Biomarkers of impaired placentation at 35-37 weeks' gestation in the prediction of adverse perinatal outcome

Objective: This screening study at 35-37 weeks’ gestation investigates the potential value of uterine artery pulsatility index (UtA-PI) and serum levels of the angiogenic placental growth factor (PlGF) and antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFLT-1) in the prediction of adverse perinatal outcome in small for gestational age (SGA) and non-SGA neonates. Methods: This was a prospective observational study in 19,209 singleton pregnancies attending for a routine hospital visit at 35+0 - 36+6 weeks’ gestation. This visit included recording of maternal demographic characteristics and medical history, sonographic estimation of fetal weight (EFW), color Doppler ultrasound for measurement of the mean UtA-PI, and measurement of serum concentration of PlGF and sFLT. Multivariable logistic regression analysis was carried out to determine which of the factors from maternal or pregnancy characteristics and measurements of UtA-PI, PlGF and sFLT-1, provided a significant contribution in the prediction of each of four adverse outcome measures: first, stillbirth, second, cesarean section for presumed fetal compromise in labor, third, neonatal death or hypoxic ischemic encephalopathy grades 2 and 3, and fourth, admission to the neonatal unit (NNU) for ≥48 hours. Predicted probabilities from logistic regression analysis were used to construct receiver operating characteristic (ROC) curves to assess performance of screening for these adverse outcomes. Results: First, 83% of stillbirths, 82% of cesarean sections for presumed fetal compromise in labor, 91% of cases of neonatal death or hypoxic ischemic encephalopathy and 86% of NNU admissions for ≥48 hours occurred in pregnancies with non-SGA babies. Second, UtA-PI >95th percentile, sFLT-1 >95th percentile and PLGF 95th, sFLT-1 >95th and PLGF <5th percentiles for most adverse outcomes was <2.5 in both SGA and non-SGA neonates. Conclusions: In pregnancies undergoing routine antenatal assessment at 35-37 weeks’ gestation measurements of UtA-PI, sFLT-1 or PlGF provide poor prediction of adverse perinatal outcome in both SGA and non-SGA fetuses

Initial Experience of Superb Microvascular Imaging for Key Cardiac Views in Foetal Assessment before 15 Weeks Gestation

Background: In the first trimester, ultrasound confirmation of normal or abnormal cardiac anatomy is difficult. B-mode and colour flow Doppler (CFD) are used to assess the foetal heart. Superb microvascular imaging (SMI) can visualise blood flow within the heart and vessels in early gestation. Objective: We report an initial experience of SMI for visualisation of normal and abnormal cardiac anatomy in the first trimester. Methods: Transabdominal foetal echocardiography was performed between 11 + 6 and 14 + 3 weeks (Aplio 500 US system, Toshiba Medical Systems, Tokyo, Japan) from January 2017 to December 2017. All scans were performed at a tertiary foetal cardiology unit. To assess the potential utility of the technique for early gestation screening, normal scans were reviewed by foetal medicine trainees with respect to the B-mode, CFD and SMI. Three key views were selected to compare modalities: the 4-chamber view, outflow tracts and the 3-vessel and trachea view (VTV). Visualisation rates of key echocardiographic features of significant cardiac abnormalities by SMI were reviewed. Results: Fifty-five normal echocardiograms and 34 cardiac abnormalities were included. In the normal heart, when B-mode, CFD and SMI were assessed separately, SMI had the highest rate of visualisation of 4-chamber, outflow tracts and 3-VTV (93, 85 and 83%, respectively). Intra-observer reliability was moderate for SMI of the 3 standard views (kappa 1, 0.64 and 0.64); inter-observer for 4-chamber and outflow tract views was moderate (kappa 0.64 and 0.77). In 29/34 abnormal cases, SMI showed key features, enhancing greyscale visualisation. Conclusion: SMI has potential to become a useful, complementary modality for early foetal echocardiography. Further prospective studies are warranted to establish the place of the technique in assessment of the first trimester foetal heart.info:eu-repo/semantics/publishedVersio

Congenital fibrosis of the extraocular muscles type 2, an inherited exotropic strabismus fixus, maps to distal 11q13.

The extraocular fibrosis syndromes are congenital ocular-motility disorders that arise from dysfunction of the oculomotor, trochlear, and abducens nerves and/or the muscles that they innervate. Each is marked by a specific form of restrictive paralytic ophthalmoplegia with or without ptosis. Individuals with the classic form of congenital fibrosis of the extraocular muscles (CFEOM1) are born with bilateral ptosis and a restrictive infraductive external ophthalmoplegia. We previously demonstrated that CFEOM1 is caused by an autosomal dominant locus on chromosome 12 and results from a developmental absence of the superior division of the oculomotor nerve. We now have mapped a variant of CFEOM, exotropic strabismus fixus ("CFEOM2"). Affected individuals are born with bilateral ptosis and restrictive ophthalmoplegia with the globes "frozen" in extreme abduction. This autosomal recessive disorder is present in members of three consanguineous Saudi Arabian families. Genetic analysis of 70 individuals (20 affected individuals) reveals linkage to markers on chromosome 11q13, with a combined LOD score of 12.3 at the single nonrecombinant marker, D11S1314. The 2.5-cM CFEOM2 critical region is flanked by D11S4196/D11S4162 and D11S4184/1369. Two of the three families share a common disease-associated haplotype, suggesting a founder effect for CFEOM2. We hypothesize that CFEOM2 results from an analogous developmental defect to CFEOM1, one that affects both the superior and inferior divisions of the oculomotor nerve and their corresponding alpha motoneurons and extraocular muscles