Pathophysiology of increased nuchal translucency: a review of the literature

First-trimester nuchal translucency (NT) measurement is a widely used technique to determine the risk of fetal aneuploidy. The aim of this review was to explore the different hypotheses on the aetiology of increased NT. Using a computerized database (PubMed), articles on the aetiology of first-trimester NT were retrieved. Furthermore, the cited references of the studied articles were used to find additional articles. Based on ultrasonographic and post-mortem morphological studies, the findings in increased NT fetuses are described and classified into three categories. First, an association between increased NT and cardiac abnormalities, combined with abnormal ductus venosus flow velocities, is found, leading to the theory that cardiac failure causes NT enlargement. Second, various types of abnormalities are found in the extracellular matrix of the nuchal skin of fetuses with increased NT. Third, abnormal lymphatic development is demonstrated in fetuses with increased NT. In conclusion, many hypotheses on NT enlargement are based on associations and speculations. This report provides an overview of the different theories and an attempt to fit the different associations and findings into a single hypothesis of abnormal embryological development.