Prenatal Testing Research Articles

Fidarsi o non fidarsi del test prenatale non invasivo? Riflessioni a partire da un caso di falso negativo

Non-invasive prenatal testing (NIPT) is a screening for foetal chromosomal abnormalities that identifies at-risk pregnancies and is used to propose a possible invasive genetic confirmation testing in case of its positive results. For Down syndrome (trisomy 21), its accuracy is close to 100%, while for other investigated conditions, it presents various limitations. In a neonate who presented with severe hypotonia and syndromic features, the NIPT was negative for all the screened anomalies. However, among the various investigations performed for the diagnosis, there was an altered methylation of the chromosomal region 15q11.2, indicative of Prader-Willi syndrome (PWS), previously excluded by NIPT. The paper therefore questions the significance of the results of this investigation in front of a clinical suspicion and reviews the use of NIPT in clinical practice.

Prenatal diagnosis of fetal skeletal anomalies via whole-exome sequencing in a tertiary referral center

The accurate prenatal diagnosis of skeletal anomaly (SKA) using prenatal imaging alone remains challenging. We aimed to investigate the efficacy of whole-exome sequencing (WES) in the prenatal molecular genetic diagnosis of skeletal system abnormalities, with or without additional ultrasound anomalies. All fetuses with SKA were subjected to sequential genetic tests, and after excluding fetal chromosomal abnormalities and clinically significant copy number variations (CNVs) consistent with the observed phenotype, the affected fetuses were further subjected to WES. The clinical features of fetal SKA were collected, and the results of molecular genetic testing and perinatal outcomes were analyzed. Following negative routine genetic test results of the 78 fetuses, trio-WES was conducted for 73 fetuses, and fetus-only WES (single WES) was performed for five fetuses due to parental refusal. Fetal skeletal system abnormalities in our cohort were subdivided into seven groups: 39 (50%) had short long bones, 14 (17.9%) had abnormal limb morphology, 4 (5.1%) had polydactyly, 4 (5.1%) had the absence of the radius tibia or tibiofibula, 5 (6.4%) had spine anomalies, 6 (7.7%) had strephenopodia, and 6 (7.7%) had multiple deformities. In total, we identified the molecular diagnoses for 32/78 fetuses with SKAs, and confirmed 41 pathogenic/likely pathogenic variants in 28 genes, including nine novel variants in our cohort. The overall diagnostic rate was 41% (32/78). Our findings demonstrate that WES can greatly improve the genetic diagnostic rate of fetal SKAs following routine genetic testing, which can comprehensively guide perinatal management and help assess the risk of recurrence in future pregnancies. Our data also provide a basis for the association between the SKA phenotype and related genotypes and expand the spectrum of fetal SKA phenotypes and related genes.

Developmental Validation of a DIP-InDel/DIP-STR System for the Detection of Unbalanced DNA Mixtures.

Extracting "masked" minor donor information from an unbalanced DNA mixture stain is important for the identification of the person of interest. In recent years, a series of compound markers genotyped based on allele-specific amplifications have been proposed to detect minor contributors of mixed stains. In this study, we selected out 18 DIP-InDel markers from previous literatures and established a multiplex system encompassing 18 DIP-InDel markers and 6 DIP-STR markers in two separate reactions. The allele frequencies were estimated based on 200 samples, and 23 of the 24 DIP-linked length polymorphic markers had a relatively high probability of informative markers (I value >0.267), which indicated their potential usefulness in the Chinese Han population. Moreover, the multiplex was highly sensitive (requiring >0.025ng) and specific to human DNA. This system is capable of detecting the minor contributor comprising 1% in unbalanced mixtures of two individuals. The capacity of profiling cell-free DNA was also analyzed in few cases. At least one paternal allele could be detected in maternal plasma samples with gestation periods ranging from 27 to 40 weeks. To conclude, the DIP-linked length polymorphic markers may serve as a convenient method for detecting the presence of a minor donor in unbalanced mixtures and show promise for noninvasive prenatal diagnosis.

The distribution of regions of homozygosity (ROH) among consanguineous populations-implications for a routine genetic counseling service.

Regions of homozygosity (ROH) increase the risk of recessive disorders, and guidelines recommend reporting of excessive ROH in prenatal testing. However, ROH are common in populations that practice endogamy or consanguinity, and cutoffs for reporting ROH in such populations may not be evidence-based. We reviewed prenatal testing results (based on cytogenetic microarrays) from 2191 pregnancies in the Jewish and non-Jewish populations of Northern Israel and estimated the prevalence of ROH according to self-reported ethnicity and parental relationships. The proportion of the genome in ROH, ROH rate, was higher in non-Jews [Mean (SD) = 2.91% (3.92%); max = 25.54%; N = 689] than in Jews [Mean (SD) = 0.81% (0.49%); max = 3.93%; N = 1502]. In the non-Jewish populations, consanguineous marriages had the highest ROH rates [Mean (SD) = 7.14% (4.55%), N = 217], followed by endogamous [Mean (SD) = 1.13% (1.09%), N = 283] and non-endogamous [Mean (SD) = 0.69%(0. 56%), N = 189] marriages. ROH rates were greater than 5%, the ACMG-recommended cutoff, in 149/689 (21.63%) of the non-Jewish samples. Within the Jewish populations, the rates were similar between Ashkenazi, North African, and Middle Eastern Jews, but were higher for six consanguineous unions [Mean (SD) = 2.38% (1.23%)] and when spouses belonged to the same sub-population. Given the high ROH rates we observed in some subjects, we suggest that assessing the risk for recessive conditions in consanguineous/endogamous populations should be done before the first pregnancy, through genetic counseling and sequencing. Such an approach will: (1) identify couples who are at risk and counsel them on reproductive options; and (2) avoid the stress that couples who are not at risk may experience due to a prenatal ROH report.

Clinical application of chromosome microarray analysis and karyotyping in prenatal diagnosis in Northwest China

IntroductionKaryotyping and chromosome microarray analysis (CMA) are the two main prenatal diagnostic techniques currently used for genetic testing. We aimed to evaluate the value of chromosomal karyotyping and CMA for different prenatal indications.MethodsA total of 2084 amniocentesis samples from pregnant women who underwent prenatal diagnosis from 16 to 22 + 6 weeks of gestation between January 2021 and December 2022 were retrospectively collected. The pregnant women were classified according to different prenatal diagnostic indications and underwent CMA and karyotype analysis. Clinical data were collected, and the results of the CMA and karyotype analysis were statistically analyzed to compare the effects of the two diagnostic techniques.ResultsThe total detection rate of abnormal chromosomes was significantly higher using CMA than karyotype analysis. The detection rate of abnormal chromosomes using CMA was significantly higher than that using karyotyping for ultrasound abnormalities, high-risk serologic screening, adverse pregnancy history, positive noninvasive prenatal test (NIPT) screening, and ultrasound abnormalities combined with adverse pregnancy history indications. Among the fetuses with inconsistent results between the two testing methods, 144 had an abnormal CMA but a normal karyotype, with the highest percentage of pregnant women with ultrasound abnormalities at 38.89% (56/144). CMA had the highest detection rate for structural abnormalities combined with soft-index abnormalities among all ultrasound abnormalities. The highest detection rate of copy number variants in the group of structural abnormalities in a single system was in the genitourinary system (3/29, 10.34%).ConclusionCMA can improve the detection rate of chromosomal abnormalities in patients with ultrasound abnormalities, high-risk serologic screening, adverse maternal history, positive NIPT screening, and ultrasound abnormalities combined with adverse maternal history and can increase the detection rate of chromosomal abnormalities in karyotypic normality by 6.91% (144/2,084), this result is higher than similar studies. However, karyotype analysis remains advantageous over CMA regarding balanced chromosomal rearrangement and detection of low-level chimeras, and the combination of the two methods is more helpful in improving the detection rate of prenatal chromosomal abnormalities.

'I Could Trust It': Experiences of Reciprocal Translocation Carriers and Their Partners With Prenatal Cell-Free DNA Screening for Unbalanced Translocations.

To explore the experiences of people having cfDNA screening to detect unbalanced translocations, and to understand motivations for choosing this option. We used a qualitative approach with in-depth semi-structured interviews with reciprocal translocation carriers and their partners. People who underwent cfDNA screening with translocation analysis through Victorian Clinical Genetics Services between 2015 and 2019 were invited to take part. Purposive sampling based on the participant's geographic location, requesting practitioner specialty and cfDNA screening result was used to capture a range of experiences. Interview transcripts were analysed using thematic analysis. Participants (n=13) had complex reproductive journeys associated with the translocation and opted for cfDNA screening rather than prenatal diagnosis to avoid risk to their pregnancy. Participants benefited from having a result early in pregnancy and had sufficient confidence in the result to decline a diagnostic testing procedure. Participants' experiences with cfDNA screening were intertwined with the experience of being a carrier of a reciprocal translocation. cfDNA screening with translocation analysis was perceived as an acceptable alternative to prenatal diagnosis and should be made more accessible to balanced translocation carriers. Access to specialist genetic counselling services is needed to ensure couples are provided with information about all prenatal testing options, including the benefits and limitations associated with cfDNA screening with translocation analysis.

Genome-Wide, Non-Invasive Prenatal Testing for rare chromosomal abnormalities: A systematic review and meta-analysis of diagnostic test accuracy.

Genome-Wide Non-Invasive Prenatal Testing (GW-NIPT) can provide positive results not only for common autosomal aneuploidies but also for rare autosomal trisomies (RATs) and structural chromosomal abnormalities (StrCAs). Due to their rarity, there is currently insufficient information on positive predictive value PPV of RAT and StrCA-positive cases in the literature. In this study, the screening accuracy and pregnancy outcomes of cases positive for rare chromosomal abnormalities were examined based on publications in which GW-NIPT testing was performed. True positive cases were determined using two different methodologies. One was a confirmed methodology, where only cases validated by genetic testing were considered true positives with a definite diagnosis, and the other was an extended methodology, where, in addition to cases confirmed by genetic testing, intrauterine fetal death and termination of pregnancy due to an abnormality confirmed by ultrasound examination were also considered true positives, where no diagnosis had been made but the fetus was probably affected. Seventeen studies were analyzed, with a total GW-NIPT population of 740,076. Of these, 1,738 were RAT positive. Using the confirmed method, we found the highest rates of true positives in T16, followed by T22, and T2, using the extended method, the highest rate of true positives in T15, T16 and T22. This is the first meta-analysis to determine the frequency of rare chromosomal abnormalities, test-positive rates, and the PPV of each chromosomal abnormality with high precision. Our results could aid pre- and post-test genetic counselling and help patients and clinicians in their decision-making.

Pregnancy monitoring and parturition in dogs

Management of term pregnant dogs is a major and frequent clinical situation in small animal reproductive veterinary practices, and can be challenging. Whether a pregnancy is planned or unplanned, these cases require careful monitoring to prevent maternal distress and neonatal loss. Reproductive system evaluation of female dogs is useful for determination of ovulation during breeding management, pregnancy diagnosis, and for timing of cesarean surgery, among other clinical scenarios. Basic understanding of female dog’s reproductive physiology is mandatory to interpret relevant hormonal assays and other complementary diagnostics such as vaginal cytological evaluation and imaging (ultrasonography and radiography) for clinical decisions. This review covers physiology, diagnostics, and clinical outcomes relevant for pregnancy monitoring and parturition.

Development and validation of an ultrasound-based estimated fetal weight reference for Chinese twin pregnancy: a retrospective cohort study

BackgroundFetal growth monitoring is important for twin pregnancies. However, there has been no clinically validated tool for monitoring fetal growth of twin pregnancies in China. This study aims to develop and validate a chorionicity-specific growth chart of ultrasound estimated fetal weight (EFW) for Chinese twin pregnancies.MethodsThis retrospective cohort study included all twin pregnancies who delivered two live fetuses with gestational age ≥ 34 weeks without severe obstetric complications at a tertiary hospital from January 2007 to March 2021. The participants were divided into a development set (delivered in or before December 2017) and a validation set (delivered in or after January 2018). Chorionicity-specific growth charts were created using the generalized additive models for location, scale, and shape (GAMLSS) based on the development set. The fetuses from the validation set were classified into three groups based on the last EFW: small-for-gestational-age (SGA) indicated by both the newly established twin charts and the Hadlock singleton chart currently used for twin pregnancies in China, suspected SGA indicated by only the singleton chart, and no SGA indicated by either chart. The incidence of neonatal outcomes among the three groups was then compared accordingly, including intensive care unit (NICU) stay length, respiratory diseases, and neurological disorders.ResultsThe development set included 883 twin pregnancies and a total of 6374 EFW measurements between 16 and 38 weeks of gestation, and the validation set included 801 twin pregnancies and 7630 EFW measurements. In the development set, monochorionic diamniotic (MCDA) twins had a significantly lower EFW compared to dichorionic diamniotic (DCDA) twins beginning at 26 weeks, with the difference gradually increasing thereafter, supporting the establishment of chorionicity-specific growth charts. Of the 1,602 twin neonates in the validation set, 103 (6.4%) were classified into the SGA group, 164 (10.2%) into the suspected SGA group, and 1335 (83.3%) into the no SGA group. The incidence of respiratory diseases and neurological disorders was comparable between the suspected SGA group and the no SGA group, but apparently higher in the SGA group. Meanwhile, NICU stay lengths were consistently longer for twins in the SGA group compared to the no SGA group (difference: 0.57, 95% CI: 0.31–0.83), with no significant differences observed between the suspected SGA and no SGA groups.ConclusionsThe fetal growth trajectories differed by chorionicity, with a lower EFW for MCDA twins beginning at 26 weeks. The establishment of chorionicity-specific growth chart could reduce overdiagnosis of SGA and improve fetal growth monitoring of twin pregnancies.

Unexpected findings of Duchenne muscular dystrophy in prenatal screening of chromosome abnormality based on cell-free fetal DNA.

Objective：This study aims to assess the feasibility of detecting and diagnosing Duchenne muscular dystrophy (DMD) during prenatal screening for chromosome abnormalities using cell-free fetal DNA extracted from peripheral blood samples of pregnant women. Methods：Two pregnant women identified as high-risk through non-invasive prenatal testing (NIPT) underwent amniocentesis to obtain fetal cells. Subsequent fetal chromosomal karyotyping was conducted, and genomic DNA from fetal cells was extracted for Copy Number Variation Sequencing (CNV-Seq) analysis, complemented by Multiplex Ligation-dependent Probe Amplification (MLPA) to detect deletions or duplications within the DMD gene. Results：NIPT results for the two samples indicated potential abnormalities involving chromosomes 21 and 18. However, karyotype analysis of the fetuses revealed no abnormalities. CNV-Seq identified deletions of 0.28Mb and 0.18Mb within chromosome Xp21.1, encompassing the DMD gene, in each fetus. In family 1, MLPA results indicated a maternal heterozygous deletion spanning exons 12-41 in the DMD gene, while the fetus exhibited deletions in exons 12-41. In family 2, MLPA results confirmed normal DMD gene status in the pregnant woman's peripheral blood genomic DNA but revealed a fetal deletion spanning exons 48-52. Both fetuses were diagnosed with DMD and subsequently underwent termination. Conclusions：Abnormalities identified through NIPT necessitate further invasive prenatal diagnostic procedures. For cases involving chromosomal microdeletions or microduplications, a combination of karyotyping and CNV-Seq testing is essential for comprehensive diagnosis. NIPT followed by CNV-Seq may offer insights into large exon deletions within the DMD gene in specific instances.

Comparison of two proxies for the preconception weight using data from a pre-pregnancy cohort in Benin: Weight measured in the first trimester of pregnancy vs estimated by Thomas' formula.

Accurate determination of pre-pregnancy weight is essential for optimal pregnancy monitoring and antenatal care. Determining pre-pregnancy weight in limited-resources settings is challenging for both clinical practice and public health research. From a 2014-2017 pre-pregnancy cohort in Benin, we evaluated the agreement between the measured pre-pregnancy weight (MPPW) and two proxies: (i) the first trimester pregnancy weight (FTPW) and (ii) the estimated pre-pregnancy weight (EPPW) using Thomas & al. formula. We analysed data from 302 pregnant women with both pre-pregnancy weight measured within 3 months before conception and weight measured during the first trimester. Using segmented linear regression, we first assessed up to which gestational age the weight measured during the first trimester could reasonably estimate the MPPW. Then the Bland & Altman method was used to assess agreement between MPPW and the two proxies. Additional analyses were performed to assess the sensitivity of results to the timing of measurement of either MPPW or the two proxies. On average, FTPW did not feature significant difference with MPPW up to 13.03 (11.99-14.06) weeks of gestational age. FTPW, measured on average at 7 ± 2.4 weeks of gestation, and the EPPW showed similar Bland & Altman limits of agreement with the MPPW. However, while the FTPW slightly underestimated the MPPW by a mean of-0.16 (-0.08; +0.39) kg, the EPPW overestimated it by a mean of + 0.43 (+0.20; +0.66) kg. Minor differences in these results were observed when the MPPW was assessed earlier or within three months before pregnancy, or according to the gestational age at the time of the proxy's measurement. In conclusion, in Southern Benin and up to 12-14 weeks of pregnancy, the FTPW appeared to be a good proxy of the MPPW while using Thomas' formula did not enhance pre-pregnancy weight estimation.

Prenatal risk assessment of Xp21.1 duplication involving the DMD gene by optical genome mapping.

Structural variants (SVs) of unknown significance are great challenges for prenatal risk assessment, especially when involving dose-sensitive genes such as DMD The pathogenicities of 5'-terminal DMD duplications in the database remain controversial. Four prenatal cases with Xp21.1 duplications were identified by routine prenatal genomic testing, encompassing the 5'-UTR to exons 1-2 in family 1 and family 2, and to exons 1-9 in family 3. The duplication in family 4 was non-contiguous covering the 5'-UTR to exon 1 and exons 3-7. All were traced to unaffected males in the family pedigrees. A new genome-wide approach of optical genome mapping was performed in families 1, 2, and 3 to delineate the breakpoints and orientation of the duplicated fragments. The extra copies were tandemly inserted into the upstream of DMD, preserving the integrity of ORF from the second copy. The pathogenicities were thus reclassified as likely benign. Our data highlight the importance of structural delineation by optical genome mapping in prenatal risk assessment of incidentally identified SVs involving DMD and other similar large dose-sensitive genes.

Congenital Syphilis in the United States: A Narrative Review.

Congenital syphilis (CS) continues to pose a significant global challenge. There has been a marked increase in reported cases in the US, with 102.5 cases per 100,000 live births in 2022 compared to 11.6 cases per 100,000 live births in 2014. CS can lead to a range of severe complications, including premature birth, intrauterine growth restriction, miscarriage, perinatal death, stillbirth, and postnatal complications that may persist into later life. Maternal/parental factors such as age, race/ethnicity, occupation, income level, access to healthcare services, and incarceration have been linked to higher rates of CS. Additionally, pregnant individuals who engage in high-risk behaviors such as sex work, having multiple sexual partners, or substance use are at a higher risk of exposure and subsequent infection. Routine screening for syphilis during pregnancy is crucial for its detection, timely management, and prevention of CS. The asymptomatic nature of the latent stage of syphilis further underscores the importance of prenatal syphilis screening. Studies in various countries have shown that early or first antenatal care visit screening for CS is cost-effective. This review article critically evaluates the current knowledge of CS in the US, including its prevalence, social determinants of health, prevention efforts, challenges, the significance of screening, and the call to action to address the rising trend.

The first 2-year prospective audit of prenatal cell-free deoxyribonucleic screening using single nucleotide polymorphisms approach in a single academic laboratory.

We reported a performance during an implementation of prenatal cell-free (cf) DNA screening using single nucleotide polymorphism (SNP) approach in our accredited laboratory. Prospective audit with prompt intervention was set for the processing of 2,502 samples from singleton pregnancy from August 2017 to July 2019. Risks of trisomy 21 (T21), T18, T13, monosomy X (XO), and other sex chromosome aneuploidies (SCAs) were clarified by a proprietary bioinformatics algorithm. Laboratory failure occurred in 192 samples (7.7 %) as a result of inadequate sequencing (n=144), fundamental limitation of the testing (n=19), and obvious human error (n=29). Faulty setting of the calibration curve was the most common human error (n=22/29). After a redraw (n=110), 79 (71.8 %) were settled. Overall, 2,389/2,502 samples (95.5 %) were reportable. Thirty-five samples were high-risk for T21 (n=19), T18 (n=5), T13 (n=1), XO (n=3), and other SCAs (n=7), respectively. Positive predictive values calculated from either prenatal confirmatory tests or postnatal findings were 93.8 % (n=16), 100 % (n=4), 50 % (n=2), and 83.3 % (n=6) for T21, T18, XO, and other SCAs, respectively, with high sensitivity and specificity (>99.9 %). Vanishing twin was detected from 1 out of 4 samples with detected additional haplotypes. An overall performance of SNP-based prenatal cf-DNA screening during our initial implementation can be optimized with proactive approach. The technical know-how was a significant limiting factor for adopting the technology. The lessons learnt may be of interest to the academic laboratory considering adopting their own test instead of sending blood to a testing service of a supplier.

Born in Ethiopia

Abstract Background Goal 3 of the United Nation 2030 Agenda states that we want to ensure health and well-being for all. This is even more true for countries in the IV World. The aim of our study is to investigate the timing of childbirth in Ethiopia. Methods The stages of our ethnographic study include: choosing the study topic and location, participating in group life, collecting and analysing data. The field experience, led by a midwife, took place from September 2023 to October 2023 in Ethiopia, within the Saint Luke Catholic Hospital in Wolisso. Results The instruments that the midwives have at their disposal are few and obsolete: the most is Pinard’s stethoscope. The mothers are all very young: the youngest woman was fourteen years old while the oldest woman was thirty-eight years old. As for parity, the fertility rate is around 4.6 live births per woman. Women’s family members take care of them in all aspects of care. Pregnant and new mothers receive support from their attendants, an all-female network. Pregnancy monitoring is almost non-existent. There is no prenatal diagnosis. In 2022, St. Luke’s hospital saw a 20% caesarean section rate, an increase from the previous two years. Poverty and the lack of government facilities that can support a problem child are two of the reasons why many of these children are abandoned. In terms of maternal and child health, mortality indicators are still too high for mothers and children. There are 353 mothers dying per 100,000 live births and 41 babies dying per 1,000 live births. Conclusions The biomedical model exported from the Western world, as shown for example by the increase in caesarean sections, has led to a slow but progressive hospitalisation of childbirth in the search for safety from maternal and neonatal mortality. Key messages • Poverty, malnutrition, lack of sanitation and drinking water, as well as early pregnancies and high parity remain among the leading causes of mortality in Ethiopia. • The biomedical model exported from the Western world has led to a slow but progressive hospitalisation of childbirth in the search for safety.

National survey to estimate seroprevalence for toxoplasmosis among pregnant women in France, 2021

Abstract Background Toxoplasmosis during pregnancy can result in congenital malformations and fetal death. In France, universal antenatal screening and monthly re-testing of seronegative pregnant women has been established since the 1970s. However, decreasing Toxoplasma gondii seroprevalence among pregnant women and lower incidence of congenital toxoplasmosis may challenge the cost-effectiveness of such programs. The aim of this study was to estimate the current seroprevalence among pregnant women participating in the 2021 national perinatal survey (ENP). Methods All adult women giving birth in France between 15-21 March 2021 were invited to participate in the ENP. Data collected included demographic information, nationality, socio-economic status, education level and Toxoplasma gondii serology. We classified a woman as seropositive if she had IgG antibodies prior to pregnancy or seroconverted during it. Univariable and multivariable regression analyses using Poisson model were conducted to estimate prevalence ratios (PRs) and identify significant factors associated with seropositivity. Results Among the 15,605 participating women, 0.22% seroconverted during pregnancy. The overall seroprevalence was 25.95%. Seropositivity was higher with increasing age (∼5% per 5 years), among residents of French overseas territories Guadeloupe/Saint Martin (PRs:1.07; 95%-CI: 1.03-1.10), La Réunion (PRs:1.10; 95%-CI: 1.08-1.13) and Mayotte (PRs:1.27; 95%-CI: 1.23-1.31), with lower education (PRs:1.22; 95%-CI: 1.04-1.42) and African nationality (PRs:1.11; 95%-CI: 1.02-1.20). Conclusions High seroprevalence for Toxoplasma gondii was found in older women, which may reflect their higher risk of past exposure. The observed geographical differences in seroprevalence may mirror dietary and environmental diversity. Declining seroprevalence among pregnant women in France can affect screening effectiveness and warrants a comprehensive review to determine appropriate future prevention strategies. Key messages • Older women and residents of French overseas territories show higher toxoplasmosis seroprevalence, possibly due to past exposure risks and diverse diets/environments. • Declining toxoplasmosis seroprevalence among pregnant women in France can affect screening effectiveness and warrants a comprehensive review to determine appropriate future prevention strategies.

Health literacy in pregnant women facing prenatal screening: a short report from “SaperePer” project

Abstract Advancements in health promotion and prenatal medicine have made noninvasive prenatal testing (NIPT) a common practice during pregnancy, but understanding prenatal health information becomes crucial not only for the well-being of the mother but also for that of the unborn child. Analyze health-related information during pregnancy is fundamental, and this work fits perfectly with this topic, reporting preliminary results from the pilot study “SaperePer”. A health-related questionnaire was administered to 358 women in the first trimester of pregnancy, aiming to study different outcomes: 1.level of knowledge of NIPT; 2.number of screening tests undergone; 3.willingness to undergo a diagnostic test with a high outcome risk of screening test; 4.willingness to end the pregnancy following a diagnosis of pathology. The questionnaire was divided into 3 sections: personal characteristics and lifestyle habits, prenatal health behavior scale (PHBS), and knowledge of NIPT. Preliminary results showed that the level of knowledge of NIPT was higher in older, atheist, working, wealthy highly educated, and preliminary informed women, as well as the higher number of screening tests undergone and the propensity to undergo an invasive diagnostic test after a high-risk screening result (KS and MW tests p < 0.05). On the contrary, women with lower education, faithful and, even more, not preliminary and appropriately informed during prenatal counseling showed lower knowledge of NIPT, lower number of tests undergone, and meager chances to undergo an invasive diagnostic test or to end the pregnancy after a positive diagnosis of pathology (KS and MW tests p < 0.05). In conclusion, this study evaluated health-related information during the first but crucial stages of pregnancy, opening a new understanding of how health literacy and correct prenatal counseling could increase awareness and health promotion in pregnant women, particularly in those women with lower cultural tools. Key messages • Health literacy and correct prenatal counseling could increase awareness and health promotion in pregnant women. • Understanding prenatal health information becomes crucial both for maternal and prenatal well-being.

Identification and Functional Investigation of SOX4 as a Novel Gene Underpinning Familial Atrial Fibrillation

Background: Atrial fibrillation (AF) signifies the most prevalent supraventricular arrhythmia in humans and may lead to cerebral stroke, cardiac failure, and even premature demise. Aggregating strong evidence points to genetic components as a cornerstone in the etiopathogenesis of familial AF. However, the genetic determinants for AF in most patients remain elusive. Methods: A 4-generation pedigree with idiopathic AF and another cohort of 196 unrelated patients with idiopathic AF as well as 278 unrelated healthy volunteers were recruited from the Chinese population of Han ethnicity. A family-based whole-exome sequencing examination followed by a Sanger sequencing assay in all research subjects was implemented. The functional impacts of the identified SOX4 mutations were explored via a dual-reporter assay. Results: Two new heterozygous SOX4 mutations, NM_003107.3: c.211C>T; p.(Gln71*) and NM_003107.3: c.290G>A; p.(Trp97*), were observed in the family and 1 of 196 patients with idiopathic AF, respectively. The two mutations were absent in the 278 control individuals. The biochemical measurements revealed that both Gln71*- and Trp97*-mutant SOX4 failed to transactivate GJA1 (Cx43). Moreover, the two mutations nullified the synergistic activation of SCN5A by SOX4 and TBX5. Conclusions: The findings first indicate SOX4 as a gene predisposing to AF, providing a novel target for antenatal genetic screening, individualized prophylaxis, and precision treatment of AF.

Recurrent Xp22.31-Yq11 Unbalanced Translocations: Molecular Diagnosis and Clinical Implications in Three Families.

Unbalanced translocation between chromosomes X and Y is a recurring chromosomal rearrangement. The presence of a derivative chromosome X (derX), where a Yq11-qter segment is attached to the short arm of chromosome X, replacing a terminal Xpter-p22.31, poses challenges for interpretation of findings by prenatal cell-free DNA (cfDNA) screening, establishing genotype-phenotype correlation in male and female individuals, and for genetic counseling. In this report, we provide clinical outcomes, inheritance, and clinical implications of derX in three families referred to diagnostic testing due to discrepant results for sex chromosomes reported by cfDNA, abnormal prenatal ultrasound findings, recurrent pregnancy losses, or affected family members with derX transmitted through multiple generations. Reports of discrepant sex and risk for sex chromosome aneuploidy such as 45,X, 47,XXY and 47,XYY are common false positive outcomes of a prenatal cfDNA screening if either a mother or a fetus has unbalanced Xp-Yq translocation. In addition, mothers who carry der(X) facing a recurrent risk of ambiguity in prenatal testing. Pregnancy loss and neonatal death/stillbirth of male offspring are common in affected families, but this risk does not directly correlate with the size of deleted Xp region. This study emphasizes the importance of CMA and familial testing for accurate diagnosis and genetic counseling.

Sociodemographic inequalities in the uptake of prenatal HIV testing in Ethiopia: Systematic review and meta-analysis.

In order to attain the ambitious 95-95-95 UNAIDS goals, HIV testing serves as the pivotal starting point and plays a crucial role in preventing, treating, and managing HIV. Equal access to HIV testing is crucial to stop the spread of the virus. Measuring healthcare disparities is vital for promoting fairness in health services and achieving global goals for HIV prevention and treatment. Ethiopia is actively engaged in efforts to achieve these goals and is dedicated to combating HIV/AIDS. To the best of our knowledge, no previous systematic review or meta-analysis has been conducted on sociodemographic inequalities in prenatal HIV testing in Ethiopia. Hence, this study aims to assess sociodemographic inequalities in prenatal HIV testing in Ethiopia. We conducted an extensive search across various databases, such as PubMed, Scopus, Google Scholar, and Embase, to collect articles and reports. The data we gathered was then exported to R software for further analysis. Our analysis involved performing a meta-analysis of proportions using a random effect model. To assess the variability among the included studies, we used statistical measures such as I2 statistics and the Cochran's Q test. The results of the pooled prenatal HIV testing, along with its corresponding 95% confidence interval, were presented using a forest plot. A comprehensive analysis of 20 research papers on prenatal HIV testing in Ethiopia revealed that the overall pooled prevalence of testing was 69% (95% CI [60.0-80.0]). Factors such as higher education, urban residence, income, a positive attitude towards testing, marriage, and discussions about testing during antenatal care (ANC) were found to positively influence testing rates. The prevalence of prenatal HIV testing among antenatal care attendees in Ethiopia falls short of the UNAIDS target. In order to enhance the testing rates, it is advised to implement targeted initiatives within Ethiopia's public health programs. To ensure effectiveness, these initiatives should adopt a sustainable and customized approach that takes into account the specific needs and circumstances of women, particularly those who are economically disadvantaged. Ethiopia can make significant strides in enhancing the prenatal HIV testing landscape by effectively implementing policies and programs that prioritize the welfare of the less privileged. As limitation this systematic review did not include longitudinal and qualitative studies that might have provided different results. Trial registration in PROSPERO with ID: CRD42024550564.