Placental cytogenetic testing for confined placental mosaicism and obstetric outcomes after discordant cell-free DNA screening results.

ObjectiveInvestigating the association between maternal age, anti-Müllerian hormone (AMH) levels, and chromosomal abnormalities in early missed abortion (EMA) embryos, providing evidence for clinical risk stratification and intervention strategies.MethodsA retrospective cohort study was conducted, including 990 EMA diagnosed patients between June 2020 and December 2024. All patients underwent chorionic villus copy number variant sequencing (CNV-seq) after curettage. The study groups were defined as follows based on two criteria: (1) maternal age at miscarriage: <35, 35–39, and ≥ 40 years; and (2) serum AMH level within one year of enrollment: <1.1, 1.1–4.5, and ≥ 4.5ng/mL. Chromosomal abnormality detection rates and types were compared across groups.ResultsOverall, chromosomal abnormalities were detected in 58.59% (580/990) of embryos, predominantly Numerical Chromosomal Abnormalities (88.62%), with trisomies of autosomes being the most common (67.24%), especially trisomy 22 (19.48%) and trisomy 16 (14.14%). Detection rates increased significantly with maternal age (< 35: 54.52%, 386/708; 35–39: 66.99%, 140/209; ≥40: 73.97%, 54/73; p < 0.05). The proportion of autosomal trisomies rose with age, while 45,X, polyploidy, and Copy number variants (CNVs) decreased. Similarly, lower AMH levels were associated with higher chromosomal abnormality rates (≥ 4.5 ng/mL: 50.16%, 158/315; 1.1–4.5 ng/mL: 60.92%, 232/381; <1.1 ng/mL: 69.23%, 90/130; p < 0.05). The rate of autosomal trisomy and double trisomy/polysomy increased with declining AMH (p < 0.05). After stratifying by age to control for its confounding effect, a significant inverse association between AMH level and abnormality rate was observed only in the < 35 years subgroup (134/47.69%; 216/57.45%; 36/70.59%; p < 0.05), but not in the ≥ 35 years subgroup (24/70.59%; 116/68.64%; 54/68.35%; p > 0.05). Logistic regression indicated maternal age (OR = 1.039, 95% CI: 1.019–1.059) and AMH (OR = 0.931, 95% CI: 0.902–0.960) were independent predictors of chromosomal abnormalities.ConclusionIncreased maternal age and decreased AMH levels are closely associated with higher risk of chromosomal abnormalities in EMA embryos. As a sensitive indicator of ovarian reserve, AMH reflects oocyte quality and chromosomal stability, particularly in younger women. Combined assessment of maternal age and AMH may improve risk evaluation and inform preventive and intervention strategies for EMA.

BackgroundDown Syndrome (DS) individuals develop Alzheimer's Disease (AD) neuropathology by the age of 40 due to the triplication of Chromosome 21 and the amyloid precursor protein gene. This genetic alteration leads to an overproduction of Aß, resulting in amyloid accumulation. However, triplication of other Chr21 genes may be involved in AD pathogenesis in DS, and affect amyloid processing and alter subspecies production. This study compares plasma Aß subspecies using mass spectrometry (MS) in DS, sAD and PS1 mutations.MethodPlasma from adults with DS who were cognitively stable (CS‐DS; n = 46; mean age 33.5), cognitive stable older adults from the general population (CS; n = 42; mean age 71.7), DS deemed prodromal or with AD (DS pAD/AD; n = 25; mean age 53.5), early onset sporadic pAD/AD (n = 27; mean age 63.9) and with presenilin 1 mutations (n = 6; mean age 50.5) were analysed using IP‐MS for Aß 1‐37, 1‐38, 1‐40, and 1‐42. In those with DS, Simoa assays for Aß 40 and 42, neurofilament light (Nfl), glial fibrillary protein (GFAP, pTau181 and pTau231 were also obtained, and an Event‐Based Model (EBM) was used to determine the sequence of changes associated with AD.ResultDS individuals had consistently higher levels of Aß1‐37, 1‐38, 1‐40, and 1‐42 compared to CS general population adults, sporadic pAD/AD, and those with PS1 mutations. DS pAD/ AD had increased Aß ratios for 1‐ 40/1‐37 and 1‐37/ 1‐38 compared to sporadic pAD/AD, but similar ratios when compared to those with PS1 mutations. Age‐related patterns of changes in Aβ1‐37 and 1‐38 subspecies in DS pAD/AD differed compared to sporadic pAD/AD, but changes in Aβ 1‐40 and 1‐42 levels were similar. APOE ε4 was associated with Ab 1‐37 levels in DS. Changes Aβ1‐42/1‐38, 1‐42/1‐37, and 1‐42/1‐40 were early events followed by changes in NfL, GFAP, pTau 181 and pTau 231.ConclusionAll Aß subspecies are increased in DS compared to sAD, with higher 1‐40/1‐37 ratios and different age associated changes. Measurement of Aβ subspecies with IP‐MS may help to identify early AD in DS. Further work could determine the nature of differences in subspecies compared to sAD.

Data from high-income countries have shown that expanded non-invasive prenatal testing (NIPT) is highly reliable for detecting common autosomal trisomies (CATs), whereas its diagnostic accuracy for rare autosomal trisomies (RATs) remains relatively low. Information on the clinical performance of expanded NIPT in middle- and low-income countries is still limited. The objective of this study was to evaluate the clinical validity and utility of an expanded NIPT for CATs, sex chromosome aneuploidies (SCAs), and RATs following its nationwide clinical implementation. The results of NIPT were retrospectively reviewed. Those with high-risk test results were followed up via phone and/or by reviewing medical records regarding the downstream prenatal diagnosis and the pregnancy outcomes. The NIPT results of 19,714 samples were analyzed. We found screening positive rate of 0.95%; sensitivity at 97.92%, 94.12%, 85.71%, and 90% for T21, T18, T13, and SCAs; and PPV at 87.04%, 69.57%, 50%, and 54.55% for T21, T18, T13, and SCAs respectively. As for RATs, clinical validity included sensitivity at 100% and PPV of 13.3%. Over 95% of the participants with high-risk NIPT results underwent prenatal diagnosis. The majority (86.52%) of those with a confirmed diagnosis chose termination of the pregnancy. This large-scale study of mixed-risk pregnancies revealed that expanded NIPT had a good sensitivity for CATs (specifically for T21 and T18) and RATs; and fair sensitivity for T13 and SCAs. The PPV is acceptable for CATs and SCAs, but poor for RATs. These data indicated that expanded NIPT results strongly influenced pregnancy outcomes in a real-world experience.

BackgroundTrisomy 18 (T18, Edwards syndrome) is a lethal chromosomal disorder characterized by multiple congenital anomalies and high perinatal mortality. Although epigenetic alterations have been described in aneuploidy conditions, their causal role in the pathogenesis of T18 remains unclear. This study aimed to characterize genome-wide DNA methylation changes associated with T18 during early development.Material and methodsGenomic DNA was extracted from chorionic villi of five T18 and five euploid fetuses, as well as from normal maternal blood, at 11–13 weeks of gestation. High-resolution methyl-capture sequencing (MC-seq) was performed to profile DNA methylation at approximately 3.2 million CpG sites. Differentially methylated CpG sites (DMCs) and regions (DMRs) were identified. Functional and disease-association enrichment analyses were conducted using multiple bioinformatics tools.ResultsA global trend of DNA hypermethylation was observed in the chorionic villi of T18 fetuses. A total of 6,510 DMCs were identified, including 4,022 hypermethylated and 2,488 hypomethylated CpG sites. Additionally, 301 DMRs were identified, comprising 233 hypermethylated and 68 hypomethylated regions. Notably, chromosome 18, the disease-causing chromosome, contained the highest number of hypermethylated DMRs. Functional enrichment analysis of the 283 genes, including 301 DMRs, revealed significant involvement in biological processes and disease phenotypes relevant to T18, including nervous system development, anatomical structure morphogenesis, and embryonic morphogenesis (adjusted P < 0.001 for all). Among them, 76 DMRs exhibited completely inverse methylation patterns in maternal blood and were identified as potential epigenetic biomarkers for non-invasive prenatal testing of T18.ConclusionsTo our knowledge, this is the first comprehensive MC-seq-based analysis of T18-specific DNA methylation patterns in first-trimester chorionic villi. These findings suggest that DNA methylation changes may represent downstream consequences of chromosomal imbalance in T18 and provide a foundation for future investigations into its pathophysiology and the development of epigenetic biomarkers for early non-invasive detection.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13148-025-02018-4.

BackgroundEvidence on the diagnostic yield of genome-wide non-invasive prenatal testing (GW-NIPT) is growing, but its comparative clinical and economic impact as a first-tier screening strategy for fetal chromosomal abnormalities remains unassessed. We compared GW-NIPT with targeted NIPT and first-trimester combined testing (FCT), in a Dutch setting where all pregnancies also undergo a routine second-trimester anomaly ultrasound scan (scan), to guide policymakers on optimal prenatal screening approaches.Methods and findingsWe developed a decision-analytic model for a cohort of 175,000 pregnancies, reflecting the Dutch obstetric population. All strategies screened for common trisomies 21 (Down syndrome), 18 (Edwards syndrome), and 13 (Patau syndrome); GW-NIPT additionally considered rare autosomal trisomies and structural aberrations. Model inputs were based on the TRIDENT-2 study data and historical FCT data. Base-case unit costs were €166 (scan), €191 (FCT), and €350 (NIPT). Sensitivity analyses were conducted to account for uncertainties in model parameters and potential country-specific variations. Outcomes included total screening costs, number of fetal chromosomal abnormalities diagnosed, number of invasive procedures, and expected procedure-related euploid fetal losses. We summarized economic results as cost per diagnosed case and incremental cost per additional diagnosis across strategies. GW-NIPT yielded the highest number of diagnoses (545) versus targeted NIPT (514) and FCT (452), and the lowest cost per diagnosed case (€152,785), compared with targeted NIPT (€159,852) and FCT (€170,050). Invasive tests required per diagnosis were lower for GW-NIPT and targeted NIPT (both 6) than for FCT (13), implying a lower risk of procedure-related miscarriage (iatrogenic miscarriage). Sensitivity analyses indicated that test uptake and unit costs strongly influenced outcomes. GW-NIPT remained the most favorable in terms of cost per diagnosis for NIPT prices up to €467. Key limitations include the use of a decision-analytic model without quality-of-life outcomes and the lack of comparisons against explicit cost-effectiveness thresholds. Therefore, the results should be interpreted as relative clinical and economic comparisons rather than cost-effectiveness judgements.ConclusionsAmong the strategies evaluated, first-tier GW-NIPT had the greatest diagnostic yield and the lowest cost per diagnosis, improving detection rates and supporting reproductive autonomy at lower costs. Implementation decisions should also consider local pricing, laboratory capacity, and counseling resources. Future research that links screening outcomes to long-term health consequences (e.g., quality-adjusted life years or life-years), healthcare utilization, costs, and psychosocial outcomes will enable formal cost-effectiveness evaluations and support further refinement of prenatal screening policy.

Down syndrome is characterized by triplication of chromosome 21, leading to early-onset Alzheimer disease pathology, with nearly all individuals with Down syndrome developing amyloid and tau pathology. In the new era of amyloid modifying therapies, it is vital to identify early biomarkers for Alzheimer disease (AD) pathology in Down syndrome. Striatal amyloid may begin to accumulate sooner than cortical amyloid in Down syndrome. Tau phosphorylation at specific sites, including 217, can be quantified in plasma and may represent an important mechanistic step in the development of tau pathology. This study had two aims: 1. To compare the relative age at increase of multiple biomarkers (cortical amyloid, striatal amyloid, plasma pTau217 and summary tau pathology) 2. To test whether plasma pTau217 can identify both the current presence and likely future accumulation of amyloid and tau pathology. To identify optimal biomarkers for early intervention, we examined longitudinal cortical and striatal amyloid PET, plasma pTau217, and tau PET in 328 individuals with Down syndrome enrolled in the Alzheimer Biomarker Consortium - Down Syndrome study. To compare the timing of biomarker changes, we modeled longitudinal biomarkers using generalized additive mixed models relative to age. We used receiver operating characteristic curve analysis to identify thresholds for both current and likely future accumulation of amyloid and tau pathology. For all comparisons, we used age as the null model, performing Delong tests to evaluate the performance of age relative to biomarker-based prediction. Imaging biomarkers increased around 40 years old, with plasma pTau217 increasing somewhat later than the three PET biomarkers. Striatal amyloid increased before cortical amyloid in some participants; however, this was not uniform across individuals. If an individual was classified as a reliable accumulator with one biomarker, he or she was likely to be a reliable accumulator in other biomarkers. Age was as sensitive as plasma pTau217 in its ability to both detect preclinical Alzheimer disease pathology and predict near future accumulation of both amyloid and tau. These results suggest that all adults with Down syndrome should be screened for Alzheimer disease pathology starting shortly before age 40 and considered for clinical trials. Age alone was as effective at detecting both current pathology and likely future accumulation as plasma pTau217. Because this disease is so closely concurrent with age in individuals with Down Syndrome, plasma pTau217 may not provide more diagnostic benefits than age.

Placental mosaicism for structural chromosomal variants: follow-up of 251 Danish cases (1983-2021).

Discordant findings in genome-wide non-invasive prenatal testing (GW-NIPT) for rare chromosomal abnormalities, adverse pregnancy outcomes, and maternal malignancies: a systematic review and meta-analysis.

Introduction: Invasive prenatal diagnostic tests have higher detection rates than screening tests. Cell-free DNA (cfDNA) screening has higher detection than combined testing (CT). We estimated the cost per cytogenetic abnormality diagnosed for prenatal testing and screening methods (US data). Methods: We compared seven strategies: universal diagnosis with microarray and karyotype; cfDNA screening with four methodologies: Digital Analysis of Selected Regions (DANSR), massively parallel shotgun sequencing (MPSS), single-nucleotide polymorphisms (SNPs), and rolling circle amplification (RCA); and CT. Five abnormality groupings were considered: common autosomal trisomies (21,18,13), sex chromosome aneusomies, triploidy, clinically significant sub-chromosome changes, and copy number variants. Prevalence, detection, false-positive rates, and unit costs (literature) were obtained. The detection rate was aggregated across groups as were costs, including diagnostic tests following positive screening results. Results: All six high detection strategies had greater cost per abnormality diagnosed than CT (USD 26,100). The costliest was cfDNA using MPSS (USD 96,100), followed by universal karyotyping (USD 95,900), cfDNA using SNPs, DANSR (USD 94,800–USD 92,800), universal microarray (USD 56,600), and cfDNA with RCA (USD 32,200). The additional cost per extra abnormality diagnosed compared to CT (“marginal” cost) was the lowest for cfDNA with RCA (USD 45,000); others were considerably higher (USD 59,400–USD 160,700). Conclusion: Preferred prenatal strategies vary among stakeholders. However, as monopolies (large systems and Accountable Care Organizations) now control the majority of American healthcare policy decisions, the lowest cost cfDNA screening will likely prevail in actual practice.

Trisomy 18, also known as Edwards syndrome, is the second most common autosomal trisomy. The phenotype includes dysmorphia, congenital malformations and severe neurological impairment. The most common malformation is congenital heart disease. With a median survival of 2 to 14.5 days, trisomy 18 has been historically considered as lethal and care has long been palliative. This approach was proposed to a little girl with postnatal diagnosis. Initially, the child's parents disagreed with the management strategy. After further discussions, the parents agreed on a therapeutic approach based on comfort care. Intensive care is, however, offered in selected patients in other countries. Multiple studies have recently shown that measures such as cardiac repair increase survival. Impact on quality of life remains, however, highly uncertain. The therapeutic orientation for these children remains the subject of ethical dilemma. A multitude of arguments are developed around the four fundamental principles of bioethics: autonomy, beneficence, nonmaleficence, and justice. Not only the choice of care (interventional or palliative) but also the person responsible for this decision are controversial.

ABSTRACTThis case report details the first confirmed diagnosis of Trisomy 13 (Patau syndrome) in Mali using Fluorescence In Situ Hybridization (FISH). The male newborn presented with multiple congenital anomalies, including polydactyly and micrognathia. The diagnosis expands the understanding of Trisomy 13 in Africa, highlighting the importance of genetic testing in resource‐limited settings.

OBJECTIVE The aim of this study was to compare age at diagnosis of common aneuploidies with gestational age (GA) at birth to determine whether prematurity is associated with delayed diagnosis. METHODS We conducted a retrospective cohort study of neonates with Patau syndrome (PS), Edwards syndrome (ES), or Down syndrome (DS) admitted to any Nationwide Children’s Hospital neonatal intensive care unit (NICU) from 2010 to 2021. The exposure of interest was birth GA: less than 34 weeks, 34 to 36 weeks, and 37 weeks or more. Age at diagnosis for PS/ES and DS was compared between GA groups using the Jonckheere-Terpstra rank-based nonparametric test for ordered alternatives. RESULTS Among neonates with PS/ES, the median age (days) at karyotypic diagnosis for preterm, late-preterm, and term/postterm neonates was 3 (IQR, 2–7), 4 (IQR, 3–9), and 3 (IQR, 3–5) days, respectively (trend not significant). Among neonates with DS, the median age (days) at karyotypic diagnosis for preterm, late-preterm, and term/postterm neonates was 6 (IQR, 5–10), 5 (IQR, 3–7), and 4 (IQR, 3–5) days, respectively. The trend of increasing age at diagnosis with increasing prematurity was significant (P &amp;lt; .01). CONCLUSION Increasing prematurity was associated with increasing age at diagnosis of DS but not PS/ES in a large network of level III/IV NICUs.

ABSTRACT Edwards syndrome, also known as trisomy 18, is characterized by aneuploidy, a numerical chromosomal alteration that results in autosomal trisomy of chromosome 18. The vast majority of fetuses with this trisomy result in miscarriage, and its incidence is highest in females. This study aims to analyze the prevalence of Edwards syndrome in Brazil, according to data from the DATASUS system. This descriptive study analyzes data from the Brazilian Unified Health System (DATASUS) information department on live births of Edwards syndrome in Brazil, including the region of prevalence, gestational age, type of pregnancy, and race/color, between 2014 and 2023. The study indicates that the prevalence of live births is very low; the vast majority of cases occur in the south and southeast regions of Brazil, with a predominance of white individuals, cesarean sections, singleton pregnancies, and 32- to 41-week gestation. The text concludes that despite the low survival rate, cases and their characteristics do exist, and that further research is crucial to better understand the factors that influence the syndrome. Keywords: DATASUS. Prevalence. Edwards Syndrome.

SummaryDown syndrome (DS), caused by trisomy 21 (TS21), is the most common genetic cause of intellectual disability1,2. The neurological impacts of DS first manifest during prenatal development through reduced radial glia (RG) neural stem cell proliferation, reduced cortical volume and imbalanced cortical cell types3-6. However, the developmental mechanisms underlying altered cortical neurogenesis in DS remain elusive. Here we show by high-throughput lineage tracing in organotypic culture that TS21 accelerates RG lineage progression, driving premature production of cortical inhibitory neurons (INs) and oligodendrocytes. Somatic lineage coupling connects dysregulated neurogenic tempo to altered cellular composition in the adult DS brain. Finally, lineage-resolved differential expression reveals elevated interferon responses specifically in RG biased to producing INs. Together, our findings link TS21 genomic abnormalities to candidate molecular pathways and developmental mechanisms altering the cellular landscape in DS with therapeutic relevance.

Trisomy 13, the third most common autosomal trisomy after trisomy 21 and trisomy 18, is associated with a significantly high infant mortality rate. However, large-scale studies examining causes of death in trisomy 13 remain scarce. Therefore, we aimed to better understand the mortality patterns. To this end, a population-based study was conducted using Japanese population-based mortality data from the Vital Statistics Database (n = 4,230,092 death records); we examined early mortality and identified phenotypic subgroups based on combinations of co-occurring causes of death. We identified 150 individuals with trisomy 13 who died between 2019 and 2021. Cardiovascular disease was significantly associated with early mortality. Using K-means clustering based on principal components of cause-of-death categories, we identified three distinct subgroups: respiratory-dominant (19%), cardiovascular-dominant (64%), and multi-organ involvement (17%). The cardiovascular-dominant cluster showed the highest rate of death before age 1 (83%; p = 0.001), while surgical intervention rates did not significantly differ across clusters. These findings highlight phenotypic heterogeneity and may support individualized care planning for trisomy 13 and provide insights that may support future care and decision-making.

Rationale:Trisomy 18, often known as Edwards syndrome. It is a common chromosomal disorder characterized by the presence of an extra chromosome 18. Unfortunately, survival past the first year is quite rare, and there are only a few reports of individuals living long-term without needing corrective surgery. This case sheds light on an unusual situation where a patient survived for an extended period despite having severe congenital heart defects.Patient concerns:A 5-year-old girl, already diagnosed with trisomy 18, was admitted to the hospital after experiencing a cough and diarrhea that started after she began taking a nutritional powder supplement. The patient had a history of admission to neonatal intensive care for 1 month due to transient tachypnea of the newborn, mild retractions, and grunting. Additionally, she had intrauterine growth restrictions, dysmorphic features, and hypotonia.Diagnoses:Clinical examination revealed dysmorphic features, hypoxia, and a cardiac murmur. Chest radiography reveals central infiltration with cardiothoracic ratio 60%. Genetic testing confirmed the presence of trisomy 18, and an echocardiogram showed multiple congenital defects with significant right ventricular hypertrophy.Interventions:Initial management began with administering oxygen, performing metabolic tests, and a chest x-ray. However, because of ongoing low oxygen levels linked to her heart defects and pulmonary hypertension, long-term home oxygen therapy was initiated. A comprehensive supportive care with multidisciplinary team support was the main management.Outcomes:Throughout her treatment, oxygen saturation did not exceed 85%, and the patient’s development has remained severely delayed, with no significant motor or cognitive milestones. The patient had a long life expectancy for her complex heart defects, but eventually died of cardiac arrest.Lessons:This case shows the possibility of prolonged survival in trisomy 18, even with severe congenital heart defects, emphasizing the importance of multidisciplinary management and family-centered counseling. Documenting such cases expands understanding of this syndrome and guides long-term care strategies.

IntroductionDelayed perinatal grief occurs when the grieving process for a lost baby is reactivated after the birth of a healthy child. This case presents a 39-year-old mother who, after losing her first baby at 36 weeks due to Patau syndrome, experienced delayed grief following the birth of a full-term baby two years later. Despite receiving one psychological consultation at the time of the loss, the lack of follow-up contributed to the reactivation of her grief postpartum, presenting with sadness and anxiety.ObjectivesTo describe the process of delayed perinatal grief in a mother who lost a baby due to Patau syndrome.To evaluate the psychological impact of the lack of follow-up after the loss on the subsequent development of reactivated grief.To propose therapeutic interventions for the management of mothers experiencing delayed perinatal grief.MethodsWe present the case of a 39-year-old mother who lost a baby at 36 weeks of gestation due to Patau syndrome. Following the loss, she received a single psychological consultation with no further follow-up. Two years later, she gave birth to a healthy baby at 40 weeks, and six weeks after delivery, she was referred to psychiatry due to symptoms of profound sadness and anxiety, consistent with delayed perinatal grief. The patient was evaluated by the psychiatry team and began treatment with psychological intervention and pharmacological management when necessary.ResultsThe psychiatric intervention led to a gradual improvement in symptoms of sadness and anxiety. The patient responded favorably to psychological treatment, incorporating cognitive-behavioral therapy techniques to manage grief. However, feelings of sadness persisted on dates related to the previous loss. Ongoing emotional support was crucial for the recovery process.ConclusionsDelayed perinatal grief can reactivate after the birth of a new child, especially in cases where the original loss was not adequately followed up. Proper psychological support is essential to help mothers process their grief and prevent long-term emotional complications.Disclosure of InterestNone Declared

Background: Amniocentesis (AC) remains the most commonly performed prenatal invasive diagnostic test. The data available till now have been collected before the era of high-end ultrasound machines, NIPS, and chromosomal microarrays. In selected cases, whole-exome sequencing is also offered prenatally. The evolution of ultrasound, NIPS, and genetic testing has made us revisit this topic.Objective: We aimed to research and revisit AC data regarding the indications, procedures, genetic testing methods, and outcomes. We reinforce the knowledge of AC, offer tips to minimize complications, and help communicate and counsel patients based on the AC data.Methods: It was a retrospective study from October 2019 to March 2023 in a tertiary care fetal medicine center in a university hospital. A total of 321 patients who underwent AC were analyzed. We observed the demographic details, indications, procedure details, and maternal–fetal and neonatal outcomes.Results: During the study period, 321 patients underwent AC. Abnormal ultrasound findings (71%) were the most common indication for AC. Then, 9% (30/321) had abnormal genetic results. Down syndrome was the most common abnormality (14), followed by Edwards syndrome. Then, 47.96% of cases were in age > 35 years. We had three cases of bloody tap, one leak per vagina, and two missed abortions following AC. Then, 58% had live births.Conclusion: AC is a relatively safe procedure, and even with the advent of NIPS, it remains the gold standard prenatal diagnostic genetic testing method. Major structural anomalies and parental chromosomal anomalies are irreplaceable indications of AC. The technique and expertise of health professionals dictate the complication rate of that center. Chromosomal microarray, DNA storage, and whole-exome sequencing have added an extended armamentarium to our discovery of genetic diseases. Maternal and neonatal outcomes after AC are favorable, so do not hesitate to carry out this invasive test when indicated.

IntroductionEmbryonic chromosomal abnormalities are the major cause of miscarriage. As a relatively novel genetic screening technology, high-throughput ligation-dependent probe amplification combined with short tandem repeat analysis (HLPA + STR) demonstrates significant clinical advantages, including shorter turnaround time, user-friendly technical workflows, and superior cost-effectiveness. The purpose of this study is to evaluate the frequency and characteristics of fetal chromosomal abnormalities using HLPA + STR in early pregnancy loss (EPL).MethodsA retrospective analysis was conducted on women who experienced EPL and underwent HLPA + STR. Group differences were compared using χ2 or Fisher’s exact test, and multivariate logistic regression analysis was performed to examine the correlation between the fetal cytogenetic results and maternal age, gestational age, and history of miscarriage.ResultsIn total, 820 (61.75%) cases were detected to be chromosomal abnormalities, including 748 (91.22%) had numerical abnormalities, 59 (7.19%) had structural abnormalities, and 13 (1.59%) had chromosome mosaicism. The most frequent chromosomal abnormality was autosomal trisomy, of which trisomy (T) 16 was the most common, followed by sex chromosome monosomy and triploid. The incidence of fetal chromosomal abnormalities was significantly higher advanced maternal age (AMA) than in non-advanced maternal age (non-AMA) (p < 0.001). The AMA had a 1.93 times higher risk of fetal chromosomal abnormalities compared to the non-AMA (odds ratio [OR], 1.93; 95% confidence interval [95% CI], 1.39–2.68; p < 0.001). The risk of fetal chromosomal abnormalities in fetuses with a gestational age > 8 weeks was found to be 1.34 times higher compared to those with a gestational age ≤ 8 weeks (OR, 1.34; 95% CI, 1.07–1.69; p = 0.012). No statistically significant variation in fetal chromosomal abnormalities was observed in the history of miscarriage (p > 0.05).ConclusionIn conclusion, our results show that HLPA + STR is an effective strategy for cytogenetic analysis of EPL. In addition, Multivariate analysis identified advanced maternal age and gestational age are independent risk factors for fetal cytogenetic results in EPL, but not related to the history of miscarriage. Therefore, we recommend HLPA + STR as the first-tier screening tool for genetic evaluation in EPL. However, the results of complex abnormalities need to be combined with other techniques.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13039-025-00724-5.