia in the study group did appear to result from a well-documented arrest of labor. Fetal pulse oximetry improved the obstetrician's ability to more appropriately intervene by cesarean or operative vaginal delivery for fetuses who were actually depressed and acidotic. The unexpected increase in operative delivery for dystocia in the study group is of concern and remains to be explained.

Selective delivery in a twin gestation.

One or more infants of a multifetal pregnancy occasionally require delivery selectively because of in utero risk of fetal death in circumstances in which the sibling fetus appears well. At 26 weeks 5 days of gestation a small fundally placed twin in a dichorionic gestation had an estimated fetal weight of 650 g with decreased amniotic fluid and ominous Doppler velocity findings in his umbilical artery. A normally grown presenting sibling had reassuring fetal surveillance data. Over a 2-week interval the growth-restricted twin showed no growth, and his status deteriorated. He was selectively delivered by hysterotomy. Selective delivery may offer parents of multifetal gestations an additional option when 1 or more of their fetuses are at high risk for in utero death.

Delayed-interval delivery in multifetal pregnancy.

OBJECTIVE: Our goal was to review a single subspecialty practice experience with a uniform approach to delayed-interval delivery. STUDY DESIGN: A 66-month retrospective review of our maternal-fetal medicine practice database was completed. Fifty-nine sets of twins or triplets delivered at < 30 weeks' gestation were identified. No cases of twins or triplets who came to our care, either in consultation or as primary providers, were excluded. RESULTS: Forty-three patients were excluded as candidates for delayed-interval delivery because of monochorionicity, abruptio placentae, severe preeclampsia, and the need for hysterotomy. Sixteen pregnancies were identified as candidates for delayed-interval delivery, and we actually attempted to delay delivery in 9 of them. The details of the interval deliveries are summarized; there was a mean latency interval of 34 days with a range of 3 to 76 days. Pregnancies in which delayed-interval deliveries wer attempted were significantly less mature at the time of presentation than those managed by delivery of all infants initially. Perinatal mortality was significantly lower in the retained fetuses. CONCLUSIONS: This retrospective consecutive case review from a single maternal-fetal practice documents that selected multichorionic pregnancies may benefit from delayed-interval delivery. Modest intervals between siblings during critical gestational ages can improve newborn survival and decrease neonatal morbidity.

Pregnancy outcome following donor embryo replacement.

OBJECTIVE: To investigate the occurrence of adverse perinatal outcome among donor embryo pregnancies. STUDY DESIGN: Thirty-five pregnancies following donor embryo replacement were delivered between 1990 and 1994. Thirty-two pregnancies following standard in vitro fertilization (IVF) in women of 34 years of age or older were delivered during the same time period. All pregnancies meeting study criteria and who conceived through the same assisted reproductive technology program were included. Patients electing multifetal pregnancy reduction in either group were excluded. RESULTS: The patients were similar with regard to age and parity. There was no difference in the mean number of embryos transferred between the groups or between those conceiving singleton or multiple gestations. The occurrence of spontaneous abortion was 34% in the donor embryo group and 25% in the control IVF group. Of the continuing pregnancies, there was a trend toward more cesarean births in the donor embryo group, but it was not statistically significant. Birthweights and gestational ages also were not different between the groups. Preterm birth occurred in approximately one-third of the pregnancies in each group owing largely to the number of multiple gestations. The incidence of preeclampsia was 26% among donor embryo pregnancies and 29% among control group pregnancies. Adverse outcome defined as preterm birth with or without preeclampsia occurred in over one-third of the pregnancies in each group. CONCLUSION: There is no increase in adverse perinatal outcome among donor embryo pregnancies compared to age-like control IVF pregnancies. Modest increases in the occurrence of adverse outcome among such pregnancies cannot be excluded by the data in the current report.

Fetal cells in maternal blood: recovery by charge flow separation.

Fetal blood cells can be recovered from the maternal circulation by charge flow separation (CFS), a method that obviates the risks associated with amniocentesis and chorionic villus sampling. By CFS, we processed blood samples from 13 women carrying male fetuses, 2 carrying fetuses with trisomy 21, and 1 who had delivered a stillborn infant with trisomy 18. On average more than 2000 fetal nucleated red blood cells were recovered per 20-ml sample of maternal blood. Recovery of fetal cells was confirmed by fluorescence in situ hybridization with probes for chromosomes Y, 18 and 21. After culturing of CFS-processed cells, amplification by the polymerase chain reaction revealed Y-chromosomal DNA in clones from four of six women bearing male fetuses, but not in clones from three women bearing female fetuses.

Elevated protease activities in human amnion and chorion correlate with preterm premature rupture of membranes.

OBJECTIVES: The mechanism(s) of preterm premature rupture of fetal membranes resulting in preterm birth remains unknown. Studies suggest that fetal membranes are susceptible to weakening by protease attack and that collagenases may be active at the site of rupture. In this study fetal membranes from women delivered after preterm premature rupture of membranes were compared with control membranes and analyzed qualitatively and quantitatively for protease activities. STUDY DESIGN: Fourteen membranes from women with preterm premature rupture of membranes and nine membranes from women delivered preterm without premature rupture of membranes or otherwise normal women delivered at term vaginally or by cesarean section were studied. Zymogram gel electrophoresis with gelatin incorporation was used to assess the number and apparent molecular weights of protease activities. Functional and quantitative studies of protease activity were measured by fluorescent substrate cleavage. RESULTS: Zymogram gel electrophoresis studies demonstrated the presence of five to seven different protease bands in preterm premature rupture of membranes samples, whereas control membranes demonstrated only one to three protease bands. Fluorescent studies of protease activity demonstrated a 10- to 40-fold increase in activity in membranes from women with preterm premature rupture of membranes compared with normal control membranes. Studies with protease inhibitors suggest that most of the activity is due to metalloproteinases. CONCLUSION: In membranes from women with preterm premature rupture of membranes there appears to be a general increase in the amount of protease activity and increased numbers of putatively different proteases. Increased activity or deregulated protease control may mediate preterm premature rupture of membranes and be a potentially remediable cause of preterm birth.

Perinatal outcomes in the pregnancies of asthmatic women: a prospective controlled analysis.

Prior studies have found an increased incidence of adverse perinatal outcomes of pregnancies in asthmatic mothers, but these studies have been poorly controlled for asthma therapy and other confounding factors. The purpose of this study was to assess perinatal outcomes in actively managed pregnant asthmatic women as compared with matched nonasthmatic controls. Using an inception cohort design, we studied a volunteer sample of 486 pregnant (< 28 wk) women with documented asthma and 486 pregnant nonasthmatic controls with normal pulmonary function. Cases and controls were matched for age, smoking status, parity, and year of delivery. Asthma was managed with step therapy to prevent acute asthmatic episodes and asthma symptoms that interfered with sleep or normal activity. Chronic hypertension was significantly more common (p = 0.007) in asthmatic subjects (3.7%) than in matched controls (1.0%). However, no significant differences in incidences of preeclampsia, perinatal mortality, preterm births, low-birth-weight infants, intrauterine growth retardation, or congenital malformations were observed in the pregnancies of the asthmatic women as compared with the matched controls. Trends were observed toward relationships between more severe asthma requiring emergency therapy or corticosteroids and increased incidences of preeclampsia and low-birth-weight infants, but these associations were not statistically significant. These data suggest that the overall perinatal prognosis for women with actively managed asthma during pregnancy is comparable to that for the nonasthmatic population.

Palliative fetal surgery for diaphragmatic hernia.

Congenital diaphragmatic hernia is associated with a poor prognosis in spite of advances in antenatal detection and newborn care. Open fetal surgery has been suggested as a strategy for salvaging selected fetuses at high risk for pulmonary hypoplasia as a result of this lesion. We report a strategy for palliative fetal surgery with definitive repair postponed to the newborn period.

Rapid cytogenetic assessment of fetal blood samples.

OBJECTIVE: To obtain a timely fetal karyotype in selected circumstances by investigating the usefulness of fetal blood samples. METHODS: Forty-five patients had fetal blood sampling for a variety of abnormalities including hydrocephalus, oligohydramnios, fetal growth retardation, nonimmune hydrops, duodenal atresia, polyhydramnios, and multiple anomalies. Four cytogenetic techniques were attempted in determining fetal karyotype: a direct harvest of lymphocytes in the fetal blood sample, a 24-hour incubation of fetal lymphocytes without mitogen, and a 48- and 72-hour mitogen-stimulated incubation followed by harvest and analysis. RESULTS: Ten of these 45 cases showed diagnostic cytogenetic abnormalities. Twenty-nine cases had results reported within 30 hours of obtaining the specimen following analysis of unstimulated cultures. One-half of the abnormal results were reported within 30 hours of receiving the specimen. CONCLUSION: Unstimulated lymphocyte cultures from fetal blood samples may provide rapid cytogenetic diagnosis and alter obstetric management in selected circumstances.

Fixed mini-dose warfarin for prophylaxis of thromboembolic disease in pregnancy: a safe alternative for the fetus?

BACKGROUND: Fixed mini-dose warfarin has been used for thromboprophylaxis in high-risk nonpregnant patients with encouraging results. The usefulness of this strategy in pregnant women requires documentation of fetal safety. CASE: A woman with antithrombin III deficiency suffered a venous thrombosis during early pregnancy and could not be successfully managed long term with heparin. One milligram of warfarin daily was used for prophylaxis, and serial fetal blood samples were used to monitor the fetal coagulation status. No apparent coagulation abnormalities were demonstrated in the fetus at 33, 36, and 38 weeks' gestation. The woman suffered no further thromboses throughout the remainder of her pregnancy and puerperium. CONCLUSIONS: The efficacy of fixed mini-dose warfarin for prophylaxis in pregnancies at risk for thromboembolic disease will require further investigation. This fetus did not appear vulnerable to coagulation abnormalities as a consequence of the warfarin regimen.

Percutaneous, ultrasound-directed ablation of ectopic pregnancy with methotrexate. A report of three cases.

The early diagnosis of unruptured ectopic pregnancy has been facilitated by the availability of high-resolution ultrasound and sensitive quantitative assays for beta-human chorionic gonadotropin. Nonsurgical treatment of selected patients has been advocated. Three patients with fairly advanced unruptured ectopic pregnancies were treated with ablation with methotrexate using an ultrasound-directed, percutaneous technique. That approach appears to be reasonable and safe in selected patients, though the subsequent reproductive performance is unknown.

Amniotic fluid glucose concentration as a marker for intra-amniotic infection.

This study evaluated the use of amniotic fluid (AF) glucose concentration as a rapid indicator of intra-amniotic infection. Amniotic fluid glucose concentrations were measured in 86 pregnancies and compared with AF cultures. There were 14 positive cultures with a mean AF glucose of 7.1 mg/dL (range 1-24) and 72 negative cultures with a mean AF glucose of 30.4 mg/dL (range 5-66), a significant difference (P less than .001). An AF glucose of less than or equal to 5 mg/dL had a positive predictive value of 90%; an AF glucose of greater than 20 mg/dL had a 98% negative predictive value. Amniotic fluid glucose can be obtained rapidly and inexpensively, and may be of use in the diagnosis of intra-amniotic infection.

Multifetal reduction of triplets and pregnancy outcome.

Multifetal pregnancy reduction has been suggested as a strategy to improve pregnancy outcome in grand multiple gestations of three or more fetuses. We prospectively investigated multifetal pregnancy reduction in 13 women with triplet pregnancies in the first trimester following ovulation induction, in vitro fertilization, or gamete intrafallopian transfer procedures. Eleven women whose triplet pregnancies followed similar reproductive technologies and who declined or were not offered the procedure were managed expectantly. Mean (+/- standard deviation) infant birth weight was 2227 +/- 478 g in the multifetal reduction group and 2239 +/- 399 g in the group managed expectantly. Gestational age was 35.5 +/- 2.3 weeks in the study group and 35.7 +/- 2.5 weeks in the triplets managed expectantly. Newborn hospital days as well as newborn and maternal complications were not statistically different between the management groups. Maternal interventions included tocolytic medication, home uterine activity monitoring, and extended hospitalization, and were more common in the triplets managed expectantly than in the study group of triplets reduced to twins. Multifetal pregnancy reduction for triplet pregnancies does not necessarily improve pregnancy outcome, though it may be offered on the basis of parental choice.

Occlusion of umbilical artery in acardiac, acephalic twin.

In the acardiac, acephalic twin malformation the normal co-twin is put at risk because of the extra cardiac work-load. Surgical procedures may be hazardous to the mother. We describe a novel approach--the insertion of a helical metal coil to induce thrombosis in the umbilical artery of the acardiac twin--which immediately interrupted flow. The co-twin was delivered at 39 weeks and his neonatal course has been normal.

Antenatal phenobarbital for the prevention of periventricular and intraventricular hemorrhage: a double-blind, randomized, placebo-controlled, multihospital trial.

To determine whether the neuroprotective properties of phenobarbital would alter the incidence and severity of intracranial hemorrhage in premature infants, we randomly assigned 110 women at less than 31 weeks of gestation to receive 10 mg/kg phenobarbital or placebo in a blinded fashion before delivery. Infants were examined postnatally with real-time ultrasonography for evidence of intracranial hemorrhage. Maternal demographics, pregnancy complications, antenatal management, and route of delivery did not differ between the phenobarbital group (n = 50) and the placebo group (n = 60). The total incidence of periventricular-intraventricular hemorrhage did not differ between the phenobarbital-treated (n = 54) and the placebo-treated (n = 67) infants. However, the frequency of grade 3 and grade 4 hemorrhages was 15% (10 infants) in the placebo group and 3.7% (2 infants) in the phenobarbital group (p less than 0.05). There were no differences in the severity of associated conditions in the babies to explain the difference in the incidence of severe hemorrhage between the study groups. We conclude that antenatal administration of phenobarbital appears to be effective in decreasing the severity of periventricular-intraventricular hemorrhage in infants delivered at less than 31 weeks of gestation.