Mind the gap: Comparing parents' information needs about impending preterm birth to current clinical practices using a mixed methods approach.

Objective: To identify parents' information needs about impending very preterm birth and compare these needs to current information practices in the Netherlands. Methods: Step 1: We surveyed N = 203 parents of preterm infants to assess their information needs. Data were analyzed using inductive thematic analysis. Step 2a: We collected information resources from hospitals (N = 9 NICUs) and via an online search. These materials were analyzed using deductive thematic analysis. Step 2b: We compared findings from Steps 1-2a. Results: We identified four themes pertaining to parents' information needs: (1) participation in care, (2) emotional wellbeing, (3) experience/success stories, and (4) practical information about prematurity. Clinicians' communicative skills and time were considered prerequisites for optimal information-provision. Notably, hospital resources provided mainly medical information about prematurity with some emphasis on participation in care, while parent associations mainly focused on emotional wellbeing and experience/success stories. Conclusion: While parents demonstrate clear information needs about impending very preterm birth, current information resources satisfy these partially. Innovation: Our multidisciplinary research team included both scholars and veteran NICU parents. As such, we identified parents' information needs bottom-up. These parent-driven insights will be used to design an innovative, tailored information platform for parents about impending very preterm birth.

An exploratory open-label multicentre phase I/II trial evaluating the safety and efficacy of postnatal or prenatal and postnatal administration of allogeneic expanded fetal mesenchymal stem cells for the treatment of severe osteogenesis imperfecta in infants and fetuses: the BOOSTB4 trial protocol.

INTRODUCTION: Severe osteogenesis imperfecta (OI) is a debilitating disease with no cure or sufficiently effective treatment. Mesenchymal stem cells (MSCs) have good safety profile, show promising effects and can form bone. The Boost Brittle Bones Before Birth (BOOSTB4) trial evaluates administration of allogeneic expanded human first trimester fetal liver MSCs (BOOST cells) for OI type 3 or severe type 4. METHODS AND ANALYSIS: BOOSTB4 is an exploratory, open-label, multiple dose, phase I/II clinical trial evaluating safety and efficacy of postnatal (n=15) or prenatal and postnatal (n=3, originally n=15) administration of BOOST cells for the treatment of severe OI compared with a combination of historical (1-5/subject) and untreated prospective controls (≤30). Infants<18 months of age (originally<12 months) and singleton pregnant women whose fetus has severe OI with confirmed glycine substitution in COL1A1 or COL1A2 can be included in the trial.Each subject receives four intravenous doses of 3×106/kg BOOST cells at 4 month intervals, with 48 (doses 1-2) or 24 (doses 3-4) hours in-patient follow-up, primary follow-up at 6 and 12 months after the last dose and long-term follow-up yearly until 10 years after the first dose. Prenatal subjects receive the first dose via ultrasound-guided injection into the umbilical vein within the fetal liver (16+0 to 35+6 weeks), and three doses postnatally.The primary outcome measures are safety and tolerability of repeated BOOST cell administration. The secondary outcome measures are number of fractures from baseline to primary and long-term follow-up, growth, change in bone mineral density, clinical OI status and biochemical bone turnover. ETHICS AND DISSEMINATION: The trial is approved by Competent Authorities in Sweden, the UK and the Netherlands (postnatal only). Results from the trial will be disseminated via CTIS, ClinicalTrials.gov and in scientific open-access scientific journals. TRIAL REGISTRATION NUMBERS: EudraCT 2015-003699-60, EUCT: 2023-504593-38-00, NCT03706482.

Changing epidemiology of parvovirus B19 in the Netherlands since 1990, including its re-emergence after the COVID-19 pandemic.

Parvovirus B19V (B19V) infection during pregnancy can be complicated by potentially life-threatening fetal hydrops, which can be managed by intrauterine transfusion (IUT). This study investigates the long-term temporal patterns in the epidemiology of B19V and evaluates the impact on fetal hydrops, by combining data on B19V infections from the Dutch Sentinel Surveillance system in the period 1990 to 2023, Dutch blood banking data and hospital data on fetal hydrops. Using wavelet analysis, we identified annual epidemic cycles in the Netherlands in the period 1990-2019 and we identified superimposed multiannual cycles in the period 1990-2009. After 2009, no multiannual cycle could be identified, although the incidence fluctuated and correlates with number of IUT performed. As of 2020, weekly reports of B19V infection demonstrated a historically low incidence and B19V-DNA positive blood donors were nearly absent. From May 2020 to May 2023, no IUT for B19V-related hydrops was performed. In the spring of 2023, B19V infections re-emerged, reaching pre-pandemic epidemic levels. Due to the changes in B19V epidemiology over the last 30 years and the near-absence of B19V during the COVID-19 pandemic, the resulting low immunity levels may lead to rebound outbreaks. Alertness to severe complications such as fetal hydrops is warranted.

Cardiac adaptation and malformation in twin-twin transfusion syndrome and selective fetal growth restriction: A systematic review.

OBJECTIVES: This systematic review explores cardiac adaptation in monochorionic (MC) twins with twin-twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR) and assesses the risk of congenital heart defects (CHDs). METHODS: Adhering to PRISMA guidelines, 63 studies were reviewed (49 on cardiac adaptation, 13 on CHD, one on both). A narrative synthesis of cardiac adaptation patterns was performed. Additionally, a meta-analysis compared the livebirth prevalence of CHD in TTTS and sFGR against uncomplicated MC twins. RESULTS: In TTTS recipients, cardiac function may be impaired for diastolic, systolic, as well as global functions, while in donors, cardiac function is generally preserved. In sFGR, large twins may show hypertrophic cardiomyopathy, and small twins may show impaired systolic function. Co-occurrence of TTTS and sFGR magnifies cardiac impact but is often underreported. Meta-analysis for CHD prevalence revealed a relative risk ratio of 3.5 (95% CI: 2.5-4.9) for TTTS and 2.2 (95%CI: 1.3-3.5) for sFGR compared with uncomplicated MC twins. CONCLUSIONS: This study highlights the well-documented cardiac adaptation in TTTS, contrasting with limited understanding in sFGR. Elevated CHD risks were observed in both conditions. Enhanced cardiovascular surveillance is warranted in complicated MC twin pregnancies. Future research should explore cardiac adaptation in sFGR and its long-term consequences.

Suppression of Hb Bart's to improve tissue oxygenation and fetal development in homozygous alpha-thalassemia.

Intra-uterine reduction of Hb Bart's only reached with exchange transfusions.

Artery-to-vein anastomoses in unequally divided placentas and their association with birthweight discordance.

INTRODUCTION: This study investigated the impact of the shared intertwin circulation in unequally divided monochorionic (MC) placentas on fetal growth. METHODS: This retrospective analysis included color-dyed, unequally shared placentas from two tertiary centers. Exclusions included twin-twin transfusion syndrome, twin anemia polycythemia sequence, and lethal anomalies. Measurement of the external diameters and areas of the artery-to-artery (AA), artery-to-vein (AV), and vein-to-vein (VV) anastomoses was performed. The ratio of the shared circulation (AV ratio) was determined by comparing the areas of the summed venous components of shared AV anastomoses to those in the individual AV anastomoses of the smaller placental part. The birth weight ratio/placental ratio (BWR/PR), total AV size areas and net AV transfusion were calculated. Univariable and multivariable linear regressions were performed to assess the relationship between BWR/PR, the AV ratio, the areas of the different anastomoses and cord insertion discordance. RESULTS: Among 352 placentas, 97 % (340) had intertwin AV anastomoses, and 50 % (176) were from pregnancies with selective growth restriction. The AV ratio, AA, VV, total AV areas, and cord insertion discordance negatively correlated with BWR/PR. Multivariable linear regression confirmed the independent negative association between BWR/PR and the AV ratio, suggesting that a larger shared circulation benefits the twin with the smaller placental part. Type III sFGR placentas exhibited the highest AV ratio, resulting in the lowest BWR/PR. DISCUSSION: A larger shared circulation mitigates the impact of an unequally divided placenta on fetal growth. This effect surpasses the influence of AA and VV diameters and is most prominent in Type III sFGR placentas.

Perspectives of extremely prematurely born adults on what to consider in prenatal decision-making: a qualitative focus group study.

OBJECTIVE: A shared decision-making (SDM) approach is recommended for prenatal decisions at the limit of viability, with a guiding role for parental values. People born extremely premature experience the consequences of the decision made, but information about their perspectives on prenatal decisions is lacking. Therefore, this study aims to describe their perspectives on what is important in decision-making at the limit of viability. DESIGN: Semi-structured focus group discussions were conducted, recorded and transcribed verbatim. The data were independently analysed by two researchers in Atlas.ti. RESULTS: Four focus groups were conducted in the Netherlands, with five to six participants each, born between 240/7 and 300/7 weeks gestation in the period between 1965 and 2002. Considering their personal life experiences and how their extremely premature birth affected their families, the participants reflected on decision-making at the limit of viability. Various considerations were discussed and summarised into the following themes: anticipated parental regret, the wish to look at the baby directly after birth, to give the infant a chance at survival, quality of life, long-term outcomes for the infant and the family, and religious or spiritual considerations. CONCLUSIONS: Insights into the perspectives of adults born extremely premature deepened our understanding of values considered in decision-making at the limit of viability. Results point out the need for a more individualised prediction of the prognosis and more extensive information on the lifelong impact of an extremely premature birth on both the infant and the family. This could help future parents and healthcare professionals in value-laden decision-making.

Severity of haemolytic disease of the fetus and newborn in patients with a history of intrauterine transfusions in a previous pregnancy: A nationwide retrospective cohort study.

OBJECTIVE: Pregnant women who received at least one intrauterine transfusion (IUT) for haemolytic disease of the fetus and newborn (HDFN) in the preceding pregnancy are presumed to have a high likelihood of requiring IUTs again, often starting at an earlier gestational age. Our aim was to quantify these risks in a large national cohort. DESIGN: Retrospective cohort study of a nationwide Dutch database. SETTING: The Netherlands. POPULATION: All women treated in The Netherlands with IUTs for Rhesus D (RhD)- or Kell-mediated HDFN between 1999 and 2017 and their follow-up pregnancies were included. Pregnancies with an antigen-negative fetus were excluded. METHODS: Electronic patient files were searched for the number and gestational age of each IUT, and analysed using descriptive statistics and linear regression. MAIN OUTCOME MEASURES: Percentage of women requiring one or more IUTs again in the subsequent pregnancy, and gestational age at first IUT in both pregnancies. RESULTS: Of the 321 women in our study population, 21% (69) had a subsequent ongoing pregnancy at risk. IUTs were administered in 86% (59/69) of cases. In subsequent pregnancies, the median gestational age at first IUT was 3 weeks earlier (interquartile range -6.8 to 0.4) than in the preceding pregnancy. CONCLUSIONS: Our study shows that pregnant women with a history of IUTs in the previous pregnancy are highly likely to require IUTs again, and on average 3 weeks earlier. Clinicians need to be aware of these risks and ensure timely referral, and close surveillance from early pregnancy onwards. Additionally, for women with a history of IUT and their caregivers, this information is essential to enable adequate preconception counselling.

Darbepoetin alfa to reduce transfusion episodes in infants with haemolytic disease of the fetus and newborn who are treated with intrauterine transfusions in the Netherlands: an open-label, single-centre, phase 2, randomised, controlled trial.

BACKGROUND: Up to 88% of infants with haemolytic disease of the fetus and newborn who are treated with intrauterine transfusions require erythrocyte transfusions after birth. We aimed to investigate the effect of darbepoetin alfa on the prevention of postnatal anaemia in infants with haemolytic disease of the fetus and newborn. METHODS: We conducted an open-label, single-centre, phase 2 randomised controlled trial to evaluate the effect of darbepoetin alfa on the number of erythrocyte transfusions in infants with haemolytic disease of the fetus and newborn. All infants who were treated with intrauterine transfusion and born at 35 weeks of gestation or later at the Leiden University Medical Center, Leiden, Netherlands, were eligible for inclusion. Included infants were randomised by computer at birth to treatment with 10 µg/kg darbepoetin alfa subcutaneously once a week for 8 weeks or standard care (1:1 allocation, in varying blocks of four and six, with no stratification). Treating physicians and parents were not masked to treatment allocation, but the research team, data manager, and statistician were masked to treatment allocation during the process of data collection. The primary outcome was the number of erythrocyte transfusion episodes per infant from birth up to 3 months of life in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT03104426) and has been completed. FINDINGS: Between Oct 31, 2017, and April 31, 2022, we recruited 76 infants, of whom 44 (58%) were randomly assigned to a treatment group (20 [45%] were allocated to receive darbepoetin alfa and 24 [55%] were allocated to receive standard care). Follow-up lasted 3 months and one infant dropped out of the trial before commencement of treatment. A significant reduction in erythrocyte transfusion episodes was identified with darbepoetin alfa treatment compared with standard care (median 1·0 [IQR 1·0-2·0] transfusion episodes vs 2·0 [1·3-3·0] transfusion episodes; p=0·0082). No adverse events were reported and no infants died during the study. INTERPRETATION: Darbepoetin alfa reduced the transfusion episodes after intrauterine transfusion treatment for haemolytic disease of the fetus and newborn. Treatment with darbepoetin alfa or other types of erythropoietin should be considered as part of the postnatal treatment of severe haemolytic disease of the fetus and newborn. FUNDING: Sanquin Blood Supply. TRANSLATION: For the Dutch translation of the abstract see Supplementary Materials section.

[Ethnicity as a prognostic factor in extreme preterm birth]. / Etniciteit als prognostische factor bij vroeggeboorte.

A substantial body of research suggests that 'race' or 'ethnicity' may impact the prognosis following extreme preterm birth. However, the definitions of these classifications remain unclear. Often, there is an unsupported assumption of biological differences among various ethnic groups. Moreover, there is a lack of transparency in how researchers utilize these categories and determine individual affiliations, resulting in inconsistent findings in the literature. The primary aim of considering and discussing prognostic factors is to enhance decision-making at the limit of viability. Incorporating ethnicity as a prognostic factor, however, does not advance this objective. Instead, it may have adverse effects on families experiencing extreme preterm birth. This article contends, therefore, that the implications of including ethnicity as a prognostic factor in guidelines, discussions, or decision-making for extreme preterm birth deserve careful consideration.

Opportunities and Challenges of Prognostic Models for Extremely Preterm Infants.

Predicting the short- and long-term outcomes of extremely preterm infants remains a challenge. Multivariable prognostic models might be valuable tools for clinicians, parents, and policymakers for providing accurate outcome estimates. In this perspective, we discuss the opportunities and challenges of using prognostic models in extremely preterm infants at population and individual levels. At a population level, these models could support the development of guidelines for decisions about treatment limits and may support policy processes such as benchmarking and resource allocation. At an individual level, these models may enhance prenatal counselling conversations by considering multiple variables and improving transparency about expected outcomes. Furthermore, they may improve consistency in projections shared with parents. For the development of prognostic models, we discuss important considerations such as predictor and outcome measure selection, clinical impact assessment, and generalizability. Lastly, future recommendations for developing and using prognostic models are suggested. Importantly, the purpose of a prognostic model should be clearly defined, and integrating these models into prenatal counselling requires thoughtful consideration.

Adults born prematurely prefer a periviability guideline that considers multiple prognostic factors beyond gestational age.

AIM: The aim of the study was to explore the perspectives of adults born prematurely on guidelines for management at extreme premature birth and personalisation at the limit of viability. METHODS: We conducted four 2-h online focus group interviews in the Netherlands. RESULTS: Twenty-three participants born prematurely were included in this study, ranging in age from 19 to 56 years and representing a variety of health outcomes. Participants shared their perspectives on different types of guidelines for managing extremely premature birth. They agreed that a guideline was necessary to prevent arbitrary treatment decisions and to avoid physician bias. All participants favoured a guideline that is based upon multiple prognostic factors beyond gestational age. They emphasised the importance of discretion, regardless of the type of guideline used. Discussions centred mainly on the heterogeneity of value judgements about outcomes after extreme premature birth. Participants defined personalisation as 'not just looking at numbers and statistics'. They associated personalisation mainly with information provision and decision-making. Participants stressed the importance of involving families in decision-making and taking their care needs seriously. CONCLUSION: Adults born prematurely prefer a periviability guideline that considers multiple prognostic factors and allows for discretion.

The (mis)use of fetal viability as the determinant of non-criminal abortion in the Netherlands and England and Wales.

Time plays a fundamental role in abortion regulation. In this article, we compare the regulatory frameworks in England and Wales and the Netherlands as examples of the centrality accorded to viability in the determination of the parameters of non-criminal abortion, demonstrating that the use of viability as a threshold renders the law uncertain. We assess the role played by the concept of viability, analysing its impact upon the continued criminalization of abortion and categorization of abortion as a medical matter, rather than a reproductive choice. We conclude that viability is misconceived in its application to abortion and that neonatal viability (relating to treatment of the premature infant) and fetal viability (related to the capacity to survive birth) must be distinguished to better reflect the social context within which the law and practice of abortion operate. We show how viability thresholds endanger pregnant people.

Perinatal outcome after selective fetal reduction in monochorionic twin pregnancies: A comparison of techniques over a 20-year period.

OBJECTIVE: To assess the perinatal outcome after fetal reduction in complicated monochorionic (MC) twin pregnancies by comparing different techniques. METHODS: A retrospective cohort study at a national referral center comparing data between four techniques: interstitial laser coagulation, radiofrequency ablation (RFA), fetoscopic laser coagulation (FLC) and bipolar cord coagulation (BCC). The primary outcome was the mortality of the co-twins. Secondary outcomes were preterm pre-labor rupture of membranes (PPROM), gestational age at delivery and neonatal morbidity. RESULTS: 259 MC twin pregnancies underwent selective fetal reduction: 29 IL, 64 RFA, 85 FLC and 81 BCC. The perinatal mortality rate was 29% and fetal demise of the co-twins occurred in 19%. The lowest mortality rate was seen after BCC (17%, p = 0.012). PPROM occurred in 18% patients without significant differences between techniques. The mean gestational age at delivery in liveborn children was 35 weeks and did not differ between techniques. Severe cerebral injury and neonatal morbidity were reported in 4% and 14%, respectively, without significant differences between techniques. CONCLUSIONS: Selective fetal reductions in MC twins are precarious procedures with an increased risk of perinatal mortality of the co-twins. Our results show the lowest mortality rates after BCC. However, high PPROM rates were seen irrespective of the technique.

Dutch professionals' discussion preferences with the parents of extremely premature infants varied, but the trend was towards shared decision-making.

AIM: We explored professionals' views on sharing decision-making with parents before and after an extremely preterm birth and what healthcare professionals considered severe outcomes. METHODS: A nationwide, multi-centre online survey was carried out among a wide range of perinatal healthcare professionals in the Netherlands from 4 November 2020 to 10 January 2021. The medical chairs of all nine Dutch Level III and IV perinatal centres helped to disseminate the survey link. RESULTS: We received 769 survey responses. Most respondents (53%) preferred to place equal emphasis on two treatment options during shared prenatal decision-making: early intensive care or palliative comfort care. The majority (61%) wanted to include a conditional intensive care trial as a third treatment option, but 25% disagreed. Most (78%) felt that healthcare professionals were responsible for initiating postnatal conversations to justify continuing or withdrawing neonatal intensive care if complications were associated with poor outcomes. Finally, 43% were satisfied with the current definitions of severe long-term outcomes, 41% were unsure and there were numerous for a broader definition. CONCLUSION: Although Dutch professionals expressed diverse preferences on how to reach decisions about extremely premature infants, we observed a trend towards shared decision-making with parents. These results could inform future guidelines.

A scoping review of parental values during prenatal decisions about treatment options after extremely premature birth.

AIM: To describe what is known in the literature about parental perspectives in making prenatal decisions regarding treatment after birth at the limit of viability, as a better understanding of parental values can help professionals support parents as they decide. METHODS: PubMed, Cochrane, Embase, CINAHL, PsycINFO and Web of Science were searched to identify relevant literature from 1 January 2010 to 22 April 2022 on parental decision making. Data were extracted from selected studies and organised into themes. The final themes were formed through collaboration with the parents of a premature infant born at 24 weeks. RESULTS: Of the 15,159 papers examined, 17 were included. Parental perspectives were described in terms of long-term outcomes for the infant, survival, protection against the burden of neonatal treatment, long-term impact on the family, religion and spiritual beliefs, to do everything possible, hope, sense of responsibility, wanting the best, doing what is right, giving a chance and the influence of experience. CONCLUSION: The extracted parental perspectives show the complexity of these decisions. Some perspectives were clear, but others were multi-interpretable. Increasing the understanding of common parental perspectives can help improve shared prenatal decisions and lead to further improvement and personalisation of the process.

Identification and management of fetal anemia due to hemolytic disease.

INTRODUCTION: Hemolytic disease of the fetus and newborn (HDFN) is a condition caused by maternal alloantibodies against fetal red blood cells (RBCs) that can cause severe morbidity and mortality in the fetus and newborn. Adequate screening programs allow for timely prevention and intervention resulting in significant reduction of the disease over the last decades. Nevertheless, HDFN still occurs and with current treatment having reached an optimum, focus shifts toward noninvasive therapy options. AREAS COVERED: This review focusses on the timely identification of high risk cases and antenatal management. Furthermore, we elaborate on future perspectives including improvement of screening, identification of high risk cases and promising treatment options. EXPERT OPINION: In high-income countries mortality and morbidity rates due to HDFN have drastically been reduced over the last decades, yet worldwide anti-D mediated HDFN still accounts for 160,000 perinatal deaths and 100,000 patients with disabilities every year. Much of these deaths and disabilities could have been avoided with proper identification and prophylaxis. By implementing sustainable prevention, screening, and disease treatment measures in all countries this will systemically reduce unnecessary perinatal deaths. There is a common responsibility to engage in this cause.