Introduction: Preterm infants are at risk for a variety of somatic and neurological disorders. In recent years, biofluid proteomics has emerged as a potential diagnostic tool for biomarker analysis. The aim of this study was to determine gestational age (GA)-related patterns of the urinary peptidome in preterm infants for researching potential novel prognostic biomarkers. Methods: We performed urinary peptidomics in longitudinal samples of 24 preterm (mean GA weeks 28 + 1 [24+1–31 + 6]) and 27 term born controls (mean GA weeks 39 + 2 [37+0–41 + 1]) using capillary electrophoresis combined with mass spectrometry (CE-MS). Peptides were sequenced using CE-MS/MS or LC-MS/MS analysis and were deposited, matched, and annotated in a Microsoft SQL database for statistical analysis. We compared their abundance in urine of preterm and term born infants and performed a validation analysis as well as correlations to GA and clinical risk scores. Results: Our results confirmed significant differences in the abundance of peptides and the hypothesis of age-dependent urinary peptidome changes in preterm and term infants. In preterm infants, SLC38A10 (solute carrier family 38 member 10) is one of the most abundant peptides. Combined urinary peptides correlated with clinical risk scores (p < 0.05). Conclusion: This is the first study reporting GA-related urinary peptidome changes of preterm infants detected by CE-MS and a modulation of the peptidome with GA. Further research is required to locate peptidome clusters correlated with specific clinical complications and long-term outcome. This may identify preterm infants at higher risk for adverse outcome who would benefit from early intervention.

1.
Althabe
F
,
Howson
CP
,
Kinney
M
,
Lawn
J
.
Born too soon. The global action report on preterm birth
.
Geneva, Switzerland
:
World Health Organization
.
2012
. Available from: https://apps.who.int/iris/handle/10665/44864 (accessed June 5 2023).
2.
Marlow
N
,
Wolke
D
,
Bracewell
MA
,
Samara
M
;
EPICure Study Group
.
Neurologic and developmental disability at six years of age after extremely preterm birth
.
N Engl J Med
.
2005
;
352
(
1
):
9
19
. .
3.
Spittle
AJ
,
Orton
J
.
Cerebral palsy and developmental coordination disorder in children born preterm
.
Semin Fetal Neonatal Med
.
2014
;
19
(
2
):
84
9
. .
4.
Ortgies
T
,
Rullmann
M
,
Ziegelhöfer
D
,
Bläser
A
,
Thome
UH
.
The role of early-onset-sepsis in the neurodevelopment of very low birth weight infants
.
BMC Pediatr
.
2021
;
21
(
1
):
289
. .
5.
Vardhelli
V
,
Murki
S
,
Tandur
B
,
Saha
B
,
Oleti
TP
,
Deshabhotla
S
, et al
.
Comparison of CRIB-II with SNAPPE-II for predicting survival and morbidities before hospital discharge in neonates with gestation ≤32 weeks: a prospective multicentric observational study
.
Eur J Pediatr
.
2022
;
181
(
7
):
2831
8
. .
6.
Felderhoff-Müser
U
,
Hüning
B
.
Biomarker und Neuromonitoring zur Entwicklungsprognose nach perinataler Hirnschädigung
.
Monatsschr Kinderheilkd
.
2022
;
170
(
8
):
688
703
. .
7.
Mavrogeorgis
E
,
Mischak
H
,
Beige
J
,
Latosinska
A
,
Siwy
J
.
Understanding glomerular diseases through proteomics
.
Expert Rev Proteomics
.
2021
;
18
(
2
):
137
57
Epub 2021 Apr 8. .
8.
Magalhães
P
,
Schanstra
JP
,
Carrick
E
,
Mischak
H
,
Zürbig
P
.
Urinary biomarkers for renal tract malformations
.
Expert Rev Proteomics
.
2016
;
13
(
12
):
1121
9
. .
9.
Buhimschi
CS
,
Bhandari
V
,
Dulay
AT
,
Nayeri
UA
,
Abdel-Razeq
SS
,
Pettker
CM
, et al
.
Proteomics mapping of cord blood identifies haptoglobin “switch-on” pattern as biomarker of early-onset neonatal sepsis in preterm newborns
.
PloS One
.
2011
;
6
(
10
):
e26111
. .
10.
Ahmed
S
,
Odumade
OA
,
van Zalm
P
,
Smolen
KK
,
Fujimura
K
,
Muntel
J
, et al
.
Urine proteomics for noninvasive monitoring of biomarkers in bronchopulmonary dysplasia
.
Neonatology
.
2022
;
119
(
2
):
193
203
. .
11.
Sylvester
KG
,
Ling
XB
,
Liu
GY
,
Kastenberg
ZJ
,
Ji
J
,
Hu
Z
, et al
.
Urine protein biomarkers for the diagnosis and prognosis of necrotizing enterocolitis in infants
.
J Pediatr
.
2014
;
164
(
3
):
607
12.e127
. .
12.
Jung
YH
,
Han
D
,
Shin
SH
,
Kim
EK
,
Kim
HS
.
Proteomic identification of early urinary-biomarkers of acute kidney injury in preterm infants
.
Sci Rep
.
2020
;
10
(
1
):
4057
. .
13.
Dzietko
M
,
Schulz
S
,
Preuss
M
,
Haertel
C
,
Stein
A
,
Felderhoff-Mueser
U
, et al
.
Apolipoprotein E gene polymorphisms and intraventricular haemorrhage in infants born preterm: a large prospective multicentre cohort study
.
Dev Med Child Neurol
.
2019
;
61
(
3
):
337
42
. .
14.
Latosinska
A
,
Siwy
J
,
Mischak
H
,
Frantzi
M
.
Peptidomics and proteomics based on CE-MS as a robust tool in clinical application: the past, the present, and the future
.
Electrophoresis
.
2019
;
40
(
18–19
):
2294
308
. .
15.
Latosinska
A
,
Siwy
J
,
Faguer
S
,
Beige
J
,
Mischak
H
,
Schanstra
JP
.
Value of urine peptides in assessing kidney and cardiovascular disease
.
Proteomics Clin Appl
.
2021
;
15
(
1
):
2000027
. .
16.
Zürbig
P
,
Jerums
G
,
Hovind
P
,
Macisaac
RJ
,
Mischak
H
,
Nielsen
SE
, et al
.
Urinary proteomics for early diagnosis in diabetic nephropathy
.
Diabetes
.
2012
;
61
(
12
):
3304
13
. .
17.
Mischak
H
,
Vlahou
A
,
Ioannidis
JPA
.
Technical aspects and inter-laboratory variability in native peptide profiling: the CE-MS experience
.
Clin Biochem
.
2013
;
46
(
6
):
432
43
. .
18.
Jantos-Siwy
J
,
Schiffer
E
,
Brand
K
,
Schumann
G
,
Rossing
K
,
Delles
C
, et al
.
Quantitative urinary proteome analysis for biomarker evaluation in chronic kidney disease
.
J Proteome Res
.
2009
;
8
(
1
):
268
81
. .
19.
Klein
J
,
Papadopoulos
T
,
Mischak
H
,
Mullen
W
.
Comparison of CE-MS/MS and LC-MS/MS sequencing demonstrates significant complementarity in natural peptide identification in human urine
.
Electrophoresis
.
2014
;
35
(
7
):
1060
4
. .
20.
Zürbig
P
,
Renfrow
MB
,
Schiffer
E
,
Novak
J
,
Walden
M
,
Wittke
S
, et al
.
Biomarker discovery by CE-MS enables sequence analysis via MS/MS with platform-independent separation
.
Electrophoresis
.
2006
;
27
(
11
):
2111
25
. .
21.
He
T
,
Pejchinovski
M
,
Mullen
W
,
Beige
J
,
Mischak
H
,
Jankowski
V
.
Peptides in plasma, urine, and dialysate: toward unravelling renal peptide handling
.
Clin Appl
.
2021
;
15
(
1
):
e2000029
. .
22.
McKleroy
W
,
Lee
T-H
,
Atabai
K
.
Always cleave up your mess: targeting collagen degradation to treat tissue fibrosis
.
Am J Physiol Lung Cell Mol Physiol
.
2013
;
304
(
11
):
L709
21
. .
23.
Gerasymchuk
M
,
Cherkasova
V
,
Kovalchuk
O
,
Kovalchuk
I
.
The role of microRNAs in organismal and skin aging
.
Int J Mol Sci
.
2020
;
21
(
15
):
5281
. .
24.
Verhaeghe
J
,
Van Bree
R
,
Van Herck
E
,
Laureys
J
,
Bouillon
R
,
Van Assche
FA
.
C-peptide, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1 in umbilical cord serum: correlations with birth weight
.
Am J Obstet Gynecol
.
1993
;
169
(
1
):
89
97
. .
25.
Fawer
CL
,
Torrado
A
,
Guignard
JP
.
Maturation of renal function in full-term and premature neonates
.
Helv Paediatr Acta
.
1979
;
34
(
1
):
11
21
.
26.
Guignard
JP
,
Torrado
A
,
Da Cunha
O
,
Gautier
E
.
Glomerular filtration rate in the first three weeks of life
.
J Pediatr
.
1975
;
87
(
2
):
268
72
. .
27.
Hellsten
SV
,
Hägglund
MG
,
Eriksson
MM
,
Fredriksson
R
.
The neuronal and astrocytic protein SLC38A10 transports glutamine, glutamate, and aspartate, suggesting a role in neurotransmission
.
FEBS Open Bio
.
2017
;
7
(
6
):
730
46
. .
28.
Tripathi
R
,
Aggarwal
T
,
Fredriksson
R
.
SLC38A10 transporter plays a role in cell survival under oxidative stress and glutamate toxicity
.
Front Mol Biosci
.
2021
;
8
:
671865
. .
29.
Bjelosevic
S
,
Pascovici
D
,
Ping
H
,
Karlaftis
V
,
Zaw
T
,
Song
X
, et al
.
Quantitative age-specific variability of plasma proteins in healthy neonates, children and adults
.
Mol Cell Proteomics
.
2017
;
16
(
5
):
924
35
. .
30.
Bhatti
G
,
Romero
R
,
Gomez-Lopez
N
,
Chaiworapongsa
T
,
Jung
E
,
Gotsch
F
, et al
.
The amniotic fluid proteome changes with gestational age in normal pregnancy: a cross-sectional study
.
Sci Rep
.
2022
;
12
(
1
):
601
. .
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