Prenatal Genome-Wide Cell-Free DNA Screening: Three Years of Clinical Experience in a Hospital Prenatal Diagnostic Unit in Spain.

Genome-wide prenatal cell-free DNA (cfDNA) screening can be used to screen for a wide range of fetal chromosomal anomalies in pregnant patients. In this study, we describe our clinical experience with a genome-wide cfDNA assay in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RAAs), and copy-number variations (CNVs) in about 6000 patients over a three-year period at our hospital's Prenatal Diagnostic Unit in Spain. Overall, 204 (3.3%) patients had a high-risk call, which included 76 trisomy 21, 21 trisomy 18, 7 trisomy 13, 29 SCAs, 31 RAAs, 31 CNVs, and 9 cases with multiple anomalies. The diagnostic outcomes were obtained for the high-risk cases when available, allowing for the calculation of positive predictive values (PPVs). Calculated PPVs were 95.9% for trisomy 21, 77.8% for trisomy 18, 66.7% for trisomy 13, 10.7% for RAAs, and 10.7% for CNVs. Pregnancy and birth outcomes were also collected for the majority of RAA and CNV cases. Adverse perinatal outcomes for some of these cases included preeclampsia, fetal growth restriction, preterm birth, reduced birth weight, and major congenital structural abnormalities. In conclusion, our study showed strong performance for genome-wide cfDNA screening in a large cohort of pregnancy patients in Spain.

Protracted neuronal recruitment in the temporal lobes of young children.

The temporal lobe of the human brain contains the entorhinal cortex (EC). This region of the brain is a highly interconnected integrative hub for sensory and spatial information; it also has a key role in episodic memory formation and is the main source of cortical hippocampal inputs1-4. The human EC continues to develop during childhood5, but neurogenesis and neuronal migration to the EC are widely considered to be complete by birth. Here we show that the human temporal lobe contains many young neurons migrating into the postnatal EC and adjacent regions, with a large tangential stream persisting until the age of around one year and radial dispersal continuing until around two to three years of age. By contrast, we found no equivalent postnatal migration in rhesus macaques (Macaca mulatta). Immunostaining and single-nucleus RNA sequencing of ganglionic eminence germinal zones, the EC stream and the postnatal EC revealed that most migrating cells in the EC stream are derived from the caudal ganglionic eminence and become LAMP5+RELN+ inhibitory interneurons. These late-arriving interneurons could continue to shape the processing of sensory and spatial information well into postnatal life, when children are actively interacting with their environment. The EC is one of the first regions of the brain to be affected in Alzheimer's disease, and previous work has linked cognitive decline to the loss of LAMP5+RELN+ cells6,7. Our investigation reveals that many of these cells arrive in the EC through a major postnatal migratory stream in early childhood.

Expanding the phenotype of PIGP deficiency to multiple congenital anomalies-hypotonia-seizures syndrome.

Glycosylphosphatidylinositol-anchored proteins are involved in multiple physiological processes and the initial stage of their biosynthesis is mediated by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY, and DMP2 genes, which have been linked to a wide spectrum of phenotypes depending on the gene damaged. To date, the PIGP gene has only been related to Developmental and Epileptic Encephalopathy 55 (MIM#617599) in just seven patients. A detailed medical history was performed in two affected siblings with a multiple malformation syndrome. Genetic testing was performed using whole-exome sequencing. One patient presented dysmorphic features, congenital anomalies, hypotonia and epileptic encephalopathy as described in PIGA, PIGQ and PIGY deficiencies. The other one was a fetus with a severe malformation disorder at 17 weeks of gestation whose pregnancy was interrupted. Both were compound heterozygous of pathogenic variants in PIGP gene: NM_153682.3:c.2 T > C(p.?) and a 136 Kb deletion (GRCh37/hg19 21q22.13(chr21:38329939-38 466 066)×1) affecting the entire PIGP gene. Our results extend the clinical phenotype associated to PIGP gene and propose to include it as a novel cause of Multiple Congenital Anomalies-Hypotonia-Seizures syndrome.

The vertebroplacental ratio as an alternative to the cerebroplacental ratio in the evaluation of the fetus at the end of pregnancy.

OBJECTIVE: Low cerebroplacental ratio (CPR) near term has emerged as a marker of fetal adverse outcome. The aim of this study was to evaluate the predictive accuracy of an alternative ratio using the vertebral artery (VA) (vertebroplacental ratio or VPR) for acid-base status at birth. METHODS: This was a prospective cohort study of 1470 pregnancies undergoing an ultrasound assessment of the umbilical artery, middle cerebral artery and VA Doppler beyond 34 weeks' gestation within 14 days of delivery. The CPR multiples of the median (MoM) and VPR MoM were calculated to adjust for gestational age. The relationship between the fetal Dopplers and the umbilical cord pH (arterial and venous) was evaluated statistically, and depicted graphically using three-dimensional (3D) trend surfaces, 2D contour graphs and ROC curves. RESULTS: All the studied parameters were poorly associated with neonatal acid-base status, although this association was slightly better for venous pH. The importance of BW centile was smaller than that of CPR and VPR MoM, however, both hemodynamic parameters were similarly associated with neonatal pH. CONCLUSIONS: Concerning fetal surveillance near term, the importance of cerebroplacental hemodynamics surpasses that of BW. Furthermore, in the evaluation of fetal wellbeing VPR behaves as a valid alternative to CPR.

Ultrasound evaluation of congenital cervical teratoma and therapeutic management (ex utero intrapartum treatment).

The ultrasound evaluation of the fetal neck has a high importance as a key point of the airway and digestive tract. We report the case of a fetus diagnosed with a cervical teratoma by ultrasound, which generated a compressive effect on airway, requiring a surgical approach EXIT (ex utero intrapartum treatment) to ensure the extrauterine viability.

Cesárea en isquemia-histerectomía: nueva técnica para finalizar la gestación en pacientes con hipertensión arterial pulmonar / Cesarean section in ischemia-hysterectomy: A new technique to terminate pregnancy in patients with serious pulmonary hypertension

La asociación de hipertensión arterial pulmonar (HAP) y embarazo sigue presentando unos índices de mortalidad materna muy elevados. Las nuevas terapias y el abordaje multidisciplinario han conseguido mejorar el curso del embarazo y el pronóstico fetal, pero no el materno. La observación de que la evacuación del feto e involución uterina coincide con un empeoramiento marcado de la función cardíaca materna sugiere como causa desencadenante el paso súbito de la sangre contenida en el músculo uterino a la circulación general, que al comportarse como una autotransfusión eleva a límites insostenibles las presiones en el corazón derecho. Para evitarlo se ha diseñado una nueva técnica quirúrgica, la cesárea en isquemia-histerectomía, que cierra la circulación uterina antes de la extracción fetal. Se describe la técnica quirúrgica y se aportan 4 casos clínicos ilustrativos (AU)

The association of pulmonary hypertension (PH) and pregnancy still leads to high maternal mortality. New treatments and a multidisciplinary approach have improved the course of pregnancies and fetal outcomes but not maternal prognosis. We observed that fetal evacuation and uterine involution coincides with marked worsening of maternal cardiac function, suggesting that the trigger is blood flow from the uterine muscle to the general circulation. This process acts as an autotransfusion and increases the pressure in the right heart to unsustainable limits. A new surgical technique, cesarean section in ischemia-hysterectomy, has been designed to prevent this event. This technique blocks uterine circulation before fetal extraction. We describe this technique and four cases (AU)