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.
Key points
What is already known about this topic?
Existing literature extensively documents that the hemodynamic imbalance in twin–twin transfusion syndrome (TTTS) induces distinct cardiac adaptation in both the recipient and the donor.
TTTS twins are more prone to congenital heart disease (CHD) than singletons and uncomplicated monochorionic (MC) twins.
What does this review add?
Cardiac adaptation also applies to selective fetal growth restricted (sFGR) twins, affecting both the larger and smaller twins, highlighting a crucial, yet underexplored aspect for future studies.
TTTS twins are 3.5 times and sFGR twins are 2.2 times more likely to develop structural heart defects than uncomplicated MC twins.
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.
Semi-structured focus group discussions were conducted, recorded and transcribed verbatim. The data were independently analysed by two researchers in Atlas.ti.
Four focus groups were conducted in the Netherlands, with five to six participants each, born between 24
and 30
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.
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.
Background and objectives
Guidelines and indications for exchange transfusion in haemolytic disease of the foetus and newborn (HDFN) have changed drastically in the past decades, causing a decline in ...exchange transfusion rate. This study aims to evaluate the incidence of exchange transfusions (ETs) in neonates with Rh‐mediated HDFN over the past 20 years at our centre, and report potentially ET‐related complications as well as indicators for bilirubin encephalopathy.
Material and methods
In this observational study, 438 neonates were included with HDFN, born ≥ 35 weeks gestational age at the Leiden University Medical Centre between January 2000 and July 2020. The incidence of ET and procedure‐related complications were assessed in three consecutive time periods determined by changes in guidelines and indications for ET.
Results
The incidence of ET in our centre declined from (104/156) 67% (time period 2000–2005), to (39/181) 22% (2006–2015) and to (10/101) 10% (2015–2020, p < 0·001). The maximum bilirubin levels in neonates after birth increased from 13·6 mg/dL (or 233 μmol/L), to 15·0 mg/dL (257 μmol/L) and to 15·3 mg/dL (263 μmol/L). The incidence of complications associated with the use of ET (including sepsis, haematologic disorders and respiratory failure) remained stable throughout the years, and no neonates died during the study period.
Conclusion
Exchange transfusion incidence declined significantly over the past two decades. Decrease in ET incidence, and concomitant decrease in exposure and expertise, was not associated with an increase in procedure‐related complications.
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.
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.
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.
IntroductionSevere 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 analysisBOOSTB4 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 disseminationThe 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 numbersEudraCT 2015-003699-60, EUCT: 2023-504593-38-00, NCT03706482.
When anaemia or hydrops occurs, intrauterine transfusion can substantially reduce the risk of fetal death. ...the survival rate after intrauterine transfusion for parvovirus B19 is 67–84% as opposed ...to 30–50% who do not receive intrauterine transfusion.2 Intrauterine transfusion for parvovirus B19 requires specific expertise and is mostly performed in national referral centers as these fetuses are deeply anaemic or hydropic and often also suffer from thrombocytopaenia. Recent research4 shows that the traditional pattern of annual parvovirus B19 epidemics in late spring with superimposed multi-annual epidemics has become disturbed, with local disappearance of multi-annual and annual epidemics since 2014 and the virtual absence of parvovirus B19 infections during and after the COVID-19 pandemic.4 The resulting increase in susceptible host populations will have led to the large-scale parvovirus B19 epidemic we witness at present, a rebound effect similar to post-pandemic surges of other, also primarily respiratory-transmitted, infectious diseases. The considerable proportion of adverse outcomes therefore might be explained by suboptimal awareness for parvovirus B19 infections in general health care or obstetric care, possibly due to its prolonged absence, resulting in late referral and increased risk of adverse outcomes.
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.
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