Manuscript summary to come.
Hemolytic disease of the fetus and newborn (HDFN) from anti-D and other antibodies still affects 3-4 cases per 1000 births. Free radical damage from oxidative stress may contribute to the anemia of HDFN by damaging formed red blood cells. The proposed study is designed to identify oxidant stresses in fetuses diagnosed with HDFN.
Untreated, early midgestation LUTO with oligo/anhydramnios has a very high mortality and renal/pulmonary morbidity in the rare survivor. Prenatal intervention in carefully selected cases has improved survival and reduced pulmonary and renal morbidity. Presently, invasive fetal therapy for LUTO is only justified in the presence of concomitant oligohydramnios. Nothing is documented about the natural history and morbidity or mortality for fetuses with early midgestation LUTO and normal amniotic fluid volumes. A registry of cases with LUTO and normal amniotic fluid could serve as the basis to justify a prospective, randomized trial of shunting versus non-shunting in this population if significant morbidity is found.
Twin-to-twin transfusion syndrome (TTTS) occurs in 10-15% of all diamniotic-monochorionic (DiMo) pregnancies (identical twins). It is not yet clear why some DiMo pregnancies evolve into TTTS, while others don’t. Furthermore, the evolution of the syndrome is highly variable and unpredictable. In some, the syndrome progresses through increasing stages of severity within days; in others, the severity of the syndrome remains stable for weeks, and may even decrease over time. The aim of the study is to develop tools to stratify patients with severe TTTS into good and poor prognostic groups based on preoperative markers. Two of these markers are corticotropin releasing hormone (CRH) and urocortin (Ucn), known factors associated with placental and fetal stress.
Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis:This multicenter, prospective observational cohort study will compare clinical diagnostic results obtained by conventional cytogenetic microscopy (CC) analysis with those achieved by microarray analysis (MA). The prenatal diagnostic samples will come from two categories of pregnancies: 1750 patients undergoing prenatal testing for standard indications (Group 1) and another 2250 pregnancies (Group 2) in which testing is performed on account of ultrasound detection of at least one pre-specified fetal structural or growth anomaly, or two or more other unlisted anomalies. The main objective of this multi-center collaborative study is to evaluate the accuracy, efficacy and clinical advantages of prenatal diagnosis using array-based copy number (microarray) analysis as compared with conventional cytogenetic (CC) analysis using microscopy.
Genetic analysis of free fetal DNA in maternal plasma will open the door to major advances in prenatal diagnosis while minimizing potential risks to the pregnancy. Early efforts have been centered in Europe and the United Kingdom on determination of fetal gender and Rh blood type. This investigation, sponsored by the Sequenom company, will seek to determine the accuracy of a new assay for fetal gender and RhD typing in the United States. The combined obstetrical populations of the NAFNet organization will allow the study to be completed in a timely fashion so that the assay can be validated and be available for North American patients.
Management options for severe Twin-to-twin Transfusion Syndrome (TTTS) include observation, termination of the pregnancy, amnioreduction, septostomy, endoscopic laser ablation of placental vessels and selective termination of a moribund twin fetus. Informed decisions, as well as directive- and non-directive counseling, imply a reasonable understanding of the natural evolution of the disease and the expected outcome for the various therapeutic interventions. Selective termination, in particular, requires accurate predictive indicators for each fetus, to allow a comparison with other therapies. If selective termination is chosen, the decision as to which fetus should be targeted for termination should be made based on medical knowledge of the prediction of death. The aim of this study is to analyze predictive factors for fetal or neonatal death for pregnancies with twin-to-twin transfusion syndrome that were treated with endoscopic laser ablation of placental vessels.
Among live born infants treated for TTTS in utero by selective fetoscopic laser photocoagulation (SFLP) of placental vessels, complications of prematurity remain a major source of morbidity. Studies involving treatment of twin-twin transfusion have significant heterogeneity of gestational age at delivery. It is difficult to determine from the available literature the proportion of spontaneous versus preterm birth following PPROM versus clinically indicated delivery. This information would be of value for counseling families as well as for practitioners determining the timing of delivery. The purpose of this study is to determine the indications for delivery for TTTS after treatment with SFLP.