Introduction
Although we may not always think of it, our skin is an incredibly important, multifunctional organ. It has many different functions. It helps us maintain our body temperature, assists with the excretion of water and toxins, and most importantly, and it is a protective barrier against pathogens. But, as adults, our skin is mature and very different from that of a newborn infant. In newborns, especially preterm infants, there are developmental differences in the anatomy and physiology of their skin that place them at an increased risk for skin injury. Not only is the immaturity of an infant’s skin problematic, but infants in the NICU are predisposed to skin trauma due to the life-saving monitors and equipment necessary for their care. Furthermore, infants with compromised skin integrity are at an increased risk for infection, excess water loss, absorption of toxic substances, and additional sequelae.
For our 34th podcast episode, I reviewed the basic anatomy of our skin and all of its important functions. I point out how the skin of a term, and especially preterm infant differs from adults and why the structural variations place infants at an increased risk for skin trauma and additional complications. We discuss the potential short and long-term sequelae for infants including scarring and functional abnormalities and why this topic hits so close to home for me. The episode will be beneficial for parents of infants, especially preterm infants or those in the NICU to understand why their infant is at an increased risk for compromised skin integrity. NICU clinicians will also hear a great reminder of the anatomical and physiologic variations in infants that place them at an increased risk for skin injury.
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Episode 34
The Anatomy and Function of Skin
Skin’s Functions
Our skin is actually our largest human organ and has protective, regulatory, and sensory functions. An infant’s skin makes up at least 13% of their body weight whereas it is only about 3% of an adult’s body weight.
Our skin’s purpose is multifactorial with functions that include thermoregulation, it provides a barrier against toxins and pathogens, assists with water and electrolyte excretions, it provides fat storage and insulation, and tactile sensation.
With thermoregulation, it helps us to regulate our temperature by the use of vasoconstriction when we are cold and vasodilation when we are warm. Additionally, our adipose tissue stores fat just below the skin and acts as an insulator. Our skin also works as a barrier and protects us against excessive water loss, from physical and chemical injury, and against pathogens. It also helps us to excrete water, salts, and urea or nitrogenous waste. And it has a sensory function, so with temperature, pressure, and/or pain, our receptors send signals to the brain when stimulated. And it also assists with the synthesis of Vitamin D once it is exposed to sunlight.
The skin of term and preterm infants is more prone to skin trauma, excessive water loss, infections, increased permeability and absorption resulting in potential toxicity. Unfortunately, infants in the NICU are also in an environment that presents several additional challenges in maintaining skin integrity. Practices that are routine in the NICU are prone to disrupt the skin therefore, the protective barrier that our infants so desperately need! Once the barrier is disrupted or the skin integrity is compromised, it predisposes term and preterm infants to skin injury as well as an entry for pathogens to enter.
Anatomy of Skin
The two main layers of the skin are the epidermis and the dermis. The epidermis is the outermost layer that provides us with protection against injury. The epidermis is composed primarily of keratinocytes which mature to form the stratum corneum, the non-living layer of the epidermis, and then there is the basal layer. The stratum corneum is formed with lipids and proteins in a “brick and mortar” type of configuration. The epidermis is the first line of protection from pathogens and environmental toxins. The epidermis also helps to retain heat and fluid. The structural development of the epidermis has generally occurred by 24 weeks’ in utero, but the maturation of it is not complete until after birth and even then it is not fully complete until infants have spent 2 to 4 weeks exposed to the extrauterine environment.
The 2nd layer or the dermis is composed of collagen and elastin fibers, it is 2 to 4 mm thick, and it provides elasticity and connects the dermis to the epidermis. It also contains blood vessels, nerves, sweat glands, and hair follicles. Within the dermis is the subcutaneous layer that contains sebaceous glands and sweat glands. Sweat glands become mature in term infants during the first week of life, but in premature infants, the maturation does not occur until approximately 21 to 33 days of life or even longer. The subcutaneous layer is composed of fatty connective tissue that helps to provide heat insulation, protection, and calorie storage. Fat deposition occurs primarily in the third trimester of pregnancy, so as we know, preterm infants miss out on a large portion of the fat deposition putting them at an increased risk for cold stress.
Infants are also covered with vernix caseosa up until around 38 weeks’ gestation. It is the white, cheesy substance composed of water, lipids, proteins, sebum from sebaceous glands, broken-off lanugo (the fine hair on infants), and desquamous cells from the amnion or the innermost layer of the placenta. The vernix protects the fetus and provides a moisture barrier.
What are the differences in a preterm infant’s skin anatomy and physiology?
Premature infants have immature skin as well. Special consideration must be given for very low birthweight infants including the risk of chemical and adhesive-related skin breakdown, the potential for allergen sensitization, and also absorption of potential toxins.
Premature infants have significantly fewer layers of stratum corneum than term infants and adults. The stratum corneum begins to form at 21 weeks’ gestation. Infants born around 28 weeks are thought to have 2 to 3 layers of stratum corneum and up to 15 layers by 32 weeks, almost equivalent to an adult and term infant who have near 20 layers.
But, in extremely premature infants, those born less than 24 weeks’ gestation, they are just beginning to develop their stratum corneum. The overall epidermis or outer layer of the skin is 20 to 30% smaller in premature infants. Therefore, a premature infant’s skin is thinner and may appear transparent, translucent, and at times gelatinous. Due to the underdeveloped stratum corneum, their skin also often appears ruddy or red. Although, in preterm infants, the maturation of the stratum corneum is accelerated following their birth. By 10 to 14 days post delivery, they have improved barrier function and skin integrity.
The maturational process of a preterm infant’s skin
The infant’s transition from the intrauterine environment to the external environment is what has been thought to accelerate the maturation of their stratum corneum in the first 10 to 14 days. Although some believe it is a slower process in preterm infants born less than 27 weeks. With that being said, the maturation process may take as long as 8 weeks in infants born at 23 weeks placing them at an increased risk for many comorbidities including infection, excessive water losses, electrolyte imbalances, skin tears, plus more due to their lack of a protective barrier for an extended period of time.
Increased Risk of Infection
As I mentioned, the stratum corneum protects against toxins and pathogens including bacteria and viruses, leaving all premature infants, but especially those born extremely premature with minimal protection. Without the full effects of protection from the stratum corneum, premature infants are more vulnerable to infections transmitted through their skin. In the late neonatal period, about 50% of all deaths are related to sepsis or other severe infections and an incompetent or compromised skin barrier is considered a major predisposing factor for neonatal sepsis.
Structural Differences
Now, not only is the stratum corneum thinner in premature infants, but the structure of their dermis is also different which is what makes their skin more susceptible to skin injury and trauma. The collagen and elastin fibers in the dermis help provide mechanical strength, protection, and elasticity. In premature infants, there is less collagen creating less cohesion between the epidermis and dermis when compared to term infants. Collagen is composed of fibrils, anchoring filaments and in premature infants, they are smaller, there are fewer of the anchoring structures, and they are more widely spaced. But, luckily they do become stronger with advancing gestational age.
It is the diminished cohesion between the dermis and epidermis that places premature infants at an increased risk for injury with the removal of adhesives, especially if strong adhesives are used. If there is a stronger bond of the adhesive on their skin or attached to the epidermis than the bond between the epidermis and dermis, it can result in epidermal stripping or stripping of the skin. If care is not taken with the removal of adhesives from a premature infant’s skin, skin tears and abrasions can easily occur leaving the infant’s skin even more exposed and unprotected from pathogens, and therefore, increasing their risk for infection.
Skin Trauma
Medical adhesive-related skin injuries or MARSIs include contact dermatitis, moisture maceration, and also mechanical skin injuries that occur when the epidermis is separated from the dermis. Mechanical injuries include tension blisters, skin tears, and denudement caused by epidermal stripping. Epidermal stripping is the most common type of MARSI in the NICU.
Skin trauma can lead to serious consequences for infants in the NICU including problems with thermoregulation, fluid and electrolyte balance, diversion of calories for tissue repair, discomfort, potential toxicity from absorbed substances, and increased risk for infection. Skin injuries and trauma can also cause permanent scarring and functional abnormalities.
Variations in skin pH
The pH of our skin also plays a role in the protection against pathogens or microorganisms. With pH, the range is from 0 to 14, the more acidic the solution, the smaller the number and the more alkaline, or basic, the larger the number. In adults and children, the acidic pH of the skin, which is usually less than 5, helps to prevent the growth of pathogenic microorganisms. Term newborns are born with a more alkaline or basic skin surface around 6.34, which naturally declines to an average of 4.95 around 4 days of life. With premature infants, their pH is typically above 6 and it gradually declines down to 5, but it often takes weeks or even up to a month to do so which also places them at an increased risk for infection throughout this time frame. The slightly acidic pH of the skin also plays an important role in the maturation and maintenance of the stratum corneum.
Protective components of vernix
Vernix, or the protective coating on the skin in infants begins to develop around 19 to 20 weeks and continues to thicken until 34 weeks, gradually disappearing around 38 weeks. The retention of the vernix on an infant’s skin contributes to a higher skin hydration, a lower skin pH, and relates to reduced heat loss after birth. For preterm infants, the lack of vernix coupled with their immature epidermal layers, and minimal development of fat deposition places them at an increased risk for cold stress as well.
Transepidermal Water Loss
Preterm newborns are also at an increased risk for transepidermal losses or excess water losses mostly due to evaporation. At birth, they exit a warm and moist environment and are thrust into a cold and dry one which contributes to their water and heat loss due to evaporation. In infants, but especially premature infants, they have an increased body surface to body mass ratio which makes them more prone to cold stress and water losses especially in the first couple of weeks. Additionally, once an adhesive is removed from an infant’s skin, transepidermal water loss is higher at the site of the adhesive application compared to other sites due to the damaged skin barrier.
The stratum corneum, which is much thinner in premature infants, is responsible for controlling evaporative heat loss and water loss. With time, the stratum corneum matures, and becomes less permeable for water. But even at 4 weeks of age, a premature infant may still experience double the water loss than that of a term infant placing them at risk for electrolyte imbalances including elevated sodium levels and dehydration. Extremely premature infants delivered around 23 to 25 weeks have significant water losses, as much as 10 times higher than term infants.
Sensory Function
Although many aspects of the term and preterm infant’s skin are immature, the sensory nerve endings are not. By 20 weeks, a fetus can respond behaviorally, physiologically, and hormonally to touch and pain. The sensory nerve endings are well-developed in the newborn regardless of maturity, meaning they can feel positive nurturing touch as well as painful touch and procedures.
Why infants in the NICU are at an increased risk for skin injury
Risk factors for skin injury
Not only does the physical immaturity of a premature infant’s skin place them at risk, but these infants are also being cared for in the Neonatal Intensive Care Unit. The combination of immaturity coupled with the need for intensive care monitoring and procedures place the premature infant at an increased risk for skin trauma and a loss of skin integrity. Routine care practices including bathing, application of the monitoring devices, IV insertion, removal of adhesives to secure devices, and exposure to potentially toxic substances can all disrupt the infant’s skin integrity or barrier predisposing both term and preterm infants to skin injury.
Risk factors for skin injuries in neonates include low birthweight, younger gestational age, extended length of the stay, the presence of a central venous line, mechanical ventilation, and CPAP. These infants are at risk for developing pressure ulcers due to their dependence on life-sustaining medical devices. Pressure ulcers are commonly found on the head, nose, chin, and neck.
The use of disinfectants in the NICU
Additionally, infants in the NICU are exposed to many skin disinfectants that may cause skin injury and/or be inadvertently absorbed. Neonatal skin in general has distinctive absorption characteristics with high permeability to topical agents. With the stratum corneum having decreased layers, and less protection, toxicity may occur from substances that are applied to the skin. Topically applied agents that are absorbed can cause systemic toxic effects including neurotoxicity, structural damage, and even death. There is a decrease in skin permeability with age and near term and term infants are not as prone to experiencing drug absorption through the skin.
Skin disinfectants must be used prior to invasive procedures in the NICU from starting an IV, to a lab draw, insertion of a PICC line, or placement of an umbilical line or chest tube. And although the use of disinfectants is crucial in infection prevention, with some of the products used, like chlorhexidine gluconate, there have not been enough studies in neonates to determine its use over other disinfectants like povidone-iodine in the prevention of bloodstream infections. Chlorhexidine is known to be superior for skin disinfecting in children and adults, but there is limited safety data for it with infants. Therefore, the CDC guidelines have said that there is insufficient evidence to make proper recommendations on the safety and efficacy of chlorhexidine in infants younger than 2 months of age. But, it is still commonly used on infants in the hospital.
Inadvertent absorption of skin disinfectants
There is also concern for toxicity from absorption of disinfectants including povidone-iodine which has shown to alter thyroid function in premature infants. With isopropyl alcohol, repeated use has been shown to induce systemic intoxication by skin absorption and may cause severe hemorrhagic skin necrosis in premature infants. Additionally, studies have shown that when chlorhexidine has been used, it is absorbed with serum peak levels at 2 to 3 days after exposure, but there were not any systemic side effects noted.
Chemical Burns
Unfortunately there have also been numerous cases of reports documenting chemical burns in premature infants from disinfectants containing chlorhexidine as well as isopropyl alcohol and povidone iodine in extremely low-birthweight infants. Typically, most of the burns occurred in infants less than 26 weeks’ gestation or those who weigh less than 1000 grams. Some of the cases have resulted in long-term sequelae in some infants including scarring, discoloration, and keloid formation. If the basal layer which generates the epidermis is disrupted and/or damaged, healing will take place by scar formation.
William’s skin injuries and scarring
Sadly, I can personally speak to the significant scarring that can occur from the monitoring devices as well as with burns from topical agents. My son, William, who was a 23 weeker, has several scattered scars throughout his body from the pulse ox probe and even the temperature probe. But, his most significant scar that is still incredibly prominent is the one on his abdomen just adjacent to his umbilicus. He did have a UVC and UAC placed shortly after his delivery at the outlying hospital. Because I wasn’t present, I’m unsure what disinfectant they used to cleanse his umbilical cord prior to inserting the lines, or if they wiped it with saline as recommended, but by his 5th day of life, he had significant breakdown near his umbilicus. I can only assume it is from the disinfectant.
He also had significant breakdown under both of his axillas bilaterally. Honestly, I’m unsure why he had such a significant amount of breakdown under both of his axillas that also went all the way down to his elbow area. It could have been due to the PICC line attempts, but either way, it also developed around his 5th day of life.
We had a nurse on nights that made it her mission to find the right treatment combination to improve his breakdown. For a while he looked like a little mummy with his tiny arms wrapped up in gauze as we tried to get the area to heal. But despite her unending passion and all of her attempts plus many others, nothing seemed to help his significant skin breakdown.
I was so worried since it was not improving and knew that it was an open source for pathogen entry. But also, as his mother, trying to contain and comfort him during his care time was so difficult to witness. He was intubated, so he couldn’t cry, but his sweet face that was all scrunched up showed us how painful it was for him as he winced and tried to cry around his endotracheal tube. Eventually, I requested a wound consult because absolutely nothing was working to heal the area. They assessed him and found a product that worked really well and slowly with time, all of the areas healed.
But, William still to this day 8 years later has a significant scar on his abdomen and scattered scars up and down his arms. We talk with him about his scars from his skin breakdown during his NICU journey and now it’s all part of his story. He went through so much more and we are beyond thankful that he has minimal sequelae and complications after being born so prematurely. Because, they are just scars, and they do not seem to bother him at this point in his life. And although it was not the most severe or significant part of his NICU journey, it was very difficult and scary to go through at the time.
Diaper Dermatitis
Unfortunately, the incidence for diaper dermatitis or diaper rash is also common in NICUs with reports of it occurring in 21 to 25% of NICU patients. Diaper dermatitis describes inflamed skin that involves the lower abdomen, buttocks, and perianal and perineal areas. Some signs of diaper dermatitis include erythema or redness, excoriations, denuded skin, and bleeding. With a diaper rash, the area becomes broken down leaving an exposed area as a potential entrance for skin and systemic infection.
The causes are multifactorial but the condition of the skin has a direct role on the progression of the skin injury. The underdeveloped stratum corneum as well as moisture from the urine and digestive enzymes from the alkalinized stool can also irritate the vulnerable, thin layer of skin. Skin that is moist and macerated becomes more permeable and susceptible to injury due to the wetness increasing friction. Moisture-laden skin is also more likely to contain microorganisms than dry skin. Additionally, if you recall the section on the pH of the skin, an increased pH, as with diapered and soiled skin, increases the risk of injury and penetration of organisms.
All of that in combination with attempts to remove the irritants using preservative-containing wipes sets the infant up for skin breakdown. Additionally, NICU infants may also have received antibiotics and additional fortification in their milk, which predisposes them to altered gut flora. Infants who were also exposed in utero to illicit drug use by the mother are at risk due to frequent stools and an increased risk of irritation.
Closing
I hope this episode helped to break down not only the anatomy and functionality of our skin, but also how it is structurally different in term and preterm infants. I realize that it is not the most interesting topic, but for me as a parent of a premature infant, especially one who had significant skin breakdown, I think it’s important for parents and clinicians to understand or be reminded of the fragility of an infant’s skin, especially those born extremely premature.
As you just heard, there are several developmental differences in the anatomy and physiology for term and preterm infants that place them at an increased risk for skin injury, especially if they are in the NICU. But, you are probably wondering either as a parent or clinician, what are the best ways to prevent skin breakdown? Well, we will cover that next time! And yes, prevention should be the primary focus when it comes to maintaining an infant’s skin integrity. We will also discuss basic skin care recommendations and treatments for both term and preterm infants.
References
Anic Jurica, S., Colic, A., Gveric-Ahmetasevic, S., Loncarevic, D., Filipovic-Grcic, B., Stipanovic-Kastelic, J., Resic, A. (2016). Skin of the Very Premature Newborn – Physiology and Care. Paediatrica Croatica, 60, 21-26.
Eichenwald, E., Hansen, A., Martin, C., & Stark, A. (2017). Cloherty and Stark’s Manual of Neonatal Care, 8th edition. Wolters Kluwer.
Gardner, S., Carter, B., Enzman-Hines, M., & Hernandez, J. (2011). Merenstein & Gardner’s Handbook of Neonatal Intensive Care. Mosby Elsevier.
Gomella, T., Eyal, F., & Bany-Mohammed, F. (2020). Gomella’s Neonatology: Management, Procedures, On-Call Problems, Diseases, and Drugs, 8th Edition. McGraw-Hill.
Johnson, D. (2016). Extremely Preterm Infant Skin Care: A Transformation of Practice Aimed to Prevent Harm. Advances in Neonatal Care, 16(5), S26-S32.
Oranges, T., Dini, V., & Romanelli, M. (2015). Skin Physiology of the Neonate and Infant: Clinical Implications. Advances in Wound Care, 4(10), 587-595.
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