[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.

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.

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.

Gestational age at birth and outcome in monochorionic twins with different types of selective fetal growth restriction: A systematic literature review.

This systematic review aims to assess the gestational age at birth and perinatal outcome [intrauterine demise (IUD), neonatal mortality and severe cerebral injury] in monochorionic twins with selective fetal growth restriction (sFGR), according to Gratacós classification based on umbilical artery Doppler flow patterns in the smaller twin. Seventeen articles were included. Gestational age at birth varied from 33.0 to 36.0 weeks in type I, 27.6-32.4 weeks in type II, and 28.3-33.8 weeks in type III. IUD rate differed from 0%-4% in type I to 0%-40% in type II and 0%-23% in type III. Neonatal mortality rate was between 0%-10% in type I, 0%-38% in type II, and 0%-17% in type III. Cerebral injury was present in 0%-2% of type I, 2%-30% of type II and 0%-33% of type III cases. The timing of delivery in sFGR varied substantially among studies, particularly in type II and III. The quality of evidence was moderate due to heterogenous study populations with varying definitions of sFGR and perinatal outcome parameters, as well as a lack of consensus on the use of the Gratacós classification, leading to substantial incomparability. Our review identifies the urgent need for uniform antenatal diagnostic criteria and definitions of outcome parameters.

Neonatal Outcome in Twin-to-Twin Transfusion Syndrome Not Treated with Fetoscopic Laser Surgery.

The aim of this study was to describe the neonatal management and outcome in monochorionic twins with twin-to-twin transfusion syndrome (TTTS) not treated with fetoscopic laser surgery. All consecutive live-born neonates with TTTS managed at our center between 2002 and 2021 were included in this retrospective study. Neonatal outcome was assessed in 44 twin pairs with TTTS not treated with laser (nonlaser group) compared to a control group of 88 twin pairs with TTTS successfully treated with laser (laser group), matched for gestational age at birth. Primary outcome was adverse neonatal outcome, a composite outcome including neonatal mortality or severe neonatal morbidity. The incidence of adverse neonatal outcome in the nonlaser group and laser group was 30% (26/88) and 11% (19/176), respectively (relative risk = 3.46, 95% CI [1.79, 6.71]). In the nonlaser group, 11% had necrotizing enterocolitis (vs. 2% in the laser group) and 24% had hypotension (vs. 10% in the laser group). Recipients in the nonlaser group had, compared to recipients in the laser group, significantly more severe cerebral injury (18% vs. 5%) and more polycythemia at birth (21% vs. 1%). Donors in the nonlaser group had, compared to donors in the laser group, more severe growth restriction (71% vs 42%), renal failure (11% vs 1%), and anemia at birth (25% vs. 7%). Thus, the risk for neonatal mortality and/or severe morbidity is three-fold higher in TTTS not treated with laser than in TTTS treated with laser, which highlights the fact that these neonates with TTTS are very sick at birth, requiring accurate and prompt intensive treatment.

Prenatal exome sequencing: A useful tool for the fetal neurologist.

Prenatal exome sequencing (pES) is a promising tool for diagnosing genetic disorders when structural anomalies are detected on prenatal ultrasound. The aim of this study was to investigate the diagnostic yield and clinical impact of pES as an additional modality for fetal neurologists who counsel parents in case of congenital anomalies of the central nervous system (CNS). We assessed 20 pregnancies of 19 couples who were consecutively referred to the fetal neurologist for CNS anomalies. pES had a diagnostic yield of 53% (10/19) with most diagnosed pregnancies having agenesis or hypoplasia of the corpus callosum (7/10). Overall clinical impact was 63% (12/19), of which the pES result aided parental decision making in 55% of cases (6/11), guided perinatal management in 75% of cases (3/4), and was helpful in approving a late termination of pregnancy request in 75% of cases (3/4). Our data suggest that pES had a high diagnostic yield when CNS anomalies are present, although this study is limited by its small sample size. Moreover, pES had substantial clinical impact, which warrants implementation of pES in the routine care of the fetal neurologist in close collaboration with gynecologists and clinical geneticists.

Large Hemoglobin Differences at Birth in Monochorionic Twins with a Placental Chorangioma and Delayed Cord Clamping.

We report a case of a monochorionic diamniotic twin with an uncomplicated pregnancy, but with an unexpected large intertwin hemoglobin (Hb) difference at birth. Twin 1 was delivered vaginally and had an uneventful neonatal course. The umbilical cord of Twin 1 was clamped approximately 5 min after birth. After the birth of Twin 1, Twin 2 developed severe bradycardia and showed limited cardiac output on ultrasound, for which an emergency cesarean section was performed. A full blood count revealed an Hb of 20.1 g/dL for Twin 1 and 10.2 g/dL for Twin 2 (intertwin difference 9.9 g/dL). Reticulocyte counts were similar, 40‰ and 38‰, respectively. Placental examination revealed 10 vascular anastomoses, including one arterio-arterial anastomosis with a diameter of 1.4 mm. Additionally, a large chorangioma was present on the placental surface of Twin 2. There was no color difference on the maternal side of the placenta. Based on the reticulocyte count ratio and the placental characteristics, twin anemia polycythemia sequence was ruled out as the cause of the large intertwin Hb difference. In this report, we discuss the various potential causes that could explain the large intertwin Hb difference including the role of delayed cord clamping in Twin 1, and the role of a large chorangioma, which may have attracted blood from the fetal circulation of Twin 2.

Fetoscopic myelomeningocoele closure: Is the scientific evidence enough to challenge the gold standard for prenatal surgery?

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.

Decision making in prenatal screening: money matters.

The aim of this study is to determine the influence of withdrawal of reimbursement on the uptake of the first-trimester combined test. Until January 2007 the combined test was offered to all pregnant women in a designated geographical area as a pilot study before the introduction of the national screening program in the Netherlands, to test the logistic procedures. In January 2007 the insurance companies suddenly stopped paying for the combined test with respect to women aged ≤35 years by decision of the government. In 2006 the combined test was performed in 4616 women compared with 3459 who had the combined test in 2007, a reduction of 25% (95% CI 23.8-26.3%, p < 0.001). A decline was observed in the uptake of the combined test in women aged ≤35 years (p < 0.001) as opposed to an increase in uptake in women aged ≥36 years (p < 0.001). The financial impact on the uptake of the first-trimester combined test should not be underestimated.

Mrassf1a-pap, a novel methylation-based assay for the detection of cell-free fetal DNA in maternal plasma.

OBJECTIVES: RASSF1A has been described to be differentially methylated between fetal and maternal DNA and can therefore be used as a universal sex-independent marker to confirm the presence of fetal sequences in maternal plasma. However, this requires highly sensitive methods. We have previously shown that Pyrophosphorolysis-activated Polymerization (PAP) is a highly sensitive technique that can be used in noninvasive prenatal diagnosis. In this study, we have used PAP in combination with bisulfite conversion to develop a new universal methylation-based assay for the detection of fetal methylated RASSF1A sequences in maternal plasma. METHODS: Bisulfite sequencing was performed on maternal genomic (g)DNA and fetal gDNA from chorionic villi to determine differentially methylated regions in the RASSF1A gene using bisulfite specific PCR primers. Methylation specific primers for PAP were designed for the detection of fetal methylated RASSF1A sequences after bisulfite conversion and validated. RESULTS: Serial dilutions of fetal gDNA in a background of maternal gDNA show a relative percentage of ~3% can be detected using this assay. Furthermore, fetal methylated RASSF1A sequences were detected both retrospectively as well as prospectively in all maternal plasma samples tested (n = 71). No methylated RASSF1A specific bands were observed in corresponding maternal gDNA. Specificity was further determined by testing anonymized plasma from non-pregnant females (n = 24) and males (n = 21). Also, no methylated RASSF1A sequences were detected here, showing this assay is very specific for methylated fetal DNA. Combining all samples and controls, we obtain an overall sensitivity and specificity of 100% (95% CI 98.4%-100%). CONCLUSIONS: Our data demonstrate that using a combination of bisulfite conversion and PAP fetal methylated RASSF1A sequences can be detected with extreme sensitivity in a universal and sex-independent manner. Therefore, this assay could be of great value as an addition to current techniques used in noninvasive prenatal diagnostics.

Single molecule sequencing of free DNA from maternal plasma for noninvasive trisomy 21 detection.

BACKGROUND: Noninvasive fetal aneuploidy detection by use of free DNA from maternal plasma has recently been shown to be achievable by whole genome shotgun sequencing. The high-throughput next-generation sequencing platforms previously tested use a PCR step during sample preparation, which results in amplification bias in GC-rich areas of the human genome. To eliminate this bias, and thereby experimental noise, we have used single molecule sequencing as an alternative method. METHODS: For noninvasive trisomy 21 detection, we performed single molecule sequencing on the Helicos platform using free DNA isolated from maternal plasma from 9 weeks of gestation onwards. Relative sequence tag density ratios were calculated and results were directly compared to the previously described Illumina GAII platform. RESULTS: Sequence data generated without an amplification step show no GC bias. Therefore, with the use of single molecule sequencing all trisomy 21 fetuses could be distinguished more clearly from euploid fetuses. CONCLUSIONS: This study shows for the first time that single molecule sequencing is an attractive and easy to use alternative for reliable noninvasive fetal aneuploidy detection in diagnostics. With this approach, previously described experimental noise associated with PCR amplification, such as GC bias, can be overcome.