Results
For the 25 states that utilized IRT fixed cutoffs, the distribution
shown in Figure 1 was wide with the mean value being 63.7 and the median
60 ng/ml. For 12 states that employ a 2-specimen IRT/IRT/DNA algorithm
(AZ, CO, DE, ID, MD, NV, NM, OR, TX, UT, WA, and WY) the IRT cutoff
question (Table 1) was restricted to the initial dried blood spot (DBS)
specimen since states rely on this value for decisions about proceeding
further in the NBS algorithm. Even amongst states that use a fixed IRT
cutoff, there is variation in when In some states, multiple samples are
obtained at different points in time or the cutoff is dependent on the
age of the baby at the time of sample collection. For our analysis, we
used the initial cutoff value reported by the state.
For the 26 regions that utilized IRT floating cutoffs, the range is from
the 95th to the 98.8th percentile
with a mean of 95.9th percentile and median at the
96th percentile. Texas uses a unique hybrid model of
both floating and fixed cutoffs; the initial IRT has a floating cutoff
and if it is above the 95th percentile, a fixed cutoff
is applied to a second sample. For the purposes of this analysis, we
considered Texas to be a state with a floating cutoff. West Virginia
reported switching from a floating cutoff of the 90thpercentile to the 95th percentile in 2021 due to
numerous false positives. The latter value was used for analysis in this
publication.
There was tremendous variation in how states do CFTR variant
analysis. Two states test for F508del only, and the other states and
regions use panels that test between 23 to 365 CFTR variants.
Four states (CA, NC, NY, and WI) incorporate CFTR sequencing into
their algorithm. If the IRT is elevated, CFTR variant panel analysis is
performed, and if 1 variant is detected CFTR sequencing is performed,
either by the Sanger method (CA) or next generation sequencing (NC, NY,
and WI).
Some states are clustered together, in which one state performs the
analyses for one or more other states, and some states outsource theirCFTR variant analysis to an outside laboratory (PerkinElmer
Genomics, Pittsburgh, PA). These are described in Table 2. Although
states that utilize outsourcing all utilize the same laboratory, they
each set their own IRT cutoffs and select their own CFTR variant
panel.
We noted a geographic distribution of which states that utilized fixed
vs. floating IRT cutoffs, as shown in Figure 3. In general, western
states tended to use fixed cutoff values, especially before Colorado
(with Wyoming) switched to a floating cutoff near the end of 2021. In
contrast, most of the eastern states began with a floating cutoff
strategy and have retained it. The midwest and south are mixed with
about half using each approach.
The free text portion of the survey provided valuable insight and
feedback. Some respondents sought advice on newer methodologies such as
next generation sequencing. A request was also submitted by one state’s
CF clinical leader for a virtual conference that would include the NBS
lab leaders to discuss recent issues and clarify CFTR panel
options. As a consequence of follow-up emails and telephone calls to
respondents, communications ensued that provided learning experiences.
In one case, a connection was made between a CF center director and NBS
lab leader which stimulated a potential partnership. We also recognized
from some comments that keeping up with evolving CF NBS algorithms was a
challenge because CF clinical leaders may not be adequately informed
when the state NBS lab changes the CF NBS algorithm. This situation is
especially challenging when “border babies” are involved, i.e., when a
woman residing in one state where she and her family receive healthcare
has her infant delivered in an adjacent state where the NBS specimen is
collected and analyzed.