Normal Twin Research Articles

Second trimester maternal serum triple screening marker levels in normal twin and singleton pregnancies.

The aim of the present study was to evaluate the serum levels of α-fetoprotein (AFP), free-β-human chorionic gonadotropin (free-β-hCG) and unconjugated estriol (uE3) in second trimester maternal serum and comparative analysis of serum markers levels in normal twin and singleton pregnancies, and to evaluate the feasible methods for the screening performances of triple markers in twin pregnancy. The levels of maternal serum markers were measured by magnetic microparticle chemiluminescence immunoassay in the second trimester. TCSoft was used for calculating the risk of Down's syndrome (DS). The marker levels were compared between the twin and singleton pregnancies, along with gestational age, and the weight or age of the pregnant women. The concentrations of the maternal serum markers were higher on average in twin compared to in singleton pregnancies in the second trimester of the gestation. The levels of AFP were 2-fold higher in twin compared to those in singleton pregnancies in weeks 16, 17 and total gestational weeks. For free-β-hCG, the levels were higher in 15 and 18 gestational weeks. However, significant differences were found in all the gestational weeks for uE3. There was no correlation between the levels of markers and weight or age in the twin pregnancies. The serum marker levels of AFP, free-β-hCG and uE3 in normal twins were not all 2-fold higher compared to singleton pregnancies. The current singleton gestational age-specific model for DS screening requires further correction so that it is feasible for screening in twin pregnancies.

ISUOG Practice Guidelines: role of ultrasound in twin pregnancy.

ISUOG Practice Guidelines: role of ultrasound in twin pregnancy.

A Monoamniotic Pregnancy Discordant for Limb Body Wall Complex and Complicated by Acute TTTS

We are reporting a case of monoamniotic twin pregnancy discordant for Limb Body Wall Complex (LBWC), complicated by acute twinto-twin transfusion syndrome. The twins were delivered by an emergency cesarean section at 29+6 weeks’ gestation because of persistent fetal tachycardia of the unaffected twin. The phenotipically normal twin was anemic at birth (donor twin), while postmortem examination revealed a condition of overloaded fetal circulation of the LBWC twin (recipient twin). This is, to our knowledge, the first case of acute TTTS in a monoamniotic pregnancy reported in Literature. In monoamniotic pregnancies discordant for LBWC careful fetal monitoring should be granted, as the presence of the malformation masks the classic signs of twin-to-twin transfusion syndrome.

Acardiac Twin: A Rare Case Report

AbstractThe incidence of multifetal pregnancies has dramatically increased due to assisted reproductive technology. As a result, preterm labor, Preterm premature rupture of the membranes, congenital anomalies and fetal losses are commonly encountered by obstetricians. Despite advances in diagnostic modalities and prenatal care, many times the complications associated with multifetal pregnancies may remain undiagnosed. Complications are more with monochorionic twin gestation due to placental sharing. “Twin – reversed arterial perfusion” sequence or “acardiac twin” is one such complication. This case report presents an antenatally undiagnosed monochorionic twin pregnancy, resulting in preterm delivery of a healthy, normal twin along with an acardiac acephalus co-twin.How to cite this articleSrivastava NN, Bhatia T, Narshetty J, Kumar S. Acardiac Twin: A Rare Case Report. Int J Infertil Fetal Med 2016;7(3):103-104.

Prenatal diagnosis of five cases of monochorionic-diamniotic twins discordant for karyotype analysis

OBJECTIVE To explore the mechanism and diagnostic method for monochorionic-diamniotic twins discordant for karyotype analysis. METHODS Dual amniocentesis was performed on five pairs of monochorionic-diamniotic twins, which all consisted of a normal twin and one with multiple malformations revealed by ultrasound. Karyotype analysis was performed on amniocytes derived from each of the twins. Zygosity was also determined with DNA extracted from amniocytes with 16 polymorphic microsatellite markers. RESULTS Three cases of 45,X, one case of 47,XX,+9 and one case of 47,XY,+18 were detected among the abnormal twins, while the normal fetuses all had a normal karyotype. DNA analysis suggested that, in all cases, the twins have shared the 16 polymorphic microsatellite markers, which confirmed their monozygosity. CONCLUSION Monochorionic-diamniotic twins may be discordant for karyotyping, for which anaphase lagging, chromosomal non-disjunction and trisomy rescue may be the underlying reasons. As a simple method, dual amniocentesis can be used to obtain amniotic fluid samples for karyotype analysis and determination of zygosity for such twins.

DNA-Methylation Patterns in Trisomy 21 Using Cells from Monozygotic Twins.

DNA methylation is essential in mammalian development. We have hypothesized that methylation differences induced by trisomy 21 (T21) contribute to the phenotypic characteristics and heterogeneity in Down syndrome (DS). In order to determine the methylation differences in T21 without interference of the interindividual genomic variation, we have used fetal skin fibroblasts from monozygotic (MZ) twins discordant for T21. We also used skin fibroblasts from MZ twins concordant for T21, normal MZ twins without T21, and unrelated normal and T21 individuals. Reduced Representation Bisulfite Sequencing (RRBS) revealed 35 differentially methylated promoter regions (DMRs) (Absolute methylation differences = 25%, FDR < 0.001) in MZ twins discordant for T21 that have also been observed in comparison between unrelated normal and T21 individuals. The identified DMRs are enriched for genes involved in embryonic organ morphogenesis (FDR = 1.60 e -03) and include genes of the HOXB and HOXD clusters. These DMRs are maintained in iPS cells generated from this twin pair and are correlated with the gene expression changes. We have also observed an increase in DNA methylation level in the T21 methylome compared to the normal euploid methylome. This observation is concordant with the up regulation of DNA methyltransferase enzymes (DNMT3B and DNMT3L) and down regulation of DNA demethylation enzymes (TET2 and TET3) observed in the iPSC of the T21 versus normal twin. Altogether, the results of this study highlight the epigenetic effects of the extra chromosome 21 in T21 on loci outside of this chromosome that are relevant to DS associated phenotypes.

Ultrasonographic assessment of fetal cardiovascular function in selective intrauterine growth restriction

Objective To evaluate the fetal cardiovascular function in selective intrauterine growth restriction(sIUGR) in monochorionic diamniotic (MCDA) twins by using 2D and color Doppler ultrasonography. Methods Twenty-four sIUGR pregnancies and 20 normal MCDA twins pregnancies were enrolled at the First Affiliated Hospital of Sun Yat-Sen University from December 2013 to September 2014, and cardiac structure of fetus and Doppler patterns of the umbilical artery(UA), umbilical vein(UV), pulsatility index of ductus venosus(DV-PI), atrioventricular valve, semilunar valve, tricuspid annulus systolic displacement(TAPSE), fractional shortening of left ventricle short axis (FS) and myocardial performance index (Tei index) of both ventricles were assessed. Results Cardiothoracic ratio, heart rate, DV-PI, FS, TAPSE, Tei index of the left ventricle(0.34±0.03, 0.34±0.04), Tei index of the right ventricle(0.35±0.03, 0.35±0.03) were not significantly different compared with those of the normal MCDA twins(all P>0.05). Cardiothoracic ratio, ventricular wall thickness, isovolumetric relaxation time(IRT), isovolumetric contraction time(ICT), TAPSE and tricuspid regurgitation(TR)in the larger twins of sIUGR were significantly bigger than those in the smaller twins of sIUGR(all P<0.05), Tei index of both ventricles in the larger twin of sIUGR was significantly higher than that in the smaller twins of sIUGR(Tei index of left ventricle: 0.43±0.06 vs 0.35±0.04, Tei index of right ventricle: 0.43±0.06 vs 0.34±0.04, P<0.05), the peak E in early diastolic /the peak A in atrial contraction (E/A), the percentage of inflow during of cardiac cycle length(inflow/CCL) in larger twin of sIUGR were significantly lower than those in smaller twin of sIUGR(all P<0.05). Conclusions There was no difference of cardiac function in normal MCDA twins, at the beginning of the diagnosis of sIUGR, cardiac dysfunction were found in larger twin, follow-up examination are helpful to clinical decision. Key words: Monochorionic diamniotic twins; Selective intrauterine growth restriction; Cardiac function; Echocardiography

Twin reversed arterial perfusion sequence is more common than generally accepted.

Approximately 75% of monozygotic twin pregnancies share one monochorionic placenta where placental anastomoses are virtually always present to connect the two fetoplacental circulations. These anastomoses cause several serious complications such as acardiac twinning. Acardiac twins lack a functional heart but nevertheless show fetal growth because the normal pump twin perfuses the acardiac body through arterioarterial (AA) and venovenous (VV) anastomoses. The widely accepted 1% monochorionic acardiac incidence dates back to 1944 and the associated 1:35,000 pregnancies to 1953. Our aim was to update this analysis. We accepted the 1% (actually 1.1%) monochorionic acardiac incidence due to lack of more precise data, included the recently observed 58% early cessation of acardiac development as well as consequences of assisted reproductive technology, and assessed the incidence of acardiac twinning under conditions of AA-VV anastomoses. Early acardiac monochorionic twinning increased from 1.1% to 1.1/(1-0.58) = 2.6%, from 1:35,000 to 1:9,500 to 11,000 pregnancies, depending on number and method of assisted reproductive technology, and occurs in approximately 1:8 AA-VV anastomoses-containing monochorionic placentas. Early acardiac twinning is not a rare event. The 1944-based 1% acardiac monochorionic incidence has a weak basis and could therefore be (much) larger. Knowing this incidence more precisely may contribute to our knowledge of embryonic splitting in unequal cell masses.

Placental characteristics of twin-to-twin transfusion syndrome

To explore the prevalence, number and size of anastomoses, placenta sharing and placental cord insertion in twin-to-twin transfusion syndrome (TTTS). A total of 97 monochorionic placentas were collected from June 2013 to June 2014 during fetoscopic laser surgery or selective feticide. After eliminating 23 placentas of selective intrauterine growth restriction (sIUGR), 79 placents were analyzed. There were 24 placentas of TTTS and 32 placentas of normal monochorionic twins (McT) without complex twin preganancy. Placental sharing, placental cord insertion, angioarchitecture and diameter of vascular anastomosis were assessed by placental injection with colored dye and compared between TTTS and McT without complex twin preganancy. (1) Arterio-arterial (AA) anastomoses were detected in 37.5% of TTTS placentas versus 75.0% in normal McT placentas (P<0.01). (2) The median number of AA anastomoses in TTTS group was significantly less than that in normal group (0.0 vs 1.0, P<0.01). And the median total diameter of AA anastomoses in TTTS group was significantly smaller than that in normal group (0.00 vs 2.25 mm, P<0.01). (3) The incidence of placentas with at least one cord non-central insertion (70.8% vs 62.5%, P>0.05), velamentous insertion (25.0% vs 6.3%, P>0.05) in TTTS and normal McT had no difference respectively. The placental territory discordance (PTD) had no difference between TTTS and normal McT (0.33 vs 0.22, P>0.05). AA anastomosis occurs less frequently in TTTS placentas, supporting the concept of a protective role of AA anastomoses in TTTS. McT placentas without AA anastomosis have high risk for TTTS. The compensatory ablitiy of AA anastomosis may determine the time of TTTS onset. Non-central or velamentous cord insertion, placental sharing discordance are not risk factors for TTTS.

The thy-box for sonographic assessment of the fetal thymus: nomogram and review of the literature.

To assess the feasibility and reproducibility of fetal thy-box visualization and to set normative data for the fetal thymus using this technique. We performed a cross-sectional observational study in pregnant women in their second trimester of pregnancy who attended the fetal medicine unit of the Hospital Gregorio Marañón from March 2011 to March 2013. Using thy-box sonography, which sets boundaries within the thymus, we assessed the feasibility of the thy-box and analyzed the factors related to its visualization. Measurements of the thy-box anteroposterior and transverse diameters were performed in healthy fetuses. Interobserver agreement was studied for both items. We set normative data for the thy-box diameters in singleton and twin pregnancies. A total of 337 patients from 15 to 37 weeks were recruited after exclusion criteria. Thy-box feasibility was 74.2% (250 of 337). Nonfeasible cases were related to the fetal anterior spine and advanced gestational age. Assessment of the thy-box anteroposterior and transverse diameters was achievable in 250 fetuses. Interobserver agreement was good for feasibility and measurements (κ = 0.80). Linear growth of the thy-box in both diameters was observed in relation to gestational age during the second half of pregnancy. Thy-box diameters did not show significant differences according to the type of gestation, fetal sex, or chorionicity. Thy-box diameters are achievable and reproducible by sonography in normal singleton and twin pregnancies during the second trimester; however, although feasible, the thy-box transverse diameter measurement is not reliable beyond 28 weeks. Further studies are needed to evaluate thy-box diameters in pathologic cases, especially conotruncal anomalies.

Body weight-associated differences in ovarian morphology in captive common marmoset (Callithrix jacchus)

In captivity, Callithrix jacchus (common marmoset) is on average heavier than their wild-living counterparts, and has a tendency to produce triplet litters rather than the normal twins. To provide initial basic information about possible weight-related differences among the ovaries, a morphometric study of follicular phase ovaries from 48 young adult marmosets has been carried out. Nearly 90% of these ovaries were found to contain some degree of luteal tissue composed of large and/or small cells. The luteal structures, follicles of all stages, and stroma were subjected to morphometric analysis, and these results were compared with body weight, circulating triglyceride, androstenedione, and total estrogens. Where only large luteal cells were present, the median body weight was the highest (only this group included animals over 500g) compared with mixed, or only small luteal cells, or absence of luteal cells. Furthermore, in this group plasma triglycerides were significantly higher compared to other groups, suggesting possible role of triglycerides in promoting luteinisation. Plasma androstenedione was also a critical discriminating factor, and was elevated where large luteal cells were present even as a mixture with small cells suggesting the large luteal cells to be the likely major ovarian source of this hormone and its metabolites. Additionally, the ovaries with large luteal cells compared to those containing only small or no luteal cells, had lower primordial follicle reserve associated with high levels of atresia and luteinisation among growing non-ovulatory follicles, indicating an accelerated activation, but at the same time a suboptimal environment for follicular growth.

Management of Fetal Growth Arrest in One of Dichorionic Twins: Three Cases and a Literature Review.

Progressive fetal growth restriction (FGR) is often an indication for delivery. In dichorionic diamniotic (DD) twin pregnancy with growth restriction only affecting one fetus (selective fetal growth restriction: sFGR), the normal twin is also delivered prematurely. There is still not enough evidence about the optimal timing of delivery for DD twins with sFGR in relation to discordance and gestational age. We report three sets of DD twins with sFGR (almost complete growth arrest affecting one fetus for ≥2 weeks) before 30 weeks of gestation. The interval from growth arrest to delivery was 21–24 days and the discordance was 33.7–49.8%. A large-scale study showed no difference of overall mortality or the long-term outcome between immediate and delayed delivery for FGR, while many studies have identified a risk of developmental delay following delivery of the normal growth fetus before 32 weeks. Therefore, delivery of DD twins with sFGR should be delayed if the condition of the sFGR fetus permits in order to increase the gestational age of the normal growth fetus.

Twin reversed arterial perfusion (TRAP) sequence – a case report and review of literature

Twin reversed arterial perfusion (TRAP) sequence (acardiac twin) is a rare complication of monochorionic pregnancy characterized by single arterial to arterial vascular anastomosis between twins. In this unique haemodynamic arrangement, the structurally normal pump twin will perfuse its abnormal co-twin (acardiac) in a retrograde manner through these anastomoses, with potential for cardiac overload and heart failure in the pump twin and high fetal mortality. Definitive fetal intervention has been recommended in the literature for high (>50%) twin weight ratio (TWR). We present a case of twin reversed arterial perfusion managed expectantly as no signs of cardiac decompensation were encountered in the pump twin.

The Vanishing Triplet

Vanishing fetuses are frequently encountered in pregnancies results from in vitro fertilization. Ultrasound scans taken at the 4-5th weeks showed multiple gestation has occurred, it frequently happens that more than one amniotic sac can be seen in early pregnancy, whereas a few weeks later there is only one to be seen and the other has disappeared. Whereas the triplet pregnancy evolved into a normal twin gestation, and may further evolve into a singleton gestation. These very high resorption rates, which can be explained on the basis of the intense fetal competition for space, nutrition, or other factors during early gestation with frequent loss of the other fetus. Here, we report a case of a vanishing triplet of spontaneous pregnancy, one fetus vanished in the first month of pregnancy while another fetus disappeared at the end of second month. The normal pregnancy of the singleton was followed up until six months.

MRI manifestations of abnormalities in twin fetuses

Objective To investigate the supplementary roles of MRI in the diagnosis of fetal abnormalities in twin fetuses. Methods MRI manifestations of 22 twins were retrospectively analyzed after abnormalities were found by prenatal ultrasonography (US) from Sep 2005 to Dec 2012. Two rapid scanning sequences were used in the study, fast-imaging employing steady-state acquisition (FIESTA) and fast inversion recovery motion insensitive (FIRM). MRI findings were compared with those of prenatal US, induced labour or postpartum diagnosis. Results A total of 22 twins were reported with 23 abnormal fetuses in 20 twins and 2 normal twins. MRI confirmed central nervous system abnormalities in 3 abnormal fetuses which were anencephalus, meningoencephalocele and enlargement of lateral ventricles respectively. The case of meningoencephalocele was showed brain tissue protruding from the occipital defect on MRI, which was misdiagnosed as a cystic lymphagioma by US. The MRI diagnosis of anencephalus and enlarged lateral ventricles were accordant with US. MRI made the definite diagnosis in 5 chest abnormalities, which were left congenital diaphragmatic hernia (CDH) in 5 abnormal fetuses. They were diagnosed as possible CDH by US. Abdominal abnormalities (n=7, 8 abnormal fetuses) included two fetuses in one twin with expanded digestive tract, one fetus with expanded colon and rectus and five fetuses with omphalocele. MRI diagnosis was compatible with US diagnosis in the 7 cases. Twins micromelia were found in one case with 2 abnormal fetuses. Conjoined twins in chest and abdomen were found in another case, which manifested as two hearts, one shared liver and independent urinary tracts and gastrointestinal tracts on MRI. One fetus in twin was dead (n=1, 1 abnormal fetus). MRI showed small size and skin edema of the dead fetus. One acephalus acardius of twins (n=2, 2 abnormal fetuses) was proved. Normal MRI manifestations were indicated in 2 cases which were suspected by US for abnormal digestive tract and cryptorachischisis respectively. Conclusions MRI, an important supplementary method of prenatal US diagnosis, shows valuable advantages including multi-plane manifestations, more extensive visual field and good soft tissue contrast. It is especially helpful in the diagnosis and treatment of multiple pregnancy. Key words: Diseases in twins; Magnetic resonance image; Ultrasonography; Prenatal diagnosis

Automatic clustering of white matter fibers in brain diffusion MRI with an application to genetics

To understand factors that affect brain connectivity and integrity, it is beneficial to automatically cluster white matter (WM) fibers into anatomically recognizable tracts. Whole brain tractography, based on diffusion-weighted MRI, generates vast sets of fibers throughout the brain; clustering them into consistent and recognizable bundles can be difficult as there are wide individual variations in the trajectory and shape of WM pathways. Here we introduce a novel automated tract clustering algorithm based on label fusion – a concept from traditional intensity-based segmentation. Streamline tractography generates many incorrect fibers, so our top-down approach extracts tracts consistent with known anatomy, by mapping multiple hand-labeled atlases into a new dataset. We fuse clustering results from different atlases, using a mean distance fusion scheme. We reliably extracted the major tracts from 105-gradient high angular resolution diffusion images (HARDI) of 198 young normal twins. To compute population statistics, we use a pointwise correspondence method to match, compare, and average WM tracts across subjects. We illustrate our method in a genetic study of white matter tract heritability in twins.

Parasitic acardiac twin: a rare anomaly of monochorionic TRAP sequence

Acardiac twin is a rare complication of monozygotic multiple pregnancy. Vascular anastomosis between twins, with single placenta leads to transfer of deoxygenated blood from umbilical artery of donor to the recipient twin in reverse direction through its umbilical artery which is responsible for abnormal growth. Acardiac twin dies in utero or immediately after birth with a 50-75% mortality of normal donor twin due to congestive heart failure secondary to strain of perfusing acardiac twin.

Cognitive Deficits and Disruption of Neurogenesis in a Mouse Model of Apolipoprotein E4 Domain Interaction

Apolipoprotein E4 (apoE4) allele is the major genetic risk factor for sporadic Alzheimer disease (AD) due to the higher prevalence and earlier onset of AD in apoE4 carriers. Accumulating data suggest that the interaction between the N- and the C-terminal domains in the protein may be the main pathologic feature of apoE4. To test this hypothesis, we used Arg-61 mice, a model of apoE4 domain interaction, by introducing the domain interaction feature of human apoE4 into native mouse apoE. We carried out hippocampus-dependent learning and memory tests and related cellular and molecular assays on 12- and 3-month-old Arg-61 and age-matched background C57BL/6J mice. Learning and memory task performance were impaired in Arg-61 mice at both old and young ages compared with C57BL/6J mice. Surprisingly, young Arg-61 mice had more mitotic doublecortin-positive cells in the subgranular zone; mRNA levels of brain-derived neurotrophic factor (BDNF) and TrkB were also higher in 3-month-old Arg-61 hippocampus compared with C57BL/6J mice. These early-age neurotrophic and neurogenic (proliferative) effects in the Arg-61 mouse may be an inadequate compensatory but eventually detrimental attempt by the system to "repair" itself. This is supported by the higher cleaved caspase-3 levels in the young animals that not only persisted, but increased in old age, and the lower levels of doublecortin at old age in the hippocampus of Arg-61 mice. These results are consistent with human apoE4-dependent cognitive and neuro-pathologic changes, supporting the principal role of domain interaction in the pathologic effect of apoE4. Domain interaction is, therefore, a viable therapeutic/prophylactic target for cognitive impairment and AD in apoE4 subjects.

Twin Reversed Arterial Perfusion Syndrome (TRAP or Acardiac twin)- A Case Report

Twin reversed arterial perfusion (TRAP) syndrome is a rare condition (0.3:10,000 births) that occurs in monochorionic twin pregnancies, resulting in coexistence of a normal "pump" twin and an acardiac twin. The acardiac twin is dependent upon the normal twin to provide circulation by means of vascular anastomosis. Many of the bizarre defects are felt to be caused by low oxygen tension and this causes dramatic alteration in the twin fetal physiology and high prenatal mortality. The acardiac twin is a parasite, putting the pump fetus at risk of high output cardiac failure. Overall only 50% of pump twins survive. We present a case in a twenty year female, gravida two, para one, living one, full term normal pregnancy, ultrasound showed twin pregnancy. Following delivery, the first fetus survived only for one day and the second fetus showed features of TRAP syndrome.

Late Presentation of Acardiac Twin: A Case Report and Review of Literature

Acardiac twinning or TRAP-sequence is a rare complication of monochorionic twin pregnancy. We present a case in which fetal demise of one fetus of a twin pregnancy had been wrongly diagnosed in the first trimester as a vanishing twin. This resulted in the unexpected occurrence of an acardiac twin in the third trimester, culminating in an acardiac twin with a birth weight higher than that of the normal twin. A review is presented on therapeutic opportunities including ligation of the umbilical cord under ultrasound or fetoscopy. This case report highlights the need for correct and early ultrasonographic diagnosis of chorionicity and detailed ultrasonographic follow-up of twin pregnancies.