Skin Care Practices in the Neonatal Nursery: a Clinical Survey

Original Article ⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢ Skin Care Practices in the Neonatal Nursery: A Clinical Survey

Elaine C. Siegfried, MD is up to five times that of an adult.1,2 These important differences Parul Y. Shah, MD place infants at increased risk for skin damage, percutaneous infection, and toxicity from topically applied agents. The most clinically significant difference between the skin of a premature and term infant OBJECTIVE: is in the structure of the stratum corneum. Infants born before 32 To survey the details of skin care practices in a sample of level I, II, and weeks’ gestation have a very thin stratum corneum.1,3 During the first III nurseries in the United States. 2 weeks of life, these infants suffer from significant insensible transepidermal water loss (TEWL) with associated thermal instability, DESIGN: fluid, and electrolyte disturbances.1,4 A variety of seemingly benign A survey conducted by written questionnaire, personal inspection, and clinical interventions can dramatically increase these losses. Desic- phone contact. cated skin is even more easily injured, providing a portal of entry for invading microbes and increasing the risk of disseminated infec- PARTICIPANTS: tion.3–7 A premature infant’s diminished metabolic capacity and Information was obtained from staff physicians and nurses about routine decreased immune responses compound the problem. Pioneering neonatal skin care practices, including bathing, cord care, emollient use, work has been done in the field of skin development and skin care of diapering, use of antimicrobial skin preparations, management of intra- the premature infant,8 but a standard for optimized care for neonatal venous infiltration, approach to diaper rash, and methods used to mini- skin is yet to be defined. This study was designed to identify current mize transcutaneous water loss. skin care practices in hospital nurseries along with their costs, risks, and benefits. SETTING: Fifteen nurseries from twelve hospitals in four states were surveyed. MATERIALS AND METHODS RESULTS: Among the nurseries surveyed, we found no uniform approach to skin During the first 3 months of 1997, 15 nurseries from 12 hospitals in care. Only two individual maneuvers were consistently performed in all four states (Missouri, Iowa, Illinois, and California) were surveyed the nurseries: criteria for bathing and skin antisepsis with povidone– about their routine skin care practices, including bathing, cord care, iodine. Other than these, a wide range of practices and products were emollient use, diapering, use of antimicrobial skin preparations, used, some with a high ratio of risk and/or cost to benefit. management of intravenous infiltration, approach to diaper rash, and methods used to minimize insensible TEWL. The survey took place by CONCLUSION: phone and/or in person. In most instances the nursery director or A better understanding of the principles of infant skin care and a more head nurse was surveyed. If he or she was not available, a nurse uniform approach to skin care in the neonatal nursery can minimize knowledgeable in the unit’s skin care regimen was identified. If a risks and costs to this special population of patients. written protocol was available, verbal information was verified against the document. Product information was obtained from the manufacturer (Table 1). The skin of an infant differs from adult skin in several ways. The thickness of infant skin is 40% to 60% of adult skin. Attenuated rete ridges provide comparatively limited surface attachment to an RESULTS immature dermis. An infant’s ratio of body surface area to weight Data analyses were grouped according to nursery level. These included 4 “low risk” (LR) level I nurseries and 11 “high risk” (HR) Department of Dermatology (E. C. S.), St. Louis University Health Sciences Center, MO, and the Department of Pediatrics (P. Y. S.), University of Illinois-Chicago. level II and/or III nurseries. Of the 15 hospitals surveyed, 14 stated that they had a formal written skin care protocol. However, only three The majority of the work was done when P. Y. S. was a senior medical student at the Univer- sity of Missouri-Kansas City. nurseries (all HR) could produce a document. Of the three, one had a

Address correspondence and reprint requests to Elaine C. Siegfried, Department of Derma- protocol limited to bathing and one had a protocol addressing only tology, St. Louis University Health Sciences Center, 1402 S. Grand Blvd., St. Louis, MO 63104. skin breakdown. One had a protocol detailing assessment of skin

Journal of Perinatology (1999) 19(1) 31–39 © 1999 Stockton Press. All rights reserved. 0743–8346/99 $12 http://www.stockton-press.co.uk 31 Siegfried and Shah Skin Care Practices in the Neonatal Nursery

Table 1 Diaper Rash Products and Emollients: Composition and Cost Product Manufacturer Ingredients Cost/Oz

A&D ointment Schering-Plough, Memphis, TN Cholecalciferol, fish liver oil, petroleum, fragrance, lanolin, mineral oil, paraffin 2.12 Aloe Vesta Protective Ointment Convetec, Princeton, NJ Propylparaben, aloe vera gel, quaternium-15, water, hydroxylated lanolin, 1.02 ozokerite, glycerin, fragrance Aquaphor Beiersdorf, Norwalk, CT Petrolatum, mineral oil, mineral wax, wool wax alcohol .68 Aquaphor Natural Healing Beiersdorf Inc, Norwalk, CT Petrolatum, mineral oil, mineral wax, wool wax, alcohol, panthenol, bisabolol, .68 Ointment glycerin Baby Magic Baby Lotion Mennen, Morristown, NJ Water, glycerin, glyceryl stearate, cetyl alcohol, mineral oil, PEG-100 stearate, .28 lanolin alcohol, fragrance, lanolin, methylparaben, lapyrium chloride, propylparaben, benzalkonium chloride, diazolidinyl urea Balmex Diaper Rash Ointment Block Drug Co., Jersey City, NJ 11.3% zinc oxide, balsam of Peru, beeswax, benzoic acid, bismuth subnitrate, 1.47 mineral oil, purified water, silicone, synthetic white wax Cholysteramine in Aquaphor Bristol-Myers Squibb, Princeton, NJ 15% cholestyramine-liquid (aspartame, citric acid, A&C yellow no. 10, FD&C Red 8.40 and Beiersdorf, Norwalk, CT no. 40, flavor, propylene glycol alginate, collodial silicon dioxide, sucrose, (locally compounded) xanthan gum), in Aquaphor Critic-Aid Sween Products, N. Mankato, MN Benzethonium chloride in a “soothing, occlusive moisture-resistant paste” of 2.91 proprietary ingredients Desitin Diaper Rash Ointment Pfizer, New York, NY 40% zinc oxide; BHA, cod liver oil, fragrance, lanolin, methyl paraben, 1.72 petrolatum, talc, water Dr. Danis Buttocks Cream Compounded at St. John’s Mercy 32 gm of zinc oxide, 32 gm of starch, 32 gm of talc, 60 ml of glycerin, 112 gm of 13.50 Medical Center, St. Louis, MO Aquaphor Dyprotex Blistex, Oakbrook, IL 40% micronized zinc oxide, 37.6% petrolatum, 2.5% dimethicone, cod liver oil, 2.85 aloe Elase ointment Fujisawa, Deerfield, IL 1 U of fibrinolysin and 666.6 U of deoxyribonuclease in a base of petrolatum and 52.72 polyethylene Eucerin cream Beiersdorf, Norwalk, CT Water, mineral oil, isopropyl myristate, PEG-40 sorbitan peroleate, glyceryl .84 lanolate, sorbitol, propylene glycol, cetyl palmitate, magnesium sulfate, aluminum stearate, lanolin alcohol, BHT, methylchloroisothiazolinone/ methylisothiazolinone Happy Hiney Bristol-Myers Squibb, Princeton, NJ 12- ϫ 4.1-gm packets of Questran powder (cholestyramine resin, acacia, citric 2.50 and Beiersdorf, Norwalk, CT acid, D&C yellow no. 10, FD&C yellow no. 6, flavor, polysorbate 80, propylene (compounded at Carbondale glycol, alginate, sucrose) compounded in 1 lb. of Aquaphor Memorial Hospital, Carbondale, IL) Ilex Paste Calgon-Vestal, St. Louis, MO Petrolatum, calcium/sodium PVM/MA copolymer, DMDM hydantoin, 5.75 iodopropynyl-butycarbamate, mineral oil, peppermint oil, sodium carboxymethyl cellulose Neosporin Plus Maximum Burroughs-Wellcome, Triangle Polymyxin B sulfate (10,000 U), bacitracin zinc (500 U), neomycin (3.5 mg), 22.58 Strength Ointment Park, NC lidocaine (40 mg), in a special white petrolatum base Nystatin cream E. Fougera, Melville, NJ 100,000 U of Nystatin, polysorbate 60, aluminum hydroxide-compressed gel, 11.78 titanium dioxide, glyceryl monostearate, PEG monostearate 400, simethicone, sorbic acid, propylene glycol, ethylenediamine, polyoxyethylene fatty alcohol ether, sorbitol solution, methyl paraben, propyl paraben, hydrochloric acid, white petrolatum, purified water Nystatin ointment E. Fougera, Melville, NY 100,000 USP U of Nystatin/gm, in a polyethylene and mineral oil base 11.78 Proshield Health Pointe Medical, Forthworth, Cleansing foam: purified water, glycerine, cocoamphodiacetate, polaxymer 188, 6.09 TX cocamidopropylpeg-dimniumchloride phosphate, DMSM hydantoin, laureth- 23, citric acid, fragrance Skin protectant: dimethicone, polyethylene glycol, copolymer broadhesive Super Dooper Diaper Doo Peacock Pharmaceuticals, Lanolin, petrolatum 5.75 Springfield, MO Vaseline Chesebrough-Ponds, Greenwich, CT White petrolatum USP .29 Zinc oxide ointment E. Fougera, Melville, NY 20% zinc oxide, mineral oil, white wax, white petroleum base .56 integrity, bathing, treatment of intravenous infiltration, and skin care complications who was feeding well and in no distress. In 11 of 11, for the very low birth weight, Ͻ1000-gm infant. HR nurseries criteria for the first bath was the same, often delayed up Bathing of the normal term infants in all four LR nurseries took to several days. In 8 of 11, HR nurseries baths were given two to three place on the first day either when the infant was stable or the core times per week, whereas the bathing interval was on an as-needed temperature was 98.6OF. “Stable” was defined as an infant with no basis in 3 of 11. Cleansing products varied little. Nine of 15 nurseries

32 Journal of Perinatology (1999) 19(1) 31–39 Skin Care Practices in the Neonatal Nursery Siegfried and Shah

used Johnson & Johnson Baby Bath (Johnson & Johnson, Skillman, Desitin, Critic-Aid, Dyprotex, Ilex, A&D ointment, Balmex, Aquaphor, NJ). One nursery used more than one brand, including Magic Baby or Aquaphor Natural Healing ointment. In two nurseries, similar Bath (Mennen, Morristown, NJ), Neutrogena Gentle Cleanser (Neutro- custom-compounded preparations were routinely used: cholestyra- gena Dermatologics, Los Angeles, CA), Castile Soap (Baxter Health mine liquid compounded with Aquaphor and “Happy Hiney”(see Care Products, Deerfield, IL), and Basis Liquid Soap (Beiersdorf, Table 1). Norwalk, CT). The use of moisture barriers to help control transcutaneous in- Cord care practices were more varied. In 3 of 4 LR and 9 of 11 HR sensible water loss in premature infants varied widely in HR nurseries, nurseries, an alcohol wipe was applied to the umbilical stump after with more than one practice used in every nursery. Open radiant each diaper change. One LR nursery practiced this technique with warmer beds were used in all 11 HR nurseries for critically ill infants. each shift change, and one level III nursery with each bath. One level Ten of 11 nurseries used a commercially available plastic food wrap II nursery did not practice cord care but instructed parents to apply as a cover over the infant’s bed, supported to avoid contact with the alcohol wipes after each diaper change on discharge. Four of 11 HR infant’s skin. Four nurseries in separate states used Saran Wrap (Dow and 2 of 4 LR nurseries used a single application of triple dye at the Brands L.P., Indianapolis, IN). Four nurseries in the same city used first diaper change. This was delayed until after a negative Coombs the generic brand Anchor Purity Wrap (Anchor Packaging, Senton, test was verified in both LR and HR nurseries at the same hospital. In MO). Other nurseries stocked different generic brands of plastic wrap: one level III nursery, triple dye was used at the first diaper change Borden Seal Wrap (Burrows, Wheeling, IL), and Baxter Dietary Food only in infants with an umbilical artery catheter. One level II nursery Wrap (Baxter Co., Glendale, CA). Another approach, used in three swabbed the site with a povidone–iodine pledget at first bath. nurseries, was the use of a plastic bubble wrap blanket placed directly Two of 4 LR and 9 of 11 HR nurseries used emollients on an on the infant. A commercially available plastic tent marketed for as-needed basis. Two LR nurseries use no emollient. Eucerin Cream oxygen/aerosol delivery (Nova Health Systems, Blackwood, NJ) was was used in 1 of 4 LR and 4 of 11 HR nurseries. Aquaphor was used in used in one nursery, sometimes with additional humidified air. The 4 of 11 HR nurseries. A&D Ointment was used in one LR nursery and added air was not prewarmed on a routine basis. One nursery used a Baby Magic Baby Lotion in 2 HR nurseries. One HR nursery used a rigid plastic “windshield” custom designed by a neonatologist at that variety of sample products. (See Table 1 for more detailed information.) hospital. Four nurseries used an isolette rather than a warmer bed in Three nurseries at two hospitals in the same city (1 LR and 2 HR) some instances. One utilized a plastic food wrap blanket on infants used cloth diapers. Two different professional laundries serviced these housed in isolettes. Five nurseries used Aquaphor either alone or in nurseries. Managers of these companies provided sparse information addition to the above practices. Of these, it was applied on an as- on the ingredients of the laundering products used to process diapers; needed basis in two nurseries. In one nursery, the ointment was ap- phenolic compounds were not among them. Disposable diapers were plied routinely every 12 hours, in one every 6 hours, and in one once used in the other 12 nurseries. The brand most often used, in eight a day. In one nursery, cases were treated with application of Omni- nurseries, was Pampers (Proctor & Gamble, Cincinnati, OH). Three of derm dressing (Omikron Scientific Ltd., Rehovot, Israel). 15 nurseries used Huggies (Kimberly-Clark Corp., Neenah, WI). One Most nurseries did not routinely provide skin care recommenda- level III nursery used both brands. Two level II nurseries used Wee Pee tions at discharge. One nursery that did not practice routine use of diapers (Children’s Medical Venture, South Weymouth, MA), tailored emollients on its patients recommended that, after 2 weeks, parents for very low birth weight infants. use a lotion emollient on their baby and specifically avoid oil All 15 nurseries used povidone–iodine for antimicrobial skin emollients. preparation. Two of 4 LR and 6 of 11 HR nurseries used alcohol wipes in addition to this. No other products were used for this purpose. DISCUSSION Among the HR nurseries that treated the signs of extravasated intravenous fluids, seven used Wydase injectable (Wyeth Labs, Phila- This study was conducted to evaluate skin care practices in a cross delphia, PA). One used dual therapy with topical application of Elase section of hospital nurseries. The number of sites was small, and ointment immediately followed by topical application of Neosporin allowed for very detailed information to be gathered with accuracy. In Plus Maximum Strength ointment (see Table 1). this sample there were very few uniform skin care practices. Only two Treatment of diaper rash varied widely. The most popular diaper individual maneuvers were consistently performed in all the nurseries: rash product used was Desitin. First-line products for LR nurseries bathing and skin antisepsis with povidone–iodine. included Desitin, A&D ointment, and Balmex. Second-line products The routine use of povidone–iodine is a practice that deserves required a physician’s order. The HR nurseries used the following further consideration. Adverse effects of topically applied iodine anti- first-line products: Desitin, “Dr. Danis’ Buttocks Cream,” Super septics in infants have been recognized for at least 20 years.9 Skin Dooper Diaper Doo, zinc oxide ointment, Proshield, and Aloe Vesta. necrosis has been documented by case report and occurs most likely Four of these nurseries used nystatin ointment for their first-line prod- when an excess amount of solution is left in contact with the skin for uct if a yeast infection was suspected. One used either nystatin oint- a prolonged period.10 Exposure to iodine in the perinatal or neonatal ment or cream. Second-line products for these nurseries included period has been associated with dramatic, prolonged elevation in

Journal of Perinatology (1999) 19(1) 31–39 33 Siegfried and Shah Skin Care Practices in the Neonatal Nursery

plasma and urinary iodine, transient hypothyroxinemia, hypothyroid- ately rinsed off, their potential for epi- or percutaneous toxicity is very ism, and goiter.9,11,12 “Idiopathic” transient hypothyroxinemia has low. Regarding bathing water, at least one hospitalized term infant been estimated to occur in 50% of preterm infants delivered before 30 suffered second degree burns after immersion in hot water tested only weeks’ gestation,13 although reference ranges for thyroid function by touch, emphasizing the need for more careful monitoring of bath tests of premature infants have been established without regard to water temperature.25 iodine exposure.14 Transient hypothyroxinemia has been regarded as Antimicrobial cord care regimens were popularized to control a benign condition that does not require treatment. However, a histor- nursery epidemics of localized and invasive streptococcal and staphy- ical cohort study documented a 4- to 10-fold increase in the risk of lococcal infections. A wide variety of products and application sched- disabling cerebral palsy in premature infants with this condition.15 ules are currently practiced. Prospective, controlled comparative out- Although the long-term risks of topical povidone–iodine have not come studies are lacking on the safety and efficacy of these practices. been defined, there is a safer and more effective alternative for skin Clearly, bacterial colonization is controlled with antiseptic cord care; antisepsis.16 Chlorhexidine gluconate, 0.5%, is superior to 10% povi- chlorhexidine is superior to 70% ethanol,26 hexachlorophene,27 and done–iodine in reducing the risk of peripheral intravenous catheter povidone–iodine.28 Triple dye is superior to bacitracin ointment,29 colonization.17 Chlorhexidine has broad-spectrum activity against hexachlorophene,30 or isopropyl alcohol alone.31 Cord care with chlor- Gram-positive and Gram-negative bacteria and yeast,18 and it strongly hexidine, occlusive ointments, or dressings has been associated with binds to skin.19,20 This substantivity enhances the efficacy of chlor- delayed cord detachment, a potential nidus for additional medical hexidine and minimizes the risk of percutaneous absorption.16,19 care.27 Detectable, increasing plasma chlorhexidine levels were documented The risks of cutaneous exposure to alcohols, povidone–iodine, in preterm infants treated with 1% chlorhexidine in an unspecified and phenolic compounds has been discussed. As for triple dye, the concentration of ethanol every 4 hours for 5 to 9 days, but significant formulation contains brilliant green, gentian violet, and proflavine absorption was not demonstrated in a similar group of infants treated hemisulfate. These agents all have antimicrobial activity, but effica- with 1% chlorhexidine in 3% zinc oxide dusting powder, supporting cies have not been well-studied. While triple dye does control staphylo- the role of alcohols in facilitating percutaneous absorption.21 No toxic coccal colonization of the umbilical stump, it is ineffective against systemic effects have been attributed to chlorhexidine alone,16 even group B streptococcal organisms.32 Gentian violet is effective against after massive ingestion (Zenca Pharmaceuticals, Wilmington, DE, some pathogenic Candida species as well.33,34 Reported toxicities personal communication). It is also rapid-acting and has low aller- have been rare, including necrotic skin reactions following the use of genic potential even with prolonged contact.19 brilliant green.33 Gentian violet is infamous for deep purple staining The chlorhexidine-containing product ideally suited for infants is of the skin, which is rarely permanent. Prolonged use of gentian violet not commercially available in the United States. Hibistat (Zenca has been associated with nausea, vomiting, diarrhea, and ulceration Pharmaceuticals) contains 0.5% chlorhexidine and 70% isopropyl of mucus membranes,33 and carcinogenicity in mice has been report- alcohol. Hibiclens (Zenca Pharmaceuticals) and Betasept (Xttrium ed.35 However, this compound has enjoyed decades of widespread use Laboratories, Chicago, IL) contain 4% chlorhexidine and 4% isopro- with very few reported adverse events. Proflavine hemisulfate is a pyl alcohol. These formulations also contain proprietary agents: plu- mutagenic photoactive aminoacridine.2,25 One nursery routinely ronics, fragrance, and red dye. Pluronics are added solely to promote delayed application of triple dye until after a negative Coombs test was lathering and can cause serious corneal damage. In addition to en- verified, because they “didn’t want anything to interfere with the test.” hancing the absorption of the active ingredient, alcohols may also However, a detailed literature search did not yield data to support this cause skin necrosis and are highly absorbed, with their own associated concern. While there is insufficient comparative data on the costs, toxicities: hypoglycemia and central nervous system depression.10,21 risks, and benefits of antiseptic cord care regimens to recommend The risks and benefits of routine skin antisepsis in infants is a subject standard care, the use of alcohol pledgets alone provides the least that clearly deserves further investigation. However, Hibiclens or Beta- effective antimicrobial activity, whereas occlusive ointments delay sept are currently the best available choices when skin antisepsis is cord separation. Both hexachlorophene and povidone–iodine carry indicated. the risks of percutaneous toxicity. None of the nurseries surveyed used antimicrobial cleansing The two different laundering services used by three nurseries that agents for routine bathing. Hexachlorophene was widely used for this used cloth diapers specifically avoided phenolic compounds. Phenol is purpose before 1975 and was subsequently associated with serious effectively absorbed by inhalation, skin exposure, or ingestion. Sys- adverse reactions in infants, including fatal neurotoxicity.16 Cleansing temic toxicities have been well-documented in the general popula- agents for bathing varied little among the nurseries surveyed. Johnson tion36 and in infants, including an epidemic of percutaneous poison- & Johnson Baby Bath was the most popular product, reflecting the ing and death associated with the use of a laundry product containing power of advertising. Surfactants are the active ingredients in most pentachlorophenol in a hospital nursery.16,37 cleansing products; all surfactants are at least mild irritants.22 Those The first disposable diapers were marketed in 1963. The absor- marketed specifically for babies offer no special advantage over ge- bent core was originally composed primarily of cellulose fluff. In the neric mild cleansing agents.23,24 Because these products are immedi- mid-1980s, a superabsorbent core material was developed, containing

34 Journal of Perinatology (1999) 19(1) 31–39 Skin Care Practices in the Neonatal Nursery Siegfried and Shah

Table 2 Reported Hazards of Percutaneous Absorption in the Newborn Compound Product Toxicity

Aniline16 Dye used as a laundry marker Methemoglobinemia*, death Mercury69 Diaper rinses; teething powders Rash, hypotonia Phenolic compounds37: Pentachlorophenol Laundry disinfectant Tachycardia, sweating, hepatomegaly, metabolic acidosis, death Hexachlorophene Topical antiseptic (pHisoHex) Vacuolar encephalopathy, death Resorcinol37 Topical antiseptic Methemoglobinemia* Boric acid70 Baby powder Vomiting, diarrhea, erythroderma, seizures, death Lindane16,37 Scabicide Neurotoxicity Salicylic acid37,71 Keratolytic emollient Metabolic acidosis, salicylism Isopropyl alcohol (under occlusion)16 Topical antiseptic Cutaneous hemorrhagic necrosis Silver sulfadiazine72 Topical antibiotic (Silvadene) Kernicterus (sulfa component), argyria (silver component) Urea73 Exfoliant emollient (Carmol) Uremia Povidine iodine16,37 Topical antiseptic (Betadine) Hypothyroidism, goiter Neomycin16 Topical antibiotic Neural deafness Corticosteroids16,37 Topical antiinflammatory (Lotrisone) Skin atrophy, adrenal supression Benzocaine74 Mucosal anesthetic (teething products) Methemoglobinemia* Prilocaine75,76 Epidermal anesthetic (EMLA) Methemoglobinemia* Methylene blue77 Dye Methemoglobinemia*

* Heritable glucose-6-phosphate deficiencies are associated with an increased susceptability to methemoglobinemia, as are coadministration of several drugs, including sulfonamides, acetominophen, nitroprusside, phenobarbitol, and phenytoin.

a cross-linked sodium polyacrylate. This material, contained in all Table 3 Topically Applied Products That Should Be Used with “superabsorbent” diapers, holds fluid within a gel, and can absorb Caution in the Newborn many times its own weight. Superabsorbent diapers are clearly superior to cloth diapers in preventing irritant diaper dermatitis.38 Diaper Compound Product Concern dermatitis is uncommon within the first month of life. A more impor- Triclosan Lever 2000, liquid The risk of toxicities seen tant issue in the neonatal nursery is the effect of diaper type on docu- deodorant soaps with other phenolic mentation of urine output. Urine output, monitored by weighing compounds Propylene glycol78 Emollients, cleansing Excessive enteral and diapers, is diminished by evaporation from diapers left open under a agents (Cetaphil parenteral radiant warmer. Evaporative loss is greater from a fluff-type than a lotion) administration has 39 caused superabsorbent diaper. “Pseudoanuria” in an infant, has been re- hyperosmolality and ported resulting from inability to feel moisture on a superabsorbent seizures in infants diaper.40 Benzethonium chloride Skin cleansers Poisoning by ingestion, Selection of topical emollients and diaper rash products had the carcinogenesis Glycerin Emollients, cleansing Hyperosmolality, seizures greatest variation of all skin care practices among the nurseries sur- agents (Aquanil veyed, encompassing 22 different products. Many of these contain lotion) similar ingredients; a few are important to keep in mind with regard Ammonium lactate Exfoliant emollient Possible lactic acidosis to potential percutaneous toxicities, especially when applied to the (Lac-hydrin) Coal tar79 Shampoos, topical Excessive use of diaper area of an infant. A damp diaper with a plastic coating acts as anti-inflammatory polycyclic aromatic an occlusive dressing, enhancing the risk of local irritation as well as ointments hydrocarbons is associated with an percutaneous absorption. This relative risk is increased in infants with increased risk of their two- to fivefold greater ratio of body surface area to weight, and cancer cumulative in preterm infants with immature skin. There are no regulations that require disclosure of the inactive ingredients in over- the-counter products. A painstaking mission to obtain this proprietary information yielded the extensive list of ingredients in Table 1 along with effects in infants caused by absorption of topically applied agents.16,41 their associated toxicities (Table 2) and potential toxicities (Table 3). Published accounts have served to document only the most severe There have been numerous reports of devastating systemic side toxicities—in some cases manifest as nursery epidemics of obvious

Journal of Perinatology (1999) 19(1) 31–39 35 Siegfried and Shah Skin Care Practices in the Neonatal Nursery

clinical signs or deaths (Table 2). In 1998, the infamous compounds mand.53 In comparison, a plastic blanket is far superior to a rigid are scarce in topical products. However, several ingredients in over- plastic hood with respect to these parameters.54 Many adaptations to the-counter preparations may have under-appreciated toxicities.42 these reported techniques are currently employed. A wide variety of The potential for subclinical or insidious toxicities must be considered products and materials are used in diverse ways. Most of these prod- by everyone caring for small newborns (Table 3). ucts are not manufactured or indicated for this purpose, raising sev- The wide range of products used encompassed a 150-fold varia- eral concerns, including inconsistent composition, uncertain shelf tion in monetary cost as well. Even without considering this, we be- life, the possibility of degradation with prolonged exposure to heat, lieve that the safest and most effective product for use as an emollient and the possibility of significant infrared absorption. is white petrolatum and the best initial choice for diaper dermatitis is The majority of plastic wraps used in the nursery are manufac- zinc oxide ointment. Antithetically, these products are also available tured for food storage. Their composition varies. Saran Wrap is polyvi- for the lowest price. nylidone chloride sheeting. Anchor Wrap is a similar product but not Nine of 11 HR nurseries identified a routine approach to sites of identical to polyvinyl chloride. The composition of other generic plas- skin injured by extravasated intravenous fluid, including the use of tic food wraps may vary. Food wraps are specifically made for use with Wydase. This highly purified bovine testicular hyaluronidase has been cold storage and have not been tested for stability after prolonged available for three decades, most often to enhance diffusion of locally heating. The rigid plastic hood-type device used in one nursery was injected ophthalmologic anesthetics. The treatment of extravasation custom made. A similar item, made of “special formulation vinyl,” injuries in infants has been anecdotally reported. Hyaluronic acid is a polyvinyl chloride of consistent composition, is commercially avail- major component of the dermal matrix, with a higher proportion in able (Baby Shield; Nova Health Systems). The prepackaged aerosol fetal than adult skin. It may play an important role in the scarless tent used by one nursery for this off-label purpose is also manufac- wound healing that has been observed following fetal surgery.43–46 tured by Nova Health Systems. This line of tents is specifically mar- Hyaluronidase degrades hyaluronic acid at its glucosaminic bond. keted for oxygen/aerosol delivery rather than thermal control. They This temporarily decreases the viscosity of the extracellular cement, are made from polyvinyl chloride of variable composition and weight. allowing diffusion of localized transudates or exudates and facilitat- In three nurseries, generic bubble wrap was used as a blanket, a prac- ing their absorption.47 Potential heightened risks for neonates include tice introduced in 1971.55 Two studies documented the effects of this coincident diffusion of infected fluids and ultimately intensified scar- practice.55,56 Neither was in the setting of an open radiant warmer ring. Subcutaneous administration of bovine hyaluronidase has also bed. Plastic bubble wrap is generically manufactured and distributed been associated with immediate hypersensitivity reactions.48,49 Wydase as packing material; it’s composition is variable and proven impossi- is delivered in a saline solution that contains 0.04% calcium chloride ble to reliably identify. A plastic that is translucent or opaque to infra- and 0.01% thimerosal. Subcutaneously injected calcium salts can be red will acutely block heat transmission from an overhead source. intensely irritating; calcinosis cutis and skin sloughing are well- Plastics that retain heat have the potential to burn contacted skin.52 known complications of calcium gluconate infusion in infants.50 Clearly, the use of these techniques to control thermal and fluid losses Thimerosal (methionate) is an organic mercury derivative that has in small premature infants deserves further study. been associated with a variety of toxic and allergic reactions.34,51 The Another strategy to limit TEWL is the topical application of an potential acute and long-term toxicities must be considered when occlusive dressing. Empiric use of these products was initially limited deciding if and when to use Wydase. Other approaches with less po- by concerns about potential risks of systemic absorption and resulting tential toxicity deserve further investigation. These include applica- toxicity, overgrowth of microbes, and secondary heat accumulation tion of warm compresses for noncaustic extravasates and, for extrava- that could increase surface and core temperature. Several studies have sation of caustic fluids, subcutaneous injection of saline with or verified the safety and efficacy of semiocclusive, polyurethane mem- without cool compresses. brane barriers in preventing fluid losses from preterm infants nursed Several alternatives are used to control thermal and fluid insta- under radiant warmers.57–60 However, these products are expensive bility in small premature infants. Enclosed isolettes, used in 5 of 11 and technically difficult to apply. If removed prematurely, adhesive- HR nurseries surveyed, limit convective heat loss and can maintain backed products can strip off epidermis, defeating its purpose. high ambient humidity. However, this type of unit limits easy access Pure white petrolatum is an unpopular product because of it’s to patients. Although an increased incidence of infection has not been greasy texture. Misconceptions are held by some nursery staff about documented for infants housed in isolettes, this environment is opti- “side effects,” e.g., not allowing the skin to “breathe” and causing mal for contamination with pathogenic bacteria, especially in the burns if applied to infants under phototherapy or radiant warmers. setting of high humidity.52 The most common approach, practiced in Among the many studies of the mechanism of action and benefits of 10 of 11 HR nurseries surveyed, was to stretch commercially available emollients on injured and diseased skin in adults, white petroleum is plastic wrap over the side walls of open radiant warmer beds. There is regarded as the gold standard.61 It acts primarily by trapping water in limited data on the safety and efficacy of this practice. A few reports the epidermis.61 Appropriate hydration of keratinocytes is essential for have documented that blanketing an infant with a thin, pliable clear normal skin maturation,62 an optimized barrier against exogenous plastic wrap reduces insensible water loss and warmer power de- assault and maintenance of thermal, fluid, and electrolyte balance.

36 Journal of Perinatology (1999) 19(1) 31–39 Skin Care Practices in the Neonatal Nursery Siegfried and Shah

Oils, oil- and water-based creams, and lotion emollients have greater 4. Gunnar S, Hammarlund K, Nilsson GE, Stromberg B, Oberg PA. Measurements tactile acceptance than greasy ointments. Some oils, such as safflower of transepidermal water loss in newborn infants. Clin Perinatol 1985;12:79. oil, contain essential fatty acids, which greatly influence cutaneous 5. Baumgart S. Radiant energy and insensible water loss in the premature newborn structure and function.63,64 However, safflower oil does not prevent infant nursed under a radiant warmer. Clin Perinatol 1982;9:483. 65 essential fatty acid deficiency in preterm infants. Compared with 6. Harper VA, Rutter N. Barrier properties of the newborn infant’s skin. J Pediatr ointments, oils, creams, and lotions provide a much less effective 1983;102:419. moisture barrier.66 In addition, formulation of a cream or lotion 7. Rosen JL, Atkins JT, Levy ML, Baer SC, Baker CJ. Invasive fungal dermatitis in the emulsion requires the addition of several potentially irritating or toxic Յ1000-gram neonate. Pediatrics 1995;95:682–7. ingredients. Eucerin Creme is a popular product that has been studied for use 8. Nopper AJ, Horli K, Sookdeo-Drost S, Mancini AJ, Lane AT. Topical ointment in the nursery.66 It contains water, petrolatum, mineral oil, ceresin, therapy reduces the risk of nosocomial infection in premature infants. J Pediatr 1996;128:660–9. lanolin alcohol, and methylchloroisothiazolinone/methylisothiazolinone (CMI/MI), also known as Kathon CG. While susceptibility of 9. Pyati SP, Ramamurthy RS, Krauss MT, Pildes RS. Absorption of iodine in the premature infants to allergic contact sensitization is unknown, neonate following topical use of povidine iodine. J Pediatr 1977;91:825–8. CMI/MI has been associated with allergic contact sensitization in up 10. Roberts J. Drug Therapy in Infants. Philadelphia: W. B. Saunders; 1984. p. to 10% of exposed adults and is a common sensitizer in children.67 341–9. Aquaphor ointment is a petroleum wax-based emollient that contains 11. Gordon CM, Rowitch DH, Mitchell ML, Kohane IS. Topical iodine and neonatal essentially two ingredients: white petrolatum, in ointment, liquid hypothyroidism. Arch Pediatr Adolesc Med 1995;149:1336–9. (mineral oil), and solid (mineral wax) phases, and wool wax alcohol. 12. Parravicini E, Fontana C, Giuseppe L, et al. Iodine, thyroid function, and very A recent study documented a 67% decrease in TEWL 30 minutes after low birth weight infants. Pediatrics 1996;98:730–4. application of Aquaphor to premature infants Ͻ33 weeks’ gestation during the first 2 weeks of life. Six hours after application, TEWL was 13. Fisher DA. Transient thyroid dysfunction in the premature infant. In: Rudloph only decreased by 34%, implying that a 6-hour application interval is AM, Hoffman JIE, editors. Pediatrics. Norwalk, CT: Appleton & Lange; 1987. p. 1510–1. needed to maintain the effect.8 Routine application also improved skin integrity, did not alter skin flora, and was associated with a sig- 14. Adas LM, Emery JR, Clark SJ, Carlton EI, Nelson GC. Reference ranges for newer nificant reduction the incidence of sepsis. There were no adverse ef- thyroid function tests in premature infants. J Pediatr 1995;126:122–7. fects reported. Measured skin surface temperature was stable and there 15. Reuss ML, Paneth N, Pinto-Martin JA, Lorenz JM, Susser M. The relation of tran- was no evidence of hyperthermia or burns following application of the sient hypothyroxinemia in preterm infants to neurologic development at two petroleum-based ointment under infrared warmers, even for infants years of age. N Engl J Med 1996;334:821–58. receiving concomitant white light phototherapy, confirming the re- 16. Rutter N. Percutaneous drug absorption in the newborn: hazards and uses. Clin sults of a previous pilot study.68 Water-soluble agents are more easily Perinatol 1987;14:911–30. miscible in Aquaphor than white petrolatum alone. In the future this 17. Garland JS, Buck RK, Maloney P, et al. Comparison of 10% povidine-iodine and may allow compounding of pharmacologically active agents. 0.5% chlorhexidine gluconate for the prevention of peripheral intravenous cathe- Increased understanding of the mechanisms contributing to skin ter colonization in neonates: a perspective trial. Pediatr Infect Dis development may one day provide therapy to accelerate barrier matu- 1995;14:510–6. ration in very premature infants. Prolonged maintenance in a fluid 18. Anonymous. Chlorhexidine. In: Reynolds JEF, editor. Martindale: The Extra environment would be an alternate approach. Until that time, therapy Pharmacopoeia (Electronic Version.) 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