Informed consent is the process by which the treating health care provider discloses appropriate information to a competent patient so that the patient may make a voluntary choice to accept or refuse treatment. When the analysis of circulating cell free DNA (ccfDNA) became commercially available in 2011 through the Prenatal Diagnostic Laboratory at Women & Infants Hospital of Providence, Rhode Island to "high-risk" women, it provided an opportunity to examine how commercial laboratories informed potential consumers. We identified, via an internet search, four laboratories offering such testing in the United States and one in Europe. We evaluated patient educational materials (PEMs) from each using the Flesch Reading Ease method and a modified version of the Suitability Assessment of Materials (SAM) criteria. Pamphlets were also reviewed for their inclusion of content recommendations from the International Society for Prenatal Diagnosis, the National Society of Genetic Counselors, the American College of Obstetricians and Gynecologists jointly with the Society of Maternal Fetal Medicine, and the American College of Genetics and Genomics. Reading levels were typically high (10th-12th grade). None of the pamphlets met all SAM criteria evaluated nor did any pamphlet include all recommended content items. To comply with readability and content recommendations more closely, Women & Infants Hospital created a new pamphlet to which it applied the same criteria, and also subjected it to focus group assessment. These types of analyses can serve as a model for future evaluations of similar patient educational materials.

Nuchal translucency (NT), an ultrasound measurement of hypoechoic space in the posterior fetal neck, is a validated marker of aneuploidy. Nuchal translucency is measured between 11 and 13 completed weeks of gestation and detects up to 65% of pregnancies affected with Down syndrome with about a 5% false positive rate. When NT measurement is included as part of the first trimester combined test, 85% of Down syndrome pregnancies can be detected at a 5% false positive rate. 1 New methods of prenatal screening are focused on the use of cfDNA in maternal plasma. This technology has vastly improved screening, with 98-99% of pregnancies affected with fetal Down syndrome detected at less than a 0.5% false positive rate. 2 The need for measurement of NT in the era of cfDNA screening for aneuploidy is debatable.We recently conducted a study using cfDNA screening as the primary prenatal screening test in a general pregnancy population from Rhode Island (DNAFirst study). 3 The objective of the present report was to examine the additional value of an NT measurement for detection of aneuploidy.A total of 2691 women in Rhode Island participated in the DNAFirst study during September 2014 through July 2015, as previously described. 3 Prenatal records were reviewed to find women having an NT scan with an elevated result (>3 mm) or cystic hygroma during this same time period. Nuchal translucency measurements of 3 mm or greater (above the 95 th centile at 13 weeks of gestation) and cystic hygroma are considered abnormal and are associated with an increased risk of aneuploidy and other abnormalities. 4 A cystic hygroma is defined as a septated fluid filled cavity in the nuchal region that may extend down the length of the fetus. All NT ultrasound scans were performed by sonographers trained through either the Fetal Medicine Foundation or the Society for Maternal Fetal Medicine.Outcome data were evaluated for those women who participated in the DNAFirst study and had a positive first trimester ultrasound scan. Retrospective record review was performed with the approval of the Institutional Review Board at Women and Infants Hospital.During the period of the DNAFirst study, there were 35 women scanned at the Prenatal Diagnosis Center at Women and Infants Hospital with a cystic hygroma or NT measurement above 3 mm. Among the 35 women, nine had also participated in the DNAFirst trial. One additional DNAFirst study participant had an elevated NT measured at a separate prenatal diagnostic site, for a total of ten cases. No other fetal structural malformations were identified in these ten women.Among the women having both cfDNA screening and an elevated NT (Table 1), six had a cystic hygroma. Four of the ten scans had positive cfDNA results. Two of these four were screen positive for 45,X, one for trisomy 18 and one for trisomy 21; all were confirmed by karyotype analysis. The six remaining cases of elevated NT/cystic hygroma were screen negative by cfDNA, and no karyotype anomalies were identified. Newborn notes indicate that these infants ...

Individual patient follow-up allows us to document ccfDNA-related patient decision-making. Nearly half of the women did not want further testing and one in seven preferred immediate diagnostic testing. Patient costs were a barrier to testing that, if avoided, could increase test uptake by 50% or more.