Cytomegalovirus (CMV) is the most common cause of congenital infection, and is a major cause of sensorineural hearing loss and neurological disabilities. Evaluating the risk for a CMV infected fetus to develop severe clinical symptoms after birth is crucial to provide appropriate guidance to pregnant women who might have to consider termination of pregnancy or experimental prenatal medical therapies. However, establishing the prognosis before birth remains a challenge. This evaluation is currently based upon fetal imaging and fetal biological parameters, but the positive and negative predictive values of these parameters are not optimal, leaving room for the development of new prognostic factors. Here, we compared the amniotic fluid peptidome between asymptomatic fetuses who were born as asymptomatic neonates and symptomatic fetuses who were either terminated in view of severe cerebral lesions or born as severely symptomatic neonates. This comparison allowed us to identify a 34-peptide classifier in a discovery cohort of 13 symptomatic and 13 asymptomatic neonates. This classifier further yielded 89% sensitivity, 75% specificity and an area under the curve of 0.90 to segregate 9 severely symptomatic from 12 asymptomatic neonates in a validation cohort, showing an overall better performance than that of classical fetal laboratory parameters. Pathway analysis of the 34 peptides underlined the role of viral entry in fetuses with severe brain disease as well as the potential importance of both beta-2-microglobulin and adiponectin to protect the injured fetal brain infected with CMV. The results also suggested the mechanistic implication of the T calcium channel alpha-1G (CACNA1G) protein in the development of seizures in severely CMV infected children. These results open a new field for potential therapeutic options. In conclusion, this study demonstrates that amniotic fluid peptidome analysis can effectively predict the severity of congenital CMV infection. This peptidomic classifier may therefore be used in clinical settings during pregnancy to improve prenatal counseling.
Summary. Hereditary hyperferritinaemia cataract syndrome (HHCS) is characterized by hyperferritinaemia without iron overload. It is essential to differentiate true iron accumulation from HHCS as these patients rapidly develop iron-deficient anaemia when subjected to phlebotomies. The diagnosis of HHCS relies on the identification of point mutations or deletions present in the iron-responsive element of the first exon of the L-ferritin gene. However, many samples referred for diagnosis of putative HHCS are normal. To avoid unnecessary DNA sequencing, we have developed a diagnosis strategy based on the screening of the target DNA region by denaturing gradient gel electrophoresis. This method enabled the accurate identification of 11 different previously known mutations. This strategy will be of interest for family studies or for the screening of large series of patients.
The objective of the study was to review the literature concerning delayed deliveries in multiple pregnancies and to highlight the existing guidelines for a better management of asynchronous births. A literature-search was done using Medline and ScienceDirect. All articles reporting at least 4 cases of delayed delivery were included, if they provided full information on gestational age and outcome of each offspring. The main outcome was the survival rate of the second twin or other higher-order multiples, stratified for gestational age of the first born (before or after 24 weeks of gestation). Secondary outcomes were: management strategies, interval between deliveries, neonatal and maternal complications. Among 18 relevant cohort studies, 391 twin and 34 triplet pregnancies could be analysed. In case of delayed delivery, the survival rate of the second twin or higher-order multiple was respectively 44.8% and 82.7% when the first twin was born before or after 24 weeks of gestation The later was the delivery of the first twin, the higher was the second twin's survival rate, but the shorter was the interval between births (14 vs. 26 days). Conservative measures included: high ligature of umbilical cord, tocolysis, corticoids, antibiotic therapy and cerclage. Main neonatal complications were septicemia (42%), retinopathy (62%) and intraventricular hemorrhage (37%), and the most frequent maternal complication was chorioamniotitis (30%). In spite of higher rates of chorioamniotitis, there was a clear advantage in delaying delivery of remaining multiples, as this improved the outcome of preterm birth. The possible strategies and their grades of recommendation for the management of asynchronous deliveries are summarized. G y n e c o lo gy & O b s te tr ic s
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