Human skin is a complex structure with unusual functional diversity. The concept of an integumental barrier emphasizes the role of the skin as a protective boundary between the organism and a potentially hostile environment. Focusing only on the barrier properties of the skin, however, de-emphasizes the important role it plays in communication, perception and behavioral interactions. It also provides the physical scaffold that defines the form of the animal <xref ref-type="bibr" rid="bib001">1</xref>,<xref ref-type="bibr" rid="bib002">2</xref>. This dual functionality befits a true boundary and must be kept in mind to fully appreciate the dynamic organization of the skin and its close kinship with the nervous system.</sec><sec id="sec002"><title>Structure of the skin

Human skin has two distinct but interdependent components: the epidermis and the dermis. The epidermis consists of a highly ordered compact layering of keratinocytes and melanocytes. It also contains the hair follicle, sweat gland, and the sebaceous gland. Traditionally, the epidermis is segmented into four distinct structural and functional compartments: stratum basale, responsible for keratinocyte proliferation and epidermal renewal, stratum spinosum, consisting of tightly packed keratinocytes linked via desmosomal connections, stratum granulosum, responsible for barrier lipid synthesis and corneocyte production via programmed cell death, and stratum corneum, the anucleated outermost layer, which forms the physical interface with the environment ³.

The bulk of the human skin is composed of the dermis and consists of collagen and elastic fibres embedded in a hydrated matrix of glycosaminoglycans. Blood vessels and the majority of cutaneous nerve endings are present in the dermis.

Embryology of the skin

The cells of the dermis and subcutaneous fat derive from the embryonic mesoderm. In contrast, epidermal appendages as well as the interfollicular epidermis derive from embryonic ectoderm. A third distinct cell type, the Langerhans cell, is derived from bone marrow precursors and migrates into the primitive epidermis.

The process of cutaneous morphogenesis can be divided into embryonic and fetal periods. During the embryonic period, the skin consists of a two layered epidermis, the basal layer and the periderm. The basal layer includes cells that give rise to the future definitive epidermis while the periderm is a transient layer that covers the embryo and the fetus until the epidermis keratinizes. At the time of embryo to fetus transition (about 2 months of gestation) the epidermis begins to stratify, forming an intermediate layer of cells. Two to three additional layers of intermediate cells are added during the second trimester. These cells show a progressive increase in the number of keratin filaments but do not further differentiate until the onset of keratinization at around 22–24 weeks gestation. The stratum corneum becomes multilayered during the third trimester ⁴.

Functions of the skin

The skin subserves the functions of thermoregulation, barrier to water loss, infection control, immuno-surveillance, acid mantle formation, anti-oxidant function, ultraviolet light photoprotection, barrier to chemicals, and finally acts as an attraction to the caregivers. The preterm infant is vulnerable to disruption of all these physiologic mechanisms.

Neonatal skin: peculiarities

The skin of the neonate differs from adult skin in several ways. Given that their skin is relatively thin and they have higher body surface to weight ratio compared to adults, the neonates are at increased risk for skin damage, percutaneous infection, and percutaneous toxicity from topically applied agents ⁵. On the other hand, the thin, less pigmented neonatal skin provides more information about the infant's well-being than in adults ⁶. The pitfalls of this immature skin barrier and their consequences are summarized in Table I. Table 1

Preterm skin: Limitations and their consequence

Limitations	Consequences

Structural immaturity	Increased susceptibility to shear forces and hence injury
Underdeveloped epidermal permeability barrier (stratum corneum)	1. Increased transepidermal water loss (TEWL)
	2. Increased risk of infections
	3. Hypothermia
	4. More chance for percutaneous absorption of toxins
Reduced expression of cationic antimicrobial peptides, acid mantle, vernix caseosa	Increased risk of infections
Decreased number of melanocytes with immature melanosomes	More sus ceptible to UV light induced damage
Reduced subcutaneous fat	Increased risk of hypothermia

Preterm skin: Limitations and their effects

The various limitations of the preterm skin are discussed below:

I. Water loss and temperature control

The formation of a barrier against transepidermal water loss (TEWL) is well known to be a direct function of gestational age. TEWL decreases dramatically as term approaches, with levels in the near-term infant equal to or less than adult values ⁸. TEWL is up to 15 times higher in 1-day-old infant born at 25 weeks gestation than in term neonates. In very low birth weight (VLBW) infants, this can translate into a fluid loss of up to 30% of total body weight in 24 hours. This may result in dehydration, hypotension, electrolyte imbalance (esp. hyperosmolar hypernatremia), and thermal instability ⁷. As stratum corneum develops, TEWL gradually decreases, but at 4 weeks of postnatal age, TEWL of an infant born at 26 weeks is still twice that of a term infant ⁵.

Maintenance on an open radiant warmer bed in a nursery with low ambient humidity results in high evaporative loss of body water. Loss of body water is accompanied by evaporative heat loss at a rate of 576 calories of body heat for every mL of water ⁹. This leads to an increased caloric demand, that if not met, would result in inadequate weight gain. Since evaporative losses are greatest in younger, more premature infants, they are at increased risk for temperature instability.

II. Barrier to infections

Another critical function of the skin is to prevent microbial infection. Preterm infants are at high risk for infection because of their epidermal barrier immaturity and possibly disordered cutaneous immunoregulation and antimicrobial peptide expression. This is further compounded by the developmental defects in systemic immune function in these infants ¹⁰.

In developing countries, the prevalence of sepsis in premature infants is estimated at 30% to 60%, and the mortality rate is 40% to 70%; indeed septicemia is the most prevalent cause of death accounting for as much as 50% of neonatal mortality in these infants ¹¹. Approximately half of these deaths occur in the first week of life, when epidermal barrier function is highly compromised.

III. Skin injury

Because of their structurally immature skin, even removal of a piece of tape or an adhesive-backed electrode in these infants would markedly compromise the stratum corneum and might result in secondary infection and significant scarring ¹². Ultraviolet light burns have occurred in association with white light phototherapy for jaundice ¹³. A Plexiglas safety shield, placed in front of daylight fluorescent lamps will filter out the UVA.

IV. Percutaneous absorption

Increased percutaneous absorption of topically applied compounds through an immature stratum corneum has been both advantageous and hazardous to neonates. Transdermal route might be employed for administration of theophylline, lidocaine, and even for supplemental oxygen in extremely premature infants ^14,15. In contrast, there have been numerous reports of devastating systemic side-effects in infants caused by absorption of topical agents, the classical example being fatal spongiform myelinopathy seen with hexachlorophene bathing ¹⁶.

Given the limitations of the preterm skin, strategies for optimizing epidermal barrier integrity, including emolliation practices, preventing and managing infections and skin injury, and minimizing TEWL and heat or percutaneous absorption of toxins need to be developed and employed in all neonatal care units ⁷. In addition to the gestation, postnatal age is also important in determining the optimal skin-care practices because exposure to the dry extrauterine environment accelerates development of an effective epidermal barrier. Barrier maturation following premature birth usually requires 2 to 4 weeks; however, in extremely premature infants it might take as long as 8 weeks, since the stratum corneum responds more slowly to maturational signals expressed after birth ¹⁶.

Strategies for optimizing epidermal barrier integrity

These are summarized in Box 1. Some of these strategies have been discussed in detail below. Box 1. Strategies for optimizing epidermal barrier integrityPrevention of skin barrier compromise

The use of skin adhesives should be limited as much as possible (e.g., bandaging should be avoided after blood draws)

A semi-permeable barrier should be used between the skin and adhesive (e.g., Tegaderm) to secure endotracheal tubes, temperature probes, umbilical catheters, etc.

Tapes should be left in place for at least 24 hours.

Cotton balls soaked with sterile water should be used to remove adhesive tapes.

Avoid using bonding agents (e.g., tincture of benzoin) as well as adhesive removers.

Prevention of thermal and pressure injuries

Excessive heat should be avoided when warming the heel for heel sticks.

Phototherapy units should be positioned at a proper distance from the skin.

Clear transparent dressings should be placed on high friction areas and critically ill infants should be placed on a specialized mattress.

Reduction of TEWL and heat loss

Placement in a double-walled incubator, possibly with servo-controlled humidification

By using plastic heat shield or transparent plastic blanket (e.g., Cling wrap) or by transparent nonadhesive dressings "

By application of emollients¹⁸

Skin-to-skin contact (Kangaroo Mother Care)

Prevention of infections

Strict adherence to hand hygiene by caregivers

Use of antiseptics (preferably0.5% chlorhexidine) for skin preparation before venepuncture and catheter insertion

Use of antiseptics for umbilical cord care especially in settings with high incidence of omphalitis and systemic sepsis ^K

? whole body bathing with antiseptics (chlorhexidine) and application of emollients ²⁰

a) Antiseptic application

Antiseptics have been applied to the skin and umbilical cord stumps of newborn infants for many years with a view to controlling bacterial colonization and reducing the incidence of neonatal infection. In developed countries, many studies have shown that single or repeated antiseptic applications to the cord can substantially reduce bacterial colonization ^21,22. Since the link between cord colonization and infection has not been firmly established, WHO promotes dry cord care ¹⁹. However, in a recent community-based, cluster-randomized trial in southern Nepal, it was found that topical applications of chlorhexidine to the umbilical cord reduced mortality by 34% in infants enrolled in the first 24 hours ²³.

Whole body bathing with antiseptic agents like chlorhexidine has also been shown to reduce skin colonization and infections. In a study conducted in Nepal, Mullany et al found that single whole body application with chlorhexidine reduces the mortality especially in low birth weight infants ²⁰.

b) Topical application of emollients

For hundreds of years, some populations especially from Indian subcontinent) have applied natural vegetable oils to the skin of newborns. The potential benefits of such therapy include reduction of TEWL, reduced incidence of hypothermia and infections, improvement in skin condition, etc ⁷. Topical treatment of preterm infants with emollients that enhanced skin barrier function has been demonstrated to decrease the incidence of nosocomial infections by 40–55% ²⁴. However, the practice of routine emollient application remains controversial because another randomized trial demonstrated an increase in coagulase negative staphylococci (CONS) in preterm infants who received twice-daily petrolatum ointment application ²⁵. Routine application of emollients may actually increase colonization, with no added benefit for patients who have intact skin.

Topical therapy may be an effective strategy for reducing the trans-epidermal water los. Besides the ability of the oils to act as a mechanical and semi-permeable barrier, highly active lipid metabolism in the epidermis make it possible for even the immature epidermis to metabolize lipids and to utilize them as nutritional building blocks for the formation of a healthy functional epidermal barrier. Rutter et al applied a paraffin mixture (80% soft, 20% hard paraffin (BP)) on the skin of 3 preterm babies nursed naked in incubators and found that water loss fell by 40 to 60% after application and was still lower than pretreatment levels 6 hours later¹⁸. Recently we have used coconut oil for topical application in very low birth weight infants in a randomized controlled trial and found that it significantly reduces TEWL in these infants²⁶.

c) Using transparent plastic coverings

Thin plastic blanket may be effective in reducing evaporative water loss by diminishing an infant's exposure to convective air currents while being nursed on an open radiant warmer bed.

Kaushal et al conducted a randomized trial using a thin plastic film made of food grade plastic to cover the bassinet of the neonate during the first week of life. They reported reduced heat loss and decreased episodes as well as degree of hypothermia in neonates nursed under this thin film as compared to the control group ¹⁷.

Summary

During the neonatal period, many neonates, especially preterm infants experience significant morbidity caused by compromised skin barrier integrity. Several strategies are available for protecting the integrity and promoting the hygiene of the skin and augmenting its function as a barrier to TEWL and heat loss and the entrance of infectious or toxic agents. Research defining optimal applications of these approaches and the development of new approaches in skin care holds promise for improving neonatal outcome in the future. Figure 1Structure of the skin

Preterm Skin – Is it protective?