SEARCH · PubMed Health

Results for “Pregnancy, High-Risk”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2025

Diagnosing the undiagnosed: AI-enhanced multimodal modeling for placental mesenchymal dysplasia in high-risk pregnancies.

Placental mesenchymal dysplasia (PMD) is a rare vascular placental disorder that mimics molar pregnancy but often coexists with a viable fetus, making its misdiagnosis potentially devastating. In high-risk pregnancies, artificial intelligence (AI)-enhanced multimodal modeling - incorporating imaging, genomics, proteomics, and clinical features - offers a transformative diagnostic strategy. Leveraging Bayesian hyperparameter optimization for model refinement, this approach improves diagnostic accuracy while reducing uncertainty and clinician hesitation. Recent clinical studies support its efficacy and interpretability through SHAP and LIME models, while real-time surgical enhancements using Bayesian methods highlight its broader clinical utility. Despite current challenges such as data heterogeneity and integration barriers, multimodal AI provides unprecedented resolution in placental analysis, enabling precise differentiation between PMD and similar fetopathies. Ultimately, this advancement supports timely, non-invasive diagnosis, personalized management, and emotionally informed decision-making aligned with ethical AI implementation standards.

Bayesian optimization↗

PubMed2025

Impact of Maternal Aspirin Therapy on Neonatal Epigenetic Patterns.

BACKGROUND: Low-dose aspirin (LDA) is an intervention recommended to prevent the development of hypertensive disorders of pregnancy (HDP) in high-risk pregnancies. Maternal conditions such as HDP have been associated with cord blood epigenetic changes including those related to cardiovascular processes; however, it is unclear whether maternal aspirin therapy may impact neonatal epigenetics in otherwise healthy high-risk pregnancy. OBJECTIVE: This study aimed to determine if maternal LDA exposure in utero leads to altered DNA methylation in umbilical cord blood cells in term neonates compared with controls not exposed to aspirin, and to identify if these methylation changes alter key pathways in the development of chronic disease. METHODS: Umbilical cord blood was collected from 10 neonates without LDA exposure and 13 neonates with LDA exposure in utero. Patients with hypertensive disorders of pregnancy, COVID-19, and chorioamnionitis were excluded. Genomic DNA was isolated from umbilical cord blood cells and genome-wide DNA methylation was performed using Illumina Methylation EPIC assay. RESULTS: A total of 155 differentially methylated loci (81 genes were hypermethylated and 74 were hypomethylated) were identified in LDA-exposed neonatal umbilical cord blood compared with the control group. Important canonical pathways identified by Ingenuity Pathway Analysis (IPA) were related to Th1 and Th2 signaling and classical (M1) macrophage activation. The genes affected by LDA exposure were associated with cardiac and renal systems. CONCLUSION: LDA exposure led to differential DNA methylation in umbilical cord blood. The differentially methylated genes were related to inflammatory pathways as well as cardiac and renal toxicity pathways. LDA exposure in utero may promote altered health programming in the neonate in areas impacting cardiovascular health. KEY POINTS: · Maternal aspirin exposure is associated with differential DNA methylation in cord blood.. · Cord blood epigenetic changes associated with maternal aspirin relate to anti-inflammatory pathways.. · Research on potential protective impact of maternal aspirin on neonatal epigenetics is warranted..

Humans↗

PubMed2026

Nipocalimab Phase 3 Dose Selection for Severe Hemolytic Disease of the Fetus and Newborn.

Nipocalimab, a neonatal Fc receptor (FcRn) blocker, is under evaluation for severe hemolytic disease of the fetus and newborn (HDFN). In the Phase 2 UNITY trial, weekly intravenous antenatal treatment with nipocalimab at dose regimens of 30 and 45 mg/kg prevented fetal anemia requiring intrauterine transfusion (IUT) in 54% of high-risk pregnancies and delayed the need for IUTs versus their previous pregnancies in the remaining 46% of pregnancies. This analysis aimed to select a weekly dose regimen of nipocalimab for the Phase 3 study in severe HDFN (NCT05912517) that maintains FcRn blockade throughout antenatal treatment, including with an unplanned dosing delay of up to 3 days. Observed pharmacokinetic/pharmacodynamic (PK/PD) data from UNITY (i.e., nipocalimab concentrations, FcRn occupancy, and serum IgG) were analyzed using a model-based approach. A PK/PD model originally developed in nonpregnant participants was updated to incorporate gestational weight gain. Nipocalimab PK and FcRn occupancy were described by a two-compartment model with nonlinear, dose-dependent PK, which captured longitudinal PK, FcRn occupancy, and IgG profiles during dosing and return toward baseline postpartum after discontinuation. Both 30 and 45 mg/kg achieved ∼80%-85% reductions in maternal IgG; however, 30 mg/kg showed greater variability in predose trough concentrations, increasing the risk of falling below concentrations required for full FcRn occupancy across antenatal treatment. Simulations incorporating PK/PD variability indicated that 45 mg/kg weekly per current weight maintained full FcRn occupancy in >95% of pregnant individuals, even with dosing delays up to 3 days. Exploratory exposure-response analyses supported 45 mg/kg for the Phase 3 HDFN study.

Humans↗

PubMed2026

Obesity in obstetric anesthesia: A systematic review.

Maternal obesity presents complex challenges for anesthetic management, with implications spanning neonatal, cardiovascular, airway, neuraxial, and procedural domains. This review synthesizes evidence on how elevated maternal body mass index (BMI) impacts perioperative evaluations, risks, complications, and outcomes, in addition to anesthetic modalities and efficacy in the pregnant population. Given the increasing global prevalence of maternal obesity, anesthesiologists must refine clinical practices, employing tailored, evidence-based strategies to mitigate risks and enhance patient outcomes. This review aims to provide anesthesiologists and obstetricians with key considerations and best practices for managing obstetric anesthesia patients with obesity. Clinical recommendations herein are based on current research and evaluated using Oxford Centre for Evidence-Based Medicine for level of evidence and class of recommendation.

Humans↗

PubMed2026

Genomic risk profiling in advanced maternal age: a Tamil Nadu prenatal study.

BACKGROUND: Advanced maternal age (AMA; > = 35 years) is associated with increased fetal chromosomal risk and is an important indication for invasive prenatal diagnosis. This study evaluates karyotyping and chromosomal microarray analysis (CMA) findings among AMA pregnancies in Tamil Nadu, India. METHODS: In this prospective observational study, 2,200 pregnant women aged ≥35 years who underwent amniocentesis between July 2020 and June 2021 were enrolled. Conventional karyotyping was performed in all cases. CMA was performed as a reflex or complementary test when predefined clinical or cytogenetic criteria were present, including ultrasound abnormalities, high-risk screening/NIPT results, abnormal or uncertain karyotype findings, prior adverse pregnancy history suggestive of genetic etiology, parental chromosomal abnormalities, or patient request after counseling. RESULTS: Numerical chromosomal abnormalities were detected in 76/2200 cases (3.5%), and structural abnormalities were detected in 9/2200 cases (0.4%). The total abnormal cytogenetic yield was therefore 85/2200 cases (3.9%) when numerical and structural abnormalities were considered together. Age-stratified analysis showed an increasing trend in chromosomal abnormalities with advancing maternal age, reaching 10.4% in women aged > = 43 years. Cases with additional clinical indications showed higher abnormality rates than simple AMA. CMA was performed in selected cases and contributed to characterization of clinically relevant genomic abnormalities, supporting its role in indicated high-risk AMA pregnancies. CONCLUSION: The Tamil Nadu cohort provides regional evidence on age-stratified cytogenetic risk in AMA pregnancies and supports the use of clearly defined criteria for integrating CMA with conventional karyotyping in prenatal diagnosis.

India↗

PubMed2025

Analysis of prenatal diagnosis and pregnancy outcomes for rare autosomal trisomies detected by non-invasive prenatal testing in 33,079 cases.

BACKGROUND: Non-invasive prenatal testing is widely used for screening common fetal aneuploidy disorders such as trisomy 21, trisomy 18, and trisomy 13. However, its ability to detect rare autosomal trisomies has introduced a new layer of complexity and clinical uncertainty. METHODS: A retrospective analysis was conducted on the prenatal diagnostic results and pregnancy outcomes of cases identified as high-risk for rare autosomal trisomies through non-invasive prenatal testing at the reproductive medicine center, Renmin hospital, Hubei university of medicine, from 2015 to 2023. RESULTS: 66 cases identified as high-risk for rare autosomeal trisomies, yielding a detection rate of 0.20% (66/33,079). 7 declined amniocentesis, while the others underwent the procedure. Prenatal diagnostic procedures did not confirm the presence of the corresponding rare autosomal trisomy in any of these cases. Among the 66 cases of rare autosomal trisomies (RATs), 5 cases were lost to follow-up, and 1 case underwent termination of pregnancy (TOP) for personal reasons, leaving 60 cases with valid pregnancy outcomes. Of these 60 valid outcomes, 50 (83.33%) resulted in full-term births, while 10 (16.67%) experienced adverse pregnancy outcomes. CONCLUSION: Prenatal diagnosis for high-risk rare autosomal trisomies typically reveals a normal karyotype with no detectable chromosomal abnormalities, and most cases can achieve full-term pregnancy outcomes. However, adverse pregnancy outcomes such as preterm birth, fetal demise, placental abnormalities, and intrauterine growth restriction are common and should be given clinical attention and consideration.

Humans↗

PubMed2026

Prenatal diagnosis of glucose-6-phosphatase catalytic subunit 3 deficiency (Dursun syndrome) using whole-exome sequencing: A case report of severe fetal cardiomyopathy in a consanguineous family.

Glucose-6-phosphatase catalytic subunit 3 deficiency, also known as Dursun syndrome, is a rare autosomal recessive disorder characterized by severe congenital neutropenia and variable multisystem malformations, particularly affecting the cardiovascular system. Most reported cases have been identified postnatally, following infectious or hematologic complications. Prenatal identification remains exceptionally rare. We describe the case of a fetus from consanguineous parents with a history of multiple neonatal deaths. Serial prenatal imaging demonstrated progressive fetal growth restriction, cardiomegaly with biventricular hypertrophy, significant tricuspid regurgitation, right-sided cardiac dominance, right atrial enlargement, ventriculomegaly, and evolving craniofacial dysmorphism. Whole-exome sequencing revealed a homozygous nonsense variant in G6PC3 (NM_138387.3:c.481C > T; p.(Arg161Ter)), confirming that both parents were heterozygous carriers. Postnatally, the neonate developed severe neutropenia, complex right-sided cardiac outflow obstruction physiology, and refractory cardiorespiratory failure, leading to death on day 4 of life. This report expands the prenatal phenotypic spectrum of glucose-6-phosphatase catalytic subunit 3 deficiency and emphasizes the importance of considering this diagnosis in fetuses presenting with cardiomyopathy, dysmorphic features, fetal growth restriction, and parental consanguinity. Early molecular diagnosis enables accurate counseling, informed reproductive planning, and consideration of preconception or early prenatal genomic testing in high-risk families.

Humans↗

PubMed2026

Prenatal SNP-array chromosomal microarray analysis in 3,549 pregnancies: indication-specific yields and clinical implications.

BACKGROUND: SNP-based chromosomal microarray analysis (CMA) is widely used in invasive prenatal diagnosis, yet real-world performance across contemporary referral pathways, especially in the NIPT era, remains incompletely characterized. METHODS: We retrospectively analyzed 3,549 prenatal invasive samples tested by SNP array, and evaluated diagnostic yield overall and by referral indication and ultrasound phenotype. RESULTS: In total, we identified 398 pathogenic or likely pathogenic (P/LP) variants across 386 fetuses, resulting in an overall diagnostic yield of 10.9% (386/3,549). These findings comprised 223 aneuploidies and 175 pathogenic CNVs. In contrast, variants of uncertain significance (VOUS) were detected in 12.0% (426/3,549) of cases. Diagnostic yields were heavily stratified by indication: yields peaked in NIPT high-risk referrals (38.9%) and were intermediate in ultrasound-based cases (~ 11%), but dropped significantly in the advanced maternal age (AMA; 4.2%) and serum screening (~ 5-6%) groups. Conversely, VOUS rates remained remarkably stable across all referral categories. Sub-analysis of ultrasound abnormalities revealed that multisystem anomalies conferred the highest risk (27.3%), driven predominantly by aneuploidies; among soft markers, increased nuchal translucency (NT) emerged as the strongest predictor of chromosomal pathology. CONCLUSIONS: In our cohort, SNP-array identified clinically actionable findings in 10.9% of cases. NIPT enriched diagnostic yields, particularly for aneuploidies, and NT thickness was strongly associated with pathogenic findings. These results support an indication-based approach to genomic testing, with NIPT as a triage tool for aneuploidy and CMA for high-risk populations, while improving VOUS counseling.

Humans↗

PubMed2026

Exploring birth options after three or four cesarean sections in Poland: maternal and neonatal outcomes following vaginal vs repeat surgical deliveries.

OBJECTIVES: The study aimed to analyze maternal and neonatal outcomes of women with a history of three or four caesarean sections (CS) and to evaluate the feasibility and safety of vaginal birth after multiple caesarean sections (VBAC ≥ 3) in Polish clinical practice. MATERIAL AND METHODS: A retrospective analysis was conducted on medical records of 186 women with three or four prior CS who delivered at St. Sophia Specialist Hospital in Warsaw between 2017 and 2024. Data on delivery mode, obstetric management, complications, and neonatal outcomes were assessed. Multivariate logistic regression was applied to identify factors associated with successful VBAC. RESULTS: Of the study group, 62 women attempted trial of labour after caesarean (TOLAC), resulting in 32 successful vaginal births (success rate 53.2%). 124 women chose Elective CS. Logistic regression showed that prior vaginal birth (OR = 20.34; p = 0.008) and the use of epidural anaesthesia (OR = 22.88; p = 0.006) significantly increased the likelihood of successful VBAC. Spontaneous onset of labour showed a positive but non-significant trend (OR = 2.52; p = 0.230). The model demonstrated a classification accuracy of 77.4% and a good overall fit (Nagelkerke R² = 0.456). Uterine rupture occurred in three cases (4.8%), while no maternal or neonatal deaths were reported. CONCLUSIONS: Vaginal birth after three or more CS may be a viable option for carefully selected women, provided it is offered in tertiary centers with immediate surgical readiness. Key predictors of success include prior vaginal birth and epidural anaesthesia. Further large-scale studies are needed to refine guidelines and inform clinical practice in this high-risk group.

Humans↗

PubMed2026

Perinatal depression, maternal thyroid status and fetus/infant health and development: A systematic review.

BACKGROUND: Thyroid hormones are known to influence both maternal depression and child developmental outcomes, while maternal depression independently affects child outcomes. The potential interaction between thyroid dysfunction and depression in shaping child development remains insufficiently explored. The present study addresses such interplay. METHODS: Following PRISMA 2020 and JBI guidelines, three databases were searched through December 2025 for primary studies on maternal thyroid status, perinatal depression, and child development. Risk of bias (RoB) was assessed using validated tools. Due to clinical and methodological heterogeneity, data were synthesized narratively following SWiM guidelines. RESULTS: Eleven studies were included. Beyond independent risks for preterm birth and behavioral problems, limited evidence supports a synergistic model, while most studies likely reflect the simple co-occurrence of risks. Maternal thyroid peroxidase antibodies (TPO-Ab) were associated with child externalizing problems exclusively in the presence of clinical depression. High depressive symptoms also attenuated the cognitive benefits of prenatal iodine supplementation. Thyroid status appears to function as a risk moderator rather than a mediator. However, 50% of observational studies presented high RoB, primarily due to participant attrition. CONCLUSION: Findings are still scarce to support a synergistic risk model where specific maternal thyroid parameters (i.e. thyroid autoimmunity and iodine status) may moderate the impact of depressive symptoms on child development. Despite the high RoB in half of the studies, results highlight the need for integrated screening protocols. Simultaneously assessing mental health and thyroid status may optimize risk stratification for high-risk mother-infant dyads.

Female↗

PubMed2026

Long-Term Cardiovascular Impact of Postpartum Treatment After Hypertensive Disorders of Pregnancy: Population-Based Cohort Study.

OBJECTIVE: To assess whether early antihypertensive treatment after Hypertensive Disorders of Pregnancy (HDP) influences subsequent development of cardiovascular complications. DESIGN AND SETTING: Population-based nationwide cohort of health data set in France. POPULATION: 108 906 women with HDP (excluding pre-existing Chronic Hypertension (CH)) who delivered between 2010 and 2014, with 35 878 (33%) receiving at least one antihypertensive treatment in the month after giving birth. METHODS: Traditional Cox model, estimated 10-year cardiovascular risk. Extended Cox Step Function model and Restricted Mean Survival Time evaluated time trends. MAIN OUTCOME MEASURES: New-onset CH, heart failure, coronary, cerebrovascular, peripheral artery diseases and 2 composite events (one including CH, the other excluding it) over 10 years following giving birth. RESULTS: Women receiving early postnatal antihypertensive treatment had a higher long-term risk of complications over 10 years than non-treated women (CH: aHR = 3.067, 95% CI [2.996-3.139]; composite event including CH: aHR = 3.025 [2.956-3.096]; composite event excluding CH: aHR = 1.451 [1.305-1.614]). Treated women had events earlier than non-treated women, presenting a higher risk at the beginning of the postpartum period. The 10-year absolute risk for CH remained high in both groups: 44% for treated women and 18% for non-treated women. CONCLUSION: Our study shows that women receiving early postpartum antihypertensive treatment are at higher long-term cardiovascular risk, with 44% of them having CH within 10 years. Besides, approximately 1 in 5 women non-treated in the postpartum period subsequently developed CH, demonstrating that many high-risk women are not being identified in the peripartum period and may be missing opportunities for timely intervention.

Humans↗

PubMed2025

Comprehensive chromosomal abnormality detection: integrating CNV-Seq with traditional karyotyping in prenatal diagnostics.

BACKGROUND: This study aimed to evaluate the efficacy of copy number variation sequencing (CNV-Seq) in detecting chromosomal abnormalities in prenatal diagnosis, comparing its performance with traditional karyotype analysis. METHODS: A retrospective analysis was conducted on 1001 prenatal samples collected between April 2021 and December 2023. Samples were analyzed using both CNV-Seq and karyotype analysis. The detection rates of chromosomal abnormalities were compared between the two methods across various prenatal diagnostic indications. Clinical follow-up was performed to assess pregnancy outcomes. RESULTS: CNV-Seq detected chromosomal abnormalities in 89 of 1,001 cases (8.9%), compared to 50 cases (5.0%) identified by traditional karyotyping. CNV-Seq not only detected all abnormalities identified by karyotyping, including common aneuploidies such as trisomy 21 and sex chromosome abnormalities, but also uncovered 53 additional pathogenic submicroscopic CNVs associated with 33 known syndromes. The detection rates of CNV-Seq were significantly higher in high-risk groups, such as those identified by non-invasive prenatal testing (HR-NIPT) and maternal serum screening (HR-MSS), demonstrating superior sensitivity and accuracy in prenatal diagnostics. CONCLUSION: CNV-Seq demonstrated superior sensitivity in detecting chromosomal abnormalities, particularly submicroscopic alterations, compared to traditional karyotyping. The study highlights the potential of CNV-Seq as a valuable tool in prenatal diagnostics, offering improved detection of genetic abnormalities and guiding clinical decision-making. However, a combined approach using both CNV-Seq and karyotype analysis is recommended for comprehensive prenatal genetic screening.

Humans↗

PubMed2026

Respiratory-onset peripartum cardiomyopathy: a systematic review of diagnostic pitfalls and clinical outcomes.

INTRODUCTION: Peripartum cardiomyopathy (PPCM) may initially present with prominent respiratory symptoms that resemble primary pulmonary disease, particularly in late pregnancy and the early postpartum period. In clinical practice, this presentation often triggers alternative diagnostic pathways, introducing delay at a time when rapid cardiac assessment is critical. Although respiratory-dominant presentations are repeatedly described across case-based and observational reports, they have not been systematically examined as a distinct diagnostic pathway within the PPCM literature. CONTENT: This PRISMA-guided systematic review synthesized evidence relating to respiratory-onset presentations of PPCM. Major databases and registers were searched comprehensively. Following screening of 589 records and full-text assessment of 145 reports, 49 studies met inclusion criteria. Twenty studies were qualitatively prioritized for narrative synthesis using ROBIS-informed methodological appraisal. Evidence was examined across diagnostic misclassification patterns, cardiopulmonary mechanisms, differential diagnoses, investigative strategies, and acute and longitudinal management considerations. SUMMARY: Respiratory-led presentations were commonly misattributed to asthma, pneumonia, pulmonary embolism, or perioperative causes, with diagnostic delay frequently reported. Across heterogeneous study designs, cardiogenic pulmonary edema with left-ventricular systolic dysfunction emerged as a recurring unifying mechanism. Early use of echocardiography, natriuretic peptides, and targeted imaging consistently aided differentiation from primary respiratory pathology. Severe clinical deterioration was often described in the context of delayed recognition. OUTLOOK: Respiratory-onset PPCM represents a high-risk diagnostic pathway rather than a discrete disease entity. Prospective registries, standardized diagnostic algorithms, and closer integration of obstetric and cardiopulmonary care are needed to refine early recognition and improve maternal outcomes.

Humans↗

PubMed2026

Temporal Trends and Spatial Variation in Preterm Prelabour Rupture of Membranes: A Population-Based Study.

OBJECTIVE: To describe the temporal trends in Preterm prelabour rupture of membranes (PPROM) in metropolitan France and the geographical distribution at the administrative division level. DESIGN: Exploratory population-based study using administrative data of the French National Health Data System. SETTING: Metropolitan France, 2015 to 2023. POPULATION: Pregnancy with a diagnosis of PROM before 37 SA. METHODS: Annual crude incidence of PPROM was calculated by dividing the number of pregnancies with PPROM diagnosis by the number of live births recorded during the same period. Annual trend was estimated by a binomial negative mixed model. Smoothed standardised incidence ratios were estimated based on a BYM2 model, which accounts for spatial variability between departments. MAIN OUTCOME: PPROM cases, defined as pregnancies with first hospitalizations with a diagnosis of PROM before 37 weeks. RESULTS: Over the study period, we included 150 615 PPROM cases representing 16 735 (±596) per year. Incidence of PPROM cases showed an ascending trend over time (incidence rate ratio 1.023 per year; 95% CI: 1.017-1.030) with an annual crude incidence ranging from 2.2% in 2015 to 2.7% in 2023. A decrease in the incidence was observed in 2020 relative to other years (incidence rate ratio 0.903, 95% CI: 0.887-0.920). A map of smoothed SIRs of PPROM cases at the French administrative division level revealed geographical inequalities. CONCLUSIONS: This first population-based study describing PPROM cases in metropolitan France paves the way for further studies to explore environmental hypotheses. Identifying temporal and geographical disparities in PPROM incidence is relevant to public health policy and practice as such disparities argue for the development of targeted prevention strategies in high-risk areas.

French national health data system↗

PubMed2025

Worldwide prevalence of haemorrhoids: a systematic review and meta-analysis.

BACKGROUND: Haemorrhoidal disease (HD) is one of the most common anorectal disorders globally, significantly impacting individuals' quality of life and productivity. Despite its importance, global prevalence remains unclear due to limited population-specific studies. This study aimed to systematically assess the global prevalence of HD through a systematic review and meta-analysis. METHODS: We conducted a systematic review and meta-analysis by searching PubMed, Scopus, Embase, Web of Science, and Google Scholar up to March 31, 2025, without language restrictions. Studies reporting prevalence of haemorrhoids in general, clinical, or high-risk populations were included. Exclusion criteria comprised studies lacking total sample size, focusing on other anorectal conditions, or using duplicate or insufficient data. Four independent reviewers extracted and appraised study quality using the Joanna Briggs Institute tool. The primary outcome was pooled point prevalence of HD, analyzed using a random-effects model with 95% confidence intervals (CIs). The study was registered in PROSPERO (CRD420251045600). RESULTS: From 6,312 records, 150 studies (210 datasets) comprising 8,960,338 individuals were included. The global pooled point prevalence was 25.92% (95% CI: 22.62-29.22). Lifetime prevalence was 27.19% (95% CI: 14.77-39.60), and one-year prevalence was 21.65% (95% CI: 14.33-28.97). Prevalence was higher in women (27.33%, 95% CI: 21.84-32.82) than in men, and highest in the African region 28.07% (95% CI: 15.34-40.79). Invasive diagnostic methods (28.05%, 95% CI: 23.86-32.26) yielded higher prevalence estimates than non-invasive methods. Also, factors showing associations with HD in unadjusted analyses include older age, obesity, pregnancy, diabetes, family history, constipation, and hypertension. CONCLUSION: HD remains a prevalent condition globally, with minor variation across regions. The burden is consistent regardless of socioeconomic context. Diagnostic method and population characteristics influence prevalence estimates. These findings underscore the importance of targeted prevention and early intervention strategies, especially for at-risk groups.

Humans↗

PubMed2026

Clinical Application of Long-Read Sequencing for FMR1 Gene Mutation Detection in Populations From Shandong, China.

BACKGROUND: Fragile X syndrome (FXS) is a common inherited intellectual disability. In this study, long-read sequencing was used for the FMR1 gene detection. METHODS: Men with familial inherited intellectual disability and women with indications for FXS screening were defined as high-risk populations and were included in this study along with non-high-risk reproductive-aged women. PCR-capillary electrophoresis was used for preliminary screening of non-high-risk reproductive-aged women, and long-read sequencing was performed on abnormal samples and samples from high-risk populations. Prenatal diagnosis using long-read sequencing was performed for pregnant women in need. RESULTS: The prevalence of mutation in high-risk females was 3.10% (7/226). 3 mutations were detected in male samples, with a mutation ratio of approximately 8.3% (3/36). The three most common CGG repeats were 29, 30, and 36, respectively. Analysis of AGG interruption pattern in 242 samples identified 908 AGG interruptions, involving 67 different patterns. The most frequent AGG interruption pattern was (CGG)9AGG(CGG)9AGG(CGG)9. Furthermore, long-read sequencing was successfully applied for prenatal diagnosis in two pregnant women, and dynamic mutation of CGG repeat was detected within one family. CONCLUSION: Long-read sequencing-based assay cannot only accurately detect CGG repeat and AGG interruption, but also simultaneously identify other abnormalities of the FMR1 gene. Long-read sequencing offers a broader detection scope and better characterization of FXS-related genetic features.

Humans↗

PubMed2026

Obtaining a Diagnostic Yield via Scan findings prior to the introduction of SEquencing retrospectivelY (ODYSSEY): a cohort study.

OBJECTIVE: To determine the retrospective yield of prenatal exome sequencing (PES) by establishing the proportion of children with a postnatal monogenic diagnosis that could have been diagnosed prenatally if PES had been available. METHODS: The study cohort comprised a sample of children in Northern Ireland, born between January 2010 and January 2018 (predating routine availability of PES), who received a monogenic diagnosis postnatally via next generation sequencing as part of either of two UK-wide studies (the 100 000 Genomes Project (2015-2018) or the Deciphering Developmental Disorders study (2011-2015)). Clinical data were collected retrospectively and correlated with the current UK National Health Service PES protocol, including the phenotypic eligibility criteria for PES and the associated fetal anomalies gene panel. Cases were considered retrospective diagnoses if the fetal phenotype would have been eligible for PES and the diagnostic gene was included on the test panel, meaning prenatal diagnosis in this current era could have been feasible. RESULTS: Of 101 children, 17.8% (95% CI, 10.3-25.3%) had both an eligible fetal structural anomaly (FSA) (i.e. high-risk FSA) and a diagnostic gene on the associated test panel, meaning that they could have been diagnosed prenatally in the current clinical landscape. The median length of the diagnostic odyssey for this subgroup of children was 3.7 years (1354 (range, 822-2450) days). Moreover, 58.4% (n = 59) of cases had no anomalies detected prenatally and 19.8% (n = 20) had a FSA that would not meet the eligibility criteria for PES (low-risk FSA). Although these cases would have been ineligible for PES under the current clinical pathway, 89.9% (n = 71/79) were affected by severe or profound syndromes. Postnatally, the most common functional anomalies were neurodevelopmental delay/intellectual disability and/or behavioral abnormality, which were observed in 80.2% (n = 81) of the included children. However, 80.2% (n = 65/81) of these affected children did not present with fetal anomalies eligible for PES. CONCLUSIONS: Almost one-fifth of children with a monogenic condition included in this study could have received a diagnosis via modern PES, avoiding a diagnostic odyssey lasting almost 4 years. However, despite having a monogenic condition, over half of the children did not present with any structural anomalies in utero. This demonstrates the degree to which fetal imaging is limited in its ability to reassure parents of the absence of a fetal genetic syndrome. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Humans↗

PubMed2025

Multiple Psychiatric Traits Enriched for Brain Tissues in the Early Postpartum Period.

BACKGROUND: The perinatal period is a high-risk time for onset of various psychiatric disorders. However, it is unclear how genetic risk factors for these disorders interact with biological changes associated with pregnancy and postpartum. This study evaluates whether psychiatric genome-wide association study (GWAS) results are enriched within various brain regions across the perinatal period. METHODS: Tissue-specific enrichment analyses were conducted to estimate the potential impact of GWAS loci on transcriptional changes in the brain across the perinatal period. GWAS summary statistics were obtained for 26 psychiatric phenotypes. RNA-sequencing data was acquired from four brain regions (hypothalamus, hippocampus, cerebellum, and neocortex) in mice at six timepoints (virgin, 14- and 16-days post-conception, and 1-, 3- and 10-days postpartum). RESULTS: Hippocampus and neocortex in the early postpartum period are significantly enriched (q-value < 0.05) for genetic variants associated with schizophrenia (SCZ), bipolar disorder (BD), depressive symptoms, and major depressive disorder with suicidal features. The most significant enrichment occurred in the neocortex for SCZ and BD, peaking at postpartum day 1 (SCZ p-value = 3.85 × 10-8; BD p-value = 6.65 × 10-5). In the hippocampus, BD and SCZ were enriched at postpartum day 1 (SCZ p-value = 3.27 × 10-3; BD p-value = 4.33 × 10-3). No enrichment was observed in cerebellum or hypothalamus for any of the psychiatric traits tested. CONCLUSIONS: The results accord with previous epidemiological studies and provide context in which to interpret GWAS results. Understanding the burden of genetic variants across the perinatal period may help prioritise pathways underlying onset of psychiatric disorders outside of pregnancy and postpartum periods.

Journal Article↗