Alexandra Matias

Ductus venosus revisited: A Doppler blood flow evaluation in the first trimester of pregnancy

The functional role of the fetal ductus venosus (DV) is still poorly established. Few reports are available in the literature concerning assessment of fetal venous return during the late first trimester of pregnancy. Our objective was to determine the normal Doppler blood velocity waveform in the human fetal DV as early as 10-13 weeks gestation. Adopting strict methodological concerns, 61 Doppler blood flow evaluations of the DV considered technically acceptable were selected. Using transvaginal Doppler ultrasound, several DV haemodynamic parameters were assessed: peak systolic and diastolic velocities, time-averaged velocity, maximum velocity during atrial contraction, pulsatility index and fetal heart rate (FHR). Except for the FHR, no significant variations were observed for the above mentioned parameters during this period, and no correlation could be established between FHR and the different flow velocity parameters. Further knowledge about DV haemodynamics in the early phases of pregnancy may make a valuable contribution to the understanding of fetal venus return to the heart and cardiac function.

Screening for twin–twin transfusion syndrome at 11–14 weeks of pregnancy: the key role of ductus venosus blood flow assessment

A discrepancy in crown–rump length (CRL) and/or nuchal translucency thickness (NT) between monochorionic twins has been found to be associated with an increased risk of twin–twin transfusion syndrome (TTTS). As one of the most plausible mechanisms for increased NT is hemodynamic imbalance and cardiac dysfunction, indirectly manifested by abnormal blood flow in the ductus venosus (DV), we aimed to clarify the role of DV blood flow assessment in identifying those monochorionic twins more prone to develop TTTS.

Anticipating twin-twin transfusion syndrome in monochorionic twin pregnancy. Is there a role for nuchal translucency and ductus venosus blood flow evaluation at 11-14 weeks?

Twin-twin transfusion syndrome is a major complication of monochorionic twin pregnancies. In foetuses from monochorionic twinning the presence of increased nuchal translucency thickness (NT) has been associated with an increased risk of developing this syndrome. One of the presumed mechanisms of increased NT is early cardiac failure, indirectly indicated by abnormal blood flow in the ductus venosus. We present eleven cases of monochorionic twin pregnancies in which nuchal translucency thickness and ductus venosus blood flow evaluation was per formed at 11-14 weeks. In the two cases presenting with nuchal translucency discrepancy between the two foetuses along with anomalous ductus venosus blood flow in the foetus with increased nuchal translucency, twin-twin transfusion syndrome (TTTS) eventually developed. In none of the twins displaying no inter-twin difference in NT measurements and in those with discrepant NT but normal flow in both ductus venosus, was the progression to TTTS observed. In the two cases which developed TTTS, foetoscopic laser coagulation of the vascular anastomosis was successfully carried out at 18weeks and normalisation of the venous return was registered. These findings suggest that the association of increased NT and abnormal flow in the ductus venosus in monochorionic twins may be an early manifestation of haemodynamic imbalance between the donor and the recipient eventually manifested as twin-twin transfusion syndrome. Further studies, however, are necessary to establish the potential role of the combination of NT and ductus venosus blood flow assessment as a screening method for TTTS.

Why are monozygotic twins different

Abstract Although popularly designated as “identical”, monozygotic (MZ) twins are rarely identical. Much has been speculated on the origin of MZ twins and several theories have been proposed. Post-fertilization events, such as chromosomal mosaicism, skewed X-inactivation and imprinting mechanisms, as well as other epigenetic mechanisms are responsible for the differences between MZ twins. Numerous discordant MZ twins have been reported including discordance for lateral asymmetry, major malformation, growth and intrauterine death of the co-twin. This discrepancy may have long-term implications on complex diseases and their predisposition, organ transplantation and interpretation of twin-based studies. We reviewed the genotypic and phenotypic differences between MZ twins and discuss their main causes.

Search for hemodynamic compromise at 11–14 weeks in monochorionic twin pregnancy: Is abnormal flow in the ductus venosus predictive of twin–twin transfusion syndrome?

Background and objectives. Twin–twin transfusion syndrome is a devastating complication of monochorionic twin pregnancies. The presence of increased nuchal translucency thickness (NT) in one of the monochorionic twins has been associated with an increased risk of developing this syndrome. One of the most plausible mechanisms for increased nuchal translucency is heart failure, indirectly manifested by abnormal blood flow in the ductus venosus. We aimed to clarify the pathophysiology of increased NT found more frequently in monochorionic twins prone to develop twin–twin transfusion syndrome. Design. We present 50 cases of monochorionic twin pregnancies in which nuchal translucency thickness was measured and ductus venosus blood flow evaluation was performed at 11–14 weeks of gestation. Results. Whenever the fetuses of a twin pregnancy were found to have discrepant nuchal translucency thickness measurements and abnormal flow in the ductus venosus was found in the fetus with increased nuchal translucency thickness, twin–twin transfusion syndrome eventually developed. Progression to twin-to-twin transfusion syndrome was not observed in the twins displaying no intertwin difference in nuchal translucency thickness measurements and it was not observed in those with discrepant nuchal translucency thickness but normal flow in the ductus venosus of both fetuses. In the two cases which developed twin-to-twin transfusion syndrome, fetoscopic laser coagulation of the vascular anastomoses was successfully carried out at 18 weeks and normalization of the venous return was recorded. Conclusions. Both increased nuchal translucency and abnormal flow in the ductus venosus in monochorionic twins may be early manifestations of haemodynamic imbalance between donor and recipient. The combined evaluation of both parameters in monochorionic twin pregnancies may constitute an effective method for identifying those at risk of developing twin-to-twin transfusion syndrome.

Screening for pre-eclampsia: a systematic review of tests combining uterine artery doppler with other markers

Abstract Aims: To perform a systematic review of screening for pre-eclampsia (PE) with the combination of uterine artery Doppler (UAD), maternal history, mean arterial pressure and/or maternal serum markers. Methods: We identified eligible studies through a search of Medline, and, for each included study, we assessed the risk of bias and extracted relevant data. We reported the performance of screening tests according to the target population (low- or high-risk), the trimester of screening (first and/or second) and the subset of PE screened for (early and late). Results: Several tests provided moderate or convincing prediction of early PE, but screening for late PE was poor. Although UAD is more accurate in the second trimester, we found encouraging results for first-trimester screening when it was combined with other markers. Performance of screening was consistently lower in populations with risk factors for PE in the maternal history. Conclusions: We present encouraging results for the prediction of early PE, even in the first trimester of pregnancy. The different performance of tests in screening for early vs. late PE, and of low- vs. high-risk populations, supports the concept that PE is a heterogeneous disease.

Gene expression pattern of IGF2, PHLDA2, PEG10 and CDKN1C imprinted genes in spontaneous miscarriages or fetal deaths.

Genomic imprinting is defined as an epigenetic modification that leads to parent-of-origin specific monoallelic expression. Some current research on the fetal control growth has been focused on the study of genes that display imprinted expression in utero. Four imprinted genes, two paternally expressed (IGF2 and PEG10) and two maternally expressed (PHLDA2 and CDKN1C), are well known to play a role in fetal growth and placental development. Pregnancy loss in the general reproductive population is a very common occurrence and other genetic causes beyond chromosomal abnormalities could be involved in spontaneous miscarriages or fetal deaths, such as alteration of expression in imprinted genes particularly those related to fetal or placental growth. Quantitative Real Time PCR was performed to evaluate gene expressions patterns of the four mentioned genes in spontaneous miscarriages or fetal deaths from 38 women. Expression levels of PHLDA2 gene were upregulated in the first trimester pregnancy cases and all four imprinted genes studied were upregulated in the second trimester of pregnancy cases comparing with controls. In third trimester PEG10 was downregulated in fetal samples group. This is the first study presenting data from human imprinted genes expression in spontaneous miscarriages or fetal deaths cases from the three trimesters of pregnancy.

Outcome of 88 pregnancies with absent or reversed end-diastolic blood flow (ARED flow) in the umbilical arteries

OBJECTIVES To investigate both perinatal and postneonatal morbidity and mortality in fetuses with absent or reversed end-diastolic flow (ARED flow) in the umbilical artery. STUDY DESIGN A 5 year prospective follow-up of 88 fetuses with ARED flow. RESULTS Sixteen stillbirths, 16 neonatal deaths, six postneonatal deaths and one death at 2 years of age were noted. Out of the 42 fetuses born alive, 36 showed a normal neurological development whereas six were mentally handicapped. Adverse prognosis was more frequently found in the group with absent end-diastolic flow at first examination and then reversed flow until delivery, compared to the groups of always absent or always reversed end-diastolic flows. CONCLUSIONS Prompt delivery is recommended in these high-risk pregnancies in order to prevent long-term sequelae, obviously depending on the local limits of viability. Further studies appropriately designed for assessing long-term neurodevelopment of fetuses with ARED flow, although demanding, are mandatory.

An efficient protocol for the detection of chromosomal abnormalities in spontaneous miscarriages or foetal deaths

OBJECTIVE Characterization of chromosomal abnormalities in 232 spontaneous miscarriages or foetal deaths using both classical and molecular cytogenetics. STUDY DESIGN Chromosomal abnormalities are responsible for 40-50% of all early pregnancy losses. Conventional cytogenetics is associated with 10-40% of culture failure. Comparative genomic hybridization (CGH) is a DNA-based technique that screens chromosome imbalances in the whole genome and may overcome this problem, although additional methods are required to distinguish between different ploidies, mosaicisms and maternal cell contamination. For a full characterization of chromosomal aberrations in 232 spontaneous miscarriages or foetal deaths we applied a sequential protocol that uses conventional cytogenetics, plus CGH and touch fluorescence in situ hybridization (Touch FISH). RESULTS Successful karyotyping was obtained in 173/232 (74.6%) of the cases, 66/173 (38.2%) of which had an abnormal chromosomal complement. CGH and Touch FISH analyses revealed another 19 abnormal cases in the 63 failures of culture. Overall there were 85/233 (36.6%) cases with an abnormal chromosomal complement, with examples from all three trimesters. Comparing cases, with or without chromosomal abnormalities, no statistical differences were found between women with one or recurrent miscarriages. On the contrary, significant differences were found comparing mean maternal ages or mean gestational ages, in cases with or without chromosomes abnormalities. CONCLUSION Adopting this sequential protocol, chromosomal complement information was available even in cases with culture failure.

Evolving Indications for the EXIT Procedure: The Usefulness of Combining Ultrasound and Fetal MRI

The EXIT procedure (EX utero Intrapartum Treatment) encompasses a multidisciplinary approach to situations in which airway obstruction is anticipated. Uteroplacental circulation is maintained to avoid neonatal hypoxemia while intubation is attempted. Not only is it useful in congenital diaphragmatic hernia with intrauterine tracheal occlusion, but new indications have been proposed. We present two cases in which EXIT procedure was adopted (huge cervical mass with tracheal compression and a highly vascularized cephalocervical mass) for the same purpose on different grounds. Our two cases stress once more the importance of combining fetal ultrasound and magnetic resonance imaging in the characterization of cervical masses and its usefulness in programming the procedure with a multidisciplinary team.