RESULTS
A total of 9,793 children born between 2010-2020 contributed data to the
CFFPR. We excluded 1,028 children missing sweat chloride or genotype
data. Of the remaining 8,765 children, 7,591 had a CF diagnosis and
1,174 a CRMS diagnosis reported by a CF care team (Figure 1), leading to
a CF:CRMS ratio of 6.5:1. Of those with a clinical diagnosis of CRMS, 65
had a guidelines-based diagnosis of CF and were excluded from comparison
of summary statistics, leaving a total of 8,700 children. Only
42 infants who were initially diagnosed with CRMS had their diagnosis
changed to CF in the CFFPR. Figure 1 illustrates how children were
categorized based on CFF diagnosis guidelines. The agreement between CF
care team-reported and CFF guidelines-based diagnosis was similar
between children with CF (93%) and children with CRMS (94%). However,
similar to our earlier analysis, a substantial number of infants (N=504)
who met guideline criteria for CRMS were classified as CF by their CF
Care Center (32% of all CRMSg). The distribution of sweat chloride data
and number of CF causing variants for the entire study cohort is
presented in Table S1 (available online). Among the children who met
guideline criteria for CRMS, the proportion of children reported as
having CFc by their care team (by birth cohort) has generally declined
over time, with 38%-41% of children born in 2010-2012 to 18%-23% of
children born 2018-2020 (Table S2).
Loss-to-follow-up among the CFc/CFg cohort was minimal, with only 4.2%
of the overall CFc/CFg group not reporting data in 2021 compared to
17.3% of CFc/CFg and 43% of CRMSc/CRMSg children (p-value
<0.0001). Figure 2 illustrates the proportion of each birth
cohort that contributed data through 2021 and shows participation in the
CFFPR is differential by age and diagnosis category. Participation rates
by subgroup and birth year are presented in Tables S3-S5 and show much
higher participation among the CFc/CFg group compared to children
classified as CRMS by either a care team or CFF guidelines. Children
classified as CRMSc/CRMSg born in 2010 had the lowest participation
rates, as only 36.6% contributed data through 2021. A total of 41
deaths were reported in the entire cohort, with <5 deaths in
the CFc/CRMSg or CRMSc/CRMSg subgroups.
We found differences in patient characteristics comparing CFc/CFg to the
other two groups during the first year of life (Table 1). The proportion
of Hispanic patients was higher in the CFc/CRMSg (20.0%) and
CRMSc/CRMSg (16.8%) cohorts compared to CFc/CFg (13.9%) (p-value
<0.0001). We found 35.2% of CFc/CFg reported any
Medicaid/Medicare during the first year of life compared to 23.8%
CFc/CRMSg and 15.0% CRMSc/CRMSg (p-value < 0.0001).
Differences in health care utilization and treatment were present
between all three groups, with CFc/CRMSg and CRMSc/CRMSg children
reporting fewer mean visits and few cultures in the first year of life.
Very few CFc/CRMSg and CRMSc/CRMSg reported fecal elastase data (12.2%
and 1.4%, respectively) but most children in those categories did
report at least one throat culture (74.6% and 62.0%, respectively).
CFc/CFg patients had a lower mean weight-for-age percentile
(32.8th percentile) compared to CFc/CRMSg
(44.1st percentile) or CRMSc/CRMSg
(48.0th percentile) (p-value < 0.0001).
Height percentile and weight-for-length percentiles were also higher
among CFc/CRMSg and CRMSc/CRMSg children compared to CFc/CFg. The
prevalence of airway microorganisms was highest in CFc/CFg children and
lowest among CRMSc/CRMsg children. The prevalence of Pa among CFc/CRMSg
children was 18% compared to 22% among CFc/CFg children; methicillin
sensitive Staphylococcus aureus (MSSA) prevalence was also similar among
those two groups. Infants with CFc/CFg were more likely to be prescribed
CF therapies such as dornase alfa or bronchodilators. Pancreatic enzyme
replacement therapy (PERT) was only reported in 24.0% of CFc/CRMSg and
3.8% of CRMSc/CRMSg children.
We next assessed the prevalence of airway bacteria among each diagnosis
group at older ages among children for whom data are available (Table
2). The prevalence of positive Pa respiratory cultures in the first year
of life in was higher in CF patients (22.8%) compared to CFc/CRMSg
(18.1%) or CRMSc/CRMSg (7.0%) patients. A similar pattern was observed
for Stenotrophomonas maltophilia , Staphylococcus aureus ,
and Hemophilus influenzae . Prevalence of Pa and other bacteria
was higher in the CFc/CRMSg cohort compared to the CRMSc/CRMSg cohort.
In CFc/CFg patients, the annual prevalence of Pa was relatively
unchanged by age (range 24%-28%)(Figure 3). However, in the CFc/CRMSg
and CRMSc/CRMSg populations, the greatest prevalence of Pa occurred in
infancy and was lower at age 2 and older (Figure 3).
Among children old enough for pulmonary function testing
(>6 years of age), we compared the mean percent predicted
forced expiratory volume in 1 second (ppFEV1) between
groups (Table 3) at integer ages. The mean ppFEV1 in
CFc/CFg children was lower compared to the other two groups from age six
through age 10 years, with CRMSc/CRMSg children having the highest lung
function at all ages. We also compared mean height and weight
percentiles between groups (Table S4 and Table S5) at integer ages.
Similar to ppFEV1 results, mean height and weight
percentiles in CFc/CFg children were lower compared to the other two
groups from age 0 through age 10 years, with CRMSg/CRMSg children having
the highest percentiles through age 1, then CFc/CRMSg having higher
clinical measures.