Monitoring and management of hemolytic disease of the fetus and newborn based on an international expert Delphi consensus.

The study aimed to develop structured, expert-based clinical guidance on the prenatal and postnatal management of hemolytic disease of the fetus and newborn. A Delphi procedure was conducted among an international panel of experts in fetal medicine, neonatology, and hematology. Experts were selected based on their expertise, relevant publications, and affiliations.

Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn.

Background: In early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti-neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels.

Methods: In an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks' gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN.

When should we offer antenatal sequencing for urinary tract malformations? A systematic review, cohort study and meta-analysis.

Objective: Determine the incremental yield of prenatal exome sequencing (PES) over chromosome microarray (CMA) and/or karyotype for urinary tract malformations (UTMs).

Method: A prospective cohort study encompassing data from the English Genomic Medicine Service North Thames Laboratory Hub for fetuses with bilateral echogenic kidneys (BEKs) was combined with data from a systematic review. MEDLINE, EMBASE, Web of Science, MedRxiv and GreyLit were searched from 01/2010-02/2023 for studies reporting on the yield of PES over CMA or karyotype in fetuses with UTMs.

Monogenic conditions and central nervous system anomalies: A prospective study, systematic review and meta-analysis.

Objectives: Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous system (CNS) abnormalities.

Methods: Data were collected via electronic searches from January 2010 to April 2022 in MEDLINE, Cochrane, Web of Science and EMBASE. The NHS England prenatal exome cohort was also included.

Endoplasmic reticulum stress impairs trophoblast syncytialization through upregulation of HtrA4 and causes early-onset preeclampsia.

Objective: Syncytiotrophoblasts form via mononuclear cytotrophoblast fusion during placentation and play a critical role in maternal-fetal communication. Impaired syncytialization inevitably leads to pregnancy-associated complications, including preeclampsia. Endoplasmic reticulum stress (ERS) is reportedly linked with preeclampsia, but little is known about its association with syncytialization.

Advance care planning in perinatal settings: national survey of implementation using Normalisation Process Theory.

Background: Perinatal advance care planning (PnACP) is a process of formal decision-making to help families plan for their baby's care when recognised that they may have a life-limiting condition. While PnACP is recommended in policy, there is a lack of evidence to support implementation and development in the perinatal setting.

Objective: To conduct an online survey of UK and Ireland perinatal providers to examine how PnACP is operationalised in current practice.

Prenatal diagnosis of PORCN-related developmental syndrome in a fetus: A novel phenotype.

We report a case of a female fetus born to an unrelated couple with a complex fetal phenotype of a pleural effusion, a cardiac malformation, and syndactyly of the toes. Prenatal exome sequencing identified a variant of uncertain significance in the PORCN gene that was upgraded to likely pathogenic following postnatal clinical examination. The phenotype described in cases with variants in the PORCN gene is often associated with findings that cannot be prospectively diagnosed by ultrasonography.

Risk factors for adverse outcomes in twin pregnancies: a narrative review.

Purpose: Globally, the incidence of twin pregnancies is rising owing to the use of assisted reproductive technologies (ART), emigration and deferment of pregnancy until advanced maternal age (AMA). While twin pregnancies have higher absolute risks of adverse outcomes, including miscarriage, stillbirth, neonatal death and preterm delivery, the impact of specific exposures and risk factors related to these outcomes may differ between twin pregnancies and singleton pregnancies. Regarding modifiable factors, data are sometimes based on evidence extrapolated from singleton or whole obstetric populations.

Prenatal diagnosis of CLCN4-related neurodevelopmental disorder in fetuses with congenital brain anomalies.

We report two male fetuses born to a healthy unrelated couple, with agenesis of the corpus callosum identified on detailed 20-week ultrasound scans and confirmed by in-utero MRI. Whole-genome sequencing identified a likely pathogenic missense variant in the CLCN4 gene, establishing this as the causative gene in the family. Pathogenic variants in the CLCN4 gene cause a neurodevelopmental disorder (also called Raynaud-Claes syndrome) inherited in an X-linked pattern.

Medium-term Outcome of Prenatally Diagnosed Hypoplastic Left-Heart Syndrome and Impact of a Restrictive Atrial Septum Diagnosed in-utero.

Objective: Surgical outcome data differs from overall outcomes of prenatally diagnosed fetuses with hypoplastic left heart syndrome (HLHS). Our aim was to describe outcome of prenatally diagnosed fetuses with this anomaly.

Methods: Retrospective review of prenatally diagnosed classical HLHS at a tertiary hospital over a 13-year period, estimated due dates 01/08/2006 to 31/12/2019.

Cord blood adiponectin and leptin concentrations in monochorionic twins with selective intrauterine growth restriction and their associations with childhood growth trajectories.

Background: Being born with intrauterine growth restriction (IUGR) was associated with subsequent health issues later in life. However, the underlying role of adipokines in IUGR is unknown.

Objectives: To measure the adiponectin and leptin concentrations in the cord blood of monochorionic (MC) twins with selective IUGR (sIUGR) and evaluate their associations with childhood growth trajectories.

Evaluating antenatal risk in twin pregnancies-A feasibility study to identify modifiable factors associated with adverse pregnancy outcomes.

Introduction: Twin pregnancies have significantly higher rates of perinatal morbidity and mortality compared to singleton pregnancies; current attempts to reduce perinatal mortality have been less successful in twin pregnancies. The paucity of information about modifiable risk factors for adverse neonatal outcomes in twin pregnancies, as well as independent effects of chorionicity may have contributed to this outcome. This study aimed to explore the feasibility of an observational study to identify modifiable factors associated with adverse neonatal outcomes in twin pregnancies.

Prenatal next-generation sequencing in the fetus with congenital malformations: how can we improve clinical utility?

Fetal malformations have a variable prognosis that may be influenced by the detection of an underlying monogenic etiology. The careful detection and selection of fetal phenotypes and the use of prenatal next-generation sequencing with robust bioinformatic pathways and variant selection have improved the clinical utility and impact of genetic testing.

Genome-wide DNA methylation analysis of discordant monozygotic twins reveals consistent sites of differential methylation associated with congenital heart disease.

Background: Despite being essentially genetically identical, monozygotic (MZ) twins can be discordant for congenital heart disease (CHD), thus highlighting the importance of in utero environmental factors for CHD pathogenesis. This study aimed to identify the epigenetic variations between discordant MZ twin pairs that are associated with CHD at birth.

Methods: Cord blood of CHD-discordant MZ twins from the Chongqing Longitudinal Twin Study Cohort was subjected to whole-genome bisulfite sequencing, then validated by MeDIP-qPCR and qRT-PCR.

AMPK regulates homeostasis of invasion and viability in trophoblasts by redirecting glucose metabolism: Implications for pre-eclampsia.

Pre-eclampsia (PE) is deemed an ischemia-induced metabolic disorder of the placenta due to defective invasion of trophoblasts during placentation; thus, the driving role of metabolism in PE pathogenesis is largely ignored. Since trophoblasts undergo substantial glycolysis, this study aimed to investigate its function and regulatory mechanism by AMPK in PE development. Metabolomics analysis of PE placentas was performed by gas chromatography-mass spectrometry (GC-MS).

Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens.

Despite the identification of the high-incidence red cell antigen Era nearly 40 years ago, the molecular background of this antigen, together with the other 2 members of the Er blood group collection, has yet to be elucidated. Whole exome and Sanger sequencing of individuals with serologically defined Er alloantibodies identified several missense mutations within the PIEZO1 gene, encoding amino acid substitutions within the extracellular domain of the Piezo1 mechanosensor ion channel. Confirmation of Piezo1 as the carrier molecule for the Er blood group antigens was demonstrated using immunoprecipitation, CRISPR/Cas9-mediated gene knockout, and expression studies in an erythroblast cell line.

Foetal loss after chorionic villus sampling and amniocentesis in twin pregnancies: A multicentre retrospective cohort study.

Objective: We aimed to determine foetal losses for DCDA and MCDA twins following transabdominal CVS or amniocentesis performed <22+  weeks.

Methods: Retrospective cohort study conducted in the UK and Belgium 01/01/00-01/06/20. Cases with unknown chorionicity, monochorionic complications or complex procedures were excluded.

Impact of maternal gestational weight gain in twin pregnancies on early childhood obesity risk: A longitudinal birth cohort study.

Objectives: To investigate the impact of gestational weight gain (GWG) on the body mass index-for-age z score (BAZ) and obesity risk among twin offspring.

Methods: This study included 263 women who were pregnant with twins and their offspring. Maternal GWG was measured in each trimester, and infant weight and length were measured at 6, 12, and 24 months.

G-CSF induces CD15 CD14 cells from granulocytes early in the physiological environment of pregnancy and the cancer immunosuppressive microenvironment.

Objectives: Recombinant granulocyte colony-stimulating factor (G-CSF) is frequently administered to patients with cancer to enhance granulocyte recovery post-chemotherapy. Clinical trials have also used G-CSF to modulate myeloid cell function in pregnancy and inflammatory diseases. Although the contribution of G-CSF to expanding normal granulocytes is well known, the effect of this cytokine on the phenotype and function of immunosuppressive granulocytic cells remains unclear.

Comprehensive Metabolomic Profiling of Cord Blood and Placental Tissue in Surviving Monochorionic Twins Complicated by Twin-Twin Transfusion Syndrome With or Without Fetoscopic Laser Coagulation Surgery: A Retrospective Cohort Study.

To investigate metabolomic perturbations caused by twin-twin transfusion syndrome, metabolic changes associated with fetoscopic laser coagulation in both placental tissue and cord plasma, and to investigate differential metabolites pertinent to varying fetal outcomes, including hemodynamic status, birth weight, and cardiac function, of live-born babies. Placental tissue and cord plasma samples from normal term or uncomplicated preterm-born monochorionic twins and those complicated by twin-twin transfusion syndrome treated with or without fetoscopic laser coagulation were analyzed by high-performance liquid chromatography metabolomic profiling. Sixteen comparisons of different co-twin groups were performed.

Alterations in Fetal Doppler Parameters Before and Twenty-Four Hours After Radiofrequency Ablation for Twin Reversed Arterial Perfusion Sequence.

Objective: To evaluate alterations in the fetal Doppler parameters of pump fetuses before and 24 h after radiofrequency ablation surgery for twin reversed arterial perfusion sequence (TRAPs).

Methods: This is a retrospective study of 28 pump fetuses in TRAPs and 28 normal control twins between 2016 and 2021. The fetal Doppler parameters, including the umbilical artery pulsatility index (UA-PI), middle cerebral artery peak systolic velocity (MCA-PSV), middle cerebral artery pulsatility index (MCA-PI), and cerebroplacental ratio (CPR), of the controls, and pump fetuses before and 24 h after surgery were compared.

The Metabolic Signatures of Surviving Cotwins in Cases of Single Intrauterine Fetal Death During Monochorionic Diamniotic Pregnancy: A Prospective Case-Control Study.

Single intrauterine fetal death (sIUFD) in monochorionic diamniotic (MCDA) twin pregnancy may be associated with adverse clinical outcomes and possible metabolic changes in the surviving co-twin. Metabolomic profiling has not been undertaken before in these complex twin pregnancies. In this prospectively collected case-control study, three cross-cohort comparisons were made between sIUFD MCDA ( = 16), uncomplicated MCDA ( = 16, eight pairs), and uncomplicated singleton pregnancies ( = 8).

Fetal central nervous system anomalies: When should we offer exome sequencing?

Objective: To investigate the detection of pathogenic variants using exome sequencing in an international cohort of fetuses with central nervous system (CNS) anomalies.

Methods: We reviewed trio exome sequencing (ES) results for two previously reported unselected cohorts (Prenatal Assessment of Genomes and Exomes (PAGE) and CUIMC) to identify fetuses with CNS anomalies with unremarkable karyotypes and chromosomal microarrays. Variants were classified according to ACMG guidelines and association of pathogenic variants with specific types of CNS anomalies explored.