Skin Care in Premature Newborns

The skin functions as the first barrier of defense against pathogens, maintaining homeostasis by minimizing unnecessary fluid losses and electrolyte imbalances.

To date, guidelines for neonatal skin care in healthy full-term neonates have been published,1 but there are currently no guidelines for preterm neonates. In premature newborns (those born at gestational age <37 weeks), the skin barrier is significantly compromised.

Skin quality varies dramatically depending on gestational age at birth; The skin at 23 weeks or less may be translucent, gelatinous, and extremely fragile, while the skin of newborns at a later gestational age may be more resistant.

An intervention that is appropriate for a neonate born at 35 weeks gestational age may be insufficient for one born at 30 weeks. Comorbid conditions, such as congenital infections and genetic diseases, can also affect the integrity of the skin and determine what therapeutic measures are appropriate.

Therefore, skin care for any particular neonate should be personalized and directed to the baby’s needs.

There are a number of unifying characteristics that distinguish premature skin from term skin.

• Premature skin is thinner, making premature neonates more susceptible to skin infections and caustic agents.
   
• The vernix caseosa is usually thicker in premature neonates (although thinner in extremely premature neonates).2

Accordingly, there are a number of general principles that can guide skin care for most premature newborns.

In this study, a review of the current available literature on preterm skin and skin care was conducted and the existing literature on skin development and assessment in preterm infants is summarized (Table 1).

Interventions to improve skin barrier function in preterm infants of all gestational ages were also investigated, especially baths, emollients, massage, occlusive skin wraps, semipermeable dressings and transparent adhesive dressings, as well as optimal cord care. and intra-arterial or intra-arterial catheter care.

A literature search was conducted for all articles published in PubMed until March 12, 2018, using the following search terms: skin, skin care, emollients, infants, newborns, neonates, newborns, premature, premature, emollients, soap, cleanser, detergent, cleaning, bath, wash, oil, shampoo, moisture, cream, lotion, ointment, emollient, cleaning cloth, towel, sponge, wipe and semi-permeable.

Of the articles obtained through this search, only articles written in English and related to human infants were considered. No animal or basic science research was included. The assigned articles have an evidence quality grade of I, II or III depending on the design and were included in study 1.

Articles assigned an evidence quality grade of I were well-conducted randomized controlled trials (RCTs) or meta-analyses with samples large enough to minimize the risk of false-positive or false-negative results.

Articles assigned a level of evidence of II were well-designed RCTs with smaller sample sizes.

Finally, articles assigned a grade of evidence rating of III were case series, case-control, cross-sectional, or cohort studies: observational studies without randomization. A total of 68 articles were used to synthesize this review.

> Skin development

The stratum corneum begins to develop at 15 weeks gestational age (GA), but this process is not complete until approximately 34 weeks GA. Newborns born before 30 weeks have a thin epidermis with fewer cell layers and impaired epidermal barrier function.3

In contrast, full-term babies have a thicker stratum corneum than adults, since the epidermis is not shed properly in the womb as it is in postnatal life.

Most premature babies develop skin that resembles that of a full-term baby around 2 weeks of age, although this process can last up to 4 weeks or even longer in very low birth weight babies, who usually be very or extremely premature.4

Gender and prenatal and neonatal steroid administration do not appear to affect epidermal development.

Interestingly, the skin’s acid mantle appears to vary little between full-term and premature neonates. In both cases, a neutral to slightly acidic skin pH is observed at birth. The pH decreases considerably in the first week of life and continues to decrease gradually over the next 3 weeks.

Skin pH and hydration, and erythema, improve when vernix caseosa, a material containing proteins and lipids synthesized in utero by fetal sebaceous glands, is preserved.

Synthesis of vernix caseosa is thought to begin around 28 weeks gestational age, as it is usually absent in neonates born at less than this gestational age, and in neonates weighing <1000 g.5

In a sample of 430 infants, those born at 33-37 weeks GA were found to have 70% body area covered with vernix at birth, compared to 40% body area covered in full-term infants (37.1-37 weeks GA). 40.9 weeks) and 15% in those born after term (> 41 weeks).6

> Skin barrier and heat dissipation in premature neonates.

Two means of assessing skin barrier function in preterm infants are transepidermal water loss (TEWL) and transcutaneous drug absorption. TEWL can be measured using two main categories of devices: open or closed chamber devices.

Although a detailed discussion of these devices is beyond the scope of this review, in any case, the camera measures the amount of moisture that passes from inside the body through the skin.

TEWL is measured in grams per square meter per hour, and a higher value generally reflects a less competent skin barrier. High and unresponsive TEWL occurs in very preterm and extremely preterm neonates. Infants with a birth weight less than 1250 g are particularly susceptible, and there is an inverse exponential relationship between gestational age and TEWL. A newborn at 25 weeks is likely to have TEWL 15 times more than a full-term newborn.7

In general, most preterm infants have a higher TEWL at birth and require longer periods of time for TEWL to normalize.

Newborns between 34 and 41 weeks GA experience a high TEWL during the first four hours after birth, which then quickly normalizes.

In contrast, newborns between 30 and 33 weeks GA take longer (approximately 1 week) to normalize their TEWL. Newborns less than 30 weeks GA show high TEWL even 2 weeks after birth.8

Transepidermal water loss occurs mainly by diffusion and evaporation. The rate of diffusion depends largely on the function of the stratum corneum, while the rate of evaporation varies depending on the humidity of the neonate’s environment.

Relative humidity is the relationship between the actual water vapor content in the air and the water vapor capacity of the air. The capacity of water vapor varies with temperature: hotter air can carry more water. Therefore, if a warmer room has the same relative humidity as a colder room, the warmer room will have a higher water vapor pressure.

Premature neonates cared for in humidified incubators , such as humidified hybrid incubators, have lower fluid requirements, better electrolyte balance, greater urine output, and faster growth rates9 compared to preterm neonates cared for in radiant warmers.

The relative humidity that should be used in different groups of neonates is not yet known. A study including 22 extremely preterm neonates (23-27 weeks GA) found that the 11 neonates assigned to 75% relative humidity exhibited delayed skin maturation (including a slower decline in TEWL) than those assigned to 50 % relative humidity.10

Clearly, there are contrasting forces at play, as increased humidity reduces fluid and electrolyte loss, as well as the need for intravenous fluids, but unfortunately delays skin maturation.

Premature epidermis is thin and highly permeable to drugs.

Multiple studies have demonstrated greater transcutaneous absorption of drugs in very premature and extremely premature neonates. For these newborns, transcutaneous drug absorption steadily decreases after birth.11

Caring for premature infants often involves the placement of skin monitors and adhesive tapes, and these devices can further disrupt the skin barrier and increase transcutaneous absorption of medications.

More preterm neonates exhibit little transcutaneous drug absorption after 2 weeks of life, as their skin has largely matured to resemble their full-term counterparts.

Skin thermoregulation is a particular challenge for premature infants. Full-term infants, like adults, dissipate heat in part through vasodilation of cutaneous vessels and perspiration. The ability of preterm infants to alter cutaneous blood flow in response to external thermal stimulation is greatly impaired.

Similarly, babies born before 36 weeks of gestation cannot sweat at birth, although, interestingly, they develop the ability to sweat 13 days after birth.12

> Interventions to increase the premature skin barrier

• Bathrooms

Eight studies have examined the problems surrounding bathing of premature infants and primarily address three topics: (a) frequency of bathing (every other day vs. every four days); (b) bathing method (tub bath versus sponge bath); and (c) the effect of various bathing modalities on the skin microbiome.

In premature babies, bathing every 4 days does not appear to have a negative impact on skin flora compared to bathing every other day.

Colonization by pathogenic bacterial strains , the size of the total bacterial population, and the incidence of skin infection do not vary between preterm infants bathed every 2 days and preterm infants bathed every 4 days in all studies, which has been shown most recently in a randomized intervention study in 2018. 13 Interestingly, the 2018 study also demonstrates that bathing every 4 days reduces the risk of temperature instability in preterm newborns.

Bathtub bathing is less likely than sponge bathing to cause body temperature variability in preterm infants. In sponge bathing, wet skin is more exposed to ambient air, which is usually colder than body temperature. Physiological and behavioral parameters in preterm infants are often disrupted during sponge bathing.14 In contrast, tub bathing produces less variability in body temperature and warmer temperatures after bathing.

The use of different emollient cleansers or "baby wipes" has also been studied in premature neonates. Some studies have shown desirable results, although some wipes may cause allergic contact dermatitis.

In one study, commercial baby wipes impregnated with glycerin and citric acid produced a significantly lower skin pH than cloth wipes moistened with water. In premature newborns, this lower skin pH may facilitate acid mantle development, infection control, and barrier repair.16

• Emollients and massages.

Numerous studies have examined the effectiveness of emollient massage (particularly oil) in improving skin condition and preventing nosocomial infections. In developing countries where oil massage for babies and children is traditional, there appears to be a clear benefit from massage with some oils.17

In developed countries, research has emphasized petrolatum-based creams and ointments, the benefits of which are tempered by the increased risk of serious infections with some products.18-20

Sunflower seed oil has been shown to reduce the incidence of nosocomial infections and improve skin condition in studies conducted in Bangladesh and other developing countries.17 Aquaphor® Healing Ointment (Beiersdorf AG, Hamburg, Germany) appears to have a similar beneficial effect when used in developing countries, although they may be less available in rural settings and have been shown not to be as effective as sunflower seed oil in reducing nosocomial infections in two studies from Bangladesh.21

Interestingly, a more recent study from Germany shows that massage with sunflower seed oil can impair skin barrier maturation and increase TEWL.22 Topical application of coconut oil has also shown a benefit in maintaining skin integrity and reducing the risk of bloodstream infections in a Pakistani study.23

However, not all oils should be used to maintain the integrity of the skin barrier. In Nepal and parts of northeastern India, massage with mustard oil is traditionally believed to keep neonates warm, but a 2017 interventional study showed that premature newborns who receive vigorous massage with mustard seed oil have lower skin barrier integrity and greater irritation, as well as blockage of the ducts, compared to neonates who did not receive this intervention.

In developed countries, seven studies and one meta-analysis have yielded mixed results. Several studies demonstrate that neonates treated with emollients consistently show better skin conditions; However, some studies demonstrate an increased risk of serious infections after application of petrolatum-based ointments and other emollients.16-18

In a small cohort of younger infants, ≥ 27 weeks, infants with Aquaphor® applied to the skin require less fluid, show improvement in urine output and electrolyte balance.25

Another study comparing olive oil cream (70% lanolin, 30% olive oil), Bepanthen® antiseptic cream (Bayer AG, Leverkusen, Germany) and no emollient also shows a lower incidence of dermatitis and better skin conditions in neonates treated with olive oil cream.26

A more recent study from 2018 also recapitulates the favorable effect of coconut oil on the neonatal skin condition score (NSPN) in premature babies.27

Several other studies also demonstrate significantly improved skin conditions and less dermatitis, with surprisingly little or no change in fungal and bacterial colonization.28,29 In contrast, multiple studies show an increased risk of sepsis with application of Vaseline ointment to premature neonates.

In one study, following the adoption of a new skin care protocol involving the regular application of Vaseline-based ointments for extremely low birth weight (ELBW) neonates, researchers in Texas began to observed a substantial increase in the incidence of systemic candidiasis in these neonates from 0.5 per 1000 persons per day to 1.7 per 1000 persons per day, a more than three-fold increase.18

A similar randomized controlled trial in Riyadh, Saudi Arabia, using daily application of Vaseline ointment in 74 neonates born with GA <32 weeks (a heterogeneous group including both very low birth weight and extremely low birth weight infants), also shows more episodes of culture-proven nosocomial infection (19 episodes vs. 16 episodes, an increase of 30%).19

Largest study studying the effect of topical petrolatum-based ointment in extremely low birth weight infants, involving more than 100 neonatal intensive care units (NICUs) of the Vermont Oxford Network (1,191 ELBW neonates ≤ 27 weeks of GA in a randomized clinical trial), shows a statistically significant increase in coagulase-negative staphylococcus (CoNS) infection with the use of Vaseline, but does not show significant differences in death or nosocomial bacterial sepsis.20

This increase in CoNS infection in the Vermont Oxford Network study appears to be the driving force in a Cochrane Database meta-analysis, which concludes that topical emollients are associated with an increase in CoNS infection in neonates. premature.30

In conclusion, the benefit of topical emollient application in premature neonates has not been demonstrated as consistently in studies conducted in developed countries as it appears to have been demonstrated in developing countries.

Furthermore, data on topical emollient use and infection are primarily limited to extremely preterm neonates. At this time, it is unclear whether preterm infants who are older (>27 weeks) are at similar risk.

The risk of Candida infection due to the use of topical emollients, although widely known in the pediatric community, is based on a single case-control study conducted after a single hospital implemented a new protocol for the use of Vaseline in newborns. born with extremely low birth weight.

Similarly, the increased risk of CoNS infection with the use of topical emollients has only been observed in extremely preterm neonates. Despite the paucity of evidence, institutional guidelines in Western countries often prohibit or discourage the use of topical petrolatum-based emollients as they may promote a milieu similar to occlusive dressings18, despite the known benefits of these. emollients on skin condition and electrolyte balance.16,17

• Waterproof and semi-permeable plastic wraps.

Two broad categories of plastic wrap are sometimes used for the care of premature newborns, for different purposes. Impervious polyethylene wraps have been studied for their usefulness in reducing heat loss during transport from the birthplace to the NICU.

These waterproof wraps are designed to be used briefly, usually within minutes. Semipermeable envelopes and biopolymers have been studied in longer time increments for their usefulness in preventing TEWL, and maintaining fluid and electrolyte balance. Studies examining these wraps usually involve neonates receiving care with radiant warmers rather than humidified incubators.

Maintaining core temperature in preterm infants during the minutes after birth remains a challenge. Six studies, involving between 55 and 110 neonates each, have examined the effect of short-term placement in waterproof wraps or garments on temperature stability.

Waterproof wraps have consistently been shown to reduce the incidence of hypothermia, while maintaining a warmer ambient room temperature (26°C, 79°F) has not. Premature babies often require considerable handling in the minutes after birth, including drying and resuscitation.

Plastic wraps or bags may help neonates retain their body heat, and greater skin coverage with plastic devices appears to be associated with a better outcome.

In infants <28 weeks GA, the use of polyethylene occlusive wraps prevents heat loss after delivery and results in higher NICU admission temperatures31, 32 and a lower incidence of hypothermia.33

The 2017 NeoCap study compares post-stabilization temperature in a group of neonates grouped in a polyethylene body wrap and a cap to a group grouped in the polyethylene body wrap and a cotton cap. Newborns grouped in a wrap and a polyethylene cap have a higher post-stabilization temperature than those combined with a cotton cap.34

While impermeable wraps are typically used to reduce heat loss in the minutes after birth, semipermeable wraps have primarily been used to reduce transepidermal water loss over a period of days or weeks.

Impervious wraps are typically used with radiant warmers rather than humidified incubators, the latter of which minimizes TEWL by adding humidity. A total of seven studies examine the use of semipermeable wraps in preterm neonates, with the majority of these studies using a polyurethane dressing.

Two studies use adhesive dressings, while the remainder use non-adhesive dressings.35,36 These studies show that semipermeable adhesive membranes decrease TEWL, reduce skin breakdown, and decrease erythema while applied, but may release superficial layers of the skin when removed, but can remove the superficial layers of the skin when removed, leading to a transient post-removal increase in TEWL.

Furthermore, due to their semipermeable design, the application of these adhesive membranes does not appear to decrease fluid requirements or affect electrolyte status in preterm infants. 35 However, the barrier function of the skin is disrupted after removal of the plastic tape with increased transepidermal water loss at the tape removal sites.

Another type of adhesive dressing consists of pectin , which is a gelling agent extracted from byproducts of fruit juice production, such as citrus peels or apple pulp. Although one study shows improved skin condition with the use of a pectin-based barrier during the first 3 weeks of life, 38 pectin adhesive products, as well as those containing hydrocolloid or acrylate adhesive, have the potential to harm the delicate neonatal skin.

The use of any medical adhesive in premature infants is associated with medical adhesive-related skin injury (MARSI), which may lead to epidermal removal, stress injury, shearing, maceration, folliculitis, or dermatitis. contact.

Epidermal removal and skin tears are common forms of MARSI in newborns. In a study involving 82 infants (ages 0-3 months), 45% of them were found to have skin breaks, of which 17% were skin tears.

Although repeated application of adhesive dressings has been shown to pull the skin, silicone dressings appear to be less likely to strip delicate skin and are associated with less discomfort41 and less damage to the stratum corneum than other adhesives in both infants and children. Adults. For example, a study using electron microscopy shows that silicone adhesive disrupts far fewer epidermal cells than acrylate adhesive.42

In summary , plastic or plant barriers can be used to increase the fragile skin barrier of premature newborns. Impervious barriers appear to reduce the risk of hypothermia when used short-term, such as during transport to a NICU.

Semipermeable barriers have typically been studied for days to weeks in conjunction with radiant warmers and may reduce the risk of excessive fluid loss and electrolyte imbalance in this setting.

Adhesive barriers may offer more consistent skin coverage than non-adhesive barriers in daily use. However, adhesive barriers (including pectin gel) can strip the skin barrier, causing irritation and worsening transepidermal water loss after removal.

• Sterilization for catheter placement and procedures

Consensus is lacking regarding the preferred antiseptic for use in preterm neonates.43 A recent survey of US neonatal program directors shows that the majority of institutions (among those surveyed and responding) prefer CHG ( chlorhexidine gluconate) in preterm infants (predominantly without regard to different birth weight or gestational age), although some limit the use of CHG to > 1000 g or 28 weeks.44

Similarly, according to a 2018 survey, CHG is the most commonly used antiseptic in Canadian NICUs.45 Some institutions require the use of povidone-iodine for catheter placement and lumbar puncture in newborns of a certain gestational age (<26- 32 weeks), due to the perception that chlorhexidine is more likely to cause burns in infants of lower GA.

Clinical thyroid suppression has been reported after administration of povidone-iodine, while chlorhexidine gluconate at its standard concentration of 0.5% has been found to cause severe chemical burns in premature neonates.

Some studies suggest that 0.2% chlorhexidine gluconate may be an attractive alternative to povidone-iodine for the very preterm. One study compares 0.2% chlorhexidine gluconate with 0.5% in extremely premature infants and shows a statistically significant decrease in irritant skin lesions in the 0.2% group, without an increased risk of sepsis associated with central line (CLABSI - central line–associated bloodstream infection).47

As a result of these findings, a randomized trial was designed that included 304 premature neonates in Dublin, comparing 0.2% chlorhexidine gluconate in 70% isopropanol and 10% aqueous povidone.

Interestingly, the results show no differences in the incidence of catheter-associated sepsis or skin irritation; However, greater thyroid suppression is observed in the group treated with povidone-iodine (8% in the povidone-iodine group versus 0% in the chlorhexidine group).48

More research is needed to evaluate the systemic effects of CHG and definitively determine whether the 0.2% concentration is a viable alternative to povidone-iodine in preterm neonates.

• Cord care

Many practitioners reserve applying antiseptics to the cord, while cleansing the skin only with sterile water (due to concerns of possible chemical burns).

A recent meta-analysis of 21 studies found that antiseptic treatment (including alcohol cleaning) 49 is comparable to air drying of the stump with respect to the risk of infection, and antiseptic treatment may prolong the time to cord separation.50

Interestingly, one study suggests that one-time cleaning with chlorhexidine reduces neonatal mortality compared to dry cord care. 51S

However, the majority of existing evidence suggests that antiseptic treatment does not offer a benefit over dry cord care.

The findings of the present study summarize the current evidence on overall skin care in preterm infants and highlight the need for high-quality research in this area.

The skin barrier in premature neonates is quite fragile. Premature skin matures rapidly after birth, although maturation can last more than 4 weeks in ultra-low birth weight.4 Transepidermal water loss is high and can contribute to dehydration, thermal instability, and electrolyte imbalances in premature infants.

Based on the available literature, doctors can take certain measures to reinforce the weak skin barrier and improve the well-being of premature newborns.

Humidified incubators are clearly beneficial for preterm infants, although in small studies, it appears that 75% humidity is lower than 50% humidity. More research is needed to understand why this is the case, although added moisture may prevent the rapid formation of a cornified, impermeable skin barrier.

Premature neonates can be bathed in a bathtub instead of sponge bathed, to maintain a more constant body temperature, and bathing can be safely limited to every four days.

Plastic wraps or bags can reduce hypothermia when applied within 10 minutes of birth. Semipermeable and transparent adhesive dressings can improve skin quality and reduce hypothermia.

Emollients (particularly sunflower seed oil) may reduce the rate of serious infections in preterm infants in developing countries, although the data are less clear for preterm infants in developed countries, due to evidence of an increased risk of infection with drop ointments, as well as evidence of an alteration in the maturation of the skin barrier and an increase in TEWL with the application of sunflower seed oil.

Antiseptic treatment offers no clear benefit over dry cord care in most studies, although a one-time treatment with chlorhexidine appears to be effective. A dilute formulation (0.2%) of chlorhexidine solution may provide the same benefit as 0.5% chlorhexidine gluconate with less irritation.

Finally, although povidone-iodine is a commonly used antiseptic in premature neonates due to the occurrence of severe burns with 0.5% chlorhexidine, a more dilute 0.2% chlorhexidine solution appears to be effective and more suitable for extremely sensitive skin. early. Additional research is required to determine the most appropriate antiseptic for catheter placement and other procedures in preterm neonates.

Additional studies, particularly in very preterm and extremely preterm infants, with an emphasis on subclassifying the preterm patient population based on gestational age, are needed to examine and validate the real-world utility of these interventions.

In the meantime, it may be helpful to establish practice guidelines based on the evidence that has been presented here. Compared to full-term infants, preterm infants possess fragile skin barriers and are particularly susceptible to environmental fluctuations and risk of infection, and therefore have a greater need for appropriate prophylactic and therapeutic interventions.

The following findings have been associated with the use of emollients in premature neonates:

• In developed countries, premature infants treated with topical Vaseline have higher rates of candidemia and coagulase-negative Staphylococcus infection.

• In developing countries, premature neonates treated with emollients have reduced nosocomial infections and improved skin condition.