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Infant Skin Microstructure Assessed In Vivo
Differs from Adult Skin in Organization
and at the Cellular Level
Georgios N. Stamatas, Ph.D.,* Janeta Nikolovski, Ph.D.,Michael A. Luedtke, M.S.,à
Nikiforos Kollias, Ph.D.,àand Benjamin C. Wiegand, Ph.D.
*Baby Science & Technology, Johnson & Johnson Consumer France, Issy-les-Moulineaux, France, Advanced
Technologies, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, USA, àMethods and
Models Development, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, USA.
[Correction made after online publication on Oct. 4th 2009]
Abstract: Functional differences between infant and adult skin may be
attributed to putative differences in skin microstructure. The purpose of this
study was to examine infant skin microstructure in vivo and to compare it with
that of adult skin. The lower thigh area of 20 healthy mothers (ages 25–43) and
their biological children (ages 3–24 months) was examined using in vivo
noninvasive methods including fluorescence spectroscopy, video micros-
copy, and confocal laser scanning microscopy. Stratum corneum and supra-
papillary epidermal thickness as well as cell size in the granular layer were
assessed from the confocal images. Adhesive tapes were used to remove
corneocytes from the outer-most layer of stratum corneum and their size was
computed using image analysis. Surface features showed differences in
glyph density and surface area. Infant stratum corneum was found to be 30%
and infant epidermis 20% thinner than in adults. Infant corneocytes were
found to be 20% and granular cells 10% smaller than adult corneocytes indi-
cating a more rapid cell turnover in infants. This observation was confirmed
by fluorescence spectroscopy. Dermal papillae density and size distribution
also differed. Surprisingly, a distinct direct structural relationship between the
stratum corneum morphology and the dermal papillae was observed
exclusively in infant skin. A change in reflected signal intensity at
100 lm
indicating the transition between papillary and reticular dermis was evident
only in adult skin. We demonstrate in vivo qualitative and quantitative differ-
ences in morphology between infant and adult skin. These differences in skin
microstructure may help explain some of the reported functional differences.
Healthy infant skin is often described as soft and tender
and is frequently presented as an ideal state of skin aspired to
by adults. On the other hand, infant skin is also described as
‘‘fragile’’ and ‘‘sensitive’’ and is prone to dermatitides and
infections (1). Of particular importance is the recent increase
in the incidence of infantile atopic dermatitis (2). A compa-
Address correspondence to Georgios N. Stamatas, Ph.D.,
Johnson & Johnson Consumer France, 1 rue Camille Desmoulins,
Issy-les-Moulineaux 92130, France, or e-mail: gstamat@its.jnj.com.
DOI: 10.1111/j.1525-1470.2009.00973.x
2009 Wiley Periodicals, Inc. 125
CLINICAL AND LABORATORY INVESTIGATIONS
Pediatric Dermatology Vol. 27 No. 2 125–131, 2010
rative study of infant and adult skin physiology is bound to
shed light on the reasons for this special status of infant skin.
The barrier function and the water holding and
transportpropertiesofinfantstratumcorneum(SC)
have been shown to be different from an adult and con-
tinuetoevolvethroughthefirstyearoflife(3).InfantSC
was found to have higher water content and higher trans-
epidermal water loss rates at rest, absorb more water and
loose excess water faster than adult SC. Many of these
differences may be explained by careful examination of
the underlying skin microstructure.
Advances in noninvasive methods such as confocal
laser scanning microscopy (CLSM) have made the study
of skin microstructure in vivo possible, avoiding the need
for painful biopsies, as well as the artifacts introduced by
handling and fixing the sample required for histological
samples examination. By focusing the incident light on
the skin at different depths and scanning its position in
the plane parallel to the skin surface, one can obtain
images corresponding to ‘‘optical sections’’ through the
skin volume, in contrast to the vertical sections of his-
tology (4). This technology has been applied to the study
of adult skin physiology (5) and pathology of several
dermatological conditions [for reviews see (4,6,7)], but to
our knowledge it has not yet been used in the study of
infant skin.
Another useful noninvasive method is in vivo fluo-
rescence spectroscopy, which has been used to assess the
proliferation rate of the epidermal cells (8–10). This
signal has been shown to decrease with age in adults (11),
but there have been no reports to date about its use on
infant skin. In this study, we employed in vivo nonin-
vasive methods to address the question whether infant
skin microstructure is different from that of an adult at
the organ level (epidermal thickness, epidermal organi-
zation) and at the cellular level (cell size and cell density).
MATERIALS AND METHODS
Clinical Protocol
The study was performed under approval from an
independent institutional review board and following
the principles of the Declaration of Helsinki. Twenty
mothers from the New Jersey area at 25–46 years of age
and their biological infants at ages 6–24 months partic-
ipated in the study. Adult subjects signed a written in-
formed consent for themselves and their participating
children. Only healthy individuals were recruited. The
skin phototypes of the adult subjects were I–III on the
Fitzpatrick scale. The infant population was fair com-
plexioned and equally distributed between boys and girls.
Subjects were instructed to avoid use of skin care prod-
ucts on the arms and legs for at least 24 hours before the
measurements. Visibly distressed or crying infants were
excluded. Measurements were performed on the upper
inner arm, the dorsal forearm, or the lower thigh area as
described below.
Video Microscopy
A video microscope (HiScope Systems Co., Closter, NJ)
wasusedtoacquireinvivolightreflectanceimagesofthe
skin surface with a magnification of 100·. The micro-
scope camera was calibrated before image acquisition
using a white reflectance standard (Minolta, Ramsey,
NJ). The final image corresponded to a skin area of
2.7 mm ·2.1 mm.
Confocal Laser Scanning Microscopy
The skin sites of interest were examined in vivo using a
reflectance CLSM (Vivascope
1500, Lucid Inc., Hen-
rietta, NY) equipped with a laser at 785 nm (laser power
<25 mW at the tissue surface) and a oil immersion 30·
objective of numerical aperture 0.9 NA. This microscope
generates a series of consecutive optical sections every
3.125 lm of increasing depth. Imaging starts at the top
layer of the SC and progresses down through the epi-
dermal layers, the dermal epidermal junction, and the top
layers of the dermis. Each optical section corresponded
to a skin area of 0.5 mm ·0.5 mm. The laser power was
adjusted to increase the signal-to-noise ratio for the
deeper sections and its value was recorded for each cor-
responding image. The sequential optical sections were
analyzed as explained below for the measurement of SC
and epidermal thickness and they were reconstructed to
form three-dimensional images using the 3D Construc-
tor
plug-in to Image Pro software (Media Cybernetics,
Bethesda, MD). The lower thigh area was selected
forthesesmeasurementsto reduce infant motion
during acquisition. Three replicate stacks within a
4mm·4 mm area were sampled and then averaged.
CLSM Image Analysis
The SC thickness was calculated as the number of images
from the first image (top corneocyte layer) to the image
just before the one where granular cells can be detected,
times the imaging step (3.12 lm). Similarly, the epider-
mal thickness was calculated as the number of images
from the top corneocyte layer to the image just before the
one where the top of the dermal papilla can be detected,
times the imaging step. The size of cells at the SC and
granular layer was analyzed using the Image ⁄J software
developed by the National Institute of Health (http://
126 Pediatric Dermatology Vol. 27 No. 2 March ⁄April 2010
rsb.info.nih.gov/ij/). Finally, the average grayscale
intensity was calculated for each optical section (to
minimize edge artifacts the central image area was used
only) and normalized to the corresponding laser power.
Thus, depth profiles of the backscattered light intensity
could be constructed.
Cell Size Analysis
Corneocytes were removed from the skin surface at the
upper inner arm, dorsal forearm, and thigh using adhe-
sive tapes (D-Squames, CuDerm Corporation, Dallas,
TX). Each tape was applied uniformly on the skin and
was removed after 1 min. Images of the removed
corneocytes on the tapes were acquired using a video
light microscope (HiScope Systems Co., Closter, NJ).
Thefinalimagecorrespondedtoanareaof
2.7 mm ·2.1 mm. Images of individual cells were ana-
lyzed for cell area and perimeter using the Image ⁄J
software.
Fluorescence Spectroscopy
To evaluate the keratinocyte proliferation rate the
fluorescence ascribed to the tryptophan species was
recorded (8–10). To this end, the skin sites of interest
were examined in vivo using a fluorescence spectro-
photometer (SPEX
SkinSkan, HORIBA Jobin Yvon
Inc., Edison, NJ) equipped with a Xenon arc light
source, double excitation and emission monochroma-
tors, and a bifurcated fiber-optic probe with a ran-
domized distribution between excitation and collection
fibers (diameter of each fiber: 200 lm). A detailed
description of the instrumentation is given elsewhere
(12). Before each set of measurements the instrument
was spectrally calibrated for excitation and emission in
the region 250–650 nm. The chromatic resolution of
the spectrofluorimeter was ±2 nm. Measurements
were performed by placing the fiber optic probe in
contact with the skin site of interest and recording the
excitation spectra in the range from 240 to 320 nm with
emission set at 340 nm (tryptophan excitation maxi-
mum at 295 nm). The tryptophan fluorescence signal
was normalized to the 390 nm excitation band to
minimize the effect of instrumental parameters on the
measurements (11).
Statistics
All data are presented as average ± one SE of mean
except otherwise noted. Comparisons between infant
and adult skin data were performed using Student’s
t-test where applicable and ANOVA test otherwise.
Statistical significance was accepted at the level of
p<0.01.
RESULTS
Infant Skin Surface Is Different than Adult
Both video microscopy and CLSM images demonstrated
striking differences between adult and infant skin surface
(Fig. 1). In infants, the network of microrelief grooves
appearstobedenser(morelines per projected area) and
the intra-relief ‘‘island’’ structures appear to be more
rounded and plump. In contrast, these structures in
adults appear to be flatter and with larger surface area.
Moreover, in adults, the edges of these structures are
more distinct in video microscopy images. This increase
in contrast may be attributed to the dryer condition of the
corneocytes at these sites. Infant skin on the other hand
appears to be well hydrated in accordance with the skin
moisturization measurements previously reported (3).
Surprisingly, the depth of the glyphics as measured in the
CLSM images was found to be the same in adult and
infant skin (90 lm).
Infant Skin Architecture Is Different than Adult
Beneath the Surface
In vivo CLSM images revealed differences between adult
and infant epidermis (Fig. 2). The projected area of
Figure 1. The skin surface appears different between infants
and adults. Examples are shown of in vivo video microscopy
and confocal laser scanning microscopy images of the sur-
face of infant and adult skin. Infant skin appears to have a
denser network of microrelief lines than adult skin. The stra-
tum corneum ‘‘island’’ structures are flatter and larger in adult
skin.
Stamatas et al: Infant Skin Microstructure In Vivo 127
dermal papillae displays a fairly homogeneous size dis-
tribution in infant skin, whereas in adults, the dermal
papillae vary in size and are more irregular in shape.
Interestingly, in infant skin, there appears to be a one-
to-one relationship between the intra-glyph ‘‘island’’
structures at the surface and the underlying dermal
papillae at the bottom of the epidermis, possibly
indicating a single structural unit relationship. This
relationship is absent in adult skin, where a single surface
‘‘island’’ may correspond to several papillae underneath.
Infant SC and Supra-Papillary Epidermis Are Thinner
than Adult
Infant SC thickness calculated from in vivo CLSM
images is on average 30% lower than that of adult,
whereas the infant supra-papillary epidermis was found
to be on average 20% thinner than that of adults
(Table 1).
Infant Corneocytes and Granular Layer Keratinocytes
Are Smaller than Adult
Corneocyte size was evaluated by image analysis of
adhesive tapes removed from the skin sites of interest
(Fig. 3). In all sites examined (upper inner arm, dorsal
forearm, and lower thigh), the size of infant corneocytes
was found to be smaller than that of adult (Table 1). No
differences were noticed in corneocyte size among the
three sites examined for either adults or infants. The
differences between adult and infant keratinocyte size
were measurable to a lesser but still significant level at the
granular layer (Fig. 4, Table 1). Interestingly, both
infant and adult keratinocytes undergo on average a
doubling of their projected area as they transform from
granular cells to corneocytes. Cell densities in the gran-
ular (but not the corneal) layer could also be measured
form the confocal data and are shown in Table 1. The
smaller cell size in infants is often thought to be due to
higher cell turnover rates. We confirmed that this is the
case using in vivo fluorescence spectroscopy (Fig. 5).
These data also show that there appears to be a pro-
gressive decrease in the epidermal cell proliferation rate
during the first year of life.
The Border Between Papillary and Reticular Dermis
May Be Observed in Adults
Confocal laser scanning microscopy reflectance intensity
profiles decrease in an exponential-like manner because
of light losses by scattering. In the case of adult skin, the
monotonic decay is interrupted by a local plateau at
around 100–140 lm, which is absent in the profiles of
infant skin (Fig. 6). This plateau has previously been
ascribed to the border between papillary and reticular
dermis (13). Collagen and elastic fibers in the reticular
Figure 2. In vivo confocal laser scanning microscopy reveals differences between adult and infant skin beneath the skin surface.
Representative images are shown of different layers through the skin. The one-to-one relationship of the papillae to the stratum
corneum surface structures is evident in infant skin and not in adult. Also the overall brighter signal at the collagen level in adult
skin is characteristic of thicker collagen fibers in adult skin.
TABLE 1. Comparison of structural parameters between infant
and adult skin. The stratum corneum and supra-papillary epi-
dermis are thinner in infant skin compared to adult skin. Infant
corneocytes are smaller than adult in all three areas where sam-
ples were collected (upper inner arm, dorsal forearm, and upper
thigh area). Infant cell at the granular layer are smaller compared
to adult. Infant cell density at the granular layer is higher than
adult. All differences between infants and adults are statistically
significant. Data are shown as average ± one standard deviation
Infant skin Adult skin
Stratum corneum
thickness (lm)
7.3 ± 1.1 10.5 ± 2.1
Supra-papillary epidermal
thickness (lm)
29.7 ± 3.4 36.2 ± 5.2
Corneocyte size (lm
2
)
Upper inner arm 949.9 ± 19.1 1077.6 ± 26.9
Dorsal forearm 907.3 ± 23.4 1071.0 ± 25.7
Thigh 953.0 ± 23.8 1154.4 ± 33.7
Granular cell size (lm
2
) 443.6 ± 6.2 475.9 ± 8.3
Granular cell density
(cells ⁄mm
2
)
1577.8 ± 45.4 1382.6 ± 37.4
128 Pediatric Dermatology Vol. 27 No. 2 March ⁄April 2010
dermis are thicker than those of the papillary layer
and are expected to increase locally the reflected signal.
This feature was absent in the data from infant skin,
confirming the published observation that the collagen
bundles of the upper reticular dermis are not as thick in
infants as in adults (14,15) and therefore the transition
between papillary and reticular dermis is more gradual in
infants. Note that the small shoulders present in the in-
fant data are attributed to noise.
DISCUSSION
During the first year of life, skin has been shown to be in
a state of active development, in particular with regard to
its water handling properties (3,15–17). Such functional
differences between infant and adult skin may arise at
least in part from differences in microstructure. In this
study, we examined the morphology of infant and adult
skin in vivo at the microscopic level. We observed
differences in microglyph density, cell size, epidermal
layer thickness, dermal structure, and density of papillae.
On the other hand, some striking similarities exist, as for
example, the glyphic structures perceived on the surface
of the SC have the same depth in infant and adult skin.
Moreover, we report for the first time a structural rela-
tionship between papillae and skin surface that exists in
infant skin and disappears later in life.
In utero epidermal maturation occurs continuously.
Functional maturation of the SC begins in the third
trimester of gestation. By 34-weeks gestational age the
epidermis has largely matured: the SC and the dermo-
epidermal undulations become visible (18). However,
skin structures at the organ level continue to evolve even
after birth. During the first 3 months of life, skin
roughness decreases correlating with a concomitant
increase in SC hydration (19), although this may not be
Figure 3. Infant corneocytes are smaller than the adult ones.
Representative video microscopy images of corneocytes re-
moved by tape stripping from infant and adult skin.
Figure 4. Infant granular cells are smaller than the adult
ones. Representative confocal laser scanning microscopy
images at the depth where granular cells can be observed
from infant and adult skin.
Figure 5. The epidermal cell proliferation rate in infants is
higher than adults. The intensity of the tryptophan band
(295 nm excitation) was measured using in vivo fluorescence
excitation spectroscopy. The star (*) indicates statistical sig-
nificance between this infant group and the adult group.
Figure 6. Confocal laser scanning microscopy shows that
the border between papillary and reticular dermis (shoulder
between 90 and 140 lm depth) can be observed in adult skin,
but is absent in baby skin. The gray level intensity profiles for
the confocal stacks are given as average values normalized
to the laser power used at the corresponding depth. Data are
given as mean ± one SD.
Stamatas et al: Infant Skin Microstructure In Vivo 129
the only reason. Moreover, scanning electron micros-
copy revealed 10 times more hair structures per unit skin
surface area in newborns compared with adults (20).
Infant corneocytes have been reported to be thicker
(in height) than adult (21). The size of corneocytes shed
from the horny layer has been suggested as an indication
of the proliferation rate of the epidermal keratinocytes:
smaller size indicating faster proliferation (22). Detailed
three-dimensional morphometry using atomic force
microscopy showed that although adult corneocytes are
flatter than infant, the total volume remains statistically
similar between the two groups (21). In accordance with
these reports, our data also illustrate that the infant
corneocyte, as well as granular keratinocyte, projected
area is smaller than the adult and we confirm the higher
proliferation rate in infants using an intrinsic fluores-
cence marker of epidermal cell proliferation (9).
It has been reported that morphologically there is
increasing epidermal cellularity and undulation of the
rete ridges at the dermo-epidermal junction in neonates
and young infants (18). Our data corroborate these
results. Beyond these observations, we observed in in-
fants a direct relationship between the dermal papillae
structures at the bottom of the epidermis and the intra-
relief areas of SC at the surface. There appears to be a
structural unit in infant epidermis that potentially points
to a common precursor proliferative unit at the basal
layer. This one-to-one relationship between epidermal
structures is lost in adults possibly implicating both
chronological aging and photoaging processes. Alterna-
tively, the loss of the one-to-one relationship in a growing
organism may develop with the original epidermal units
controlling a greater area with more dermal papillae.
No consensus in the literature for the comparison in
terms of skin thickness between infants and adults was
observed. While a pulsed ultrasound study showed that
infant skin is thinner than adult skin (23) and a second
study showed that there was a slight increase in the
number of SC layers with age in the skin of the cheek and
back (24), another report stated that the thickness of their
SC is not significantly different and therefore cannot be
used to explain differences in percutaneous absorption
(25). Such discrepancies may be attributed to variations
in histological preparations. Ex vivo SC can have very
different appearance particularly when prepared for
histology. Using in vivo methods, we show that both the
SC and the supra-papillary epidermis are thinner in
infant skin compared with adult. Furthermore, the SC
thickness calculated in this study for adult subjects is
within the range of reported thicknesses calculated from
in vivo CLSM data: 8–14 lm depending on body site (5).
Histometric measurements by in vivo CLSM com-
prise a sensitive and noninvasive tool for characterizing
and quantifying histological changes in the epidermis
and papillary dermis as a result of aging (26). Age-related
effects on epidermal structures have been studied in
adults using noninvasive in vivo methods such as
ultrasound [for a review see (27)], optical coherence
tomography (OCT) (13,28), and CLSM (13,26). Ultra-
sonography has been reportedtogivevariableresults
concerning the measurement of skin thickness (27) and
the only parameter that can be extracted from OCT is
equivalent to a similar parameter measured from CLSM
image analysis (13). Therefore of the three in vivo
methods, more information can be obtained from
CLSM, which is taking the place of a ‘‘golden standard’’
for in vivo micro-structural measurements.
Skin surface morphology has long been recognized as
reflecting skin pathology. In a study on hairless mice,
skin surface roughness was found to be associated with
both water content and thickness of SC (29). Infant
micro-relief lines were found to be denser than adult,
which implies a larger surface per projected area.This in
turn may explain at least in part the differences between
infant and adults skin in terms of water absorption and
desorption (3).
Moreover, although infant SC has higher TEWL
rates than adult, it also has higher water content as
shown both by capacitance measurements and by in vivo
Raman microspectroscopy (3). This is not necessarily a
contradiction as TEWL values can be independent of the
water content of the SC reservoir as long as the influx-
outflux equilibrium of water in the SC can support the
high values of water content. Interestingly, the plateau
level in the water concentration profile calculated by the
Raman method (marking the beginning of viable epi-
dermis) is reached 5–10 lmearlierininfantSCthanin
adult. This observation confirms the finding of the current
study that infant SC is thinner, keeping in mind that cross
study comparisons should be made with caution.
In conclusion, infant skin continues to change and
develop during the first years of life. We report that
compared with adult skin, infant microrelief structures
are denser, SC and supra-papillary dermis are thinner,
dermal papilla size is more uniform, corneocyte and
granular cell size are smaller. In addition, we observed a
one-to-one relationship between papillae and surface
structures in infant skin exclusively and a distinct papil-
lary-to-reticular dermis transition in adult skin only.
Previous reports on differences in skin thickness, skin
pH, and SC hydration levels between newborn and adult
skin show that neonatal skin is always adjusting to the
extra-uterine environment (1). In the light of the findings
of this article as well as our previous report (3), we can
extend the above statement to infants through at least
theirfirstyearoflife.
130 Pediatric Dermatology Vol. 27 No. 2 March ⁄April 2010
ACKNOWLEDGMENTS
The authors would like to acknowledge the contribution
of Melissa Chu, Ashley Winter, and Fanny Le Goff
for their help in the corneocyte and granular cell size
analysis.
CONFLICT OF INTEREST
All authors are employees of the Johnson & Johnson
family of companies as indicated by their affiliations.
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Stamatas et al: Infant Skin Microstructure In Vivo 131
