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• The prevalence of prenatal ectopic kidney is quite low. • The most common locations of ectopic kidneys are the iliac fossa and lateral pelvic areas, respectively. • In ectopic kidney cases, both kidneys are equally affected in both genders. • Blood supply to ectopic kidneys is most commonly provided by the iliac artery and then the aorta. • The most common extraurinary anomalies accompanying prenatally diagnosed ectopic kidney are cardiac anomalies. To assess the characteristics, additional structural anomalies and postnatal urinary outcome of the cases diagnosed with fetal ectopic kidneys in the prenatal period. Cases having fetal ectopic kidneys, detected from a total of 14,617 pregnant women examined by routine detailed (Group 1) or indicated (Group 2) obstetric ultrasonography (USG) in a tertiary perinatology unit were analyzed. The prevalence of the cases, time of the diagnosis, sidedness of the affected kidney, anatomical location, origins of blood supply, additional urinary or extraurinary anomalies, and urinary complications during the postnatal follow-up period were investigated. We have detected 33 fetuses with ectopic kidneys in our cohort. The prevalence of fetal ectopic kidney was 0.22 %, with a median (min.-max.) diagnosis time of 21.3 (17.6–34) weeks. In the group in whom indicated USG was performed, the time of diagnosis was later compared to routine detailed USG (p = 0.04) group. There was no difference in terms of gender [male, (n = 14), female (n = 19), p = 0.38] and the sidedness of the ectopic kidneys (p = 0.38). The location of ectopic kidneys was most frequent in the iliac fossa (n = 20, 60.6 %) and in the lateral pelvic areas (n = 13, 39.3 %). The blood supply origin of ectopic kidneys was the common iliac artery in 22 (66.6 %), whereas the aorta in 11 cases (33.3 %). There was an additional urinary anomaly in 8 cases (24 %), an extraurinary structural anomaly, most commonly cardiac, and/or a soft marker for aneuploidy were presented in 16 cases (48 %). The most common urinary complication in the postpartum period was vesicoureteral reflux (n = 5). Ectopic kidney in the prenatal period is a rare structural anomaly that can equally affect both genders and both kidneys. Prenatal diagnosis is important for the diagnosis of additional anomalies and follow-up of postnatal complications. [ABSTRACT FROM AUTHOR]

• Cord entanglement is a frequent postpartum finding, involving 1 in every 6 deliveries. • Cord entanglement was not associated with small for gestational age newborns. • Cord entanglement was found to be associated with antepartum fetal death. • Further research is needed in order to assess cord entanglement prenatal diagnosis and implications. To evaluate the impact of umbilical cord entanglement around various fetal organs on perinatal outcomes. A retrospective population-based study of all deliveries between 1988 and 2016 at a tertiary medical center. Immediate perinatal outcomes of newborns with and without cord entanglement were compared. The prevalence of any cord entanglement in our population was 16.62 % (45,312 cases out of 272,713 deliveries during the study period). Cord entanglement was found to be significantly associated with antepartum fetal death (OR = 2.13, 95 % CI 1.77–2.57, p < 0.001) and one-minute Apgar score less than 7 (OR = 1.21, 95 % CI 1.16–1.27, p < 0.001). There was no association between cord entanglement and small for gestational age (SGA) babies. Cord entanglement is associated with antepartum fetal death, but not with SGA. [ABSTRACT FROM AUTHOR]

This study aimed to explore the genetic causes of agenesis of the corpus callosum (ACC) and assess the utility of karyotype analysis, copy number variation sequencing (CNV-seq), and whole-exome sequencing (WES) to genetically diagnose fetal ACC. We retrospectively examined 40 fetuses diagnosed with ACC who underwent prenatal ultrasonography or magnetic resonance imaging between January 2019 and October 2023. Genetic tests were conducted on the fetuses using karyotype analysis or CNV-seq as the first-line diagnosis. WES was performed if aneuploid and pathogenic CNVs were excluded. Among the 40 fetuses, 29 (72 %) had non-isolated ACC and 11 (28 %) had isolated ACC. Cerebellar dysplasia and hydrocephalus were the most common abnormal developments in the central nervous system. Twenty-eight patients underwent karyotype analysis, with a detection rate of 14 % (4/28). Twenty-six patients underwent CNV-seq; three patients were found to have pathogenic CNVs, with a detection rate of 12 % (3/26). Thirty-three fetuses with no findings of karyotype analysis or CNV-seq were subsequently tested using WES, with a detection rate of 36 % (12/33). Overall, the total diagnostic yield was 48 % (19/40), and monogenic etiology accounted for 30 % (12/40). The genetic detection rate of fetal non-isolated ACC (62 %, 18/29) was higher than that of isolated ACC (9 %, 1/11). Prenatal genetic analysis of fetuses with ACC is clinically significant, with monogenic disorders being the main cause. WES may enhance the detection rate of fetuses with ACC with negative karyotype analysis or CNV-seq results. [ABSTRACT FROM AUTHOR]

• Prenatal ultrasound diagnosis of complete cryptophthalmos, aphakia, and corneal vascularization. • Fetal ocular malformations are often associated with malformations of other organs. • This case provides a new basis for prenatal diagnosis of this rare eye disease. Complete cryptophthalmos, congenital aphakia, and corneal vascularization are relatively uncommon congenital eye malformations during the fetal period. Herein, we report a case of a fetus with complete cryptophthalmos, congenital aphakia, and corneal vascularization in both eyes and review previous prenatal reports of related cases. The patient was a 27-year-old pregnant woman, gravida 2, para 1, who was referred to our hospital for consultation at 23 weeks of gestation due to a diagnosis of fetal right renal agenesis at an external hospital. The ultrasound system of our hospital diagnosed the fetus with complete cryptophthalmos, congenital aphakia, and corneal vascularization, which was verified under the postnatal water basin test, anatomical and pathological sections. Fetal ocular malformations are often associated with malformations of other organs, and if ultrasound findings are associated with such malformations, attention should be paid to the ocular examination to avoid missing the diagnosis. [ABSTRACT FROM AUTHOR]

• Prenatal diagnosis is an important issue in cases like pelvic kidney because early detection can give the opportunity for anatomic and genetic screening for related anomalies. • Pelvic kidneys could be diagnosed in the early prenatal period. • Postnatal follow-up should be performed closely for the assessment of renal functions. Evaluation of demographic characteristics and postnatal outcomes of patients with suspected fetal pelvic kidney diagnosis followed in a tertiary center. This retrospective study was conducted in Ankara Bilkent City Hospital perinatology clinic between 2020–2023. Demographic features, prenatal ultrasound findings, and postnatal outcomes were reported. Pelvic kidney localization was on the left in 11(55 %) patients, on the right in 7(35 %), and bilateral in 2(10 %) patients in prenatal ultrasonography. The gender of the 12(60 %) fetuses were male and 8(40 %) of them were female. The pelvic kidney was an isolated finding in 8(40 %) fetuses, additional findings were present in the remaining 12(60 %) fetuses. Pelvic kidney was confirmed postnatally by ultrasound in all 18 fetuses. However two cases with prenatal ultrasound findings resulted in intrauterine fetal demise and the final diagnosis could not be confirmed as the parents refused autopsia. Cases were divided into 3 groups according to postnatal follow-up duration as 0–12 months (n = 7), 12–24 months (n = 7) and 24–44 months (n = 4). Atrial septal defect was the most common accompanying abnormality in the postnatal period (n = 4). Smaller kidney size (n = 7), vesicoureteral reflux (n = 3), and impaired renal function (n = 3) were the most common postnatal complications. Pelvic kidney can be diagnosed in fetal abnormality screening ultrasound and postnatal follow-up should be performed closely for the assessment of renal functions. [ABSTRACT FROM AUTHOR]

• Fetuses with isolated choroid plexus cyst is related to chromosome abnormalities and pathogenic or likely pathogenic copy number variants (CNVs). • There is a possibility of residual risk when providing NIPT. To evaluate the the diagnostic yield of chromosomal microarray analysis (CMA) in fetuses with isolated CPC (iCPC). A total of 315 fetuses with iCPC (iCPC group) and 364 fetuses without abnormal ultrasound findings (control group) were recruited between July 2014 to March 2018. The overall diagnostic yield of chromosomal abnormalities by CMA and karyotyping in iCPC group was up to 4.1 %, higher than 1.4 % in the control group, p < 0.05. The detection rate of pathogenic or likely pathogenic copy number variants (CNVs) with clinical significance by CMA in iCPC group (1.3 %) was higher than in control group (0 %), p < 0.05. According to the type of chromosome abnormalities, the missed diagnosis rate of non-invasive prenatal testing (NIPT) was 1.6 % in our study. The presence of iCPC on ultrasound examination suggests a potential indication for genetic counseling. Karyotyping and chromosomal microarray analysis may be considered for fetuses with iCPC. It is important to be aware of the limitations of non-invasive prenatal testing, as there is a possibility of residual risk. [ABSTRACT FROM AUTHOR]

• Prenatal testing induces elevated anxiety levels among high-risk pregnant women. • The utilization of virtual reality and music during non-stress tests alleviates anxiety and enhances satisfaction among high-risk pregnant women undergoing the procedure. • Virtual reality intervention resulted in a reduction in the duration of reactive non-stress tests. Prenatal tests cause high-risk pregnant women to experience high anxiety levels. This paper investigated the effect of Virtual Reality (VR) and music on anxiety, non-stress test parameters, and satisfaction of high-risk pregnant women undergoing non-stress tests (NSTs). This was a randomized controlled trial. The sample consisted of 102 participants randomized into three groups (VR = 34, music = 34, and control = 34). Maternal anxiety was assessed using the Spielberger State-Trait Anxiety Inventory-S (STAI-S) before and after NSTs. Satisfaction was evaluated using the Visual Analogue Scale (VAS) after NSTs. NST parameters were evaluated after NSTs. The findings were reported based on the Consolidated Standards of Reporting Trials (CONSORT). The VR and music groups had significantly lower mean posttest STAI-S scores than the control group (p <.05). There was no significant difference in NST findings (reactive/nonreactive) between the groups (p >.05). The VR group had a significantly shorter reactive NST duration than the control group (p <.05). The VR and music groups had significantly higher mean VAS-satisfaction scores than the control group (p <.05) Virtual reality and music during NSTs help high-risk pregnant women experience less anxiety and satisfy them more with the procedure. We recommend that obstetric midwives and nurses use these low-cost, simple, and noninvasive methods to reduce anxiety in high-risk pregnant women during prenatal testing. [ABSTRACT FROM AUTHOR]

• Increasing mid-trimester previa thickness is associated with previa persistence. • Mid-trimester placenta previa thickness also associated with cesarean delivery. • No association between previa thickness and other adverse outcomes. • May serve as an objective finding to guide care coordination. Increasing placental thickness is associated with adverse outcomes including earlier gestational age at delivery, lower birthweight, and lower umbilical artery pH. We aim to determine whether mid-trimester placenta previa thickness is associated with persistence of previa at time of delivery. Single-center retrospective cohort study of singleton gestations with previa diagnosed at 18–24 weeks delivering between 2015 and 2019. The thickest portion of the placenta was measured in a longitudinal plane on transabdominal imaging to determine placental thickness. We defined three cohorts: 1) thick placenta (>1 standard deviation above the mean), 2) thin placenta (>1 standard deviation below the mean), and 3) average placenta (within 1 standard deviation above or below the mean). Primary outcome was previa persistence at time of delivery. Secondary outcomes included postpartum hemorrhage, cesarean delivery, placenta accreta spectrum, and maternal morbidity composite (use of Bakri balloon, B-lynch, or O'Leary, peripartum hysterectomy, blood transfusion, ICU admission, or death). In all analyses, average thickness was used as the base comparator. Of 239 pregnancies with mid-trimester previa there were 34 thin, 166 average, and 39 thick placentas. Patients with thick placenta were older, more likely to have prior cesarean delivery, fibroid uterus, and delivery at an earlier gestational age. After adjusting for confounders, thick placenta was associated with persistent previa (aOR 6.85 [3.13–15.00]) and cesarean delivery (aOR 2.76 [1.26–6.08]). At diagnosis of mid-trimester previa, thick placenta is associated with persistence at time of delivery and delivery by cesarean section. This suggests placental thickness may assist with risk stratification and coordination of care. [ABSTRACT FROM AUTHOR]

Umbilical Artery Thrombosis (UAT) is an extremely rare complication of pregnancy strongly associated with severe fetal distress and death. The pathogenesis is still unclear but it is often associated with anatomical cord abnormalities that leads to blood stasis and thrombosis formation. Other possible risk factors are maternal thrombophilia, autoimmune disease, gestational diabetes, hypertension disorders of pregnancy and Rh-alloimmunization. The most common clinical symptom is the reduction of fetal movements. The diagnosis is histopathological, but it can be suspected by clinical and prenatal ultrasound findings. Generally, the first choice therapy is the immediate delivery with cesarean section. This study reported a case of a spontaneous intrauterine UAT in a low-risk pregnancy and a systematic review of the literature on clinical, ultrasound and histopathological findings of UAT, in order to help clinicians in the diagnostic process and management of this rare complication. [ABSTRACT FROM AUTHOR]

There is some evidence that in twin reversed arterial perfusion sequence, intervention at early gestational age could prevent a spontaneous death of the pump twin, achieving a better global survival. To review the perinatal outcomes of early intervention in pregnancies complicated by twin reversed arterial perfusion (TRAP) sequence. A comprehensive search from inception to December 2022 was conducted on databases including MEDLINE, EMBASE, Cochrane Library and LILACS. All studies that reported intervention in twin or triplet pregnancy complicated with TRAP sequence at 12 + 0 to 16 + 6 weeks of gestation were eligible. A descriptive and bivariate analysis was performed. Out of the 222 full-text articles, 44 studies reporting 108 cases of early intervention in TRAP sequence were included. A successful procedure was achieved in 105 (95.5 %) interventions: 89 (94.7 %) among twin pregnancies and 16(100 %) among triplet pregnancies. An overall livebirth rate was achieved in 75 patients (70.8 %): intrafetal laser group 55 (73.3 %), radiofrequency 10 (76.9 %) and endoscopic laser 3 (75.0 %). The median gestational age at delivery was 38 + 0 (37 + 4 – 39 + 4) weeks. The median treatment–delivery interval was 23 + 2 (IQR, 21 + 0–25 + 6) weeks. The most frequent adverse outcomes reported were preterm labor in 7 (13.7 %) patients. There were no severe adverse maternal outcomes. Early intervention with intrafetal laser and radiofrequency in TRAP sequence achieves a livebirth rate of the pump twin of about 75 %. [ABSTRACT FROM AUTHOR]

• The risk of vertical transmission is higher in primary compared to non-primary infection, but there are no differences in terms of long-term sequelae once congenital infection has been established. • Ultrasound is the primary imaging modality to evaluate fetuses with congenital CMV infection. However, the positive predictive value of ultrasound is poor in the absence of confirmed fetal infection with amniocentesis. • MRI should be used to detect anomalies not easily identified by ultrasound and should be recommended in all pregnant women with positive amniocentesis at 28–32 weeks of gestation. • Early gestational age at maternal infection is one of the main determinants of post-natal adverse outcome in fetuses with congenital CMV infection. • Maternal therapy with high dose valacyclovir (2 g every 6 h, 8 g/day) can reduce the risk of vertical transmission, the symptomatic status and other adverse outcomes associated with congenital CMV infection, while HIG is not recommended. Although the clinical work-up of CMV in pregnancy has gradually become more accurate, counseling for CMV is still challenging. Despite the potential feasibility of universal prenatal serological screening, its introduction in prenatal diagnosis continues to raise concerns related to its real cost-effectiveness. Contextually, anticipating the confirmation of fetal infection earlier in pregnancy is one of the most pressing issues to reduce the parental psychological burden. Amniocentesis is still the gold standard and recent data have demonstrated that it could be performed before 20 weeks of gestation, provided that at least 8 weeks have elapsed from the presumed date of maternal seroconversion. New approaches, such as chorionic villus sampling (CVS) and virome DNA, even if not yet validated as confirmation of fetal infection, have been studied alternatively to amniocentesis to reduce the time-interval from maternal seroconversion and the amniocentesis results. Risk stratification for sensorineural hearing loss (SNHL) and long-term sequelae should be provided according to the prognostic predictors. Nevertheless, in the era of valacyclovir, maternal high-dose therapy, mainly for first trimester infections, can reduce the risk of vertical transmission and increase the likelihood of asymptomatic newborns, but it is still unclear whether valacyclovir continues to exert a beneficial effect on fetuses with positive amniocentesis. This review provides updated evidence-based key counseling points with GRADE recommendations. [ABSTRACT FROM AUTHOR]

To analyze the risk for genetic aberrations and pregnancy outcomes in pregnancies with isolated polyhydramnios. This was a retrospective study of singleton pregnancies complicated by isolated polyhydramnios that underwent genetic amniocentesis between 2016 and 2021. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, chromosomal microarray results, and pregnancy outcomes. A total of 94 singleton pregnancies were included. Three (3.2%) cases with chromosomal abnormalities were detected, including 2 case of trisomy 21 and 1 of 22q21.1 microdeletion. One case was diagnosed as Prader-Willi syndrome caused by maternal uniparental disomy of chromosome 15. Perinatal death occurred in 1 case with severe polyhydramnios, and was retrospectively diagnosed as Bartter syndrome. Of the 90 infants survived, two were identified to have single gene disorders after birth by whole exome sequencing. We first attempted to determine the value of exome sequencing in pregnancies with isolated polyhydramnios. Our results warrant more studies to evaluate advanced genetic testing technologies used in such pregnancies. [ABSTRACT FROM AUTHOR]

• Small fetal HC that are less than −3 SD is associated with genetic variants, especially those with intracranial anomalies. • Fetuses with small head that do not reach the diagnosis criteria of microcephalycan't be simply explained as part of FGR. • Genetic variants, mainly CNV and SNV, can explain a substantial proportion of small fetal HC and most them are de novo. • CMA is practical for testing fetuses with small HC, and WES is more effective for genetic testing. • The novel findings about microcephaly-associated genes add value to the clinical use of exome sequencing in this population. • These findings help with the prenatal diagnosis of suspected fetal microcephaly and distribute to our clinical counselling. Objectives: To comprehensively evaluate the contributions of numerical chromosomal abnormality, copy number variant (CNV), and sequence variant (SV) to fetuses with small head circumference in a Chinese cohort using chromosome microarray analysis and whole exome sequencing. Methods: A total of 157 fetuses with small heads defined as head circumference < − 2 standard deviation (SD) were recruited between October 2014 and March 2023. We used the ultrasonic measurement parameter Z-score to define small head as possible microcephaly (3 < Z ≤ -2), microcephaly (-5 < Z ≤ -3), or pathologic microcephaly (Z ≤ -5). Ultrasound findings and genetic results were analyzed. Results: The overall diagnostic yield of chromosomal abnormalities by microarray analysis was 13 %. Whole exome sequencing revealed eight novel variants and two interesting candidate genes and provided a 25.4 % incremental yield compared with microarray analysis. Of the detected SVs, 56 % were de novo and the most common inheritance pattern was autosomal dominant inheritance presented in 11/16 fetuses. Compared with isolated small heads, non-isolated small heads had a significantly higher detection rate of chromosomal abnormalities (16 % vs. 3.0 %, P = 0.049) but not SVs (24 % vs. 5.5 %, P = 0.126). Subgroup analysis showed that intracranial anomalies had a similar high detection rate of SVs in fetuses with all small heads subgroups while no chromosomal abnormalities and causative SVs were found in fetuses with isolated possible microcephaly. Conclusions: Ultrasound findings of small fetal head circumference < 3 SD below the mean, especially those with intracranial structural abnormalities, indicate the need for genetic counseling. Genetic variants, mainly copy number variants and SV, may be responsible for the substantial proportion of small fetal head circumference, while most are de novo. Whole exome sequencing and microarray analysis are effective diagnostic approaches for this population. [ABSTRACT FROM AUTHOR]

To present the prenatal features and postnatal outcomes of pregnancies with fetal nemaline myopathy (NM). This was a retrospective study of nine cases with NM diagnosed by prenatal or postnatal clinical features and confirmed by genetic testing. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, exome sequencing (ES) results, and pregnancy outcomes. All of the nine cases were detected to have NM-causing variants, involving NEB gene in 2 cases, ACTA1 in 3 cases, KLHL40 in 3 cases, and TPM2 in 1 case. Almost all (8/9) had normal first-trimester ultrasound scans except one who had an increased nuchal translucency. Seven (7/9) cases had second-trimester abnormal ultrasounds with fetal akinesia and/or extremity anomalies. Two (2/9) had only third-trimester abnormal ultrasounds with fetal akinesia and polyhydramnios, with one combined with fetal growth restriction. Four pregnancies with a positive prenatal ES were terminated, while five having not receiving prenatal ES continued to term. Only one infant survived 1 year old, and four passed away within 12 months. Prenatal ultrasound can detect clues that lead to the diagnosis of NM, such as reduced or absent fetal movements, polyhydramnios and extremity anomalies. [ABSTRACT FROM AUTHOR]

• Redesign of the low-cost simulator model already described in the literature. • A training as close to reality as possible with the intervention of an actress. • Improving the practical training of interns. • Improving resident training in the relationship with the patient. • Maintain the knowledge for low-practice practitioners. Amniocentesis is the most performed invasive prenatal diagnostic procedure. Learning the procedure is difficult for the learner, the teacher and the patient because of the risks inherent to this technique and the anxiety generated by the procedure. The objective of this work was to evaluate a theoretical and practical amniocentesis training workshop using a simulator. We were inspired by Pierre Jean's precepts for the planning of a medical training. We then carried out the pedagogical session with the gynecology residents of our Regional University Hospital, a type 3 maternity hospital in France. We evaluated the theoretical learning through a questionnaire before and after the training and then the practical session on a home-made simulator. The satisfaction of the participants was assessed by a questionnaire at the end of the session. Fifteen learners, from the first to the last semester of internship, participated in the training. The median score of the pre-training questionnaire ("pre-test" questionnaire) was 3.3 out of 10 (min = 1, max = 6) and that of the post-training questionnaire ("post-test" questionnaire) was 7.9 out of 10 (min = 6, max = 9). The post-training scores were significantly higher (p < 0.0007). The average score for the practical training was 30.5 out of 40 (24–36). 93 % of the learners were fully satisfied with the theoretical training and 100 % stated that they had improved their technical skills. The residents in our department expressed a need for training in this invasive procedure of antenatal diagnosis. The training proved to be beneficial following the evaluation of the learning but also following the feedback of the learners. [ABSTRACT FROM AUTHOR]

Polyhydramnios can be caused by genetic defects at times. However, to establish an accurate diagnosis and provide a precise prenatal consultation in a given case is still a great challenge toward obstetricians. To uncover the genetic cause of polyhydramnios in the two consecutive pregnancies, we performed whole-exome sequencing of DNA for the second suffering fetuses, their parents, and targeted sanger sequencing of other members of this family. We discovered a hemizygous truncating variant in MTM1 gene, c.438_439 del (p. H146Q fs*10) in this Chinese family. In the light of the molecular discoveries, the fetus's clinical phenotype was considered to be a good fit for X-linked myotubular myopathy (XLMTM). There is no related research to the prenatal manifestations of MTM1-related XLMTM among Chinese population, and this is the first one to present. Though the etiology of polyhydramnios is complicated, WES may provide us with a creative avenue in prenatal diagnosis. [ABSTRACT FROM AUTHOR]

• Prenatal ultrasound-based diagnosis of epidermolysis bullosa is difficult, but not impossible. Several sonographic signs, even if nonspecific, are more frequently reported in the few cases described in literature to date. • The prenatal ultrasound confirms a good level of accuracy in assessing fetuses with suspicion of epidermolysis bullosa. • This paper suggests for future investigations to carefully evaluate the muco-cutaneus areas, including the perioral area. The fetal mobility and the 3D ultrasound should be part if the examination. This is the first systematic review specifically focused on prenatal ultrasound signs of EB. Epidermolysis bullosa is a rare hereditary autosomal disease that is included in the heterogeneous group of genodermatosis. It is characterized by skin and mucous membranes fragility and denudation, and it can be associated with pyloric atresia. Prognosis is often poor, and death can occur in neonatal period due to severe sepsis. We present a case of fetal junctional epidermolysis bullosa in a consanguineous couple, highly suggested by previous obstetric history and several antenatal ultrasound signs, such as polyhydramnios, gastric enlargment, the "snowflake sign", abnormal external ears, signs of skin desquamation, lower limbs anomalies and chorioamniotic membrane separation. We describe a marked perioral hipoecogenicity as a novel sign of skin-mucous denudation, which could be helpful for future diagnosis. A review of literature, focused specifically on the antenatal sonography role, is also reported. Prenatal ultrasound-based diagnosis of epidermolysis bullosa is difficult, especially in apparently low risk contexts, but may be possible. [ABSTRACT FROM AUTHOR]

We report a case of a fetus with 46,XX testicular disorder of sex development detected prenatally. This fetus was found abnormally due to non‐invasive prenatal testing. Amniocentesis revealed SRY gene on the X chromosome of the fetus. The related literature was reviewed, and the advantages and limitations of various prenatal diagnostic techniques were discussed. The combination of non‐invasive prenatal testing and various prenatal diagnostic techniques has enabled more fetuses with sex reversal to be detected. [ABSTRACT FROM AUTHOR]

• With an own financial contribution, there is no equal access to fetal aneuploidy screening. • To overcome this inequality, the own contribution of the NIPT should be abandoned. • Since the majority of the parents makes an informed choice, the fear of routinization is redundant. First trimester non-invasive prenatal testing (NIPT) provides pregnant women with a reliable, non-invasive method to screen for fetal aneuploidies. In the Netherlands, there is a nationwide prenatal screening program in which pregnant women and their partners are counseled about their options around 10 weeks of pregnancy. The first trimester and second trimester scan are fully reimbursed but the NIPT has an own financial contribution of €175 per participant, irrespective of type of insurance. The arguments for this own contribution are fear of uncritical use of NIPT or routinization. NIPT has a relatively stable uptake of 51%, against over 95% for second trimester anomaly scan. We aimed to explore the effect of this financial contribution on the decision to opt out of NIPT. We performed a survey among 350 pregnant women undergoing a second trimester anomaly scan in our center, Amsterdam UMC, between January 2021 and April 2022. All pregnant women who declined NIPT in the first trimester, were asked to participate and answered 11–13 questions about the decision-making process, the reasons to opt out and the financial contribution. Information about NIPT was desired in 92% of women and 96% felt sufficiently informed. Most women took the decision not to perform NIPT with their partner and did not experience difficulties in taking this decision. The most important reason to decline NIPT was: "Every child is welcome" (69%). "The test was too expensive" was answered in 12% and was significantly correlated with lower maternal age. Additionally, one in five women (19%) said they would have done NIPT if it had been for free, which was significantly higher in younger women. The own financial contribution plays a role in the decision-making to decline NIPT and partly explains the low uptake in the Netherlands. This suggests that there is no equal access to fetal aneuploidy screening. To overcome this inequality, this own contribution should be abandoned. We speculate that this will have a positive effect on the uptake, which will increase to at least 70% and potentially 94%. [ABSTRACT FROM AUTHOR]

The main purpose of this study was to report the incidence of lower urinary tract injuries (UTI) during cesarean section (CS) hysterectomy in cases of Placenta Accreta Spectrum (PAS) disorders. Study design Retrospective analysis including all women with a prenatal diagnosis of PAS between January 2010 and December 2020. A dedicated multidisciplinary team was involved to define a tailored management for each patient. All relevant demographic parameters, risk factors, degree of placental adhesion, type of surgery, complications and operative outcomes were reported. One hundred and fifty-six singleton gestations with a prenatal diagnosis PAS were included in the analysis. 32.7% of cases were classified as PAS 1 (grade 1-3a FIGO classification), 20.5% as PAS 2 (grade 3b FIGO classification) and 46.8% as PAS 3 (grade 3c FIGO classification). A CS hysterectomy was performed in all cases. Surgical complication occurred in seventeen cases (0% in PAS 1, 12.5% in PAS 2 cases and in 17.8% in PAS 3). The incidence of UTI in our series was 7.6% in all women with PAS, including 8 cases of bladder and 12 of ureteral lesion, and 13.7 % in those with PAS 3 only. Despite advances in prenatal diagnosis and management, surgical complications, mainly those involving the urinary system, still occur in a significant proportion of women undergoing surgery for PAS. The findings from this study highlight the need for a multidisciplinary management of women with PAS in centers with high expertise in prenatal diagnosis and surgical management of these conditions. [ABSTRACT FROM AUTHOR]

Prenatal diagnosis of craniosynostosis remains rare and challenging, easier in syndromes with craniosynostosis due to the association with other sonographic anomalies. Crouzon syndrome is the most frequent syndrome with craniosynostosis but is difficult to detect antenatally because of mild skull deformation without specific associated anomaly during gestation. This report presents the case of a fetus with Crouzon syndrome related to the variant c.1646A>C in exon 14 of the FGFR2 gene and presenting with apparently isolated scaphocephaly on fetal US. This observation supports the interest of systematic prenatal panel genes testing when facing an apparently isolated craniosynostosis diagnosed on fetal imaging, even if non-syndromic craniosynostosis are much more frequent in such situation. Syndromic craniosynostosis can appear as apparently isolated form on fetal imaging. Systematic prenatal panel genes testing can be contributive even when facing an apparently isolated craniosynostosis on fetal imaging. [ABSTRACT FROM AUTHOR]

To present the fetal features of Cornelia de Lange Syndrome (CdLS) with a molecular confirmation. This was a retrospective study of 13 cases with CdLS diagnosed by prenatal and postnatal genetic testing and physical examination. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, chromosomal microarray and exome sequencing (ES) results, and pregnancy outcomes. All of the 13 cases were detected to have a CdLS-causing variant, with 8 variants identified in the NIPBL gene, 3 in SMC1A , and 2 in HDAC8. Five had normal ultrasound scans during pregnancy; all were caused by variants of SMC1A or HDAC8. For the eight cases with NIPBL variants, all had prenatal ultrasound markers. Three had first trimester ultrasound markers including increased nuchal translucency in one and limb defects in three. Four presented with normal ultrasound in the first trimester, but abnormal ultrasound in the second trimester, including micrognathia in two, hypospadias in one and intrauterine growth retardation (IUGR) in one. IUGR as the isolated feature was identified in one case in the third trimester. The prenatal diagnosis of CdLS caused by NIPBL variants is possible. It seems to remain challenging to detect non-classic CdLS only relying on ultrasound examination. [ABSTRACT FROM AUTHOR]

To evaluate the value of noninvasive prenatal testing (NIPT) in the screening of rare autosomal abnormalities and provide further support for the clinical application of NIPT. A total of 81,518 pregnant women who underwent NIPT at the Anhui Maternal and Child Health Hospital between May 2018 and March 2022 were selected. The high-risk samples were analyzed using amniotic fluid karyotype and chromosome microarray analysis (CMA), and the pregnancy outcomes were followed up. NIPT detected 292 cases (0.36%) with rare autosomal abnormalities among the 81,518 cases sampled. Of these, 140 (0.17%) showed rare autosomal trisomies (RATs), and 102 of these patients agreed to undergo invasive testing. Five cases were true positives, with a positive predictive value (PPV) of 4.90%. Copy number variants (CNV) were detected in 152 samples of the total cases (0.19%), and 95 of the patients involved agreed to the use of CMA. Twenty-nine of these cases were confirmed to be true positive, with a PPV of 30.53%. Detailed follow-up information was obtained in 81 cases from 97 patients with false-positive results for RATs. Thirty-seven of these cases (45.68%) had adverse perinatal outcomes, with a higher incidence of small for gestational age (SGA), intrauterine growth retardation (IUGR), and preterm birth (PTB). NIPT is not recommended for screening for RATs. However, considering that positive results are associated with an increased risk of IUGR and PTB, additional fetal ultrasound examination should be performed to monitor fetal growth. In addition, NIPT has a reference value in screening for CNVs, especially pathogenic CNVs, but a comprehensive analysis of prenatal diagnosis combined with ultrasound and family history is still needed. [ABSTRACT FROM AUTHOR]

Genital anomalies are a heterogeneous group of congenital pathologies that have become increasingly relevant since the Chicago Consensus of 2005. Their postnatal diagnosis has developed significantly in the last two decades, while prenatal diagnosis seems to be underdeveloped, with few protocols available, fragmented scientific literature, and low diagnostic rates. This review aims to examine the current status of this subspecialty from the perspective of prenatal imaging. Indications for the evaluation of fetal genitalia can be divided into medical and non-medical reasons. Medical reasons include sex-linked disorders, detection of other anomalies, relevant family history, or multiple pregnancy. Non-medical reasons include parental request for sex disclosure. Disclosure of fetal sex may be associated with ethical, legal, and medical issues. The main imaging technology used is 2D ultrasound, although there are other complementary techniques such as 3D, MRI, or Color Doppler. Regarding working methodology, several authors have drawn attention to the lack of standardized protocols and guidelines. Most guidelines tend to limit their recommendations to study indications and ethical issues. Technical proposals, measurements, or working methods have not yet been standardized. Fetal sex determination is usually divided into early and late gestation. Early gestation is based on the sagittal sign. Late gestation is based on direct visualization. There are several measurements to describe male and female genitalia, such as penile length, bilabial diameter, or scrotal diameter. Prenatal diagnosis of genital pathologies presents some particularities such as the wide spectrum of phenotypes, the high frequency of associated deformities, or the time of diagnosis. Some of the most frequent pathologies are ambiguous genitalia, fetal sex discordance, hypospadias, micropenis, clitoromegaly, ovarian cysts, hydro(metro)colpos, and cloacal anomalies. Higher-quality studies and direction from scientific societies through the implementation of clinical guidelines are needed. [ABSTRACT FROM AUTHOR]

Objective: To determine the fetal ultrasound findings associated with Sotos syndrome caused by deletions at 5q35 including the NSD1 and a point mutation in this gene.Study Design: This was a retrospective study of eight pregnancies with fetal Sotos syndrome identified by chromosomal microarray (CMA)/whole exome sequencing (WES). Clinical and laboratory data were collected and reviewed for these cases.Results: Two cases had no significant fetal abnormalities, and were only diagnosed after birth. One case presented in the first trimester with increased nuchal translucency. The remaining five fetuses were identified at late gestation. One of the five fetuses presented in the second trimester with mild ventriculomegaly, and four in the third trimester with mild ventriculomegaly, macrocephaly and polyhydramnios. CMA was done on all cases and revealed 5q35 deletions in seven cases, and WES detected a maternally inherited NSD1 variant in one case.Conclusion: The fetal ultrasound findings in cases with Sotos syndrome, associated with deletions at 5q35 and a point mutation in the NSD1 are not specific with the most common finding being mild ventriculomegaly. [ABSTRACT FROM AUTHOR]

Objective: To present the experience on prenatal diagnosis of Miller-Dieker syndrome (MDS)/PAFAH1B1-related lissencephaly to further determine fetal phenotypes of this syndrome.Study Design: This was a retrospective study of ten pregnancies with fetal MDS/PAFAH1B1-related lissencephaly identified by chromosomal microarray (CMA)/exome sequencing (ES). Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, CMA or ES results and pregnancy outcomes.Results: Two cases were diagnosed in the first trimester because of an increased nuchal translucency. The remaining eight cases were identified at late gestation, including four in the second trimester because of fetal cardiac anomalies or ventriculomegaly, and four in the third trimester because of ventriculomegaly. CMA revealed 17p13.3 deletions in nine cases, and ES detected a de novo PAFAH1B1 missense mutation in one case.Conclusion: The prenatal presentation of MDS/PAFAH1B1-related lissencephaly depended on the gestational age when the diagnosis was made. Mild ventriculomegaly was the most common prenatal sonographic sign identified in cases of MDS/PAFAH1B1-related lissencephaly. It is important that fetal MRI and invasive testing with CMA should be considered in fetuses with apparently 'isolated' mild ventriculomegaly. [ABSTRACT FROM AUTHOR]

Objective: This study aims to assess accuracy and clinical utility of postmortem radiological exams [Magnetic Resonance Imaging (MRI), Computed Tomography (CT) and Radiography (XR)] after termination of pregnancy at <23 weeks' gestation for congenital fetal malformations in comparison to autopsy.Study Design: This a prospective single-center study on fetuses underwent termination of pregnancy for fetal defects. Overall concordance between any radiological exam and autopsy was evaluated. For postmortem MRI only, the following subgroups were analyzed: 1) total agreement; 2) agreement for main findings; 3) agreement for main findings but major relevant additional findings at autopsy; 4) total disagreement.Results: 174 cases were collected. The overall concordance with autopsy for main findings was 71% (115/163) for postmortem MRI and 99% (173/174) for prenatal ultrasound (US). Postmortem MRI detection rate was high for central nervous system (CNS) defects (98%), gastrointestinal, genitourinary and respiratory defects (100%), while it was poor for cardiovascular and musculoskeletal defects (25% and 42%, respectively). For musculoskeletal abnormalities, the performance of postmortem XR and postmortem CT exams improved the detection rate from 42% for postmortem MRI alone to 92%.Conclusions: Postmortem MRI has a good overall concordance for fetal defects after termination of pregnancy performed at <23 weeks. Along with autopsy, postmortem MRI may be offered for all cases of CNS defects in order to prevent inconclusive exams due to autolysis of the brain tissue, while postmortem CT and postmortem XR are indicated for musculoskeletal defects. In the presence of multiple abnormalities or cardiac defects the couple should be counseled on the poor performance of radiological investigations. [ABSTRACT FROM AUTHOR]

Non-invasive prenatal testing (NIPT) is currently the best screening test for fetal chromosome abnormalities with the highest sensitivity and specificity and can be done from 10 weeks gestation. We report a detection of 44.7 Mb duplication at 11p15.5-p11.2 by NIPT with a fetal fraction (FF) of only 3%. This chromosome abnormality was confirmed after amniocentesis by karyotyping and array comparative genomic hybridization (aCGH) on cultured fetal cells. Further parental investigation showed that the fetal chromosome abnormality was inherited from the mother who was a carrier of a balanced translocation 46,XX,t(11;X)(p11.2;q28). This case highlights the importance of expanded NIPT in the detection of fetal segmental aneuploidy. NIPT together with complementary studies can lead to the detection of parental chromosome rearrangement despite a low FF, which can impact the couple's reproductive plans. We also reviewed other cases with chromosome rearrangement, detected by NIPT, derived from a parental reciprocal translocation. [ABSTRACT FROM AUTHOR]

Objective: To estimate the incremental yield of single nucleotide polymorphism (SNP) array over karyotype and to assess the diagnostic accuracy of SNP array as a stand-alone test versus SNP array with karyotype in detecting chromosomal abnormalities for prenatal diagnosis in women with an abnormal fetal ultrasound.Study Design: Studies in which SNP array and karyotype had been used for diagnosing chromosomal aberrations in fetuses with abnormal ultrasound findings were included. A systematic search of relevant studies published in the English language in EMBASE, PubMed, CENTRAL, CDSR (Cochrane database of systematic reviews), SCOPUS and Web of science between 1996 and May 2020 was performed. Primary outcome was incremental yield of SNP array over karyotype (number of patients with abnormalities detected by SNP array over number of patients with normal karyotype). Other outcomes included diagnostic accuracy of SNP array alone versus SNP array and karyotype for prenatal diagnosis. Pooled sensitivities, specificities, and their 95% confidence intervals (CI) were presented.Result(s): Seven studies were included. The incremental yield of SNP array over karyotype was 8% (95% Confidence interval, CI 4-12%) while incremental yield of karyotype over SNP array in foetus with abnormal ultrasound was 0% (95% CI 0-1%). The agreement between SNP array and karyotype was 92%. The variant of unknown significance rates ranged between 4 and 8 %. The pooled sensitivity and specificity of SNP array versus SNP array and karyotype was 0.97 (95% CI 0.92-0.99) and 1.00 (95% CI1.00-1.00), respectively.Conclusion(s): SNP array provides additional information on chromosomal abnormalities over and above conventional karyotype. When used as a stand-alone test, SNP array performs favourably as a diagnostic modality when compared against SNP array and karyotype for prenatal diagnosis with an abnormal fetal ultrasound. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography.Method: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (Results: 187 fetuses with a prenatal diagnosis of isolated severe ventriculomegaly on neurosonography were included in the analysis. Additional structural anomalies were detected exclusively at prenatal MRI in 18.1% of cases. When considering the type of anomaly, malformations of cortical development were detected on MRI in 32.4% cases, while midline or acquired (hypoxemic/hemorrhagic) lesions were detected in 26.5% and 14.7% of cases, respectively. There was no difference in the rate of additional anomalies when stratifying the analysis according to either gestational age at MRI or laterality of the lesion. At multivariate logistic regression analysis, the presence of additional anomalies only found at MRI was significantly higher in bilateral compared versus unilateral ventriculomegaly (OR: 4.37, 95% CI 1.21-15.76; p = 0.04), while neither maternal body mass index, age, severity of ventricular dilatation, interval between ultrasound and MRI, nor gestational age at MRI were associated with the likelihood of detecting associated anomalies at MRI.Conclusion: The rate of associated anomalies detected exclusively at prenatal MRI in fetuses with isolated severe ventriculomegaly is lower than previously reported, but higher compared to isolated mild and moderate ventriculomegaly. Fetal MRI should be considered as a part of the prenatal assessment of fetuses presenting with isolated severe ventriculomegaly at neurosonography. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of implementing cell-free DNA (cfDNA) testing on gestational age (GA) at termination of pregnancy in a French perinatal network.Methods: We conducted a retrospective study. All women having undergone a termination of pregnancy between 1 January 2012 and 31 December 2017 were included. We compared the periods before and after the introduction of second-line cfDNA testing, which started on 1 January 2015. Throughout the study period, the invasive procedures were foetal karyotyping and chromosomal microarray analysis. The primary study outcome was GA at termination. The secondary outcomes were GA at termination for trisomy 21 and the frequency and GA at the time of invasive procedures.Results: During the 6-year study period, 840 women underwent termination. The median GA at termination before and after the implementation of cfDNA testing was 19.4 and 19.0 weeks, respectively (p = 0.38). Although the frequency of termination for trisomy 21 increased significantly from 23% to 32% (p < 0.01), the median GA at termination did not change significantly (p = 0.80). The implementation of cfDNA testing was associated with a decrease in the frequency of invasive procedures in general and chorionic villus sampling in particular (p = 0.04).Conclusion: The introduction of cfDNA testing does not increase the GA at termination for trisomy21. [ABSTRACT FROM AUTHOR]

Objective: To evaluate concordance between prenatal and postnatal diagnosis of congenital talipes equinovarus (cTEV), rates of surgery and postnatal outcomes in relation to the prenatal classification of severity.Study Design: This is a retrospective observational cohort study on fetuses with a prenatal diagnosis of cTEV between 2004 and 2018. All cases of isolated cTEV in singleton pregnancies were included. Postnatally, the Ponseti method was applied. Children were followed-up postnatally for at least two years, with a specific focus on neurodevelopmental outcome.Results: The cohort included 81 fetuses with a prenatal diagnosis of cTEV confirmed postnatally in 86.4% of cases. Concordance between prenatal and postnatal assessment was good for both laterality and degree of severity (k = 0.61 and 0.66, respectively). The average Pirani score, number of casts and rates of Achilles tendon tenotomy were higher for III degree cTEV (p < 0.001). Within this group only, the rate of relapse was 11% and the rates of major surgery was 6%. The postnatal outcome was normal in 68.6% newborns, while 14% of cases had a diagnosis of minor additional findings and 17% had an impairment of neurological development. None of the outcome was statistically correlated to the prenatal assessment of laterality or degree.Conclusions: The accuracy of prenatal ultrasound for isolated cTEV is 86% with a false positive diagnosis of 14%. The grade of cTEV assigned prenatally correlates to postnatal severity and longer orthopedic rehabilitation in terms of number of casts and need of surgery. The assessment of the correlation between cTEV and neurological impairment requires further prospective studies on larger cohorts. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prognosis of fetuses with a prenatal diagnosis of micrognathia in the first trimester.Study Design: Over a 3-year period, patients with fetal micrognathia were detected at the time of nuchal translucency screening. The medical records of these pregnancies were reviewed, including maternal demographics, sonographic findings, genetic testing results and pregnancy outcomes.Results: Forty-three cases of first-trimester micrognathia were included in this study. Chromosomal abnormalities were detected in seven cases. Of the fetuses with a normal array, further investigation of monogenic disorders with whole-exome sequencing was undertaken in 13 cases. Monogenic syndromes were identified in eight cases, including six with de-novo dominant alleles and two with recessive conditions. Whole-exome sequencing was refused in 23 cases; among these, other additional anomalies were found on anatomic ultrasound in 10 cases.Conclusion: This study demonstrated that caution should be adopted when finding an apparently isolated micrognathia in early gestation, even with a normal array. A diagnosis of genetic syndrome or multiple anomalies on subsequent scans is most likely, and will affect the final prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Alongside initial screening obstetric US, use of placental MRI has been increasing in the last few decades to aid with antenatal diagnosis and delivery planning in Placenta Accreta Spectrum (PAS). The aim of this study was to determine if the MRI pathophysiological sign subcategories described in the current literature can predict the severity of pathologic diagnosis.Methods: Institutional imaging records were reviewed for placental MRIs performed for suspicion of PAS in the last decade. Electronic health records were searched for patient history and pathology. The 59 MRI studies were reviewed using the 11 MRI signs described by the SAR and ESUR joint consensus statement. Further breakdown of the signs was divided by underlying pathophysiologic subcategories including gross morphologic, interface and tissue architecture signs.Results: Pathologic diagnosis yielded 34 cases: accreta 4/34, incerta 14/34, percreta 10/34 and normal 6/34. Of the accreta cases all of them demonstrated at least two interface and half of the cases had tissue architecture signs, 13/14 increta cases demonstrated interface signs and 12/14 demonstrated tissue architecture signs, 9/10 percreta cases had two interface and at least six demonstrated three tissue architecture signs. Statistical analysis showed significant difference between pathologic diagnosis and the number of positive interface signs with p = 0.02.Discussion: Interface signs were the most objective and sensitive MRI subcategory. Statistical analysis determined there was a significant difference between PAS diagnosis and number of interface signs present. This subcategory has the most overlap with classic US signs which are traditionally used before MRI referral. [ABSTRACT FROM AUTHOR]

Objective: To determine monogenic syndromes in cases of fetal akinesia in order to understand the genetic aetiology.Study Design: Clinical trio exome sequencing (ES) was performed on DNA extracted from postnatal samples in 12 cases with fetal akinesia identified by prenatal ultrasound and a normal chromosomal micro-array analysis result. This test targets coding exons for 4200 clinically relevant disease-causing genes. The interpretation of variants was performed according to the guidelines of the American College of Medical Genetics.Results: A definite molecular diagnosis was achieved in six (50 %) of the 12 cases using clinical trio ES. In five cases, the pathogenic variants were located in known fetal-akinesia-associated genes. In one case, the underlying pathogenic variants were in known disease genes that had not been linked to fetal akinesia previously. Six pregnancies were terminated by the parents, and six pregnancies were continued to term.Conclusion: Genetic defects leading to fetal akinesia were found in half of the study cases using clinical trio ES. This information will be useful in genetic counselling with regard to prognosis and risk of recurrence. [ABSTRACT FROM AUTHOR]

Objective: We examined the potential value of combining ultrasound and non-invasive prenatal screening (NIPS) of maternal blood to screen for major aneuploidies as an early approach before selective fetal reduction from twin pregnancy to singleton.Study Design: The sample was composed of pregnant women with di-chorionic di-amniotic twins who chose to undergo fetal reduction to singleton at 12-24 weeks of gestation. These women were asked to provide a blood sample for cell-free fetal DNA (cffDNA) testing prior to fetal reduction.Results: A total of 24 pregnant women with a twin pregnancy prior to fetal reduction to singleton were enrolled. There were 8 cases with structural anomalies (33.3%) in one twin that dictated fetal reduction. The proportion of patients who underwent selective fetal reduction for fetal abnormalities was larger than in several other studies. The NIPS identified 1 case of Trisomy 13 (4.2%). The other 15 cases (62.5%) had no structural or chromosomal anomalies. The decision to undergo elective reduction of twin pregnancy to singleton was made for social reasons or upon the parents' request. Given the 33% of structural anomalies in the cohort, a cost analysis indicated that this procedure was 6.6-fold less expensive (vs. 4.6-fold with 4% structural anomalies in other publications) than conducting invasive procedures for the entire cohort.Conclusion: The findings suggest that an early anatomical scan and cffDNA can increase the overall safety margin and reduce interventional procedures before elective reduction of twin pregnancy to singleton. However, a larger cohort is needed to confirm these results. [ABSTRACT FROM AUTHOR]

Placenta accreta spectrum (PAS) is an umbrella term for a variety of pregnancy complications due to abnormal placental implantation, including placenta accreta, placenta increta and placenta percreta. During the past several decades, the prevalence of PAS has been increasing, and the clinical importance of this disease is significant because of the severe complications. In this review, we summarized the available evidence-based data for PAS in various aspects: prevalence, risk factors, pathogenesis, clinical presentation and prenatal screening, and clinical management. Meanwhile, we provided a series of prospects in each section for further studies on PAS. Moreover, we first present a visualized workflow for the management of PAS from three steps: predelivery, during delivery and postdelivery. [ABSTRACT FROM AUTHOR]

Non invasive prenatal Testing (NIPT) is changing the practice of prenatal diagnosis worldwide. It provides high sensitivity and specificity in screening for common aneuploidies. As a result, it has reduced the number of invasive procedures, thereby reducing their associated risk of pregnancy miscarriage. NIPT is based on the detection and analysis of cell free fetal DNA (cffDNA) that is obtained from a maternal peripheral blood sample. Advanced laboratory detection and purification technology has improved the performance of NIPT and allowed the introduction of new applications in recent years. The introduction of Next Generation Sequencing (NGS) into clinical practice has rendered NIPT to have high sensitivity in the screening of aneuploidy. It has also allowed detecting and investigating the fetal genome from maternal plasma. Fetal Whole Exome Sequencing (WES) provides non invasive prenatal diagnosis of inherited monogenic disorders and can also offer a diagnosis of an underlying cause of fetal anomalies that have a normal karyotype. The following will review the current and potential future applications of NIPT and discuss the advantages and disadvantages of the various NIPT techniques. The role of public healthcare system plays in the provision of the test, and the psychological impact of NIPT on the end-users will also be highlighted. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical utility of detecting chromosome copy number variants (CNVs) in the fetus by noninvasive prenatal testing (NIPT) using the low-pass whole-genome sequencing.Methods: Eight hundred and seventy-three singleton pregnancies with chromosomal microarray analysis (CMA) available between January 2017 to December 2019 and stored enough plasma sample for NIPT testing were included in this study. The CMA results show that forty-eight pregnancies with CNVs and eight hundred and twenty-five pregnancies are normal. Each pregnancy's plasma sample was blindly tested with NIPT at a depth of 0.51-1.19x for CNVs detection. The performance of the NIPT method for CNVs detection compared with the CMA method is evaluated.Results: A total of fifty-two CNVs ranging from 0.1-47.3 Mb identified in forty-eight samples were identified by NIPT, of which thirty-four CNVs were consistent with CMA results. Additionally, eighteen CNVs were missed by NIPT. The overall sensitivity and specificity for the detection of CNVs were 65.38% (95% CI: 51.76%-76.89%) and 97.45% (95% CI: 96.12%-98.35%), respectively. However, for the detection of CNVs larger than 2 Mb and CNVs less than 2Mb, the sensitivities were 81.58% (95% CI: 66.27%-91.09%) and 21.43% (95% CI: 6.84%-48.32%), respectively.Conclusion: Our study demonstrated that the NIPT might be an alternative method for screening CNVs comparable with other studies. However, CNVs less than 2Mb in length shows poor sensitivity by NIPT. Noninvasive CNVs detection based on the NIPT method still needs more clinical validation studies and technical improvement to achieve clinically acceptable accuracy. [ABSTRACT FROM AUTHOR]

Objective: Maternal characteristics and neonatal outcomes associated with cell-free DNA (cfDNA) results were analysed retrospectively to assess the details of false-positive and false-negative results after initial blood sampling in non-invasive prenatal testing (NIPT).Study Design: A multicentre retrospective study was performed for women undergoing NIPT who received discordant cfDNA results between April 2013 and March 2018. The NIPT data obtained using massive parallel sequencing were studied in terms of maternal background, fetal fraction, z-scores, invasive procedure results and neonatal outcomes after birth.Results: Of the 56,545 women who participated in this study, 54 false-positive (0.095 %) and three false-negative (0.006 %) cases were found. Seven of the 54 false-positive cases (13.0 %) had vanishing twin on ultrasonography. Among the 18 false-positive cases of trisomy 18, confined placental mosaicism (CPM) was confirmed in three cases (16.7 %), while CPM was present in one of the three false-negative cases of trisomy 21.Conclusion: These data suggest that the incidence of women with false-positive or false-negative results is relatively low, that such false results can often be explained, and that vanishing twin and CPM are potential causes of NIPT failure. Genetic counselling with regard to false results is important for clients prior to undergoing NIPT. [ABSTRACT FROM AUTHOR]

Non-invasive prenatal testing is regularly used to screen for aneuploidies and Rhesus status of a fetus. Since 1997 when free fetal DNA (ffDNA) in the maternal circulation was first identified, it has been hypothesized that it may be possible to use non-invasive prenatal testing (NIPT) to identify high-risk pregnancies including pre-eclampsia, growth restriction and preterm birth. Since then there has been much interest in this area as a way to identify and understand disease processes. This review presents the current evidence for this approach. For pre-eclampsia the hypothesis is that ffDNA would increase but the evidence for this is heterogenous across studies and trimesters. There is however increasing agreement between studies that by the third trimester ffDNA is more likely to be raised in pre-eclamptic patients than controls. For preterm birth, again, the main hypothesis is that ffDNA should increase. The results are also heterogenous, with some studies finding increased ffDNA prior to preterm birth, and others finding no change. For fetal growth restriction, there are competing theories for reduced and increased ffDNA and some studies suggest that levels are raised and some reduced. There are complexities in interpreting all of this evidence as the studies' designs, patient populations, and especially in the context of growth restriction, the definitions are not clear. Furthermore, authors use different biochemical tests and different units to describe their results, making meta-analysis difficult. All of these issues and conflicting findings lead us to the conclusion that currently there is yet no definitive place in clinical practice for NIPT to support the diagnosis and management of high-risk pregnancies. However, it is vital that this research continues as it could open the door to better understanding of the disease process and novel approaches to management. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this survey is to evaluate the knowledge of Chinese pregnant women about fetal chromosomal aneuploidy and microdeletion and microduplication syndromes, and Non-invasive prenatal testing (NIPT).Study Design: Written questionnaires were distributed to pregnant women who visited the fetal medicine clinic of the third affiliated hospital of Guangzhou medical university. A total of 330 questionnaires were given. Twenty-two questionnaires with incomplete information were excluded from further analysis. The remaining 308 cases were incorporated into the final analysis. Data were analyzed using IBM SPSS Statistics 26. Comparisons between categorical variables were tested by the use of crosstabs and χ 2 test.Results: Among pregnant women, the recognition of Down syndrome was the highest (93.5 %), followed by maternal serum screening (74.0 %) and NIPT (69.2 %) for chromosomal aneuploidy. The awareness rates of chromosomal microdeletions and microduplications (18.2 %) and monogenic disorders (13.3 %) were the lowest. There were no significant differences in age, education, and conception way between pregnant women (P > 0.05). When asked the opinion on increasing the testing range of NIPT, more than 50 % of pregnant women chose to follow the provider's advice.Conclusion: More than half of pregnant women lacked knowledge of screening methods for fetal chromosomal abnormalities. Less than 20 % of pregnant women knew microdeletion microduplication syndromes. To enhance the understanding of chromosomal abnormalities can ensure that women can actively choose tests rather than passively agreeing to their provider's recommendations so as to avoid missing the optimal prenatal screening time. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the incidence of the single umbilical artery (SUA) malformation and postpartum outcomes in a retrospective analysis of 781 fetuses.Materials and Methods: This retrospective analysis included 781 pregnant women carrying singleton fetuses diagnosed with SUA at Gansu Provincial Maternal and Child-care Hospital between 2013 and 2019. Detailed data on maternal and fetal characteristics and postpartum outcomes were obtained.Results: In total, 624 (79.9 %) fetuses were diagnosed with isolated SUA and 157 (20.1 %) fetuses had SUA together with other structural and/or chromosome abnormalities. The highest incidence of malformation was found in the urinary system, followed by the cardiovascular system and digestive system. The incidence of SUA was 59.1 % on the right side and 40.9 % on the left side. Fetuses with SUA and other abnormalities tended to have a lower mean birth weight (3061 g vs 3201 g, p < 0.01), but no difference in the rate of preterm delivery was noted.Conclusions: After a diagnosis of SUA, structural observation of the fetus is required. The urinary, cardiovascular and digestive systems should be the focus of observation. If relevant malformations are found, then genetic testing must be performed. With isolated SUA, dynamic monitoring of biological indicators is recommended for lower birth weight, but genetic testing is not recommended. [ABSTRACT FROM AUTHOR]

Purpose: The 12q terminal duplication is a chromosomal structural abnormality that has been rarely reported. The common clinical manifestations include intellectual disability and speech delay. We report two cases of patients with a duplication of chromosome 12q which was discovered incidentally during non-invasive prenatal genetic testing (NIPT).Methods: Next generation sequencing-based NIPT and karyotype analysis confirmed the type and inheritance of the rearrangement, and chromosomal microarray-based analysis also confirmed the end replication.Results: One patient had a 18Mb 12q24.21q24.33 duplication. The other patient had a12.04Mb12.q24.31q24.33 duplication and a 9.56Mb deletion in 18p11.32p11.22. The duplicated regions on chromosome 12 and the deletion on chromosome 18 in the patients were pathogenic, and the fetuses may have clinical characteristics, such as mental retardation, facial deformities, and psychomotor retardation. Ultimately, both pregnant women chose to terminate their pregnancy.Conclusion: The cases we reported show that NIPT cannot only detect conventional chromosomes, but can also detect microdeletions and microduplications, which broadens the scope of clinical application for NIPT and provides genetic information for high-risk pregnant women as early as possible. [ABSTRACT FROM AUTHOR]

Cell-free fetal DNA (cffDNA) can be detected in the maternal circulation from 4 weeks gestation, and is present with cell-free maternal DNA at a level of between 5 % and 20 %. Cell-free DNA (cfDNA) can be extracted from a maternal blood sample and, although it is not possible to separate the fetal from the maternal cfDNA, it has enabled non-invasive prenatal diagnosis (NIPD) without the associated miscarriage risk that accompanies invasive testing. NIPD for monogenic diseases was first reported in 2000 and since then there have been many proof of principle studies showing how analysis of cfDNA can provide a definitive diagnosis early in pregnancy for a wide range of single gene diseases. Testing for a number of these diseases has been available in the UK National Health Service (NHS) since 2012. This review highlights the main techniques that are being used for NIPD and discusses the technical limitations of the methods, as well as the advances that are being made to overcome some of the issues. NIPD is technologically challenging for a number of reasons. Firstly, because it requires the detection of low level fetal variants in a high maternal background. For de novo and paternally-inherited variants this has been achieved through the use of techniques such as next-generation sequencing (NGS) and digital PCR to detect variants in the cffDNA that are not present in the maternal cfDNA. However, for maternally-inherited variants this is much more challenging and relies on dosage-based techniques to detect small differences in the levels of mutant and wild-type alleles. Alongside the technical advances that are making NIPD more widely available in both the public healthcare and commercial settings, it is crucial that we continue to monitor the social and ethical impact to ensure that patients are being offered safe and accurate testing. [ABSTRACT FROM AUTHOR]