Improving Our Understanding of the Implications of Unanticipated or Unclear Prenatal Genetic Screening Results

Abstract

Prenatal genetic screening for trisomies 21 and 18 is offered in many jurisdictions in the form of multiple marker screening, incorporating information on patient characteristics, biochemical markers, and nuchal translucency measurement, where a pocket of fluid located behind the fetal neck is measured. Although screening results are generally straightforward to interpret, unanticipated or unclear results can occur and evidence regarding their clinical implications is limited, hindering patient counselling. The aim of this doctoral thesis was to address this evidence gap by investigating associations between these unanticipated or unclear results and adverse perinatal outcomes. To achieve this, three population-based retrospective cohort studies were conducted using data from Ontario's prescribed perinatal registry, Better Outcomes Registry & Network. The first study investigated the association between all levels of nuchal translucency and chromosomal abnormalities and found an increased risk of chromosomal abnormalities among pregnancies with measurements below the widely used threshold of 3.5 mm at which follow-up investigations are offered. The second study further evaluated the association between nuchal translucency and adverse perinatal outcomes, where pregnancies with increased measurements were less likely to result in a live birth, even when all identified chromosomal abnormalities were excluded. The third study examined the association between multiple marker screening results positive for both trisomies 21 and 18 at once, or 'double-positive results', and adverse perinatal outcomes. The study found an increased risk of preterm birth overall, and when all diagnosed chromosomal abnormalities were excluded. These findings that the unanticipated or unclear results evaluated were associated with an increased risk of adverse perinatal outcomes have important implications for clinical practice and policy, for example, in decisions about thresholds for offering follow-up investigations, the types of services offered, and counselling for pregnant patients. These studies will also inform future research to further understand the implications of all possible prenatal genetic screening results and reduce uncertainty in prenatal genetic screening.