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Purpose Congenital high airway obstruction syndrome (CHAOS) is a devastating fetal condition of complete airway discontinuity resulting in significant hydrops and extreme lung hyperplasia. It is universally fatal with survival reported only in the rare spontaneous fistulization or EXIT intervention (Ex Utero Intrapartum Treatment). Even in these cases, mortality remains high, and current investigations are targeting prenatal interventions. This report describes our experience with management and fetal interventions for CHAOS, including laser laryngotomy. Methods We retrospectively reviewed all patients diagnosed with CHAOS at a single academic institution between 2006 and 2017. Results Fifteen patients were identified. Eight had obstruction at the trachea and seven at the larynx. In the laryngeal obstructions, three expired shortly after birth, and one survived after spontaneous fistulization and subsequent EXIT to tracheostomy. The remaining three underwent in-utero treatment with laser laryngotomy. One had preterm premature rupture of membranes (PPROM), delivered 3 days post-operatively, and died. Two underwent EXIT to tracheostomy with one surviving to discharge and is currently 2 years old. Conclusion Our study demonstrates the outcomes of a large series of patients diagnosed with CHAOS. While mortality remains high, options for fetal intervention are being explored to allow alterations in the prenatal natural history and improve postnatal outcomes. Type of Study Retrospective Treatment Study. Level of Evidence Level IV.

Introduction: Bilateral renal agenesis (BRA) is a lethal diagnosis, specifically meaning that natural survival beyond birth is not expected secondary to pulmonary hypoplasia. Limited contemporary data are available about intervention and the impact of restoring amniotic fluid volume in relation to the risk for lethal pulmonary hypoplasia and other factors that might influence survival in cases of fetal BRA. Objective: We report the largest series of patients undergoing fetal intervention and postnatal care for BRA at a single comprehensive fetal center. Methods: All patients with fetal BRA were reviewed from January 2004 to November 2017. Maternal and neonatal data were collected in an institutional review board-approved retrospective review. Results: From 2014 to 2017, 20 singleton pregnancies with isolated fetal BRA were evaluated and 14 had amnioinfusion. Eight had serial infusions. Of those, there were 6 neonatal deaths. There were 2 neonatal survivors beyond 30 days; however, both died of sepsis on dialysis. One of these survivors received amnioinfusions by percutaneous approach and one via amnioport. There were no survivors to transplantation. Conclusion: Fetal intervention via amnioinfusion may promote pulmonary survivorship after birth, but postnatal survival remains poor. Future studies must place an emphasis on standardizing the postnatal approach to this patient population.

Congenital bilateral renal agenesis has been considered a uniformly fatal condition. However, the report of using serial amnioinfusions followed by the live birth in 2012 and ongoing survival of a child with bilateral renal agenesis has generated hope, but also considerable controversy over an array of complex clinical and ethical concerns. To assess the ethical concerns associated with using serial amnioinfusions for bilateral renal agenesis, we assembled a multidisciplinary group to map the ethical issues relevant to this novel intervention. The key ethical issues identified were related to 1) potential risks and benefits, 2) clinical care compared with innovation compared with research, 3) counseling of expectant parents, 4) consent, 5) outcome measures, 6) access and justice, 7) conflicts of interest, 8) effects on clinicians, 9) effects on institutions, and 10) long-term societal implications. These ethical issues should be addressed in conjunction with systematic efforts to examine whether this intervention is safe and effective. Future work should capture the experiences of expectant parents, women who undergo serial amnioinfusions, those born with bilateral renal agenesis and their families as well as clinicians confronted with making difficult choices related to it.

Background Bilateral renal agenesis has uniformly been a lethal diagnosis in the perinatal or neonatal period. With the advent of more advanced renal replacement therapy as a bridge to renal transplantation, amnioinfusion has been explored at our center as a way to prevent lethal pulmonary hypoplasia secondary to oligohydramnios. Case presentation We describe two cases of bilateral renal agenesis with serial amnioinfusion during pregnancy. The families opted for full neonatal intervention and post-natal renal support. While lethal pulmonary hypoplasia was avoided, early and refractory hypotension limited the ability to perform dialysis in these neonates. Conclusions Our limited experience shows that barriers to care such as lethal respiratory failure and technical limitations of early dialysis are not the only barriers prohibiting care for this population.

Objective: We describe a technique to maintain amniotic fluid in fetuses with severe oligo-/anhydramnios secondary to lower urinary tract obstruction or fetal renal disease when urine production is inadequate to maintain a normal amniotic fluid volume (AFV). Methods: An amnioport was inserted into the amniotic space. The catheter was secured to prevent dislodgment and tunneled to a subcutaneous reservoir. The reservoir was accessed as necessary, infusing normal saline to maintain AFV. Pregnancy continued until term or indicated delivery. Results: Since 2010, 15 patients in this category were considered for an amnioport. Six chose comfort care and one elected percutaneous amnioinfusions. Nine amnioport procedures were performed in eight patients. There were no fetal deaths. All eight had successful restoration and maintenance of amniotic fluid. Delivery ranged from 9 to 96 days after placement (mean 63.7 days). One died due to unrecognized laryngeal web and another one died of pulmonary hypoplasia after preterm premature rupture of membranes. None of the remaining six had pulmonary hypoplasia. Three remain alive. Discussion: Severe oligo-/anhydramnios in the second trimester secondary to fetal anomalies is almost uniformly lethal due to pulmonary hypoplasia without restoration of amniotic fluid. The amnioport procedure may allow pulmonary survival but commits families to postnatal care decisions regarding pulmonary and renal complications.

Background: Gastroschisis is an abdominal wall defect with increasing incidence. Given the lack of surveillance guidelines among maternal-fetal medicine (MFM) specialists, this study describes current practices in gastroschisis management. Materials and Methods: An online survey was administered to MFM specialists from institutions affiliated with the North American Fetal Therapy Network (NAFTNet). Questions focused on surveillance timing, testing, findings that changed clinical management, and delivery plan. Results: Responses were obtained from 29/29 (100%) NAFTNet centers, comprising 143/371 (39%) providers. The majority had a regimen for antenatal surveillance in patients with stable gastroschisis (94%; 134/141). Antenatal testing began at 32 weeks for 68% (89/131) of MFM specialists. The nonstress test (55%; 72/129), biophysical profile (50%; 63/126), and amniotic fluid index (64%; 84/131) were used weekly. Estimated fetal weight (EFW) was performed monthly by 79% (103/131) of providers. At 28 weeks, abnormal EFW (77%; 97/126) and Doppler ultrasound (78%; 99/127) most frequently altered management. In stable gastroschisis, 43% (60/140) of providers delivered at 37 weeks, and 29% (40/ 140) at 39 weeks. Discussion: Gastroschisis management differs among NAFTNet centers, although the majority initiate surveillance at 32 weeks. Timing of delivery still requires consensus. Prospective studies are necessary to further optimize practice guidelines and patient care.

Background Indications for intervention in early-stage (Quintero I and II) twin-twin transfusion syndrome (TTTS) are not standardized. Fetal echocardiography can be used to guide the management of early-stage patients. The aim of this study was to identify early cardiovascular findings that may precede progression to overt recipient twin (RT) cardiomyopathy in early-stage TTTS. Methods This was a retrospective review of pregnancies evaluated from 2004 to 2010. Subjects were included when initial evaluation identified Quintero I or II TTTS without evidence of "overt" RT cardiomyopathy, defined on the basis of atrioventricular valve regurgitation, ventricular hypertrophy, and abnormal Doppler myocardial performance indices. Patients elected management with observation or amnioreduction. Pregnancies were grouped by whether the RT developed overt cardiomyopathy. Initial values, including myocardial performance index, diastolic filling time corrected for heart rate (Doppler inflow duration/cardiac cycle length), pulsatility indices of the ductus venosus, umbilical artery, and middle cerebral artery, and cerebroplacental ratio (middle cerebral artery PI/umbilical artery PI), were compared. Results Of 174 pregnancies evaluated with early-stage TTTS, 45 (26%) did not show evidence of RT cardiomyopathy. Follow-up echocardiography identified cardiomyopathy in 20 of 45 RTs (44%). Those RTs with subsequent cardiomyopathy had shorter diastolic filling times corrected for heart rate, higher ductus venosus PIs, lower middle cerebral artery PIs, and lower cerebroplacental ratios on initial echocardiography. Conclusion Diastolic dysfunction and cerebroplacental redistribution precede findings of overt cardiomyopathy in RTs with early-stage TTTS. Assessment of these parameters may allow earlier identification of RTs with cardiac disease and help guide management. Prospective studies are needed to assess the role of echocardiography in patient selection for the treatment of early-stage TTTS.

For conscientious practitioners, innovative medical therapy often occupies an uncomfortable space between formal research and established clinical practice. Newer and more rapid methods of information dissemination increase the risk of advertising unproven therapies. These and other concerns should not stifle medical progress and innovation but require guidelines and boundaries. The problem is not unique to fetal therapy, but rarely do other fields consider the well-being of two individuals at the same time. Herein, the North American Fetal Therapy Network offers expanded guidelines and suggestions regarding medical innovation that are particular to maternal-fetal therapy.

Objective: The aim of this study was to define the natural history of lower urinary tract obstruction (LUTO) with normal midgestational amniotic fluid volumes. Materials and Methods: We performed a retrospective review of 32 consecutive patients with LUTO with normal midgestational amniotic fluid volume followed at 11 North American Fetal Therapy Network (NAFTNet) centers from August 2007 to May 2012. Normal amniotic fluid volume was defined as an amniotic fluid index (AFI) of ≥9 cm. Results: The mean gestational age (GA) and AFI at enrollment were 23.1 ± 2.1 weeks and 15.8 ± 3.9 cm, respectively. The mean GA at delivery was 37.3 ± 2.8 weeks. The mean creatinine level at discharge was 1.2 ± 0.8 mg/dL. Perinatal survival was 97%. Twenty-five patients returned for serial postnatal assessment. Renal replacement therapy (RRT) was required in 32%. Development of oligohydramnios and/or anhydramnios, development of cortical renal cysts, posterior urethral valves, prematurity, and prolonged neonatal intensive care unit stay were associated with need for RRT (p < 0.05) by univariate analysis. By multivariate analysis, preterm delivery remained predictive of need for RRT (p = 0.004). Conclusion: Prenatal diagnosis of LUTO with normal midgestational amniotic fluid volumes is associated with acceptable renal function in the majority of patients. Approximately one-third of these children require RRT. Surrogate markers of disease severity appear to be predictive of need for RRT.

Tracheal agenesis is a rare and essentially lethal anomaly with divergent prenatal imaging findings depending on the presence or absence of a tracheoesophageal fistula. All prenatally diagnosed cases of tracheal agenesis reported to date have not had a tracheoesophageal fistula and presented with thoracoabdominal findings similar to congenital high airway obstruction syndrome. We present the case of a 32-week gestation fetus with rapid onset of polyhydramnios and no persistent findings of congenital high airway obstruction syndrome that was ultimately diagnosed with tracheal agenesis plus tracheoesophageal fistula by fetal MRI. Additionally, we present the novel uses of intraoperative US during a staged ex utero intrapartum therapy delivery and postdelivery MRI, facilitated by proximity within the neonatal ICU, to confirm diagnosis and direct patient management while minimizing unnecessary investigations.

Objective To determine the sensitivity and specificity of circulating cell-free fetal DNA in determining the fetal RHD status and fetal sex. Methods Maternal blood was collected in each trimester of pregnancy from RhD negative nonalloimmunized women. Whole blood was centrifuged, separated into plasma and buffy coat, and frozen at –80°C. DNA analysis was conducted via allele-specific primer extensions for exons 4, 5, and 7 of the RHD gene and for a 37-base pair insertion in exon 4 (RHD pseudogene; psi) three Y-chromosome sequences (SRY, DBY, and TTY2), and an extraction control (TGIFL-like X/Y). RhD serotyping on cord blood and gender assessment of the newborns were entered into a Web-based database. Results One hundred twenty women were enrolled. The median gestational age at the first venipuncture was 12.4 (range: 10.6–13.9) weeks with 120 samples drawn; 118 samples were drawn at 17.6 (16–20.9) weeks; and 113 samples at 28.7 (27.9–33.9) weeks. Overall accuracy for RHD was 99.1%, 99.1%, and 98.1% for each trimester and was 99.1%, 99.1%, and 100% for fetal sex determination. Conclusions Fetal RHD genotyping and sex can be very accurately determined in all three trimesters using circulating cell-free fetal DNA in the maternal circulation. © 2012 John Wiley & Sons, Ltd.

OBJECTIVE To estimate the accuracy of a new assay to determine the fetal RHD status using circulating cell-free DNA. METHODS This was a prospective, observational study. Maternal blood samples were collected in each trimester of pregnancy in 520 nonalloimmunized RhD-negative patients. Plasma samples were analyzed for circulating cell-free DNA using the SensiGENE RHD test, which used primers for exons 4 and 7 as previously described and incorporated a new primer design for exon 5 of the RHD gene. Neonatal serology for RhD typing using cord blood at birth was undertaken and results were stored in a separate clinical database. After unblinding the data, results of the DNA analysis were compared with the neonatal serology. RESULTS Inconclusive results secondary to the presence of the RHD pseudogene or an RHD variant were noted in 5.6%, 5.7%, and 6.1% of the first-, second-, and third-trimester samples, respectively. The incidence of false-positive rates for RhD (an RhD-negative fetus with an RHD-positive result) was 1.54% (95% confidence interval [CI] 0.42-5.44%), 1.53% (CI 0.42-5.40%), and 0.82% (CI 0.04-4.50%), respectively. There was only one false-negative diagnosis (an RhD-positive fetus with an RHD-negative result), which occurred in the first trimester (0.32%; 95% CI 0.08-1.78%). Genotyping for mismatches across repeated samples revealed that this error was related to mislabeling of samples from two patients collected on the same day at one of the collection sites. Overall test results were in agreement across all three trimesters (P>.99). CONCLUSION Circulating cell-free DNA can accurately predict the fetal RhD status in all three trimesters of pregnancy.

Objective The management of twin–twin transfusion syndrome (TTTS) in its early stages (Quintero Stages I and II) is controversial. We describe the prevalence, severity, incidence and rate of progression of recipient-twin cardiomyopathy in Stages I and II TTTS. Methods Among 451 cases of TTTS evaluated between 2004 and 2009, 123 (27.3%) cases of Stages I and II were reviewed. Echocardiography was used to ‘upstage’ cases based on the presence or absence of mild (IIIA), moderate (IIIB), or severe (IIIC) recipient cardiomyopathy. Progression was defined by worsening in the degree of recipient-twin cardiomyopathy from initial presentation or failure to respond to amnioreduction. Outcome data included progression of recipient-twin cardiomyopathy, treatment and survival to birth. Data were compared by the chi-square, Fisher's exact test or t-test as appropriate. Results Seventy-seven of 123 (62.6%) cases were Quintero Stage I and 46/123 (37.4%) Quintero Stage II. Eighty (65.0%) were upstaged to Cincinnati Stage IIIA (n = 25), IIIB (n = 23) or IIIC (n = 32). Management included observation in 11 (8.9%), amnioreduction in 26 (21.1%), amnioreduction followed by selective fetoscopic laser photocoagulation (SFLP) in 43 (35.0%) and primary SFLP in 43 (35.0%). Of 80 cases managed by observation or amnioreduction initially, 43 (53.8%) progressed within a mean duration of 1.4 ± 1.5 weeks. The incidence of progression increased significantly as degree of recipient-twin cardiomyopathy at presentation worsened: Stage I, 9/27 (33.3%); Stage II, 8/15 (53.3%); Stage IIIA, 8/16 (50.0%); Stage IIIB, 10/10 (100%); and Stage IIIC, 8/12 (66.7%) (χ2 = 14, P < 0.01). Overall fetal survival was 205 out of 244 (84.0%). Fetal survival with observation only was 81.8% (18/22), with amnioreduction only it was 92.3% (48/52), with initial observation or amnioreduction followed by SFLP it was 86.9% (73/84) and with primary SFLP it was 76.7% (66/86). Conclusion Echocardiography demonstrates a high incidence of recipient-twin cardiomyopathy in early-stage TTTS. The more advanced the recipient-twin cardiomyopathy is, the more likely is progression to occur during observation or following amnioreduction. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

We evaluated triploid pregnancy to determine whether there are clinically important differences between the three karyotypes: 69,XXX, 69,XXY, and 69,XYY. Prospectively maintained cytogenetic databases at five tertiary care centers were retrospectively reviewed over a 10-year period to identify all triploid pregnancies. Targeted ultrasounds were reviewed to identify fetal and placental findings. Sonographic findings were compared by karyotype. There was a total of 549 triploid gestations; preimplantation genetic diagnosis (PGD) detected 413 triploid embryos, and the cytogenetic databases provided 136 clinical pregnancies with triploidy. In triploid embryos with PGD, the frequency of the 69,XYY karyotype was 8.7% (36/413), compared with 0.74% (1/136) during the first trimester of clinical pregnancies (p = 0.002). In clinical pregnancies, 60% (36/60) of 69,XXY fetuses survived the first trimester of development compared with 69% (52/75) of 69,XXX fetuses (p = NS). No clinically important differences were observed between 69,XXX and 69,XXY karyotypes in terms of type, number, or severity of fetal or placental anomalies. Gestations with a 69,XYY karyotype are found less frequently compared with gestations with a 69,XXX or 69,XXY karyotype. The decline in fetal survival of the 69,XYY triploid karyotype needs further investigation. There are significant abnormalities detected during prenatal sonography in most all clinically recognized cases of triploidy. Sonography cannot reliably distinguish between the 69,XXY and 69,XXX karyotypes.

Congenital high airway obstruction syndrome (CHAOS) is a life-threatening condition characterized by complete blockage of the fetal airways associated with hydrops. We present a case of CHAOS due to the rare cause of complete tracheal agenesis. The ex utero intrapartum therapy (EXIT) strategy was employed to allow for neck and mediastinal exploration. Thymectomy allowed dissection to the level of the carina demonstrating the confluence of dilated mainstem bronchi but no trachea and no connection to the esophagus. A 2.5 endotracheal tube was inserted into the right mainstem bronchus and secured to the left clavicle. At 3 months of age, the infant succumbed to sepsis from Enterobacter mediastinitis due to friction between the tracheostomy tube and the nasogastric tube resulting in erosion of the esophagus. Complete tracheal agenesis, as seen in this case, is consistent with the failure of normal tracheal elongation as suggested by newer theories of foregut development. This case illustrates the most severe form of tracheal atresia causing CHAOS ever salvaged by the EXIT procedure at birth. The subsequent postnatal course highlights the need for early tracheal replacement in this particularly challenging form of CHAOS.

Background/Purpose Anecdotal reports suggest that maternal steroids may arrest the growth of congenital pulmonary airway malformations (CPAMs), preventing or reversing hydrops. We reviewed our experience with CPAMs to determine the fetal response to steroid therapy. Methods This study is a retrospective review of all fetal CPAMs from 2004 to 2008. Fetuses with high-risk CPAMs that received at least one course of steroids were identified. Fetal magnetic resonance imaging and ultrasound data were used to classify the CPAMs, identify hydrops fetalis and follow the fetuses poststeroid dosing. Results Forty-four fetuses with CPAM were identified. Fifteen patients were found to have received at least one course of steroids. Thirteen were hydropic and 2 were nonhydropic. Seven of the 13 hydropic fetuses (54%) showed an initial response to steroid administration, whereas the 2 nonhydropic high-risk fetuses progressed to birth without developing hydrops. Seven of the 15 patients, however, resulted in fetal demise or early postnatal death, giving a survival rate of 53%. Conclusions High-risk CPAMs have a variable response to steroids. This variable response demonstrates the need for a placebo-controlled randomized study to more accurately determine the effect of steroids on hydrops and CPAM growth rates. Repeated steroid courses may not be helpful, and progression in CPAM volume to head circumference ratio (CVR) or hydrops should prompt open fetal surgery to prevent irreversible fetal insult.

Objective. The purpose of this study was to examine the sonographic findings in fetuses with trisomy 18 in the second trimester of pregnancy. Methods. A retrospective review of the cytogenetic laboratory databases at 6 tertiary referral centers identified all cases of trisomy 18. The prenatal sonographic studies in fetuses at 15 to 21 weeks’ gestation, done before invasive testing for the karyotype, were reviewed for anatomic and biometric findings. We defined abnormal fetal biometric findings as a biometric measurement (biparietal diameter, abdominal circumference, or femur length) below the fifth percentile in the second trimester. Results. Of 98 fetuses with trisomy 18, 95 (97%) were detected sonographically; an anomaly was found in 92 (94%). A biometric measurement below the fifth percentile was noted in 50 (51%). Cardiac (63%) and central nervous system (34%) anomalies were most frequently detected. Although choroid plexus cysts were commonly seen, no fetuses with trisomy 18 and isolated choroid plexus cysts were found. Conclusions. Targeted sonography identified abnormal fetal anatomy or abnormal biometric findings in 97% of fetuses with trisomy 18 in the second trimester. A biometric measurement below the fifth percentile was noted in half of the cases in the

Objectives To examine cardiac structural and functional changes in twin–twin transfusion syndrome (TTTS), relative to Quintero stage, as a means of evaluating the spectrum of cardiomyopathy in TTTS. Methods This was a cross-sectional, retrospective study of 42 consecutive cases of TTTS referred to a single fetal therapy center. Quintero stages were assigned by standard criteria. Presence of ventricular hypertrophy, cardiomegaly, atrioventricular valve regurgitation (AVVR), ventricular systolic dysfunction and right ventricular outflow tract obstruction on fetal echocardiography were noted. The Doppler myocardial performance index (MPI), an index of global ventricular function, was calculated for both ventricles in subjects with adequate Doppler data. We compared cardiac changes across Quintero stages. Results There was no cardiomyopathy observed in donor twins. The majority of subjects presented at Quintero Stage I (n = 14), II (n = 14) or III (n = 11), with fewer at Stages IV (n = 2) or V (n = 1). As early as Quintero Stages I and II, a significant proportion of recipient twins had ventricular hypertrophy (17/28, 61%), AVVR (6/28, 21%) or quantitative abnormalities in either right (12/24, 50%) or left (14/24, 58%) ventricular function. Increasing prevalence of biventricular systolic dysfunction and cardiomegaly accompanied advancing Quintero stage. Conclusions Changes in cardiac structure and function not reflected in Quintero staging occur in recipient twins early in the evolution of TTTS. Incorporation of cardiac findings into assessment of TTTS severity may prove useful in stratification of risk and treatment selection. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.

Introduction Hypoplastic left heart syndrome (HLHS) is a severe cardiovascular malformation (CVM) associated with fetal growth abnormalities. Genetic and environmental factors have been identified that contribute to pathogenesis, but the role of the placenta is unknown. The purpose of this study was to systematically examine the placenta in HLHS with and without growth abnormalities. Methods HLHS term singleton births were identified from a larger cohort when placenta tissue was available. Clinical data were collected from maternal and neonatal medical records, including anthropometrics and placental pathology reports. Placental tissues from cases and controls were analyzed to assess parenchymal morphology, vascular architecture and leptin signaling. Results HLHS cases ( n = 16) and gestational age-matched controls ( n = 18) were analyzed. Among cases, the average birth weight was 2993 g, including 31% that were small for gestational age. When compared with controls, gross pathology of HLHS cases demonstrated significantly reduced placental weight and increased fibrin deposition, while micropathology showed increased syncytial nuclear aggregates, decreased terminal villi, reduced vasculature and increased leptin expression in syncytiotrophoblast and endothelial cells. Discussion Placentas from pregnancies complicated by fetal HLHS are characterized by abnormal parenchymal morphology, suggesting immature structure may be due to vascular abnormalities. Increased leptin expression may indicate an attempt to compensate for these vascular abnormalities. Further investigation into the regulation of angiogenesis in the fetus and placenta may elucidate the causes of HLHS and associated growth abnormalities in some cases.

Leptin is an adipokine that regulates energy homeostasis. The objective of this study was to establish a gestational age-specific standard for amniotic fluid leptin (AFL) levels and examine the relationship between AFL, maternal overweight and fetal growth restriction.Amniotic fluid was obtained at mid-gestation from singleton gravidas, and leptin was quantified using enzyme-linked immunosorbent assay. Amniotic fluid samples from 321 term pregnancies were analyzed. Clinical data, including fetal ultrasound measurements and maternal and infant characteristics, were available for a subset of patients (n=45).The median interquartile range AFL level was significantly higher at 14 weeks' gestation (2133 pg ml(-1) (1703 to 4347)) than after 33 weeks' gestation (519 pg ml(-1) (380 to 761), P trend0.0001), an average difference of 102 pg ml(-1) per week. AFL levels were positively correlated with maternal pre-pregnancy body mass index (BMI) (r=0.36, P=0.03) adjusting for gestational age at measurement, but were not associated with fetal growth.AFL levels are higher at mid-gestation than at late gestation, and are associated with maternal pre-pregnancy BMI.

To measure amniotic fluid leptin levels in fetuses with twin-twin transfusion syndrome (TTTS) with and without placental insufficiency (PI) and determine its usefulness as a biomarker of PI.A retrospective case control study of TTTS stage III patients from 2009 to 2011 was conducted. Cases were pregnancies with PI (TTTS-PI, n = 18) matched by stage, gestational age, and degree of cardiomyopathy to controls without PI (TTTS, n = 26). PI was strictly defined using biometric parameters. Amniotic fluid from recipient twins (RT) was taken during second trimester fetoscopic laser therapy. Leptin concentrations were determined and compared to growth parameters and birth weight.RT-adjusted leptin was 66% higher in TTTS-PI (p = 0.016) compared to TTTS controls. Cases had significantly higher growth discordance (p = 0.004) and lower RT birth weight (p = 0.041) compared to controls. Significantly higher adjusted leptin levels were observed at birth in the TTTS-PI group when comparing those with SGA donor twins to those of normal weight (p = 0.016).These data suggest a role for leptin in pregnancies complicated by TTTS with placental insufficiency. However, further studies are needed to define its mechanism and potential role as a biomarker in amniotic fluid for placental pathophysiology.

Fetal growth restriction with oligohydramnios occurring in the preterm gestation is associated with significant fetal morbidity and mortality. We investigated the possibility that transabdominal amnioinfusion might relieve acute cord compression and allow prolongation of gestation long enough to administer corticosteroids. Four patients with fetal growth restriction, oligohydramnios and evidence of significant cord compression with otherwise reassuring fetal heart rate testing underwent transabdominal amnioinfusion. Pregnancy was prolonged 22, 38, 10 and 9 days, and cord compression was relieved in all cases. One patient showed findings consistent with reversal of chronic hypoxemia with stabilization of amniotic fluid index measurements in the normal range and normalization of fetal growth. Transabdominal amnioinfusion may be useful as an adjunctive technique to prolong pregnancy in preterm gestations with fetal growth restriction, oligohydramnios and evidence of umbilical cord compression.

Objective The purpose of this study was to evaluate the effect of maternal nifedipine on fetal survival when started 24-48 hours before selective fetoscopic laser photocoagulation (SFLP). Study Design We conducted a case control study of consecutive cases of twin-twin transfusion syndrome (TTTS) in which TTTS cardiomyopathy was treated with maternal nifedipine 24-48 hours before SFLP, compared with gestational age and stage-matched control cases. The primary outcome was recipient and donor survival. Results One hundred forty-one cases of TTTS were treated with nifedipine, and 152 gestational age- and stage-matched control cases were analyzed. There was a significant increase in overall fetal survival in nifedipine-treated cases compared with control cases (237/284 [83%] vs 232/308 [75%]; P = .015). There is an increase in survival of recipients who were treated with nifedipine in stage IIIA (100% vs 81%; P = .021) and IIIB (93% vs 71%; P = .014); however, there was no difference in donor survival. Conclusion Maternal nifedipine is associated with improved recipient survival in TTTS that undergoes SFLP. This is the first study to suggest a benefit of adjunctive maternal medical therapy in patients with TTTS who undergo SFLP.

We sought to evaluate amniotic fluid brain natriuretic peptide (BNP) levels as a biomarker of recipient twin (RT) cardiomyopathy (RTCM) in twin-twin transfusion syndrome.Amniotic fluid samples were obtained from 157 twin-twin transfusion syndrome RTs and from 6 singletons (controls) from 2007 through 2009. N-terminal prohormone BNP (NT-proBNP) levels were quantified by enzyme-linked immunosorbent assay. RTCM was classified as mild (IIIA), moderate (IIIB), or severe (IIIC) by fetal echocardiography. The relationship between NT-proBNP and RTCM was evaluated using analysis of variance. The ability of NT-proBNP to predict moderate or greater RTCM was evaluated by receiver operating characteristic analysis.There is a significant positive correlation between NT-proBNP levels and worsening RTCM (r = 0.33; P.001). NT-proBNP thresholds of 569 fmol/mg and 369 fmol/mg had a sensitivity of 70% and 87%, and specificity of 67% and 42%, respectively, in predicting moderate or greater RTCM.This is the first large case series that demonstrates a relationship between NT-proBNP and RTCM. This pathophysiologic insight supports ongoing efforts to develop screening biomarkers.

The ex utero intrapartum treatment (EXIT) procedure has become an important management option in cases of fetal airway obstruction. Select cases of severe micrognathia may be candidates for EXIT-to-Airway due to high-risk of airway obstruction at birth. Here we present three successful EXIT-to-Airway procedures for the management of congenital micrognathia in its most severe manifestations. Case 1: A 23-year-old G3P1011 with a pregnancy complicated by severe micorgnathia, jaw index Case 2: A 26-year-old G4P0120 with a pregnancy complicated by severe micrognathia, jaw index Case 3: A 36-year-old G6P3023 with fetal magnetic resonance imaging (MRI) revealing esophageal atresia, polyhydramnios, and severe micrognathia with a jaw index

Objective. The purpose of this study was to identify the most common prenatal sonographic findings in fetuses with complete trisomy 9. Methods. A retrospective review of all cases of trisomy 9 at 5 participating institutions over a 15-year interval was conducted. Indications for referral and sonographic findings in each case were reviewed to identify characteristic fetal structural anomalies. Results. Six cases of trisomy 9 are presented. Most patients were referred for abnormal sonographic findings on screening examinations (66%) or advanced maternal age (33%). Fetal heart defects and central nervous system malformations were the most frequent sonographic anomalies seen. Conclusions. Sonographic findings in trisomy 9 are similar to those found in other autosomal trisomies. Because trisomy 9 is uniformly lethal and is not included as part of the standard prenatal aneuploidy screening by fluorescence in situ hybridization analysis, clinicians should be cautious in counseling patients with structurally abnormal fetuses until the full karyotype is available. Key words: prenatal diagnosis; sonography; trisomy 9.

Hypoplastic left heart syndrome (HLHS) with intact atrial septum (IAS) is a severe congenital cardiac malformation with little possibility of postnatal survival, unless an intra-atrial connection is created promptly after delivery. The timing of that intervention is often dictated by logistic restrictions, such as the proximity of the delivery room to the cardiac catheterization laboratory. This report details the use of a hybrid cardiac catheterization suite to expedite the delivery, transfer, and initial treatment of a fetus with HLHS/IAS. The mother underwent cesarean delivery in one hybrid room, and the newborn infant was transferred directly into an adjoining room where successful atrial septal stenting was performed without delay via a percutaneous, transhepatic approach. © 2008 Wiley-Liss, Inc.

Objectives The purpose of this study was to examine sonographic findings in fetuses with trisomy 13. Methods A retrospective review of the cytogenetic laboratory databases at 6 tertiary referral centers identified all cases of trisomy 13. The prenatal sonographic studies in fetuses of less than 22 weeks' gestation, done before invasive testing for karyotype, were reviewed for anatomic and biometric findings. We defined abnormal fetal biometric findings as a biometric measurement (biparietal diameter, abdominal circumference, or femur length) below the fifth percentile in the second trimester. Results There were 8 cases of trisomy 13 found in the first trimester and 54 cases found in the second trimester, a total of 62 in all. In the first trimester, 6 of 8 had an anomaly identified (4 with cystic hygroma). In the second trimester, 49 of 54 were identified by sonography; 45 had an anomaly, and 4 had an abnormal fetal biometric measurement without an anomaly. The 5 missed diagnoses had early gestational age (

This study was designed to determine whether immediate cesarean delivery for patients with severe preeclampsia confers any benefit to the mother or neonate.This retrospective chart review included all deliveries complicated by severe preeclampsia between July 1, 1999, and June 30, 2000. Cesarean deliveries performed for malpresentation, previous classic incision, multiple gestation, placenta previa, and herpetic outbreak were not included. Demographic variables, maternal outcomes, and neonatal outcomes were collected.Of 114 patients, 93 had an option regarding route of delivery. Thirty-four had an immediate cesarean section and 59 had induction of labor. Thirty-seven of 59 were delivered vaginally and 22 of 59 underwent cesarean delivery. Pulmonary complications in the mother and neonate were more common in cesarean delivery (P.05). No morbidity was decreased by cesarean delivery. Bishop score and gestational age did not affect the labor induction success rate.Immediate cesarean delivery confers no benefit to patients with severe preeclampsia.

The etiology of PROM is multifactorial. It is clear that maternal enzymes, maturational and mechanical forces, chorionicamniotic membrane phospholipid content, collagen disruption, amniotic cell cytokines induced by fetal signals, and bacterial phospholipases and collagenases all play major and interrelated roles. It is also clear that the production of oxytocic prostaglandins is a major, if not exclusive, common pathway leading to PROM and preterm delivery. The increasing awareness of the fetal role, i.e., fetal interleukins, fetal polymorphonuclear leukocytes and type V collagenase, make this area of research ripe for further investigation. The complex host defense mechanisms and biologic variability make any universal treatment impossible. Even with a specific etiology determined, the reduced availability of pharmacologic interventions for the fetal compartment portend suboptimal success. Therefore, it appears that continued research and aggressive measures to optimize the quality and availability of prenatal care are the best foci of our efforts.

repair of fetal MMC using a modified surgical technique without the use of a trocar from February through July 2011 are presented. Uterine entry and closure were modified to minimize trauma to the amniotic membrane and chorioamnion separation. Patients were admitted for five days, then discharged home for continued care by their referring maternal-fetal medicine specialist. Weekly ultrasound reports were obtained from primary MFM providers and reviewed for chorioamnion separation, amniotic fluid index (AFI), ventriculomegaly and fetal well-being. Delivery data were obtained from the delivering physicians. RESULTS: Of the 13 patients included in this series, there have been no cases of chorioamnion separation to date. Seven patients delivered between 34 to 37 weeks’ gestation. Of these, three patients were delivered electively at 34 weeks’ gestation: one patient for oligohydramnios, one patient experienced premature rupture of membranes (PROM) at 31 weeks’ gestation and was managed expectantly, and one patient was delivered for increasing ventriculomegaly. Five patients are currently undelivered, between 30 to 34 weeks’ gestation, with normal AFI. The thirteenth patient is at 28 weeks’ gestation with normal AFI at the time of this submission. There were no instances of uterine dehisence or wall thinning in the patients delivered. No patient received a blood transfusion. CONCLUSION: Early results suggest that a modified surgical approach to uterine entry, amniotic membrane handling and uterine closure may result in a decreased risk of chorioamnion separation and PROM. Further assessment of results with this technique in a growing series is ongoing.

points; 2nd and 3rd trimester scans were scored out of 27 possible points. Scans achieving a score 80% were considered passing; scans scoring 80% were considered failing and required submission of a supplemental scan. RESULTS: A total of 36 sonographers participated from 14 centers. Median sonographer experience performing obstetric ultrasounds was 12 years (range 3-30). Overall, 580 scans were submitted, of which 77.8% passed. More than 90% (20/22) of sonographers were required to submit 1 supplemental scan. Pass rates were significantly lower for initial submissions (74.7%; 349/467) than supplemental scans (90.3%; 102/113) (p 0.0005). Pass rates were similar for the three trimesters (1st: 80.6% [158/196]; 2nd: 77.5% [155/200]; 3rd: 75% [138/184]) (p 0.419). Figure 1 demonstrates the percentage of scans in which a deduction was made for select parameters. Of those sonographers who achieved credentialing in all trimesters (22/36; 61%), median time to full credentialing was 5.0 months (range 3-10). CONCLUSION: Intensive training and image review can be used to credential sonographers to perform standardized 2D ultrasounds of fetal biometry. Despite extensive prior experience, sonographers were often required to submit supplemental scans to demonstrate proper image acquisition and caliper placement.

evidence of brain-sparing persists after treatment of twin-reversed arterial perfusion sequence Jodie Votava-Smith, James Cnota, Susan Gomien, Mounira Habli, William Polzin, James Van Hook, Timothy Crombleholme, Erik Michelfelder Cincinnati Children’s Hospital Medical Center, Fetal Cardiology Program, The Heart Institute, Cincinnati, OH, Cincinnati Children’s Hospital Medical Center, Fetal Care Center, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH, Good Samaritan Hospital, Obstetrics and Gynecology, Cincinnati, OH, University of Cincinnati, Obstetrics and Gynecology, Cincinnati, OH OBJECTIVE: Pump twins of twin-reversed arterial perfusion (TRAP) sequence may have altered cerebrovascular tone to preserve brain oxygenation in response to highly desaturated umbilical venous return from the acardiac twin. We sought to characterize the cerebroplacental Doppler patterns in pump twins before and after therapeutic radiofrequency ablation (RFA) of the acardiac twin. STUDY DESIGN: We retrospectively reviewed pre and post-RFA echocardiograms of TRAP fetuses performed between 2/04 and 2/11. Doppler evaluation included estimation of pump twin combined cardiac output indexed for weight (CCO), and pulsatility index (PI) of the middle cerebral artery (MCA) and umbilical artery (UA). PI zscores were calculated. Paired t-tests were used to compare pre and post-RFA Doppler data. RESULTS: 35 fetuses had complete pre-RFA Doppler datasets. Mean gestational age (GA) was 20.6 / 2.5 weeks. Mean z-score for UA-PI was 2.8 / 1.1, with 80% of fetuses having UA-PI z-score 2. Mean z-score for MCA-PI was 1.0 / 1.0, including 17% of fetuses with MCA-PI z-score 2 and none with MCA-PI z-score 2. Estimated fetal weight was 5th percentile for GA in 34/35 (97%). Post-RFA Doppler data was available in 12 pump twins, with follow-up study done a median of 2 days (interquartile range 1,5) post-RFA. Following intervention, pump twin CCO decreased but there was no significant change in MCA-PI, UA-PI, or CPR (Table 1). CONCLUSION: Prior to RFA therapy, the majority of the pump twins demonstrate low CPR secondary to abnormally high UA-PI rather than low MCA-PI. These findings persist in short term follow-up after RFA, despite a significant decline in CCO indicating interventional success. These results suggest elevated placental vascular resistance, which may be due to abnormal placental vascular connections which persist after cord ablation of the acardius, versus placental vascular remodeling secondary to chronic hypoxia. Further studies to characterize the placental pathology of this condition are warranted. 351 Accuracy of fetal weight estimation by ultrasound in periviable deliveries John Ethridge, Judette Louis, Brian Mercer MetroHealth Medical Center-Case Western Reserve University, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Cleveland, OH OBJECTIVE: We sought to evaluate the accuracy of fetal weight estimation (EFW) by ultrasound (US) in women delivering near the limit of viability, and to determine factors that impact this accuracy. STUDY DESIGN: Retrospective chart review was performed for women delivering between 22 0/7 and 25 6/7 weeks gestation (GA). Individual patient records were reviewed to assess if an US was performed for EFW within 7 days of delivery. If so, additional potentially relevant clinical factors were abstracted (see results) and training level of person performing the ultrasound documented. These factors were examined to determine their impact on the accuracy of EFW. EFW and birth weights (BWT) were entered into an NICHD algorithm to predict survival, and were then compared between each other. RESULTS: 100 patients meeting inclusion criteria (2/2007 8/2011) were included. The cohort was 60% African-American, with median parity 1. Mean [S.D.] maternal age was 25.9 [6.9] yrs, and BMI 30.0 [7.4] kg/m2. Mean absolute percent difference (accuracy) between EFW and BWT was 10.2% (95% CI 8.0 12.4). Linear regression analysis revealed no correlation between EFW accuracy and GA, maternal age, or BMI. While significant associations were seen between BWT and accuracy (p 0.019; 1% decrease in absolute error per 100 gm increase in BWT), and in mean % error and BWT (p 0.001, 3% overestimation of BWT per 100 gm decrease in BWT), these were not clinically meaningful. ANOVA found no difference in accuracy based on race, fetal presentation, oligohydramnios, parity, smoking, prior CD, or level of training of the examiner. Mean predicted survival for the cohort from the NICHD algorithm was 43.1% using actual BWT compared with 43.6% using EFW (p 0.91). A difference greater than 20% in predicted survival was seen in only 2 cases. CONCLUSION: EFW in periviable deliveries is affected by BWT, but estimated survival based on ultrasound EFW within 7 days of delivery is similar to that based on actual BWT.

nancies. Only one sample (0.6%) failed to pass QC. All 36 T21 samples (100%) and 8 T18 samples (100%) had Z-scores greater than 3 and all of the 126 normal samples had Z-scores less than 3 (100%). These results were generated from an average of 789K raw sequencing reads per sample, i.e., 5% of the raw reads required for aneuploidy detection using MPSS. CONCLUSION: DANSR represents a high accuracy, cost efficient, scalable approach to non-invasive detection of fetal aneuploidy.

in fetoscopic devascularization and outcomes Foong-Yen Lim, William Polzin, Ronald Jaekle, Mounira Habli, David Lewis, James Van Hook, Timothy Crombleholme Cincinnati Children’s Hospital Medical Center, Fetal Care Center, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH, Good Samaritan Hospital, Obstetrics and Gynecology, Cincinnati, OH, University of Cincinnati, Obstetrics and Gynecology, Cincinnati, OH, University of Cincinnati, Obstetrics and Gynecology, Cincinnati, OH, University of Cincinnati, Obstetrics and Gynecology, Cincinnati, OH OBJECTIVE: To evaluate the intrauterine management and perinatal outcome of pregnancies complicated by giant placental chorioangioma ( 4cm). STUDY DESIGN: Retrospective review of 8 cases of giant placental chorioangioma referred to a single center between May 2006 and December 2010. Information on maternal demographics, prenatal imaging (ultrasound, fetal MRI, echocardiography), response to fetoscopic treatment for high cardiac output state or non-immune hydrops, obstetrical complications, and perinatal outcome were evaluated. RESULTS: All 8 cases were isolated, had an average tumor size of 8.3cm (range 5.1-12.5cm). Mean gestational age at evaluation and delivery was 23.5 weeks and 35.5 weeks, respectively. Overall survival was 75%. Six (75%) cases were associated with obstetrical complications, including polyhydramnios (n 6), non-immune hydrops (n 3), high cardiac output state (n 5). Five patients had fetoscopic devascularization of the chorioangiomas: all 5 were contiguous with the placental cord insertion (PCI) at mean gestational age of 23.9 weeks with 80% survival. The tumors were devascularized by bipolar coagulation (n 1), combination of bipolar and diode laser (n 2), bipolar and radiofrequency ablation (n 1), and surgical clip application (n 1). Post-operatively, hydrops resolved in 2 of 2 and cardiac output normalized in 4 of 4, and all were liveborn at mean gestational age of 35.4 weeks. The three cases managed non-operatively had mild polyhydramnios persisted in one, and stillbirth occurred at 30 weeks gestation in one, with 66% survival. Mean gestational age at delivery was 35.6 weeks. CONCLUSION: Giant placental chorioangioma is associated with obstetrical complications particularly when contiguous with the PCI. Fetoscopic devascularization is indicated for high cardiac output or non-immune hydrops, which may require multiple techniques including bipolar coagulation or clip application to interrupt arterial inflow and laser to coagulate surface collateral vessels.