Search

Background: Contemporary diagnostic methods aimed at assessing neonatal outcomes predominantly rely on the medical history of pregnant women. Ideally, universal biomarkers indicating an increased risk of delivering infants in poor clinical condition, with a heightened likelihood of requiring hospitalization in a Neonatal Intensive Care Unit (NICU), would be beneficial for appropriately stratifying pregnant women into a high-risk category. Our study evaluated whether biochemical and ultrasonographical markers universally used in first-trimester screenings for non-heritable chromosomal aberrations could serve this purpose. Methods: This study encompassed 1164 patients who underwent first-trimester screening, including patient history, ultrasound examinations, and biochemical tests for pregnancy-associated plasma protein-A (PAPP-A) and the free beta-HCG subunit (fbHCG), from January 2019 to December 2021. The research concentrated on the correlation between these prenatal test results and neonatal outcomes, particularly Apgar scores, umbilical blood pH levels, and the necessity for NICU admission. Results: In our cohort, neonates scoring lower than 8 on the Apgar scale at birth exhibited lower concentrations of PAPP-A in the first trimester, both in raw and normalized values (PAPP-A MoM 0.93 vs. 1.027, p = 0.032). We also observed a higher pulsatility index in the venous duct in the first trimester in full-term neonates born with <8 points on the Apgar scale. Additionally, newborns born with an umbilical blood pH < 7.2 had lower normalized first-trimester PAPP-A concentrations (0.69 vs. 1.01 MoM, p = 0.04). We also noted that neonates requiring NICU hospitalization post-delivery had lower first-trimester bHCG concentrations (0.93 MoM vs. 1.11 MoM, p = 0.03). However, none of the correlations in our study translated into a robust prognostic ability for predicting dichotomous outcomes. All areas under the curve achieved a value < 0.7. Conclusions: Low concentrations of PAPP-A and free bHCG subunit in the first trimester may be associated with poorer clinical and biochemical conditions in neonates post-delivery. However, the relationship is weak and has limited predictive capability. Further research evaluating these relationships is necessary for the appropriate stratification of pregnant women into high-risk categories for neonatological complications. [ABSTRACT FROM AUTHOR]

Key Clinical Message: An encephalocele is a congenital malformation characterized by protrusion of the intracranial contents through a cranial defect. We report that a fetus of a pregnant mother who had two consecutive pregnancies with ultrasound‐detected encephalocele carried compound heterozygous variants in B3GALNT2 NM_152490.5:c.[1423C > T (p.Gln475Ter)]; [261‐2A > G] of maternal and paternal origins, respectively, as confirmed by exome sequencing followed by Sanger sequencing validation. The present case implies that mutations in B3GALNT2, a well‐known dystroglycanopathy causative gene, may result in a phenotype of neural tube defect, providing new insights into the clinical spectrum of B3GALNT2‐related disorders. Our study may contribute to prenatal screening/diagnosis and genetic counseling of congenital brain malformations. [ABSTRACT FROM AUTHOR]

Background: The Perinatal Center of the University Hospital Carl Gustav Carus Dresden has initiated the telemedical healthcare network "SAFE BIRTH" to coordinate and improve specialized care in non-metropolitan regions for pregnant women and newborns. The network incorporates five intervention bundles (IB): (1) Multi-professional, inter-disciplinary prenatal care plan; (2) Neonatal resuscitation; (3) Neonatal antibiotic stewardship; (4) Inter-facility transfer of premature and sick newborns; (5) Psycho-social support for parents. We evaluate if the network improves care close to home for pregnant women, premature and sick newborns. Methods: To evaluate the complex healthcare intervention "SAFE BIRTH" we will conduct a cluster-randomized controlled stepped-wedge trial in five prenatal medical outpatient offices and eight non-metropolitan hospitals in Saxony, Germany. The offices and hospitals will be randomly allocated to five respectively eight sequential steps over a 30-month period to implement the telemedical IB. We define one specific primary process outcome for each IB (for instance IB#1: "Proportion of patients with inclusion criterion IB#1 who have a prenatal care plan and psychosocial counseling within one week"). We estimated a separate multilevel logistic regression model for each primary process outcome using the intervention status as a regressor (control or intervention group). Across all IB, a total of 1,541 and 1,417 pregnant women or newborns need to be included in the intervention and control group, respectively, for a power above 80% for small to medium intervention effects for all five hypothesis tests. Additionally, we will assess job satisfaction and sense of safety of health professionals caring for newborns (questionnaire survey) and we will assess families' satisfaction, resilience, quality of life and depressive, anxiety and stress symptoms (questionnaire surveys). We will also evaluate the cost-effectiveness of "SAFE BIRTH" (statutory health insurance routine data, process data) and barriers to its implementation (semi-structured interviews). We use multilevel regression models adjusting for relevant confounders (e.g. socioeconomic status, age, place of residence), as well as descriptive analyses and qualitative content analyses. Discussion: If the telemedical healthcare network "SAFE BIRTH" proves to be effective and cost-efficient, strategies for its translation into routine care should be developed. Trial registration: German clinical trials register. DRKS-ID: DRKS00031482. [ABSTRACT FROM AUTHOR]

Background: To evaluate the clinical significance of noninvasive prenatal testing (NIPT) for detecting fetal sex chromosome aneuploidies (SCAs) in Korean pregnant women. Methods: We retrospectively analyzed NIPT data from 9,176 women with singleton pregnancies referred to the CHA Biotech genome diagnostics center. Cell-free fetal DNA (cffDNA) was extracted from maternal peripheral blood, and high-throughput massively parallel sequencing was conducted. Subsequently, the positive NIPT results for SCA were validated via karyotype and chromosomal microarray analyses. Results: Overall, 46 cases were SCA positive after NIPT, including 20, 12, 8, and 6 for Turner, triple X, Klinefelter, and Jacob syndromes, respectively. Among 37 women with invasive prenatal diagnosis, 19 had true positive NIPT results. The overall positive predictive value (PPV) of NIPT for detecting SCAs was 51.35%. The PPV was 18.75% for Turner, 88.89% for triple X, 71.43% for Klinefelter, and 60.00% for Jacob's syndromes. NIPT accuracy for detecting sex chromosome trisomies was higher than that for sex chromosome monosomy (P = 0.002). No significant correlation was observed between fetal SCA incidence and maternal age (P = 0.914), except for the borderline significance of Jacob's syndrome (P = 0.048). No significant differences were observed when comparing NIPT and karyotyping validation for fetal SCA according to pregnancy characteristics. Conclusion: Our data suggest that NIPT can reliably screen for SCAs, and it performed better in predicting sex chromosome trisomies compared with monosomy X. No correlation was observed between maternal age and fetal SCA incidence, and no association was observed between different pregnancy characteristics. The accuracy of these findings requires improvements; however, our study provides an important reference for clinical genetic counseling and further management. Larger scale studies, considering confounding factors, are required for accurate evaluation. [ABSTRACT FROM AUTHOR]

Increased sequencing depth can improve the detection rate of noninvasive prenatal testing (NIPT) for chromosome aneuploidies and copy number variations (CNVs). However, due to the technical limitations of NIPT, false-positives and false-negatives are inevitable. False-positives for aneuploidy and CNVs have been widely reported, but few missed cases have been reported. In this study, we report 3 patients missed by NIPT, which were still missed after increasing the sequencing depth. To verify the detection efficiency of the platform, the results of NIPT in 32,796 patients treated in Yulin Women and Children Health Care Hospital from 2020 to 2022 were retrospectively analyzed. Data on false-negative cases found by postnatal follow-up or amniocentesis were collected, and the sequencing data, pregnancy examination data, and postnatal follow-up results of these missed patients were summarized. Five patients missed by NIPT were found, and they were missed again by retesting or increasing the sequencing depth. Except for hypospadias found in 1 patient, ultrasonography of the other 4 patients showed no obvious abnormalities during the whole pregnancy. Our results suggest that pregnant women should be fully informed of the benefits and limitations of NIPT before undergoing the examination to avoid unnecessary medical disputes. [ABSTRACT FROM AUTHOR]

Background: To explore reasons for the failure of noninvasive prenatal test (NIPT) for cell‐free fetal DNA (cffDNA) in maternal peripheral blood, and discuss appropriate treatment schemes after the failure of the test. Methods: Altogether 41,136 pregnant women participated in NIPT. Blood samples were taken again from pregnant women who failed the first blood collection upon their informed consent. Prenatal genetic counseling or prenatal diagnosis was recommended for pregnant women with final NIPT failure. Results: The first failure rate of NIPT was 0.737% (303/41136), and the reason for the failure was the low ratio of cffDNA in 135 (44.6%) of the 303 pregnant women. After the second or third blood sampling, the final failure rate was 0.182% (75/41136). The low ratio of cffDNA was the main reason for test failure in 42 (56.0%) of the 75 pregnant women who finally failed NIPT, among whom 44 (58.7%) had underlying diseases, including 21 (47.7%) with more than two coexisting underlying diseases. Only 27 (36.0%) of the 75 pregnant women with NIPT failure underwent interventional prenatal diagnosis. Conclusions: The main reason for NIPT failure was the low ratio of cffDNA. Postponing the gestational weeks of blood collection may improve the success rate. Resampling and retesting upon informed consent in pregnant women who failed the first test could improve the success rate. For pregnant women who finally failed NIPT, it is suggested strengthening the genetic counseling, prenatal examination, and ultrasound evaluation, and carry out interventional prenatal diagnosis if necessary. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the pregnancy outcomes of patients who applied to our clinic between the 11th and 14th weeks of pregnancy and whose nuchal translucency (NT) measurement was ≥1.5 multiples of the median (MoM). Material and Methods: The study included 85 patients whose NT measurement was determined ≥1.5 MoM and pregnancy results were available. Demographic characteristics of the patients, prenatal invasive diagnostic test results, fetal anomaly screening, fetal echocardiography (ECHO) results, and neonatal and obstetric results were evaluated. Results: Abnormal karyotype was detected in 10.6% (n=9) of the patients. Trisomy 21 was the most common chromosomal anomaly. Fetal structural anomaly was detected in 29.4% (n=25) of the patients. A structural fetal anomaly was detected in 21% (n=13) of fetuses with normal karyotypes and 66.7% (n=6) of fetuses with abnormal karyotypes. Cardiac anomalies were found to be the most common anomalies with 9.7% (n=6) in patients with normal karyotype. NT and NT MoM values in patients with fetal structural (both p=0.001) or chromosomal anomalies (p=0.011, and p=0.019, respectively) were found significantly higher than those without. NT and NT MoM values in patients whose pregnancies resulted in fetal loss were found significantly higher than in patients who had a live birth (both p=0.001). Conclusion: Increasing NT or NT MoM values indicate an increase in the risk of chromosomal anomalies, structural anomalies, and poor pregnancy outcomes in the fetus. Fetal anomaly screening and fetal ECHO should be recommended in patients with increased NT, even if a normal karyotype is detected. [ABSTRACT FROM AUTHOR]