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Journal of Cystic Fibrosis xxx (xxxx) xxx

Contents lists available at ScienceDirect

Journal of Cystic Fibrosis

journal homepage: www.elsevier.com/locate/jcf

Differences in clinical outcomes of paediatric cystic fibrosis patients

with and without meconium ileus
Su Min Joyce Tan a, Michael J. Coffey b, Chee Y. Ooi a,b,c,∗
a
Department of Gastroenterology, Sydney Children’s Hospital, High Street, Randwick NSW 2031, Australia
b
Discipline of Paediatrics, School of Women’s and Children’s Health, University of New South Wales, Sydney NSW 2052, Australia
c
Molecular and Integrative Cystic Fibrosis (miCF) Research Centre, Sydney Children’s Hospital, High Street, Randwick NSW 2031, Australia

a r t i c l e i n f o a b s t r a c t

Article history: Background: Meconium ileus (MI) affects up to 20% of newborns with cystic fibrosis (CF). We compared
Received 7 April 2019 clinical outcomes between Australian paediatric CF patients with and without meconium ileus (non-MI).
Revised 13 September 2019
Methods: This was a retrospective case-control study of MI and non-MI patients in New South Wales,
Accepted 14 September 2019
Australia, from 1988 to 2010. MI patients were matched 1:1 with pancreatic insufficient non-MI patients
Available online xxx
for age, sex and CF clinic. Clinical measurements, nutrition and gastrointestinal outcomes over this period
Keywords: were compared between groups using linear mixed models for continuous variables to account for age.
cystic fibrosis Results: There were 162 matched pairs (N=324, 52% female) with mean (SD) age of 15.3 (8.2) and 14.9
meconium ileus (7.9) years for MI and non-MI patients respectively (P=0.6). MI patients aged 5-23 had poorer FEV1%
lung function compared to non-MI patients (estimate -0.070 SE [0.02], P=0.003). There were no significant differences
growth in P. aeruginosa isolation rates; however S. aureus isolation rates were lower in MI patients (72%) com-
nutrition
pared to non-MI (82%) (OR 0.6 [0.3-1.0], P=0.03). Chronic colonisation rates for P. aeruginosa and S. au-
clinical outcomes
reus were not significantly different between groups. MI patients aged 2-20 had significantly lower BMI
Z-scores over time (estimate -0.25 SE [0.1], P=0.02). MI patients were more likely to receive oral feed
supplements (OR 2.8 [1.4-6.1], P=0.003) and gastrostomy formation (OR 4.4 [1.1-24.6], P=0.02).
Conclusions: CF patients with MI may have worse lung function, growth and nutrition than non-MI pa-
tients over time. Meconium ileus may be an early poor prognostic factor for CF.
© 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

1. Introduction newborn period and is caused by inspissated meconium leading to

Cystic fibrosis (CF) is an autosomal recessive disorder which af-
fects approximately 1 in 2500 newborns in Caucasian populations.
The burden of disease in CF is linked to the severity and number of
clinical manifestations, which include respiratory, gastrointestinal,
hepatobiliary and endocrine complications. Meconium ileus (MI),
which affects approximately 20% of patients with CF, is the ear-
liest clinical manifestation of cystic fibrosis [1]. It presents in the
Abbreviations: MI, meconium ileus; CF, cystic fibrosis; NSW, New South Wales;
SD, standard deviation; SE, standard error; BMI, body mass index; SCH, Sydney Chil-
dren’s Hospital; CHW, Children’s Hospital Westmead; JHCH, John Hunter Children’s
Hospital; PI, pancreatic insufficient; FEV1%, percentage predicted forced expiratory
volume in 1 second; CDC, Centers of Disease Control and Prevention; P. aerug-
inosa, Pseudomonas aeruginosa; S. aureus, Staphylococcus aureus; GOR, gastro-
oesophageal reflux.
∗
Corresponding author: A/Prof (Keith) Chee Y. Ooi, Sydney Children’s Hospital,
School of Women’s and Children’s Health, High Street, Randwick, NSW 2031, Aus-
tralia
E-mail address: keith.ooi@unsw.edu.au (C.Y. Ooi).
intestinal obstruction.
The impact of MI on the clinical course of CF disease remains
uncertain with heterogenous results from previous studies. Cross
sectional studies have showed poorer lung function [2, 3], worse
Shwachman chest radiograph scores [2] and lower fat mass [3] in
MI patients compared to non-MI patients. A follow up study re-
ported no difference in growth and pulmonary outcomes between
patients with and without MI, but the study was short term with
no tracking of growth parameters and pulmonary outcome was
gauged solely by the number of pulmonary-related hospital ad-
missions [4]. More extensive longitudinal studies from the Wis-
consin newborn screening randomised control trial conducted two
decades ago found that patients with MI have a worse clinical
course compared to non-MI patients, in terms of poorer lung func-
tion emerging at 8-10 years of age [5] and malnutrition [6]. How-
ever, more recent longitudinal studies failed to find a difference in
clinical outcomes between both groups [7, 8]. For example, a mul-
ticentre retrospective Israeli study with extended follow up periods
showed no differences in survival rates, pulmonary function and
nutritional status between MI and non-MI patients [8].

https://doi.org/10.1016/j.jcf.2019.09.008
1569-1993/© 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Please cite this article as: S.M.J. Tan, M.J. Coffey and C.Y. Ooi, Differences in clinical outcomes of paediatric cystic fibrosis patients with
and without meconium ileus, Journal of Cystic Fibrosis, https://doi.org/10.1016/j.jcf.2019.09.008
JID: JCF
ARTICLE IN PRESS [m5G;October 28, 2019;13:59]

2 S.M.J. Tan, M.J. Coffey and C.Y. Ooi / Journal of Cystic Fibrosis xxx (xxxx) xxx

A recently published Italian retrospective multicentre observa-

tional study of CF patients with MI showed high incidence (37%) of
poor outcomes (faltering growth and/or chronic P. aeruginosa infec-
tion) at 12-month follow up [9]. The results from this short term
follow up study highlights the importance of evaluating longer
term outcomes of this population as this may impact on their CF
surveillance and management. Our study aimed to compare clini-
cal outcomes between Australian paediatric CF patients with and
without meconium ileus (non-MI).

2. Material and methods

2.1. Study Design and Population Figure 1. Linear model comparing FEV1% of MI patients and non-MI patients. ∗ P-
value of statistical significance. MI, meconium ileus; FEV1%, percentage predicted
forced expiratory volume in 1 second. Complete parameter estimates available in
This was a retrospective case-control study of paediatric CF Supplementary Table 4.
patients with and without MI in the state of New South Wales
(NSW), Australia’s most populous state, from April 1988 to Decem-
ber 2010. Patients with MI were identified through the Australian
2.3. Statistical Analyses
CF Data Registry (inception April 1988). All patients came from one
of the three CF clinics in NSW, namely Sydney Children’s Hospital
Welch’s t-test was performed to assess effectiveness of case-
(SCH), Children’s Hospital Westmead (CHW) and John Hunter Chil-
control matching for age. Comparisons between the cohorts
dren’s Hospital (JHCH). During the study period, each patient had
utilised the Fisher’s exact test for categorical variables. Results
data collected at variable intervals. This study was approved by the
were expressed as odds ratios with 95% confidence interval. For
human research ethics board (LNR/11/SCHN/310).
continuous variables, Student’s t-test and Mann-Whitney U test
MI patients were matched 1:1 with pancreatic insufficient (PI)
were used for parametric and non-parametric data respectively. To
non-MI patients for age, sex and CF clinic using the Australian CF
compare clinical measurements (FEV1%, growth parameters) be-
data Registry. We matched for age and if there was more than one
tween MI and non-MI groups across all ages, linear mixed mod-
suitable match, we selected the control with the smallest age dif-
els (LMM) using lme4 package were used [14]. Diagnostic plots
ference to the subject.
of ‘Residuals versus Fitted’ were used to check linearity for the
Demographic, clinical and microbiology data were collected
models. LMM were constructed using forward selection and com-
from the above databases. Clinical data included pulmonary func-
pared using Bayesian information criterion (BIC). Sensitivity anal-
tion tests (percentage predicted forced expiratory volume in 1 sec-
yses were performed for covariates (demographic variables and
ond (FEV1%) calculated using reference standards [10, 11]) and
growth parameters). A P-value of <0.05 was considered statisti-
growth parameters (age- and sex-specific Z-scores for height,
cally significant. All statistical analyses were performed with RStu-
weight and BMI calculated using Centers of Disease Control and
dio version 3.4.2 (Boston, MA) [15].
Prevention (CDC) smoothed percentile curves [12]).
For patients 0-20 years of age, height, weight and BMI Z-scores
(BMI Z-scores 0-2 years were not available) were compared. All Z-
scores greater than 10 or less than -10 were excluded from analy- 3. Results
sis due to likely implausibility. For patients 20 years and older, ab-
solute values for height, weight and BMI were recorded, however 3.1. Demographics
comparison was limited by small numbers (2 MI and 3 non-MI pa-
tients). There were 162 matched pairs (N=324, 52% female) with mean
We recorded nutritional interventions, gastrointestinal com- (SD) age at matching of 15.3 (8.2) and 14.9 (7.9) years for MI and
plications, CF-related diabetes, hospital admissions, transplants non-MI patients respectively (P=0.6). Median (IQR) age difference
and deaths in each group. We only included microbiology between the matched pairs was 2.4 (1.2-6.0) months. During the
data from cultures obtained from bronchoalveolar lavage or study period (1988-2010), the mean (SD) duration of follow up
sputum. was 6.4 (3.8) years for MI patients and 7.7 (3.5) years for non-MI
patients (P<0.002). Demographic data is summarised in Table 1.
Genotypes of patients are summarised in Supplementary Table 1.
2.2. Definitions

The definition of CF and MI were pre-defined within the Aus-
tralian CF Data Registry. This is a database containing de-identified
information about patients who attend CF centres or clinics at Aus-
tralian hospitals (with at least 50 patients). The Data Registry is
managed by Cystic Fibrosis Australia with advice from a Data Reg-
istry Advisory Committee consisting principally of specialist doc-
tors from the centres.
Chronic Pseudomonas aeruginosa infection was defined by three
consecutive respiratory cultures within a 12-month period and/or
isolation of mucoid P. aeruginosa [13]. Chronic Staphylococcus au-
reus infection was defined by three consecutive positive respiratory
cultures within a 12-month period.
3.2. Pulmonary Function Testing
A total of 2,004 measurements were recorded from 133 (82.1%)
of the MI patients and 2,210 measurements were recorded from
141 (87.0%) of the non-MI patients. Missing data is summarised in
Supplementary Results 2. We excluded FEV1% measurements be-
low 5 years of age due to potential unreliability of lung function
testing. The LMM for FEV1% was constructed as described in Sup-
plementary Results 1 and Supplementary Figure 3A. Overall, MI pa-
tients aged 5 to 23 years had a FEV1% 7.0% lower compared to non-
MI patients (estimate -0.070 SE [0.02], P=0.003) (Figure 1; Supple-
mentary Table 4).

Please cite this article as: S.M.J. Tan, M.J. Coffey and C.Y. Ooi, Differences in clinical outcomes of paediatric cystic fibrosis patients with
and without meconium ileus, Journal of Cystic Fibrosis, https://doi.org/10.1016/j.jcf.2019.09.008
JID: JCF
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S.M.J. Tan, M.J. Coffey and C.Y. Ooi / Journal of Cystic Fibrosis xxx (xxxx) xxx 3

Table 1
Demographic data

Characteristics MI, n=162 (%) Non-MI, n=162 (%) Matching (%)

Age (years) at 31/12/2010∗ , mean (SD) 15.3 (8.2) 14.9 (7.9) P=0.65
Sex
Male (% male) 77 (47.5) 77 (47.5) 100
Pancreatic function
Pancreatic Insufficient 117 (72.2) 162 (100)† -
Pancreatic Sufficient 44 (27.2) 0 (0) -
Unknown 1 (0.62) 0 (0) -
Hospital
SCH 51 (31.5) 51 (31.5) 100
CHW 95 (58.6) 95 (58.6) 100
JHCH 16 (9.9) 16 (9.9) 100
∗
Age at 31/12/2010 (for matching analysis) significantly effective using Welch’s t-test.
†
All MI patients matched with pancreatic insufficient non-MI patients.CHW, Children’s Hospital at
Westmead; JHCH, John Hunter Children’s Hospital; SCH, Sydney Children’s Hospital.

Table 2
Microbiology data

MI, n=162 Non-MI, n=161∗

Parameter Result Result P value

P. aeruginosa
Isolation 132 (81%) 120 (75%) 0.1
Age 1st isolation (years) 7.8 (5.1) 7.8 (4.6) 1.0
Chronic colonisation∗ 72 (44%) 71 (44%) 1.0
Age 1st chronic colonisation (years) 11.0 (6.0-14.5) 10.4 (7.2-13.0) 0.8
S. aureus
Isolation 116 (82%) 132 (72%) 0.03
Age 1st isolation (years) 7.3 (4.6) 7.3 (5.0) 1.0
Chronic colonisation† 36 (22%) 51 (32%) 0.06
Age 1st chronic colonisation (years) 9.8 (5.4-13.1) 7.7 (4.6-13.1) 0.6

Data presented as number (percentage), mean (SD) or median (IQR).

∗
1 patient excluded due to unknown data.
†
Chronic colonisation defined by 3 consecutive cultures within a 12-month period or iso-
lation of mucoid Pseudomonas species.

3.3. Growth
Measurements were obtained from 98.1%, 98.8% and 92% of the
MI patients and 100%, 100% and 96.7% of the non-MI patients for
height, weight and BMI respectively. Missing data is summarised in
Supplementary Results 2. All growth variables were analysed us-
ing LMMs, which were constructed in a similar fashion to FEV1%
(Supplementary Results 1; Supplementary Figure 3B-D). MI pa-
tients aged 2 to 20 years had significantly lower BMI Z-scores over
time (estimate -0.25 SE [0.1], P=0.02) compared to non-MI patients
(Figure 2A; Supplementary Table 4). However, there were no signif-
icant differences in height Z-scores (estimate 0.040 SE [0.1], P=0.7)
(Figure 2B; Supplementary Table 4) and weight Z-scores (estimate
-0.17 SE [0.1], P=0.2) (Figure 2C; Supplementary Table 4) in this
age group, or in the 0 to 2 age group (P=0.8 and P=0.3 for height
and weight respectively) (Supplementary Table 4).
3.4. Nutrition
significant differences between MI and non-MI groups for P. aerug-
inosa isolation rates (81% vs 75%, P=0.1), or mean (SD) age of first
isolation (7.8 [5.1] vs 7.8 [4.6], P=1.0). Chronic P. aeruginosa isola-
tion rate was 44% in both groups (P=1). Sub-analysis of mucoid,
non-mucoid, non-differentiated and other species of P. aeruginosa
showed no significant differences between MI and non-MI patients.
MI patients had significantly lower S. aureus isolation rates com-
pared to non-MI (72% vs 82%, OR 0.6 [0.3-1.0], P=0.03).
3.6. Other Gastrointestinal and Hepatic Complications
Age range of patients was 0 to 23 years. Rates of gastro-
oesophageal reflux (GOR) disease were higher in the MI group (OR
2.9 [1.1-8.5], P = 0.02). There were no significant differences be-
tween groups for rates of cirrhosis or portal hypertension (OR 1.8
[0.4-8.5], P=0.4]) or abnormal liver function (OR 1.0 [0.3-3.9], P=1)
(Supplementary Table 3).

3.7. CF-related Diabetes

Between 0 and 23 years of age, 9 MI patients (5.8%) ever re-
quired total parenteral nutrition compared to none of the non-MI
MI patients between 0 and 24 years of age had similar rates
patients (P=0.002). MI patients were more likely to receive oral
of CF-related diabetes compared to non-MI patients (8.6% vs 10.5%,
feed supplements (OR 2.8 [1.4-6.1], P=0.003) and gastrostomy for-
P=0.7) (Supplementary Table 3).
mation (OR 4.4 [1.1-24.6], P=0.02). Six patients with MI and 1 pa-
tient without MI required nasogastric feeds (P=0.06) (Supplemen-
tary Table 2). 3.8. Hospital Admissions

3.5. Microbiology We looked at hospital admissions for respiratory and gastroin-

testinal complications of CF. Data was available for all patients.
Microbiology data was available for all 162 MI patients and 161 Ages of patients ranged from 0 to 24 years. The mean (SD) num-
non-MI patients (Table 2). There was missing data for one non-MI ber of hospital admissions per year for CF-related respiratory ill-
patient. Age of patients ranged from 0 to 23 years. There were no ness was significantly higher for MI patients compared to non-MI

Please cite this article as: S.M.J. Tan, M.J. Coffey and C.Y. Ooi, Differences in clinical outcomes of paediatric cystic fibrosis patients with
and without meconium ileus, Journal of Cystic Fibrosis, https://doi.org/10.1016/j.jcf.2019.09.008
JID: JCF
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4 S.M.J. Tan, M.J. Coffey and C.Y. Ooi / Journal of Cystic Fibrosis xxx (xxxx) xxx
Figure 2. Linear models comparing (A) BMI, (B) Height, (C) Weight of MI pa-
tients and non-MI patients. ∗ P-value of statistical significance. MI, meconium ileus;
BMI, body mass index. Complete parameter estimates available in Supplementary
Table 4.
patients (0.7 [1.0] vs 0.4 [0.7], P=0.001). The total number of hos-
pital days per year for this was also significantly higher in the MI
group (8.5 [14.2] vs 5.1 [9.9], P=0.01).
For CF-related gastrointestinal admissions, the MI group com-
pared to non-MI had higher mean (SD) number of hospital admis-
sions per year (0.2 [0.5] vs 0.04 [0.1], P=0.0004), and hospital days
per year (2.0 [6.1] vs 0.1 [0.5], P=0.0001).
3.9. Transplant and Death
Data was available for all patients, ages ranging from 0 to 24
years. Over the follow-up period, 13 MI patients and 8 non-MI pa-
tients were evaluated for potential transplants (bilateral lung, liver,
heart and lung) with no significant difference between the groups
(P=0.4). There was a total of 10 CF-related deaths in the MI group,
of which 7 were attributed to a pulmonary cause, 2 from liver
failure and 1 from gastrointestinal disease. The CF-related death
rate in the MI group was significantly higher compared to non-MI
group where there was 1 death (cause not further specified) (OR
10.5 [1.4, 462], P=0.01).
Please cite this article as: S.M.J. Tan, M.J. Coffey and C.Y. Ooi, Differences in clinical outcomes of paediatric cystic fibrosis patients with
and without meconium ileus, Journal of Cystic Fibrosis, https://doi.org/10.1016/j.jcf.2019.09.008
[m5G;October 28, 2019;13:59]
3.10. Sensitivity analyses
We did not match for mutation class in the primary analyses
due to a marked reduction in sample size from 162 to 83 matched
pairs. Lung function and growth analyses of this subset of pa-
tients (additionally matched for mutation class: ‘I-III’, ‘IV-V’ or ‘Un-
known’) are presented in Supplementary Figures 1 and 2.
4. Discussion
4.1. Summary of findings
In this study, we identified that the MI phenotype was asso-
ciated with worse clinical outcomes than patients without MI. Pa-
tients with MI were associated with worse pulmonary function and
lower BMI z-scores compared to those without MI. Consistent with
this, there were also significantly more CF-related respiratory and
gastrointestinal hospitalisations, requirements for nutritional inter-
ventions (oral feed supplements and gastrostomy formation) and
deaths among patients with MI than without MI.
4.2. Comparison with literature
This study reports that MI has negative impact on clinical out-
comes in the longer term (at least 20 years of life), complement-
ing the findings of a recently published Italian multicentre obser-
vational study which showed high incidence of adverse outcomes
in the short term (end of first year of life) [9]. Faltering growth
(weight or length <3rd percentile) and/or chronic P. aeruginosa in-
fection were reported in almost 40% of CF patients with MI at
12-month follow up. Risk factors identified were prenatally diag-
nosed intestinal obstruction and a need for intensive care and oxy-
gen therapy. Complex MI, need for surgery, intestinal resection and
stoma confection did not favour an adverse outcome [9].
In our study, patients with MI had a significantly poorer mean
FEV1% over time and higher mortality rates (7/10 deaths from pul-
monary causes) than non-MI patients. Similarly, Li et al reported
that MI patients had worse longitudinal decline in lung function,
with the decrement in FEV1% beginning at 8-10 years of age [5].
Additionally, poorer survival in CF patients with MI compared to
non-MI patients diagnosed at similar ages by neonatal screening
was demonstrated by Lai et al [16]. Other studies have also showed
poorer lung function in MI patients compared to non-MI controls
[2, 3], however it is noteworthy that these patients were not fol-
lowed over time.
The poorer FEV1% in the MI group may be explained by the
worse nutritional status in the affected group. Infants and children
with MI are at risk of malnutrition and poor growth, which may be
due to multiple factors including: (i) recovery and limited enteral
feeds in the postoperative period, (ii) malabsorption secondary to
bowel resection, (iii) dysmotility, (iv) small bowel bacterial over-
growth, and (v) total parenteral nutrition-related cholestasis [17].
Lai et al [6] reported that poorer growth in the MI patients was
related to surgical treatment for MI and lower plasma linoleic acid
levels before 2 years of age. Higher serum linoleic acid levels (≥ 21
mol%) have been positively associated with growth, body composi-
tion, and lung function [18].
Nutrition is a well-known cornerstone of CF management.
Achieving and maintaining optimal growth and nutrition are asso-
ciated with improved lung function and survival, i.e. malnutrition
is detrimental to lung health and survival in patients with CF [19,
20]. We identified lower BMI Z-scores in MI patients with no sig-
nificant difference in weight or height Z scores. This is possibly be-
cause the MI patients tended to be slightly taller but were thinner
than their non-MI counterparts. On the other hand, the Wisconsin
group found that MI patients were shorter and thinner compared
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S.M.J. Tan, M.J. Coffey and C.Y. Ooi / Journal of Cystic Fibrosis xxx (xxxx) xxx
to non-MI patients, but they did not compare BMI [6]. Poor growth
has been found to be a modifiable extrinsic risk factor for determi-
nants of lung disease [21].
A recognised risk factor for progression of lung disease in CF is
P. aeruginosa colonisation, especially chronic or mucoid P. aerugi-
nosa [21, 22]. However, in this study, lung microbiology could not
explain the difference in lung function between the groups. Sim-
ilar rates of P. aeruginosa isolation and chronic colonisation were
found in MI and non-MI patients. Interestingly, MI patients had
lower isolation rates for S. aureus compared with non-MI patients.
A small series suggested that increased reflux burden was associ-
ated with poorer lung function and Pseudomonas positivity [23].
Our study showed higher rates of GOR in the MI group compared
with non-MI, however, evidence that GOR leads to worse respira-
tory outcomes is still limited [24]. Modifier genes have been iden-
tified in patients with MI but the impact of these on clinical out-
comes is unclear [25]. During the study period, CFTR modulator
therapy was not yet available in Australia.
Efrati et al reported similar respiratory and nutritional status
and survival rates in MI and non-MI patients when follow up was
extended to 20 years [8]. This finding could partially be explained
by the high prevalence of a unique mutant W1282X gene in the
Israeli study population and its influence on MI patients is unclear.
Furthermore, there is no newborn screening for CF in Israel [8]. In
Australia, newborn screening for CF started in 1981 in NSW, with
Western Australia the last state to commence in 2001. Previous
follow-up studies conducted without newborn screening also did
not find differences in long term pulmonary and nutritional out-
comes between MI and non-MI patients [4, 7, 26, 27]. One possi-
ble explanation for the differences with our findings could be that
patients with MI are diagnosed at a younger age and inadvertently
receive benefits from earlier treatment for CF.
4.3. Strengths and limitations
A strength of this study was the use of LMM analyses of lung
function and growth, which considers all recorded measures for
each individual over their duration of follow up. To our knowl-
edge, this study has the largest number of MI patients. Our study
was limited by its retrospective design and inherent nature of
registry databases including: (i) complete criteria of diagnoses
not recorded, only the diagnoses themselves, (ii) hospital admis-
sions coded as respiratory, gastrointestinal or other (not speci-
fied further), (iii) precise durations of nutritional interventions not
recorded, (iv) lack of observed socioeconomic variables, (v) patient
movement between clinics may not have been captured, (vi) left-
and/or right-censoring of data. Data was obtained from 3 different
CF clinics. Nevertheless, we matched for CF clinic to reduce vari-
ances in clinical practice.
The MI phenotype is highly associated with functionally severe
class I-III CFTR mutations and those with high pancreatic insuffi-
ciency prevalence (PIP) scores [28-31]. In this study, we conserva-
tively matched all MI patients, including those recorded as PS, to
non-MI PI controls because 43 out of 44 of the MI PS patients were
on pancreatic enzymes and/or homozygous for delta F508 muta-
tion.
4.4. Clinical implications
This study has shown that children with MI are at higher nu-
tritional and respiratory risk, suggesting that MI may be a poor
prognostic factor in CF. Increased awareness and vigilance among
CF healthcare providers may be helpful so that patients with MI
have close monitoring of nutrition, growth and careful respira-
tory surveillance using spirometry, airway microbiology and chest
Please cite this article as: S.M.J. Tan, M.J. Coffey and C.Y. Ooi, Differences in clinical outcomes of paediatric cystic fibrosis patients with
and without meconium ileus, Journal of Cystic Fibrosis, https://doi.org/10.1016/j.jcf.2019.09.008
[m5G;October 28, 2019;13:59]
5
imaging. Earlier aggressive nutritional intervention and respiratory
therapeutics may be of benefit in this population.
5. Conclusions
In this study, we have demonstrated that paediatric CF patients
with MI have worse respiratory, growth and nutritional outcomes
compared with those without MI. Meconium ileus may be an im-
portant early risk and prognostic factor, potentially influencing CF
surveillance and management.
Funding
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Declaration of Competing Interest
Chee Y. Ooi has been a consultant and advisory board member
for Vertex.
Supplementary materials
Supplementary material associated with this article can be
found, in the online version, at doi:10.1016/j.jcf.2019.09.008.
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Please cite this article as: S.M.J. Tan, M.J. Coffey and C.Y. Ooi, Differences in clinical outcomes of paediatric cystic fibrosis patients with
and without meconium ileus, Journal of Cystic Fibrosis, https://doi.org/10.1016/j.jcf.2019.09.008