Carbon Dioxide-Based versus Saline Tissue Expansion for Breast Reconstruction: Results of the XPAND Prospective, Randomized Clinical Trial.

BACKGROUND: AeroForm is a new type of remote-controlled, needle-free, carbon dioxide-based expander involving a potentially faster method of tissue expansion. Results are presented here from the AirXpanders Patient Activated Controlled Tissue Expander pivotal trial comparing AeroForm to saline tissue expanders. METHODS: Women undergoing two-stage breast reconstruction were randomized at 17 U.S. sites in this U.S. Food and Drug Administration-approved investigational device exemption trial. Expansion in the investigational arm was performed by the patient in 10-cc increments up to 30 cc/day of carbon dioxide and in the control arm by the physician with periodic bolus injections of saline. Safety endpoints, expansion and reconstruction times, pain, and satisfaction were assessed. RESULTS: One hundred fifty women were treated: 98 with carbon dioxide expanders (n = 168) and 52 with saline expanders (n = 88). The treatment success rate (all breasts exchanged successfully excluding non-device-related failures) was 96.1 percent for carbon dioxide and 98.8 percent for saline. Median time to full expansion and completion of the second-stage operation was 21.0 and 108.5 days (carbon dioxide) versus 46.0 and 136.5 days (saline), respectively, with a similar rate of overall complications. Ease of use for the carbon dioxide expander was rated high by patients (98 percent) and physicians (90 percent). CONCLUSIONS: The AirXpanders Patient Activated Controlled Tissue Expander trial results demonstrate that a carbon dioxide-based expander is an effective method of tissue expansion with a similar overall adverse event rate compared to saline expanders, and provides a more convenient and expedient expansion. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Maintaining quality assurance for sonographic nuchal translucency measurement: lessons from the FASTER Trial.

OBJECTIVE: To evaluate nuchal translucency measurement quality assurance techniques in a large-scale study. METHODS: From 1999 to 2001, unselected patients with singleton gestations between 10 + 3 weeks and 13 + 6 weeks were recruited from 15 centers. Sonographic nuchal translucency measurement was performed by trained technicians. Four levels of quality assurance were employed: (1) a standardized protocol utilized by each sonographer; (2) local-image review by a second sonographer; (3) central-image scoring by a single physician; and (4) epidemiological monitoring of all accepted nuchal translucency measurements cross-sectionally and over time. RESULTS: Detailed quality assessment was available for 37 018 patients. Nuchal translucency measurement was successful in 96.3% of women. Local reviewers rejected 0.8% of images, and the single central physician reviewer rejected a further 2.9%. Multivariate analysis indicated that higher body mass index, earlier gestational age and transvaginal probe use were predictors of failure of nuchal translucency measurement and central image rejection (P = 0.001). Epidemiological monitoring identified a drift in measurements over time. CONCLUSION: Despite initial training and continuous image review, changes in nuchal translucency measurements occur over time. To maintain screening accuracy, ongoing quality assessment is needed.

Post-splenectomy splenic artery aneurysm rupture in an atypical presentation of pre-eclampsia.

Splenic artery aneurysm rupture in pregnancy is an uncommon catastrophic event. We report a patient who presented at 15 3/7 weeks with atypical pre-eclampsia. After termination was recommended, the patient chose to continue the pregnancy. Reversal of clinical and laboratory abnormalities occurred and the patient was discharged. The patient presented again at 24 weeks with severe pre-eclampsia and residual splenic artery aneurysm rupture, at the site of a splenectomy that had been performed 24 years previously.

Are women who are Jehovah's Witnesses at risk of maternal death?

OBJECTIVE: The purpose of this study was to determine the rates of obstetric hemorrhage and maternal mortality in women who are Jehovah's Witnesses and to evaluate a protocol that uses erythropoietin to optimize the red blood cell mass before delivery. STUDY DESIGN: Obstetric outcomes were described for all of the women who were Jehovah's Witnesses and who delivered at Mount Sinai Medical Center during an 11-year period. The risk of maternal death was compared with our general obstetric population during this interval. RESULTS: A total of 332 women who were Jehovah's Witnesses had 391 deliveries. An obstetric hemorrhage was experienced in 6% of this population. There were 2 maternal deaths among the women who were Jehovah's Witnesses, for a rate of 512 maternal deaths per 100,000 live births versus 12 maternal deaths per 100,000 live births (risk ratio, 44; 95% CI, 9-211). Erythropoietin was associated with a nonsignificant increase in hematocrit level. CONCLUSION: Women who are Jehovah's Witnesses are at a 44-fold increased risk of maternal death, which is due to obstetric hemorrhage. Patients should be counseled about this risk of death, and obstetric hemorrhage should be aggressively treated, including a rapid decision to proceed to hysterectomy when indicated.

Initial fetal platelet counts predict the response to intravenous gammaglobulin therapy in fetuses that are affected by PLA1 incompatibility.

OBJECTIVE: Fetal alloimmune thrombocytopenia is the result of maternal fetal platelet antigen incompatibility; intracranial hemorrhage is its most serious complication. Our previous studies have demonstrated an inability to accurately predict fetal platelet counts in this disorder. The goal of the present investigation was to identify factors that would predict the response of the fetal platelet count to therapy so that use of fetal blood sampling could be minimized. STUDY DESIGN: Patients who were eligible for the study were all those who (1) had alloimmune thrombocytopenia secondary to Pl(A1) (HPA-1a, Zw(A)) platelet antigen incompatibility, (2) were treated with maternally administered intravenous immunoglobulin at 1 g/kg of body weight per week, with or without low dose steroids, and (3) had percutaneous fetal blood sampling before the initiation of therapy (first fetal blood sampling) and again 3 to 7 weeks afterwards (second fetal blood sampling). RESULTS: In this retrospective review, 74 patients who were affected by alloimmune thrombocytopenia had a median platelet count of 21,000 per microliter at the first fetal blood sampling and 47,000 per microliter at the second fetal blood sampling, with a median increase in platelet count of 24,000 per microliter. Response to treatment was defined as either (1) an improvement in platelet count (the second fetal blood sampling greater than the first fetal blood sampling, and second fetal blood sampling > 20,000 per microliter) or (2) a minimal decline in platelet count (the first fetal blood sampling > or = 40,000 per microliter and the difference between the first and second fetal blood sampling < or = 10,000 per microliter). The first fetal blood sampling had prognostic value for the second fetal blood sampling (P = .0001), although the previous sibling birth platelet count and history of sibling intracranial hemorrhage did not predict the platelet count at the first or second fetal blood sampling or the change in platelet count between the samplings. When the patients were segregated to first fetal blood sampling of > 20,000 per microliter versus < or = 20,000 per microliter, the response rates for the 2 groups were 89% (33/37 patients) versus 51% (19/37 patients; P = .001). CONCLUSION: In fetal alloimmune thrombocytopenia secondary to Pl(A1) platelet antigen incompatibility, fetuses with platelet counts > 20,000 per microliter at the initiation of therapy were predicted to maintain their platelet count at the second fetal blood sampling at > 20,000 per microliter. The characteristics of the previous sibling, as previously reported, did not predict the initial fetal blood sampling, the second fetal blood sampling, or the response to treatment.

Shortened gestational age following multifetal pregnancy reduction: can chronic placental inflammation be the explanation?

OBJECTIVE: This study tests the hypothesis that chronic inflammatory foci in the placentas of siblings that undergo multifetal pregnancy reduction are associated with shortened gestational length. METHODS: Among 446 patients who underwent multifetal pregnancy reduction (MPR), 56 delivered at Mount Sinai Hospital, 37 (66%) had their placentas referred to surgical pathology and 29 (78%) of the 37 patients had tissue sampled from the placenta of the reduced sibling. Slides were reviewed (by C.M.S.) blinded to clinical data. Lesions were diagnosed using previously published criteria. Specifically, inflammatory lesions were correlated with the various perinatal parameters. Non-parametric testing considered p < 0.05 to be significant. RESULTS: Ten (35%) of 29 patients had chronic inflammation in the reduced placenta. Their gestational age at delivery was 33.1 +/- 3.2 weeks, compared to 35.8 +/- 2.3 weeks in those without chronic inflammation (Z = -2.53, p = 0.01). There was no difference between the cases with and those without chronic inflammation in the reduced placenta, in regard to past reproductive history or clinical assessment of the MPR procedure (e.g. the number of attempts, duration of the procedure, or post-procedural complications). CONCLUSION: The majority of patients who underwent MPR did not develop a chronic inflammatory response to the process of 'resorbing' the placental tissues of the reduced sibling. However, a significant number (35%) of women who delivered viable offspring after MPR had chronic inflammation in the placenta, and had a shortened gestational length.

Improvement in outcomes of multifetal pregnancy reduction with increased experience.

OBJECTIVE: This study was undertaken to evaluate a decade of data on multifetal pregnancy reductions at centers with extensive experiences. STUDY DESIGN: A total of 3513 completed cases from 11 centers in 5 countries were analyzed according to year (before 1990, 1991-1994, and 1995-1998), starting and finishing numbers of embryos or fetuses, and outcomes. RESULTS: With increasing experience there has been a considerable improvement in outcomes, with decreases in rates of both pregnancy loss and prematurity. Overall loss rates in the last few years were correlated strongly with starting and finishing numbers (starting number > or =6, 15.4%; starting number 5, 11.4%; starting number 4, 7.3%; starting number 3, 4.5%; starting number 2, 6.2%: finishing number 3, 18.4%; finishing number 2, 6.0%; finishing number 1, 6.7%). Birth weight discordance between surviving twins was increased with greater starting number. The proportion of cases with starting number > or =5 diminished from 23.4% to 15.9% to 12.2%. The proportion of patients >40 years old increased in the last 6 years to 9.3%. Gestational age at delivery did not vary with increasing maternal age but was inversely correlated with starting number. CONCLUSION: Multifetal pregnancy reduction outcomes at our centers for both losses and early prematurity have improved considerably with experience. Reductions from triplets to twins and now from quadruplets to twins carry outcomes as good as those of unreduced twin gestations. Patient demographic characteristics continues to change as more older women use assisted reproductive technologies. In terms of losses, prematurity, and growth, higher starting numbers carry worse outcomes.

Chorionic villus sampling before multifetal pregnancy reduction.

OBJECTIVE: This study was undertaken to determine the technical feasibility and accuracy of chorionic villus sampling before multifetal pregnancy reduction and to determine whether sampling increases the pregnancy loss rate after the reduction procedure. STUDY DESIGN: Between January 22, 1986, and January 20, 2000, a total of 1183 patients underwent first-trimester multifetal pregnancy reduction at Mount Sinai Medical Center. Chorionic villus sampling was attempted in 86 patients before the reduction procedure. Information on the technical success and accuracy of chorionic villus sampling, as well as pregnancy outcome, was collected on all patients. Pregnancy loss rates before 24 weeks' gestation in patients undergoing chorionic villus sampling before multifetal pregnancy reduction were compared with rates in patients not undergoing sampling. RESULTS: Chorionic villus sampling was successfully completed in 85 (98.8%) of 86 patients in whom sampling was attempted. Of 166 fetuses, 165 (99.4%) were successfully sampled. Of 165 fetuses, 3 (1.8%) had karyotypic abnormalities. Sampling errors were probably made in 2 (1.2%) of 165 fetuses. Of the 73 patients who have been delivered or are beyond 24 weeks' gestation, only 1 patient (1.4%) had a pregnancy loss after the multifetal pregnancy reduction. CONCLUSIONS: Chorionic villus sampling before multifetal pregnancy reduction is technically feasible and accurate, with an acceptably low sampling error rate. Chorionic villus sampling before multifetal pregnancy reduction appears to be safe and does not increase the risk of loss after the reduction procedure.

First-trimester screening for aneuploidy: research or standard of care?

First-trimester screening for Down syndrome has been proposed as a significant improvement with respect to second-trimester serum screening programs, the current standard of care, because of apparently higher detection rates and an earlier gestational age at diagnosis. First-trimester nuchal translucency on ultrasonography forms the basis of this new form of screening, although studies of its efficacy have yielded widely conflicting results, with detection rates ranging from 29% to 91%. Studies of first-trimester serum screening with measurements of pregnancy-associated plasma protein A and free beta-human chorionic gonadotropin serum concentrations have been much more consistent, with Down syndrome detection rates of 55% to 63% at a 5% false-positive rate. The combination of first-trimester ultrasonographic and serum screening has the potential to yield a Down syndrome detection rate of 80% at a 5% false-positive rate, although this approach has not been adequately studied. There have been no studies performed to date to directly compare the performance of first-trimester and second-trimester methods of screening. Two major trials are underway that will address this issue, one in the United Kingdom and one in the United States. Until the results of these trials are available, the current standard of care with respect to Down syndrome screening should not be changed, and first-trimester screening should remain investigational.

Prenatal diagnosis and management of abnormalities in the urologic system.

We have reviewed the prenatal diagnosis and management of abnormalities in the urologic system. Urologic anomalies may be caused by embryologic aberrations, genetic disease, or a nonrandom association with other structural abnormalities. There is a wide range of prognoses, depending on the cause and the impact of the anomaly on the production of amniotic fluid. Management focuses on obtaining an accurate prenatal diagnosis, providing appropriate counseling, and ensuring the proper surveillance or treatment before and after birth.

Selective termination for structural, chromosomal, and mendelian anomalies: international experience.

OBJECTIVE: Our purpose was to evaluate the outcomes of selective termination for fetal anomalies at 8 centers with the largest known experiences worldwide. STUDY DESIGN: Outcomes in 402 cases of selective termination in pregnancies with dizygotic twins from 8 centers in 4 countries were analyzed by year, gestational age at procedure, and indication. Reductions of fetuses were as follows: 2 to 1, n = 345; 3 to 2, 39; >/=4 to 2 or 3, n = 18. Potassium chloride was used in all procedures. RESULTS: Selective termination resulted in delivery of a viable infant or infants in >90% of cases. Loss up to 24 weeks occurred in 7.1% of cases in which the final result was a singleton fetus and in 13.0% of cases in which the final result was twins. Loss was 6.6% as a result of structural abnormalities, 7.0% for chromosomal abnormalities, and 10% for mendelian abnormalities (difference not statistically significant). Loss rates for procedures were as follows: 9-12 weeks, 5.4%; 13-18 weeks, 8.7%; 19-24 weeks, 6.8%; and >/=25 weeks, 9.1% (difference not statistically significant). Mean gestational age at delivery was 35.7 weeks. No differences were seen in outcomes by maternal age. The rate of very early premature deliveries has fallen in recent years. There were no known cases of disseminated intravascular coagulation or serious maternal complications. CONCLUSION: (1) Selective termination, in the most experienced hands, can be technically performed in all 3 trimesters with good outcomes in >90% of cases. (2) The previously observed increase in second- versus first-trimester losses has diminished. (3) Third-trimester procedures, where legal, can be performed with a good outcome for the surviving fetus.

Perinatal outcome in grand and great-grand multiparity: effects of parity on obstetric risk factors.

OBJECTIVE: We sought to compare obstetric and neonatal complications among great-grand multiparous, grand multiparous, and multiparous women. STUDY DESIGN: One hundred thirty-three great-grand multiparas, 314 grand multiparas, and 2195 multiparas who were delivered of their infants between 1988 and 1998 were selected for the study. To facilitate comparison, the patients were all >35 years old and had similar socioeconomic characteristics. RESULTS: The incidence of malpresentation at the time of delivery, maternal obesity, anemia, preterm delivery, and meconium-stained amniotic fluid increased with higher parity, whereas the rate of excessive weight gain and cesarean delivery decreased. Compared with grand multiparas, great-grand multiparas had significantly elevated risks for abnormal amounts of amniotic fluid, abruptio placentae, neonatal tachypnea, and malformations but lower rates of placenta previa (P <.05). The incidence of postpartum hemorrhage, preeclampsia, placenta previa, macrosomia, postdate pregnancy, and low Apgar scores was significantly higher in grand multiparas than in multiparas, whereas the proportion of induction, forceps delivery, and total labor complications was significantly lower than in the multiparous group (P <.05). Similar frequency of maternal diabetes, infection, uterine wall scar rupture, variations in fetal heart rate, fetal death, and neonatal mortality was found in the 3 groups. CONCLUSION: Both high-parity groups have their own risk factors, but the rate of some complications decreases with higher parity. In addition, perinatal mortality remains low in these patients, and therefore, under satisfactory socioeconomic and health care conditions, high parity should not be considered dangerous.

Haemolytic disease of the newborn caused by anti-c, anti-E and anti-Fya antibodies: report of five cases.

Fetal haemolytic disease caused by irregular antibodies is discussed on the basis of three cases with maternal anti-c alone, one with anti-E along with anti-c, and one with anti-Fya sensitization. All fetuses suffering from maternal c-allo-immunization alone were treated with intra-uterine transfusions and the newborns received exchange transfusions. These interventions were also required in the case of simultaneous E and c-allo-immunization, and this was the most severe of the five cases. Delta OD450 results were consistent with the severity of the fetal condition in the c and/or E allo-immunization cases. Maternal anti-Fya sensitization caused only mild jaundice of the neonate, but the results of amniotic fluid analysis were quite misleading in that case. Antibody titres did not prove to have good prognostic values (though they were all above the critical level), and the direct antiglobulin test from cord blood was negative in three cases. Regular sonographic evaluations were performed and fetal blood samplings were a cornerstone of management.

Pregnancy complications and neonatal outcomes in multifetal pregnancies reduced to twins compared with nonreduced twin pregnancies.

Our objective was to compare the pregnancy complications and neonatal outcomes of multifetal pregnancies reduced to twins to those in twin pregnancies without multifetal pregnancy reduction (MPR). A cohort study was performed in patients with dichorionic twin pregnancies who reached 24 weeks' gestation and delivered at the Mount Sinai Medical Center between 1986 and 1997. A study population of 77 multifetal pregnancies reduced to twins were compared with 140 dichorionic twin pregnancies without MPR regarding pregnancy complications and neonatal outcomes. Statistical analysis was performed with Chi-square and two-tailed Student's t-tests. Multifetal pregnancies reduced to twins were similar to nonreduced twins in all parameters studied except the cesarean section rate and neonatal polycythemia. Increased cesarean section rate in MPR group was attributed to elective indications. Pregnancy-induced hypertension was found to be higher only in a subgroup of patients (i.e., 4-2). Multifetal pregnancies reduced to twins do not differ from the twin pregnancies without MPR in the overwhelming majority of pregnancy complications and neonatal outcomes.

Diagnosing amnionicity at 6 weeks of pregnancy with transvaginal three-dimensional ultrasonography: case report.

OBJECTIVE: To report a case of monochorionic, diamniotic twin pregnancy diagnosed at 6 weeks of pregnancy with three-dimensional (3D) transvaginal sonography and to discuss the use of this diagnostic method in the evaluation of multifetal pregnancy in the first trimester. DESIGN: Case report. SETTING: University-based IVF program. PATIENT(S): A 30-year-old ovum recipient underwent ultrasonographic evaluation of a first-trimester twin pregnancy. INTERVENTION(S): Two-dimensional (2D) and 3D transvaginal sonography. MAIN OUTCOME MEASURE(S): Accurate diagnosis of chorionicity and amnionicity. RESULT(S): Monoamniotic pregnancy and conjoined twinning could not be ruled out by using 2D transvaginal sonography at 6 weeks, because only one yolk sac (YS) and no membranes could be visualized, and the two embryos were closely positioned within one gestational sac. Applying 3D technique, two YSs and two separate embryos could clearly be observed, establishing the correct diagnosis of a monochorionic, diamniotic pregnancy. CONCLUSION(S): The 3D transvaginal ultrasonography provides a quick and accurate diagnostic modality for the evaluation of a first-trimester multiple gestation.

Genetic amniocentesis after multifetal pregnancy reduction.

OBJECTIVE: Our purpose was to evaluate the pregnancy loss rate resulting from genetic amniocentesis after multifetal pregnancy reduction. STUDY DESIGN: A cohort study was performed in pregnancies with maternal age >30 years. Pregnancy loss in a study population of 127 patients who underwent genetic amniocentesis after multifetal pregnancy reduction were compared with a control group of 167 patients who did not have genetic amniocentesis after multifetal pregnancy reduction. RESULTS: The pregnancy loss rate in patients who underwent genetic amniocentesis after multifetal pregnancy reduction was 3.1% (4/127 cases) compared with 7.2% (12/167 cases) in the controls (P >.05). In the study group evidence of infection was found in only 1 case, in which the pregnancy loss occurred 1 day after the amniocentesis. In the other cases the pregnancy losses occurred 5 weeks after genetic amniocentesis, and these losses could not be directly attributed to either genetic amniocentesis or the multifetal reduction procedure. CONCLUSION: Our data suggest that the performance of genetic amniocentesis after multifetal pregnancy reduction does not increase the risk of pregnancy loss over that observed in association with the reduction itself.

Outcomes among 562 recipients of placental-blood transplants from unrelated donors.

BACKGROUND: A program for banking, characterizing, and distributing placental blood, also called umbilical-cord blood, for transplantation provided grafts for 562 patients between August 24, 1992, and January 30, 1998. We evaluated this experience. METHODS: Placental blood was stored under liquid nitrogen and selected for specific patients on the basis of HLA type and leukocyte content. Patients were prepared for the transplantation of allogeneic hematopoietic cells in the placental blood and received prophylaxis against graft-versus-host disease (GVHD) according to routine procedures at each center. RESULTS: Outcomes at 100 days after transplantation were known for all 562 patients, and outcomes at 1 year for 94 percent of eligible recipients. The cumulative rates of engraftment among the recipients, according to actuarial analysis, were 81 percent by day 42 for neutrophils (median time to engraftment, 28 days) and 85 percent by day 180 for platelets (median, day 90). The speed of myeloid engraftment was associated primarily with the leukocyte content of the graft, whereas transplantation-related events were associated with the patient's underlying disease and age, the number of leukocytes in the graft, the degree of HLA disparity, and the transplantation center. After engraftment, age, HLA disparity, and center were the primary predictors of outcome. Severe acute GVHD (grade III or IV) occurred in 23 percent of patients, and chronic GVHD occurred in 25 percent. The rate of relapse among recipients with leukemia was 9 percent within the first 100 days, 17 percent within 6 months, and 26 percent by 1 year. These rates were associated with the severity of GVHD, type of leukemia, and stage of the disease. CONCLUSIONS: Placental blood is a useful source of allogeneic hematopoietic stem cells for bone marrow reconstitution.

Multifetal pregnancy reduction is not associated with an increased risk of intrauterine growth restriction, except for very-high-order multiples.

OBJECTIVE: Our purpose was to investigate whether multifetal pregnancies reduced to twins have an increased risk of intrauterine growth restriction and discordant birth weight. STUDY DESIGN: This retrospective cohort study investigated the rates of birth weight discordance > 20% and intrauterine growth restriction using both twin and singleton birth weight curves in 441 twin deliveries after multifetal pregnancy reduction (233 reduced from triplets, 156 from quadruplets, and 52 from quintuplets or greater) compared with 136 nonreduced dichorionic twins. RESULTS: No significant difference was found in the frequency of birth weight discordance and in the overall incidence of intrauterine growth restriction by both twin and singleton birth weight curves when pregnancies that underwent multifetal pregnancy reduction were compared with the control group. There was, however, an almost twofold increase in the rate of intrauterine growth restriction in pregnancies with a starting fetal number of 5 or more (23.1%) compared with that in those reduced from triplets or quadruplets (12.1%) when the twin curve standard was used (P = .03). This difference disappeared when these groups were compared with a singleton nomogram. CONCLUSION: This study suggests that multifetal pregnancy reduction is not associated with an increased risk of intrauterine growth restriction unless the starting fetal number is > or = 5. This finding provides a further rationale to avoid transferring excessive numbers of preembryos after in vitro fertilization.

Ethical issues involving multifetal pregnancies.

Selective termination is a procedure in which an anomalous fetus in a multifetal pregnancy is terminated with the intent of allowing the pregnancy to continue, so that the patient delivers one or more healthy infants at term. Multifetal pregnancy reduction is the elective reduction of three or more fetuses to a smaller number in an attempt to reduce the incidence of premature delivery in these patients. The ethical issues relating to these two procedures are quite different. Data are presented relating to the efficacy and safety of each procedure, and the ethical issues relating to them are discussed.