Prenatal Diagnosis最新文献

Objective: To describe prenatal imaging findings and postnatal outcomes in fetuses diagnosed with saccular forms of closed spinal dysraphism (CSD).

Methods: This retrospective single-centre study included fetuses diagnosed with non-genetic, non-syndromic CSD between January 2018 and June 2023. Prenatal ultrasound and MRI findings were reviewed, with postnatal outcomes assessed in those managed expectantly, focusing on neurosurgical interventions, motor function, and urologic and bowel outcomes.

Results: Eighteen cases were identified; twelve opted for expectant management and had postnatal follow-up. The most common lesion was dysraphic spinal cord lipoma (10/18, 55.6%), followed by limited dorsal myeloschisis (3/18, 16.7%), myelocystocele (3/18, 16.7%) and meningocele (2/18, 11.0%). Chiari malformation and related brain abnormalities were absent at the time of diagnosis in all cases. Most fetuses (88.9%, 16/18) had a low-lying conus medullaris, and 70.6% (12/17) had a sac wall thickness ≥ 2 mm. Postnatally, 75% (9/12) underwent surgical detethering. At ≥ 30 months, all children could walk independently with or without orthoses. However, urologic complications were common in children age ≥ 48 months: 80% (4/5) required clean intermittent catheterization (CIC), 60% (3/5) had urinary incontinence, and 40% (2/5) experienced bowel incontinence.

Conclusion: Prenatal imaging features at the lesion level are key for diagnosing CSD. While motor outcomes are favorable, urologic and bowel dysfunctions are frequent in postnatal life.

Objective: To investigate the relationships between fetal fraction (FF) and multiple adverse pregnancy outcomes and assess its interaction with maternal pre-pregnancy body mass index (BMI).

Methods: This cohort study included 10,331 singleton pregnancies undergoing noninvasive prenatal testing (NIPT) at 11-20 gestational weeks. Outcomes included gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), small vulnerable newborns (SVN), preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), and fetal distress. Logistic regression models were used to assess the associations between FF and adverse pregnancy outcomes, with FF analyzed both as a continuous and binary variable (low FF, defined as < 25th percentile). The interaction of FF and high BMI (defined as BMI ≥ 24 kg/m²) on adverse pregnancy outcomes was examined on both multiplicative and additive scales.

Results: Continuous FF was inversely associated with GDM, HDP, SVN, PTB, LBW, and SGA. Binary low FF was associated with increased risks of HDP, SVN, PTB, and LBW. Additive interaction was observed between low FF and high BMI on HDP (RERI = 2.67, 95% CI: 1.26-4.32; AP = 0.45, 95% CI: 0.24-0.60).

Conclusions: In early pregnancy, lower FF is associated with increased risk of multiple adverse pregnancy outcomes, particularly HDP, SVN, PTB, and LBW. Besides, the effect of low FF on HDP risk may be amplified among women with high BMI.

Objective: Fetuses with hypoplastic left heart syndrome (HLHS) and restrictive/intact atrial septum (RAS) have high mortality, partly due to pulmonary lymphangiectasia (PL). This study aimed to characterize atrial septal morphology in fetuses with HLHS and RAS and evaluate the impact of fetal intervention on PL and outcomes.

Method: We retrospectively reviewed clinical data, fetal echocardiograms, and MRIs from all fetuses with HLHS/HLHS-variants and RAS over 20 years. RAS was defined as pulmonary venous forward-to-reverse VTI ratio ≤ 5:1.

Results: We identified 54 fetuses (gestational age of 24.2 weeks; 21.2-28.1) with HLHS (81%) or HLHS variant (19%) and RAS. Most had a hypoplastic left atrium (LA, 80%). Four atrial septal morphology patterns were identified. PL was present among all patterns and associated with lower VTI ratio (p = 0.046). Mean VTI ratio improved in fetuses who underwent atrial septal intervention (n = 12), compared to those without (p = 0.001). Among five fetuses with pre-intervention PL and serial MRIs, three improved. Seventeen neonates were live-born with intention-to-treat; 6-months mortality was 38% with no difference by morphology pattern, PL, or fetal intervention.

Conclusion: Most fetuses with HLHS and RAS had hypoplastic LA. VTI ratio correlated with PL on fetal lung MRI, and most improved with fetal atrial septal intervention.

Objective: We sought to perform multi-variable modeling to assess the independent value of the CVPS in fetuses with Ebstein anomaly or tricuspid valve dysplasia (EA/TVD).

Methods: CVPS was assessed at a core lab using the first and last echocardiograms during gestation. A receiver operating characteristic (ROC) curve analysis was conducted. Changes in the CVPS from the first to the last echo were assessed with Wilcoxon signed-rank tests.

Results: There were 164 fetuses with EA/TVD with complete CVPS at the first echo. Nearly half, 48.8% (n = 80), had intrauterine fetal demise (IUFD) or died neonatally. At the first echo, median gestational age (GA) was 27.6 weeks (IQR: 23.0-31.0) and median CVPS was 7 (IQR: 6-8). The optimal cut-point for classification of perinatal survival was observed at CVPS ≥ 6.5 (Youden index = 0.46). After adjustment, there remained a significant independent association between every 1-point increase in the CVPS at first echo and the odds of perinatal survival (adjusted odds ratio: 2.0, 95% CI: 1.3 to 3.2, and p = 0.003). The CVPS at the last echo decreased by a median of 1 point among both survivors (p < 0.01) and non-survivors (p < 0.001).

Conclusion: Among fetuses with EA/TVD, the CVPS may be used as an additional tool to assess perinatal survival throughout gestation.

Objective: The objective of this study is to investigate the distribution of increased nuchal translucency (NT) and its role in predicting fetal and neonatal losses in congenital heart disease (CHD).

Methods: This retrospective study analyzed 18,050 CHDs with documented NT measurements. Maternal characteristics, CHD subtypes, prenatal diagnoses, and fetal and neonatal losses were compared across NT categories. Cox regression analysis was performed to identify independent predictors of adverse outcomes.

Results: Increased NT occurred in 424 (2%) CHDs, more frequently in older mothers, those with previous adverse perinatal outcomes and prior CHDs. NT > 5.0 mm was more prevalent in critical CHDs and CHDs with extracardiac anomalies. Prenatal diagnosis rates increased from 17% (NT < 2.5 mm) to 94% (NT > 5.0 mm), whereas CHD-involved mortality rose from 10% to 90% (both p < 0.001). Cox regression analysis identified that severely increased NT increased at least a 3-fold higher risk of fetal and neonatal losses than the normal NT group.

Conclusions: NT distribution varies by maternal sociodemographics. Increased NT is more common in critical CHD and CHD with extracardiac structural abnormalities. Increased NT also plays an important role in predicting fetal and neonatal losses in CHD.

Objective: To investigate the association between low fetal fraction (FF) in non-invasive prenatal testing (NIPT) and pregnancy complications or adverse pregnancy outcomes.

Methods: Sixty-four pregnant women undergoing NIPT at the Second Affiliated Hospital of Wenzhou Medical University between 13 June 2019 and 6 January 2023 had an initial NIPT failure due to low FF. Three cases were lost to follow-up, leaving 61 cases in the failure group (Group A). Group A was subdivided into 37 cases with a valid result after redraw (Group A1) and 24 cases remaining unsuccessful after redraw (Group A2). Concurrently, 119 pregnancies with successful NIPT (normal FF, no fetal chromosomal abnormalities) were randomly selected as controls (Group C). Logistic regression and XGBoost models were established, and their area under the curve (AUC), sensitivity, and specificity were calculated and compared.

Results: The incidence of pre-eclampsia was significantly higher in Group A than in Group C (p < 0.05). No significant difference in the incidence of pre-eclampsia was found between Groups A1 and A2. A logistic regression model incorporating FF predicted pre-eclampsia with an AUC of 0.750 (95% CI: 0.639-0.860), sensitivity of 0.875, and specificity of 0.727. An XGBoost model incorporating 10 factors (FF, age, weight, BMI, gestational age, systolic/diastolic blood pressure at sampling, ART history, delivery history, heparin use history) demonstrated superior performance (AUC = 0.956, 95% CI: 0.868-1.000; accuracy = 0.944). The top three important factors were systolic blood pressure, diastolic blood pressure, and FF.

Conclusions: Low FF in NIPT may indicate an increased risk of pre-eclampsia. Regardless of the success of redraw, pregnancies with initial NIPT failure due to low FF warrant vigilance for pre-eclampsia development. The XGBoost machine learning model demonstrates good efficacy for predicting pre-eclampsia and has potential as an adjunctive prenatal screening tool for early diagnosis.

This report describes two unrelated prenatal cases of Shwachman-Diamond syndrome (SDS) presenting primarily with severe skeletal anomalies. SDS is a rare autosomal recessive disorder characterized by a triad of bone marrow dysfunction, skeletal abnormalities, and exocrine pancreatic dysfunction. The most common postnatal features include faltering growth, short stature, and neutropenia resulting in recurrent infections. Prenatal presentations could be scarce as the most common features are typically not apparent before birth. Molecular diagnosis of SDS relies on the identification of biallelic loss-of-function pathogenic variants in the SBDS gene. However, molecular genetic analysis is hampered by the presence of a pseudogene (SBDSP1), which can lead to misalignment or gene conversion events. In both reported cases, initial genetic testing was inconclusive. Subsequently, through clinical phenotype reassessment and expanded molecular analysis, the diagnosis of SDS by germline pathogenic SBDS variants (c.258+2T>C p.(?) and c.184A>T p.Lys62Ter) was established. These cases underscore the diagnostic complexity of SDS in prenatal settings and the necessity of comprehensive molecular analysis when facing severe skeletal anomalies suggesting small thoracic skeletal dysplasia and are further supported by an added literature review that expands the prenatal phenotype.

Objectives: To evaluate the neurological development of children with prenatally detected obliterated cavum septi pellucidi.

Methods: We analyzed the presence of associated cerebral or extracerebral anomalies at the referral neurosonography and, if available, at the magnetic resonance imaging (MRI). Those children were then evaluated postnatally by a standardized neurological and neuropsychological assessment.

Results: We enrolled 16 cases with obliterated CSP. In 2/16 (12.6%) cases, neurosonography identified additional findings. Among the 14 cases in which the obliteration of the CSP was apparently isolated, MRI was performed in 5/14 cases (35.7%) and confirmed the early obliteration of the CSP. In 3/14 cases (21.4%), fluid between the membranes of the septum pellucidum was eventually found in later gestation. We evaluated postnatally 9 children. Neuropsychological findings, adjusted for the patients' varying ages, were within normal limits and neurological development was age-appropriate in all subjects examined, except for one case, with a severe neurodevelopmental disorder of unknown etiology.

Conclusions: Obliterated CSP was a transient finding in 20% of cases. Most children demonstrated typical neural development at detailed follow-up studies, except for one case with severe neurological disability.

Objective: The American College of Obstetricians and Gynecologists (ACOG) recommends offering spinal muscular atrophy (SMA) carrier screening (CS) preconception or prenatally. This study aimed to determine provider knowledge of SMA and SMA CS practice patterns and to describe the relationship between knowledge and comfort while discussing screening and results.

Method: Prenatal providers completed an anonymous web-based survey on SMA knowledge, CS practice patterns, and comfort in interpretation of results. Data were summarized with descriptive statistics. The relationship between provider training and SMA knowledge with provider comfort was analyzed.

Results: 75% (112/150) of providers responded and 64.6% completed the survey. Participants varied in roles and years of experience. The mean score on knowledge was 3.8/8 (47.5%) with 20.6% of respondents scoring ≥ 75% and 51.6% scoring ≥ 50%. Knowledge did not vary with years of experience. Although 91.3% of providers offer SMA screening, less than 25% reported complete comfort discussing screening and results. Comfort correlated with role and experience. Providers who felt completely comfortable discussing SMA screening had higher knowledge scores.

Conclusion: Although the majority of providers offer SMA CS, provider knowledge regarding SMA is low, and most are not comfortable discussing screening and results.