NIPT : non-invasive prenatal testing : towards implementation in the Netherlands

NIPT is already clinically available in many countries, yet many research questions remain unanswered. In this thesis, important aspects for implementation are addressed. The main conclusions are summarized below, followed by a discussion on future studies, future dreams and remaining research questionsAstellas Pharma Inc., Becton Dickinson B.V., BMA B.V. (Mosos), ChipSoft B.V., Natera Inc., Raad van Bestuur – Reinier de Graaf Gasthuis, Sorg-Saem B.V. (Astraia), Stichting Oranjekliniek, Goodlife Pharma, Toshiba Medical Systems Nederland, Verloskunde afdeling – LUMCUBL - phd migration 201

The edge of perinatal viability: understanding the Dutch position

The current Dutch guideline on care at the edge of perinatal viability advises to consider initiation of active care to infants born from 24 weeks of gestational age on. This, only after extensive counseling of and shared decision-making with the parents of the yet unborn infant. Compared to most other European guidelines on this matter, the Dutch guideline may be thought to stand out for its relatively high age threshold of initiating active care, its gray zone spanning weeks 24 and 25 in which active management is determined by parental discretion, and a slight reluctance to provide active care in case of extreme prematurity. In this article, we explore the Dutch position more thoroughly. First, we briefly look at the previous and current Dutch guidelines. Second, we position them within the Dutch socio-cultural context. We focus on the Dutch prioritization of individual freedom, the abortion law and the perinatal threshold of viability, and a culturally embedded aversion of suffering. Lastly, we explore two possible adaptations of the Dutch guideline; i.e., to only lower the age threshold to consider the initiation of active care, or to change the type of guideline.Research into fetal development and medicin

Are fetal bilirubin levels associated with the need for neonatal exchange transfusions in hemolytic disease of the fetus and newborn?

BACKGROUND: Fetal bilirubin is routinely measured at our center when taking a pretransfusion blood sample at intrauterine transfusions in hemolytic disease of the fetus and newborn. However, the clinical value of fetal bilirubin assessment is not well known, and the information is rarely used. We speculated that there could be a role for this measurement in predicting the need for neonatal exchange transfusion.OBJECTIVE: This study aimed to evaluate the predictive value of fetal bilirubin for exchange transfusions in severe hemolytic disease of the fetus and newborn.STUDY DESIGN: A total of 186 infants with Rh alloantibody-mediated hemolytic disease of the fetus and newborn treated with one or more intrauterine transfusions at the Leiden University Medical Center between January 2006 and June 2020 were included in this observational study. Antenatal and postnatal factors were compared between infants with and without exchange transfusion treatments. The primary outcome was the fetal bilirubin levels before the last intrauterine transfusion in relation to the need for exchange transfusion.RESULTS: In a multivariate logistic regression analysis, the fetal bilirubin level before the last intrauterine transfusions (odds ratio, 1.32; 95% confidence interval, 1.09-1.61 per 1 mg/dL) and the total number of intrauterine transfusions (odds ratio, 0.63; 95% confidence interval, 0.44-0.91 per intrauterine transfusion) were independently associated with the need for exchange transfusion. The area under the curve was determined at 0.71. A Youden index was calculated at 0.43. The corresponding fetal bilirubin level was 5 mg/dL and had a sensitivity of 79% and a specificity of 64%.CONCLUSION: A high fetal bilirubin level before the last intrauterine transfusion was associated with a high likelihood of neonatal exchange transfusion.DevelopmentImmunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Charged-particle nuclear modification factors in PbPb and pPb collisions at √=sNN=5.02 TeV

The spectra of charged particles produced within the pseudorapidity window |η| < 1 at √ sNN = 5.02 TeV are measured using 404 µb −1 of PbPb and 27.4 pb−1 of pp data collected by the CMS detector at the LHC in 2015. The spectra are presented over the transverse momentum ranges spanning 0.5 < pT < 400 GeV in pp and 0.7 < pT < 400 GeV in PbPb collisions. The corresponding nuclear modification factor, RAA, is measured in bins of collision centrality. The RAA in the 5% most central collisions shows a maximal suppression by a factor of 7–8 in the pT region of 6–9 GeV. This dip is followed by an increase, which continues up to the highest pT measured, and approaches unity in the vicinity of pT = 200 GeV. The RAA is compared to theoretical predictions and earlier experimental results at lower collision energies. The newly measured pp spectrum is combined with the pPb spectrum previously published by the CMS collaboration to construct the pPb nuclear modification factor, RpA, up to 120 GeV. For pT > 20 GeV, RpA exhibits weak momentum dependence and shows a moderate enhancement above unity

Lactate acidosis and hypoglycaemia in twin anaemia polycythemia sequence donors

Developmen

History and current standard of postnatal management in hemolytic disease of the fetus and newborn

Since the discovery of the Rh blood group system in 1940, a greater understanding of hemolytic disease of the fetus and newborn (HDFN) was gained. In the years thereafter, researchers and clinicians came to the current understanding that fetal and neonatal red blood cells (RBC) are hemolyzed by maternal alloantibodies directed against RBC antigens potentially leading to severe disease. Preventative measures, such as Rhesus(D) immunoprophylaxis (RhIG), have greatly decreased the prevalence of Rh(D)-mediated HDFN, although a gap between high-income countries and middle- to low-income countries was created largely due to a lack in availability and high costs of RhIG. Other important developments in the past decades have improved the identification, monitoring, and care of pregnancies, fetuses, and neonates with HDFN. Prenatally, fetal anemia may occur and intrauterine transfusions may be needed. Postnatally, pediatricians should be aware of the (antenatally determined) risk of hemolysis in RBC alloimmunization and should provide treatment for hyperbilirubinemia in the early phase and monitor for anemia in the late phase of the disease. Through this review, we aim to provide an overview of important historic events and to provide hands-on guidelines for the delivery and postnatal management of neonates with HDFN. Secondarily, we aim to describe recent scientific findings and evidence gaps. Conclusion: Multiple developments have improved the identification, monitoring, and care of pregnancies and neonates with HDFN throughout the centuries. Pediatricians should be aware of the (antenatally determined) risk of hemolysis in RBC alloimmunization and should provide treatment for hyperbilirubinemia in the early phase and monitor for late anemia in the late phase of the disease. Future studies should be set in an international setting and ultimately aim to eradicate HDFN on a global scale. What is Known: Developments have led to a greater understanding of the pathophysiology, an improved serological identification and monitoring of at-risk cases and the current pre- and postnatal treatment. What is New: This review provides the pediatrician with hands-on guidelines for the delivery and postnatal management of neonates with HDFN. Future studies should be set in an international setting with the ultimate aim of eradicating HDFN.Developmen

Fetoscopic myelomeningocoele closure

Since the completion of the Management of Myelomeningocoele Study, maternal-fetal surgery for spina bifida has become a valid option for expecting parents. More recently, multiple groups are exploring a minimally invasive approach and recent outcomes have addressed many of the initial concerns with this approach. Based on a previously published framework, we attempt to delineate the developmental stage of the surgical techniques. Furthermore, we discuss the barriers of performing randomized controlled trials comparing two surgical interventions and suggest that data collection through registries is an alternative method to gather high-grade evidence.</p

Interprofessional Consensus Regarding Design Requirements for Liquid-Based Perinatal Life Support (PLS) Technology

Liquid-based perinatal life support (PLS) technology will probably be applied in a first-in-human study within the next decade. Research and development of PLS technology should not only address technical issues, but also consider socio-ethical and legal aspects, its application area, and the corresponding design implications. This paper represents the consensus opinion of a group of healthcare professionals, designers, ethicists, researchers and patient representatives, who have expertise in tertiary obstetric and neonatal care, bio-ethics, experimental perinatal animal models for physiologic research, biomedical modeling, monitoring, and design. The aim of this paper is to provide a framework for research and development of PLS technology. These requirements are considering the possible respective user perspectives, with the aim to co-create a PLS system that facilitates physiological growth and development for extremely preterm born infants

Interprofessional consensus regarding design requirements for liquid-based perinatal life support (PLS) technology

Liquid-based perinatal life support (PLS) technology will probably be applied in a first-in-human study within the next decade. Research and development of PLS technology should not only address technical issues, but also consider socio-ethical and legal aspects, its application area, and the corresponding design implications. This paper represents the consensus opinion of a group of healthcare professionals, designers, ethicists, researchers and patient representatives, who have expertise in tertiary obstetric and neonatal care, bio-ethics, experimental perinatal animal models for physiologic research, biomedical modeling, monitoring, and design. The aim of this paper is to provide a framework for research and development of PLS technology. These requirements are considering the possible respective user perspectives, with the aim to co-create a PLS system that facilitates physiological growth and development for extremely preterm born infants.Developmen

Interprofessional Consensus Regarding Design Requirements for Liquid-Based Perinatal Life Support (PLS) Technology

Liquid-based perinatal life support (PLS) technology will probably be applied in a first-in-human study within the next decade. Research and development of PLS technology should not only address technical issues, but also consider socio-ethical and legal aspects, its application area, and the corresponding design implications. This paper represents the consensus opinion of a group of healthcare professionals, designers, ethicists, researchers and patient representatives, who have expertise in tertiary obstetric and neonatal care, bio-ethics, experimental perinatal animal models for physiologic research, biomedical modeling, monitoring, and design. The aim of this paper is to provide a framework for research and development of PLS technology. These requirements are considering the possible respective user perspectives, with the aim to co-create a PLS system that facilitates physiological growth and development for extremely preterm born infants