Objective We sought to evaluate performance of a noninvasive prenatal test for fetal trisomy 21 (T21) and trisomy 18 (T18). Study Design A multicenter cohort study was performed whereby cell-free DNA ...from maternal plasma was analyzed. Chromosome-selective sequencing on chromosomes 21 and 18 was performed with reporting of an aneuploidy risk (High Risk or Low Risk) for each subject. Results Of the 81 T21 cases, all were classified as High Risk for T21 and there was 1 false-positive result among the 2888 normal cases, for a sensitivity of 100% (95% confidence interval CI, 95.5–100%) and a false-positive rate of 0.03% (95% CI, 0.002–0.20%). Of the 38 T18 cases, 37 were classified as High Risk and there were 2 false-positive results among the 2888 normal cases, for a sensitivity of 97.4% (95% CI, 86.5–99.9%) and a false-positive rate of 0.07% (95% CI, 0.02–0.25%). Conclusion Chromosome-selective sequencing of cell-free DNA and application of an individualized risk algorithm is effective in the detection of fetal T21 and T18.
Objective We report our experience in the treatment of patients with twin-reversed arterial perfusion (TRAP) sequence using radiofrequency ablation to stop perfusion to the acardiac twin and protect ...the pump twin. Study Design An IRB approved retrospective review of all patients (n = 29) who underwent percutaneous radiofrequency ablation of an acardiac twin, using ultrasound guidance and either a 14 or 17 gauge radiofrequency needle for twin-reversed arterial perfusion sequence, from 1998 to 2005, was performed by review of hospital and outpatient medical records. Results The outcomes of all 29 of the patients treated with radiofrequency ablation are known. Twenty-six of the patients had monochorionic-diamniotic pregnancies, whereas 2 had monochorionic-monoamniotic pregnancies. One patient had a triplet pregnancy with a monochorionic-diamniotic pair with TRAP sequence. Overall, 25 of 29 pump twins survived (86%), delivering at a mean gestational age of 34.6 weeks. Survival was 24 of 26 (92%) in monochorionic-diamniotic pregnancies with a mean gestational age of 35.6 weeks. Two women in our early experience sustained thermal injuries from the site of grounding pads. Conclusion Radiofrequency ablation of the acardiac twin effectively protects the pump twin from high-output cardiac failure and death. Greater than 90% survival can be achieved in monochorionic-diamniotic pregnancies complicated by TRAP sequence with a mean gestation age at time of delivery close to term. Our limited experience in cases of monochorionic-monoamniotic TRAP sequence does not allow the determination of efficacy in this group.
Objective The objective of the study was to examine the effect of selective fetoscopic laser photocoagulation (SFLP) vs serial amnioreduction (AR) on perinatal mortality in severe twin-twin ...transfusion syndrome (TTTS). Study Design This was a 5 year multicenter, prospective, randomized controlled trial. The primary outcome variable was 30 day postnatal survival of donors and recipients. Results There was no statistically significant difference in 30-day postnatal survival between SFLP or AR treatment for donors at 55% (11 of 20) vs 55% (11 of 20) ( P = 1.0, odds ratio OR 1, 95% confidence interval CI 0.242 to 4.14) or recipients at 30% (6 of 20) vs 45% (9 of 20) ( P = .51, OR 1.88, 95% CI 0.44 to 8.64). There was no difference in 30 day survival of 1 or both twins on a per-pregnancy basis between AR at 75% (15 of 20) and SFLP at 65% (13 of 20) ( P = .73, OR 1.62, 95% CI 0.34 to 8.09). Overall survival (newborns divided by the number of fetuses treated) was not statistically significant for AR at 60% (24 of 40) vs SFLP 45% (18 of 40) ( P = .18, OR 2.01, 95% CI 0.76 to 5.44). There was a statistically significant increase in fetal recipient mortality in the SFLP arm at 70% (14 of 20) vs the AR arm at 35% (7 of 20) ( P = .25, OR 5.31, 95% CI 1.19 to 27.6). This was offset by increased recipient neonatal mortality of 30% (6 of 20) in the AR arm. Echocardiographic abnormality in recipient twin Cardiovascular Profile Score is the most significant predictor of recipient mortality ( P = .055, OR 3.025/point) by logistic regression analysis. Conclusion The outcome of the trial did not conclusively determine whether AR or SFLP is a superior treatment modality. TTTS cardiomyopathy appears to be an important factor in recipient survival in TTTS.
Objective We sought to identify differences in echocardiographic profiles of monochorionic (MC)/diamniotic (DA) pregnancies with early or mild twin-twin transfusion syndrome (TTTS), compared to MC/DA ...twins affected only by discordant growth or discordant fluid. Study Design This was a retrospective evaluation of sonograms and echocardiograms of twin pregnancies referred for suspected TTTS. Results A total of 112 MC/DA pairs were studied. In all, 41 did not have/develop TTTS, and 61 had stage I/II TTTS. Ten developed TTTS after initially not meeting criteria. TTTS recipients had a higher rate of venous Doppler or tricuspid inflow abnormalities than purported recipients in non-TTTS pregnancies (86% vs 37%, P < .001). TTTS recipients had shorter tricuspid inflow duration/R-R intervals than non-TTTS fetuses (32 ± 6% vs 37 ± 4%, P < .001). Logistic regression and recursive partitioning identified shorter tricuspid inflow duration, longer isovolumic relaxation, and ductus venosus abnormality associated with TTTS. Conclusion Diastolic pathology, specifically shorter tricuspid inflow duration, may be considered a hallmark of TTTS distinguishing these pregnancies from other MC/DA twin complications.
Congenital diaphragmatic hernia (CDH) is a common birth anomaly. Absence or presence of liver herniation and determination of lung-to-head ratio are the most accurate predictors of prognosis for ...fetuses with CDH. Though open fetal CDH repair has been abandoned, fetal endoscopic balloon tracheal occlusion promotes lung growth in fetuses with severe CDH. Although significant improvements in lung function have not yet been shown in humans, reversible or dynamic tracheal occlusion is promising for select fetuses with severe CDH. This article reviews advances in prenatal diagnosis of CDH, the experimental basis for tracheal occlusion, and its translation into human clinical trials.
Objective The purpose of this study was to investigate the relationship between lung-to-head ratio (LHR) and gestational age (GA) in fetuses with isolated left congenital diaphragmatic hernia and to ...determine the applicability and reliability of LHR to predict postnatal outcome beyond 24-26 weeks of gestation. Study Design The institutional review board approved this retrospective review of the University of California, San Francisco, Fetal Treatment Center database for cases with left congenital diaphragmatic hernia who were referred between March 1995 and June 2004. LHR was determined at the initial evaluation. One hundred seven live-born fetuses at 20-34 weeks of gestation (excluding cases that were lost to follow-up, with factors that potentially could influence the LHR measurement or postnatal outcome, or that were terminated electively). Results The median GA at LHR measurement was 25.6 weeks; the median LHR was 1.01; the median GA at birth was 37.7 weeks; and the overall survival rate was 59% (64/107). The median LHR of nonsurvivors was significantly lower than that of survivors, but neither GA at LHR measurement nor at delivery was significantly different between the groups. Multiple logistic regression analysis confirmed LHR to be an independent predictor of postnatal survival, and receiver-operator characteristic curve analysis demonstrated that an LHR of ≥0.97 has the highest performance in predicting postnatal survival. When fetuses were grouped by GA at initial LHR measurement to determine reliability of LHR, specifically with respect to GA, in the 26-34 and 24-26 weeks of gestation groups, median LHR of survivors was significantly higher than that of nonsurvivors, and receiver-operator characteristic curve analysis confirmed LHR to be a reliable predictor of postnatal survival. However, for fetuses at 20-24 weeks of gestation, there was a trend toward a higher LHR in survivors, although this did not reach statistical significance. Conclusion A significant positive linear relationship exists between LHR and GA at the time of measurement, such that LHR reliably predicts postnatal survival in fetuses with left congenital diaphragmatic hernia at 24-34 weeks of gestation and less reliable at 20-24 weeks. However, given the limitations of a retrospective, cross-sectional study, further prospective longitudinal studies that will investigate the change of LHR with GA and its association with fetal outcome are necessary.
Congenital diaphragmatic hernia (CDH) is characterized by a defect in the diaphragm that permits abdominal viscera to herniate into the chest. These herniated viscera are thought to compress the ...growing lung and cause lung parenchymal and vascular hypoplasia. The genetic defects that cause the diaphragmatic defect may also contribute primarily to lung hypoplasia. Postnatal reduction of the herniated abdominal viscera and correction of the diaphragmatic defect are easily achievable, but the lung hypoplasia persists, often leading to persistent fetal circulation and respiratory failure. This article reviews the experimental basis of fetal therapy for CDH and the US clinical experience with tracheal occlusion.
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