neonatal skin and skin care

PEDIATRIC DERMATOLOGY 0733-8635/98 $8.00 + .OO

NEONATAL SKIN AND SKIN CARE Elaine C. Siegfried, MD

The skin of an infant differs from adult skin in several ways. The thickness of infant skin is 40% to 60% that of adult skin. Attenuated rete ridges provide comparatively limited surface attachment to an immature dermis. An infant's ratio of body surface area to weight is up to 5 times that of an a d ~ l t . ' ~ , ~ ~ These important differences place infants at increased risk for skin damage, percutaneous infection, and percutaneous toxicity from topically applied agents. The most clinically significant difference between the skin of a premature and term infant is in the structure of the stratum corneum. Infants born before 32 weeks gestation have a very thin stratum ~orneum.~~ , 70 During the first 2 weeks of life, these infants suffer from significant insensible transepidermal watgr loss (TEWL) with associated thermal instability, fluid, and electrolyte disturbance^.^^, A variety of seemingly benign clinical interventions can dramatically increase these losses. Desiccated skin is even more easily injured, providing a portal of en- try for invading microbes and increasing the risk of disseminated infection.14, 3s, 41* 67, 70 A premature infant's diminished metabolic capacity and decreased immune responses compound these problems. Optimized skin care can minimize them.56 Pioneering work has been accomplished in the field of skin development; unfortunately, a standard for optimized care for neonatal skin has yet to be defined.

BACKGROUND

Rates of transepidermal water loss (TEWL) are objective measures of stratum corneum

integrity. TEWL has been well studied in in- f a n t ~ . ~ ~ During the first 4 weeks after birth, there is an exponential relationship between TEWL and gestational age in appropriately sized appropriate for gestational age (AGA) infants. TEWL is up to 15 times higher in 1- day-old infants born at 25 weeks gestation than in term neonates. In very low birth weight infants, this can translate into a fluid loss of up to 30% of total body weight in 24 hours. As the stratum corneum develops, TEWL gradually decreases, but at 4 weeks postgestation, TEWL from an infant born at 26 weeks is still twice that of a term infant.

Loss of body water is accompanied by evaporative heat loss, at a rate of 2.4 X lo3 J/g (or 576 calories of body heat for every mL of water).39 Evaporative losses are greatest in younger, more premature infants. Routine clinical interventions can exacerbate TEWL. Maintenance on an open radiant warmer bed in a nursery with low ambient humidity results in high evaporative loss of body water and heat." Higher ambient temperatures are required to maintain normal body temperature under these condition^.^^ Traditional efforts to minimize these insensible water losses have centered on intravascular fluid replacement and modification of the infant's hospital bed. These approaches have inherent problems. Evaporative losses originate as free water from the extracellular compartment. Replacement has been conventionally determined by calculation based on standardized maintenance fluid requirements and measured changes in body weight and intravascu-

From the Department of Dermatology and Pediatrics, Saint Louis University Health Sciences Center, St. Louis, Missouri

DERMATOLOGIC CLINICS

VOLUME 16 NUMBER 3 *JULY 1998 437

438 SIEGFRIED

lar electrolytes, which have a lag time of several hours after the losses have occurred. Re- placement fluids given in the form of isotonic intravenous solutions may result in sodium and glucose overload."j

SKIN INJURY

Clinically occult skin injury accompanies routine care. Skin stripping by removal of adhesive-backed products causes acute injury and creates the potential for secondary infection and significant scarringz3 Removal of a piece of tape, or an adhesive-backed elec- trode, will markedly compromise the stratum comeum,2°r 41 an observation that has been used in a positive way to facilitate transcutaneous monitoring of serum glucose in newborns.26 We have observed several cases of full thickness skin injury from presumed in- nocuous local application of pressure or thermal heat. The precise causes of this type of wound are often difficult to identify and remain unreported. Ultraviolet light burns have occurred in association with white light phototherapy for jaundice, from relatively limited, inadvertent exposure to near-ultraviolet light (UVA), which is 1000 times less erythe- mogenic than UVB.73 A Plexiglas safety shield, placed in front of daylight fluorescent bulbs, will filter out the UVA; however, while light phototherapy is also a source of infrared heat, and heat stress will exacerbate TEWL. In contrast, phototherapy delivered with blue light alone does not increase TEWL.45

PERCUTANEOUS ABSORPTION

Increased percutaneous absorption of topically applied compounds through an immature stratum corneum has been both advanta- geous and hazardous to neonates. This phenomenon was described in 1971, as "ra- coon facies," a visible periorbital ring of pal- lor from cutaneous vasoconstriction following the application of phenylephrine eye drops.69 This effect can be quantified, and is directly proportional to measurements of TEWL. Both methods have been established as useful markers of stratum corneum integrity in infants.60, 69 Transdermal delivery may be the optimal route of administration for the- ophyllineZ4* 69 and diam~rphine'~ in premature infants. Lidocaine applied topically to premature skin is probably much more effective

than after application to mature skin.lZ Even supplemental oxygen has been administered percutaneously to very small preterm infants with poor pulmonary function.21, 22

In contradistinction, there have been nu- merous reports of devastating systemic side effects in infants caused by absorption of topically applied agents.47, 69 Revered clinicians have historically overlooked the potential for percutaneous poisoning in designing therapy for infants. This was evidenced by Cooke'sZ5 1926 review of diaper dermatitis. In this review, he recommends "rapid and permanent cure" for "ammoniacal" dermatitis by rinsing diapers in either dilute mercuric chloride or saturated boric acid solution. Over the last 70 years, published accounts have served to document only the most severe toxicities-in some cases manifest as nursery epidemics of obvious clinical signs or deaths.

SKIN CARE PRACTICES

Bathing

Clearly, the range of skin care practices in hospital nurseries deserves further evaluation. The once conventional use of antimicrobial cleansing agents for routine bathing has diminished. Hexachlorophene was widely used for this purpose prior to 1975, and sub- sequently associated with serious adverse reactions in infants, including fatal neurotoxic- it^.^^ Bathing products have high market visibility, but there are no products with clearly demonstrable benefits for infants. No studies have been published in the medical literature on mildness of baby soaps.55 Those marketed specifically for babies offer no special advantage over generic mild cleansing agents. The active ingredients in all bathing products are surfactants; all surfactants are at least mild irritants.z8 Because these products are immediately rinsed off, their potential for cutaneous or percutaneous toxicity is very low. In efforts to create and market the mild- est cleansing products, several techniques have been defined to measure the potential for causing irritation. Manufacturers empha- size the data on file that best support their product, but there is little clinical difference among the gentle cleansers in cleansing properties or potential for irritation.82 Many mild products are now available. Regarding bathing water, at least one hospitalized term in-

NEONATAL SKIN AND SKIN CARE 439

fant suffered second degree burns after im- mersion in hot water tested only by touch, emphasizing the need for more careful monitoring of bath water tempera t~re .~~

Cloth diapers, laundered by commercial services, are used in some hospitals. Most of these laundry services are aware of the importance of avoiding phenolic compounds. Phenol is effectively absorbed by inhalation, skin exposure, or ingestion. Systemic toxicities have been well documented in the gen- eral p~pu la t ion~~ and in infants, including an epidemic of percutaneous poisoning and death associated with the use of a laundry product containing pentachlorophenol in a hospital nursery.69, One of the laundries did use sodium hypochlorite, followed by a rinse step designed to neutralize the residual chlorine. Sodium hypochlorite is used as a disinfectant, bleach, and deodorizer. Contact with a dilute solution may cause mild skin irritation; more concentrated or prolonged contact may cause skin necrosis. Sensitization dermatitis may occur in previously exposed individual^.^^

Diapering

The first disposable diapers (Pampers) were marketed in 1963. For twenty years the absorbent core was composed primarily of cellulose fluff. In the mid-l980’s, a superabsorbent core material was developed, containing a cross-linked sodium polyacrylate. This material, contained in all “superabsorbent” disposable diapers, transforms and holds fluid within a gel, and has the capacity to absorb many times its own weight. Superabsorbent diapers are clearly superior to cloth diapers in preventing irri- tant diaper dermatitis40; however, this condition is uncommon within the first month of life. A more important issue in the neonatal nursery is the effect of diaper type on docu- mentation of urine output. Urine output, monitored by weighing diapers, is diminished by evaporation if diapers are allowed to remain open under a radiant warmer. Evaporative loss is greater from a regular fluff-type than a superabsorbent diaper.42 Pseudoanuria has been reported in an infant, the result of inability to feel moisture on a superabsorbent diaper.1°

USE OF EMOLLIENTS AND DIAPER RASH PRODUCTS

Selection of topical emollients and diaper rash products has the greatest variation of all skin care variables in the newborn nursery. There are no regulations that require disclo- sure of the inactive ingredients in over-the- counter products. A painstaking mission to obtain this proprietary information yields an extensive list of ingredients and their associated potential toxicities (Table 1).

Many emollients and diaper rash products contain similar ingredients. Of these, a few are important to keep in mind with regard to potential percutaneous toxicities, especially when applied to the diaper area of an infant. A damp diaper with a plastic coating acts as an occlusive dressing, enhancing the risk of local irritation as well as percutaneous absorption. This relative risk is increased in infants with a 2- to 5-fold greater ratio of body surface area to weight, and cumulative in preterm infants with immature skin. In 1997, the more infamous compounds listed in Table 2 were scarce in topical products; however, several ingredients in commercially available, over-the-counter preparations may have under-appreciated toxicities (Table 3).

The wide range of products used encom- passes a more than 150-fold variation in mon- etary cost as well. Even without considering this cost, the safest and most effective product for use as an emollient is white petrolatum, and the best initial choice for diaper dermatitis is zinc oxide ointment. Antithetically, these products are also available for the low- est price.

CORD CARE

Cord care practices vary. Options include nonintervention, use of 70% isopropyl alcohol pledgets with or without application of triple dye, or povidone-iodine. Antimicrobial cord care regimens were popularized to control nursery epidemics of localized and invasive streptococcal and staphylococcal infections. Prospective, controlled comparative outcome studies on the safety and efficacy of these practices are lacking. Clearly, bacterial colonization is controlled with antiseptic cord care; chlorhexidine is superior to 70% ethan01,’~ hexachlor~phene ,~~ and po~idone- iodine .~~ Triple dye is superior to bacitracin ointment; hexachlorophene,80 or isopropyl alcohol

440 SIEGFRIED

Table 1. DIAPER RASH PRODUCTS AND EMOLLIENTS: COMPOSITION AND COST

costl Product Manufacturer Ingredients 0 2

A&D Ointment

Aloe Vesta Protective Ointment

Aquaphor

Aquaphor Natural Healing

Baby Magic Baby Lotion

Ointment

Balmex Diaper Rash Ointment

Cholestyramine in Aquaphor

Critic-Aid

Desitin Diaper Rash

Dr. Danis Buttocks Cream

Ointment

Dyprotex

Elase Ointment

Eucerin Cream

Schering-Plough Memphis, TN

Convetec Princeton, NJ

Beiersdorf Norwalk, CT

Beiersdorf Norwalk, CT

Mennen Morristown, NJ

Block Drug Company Jersey City, NJ

Bristol-Myers Squibb Princeton, NJ Beiersdorf Norwalk, CT; locally

compounded

Sween Products N. Mankato, MN

Pfizer New York, NY

Compounded @ St. John's Mercy Medical Center

St. Louis, MO

Blistex Oakbrook, IL

Fujisawa Deerfield, IL

Beiersdorf Norwalk. CT

alone.57 Antiseptic cord care with chlorhexidine or occlusive ointments or dressings has been associated with delayed cord detach- ment.78

Triple dye contains brilliant green, gentian violet, and proflavine hemisulfate. These agents all have antimicrobial activity, but ef- ficacies have not been well studied. Although triple dye does control staphylococcal colonization of the umbilical stump, it is ineffective against group B streptococcal organisms.75 Gentian violet is effective against some pathogenic Cundidu species as well.9 Reported toxic-

Cholecalciferol, fish liver oil, petroleum, fragrance,

Propylparaben, aloe Vera gel, quaternium-15,

lanolin, mineral oil, paraffin

water, hydroxylated lanolin, ozokerite, glycerin, fragrance

Petrolatum, mineral oil, mineral wax, wool wax alcohol

Petrolatum, mineral oil, mineral wax, wool wax, alcohol, panthenol, bisabolol, glycerin

Water, glycerin, glyceryl stearate, cetyl alcohol, mineral oil, Peg-100 stearate, lanolin alcohol, fragrance, lanolin, methylparaben, lapyrium choloride, propylparaben, benzalkonium chloride, diazolidinyl urea

11.3% zinc oxide, balsam of Peru, beeswax, benzoic acid, bismuth subnitrate, mineral oil, purified water, silicone, synthetic white wax

15% cholestyramine-liquid (aspartame, citric acid, A&C yellow #lo, FD&C Red #40, flavor, propylene glycol alginate, collodial silicon dioxide, sucrose, xanthan gum), in Aquaphor

Benzethonium chloride in a "soothing, occlusive moisture-resistant paste" of proprietary ingredients

lanolin, methyl paraben, petrolatum, talc, water

glycerin, 112 g Aquaphor

40% zinc oxide; BHA, cod liver oil, fragrance,

32 g zinc oxide, 32 g starch, 32 g talc, 60 mL

40% micro,nized zinc oxide, 37.6% petrolatum, 2.5% dimethicone, cod liver oil, aloe

1 u fibrinolysin & 666.6 u of deoxyribonuclease in a base of petrolatum and polyethylene

Water, mineral oil, isopropyl myristate, Peg-40 sorbitan peroleate, glyceryl lanolate, sorbitol, propylene glycol, cetyl palmitate, magnesium sulfate, aluminum stearate, lanolin alcohol, BHT, methylchloroisothiazolinone, methylisothiazolinone

2.12

1.02

0.68

0.68

0.28

1.47

8.40

2.91

1.72

13.50

2.85

52.72

0.84

Table continued on opposite page

ities have been rare, including necrotic skin reactions following the use of brilliant green.9 Gentian violet is infamous for deep purple staining of the skin, which is rarely permanent. Prolonged use of gentian violet has been associated with nausea, vomiting, diarrhea, and ulceration of mucous membrane^.^ Carci- nogenicity in mice was also reported68; however, this compound has enjoyed decades of widespread use with very few reported adverse events. Proflavine hemisulfate is a mu- tagenic photoactive amin~acridine. '~, 54 Al- though there are insufficient comparative


Table 1. DIAPER RASH PRODUCTS AND EMOLLIENTS: COMPOSITION AND COST (Continued).

Product Manufacturer

Happy Hiney

Hex Paste

Neosporin Plus Maximum Strength Ointment

Nystatin Cream

Nystatin Ointment

Proshield

Super Dooper Diaper Doo

Vaseline

Zine Oxide Ointment

Bristol-Myers Squibb Princeton, NJ Beiersdorf Norwalk, CT Compounded Q

Carbondale Memorial Hospital

Carbondale, IL

Calgon-Vestal St. Louis, MO

Burroug hs-Wellcome Triangle Park, NC

E. Fougera Melville, NJ


Health Pointe Medical Fort Worth, TX

Peacock Pharmaceuticals Springfield, MO

Chesebrough-Ponds Company

Greenwich, CT


Ingredients cosv

Or

12 x 4.1 g packets of Questran powder (cholestyramine resin, acacia, citric acid, D&C yellow no. 10, FD&C yellow no. 6, flavor, polysorbate 80, propylene glycol, alginate, sucrose) compounded in one pound of Aquaphor

Petrolatum, calcium/sodium PVM/MA copolymer, DMDM hydantoin, iodopropynyl-butycarbamate, mineral oil, peppermint oil, sodium carboxymethyl cellulose

U, neomycin 3.5 mg, lidocaine 40 mg, in a special white petrolatum base

100,000 U nystatin, polysorbate 60, aluminum hydroxide compressed gel, titanium dioxide, glyceryl monostearate, polyethylene glycol monostearate 400, simethicone, sorbic acid, propylene glycol, ethylenediamine. polyoxyethylene fatty alcohol ether, sorbitol solution, methyl paraben, propyl paraben, hydrochloric acid, white petrolatum, purified water

100,000 USP U nystatin per gram, in a polyethylene & mineral oil base

Cleansing foam: purified water, glycerine, cocoamphodiacetate, polaxymer 188, cocamidopropylpeg-dimniumchloride phosphate, DMSM hydantoin, laureth-23, citric acid, fragrance

glycol, copolymer adhesive

Polymyxin B sulfate 10,000 U, bacitracin zinc 500

Skin protectant: dimethicone, polyethylene

Lanolin, petrolatum

White petrolatum USP

20% zinc oxide, mineral oil, white wax, white petroleum base

2.50

5.75

22.58

11.78

11.78

6.09

5.75

0.29

0.56

data on the costs, risks, and benefits of antiseptic cord care regimens to recommend standard care, the use of alcohol pledgets alone provides the least effective antimicrobial activity whereas occlusive ointments delay cord separation. Hexachlorophene and povidone- iodine carry the most significant risks of percutaneous toxicity.

The routine use of povidone-iodine is a popular practice that deserves further consid- eration. Adverse effects of topically applied iodine antiseptics in infants have been recog- nized for at least 20 years.62 Skin necrosis has been documented by case report, an injury most likely to occur when an excess amount

of solution is inadvertently left in contact with the skin for a prolonged period of time.66 Exposure to iodine in the perinatal or neonatal period has been associated with dramatic, prolonged elevation in plasma and urinary iodine, transient hypothyroxinemia, hypothyroidism, and goiter.37, 58, 62 A single application of 1% povidone-iodine solution to the umbili- cus has been shown to elevate plasma iodine of healthy term infants for 24 hours.62 In a prospective, case-control study, premature infants treated with limited application of 10% povidone-iodine solution for routine skin antisepsis prior to nonsurgical invasive proce- dures experienced a mean 10-fold increase in

442 SIEGFRIED

Table 2. REPORTED HAZARDS OF PERCUTANEOUS ABSORPTION IN THE NEWBORN

Compound Product Toxicity

Aniliness Mercuryz7 Phenolic

compoundse1: Pentachlorophenol

Hexachlorophene ResorcinoP'

Boric Lindanesg, Salicylic acid', 81

lsopropyl alcohol

Silver s~ l fad iaz ine~~ Urea5 P~vidine-iodine~~, Neomycins9 Corti~osteroids~~~ Ben~oca ine~~

Pr i l~ca ine~~, 65

Methylene blues7

(under occ I~s ion)~~

Dye used as a laundry marker Diaper rinses; teething powders

Methemoglobinemia*, death Rash, hypotonia

Laundry disinfectant

Topical antiseptic (pHisoHex) Topical antiseptic Methemoglobinemia* Baby powder Scabicide Neurotoxicity Keratolytic emollient Metabolic acidosis, salicylism Topical antiseptic Cutaneous hemorrhagic necrosis

Tachycardia, sweating, hepatomegaly, metabolic

Vacuolar encephalopathy, death

Vomiting, diarrhea, erythroderma, seizures, death

acidosis, death

Topical antibiotic (Silvadene) Keratolytic emollient (Carmol) Topical antiseptic (Betadine) Topical antibiotic Topical antiinflammatory (Lotrisone) Mucosal anesthetic (teething

Epidermal anesthetic (EMLA) Amniotic fluid leak

products)

Kernicterus (sulfa component), argyria (silver component) Uremia Hypothyroidism, goiter Neural deafness Skin atrophy, adrenal suppression Methemoglobinemia*

Methemoglobinemia* Methemoglobinemia*

'Heritable glucose-6-phosphate deficiencies are associated with an increased susceptibility to rnethernoglobinernia, as are coadrninis- tration of several drugs, including: sulfonarnides, acetaminophen, nitroprusside, phenobarbital and phenytoin.

urinary iodine levels during the first week of life, followed by altered thyroid functions detectable at day 28.58 A prospective pilot study documented a 66% incidence of transient hypothyroxinemia among 47 neonates (birth weights 0.7 to 5.1 kg) exposed to topical povidone-iodine during the first 2 weeks of life.37 "Idiopathic" transient hypothyroxinemia has been estimated to occur in 50% of preterm infants delivered before 30 weeks ge~tation?~ although reference ranges for thyroid function tests of premature infants have been established without regard to iodine exposure.z Transient hypothyroxinemia has gen- erally been regarded as a benign condition that does not require treatment; however, a

recent historical cohort study documented a 4- to 10-fold increase in the risk of disabling cerebral palsy in premature infants with this ~ond i t ion .~~

Although the long-term risks of topical povidone-iodine have not been well defined, there is a safer and more effective alternative for skin antisepsis in chlorhexidine gluconate.69 One-half percent chlorhexidine gluconate is superior to 10% povidone-iodine in reducing the risk of peripheral intravenous catheter col~nization.~~ Chlorhexidine has a broad spectrum of activity against gram positive and gram negative bacteria and yeast.6 Chlorhexidine strongly binds to skin.9, 44 Its substantivity enhances the efficacy of chlor-

Table 3. TOPICALLY APPLIED PRODUCTS THAT SHOULD BE USED WITH CAUTION ON NEWBORN SKIN

Compound Product Concern

Triclosan

Propylene glycol5' Emollients, cleansing agents (Cetaphil Cleansing Lotion)

Benzethonium chloride Skin cleansers Glycerin Emollients, cleansing agents

(Aquanil Lotion) Ammonium lactate Keratolytic emollient (Lac-hydrin) Coal tar7' Shampoos, topical

antiinflammatory ointments

Lever 2000, liquid deodorant soaps The risk of toxicities seen with other phenolic compounds

Excessive enteral and parenteral administration has caused hyperosmolality and seizures in infants

Poisoning by ingestion, carcinogenesis Hyperosmolality, seizures

Possible lactic acidosis Excessive use of polycyclic aromatic hydrocarbons

is associated with an increased risk of cancer


hexidine and minimizes the risk of percutaneous ab~orption.~, 69 No toxic systemic effects have been attributed to chlorhexidine even after massive oral ingestion (Zenca Pharmaceuticals, personal communication, 1997). In addition, it is rapid acting and has low potential for producing contact sensitiv- ity even with long-term c~ntac t .~

Unfortunately, a chlorhexidine-containing product ideally suited for infants is not commercially available in the United States. Hibi- stat (Zenca Pharmaceuticals, Wilmington, DE) contains 0.5% chlorhexidine and 70% isopropyl alcohol. Hibiclens (Zenca Pharmaceuti- cals, Wilmington, DE) and a similar product, Betasept (Xttrium Laboratories, Chicago, IL), contain 4% chlorhexidine and 4% isopropyl alcohol. Detectable, increasing plasma chlorhexidine levels were documented in preterm infants treated with 1% chlorhexidine in an unspecified concentration of ethanol every 4 hours for 5 to 9 days. Significant absorption could not be documented in a similar group of infants treated with 1% chlorhexidine in a 3% zinc oxide dusting powder, supporting the role of alcohols in facilitating percutaneous ab~orption.~ Commercially available formulas also contain the proprietary pluronics, fragrance, and red dye. Pluronics are added solely to enhance lathering and can cause serious corneal damage. In addition to enhancing the absorption of the active ingredient, alcohols may also cause skin necrosis and are highly absorbed, with their own associated toxicities, hypoglycemia, and CNS depres- ~ ion .~ , 66 The risks and benefits of routine skin antisepsis in infants are subjects that clearly deserve further investigation; however, Hibi- clens and Betasept are currently the best available choices when skin antisepsis is indicated. The potential for subclinical toxicities must be considered by everyone caring for small newborns. When several topical thera- peutic options are available, the one with the least potential for toxicity should be used. Poisindexm is an extensive, frequently up- dated, computer-based reference source for the identification of potentially toxic com-

CONTROL OF TRANSCUTANEOUS WATER LOSS

Several alternatives are used to control transcutaneous water loss and its accompa- nying thermal and fluid instability in small

premature infants. Enclosed isolettes limit convective heat loss and can maintain high ambient humidity; however, this type of unit impedes easy access to patients. Although an increased incidence of infection has not been documented for infants housed in isolettes, this environment is optimal for contamination with pathogenic microbes, especially in the setting of high In many high risk nurseries, plastic barriers are placed over infants nursed on open radiant warmers. There are limited data on the safety and efficacy of this practice. A few reports have documented that blanketing an infant with a thin, pliable clear plastic wrap reduces insensible water loss and warmer power demand.15 In direct comparison, a plastic blanket is superior to a rigid plastic hood with regard to these param- eters.16 Many adaptations to these reported techniques are currently employed. A wide variety of products and materials are used in diverse ways. The majority of these products are not manufactured or indicated for this purpose, raising several concerns. Concerns include inconsistent composition, uncertain shelf life, the possibility of degradation with prolonged exposure to heat, and the possibility of significant infrared absorption.

The majority of plastic wraps used in the nursery are manufactured for food storage. Their composition varies. Saran Wrap (Dow Brands, Indianapolis, IN) is a polyvinylidone chloride sheeting. Anchor Wrap (Anchor Packaging, Senton, MO) is a similar but not identical product of polyvinyl chloride. The composition of other generic plastic food wraps may vary from box to box. Food wraps are specifically made for use with cold storage, and have not been tested for stability after prolonged heating. A rigid plastic hood- type device is used in some nurseries, either custom-made or commercially available (e.g., Baby Shield, Nova Health Systems, Inc., Blackwood, NJ). Baby Shield is made of a "special formulation" polyvinyl chloride of consistent composition. Prepackaged aerosol tents (Nova Health Systems, Inc., Blackwood, NJ) are used in some nurseries for this off- label purpose. These tents are specifically manufactured and marketed for oxygen/ aerosol delivery rather than thermal control. They are made from polyvinyl chloride of variable composition and weight. In some nurseries plastic "bubblewrap" is used as a thermal blanket. This practice was introduced in 1971.18 Two studies documented its efficacy in very specific, different settings. The first

444 SIEGFRIED

included 85 infants >2000 g during the first 40 minutes of life, with and without head- cover and with and without a 750-watt overhead warmer.53 Mean rectal temperature was best maintained for infants whose bubblewrap included a head cover. The authors assumed that ”evaporation of amniotic fluid from the skin” was the major cause of heat loss, but antithetically noted no cooling effect in uncovered babies who were not towel dried. A second, case-controlled study included 5 premature infants weighing 880 to 1930 g housed in single-walled incubators. Insensible water loss (IWL) was determined from decremental weight change during 3- hour periods. The decrease in IWL was greatest for the smallest blanketed infant.18 Plastic bubblewrap is generically manufactured and distributed as packing material, and its composition is variable and impossible to reliably identify. A plastic that is translucent or opaque to infrared will acutely block heat transmission when used in the setting of an overhead infrared source. Plastics that retain heat have the potential to burn contacted ~kin.4~ Clearly the use of these techniques to control thermal and fluid losses in small premature infants deserves further study.

Another strategy to limit TEWL is with topical application of an occlusive dressing. Em- piric use of these products has been limited by concerns about potential risks of systemic absorption and resulting toxicity, overgrowth of microbes, and secondary heat accumula- tion that could increase surface and core temperature. A few studies have verified the safety and efficacy of semiocclusive, polyurethane membrane barriers in preventing fluid losses from preterm infants.”, 467 51, 79

Pure white petrolatum has been an unpop- ular product in the nursery because of its greasy texture. Misconceptions are held by some nursery staff about ”side effects,” e.g., not allowing the skin ”to breathe” and causing burns if applied to infants under phototherapy or radiant warmers. There have been many studies on the mechanism of action and benefits of emollients on injured and diseased skin in adults. White petroleum is regarded as the gold standard.35 It acts primarily by trapping water in the epidermis.35 Appro- priate hydration of keratinocytes is essential for normal skin mat~ration,6~ which is an optimized barrier against exogenous assault and maintenance of thermal, fluid, and electrolyte balance. Oils, oil and water based creams, and lotion emollients have greater tactile accep-

tance than greasy ointments. Some oils, such as safflower oil, contain essential fatty acids that greatly influence cutaneous structure and function71, 83; however, topically applied safflower oil does not prevent essential fatty acid deficiency in preterm infants.50 Oils, creams, and lotions, when compared to ointments, provide a much less effective moisture barrier.48 In addition, formulation of a cream or lotion emulsion requires the addition of several potentially irritating or toxic ingredients.

Eucerin Creme (Biersdorf, Norwalk, CT) is a popular product that has been studied for use in nurseries.48 It contains water, petrolatum, mineral oil, ceresin, lanolin alcohol, and methylchloroisothiazolinone/methylisothiazolinone (CMI/MI). Although susceptibility of premature infants to allergic contact sensitization is unknown, CMI/MI has been associated with allergic contact sensitization in up to 10% of exposed adults.31 Aquaphor ointment (Biersdorf, Norwalk, CT), a petroleum wax-based emollient, contains essentially two ingredients, white petrolatum in ointment liquid (mineral oil) and solid (mineral wax) phases and wool wax alcohol. A recent study documented a 67% decrease in TEWL 30 minutes after application of Aquaphor. Six hours after application, TEWL was only decreased by 34%, implying that a six-hour application interval is needed to maintain the effect.56 Routine application also improved skin integrity, did not alter skin flora, and was associated with a significant reduction in the incidence of sepsis. There were no adverse effects reported. Measured skin surface temperature was stable and there was no evi- dence of hyperthermia or burns following application of the petroleum-based ointment under infrared warmers, even for infants re- ceiving concomitant white light phototherapy, confirming the results of a previous pilot

Water-soluble agents are more easily miscible in Aquaphor than in white petrolatum alone. In the future, a water soluble vehi- cle may allow compounding of pharmacolog- ically active agents.

Increased understanding of the mecha- nisms contributing to skin development may one day provide therapy to accelerate barrier maturation in very premature infants. Pro- longed maintenance in a fluid environment would be an alternate approach. Until that time, therapy should be directed towards providing a safe, temporary barrier and minimiz- ing additional skin injury while allowing easy access and handling of infants. Efforts should

be directed at creating a well defined and uniformly accepted standard of care for the skin of premature infants.

References

1. Abidel-Magid EHM, El Awad Ahmed FR Salicylate intoxication in an infant with ichthyosis transmitted through skin ointment. Pediatrics 94(6):939, 1994

2. Adas LM, Emery JR, Clark SJ, et al: Reference ranges for newer thyroid function tests in premature infants. J Pediatr 126(1):122, 1995

3. Aggett PJ, Cooper LV, Ellis SH, et a1 Percutaneous absorption of chlorhexidine in neonatal cord care. Arch Dis Child 56:878, 1981

4. Andrich MP, Golden SM: Umbilical cord care. A study of bacitracin ointment vs. triple dye. Clin Pedi- atr 23(6):342, 1984

5. Anonymous: High plasma urea concentrations in col- lodion babies. Arch Dis Child 62(2):212, 1987

6. Reynolds J (eds): Chlorhexidine. Englewood, CO, Mi- cromedex, Inc., 1996

7. Anonymous, Editorial staff (eds): Poisindex System. Englewood, CO, Micromedex, Inc., 1996

8. Reynolds J (eds): Martindale: The Extra Pharmaco- poeia (electronic version). Englewood, CO, 1997

9. Bennett DR (ed): AMA Drug Evaluations. Chicago, AMA Division of Drugs, 1983, pp 1383-1384

10. Barada JH: Pseudoanuria due to superabsorbent diapers. N Engl J Med 325(12):892, 1991

11. Barak M, Hershkowitz S, Rod R, et al: The use of a

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neonatal skin and skin care

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