Inconsistencies between prenatal diagnostic and genetic testing laboratories on variant validation of rare monogenic diseases.

BACKGROUND: The advent of next-generation sequencing (NGS) has enhanced the diagnostic efficacy for monogenic diseases, while presenting challenges in achieving consistent diagnoses. METHOD: We retrospectively analyzed the concordance rate and reasons for the inconsistency between the original diagnostic result from the genetic testing laboratory and the variant validation result from the prenatal diagnostic center. The validation procedure comprised three stages: validation of variant detection, reevaluation of variant classification, and assessment of recurrence risk, which involved verifying the mode of inheritance and parental carriage. RESULT: In total, 17 (6%) of the 286 families affected by rare monogenic diseases showed different results during the variant validation procedure. These cases comprised four (23.5%) with variant detection errors, 12 (70.5%) with inconsistent interpretation, and one (6%) with non-Mendelian inheritance patterns. False-positive NGS results confirmed by Sanger sequencing were related to pseudogenes and GC-rich regions. The classification of the 17 variants was altered in the 12 cases owing to various factors. The case with an atypical inheritance pattern was originally considered autosomal recessive inheritance, but was diagnosed as maternal uniparental disomy after additional genetic analysis. CONCLUSION: We underscored the significance of variant validation by prenatal diagnostic centers. Families affected by monogenic diseases with reproductive plans should be referred to prenatal genetic centers as early as possible to avoid different results that may postpone subsequent prenatal diagnosis.

Development and validation of a prenatal predictive nomogram for the risk of NICU admission in infants born to Chinese mothers over 35 years of age: a retrospective cohort study.

BACKGROUND: The rising number of women giving birth at advanced maternal age has posed significant challenges in obstetric care in recent years, resulting in increased incidence of neonatal transfer to the Neonatal Intensive Care Unit (NICU). Therefore, identifying fetuses requiring NICU transfer before delivery is essential for guiding targeted preventive measures. OBJECTIVE: This study aims to construct and validate a nomogram for predicting the prenatal risk of NICU admission in neonates born to mothers over 35 years of age. STUDY DESIGN: Clinical data of 4218 mothers aged ≥ 35 years who gave birth at the Department of Obstetrics of the Second Hospital of Shandong University between January 1, 2017 and December 31, 2021 were reviewed. Independent predictors were identified by multivariable logistic regression, and a predictive nomogram was subsequently constructed for the risk of neonatal NICU admission. RESULTS: Multivariate logistic regression demonstrated that the method of prenatal screening, number of implanted embryos, preterm premature rupture of the membranes, preeclampsia, HELLP syndrome, fetal distress, premature birth, and cause of preterm birth are independent predictors of neonatal NICU admission. Analysis of the nomogram decision curve based on these 8 independent predictors showed that the prediction model has good net benefit and clinical utility. CONCLUSION: The nomogram demonstrates favorable performance in predicting the risk of neonatal NICU transfer after delivery by mothers older than 35 years. The model serves as an accurate and effective tool for clinicians to predict NICU admission in a timely manner.

Very elevated hCGß (≥10 multiple of the median) in maternal marker screening for Down syndrome: Frequency, etiologies, outcomes, and guidelines.

AIM: This aim of this study was to detail maternal and fetal anomalies observed on a national scale in a large French cohort of patients presenting high hCG values (≥10 multiple of the median [MoM]) at Down syndrome screening in order to define clear and optimal guidelines. METHODS: This is a retrospective multicenter study based on a French annual database of all trisomy 21 screenings. Our study targeted and studied cases with hCG or hCGß values ≥10 MoM. Complementary exams and outcomes were analyzed. RESULTS: The calculated frequency was 0.05% for hCGß ≥10 MoM in unselected patients. For this series of 289 cases, a complication of the pregnancy or a poor outcome was observed in 145 cases (51%) as follows: 96 (66%) cases of fetal disease, 23 (16%) of maternal disease, 5 (3.5%) of placental anomalies and 21 (14.5%) of systemic disease concerning mother, fetus and placenta. CONCLUSION: This study establishes the frequency of hCG or hCGß values ≥10 MoM, presents a flow chart that optimizes follow-up, and gives clear information for patients presenting with such abnormal values at trisomy 21 screening.

Exploring the clinical utility of exome sequencing/Mono, Duo, Trio in prenatal testing: a retrospective study in a tertiary care centre in South India.

OBJECTIVES: With the availability of Next Generation Sequencing (NGS) diagnosis of genetic disorders has improved significantly. Its use is also applicable to ascertain diagnosis and management in a perinatal setting. The study aims to detect the genetic aetiology of various congenital structural and functional defects using NGS technology in the reproductive cohort at a tertiary centre. The secondary objective is to address challenges in the interpretation of variants. METHODS: This was a retrospective study of couples who underwent exome sequencing (Mono-testing proband only or Duo-testing parents only or Trio-testing proband and parents) for suspected single gene disorders between years 2020-2022 at a tertiary care perinatal center in the South India. American College of Medical Genetics (ACMG) guidelines were followed to classify the pathogenicity of the variants identified by exome sequencing. RESULTS: The overall diagnostic yield as defined by pathogenic/likely pathogenic variants obtained was (23/43) 53.4 %. The individual subsets have the following diagnostic yield viz., Mono 5/6 (83 %); Carrier 16/32 (50 %); Trio 2/5 (40 %). Diagnostic yield was significantly higher in consanguineous couples. However, miscarriage history, and organ system involvement did not have a significant effect on the diagnostic yield. Prenatal diagnosis was offered for seven patients based on the exome result. One fetus was confirmed with a compound heterozygous pathogenic variant. CONCLUSIONS: Diagnostic yield of exome sequencing in our cohort was 53 %. The detection of pathogenic variants was maximum in those cases undergoing Mono exome sequencing. In places where there is a high prevalence of consanguinity and endogamy, NGS may be offered as first line test in the context of prenatal diagnosis.

Is there an increased risk of genetic abnormalities in fetuses with congenital heart disease in the setting of growth restriction?

OBJECTIVE: To determine if the presence of fetal growth restriction (FGR) is associated with an increased risk of genetic abnormalities in the setting of congenital heart disease (CHD). METHODS: This was a retrospective cohort study involving pregnancies that met the following criteria: (i) prenatal diagnosis of CHD, (ii) singleton live-birth, and (iii) genetic testing was performed either pre- or postnatally. Genetic results were reviewed by a clinical geneticist for updated variant classification. Fetal growth was stratified as appropriate for gestational age (AGA) or FGR. RESULTS: Of the total of 445 fetuses that met the study criteria, 325 (73.0%) were AGA and 120 (27.0%) were FGR. Genetic abnormalities were detected in 131 (29.4%) pregnancies. There was a higher rate of genetic abnormalities (36.7% vs. 26.8%, p = 0.04), which was driven by aneuploidies (20.8% vs. 8.9%, p = 0.0006) in the FGR population. Early onset growth restriction was associated with a higher rate of genetic abnormalities (44.5% vs. 25.9%, p = 0.03). The rate of genetic abnormalities was significantly higher in the shunt category as compared to remainder of the cardiac anomalies (62.5% in shunt lesions vs. 24.7%, p < 0.00001). The rates of FGR (40.9% vs. 21.4%, p < 0.0001) and genetic abnormalities (52% vs. 20.4%, p < 0.0001) were significantly higher in the presence of extra-cardiac anomalies (ECA). CONCLUSION: The presence of FGR in fetal CHD population was associated with underlying genetic abnormalities, specifically aneuploidies. Patients should be appropriately counseled regarding the higher likelihood of a genetic condition in the presence of FGR, early onset FGR, shunt lesions and ECA.

Prenatal diagnosis (or lack thereof) of arthrogryposis multiplex congenita and its impact on the perinatal experience of parents: A retrospective survey.

OBJECTIVE: To examine parental experiences during pregnancies affected by Arthrogryposis Multiplex Congenita (AMC) by identifying commonalities, risk factors, and areas for improvement in detection rates, care protocols, and patient experience. STUDY DESIGN: An online survey was distributed via AMC support groups on Facebook. Topics included demographics, risk factors, parental recall of sonographic findings, delivery characteristics and neonatal findings. Responses were divided into antenatally detected cases (ADCs) and postnatally detected cases (PDCs). Quantitative responses were analyzed with the Fisher exact test. Qualitative data were analyzed with thematic analysis. RESULTS: The antenatal detection rate of arthrogryposis was 37%. Decreased fetal movement was reported by 53% and early bleeding by 21%. Sonographic findings in ADCs included clubfoot (83%), clenched hand (51%), decreased fetal movement (50%), elbow contracture (51%), and knee contracture (46%). Among ADCs, 29% delivered vaginally and 71% delivered by cesarean versus PDCs (44% vaginal, 56% cesarean). Neonatal intensive care unit admission rate was 63%. Bone fracture occurred in 9%. Detection led to a planned change in delivery mode in 33% and location in 50%. Among ADCs, 17% felt their concerns were not adequately addressed versus 43% of PDCs. CONCLUSIONS: Antenatal detection of arthrogryposis was low. We propose enhanced screening criteria to aid prenatal diagnosis and promote utilization of more robust practice guidelines.

Numbers of prenatal cell-free DNA screens performed: Results of a 2022 CAP exercise.

OBJECTIVE: Determine current analytical methods and number of cell-free (cf) DNA prenatal screening tests performed for common trisomies. METHODS: The College of American Pathologists 2022-B Noninvasive Prenatal Testing exercise was distributed in December 2022 to 93 participants in 22 countries. Supplemental questions included the number of tests performed in a recent month and the proportion of samples originating outside the United States (US). RESULTS: Eighty-three participants from three continents returned results; 74 (89%) were suitable for the analyses. Nine manufacturer/platform combinations were identified, most commonly Illumina/Nextseq (55%). The most common methodology was whole genome sequencing (76%). Annualized cfDNA tests were 2.80 million, with Asian, European and North American participants representing 10.6%, 6.5% and 82.9% of tests, respectively. When restricted to US in-country tests, the annualized rate was 2.18 million, with four of 20 participants testing 79.2%. Among 73 respondents, 63 (86%) were for-profit, eight (11%) were non-profit academic or government supported and the remaining two included hospital-based and private non-profit. Eighteen (25%) supported relevant academic training. CONCLUSION: In 2011, screening for common trisomies was based on serum/ultrasound markers with an estimated 2.96 million US pregnancies screened in 131 laboratories. In 2022, cfDNA-based screening was offered by 20 laboratories testing 2.18 million US pregnancies.

High positive predictive value 22q11.2 microdeletion screening by prenatal cell-free DNA testing that incorporates fetal fraction amplification.

OBJECTIVE: 22q11.2 deletion syndrome (DS) is a serious condition with a range of features. The small microdeletion causing 22q11.2DS makes it technically challenging to detect using standard prenatal cfDNA screening. Here, we assess 22q11.2 microdeletion clinical performance by a prenatal cfDNA screen that incorporates fetal fraction (FF) amplification. METHODS: The study cohort consisted of patients who received Prequel (Myriad Genetics, Inc.), a prenatal cfDNA screening that incorporates FF amplification, and met additional eligibility criteria. Pregnancy outcomes were obtained via a routine process for continuous quality improvement. Samples with diagnostic testing results were used to calculate positive predictive value (PPV). RESULTS: 379,428 patients met study eligibility criteria, 76 of whom were screen-positive for a de novo 22q11.2 microdeletion. 22 (29.7%) had diagnostic testing results available, and all 22 cases were confirmed as true positives, for a PPV of 100% (95% CI 84.6%-100%). This performance was based on cases that ranged broadly across FF (5.9%-41.1%, mean 23.0%), body mass index (22.3-44.8, mean 29.9), and gestational age at testing (10.0w-34.6w, median 12.7w). Ultrasound findings in screen-positive pregnancies were consistent with those known to be associated with 22q11.2DS. CONCLUSION: 22q11.2 microdeletion screening that incorporates FF amplification demonstrated high PPV across both general and high-risk population cohorts.

Update on Prenatal Detection Rate of Critical Congenital Heart Disease Before and During the COVID-19 Pandemic.

Prenatal diagnosis of critical congenital heart disease (CCHD) has improved over time, and previous studies have identified CCHD subtype and socioeconomic status as factors influencing rates of prenatal diagnosis. Our objective of this single-center study was to compare prenatal diagnosis rates of newborns with CCHD admitted for cardiac intervention from the COVID-19 pandemic period (March 2020 to March 2021) to the pre-pandemic period and identify factors associated with the lack of CCHD prenatal diagnosis. The overall rate of CCHD and rates of the various CCHD diagnoses were calculated and compared with historical data collection periods (2009-2012 and 2013-2016). Compared with the 2009-2012 pre-pandemic period, patients had 2.17 times higher odds of having a prenatal diagnosis of CCHD during the pandemic period controlling for lesion type (aOR = 2.17, 95% CI 1.36-3.48, p = 0.001). Single ventricle lesions (aOR 6.74 [4.64-9.80], p < 0.001) and outflow tract anomalies (aOR 2.20 [1.56-3.12], p < 0.001) had the highest odds of prenatal diagnosis compared with the remaining lesions. Patients with outflow tract anomalies had higher odds for prenatal detection in the pandemic period compared with during the 2009-2012 pre-pandemic period (aOR 2.01 [1.06-3.78], p = 0.031). In conclusion, prenatal detection of CCHD among newborns presenting for cardiac intervention appeared to have improved during the pandemic period.

Eliminating first trimester combined testing: Consequences for early detection of significant fetal anomalies.

OBJECTIVE: To determine whether implementation of cell-free DNA (cfDNA) testing for aneuploidy as a first-tier test and subsequent abolition of first trimester combined testing (FCT) affected the first trimester detection (<14 weeks) of certain fetal anomalies. METHODS: We performed a geographical cohort study in two Fetal Medicine Units between 2011 and 2020, including 705 fetuses with prenatally detected severe brain, abdominal wall and congenital heart defects. Cases were divided into two groups: before (n = 396) and after (n = 309) cfDNA introduction. The primary outcome was the first trimester detection rate (<14 weeks) overall and for non-chromosomal anomalies solely. RESULTS: Overall, gastroschisis, AVSD and HLHS were detected more often in the first trimester in the before group compared to the after group, respectively 54.5% versus 18.5% (p = 0.004), 45.9% versus 26.9% (p = 0.008) and 30% versus 3.4% (p = 0.005). After exclusion of chromosomal anomalies identifiable through cfDNA testing, the detection of AVSD remained higher in the before group (43.3% vs. 9.5%, p = 0.02), leading to a possible earlier gestation at termination. The termination of pregnancy (TOP) rate did not differ among the groups. In the after group, referrals for suspected anomalies following a dating scan between 11 and 14 weeks significantly increased from 17.4% to 29.1% (p < 0.001). CONCLUSION: This study underscores the value of a scan dedicated to fetal anatomy in the first trimester as we observed a decline in the early detection of certain fetal anomalies (detectable in the first trimester) subsequent to the abolition of FCT.

Prevalence and prenatal diagnosis of congenital eye anomalies: A population-based study.

OBJECTIVE: To estimate the prevalence and trend of congenital eye anomalies (CEAs) and the rate of prenatal diagnosis over a 10-year period. DESIGN: Retrospective population-based registry study. SETTING: All maternity units in Paris, France, from 2010 to 2020. POPULATION: A cohort of 115 cases of CEA detected among all live births or stillbirths, after 22 weeks of gestation, and terminations of pregnancy. METHODS: The total prevalence of CEAs and prevalence of each specific CEA were calculated using 95% Poisson exact confidence intervals. MAIN OUTCOME MEASURES: The total prevalence of CEAs and the proportion of prenatal diagnosis of CEAs, and their evolution. RESULTS: The prevalence of CEAs was 4.1 (95% CI 3.4-5.0) cases, ranging between 3.1 and 5.7 cases, per 10 000 births. CEAs were prenatally diagnosed in 23.5% of cases. CEAs were bilateral in 51 cases (44.3%), unilateral in 43 cases (37.4%) and missing or unknown in 21 cases (18.3%). Of those with CEAs, 20.9% had genetic anomalies and 53.0% had at least one other extraocular anomaly. When detected prenatally, CEAs were bilateral in 15 cases (55.6%), unilateral in eight cases (29.6%) and missing in the four remaining cases. The prenatal diagnosis rate of CEAs associated with genetic anomalies, CEA cases with at least one other malformation and isolated CEA cases were 29.2%, 26.2% and 13.3%, respectively. CONCLUSIONS: In total, 115 cases of CEAs were observed during the study period, representing a total prevalence of 4.1 cases per 10 000 births. The overall prenatal detection rate of CEAs in our population was 23.5%, which dropped to 13.3% for isolated cases of CEAs.

The Association of Prenatal Diagnoses with Mortality and Long-Term Morbidity in Children with Specific Isolated Congenital Anomalies: A European Register-Based Cohort Study.

OBJECTIVES: To compare 5-year survival rate and morbidity in children with spina bifida, transposition of great arteries (TGA), congenital diaphragmatic hernia (CDH) or gastroschisis diagnosed prenatally with those diagnosed postnatally. METHODS: Population-based registers' data were linked to hospital and mortality databases. RESULTS: Children whose anomaly was diagnosed prenatally (n = 1088) had a lower mean gestational age than those diagnosed postnatally (n = 1698) ranging from 8 days for CDH to 4 days for TGA. Children with CDH had the highest infant mortality rate with a significant difference (p < 0.001) between those prenatally (359/1,000 births) and postnatally (116/1,000) diagnosed. For all four anomalies, the median length of hospital stay was significantly greater in children with a prenatal diagnosis than those postnatally diagnosed. Children with prenatally diagnosed spina bifida (79% vs 60%; p = 0.002) were more likely to have surgery in the first week of life, with an indication that this also occurred in children with CDH (79% vs 69%; p = 0.06). CONCLUSIONS: Our findings do not show improved outcomes for prenatally diagnosed infants. For conditions where prenatal diagnoses were associated with greater mortality and morbidity, the findings might be attributed to increased detection of more severe anomalies. The increased mortality and morbidity in those diagnosed prenatally may be related to the lower mean gestational age (GA) at birth, leading to insufficient surfactant for respiratory effort. This is especially important for these four groups of children as they have to undergo anaesthesia and surgery shortly after birth. Appropriate prenatal counselling about the time and mode of delivery is needed.

Parental refusal of prenatal screening for aneuploidies.

OBJECTIVES: To analyze the reasons for refusal of aneuploidy screening in a multicultural Middle Eastern population. METHODS: The study included patients delivering in a university hospital, who had refused aneuploidy screening during their pregnancy. We evaluated through a questionnaire submitted during the postpartum period the sociodemographic characteristics, beliefs, attitudes, and the main reason underpinning their choice. Religious, ethical, and financial factors, personal beliefs, medical information, perceived media information, and familial input were assessed through a Likert scale. RESULTS: Our pilot study included 70 patients. The main reason (33 %) was the refusal to terminate pregnancy if the screening tests ultimately led to a diagnosis of aneuploidy. Lack of adequate information on the availability and benefits of this screening method (28 %), religious beliefs (17 %), in addition to other minor reasons such as financial considerations, familial recommendations, late pregnancy follow-ups, and media influence were also identified as contributing factors. CONCLUSIONS: Aneuploidy screening is routinely offered to couples, with varying uptake rates observed worldwide. Sufficient information on prenatal screening and diagnosis should be provided to all pregnant women, presenting all available options, thus enabling them to make a free and informed choice during their pregnancy.

Population-based surveillance of congenital anomalies over 40 years (1981-2020): Results from the Paris Registry of Congenital Malformations (remaPAR).

INTRODUCTION: Registries of congenital anomalies (CAs) play a key role in the epidemiological surveillance of CAs. The objective was to estimate the prevalence of CAs and proportions of prenatal diagnosis, terminations of pregnancy for fetal anomaly (TOPFA) and infant mortality in the Paris Registry of Congenital Malformations (remaPAR) over 40 years, from 1981 to 2020. MATERIAL AND METHODS: remaPAR records all births (live births, stillbirths ≥22 weeks of gestation and TOPFA at any gestational age) with CAs detected prenatally until the early neonatal period. We estimated the prevalence of CAs and proportions of prenatal diagnosis, TOPFA and infant mortality, overall and for a selected group of CAs in 3-year intervals. RESULTS: The prevalence of CAs remained stable during the study period: 2.9 % of total births and 2.1 % of live births. Genetic anomalies were the most frequent subgroup (about 23 %), followed by congenital heart defects (about 22 %) and limb defects (about 20 %). Among non-genetic anomalies, the prevalence per 10,000 births was the highest for hypospadias (about 18 %) and the lowest for bilateral renal agenesis (about 1 %). Prenatal diagnoses increased from about 17 % in the 1980s to approximately 70 % in the most recent period (2018-2020), whereas the proportion of early TOPFA <16 weeks of gestation increased from 0.4 % to 14 %. Infant mortality ranged from 0 % for transverse limb reduction defects to 86 % for hypoplastic left heart syndrome. CONCLUSION: The overall prevalence of CAs was fairly stable in Paris from 1981 to 2020. Prenatal diagnoses substantially increased, accompanied by much smaller increases in TOPFA.

Whole-genome sequencing in prenatally detected congenital malformations: prospective cohort study in clinical setting.

OBJECTIVE: To investigate the diagnostic yield of trio whole-genome sequencing (WGS) in fetuses with various congenital malformations referred to a tertiary center for prenatal diagnosis. METHODS: In this prospective study, 50 pregnancies with different congenital malformations, negative for trisomies and causative copy-number variants, were analyzed further with fetal-parental trio WGS analysis. Parents were eligible for inclusion if they accepted further investigation following the detection of isolated or multiple malformations on prenatal ultrasound. Cases with isolated increased nuchal translucency, gamete donation or multiple pregnancy were excluded. WGS with the Illumina Inc. 30× polymerase-chain-reaction-free short-read sequencing included analysis of single-nucleotide variants, insertions and deletions, structural variants, short tandem repeats and copy-number identification of SMN1 and SMN2 genes. RESULTS: A molecular diagnosis was achieved in 13/50 (26%) cases. Causative sequence variants were identified in 12 genes: FGFR3 (n = 2), ACTA1 (n = 1), CDH2 (n = 1), COL1A2 (n = 1), DHCR7 (n = 1), EYA1 (n = 1), FBXO11 (n = 1), FRAS1 (n = 1), L1CAM (n = 1), OFD1 (n = 1), PDHA1 (n = 1) and SOX9 (n = 1). The phenotypes of the cases were divided into different groups, with the following diagnostic yields: skeletal malformation (4/9 (44%)), multisystem malformation (3/7 (43%)), central nervous system malformation (5/15 (33%)) and thoracic malformation (1/10 (10%)). Additionally, two cases carried variants that were considered potentially clinically relevant, even though they were assessed as variants of uncertain significance, according to the guidelines provided by the American College of Medical Genetics and Genomics. Overall, we identified a causative or potentially clinically relevant variant in 15/50 (30%) cases. CONCLUSIONS: We demonstrate a diagnostic yield of 26% with clinical WGS in prenatally detected congenital malformations. This study emphasizes the benefits that WGS can bring to the diagnosis of fetal structural anomalies. It is important to note that causative chromosomal aberrations were excluded from our cohort before WGS. As chromosomal aberrations are a well-known cause of prenatally detected congenital malformations, future studies using WGS as a primary diagnostic test, including assessment of chromosomal aberrations, may show that the detection rate exceeds the diagnostic yield of this study. WGS can add clinically relevant information, explaining the underlying cause of the fetal anomaly, which will provide information concerning the specific prognosis of the condition, as well as estimate the risk of recurrence. A genetic diagnosis can also provide more reproductive choice for future pregnancies. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Neural Tube Defects from Antenatal Diagnosis to Discharge - a Tertiary Academic Centre Experience.

Background: Bleeding Worldwide, approximately 300,000 infants are born annually with neural tube defects (NTDs), which carry a high risk of morbidity and mortality. Objective: The aim of the study was to describe the experience with NTD patients born at a tertiary academic center. Methods: A retrospective record review of all neonates with NTD admitted to the neonatal intensive care unit over six years. Results: Out of the 39 patients identified, 32 (82.1%) were diagnosed antenatally. Most NTD cases were of the myelomeningocele 26 (66.7%) type. The most common site of the myelomeningocele was lumbar, and the thoracolumbar site had the worst prognosis. Conclusion: Early detection of the disease allows better planning of delivery and treatment decisions. Nevertheless, understanding the magnitude of the problem necessitates adopting public health prevention strategies for better outcomes.

Post-traumatic stress disorder and congenital anomalies in prenatal care / Transtorno de estresse pós-traumático e anomalias congênitas no pré-natal

Abstract Objective: to assess post-traumatic stress disorder (PTSD) symptoms in pregnant women diagnosed with congenital anomaly. Methods: his is a quantitative and cross-correlational study. The sample consisted of 111 pregnant women diagnosed with congenital anomaly between 2013 and 2014. We used a semi-structured questionnaire and the Impact of Events Scale - Revised (IES-R). For statistical analysis, the chi-square test, Student's t test or Mann-Whitney test, Cronbach Alpha coefficients, Pearson's correlation and simple linear regression models. Results: viable congenital anomalies corresponded to 66.6%, and non-viable, to 33.3%. The average of all areas of IES-R, as well as the sum of matters concerning IES-R, were high in all pregnant women diagnosed with congenital anomaly. Using a cut of 5.6 units in the IES-Rtotal score, we found that 46.8% of pregnant women diagnosed with a congenital anomaly showed PTSD symptoms; however, symptoms were more frequent among pregnant women diagnosed with non-viable congenital anomaly (64.9%). The IES-R intrusion and hyperstimulation dimensions were more correlated. We observed a decreasing connection with PTSD symptoms in relation to the time of the notification of congenital anomaly diagnosis. Conclusions: PTSD symptoms were more frequent in pregnant women diagnosed with non-viable congenital anomaly.

Resumo Objetivos: avaliar os sintomas do Transtorno de Estresse Pós-Traumático (TEPT) em gestantes com diagnóstico fetal de anomalia congênita. Métodos: estudo quantitativo e transversal-correlacional. A amostra foi composta por 111 gestantes com diagnóstico de anomalia, entre 2013 a 2014. Foi utilizado um questionário semiestruturado e a Escala do Impacto do Evento - Revisada (IES-R). Para a análise estatística o teste Qui quadrado, t de Student ou Mann-Whitney, coefficientes alfa de Cronbach, correlação de Pearson e modelos de regressão linear simples. Resultados: as anomalias congênitas viáveis corresponderam a 66,6% e as inviáveis, a 33,3%. A média de todos os domínios da IES-R como a soma das questões dos domínios da IES-R foram altas nas gestantes com diagnóstico de anomalia congênita. Ao se utilizar um corte de 5,6 unidades no escore total da IES-R, 46,8% de todas as gestantes com diagnóstico de anomalia congênita apresentaram sintomas de TEPT, sendo mais frequente entre as gestantes com diagnóstico de anomalia congênita inviável (64,9%). As questões de intrusão e hiperestimulação da escala IES-R estiveram mais correlacionadas entre si. Pareceu existir uma relação decrescente dos sintomas de TEPT, em relação ao tempo da notícia do diagnóstico de anomalia congênita. Conclusão: os sintomas do TEPT estiveram mais presentes em gestantes com diagnóstico de anomalia congênita inviável.

Frequency and clinical significance of chromosomal inversions prenatally diagnosed by second trimester amniocentesis.

To compare the frequency and clinical significance of familial and de novo chromosomal inversions during prenatal diagnosis. This was a retrospective study of inversions diagnosed prenatally in an Asian population by applying conventional GTG-banding to amniocyte cultures. Data from 2005 to 2019 were extracted from a single-center laboratory database. The types, frequencies, and inheritance patterns of multiple inversions were analyzed. Pericentric variant inversions of chromosome 9 or Y were excluded. In total, 56 (0.27%) fetuses with inversions were identified in the 15-year database of 21,120 confirmative diagnostic procedures. Pericentric and paracentric inversions accounted for 62.5% (35/56) and 37.5% of the inversions, respectively. Familial inversions accounted for nearly 90% of cases, and de novo mutation was identified in two pericentric and two paracentric cases. Inversions were most frequently identified on chromosomes 1 and 2 (16.1% of all inversions), followed by chromosomes 6, 7, and 10 (8.9% of all cases). The indications for invasive testing were as follows: advanced maternal age (67.3%), abnormal ultrasound findings (2.1%), abnormal serum aneuploidy screening (20.4%), and other indications (10.2%). The mode of inheritance was available for 67.9% of cases (38/56), with 89.5% of inversions being inherited (34/38). A slight preponderance of inheritance in female fetuses was observed. Three patients with inherited inversions opted for termination (two had severe central nervous system lesions and one had thalassemia major). Gestation continued for 53 fetuses, who exhibited no structural defects at birth or significant developmental problems a year after birth. Our study indicates that approximately 90% of prenatally diagnosed inversions involve familial inheritance, are spreading, and behave like founder effect mutations in this isolated population on an island. This finding can help to alleviate anxiety during prenatal counseling, which further underscores the importance of parental chromosomal analysis, further genetic studies, and appropriate counseling in cases where a nonfamilial inversion is diagnosed.

Cardiometabolic outcomes of women exposed to hyperglycaemia first detected in pregnancy at 3-6 years post-partum in an urban South African setting.

BACKGROUND: Hyperglycaemia first detected during pregnancy(HFDP) has far-reaching maternal consequences beyond the pregnancy. Our study evaluated the cardiometabolic outcomes in women with prior HFDP versus women without HFDP 3-6 years post-partum in urban South Africa. DESIGN AND METHODS: A prospective cohort study was performed of 103 black African women with prior HFDP and 101 without HFDP, 3-6 years post-partum at Chris Hani Baragwanath Academic Hospital, Soweto. Index pregnancy data was obtained from medical records. Post-partum, participants were re-evaluated for anthropometric measurements, body composition utilizing dual energy X-ray absorptiometry(DXA) and biochemical analysis (two-hour 75gm OGTT fasting insulin, lipids, creatinine levels and glucose levels). Cardiovascular risk was assessed by Framingham risk score(FRS). Carotid intima media thickness(cIMT) was used as a surrogate marker for subclinical atherosclerosis. Factors associated with progression to cardiometabolic outcomes were assessed using multivariable logistic and linear regression models. RESULTS: Forty-six(45.1%) HFDP women progressed to diabetes compared to 5(4.9%) in non HFDP group(p<0.001); only 20(43.4%) were aware of their diabetic status in the whole group. The odds(OR, 95% confidence interval(CI)) of progressing to type 2 diabetes(T2DM) and metabolic syndrome(MetS) after correcting for confounders in the HFDP group was 10.5(95% CI 3.7-29.5) and 6.3(95%CI 2.2-18.1), respectively. All visceral fat indices were found to be significantly higher in the HFDP group after adjusting for baseline body mass index. Ten-year estimated cardiovascular risk(FRS) and mean cIMT was statistically higher in the HFDP group(8.46 IQR 4.9-14.4; 0.48 mm IQR 0.44-0.53 respectively) compared to the non-HFDP group(3.48 IQR 2.1-5.7; 0.46mm IQR 0.42-0.50) respectively and this remained significant for FRS but was attenuated for cIMT after correcting for confounders. HIV did not play a role in progression to any of these outcomes. CONCLUSION: Women with a history of HFDP have a higher risk of cardiometabolic conditions within 6 years post-partum in an urban sub-Saharan African setting.