Hello and thank you for your question. The false negative rate is at
least 5%, and sometimes a few percentage points more.
"At its best, the test will miss about 5% of neonates with CF (false
Pre-implantation, Pre-natal and Newborn Screening for CF
"Colorado has screened for CF since July 1982, with one mandatory
bloodspot required. An elevated IRT prompted a second bloodspot; if
again elevated, a sweat test was done. After July 1996, two bloodspots
are mandated due to PKU testing changes. Elevated IRTs on both
bloodspots prompts a recall for a sweat test. Average age of diagnosis
is 23 days.
"They have screened 1.153 million infants, of whom 315 were diagnosed
with CF, for an incidence of 1:3600 (CI of 1:3200 to 1:4000). Of those
315, 55 presented with meconium ileus for a prevalence of 17.5% (CI of
13-22%) and 260 did not have MI. That number is used as a denominator
for calculating false negatives, because they present at birth and
tend to have lower IRT levels. Of the 260, there were 18 (6.9%) who
were false negative (CI 3.8%-10.0%) and these fell into two
categories: biologic-based false negatives, with IRTs lower than the
established cutoff (14, or 5.4%), and lab error 4 (1.8%). The latter
has not recurred since 1985 .
"The recall rate has averaged 0.7% over the last twenty years (99.3%
recall rate), ranging 0.2 - 1.2% per years. The high range was in the
early 1990s when children left the hospital earlier in life, which
tended to produce more false positives. The current recall rate is
0.3% and the false negative rate is 5.4%. The conclusion was that the
trypsinogen based screening of 0.7% gives an acceptable false negative
rate using a two-tiered IRT screen.
"In summary, Colorado found that with IRT-based screening, a recall
rate of 0.7% achieved a false negative rate of 5%. Patients without a
?F508 mutation comprise 8% of patients and patients without one of the
25 ACOG mutations comprise 2% of patients. Sweat tests in borderline
infants are variable and require follow-up."
Colorado IRT-Based CF NBS
"With IRT alone, 1,015,000 babies were tested. Of 389 babies with CF,
30 had a clinical diagnosis of CF made after a negative screening test
result or an administrative error." [30/389 = 7.7%]
Neonatal screening for cystic fibrosis: a comparison of two strategies
for case detection in 1.2 million babies.
"The UK trial, comparing 102 cystic fibrosis children, 58 detected
through screening and 44 diagnosed clinically(including nine with
false negative screening results) showed no clinical differences
between groups up to age 4.
[9/102 = 8.8%]
For further info, consider these 9 references:
One important factor is meconium ileus.
"Newborns who present with meconium ileus should automatically be
suspected of having CF whatever the IRT result was. In this special
group, the false negative incidence is over 50% for reasons not
"The sweat test is positive in 99% of patients with CF. There is a
very high concentration of sodium chloride in the sweat. The test has
some false negative results, especially if individuals have other
problems such as anorexia nervosa and if there is associated oedema
(excess accumulation of fluid in the body)."
"Finally, while the IRT DNA is extremely accurate, there are so many
different geneotypes for CF that it is impossible to test for each one
in a statewide screening program of all infants. Therefore, there
would be some of the more rare geneotypes that would not be detected
in the screening , thereby giving the family a false negative test
Search terms used:
cf "false negative" test
cf "false negative" test meconium ileus
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