First trimester assessment of ductus venosus in screening for fetal chromosomal and cardiac defects / Valoración del ductus venoso en el primer trimestre en el cribado de anomalías cromosómicas fetales y defectos cardiacos

Abstract

THESIS SUMMARY:<br/><br/>BACKGROUND: <br/><br/>Abnormal ductus venosus flow at 11-13 weeks has been associated to fetal chromosomal abnormalities and cardiac defects.<br/>The hypothesis of the studies is that flow through the ductus venosus can be assessed routinely at 11-13 weeks of gestation and that abnormal flow at this scan can help identify fetal chromosomal and structural defects as well as adverse pregnancy outcome.<br/><br/>STUDIES:<br/>In the first study, ten sonographers received practical training in accurate assessment of the ductus venosus and performed 300 examinations each. The sonographers required an average of 80 examinations before they could successfully examine the ductus venosus flow. <br/><br/>In the second study ductus venosus flow was assessed immediately before chorion villous sampling (CVS) in fetuses with nuchal translucency (NT) thickness of 3.5 mm or more. A fetal echocardiography was performed in euploid fetuses at 11-13 weeks and/or 18-22 weeks. Reverse or absent flow during atrial contraction was observed in 68.8% of the fetuses with cardiac defects and in 22.9% with no cardiac defects. <br/><br/>In the third study screening by the combined test was performed in singleton pregnancies, including 19,614 with euploid fetuses, 122 with trisomy 21, 36 with trisomy 18, 20 with trisomy 13 and 8 with Turner syndrome. We examined the performance of two screening strategies: firstly, assessment of the a-wave in all patients and secondly, first-stage screening using the combined test in all patients followed by second-stage assessment of the a-wave only in those with an intermediate risk of 1 in 51 to 1 in 1,000 after the first-stage. Reversed a-wave was observed in 3.2% of the euploid fetuses and in 66.4%, 58.3%, 55.0% and 75.0% of fetuses with trisomies 21, 18 and 13 and Turner syndrome, respectively. Inclusion of ductus venosus flow in all pregnancies would detect 96%, 92%, 100% and 100% of trisomies 21, 18 and 13 and Turner syndrome, respectively, at a false positive rate of 3%. The same detection rates were achieved with the two-stage strategy at a false positive rate of 2.6%.<br/><br/>In the fourth study the patients were subdivided into five groups: normal outcome (n=10,120), miscarriage or fetal death (n=185), abnormal karyotype (n=95), major cardiac (n=20) or non-cardiac defect (n=70). The prevalence of reversed a-wave was significantly higher in the groups with miscarriage or fetal death (10.8%), abnormal karyotype (62.1%) and fetal cardiac defect (25.0%) but not non-cardiac defect (4.3%) than in the normal outcome group (3.7%). <br/><br/>The fifth study was a prospective study in 516 dichorionic and 179 monochorionic twin pregnancies. The prevalence of reversed a-wave in the fetal ductus venosus was compared between monochorionic and dichorionic pregnancies and between those with and without pregnancy complications. The prevalence of reversed a-wave in at least one of the fetuses was significantly higher in monochorionic than in dichorionic pregnancies (18.4% vs. 8.3%, p<0.001) and in pregnancies complicated by miscarriage (28.6%, p=0.005), fetal aneuploidy (70.0%, p<0.001) and twin-to-twin-transfusion syndrome (TTTS) (38.5%, p<0.001) compared to the pregnancies with two healthy live births (7.7%). Pregnancy outcome was normal in 76.7% dichorionic and in 42.4% monochorionic twins with reversed a-wave in at least one of the fetuses.<br/><br/>CONCLUSIONS: <br/>After an extensive supervised training, ductus venosus flow assessment can be incorporated into the first trimester scan, where it improves the performance of screening for chromosomal defects and cardiac defects, and it helps to identify the fetuses with a higher risk of death. Similarly, in twin pregnancies ductus venosus assessment identifies the pregnancies with a higher risk of having a fetus with an aneuploidy, those with a higher risk of miscarriage, and those that will subsequently develop TTTS.<br/><br/>KEY WORDS: Ductus venosus, First trimester, Chromosomal abnormality, Cardiac effect, Adverse outcome, Twin pregnancy