INTRODUCTION

Preterm infants are uniquely vulnerable to iatrogenic skin injuries such as medical adhesive-related skin injury, skin necrosis from transepidermal absorption of topical compounds,1,2 and pressure injuries (PIs). Pressure injury development is prevalent in this population because of preterm infants' skin immaturity and limited mobility and the frequent use of medically necessary medical devices in the neonatal ICU (NICU) setting.3 Delmore et al3 noted that medical devices are the leading cause of PIs in young children and neonates, with devices accounting for 38.5% to 90% of PIs in this population. These vulnerabilities are heightened in preterm infants who are 25 weeks' gestation or younger. For infants with extremely low gestational ages of 22 to 25 weeks, inflammation from these skin injuries may result in permanent scarring.4

The National Pressure Injury Advisory Panel (NPIAP) staging system relies on visual identification of the depth of the skin and tissue injury, assessed at the bedside.5 Staging depends on the involvement of the epidermis, dermis, and subcutaneous or deeper structures. However, because the current staging system was developed for adults, it is unclear whether it is relevant for preterm infants.6

Accuracy in staging is important for PI evaluation and management. The scarring potential of the injury is especially important in the NICU because PIs may develop over cosmetically impactful areas such as the nose and dorsum of the hands. Further, stage 3, stage 4, and unstageable PIs are considered clinical adverse events with mandatory reporting in 28 states.7 These reportable events can result in financial losses for the hospital by way of lawsuits and lowered public hospital rankings.

The authors of this article recently published a histomorphometric investigation into the qualitative and quantitative features of skin development in preterm infants. Approval was obtained from the admitting hospital's institutional review board to conduct the research. The study compared the stratum corneum, epidermis, dermis, and adnexae in live-born preterm infants at 18 to 36 weeks' gestation against term neonates and older infants.9 The findings from this research, a review of the literature, and clinical experience in a large children's hospital indicate that PI staging in preterm infants presents unique challenges for two reasons. First, the structure of preterm skin is qualitatively and quantitatively different from that of term neonates and older infants. Second, mechanisms of injury in this population have distinctive features that complicate PI evaluation, particularly small areas of injury that are difficult to visualize at the bedside. In this article, the authors identify the inherent challenges in PI staging in very preterm neonates related to the structure of the preterm infant skin, location, mechanism, and the nature of common PIs, such as the nasal columella. The authors obtained consent for all photographs from the patients' parents/guardians.

SKIN DEVELOPMENT

Skin development begins during embryogenesis when the ectoderm gives rise to the epidermis. Keratinization begins around week 16, starting in the hair follicles and spreading outward, and the stratum corneum is immature but complete by week 24. In preterm infants, the immaturity of the stratum corneum results in rapid transepidermal water loss.10 The rete ridges and dermal papillae form at 30 to 34 weeks' gestation; infants younger than this are particularly prone to medical adhesive-related skin injury.11 Elastic fibers in the dermis appear at approximately 20 weeks. The hypodermis is distinguished from the deep dermis by week 15, and development of subcutaneous fat begins around 18 weeks.8

Water content in the skin varies widely, depending on both gestational age and time since birth. During fetal development, skin water content progressively decreases from a composition of 92% water at 13 weeks to 90% at 20 weeks and 83% water at term.11 Stratum corneum hydration decreases rapidly in the first day after birth and then increases over the first 3 weeks of life, according to a study of term infants.12 Increased edema, which is typically noted in low-gestational-age infants, causes less adhesion between the dermis and epidermis, making the skin susceptible to deformation by external pressure from medical devices.11

KEY CLINICAL FEATURES AND PATHOGENESIS OF PI

Pressure injuries can develop under any medical device or from lying on a standard surface without moving. For example, Figure 1 depicts a 5-day-old, 23-week-gestation neonate with a medical device-related deep-tissue PI caused by a near-infrared spectroscopy (NIRS) probe (used for continuous noninvasive monitoring of end-organ oxygenation and perfusion). This PI could easily be mistaken for ecchymosis because preterm infants bruise easily. Differential diagnosis includes discoloration from pressure, ecchymosis related to medical adhesive removal, routine handling in the NICU, or manipulation at the time of birth. The NIRS probe had been removed approximately 48 hours prior to this photograph. The direct care nurse reported that on removal, a pronounced outline of the probe was noted over the spine and that the affected area had already begun to return to normal skin coloration. Further, the NIRS probe had been placed inappropriately, crossing the spine, and the neonate had been alternating right- and left-side lying positions. Upon full skin examination, no areas of bruising were noted. This patient demonstrates the increased challenges in staging PIs in preterm neonates (Figure 1). The staging clinician must understand common preterm neonatal clinical problems, as well as the myriad devices used to support them. Information provided by the direct care nurse is imperative for an accurate diagnosis because the medical devices used and the patient's clinical status can both change quickly (Supplemental Figure 1, http://links.lww.com/NSW/A84).

Figure 1.

Respiratory support devices are the most common cause of PIs in neonates4 because they require a tight fit to the face to prevent air leaks. Continuous positive-airway pressure (CPAP) is a noninvasive device commonly used for respiratory support. The device requires either a mask or a nasal cannula resting on the columella and/or the nasal bridge. In a recent study of 235 preterm neonates,6 the incidence of PI to the columella ranged from 1.5% to 48%, depending on whether a protective foam barrier dressing was used. A neonate's columella can have a surface area as small as 0.3 cm in length by 0.2 cm in width, and the majority of PIs observed in this location measure approximately 0.1 x 0.1 cm. Accordingly, direct visual examination of this small area is very challenging; clinicians may have difficulty in assessing whether an injury is present and determining the depth of the skin injury. Figure 2 depicts a PI to the columella from CPAP. Tracheostomies can also cause PIs as seen in Supplemental Figure 2 (http://links.lww.com/NSW/A85).

Figure 2.

Staging neonatal PIs is challenging because of the size of the neonate and the area of skin damage assessed. Further, the skin layers are underdeveloped and thin. Clinically, preterm infant skin appears shiny and ruddy at baseline (Supplemental Figure 3, http://links.lww.com/NSW/A86). The staging clinician requires knowledge of skin development in fetuses and infants to understand the appearance of each tissue layer in these young patients.

LITERATURE REVIEW

The authors previously investigated the quantitative and qualitative properties of skin in preterm and term infants, comparing skin samples obtained at autopsy from live-born infants at 18 to 36 weeks' gestation with samples from term infants and older infants/children.9 Qualitatively, the epidermis and adnexal structures showed reproducible patterns of maturation. The youngest infants lacked rete ridges and a stratum corneum. Compact keratin was present beginning at 21 to 22 weeks. Basket-weave keratin first appeared around hair follicles beginning at 22 to 25 weeks and then became more generalized around 28 weeks. Taken together, these findings suggest that skin barrier function undergoes a shift at around 28 to 30 weeks' gestation. Indeed, reports2 of chemical skin injury in preterm infants appear to support this finding. For example, topical chlorhexidine antiseptic wash is known to cause serious skin injury in some very preterm infants, leading to scarring and possibly contributing to death in a few cases.2 In an investigation of 44 such cases, injury primarily occurred in infants who were 26 weeks' gestation or younger and was almost completely limited to infants at less than 32 weeks' gestation.2 This age range brackets the period during which rete ridges and mature stratum corneum develop.

Quantitatively, the authors' investigation identified an age-dependent increase in thickness of stratum corneum, epidermis, and dermis.9 However, even at term, neonatal skin is notably thin. Among infants born at term or preterm infants with a corrected gestational age of 40 weeks, the epidermis was often only three to four cell layers thick. The dermis was often no thicker than 1.0 to 1.2 mm.

CASE STUDIES AND DISCUSSION

Accurate staging of PI depends on identifying which skin layers are involved. A stage 1 PI is defined as "intact skin with a localized area of non-blanchable erythema of intact skin, which may appear differently in darkly pigmented skin."5 Neonates between 22 and 30 weeks' gestation generally have two to three cell layers in the epidermis. The skin of these preterm neonates appears ruddy and is gelatinous to the touch (Supplemental Figure 3, http://links.lww.com/NSW/A86). The baseline skin coloring makes it difficult to distinguish the patient's normal skin color from erythema caused by pressure. In addition, diagnosis of a stage 1 PI requires an intact stratum corneum. Although stratum corneum is present in all cases from approximately 21 weeks on, this layer is essentially translucent in infants at 22 to 28 weeks' gestation. It is possible that the ongoing epidermal transition from compact to basket-weave keratin may directly impact the appearance of preterm neonatal skin. The ruddy and gelatinous appearance of the skin in this age group creates challenges in determining whether the epidermis is indeed intact.

A stage 1 PI at the columella from a respiratory device presents as a singular dark red, nonblanchable linear discoloration. The skin discoloration does not take on the maroon or purple discoloration that would be present in a deep-tissue PI (Supplemental Figure 4, http://links.lww.com/NSW/A87). As such, it is assumed that the cell deformation affects only the epidermal layer. However, scarring may be present following the healing of the affected skin (Figure 2).

A stage 2 PI is "partial-thickness loss of skin with exposed dermis. The wound bed is viable, pink or red, moist and may present as an intact or ruptured serum-filled blister."5 In a preterm neonate, a stage 2 PI may be only a few cell layers deep, and it may be very difficult to distinguish between the wound base of a stage 2 PI and the skin of an extremely premature infant at baseline. Further, extremely preterm neonates are unlikely to blister, because their epidermis is too thin to support this pooling of fluid. Given the extreme thinness of the epidermis and dermis in the preterm infant, a stage 2 PI may progress to a stage 3 PI quickly.

A stage 3 PI is "full-thickness loss of skin, in which adipose is visible in the ulcer."5 Stage 3 PIs, extending into the subcutis, are commonly less than 1 mm deep in a preterm neonate (Figure 3). These visually small and shallow wounds result in scarring, similar to full-thickness injuries in older children and adults. A further challenge in distinguishing between stage 2 and stage 3 PIs arises from the nature of the subcutis in preterm infants. Although subcutaneous fat is at least focally present at as early as 21 weeks' gestation, it is very sparse in extremely low-birth-weight infants, with scattered clusters of adipocytes that do not present as the macroscopic fat globules seen in more mature infants.9 Visually, what is present in very young neonates instead is dark red tissue from which dermis and subcutaneous tissue cannot be distinguished.

Figure 3.

The second challenge in staging PIs in preterm infants is related to the common mechanisms of PI, particularly those related to nasal CPAP. The CPAP masks require a secure fit for adequate airway support: If the mask is not properly secured, it will "leak" air, resulting in insufficient respiratory pressure. To compensate for an air leak, staff commonly tighten the fit of the device. This increased tightness creates downward pressure on the nasal tip, causing the developing septal cartilage and the columella to collapse and fold, resulting in a singular red, nonblanchable injury to the columella (Figure 2). Per the NPIAP definition, this would be classified as a stage 1 PI and would be expected to heal without sequelae. However, the authors have observed preterm infants with an apparent stage 1 PI to the columella who then present with observable scarring weeks to months later (Supplemental Figure 5, http://links.lww.com/NSW/A88). It is important to recognize that in these patients the skin over the columella remained intact throughout the process. Scar tissue is expected to develop only when the injury extends to subcutaneous tissue, as in a stage 3 or 4 PI.13 However, in cases that were observed, the skin was never disrupted, and therefore adipose tissue or deep soft tissue structures were never apparent. The authors hypothesize that these profound variations in healing have a similar pathogenesis to anetoderma of prematurity, a skin scarring condition resulting from inflammation within the developing dermal layer of skin.14 The authors observed that a stage 2, 3, or 4 PI at the columella healed in a similar manner as a stage 1 PI with a singular, linear scar (Supplemental Figure 6, http://links.lww.com/NSW/A89).

A unique finding in another CPAP-related case was an observable white discoloration over the columella in an older-than-25-week gestation neonate (Figure 4). The white, indurated skin remained attached with gentle cleansing and did not blanch. The authors surmise that the white discoloration may be moist eschar. The skin layer did not slough but reverted to its normal appearance approximately 5 days after discovery and removal of the pressure from the CPAP mask. Although infants are closely followed up while in the NICU for PI healing, long-term sequelae are often not observed during the hospitalization. It is unknown whether permanent scarring arises months later, following discharge from the hospital.

Figure 4.

Recent research9,13 makes clear in granular detail how the skin structure of the premature neonate differs from that of term infants and older children and differs considerably from adults (Table). Observations from clinical practice highlight ways in which the current PI staging system does not meet the unique needs of this population. These authors propose further research in this area to develop a staging system that addresses the unique features of this population.

Table

CONCLUSIONS

Staging PIs in very preterm neonates is challenging because of the structure of preterm infant skin, as well as the nature, mechanisms, and locations of common PIs, such as the nasal columella. Difficulties in visualizing skin layers are likely amplified further in the comparatively thin skin of the face. Cosmetically and structurally impactful PIs are often very difficult to stage without the assistance of macrophotography, such as the photographs presented in this article. The current staging system may not adequately account for these differences. These authors propose further research to determine whether an alternate staging system may produce more accurate and actionable information in this very young and vulnerable population.

PRACTICE PEARLS

* Preterm infant skin is structurally different from that of term infants and older children, macroscopically and microscopically. Staging PIs in the neonatal population is challenging because of difficulty visualizing normal anatomic cues. A revised staging system may be appropriate.

* Body parts such as the nasal columella, a common site of PIs in neonates, are very small, making it difficult to visualize the injury.

* Skin scarring can result from PIs that do not present as an open wound.

* Accurate staging in neonates requires extensive experience.

REFERENCES