This study conducted a retrospective analysis on ultrasound findings, karyotype characteristics, pregnancy outcomes, and follow-up data for 92 fetuses diagnosed with Turner mosaicism. It provides essential clinical data on the prenatal and postnatal outcomes of these cases. A comprehensive review and analysis were conducted on 92 cases of Turner mosaic fetuses diagnosed by karyotyping, SNP-array, or FISH at the Prenatal Diagnosis Center of Shenzhen Longgang Maternal and Child Health Hospital, a tertiary medical center, between January 2013 and September 2025. The analysis focused on maternal demographic data, types and proportions of mosaic karyotypes, ultrasound findings, pregnancy outcomes, and postnatal follow-up data. Of 12,855 high-risk pregnancies undergoing amniocentesis, 92 Turner mosaic fetuses ( 0.72%, 92/12855) were identified. The majority (65/92, 70.7%) exhibited X-chromosome aneuploidy mosaicism, most commonly 45,X/46,XX (52 cases). Mosaicism involving structural abnormalities of the X chromosome was observed in 27 cases (29.3%), including eight cases of 45,X/46,X, i(X)(q10). Ultrasonography detected abnormalities in 10 fetuses - three with cardiovascular malformations, two with growth restriction, and one with cystic hygroma - while the remaining 82 cases had no abnormal ultrasound findings. Two cases were notable for complex multi-system anomalies: one with 45,X[24]/46,XX[76] presented with coarctation of the aorta, a horseshoe kidney, and increased nuchal translucency (3.2 mm); another with 46,X, i(X)(q10)[66]/46,XX[24] had a ventricular septal defect, left clubfoot, and bilateral ventricular widening. Of the 92 fetuses with Turner mosaicism, 69 pregnancies were terminated and 23 were continued. Among the 23 continuing pregnancies, one resulted in embryonic arrest, one was subsequently terminated, and one delivered preterm at 34 weeks. Twenty infants were live-born and followed up: three showed delayed language and motor development, one had epilepsy, one had hearing loss, and one exhibited short stature with dry skin. Notably, the abnormal mosaic ratio in all cases with postnatal findings ranged from 20% to 30%. The prenatal phenotype of Turner mosaicism is largely determined by the proportion of abnormal cells and the tissues involved. Clinical decisions should caution against termination for mosaic ratio below 30%, as cases under 10% typically have favorable outcomes. Although prenatal ultrasound findings for Turner mosaicism lack specificity, they may be closely associated with cardiovascular abnormalities and intrauterine growth restriction. After birth, it is crucial to conduct close postnatal monitoring of neurodevelopment for these children.
Apert syndrome is a rare congenital malformation caused by a mutation in the fibroblast growth factor receptor 2 (FGFR2) gene. Characteristic imaging findings include bilateral premature closure of the coronal suture, midfacial hypoplasia, and symmetrical syndactyly of the fingers and toes. These features may be accompanied by lateral ventricle dilation, absence of the corpus callosum, cervical vertebral fusion, and other anomalies. However, in the second trimester, syndactyly and extracranial anomalies may be the only detectable signs, which complicate early diagnosis. The purpose of this study is to improve the early diagnosis rate of Apert syndrome. We report an atypical case of Apert syndrome carrying the FGFR2 S252W mutation, which typically associated with severe cranial deformities and cleft palate, but prenatal ultrasound at 23 weeks revealed symmetrical syndactyly of both hands and feet and a sacrococcygeal soft tissue mass resembling a "tail" without cranial abnormalities. Although prior studies have linked this mutation to advanced paternal age, the father in this case was 25 years old, which does not align with this association. This case demonstrated that Apert syndrome may present prenatally features other than cranial abnormalities. A practical screening strategy should therefore combine detailed second-trimester ultrasound evaluation of extremities and cardiac structures with prenatal genetic testing, even in the absence of cranial abnormalities.
To report a rare prenatal case of paternal uniparental isodisomy of chromosome 3 (upd(3)pat) associated with isolated intrauterine growth restriction (IUGR). Expanded non‑invasive prenatal screening (NIPS) in a 19‑year‑old woman indicated a duplication on chromosome 3q. Amniocentesis was performed for karyotyping, chromosomal microarray analysis (CMA), and trio whole‑exome sequencing (WES). Copy number variation sequencing (CNV-seq) was performed for the validation of the placental tissue postpartum. Karyotype was normal (46,XY). CMA revealed a whole-chromosome region of homozygosity (ROH) on chromosome 3, and WES confirmed upd(3)pat with no recessive pathogenic variants. Third‑trimester ultrasound showed IUGR. A male infant weighing 2,450 g was delivered at 38 weeks with normal birth examination. CNV-seq confirmed trisomy 3 on the fetal side of the placenta. Follow-up assessment at 2.5 years of age showed unremarkable neurodevelopmental outcomes. NIPS is a screening rather than a diagnostic test and all positive findings must be confirmed by invasive diagnostic procedures. Trisomy rescue can lead to coexistence of UPD3 with confined placental mosaicism (CPM). A multimodal approach incorporating karyotyping, CMA, trio‑WES, and CNV‑seq is essential for resolving discordant findings. This study expands the limited prenatal literature on upd(3)pat and highlights the critical importance of comprehensive genetic testing for accurate diagnosis and genetic counseling.
Prenatal testing is a standard approach for detecting genetic diseases in expectant mothers, with more testing options becoming available. Homozygosity mapping is invaluable for identifying genes causing disease and improving molecular diagnostics. Here, we present the prenatal diagnosis outcomes of three families affected by cystic fibrosis (CF). A combination of phenotypic analysis, haplotype analysis, and CFTR gene sequencing was used to identify the causative mutations. This allowed for the effective detection of individuals misdiagnosed with routine screening procedures. A method that is potentially useful for similar autosomal recessive disorders. Our findings indicate that enhanced diagnostic accuracy enables earlier clinical interventions that lead to better management of affected pregnancies and improved neonatal care. We show the significance of comprehensive genetic testing to boost diagnostic accuracy for recessive diseases and minimize the risk of diagnostic errors in prenatal settings.
This study investigated the diagnostic utility of prenatal ultrasound in identifying mirror syndrome, drawing on the existing literature. A comprehensive series of assessments was undertaken on fetal growth and development, organogenesis, and ancillary structures, including amniotic fluid and placenta, using systematic prenatal ultrasonography in conjunction with hemodynamic evaluations. In cases where fetal edema was identified, additional chromosomal karyotyping and chromosomal microarray analyses were recommended. An analysis of 13 patients diagnosed with mirror syndrome and admitted to the Women's Hospital, Zhejiang University School of Medicine, from January 2020 to July 2025 was conducted. The medical information of these patients was examined, encompassing clinical characteristics, evaluation of fetal and fetal appendage status, laboratory analyses, and perinatal outcomes. The prevalent maternal clinical manifestations included bilateral lower limb edema (100%), hypertension (84.6%), anemia (69.2%), and proteinuria (38.4%). Almost all cases presented with decreased hematocrit and serum albumin levels. In the study, 13 instances exhibited placental thickness > 4 cm, while eleven instances presented placental thickness > 6 cm. Pathological examination of the placenta revealed villous edema in eight cases. Mirror syndrome is rare; however, the fetal prognosis is poor. Early and precise diagnosis of mirror syndrome is essential for improving outcomes for both the mother and the fetus.
To quantify the discrepancy between anatomical and motor levels in foetuses with open spinal dysraphism and identify prenatal factors associated with this difference. We also examined associations between anatomical level and ultrasound findings. Retrospective observational study. Single tertiary referral centre. A total of 187 foetuses diagnosed with open spinal dysraphism between 2011 and 2022. Anatomical level was defined as the highest non-closed vertebra on ultrasound. Motor level was determined through dynamic assessment of the most caudal active muscle group. The anatomical-motor level difference was calculated, and linear regression analyses were used to evaluate associated clinical and ultrasound variables, adjusting for anatomical level. Difference between anatomical and motor levels; association of ultrasound features with anatomical level. In 85.0% of foetuses, the motor level was more caudal than the anatomical level, with a median difference of two vertebral segments (range -3 to +15). Greater discrepancies were associated with myeloschisis compared to myelomeningocele (adjusted coefficient: 0.78, p < 0.001). Bilateral talipes and kyphosis were linked to smaller discrepancies. Higher anatomical levels were significantly associated with ventriculomegaly and vertebral anomalies. In foetuses with open spinal dysraphism, the motor level assessed by prenatal ultrasound is frequently more caudal than the anatomical level, with a discrepancy in over 80% of cases. The magnitude is influenced by lesion type and anatomical height, with myeloschisis and higher lesions showing greater differences. Additionally, anatomical level correlates with several ultrasound findings, including ventriculomegaly and vertebral anomalies.
BackgroundCopy number variations represent a key source of genomic variability, encompassing both benign and pathogenic alterations. Accurate interpretation of copy number variations identified through prenatal screening is critical for effective genetic consultation and clinical management. Microdeletions within the 16q24.3 locus remain understudied, thereby complicating genetic counseling for affected cases.Case presentation: This study describes the prenatal diagnostic workup and genetic counseling process for a Chinese family with a fetus carrying a de novo 16q24.3 microdeletion.ConclusionConventional cytogenetic techniques exhibit limited sensitivity for the detection of chromosomal microdeletions and microduplications. A multimodal approach integrating prenatal ultrasound, karyotyping, chromosomal microarray analysis, and genetic counseling enhances the diagnostic accuracy of such chromosomal anomalies during pregnancy.
Prenatal diagnosis of fetal cervicofacial lymphangioma is rare, and the diagnosis of the disease can be achieved through prenatal ultrasound. Due to the significant variation in the nature of fetal neck masses, the diagnostic process is challenging in cases involving this location. Nevertheless, we have successfully reported one such case using conventional two-dimensional and three-dimensional sonography. A 27-year-old woman underwent routine fetal ultrasound at 20 weeks of gestation. Conventional two-dimensional ultrasound revealed a mixed cystic-solid mass located in the fetal neck and face. Three-dimensional ultrasound with surface rendering clearly delineated the external protrusion of the mass demonstrating marked distortion and elevation of the facial and cervical contours. The prenatal imaging findings were consistent with a diagnosis of cervicofacial lymphangioma. Following termination of pregnancy, histopathological examination and immunohistochemical analysis of the post-abortion specimens further confirmed the diagnosis. Prenatal ultrasonography remains the primary modality for diagnosing fetal cervicofacial lymphangioma. The integration of three-dimensional ultrasound surface imaging enhances diagnostic accuracy by providing detailed morphological information, offering critical visual evidence to support the initial diagnosis. Chromosomal karyotyping and genetic testing serve as important adjuncts in the comprehensive prenatal evaluation. These assessments facilitate thorough counseling and enable timely clinical decision-making, which are essential for optimizing perinatal outcomes.
To evaluate the epidemiology, diagnostic pathway, prenatal surveillance, and pregnancy outcomes of women referred for suspected cytomegalovirus (CMV) infection during pregnancy in a population-based cohort. This population-based cohort study included women counselled for suspected CMV infection during pregnancy between January 2002 and December 2021 in Campania, Italy. Maternal infection was classified as primary infection (documented seroconversion), suspected infection (IgG-positive/IgM-positive at first sample), or no infection during pregnancy, based on serial serology and IgG avidity testing. Prenatal diagnosis by amniocentesis for CMV DNA detection and serial ultrasound surveillance were offered in accordance with a standardized local protocol. Pregnancy and neonatal outcomes were recorded. A total of 716 women were included. Primary CMV infection was documented in 320 women (44.7%), suspected infection in 58 (8.1%), and no CMV infection during pregnancy in 294 (41.1%); 44 cases (6.1%) were not classifiable due to incomplete follow-up. IgG avidity testing, available in 211 women, supported diagnosis but showed limited specificity for recent infection. Amniocentesis was performed in 209 cases (29.2%), with CMV DNA detected in 40 (19.1%); all PCR-positive cases were confirmed as congenital CMV infection at birth. Overall, 45 (6.3%) neonates were diagnosed with congenital CMV infection. The majority of infections (84.4%) occurred following early maternal primary infection. Prenatal ultrasound abnormalities were infrequent and heterogeneous; most infected neonates had negative prenatal scans. Several clinically significant neonatal sequelae, including sensorineural hearing loss and neurodevelopmental impairment, occurred in the absence of prenatal ultrasound findings. In this large population-based cohort, a substantial proportion of women referred for suspected CMV infection did not acquire infection during pregnancy, highlighting the need for careful interpretation of serological findings and centralized counselling. Primary infection, particularly when acquired early in pregnancy, remains the main determinant of congenital CMV infection and adverse outcomes. While amniocentesis is the most reliable prenatal diagnostic tool, ultrasound surveillance alone has limited sensitivity. These results provide a robust pre-treatment baseline for future studies evaluating the impact of maternal antiviral therapy with valaciclovir on vertical transmission and neonatal outcomes.
Holoprosencephaly (HPE) is a rare congenital condition encompassing incomplete midline cleavage of the prosencephalon and associated craniofacial abnormalities. We report a rare case of a 34-year-old Memon woman, gravida 3 para 2, with no known comorbidities or exposure to teratogens, who presented for her 12-week scan which revealed a single alive fetus having an absent falx cerebri with fused thalami, a single large posterior ventricle, and facial anomalies suggestive of alobar HPE. A follow-up ultrasound showed abnormally fused portions of the brain and a high amniotic fluid index (AFI), indicating polyhydramnios. The fetus had intrauterine death at 7 months of gestation. This case highlights the importance of early prenatal diagnosis of alobar HPE, the most severe form, using transabdominal ultrasonography (USG) and transvaginal USG. Prompt prenatal imaging is crucial for early diagnosis of alobar HPE, enhancing antenatal care, and facilitating improved family planning strategies to alleviate potential psychological distress due to its poor prognosis. Our documentation of such a rare condition is essential to help create a comprehensive database of similar cases.
Sickle cell disease (SCD) and thalassaemia are inherited conditions causing chronic anaemia, increased infection risk and multi-organ failure. Standard of care (SoC) prenatal screening involves carrier blood testing for pregnant women and, if positive, carrier blood testing for biological fathers followed by invasive prenatal diagnosis for pregnancies at risk. Non-invasive prenatal testing (NIPT) presents an alternative pathway which may reduce diagnostic delays and improve equity for pregnant women when the biological father is unavailable by focusing invasive testing exclusively on fetuses shown to have a high risk of SCD by NIPT. This study compares the outcomes of SoC screening with a proposed NIPT pathway replacing the paternal blood testing stage. A deterministic decision tree model is used to identify the outcomes of the screening pathways, focusing on the SCD population, from the perspective of the National Health Service (NHS) England. Sensitivity and specificity inputs for NIPT are informed by a separately published minimally acceptable criteria study. Diagnostic outcomes include the number of performed and declined tests and true and false positive/negative diagnoses in each pathway. Economic outcomes include the testing cost of the pathway, the cost per case detected and per accurate diagnosis, and an incremental cost threshold analysis for NIPT. Additional scenario analyses are conducted for the SCD and thalassaemia combined population and for the thalassaemia populations. When considering an overall cohort of 616,573 pregnancies, implementing the NIPT pathway for the screen-positive SCD population results in an incremental cost of £7,584,551. Of 276 prenatal diagnoses (PND) performed in the SoC arm, 76 show a true positive result for SCD, and 2 false positives are identified. In the NIPT arm, there are 6090 NIPTs and 543 PNDs performed, with 213 true positives and 235 false positives identified. The NIPT pathway costs £33,158 more per case detected, and £368 more per accurate diagnosis than SoC; to obtain no incremental cost per case detected versus the SoC, NIPT would need to cost £45.21. The presented exploratory analysis may gauge the potential cost-effectiveness of introducing NIPT into the screening pathway, pending further research on the technique's diagnostic efficacy.
Prenatal opioid exposure has been linked to adverse developmental outcomes, but its effects on childhood musculoskeletal health are unclear. This study examined the association between prenatal opioid exposure and fracture risk in children. This study emulated a target trial using a nationwide mother-child linked birth cohort from the Korean National Health Insurance Service claims data from January 1, 2009 to December 31, 2023. Prenatal opioid exposure was defined as maternal receipt of ≥ 2 opioid prescriptions during any trimester. The primary outcome was the postnatal diagnosis of any fracture, and secondary outcomes were site-specific fractures, including the head, spine, upper limb, lower limb, or other anatomical sites, as identified by relevant International Classification of Diseases 10th edition codes. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models with propensity score matching and a sibling comparison design. After propensity score matching, we identified 584,400 children (51.3% boys) without and 117,065 (51.3% boys) children with prenatal opioid exposure. Children with prenatal opioid exposure had an increased risk of fractures [aHR 1.07 (95% CI 1.06-1.08)], whereas no significant association was observed in the sibling comparison cohort analyses [1.02 (0.99-1.04)]. Risk of fractures showed a dose-dependent manner [low-dose exposure: 1.06 (1.05-1.08); high-dose exposure: 1.09 (1.06-1.12)]. Opioid exposure during pregnancy was not associated with a substantial increase in the risk of fractures in the children. However, exposure to high opioid doses, prolonged or frequent prenatal opioid exposure, may still warrant caution.
This study aimed to evaluate the relationship between the Z-score of positive noninvasive prenatal testing (NIPT) results and the positive predictive value (PPV), as well as the correlation between Z-score and cell-free fetal DNA (cff-DNA) concentration, and the association between PPV and maternal age. A total of 278 singleton pregnant women with high-risk NIPT results were included. Fetal karyotyping or copy number variation sequencing (CNV-Seq) was performed to confirm the presence of chromosomal abnormalities. The study evaluated the correlation between Z-scores of true positive NIPT results and the concentration of cff-DNA. Additionally, the study analyzed the association between NIPT Z-score and PPV, as well as the relationship between PPV and maternal age. Logistic regression analysis was used to assess the correlation between Z-scores and PPV. The diagnostic performance of Z-scores in detecting chromosomal aneuploidy was evaluated using receiver operating characteristic (ROC) curve analysis. Of the 242 pregnant women who opted for prenatal diagnosis through invasive amniocentesis, 184 cases were diagnosed as true positives. The total PPVs of NIPT screening for trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13) were 89.82%, 67.65%, and 26.83%, respectively. The Z-scores of T18 and T21 are positively correlated with the concentration of cff-DNA. The PPVs of T18 and T21 increase with rising Z-score. When 5 < Z ≤ 20, the PPV of T21 is the highest, while that for T13 is the lowest under the same Z-score. Furthermore, the PPV was found to be higher among pregnant women aged ≥35 years compared to those younger than 35 years. The ROC curve analysis showed that the optimal cutoff value of Z-scores for T21, T18, and T13 was 9.189, 14.08, and 13.72. The logistic regression analysis revealed that Z-scores of NIPT-positive results were significantly associated with the PPV at T21 (p < 0.001), T18 (p = 0.008), and T13 (p = 0.034). Z-score showed a positive correlation with cff-DNA concentration and PPV for T21 and T18. Based on these findings and current knowledge, we suggest that, a multi-parameter model (including Z-score, maternal age, cff-DNA%, and ultrasound markers) be evaluated in future studies to potentially improve NIPT accuracy and reduce false positives. This suggestion is speculative and requires prospective validation.
Prenatal sequencing of fetuses with abnormalities detected on imaging is expanding globally. Debate continues over whether variants of uncertain significance (VUS) should be reported prenatally, with some recent national position statements opposing this. In England, VUS that fit the fetal phenotype and require little further evidence for upgrade are discussed at multidisciplinary team (MDT) meetings to determine whether to report. We review the VUS reported by one English laboratory that provides prenatal sequencing to half of England. The laboratory's database was searched from 01/10/2020 to 30/04/2025 to ascertain all cases where a VUS was reported. Pregnancy outcomes were obtained from local clinical teams to determine whether the VUS status had been resolved. VUS were reported in 41/881 fetuses sequenced. Follow-up data were available for 38/41 cases, of which 23 were subsequently upgraded to likely pathogenic and 1 downgraded to likely benign. The most common reason for upgrade was new information from post-mortem or postnatal review (17/23). There is clinical utility in reporting VUS from prenatal sequencing following MDT discussion. Although reporting VUS leaves parents with uncertainty, follow up (including post-mortem when applicable) resolves this in over 50% of cases (79% of cases re-examined pre- or postnatally).
Non-invasive prenatal testing (NIPT) is widely used for prenatal screening of common fetal aneuploidies through analysis of cell-free DNA (cfDNA) in the maternal plasma. Because cfDNA originates from both placental and maternal sources, genome-wide NIPT may incidentally reveal acquired chromosomal abnormalities associated with maternal malignancies. We report the case of an asymptomatic pregnant woman whose first-trimester NIPT revealed multiple complex chromosomal imbalances incompatible with a fetal origin and suggestive of circulating tumor-derived cfDNA. Extensive biological and radiological investigations performed during pregnancy and early postpartum follow-up were initially non-contributive. After structured multidisciplinary monitoring, radiological progression of a vertebral lesion led to the diagnosis of an isolated diffuse large B-cell lymphoma of the spine, nearly one year after the initial NIPT. Chromosomal abnormalities detected by NIPT persisted postpartum and closely matched copy number alterations identified by molecular karyotyping of the tumor biopsy. This case suggests that NIPT may detect tumor-derived cfDNA at a very early stage, potentially preceding clinically detectable disease by several months in selected cases. However, such findings should be interpreted with caution, as alternative explanations cannot be excluded. Taken together, these observations highlight both the potential and the current limitations of cfDNA-based approaches and underscore the importance of structured longitudinal follow-up with multidisciplinary evaluation when NIPT results are highly suggestive of maternal malignancy.
Myoclonus-dystonia syndrome (MDS) is a movement disorder syndrome characterized primarily by myoclonus as the core feature. In this study, we reported a case of MDS with myoclonus as the prominent feature, which was accompanied by learning disability and special face. We then used copy number variation sequencing (CNV-seq), whole exome sequencing (WES) and Sanger sequencing to verify the MDS related genes of the patient and his family members. We found that the patient carried a heterozygous mutation of SGCE gene c.731dup (p.Asn244Lysfs*6) related to MDS, which inherited from his father. It was the first reported new mutation at home and abroad. And we confirmed via prenatal diagnosis that his fetus also had a heterozygous mutation of SGCE gene c.731dup (p.Asn244Lysfs*6). In addition, we also found that there was a 1.40 Mb repeat fragment at p23.1 on chromosome 8 of the patient, which partially overlapped with 8p23.1 repeat syndrome. It is speculated that it may be related to the learning disability and special facial phenotype of the patient, and it was a de novo variant. This study not only clarified the etiology of the patient's myoclonus, but also enriched the genetic variation database of SGCE gene by the newly discovered heterozygous heterozygous site of c.731dup (p.Asn244Lysfs*6) of SGCE gene, which was helpful to improve the clinician's awareness of diagnosis of MDS and provide guidance for the patient's fertility. 肌阵挛-肌张力障碍综合征(myoclonus-dystonia syndrome，MDS)是一种以肌阵挛为核心特征的运动异常综合征。本研究报道了1例以肌阵挛为显著特征的MDS患者，其同时伴有学习障碍及特殊面容。通过对患者及其家系成员进行拷贝数变异测序(copy number variation sequencing，CNV-seq)、全外显子组测序(whole-exome sequencing，WES)及Sanger测序验证，发现该患者携带有与MDS相关的SGCE基因c.731dup(p.Asn244Lysfs*6) 杂合变异，为国内外首次报道的新变异。该变异来源于其父亲，且产前诊断结果证实其胎儿也存在SGCE基因c.731dup (p.Asn244Lysfs*6) 杂合变异。此外，患者8号染色体p23.1处存在1.40 Mb重复片段，该片段与8p23.1重复综合征部分重叠，推测可能与患者的学习障碍及特殊面容表型相关，且经家系验证该重复片段为新发变异(其父母均未携带该变异)。本研究不仅明确了患者肌阵挛的病因，而且新发现的SGCE基因c.731dup (p.Asn244Lysfs*6)杂合变异位点丰富了SGCE基因的遗传变异数据库，有助于提升临床医生对MDS的诊断意识。.
Aceruloplasminemia is an autosomal recessive disorder, characterized by diabetes mellitus and progressive neurological symptoms, absent of phenotype before delivery. It is caused by mutations in CP, resulting in a deficiency in ceruloplasm. This study sought to diagnose sporadic fetal aceruloplasminemia via whole exome sequencing and plasma ceruloplasm measurement. Amniotic fluid and cord blood samples were obtained from a 29-year-old woman. Trio-based whole exome sequencing was performed due to right aortic arch and left subclavian artery identified in fetal ultrasound scanning, on the maternal request. Plymerase chain reaction was performed on RNA, extracted from fetal cord blood and peripheral blood of the couple. Fetal cord blood ceruloplasmin, copper, iron and transferrin were determined by enzyme linked immunosorbent assay, nephelometric method and spectrometry, respectively. Ceruloplasmin was detected as control in twelve gestational age-matched normal fetal cord blood samples. No cardiac-related variants were identified, but two compound heterozygous CP variants (c.1306 C > T, p.(R436*) and c.3019-17T > G) were incidentally detected in the fetus. The c.1306 C > T p.(R436*) variant was a previously reported pathogenic variant that induced nonsense-mediated mRNA decay. The intronic variant (c.3019-17T > G), predicted by SpliceAI to disrupt splicing, was functionally confirmed to cause exon 18 skipping. Besides, ceruloplasmin concentrations in gestational week-matched healthy fetuses ranged from 2.75 to 56.18 mg/L (median: 14.93 mg/L, IQR: 9.96-21.43 mg/L), while it was undetectable (below the lower limit of detection) in the affected fetus. Copper and iron levels in affected fetus were within normal ranges, while transferrin levels were below the normal threshold. Our findings expanded the spectrum of pathogenic variants in CP and provided new insights into the prenatal diagnosis of the aceruloplasminemia.
We aimed to perform what is, to our knowledge, the first bibliometric analysis focusing on artificial intelligence (AI) applications in paediatric congenital heart disease (CHD) over a 25-year period (2000-2025). We examined the advancements in research, emerging trends, and principal research topics in this field. Articles on AI and CHD published between 2000 and 2025 were retrieved. The data sourced from the Web of Science Core Collection encompassed 423 qualifying studies that were evaluated using Cite Space and VOSviewer to examine the contributions of various countries, institutions, authors, journals, and keywords. These visualisation tools facilitated the mapping of collaboration networks, co-citation patterns, and keyword trends. The United States is the main research hotspot in national terms, contributing 40% of the publications in this area, Harvard Medical School is the institution with the most research results, with Pan, Silin being the most prolific researcher. Key research areas include the application of AI in prenatal screening for CHD, diagnosis and treatment of paediatric CHD, long-term management of CHD in children, the role of health professionals, and related risks. As far as we know, this is the first bibliometric analysis dedicated to AI in paediatric CHD. It shows continuous growth and interdisciplinary potential. We emphasise the need for improved collaboration between different fields of study, use of AI in medical practice to assess individual risks (especially regarding medication safety), and policy initiatives to address the equity gap between high-income regions and those with the most CHD cases.
Non-invasive prenatal testing (NIPT) achieves high sensitivity for common fetal aneuploidies; however, its positive predictive value (PPV) varies substantially with population prevalence, generating a considerable false-positive burden. Current guidelines offer limited guidance on ultrasound-based risk refinement after a positive NIPT result. To determine whether integrating second-trimester ultrasound soft markers with NIPT improves PPV for fetal chromosomal abnormalities and to characterize aneuploidy-type-specific phenotypic profiles to inform risk stratification. This retrospective cohort study included 303 singleton pregnancies at a Chinese tertiary center (September 2022-September 2025). All patients underwent NIPT (12+0-14+6 weeks) and detailed second-trimester ultrasound (19-23 weeks). Eight soft marker categories were assessed. Chromosomal abnormalities were confirmed by karyotyping, and neonatal phenotypic assessment served as the reference for NIPT-negative pregnancies. Predefined combined strategies were compared using diagnostic accuracy metrics and receiver operating characteristic analysis. Twenty-four pregnancies (7.9%) harbored confirmed chromosomal abnormalities. NIPT achieved 100% sensitivity and 100% negative predictive value (upper-bound estimates given differential verification bias; see Methods), but only 55.8% PPV (24/43), with 19 false positives. Among the false-positive cases, 63.2% exhibited no soft markers, and none had ≥2 markers. The high-risk combined strategy (NIPT-positive with ≥1 high-risk marker or ≥2 markers) improved PPV to 83.3% with 98.9% specificity, potentially reducing invasive procedures by 58% through individualized counseling. Strategy (a) (NIPT-positive with ≥ 1 marker) achieved 100% sensitivity for trisomies 18 and 13 (uniformly severe marker burdens) but 62.5% for trisomy 21 (37.5% marker-negative). The combined model achieved an AUC of 0.987, significantly exceeding that of NIPT alone (0.966; p = 0.012), although these estimates warrant external validation given the enriched cohort. Women aged <35 years derived the greatest incremental benefit (+28.2 percentage points). In this enriched tertiary referral cohort, integrating second-trimester ultrasound soft markers with NIPT was associated with improved PPV, with particular efficacy for trisomies 18 and 13; however, the observed PPV improvement was predominantly driven by trisomies 18 and 13, which uniformly present with multiple markers, whereas the clinical utility for trisomy 21 was more limited owing to phenotypic heterogeneity (37.5% marker-negative). If confirmed by prospective multicenter validation, this approach may enable individualized post-positive NIPT counseling and complement existing guideline frameworks.
Fetomaternal hemorrhage (FMH), a life-threatening obstetric complication with high concealment and poor prognosis, is mostly postnatally diagnosed. This case reports the 30 years old primigravida at 32 + 1 weeks, preoperatively identified with FMH via combined indicators: markedly elevated maternal serum alpha-fetoprotein (AFP) (16698.2 μg/L post-dilution), decreased fetal movement, two non-reassuring fetal heart rate tracings, and polyhydramnios. Emergency cesarean section was done. The neonate had severe anemia (Hb 5.9 g/dL) and metabolic acidosis, with Hb rising to 137 g/dL after 26 mL packed red blood cell transfusion. Maternal K-B test confirmed 1.1% fetal Hb (116 mL blood loss). The neonate was discharged at 40 + 2 weeks corrected gestational age. This case emphasizes that the integration of multiple prenatal clinical and laboratory cues facilitates early detection of FMH, thereby contributing to improved perinatal prognosis.