BACKGROUNDThe cause of most fetal anomalies is not determined prenatally. Exome sequencing has transformed genetic diagnosis after birth, but its usefulness for prenatal diagnosis is still emerging. Nonimmune hydrops fetalis (NIHF), a fetal abnormality that is often lethal, has numerous genetic causes; the extent to which exome sequencing can aid in its diagnosis is unclear. METHODSWe evaluated a series of 127 consecutive unexplained cases of NIHF that were defined by the presence of fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, increased nuchal translucency, or a combination of these conditions. The primary outcome was the diagnostic yield of exome sequencing for detecting genetic variants that were classified as either pathogenic or likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. Secondary outcomes were the percentage of cases associated with specific genetic disorders and the proportion of variants that were inherited. RESULTSIn 37 of the 127 cases (29%), we identified diagnostic genetic variants, including those for disorders affecting the RAS-MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnoses); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others. Prognoses ranged from a relatively mild outcome to death during the perinatal period. Overall, 68% of the cases (25 of 37) with diagnostic variants were autosomal dominant (of which 12% were inherited and 88% were de novo), 27% (10 of 37) were autosomal recessive (of which 95% were inherited and 5% were de novo), 1 was inherited X-linked recessive, and 1 was of uncertain inheritance. We identified potentially diagnostic variants in an additional 12 cases. CONCLUSIONSIn this large case series of 127 fetuses with unexplained NIHF, we identified a diagnostic genetic variant in approximately one third of the cases.
Objective To estimate the diagnostic accuracy of electronic fetal heart rate abnormalities in the identification of neonates with encephalopathy treated with whole-body hypothermia. Methods Between January 1, 2007, and July 1, 2013, there were 39 neonates born at two hospitals within our system treated with whole-body hypothermia within 6 hours of birth. Neurologically normal controls were matched to each case by gestational age and mode of delivery in a 2:1 fashion. The last hour of electronic fetal heart rate monitoring before delivery was evaluated by three obstetricians blinded to outcome. Results The differences in tracing category were not significantly different (cases 10.3% I, 76.9% II, 12.8% III; controls 9.0% I, 89.7% II, 1.3% III, p=0.18). Bivariate analysis showed cases had significantly increased late decelerations, total deceleration area 30 (debt 30) and 60 minutes (debt 60) prior to delivery and were more likely to be nonreactive. Multivariable logistic regression showed cases had a significant decrease in early decelerations (P=0.03) and a significant increase in debt 30 (0.01) and debt 60 (P=0.005). The area under the ROC curve, sensitivity and specificity were 0.72, 23.1%, 94.9% for early decelerations; 0.66, 33.3% and 87.2% for debt 30 and 0.68, 35.9% and 89.7% for debt 60. Conclusion Abnormalities during the last hour of fetal heart rate monitoring before delivery are poorly predictive of neonatal hypoxic-ischemic encephalopathy qualifying for whole-body hypothermia treatment within 6 hours of birth.
BACKGROUNDThe cause of most fetal anomalies is not determined prenatally. Exome sequencing has transformed genetic diagnosis after birth, but its usefulness for prenatal diagnosis is still emerging. Nonimmune hydrops fetalis (NIHF), a fetal abnormality that is often lethal, has numerous genetic causes; the extent to which exome sequencing can aid in its diagnosis is unclear. METHODSWe evaluated a series of 127 consecutive unexplained cases of NIHF that were defined by the presence of fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, increased nuchal translucency, or a combination of these conditions. The primary outcome was the diagnostic yield of exome sequencing for detecting genetic variants that were classified as either pathogenic or likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. Secondary outcomes were the percentage of cases associated with specific genetic disorders and the proportion of variants that were inherited. RESULTSIn 37 of the 127 cases (29%), we identified diagnostic genetic variants, including those for disorders affecting the RAS-MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnoses); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others. Prognoses ranged from a relatively mild outcome to death during the perinatal period. Overall, 68% of the cases (25 of 37) with diagnostic variants were autosomal dominant (of which 12% were inherited and 88% were de novo), 27% (10 of 37) were autosomal recessive (of which 95% were inherited and 5% were de novo), 1 was inherited X-linked recessive, and 1 was of uncertain inheritance. We identified potentially diagnostic variants in an additional 12 cases. CONCLUSIONSIn this large case series of 127 fetuses with unexplained NIHF, we identified a diagnostic genetic variant in approximately one third of the cases.
Human rights are today criticized as not compatible with different cultural values and the debate has circulated around Asian values and Islamic values as in dichotomy with human rights as universal ethics (Ignatieff, 2003). The theoretical dichotomy between universality and particularity is questioned pragmatically in this paper through a historical study. The working process of drafting the Universal Declaration of Human Rights (UDHR) in 1946-48, which included thousands of people, is explored as a cosmopolitan space in which individuals from different cultural contexts met to negotiate human rights through cultural narratives. The process where particular values were negotiated with universal notion on human rights resulted in a common proclamation (UDHR) without a common philosophical or ideological ground. This paper puts forth a thesis that human rights discourse can work as a cosmopolitan space, in which particular value systems meet in processes characterized by conflict and cohesion. Hence human rights can be understood as a master narrative compatible with different conflicting cultural narratives (Gibson & Somers, 1994).
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