19 research outputs found
Fetal Metabolic Adaptations to Cardiovascular Stress in Twin-Twin Transfusion Syndrome
Monochorionic-diamniotic twin pregnancies are susceptible to unique complications arising from a single placenta shared by two fetuses. Twin-twin transfusion syndrome (TTTS) is a constellation of disturbances caused by unequal blood flow within the shared placenta giving rise to a major hemodynamic imbalance between the twins. Here, we applied TTTS as a model to uncover fetal metabolic adaptations to cardiovascular stress. We compared untargeted metabolomic analyses of amniotic fluid samples from severe TTTS cases vs. singleton controls. Amniotic fluid metabolites demonstrated alterations in fatty acid, glucose, and steroid hormone metabolism in TTTS. Among TTTS cases, unsupervised principal component analysis revealed two distinct clusters of disease defined by levels of glucose metabolites, amino acids, urea, and redox status. Our results suggest that the human fetal heart can adapt to hemodynamic stress by modulating its glucose metabolism and identify potential differences in the ability of individual fetuses to respond to cardiovascular stress
Spontaneous twin anemia polycythemia sequence: diagnosis, management, and outcome in an international cohort of 249 cases.
BACKGROUND: Twin anemia polycythemia sequence is a chronic form of unbalanced fetofetal transfusion through minuscule placental anastomoses in monochorionic twins, leading to anemia in the donor and polycythemia in the recipient. Owing to the low incidence of twin anemia polycythemia sequence, data on diagnosis, management, and outcome are limited. OBJECTIVE: This study aimed to investigate the diagnosis, management, and outcome in a large international cohort of spontaneous twin anemia polycythemia sequence. STUDY DESIGN: Data from the international twin anemia polycythemia sequence registry, retrospectively collected between 2014 and 2019, were used for this study. A total of 17 fetal therapy centers contributed to the data collection. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. RESULTS: A total of 249 cases of spontaneous twin anemia polycythemia sequence were included in this study, 219 (88%) of which were diagnosed antenatally and 30 (12%) postnatally. Twin anemia polycythemia sequence was diagnosed antenatally at a median gestational age of 23.7 weeks (interquartile range, 9.7-28.8; range, 15.1-35.3). Antenatal management included laser surgery in 39% (86 of 219), expectant management in 23% (51 of 219), delivery in 16% (34 of 219), intrauterine transfusion (with partial exchange transfusion) in 12% (26 of 219), selective feticide in 8% (18 of 219), and termination of pregnancy in 1% (3 of 219) of cases. Perinatal mortality rate was 15% (72 of 493) for the total group, 22% (54 of 243) for donors, and 7% (18 of 242) for recipients (P<.001). Severe neonatal morbidity occurred in 33% (141 of 432) of twins with twin anemia polycythemia sequence and was similar for donors (32%; 63 of 196) and recipients (33%; 75 of 228) (P=.628). Independent risk factors for spontaneous perinatal mortality were donor status (odds ratio, 3.8; 95% confidence interval, 1.9-7.5; P<.001), antenatal twin anemia polycythemia sequence stage (odds ratio, 6.3; 95% confidence interval, 1.4-27.8; P=.016 [stage 2]; odds ratio, 9.6; 95% confidence interval, 2.1-45.5; P=.005 [stage 3]; odds ratio, 20.9; 95% confidence interval, 3.0-146.4; P=.002 [stage 4]), and gestational age at birth (odds ratio, 0.8; 95% confidence interval, 0.7-0.9; P=.001). Independent risk factors for severe neonatal morbidity were antenatal twin anemia polycythemia sequence stage 4 (odds ratio, 7.9; 95% confidence interval, 1.4-43.3; P=.018) and gestational age at birth (odds ratio, 1.7; 95% confidence interval, 1.5-2.1, P<.001). CONCLUSION: Spontaneous twin anemia polycythemia sequence can develop at any time in pregnancy from the beginning of the second trimester to the end of the third trimester. Management for twin anemia polycythemia sequence varies considerably, with laser surgery being the most frequent intervention. Perinatal mortality and severe neonatal morbidity were high, the former especially so in the donor twins
The evidence behind the level of a random urine protein:creatinine in the diagnosis of preeclampsia: A systematic review
Objective. To determine the accuracy of the urine protein:creatinine ratio (pr:cr) in predicting 300 mg of protein in 24-hour urine collection in pregnant patients with suspected preeclampsia. Methods. A systematic review was performed. Articles were identified through electronic databases and the relevant citations were hand searching of textbooks and review articles. Included studies evaluated patients for suspected preeclampsia with a 24-hour urine sample and a pr:cr. Only English language articles were included. The studies that had patients with chronic illness such as chronic hypertension, diabetes mellitus or renal impairment were excluded from the review. Two researchers extracted accuracy data for pr:cr relative to a gold standard of 300 mg of protein in 24-hour sample as well as population and study characteristics. The data was analyzed and summarized in tabular and graphical form. Results. Sixteen studies were identified and only three studies met our inclusion criteria with 510 total patients. The studies evaluated different cut-points for positivity of pr:cr from 130 mg/g to 700 mg/g. Sensitivities and specificities for pr:cr of 130mg/g -150 mg/g were 90-93% and 33-65%, respectively; for a pr:cr of 300 mg/g were 81-95% and 52-80%, respectively; for a pr:cr of 600-700mg/g were 85-87% and 96-97%, respectively. Conclusion. The value of a random pr:cr to exclude pre-eclampsia is limited because even low levels of pr:cr (130-150 mg/g) may miss up to 10% of patients with significant proteinuria. A pr:cr of more than 600 mg/g may obviate a 24-hour collection
1070: Outcomes after laser surgery are similar for patients with TAPS, TTTS + TAPS, and TTTS
Fetal membrane patch and biomimetic adhesive coacervates as a sealant for fetoscopic defects
878: Predicting fetal and neonatal demise rates after fetoscopy for twin-twin transfusion syndrome with recursive partitioning
Middle Cerebral Artery Doppler Velocimetry for the Diagnosis of Twin Anemia Polycythemia Sequence: A Systematic Review
Twin anemia polycythemia sequence (TAPS) is a rare complication of monochorionic diamniotic (MCDA) twins. Middle cerebral artery peak systolic velocity (MCA-PSV) measurements are used to screen for TAPS while fetal or neonatal hemoglobin levels are required for definitive diagnosis. We sought to perform a systematic review of the efficacy of MCA-PSV in diagnosing TAPS. Search criteria were developed using relevant terms to query the Pubmed, Embase, and SCOPUS electronic databases. Publications reporting diagnostic characteristics of MCA-PSV measurements (i.e., sensitivity, specificity or receiver operator curves) were included. Each article was assessed for bias using the Quality Assessment of Diagnostic Accuracy Studies II (QUADAS II) tool. Results were assessed for uniformity to determine whether meta-analysis was feasible. Data were presented in tabular form. Among publications, five met the inclusion criteria. QUADAS II analysis revealed that four of the publications were highly likely to have bias in multiple areas. Meta-analysis was precluded by non-uniformity between definitions of TAPS by MCA-PSV and neonatal or fetal hemoglobin levels. High-quality prospective studies with consistent definitions and ultrasound surveillance protocols are still required to determine the efficacy of MCA-PSV in diagnosing TAPS. Other ultrasound findings (e.g., placenta echogenicity discordance) may augment Doppler studies
Fetal Pulmonary Response After Fetoscopic Tracheal Occlusion for Severe Isolated Congenital Diaphragmatic Hernia
OBJECTIVE: To estimate the response in lung growth and vascularity after fetal endoscopic tracheal occlusion for severe congenital diaphragmatic hernia in the prediction of neonatal survival. METHODS: Between January 2006 and December 2010, fetal lung parameters (observed-to-expected lung-to-head ratio; observed-to-expected lung volume; and contralateral lung vascularization index) were evaluated before fetal tracheal occlusion and were evaluated longitudinally every 2 weeks in 72 fetuses with severe isolated congenital diaphragmatic hernia. Thirty-five fetuses underwent fetal endoscopic tracheal occlusion and 37 cases did not. RESULTS: Survival rate was significantly higher in the fetal endoscopic tracheal occlusion group (54.3%) than in the no fetal endoscopic tracheal occlusion group (5.4%, P<.01). Fetal endoscopic tracheal occlusion resulted in a significant improvement in fetal lung size and pulmonary vascularity when compared with fetuses that did not go to the fetal intervention (increase of the observed-to-expected lung-to-head ratio, observed-to-expected total lung volume, and contralateral pulmonary vascularization index 56.2% compared with 0.3%, 37.9% compared with 0.1%, and 98.6% compared with 0.0%, respectively; P<.01). Receiver operating characteristic curves indicated that the observed-to-expected total fetal lung volume was the single best predictor of neonatal survival before fetal endoscopic tracheal occlusion (cutoff 0.23, area under the curve [AUC] 0.88, relative risk 5.3, 95% confidence interval [CI] 1.4-19.7). However, the contralateral lung vascularization index at 4 weeks after fetal endoscopic tracheal occlusion was more accurate in the prediction of neonatal outcome (cutoff 24.0%, AUC 0.98, relative risk 9.9, 95% CI 1.5-66.9) with the combination of observed-to-expected lung volumes and contralateral lung vascularization index at 4 weeks being the best predictor of outcome (AUC 0.98, relative risk 16.6, 95% CI 2.5-112.3). CONCLUSION: Fetal endoscopic tracheal occlusion improves survival rate by increasing the lung size and pulmonary vascularity in fetuses with severe congenital diaphragmatic hernia. The pulmonary response after fetal endoscopic tracheal occlusion can be used to predict neonatal survival. (Obstet Gynecol 2012; 119: 93-101) DOI: 10.1097/AOG.0b013e31823d3ae
Fetal metabolic adaptations to cardiovascular stress in twin-twin transfusion syndrome
Summary: Monochorionic-diamniotic twin pregnancies are susceptible to unique complications arising from a single placenta shared by two fetuses. Twin-twin transfusion syndrome (TTTS) is a constellation of disturbances caused by unequal blood flow within the shared placenta giving rise to a major hemodynamic imbalance between the twins. Here, we applied TTTS as a model to uncover fetal metabolic adaptations to cardiovascular stress. We compared untargeted metabolomic analyses of amniotic fluid samples from severe TTTS cases vs. singleton controls. Amniotic fluid metabolites demonstrated alterations in fatty acid, glucose, and steroid hormone metabolism in TTTS. Among TTTS cases, unsupervised principal component analysis revealed two distinct clusters of disease defined by levels of glucose metabolites, amino acids, urea, and redox status. Our results suggest that the human fetal heart can adapt to hemodynamic stress by modulating its glucose metabolism and identify potential differences in the ability of individual fetuses to respond to cardiovascular stress
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Neurological Outcomes after Human Umbilical Cord Patch for In Utero Spina Bifida Repair in a Sheep Model
Objectives: The objective of our study was to test the hypothesis that in utero repair of surgically created spina bifida in a sheep model using cryopreserved human umbilical cord (HUC) patch improves neurological outcome. Methods: Spina bifida with myelotomy was surgically created in timed pregnant ewes at gestational day (GD) 75. The fetuses were randomly assigned to unrepaired versus HUC and treated at GD 95 and then delivered at GD 140. Neurological evaluation was performed using the Texas Spinal Cord Injury Scale (TSCIS), bladder control using ultrasound, and the hindbrain herniation. Results: Three lambs without the spina bifida creation served as controls. There were four lambs with spina bifida: two were unrepaired and two underwent HUC repair. The control lambs had normal function. Both unrepaired lambs had nonhealed skin lesions with leakage of cerebrospinal fluid, a 0/20 TSCIS score, no bladder control, and the hindbrain herniation. In contrast, both HUC lambs had a completely healed skin defect and survived to day 2 of life, a 3/20 and 4/20 TSCIS score (nociception), partial bladder control, and normal hindbrain anatomy. Conclusions: Cryopreserved HUC patch appears to improve survival and neurological outcome in this severe form of the ovine model of spina bifida