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Acta Derm Venereol 96
INVESTIGATIVE REPORT
Acta Derm Venereol 2015 Preview
© 2016 The Authors. doi: 10.2340/00015555-2279
Journal Compilation © 2016 Acta Dermato-Venereologica. ISSN 0001-5555
Topical oils on baby skin may contribute to development
of childhood atopic eczema. A pilot, assessor-blinded,
randomized controlled trial assessed feasibility of a de-
nitive trial investigating their impact in neonates. One-
hundred and fteen healthy, full-term neonates were ran-
domly assigned to olive oil, sunower oil or no oil, twice
daily for 4 weeks, stratied by family history of atopic
eczema. We measured spectral prole of lipid lamellae,
trans-epidermal water loss (TEWL), stratum corneum
hydration and pH and recorded clinical observations, at
baseline, and 4 weeks post-birth. Recruitment was chal-
lenging (recruitment 11.1%; retention 80%), protocol
adherence reasonable (79–100%). Both oil groups had
signicantly improved hydration but signicantly less
improvement in lipid lamellae structure compared to
the no oil group. There were no signicant differences
in TEWL, pH or erythema/skin scores. The study was
not powered for clinical signicance, but until further
research is conducted, caution should be exercised when
recommending oils for neonatal skin. Key words: infant;
skin barrier function; topical oils.
Accepted Oct 29, 2015; Epub ahead of print Nov 9, 2015
Acta Derm Venereol
Alison Cooke, The University of Manchester, Jean
McFarlane Building Room 4.336, Oxford Road, M13 9PL
Manchester, UK. E-mail: alison.cooke@manchester.ac.uk
Neonatal dry skin is a normal adaptation to the extraute-
rine environment following birth. The primary function
of baby skin is to provide a barrier, rstly to water loss
and secondly to penetration from external irritants and
allergens (1). Some research has suggested that there
is a potential for development of atopic eczema (AE)
(synonym atopic dermatitis) if topical products with
adverse effects on skin barrier function are used for the
prevention or treatment of baby dry skin (2, 3).
AE is a disease resulting from gene environment
interactions leading to breakdown of the skin barrier,
cutaneous inammation and allergy (4, 5). Prevalence
has increased from 5% of children aged 2 to 15 years in
the 1940s (6) to approaching 30% more recently (7). Ap-
proximately 60% of diagnoses are made in the rst year
and 45% in the rst 6 months of life (4), a period when
midwives and other related health professionals poten-
tially have an inuence over parental caring practices.
Genetic changes cannot account for this increased inci-
dence, but there has been an increase in potentially linked
environmental factors including the increased availability
and use of baby skincare products. It has been suggested
that certain topical oils instigate a weakness in the skin
barrier (2, 8, 9). There may be a link between early use
of certain types and formulations of oils on baby skin and
the development of AE; this requires further research.
Extra care of baby skin is important due to differences
in the biological composition between baby and adult
skin. The stratum corneum (SC), a principal component
of the epidermal barrier, is 30% thinner, and the over-
all epidermis is 20% thinner in babies (10). Although
newborn skin is sufciently developed to withstand the
extrauterine environment at full term (≥ 37 weeks gesta-
tion), its biophysical and biological properties such as
corneocytes size, SC hydration and pH, lipid composi-
tion and structure, natural moisturising factor (NMF)
and water composition continue to be in a transitional
state during the early years of life (11–13). Given that
babies have a propensity for reduced skin barrier func-
tion, careful consideration should be given to topical
products used on baby skin to ensure that the developing
epidermal barrier is not adversely altered or affected.
Alteration in the lipid composition and structure of the
SC is linked to reduced skin permeability function and
AE (14–16). Only skincare products which are proven
to enhance the integrity, barrier and/or immune function
of baby skin should be recommended.
There is no national guidance on neonatal skincare.
The United Kingdom (UK) Postnatal Care Guidelines
(17) briey mention only cleansing in relation to baby
skincare. There is no national or international guidance
with regard to using topical oils. The practice of recom-
mending and using topical oils for the prevention or
treat ment of baby dry skin or for massage has developed
as a traditional practice, rather than be based on evidence
(18, 19). It has been suggested that there is a readiness
to believe that what is ‘natural’ is ‘safe’ (20, 21). There
Olive Oil, Sunower Oil or no Oil for Baby Dry Skin or Massage:
A Pilot, Assessor-blinded, Randomized Controlled Trial (the Oil in
Baby SkincaRE [OBSeRvE] Study)
Alison COOKE1, Michael J. CORK2, Suresh VICTOR3,4, Malcolm CAMPBELL1, Simon DANBY2, John CHITTOCK2 and Tina
LAVENDER1
1School of Nursing, Midwifery and Social Work, 3Institute of Human Development, The University of Manchester, Manchester, 2School of Medicine and
Biomedical Sciences, University of Shefeld, Shefeld, UK, and 4Sidra Neonatology Center of Excellence, Sidra Medical and Research Center, Doha, Qatar
2A. Cooke et al.
has been a growth in societal interest in ‘natural’ pro-
ducts (22), particularly for babies (23). Parents follow
the advice of health professionals regarding the care of
their baby (20). It is necessary to provide evidence from
which health professionals can offer the best advice for
baby skincare, to avoid harmful practices.
A literature review conducted prior to the study iden-
tied 3 studies that investigated the use of topical oils on
term newborn babies. One study considered olive oil (24)
but the outcome under investigation was detachment of
the umbilical cord stump, rather than dry skin. The other
studies considered skincare; both being randomized con-
trolled trials (RCTs) (25–27). The BEEP pilot study (26,
27) (n = 124) saw a trend toward improved skin barrier
function in the intervention group (26) and concluded
that a daily full-body emollient therapy from birth can
prevent AE (27). Babies randomized to the treatment
arm could choose a dened sunower seed oil with high
linoleic acid/low oleic acid content, a specic emollient
cream/gel or a specic emollient ointment. Only 23.4%
(n = 15) of participants in the intervention arm chose
sunower seed oil. Results were provided as a total of
participants for the treatment arm so it is not possible to
assess results specic to the sunower oil only, but the
study was not powered to detect this. Solanki et al. (25)
compared safower oil (ratio of linoleic acid to oleic acid
not reported) to coconut oil to no oil amongst preterm
(< 34 weeks gestation; n = 42 and 34–37 weeks gestation;
n = 30) and term babies (> 37 weeks gestation; n = 46).
The study was not powered and the main outcome was
fatty acid proling, but clinical observations and AE
were also monitored throughout the 5-day treatment pe-
riod. None of the studies measured TEWL, SC hydration
or pH. No trials have considered whether using topical
oils is benecial to healthy term baby skin.
Prior to the study we conducted a national survey of
UK maternity and neonatal units. The survey found that
routine practice was to recommend topical olive oil or
sunower oil to new parents for their baby’s dry skin
(19). We therefore conducted a pilot RCT to compare
the topical use of a specic sunower oil (high linoleic
acid, low oleic acid) to a specic olive oil (low linoleic
acid, high oleic acid) to no oil. We hypothesized that the
regular application of the specic sunower oil, when
compared to no oil or specic olive oil, would improve
the skin barrier function of newborn term babies. From
the study design stage we involved a Trial Steering Com-
mittee made up of independent specialists in nursing,
midwifery, pediatrics, clinical trials, dermatology, and
patient user groups including a representative from the
National Eczema Society and a parent representative.
The pilot was designed to address the following
aspects in the design of a denitive study: proof of
concept of what, if any, effect oils have on baby skin
barrier function, the suitability of Attenuated Total
Reectance Fourier Transform Infra-red spectroscopy
(ATR-FTIR) as an outcome measure, optimal primary
outcome measure, sample size calculation, optimal
trial design (recruitment rates, protocol adherence and
acceptability), and optimal trial management processes
(patient information provision, consent, data recording).
METHODS (for complete details see Appendix S1
1
)
Study site and population
A pilot, assessor-blinded, RCT was conducted in St. Mary’s
Hospital, Manchester, North West England. We set a target
sample size of 100 babies to allow for 30 per group after a
10% anticipated loss to follow-up. We included those with and
without a family history of AE. The sample size was considered
to be sufficient to explore differences in outcomes and provide
data capable of determining feasibility for a definitive trial (28).
The trial was approved by Greater Manchester East Research
Ethics Committee (13/NW/0512).
Recruitment and randomization
Babies of women who gave consent were randomized to one
of the intervention groups or the control group within 72 h of
birth. Randomization was 1:1:1 via a central telephone-based
service provided by The Christie Hospital NHS Foundation Trust
Clinical Trials Unit. The randomization sequence was computer
generated. Randomization was stratied according to whether
or not there was a family history of AE, where at least one of
father, mother, or sibling had a medical diagnosis of AE and
had been prescribed topical steroid treatment. The randomiza-
tion was in blocks within eczema history strata (yes, no) and
the block size varied at random between 6 and 15 (i.e. 6, 9, 12
or 15) to guard against predictability. Allocation was concealed
from the participant and independent research midwife until
the point of allocation. Babies were randomized to one of 3
groups: olive oil, sunower oil or no oil (control). The study
was assessor-blinded, and participants in the intervention groups
were blinded to which oil they were using; oils were labelled X
and Y. Participant blinding was impossible for the control group
as there is no control oil that we could be condent was safe to
apply and would have no effect on skin barrier function (29).
Intervention
Olive oil and sunflower oil of specific defined formulation
(William Hodgson and Co, Congleton, United Kingdom; see
Table I) were provided for the intervention groups as appro-
priate. Parents began using the oil as instructed from the day
after the initial assessment. Parents applied 4 drops of oil to
their baby’s left forearm, left thigh and abdomen, twice a day.
No oils were applied on the day of assessment to avoid any
Table I. Specications of natural oils used in the Oil in Baby
SkincaRE (OBSeRvE) study
Fatty acid/Carbon number
Content (%)
Olive oil Sunower seed oil
Palmitic acid/C16: 0 11.5 6.0
Oleic acid/C18: 1 72.8 29.3
Linoleic acid/C18: 2 10.8 59.2
Linolenic acid/C18: 3 0.2 0.1
1http://www.medicaljournals.se/acta/content/?doi=10.2340/00015555-2279
Acta Derm Venereol 96
3
The oil in baby SkincaRE (OBSeRvE) study
interference with results that may have been caused by oil
residues, and to maintain assessor blinding. Parents in all 3
groups were asked not to use any other skincare products on
the 3 study sites; water only was advocated.
Assessment of trial outcomes
All measurements were taken by the investigator who remained
blind to the treatment allocation. Data were collected at two
time points. The first assessment was conducted at baseline
prior to discharge from the hospital. A second assessment was
made at 4 weeks ± 5 days.
Primary outcomes
ATR-FTIR spectroscopy. The change in structure of the lipid
lamellae, a determinant of SC permeability barrier function
(30), was assessed between 48 h and 4 weeks following birth
using ATR-FTIR spectroscopy. This technique has been used
previously to demonstrate the effect of oleic acid on skin bar-
rier (8). At each spectroscopy measurement site on the skin
surface an absorbance spectrum was collected on intact skin
and following the application and removal (tape-stripping) of
3 consecutive D-Squame discs (CuDerm Corporation, Dallas,
TX, USA) to reassess the deeper corneocyte layers of the SC.
Data analysis of absorbance spectra was performed in Omnic
9.0 and TQuant (Thermo Fisher Scientific Inc., Waltham, USA).
The difference in the quantity of lipids and lipid esters in the
skin was determined based upon the change in peak intensities
of the spectral regions centred on ~2,920 and ~2,850 wavenum-
bers (31). Lipid chain conformation (vasymCH2 COG) was based
on the location (centre of gravity: COG) of the peak between
~2,853 and ~2,848 wavenumbers, corresponding to the asym-
metric stretching of the CH2 bond of lipids (32, 33). Lateral
chain packing was determined from the second derivative re-
flectance spectra by measuring the full width at half maximum
(FWHM) of the spectral region centred at 1,468 wavenumbers
(30). The difference in the quantity of surfactants in the skin,
measured to assess adherence regarding use of wash products,
was determined based upon the change in peak intensity of the
spectral region centred on 1,240 wavenumbers, corresponding
to the sulphur group of surfactants found in wash products (34).
Trans-epidermal water loss (TEWL). This outcome measured
the rate of change of basal trans-epidermal water loss (TEWL)
between 48 h and 4 weeks after birth. TEWL, a validated mea-
sure of skin barrier function (35), was measured using a closed
chamber TEWL instrument (Biox Aquaflux Model AF200). The
lead investigator took the measurements at both time points,
at each study site twice, before and after tape-stripping, in ac-
cord with published guidelines for TEWL measurements (36).
Secondary outcomes
Stratum corneum hydration and skin surface pH. The change
in SC hydration and skin surface pH between 48 h and 4 weeks
were measured at the same times and sites as the primary out-
come measures using a Corneometer® Model CM825 [Courage
& Khazaka electronic GmbH, Köln, Germany] and skin pH
meter® Model PH905 [Courage & Khazaka electronic GmbH].
Clinical observations. Changes in the skin were observed
and recorded by the investigator at baseline and follow-up
(erythema, dryness and scaling, need for medical products/
attention) between 48 h and 4 weeks. The investigator asses-
sed the babies’ skin according to a modified Neonatal Skin
Condition Score (NSCS; 37). Erythema was measured using
a Mexameter® Model MX18 probe at each visit [Courage &
Khazaka electronic GmbH].
Analysis
Data were double-entered into IBM SPSS Statistics version
20 and analysed in version 22, with the two data files cross-
checked for errors. In accordance with recommended practice
for pilot studies (28), the main analyses were descriptive,
involving the estimation of recruitment rates, attrition rates,
adherence rates, means and standard deviations of primary and
secondary outcomes by group at baseline and 4 weeks, and 95%
confidence intervals (CI) for differences of means of change
scores of primary and secondary outcomes between groups at 4
weeks. Missing values at 4 weeks were not carried forward or
imputed; descriptive analysis at 4 weeks was based on complete
data, compared by randomization group. The latter comparisons
were confirmed by analysis of covariance.
RESULTS
Data were collected between September 2013 and July
2014. We approached 1,037 mothers and 115 consented
to participate (recruitment rate: 11.1%). The recruit-
ment ow chart is illustrated in Fig. S1
1
, which includes
detail of reasons for declining and loss to follow-up.
Baseline characteristics were homogenous across the 3
groups (Table SI
1
). Approximately 32% of infants had
a family history of AE; stratication ensured that these
were evenly distributed across the 3 groups. There were
no differences in ambient conditions across the groups
for each visit (Table SII
1
).
Protocol adherence
Protocol adherence was explored for the assessment of
feasibility, both to treatment allocation regime and regar-
ding other product use. Adherence was measured from
the ATR-FTIR sebum data and mother’s self-reporting in
the weekly telephone questionnaires and nal follow-up
questionnaire. The most adherent group was the control
group for both treatment use and product avoidance.
The proportion of lipid esters in the SC was elevated
in the two oil groups compared to the no oil group on
all test sites (data not shown), evidencing the use of
oils, which both contain high levels of lipid esters on
the skin. The weekly ranges of adherence for treatment
use were 79% to 93% of participants for the olive oil
group, 83% to 94% for the sunower oil group and 100%
for the no oil group (Table SIII
1
). The ranges for other
product avoidance were 57% to 89%, 70% to 87% and
74% to 100%, respectively (Table SIII
1
). Overall, there
were no signicant differences in adherence across the
groups. However, there was a noticeable decrease in
compliance with regard to product use in week 4 for all
groups. The actual number of mothers using alternative
products on their babies may be higher as adherence was
self-reported. Analysis of the ATR-FTIR spectra sup-
ported the data collected from the mothers by indicating
no signicant differences in the change in proportion
of sulphur groups in the skin at 4 weeks between the
groups (data not shown), suggesting no difference in the
Acta Derm Venereol 96
4A. Cooke et al.
use of cleansers containing sulphate surfactants, which
represent the largest class of cleansers in skincare (34).
Primary outcomes
As shown in Table SIV
1
, there were no signicant dif-
ferences for TEWL between the trial arms for all body
sites. The ATR-FTIR spectroscopy data showed that both
oil groups contained a signicantly higher proportion of
lipids within the SC, compared to the no oil group. All
groups exhibited improvement in lipid chain conforma-
tion and lateral packing over the 4 week treatment period,
as indicated by a shift in v
asym
CH
2
COG to a lower wa-
venumber and an increase in the FWHM, respectively.
However the extent of this improvement was signi-
cantly reduced in the groups using oils compared to the
no oil group. For olive oil compared to no oil, there was
a difference in lipid chain conformation and lateral pack-
ing pre tape-stripping (e.g. at the abdomen: lipid chain
conformation mean difference = 1.02, 95% CI 0.66–1.38,
p < 0.001; lateral chain packing mean difference= –0.92,
95% CI –1.40 to –0.44, p < 0.001) and post tape-stripping
(conformation mean difference=0.85, 95% CI 0.46–1.23,
p < 0.001; packing mean difference= –0.95, 95% CI
–1.50 to –0.40, p = 0.001), suggesting a more persistent
uid-like (less ordered) state. For sunower oil compared
to no oil, these differences occurred pre tape-stripping
(e.g. at the abdomen: lipid chain conformation mean
difference = 0.88, 95% CI 0.52–1.25, p < 0.001 ; lateral
chain packing mean difference = –1.27, 95% CI –1.82
to –0.73, p < 0.001) but were not so marked post tape-
stripping (conformation mean difference = 0.54, 95% CI
0.15–0.93, p = 0.007; packing mean difference = –0.49,
95% CI –1.12–0.14, p = 0.121) indicating that they may
be more restricted to the supercial layers of the SC.
There were no signicant differences between the two
oil groups in lipid chain conformation or lateral chain
packing. Full results can be viewed in Table SIV
1
.
Secondary outcomes
As shown in Table III, both oil groups were signi-
cantly more hydrated than the no oil group at all 3 body
sites. There were no signicant differences for skin
surface pH between the trial arms for all body sites.
However, CI only just crossed the line of no difference.
With regard to the clinical observations of the skin,
none of the infants had severe dryness and/or scaling
or rash and very few had mild to moderate dryness and/
or scaling or rash (see Table II). The majority had no or
slight dryness and/or scaling or rash. At 4 weeks, skin
condition score (NSCS) had improved overall. There
were no signicant differences across treatment groups
for erythema at baseline or 4 weeks (see Table III).
Family history of atopic eczema
Analysis of covariance found no signicant effect for
family history of AE in any of the primary or secondary
outcomes apart from erythema on the thigh (p = 0.007).
Mean erythema scores at follow-up were consistently
numerically higher in babies without a family history
at all 3 body sites for both oil groups and also on the
abdomen and thigh for babies in the no oil group. This
agreed with clinical observation of rash at follow-up,
where a slight or mild rash was observed in 11/61 ba-
bies with no family history of AE compared with 2/31
babies with a family history. A similar pattern occurred
in each study arm and while there was no signicant
effect for family history in this small study, it would
have to be monitored in further research.
DISCUSSION
Data generated in the OBSeRvE study provided eviden-
ce that specic topical oils may have an adverse effect
on skin barrier function, and informed the feasibility of
Table II. Clinical skin assessment (tool adapted from Lund et al. [37]; assessed and recorded by midwife)
Baseline
Count (%)
4 weeks
Count (%)
Olive oil
group
n = 38
Sunower
oil group
n = 38
No oil
group
n = 39
Olive oil
group
n = 27
Sunower
oil group
n = 30
No oil
group
n = 35
Dryness and/or scaling
No evidence of dryness or scaling 12 (31.6) 13 (34.2) 5 (12.8) 11 (40.7) 19 (63.3) 17 (48.6)
Slight dryness and/or scaling 20 (52.6) 20 (52.6) 31 (79.5) 16 (59.3) 11 (36.7) 17 (48.6)
Mild–moderate dryness to severe dryness and/or scaling 5 (13.2) 4 (10.5) 1 (2.6) 0 (0) 0 (0) 1 (2.9)
Moderate–severe dryness and/or scaling 1 (2.6) 1 (2.6) 2 (5.1) 0 (0) 0 (0) 0 (0)
Severe dryness and/or scaling 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
Rash
No evidence of rash 34 (89.5) 30 (78.9) 35 (89.7) 23 (85.2) 26 (86.7) 30 (85.7)
Slight rash–slight erythema and/or scaling 4 (10.5) 8 (21.1) 3 (7.7) 4 (14.8) 3 (10.0) 5 (14.3)
Mild rash–moderate to severe erythema and/or scaling, slight papules and oedema 0 (0) 0 (0) 1 (0.9) 0 (0) 1 (3.3) 0 (0)
Moderate rash–moderate to severe erythema and/or scaling, moderate ulceration,
moderate to severe papules and oedema
0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
Severe rash–severe erythema and/or scaling, severe ulceration, papules, and oedema 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
Acta Derm Venereol 96
5
The oil in baby SkincaRE (OBSeRvE) study
a denitive trial with regard to recruitment, retention,
protocol adherence, choice of optimal primary outcome
measure and trial design.
Proof of concept
The primary purpose of conducting this study was to
provide proof of concept that using specic types of
dened topical oils have an effect on baby skin barrier
function and the magnitude of that effect, and to assess
the feasibility of conducting a robust denitive RCT
of specic types of dened topical oils versus no oil
for newborn term babies. This is the only trial we are
aware of to investigate and compare the effect of the
two most commonly recommended topical oils in the
UK on term baby skin barrier function. The ATR-FTIR
data provided evidence that topical oils may have a
negative effect on baby skin. Signicant differences in
lipid structure were found in both oil groups, compared
to the no oil group. All groups displayed an increased
ordering of the lipids, both on the surface and within
the SC, over the 4 weeks following birth, but this im-
provement was signicantly less in the groups using
the topical oils. This suggests that the oils may impede
development of the lamellar lipid structures of the per-
meability barrier from birth. Reduction in the ordering
of lipids throughout the SC is statistically signicantly
associated with decreased skin barrier function (30);
this may increase the risk of developing AE. Moreover
the skin of patients with AE, who display a skin bar-
rier defect, is characterized by reduced ordering of SC
lipids determined using the same technique employed
here (15, 16). No signicant change in skin barrier
function between the two oil groups was reported, but
this pilot study was not sufciently powered to detect
such a difference. In adults, using a minimally inva-
sive technique not suitable for the assessment of baby
skin, a signicant adverse effect of olive oil on TEWL
was observed (2). Free fatty acids, like oleic acid
that accounts for the greatest proportion of the fatty
acid components of olive oil triglycerides, are well-
documented penetration enhancers that increase TEWL
when applied to the skin (38–40). Whilst triglycerides
themselves do not penetrate the skin, as indicated by
the sharp reduction in lipid esters in the skin following
tape-stripping, lipases derived from the resident skin
ora breakdown triglycerides to release glycerol and
free fatty acids such as linoleic acid and oleic acid
(41, 42). Glycerol is an important moisturising factor
(humectant) found in the SC, increased levels of which
increase skin hydration (43). Notably both oil groups
exhibited elevated skin hydration compared with the
no oil group. The process of triglyceride lipolysis helps
explain why the topical oils appear to both hydrate the
SC and disrupt the lipids of the lipid lamellae. The ty-
pes of fatty acids derived from olive oil and sunower
Table III. Secondary outcome assessments
Baseline
Mean (SD)
4 weeks
Mean (SD)
95% CI for difference in mean change from baseline
Mean [CI] (p-value)
Olive oil
n = 38
Sunower oil
n = 38
No oil
n = 39
Olive oil
n = 27
Sunower oil
n = 30
No oil
n = 35 Olive oil–sunower oil Olive oil–no oil Sunower oil–no oil
Hydration
Arm 17.65 (4.42) 19.13 (5.00) 16.22 (3.82) 50.12 (10.06) 51.80 (9.77) 41.79 (9.65) –1.27 [–6.63–4.09] (0.636) 5.81 [0.91–10.71] (0.021)* 7.08 [1.88–12.28] (0.008)*
Abdomen 25.61 (5.89) 26.90 (7.50) 24.26 (6.99) 58.34 (9.81) 58.97 (10.29) 49.25 (9.32) –0.07 [–6.54–6.41] (0.984) 7.19 [1.71–12.68] (0.011)* 7.26 [0.85–13.67] (0.027)*
Thigh 19.92 (4.98) 20.38 (5.77) 17.94 (4.76) 41.23 (9.30) 41.40 (9.83) 32.36 (7.79) –1.28 [–6.42–3.86] (0.620) 5.91 [1.26–10.56] (0.014)* 7.19 [2.44–11.94] (0.004)*
Erythema
Arm 463.28 (85.44) 467.14 (83.30) 437.05 (85.93) 439.42 (78.45) 406.40 (73.93) 412.36 (74.05) 20.22 [–31.07–71.51] (0.433) –6.44 [–53.08–40.20] (0.783) –26.67 [–76.77–23.43] (0.291)
Abdomen 402.75 (75.23) 380.79 (58.69) 385.15 (74.03) 393.12 (60.29) 373.92 (66.23) 387.75 (81.71) –32.33 [–67.34–2.68] (0.070) –29.00 [–67.42–9.41] (0.136) 3.32 [–36.51–43.16] (0.868)
Thigh 472.76 (90.39) 460.73 (72.79) 457.30 (77.35) 414.10 (87.90) 390.40 (64.92) 389.73 (62.03) 0.64 [–48.45–49.74] (0.979) 1.55 [–43.53–46.63] (0.945) 0.90 [–47.30–49.11] (0.970)
Skin pH
Arm 5.90 (0.49) 5.80 (0.42) 6.10 (0.57) 4.98 (0.31) 4.93 (0.31) 4.98 (0.34) –0.04 [–0.30–0.22] (0.733) 0.18 [–0.11–0.46] (0.220) 0.22 [–0.06–0.50] (0.115)
Abdomen 6.18 (0.56) 6.03 (0.46) 6.39 (0.50) 5.02 (0.39) 4.94 (0.31) 5.02 (0.35) 0.01 [–0.30–0.31] (0.973) 0.22 [–0.07–0.51] (0.133) 0.22 [–0.07–0.50] (0.131)
Thigh 5.91 (0.50) 5.97 (0.58) 6.29 (0.56) 5.29 (0.61) 5.20 (0.43) 5.13 (0.38) 0.18 [–0.19–0.54] (0.338) 0.47 [0.13–0.81] (0.007)* 0.29 [–0.02–0.61] (0.066)
*p < 0.05.
Acta Derm Venereol 96
6A. Cooke et al.
seed oil are distinct; olive oil containing predominantly
oleic acid and sunower seed oil containing more
linoleic acid. It is this different content of oleic and
linoleic acid that has been implicated in positive and
negative effects of different oils on the skin barrier (2,
9). No signicant differences in the effects of the two
topical oils in this pilot study were found, but due to
the limited sample size no conclusions can be drawn
from this. The clinical importance of the difference
found between the oil groups and no oil is unknown.
This study provides important pilot data which consi-
ders for the rst time the impact of using the two most
commonly recommended topical oils in the UK, olive
oil and sunower oil, for the prevention or treatment of
baby dry skin or baby massage. These oils continue to
be recommended by midwives, health visitors and other
neonatal health professionals as there is a common, but
unfounded, belief that what is ‘natural’ is also ‘safe’
(20, 21). Our pilot data demonstrates that these oils may
have a negative effect on skin barrier function. Further
research to establish clinical importance is absolutely
necessary, particularly in view of the potential link with
the increasing prevalence of AE in children aged 2 to
15 years (7). One recent randomized study of neonates
using topical oil compared newborns washed with wa-
ter only (n = 52) to newborns washed daily with liquid
baby cleanser and moisturized with topical almond oil
(n = 42) (44). It is unclear if the study was powered,
the level of protocol adherence or how homogenous
the groups were. Contrary to our ndings, there was
a statistically signicant difference in TEWL between
the groups at day 10; higher in the intervention group.
The intervention group alone used the cleansing agent
so the specic effect of the oil cannot be determined.
Cleansing may have adversely affected skin barrier
function, resulting in higher TEWL values. The authors
conclude that cleansing and moisturizing with oil may
delay the natural maturation of skin barrier function.
One study (45; n = 118) addressing prevention of AE
has suggested, like Simpson et al. (27), that the use
of a daily emollient therapy from birth reduces the
incidence of AE in those with a family history of the
condition. The Simpson et al. (27) and Horimukai et
al. (45) studies only recruited babies at high risk of
developing AE. Application of particular dened oils to
skin of newborn babies predisposed to a defective skin
barrier and AE may have different effects to those with
no genetic predisposition to develop a defective skin
barrier and AE. Topical oils are routinely recommended
to healthy newborn babies who have dry skin or for
baby massage. It is not known what number of these
healthy babies may go on to develop AE and whether
the two factors are linked. It is important to establish
whether this link exists. Future studies should consider
the effects of dened oils on the skin of babies with and
without a genetic predisposition to AE.
Our hypothesis stated that the regular application of
sunower oil, when compared to no oil or olive oil,
improved the skin barrier function of newborn term
babies. This was not demonstrated by our pilot data.
Sunower oil was found to have a similar effect to
olive oil on skin barrier function, both oils having a
statistically signicant negative effect compared to the
no oil group. This negative effect of sunower oil was
unexpected in view of the existing evidence base high-
lighting the benecial effects of topical sunower oil
in adults (2) and preterm infants (29, 46, 47). A recent
study of topical sunower oil with preterm infants (48),
although a small sample (n = 22), found that sunower
oil may impede skin barrier development. This supports
our ndings and contrasts with the work of Darmstadt,
who suggested that the positive effect of sunower oil
was linked to a barrier-enhancing effect. The positive
effect found by Darmstadt may have more to do with
the antimicrobial effect of sunower oil. Unlike the
Darmstadt population, our term baby population were
not faced with a signicant fatal infection risk. We
suggest that whilst sunower oil may not be a great
barrier enhancing topical agent (perhaps the opposite),
this does not detract from the very positive effect it has
in situations where infection is a great risk. As these
studies were not designed to determine the antimicrobial
action of sunower oil, it would be prudent to explore
this in future studies.
Optimal primary outcome measure
This trial presents one of the largest neonatal datasets
of novel information provided by the use of infrared
spectroscopy. ATR-FTIR is important from an ethical
perspective for a neonatal population as it provides a
method to detect changes in the molecular composi-
tion of the SC before those changes are visible to the
naked eye. There were some challenges with regard
to the ATR-FTIR equipment: size, the need for liquid
and dry nitrogen to operate the equipment, and the
need for mothers to leave the postnatal ward to visit
the assessment room for baseline assessment and
return to the hospital with their 4-week-old baby for
follow-up assessment as the equipment was not port-
able. However, having determined that the outcome
measure provides useful and informative biological
data within a short treatment period, the technology
is available to provide the FTIR equipment in a smal-
ler, portable, bespoke device which would not require
the use of liquid or dry nitrogen. Our study found that
ATR-FTIR spectroscopy is suitable as an outcome
measure. TEWL is a validated measure of skin barrier
function (35). Although our data did not show any
signicant differences in TEWL between groups, it
was not powered to detect this. TEWL as an outcome
measure would still be recommended for a study with
Acta Derm Venereol 96
7
The oil in baby SkincaRE (OBSeRvE) study
a larger sample size as it has been shown previously
to detect changes in skin barrier function with the use
of topical oils (2, 38–40).
Optimal trial design
The original target sample of 100 was increased to
115 due to the higher than anticipated loss to follow-
up in order to recruit 30 per group with baseline and
follow-up data. Only two home follow-up visits took
place. The decision not to offer more home visits to
increase retention was made due to the requirement
to collect ATR-FTIR spectroscopy data at follow-up.
Using a bespoke portable ATR-FTIR device would
undoubtedly enhance recruitment and retention; base-
line assessment could be conducted at the bedside on
the postnatal ward and home visits could be offered as
a choice at follow-up. This helped to reduce attrition
rates substantially in a previous similar trial (49). Loss
to follow-up in the OBSeRvE pilot study compared fa-
vourably to a previous pilot study (20% vs. 58% (49)).
Loss to follow-up of less than 10% would be optimal;
this was achieved in a denitive trial when home visits
were offered (50). Loss to follow-up was lowest in
the no oil group. This may have been because there
was no treatment regime to follow. Qualitative data to
assess maternal satisfaction, from this study, suggests
that women in the no oil group found their allocation
‘easy’, but women in the oil groups conversely liked
the ‘routine’ of applying oil. Qualitative data analysis
is ongoing and will be published later.
Babies were originally recruited within 48 h after birth
to reduce the risk of infants having been bathed prior
to baseline assessments. Even with a 48 h restriction in
place some infants had already been bathed. The exten-
sion of the recruitment period to 72 h was deemed to have
little effect on outcome data, but it increased the number
of infants eligible to take part. The screening process was
also amended to allow the lead investigator to identify
eligible postnatal women from the hospital in-patient
software (BedMan) by comparing each one against the
eligibility criteria rather than the clinical team having
to do this task. The lead investigator then approached
the clinical midwife with the list of identied women to
conrm if there was any reason not to approach them.
This reduced the burden of time on the clinical team,
and made the process of eligibility screening more ef-
cient. Nevertheless, the overall recruitment rate was
poor (11.1%). During a review of recruitment at the end
of the study, the Trial Steering Committee agreed that
it would not be necessary to exclude babies undergoing
phototherapy treatment from a future study as the dura-
tion of phototherapy treatment is short and trial treatment
could commence after this had ended. In addition, the
clinical assessment room was only available on alternate
days. This affected recruitment as babies could not be
assessed on the day following recruitment, which was
often the parent’s preference. Addressing both of these
issues would improve the recruitment rate.
Protocol adherence was fairly evenly distributed
across the treatment groups but appeared to reduce
with regard to alternative product use in the 4
th
week of
the trial. This also occurred in a previous skincare trial
(49) which suggested that a primary endpoint prior to 4
weeks may be benecial. The rst follow-up assessment
could be conducted at 3 weeks in a future study; how-
ever, adherence may still remain an issue. One solution
would be to include a control soap for parents to use
to bathe and cleanse their baby, however this would be
problematic. If a good cleanser was used, the effects of
the oils may be masked. If a poor cleanser was used, the
negative effects could overwhelm the effect of the oils.
The OBSeRvE pilot study was conducted to test the
feasibility of a superiority hypothesis, that the regular
application of dened sunower oil, compared to no
oil or dened olive oil, improved the skin barrier func-
tion of newborn term babies. However, our data sug-
gest that this was not the case. The sunower oil was
found to have a similar effect on skin barrier function
to olive oil. Results were not powered to identify the
optimal treatment for baby dry skin or massage; ndings
should therefore be interpreted with caution. A future
study must address clinical importance. Our ndings
suggest that using olive oil or sunower oil may have
the potential to damage the skin barrier function of
neonatal skin. This could consequently increase the
development of AE. However, we cannot draw rm
conclusions about the long-term effects of these topical
oils as the relationship between the outcomes we asses-
sed and clinically important outcomes is unknown. It is
necessary to investigate the link between use of dened
topical oils from birth and development of AE. AE can
develop at any age, with earliest diagnosis not usually
before 4–6 months of age. This suggests that a longi-
tudinal observational study is necessary to explore the
natural course of AE over a number of years following
the use of topical oils together with more mechanistic
studies in term babies to determine the biological re-
levance of the changes in lipid lamellae when topical
oils are used from birth. These studies would inform a
possible future denitive RCT. The optimal trial design
should not only assess skin barrier function, but also the
diagnosis of AE. The denitive trial should be designed
with clinical outcomes to generate data that can inform
clinical practice.
Conclusions
Our study provides valuable baseline data on the new-
born skin barrier using a novel technique. It also pro-
vides informative data on optimal trial processes. Our
ndings suggest that a denitive RCT may not be the
optimal design for the next study about this topic. Be-
Acta Derm Venereol 96
8A. Cooke et al.
fore moving to further RCTs it is important to establish
the biological importance of using dened topical oils
from birth in babies with and without a genetic predis-
position to AE, and whether there is a link between this
practice and the development of AE. We suggest that
the immediate way forward is to conduct a long-term
observational study to observe whether and when AE
develops naturally depending on the use of topical oils
from birth, together with further mechanistic studies
to consider the optimal formulation.
Our study was not designed to provide denitive
answers on whether or not specic dened olive or
sunower oils should be used on babies’ skin. The data
suggested that the skin of babies who used the oils in
this trial may be better hydrated; however the lipid
structure of the skin barrier appeared altered, the clinical
importance of which is unknown at present. Given that
interventions should only be recommended if shown to
do more good than harm, it would be difcult to support
the use of sunower or olive oils, based on our data.
Further research is required to inform future practice.
ACKNOWLEDGEMENTS
The trial team would like to acknowledge all of the women and
babies who participated in the study and giving their valuable
time. We would also like to thank the Trial Steering Commit-
tee; Dr Mark Turner, Dr Kevin Hugill, Professor Lelia Duley,
Margaret Cox, Dr Vinod Elangasinghe, Gill Singleton, and Lisa
Rowe for their valuable monitoring and guidance of this study.
Finally, we would like to thank the St Mary’s research midwife
team, particularly Louise Stephens, for their help and support.
Funding. AC is funded by a Doctoral Research Fellowship
Award (DRF-2012-05-160) from the National Institute for
Health Research. This paper is independent research arising
from this Doctoral Research Fellowship, supported by the
National Institute for Health Research (NIHR). The views
expressed are those of the authors and not necessarily those of
the NHS, NIHR or Department of Health.
Trial Registration: Current Controlled Trials ISRCTN37373893
The authors declare no conflict of interest.
REFERENCES
(complete reference list available in electronic version)
2. Danby S, Al Enezi T, Sultan A, Lavender T, Chittock J,
Brown K, et al. Effect of olive and sunower seed oil on
the adult skin barrier: implications for neonatal skin care.
Pediatr Dermatol 2013; 30: 42–50.
8. Naik A, Pechtold L, Potts R, Guy R. Mechanism of oleic
acid-induced skin penetration enhancement in vivo in
humans. J Control Release 1995; 37: 299–306.
9. Darmstadt G, Mao-Qiang M, Saha S, Ziboh V, Black R,
Santosham M, et al. Impact of topical oils on the skin bar-
rier: possible implications for neonatal health in developing
countries. Acta Paediatr 2002; 91: 546–554.
12. Stamatas G, Nikolovski J, MC. M, Kollias N. Infant skin
physiology and development during the rst years of life:
a review of recent ndings based on in vivo studies. Int J
Cosmet Sci 2011; 33: 17–24.
19. Cooke A, Cork M, Danby S, Lavender T. Use of oil for baby
skincare: A survey of UK maternity and neonatal units. Br
J Midwifery 2011; 19: 354–362.
25. Solanki K, Matnani M, Kale M, Joshi K, Bavdekar A, Bhave
S, et al. Transcutaneous absorption of topically massaged
oil in neonates. Indian Pediatr 2005; 42: 998–1005.
26. Simpson E, Chalmers J, Hanin J, French M, Lubianski T,
Samrao A, et al. Barrier enhancement for eczema preven-
tion – the BEEP feasibility study. J Invest Dermatol 2012;
132: S90.
27. Simpson E, Chalmers J, Hanin J, Thomas K, Cork M,
McLean W, et al. Emollient enhancement of the skin barrier
from birth offers effective atopic dermatitis prevention. J
Allergy Clin Immunol 2014; 134: 818–823.
28. Lancaster G, Dodd S, Williamson P. Design and analysis
of pilot studies: recommendations for good practice. J Eval
Clin Pract 2004; 10: 307–312.
29. Darmstadt G, Saha S, Ahmed A, Chowdhury M, Law P,
Ahmed S, et al. Effect of topical treatment with skin barrier-
enhancing emollients on nosocomial infections in preterm
infants in Bangladesh: a randomised controlled trial. Lancet
2005; 365: 1039–1045.
30. Damien F, Boncheva M. The extent of orthorhombic lipid
phases in the stratum corneum determines the barrier ef-
ciency of human skin in vivo. J Invest Dermatol 2010;
130: 611–614.
31. Brancaleon L, Bamberg M, Kollias N. Spectral differences
between stratum corneum and sebaceous molecular compo-
nents in the mid-ir. Appl Spectrosc 2000; 54: 1175–1182.
33. Boncheva M, Damien F, Normand V. Molecular organiza-
tion of the lipid matrix in intact Stratum corneum using
ATR-FTIR spectroscopy. Biochim Biophys Acta 2008;
1778: 1344–1355.
34. Hoppel M, Baurecht D, Holper E, Mahrhauser D, Valenta
C. Validation of the combined ATR-FTIR/tape stripping
technique for monitoring the distribution of surfactants in
the strateum corneum. Int J Pharm 2014; 472: 88–93.
45. Horimukai K, Morita K, Narita M, Kondo M, Kitazawa
H, Nozaki M, et al. Application of moisturizer to neonates
prevents development of atopic dermatitis. J Allergy Clin
Immunol 2014; 134: 824–830.
46. Darmstadt G, Badrawi N, Law P, Ahmed S, Bashir M, Is-
kander I, et al. Topically applied sunower seed oil prevents
invasive bacterial infections in preterm infants in egypt.
Pediatr Infect Dis J 2004; 23: 719–725.
47. Darmstadt G, Saha S, Ahmed A, Ahmed S, Chowdhury M,
Law P, et al. Effect of skin barrier therapy on neonatal mor-
tality rates in preterm infants in bangladesh: a randomized,
controlled, clinical trial. Pediatrics 2008; 121: 522–529.
48. Kanti V, Grande C, Stroux A, Bührer C, Blume-Peytavi
U, Garcia Bartels N. Inuence of sunower seed oil on
the skin barrier function of preterm infants: a randomized
controlled trial. Dermatology 2014; 229: 230–239.
49. Lavender T, Bedwell C, O’Brien E, Cork M, Turner M,
Hart A. Infant skin-cleansing product versus water: A pilot
randomized, assessor-blinded controlled trial. BMC Pediatr
2011; 11: 35.
50. Lavender T, Furber C, Campbell M, Victor S, Roberts I,
Bedwell C, et al. Effect on skin hydration of using baby
wipes to clean the napkin area of newborn babies: assessor-
blinded randomised controlled equivalence trial. BMC
Pediatr 2012; 12: 59.
Acta Derm Venereol 96
Supplementary material to article by A. Cooke et al. ”Olive Oil, Sunower Oil or no Oil for Baby Dry Skin or Massage: A Pilot, Assessor-
blinded, Randomized Controlled Trial (the Oil in Baby SkincaRE [OBSeRvE] Study)”
Appendix S1
METHODS
Study site and population
A pilot, assessor-blinded, RCT was conducted in St. Mary’s
Hospital, Manchester, a large tertiary hospital in North West
England which has more than 8,000 births annually. Babies
were included if they were born to mothers carrying singleton
pregnancies and booked for care at St. Mary’s Hospital, were
full term (37 weeks gestation or more), were in good health
(as determined by the investigator) and were less than 48 h
old if recruited between September 2013 and February 2014
inclusive or less than 72 h old if recruited between March 2014
and June 2014 inclusive. Mothers were excluded if they were
16 years of age or less or did not have capacity to consent.
Babies were excluded if they had been admitted to Special
Care Baby Unit, were having phototherapy treatment, were
in another clinical trial, had any medical history preventing
their participation to endpoint, had limb defects, non-traumatic
impairment of epidermal integrity or evidence of skin disorder
at first assessment. Normal neonatal skin variations such as
erythema neonatorum/toxicum and milia were not considered
to be skin disorders for this study. We set a target sample size
of 100 babies to allow for 30 per group after a 10% anticipated
loss to follow-up. We included those with and without a family
history of atopic eczema (AE), and used stratification to ensure
that cases were evenly distributed across groups. The sample
size was considered to be sufficient to explore differences in
outcomes and provide data capable of determining feasibility
for a definitive trial (28). The trial was approved by Greater
Manchester East Research Ethics Committee (13/NW/0512).
Recruitment and randomization
Women who were potentially eligible for their baby to take part
were given summary study information antenatally at 28 weeks
gestation. Willing participants completed a response slip in
order to provide consent for the investigator to approach them
after childbirth. Alternatively, women were screened postnatally
by the investigator and approached following permission from
the clinical team. All eligible women who gave permission to
be approached following birth were provided with full study
information and a verbal explanation; they were then given
time to consider taking part.
Babies of women who gave consent were randomized to one
of the intervention groups or the control group within 72 h of
birth. Randomization was 1:1:1 via a central telephone-based
service provided by The Christie Hospital NHS Foundation
Trust Clinical Trials Unit. The randomization sequence was
computer generated. Randomization was stratified according
to whether or not there was a family history of AE, where at
least one of father, mother, or sibling had a medical diagnosis
of AE and had been prescribed topical steroid treatment. The
randomization was in blocks within eczema history strata (yes,
no) and the block size varied at random between 6 and 15
(i.e. 6, 9, 12 or 15) to guard against predictability. Allocation
was concealed from the participant and independent research
midwife until the point of allocation. Babies were randomized
to one of 3 groups: olive oil, sunflower oil or no oil (control).
Following randomization women were given the appropriate
advice and materials by the independent research midwife to
maintain investigator blinding. The study was assessor-blinded,
and participants in the intervention groups were blinded to
which oil they were using; oils were labelled X and Y. Identi-
fication and labelling of oil X and oil Y was conducted by an
independent researcher at The University of Manchester, confir-
med by a second independent researcher. The information was
sealed in two envelopes which were kept by two independent
university staff until after data analysis. Participant blinding
was impossible for the control group as there is no control oil
that we could be confident was safe to apply and would have
no effect on skin barrier function (29).
Intervention
Olive oil and sunower oil of specic dened formulation (Wil-
liam Hodgson and Co, Congleton, United Kingdom; see Table I)
were provided for the intervention groups as appropriate. Oil was
provided in opaque plastic dropper bottles. The rst application
was demonstrated by an independent research midwife who had
been instructed to provide the appropriate advice. Parents then
began using the oil as instructed from the day after the initial
assessment. Parents applied 4 drops of oil to their baby’s left
forearm, left thigh and abdomen, twice a day, up until the night
before their follow-up assessment at approximately 4 weeks,
using a clean hand to spread the oil evenly across the treatment
area. A diagrammatic laminate was provided to ensure parents
applied oil to the correct areas of their baby’s skin at each app-
lication. No oils were applied on the day of assessment to avoid
any interference with results that may have been caused by oil
residues, and to maintain assessor blinding. Parents were asked to
return any unused oil to a box when they attended for follow-up
assessment, prior to meeting the investigator. They were asked
not to discuss their treatment allocation with the investigator at
any opportunity. Parents in all 3 groups were asked not to use
any other skincare products on the 3 study sites; water only was
advocated. Parents received a weekly phone call to ask about
any product use, health professional consultations, medication
prescriptions and whether there were any rashes or skin concerns.
These data were recorded for compliance and safety purposes.
Assessment of trial outcomes
All measurements were taken by the investigator who remained
blind to the treatment allocation. It was intended that all measu-
rements would take place in the same clinical room to maintain
a controlled environment. In the nal phase of the study, home
visits were offered to those who advised that they were unable
to return to the hospital for follow-up. Home visits were offered
due to the higher than anticipated loss to follow-up, and to assess
their feasibility for a denitive trial. Data were collected at two
time points. The rst assessment was conducted at baseline prior
to discharge from the hospital. A second assessment was made
at 4 weeks ± 5 days. Measurement consistency was achieved for
each study site by measuring from anatomical markers such as
the skin crease of the wrist to midpoint on the volar forearm,
above the patella to midpoint on thigh, and above umbilicus
to midpoint to nipple line for upper abdomen. For the primary
outcome measures, two measurements were taken at each treat-
ment site. In between measurements, 3 consecutive D-Squame
discs (CuDerm Corporation, Dallas, TX, USA) were applied
to and removed from the site. The D-Squame discs remove
(tape-stripping) the very top skin cells, which are already dead
and about to be lost naturally from the surface of the skin in a
process known as desquamation. To ensure that tape stripping did
not occur in the same site at follow-up as baseline assessment,
measurements were conducted on the skin just below midpoint
at baseline and just above midpoint at follow-up.
Primary outcomes
ATR-FTIR spectroscopy. The change in structure of the lipid
lamellae, a determinant of stratum corneum (SC) permeability
barrier function (30), was assessed between 48 h and 4 weeks
Acta Derm Venereol 96
Supplementary material to article by A. Cooke et al. ”Olive Oil, Sunower Oil or no Oil for Baby Dry Skin or Massage: A Pilot, Assessor-
blinded, Randomized Controlled Trial (the Oil in Baby SkincaRE [OBSeRvE] Study)”
following birth using ATR-FTIR spectroscopy. This technique
has been used previously to demonstrate the effect of oleic
acid on skin barrier (8). ATR-FTIR spectra were collected non-
invasively using a silver halide fibre-optic probe (FTIR Flexi-
spec PIR 900, Art Photonics, Berlin, Germany) attached to a
Nicolet iS50 FTIR Spectrometer (Thermo Fisher Scientific Inc.,
Waltham, USA), equipped with a cooled mercury-cadmium-
telluride detector and purged with dry nitrogen. We collected a
mean of 40 scans per measurement (resolution 4 wavenumbers).
At each spectroscopy measurement site on the skin surface an
absorbance spectrum was collected on intact skin and following
the application and removal of 3 consecutive D-Squame discs
(tape-stripping) to reassess the deeper corneocyte layers of the
SC. Data analysis of absorbance spectra was performed in Om-
nic 9.0 and TQuant (Thermo Fisher Scientific Inc., Waltham,
USA). The difference in the quantity of lipids and lipid esters
in the skin was determined based upon the change in peak in-
tensities of the spectral regions centred on ~2,920 and ~2,850
wavenumbers, corresponding to the symmetric and asymmetric
stretching of the CH2 group of all lipids, and 1,740 wavenum-
bers, corresponding to lipid esters of triglycerides in sebum
and topically applied oils, respectively (31). Quantities were
normalized to regions of the spectra showing no absorbance,
at 3,800 and 1,800 wavenumbers respectively, to account for
differences in contact pressure between the skin and the probe.
Lipid chain conformation (vasymCH2 COG) was based on the
location (centre of gravity: COG) of the peak between ~2,853
and ~2,848 wavenumbers, corresponding to the asymmetric
stretching of the CH2 bond of lipids (32, 33). A peak centre of
gravity at ~2,848 wavenumbers corresponds to tightly packed
lipid chains, and is associated with optimum skin barrier fun-
ction, whereas higher wavenumbers indicate increasing lipid
fluidity and decreasing skin barrier function. Lateral chain
packing was determined from the second derivative reflectance
spectra by measuring the full width at half maximum (FWHM)
of the spectral region centred at 1,468 wavenumbers (30). A
change in the width of this region corresponds to changes in
lateral lipid chain packing. Highly ordered orthorhombic pack-
ing of lipids is indicated by a FWHM of ≥ 11 wavenumbers. A
higher proportion of orthorhombic structuring throughout the
depth of the SC is associated with improved skin barrier fun-
ction. The difference in the quantity of surfactants in the skin,
measured to assess adherence regarding use of wash products,
was determined based upon the change in peak intensity of the
spectral region centred on 1,240 wavenumbers, corresponding
to the sulphur group of surfactants found in wash products,
normalized to the reference region at 1,800 wavenumbers (34).
Trans-epidermal water loss (TEWL). This outcome measured
the rate of change of basal trans-epidermal water loss (TEWL)
between 48 h and 4 weeks after birth. TEWL, a validated mea-
sure of skin barrier function (35), is defined as the flux of water
vapour evaporating from the skin surface, and was measured
using a closed chamber TEWL instrument (Biox Aquaflux
Model AF200). The lead investigator took the measurements
at both time points, in accord with published guidelines for
TEWL measurements (36). Measurements were taken at each
study site twice, before and after tape stripping.
Secondary outcomes
Stratum corneum hydration and skin surface pH. The change
in SC hydration and skin surface pH between 48 h and 4 weeks
were measured at the same times and sites as the primary out-
come measures using a Corneometer® Model CM825 [Courage
& Khazaka electronic GmbH, Köln, Germany] and skin pH
meter® Model PH905 [Courage & Khazaka electronic GmbH].
Clinical observations. Changes in the skin were observed and
recorded by the investigator at baseline and follow up (ery-
thema, dryness and scaling, need for medical products/atten-
tion) between 48 h and 4 weeks. The investigator assessed the
babies’ skin according to a modified Neonatal Skin Condition
Score (NSCS; 37). Rating was based on severity of dryness and
scaling. A score of zero indicated no evidence of abnormal skin
increasing to a score of 4 which indicated a degree of severity.
Details of skin condition and need for medical products/atten-
tion were also collected via a weekly telephone questionnaire
conducted with mothers by the investigator. Erythema was
measured using a Mexameter® Model MX18 probe at each visit
[Courage & Khazaka electronic GmbH].
Analysis
Data were double-entered into IBM SPSS Statistics version 20 and
analysed in version 22, with the two data les cross-checked for
errors. In accordance with recommended practice for pilot studies
(28), the main analyses were descriptive, involving the estimation
of recruitment rates, attrition rates, adherence rates, means and
standard deviations of primary and secondary outcomes by group
at baseline and 4 weeks, and 95% condence intervals for differen-
ces of means of change scores of primary and secondary outcomes
between groups at 4 weeks. Missing values at 4 weeks were not
carried forward or imputed; descriptive analysis at 4 weeks was
based on complete data, compared by randomization group. The
latter comparisons were conrmed by analysis of covariance.
Acta Derm Venereol 96
Supplementary material to article by A. Cooke et al. ”Olive Oil, Sunower Oil or no Oil for Baby Dry Skin or Massage: A Pilot, Assessor-
blinded, Randomized Controlled Trial (the Oil in Baby SkincaRE [OBSeRvE] Study)”
Table SI. Baseline characteristics by randomised treatment assignment (ITT)
Treatment group
Olive oil
(n = 38)
Sunower oil
(n = 38)
No oil
(n = 39)
Mothers age, years, mean (SD) 28.4 (4.7) 30.5 (5.9) 28.8 (5.7)
Parity, n (%)
Primiparous 22 (58) 21 (55) 19 (49)
Multiparous 16 (42) 17 (45) 20 (51)
Mother ethnicity, n (%)
White 27 (71) 31 (81) 29 (74)
Asian 8 (21) 3 (8) 7 (18)
Mixed race 1 (3) 1 (3) 0 (0)
Black minority ethnic 2 (5) 3 (8) 3 (8)
Other 0 (0) 0 (0) 0 (0)
Baby ethnicity, n (%)
White 21 (55) 26 (68) 25 (64)
Asian 7 (18) 3 (8) 6 (15)
Mixed race 8 (21) 7 (18) 5 (13)
Black minority ethnic 2 (5) 2 (5) 2 (5)
Other 0 (0) 0 (0) 1 (3)
Family history of atopic eczema, n (%) 11 (29) 13 (34) 13 (33)
Gestation, weeks, mean (SD) 39.2 (1.3) 39.6 (1.3) 39.9 (1.1)
Birth weight, grams, mean (SD) 3,322 (410) 3,536 (475) 3,359 (450)
Gender, n (%)
Male 19 (50) 22 (58) 25 (64)
Female 19 (50) 16 (42) 14 (36)
Place of birth, n (%)
Study hospital 36 (95) 38 (100) 37 (95)
Other hospital 1 (3) 0 (0) 0 (0)
Home 1 (3) 0 (0) 2 (5)
Mode of birth, n (%)
Vaginal 33 (87) 29 (76) 33 (85)
Elective caesarean section 0 (0) 3 (8) 1 (3)
Emergency caesarean section 5 (13) 6 (16) 5 (13)
Vernix, n (%)
Absent 37 (97) 37 (97) 39 (100)
Minimal 1 (3) 1 (3) 0 (0)
First bath prior to randomisation, n (%)
Yes 1 (3) 7 (18) 4 (10)
Products used during bath 1 (3) 2 (5) 0 (0)
Feeding method at birth, n (%)
Breast 26 (68.4) 26 (68.4) 27 (69.2)
Bottle 11 (28.9) 6 (15.8) 12 (30.8)
Combined 1 (2.6) 6 (15.8) 0 (0)
Feeding method at 4 weeks, n (%)
Breast 9 (32.1) 11 (37.9) 12 (34.3)
Bottle 14 (50.0) 9 (31.0) 15 (42.9)
Combined 5 (17.9) 9 (31.0) 8 (22.9)
Acta Derm Venereol 96
Supplementary material to article by A. Cooke et al. ”Olive Oil, Sunower Oil or no Oil for Baby Dry Skin or Massage: A Pilot, Assessor-
blinded, Randomized Controlled Trial (the Oil in Baby SkincaRE [OBSeRvE] Study)”
Table SII. Room temperature and humidity
Olive oil group
Mean (SD)
Sunower oil group
Mean (SD)
No oil group
Mean (SD)
Baseline room condition (n = 38) (n = 38) (n = 39)
Temperature 22.71 (0.49) 22.73 (0.51) 22.89 (0.38)
Humidity 44.68 (4.76) 44.68 (4.32) 45.63 (5.12)
4 week room condition (n = 27) (n = 30) (n = 35)
Temperature 23.26 (0.62) 22.90 (0.76) 23.15 (0.56)
Humidity 43.90 (5.23) 44.68 (7.47) 43.63 (5.56)
Acta Derm Venereol 96
Supplementary material to article by A. Cooke et al. ”Olive Oil, Sunower Oil or no Oil for Baby Dry Skin or Massage: A Pilot, Assessor-
blinded, Randomized Controlled Trial (the Oil in Baby SkincaRE [OBSeRvE] Study)”
Table SIII. Self-reported treatment and product adherence by study
week
Treatment group
Olive oil
n (%)
Sunower oil
n (%)
No oil
n (%)
Treatment adherence
Week 1 25 (80.6) 24 (82.8) 33 (100.0)
Week 2 23 (79.3) 24 (88.9) 29 (100.0)
Week 3 25 (92.6) 30 (93.8) 36 (100.0)
Week 4a– – –
Product adherence
Week 1 22 (73.3) 23 (79.3) 32 (97.0)
Week 2 24 (82.8) 22 (81.5) 31 (96.9)
Week 3 24 (88.9) 27 (87.1) 37 (100.0)
Week 4 16 (57.1) 21 (70.0) 26 (74.3)
aParticipants were not asked about treatment compliance at 4 week assessment.
Acta Derm Venereol 96
Supplementary material to article by A. Cooke et al. ”Olive Oil, Sunower Oil or no Oil for Baby Dry Skin or Massage: A Pilot, Assessor-
blinded, Randomized Controlled Trial (the Oil in Baby SkincaRE [OBSeRvE] Study)”
Table SIV. Primary outcome assessments
Baseline
Mean (SD)
4 weeks
Mean (SD)
95% CI for difference in mean change from baseline
Mean [CI] (p-value)
Olive oil
n = 38
Sunower oil
n = 38
No oil
n = 39
Olive oil
n = 27
Sunower oil
n = 30
No oil
n = 35 Olive oil–sunower oil Olive oil–no oil Sunower oil–no oil
TEWL
Pre tape-stripping
Arm 12.03 (2.44) 11.95 (2.29) 12.43 (2.24) 13.98 (2.98) 13.60 (2.75) 13.38 (3.02) 0.18 [–1.62–1.98] (0.841) 1.17 [–0.64–2.98] (0.200) 0.99 [–0.59–2.57] (0.214)
Abdomen 11.25 (2.11) 10.78 (1.96) 11.61 (2.63) 12.00 (3.14) 11.00 (1.69) 11.45 (2.21) 0.06 [–1.27–1.40] (0.925) 0.68 [–0.82–2.18] (0.366) 0.62 [–0.67–1.91] (0.339)
Thigh 13.16 (3.00) 13.15 (2.22) 13.62 (2.33) 13.40 (2.25) 12.60 (2.79) 13.38 (2.11) 0.54 [–0.89–1.97] (0.454) 0.52 [–0.89–1.93] (0.465) –0.02 [–1.25–1.21] (0.973)
Post tape–stripping
Arm 13.39 (2.85) 13.24 (3.08) 14.63 (6.10) 16.87 (3.70) 16.63 (4.36) 17.95 (11.11) –0.96 [–3.23–1.31] (0.401) 0.25 [–5.22–5.73] (0.927) 1.21 [–3.94–6.37] (0.640)
Abdomen 12.48 (2.83) 12.30 (2.24) 12.59 (2.87) 13.75 (3.14) 13.95 (2.58) 13.56 (2.17) –1.32 [–3.15–0.50] (0.152) –0.46 [–2.43–1.51] (0.639) 0.86 [–1.02–2.74] (0.365)
Thigh 14.30 (3.01) 13.96 (1.94) 14.63 (2.84) 14.70 (3.33) 13.87 (2.58) 15.52 (4.91) –0.20 [–1.79–1.38] (0.798) –0.71 [–3.28–1.86] (0.582) –0.51 [–2.86–1.85] (0.667)
Lipid chain conformation (vasymCH2 COG)
Pre tape-stripping
Arm 2,851.72 (1.04) 2,851.79 (0.70) 2,851.79 (0.75) 2,851.73 (0.51) 2,851.96 (0.78) 2,851.29 (0.66) –0.02 [–0.48–0.44] (0.924) 0.53 [0.13–0.94] (0.011)* 0.56 [0.14–0.97] (0.010)*
Abdomen 2,851.74 (0.51) 2,851.82 (0.42) 2,852.00 (0.74) 2,851.89 (0.46) 2,851.91 (0.68) 2,851.16 (0.61) 0.14 [–0.19–0.47] (0.401) 1.02 [0.66–1.38] (<0.001)* 0.88 [0.52–1.25] (< 0.001)*
Thigh 2,851.45 (0.60) 2,851.56 (0.67) 2,851.74 (0.73) 2,851.86 (0.64) 2,851.91 (0.62) 2,850.91 (0.73) 0.21 [–0.30–0.71] (0.419) 1.29 [0.77–1.81] (<0.001)* 1.08 [0.55–1.61] (< 0.001)*
Post tape-stripping
Arm 2,851.61 (0.81) 2,851.86 (1.20) 2,851.50 (1.18) 2,851.16 (0.70) 2,851.08 (0.63) 2,850.80 (0.60) 0.38 [–0.23–1.00] (0.214) 0.57 [–0.08–1.21] (0.083) 0.18 [–0.48–0.85] (0.582)
Abdomen 2,851.58 (0.58) 2,851.67 (0.70) 2,851.68 (0.64) 2,851.49 (0.64) 2,851.38 (0.59) 2,850.85 (0.54) 0.30 [–0.14–0.75] (0.179) 0.85 [0.46–1.23] (<0.001)* 0.54 [0.15–0.93] (0.007)*
Thigh 2,851.33 (0.58) 2,851.48 (0.86) 2,851.30 (0.73) 2,851.34 (0.74) 2,851.38 (0.60) 2,850.94 (0.74) 0.26 [–0.30–0.81] (0.357) 0.54 [0.03–1.05] (0.040)* 0.28 [–0.24–0.80] (0.279)
Lateral lipid chain packing (FWHM)
Pre tape-stripping
Arm 5.76 (1.07) 5.71 (0.74) 5.64 (0.91) 6.15 (0.87) 5.84 (1.10) 6.57 (1.29) 0.09 [–0.56–0.73] (0.791) –0.74 [–1.51–0.03] (0.058) –0.83 [–1.55 to –0.11] (0.024)*
Abdomen 5.86 (0.57) 5.79 (0.53) 5.68 (0.60) 6.31 (0.85) 5.90 (1.20) 6.95 (0.97) 0.35 [–0.19–0.89] (0.198) –0.92 [–1.40 to –0.44] (<0.001)* –1.27 [–1.82 to –0.73] (< 0.001)*
Thigh 5.89 (0.86) 6.21 (0.70) 5.69 (1.04) 6.03 (1.09) 5.80 (1.19) 6.63 (1.13) 0.37 [–0.35–1.10] (0.307) –0.92 [–1.73 to –0.10] (0.028)* –1.29 [–2.12 to –0.46] (0.003)*
Post tape-stripping
Arm 5.83 (1.09) 5.97 (1.07) 5.95 (0.97) 6.85 (1.21) 7.12 (1.02) 7.63 (0.90) –0.47 [–1.26–0.32] (0.238) –0.98 [–1.73 to –0.23] (0.011)* –0.52 [–1.21–0.18] (0.141)
Abdomen 6.03 (0.68) 5.86 (0.77) 6.07 (0.75) 6.61 (1.12) 6.87 (1.21) 7.51 (0.97) –0.45 [–1.16–0.25] (0.205) –0.95 [–1.50 to –0.40] (0.001)* –0.49 [–1.12–0.14] (0.121)
Thigh 6.33 (0.95) 6.19 (0.86) 6.38 (0.87) 6.98 (1.29) 6.83 (1.54) 7.39 (1.08) –0.08 [–0.96–0.80] (0.856) –0.35 [–1.11–0.41] (0.360) –0.27 [–0.93–0.40] (0.427)
*p < 0.05. TEWL: trans-epidermal water loss; FWHM: full width at half maximum; CI: condence interval; SD: standard deviation.
Acta Derm Venereol 96
Supplementary material to article by A. Cooke et al. ”Olive Oil, Sunower Oil or no Oil for Baby Dry Skin or Massage: A Pilot, Assessor-
blinded, Randomized Controlled Trial (the Oil in Baby SkincaRE [OBSeRvE] Study)”
Fig. S1. Oil in Baby SkincaRE (OBSeRvE) pilot study recruitment ow chart. *Mum asleep/
feeding/had visitors/clinical care provision/investigator unable to return as conducting
assessments.
ENROLMENT Assessed for eligibility (n=4,085)
Excluded (n=3,970)
• Not meeting inclusion criteria (n=2,886)
• Declined to participate (n=318)
• Other reasons (n=766)
Mothers of eligible babies
approached (n=1,037)
ALLOCATION
Babies recruited
(n=115)
Declined (n=318)
• Product preference (n=34)
• Water preference (n=21)
• Too much to commit to (n=97)
• Family would not support (n=8)
• No reason given (n=158)
Other reasons (n=766)
Approached (n=604):
• Discharged (n=78)
• No randomisation midwife (n=5)
• Logistical reasons* (n=521)
Not approached (n=162):
• Could not arrange interpreter (n=19)
• Clinical midwife unavailable (n=91)
• Baby could not leave ward (n=52)
Olive oil
(n=38)
Sunflower oil
(n=38)
No oil
(n=39)
Baseline
assessment
(n=38)
Baseline
assessment
(n=38)
Baseline
assessment
(n=39)
Loss to
follow up
(n=11)
Loss to
follow up
(n=8)
Loss to
follow up
(n=4)
Follow up
assessment at
28 days
(n=27)
Follow up
assessment at
28 days
(n=30)
Follow up
assessment at
28 days
(n=35)
FOLLOW UP
ANALYSIS
Excluded from
analysis
(n=0)
Excluded from
analysis
(n=0)
Excluded from
analysis
(n=0)
Acta Derm Venereol 96
16 A. Cooke et al.
REFERENCES
1. Lewis-Jones S. Dry Skin in Childhood and the Misery of
Eczema and Its Treatments. In: Treatment of Dry Skin
Syndrome. Edited by Loden M, Maibach H. Berlin:
Springer-Verlag; 2012.
2. Danby S, Al Enezi T, Sultan A, Lavender T, Chittock J,
Brown K, et al. Effect of olive and sunower seed oil on
the adult skin barrier: implications for neonatal skin care.
Pediatr Dermatol 2013; 30: 42–50.
3. Silverberg J, Lee-Wong M, Silverberg N. Complementary
and alternative medicines and childhood eczema: a US
population-based study. Dermatitis 2014; 25: 246–254.
4. Bieber T. Atopic Dermatitis. N Engl J Med 2008; 358:
1483–1494.
5. Danby S, Cork M. The Skin Barrier in Atopic Dermatitis.
In: Textbook of Pediatric Dermatology. Edited by Irvine
A, Hoeger P, Yan A. Oxford: Blackwell Publishing; 2011.
6. Taylor B, Wadsworth J, Wadsworth M, Peckham C. Chan-
ges in the reported prevalence of childhood eczema since
the 1939–45 war. Lancet 1984; 2: 1255–1257.
7. Gupta R, Sheikh A, Strachan D, Anderson H. Burden of
allergic disease in the UK: secondary analyses of national
databases. Clin Exp Allergy 2004; 34: 520–526.
8. Naik A, Pechtold L, Potts R, Guy R. Mechanism of oleic
acid-induced skin penetration enhancement in vivo in hu-
mans. J Control Release 1995; 37: 299–306.
9. Darmstadt G, Mao-Qiang M, Saha S, Ziboh V, Black R,
Santosham M, et al. Impact of topical oils on the skin bar-
rier: possible implications for neonatal health in developing
countries. Acta Paediatr 2002; 91: 546–554.
10. Stamatas G, Nikolovski J, Luedtke M, Kollias N, Wiegand
B. Infant skin microstructure assessed in vivo differs from
adult skin in organization and at the cellular level. Pediatr
Dermatol 2010; 27: 125–131.
11. Nikolovski J, Stamatas G, Kollias N, Wiegand B. Barrier
function and water-holding and transport properties of in-
fant stratum corneum are different from adult and continue
to develop through the rst year of life. J Invest Dermatol
2008; 128: 1728–1736.
12. Stamatas G, Nikolovski J, MC. M, Kollias N. Infant skin
physiology and development during the rst years of life:
a review of recent ndings based on in vivo studies. Int J
Cosmet Sci 2011; 33: 17–24.
13. Fluhr J, Darlenski R, Lachmann N, Baudouin C, Msika P,
DeBelilovsky C, et al. Infant epidermal skin physiology:
adaptation after birth. Br J Dermatol 2011; 166: 483–490.
14. Janssens M, Van Smeden J, Gooris G, Bras W, Portale G,
Caspers P, et al. Lamellar lipid organization and ceramide
composition in the stratum corneum of patients with atopic
eczema. J Invest Dermatol 2011; 131: 2136–2138.
15. Janssens M, van Smeden J, Gooris G, Bras W, Portale G,
Caspers P, et al. Increase in short-chain ceramides correlates
with an altered lipid organization and decreased barrier
function in atopic eczema patients. J Lipid Res 2012; 53:
2755–2766.
16. Higgs-Bayliss T, Brown K, Chittock J, Cork M, Danby S.
Noninvasive assessment of the lipid structure and water
holding properties of the stratum corneum in vivo by ATR-
FTIR using a bre optic probe in patients with atopic der-
matitis and healthy controls. Br J Dermatol 2014; 170: e29.
17. National Institute for Health and Care Excellence. NICE
clinical guideline 37: Postnatal care. London: NICE; 2014.
18. Walker L, Downe S, Gomez L. A survey of soap and skin
care product provision for well term neonates. Br J Mid-
wifery 2005; 13: 768–773.
19. Cooke A, Cork M, Danby S, Lavender T. Use of oil for baby
skincare: A survey of UK maternity and neonatal units. Br
J Midwifery 2011; 19: 354–362.
20. Lavender T, Bedwell C, Tsekiri-O’Brien E, Hart A, Turner
M, Cork M. A qualitative study exploring womens’ and
health professionals’ views of newborn bathing practices.
Evid based Midwifery 2009; 7: 112–121.
21. Bedwell C, Lavender T. Newborn skin care – a review of
evidence and practice. Eur J Obstet Gynaecol Sup 2012:
18–21.
22. Allemann I, Baumann L. Botanicals in skin care products.
Int J Dermatol 2009; 48: 923–934.
23. Cottingham M, Winkler E. The organic consumer. In: The
handbook of organic and fair trade food marketing. Edited
by Wright S, McCrea D. Oxford: Blackwell Publishing
Ltd.; 2007.
24. Erenel A, Vural G, Efe S, Özkan S, Özgen S, Erenoğlu R.
Comparison of olive oil and dry-clean keeping methods
in umbilical cord care as microbiological. Matern Child
Health J 2010; 14: 999–1004.
25. Solanki K, Matnani M, Kale M, Joshi K, Bavdekar A, Bhave
S, et al. Transcutaneous absorption of topically massaged
oil in neonates. Indian Pediatr 2005; 42: 998–1005.
26. Simpson E, Chalmers J, Hanin J, French M, Lubianski T,
Samrao A, et al. Barrier enhancement for eczema preven-
tion – the BEEP feasibility study. J Invest Dermatol 2012;
132: S90.
27. Simpson E, Chalmers J, Hanin J, Thomas K, Cork M,
McLean W, et al. Emollient enhancement of the skin barrier
from birth offers effective atopic dermatitis prevention. J
Allergy Clin Immunol 2014; 134: 818–823.
28. Lancaster G, Dodd S, Williamson P. Design and analysis
of pilot studies: recommendations for good practice. J Eval
Clin Pract 2004; 10: 307–312.
29. Darmstadt G, Saha S, Ahmed A, Chowdhury M, Law P,
Ahmed S, et al. Effect of topical treatment with skin barrier-
enhancing emollients on nosocomial infections in preterm
infants in Bangladesh: a randomised controlled trial. Lancet
2005; 365: 1039–1045.
30. Damien F, Boncheva M. The extent of orthorhombic lipid
phases in the stratum corneum determines the barrier ef-
ciency of human skin in vivo. J Invest Dermatol 2010;
130: 611–614.
31. Brancaleon L, Bamberg M, Kollias N. Spectral differences
between stratum corneum and sebaceous molecular compo-
nents in the mid-ir. Appl Spectrosc 2000; 54: 1175–1182.
32. Mendelsohn R, Flach C, Moore D. Determination of
molecular conformation and permeation in skin via IR
spectroscopy, microscopy, and imaging. Biochim Biophys
Acta 2006; 1758: 923–933.
33. Boncheva M, Damien F, Normand V. Molecular organiza-
tion of the lipid matrix in intact Stratum corneum using
ATR-FTIR spectroscopy. Biochim Biophys Acta 2008;
1778: 1344–1355.
34. Hoppel M, Baurecht D, Holper E, Mahrhauser D, Valenta
C. Validation of the combined ATR-FTIR/tape stripping
technique for monitoring the distribution of surfactants
in the strateum corneum. Int J Pharm 2014; 472: 88–93.
35. Fluhr J, Feingold K, Elias P. Transepidermal water loss
reects permeability barrier status: validation in human
and rodent in vivo and ex vivo models. Exp Dermatol
2006; 15: 483–492.
36. Rogiers V. EEMCO guidance for the assessment of trans-
epidermal water loss in cosmetic sciences. Skin Pharmacol
Appl 2001; 14: 117–128.
37. Lund C, Kuller J, Lane A, Wright-Lott J, Raines D, Tho-
mas K. Neonatal skin care: evaluation of the awhonn/nann
research-based practice project on knowledge and skin care
Acta Derm Venereol 96
17
The oil in baby SkincaRE (OBSeRvE) study
practices. J Obstet Gynecol Neonatal Nurs 2001; 30: 30–40.
38. Jiang S, Hwang S, Choi E, Elias P, Ahn S, Lee S. Structural
and functional effects of oleic acid and iontophoresis on
hairless mouse stratum corneum. J Invest Dermatol 2000;
114: 64–70.
39. Sinha V, Kaur M. Permeation enhancers for transdermal
drug delivery. Drug Dev Ind Pharm 2000; 26: 1131–1140.
40. Correa M, Mao G, Saad P, Flach C, Mendelsohn R, Walters
R. Molecular interactions of plant oil components with
stratum corneum lipids correlate with clinical measures
of skin barrier function. Exp Dermatol 2014; 23: 39–44.
41. dos Santos Rodrigues J, Pinto T, de Oliveira C, de Sousa
Freitas I, do Socorro Vieira Pereira M, de Souza E, et al.
Lipolytic activity of Staphylococcus aureus from human
wounds, animals, foods, and food-contact surfaces in Bra-
zil. J Infect Dev Ctries 2014; 8: 1055–1058.
42. Sharma M, Singh S, Maan P, Sharma R. Biocatalytic
potential of lipase from Staphylococcus sp. MS1 for tran-
sesterication of jatropha oil into fatty acid methyl esters.
World J Microb Biot 2014; 30: 2885–2897.
43. Choi E, Brown B, Crumrine D, Chang S, Man M, Elias
P, et al. Mechanisms by which psychologic stress alters
cutaneous permeability barrier homeostasis and stratum
corneum integrity. J Invest Dermatol 2005; 124: 587–595.
44. Roberta R, Patrizi A, Cocchi G, Faldella G, Raone B.
Comparison of two different neonatal skin care practices
and their inuence on transepidermal water loss in healthy
newborns within rst 10 days of life. Minerva Pediatr 2014;
66: 369–374.
45. Horimukai K, Morita K, Narita M, Kondo M, Kitazawa
H, Nozaki M, et al. Application of moisturizer to neonates
prevents development of atopic dermatitis. J Allergy Clin
Immunol 2014; 134: 824–830.
46. Darmstadt G, Badrawi N, Law P, Ahmed S, Bashir M, Is-
kander I, et al. Topically applied sunower seed oil prevents
invasive bacterial infections in preterm infants in Egypt.
Pediatr Infect Dis J 2004; 23: 719–725.
47. Darmstadt G, Saha S, Ahmed A, Ahmed S, Chowdhury M,
Law P, et al. Effect of skin barrier therapy on neonatal mor-
tality rates in preterm infants in Bangladesh: a randomized,
controlled, clinical trial. Pediatrics 2008; 121: 522–529.
48. Kanti V, Grande C, Stroux A, Bührer C, Blume-Peytavi U,
Garcia Bartels N. Inuence of sunower seed oil on the skin
barrier function of preterm infants: a randomized controlled
trial. Dermatology 2014; 229: 230–239.
49. Lavender T, Bedwell C, O’Brien E, Cork M, Turner M,
Hart A. Infant skin-cleansing product versus water: A pilot
randomized, assessor-blinded controlled trial. BMC Pediatr
2011; 11: 35.
50. Lavender T, Furber C, Campbell M, Victor S, Roberts I,
Bedwell C, et al. Effect on skin hydration of using baby
wipes to clean the napkin area of newborn babies: assessor-
blinded randomised controlled equivalence trial. BMC
Pediatr 2012; 12: 59.
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