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Objective To compare the feasibility of performing a complete first trimester fetal anatomy screening between two operators with different levels of experience using the protocol of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), and to compare the duration of scan and learning curve of each operator as secondary outcomes. Methods A prospective study was conducted on singleton pregnancies at 11+0–13+6 weeks of gestation. Transabdominal ultrasound anatomy screening was performed by a maternal fetal medicine (MFM) staff (operator 1) or a first year MFM fellow (operator 2) following ISUOG guidelines. The visibility of fetal structures and time taken by each operator were recorded and analyzed. Results Data from 98 participants in operator 1 group and 96 participants in operator 2 group were analyzed. The success rate of visualizing all structures was feasible in 87.8% and 91.7% (p = .370) of cases in operator 1 and operator 2, respectively. The significant improvement in visualization success rate was observed between the first 50 and the last 50 scans in both groups (p = .004 vs. p = .006). Average time spent on the exam by operator 1 was significantly shorter than the time spent by operator 2 (11.3 ± 4.8 min vs. 15.0 ± 6.2 min; p < .001). Conclusion Completeness of first trimester fetal anatomy screening following ISUOG protocol were feasible with no statistical difference between the two different levels of experienced operators. Moreover, time allocatable with a brief learning curve were demonstrated in both groups. [ABSTRACT FROM AUTHOR]

Objective To investigate the application value and limitations of fluorescence in situ hybridization (FISH) in prenatal diagnosis of positive results for trisomies 13, 18, 21 (T13, T18, T21) and sex chromosome aneuploidies (SCAs) indicated by noninvasive prenatal screening (NIPS). Methods Samples from women who underwent prenatal diagnosis for the indication of positive NIPS of T13, T18, T21, and SCAs were collected. Each sample was split into two for both karyotype analysis and FISH analysis. The efficiency and consistency of FISH were assessed for the detection of chromosome abnormalities in the indications of positive NIPS results compared with karyotyping. Results A total of 649 pregnant women who scored positive for clinical significance of fetal chromosome abnormalities by NIPS were enrolled in our study, including T 13 (6%), T18 (14.3%), T21 (44.7%), SCAs (35.0%). From the following diagnostic test, the positive predictive value (PPV) of NIPS for T13, T18, T21, and SCAs was 17.9, 60.2, 89.3, and 43.6% respectively. FISH analysis was successful in all samples. Compared with karyotyping, the sensitivity and specificity were 98.3 and 100%, respectively. 95.7% (621/649) were fully concordant with karyotyping. 3.2% (21/649) cases were incompletely concordant with the karyotyping, among these cases, the FISH analysis identified all the aneuploidies, but karyotyping analysis provided more information about the chromosomal structure. There were 7 cases (1.1%, 7/649) of anomalies diagnosed by karyotype but missed out by FISH, all of which occurred in cases with the indication of SCAs. If the indications were confined to cases with a positive NIPS of T13, T18, T21, the diagnostic consistency of the two methods almost perfectly agree, and all the aneuploidies were detected by the FISH assay. FISH analysis was highly consistent in determining whether the fetus was euploid or not in the prenatal diagnosis for the patients with positive NIPS results compared with karyotyping (kappa= 0.976, p < .01). Conclusion For the prenatal diagnostic indications of positive NIPS of T13, T18, T21, and SCAs, FISH was equally efficacious in identifying aneuploidies and provided a quick diagnosis to alleviate anxiety. However, the missed risk of FISH analysis for structural chromosomal abnormalities should be taken seriously and fully informed during genetic counseling. [ABSTRACT FROM AUTHOR]

Objective: To analyse the accuracy of antenatal ultrasound screening in Malta, comparing detection rates within the private and public sectors, and with the rest of Europe. To assess local trends in accuracy for each organ system. Material and methods: Ethics approval was obtained to gather routinely collected data from the national congenital anomalies registry between 2016 and 2018. This was analysed to determine local antenatal ultrasound accuracy rates and trends. Electronic medical appointment record data was also used to indirectly determine whether a significant difference existed in the detection of antenatal anomalies in mothers scanned privately and those scanned within the public sector. χ²-for-trend was used to analyse changes in the accuracy rates. European Surveillance of Congenital Anomalies (EUROCAT) data was used to compare scanning accuracy in Malta and other EUROCAT centres. Results: The local rate of undetected congenital anomalies was 62.0% for public scans and 83.9% for private scans. Local trends over the three-year period showed an improvement in accuracy rates in detecting isolated syndromes (p=0.05), anomalies of the renal system (p=0.02) and craniofacial anomalies (p=0.05). Malta's overall performance was similar to other EUROCAT centres. Conclusion: Scans carried out within the public sector are more accurate than private scans, and Malta's overall performance was similar to other EUROCAT centres. [ABSTRACT FROM AUTHOR]

Objective: We present a case with prenatal diagnosis of submucous cleft palate (SMCP) which was described using 2- and 3-dimensional (3D) ultrasonography in utero. Case Report: A 25-year-old pregnant woman was referred to our department for fetal ultrasound screening. After the detection of cardiac and spinal malformations of fetal, further detailed examination detected SMCP, which showed a gap within the hard palate on axial transversal view with the soft palate visible on sagittal view. The imaging of a defective hard palate in prenatal 3D ultrasonography is similar to that in postmortem 3D computed tomography reconstruction. Conclusion: A gap within the hard palate and verification of the visibility of the soft palate should be key points in the prenatal diagnosis of SMCP. Three-dimensional ultrasonic imaging is helpful for displaying the shape and extent of the bony defect in SMCP. [ABSTRACT FROM AUTHOR]

Objective  Fetal growth restriction (FGR) is associated with poor neonatal outcomes and stillbirth, and screening via fundal height or ultrasound is routinely performed. During the novel coronavirus disease 2019 (COVID-19) pandemic, we developed a hybrid model of prenatal care which decreased the frequency of in-person visits and incorporated telemedicine visits. We sought to determine if prenatal FGR diagnoses decreased with this hybrid model compared with routine prenatal care. Study Design  This was a retrospective cohort study of singleton nonanomalous neonates with birth weights <10th percentile at term. The "routine care" group was consisted of those who born between April and July 2019 with in-person prenatal care, and the "hybrid care" group was consisted of those who born between April and July 2020 with both in-person and telemedicine prenatal cares at a collaborative academic practice. The primary outcome was the rate of diagnosis of small for gestational age (SGA) as defined as infant birth weight <10th percentile without a prenatal diagnosis of FGR. The secondary outcome was timing of diagnosis of FGR. Results  Overall, 1,345 and 1,296 women gave birth in the routine and hybrid groups, respectively. The number of in-person prenatal care visits decreased from 15,024 in the routine period to 7,727 in the hybrid period; 3,265 telemedicine visits occurred during the hybrid period. The total number of prenatal patients remained relatively stable at 3,993 and 3,753 between periods. Third trimester ultrasounds decreased from 2,929 to 2,014 between periods. Birth weights <10 percentile occurred in 115 (8.6%) births during the routine period and 79 (6.1%) births during the hybrid period. Of 115, 44 (38.3%) cases were prenatally diagnosed with FGR in the routine versus 28 of 79 (35.4%) in the hybrid group (p  = 0.76). Median gestational age at diagnosis did not vary between groups (36 vs. 37 weeks, p  = 0.44). Conclusion  A hybrid prenatal care model did not alter the detection of FGR. Future efforts should further explore the benefits of incorporating telemedicine into prenatal care. Key Points Telemedicine visits can provide comprehensive prenatal care. FGR was diagnosed equally with hybrid versus routine prenatal care. FGR diagnosis was not delayed with hybrid care. [ABSTRACT FROM AUTHOR]

In the last decades, the screening for Down syndrome brought the 11- to 14-week scan to the forefront of modern pregnancy care. Initially just a nuchal scan as part of the combined test, it upgraded to a detailed anatomy scan that should be done always where the ultrasound machine and the expertise allow, as instructed by current guidelines. Though a lot of the anatomy can be assessed at this age, it is still mainly used only for the measurements necessary for the combined tests or for noninvasive prenatal testing, hence a lot of the structural anomalies are missed. Our paper focuses on cases in which the anatomy scan was not performed, and structural and chromosomal anomalies were missed. [ABSTRACT FROM AUTHOR]

Objective: To screen Haemophilia-A patients for five known recurrent F8 gene variants and to analyze CA repeats in intron 13 of F8 gene in the mother and the affected child pairs. Methods: In this descriptive cross sectional study, 80 unrelated pairs of “mother and son” affected by Haemophilia-A were recruited as subjects. After collection of samples DNA was extracted using the Chelex (Bio-Rad, USA) method. Five known F8 gene variants were screened in the mothers and the affected sons by the allele specific PCR. The amplified products were separated on 2% agarose gels.CA repeats in intron 13 of the F8 gene in the mother and the affected child pairs were analyzed by Sanger sequencing method. The CA repeat alleles were used to look for the feasibility of linkage based diagnosis of Haemophilia-A in the affected families. The data were analyzed using Statistical Package for Social Sciences (SPSS) version 22.0. Results: In the 80 subject “mother and son” pairs a recurrent F8 gene variant was found in 32 pairs (40%). The most recurrent variant c.6869G>A was seen in 12 (15%). Linkage based analysis of the CA repeats in intron 13 was found to be informative in 29 (36.2%) mother-son pairs. Conclusion: The five known Haemophilia-A disease causing variants were found in 40% of the Pakistani Haemophilia-A patients. The five recurrent F8 gene variants and the CA repeats in intron 13 of F8 gene can provide a comprehensive basis for carrying out prenatal diagnosis and carrier screening in majority of the Pakistani Haemophilia-A families. [ABSTRACT FROM AUTHOR]

• We investigated interference of anti-alkaline phosphatase antibodies (anti-ALP's). • The anti-ALP's interfered with the unconjugated estriol assay for maternal serum screening. • These efforts identified 17 of 160 samples at increased risk for erroneous results. • Four of the 17 had screen interpretations changes using pseudo-risk calculations. Unconjugated estriol (uE3) is an important biomarker in second trimester prenatal screening. Previous studies from our laboratory identified rare interference in the Beckman uE3 assay due to anti-ALP antibodies, which could be mitigated with a scavenger or heat-inactivated ALP (hALP). In the current study, 160 de-identified patient samples previously submitted for the Quad screen with low uE3 multiples of the median (MoM ≤0.50) were investigated for potential interference. A reagent pack spiking strategy with hALP was employed to understand if the interference could be identified and mitigated in a scalable manner. The 160 samples were measured using uE3 lot #920861 previously known to be subject to interference, lot #920861 spiked with hALP, and the vendor reformulated lot #922579. Samples were suspected to have interference if the percent difference in uE3 measurements was >50%. Pseudo-risks were calculated using a test patient environment to understand the screening impact due to the change in uE3 result. Seventeen of the 160 samples had uE3 results that were >50% different between the hALP spiked and non-spiked reagent pack. Both original lot #920861 with hALP and reformulated lot #922579 identified the same 17 patients as having interference in lot #920861. Analysis of screening risks using a test patient environment showed that assay interference could result in false positives for one trisomy 21 and three trisomy 18 post-test risk calculations. Our experiment of reagent pack spiking with hALP produced similar uE3 results to a reformulated reagent designed to address potential interference, demonstrating that this is a feasible strategy to screen for interference in a scalable manner. The vendor-provided reformulation addressed anti-ALP interference and improved the performance of the screen. [ABSTRACT FROM AUTHOR]

Congenital syphilis (CS), once a forgotten disease, has now remerged. A 2-month-old male child presented with multiple discrete skin-colored papules over the trunk, back, bilateral lower limbs, and groin. He also had a deformity of bilateral lower limbs and a widening at the wrist. Radiological findings suggested syphilitic changes in long bones. Nontreponemal as well as treponemal tests were positive in the baby and both parents confirming the diagnosis of CS. The father had a history of multiple sex partners and untreated genital lesions in the past. The case emphasizes the importance of awareness regarding sexually transmitted infections and its timely treatment and judicious antenatal screening for the same. [ABSTRACT FROM AUTHOR]

Synopsis: Non‐invasive prenatal testing provides an early opportunity to identify patients with genotype–phenotype sex discordance and can be used to screen for complete androgen insensitivity syndrome. [ABSTRACT FROM AUTHOR]

Introduction. To explore the clinical value of noninvasive prenatal testing (NIPT) in screening the chromosomal abnormalities of the fetus in the elderly pregnant women. Materials and Methods. Between January 2020 and December 2021, 1949 elderly pregnant women underwent NIPT in our hospital. At the same time, 236 elderly pregnant women received invasive prenatal diagnosis, and the pregnancy outcomes were followed-up. Results. When NIPT was used for prenatal screening of fetal chromosomal aneuploidy, its diagnostic coincidence rate for trisomy 21 was the highest, with a coincidence rate of 90.00%, and the diagnostic coincidence rate for other chromosomal abnormalities was the lowest, only 22.22%. The sensitivity, specificity, positive predictive rate, and negative predictive rate for T21 by NIPT were 100%, 99.97%, 94.28%, and 100%; for T18 were 100%, 99.92%, 72.22%, and 100%, respectively; and for T13 were 100%, 99.95%, 50%, and 100%, respectively. Patients with high risks according to NIPT results further received invasive prenatal diagnosis, and 18 cases were excluded from the follow-up. For the remaining 1933 cases in the NIPT group, there was an incidence of 2.28% of adverse pregnancy outcomes. For the remaining 234 cases in the Amniocentesis group, there was an incidence of 1.28% of adverse pregnancy outcomes. There was no significant difference between the two groups (P > 0.05). The diagnostic rate of fetal chromosomal abnormalities in pregnant women under 40 years old was about 0.39-0.79%; however, the risk for people over 40 is relatively high at 1.32-4.44%. Conclusion. The noninvasive prenatal screening of fetal DNA in the second trimester of pregnancy for elderly pregnant women has high application value in the prediction of pregnancy outcome. The high risk of pregnancy can be determined by detecting trisomy 21, 18, and 13 syndromes, and the probability of adverse pregnancy outcome increases. [ABSTRACT FROM AUTHOR]

Background: So called cell-free fetal DNA (cffDNA) in the maternal plasma, which is derived from placenta, is widely used to screen fetal aneuploidies, including trisomy 21, 18, 13 and sex chromosomes. Here we reported a case of trisomy 8 mosaicism (T8M), which was initially identified via cffDNA screening in noninvasive prenatal testing (NIPT). Methods: A 35-year-old woman received cffDNA screening at 17th week of gestation. Amniocentesis was performed subsequently, and karyotyping, single-nucleotide polymorphism array (SNP-array) and BACs-on-Beads™ (BoBs™) were used to determine fetal chromosome content. Interphase fluorescence in situ hybridization (FISH) was applied to determine the copy number of chromosome 8. Results: An enhanced risk for fetal trisomy 8 was identified by cffDNA screening in the studied pregnant woman. After amniocentesis trisomy 8 was found in 1 of 73 metaphases. SNP-array on DNA derived from cultured amniocytes and neonatal cord blood cells suggested the presence of T8M. Interphase FISH on native neonatal cord blood cells confirmed T8M with a percentage of 10%. The Bobs™ fluorescence data also suggested that 8q23-8q24 was amplified. Conclusions: The current study shows that NIPT is suited to provide hints on rare autosomal trisomies, which have to be further validated and confirmed by other approaches. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of the Fetal Medicine Foundation (FMF) first trimester screening algorithm for pre‐eclampsia on health disparities in perinatal death among minority ethnic groups. Design A retrospective cohort study from July 2016 to December 2020. Setting: A large London teaching hospital. Patients and methods: All women who underwent first trimester pre‐eclampsia risk assessment using either the NICE screening checklist or the FMF multimodal approach. Women considered at high‐risk in the FMF cohort were offered 150 mg aspirin before 16 weeks' gestation, serial growth scans and elective birth at 40 weeks. Main outcome measures: Stillbirth, neonatal death and perinatal death rates stratified by screening method and maternal ethnicity. Results: In the NICE cohort, the perinatal death rate was significantly higher in non‐white than white women (7.95 versus 2.63/1000 births, OR 3.035, 95% CI 1.551–5.941). Following the introduction of FMF screening, the perinatal death rate in non‐white women fell from 7.95 to 3.22/1000 births (OR 0.403, 95% CI 0.206–0.789), such that it was no longer significantly different from the perinatal mortality rate in white women (3.22 versus 2.55/1000 births, OR 1.261, 95% CI 0.641–2.483). Conclusions: First trimester combined screening for placental dysfunction is associated with a significant reduction in perinatal death in minority ethnic women. Health disparities in perinatal death among ethnic minority women demand urgent attention from both clinicians and health policy makers. The data of this study suggest that this ethnic health inequality may be avoidable. Multimodal early pregnancy placental dysfunction screening can lead to a significant reduction in perinatal deaths in non‐white women. Multimodal early pregnancy placental dysfunction screening can lead to a significant reduction in perinatal deaths in non‐white women. This article includes Author Insights, a video abstract available at https://vimeo.com/bjogabstracts/authorinsights17109. [ABSTRACT FROM AUTHOR]

Objective: Socioeconomic status (SES) and distance of residence from tertiary care may impact fetal detection of congenital heart disease (CHD), partly through reduced access to and quality of obstetric ultrasound screening. It is unknown whether SES and remoteness of residence (RoR) affect prenatal detection of CHD in jurisdictions with universal health coverage. We examined the impact of SES and RoR on the rate and timing of prenatal diagnosis of major CHD within the province of Alberta in Canada.Methods: In this retrospective study, we identified all fetuses and infants diagnosed with major CHD in Alberta, from 2008 to 2018, that underwent cardiac surgical intervention within the first year after birth, died preoperatively, were stillborn or underwent termination. Using maternal residence postal code and geocoding, Chan SES index quintile, geographic distance from a tertiary-care fetal cardiology center and the Canadian Index of Remoteness (IoR) were calculated. Outcome measures included rates of prenatal diagnosis and diagnosis after 22 weeks' gestation. Risk ratios (RR) were calculated using log-binomial regression and stratified by rural (≥ 100 km from tertiary care) or metropolitan (< 100 km from tertiary care) residence, adjusting for year of birth and the obstetric ultrasound screening view in which CHD would most likely be detected (four-chamber view; outflow-tract view; three-vessel or three-vessels-and-trachea or non-standard view; septal view).Results: Of 1405 fetuses/infants with major CHD, prenatal diagnosis occurred in 814 (57.9%). Residence ≥ 100 km from tertiary care (adjusted RR, 1.19; 95% CI, 1.05-1.34) and higher IoR (adjusted RR, 1.9; 95% CI, 1.1-3.3) were associated with missed prenatal diagnosis of major CHD. Similarly, residence ≥ 100 km from tertiary care (adjusted RR, 1.41; 95% CI, 1.22-1.62) and higher IoR (adjusted RR, 3.6; 95% CI, 2.2-8.2) were associated with prenatal diagnosis after 22 weeks. Although adjusted and unadjusted analyses showed no association between Chan SES index quintile and prenatal-diagnosis rate overall nor for residence in rural areas, in metropolitan regions, lower SES quintiles were associated with missed prenatal diagnosis (quintile 1: RR, 1.24; 95% CI, 1.02-1.50) and higher risk of diagnosis after 22 weeks' gestation (quintile 1: RR, 1.46; 95% CI, 1.10-1.93; quintile 2: RR, 1.66; 95% CI, 1.24-2.23).Conclusions: Despite universal healthcare, rural residence in Alberta is associated with lower rate of prenatal diagnosis of major CHD and higher risk of late prenatal diagnosis (≥ 22 weeks). Within metropolitan regions, lower SES impacts negatively prenatal-diagnosis rate and timing. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

• Pregnancies with preimplantation genetic testing for aneuploidy (PCT-A) follow standard prenatal screening. • Specificity of the combined screening test decreases in pregnancies conceived through IVF with PGT-A. • Maternal age is the main contributor to risk of trisomy 21 in pregnancies conceived through IVF with PGT-A. How does first-trimester aneuploidy screening perform in pregnancies achieved through IVF with preimplantation genetic testing for aneuploidy (PGT-A) in a medical setting? This retrospective cohort study was undertaken in a single tertiary care centre between January 2013 and June 2022. In total, 20,237 women had prenatal follow-up at the study centre and were included in the study. The women were divided into three groups: singleton pregnancies conceived through the transfer of a PGT-A-screened euploid embryo (n = 510); singleton pregnancies conceived through IVF without PGT-A (n = 3291); and singleton pregnancies conceived naturally (n = 16,436). The conventional combined screening test for pregnancies conceived through IVF with PGT-A had specificity of 91%; sensitivity could not be calculated as there were no cases of fetal aneuploidy in this group. In 89.1% of pregnancies conceived through IVF with PGT-A with high risk for trisomy 21, 18 or 13, the result was related to advanced maternal age (>35 years at time of screening). The current screening strategy for trisomies 21, 18 and 13 can generate unnecessary tests in pregnancies achieved through IVF with PGT-A. A new protocol is needed for these patients, with greater weight given to ultrasound markers. [ABSTRACT FROM AUTHOR]

Cell-free DNA is an advancing technology with increasing applications in screening, diagnosis, and treatment for several disease processes. The shared physiologic, genetic, and epigenetic characteristics of placental physiology and tumor development have become apparent to both clinicians and researchers. Maternal malignancy has been reported as a cause of false-positive prenatal cell-free DNA screening results. The detection of multiple aneuploidies or a single autosomal monosomy increases the chance for an underlying maternal malignancy when the result is discordant with fetal diagnostic testing. There is currently no consensus guideline on counseling and evaluation of patients with concern for malignancy from cell-free DNA testing. Furthermore, laboratories differ significantly in reporting policies, terminology, and in reporting strategies and methods used for unexpected or incidental findings. The ordering practitioner is therefore tasked to understand the policies of their laboratory of choice to provide adequate pretest and posttest genetic counseling. In pretest counseling, the potential for incidental or unexpected findings or nonreportable results should be explained. With an abnormal, unanticipated, or nonreportable result, posttest counseling should include a description of possible fetal or maternal diagnoses, including malignancy. Health care professionals should explain options for further evaluation and management, including a recommendation for fetal diagnostic testing. The medical workup recommended by various authors to evaluate cancer risk is based on consensus, experience, and expert opinion. These strategies should incorporate the patient's desire for information, cost, and family and personal medical history. Ongoing research and multi-disciplinary collaboration in this area is critical to identify best practices in management of complex results from this increasingly common screening test. [ABSTRACT FROM AUTHOR]

This article is an ethical evaluation of two familiar views in the debate on foetal diagnosis; one being the mainstream view in medical texts emphasizing early detection of foetuses with Down´s syndrome so they may be aborted, and the other coming from Down´s syndrome activists claiming that such screening is never acceptable. The core question asked is: What ethical weaknesses in modern medical practice does this discussion reveal? I argue that the marketization of noninvasive prenatal testing (NIPT) and the mainstream discussion in the health sector on its application shows two trends undermining the traditional ethos of medicine. Firstly, that doctors are, in their work, concentrating on diseases as isolated entities, whereas the patient and her life remains in the shadow. Secondly, the emphasis has been on the scientific foundation of medicine where the clinical evaluation of these scientific facts has not received due attention. This article is about how we can evaluate ethically two different views on tests done on foetuses. It describes how some medical texts talk about tests done on foetuses to see if they have Down's syndrome; and secondly, how some people with Down´s syndrome and their families talk about such tests. The medical view is criticized for failing to understand the importance of the lives of people with Down´s syndrome and for not taking their views of the value of their lives seriously. The medical texts focus on diseases instead of patients. Thus they tend to ignore the life and value of the person having the disease. The medical view is mainly about science and facts. It ignores the question of whether and how these facts matter for the patient. People with Down´s syndrome and their families have criticized this medical approach. Their criticism is very important. [ABSTRACT FROM AUTHOR]

In the TRIDENT-2 study, all pregnant women in the Netherlands are offered genome-wide non-invasive prenatal testing (GW-NIPT) with a choice of receiving either full screening or screening solely for common trisomies. Previous data showed that GW-NIPT can reliably detect common trisomies in the general obstetric population and that this test can also detect other chromosomal abnormalities (additional findings). However, evidence regarding the clinical impact of screening for additional findings is lacking. Therefore, we present follow-up results of the TRIDENT-2 study to determine this clinical impact based on the laboratory and perinatal outcomes of cases with additional findings. Between April 2017 and April 2019, additional findings were detected in 402/110,739 pregnancies (0.36%). For 358 cases, the origin was proven to be either fetal (n = 79; 22.1%), (assumed) confined placental mosaicism (CPM) (n = 189; 52.8%), or maternal (n = 90; 25.1%). For the remaining 44 (10.9%), the origin of the aberration could not be determined. Most fetal chromosomal aberrations were pathogenic and associated with severe clinical phenotypes (61/79; 77.2%). For CPM cases, occurrence of pre-eclampsia (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5), and birth weight <2.3rd percentile (13.6% [24/177] vs 2.5% [3,892/155,491]; RR 5.5) were significantly increased compared to the general obstetric population. Of the 90 maternal findings, 12 (13.3%) were malignancies and 32 (35.6%) (mosaic) pathogenic copy number variants, mostly associated with mild or no clinical phenotypes. Data from this large cohort study provide crucial information for deciding if and how to implement GW-NIPT in screening programs. Additionally, these data can inform the challenging interpretation, counseling, and follow-up of additional findings. [ABSTRACT FROM AUTHOR]

Introduction: The rates of syphilis among pregnant women and infants have increased in recent years, particularly in the U.S. South. Although state policies require prenatal syphilis testing, recent screening rates comparable across Southern states are not known. The purpose of this study is to measure syphilis screening among Medicaid enrollees with delivery in states in the U.S. South.Methods: A total of 6 state-university research partnerships in the U.S. South developed a distributed research network to analyze Medicaid claims data using a common analytic approach for enrollees with delivery in fiscal years 2017-2018 and 2018-2019 (combined N=504,943). In 2020-2021, each state calculated the percentage of enrollees with delivery with a syphilis screen test during the first trimester, third trimester, and at any point during pregnancy. Percentages for those with first-trimester enrollment were compared with the percentages of those who enrolled in Medicaid later in pregnancy.Results: Prenatal syphilis screening during pregnancy ranged from 56% to 91%. Screening was higher among those enrolled in Medicaid during the first trimester than in those enrolled later in pregnancy.Conclusions: Despite state laws requiring syphilis screening during pregnancy, screening was much lower than 100%, and states varied in syphilis screening rates among Medicaid enrollees. Findings indicate that access to Medicaid in the first trimester is associated with higher rates of syphilis screening and that efforts to improve access to screening in practice settings are needed. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of maternal age on the rate of clinically significant chromosomal microarray analysis results in pregnancies with abnormal maternal serum screening and to establish the residual risk for abnormal microarray findings after omitting noninvasive prenatal testing (NIPT)-detectable aberrations in pregnancies with abnormal maternal serum screening.Methods: This retrospective study included all chromosomal microarray analysis tests performed in pregnancies with abnormal maternal serum screening and normal ultrasonogram results over the years 2013-2021. The rate of clinically significant (pathogenic and likely pathogenic) chromosomal microarray analysis findings was compared with a local control cohort of 7,235 pregnancies with normal maternal serum screening and ultrasonogram results, stratified by maternal age. Calculation of residual risk for clinically significant chromosomal microarray analysis results after normal NIPT was performed by omission of common NIPT-detectable anomalies. Systematic review for studies examining the yield of chromosomal microarray analysis in pregnancies with abnormal maternal serum screening was performed from inception to October 2021, with no time or language restrictions.Results: Of the 559 amniocenteses performed due to abnormal maternal serum screening, 21 (3.8%; 95% CI 2.4-5.7%) clinically significant chromosomal microarray analysis results were found. The residual risk for chromosomal microarray analysis aberrations after theoretically normal NIPT was estimated to be 2.0% (95% CI 1.1-3.6%) (1/50) and was significantly higher for women younger than age 35 years with abnormal maternal serum screening, compared with women with low-risk pregnancies. Systematic review yielded six articles encompassing 4,890 chromosomal microarray analysis results in pregnancies with abnormal maternal serum screening, demonstrating 2.3% residual risk for chromosomal microarray analysis anomalies after theoretically normal NIPT.Discussion: Clinically significant chromosomal microarray analysis findings can be found in 1 of every 50 pregnancies with high-risk maternal serum screening after theoretically normal NIPT, implying that invasive testing and not NIPT should be recommended in such pregnancies. In addition, NIPT use as a first-tier screening modality instead of maternal serum screening would miss pregnancies at increased risk not only for common autosomal trisomies but for additional chromosomal microarray analysis-detectable disorders. [ABSTRACT FROM AUTHOR]

Background: Identification of α0-thalassemia (SEA and THAI deletions) is essential in preventing and controlling of severe thalassemia diseases. We have developed the LAMP colorimetric assays for the detection of these two thalassemia defects and validated them in population screening and prenatal diagnosis. Methods: Three LAMP colorimetric assays specific for α0-thalassemia (SEA deletion), α0-thalassemia (THAI deletion) and normal DNA sequence were developed. These assays were validated on 341 subjects who had initial thalassemia screening positive and various thalassemia genotypes. Prenatal diagnosis of α0-thalassemia (SEA deletion) was done on 33 fetuses at risk of having Hb Bart's hydrops fetalis syndrome. Results: The LAMP colorimetric assays for α0-thalassemia (SEA and THAI deletions) could be clearly interpreted by naked eyes. The assay for α0-thalassemia (SEA deletion) showed a 100% (62/62 x 100) sensitivity and 98.2% (274/279 x 100) specificity whereas, that of the α0-thalassemia (THAI deletion) showed 100% (1/1 x 100) sensitivity and 99.7% (339/340 x 100) specificity. We obtained a 100% concordant prenatal diagnosis results using LAMP assays of α0-thalassemia (SEA deletion) in 33 fetuses as compared to the conventional PCR analysis. Conclusions: The LAMP colorimetric assays developed are simple, rapid, and do not require sophisticated equipment. Inclusion of the LAMP tests in the existing screening protocol significantly reduce the screening cost and the molecular analysis workload, which should prove useful in the prevention and control program of hemoglobinopathies in the region. [ABSTRACT FROM AUTHOR]

Background: Down syndrome (DS), also known as trisomy 21 (T21), is the most common genetic disorder associated with intellectual disability. There are two methods commonly used for prenatal testing of DS: serum screening (SS) for biomarkers in maternal serum and noninvasive prenatal testing (NIPT) for aneuploidy by cell-free DNA (cfDNA) in maternal plasma. However, cost-effectiveness analyses of these two methods are mostly based on data derived from simulations with various models, with theoretical values calculated. In this study, we statistically analyzed clinical DS screening data and pregnancy outcomes during the follow-up of pregnant women in Zhuhai City, China. The economics of the two mainstream prenatal DS screening methods was evaluated from a public health perspective. Methods: A retrospective analysis was performed on the data of 17,363 pregnant women who received SS and NIPT during gestation in Zhuhai from 2018 to 2019, and a cost-effectiveness analysis was performed with four screening strategies. In strategy I, all pregnant women received SS, and those with T21 risk ≥1/270 had invasive prenatal diagnosis (IPD). In strategy II, all pregnant women received SS, those with T21 risk ≥ 1/270 had IPD, and those with 1/270 > T21 risk ≥ 1/1,000 had NIPT; then, women at high risk based on NIPT also had IPD. In strategy III, all pregnant women received SS, and those with T21 risk ≥1,000 had NIPT; then, women at high risk based on NIPT results had IPD. In strategy IV, all pregnant women received NIPT and those at high risk based on NIPT results had IPD. Finally, to assess the cost and effectiveness of DS screening, the total costs were calculated as the sum of screening and diagnosis as well as the direct and indirect economic burden during the average life cycle of DS patients. Results: A total of 22 of the 17,363 (1/789) pregnant women had DS, of which only one woman was over 35 years of age. SS detected 1,024 cases at high risk of T21 (≥1/270), 8 cases were true positive, with a positive predictive value of 0.78% and a detection rate of 36.4%. NIPT detected 27 cases at high risk of T21 (Z ≥ 3) and 22 cases of DS, with a positive predictive value of 81.5% and a detection rate of 100%. Strategy I had the largest total cost of 65.54 million CNY, strategy II and III had similar total costs of 40 million CNY, and strategy IV had the lowest total cost of 14.91 million CNY. By comparison, the screening strategy with NIPT alone had the highest health economic value for DS. Conclusions: SS was greatly affected by nuchal translucency and the accuracy of gestational age measured by ultrasonography. Unstandardized ultrasonography was an important reason for the low DS detection rate with SS. The influence of interfering factors on NIPT was much lower than in SS. NIPT can be used as an alternative to SS and as a primary screening strategy of prenatal DS screening for secondary prevention and control of birth defects. NIPT greatly decreased the frequency of IPD and the miscarriages associated with IPD, saved the limited medical and health resources, and greatly increased DS detection rate. Therefore, NIPT has great social and economic benefits. [ABSTRACT FROM AUTHOR]

The article focuses on prenatal diagnosis of trisomy 21. It mentions the caregiver must give clear and objective information to pregnant women and couples, that can serve as a support for dialogue between the carer and the pregnant woman, between the carer and the couple and allow future parents to discuss and decide whether to commit or not in the screening process.

BACKGROUND: Nuchal translucency (NT) is an important finding of early fetal anatomy scan because of the association with genetic and structural anomalies. Enlarged nuchal translucency can be easily detected even without measurement on fetal anatomy scan as a neck pathology. Because of demanding criteria for measurning NT in established prenatal aneuploidy screening we came with an idea of improvement and simplification with availabe methods. The aim of this study is to compare established screening methods with new model of screening composed of fetal anatomy scan with integrated nuchal translucency and combination of PAPP-A and fβhCG. METHODS: A prospective one center study analyzed a total of 351 pregnancies between January 2017 and December 2020. Sonographic measurement of NT and fetal anatomy scan (FAS) were performend with biochemical testing from blood sample in the first trimester. Combined screening and fetal anatomy scan was performed. Patients with a pathological screening or with structural defects underwent an invasive procedure. In patient with positive screenining who missed the first trimester invasive procedure, amniocentesis was performed. Fetuses were divided into two groups according to positive or negative karyotype and to calculate sensitivity and specificity of screening methods. From statistical methods regression analysis, significance p of individual predictor, sensitivity and specificity with graphic drawing of ROC charts were used. Data were analyzed using statistical tools of Microsoft Excel 365 and BESH stat. RESULTS: Four models for aneuploidy screening were tested. 1) Model of „Age at the time of diagnosis" was slightly significant predictor with insignificant odds ratio (P=0.04, OR=1). 2) Model of„ First trimester biochemical screening" (age, free beta human chorionic gonadotropine -- fβhCG and pregnancy associated plasmatic protein A -- PAPP-A) were significant (P=0.0001; LR=21) with sensitivity of 87.5 % and specificity of 65.7 %. 3) Model of „First trimester combined test“ (age of patients at the time of diagnosis, fβhCG, PAPP-A, NT) was significant (P=7.9 x10-14, LR=67, sensitivity 87 %, specificity 80 %). 4) Model of „Fetal anatomy scan with biochemistry" (structural abnormality finding with combination including age, fβhCG and PAPP-A) was significant (P=4.9x10-18, LR=87, sensitivity 95 %, specificity 80 %). CONCLUSION: Fetal anatomy scan combined with age, fβhCG and PAPP-A has the highest sensitivity and specificity for both, the detection of fetal aneuploidies and structural abnormalities. Our study shows that fetal anatomy scan is the best possible option for first trimester diagnostics (Tab. 4, Fig. 5, Ref. 16). Text in PDF www.elis. sk [ABSTRACT FROM AUTHOR]

Résumé: La procédure du dépistage du risque de trisomie 21 est complexe : une succession de tests pouvant aboutir à une amniocentèse est proposée. Le soignant doit donner une information claire et objective aux femmes enceintes, aux couples. Ce dépistage n'est pas obligatoire. Les modalités pour les groupes à risque de trisomie 21 ont été modifiées fin 2018 avec l'introduction du test ADN libre circulant de la trisomie 21 (test ADNlcT21). Un document d'information sur le dépistage combiné de la trisomie 21 avait été élaboré en 2014, en respectant certains critères de la méthodologie de la Haute Autorité de Santé (HAS). Une actualisation de ce document était nécessaire. Les modifications des seuils définissant les groupes à risque, et l'introduction du test ADNlcT21 ont été intégrées au document d'information. Il a été soumis à des groupes de travail composés de soignants et d'usagers. La lisibilité, la compréhension, l'objectivité des informations ont été discutées au sein de chaque groupe et les modifications proposées étaient validées successivement. Le document final a été repris par un graphiste pour en améliorer la présentation. Le document d'information actualisé peut servir de support au dialogue entre le soignant et la femme enceinte, entre le soignant et le couple et permettre aux futurs parents de discuter et décider de s'engager ou non dans le processus de dépistage. Ce document devra faire l'objet d'une évaluation. The procedure for screening risks of Down syndrome is complex : a series of tests that may lead to amniocentesis is offered. The caregiver must provide clear and objective information to pregnant women and/or couples. This screening is not mandatory. The modalities for groups at risk for Down syndrome changed at the end of 2018 with the introduction of the cell-free DNA test for Down syndrome (T21 cf-DNA test). A background document on combined screening for Down syndrome was developed in 2014 following some of the criteria in the methodology from the French High Health Authority (Haute Autorité de Santé – HAS). This document has been updated with changes to the thresholds identifying the groups at risk, and the introduction of the T21 cf-DNA test. Working groups composed of health users and professionals were set up. The readability, clarity and objectivity of the information were discussed within each group, after which proposed changes were validated. The final document was adapted by a graphic designer to improve its presentation. The updated document can be used as a supporting tool in the conversation between the caregiver and the pregnant woman and/or couple and allow future parents to discuss and decide whether to enter the screening process. This document will need to be assessed. [ABSTRACT FROM AUTHOR]

The article focuses on study of financial analysis is carried out to assess costs and benefits of providing cell-free DNA screening in Finland, using different strategies. Topics discussed include considering the place of cell-free DNA screening it is important to make explicit the additional and marginal costs of different screening strategies and the associated benefits; and most assumptions the balance is favorable for Contingent screening.

Placenta accreta spectrum (PAS) disorders have been on the rise in recent years with increasing caesarean rates. The purpose of this prospective observational study was to describe our detection rates and to review outcomes in PAS after the introduction of an institutional screening and management protocol. Twenty-one patients with suspected PAS over 5 years were identified. 20/21 patients had an accurate determination of placental invasion and positive correlation with surgical and histopathological examination. Early morbidity (massive haemorrhage) was found in 7/21 patients, whilst late morbidity (hospital readmission) was found in 5/21 patients. There were no maternal deaths and admissions to intensive therapy unit (ITU). In summary, our centre demonstrated a high antenatal detection rate for PAS using an evidence-based protocol. This has led to timely intervention by an experienced multidisciplinary team and excellent outcomes. Immediate and delayed postoperative counselling was effective for optimal patient understanding and experience. What is already known on this subject? With rising caesarean section rates, the incidence of placenta accreta spectrum (PAS) disorders is increasing. Despite this, most obstetricians have personally managed only a small number of patients with PAS. Moreover, there appears to be some debate over the optimal diagnostic and management strategy. What do the results of this study add? As the incidence increases, development of institutional screening and management protocol is a necessity for large units. Timely diagnosis, extensive pre and postoperative counselling and multidisciplinary teamwork ensure reduced early and late morbidity. What are the implications of these findings for clinical practice and/or further research? Evidence based screening protocols for PAS disorders reduce the likelihood of undiagnosed cases and should be developed in every unit. Consideration must also be given to standardisation of the diagnostic and management protocols, including contingency plan for emergencies. [ABSTRACT FROM AUTHOR]

Background: We developed a decision aid (DA) to help pregnant women and their partners make informed decisions about prenatal screening for trisomy. We aimed to determine its usefulness for preparing for decision-making and its acceptability among end-users.Methods: In this mixed-methods pilot study, we recruited participants in three prenatal care settings in Quebec City. Eligible women were over 18 and more than 16 weeks pregnant or had given birth recently. We asked them about the usefulness of the DA using an interview grid based on the Technology Acceptance Model. We performed descriptive statistics and deductive analysis.Results: Thirty-nine dyads or individuals participated in the study. Mean usefulness score was 86.2 ± 13. Most participants found the amount of information in the DA just right (79.5%), balanced (89.7%), and very useful (61.5%). They were less satisfied with the presentation and the values worksheet and suggested different values clarification methods.Conclusion: Rigorous pilot tests of DAs with patients are an important stage in their development before the more formal assessments that precede scaling up the DA in clinical practice.Practice Implications: The next version of the DA will integrate the suggestions of end-users for better decision-making processes about prenatal screening for trisomy. [ABSTRACT FROM AUTHOR]

To evaluate the impact of the COVID-19 pandemic on prenatal screening and diagnostic tests. We conducted a retrospective study with pregnant women attending to the perinatology department of a tertiary referral center. The pre-COVID-19 period between 11 March 2019 and 10 March 2020 and COVID-19 period between 11 March 2020 and 10 March 2021 were evaluated. Both periods were compared in terms of outpatient visits, ultrasound examinations, prenatal screening and diagnostic tests. The correlation of deaths related to COVID-19 pandemic on these parameters was also assessed. A total of 38,918 patients were examined and 28,452 ultrasound examinations, 26,672 prenatal screening tests and 1,471 prenatal diagnostic tests were performed over two years. During COVID-19 pandemic, number of outpatient visits decreased by 25.2%, ultrasound examinations decreased by 44.2%, prenatal screening tests decreased by 36.2% and prenatal diagnostic tests decreased by 30.7%. Statistically significant correlation was not observed between deaths related to COVID-19 and outpatient visits (p=0.210), ultrasound examinations (p=0.265), prenatal screening (p=0.781) and diagnostic tests (p=0.158). Among indications of prenatal diagnostic tests, maternal anxiety was significantly higher in COVID-19 period (p=0.023). There was significant decrease in the detection of fetuses with trisomy 21 (p=0.047) and a significant increase in the detection of fetuses with Turner syndrome (p=0.017) during COVID-19 period. The COVID-19 pandemic has severely impacted antenatal care. Prenatal fetal screening and diagnosis was adversely affected by the pandemic in terms of detecting genetic and structural anomalies. [ABSTRACT FROM AUTHOR]

Objective: To assess the cost‐effectiveness of prenatal detection of congenital cytomegalovirus (cCMV) following maternal primary infection in the first trimester within standard pregnancy follow‐up or involving population‐based screening (serological testing at 7 and 12 weeks of gestation), with or without secondary prevention (valaciclovir) in maternal CMV primary infection. Design: Cost‐effectiveness study from the perspective of the French national health insurance system. Setting: Cost‐effectiveness based on previously published probability estimates and associated plausible ranges hypothetical population of 1,000,000 pregnant women. Population: Hypothetical population of 1,000,000 pregnant women. Methods: Cost‐effectiveness of detecting fetal cCMV in terms of the total direct medical costs involved and associated expected outcomes. Main outcome measures: Detection rates and clinical outcomes at birth. Results: Moving to a population‐based approach for targeting fetal CMV infections would generate high monetary and organizational costs while increasing detection rates from 15% to 94%. This resource allocation would help implementing horizontal equity according to which individuals with similar medical needs should be treated equally. Secondary prevention with valaciclovir had a significant effect on maternal‐fetal CMV transmission and clinical outcomes in newborns, with a 58% decrease of severely infected newborns for a 3.5% additional total costs. Accounting for women decision‐making (amniocentesis uptake and termination of pregnancy in severe cases) did not impact the cost‐effectiveness results. Conclusions: These findings could fuel thinking on the opportunity of developing clinical guidelines to rule identification of cCMV infection and administration of in‐utero treatment. These findings could fuel the development of clinical guidelines on the identification of congenital CMV infection and the administration of treatment in utero. CMV serological screening followed by valaciclovir prevention may prevent 58% to 71% of severe cCMV cases for 38 € per pregnancy. CMV serological screening followed by valaciclovir prevention may prevent 58% to 71% of severe cCMV cases for 38 € per pregnancy. [ABSTRACT FROM AUTHOR]

Objectives  Our primary objective was to evaluate how prenatal diagnosis of a major fetal structural anomaly and resulting pregnancy outcome affected postpartum depression risk, as assessed by the Edinburgh Postnatal Depression Scale (EPDS). Secondary objectives were to review the rate of mental health follow-up and subsequent diagnosis of postpartum depression in screen-positive women. Study Design  Singleton pregnancies with prenatal diagnosis of one or more major fetal structural anomalies were ascertained from prospectively maintained databases that included perinatal outcomes and subsequent EPDS responses from January 2010 to May 2018. EPDS scores of 13 or higher were considered positive and prompted referral for mental health follow-up, which was verified by medical record review. Statistical analyses were performed using Student's t -test, χ 2 , and odds ratios (ORs) with p  < 0.05 considered significant. Results  A total of 1,306 women had a prenatal diagnosis of one or more major fetal structural anomalies, 896 (68%) also had a postpartum EPDS screening, and 82 (9.2%) screened positive. Positive EPDS screening was more common with anomalies of multiple organ systems (16.5 vs 7.8%, p  = 0.002) and aneuploidy (17.1 vs 9.3%, p  = 0.02). Pregnancies complicated by fetal death, neonatal death, and termination for anomaly were significantly more likely to screen positive than those with neonatal survival to discharge (OR, 3.1 [95% confidence interval [CI], 1.6–6.2], 3.0 [95% CI, 1.5–5.8], and 4.4 [95% CI, 2.1–8.9], respectively, p ≤ 0.002). Of the 35 (43%) screen-positive women who attended follow-up appointments with mental health providers, 18 (51%) were diagnosed with a depressive disorder, accounting overall for 22% of those with a positive EPDS screen. Conclusion  Among women with a prenatal diagnosis of a major fetal structural anomaly, those experiencing a perinatal loss or pregnancy termination have an increased risk of positive EPDS screen result compared with who have a neonate surviving to discharge. A depressive disorder was diagnosed postpartum in 22% of these women with a positive EPDS screen. Our findings highlight the mental health needs in this vulnerable population. Key Points Adverse pregnancy outcome increased positive EPDS screen risk among women with prenatal anomalies. A depressive disorder was diagnosed postpartum in 22% of such women with a positive EPDS screen. Our findings highlight the mental health needs in this vulnerable population. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of a first-trimester combined screening program for pre-eclampsia, based on the Fetal Medicine Foundation (FMF) algorithm, on the rate of small-for-gestational age (SGA) at birth and adverse pregnancy outcome.Methods: This was a retrospective cohort study of data obtained from a London tertiary hospital between January 2017 and March 2019. The data were derived from a secondary analysis of the cohort evaluated in a clinical-effectiveness study on the implementation of a first-trimester screening program for pre-eclampsia. The cohort included 7720 women screened according to the UK National Institute for Health and Care Excellence (NICE) risk-based approach and 4841 women screened by the FMF multimodal approach, which combines maternal risk factors, blood pressure, pregnancy-associated plasma protein-A and uterine artery Doppler indices. The care package for the FMF-screened group included 150-mg aspirin prophylaxis, ultrasound scans at 28 and 36 weeks' gestation and scheduled delivery at 40 weeks. Outcome measures included the rates of SGA neonates at birth, admission to the neonatal unit, intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy assessed by interrupted time series analysis (ITSA).Results: There was no significant difference in the rates of intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy between the FMF-screened and NICE-screened cohorts. ITSA showed a significant reduction in the rate of term SGA birth < 10th percentile at 21 months following implementation of the FMF screening program, with a relative effect reduction of 45.1% (P = 0.004). However, there was no significant relative effect reduction in term SGA birth < 5th or < 3rd percentile.Conclusions: First-trimester combined screening for pre-eclampsia based on the FMF algorithm accompanied by a care package including serial ultrasound scans for growth evaluation and elective birth from 40 weeks' gestation resulted in a significant 45% relative effect reduction in term SGA birth < 10th percentile but did not affect term SGA birth < 5th or < 3rd percentile. Further screening strategies to detect and improve the outcome of cases with SGA birth < 5th percentile need to be considered. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Sickle cell disease (SCD) is a major genetic disease that occurs early in childhood and can cause considerable morbidity and even death. Newborn screening (NBS) is one of the effective health services that have lowered the burden of SCD in wealthy countries. Surprisingly, NBS programs are essentially non-existent in subSaharan Africa, where the majority of babies are born with this condition. The objective of this study was to determine the level of acceptability of NBS and the factors influencing it in the population of Lubumbashi city in the Democratic Republic of the Congo. Material and Methods: From December 1, 2020, to December 31, 2020, data on sociodemographic characteristics, knowledge, and attitudes related to NBS for SCD were collected from 2032 adults in Lubumbashi city using a semi-structured and pre-tested questionnaire. Results: There was a good knowledge of SCD as a hereditary blood disorder (77.7%). NBS's acceptability rate was 84.5%. Age (P = 0.002), sex (P = 0.025), and religion (p<0.001) were found to be significantly associated with the NBS acceptability. Conclusion: According to the findings of this study, NBS is widely accepted in Lubumbashi. The primary challenges to its adoption are likely to be financial and practical rather than social or cultural. [ABSTRACT FROM AUTHOR]

Noninvasive prenatal testing (NIPT) consists of determining fetal aneuploidies by quantifying copy number alteration from the sequencing of cell-free DNA (cfDNA) from maternal blood. Due to the presence of cfDNA of fetal origin in maternal blood, in silico approaches have been developed to accurately predict fetal aneuploidies. Although NIPT is becoming a new standard in prenatal screening of chromosomal abnormalities, there are no integrated pipelines available to allow rapid, accurate and standardized data analysis in any clinical setting. Several tools have been developed, however often optimized only for research purposes or requiring enormous amount of retrospective data, making hard their implementation in a clinical context. Furthermore, no guidelines have been provided on how to accomplish each step of the data analysis to achieve reliable results. Finally, there is no integrated pipeline to perform all steps of NIPT analysis. To address these needs, we tested several tools for performing NIPT data analysis. We provide extensive benchmark of tools performances but also guidelines for running them. We selected the best performing tools that we benchmarked and gathered them in a computational pipeline. NiPTUNE is an open source python package that includes methods for fetal fraction estimation, a novel method for accurate gender prediction, a principal component analysis based strategy for quality control and fetal aneuploidies prediction. NiPTUNE is constituted by seven modules allowing the user to run the entire pipeline or each module independently. Using two cohorts composed by 1439 samples with 31 confirmed aneuploidies, we demonstrated that NiPTUNE is a valuable resource for NIPT analysis. [ABSTRACT FROM AUTHOR]

Hypertensive disorders of pregnancy can be classified as chronic hypertension (present before pregnancy), gestational hypertension (onset after 20 weeks of pregnancy), and preeclampsia (onset after 20 weeks of pregnancy, along with proteinuria and other organ dysfunction). Preeclampsia and related disorders are a major cause of maternal and fetal morbidity and mortality. Preeclampsia is believed to result from an angiogenic imbalance in the placenta circulation. Antenatal screening and early diagnosis may help improve outcomes. Severe preeclampsia is characterized by SBP ≥160 mm Hg, or DBP ≥110 mm Hg, thrombocytopenia (platelet count <100 x 109/L), abnormal liver function, serum creatinine >1.1 mg/dL, or a doubling of the serum creatinine concentration in the absence of other renal diseases, disseminated intravascular coagulation, pulmonary edema, new-onset headache, or visual disturbances. Severe preeclampsia or eclampsia (preeclampsia with seizures) needs ICU management and is the main cause of morbidity and mortality. Severe hypertension can also result in life-threatening intracranial hemorrhage. Blood pressure control, seizure prevention, and appropriate timing of delivery are the cornerstones of the management of preeclampsia. Besides intravenous antihypertensive drugs, intravenous magnesium sulfate is the drug of choice to prevent or treat seizures, when preparing for urgent delivery. At present, delivery remains the most effective treatment for preeclampsia, and organ dysfunction rapidly recovers after delivery. Novel therapeutic interventions are under development to reduce complications. [ABSTRACT FROM AUTHOR]

Background: Perinatal mental ill‐health is a global health priority. Mental health screening during pregnancy is a routine part of clinical practice in many public hospital obstetric services across Australia, but implementation in the private hospital system has lagged. Aims: This study explored health professionals' perspectives on the Pre‐admission Midwife Appointment Program (PMAP), an antenatal mental health screening program at the Mater Hospital, Sydney. Materials and Methods: Nine midwives and three medical specialists participated in focus groups or individual interviews; key themes were determined using thematic qualitative analysis. Results: Five major themes and three sub‐themes were identified: immediate benefits to women (identifying women at risk; referrals to support services; supporting and educating women); enhanced overall quality of care at the hospital; the dilemma of partners attending; factors that make the program successful; and recommendations for improvement. Conclusions: Results will inform the implementation of antenatal mental health screening programs at other private hospitals across Australia. [ABSTRACT FROM AUTHOR]

Anal atresia is the most common malformation occurring in VACTERL association, but it is difficult to diagnose antenatally. We herein present a case of fetal anal atresia in VACTERL association diagnosed by ultrasonography and supported by autopsy. This case emphasizes the clues to ultrasonographic diagnosis of anal atresia at 11–13+6 weeks of gestation, promoting increased awareness of VACTERL association during first‐trimester screening. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to evaluate the effect of education and counselling on prenatal screening and diagnostic tests on pregnant women's decisional conflict, anxiety levels and attitudes towards the tests. Background: Clinical practice guidelines recommend prenatal genetic counselling for pregnant women before participation in the tests. Methods: A total of 210 pregnant women participated in the study by completing the State–Trait Anxiety Inventory‐I, Decisional Conflict Scale, SURE Scale, Knowledge Assessment Forms, Decision Satisfaction Form and Attitudes Scale between June 2017 and March 2018. In the first stage, pregnant women were evaluated who had only prenatal genetic screening tests and in the second stage, pregnant women who had been recommended to receive diagnostic tests. The intervention group received face‐to‐face individual education and counselling about prenatal genetic tests. Independent samples t test, t tests and Pearson correlation tests were used. Results: Education and counselling for prenatal screening tests and diagnostic tests from the first weeks of pregnancy were effective in decreasing anxiety, decisional conflict, increasing attitudes towards tests and had positive effects on pregnant women's knowledge level and decision satisfaction (P < 0.005). Conclusion: Prenatal genetic counselling and education are more effective if provided from the first weeks of pregnancy. Decreasing anxiety, decisional conflict and increasing knowledge levels of pregnant women are important to make informed decisions. Summary statement: What is already known about this topic? Prenatal genetic screening and diagnostic tests have been done for many years.ACOG and clinical practice guidelines recommend prenatal genetic counselling for pregnant women before participation in the tests. What this paper adds? This study is the first randomized controlled trial to assess the effect of prenatal genetic education and counselling from the first gestational weeks of pregnant women.Our results show that prenatal genetic education and counselling is more effective if provided from the first weeks of pregnancy.Prenatal genetic screening and diagnostic test education and counselling provided to pregnant women decrease their anxiety and decisional conflict, increase their decision satisfaction on prenatal tests and lead to more positive attitudes. The implications of this paper: This study provides an evaluation of education and counselling for both prenatal screening and diagnostic testing.Education and counselling programme that we used in this study can be successfully implemented into nursing and midwifery practice. [ABSTRACT FROM AUTHOR]

Non-invasive prenatal testing (NIPT) is often erroneously received as a diagnostic procedure due to its high discriminatory power in the field of fetal trisomy 21 diagnosis (wording: "NIPT replaces amniocentesis"). Already a look at the methodology of NIPT (statistical gene dose comparison of a primarily maternofetal DNA mixture information at selected sites of the genome) easily reveals that NIPT cannot match the gold standard offered by cytogenetic and molecular genetic analysis procedures from the matrix of the entire human genome (origin: vital fetal cells), neither in diagnostic breadth nor in diagnostic depth. In fact, NIPT in fetal medicine in its current stage of development is a selective genetic search procedure, which can be applied in primary (without indication) or secondary (indication-related) screening. Thus, NIPT competes with established search procedures for this field. Here, the combined nuchal translucency (NT) test according to Nicolaides has become the worldwide standard since 2000. The strength of this procedure is its broad predictive power: NT addresses not only the area of genetics, but also the statistically 10 times more frequent structural fetal defects. Thus, NIPT and NT have large overlaps with each other in the field of classical cytogenetics, with slightly different weighting in the fine consideration. However, NIPT without a systematic accompanying ultrasound examination would mean a step back to the prenatal care level of the 1980s. In this respect, additional fine ultrasound should always be required in the professional application of NIPT. NIPT can thus complement NT in wide areas, but not completely replace it. [ABSTRACT FROM AUTHOR]

There are a number of problems with the classification of prenatal screening as a form of 'selective reproduction' that has become an increasingly dominant classification scheme in the last decade. (1) Since the term 'selection' implies choosing one out of several (at least two), it misdescribes the decision to terminate a pregnancy. (2) Deciding whether to have this child is a decision taken within the relationships that constitute the pregnancy. (3) 'Selection' is a loaded term, connecting prenatal diagnosis to negative eugenics or to population genetics. (4) Deciding against the birth of a child who would suffer or would not be able to flourish is a decision taken within a negotiation of personal responsibilities and social constraints. The characterization of prenatal screening as selective reproduction is, in a very narrow way, defensible to reconstruct why prenatal screening is permissible in a liberal state and should not be banned, but it needs to be rejected as a general frame for understanding the substance of the ethical issues around prenatal diagnosis and screening. Ethics should rather attempt to create a respectful space of mutual understandings and reflect how women and couples, who are ultimately responsible for these decisions, perceive their responsibilities in care. [ABSTRACT FROM AUTHOR]

New genomic laboratory technology namely microarrays and high throughput sequencing (HTS) as well as a steady progress in sonographic image capture and processing have changed the practice of prenatal diagnosis during the last decade fundamentally. Pregnancies at high risk for common trisomies are reliably identified by non-invasive prenatal testing (NIPT) and expert sonography has greatly improved the assessment of the fetal phenotype. Preconceptional comprehensive carrier screening using HTS is available for all parents, if they should wish to do so. A definite fetal diagnosis, however, will still require invasive testing for most conditions. Chromosomal microarrays (CMA) have greatly enhanced the resolution in the detection of chromosome anomalies and other causal copy number variations (CNV). Gene panel or whole exome sequencing (WES) is becoming the routine follow up of many anomalies detected by ultrasound after CNVs have been excluded. The benefits and limitations of the various screening as well as diagnostic options are perceived as complex by many who find it challenging to cope with the need for immediate choices. The communication of facts to ensure an informed decision making is obviously a growing challenge with the advent of the new genomic testing options. This contribution provides an overview of the current practice and policies in Switzerland. [ABSTRACT FROM AUTHOR]

HIV remains one of the major causes of mortality and morbidity among women of reproductive age; given the risk of vertical transmission to the fetus, timely prevention, monitoring and management are imperative (Melaku et al. [2014]. Causes of death among females-investigating beyond maternal causes: A community-based longitudinal study. BMC Research Notes, 7(1), 629. https://doi.org/10.1186/1756-0500-7-629). Most HIV studies in Lebanon focus on men who have sex with men, people diagnosed with sexually transmitted infections, intravenous (IV) drug users, and people infected by blood transfusion products Ministry of Public Health [2017]. National AIDS Control Program in Lebanon. ; Shaheen [2014]. Around 3,750 HIV/AIDS cases in Lebanon. The Daily Star. ). We conducted a retrospective review of women who delivered at a tertiary academic hospital in Beirut between January 2016-Decemeber 2017 to assess prenatal HIV screening practices. In total, 1500 charts were randomly selected and reviewed: 137 (9%) women were screened for HIV, 2 (1.5%) tested positive. Odds rations were calculated for screening in relation to religion, parity, previous abortions, and mode of delivery: none were significant. No one was tested for Gonorrhoea and Chlamydia; 1250 (93.8%) were tested for Hepatitis B, 27 (1.9%) for Hepatitis C, 7 (0.5%) for HSV and, 74(5.3%) for Syphilis. Barriers to screening may include: Lack of consensus on mandated screening policy, HIV stigma, physician and patient prejudice and misconception of risk and, financial barriers as health insurance does not cover HIV screening. [ABSTRACT FROM AUTHOR]

Persistent pulmonary hypertension of the newborn more often affects term and near-term infants. It occurs when the anticipated postnatal decrease in pulmonary vascular resistance fails to occur. There is evidence in animal models of premature ductal closure and persistent pulmonary hypertension of the newborn in fetal mice with in-utero exposure to selective serotonin reuptake inhibitors, commonly prescribed antidepressants in pregnancy. This case raises suspicion about an association in a neonate between in-utero exposure to selective serotonin reuptake inhibitors and persistent pulmonary hypertension of the newborn secondary to premature ductal closure. [ABSTRACT FROM AUTHOR]

Background: Antenatal screening is vital to identifying couples at risk of having children with a clinically significant haemoglobinopathy. In Australia, immigration is increasing carrier incidence. Methods: A retrospective analysis was performed of full blood count, high-performance liquid chromatography and haemoglobin electrophoresis of women and their partners who underwent antenatal haemoglobinopathy screening over three years at a major NSW laboratory. Genetic testing results were included where available. Results: One thousand six hundred and twenty-eight women and 729 male partners were screened at a median gestation of 14 weeks. 8.2% of women had a clinically significant result, with a median 16-day interval to partner testing. In 35% of couples screened simultaneously, the partner did not require testing. Genetic confirmatory testing was performed in 65% of high risk couples. Conclusion: There was a significant delay to antenatal haemoglobinopathy screening for mothers, limiting time for genetic diagnosis, prenatal diagnosis and management of affected pregnancies. Screening should be performed earlier. Simultaneous couple testing is not cost-effective. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the improved precision of nuchal translucency (NT) measurement used in antenatal screening for Down's syndrome observed over time as evidenced by a decrease in the multiple of the median (MoM) standard deviation requires a modification to the NT MoM truncation limits to maintain accurate risk estimation. Methods: Probability plots were derived from the measurements of NT MoM values used in a 2018 audit of 22,362 unaffected pregnancies. The plots were used to determine whether the NT MoM upper truncation limit should be lowered. Validation plots were used to assess the screening accuracy of Down's syndrome risk estimates calculated from observed NT MoM values in the 22,362 unaffected pregnancies and 69 Down's syndrome pregnancies for original and revised NT MoM truncation limits. Results: Probability plots indicated that with improved precision of NT measurements, there was deviation from a Gaussian distribution at less high MoM values than with less precise measurements. Validation plots showed that using the current NT MoM upper truncation limit of 2.5 MoM with improved precision NT measurements overestimates the Down's syndrome risk (median risk in highest risk category expressed as an odds was 53.3:1 and observed prevalence was 1:1.1). The large discrepancy was corrected by changing the NTupper truncation limit to 2.0 MoM (median risk in highest risk category expressed as an odds was 1:1.78 and observed prevalence 1:2.7). Conclusion: The NT MoM upper truncation limit should be reduced from 2.5 to 2.0 MoM. [ABSTRACT FROM AUTHOR]

The American College of Obstetrics & Gynecology (ACOG) recommends offering aneuploidy screening to all pregnant women. Obesity and diabetes are not associated with an increased risk of aneuploidy; however, they can complicate and compromise testing options. As the prevalence of obesity and diabetes, or "diabesity" increases, counseling women regarding potential limitations in testing performance of aneuploidy screening is of paramount importance. This chapter reviews options for aneuploidy screening for women with diabesity including sonography/nuchal translucency, serum analyte screening, and cell-free DNA. Potential challenges associated with diagnostic testing with amniocentesis and chorionic villus sampling in women with obesity are also discussed. [ABSTRACT FROM AUTHOR]

Inherited deletions of upstream regulatory elements of α-globin genes give rise to α-thalassemia, which is an autosomal recessive monogenic disease. However, conventional thalassemia target diagnosis often fails to identify these rare deletions. Here we reported a family with two previous pregnancies of Hb Bart's hydrops fetalis and was seeking for prenatal diagnosis during the third pregnancy. Both parents had low level of Hemoglobin A2 indicating α-thalassemia. Conventional Gap-PCR and PCR-reverse dot blot showed the father carried –SEA deletion but did not identify any variants in the mother. Multiplex ligation-dependent probe amplification identified a deletion containing two HS-40 probes but could not determine the exact region. Finally, a long-read sequencing (LRS)-based approach directly identified that the exact deletion region was chr16: 48,642-132,584, which was located in the α-globin upstream regulatory elements and named (αα)JM after the Jiangmen city. Gap-PCR and Sanger sequencing confirmed the breakpoint. Both the mother and fetus from the third pregnancy carried heterozygous (αα)JM, and the fetus was normally delivered at gestational age of 39 weeks. This study demonstrated that LRS technology had great advantages over conventional target diagnosis methods for identifying rare thalassemia variants and assisted better carrier screening and prenatal diagnosis of thalassemia. • Conventional target diagnosis methods do not test upstream regulatory elements of α-globin genes. • Long-read sequencing identified a novel 83.9-kb deletion upstream of α-globin genes. • Long-read sequencing assisted for better prenatal diagnosis of α-thalassemia. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to examine whether prenatal biochemical screening analytes are associated with an increased risk of severe maternal morbidity (SMM) or maternal mortality. Study Design  This population-based cohort study includes all women in Ontario, Canada, who underwent prenatal screening from 2001 to 2011. Increasing fifth percentiles of the multiple of the median (MoM) for alphafetoprotein (AFP), total human chorionic gonadotropin, unconjugated estriol (uE3), dimeric inhibin-A (DIA), and pregnancy-associated plasma protein A were evaluated. An abnormally high concentration (>95th percentile MoM) for each analyte, individually and combined, was also evaluated. The main outcome assessed was the adjusted relative risk (aRR) of SMM or maternal mortality from 20 weeks' gestation up to 26 weeks thereafter. Results  Among 748,972 pregnancies, 11,177 resulted in SMM or maternal mortality (1.5%). Except for uE3, the aRR of SMM or maternal mortality increased in association with increasing fifth percentiles of the MoM for all analytes. AFP (aRR: 2.10; 95% confidence interval [CI]: 1.97–2.25) and DIA (aRR: 2.33; 95% CI: 1.98–2.74) > 95th versus ≤ 5th percentile of the MoM were especially associated with SMM or death. Conclusion  Women with abnormally high concentrations of certain prenatal biochemical analytes may be at a higher risk of SMM or death in pregnancy or postpartum. [ABSTRACT FROM AUTHOR]

Aim: Analyze if the evaluation of aberrant right subclavian artery in the prenatal echography has improved the detection of chromosomal, genetic and/or morphological abnormalities in our population. Methods: Descriptive, observational, cross‐sectional study of the cases of aberrant right subclavian artery diagnosed in our Prenatal Diagnosis Unit between January of 2011 and December of 2018. Results: Two hundred and fifty‐seven cases of aberrant right subclavian artery were diagnosed and among them, 179 were considered isolated cases and thus were confirmed after birth. The detection of aberrant right subclavian artery did not improve itself neither the diagnosis of trisomy 21 in the second trimester of pregnancy nor other chromosomal or genetic abnormalities, including the not isolated cases. There were two cases of trisomy 21 diagnosed in the second trimester that presented major sonographic disorders and an inadequate examination during the first trimester. When aberrant right subclavian artery was associated with soft markers of aneuploidy in the second trimester, any case was a trisomy 21. Aberrant right subclavian artery seems to be associated with some minor and major heart defects, especially ventriculoseptal defect and aneurismatic ductus, and in some cases, also with clubfeet. Conclusion: When an adequate screening of aneuploidies and a thorough ultrasound have been performed during the first trimester, aberrant right subclavian artery hardly helps to perform other diagnosis in the second trimester. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new coronavirus, was first identified in December 2019 in Wuhan, China and spread rapidly, affecting many other countries. The disease is now referred to as coronavirus disease 2019 (COVID-19).The Italian government declared a state of emergency on 31st January 2020 and on 11th March World Health Organization (WHO) officially declared the COVID-19 outbreak a global pandemic. Although the COVID-19 incidence remained considerably lower in Sardinia than in the North Italy regions, which were the most affected, the field of prenatal screening and diagnosis was modified because of the emerging pandemic. Data on COVID-19 during pregnancy are so far limited. Since the beginning of the emergency, our Ob/Gyn Department at Microcitemico Hospital, Cagliari offered to pregnant patients all procedures considered essential by the Italian Ministry of Health. To evaluate the influence of the COVID-19 pandemic on the activities of our center, we compared the number of procedures performed from 10th March to 18th May 2020 with those of 2019. Despite the continuous local birth rate decline, during the 10-week pandemic period, we registered a 20% increment of 1st trimester combined screening and a slight rise of the number of invasive prenatal procedures with a further increase in chorionic villi sampling compared to amniocentesis. Noninvasive prenatal testing remained unvariated. The request for multifetal pregnancy reduction as a part of the growing tendency of voluntary termination of pregnancy in Sardinia increased. The COVID-19 pandemic provides many scientific opportunities for clinical research and study of psychological and ethical issues in pregnant women. [ABSTRACT FROM AUTHOR]