Online Appendix 2. Characteristics of included studies
Article title:
Skin barrier function in infancy: a systematic review
Journal:
Archives of Dermatological Research
Authors:
Laine Ludriksone*, Natalie Garcia Bartels*, Varvara Kanti,
Ulrike Blume-Peytavi, Jan Kottner
* Both authors contributed equally to this paper.
Corresponding author:
Priv.-Doz. Dr. med. Natalie Garcia Bartels, M.D.
Charité-Universitätsmedizin Berlin
Department of Dermatology and Allergy
Clinical Research Center for Hair and Skin Science
Email: [email protected]
1
Online Appendix 2. Characteristics of included studies
Author
(year)
Study
-ID
Country
Time
frame/
season
Sample
n
Mean age
(SD) in weeks
Female
(n)
Skin type, ethnic
origin
22
Cunico (1977)
[4]
1
USA
-
0.3
-
-
35
9
Hammarlund
(1977) [11]
2
Sweden
-
Other
characteristics
Healthy infants;
n = 7 small for
gestational age
(SGA)
Measured
parameter
TEWL
19
-
Healthy infants
TEWL
9
Hammarlund
(1980) [12]
3
Sweden
-
14
0.1
8
-
Healthy small for
gestational age
infants
TEWL
Rutter (1979)
[28]
31
UK
-
36
0.4
-
-
Healthy infants
TEWL
Rutter (1979)
[27]
35
UK
-
32
0.8
-
-
Healthy infants
TEWL
Örsmark
(1980) [25]
4
USA
-
13
0.3
5
-
Healthy infants
TEWL
-
Most infants were
well when studied;
n = 5 small for
gestational age
(SGA)
TEWL
Harpin (1983)
[13]
32
UK
-
20
1.0
-
2
Ambient temperature:
23.3°C;
Relative humidity: 50%
Ambient temperature:
26.3°C
6
0.1
Measurement
conditions and
procedures
Infants placed in an
incubator;
Ambient temperature
32.1-36.5 C;
Relative humidity: 50%
Infants placed in an
incubator;
Ambient temperature
33.6 (SD 0.8) C;
Relative humidity: 2060%
Infants placed in an
incubator;
Ambient temperature
34.2 C;
Relative humidity: 2060%
Infants placed in an
incubator;
Ambient temperature
31.1 (SD 0.5) C;
Relative humidity: 47
(5)%
Infants placed in an
incubator;
Ambient temperature:
24.9 -29.9 C;
Relative humidity: 2658%
Ambient temperature:
24.4 (SD 0.5) °C
Infants studied under
neutral thermal
conditions in
unhumidified incubators
or cots;
Relative humidity: 32-
Comments
Mean age recalculated
based on ranges;
Infants bathed 6-10h
prior to measurements
Infant skin not washed
or wiped prior to
measurements
-
Mean age recalculated
based on ranges
Mean age recalculated
based on ranges
-
Mean age recalculated
based on ranges
Online Appendix 2. Characteristics of included studies
Strömberg
(1983) [31]
Braun (1986)
[2]
Kahn (1987)
[16]
Kahn (1987)
[17]
5
6
7
34
Sweden
Austria
Belgium
Belgium
-
15
0.0 (0.0)
6
2.4 (1.0)
3
5.3 (0.6)
-
-
8
-
4
19.3 (4.6)
3
35.7 (3.5)
8
10.5 (3.3)
5
110
13.0 (8.4)
56
-
-
Healthy infants
No skin diseases
Healthy infants
11.2 (12.4)
34
Only results with a
corresponding body
temperature 37.0 C
included
skin surface
pH
-
Mean values of
measurements
performed on two
consecutive days;
Measurements on day
2 assessed
approximately 24 h
after bathing the infant
with a syndet
TEWL
Ambient temperature: 23
-25 C;
Relative humidity: 30%;
Continuous 10 min
TEWL reading
Skin of infants not
touched or washed
prior to measurements
TEWL
Ambient temperature: 23
-25 C;
Relative humidity: 30%
Skin of infants not
touched or washed
prior to measurements
Ambient temperature:
26 C;
Relative humidity: 52%
Infants placed in an
incubator;
Ambient temperature:
32.7 (SD 0.6) °C;
Relative humidity: 50%
(SD 1%);
Acclimatization 30 min
Ambient temperature: 21
°C;
Relative humidity: 2045%
Measurements
performed more than
2 hours after bathing
Healthy infants;
normal skin
1982 - 1985
80
TEWL
57%
Infants placed in an
incubator;
Ambient temperature
36.6 C;
Relative humidity: 50%
Siblings of infants
who had died of
SIDS;
normal skin
Saijo (1991)
[29]
33
Japan
Summer
46
0.4
-
-
Healthy infants
TEWL
Kjartansson
(1992) [20]
8
Sweden
-
10
0.6
-
-
Infants with
hyperbilirubinaemi
a, otherwise
healthy
TEWL
Tollesson
(1993) [32]
9
Sweden
-
25
15.0
11
-
Healthy infants
TEWL
Priestley
(1996) [26]
10
Scotland
-
302
34.8
-
-
Infants free from
psoriasis,
ichthyosis, or
skin surface
pH
3
-
Mean age recalculated
based on ranges
Mean age recalculated
based on ranges
Mean age recalculated
based on ranges
Online Appendix 2. Characteristics of included studies
other significant
eruptions in the
diaper area
Iliev (1998)
[15]
Visscher
(2000) [34]
11
12
Switzerland
USA
-
-
20
39.1
31
0.1
0.6
1.0
2.0
3.0
4.0
11
20
-
White n = 29
Black n = 2
No skin diseases
Healthy infants
skin surface
pH
-
Mean age recalculated
based on ranges
skin surface
pH
Measurements on day 4,
7, 14, 21 and 29
performed at home;
Measurements
performed 25 min after
diaper removal
Follow-up of the same
cohort over the first 4
weeks of life
TEWL; skin
surface pH
Ambient temperature:
22-24°C;
Room humidity: 50%;
Acclimatization 15 min
Measurements
performed on the first
and second day of life;
Infants washed after
birth with a wet towel
and tap water
TEWL; skin
surface pH
Ambient temperature:
20.4-24°C;
Room humidity: 45-50%;
Acclimatization 10 min;
No skin care product
application at least 12 h
prior to measurements
-
0.1
Yosipovitch
(2000) [36]
13
Israel
-
41
20
-
Healthy infants
0.2
Giusti (2001)
[10]
Hoeger
(2002) [14]
Visscher
(2002) [33]
14
15
16
Italy
Germany
USA
May, June,
September
1999
February
1997 –
February
1998
July 1997 –
October
1997
70
62.1 (28.9)
180
0.4
163
4.3
179
12.9
52
19.1 (16.1)
45
-
-
-
Caucasian
White n = 47
Black n = 4
Asian n = 1
4
Healthy infants;
No skin diseases
Healthy infants
Healthy infants;
No eczema,
congenital skin
diseases or diaper
dermatitis
skin surface
pH
TEWL
Ambient temperature:
21.6°C (SD 1.5°C);
Ambient humidity: 46.4
(SD 7.45) %;
No bathing at least 14
hours prior to
measurements;
Ambient temperature:
26 C;
Relative humidity: 45%;
Measurements
preformed 17-18 min
after diaper removal
No use of diaper wipes,
bathing products,
ointments, creams or
powders at least 24 h
Follow-up of the same
cohort over the first 90
days of life;
Bathing frequency 1-2
times per week in
clear water;
Use of moisturizer
discouraged
-
Online Appendix 2. Characteristics of included studies
prior to measurements
skin surface
pH
Room temperature and
relative humidity and
outside conditions
recorded daily
Measurements
performed on the first
two days of life;
Vernix caseosa
retained n = 30
infants;
n = 30 infants wiped
with a cotton towel to
remove the vernix
caseosa;
Infants bathed with a
syndet after the initial
measurements
TEWL
Ambient temperature: 21
(SD 1) C;
Relative humidity: 50
(SD 3) %;
Acclimatization 10 min
Follow-up of the same
cohort over the first 6
months
TEWL
Measurements
performed in a
windowless room
maintained at constant
temperature;
No use of moisturizers
at least 24 h prior to
measurements
-
0.0
Visscher
(2005) [35]
17
USA
November
2001 – April
2003
60
-
-
Healthy infants
-
n = 15 with atopic
family history;
n = 5 without
atopic family
history
-
No personal
history of atopic
diseases, any skin
disease, fever,
and steroid or
immunosuppressiv
e therapy within
the last 2 months;
Parental history of
atopy n = 12
0.1
Kikuchi (2006)
[19]
Boralevi
(2008) [1]
Nikolovski
(2008) [24]
Garcia Bartels
(2009) [7]
18
19
20
21
Japan
France
USA
Germany
October
1999 –
December
2000
May 2002 –
June 2004
(no TEWL
assessment
during
summer
June to
September)
0.7
20
4.4
13.0
26.1
30
30.4 (10.4)
19
19.6
-
October
2005 – April
2006
-
31
41.3
57
0.3
48
1.0
13
-
Caucasian;
Fair complexioned
25
Caucasian n = 50;
Non-Caucasian n = 7
-
-
5
Healthy infants;
No history of skin
disorders
Healthy infants;
No present skin
diseases;
Family history of
skin diseases n =
32
TEWL
TEWL; skin
surface pH
Ambient temperature:
20-25°C;
Relative humidity: 40%;
Acclimatization 15 min;
No skin care products at
least 24 h prior to
measurements
Ambient temperature
21.9- 29.9°C;
Relative humidity: 23.850.5%
Acclimatization 10 min
with the infant partly
undressed;
Mean age recalculated
based on ranges
Follow-up of the same
cohort over the first 4
weeks of life
Washing 2 h pp with a
wet towel and tap
water;
Infants bathed/washed
Online Appendix 2. Characteristics of included studies
44
64
16
Garcia Bartels
(2010) [9]
Garcia Bartels
(2011) [8]
22
23
Germany
Germany
4.0
0.3
2.0
-
-
32
Caucasian n = 61
Non-Caucasian n = 3
Healthy infants;
No present skin
diseases;
Maternal history of
AD n = 3;
Paternal history of
AD n = 3
8
Caucasian n = 14
Non-Caucasian n = 2
Maternal history of
AD n = 2;
Paternal history of
AD n = 1
October
2006 – May
2007
September
2009 –
December
2009
TEWL; skin
surface pH
16
4.0
8
Caucasian n = 14
Non-Caucasian n = 2
Maternal history of
AD n = 2;
Paternal history of
AD n = 1
16
8.0
8
Caucasian n = 14
Non-Caucasian n = 2
Maternal history of
AD n = 2;
Paternal history of
AD n = 1
44
24
19.6
25.6
21
11
Phototype according
to Fitzpatrick:
I (n = 4)
II (n = 25)
III (n = 8)
IV (n = 4)
V (n = 3)
Phototype according
to Fitzpatrick:
I (n = 2)
6
Healthy infants;
Maternal history of
AD n = 14;
Paternal history of
AD n = 3
Maternal history of
AD n = 10;
Paternal history of
TEWL; skin
surface pH
Infants were at rest
during measurements;
No skin care at least 12
h prior to measurements
with tap water two
times per week from
day 7 of life;
Use of skin care
products discouraged
Room temperature and
humidity were recorded
with standard devices;
Acclimatization 5-10
min;
No skin care at least 12
h prior to measurements
Follow-up of the same
cohort over the first 8
weeks of life;
Infants bathed with
clear water two times
per week from day 7
of life
Mean age recalculated
based on ranges;
Follow-up of the same
group over 6 weeks
Online Appendix 2. Characteristics of included studies
II (n = 14)
III (n = 6)
IV (n = 0)
V (n = 2)
Cuevas
Guaman
(2011) [3]
30
USA
September
2008 –
November
2009
0.1
68
Lavender
(2011) [21]
Liu (2011)
[23]
Stamatas
(2011) [30]
24
25
26
UK
China
USA
-
May 2008 –
June 2008
26
African American n =
40
Healthy infants
57
White British n = 82
Black Minority Ethnic
n=2
Mixed Race n = 6
Other n = 1
Missing n = 9
Healthy infants;
n = 27 family
history of atopic
eczema
n = 14 family
history of atopic
eczema
TEWL
-
Measurements
performed on the first
and second day of life
TEWL; skin
surface pH
Follow-up assessments
partly conducted at
home environment
Follow-up of the same
cohort over the first 8
weeks of life;
Infants being bathed
minimum 3 times per
week requested
TEWL
Measurements
performed in home
environment;
No bathing on the
morning of the
scheduled
measurements
Exclusive use of cloth
diapers for at least 7
days before
enrollment
TEWL; skin
surface pH
Ambient temperature:
20-22 C;
Relative humidity:
50%;
Acclimatization 15 min
without diaper;
No product application
on the diaper area or
upper leg at least 24 h
prior to measurements
Mean age recalculated
based on ranges
0.3
100
November
2008 –
November
2009
AD n = 2
0.1
51
4.0
30
White British n = 47
Mixed Race n = 4
Other n = 2
51
8.0
30
White British n = 47
Mixed Race n = 4
Other n = 2
n = 14 family
history of atopic
eczema
Asian
Healthy infants;
No evidence of
chronic
dermatological
conditions or
common
childhood
diseases
694
35
24.0
58.7
335
-
Caucasian
7
Healthy infants;
n = 16 very mild to
moderate diaper
dermatitis
Online Appendix 2. Characteristics of included studies
18
Fluhr (2012)
[5]
27
Germany
March 2009
– September
2009
18
0.7 (0.6)
5.3 (0.5)
-
18
24.0 (2.4)
18
62.6 (22.4)
-
Healthy infants, no
present and/or
past history of skin
disease
TEWL; skin
surface pH
0.3
Garcia Bartels
(2012) [6]
28
Germany
May 2007 –
October
2007
40
2.0
20
Caucasian
Healthy infants
TEWL; skin
surface pH
Ambient temperature: 20
(SD 2) C;
Relative humidity: 50
(SD 10)%;
Acclimatization 30 min
with test sites
uncovered;
No cosmetic and topical
medications at the test
sites at least 3 days
prior to measurements
Ambient temperature: 26
(SD 1) C;
Relative humidity: 50%;
Acclimatization 5-10 min
with the diaper removed;
4.0
254
Lavender
(2012) [22]
29
UK
130
Kelleher
(2013) [18]
36
Ireland
0.1
103
February
2010 –
October
2010
June 2009 –
October
2011
1036
4.0
0.3
55
-
White British n = 128
White other n = 14
Asian n = 50
Black n = 45
Other n = 17
White British n = 64
White other n = 7
Asian n = 25
Black n = 21
Other n = 13
Small number of
infants not of white
European descent
8
Healthy infants
Healthy infants
born to
primiparous
mothers
Follow-up of the same
cohort over the first 4
weeks of life;
Bathing in clear water
without a cleanser
twice per week;
No additional skin care
TEWL; skin
surface pH
Initial measurements
performed in the
hospital, follow-up
assessment conducted
at home
Follow-up of the same
cohort over the first 4
weeks of life;
Cleansing of the
nappy area with cotton
wool and water
TEWL
Exposing of the
measurement site in a
non-environmentally
controlled room for 10
min and in an
environmentally
controlled room
(ambient temperature:
20-25 C;
relative humidity: 3045%) for further 5 min at
the maternity ward
Mean age recalculated
based on ranges;
Part of infants washed
prior to
measurements: no
significant difference
in TEWL values to the
not washed infants
Online Appendix 2. Characteristics of included studies
1. Boralevi F, Hubiche T, Leaute-Labreze C, Saubusse E, Fayon M, Roul S, Maurice-Tison
S, Taieb A (2008) Epicutaneous aeroallergen sensitization in atopic dermatitis infants
- Determining the role of epidermal barrier impairment. Allergy: European Journal of
Allergy and Clinical Immunology 63 (2):205-210
2. Braun F, Lachmann D, Zweymuller E (1986) The influence of a synthetic detergent
(Syndet) on the skin pH of infants. [German] Der Einfluss Eines Synthetischen
Detergens (Syndet) Auf Das Ph Der Haut Von Sauglingen. Hautarzt 37 (6):329-334
3. Cuevas Guaman M, Hamm C (2011) Skin maturity measured by transepidermal water
loss: A comparison between late-preterm and term infants. Journal of Investigative
Medicine 59 (2):526
4. Cunico RL, Maibach HL, Khan H, Bloom E (1977) Skin barrier properties in the newborn.
Transepidermal water loss and carbon dioxide emission rates. Biology of the Neonate
32 (3-4):177-182
5. Fluhr JW, Darlenski R, Lachmann N, Baudouin C, Msika P, De Belilovsky C, Hachem JP
(2012) Infant epidermal skin physiology: adaptation after birth. British Journal of
Dermatology 166 (3):483-490. doi:10.1111/j.1365-2133.2011.10659.x
6. Garcia Bartels N, Massoudy L, Scheufele R, Dietz E, Proquitte H, Wauer R, Bertin C,
Serrano J, Blume-Peytavi U (2012) Standardized diaper care regimen: A prospective,
randomized pilot study on skin barrier function and epidermal IL-1alpha in newborns.
Pediatric Dermatology 29 (3):270-276
7. Garcia Bartels N, Mleczko A, Schink T, Proquitté H, Wauer RR, Blume-Peytavi U (2009)
Influence of bathing or washing on skin barrier function in newborns during the first
four weeks of life. Skin Pharmacology and Physiology 22 (5):248-257
8. Garcia Bartels N, Rosler S, Martus P, Stroux A, Lonnfors S, Reisshauer A, Blume-Peytavi
U (2011) Effect of baby swimming and baby lotion on the skin barrier of infants aged
3-6 months. Journal der Deutschen Dermatologischen Gesellschaft 9 (12):1018-1025
9. Garcia Bartels N, Scheufele R, Prosch F, Schink T, Proquitté H, Wauer RR, BlumePeytavi U (2010) Effect of standardized skin care regimens on neonatal skin barrier
function in different body areas. Pediatric Dermatology 27 (1):1-8
10. Giusti F, Martella A, Bertoni L, Seidenari S (2001) Skin barrier, hydration, and pH of the
skin of infants under 2 years of age. Pediatric Dermatology 18 (2):93-96.
doi:10.1046/j.1525-1470.2001.018002093.x
11. Hammarlund K, Nilsson GE, Oberg PA, Sedin G (1977) Transepidermal water loss in
newborn infants. I. Relation to ambient humidity and site of measurement and
estimation of total transepidermal water loss. Acta Paediatrica Scandinavica 66
(5):553-562
12. Hammarlund K, Sedin G (1980) Transepidermal water loss in newborn infants. IV. Small
for gestational age infants. Acta Paediatrica Scandinavica 69 (3):377-383
13. Harpin VA, Rutter N (1983) Barrier properties of the newborn infant's skin. Journal of
Pediatrics 102 (3):419-425
14. Hoeger PH, Enzmann CC (2002) Skin physiology of the neonate and young infant: A
prospective study of functional skin parameters during early infancy. Pediatric
Dermatology 19 (3):256-262. doi:10.1046/j.1525-1470.2002.00082.x
15. Iliev D, Bangha E, Elsner P (1998) Effect of a baby whey bath on skin physiology
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Medizin Praxis = Revue suisse de medecine Praxis 87 (18):617-621
16. Kahn A, Rebuffat E, Blum D (1987) Continuous transepidermal water loss measurement
in sleeping infants. Acta Paediatrica Scandinavica 76 (3):405-410
17. Kahn A, Vandemerckt C, Dramaix M, Magrez P, Blum D, Rebuffat E, Montauk L (1987)
Trans-epidermal water-loss during sleep in infants at risk for sudden-death. Pediatrics
80 (2):245-250
9
Online Appendix 2. Characteristics of included studies
18. Kelleher MM, O'Carroll M, Gallagher A, Murray DM, Dunn Galvin A, Irvine AD, Hourihane
JO (2013) Newborn Transepidermal Water Loss Values: A Reference Dataset.
Pediatric Dermatology
19. Kikuchi K, Kobayashi H, O'Goshi K I, Tagami H (2006) Impairment of skin barrier function
is not inherent in atopic dermatitis patients: A prospective study conducted in
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20. Kjartansson S, Hammarlund K, Sedin G (1992) Insensible water loss from the skin during
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traditional Chinese cloth diapers: Observations in 3- to 9-month-old children. Pediatric
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and continue to develop through the first year of life. The Journal of investigative
dermatology 128 (7):1728-1736
25. Orsmark K, Wilson D, Maibach H (1980) In vivo transepidermal water loss and epidermal
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26. Priestley GC, McVittie E, Aldridge RD (1996) Changes in skin pH after the use of baby
wipes. Pediatric Dermatology 13 (1):14-17. doi:10.1111/j.1442-200X.1996.tb02839.x
27. Rutter N, Hull D (1979) Response of term babies to a warm environment. Archives of
disease in childhood 54 (3):178-183
28. Rutter N, Hull D (1979) Water loss from the skin of term and preterm babies. Archives of
Disease in Childhood 54 (11):858-868
29. Saijo S, Tagami H (1991) Dry skin of newborn infants: functional analysis of the stratum
corneum. Pediatric dermatology 8 (2):155-159
30. Stamatas GN, Zerweck C, Grove G, Martin KM (2011) Documentation of impaired
epidermal barrier in mild and moderate diaper dermatitis in vivo using noninvasive
methods. Pediatric Dermatology 28 (2):99-107
31. Stromberg B, Hammarlund K, Oberg PA, Sedin G (1983) Transepidermal water loss in
newborn infants. IX. The relationship between skin blood flow and evaporation rate in
fullterm infants nursed in a warm environment. Acta Paediatrica Scandinavica 72
(5):729-733
32. Tollesson A, Frithz A (1993) Transepidermal water loss and water content in the stratum
corneum in infantile seborrhoeic dermatitis. Acta Dermato-Venereologica 73 (1):18-20
33. Visscher MO, Chatterjee R, Ebel JP, LaRuffa AA, Hoath SB (2002) Biomedical
assessment and instrumental evaluation of healthy infant skin. Pediatric Dermatology
19 (6):473-481. doi:10.1046/j.1525-1470.2002.00214.x
34. Visscher MO, Chatterjee R, Munson KA, Pickens WL, Hoath SB (2000) Changes in
diapered and nondiapered infant skin over the first month of life. Pediatric
Dermatology 17 (1):45-51. doi:10.1046/j.1525-1470.2000.01711.x
35. Visscher MO, Narendran V, Pickens WL, LaRuffa AA, Meinzen-Derr J, Allen K, Hoath SB
(2005) Vernix caseosa in neonatal adaptation. Journal of Perinatology 25 (7):440-446
36. Yosipovitch G, Maayan-Metzger A, Merlob P, Sirota L (2000) Skin barrier properties in
different
body
areas
in
neonates.
Pediatrics
106
(1):105-108.
doi:10.1542/peds.106.1.105
10