Selective feticide in dichorionic diamniotic (DCDA) twins complicated with previable premature rupture of membrane before 24 weeks may be a safe therapeutic alternative to ongoing pregnancy.

BACKGROUND: To date, there are no clinical guidelines for dichorionic diamniotic (DCDA) twins complicated with previable premature rupture of membrane (PV-ROM) before 24 weeks of gestation. The typical management options including expectant management and/or pregnant termination, induce the risks of fetal mortality and morbidity. OBJECTIVE: To explore the feasibility selective feticide in DCDA twins complicated with PV-ROM. STUDY DESIGN: A Retrospective cohort study, enrolling 28 DCDA twins suffering from PV-ROM in a tertiary medical center from Jan 01 2012 to Jan 01 2022. The obstetric outcome was compared between selective feticide group and expectant management group. RESULTS: There were 12 cases managed expectantly and 16 underwent selective feticide. More cases suffered from oligohydramnios in expectant management group compared to selective feticide group (P = 0.008). Among 13 cases with ROM of upper sac, the mean gestational age at delivery was (33.9 ± 4.9) weeks in the selective feticide group, which was significantly higher than that in the expectant management (P = 0.038). Five fetuses (83.3%) with selective feticide delivered after 32 weeks, whereas only one (14.3%) case in expectant management group (P = 0.029). However, in the subgroup with ROM of lower sac, no significant difference of the mean gestation age at delivery between groups and none of cases delivered after 32 weeks. CONCLUSION: There was a trend towards an increase in latency interval in DCDA twins with PV-ROM following selective feticide, compared to that with expectant management. Furthermore, selective feticide in cases with PV-ROM of upper sac has a favorable outcome.

Prenatal diagnosis of dent disease type I with a nonsense pathogenic variant in CLCN5: a case study.

INTRODUCTION: Dent disease type I is a rare X-linked recessive renal tubular disease resulting from pathogenic variants in the CLCN5 gene. Due to the rarity of Dent disease type I and the diversity of its phenotypes, its clinical diagnosis is complex and poses a challenge to clinicians. METHODS: A foetus and a child from a 36-year-old pregnant woman with a birth history of abnormal children were enrolled in this study. Pregnant women undergo amniocentesis for prenatal diagnosis at the gestational age of 12+ 3 weeks. Chromosomal microarray (CMA) analysis and whole-exome sequencing (WES) were employed to investigate the chromosomal copy number and single gene variants. Literature retrieval and data analysis were performed for genotype and phenotype collection analysis. RESULTS: No chromosomal abnormalities or CNVs were detected in the entire family through karyotype and familial CMA analyses. WES identified a nonsense pathogenic variant in CLCN5 of the X chromosome, c.1942 C > T (exon 11, NM_000084), which was inherited from his mother, who exhibited regular clinical features. CONCLUSION: This study suggests that children with low-molecular-weight proteinuria and hypercalciuria should undergo prompt genetic testing to exclude Dent disease.

Contribution of genetic variants to congenital heart defects in both singleton and twin fetuses: a Chinese cohort study.

BACKGROUND: The contribution of genetic variants to congenital heart defects (CHDs) has been investigated in many postnatal cohorts but described in few prenatal fetus cohorts. Overall, specific genetic variants especially copy number variants (CNVs) leading to CHDs are somewhat diverse among different prenatal cohort studies. In this study, a total of 1118 fetuses with confirmed CHDs were recruited from three units over a 5-year period, composing 961 of singleton pregnancies and 157 of twin pregnancies. We performed chromosomal microarray analysis on all cases to detect numerical chromosomal abnormalities (NCAs) and pathogenic/likely pathogenic CNVs (P/LP CNVs) and employed whole-exome sequencing for some cases without NCAs and P/LP CNVs to detect P/LP sequence variants (P/LP SVs). RESULTS: Overall, NCAs and P/LP CNVs were identified in 17.6% (197/1118) of cases, with NCA accounting for 9.1% (102/1118) and P/LP CNV for 8.5% (95/1118). Nonisolated CHDs showed a significantly higher frequency of NCA than isolated CHD (27.3% vs. 4.4%, p < 0.001), but there was no significant difference in the frequency of P/LP CNVs between isolated and nonisolated CHD (11.7% vs. 7.7%). A total of 109 P/LP CNVs were identified in 95 fetuses, consisting of 97 (89.0%) de novo, 6 (5.5%) parental inherited and 6 (5.5%) with unavailable parental information. The 16p11.2 proximal BP4-BP5 deletion was detected in 0.9% (10/1118) of all cases, second only to the most common 22q11.21 proximal A-D deletion (2.1%, 23/1118). Most of the 16p11.2 deletions (8/10) detected were de novo, and were enriched in CHD cases compared with a control cohort from a previous study. Additionally, SV was identified in 12.9% (8/62) of cases without NCA and P/LP CNV, most of which were de novo with autosomal dominant inheritance. CONCLUSIONS: Our cohort study provides a deep profile of the contribution of genetic variants to CHDs in both singleton and twin fetuses; NCA and P/LP CNV contribute to 9.1% and 8.5% of CHD in fetuses, respectively. We confirmed the 16p11.2 deletion as a CHD-associated hotspot CNV, second only to the 22q11.21 deletion in frequency. Most 16p11.2 deletions detected were de novo. Additionally, P/LP SV was identified in 12.9% (8/62) of fetuses without NCA or P/LP CNV.

Intertwin nuchal translucency difference predicts the chance of co-twin death after fetal reduction in dichorionic triplet pregnancies: a retrospective analysis study.

OBJECTIVES: To compare the clinical outcomes of different multifetal pregnancy reduction (MFPR) programs in dichorionic (DC) triplets, and explore the association between early ultrasound characteristics and co-twin death after potassium chloride (KCl) injection into one monochorionic (MC) twin. METHODS: We retrospectively reviewed the data of DC triplets who underwent MFPR at our center during 2012-2021. Patients were grouped as follows: intracardiac KCl injection into one MC twin (group A), intracardiac KCl injection into both MC twins simultaneously (group B), and reduction of the singleton fetus (group C) and pregnancy outcomes were compared. Logistic regression was used to determine whether ultrasound measurements at 11-13+6 weeks predicted co-twin death and the receiver operator characteristic (ROC) analysis was conducted to assess the predictive performance. RESULTS: Finally, we enrolled 184 patients. 153 cases were in group A, and 18, 13 cases were in group B and C respectively. Gestational age at the time of MFPR did not differ among the 3 groups (median: [Formula: see text] weeks). The survival rate was 89.6%, 88.9%, and 92.3% in group A, B, and C respectively, which was comparable among groups. Preterm birth was more common in group C (10/12, 83.3%). After KCl injection into one MC twin, co-twin death occurred in 86.3% cases (132/153) within 1 day; however, 3 patients had 2 live births each, with normal postnatal development. Intertwin nuchal translucency (NT) difference/discordance significantly predicted co-twin death within 1 day after MFPR, and the areas under the ROC curve were 0.694 and 0.689, respectively. CONCLUSIONS: For MFPR in DC triplet pregnancies, reduction of the MC twins results in less preterm birth, and women with KCl injection into either one or both MC twins had similar outcomes. Large intertwin NT difference/discordance was associated with co-twin death within 1 day after KCl injection into one of the MC twins.

Integrative profiling of extrachromosomal circular DNA in placenta and maternal plasma provides insights into the biology of fetal growth restriction and reveals potential biomarkers.

Introduction: Fetal growth restriction (FGR) is a placenta-mediated pregnancy complication that predisposes fetuses to perinatal complications. Maternal plasma cell-free DNA harbors DNA originating from placental trophoblasts, which is promising for the prenatal diagnosis and prediction of pregnancy complications. Extrachromosomal circular DNA (eccDNA) is emerging as an ideal biomarker and target for several diseases. Methods: We utilized eccDNA sequencing and bioinformatic pipeline to investigate the characteristics and associations of eccDNA in placenta and maternal plasma, the role of placental eccDNA in the pathogenesis of FGR, and potential plasma eccDNA biomarkers of FGR. Results: Using our bioinformatics pipelines, we identified multi-chromosomal-fragment and single-fragment eccDNA in placenta, but almost exclusively single-fragment eccDNA in maternal plasma. Relative to that in plasma, eccDNA in placenta was larger and substantially more abundant in exons, untranslated regions, promoters, repetitive elements [short interspersed nuclear elements (SINEs)/Alu, SINEs/mammalian-wide interspersed repeats, long terminal repeats/endogenous retrovirus-like elements, and single recognition particle RNA], and transcription factor binding motifs. Placental multi-chromosomal-fragment eccDNA was enriched in confident enhancer regions predicted to pertain to genes in apoptosis, energy, cell growth, and autophagy pathways. Placental eccDNA-associated genes whose abundance differed between the FGR and control groups were associated with immunity-related gene ontology (GO) terms. The combined analysis of plasma and placental eccDNA-associated genes in the FGR and control groups led to the identification of potential biomarkers that were assigned to the GO terms of the epigenetic regulation of gene expression and nutrient-related processes, respectively. Conclusion: Together, our results highlight links between placenta functions and multi-chromosomal-fragment and single-fragment eccDNA. The integrative analysis of placental and plasma eccDNA confirmed the potential of these molecules as disease-specific biomarkers of FGR.

Enlarged cavum septi pellucidi Z-scores in fetuses with trisomy 18.

OBJECTIVE: We aim to establish a formula calculating the fetal cavum septi pellucidi (CSP) width Z-scores and compare CSP width between the normal fetus and 18-trisomy fetus. METHODS: In this retrospective study, 608 normal fetuses and 71 fetuses with the 18-trisomy syndrome were included. Z-scores were calculated after the acquisition of CSP images. Normal CSP width Z-scores formulae were constructed based on gestational age (GA) by performing a standard regression analysis followed by weighted regression of absolute residual values. Subsequently, the Mann-Whitney U test was used to compare the CSP width Z-scores between normal and 18-trisomy groups. RESULTS: Formulae calculating CSP width Z-scores were constructed. Normal fetal CSP width was significantly correlated with GA (R2 = 0.50, p < .01). In 18-trisomy group, 69% (34/49) fetuses displayed enlarged fetal CSP width and CSP width Z-scores (p < .01). CONCLUSIONS: The CSP width Z-scores formulae established in the current study can provide a quantitative basis for the prenatal diagnosis of 18-trisomy syndrome. Enlarged CSP width Z-score may serve as a novel prenatal diagnostic marker for the 18-trisomy syndrome.

[Retrospective Analysis of Hematological Phenotypes in Patients with Gene Mutation and Deletion α-Thalassemia].

OBJECTIVE: To explore the differences between hematological phenotypes of patients with different genotypes in gene mutations and deletion α- thalassemia. METHODS: By screening the α- thalassemia gene test results in the First Affiliated Hospital, Sun Yat-Sen University from January 2015 to April 2020, the patients with mutation and deletion α- thalassemia were obtained, then the differences between hematological phenotypes of patients with different genotypes were analyzed. RESULTS: There were 96 patients with mutation combined with deletion α- thalassemia from the results of 24 054 α- thalassemia patients screened out, including 79 patients with non-deletion Hb H disease (αTα/--SEA) and 17 patients with mild α- thalassemia (αTα/-α), the incidence was 0.42%. Except the number of red blood cells (RBC) and mean corpuscular volume (MCV), the hemoglobin (Hb) concentration, hematocrit (Ht), average red blood cell hemoglobin concentration (MCHC), average red blood cell hemoglobin amount (MCH), average red blood cell volume (MCV) of the patients with αTα/--SEA genotype were significantly lower than those with αTα/-α genotype. The Hb of the patients with αCSα/--SEA and αQSα/--SEA genotype was (86±20)g/L and (84±9)g/L, respectirely, which was significantly lower than (114±16) g/L of αWSα/--SEA genotype (P<0.05); The MCHC of patients with αCSα/--SEA and αQSα/--SEA genotype was (278.8±8.5) g/L and (282.1±21.1)g/L, respectirely, which was also significantly lower than (315.4±19.5) g/L of αWSα/--SEA genotype (P<0.05); There was no significant difference between the patients with αCSα/--SEA and αQSα/--SEA genotype in hematological phenotypes. Except MCH and MCV, there was no significant differences between the patients with αWSα/--SEA and αTα/-α genotype in RBC, Hb, and Ht. The result of Hb A2 was (2.3±0.9)% for only 27 patients who performed electrophoretic analysis. There was no significant difference between the patients with αTα/--SEA and αTα/-α genotype in Hb A2, aslo among 3 types of the patients with αTα/--SEA genotype. CONCLUSION: The hematological phenotype changes caused by αWSα/--SEA genotype are similar to those of mild α- thalassemia, and both of them are significantly lighter than those patients with αCSα/--SEA and αQSα/--SEA genotype.

Case Report: Low-Level Maternal Mosaicism of a Novel CREBBP Variant Causes Recurrent Rubinstein-Taybi Syndrome in Two Siblings of a Chinese Family.

Familial Rubinstein-Taybi syndrome (RSTS) with recurrent RSTS siblings and apparently unaffected parents is rare; such cases might result from parental somatic and/or germline mosaicism. Parental low-level (<10%) germline mosaicism in the CREBBP-associated RSTS family has not been reported. Here, we present our studies of a Chinese family with two RSTS siblings and apparently unaffected parents. We detected the apparent de novo variant (DNV) c.3235C>T (p.Gln1079*) in CREBBP in the siblings via trio whole-exome sequencing. High-depth next-generation sequencing (NGS) for the parents revealed a low-level (<10%) mosaic variant in both the peripheral blood (3.64%) and buccal mucosa (1.94%) of the unaffected mother, indicating maternal somatic and germline mosaicism. Peripheral blood RNA-sequencing analysis for the patients and normal individuals indicated that the c.3235C>T (p.Gln1079*) non-sense variant did not trigger nonsense-mediated mRNA decay to reduce CREBBP mRNA levels. Transcriptome analysis revealed 151 downregulated mRNAs and 132 upregulated mRNAs between the patients and normal individuals. This study emphasizes that high-depth NGS using multiple specimens might be applied for a family with an affected sibling caused by an apparent CREBBP DNV to identify potential low-level parental mosaicism and provide an assessment of recurrence risk.

Evaluation of a Microhaplotype-Based Noninvasive Prenatal Test in Twin Gestations: Determination of Paternity, Zygosity, and Fetal Fraction.

As a novel type of genetic marker, the microhaplotype has shown promising potential in forensic research. In the present study, we analyzed maternal plasma cell-free DNA (cfDNA) samples from twin pregnancies to validate microhaplotype-based noninvasive prenatal testing (NIPT) for paternity, zygosity, and fetal fraction (FF). Paternity was determined with the combined use of the relMix package, zygosity was evaluated by examining the presence of informative loci with two fetal genome complements, and FF was assessed through fetal allele ratios. Paternity was determined in 19 twin cases, among which 13 cases were considered dizygotic (DZ) twins based on the presence of 3~10 informative loci and the remaining 6 cases were considered monozygotic (MZ) twins because no informative locus was observed. With the fetal genomic genotypes as a reference, the accuracy of paternity and zygosity determination were confirmed by standard short tandem repeat (STR) analysis. Moreover, the lower FF, higher FF, and combined FF in each DZ plasma sample were closely related to the estimated value. This present preliminary study proposes that microhaplotype-based NIPT is applicable for paternity, zygosity, and FF determination in twin pregnancies, which are expected to be advantageous for both forensic and clinical settings.

Clinical value of genetic analysis in prenatal diagnosis of short femur.

BACKGROUND: Fetal femur length (FL) is an important biometric index in prenatal screening. The etiology of short femur is diverse, with some pathogenic causes leading to adverse outcomes. To improve the accuracy and practicability of diagnosis, we investigated the value of genetic analysis in prenatal diagnosis of short femur. METHODS: We examined chromosomal microarray analysis (CMA) (64 fetuses) and karyotyping (59 fetuses) data retrospectively for short femur without fetal growth restriction (FGR). Genetic testing was conducted for 15 fetuses. RESULTS: Karyotyping and CMA detected chromosomal aberrations at rates of 13.6% and 27.2%, respectively. Among fetuses with other abnormalities, detection rates were 21.0% higher with CMA than karyotyping. CMA identified chromosomal abnormalities in 36.4% of cases with a FL 2-4 standard deviations (SDs) below the gestational age (GA) mean. Abnormality detection by CMA reached 38.5% in the second trimester. Duplication of 12p, 16p13.1 deletion, and uniparental disomy 16 were identified by CMA in three cases of short femur. Gene sequencing detected clinically notable mutations in 12/15 fetuses, among which 9/12 fetuses had FLs >4 SDs below the GA mean. CONCLUSIONS: CMA yielded a higher detection value than karyotyping in fetuses with other abnormalities or a FL 2-4 SDs below the GA mean during the second trimester. Gene sequencing should be performed when FL is >4 SDs below the mean.

Potential role of microRNA-424 in regulating ERRγ to suppress trophoblast proliferation and invasion in fetal growth restriction.

BACKGROUND: Abnormal expression of estrogen-related receptor γ (ERRγ) protein is associated with fetal growth restriction (FGR). The upstream regulators of ERRγ are still unknown. OBJECTIVE: To evaluate the placental expression level of microRNA-424 (miR-424) and to demonstrate the relationship between miR-424 and FGR. METHODS: The expression levels of miR-424 were detected in FGR and control placentas. HTR-8/SVneo cells were transfected with mimics or inhibitors to increase or decrease the miR-424 expression level, respectively. The transwell and CCK-8 assays were used to determine trophoblast-derived cell line invasion and proliferation. The expression levels of miR-424, ERRγ, and 17 beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) were detected by qRT-PCR and Western blotting. The relationship between miR-424, ERRγ, and HSD17B1 was determined by luciferase reporter assay. RESULTS: Compared to the normal pregnancy group, FGR placental tissues showed a significantly higher expression level of miR-424. The up-regulation of miR-424 decreased trophoblast-derived cell line invasion and proliferation. Down-regulation of miR-424 enhanced invasive and proliferative abilities of the cell lines. Over-expression of miR-424 reduced ERRγ protein levels and decreased both mRNA and protein levels of HSD17B1. Thus down-regulation of miR-424 induced protein expression of ERRγ and enhanced the mRNA and protein expressions of HSD17B1. MiR-424 probably mediated the expression of ERRγ via binding to sites other than mRNA 3'UTR. CONCLUSION: MiR-424 may be associated with the pathogenesis of FGR by modulating trophoblast-derived cell line proliferation and invasion. MiR-424 may play a role in mediating the protein expressions of ERRγ and HSD17B1.

Is an analysis of copy number variants necessary for various types of kidney ultrasound anomalies in fetuses?

BACKGROUND: This study aimed to estimate the associations of copy number variants (CNVs) with fetal kidney ultrasound anomalies. A total of 331 fetuses with kidney ultrasound anomalies who underwent prenatal chromosomal microarray analyses were enrolled. The fetuses were classified into groups with isolated and nonisolated anomalies or according to the types of kidney anomalies. RESULTS: Clinically significant CNVs were identified in 3.4% or 7.3% of fetuses with isolated or nonisolated kidney anomalies, respectively. CNVs were more frequently identified in fetuses with abnormal embryonic migration of the kidneys (6.6%) than in fetuses with malformations of the renal parenchyma (4.7%) or anomalies of the urinary collecting system (3.4%). In particular, CNVs were most frequently detected in fetuses with ectopic kidneys (9.5%) but not in fetuses with horseshoe kidneys or isolated duplex kidneys. Among these CNVs, the most common were del(17)(q12q12) (1.2%) and del(22)(q11q11) (0.6%). The dup(17)(p12p12) and del(15)(q11.2q11.2) CNVs were identified in this study but not in previous studies. The del(X)(p11.4p11.4) and del(16)(p13.3p13.3) CNVs were further implicated as associated with kidney anomalies. CONCLUSIONS: Fetuses with abnormal embryonic migration of the kidneys (particularly ectopic kidneys) showed a higher frequency of clinically significant CNVs, whereas fetuses with horseshoe kidneys or duplex kidneys were less frequently associated with these CNVs.

Hemolytic disease of the fetus and newborn due to alloanti-M: three Chinese case reports and a review of the literature.

BACKGROUND: Alloanti-M was once regarded as not clinically significant, with a few exceptions in extremely rare cases. However, an increasing number of cases of severe hemolytic disease of the fetus and newborn (HDFN), resulting in fetal hydrops and recurrent abortion caused by alloanti-M, have been reported mainly in the Asian population. STUDY DESIGN AND METHODS: Three pregnant Chinese women with a history of abnormal pregnancy with hydrops fetalis were encountered. During this pregnancy, a series of clinical examinations and an alloantibody identification against RBCs and platelets were conducted. Intrauterine transfusion and postnatal transfusion were then performed in the fetuses. In addition, the HDFN cases caused by alloanti-M reported in different ethnic groups as well as their clinical and serologic features are also summarized. RESULTS: Three pregnant women were identified with an M-N+ phenotype and IgM mixed with IgG alloanti-M in serum. Their fetuses were found by ultrasound examination and cord blood testing to have severe anemia. Additionally, an M+N+ phenotype and IgG alloanti-M were detected in the cord blood of the three fetuses with titers ranging from 1:1 to 1:128. Moreover, low reticulocyte counts and negative direct antiglobulin tests were also shown in two of the fetuses. After receiving intrauterine transfusions and postnatal transfusions several times, these three fetuses eventually survived and then healthfully developed in the follow-up tracking. CONCLUSION: Alloanti-M immunization can cause severe HDFN with hyporegenerative anemia, often seen in the Asian population, and suppression of erythropoiesis might account for it.

Prenatal diagnosis of Pallister-Killian syndrome in one twin.

Pallister-Killian syndrome (PKS) is often incidentally diagnosed prenatally due to ultrasound abnormalities or advanced maternal age. Severely shortened limbs could be the most outstanding abnormal observation in a fetus with PKS. PKS can be detected with the highest mosaic ratio by chromosomal microarray analysis (CMA) on uncultured amniocytes prenatally.

Estrogen-related receptor γ regulates expression of 17ß-hydroxysteroid dehydrogenase type 1 in fetal growth restriction.

INTRODUCTION: Estrogen-related receptor γ (ERRγ) and 17ß-hydroxysteroid dehydrogenase type 1 (HSD17B1) have important roles in cell invasion and in the proliferation of many types of cancer cells. However, it remains unknown whether ERRγ and HSD17B1 contribute to abnormal placental structure and dysfunction which characterize fetal growth restriction (FGR). Therefore, the aim of this study was to investigate the expression profiles of ERRγ and HSD17B1 in placenta tissues affected by FGR and to examine a possible molecular mechanism by which ERRγ is able to regulate HSD17B1 during development of FGR. METHODS: Placenta tissues were collected from women affected by FGR (n = 28) and from women with appropriately gestational age (AGA) (n = 30). Relative mRNA and protein levels of ERRγ and HSD17B1 in both groups were assessed by quantitative real-time PCR, immunohistochemistry, and Western blot analyses. The effect of ERRγ on trophoblast function and its associated mechanistic details were studied in the trophoblast cell line, HTR-8/SVneo, which was transfected with small interfering RNA (siRNA) targeting ERRγ. RESULTS: Both mRNA and protein levels of ERRγ and HSD17B1 were significantly lower in FGR placentae (P < 0.05). When ERRγ expression was knocked down in HTR-8/SVneo cells with siRNA, invasion and proliferation were inhibited. In addition, HSD17B1 expression was significantly decreased. In dual luciferase reporter assays, ERRγ stimulated transcription of HSD17B1 by targeting the ERRγ response element within its 5'-flanking promoter region. DISCUSSION: Aberrant ERRγ expression may contribute to the pathogenesis of FGR by regulating the transcriptional activity of HSD17B1.

Unusual twinning: Additional findings during prenatal diagnosis of twin zygosity by single nucleotide polymorphism (SNP) array.

OBJECTIVE: To evaluate the incidence and characteristics of unusual twinning by using single nucleotide polymorphism (SNP) array to identify twin zygosity. METHODS: This study reviewed 386 twin pairs who were seen for prenatal or postnatal diagnosis and underwent SNP array to detect zygosity. RESULTS: The incidence of monozygotic (MZ) twins was 11.36% (25/220) in the assisted reproductive technology (ART)-conceived group. Monochorionic dizygotic twins represented 3 of 24 monochorionic ART-conceived twin pairs (3/24, 12.50%) but none in the spontaneous twin pairs. Among 4 single-embryo transfer twin pairs, 3 represented unusual twinning, including 2 MZ twin pairs with discordant karyotypes and 1 dizygotic twin pair of the same gender. Of the pregnancies with 2 or more embryos transferred, 7.77% (15/193) were MZ. Additionally, there was a dichorionic monozygotic twin pair with placental vascular anastomoses from a day-5 blastocyst transfer. CONCLUSION: Single nucleotide polymorphism array can provide zygosity diagnosis in addition to chromosomal copy number variation and uniparental disomy detection. ART twin pregnancies have a risk of unusual twinning, such as monochorionic dizygotic, single-embryo transfer twin pairs with discordant karyotypes or dizygotic, and dichorionic monozygotic with vascular anastomoses from day-5 transfer.

Chromosomal aberrations and CNVs in twin fetuses with cardiovascular anomalies: Comparison between monochorionic diamniotic and dichorionic diamniotic twins.

OBJECTIVE: To investigate the types of cardiovascular anomalies and the results of invasive prenatal diagnosis in twin fetuses. METHODS: A total of 298 fetuses in 149 twin pairs were enrolled, in which 1 or 2 fetuses of a twin pair had cardiovascular anomalies. Prenatal diagnosis was performed on 290 fetuses of 149 twin pairs, including 150 monochorionic diamniotic (MCDA) fetuses (79 pairs) and 140 dichorionic diamniotic (DCDA) fetuses (70 pairs). G-Banding karyotyping and/or chromosomal microarray analysis were performed. The types of cardiovascular anomalies and the results of prenatal diagnosis were analyzed. RESULTS: Fifty percent (79/158) fetuses in MCDA group and 52.1% (73/140) fetuses in DCDA group were diagnosed with cardiovascular anomalies by ultrasound. Primary cardiac structural defects such as septal defects and tetralogy of Fallot were more common in DCDA group than in MCDA group, while acardiac anomaly was the most common in MCDA group. Chromosomal aberrations were identified in 7.7% fetuses (11/142) of MCDA group and in 18.3% fetuses (22/120) of DCDA group by G-banding karyotyping. Except benign copy number variations (CNVs), 37 CNVs (pathogenic, likely pathogenic, and variant of uncertain significance) and chromosomal aberrations were detected in 21.3% (32/150) fetuses of MCDA group and 47 CNVs (pathogenic, likely pathogenic, and variant of uncertain significance) and chromosomal aberrations were detected in 32.1% (45/140) fetuses of DCDA group by chromosomal microarray analysis. CONCLUSIONS: Most of cardiovascular anomalies were identified in one fetus of a twin pair no matter in MCDA or DCDA twin. Primary cardiac structural defects were more common in DCDA group. Monozygotic twins may have discordant phenotypes, karyotypes, and CNVs between 2 fetuses of each pair.

Prenatal diagnosis of posterior fossa anomalies: Additional value of chromosomal microarray analysis in fetuses with cerebellar hypoplasia.

OBJECTIVE: To elucidate the relationship between copy number variations (CNVs) detected by high-resolution chromosomal microarray analysis (CMA) and the type of prenatal posterior fossa anomalies (PFAs), especially cerebellar hypoplasia (CH). METHODS: This study involved 77 pregnancies with PFAs who underwent CMA. RESULTS: Chromosomal aberrations including pathogenic CNVs and variants of unknown significance were detected in 31.2% (24/77) of all cases by CMA and in 18.5% (12/65) in fetuses with normal karyotypes. The high detection rate of clinically significant CNVs was evident in fetuses with cerebellar hypoplasia (54.6%, 6/11), vermis hypoplasia (33.3%, 1/3), and Dandy-Walker malformation (25.0%, 3/12). Compare with fetuses without other anomalies, cases with CH and additional malformations had the higher CMA detection rate (33.3% vs 88.9%). Three cases of isolated unilateral CH with intact vermis and normal CMA result had normal outcomes. The deletion of 5p15, 6q terminal deletion, and X chromosome aberrations were the most frequent genetic defects associated with cerebellar hypoplasia. CONCLUSION: Among fetuses with PFA, those with cerebellar hypoplasia, vermis hypoplasia, or Dandy-Walker malformation are at the highest risk of clinically significant CNVs. Chromosomal microarray analysis revealed the most frequent chromosomal aberrations associated with CH.

Discordant intrauterine transfusion in dichorionic twin pregnancy with Rh isoimmunization.

Discordant intrauterine transfusion (IUT) in twin pregnancy with Rh isoimmunization is uncommon and complicated. We report a gravida 3, para 2 woman with a dichorionic diamniotic (DCDA) twin pregnancy and two fetuses received discordant transfusions. Middle cerebral artery peak systolic velocity (MCA-PSV) was used to evaluate the anemic degree in each foetus. IUT was performed 3 times in twin A and 4 times in twin B to reverse foetal anaemia. Transfusions were distinct due to the different tolerance to IUT, and the procedure could be continued in one foetus even if the other one underwent complications. Two male babies were born at 36 weeks of gestation and were given different treatments after birth. Twins were subsequently healthy after 2 years of follow up. The discordant IUT was due to the different tolerance to transfusion in the DCDA twins. Zygosity is important for the management and treatment of haemolytic anaemia in twin pregnancies.

Prenatal treatment of severe fetal hemolytic disease due to anti-M alloimmunization by serial intrauterine transfusions.

OBJECTIVE: Fetal hemolytic disease is a common cause of fetal hydrops and fetal morbidity and mortality. Despite its relatively low frequency, the anti-M IgG antibody is one of the causes of severe fetal anemia and intrauterine death; only a few cases have been reported. CASE REPORT: This is a case of a pregnant woman with a history of three intrauterine deaths. A diagnosis of severe fetal anemia attributed to anti-M alloimmunization was confirmed in her fifth pregnancy. She came to our center for regular monitoring at the beginning of the pregnancy. Five intrauterine transfusions were performed to correct moderate to severe fetal anemia throughout her pregnancy. A male infant, delivered at the 36th gestational week received two transfusions after birth, and no neurologic abnormalities were observed until the child was 6 months of age. CONCLUSION: Anti-M alloimmunization is an important cause of severe fetal hemolytic disease. The characteristics of fetal hemolytic disease due to anti-M alloimmunization may be somewhat different from those of disease due to anti-D alloimmunization.