Antepartum period

The basis for changes in the skin, hair, and secretory glands during pregnancy are thought to be hormonal—especially the effects of estrogens and adrenocortical steroids. Similar alterations are often seen in women using oral contraceptives. There is a familial tendency or genetic predisposition for some of the cutaneous and vascular changes.^77,118

Vasomotor instability.

Vasomotor instability during pregnancy may result in flushing, feelings of hot or cold, and cutis marmorata.^5,44,89 Cutis marmorata is a transient bluish mottling of the legs that is exaggerated on exposure to cold. It arises from vasomotor instability secondary to elevated estrogens. Persistence postpartum is abnormal and may suggest underlying pathology such as collagen vascular disorder, systemic lupus erythematosus, or vasculitis. Other changes due to vasomotor instability during pregnancy include pallor, facial flushing, and heat and cold sensations. Purpura secondary to increased capillary fragility and permeability occurs during the last months of pregnancy in many women.^96,118

Spider nevi.

Spider nevi (also called spider angiomas, spider telangiectases, or nevus araneus) are found in 10% to 15% of normal adults, in individuals with liver dysfunction, and in up to two thirds of pregnant women. These nevi are more common in white pregnant women (60% to 70% by term) than African-American pregnant women (10% by term).⁴⁴ Spider nevi consist of a central dilated arteriole that is flat or slightly raised with extensive radiating capillary branches. They are most prominent in areas of the skin drained by the superior vena cava (i.e., around the eyes, neck, throat, and arms). The basis for formation has been related to increased estrogen, because these structures are seen more frequently both during pregnancy and with use of oral contraceptives. However, many individuals with spider nevi associated with liver disorders do not have elevated estrogen levels.^61,118

Spider nevi generally appear between 2 and 5 months of pregnancy and may increase in size and number as pregnancy progresses. These structures tend to regress spontaneously and fade within the first 7 weeks to 3 months following delivery, although they rarely completely disappear. They may recur or enlarge during subsequent pregnancies. Unresolved spider nevi can be treated by pulse-dye laser or electrodesiccation therapy.⁹³

Palmar erythema.

palmar erythema is seen with pregnancy, liver disease, estrogen therapy and collagen vascular diseases.⁹³ Two patterns of palmar erythema are seen during pregnancy: erythema of hypothenar and thenar eminences, palms, and fleshy portions of the fingertips; and diffuse mottling of the entire palm. The latter form is more common and similar to changes seen with hyperthyroidism and cirrhosis. Palmar erythema generally appears during the first two trimesters and disappears by 1 week after delivery. This phenomenon has a familial tendency and is seen in approximately two thirds of white pregnant women and one third of African-American pregnant women. Spider nevi and palmar erythema often occur together, suggesting a common etiology generally believed to be elevated estrogen levels with increased skin blood flow.^{5,28,44,61,90,93,118} No treatment is needed. Palmar erythema resolves after delivery.

Nonpitting edema.

Increased vascular permeability and sodium retention due to the effects of estrogens and corticosteroids result in transient nonpitting edema of the face, hands, and feet during late pregnancy.^44,89 In the lower extremities, this is aggravated by pressure from the growing uterus. Nonpitting edema occurs in the face, especially the eyelids in approximately 50% of women, and in the lower extremities in 70% and is not associated with preeclampsia.^96,118 Although most pronounced in the morning, it usually improves during the day. Interventions for non-pitting edema during pregnancy are listed in Table 14-1. Vulvar edema may also be seen.

Capillary hemangiomas.

Pre existing capillary hemangiomas may increase in size during pregnancy.^5,96 In up to one third of pregnant women, new hemangiomas appear by the end of the first trimester, with slight, slow enlargement during the remaining trimesters.^44,118 New hemangiomas usually appear on the head and neck and are unusual elsewhere.⁹⁶ Enlarged existing hemangiomas and new hemangiomas regress postpartum but may not completely disappear. Hemangioma development in pregnancy is related to elevated estrogen.¹¹⁸

Varicosities.

^{5,61,65,89,93,96,118} Varicosities develop in approximately 40% of pregnant women. Varicosities occur most commonly in the legs but may also appear in the pelvic vessels, vulva, and anal area with hemorrhoid formation. Varicosities arise from estrogen-induced elastic tissue fragility, vascular distension, relaxin-weakened collagen and elastin, increased venous pressure in the lower extremities and pelvis from pressure of the gravid uterus, and familial tendency for valvular incompetence. Varicosities generally regress postpartum but do not completely disappear. Thrombi are rare with leg varicosities but are more frequent with hemorrhoids. Hemorrhoids are discussed in Chapter 12.

Hair loss

The scalp contains approximately 100,000 hair follicles. Hair fibers in each follicle independently cycle through three stages: anagen, catagen, and telogen. The anagen or growth stage lasts for 3 to 4 years and is characterized by intense metabolic activity. In this stage, hair grows an average of 0.34 mm/day.⁹³ Catagen is a transitional stage that lasts several weeks. During this stage, metabolic activity and growth slow as the hair bulb is retracted upward into the follicle. Growth of the hair fiber stops during telogen (resting stage). Eventually a new hair bulb begins growing, which ejects the previous hair.⁹³ Normally about 80% of hair follicles are in the anagen stage and 15% to 20% of hair fibers are in the telogen stage, with about 100 to 150 hairs shed per day.⁹⁶

Under the influence of estrogen during pregnancy, the rate of hair growth slows and the anagen stage is prolonged. This results in an increased number of anagen hairs and a decrease in telogen hairs to less than 10% during the second and third trimesters. During the postpartum period, with the decline in estrogens, these anagen hairs enter catagen and then telogen and are shed. Since there are more anagen hairs (and thus eventually telogen hairs) than usual, most postpartum women experience an increased hair loss, beginning 4 to 20 weeks after delivery. During this time, 30% to 35% of the hairs may enter telogen. Generally, complete regrowth occurs by 4 to 6 months in two thirds of women and by 15 months in the remainder, although the hair may be less abundant than before pregnancy.^13,93,96,113 Telogen effluvium is the term used to describe the rapid transition of hair follicles into the telogen stage following delivery, surgery, or severe emotional or physical stress.^93,96,118

Dermatoses associated with pregnancy

In addition to the normal physiologic skin changes associated with pregnancy, there are several integumentary disorders that are unique to pregnancy. Specific dermatoses seen only during pregnancy include pemphigoid gestationis, impetigo herpetiformis, atopic eruptions of pregnancy/prurigo of pregnancy, pruritic urticarial papules and plaques of pregnancy (PUPPP) or polymorphic eruption of pregnancy (PEP), and intrahepatic cholestasis of pregnancy.^61,93,96 Several of these disorders have been associated with increased fetal morbidity and mortality (see Table 14-2). Most of these disorders resolve spontaneously within a few weeks after delivery, but can recur with subsequent pregnancies.⁹³

The etiology of some of these disorders is unclear, although others have a hormonal or immunologic basis. For example, pemphigoid gestationis is an autoimmune disorder with production of anti–human leukocyte antigen (HLA) autoantibody against basal membranes that hold the epidermis and dermis together (see Table 14-2).^20,40,97 There has sometimes been confusion in classifying some of the rarer dermatoses, in that much of the literature regarding these disorders involves reports of small numbers of women, which may represent different variations of the same disorder. Treatment involves use of topical emollients, antipruritics, cold compresses, oatmeal baths (for relief of itching), and topical steroids. In women with moderate to severe eruptions, systemic steroids and antihistamines may be used. Cautions must be used in prescribing these and other dermatologic agents during pregnancy as some, such as retinoic acid, are teratogenic (see Chapter 7) and thus are contraindicated in pregnancy. There are limited data for most other agents on their use in pregnancy. Thus risk-benefit must be carefully evaluated.^17,93

Effects of pregnancy on pre existing skin disorders

The effects of pregnancy on pre existing skin disorders varies from no effect to marked improvement or worsening.^28,93,96,118 With disorders such as psoriasis, eczema, contact dermatitis, and acne vulgaris, this range of effects during pregnancy has been described within the same disease in different women.⁹³ Neurofibromas increase in size during pregnancy and new tumors may appear.⁹³ The effect of pregnancy on malignant melanoma is also variable.^22,93 No significant effect on survival in women with a diagnosis of localized melanoma (stage I or II) during pregnancy was found in an analysis of six case controlled studies.²⁷ Decreased survival or shorter disease-free survival for pregnant women with recurrent melanoma is reported in some studies.^22,27 Effects of pregnancy on other integumentary disorders are reviewed in the literature.^93,96

Epidermis

Development of the epidermis “is characterized by coordinated establishment of increasing numbers of cell layers concomitant with expansion of skin surface area and cellular (keratinocyte) differentiation.”¹⁹ The epidermis develops from undifferentiated ectoderm at 5 to 8 weeks.⁴⁹ It initially consists of a single layer of cuboidal cells that develop from the outer germinal stratum (surface ectoderm) and can be identified during the third week of gestation (Figure 14-2, A). By 30 to 40 days, two layers are seen: the inner basal layer and the outer periderm (see Figure 14-2, B).^35,66 The definitive epidermis develops from the basal layer.

The periderm is a transient embryonic layer that disappears in the second half of gestation.^19,66 The periderm serves as the protective barrier for the embryo and fetus until the end of the second trimester and forms part of the vernix caseosa.^49,66 Until the underlying layers develop, active transport occurs across the periderm between the amniotic fluid and the embryo; thus the periderm acts as a nutrient interface with amniotic fluid.^49,66 The outer border of the periderm rapidly proliferates between 11 and 14 weeks with formation of blebs and microvillus projections, which are coated with very fine filaments.^35,49 Development of the epidermis is under the influence of epidermal growth factor (EGF); matrix adhesion is thought to be mediated by actin-associated α6B4 integrin.^49,66 Cell surface receptors for EGF are found on both the basal layer and periderm.¹⁹ 

By 60 days, the epidermis has three layers (see Figure 14-2, D): the basal layer, an intermediate layer, and the superficial periderm. The intermediate layer becomes more complex by the end of the fourth month, when the epidermis has stratified. The epidermal strata are the stratum basale; the stratum spinosum, which is made up of large polyhedral cells connected by tonofibrils; the stratum granulosum, which contains small keratohyalin granules; and the stratum corneum, which is made up of dead cells packed full of keratin.¹⁰¹ Peridermal cells are replaced continuously until regression begins around 18 weeks. Shedding of peridermal cells begins in the scalp, plantar surfaces, and face, areas where keratinization first begins.¹⁶ The periderm gradually undergoes regression and apoptosis as the stratum corneum and vernix caseosa develop (see Figure 14-2, F ). The epidermis is keratinized in skin appendages at 11 to 15 weeks and in the interfollicular area at 22 to 24 weeks.¹⁹ As stem cells in the stratum germinativum proliferate, they develop down growths (epidermal ridges) that extend into the dermis.

Protoplasmic fibers and cellular bridges begin to form. These make up the stratum spinosum, eventually protecting the neonate from dehydration and reducing permeability to noxious substances. From 11 to 18 weeks, this layer has an abundance of glycogen to provide energy for growth.¹⁴ Glycogen reserves decrease around 18 weeks.⁴⁹ Keratogenic structures become evident, leading to regional differences in epidermal thickness. By 24 weeks, the skin has largely concluded its period of histogenesis and moves into a period of structural and functional maturation.¹⁹

Ridge patterns (future fingerprints) are genetically determined, although modified by the intrauterine fluid environment, and can be seen on the surface of the hands and soles of the feet.⁷⁶ These ridges are seen between 11 and 17 weeks in the hands and between 12 and 18 weeks in the feet.¹⁴ Chromosomal abnormalities such as Down syndrome modify the ridge pattern.

Keratins are produced in the stratum germinativum by 2 months and increase rapidly as the epidermis stratifies.²¹ Keratinocytes are arranged in columnar fashion adjacent to the dermis.¹⁹ Keratinocyte maturation is stimulated by several different growth factors, including EGF, transforming growth factors, insulin-like growth factors, and fibroblast growth factor.¹⁴ The first signs of keratinization are seen by 22 to 24 weeks.^16,19

As replacement keratinocytes mature, they rise and move through the stratum granulosum and acquire keratohyalin granules. As they continue to travel upward, the keratinocytes lose 85% of their water content and their organelles, which are replaced by keratin.^14,19,100 As the keratinocytes dehydrate and flatten, they adhere to each other to form a tough, resilient, and relatively impermeable membrane—the stratum corneum.⁹⁰ Transit time for a keratinocyte from the basal layer to the uppermost stratum takes approximately 28 days.⁷⁶ By 5 months, the periderm is completely shed, mixing with secretions from the sebaceous glands to form the vernix caseosa.¹⁰¹

The stratum corneum becomes thicker and more organized with increasing gestation, but it is not well defined until 23 to 24 weeks’ gestation.^16,50 The stratum corneum is more fully developed by 34 weeks, but still immature compared to older children and adults.^{9,32,82,106,114} Formation of the stratum corneum may be facilitated by vernix caseosa.⁵⁰ At 28 weeks, the stratum corneum consists of two to three cell layers, increasing to 15 or more layers (similar to the adult) after 32 weeks.²¹

During embryonic development, primitive Langerhans cells and melanocytes migrate into the epidermis.⁴⁹ Early in the second trimester, the epidermis is invaded by cells from the neural crest called melanoblasts or dendritic melanocytes because of their long processes much like dendrites. These cells come to lie adjacent to keratinocytes at the dermal-epidermal junction. By midgestation the melanoblasts have been converted to melanocytes, with formation of characteristic organelles or melanosomes and pigmentary granules, and gradually increase to adult numbers of cells.¹⁹ Melanocytes transport melanin along their dendrites, from which it is taken up by the basal cells.^14,49

Melanin production and transfer into surrounding keratinocytes occur by 4 to 5 months.²¹ Production of melanin remains low in newborns, who have less pigmentation than older children.⁶⁶ Melanin is responsible for skin color; variations are due to the amount and color of the melanin. Prenatal pigmentation is seen in the nipples, axillae, and genitalia and around the anus. Racial variations are seen not in the number of melanocytes, but rather in the size, shape and activity of these cells and in the number of pigmentary granules per cell.^14,49 Melanin protects deoxyribonucleic acid (DNA) from ultraviolet radiation damage. Langerhans cells migrate into the epidermis by week 8, begin to develop CD1 antigens by 60 days, and increase markedly during the third trimester. Although their function is not entirely understood, these cells have phagocytic activity and are involved in skin host defense mechanisms.^{14,19,21,49,66}

Alterations in development of the epidermis include palmoplantar keratodermas and the ichthyoses, including collodian babies (infants are covered by a shiny cellophane-like membrane) and infants with harlequin ichthyosis (characterized by thick, armor-like scales with fissures).^19,49,95 These disorders are characterized by a defective epidermal barrier with abnormalities in formation of the keratinocytes and a defective desquamation process. Many forms of these disorders have a genetic basis.^95,104

Dermis

Lying below the epidermis is the metabolically active dermis, which exerts a symbiotic and controlling influence on the epidermis. The dermis is composed of connective tissue, amorphous ground substance, free cells, nerves, blood vessels, and lymphatic vessels (see Figure 14-1). The connective tissue consists of collagen (90%) and elastic and reticular fibers embedded in proteoglycans (ground substance) consisting of a protein with glycosaminoglycans such as hyaluronic acid and dermatan sulfate (chondroitin sulfate B).⁴⁹ The fibroblasts are the most numerous cells, producing collagen and glycosaminoglycans. Mast cells, histiocytes, macrophages, lymphocytes, and neutrophils are all present in the dermis.

The dermis originates from the somatopleuric mesenchyme and the somites.^35,76 Initially the dermis is a loose aggregate of interconnected mesodermal cells that secrete a liquid intercellular matrix rich in glycogen and hyaluronic acid.²⁶ Hyaluronic acid promotes cell migration.¹⁹ With increasing age, dermatan becomes more prominent and dermal water content decreases.⁴⁹ The dermis in the eighth-week embryo has undifferentiated cells, appears myxedema-like (as seen in the umbilical cord), and contains no fibrils.³⁵ Eventually three layers form: superficial (adjacent to the epidermal basement membrane), papillary, and reticular.⁴⁹ The latter two layers are present by 4 months’ gestation. Between 8 and 12 weeks, the fibroblasts form, leading to differentiation of connective tissue. During this time, fibrillae appear between dermal cells, which continue to grow, developing a network of collagenous and elastic fibers.^76,101 The fetal dermis contains all of the different types of collagens seen in the adult, although type III collagen is found in greater proportions in the fetus.¹⁹ Elastin fibers are first seen around 20 weeks.⁴⁹

With further maturation the dermal layer moves from an organ abundant in water, sugars, and hyaluronidase to one enriched with collagen and sulfated polysaccharides.^19,35 Immature skin may be edematous, a sign of the excess water and sodium contained within it and the continued immaturity of this system. Development of this fibrous matrix continues after birth, becoming thicker and denser.⁷

Capillaries and lymph vessels form simultaneously with the skin. Initially the blood vessels are simple endothelium-lined structures from which new capillaries grow. Two vascular networks are seen in skin by 60 to 70 days, a superficial (subpapillary plexus of adult) and a deeper layer (adult reticular network).⁴⁹ The subcapillary vascular network is disorganized at birth and matures in the first year.^19,32,84

The dermal-epidermal junction is critical for skin integrity. The junction begins to develop in the first trimester as the basal lamina, hemidesmosomes, anchoring fibrils, and anchoring filaments develop.¹⁹ This junction is still immature in very low–birth weight infants and is not fully developed until about 6 months postbirth.²¹ During the third and fourth months, the corium proliferates to form papillary projections that extend into the epidermis. These irregular structures are called the dermal papillae. Some contain capillary loops that nourish the epidermis, and others have sensory nerve endings.

Disorders of the dermal-epidermal junction include various forms of epidermolysis bullosa (EB) that result in friction-induced cutaneous blistering, mucosal erosions, and wounds that do not heal.^19,49,95 EB is a group of inherited disorders classified according to the cleavage plane of the blisters. Major types are EB simplex, junctional EB, and dystrophic EB, each having multiple subtypes.^19,104

Fat appears in the deeper portion of the dermis, becoming the subcorium (subcutaneous tissue). Most fat is laid down during the last trimester of pregnancy, and serves as a heat insulator, shock absorber, and calorie storage area.

Adipose tissue

The hypodermis or subcutaneous tissue is a passive tissue that forms from mesenchymal cells. Subcutaneous tissue, which has a lobar structure surrounded by connective tissue, has its own blood supply. The first cells can be seen around 14 weeks; initially they are cytoplasmic and contain no fat droplets. With maturation, single or multiple fat granules develop.⁷⁶ Most adipose tissue is deposited in the third trimester.

Brown adipose tissue (BAT) differentiates from the hypodermal primitive cells between 26 and 30 weeks.^24,80 BAT accumulates in the neck; underneath the scapulae; and in the axillae, mediastinum, and perirenal tissues. BAT is critical for nonshivering thermogenesis, the major method of neonatal heat production (see Chapter 20).

Cutaneous innervation

In the third month of gestation, free nerve endings connect with the papillary ridges of the finger and toe pads. By term these nerve endings are exceptionally well developed in the perioral area around the lips and sucking pads. Specialized nerve endings are less well developed and continue their maturation throughout infancy.^14,76

The glands and muscles of the skin are innervated, and some are functional at birth; however, refinement of these responses continues after delivery. The arrector pili muscles, arterioles, and eccrine glands are innervated by the sympathetic nervous system to varying degrees. The sensory nerves may carry parasympathetic fibers to the vessel walls at birth; however, vasodilatory abilities are reduced until further innervation takes place. The axon reflex (stimulus in one branch of a nerve cell that is transmitted to an effector organ down another branch of the cell) is poorly developed even in term infants, so sweating is an unusual occurrence.

Epidermal appendages

The structures that result from invaginations of epidermal germinative into the dermis or from the epidermis itself are the epidermal appendages.^49,66 These include the eccrine sweat, sebaceous, and apocrine sweat glands; lanugo and hair; and the nails.

Vernix caseosa

“At birth the human infant is covered with a complex material [vernix caseosa] possessing endogenous anti-infective, antioxidative, moisturizing and cleansing capabilities.”⁴⁹ Vernix caseosa forms as a superficial fatty film after 17 to 20 weeks. It is made up of sebaceous gland secretions and desquamated cells of the periderm or stratum corneum cells and is rich in triglycerides, fatty acids, cholesterol, ceramides (lipid-signaling molecules, which have a role in water regulation and barrier function), and unsaponified fats.^48,100 Vernix is composed of 80.5% water, 10.3% lipids, and 9.1% proteins.⁵² After 36 weeks, the vernix thins and begins to disappear. Pulmonary surfactants in amniotic fluid mediate detachment of the vernix from the skin.⁴⁹ Both preterm and postterm infants have less vernix at birth than term infants. At term, the heaviest layers are found on the ears, shoulders, sacral region, and inguinal folds. The vernix has a tendency to accumulate at sites of dense lanugo growth.

The vernix is a biofilm that covers the fetus until birth and provides insulation of the skin during gestation, acts as an emollient to provide protection from amniotic fluid maceration, and minimizes friction at delivery. Vernix also prevents the loss of water and electrolytes from the skin to the amniotic fluid and contains antioxidants such as alpha-tocopheral.^94,108,115 Vernix has antimicrobial properties such as antifungal activity, opsonization capacity, inactivation of parasites, and protease inhibition that may protect the fetus from chorioamnionitis and contains substances such as lysozyme, lactoferrin, and defensins.^{94,108,112,115} Vernix also optimizes stratum corneum hydration and may play a role in fetal wound healing.^32,50 Fetal wound healing differs from that of the adult (Table 14-4) and often the fetus heals without scarring.²¹

Transitional events

During the birth process the skin is subjected to the mechanical stress of the delivery process, changes in blood circulation, and the bacterial flora of the maternal genital tract. The skin also serves as a diagnostic barometer for systemic phenomena, especially those related to transition. Mechanical stresses include pressure from contractions, which alters blood flow to various regions and results in edema formation. Maternal structures (bony pelvis and musculature) can exert pressure on the presenting part, causing further edema and hematoma formation. Exertion of enough pressure may result in abrasions or cellular ischemia and tissue sloughing, threatening the integrity of the cutaneous barrier. In addition to natural forces, epidermal breaks can also be caused by obstetric interventions. Use of vacuum extraction and forceps can result in bruising, edema, tissue ischemia, tissue sloughing, subcutaneous fat necrosis, and nerve damage.

In the first hours following delivery, the infant develops an intense red color, which is characteristic of the newborn. This may remain for several hours; however, exposure to the cooler environment usually leads to a bluish mottling, which dissipates quickly upon warming. Newborn skin is relatively transparent and smooth looking and is soft and velvety to touch. This appearance is due to the lack of large skin folds and skin texture. The epidermis and stratum corneum of infant skin are thinner than in adults with smaller corneocytes and keratinocytes, more densely packed glyphics (island-like structures within the stratum corneum), and a denser microrelief network.¹⁰⁷ Localized edema may be seen, especially over the pubis and the dorsa of the hands and the feet. This edema decreases within the first few days of life, after which the skin lies loosely over the entire body.

Compared to the term infant, the preterm infant’s skin is thinner, more transparent, and sometimes gelatinous, and has more lanugo. Transfer from the intrauterine amniotic fluid environment to the external air environment results in accelerated maturation of skin function in the preterm infant.

Newborns have less pigmentation than older children due to decreased melanin production (melanin acts as an ultraviolet light filter). The increased pigment in the ear tips, scrotum, linea alba, and areolae are due to maternal and placental hormones.⁴⁹ Because of their lack of pigmentation, young infants are more susceptible to damage from ultraviolet light.¹⁰⁷

Lanugo hair is shed after birth and replaced with vellus hair.¹⁸ The newborn has 10 times as many hair structures per unit of skin surface as adults.¹⁰⁶ At term hair follicles on the scalp are in different stages of the hair cycle depending on their location. Frontal and parietal hairs are moving to telogen; occipital are in anagen and move to catagen/telogen by 8 to 12 weeks post birth.¹³ At birth the synchrony of hair growth (anagen) and hair loss (telogen) is transiently altered so hair may become thick and coarse or be lost (temporary alopecia).⁴⁹ The postnatal hair cycle lasts 2 to 6 months; length of an individual hair is determined by the length of the anagen phase.³⁹ Hair on the scalp at birth reflects metabolic activity from week 28 on and therefore may be useful for assessment of prenatal toxin exposures.³⁹

Initially the skin is covered with the yellow-white vernix caseosa. This insulating layer is lost with the bathing that occurs in the nursery. Removal results in exposure of the stratum corneum to the much drier postnatal environment, with desquamation of the upper layers of the stratum corneum. After the first week, visible desquamation gives way to normal proliferation and flaking, signaling adaptation. This drying out of the skin is part of the natural maturational process. Any interference in this keratinization (e.g., use of lotions or creams) only delays the development of an effective barrier and prolongs the difficulties associated with an immature cutaneous surface, such as increased water loss and thermal instability. Common neonatal skin variations are summarized in Table 14-5.

Permeability

Skin permeability correlates with gestational age in the first few weeks of life. With decreasing gestational age, there is increasing permeability. Other factors increasing permeability are skin disease and injury.^16,100 Thus even though the newborn’s skin may appear structurally similar to adult skin, it is more permeable to substances applied to the skin (e.g., drugs, chemicals) and more vulnerable to water fluxes. For example, antiseptics such as povidone-iodine, hexachlorophene, and isopropyl alcohol applied to an infant’s skin are absorbed to a much greater extent than in adults.^16,100

Protective mechanisms

Although there are many immaturities in the cutaneous system, the accelerated maturation with birth (along with the pH of the infant’s skin) results in a protective barrier to the environment as long as the skin stays intact. Natural moisturizing factors (NMFs) in the stratum corneum act as skin lubricants and humectants to help the skin retain moisture.⁸² NMFs contain amino acids and their derivatives, organic acids, sugars, and ions. NMFs are lower in infants and altered with skin disorders and environmental factors.^82,107

An acid skin surface with a pH lower than 5.0 enhances bacteriologic, chemical, and mechanical resistance and is needed for barrier maturation, repair, integrity, cohesion, and growth.^32,67,114 The acid mantle is formed from the uppermost layer of the epidermis, sweat, superficial fat, sebum, metabolic by-products of keratinization, and external substances (e.g., amniotic fluid, microorganisms). The acid mantle can be disrupted by bathing and by the use of soaps and other topical agents.⁶⁷

Skin pH increases immediately after birth, from the fetal pH of 5.5 to 6, and then decreases over the first week to a pH of 5.0 to 5.5.^18,32,51 Skin pH reaches adult values by 3 to 4 weeks, although in some infants this may occur earlier or later.¹⁸ The mechanism for this change remains unclear but may be due to changes in the composition of the surface lipids and the activity of the eccrine glands.²⁹ Vernix-covered areas have a more acidic pH than other areas in term infants.³² The acid mantle forms more slowly in preterm infants, especially those weighing less than 1000 g.³³ Fox and colleagues reported that the skin pH in preterm infants (24 to 34 weeks’ gestational age) increased to a mean of 6 on the first day after birth and then fell to 5.4 by 1 week and to 5 by 1 month.³³

Immediately following delivery, microbial colonization also begins. These bacteria grow in a state of equilibrium, providing protection against invading pathogenic organisms. Surface biomarkers of epidermal innate immunity include structural proteins, albumin, both pro-inflammatory and anti-inflammatory cytokines and antigen processing cells.⁷⁹ Skin colonization after birth is discussed in Chapter 13.

Transepidermal water loss

Newborn skin has both greater water content and higher TEWL compared to adult skin.¹⁰⁶ TEWL decreases rapidly after birth in term infants but more slowly in preterm infants and is inversely related to gestational age. Due to the thinner stratum corneum, higher water content, and increased permeability of the skin in preterm infants, TEWL is greatly increased, especially in the first 2 to 3 weeks after birth, and remains higher than term infants for up to a month or more.^16,79 In infants less than 28 weeks’ gestational age, there is a 10- to 15-fold increase in TEWL.¹⁰⁵ TEWL in infants less than 30 weeks’ gestational age may exceed resting heat loss production.⁹⁹ As a result, fluid losses equivalent to 30% of their total body weight can occur. Even by 4 weeks post birth, TEWL in immature infants is still twice that of term infants.¹⁰⁵ TEWL in infants older than 34 weeks’ gestational age approaches that of term infants. Other factors that increase TEWL in very low–birth weight (VLBW) infants are their larger surface area in relation to body weight and increased blood supply that is closer to the skin surface.

These water losses can have a significant effect on fluid balance and the management and treatment of both preterm and term neonates (see Chapter 11). This may be compounded by environmental (e.g., radiant warmers) and therapeutic (e.g., phototherapy) modalities (see Chapters 18 and 20). An increase in caloric needs due to the excessive TEWL may account for up to 20% of energy expenditure of infants younger than 30 weeks’ gestational age. Excess TEWL increases the risk of dehydration, intraventricular hemorrhage, hyperosmolar hypernatremia, and thermal instability due to evaporative heat loss.

The degree of TEWL is dependent upon the hydration of the stratum corneum, the skin surface temperature, ambient relative humidity, and the neural capability for control of sweating. Factors that may contribute to these losses include basal metabolic rate, body temperature, activity, use of radiant warmers, and conventional phototherapy.^32,41,45 Term infants show little regional differences in TEWL, except for increased losses from the palms and soles secondary to sweating. TEWL in preterm infants is lowest on the forehead, cheeks, palms, and soles—areas where keratinization occurs early. These infants also do not sweat. TEWL is 50% higher in the abdomen of these infants and higher with warm (versus cool) skin, increased ambient temperature, radiant heating, or skin damage.¹⁶ Reduction of TEWL losses can be achieved through the use of thermal or plastic blankets or polyethylene skin wraps (see Chapter 20).¹⁰³

Bathing

There is little consensus about the frequency of bathing. The timing of the first bath is delayed until the infant’s temperature and condition are stabilized and is influenced by cultural and family preferences.⁹ Standard precautions should be used before and during the first bath to avoid heat loss. Investigators have reported that it takes an average of an hour for the infant to return to prebath temperature.⁷⁵ Others have found that the timing of the first bath did not significantly affect temperature.⁶ Term infants do not need daily bathing. Bathing, versus cloth or sponge washing, has been reported to be less stressful with less TEWL heat loss and better maintenance of stratum corneum hydration, with no differences in infection or bacterial colonization rates.^9,38

Frequent baths are not needed for VLBW infants. Less frequent bathing has not been associated with an increase in infection or other adverse effects.^34,92 Bathing can be a stressful experience for VLBW infants, with alterations in blood pH, hypoxemia, respiratory distress, increased oxygen consumption, crying, and behavioral stress cues.^{64,88,109,121} Bathing may also alter skin barrier properties.

Soaps are not generally needed in infants because of the low output of their sebaceous glands. Washing infants with alkaline soap destroys the acid mantle by neutralizing the pH. For the term infant, it takes 1 hour for the pH to return to baseline; for preterm infants it takes even longer. Due to concerns about increased skin permeability to other solutions, warm water only is recommended for preterm infants younger than 32 weeks’ gestation.⁷¹ 

Mild neutral pH soaps should only be used if needed for highly soiled areas. Because of concerns about human immunodeficiency virus and other pathogens, some institutions use a dilute antiseptic solution for the initial bath for term infants. The efficacy of this procedure is not clear.⁷¹ The solution should be thoroughly rinsed off the infant’s skin. Both antiseptic soaps and plain water decrease skin colonization of the infant, but only for about 4 hours, by which time the skin has re-colonized.⁷¹ No differences in skin bacterial colonization have been found after bathing with warm water versus mild soap and water.²⁵

To facilitate rapid epidermal maturation following delivery, manipulation (handling) should be minimized, especially with preterm infants. Routine use of lubricants should be avoided and dry skin care practices instituted. Dry skin care includes the use of cotton sponges and water to remove blood from the face and head as well as meconium from the perineum. The remainder of the skin should be left untouched unless grossly soiled.

Creams, emollients, and lotions are not recommended for routine use, although there is a lack of evidence to support this recommendation.¹¹⁷ Not only do these substances affect the acid mantle; they may also be absorbed percutaneously. The optimal skin condition for the neonate is dry and flaking, without cracks and fissures. If cracking does occur, a thin application of nonperfumed, preservative-free emollient can be used.

Umbilical cord care

Cord care practices are often embedded in institutional tradition. Practices range from no care to cleansing with triple dye (brilliant green, gentian violet, and proflavine hemisulfate), povidone-iodine, chlorhexidine, isopropyl alcohol, or antimicrobial ointments. There are few data on the most effective method.^55,71,105

Aseptic cord care decreases cord bacterial colonization but not necessarily the risk of infection, and delays cord separation.^4,30,55,78 The current trend in both developed and developing countries is toward dry cord care. The World Health Organization recommends dry cord care in developing countries with soap and water cleaning of visibly soiled cords.¹¹⁹ Developing countries have a high cord infection rate; however, few studies demonstrate that antiseptic cord care reduces this rate.⁷⁸ A Cochrane review by Zupan and colleagues of 21 studies (with 8959 subjects primarily from developed countries) found no difference in infection rates between dry cord care, placebo, and antiseptic use and also found that the use of antiseptics prolonged the time to cord separation.¹²² Similar findings have been reported in preterm infants.³⁰ Aseptic care has been associated with decreased maternal concerns about the cord.¹²² However, Zupan and colleagues also concluded that “there appears to be no good reason to stop use of antiseptics in situations where bacterial infection remains high.”¹²²

Use of adhesives

The epidermis is pulled off when adhesives are removed and can strip up to 70% to 90% of the stratum corneum in immature infants. In adults it takes 10 adhesive removals to disrupt the skin barrier versus only one removal of plastic tape, pectin barrier, or adhesive tape to do so in the preterm infant.⁶⁹ Lund and colleagues compared plastic tape, pectin barrier, and hydrophilic gel use in the first week after birth in infants born at 24 to 40 weeks’ gestation.⁶⁹ They found that pectin barriers and plastic tape had the highest colorimeter and vaporimeter scores, suggesting greater epidermal injury with these products than with hydrophilic gels. Skin barrier function returned to baseline by 24 hours. Although gel adhesives seemed preferable, they did not adhere as well to the skin as other products and thus required more frequent replacement.⁶⁹

Denuded areas are a potential source of infection; they are also uncomfortable and are areas of increased fluid loss. Use of transparent semipermeable occlusive dressings, water-activated gel electrodes, and minimal tape to secure monitoring equipment and intravenous lines may reduce injury. Transparent dressings are impermeable to water and bacteria while also providing protection to abrasions and skin irritation. These dressings can also be used to cover line insertion sites or incision sites from invasive procedures. The advantages of this type of dressing include providing an optimal moist environment for healing, allowing serous exudate to form over the wound, facilitating migration of new cells across the wound area, and preventing cellular dehydration.⁴⁶

The use of skin-bonding agents such as benzoin or Mastisol to promote adhesion should be avoided due to the already significant cohesion that occurs with tape.⁷¹ These substances increase tape-epidermis adhesion and potentiate epidermal stripping upon tape removal. In addition, benzoin is absorbed through the skin, allowing acids to be released into the bloodstream. Adhesive removal products should also be avoided in immature infants because of concerns about increased skin permeability.

Protection from infection

Protection from infection requires that the skin, as the first line of defense against infection, stay intact. Current monitoring modalities require manipulation and attachment of equipment to the infant’s epidermal layer. Careful handling can reduce shear damage and epidermal sloughing. Application of noninvasive monitoring equipment needs to be done such that pressure or constriction of blood flow does not occur. Crater formation may occur in preterm infants with very thin skin. The use of heated electrodes can lead to local hyperthermia and erythema. Increasing the frequency of site changes may also reduce skin damage. Extreme care should be used when removing the adherent ring or using equipment that allows for electrode site changes without moving the ring each time.

Transepidermal absorption

Percutaneous absorption of substances can occur through two pathways: via the cells of the stratum corneum (the transepidermal route) and via the hair follicle–sebaceous gland complex (the transappendageal route). The major pathway is most likely the transepidermal route, with diffusion of a substance through the stratum corneum and epidermis into the dermis and microcirculation. In addition, the subepidermal circulation is readily accessible, enhancing rapid absorption.

Neonates are at increased risk for toxic reactions from absorption of topically applied substances for the reasons listed in Table 14-6. Along with these differences, skin metabolism is different in neonates, so drugs applied topically may result in the release of metabolites different from those that would occur if the drugs were given by other routes. This increases the risk of toxicity. Occlusion of the skin (e.g., placement against the mattress) permits more complete absorption, with longer contact enhancing absorption of the substance. In preterm infants, percutaneous absorption occurs even more rapidly and completely as a result of their increased skin permeability.

The history of neonatal practice demonstrates the problems with the use of topical agents. For example, hexachlorophene was formerly used to prevent coagulase-positive staphylococci colonization; this practice was later found to increase the risk of central nervous system damage.⁵⁹ Eventually the Food and Drug Administration modified the allowable uses of hexachlorophene. Current practices also can lead to detrimental effects if not monitored carefully. Topical application of povidone-iodine yields significantly elevated levels of iodine in blood plasma if not removed completely from the skin after completion of invasive procedures (e.g., chest tube insertion, percutaneous line insertion).^1,91 Chlorhexidine at 0.5% has been reported to be superior to 10% povidone-iodine in decreasing colonization of peripheral catheters, possibly due to skin residues that prolong the half-life of the latter. Gentle cleansing of the skin with water removes these residues and reduces this risk. In addition to risks of epidermal stripping with use of benzoin, this substance contains many different acids, all of which can be absorbed, causing either immediate or delayed reactions.

Isopropyl alcohol is also absorbed through the skin. Alcohol use can result in dry skin, skin irritation, and skin burns. The concentration of the solution, duration of exposure, and condition of the exposed skin determine the effects of alcohol use. Tissue destruction occurs with the de-esterifying of the skin and the disruption of the cell structure. Exposure, pressure, and decreased perfusion can contribute to the development of burns from alcohol, complicating fluid management and providing portals for infection.⁴²

Extremely immature infants

The extremely low–birth weight (ELBW) infant has edematous, friable, gelatinous skin that is covered with abundant lanugo. These infants have decreased subcutaneous tissue and increased water content. This is compounded by a greater ratio of surface area to body weight. All of these characteristics create difficulties in fluid balance and temperature control due to the high TEWL.^99,100 TEWL increases the risk of dehydration, hypothermia, and fluid and electrolyte imbalances. Double-walled incubators, plastic or thermal blankets, and polyethylene skin wraps reduce TEWL and promote thermal stability (see Chapter 20). Polyethylene wraps and bags are recommended for use with preterm infants to reduce heat loss after birth and in the early days postbirth.^8,15,74 These wraps enhance radiant heat gain and reduce evaporative losses, insensible water loss (IWL), and TEWL by creating a microenvironment under the wrap.⁸ Unwrapping the infant disrupts this microenvironment, so it should be minimized.⁸

Humidity also decreases TEWL. Increasing the ambient humidity to 85% eliminates almost all evaporative losses, although use of very high humidity is often accompanied by concerns of infection from water borne organisms. Other products to prevent or manage barrier compromise in the preterm infant include gel-filled mattresses or pads, transparent semiocclusive dressings, and hydrocolloid dressings.^46,110

The preterm infant’s skin is exceedingly sensitive. Skin permeability and collagen instability increase with decreasing gestational age. Cohesion at the dermoepidermal junction is also markedly reduced, which can cause stratum corneum and epidermal stripping with handling and attachment of monitoring devices. Careful handling and policies about skin adhesive practices should be employed. The maintenance of skin integrity should be the goal. Denuded areas may benefit from transparent dressings, thereby reducing further damage, providing protection from microbial invasion, and reducing fluid losses.

The stratum corneum is extremely thin; therefore cutaneous permeability is greater, providing little protection against topical substances. Percutaneous absorption occurs more rapidly and completely, placing these infants at greater risk for toxic reactions.⁵⁹ The use of harsh de-esterifying substances (soaps and alcohol) should be kept to an absolute minimum. The acid mantle is easily disrupted, and cellular destruction is possible. Avoid use of 70% isopropyl alcohol with these infants, since alcohol is more irritating and less effective than povidone-iodine and chlorhexidine.⁶⁷ Use of any of these products should be judicious and followed by complete removal with sterile water.

Collagen instability and incomplete dermal structures result in increased cutaneous edema and decreased resiliency. This may result in skin necrosis due to edema pressure within the dermis. The use of gentle handling with little compression force or friction, careful regular turning, and gentle range-of-motion exercises may help to reduce this tendency.