By Allison Proffitt
May 21, 2014
| At the Prenatal Molecular Diagnostics Europe
conference last week in Lisbon conversations ranged from the current landscape in prenatal diagnostics to the future vision of the technology and the regulatory environment that will enable it.
Several speakers gave country perspectives, representing the variety of regulatory environments in Europe alone. Diana Wellesley of the UK and Brigitte Faas of the Netherlands presented systems in transition.
Wellesley, head of prenatal genetics at Princess Anne Hospital, outlined the changing landscape in the UK. Although advanced molecular testing is now the first line in postnatal testing situations, it hasn’t been routinely introduced prenatally because of awareness that testing often determines the outcomes of pregnancy, Wellesley said. Some hospitals are using aCGH (comparative genomic hybridization used in conjunction with DNA microarrays), but Wellesley says a consensus is badly needed on which findings to report.
The challenges in the UK, as elsewhere, center on reporting incidental findings (IFs) and variants of unknown or uncertain significance. Many IFs signify adult onset diseases, raising concerns about whether parents should know those details before birth. Variants of unknown or uncertain significance could have a range of phenotypes, including normal, or could be previously undetected.
The EACH study—Evaluation of aCHG in the prenatal setting—sought to determine how to best offer the superior error detection of aCHG without increasing parental anxiety and leading to the “inappropriate termination of pregnancy,” Wellesley explained.
The study began in February 2012 and is expected to end next month. Nine cytogenetic labs and 17 fetal medicine units were included and about 1,500 women have been enrolled.
The study protocol stipulated that the study responsibility is to the current pregnancy only, but Wellesley said the team has already deviated from that in cases where testing revealed important carrier status that would likely affect future pregnancies. Likewise, the team chose to reveal some incidental findings with adult age of onset where the information would be important to a parent’s health, for example BRCA1 status in a mother.
The line, Wellesley acknowledged, is not always clear. “Are we moving into an area of higher public expectations and wider family responsibility?” she asked. If we are responsible to this fetus, are we also responsible to share health information that would impact the fetus’s chance to grow up with a healthy mother?
The EACH study review panel has considered and rejected several criteria for limiting array reporting: by size of deletion or duplication, by depth of array. The panel agreed that using the same array currently used in post-natal settings would streamline the adoption process, but would then new rules be needed for prenatal use?
At a Joint Committee of Genomics in Medicine meeting in February the options were discussed by obstetricians, midwives, lab specialists, and geneticists. The decisions are not final, but Wellesley believed that resulting recommendations will likely call for aCHG as the first line test for all pregnancies with anomalies detected on a scan or in nuchal translucency, and that parental blood samples would be collected at the time of any invasive test.
The likely reported findings include all clearly pathogenic findings; IFs with pre-emptive management options; X-linked carrier status of the mother and any female fetus; and recessive carrier status only if applicable to the current fetus or of greater frequency than 1 in 50 in the UK.
What Dutch Women Want
In the Netherlands, the first question to address is, “What do Dutch women really want?” explained Brigitte Faas, from the Radboud University Nijmegen Medical Center.
To some extent, the answer to this is clear. Before April of 2014, non-invasive prenatal testing (NIPT) was not available in the Netherlands, and many women left the country to get testing elsewhere.
The unavailability of testing was the result of the second big question: the availability of a license.
Prenatal testing is available to Dutch women, but can only be offered with a license from the Ministry for Health, Welfare, and Sports, Faas said. A screening foundation performs audits and quality control for screening labs and grants licenses, considering the lab’s capacity; the test’s predictive value, sensitivity and specificity; costs; and the test’s failure rate.
Until April 1, these licenses did not cover NIPT. But this year the TRIDENT study (Trial by Dutch Laboratories for Evaluation of Non-Invasive Prenatal Testing) was launched offering noninvasive prenatal testing to women with an increased risk after first trimester testing in all genetic centers.
An arm of the TRIDENT study specifically looks at the ethical/social ramifications of NIPT including the parents’ attitudes toward NIPT; reasoning for taking or declining the test; and pre- and post-test psychological well-being.
Though early—355 samples have so far been analyzed—Faas said the number of invasive procedures has declined. When all 1,000 samples called for in the study protocol have been analyzed, the technical findings, social questionnaires, and economic data will be pooled.
Faas is hopeful that NIPT can be incorporated into normal prenatal care in the Netherlands, even before the default invasive tests currently prescribed to women of advanced maternal age. With about 1/3 of the study completed already, she hopes that a permanent license for NIPT will be granted by 2015.
In the final panel session of the event, Faas was joined by colleagues representing several other countries to predict the future landscape of prenatal molecular diagnostics in Europe. A few themes emerged: there were calls for more qualified genetic counselors, including population-wide pre-test education for patients, not simply counseling at the time a test is needed. More questions than answers were raised about moral implications of prenatal diagnostics; and assertions that cytogenetics is not dead, though its role is changing.
But as the testing becomes more mainstream, Howard Cuckle at Columbia University Medical Center pinpointed one practical hurdle. The availability of NIPT kits is key to wider adoption, he said. “Sending these results to the US or China for analysis is ridiculous!”
Editor’s Note: The next Prenatal Molecular Diagnostics event will be held in Boston November 5-7, 2014 in Boston, Mass. http://www.healthtech.com/prenatal-diagnostics/