Darlene McCord asked:
The Evidence-Based Clinical Practice Guideline for neonatal skin care, including a Neonatal Skin Condition Scale (NSCS), has been validated by the Association of Women’s Health, Obstetric and Neonatal Nurses (AWHONN) and the National Association of Neonatal Nurses (NANN). Within the Guidelines, the use of emollients is recommended for infants less than 32 weeks during the first 2-4 weeks. For infants younger than 30 weeks, gestational age emollient use is recommended to reduce excessive transepidermal water loss (e-TEWL).
Over a period spanning three decades, the handling of neonates has radically changed and the new guidelines highlight this growth and development. However, this area of skin care has lagged behind. One concern that remains is the issue of the toxic effects of ingredients found in water-based products like preservatives and fragrances. While it is possible that these may be toxic, this article will present evidence that the current skin care products that contain petrolatum and lanolin may be more toxic and potentially harmful. Further, using a product that is not preserved, yet occlusive, may in fact allow for microorganisms in colony forming units to multiply, thereby yielding systemic implications. The purpose of this article is to further illuminate these issues and to allow for greater understanding and discussion.
Skin is the largest organ of the body and provides protection between the body and its environment. In term babies, while there may be issues related to skin breakdown and infection, the stratum corneum is fully developed and protects the newborn. In contrast, the skin and skin barrier of a preterm neonate is not fully developed.
The skin of a premature neonate accounts for approximately thirteen (13) percent of its body weight. This compares to three (3) percent of body weight for adult skin. The body weight to skin ratio is four (4) times greater in the neonate when compared to an adult. As related specifically to skin care, these characteristics in neonate skin call into account:
• Fluid imbalances
• Percutaneous absorption of toxins
• Tissue injury
• Infection
The structure of adult skin is understood, while embryonic and neonate skin is not fully appreciated. Development of the skin within the uterus is complex and still under investigation. In utero, the skin undergoes two-dimensional growth to cover the surface area of the developing embryo and fetus. Premature neonate’s skin has not gone through full epidermal and dermal epidermal development.
In neonatal intensive care units (NICU) skin care product selection is carefully reviewed. With the risks outlined above, great care must be taken to ensure the wellbeing of the neonate within the first hours and days of life. Care of the skin is one of the most important areas of care for these at risk infants. Currently, NANN and AWHONN recommended a Aquaphor?, a petrolatum-based product as neonate skin care emollient.
In earlier work done at Stanford University, it was concluded that emollient cream moisturizer therapy of premature neonates decreases dermatitis without changing the microbiological flora. An emollient is an agent that softens or soothes skin. This definition is important because just as the standard-of-care has changed in NICUs over the past three decades, the selection of emollients has changed in the pharmaceutical industry.
High-tech silicone excipients have displaced petrolatum as companies have sought ways to improve treatment compliance traced to poor aesthetics associated with petrolatum-based formulations. Silicones are not new to the pharmaceutical industry. They are used in transdermal delivery systems, catheters and specialized medical devices, including pacemakers.
In a test to determine aesthetic benefits of silicone formulas over petrolatum-based formulas, 18 untrained volunteers were impaneled. They were asked to evaluate whether two products present any differences on individual sensory properties. The evaluation was conducted on the panelist’s forearms. Each panelist was asked to evaluate wetness, spreadability, speed of absorbance (not biologically, just feel), gloss, film residue, greasiness, silkiness and slip after perceived absorbance.
Figure I shows the silicone-containing formulation was perceived to be easier to spread and was clearly less tacky before and after absorption. A perceptible film was present on the skin for both formulations but the silicone-containing formulation was less greasy, silkier and more slippery (better lubrication) than petrolatum. The panelist’ perception of higher wetness for the silicone-containing formulation was attributed to its lower oiliness.
In a study conducted at a 48-bed NICU private hospital in Houston, Texas, to evaluate why the rate of systemic candidiasis (SC) per 1000 NICU patient-days increased from 5.1% in 1996 to17.4% in 1997 (a three-fold increase), it was determined that the increase in SC incidences was linked to the use of topical petrolatum ointment (TPO). In this well designed study, the investigators went on to hypothesize that TPO enhanced the adherence of C albicans to mucocutaneous surfaces. Also referenced in the study was a finding by Law S, et al, that unlike petrolatum, skin surface lipids inhibit adherence of candida albicans to stratum corneum.
By way of further examination, let’s more closely examine these two hypotheses. As observed in the Houston study, petrolatum enhanced adherence of C albicans to mucocutaneous surfaces. Petrolatum is known as an occlusive barrier. Occlusion is problematic because while it blocks TEWL, it also blocks cellular respiration necessary for barrier repair. Further, occlusion traps microorganisms under the petrolatum where they can breed in the moisture trapped therein. On the other hand, natural skin lipids, like omega 3-6 fatty acids, inhibit adherence of microorganisms to the stratum corneum.
Studies linking petrolatum to increased incidences of infections in preterm infants is ongoing and demonstrates mixed results. However, long term studies reflect a concern over the use of TPO protocols in NICUs. Petrolatum based ointments, like Aquaphor’s? twenty five year old formula, are the emollients of choice in NICUs. When one considers the changes in the standards of care in NICUs over the past three decades, perhaps now is the time to focus on new technologies in emollients that achieve skin care objectives without the aesthetic, epidermal challenges renders skin vulnerable to chemicals & infection, prevents normal TEWL & gland secretions, inhibits barrier repair, suppresses barrier recovery and reduces the epidermal proliferative response and microbial risk disadvantages of petrolatum.
To demonstrate the effectiveness of high products using molecular height silicones against petrolatum, Nutrashield TM was tested in a wash-off study against Aquaphor? and other leading skin barriers to determine each product’s ability to maintain skin protection after cleansing. As shown in Figure II, Nutrashield performed well against Aquaphor?, and did so while providing a breathable barrier instead of the occlusive barrier associated with Aquaphor? (a lanolin and petrolatum-based product). In clinical trials Nutrashield has proven effective in the treatment of skin breakdown in disordered and damaged skin, encountered in the wound care setting, as compared to previously available products.
Based on the above results, Medline Nutrashield outperforms products containing petrolatum levels as high as 49%, and petrolatum combined with 15% Zinc Oxide. Additionally, both Sensi-Care 2 and Sween 24 also contain Dimethicone as an active ingredient (Sween at 6% versus 1% in the Nutrashield). The extended performance of the Nutrashield is most likely due to the addition of Divinyldimethicone/ Dimethicone Copolymer, which has an internal phase viscosity that is greater than 100,000,000 cst in viscosity. As it is delivered in an emulsion form, it is capable of laying down a thin, but consistent and robust film.
An in-vitro study at an independent laboratory was conducted, to determine the effectiveness of Nutrashield and Skin Repair Cream in reducing e-TEWL. Collagen samples were cut into 4×4 inch squares. Each square was pre-coated with 0.1 g of product. The product was applied by rubbing a finger over the collagen material to simulate actual use for a 20 second period. The product was then allowed to dry for five minutes. Each square was placed over Fisher Payne Permeability Cups, containing 3g of water. The samples were placed in a 37 degree oven and checked every four (4) hours. After 24 hours the cups were removed and a final weight was recorded.
Figure III shows that both REMEDY Nutrashield and REMEDY Skin Repair Cream were effective at reducing e-TEWL without occlusion. Nutrashield provided a fourfold reduction in e-TEWL over the control, while Skin Repair Cream showed a twofold improvement. The objective of topical skin care intervention is not to stop all TEWL, just excessive TEWL.
Skin care for neonates is an emerging science. But, since the reduced risk of infant mortality is paramount, improved emollient treatments deserve thoughtful consideration. Skin care for the high-risk neonate requires knowledge of the unique aspects and physiology of their skin. During the neonatal period many newborns develop preventable, clinically apparent skin problems and many more, especially preterm neonates, experience morbidity caused by compromised skin barrier integrity. Anatomical and physiological differences in the skin of premature and term infants place them at increased risk of skin injury and breakdown. All Children’s Hospital, St. Petersburg, FL, sent out a questionnaire to 482 NICU’s to learn how nurses describe and measure skin breakdown. Of the 45% that responded, it was reported that in extremely low birth weight (ELBW) infants, 21% suffered skin breakdown during the first week of life.
The reduction of microbial contamination and the protection against skin breakdown has been discussed. Another critical factor is TEWL associated with immature barrier in neonates is the rate of TEWL. A Swedish study calculated TEWL in infants 24 and 25 weeks of gestation maintained at an ambient relative humidity (RH) of 50%. The study found that TEWL on the first day after birth (58.4 +/-14.8g m(-2) h(-1) and remained at the same level during the second day. It then decreased significantly to 48.3+/-9.5 at postnatal age of day three. The use of a semipermeable skin care product like Nutrashield will reduce excessive TEWL by as much as fourfold.
Semipermeable dressings have been tested as a method to reduce TEWL in neonates to address skin breakdown and high fluid requirements common in ELBW infants. The studies revealed that semipermeable (breathable) barriers can be used safely on premature infants.
The use of ingredients perceived as “toxic” to neonates has limited the choices within the NICUs. Much of the literature points to preservatives and fragrances as falling into the “do-not-use” category. Both are found in the REMEDY products. Consideration of the potential toxicity of ingredients found in the “recommended” products may not have been fully clarified. This is interesting when one considers that lanolin and petrolatum, forming an occlusive barrier, are recommended. Let’s take a closer look at what is being recommended:
Lanolin originates as a secretion from the sebaceous glands in sheepskin. It is removed from the wool by scouring and high-speed centrifugal separators. Lanolin has had 33 alcohols and 36 fatty acids identified as constituents including aliphatic, steroid and triterpinoid alcohols; saturated nonhydroxylated, unsaturated nonhydroxylated and hydroxhlated acid. Commercial lanolin is allowed to have up to 40 parts per million (ppm) pesticide residues. However, it is not clear who monitors for this compliance.
Animal medicines, which include sheep dips for controlling lice and other parasites on sheep, are regulated by the Environmental Protection Agency (EPA). One of the common sheep dip ingredients is organochlorine (OC). This pesticide is based on the benzene ring with one or more chloride atoms attached and includes; DDT, lindane, dieldrin and aldrin. Other sheep dip pesticides include; synthetic pyrethroids, insect growth regulators, spinosyns, ivermectins and magnesium fluorosilicate. In 1994 in Wagga, NSW, a team of shearers successfully sued woolgrowers for allegedly endangering their health by improperly using chemicals. Shearers are becoming more aware of the potential risks associated with exposure to chemicals (sheep dip), particularly organophosphate group which can cause a serious nervous disorder.
There are about 26 pesticide residues found in commercial lanolin. The combined effect of pesticides acting by a common mechanism can be greater than the individual effect of any single pesticide. Since children are subject to non-dietary sources (like lanolin) of exposure pesticides, it is important to consider total exposure to pesticides from all sources combined. Nine hundred and ninety eight (989) references to lanolin and DDT were found in a Google search, April 2005.
La Leche League International is an important advocate for breastfeeding and their commitment has assured thousands of infants receive the vital nutrients found in colostrum and mother’s milk. While the organization acknowledges that toxins from the environment, including pesticides, show up in breast milk, the benefits outweigh the risks. However, the organization does recommend against topical use of commercial lanolin because of its pesticide content.
Petrolatum is a crude oil/petroleum fraction. Petroleum is a complicated mixture of chemicals, thought to have formed from the decay of ancient marine animals millions of years ago. Most of the constituents of petroleum are hydrocarbon molecules, oxygen, nitrogen, and sulfur atoms. The hydrocarbon atoms take principally four different forms; paraffins, olefins, cycloparaffins and aromatics. These constituents give us gasoline, kerosene, diesel fuel, lubricating oils (like mineral oil), petrolatum, asphalt and tar, to name a few.
During the manufacturing process, longer unbranched paraffin molecules are able to join together to form crystalline solids. These solids are called paraffin waxes. With time, paraffin waxes settle out of the lubricating oils and are usually removed. At lower temperatures, shorter unbranched paraffin molecules also settle out of lubrication oil. The semi-solid material that forms in cold lubricating oil is petrolatum or petroleum jelly.
The processing of petroleum into petrolatum removes varying amounts of toxins. The yellowish petrolatum has more residue than that of the white petrolatum. Two of the refining methods include sulphuric acid and earth filtering. The acid treatment and filtering is an old process still used to remove the impurities of the “cake” (petrolatum + technical oils). Another purification method is hydrogenation which pressurizes hydrogen through the hydrocarbons with the help of a specific catalyst.
Once one understands the source of petrolatum and why there is a risk of toxins, one must move on to a biologically more concerning issue. Petrolatum is occlusive. In an article by Fore, it was found that the degree of skin occlusion has an effect on barrier recovery. Occlusive products suppress barrier recovery and reduce the epidermal proliferative response to an abnormal stratum corneum barrier. An occlusive product, like petrolatum, will prevent TEWL and will slow the epidermal maturation and barrier repair. Occlusion of the skin increases the infectious organisms, potentially raising the skin’s pH. Occlusion will also directly increase the pH of the skin. Occlusive products also interfere with cellular respiration and may lead to cell death.
This information presents a powerful message that one may want to rethink the use of lanolin and petrolatum on neonate skin. The use of modern emollients like silicone, combined with natural omega 3-6 fatty acids, barrier-building amino acids and natural antioxidants and vitamins may deserve another look. Water-based skin care products are required by the Food and Drug Administration (FDA) to be preserved. This keeps them free of bacteria and protects the products from contamination when microorganisms from sources (like unclean hands) contaminate the product in the container as well as during use.
The requirement of preservatives and their use is not well understood. Preservatives are not optional in accordance with Food and Drug Administration (FDA) monographs covering the manufacturing of “Safe and Effective Drugs” or cosmetics. A manufacturer is required to perform a twenty eight (28) day preservative effectiveness challenge on its products and maintain a record of such testing for FDA inspections. Further, each batch requires proof that the batch meets microbial challenge requirements. Batches are tested in the tank, prior to filling, and then again at the beginning, middle and end of the filling process. This testing is done to ensure each product shipped is free of microbial contamination.
Since the use and safety of preservatives, especially parabens is under consideration in this article, comments from three regulating bodies are brought forward for consideration.
• The FDA recognizes parabens as a class of preservatives that have been used in a wide variety of foods, drugs, and cosmetics and that they keep products safe from microbial contamination. The Food, Drug, and Cosmetic Act require that cosmetics and non-prescription drugs and their individual ingredients must be safe and that labeling must be truthful and not misleading. The FDA can take immediate action to stop the sale of any product that does not meet its high standards. This includes the use of an effective preservative system.
• The European Food Safety Authority (EFSA) has reviewed the use of parabens in food and other products. The European Union (EU) Scientific Committee for Food (SCF) evaluated parabens in 1994 and established a temporary Acceptable Daily Intake (ADI) of 0-10mg/kg bw, as the sum of methyl, ethyl and propyl parabens. Further study also demonstrated that nooestrogenic activity took place in-vivo, and that there was no effect on forestomach cells in rats. In a teratogenicity study on 300 rabbits with oral does of methyl paraben, at doses of 550 mg/kg, no evidence of toxicity was found. The panel recognized that this dose far exceeded any anticipated oral dose.
• The Cosmetic, Toiletries, Fragrance Association (CTFA) is the body in the United States and through its Scientific Review Board, reviews all new cosmetic ingredients and assigns their INCI nomenclature (the required language found on packaging for all ingredients). The CTFA first studied the safety of parabens in 1984 and concluded they were safe as used in cosmetics. On November 14, 2004, as part of the normal re-review process, the CIR Expert Panel determined that it wanted to conduct a through review of the literature since the previous report in 1984. The safety of parabens has been once again reconfirmed.
Why then can there be a product that is not preserved? It is best that all products have some protection. However, some products that do not contain water can pass the challenge because microorganisms breed in water. Testing is done without the introduction of water. Consider this: a) an unpreserved product is placed on the skin, b) the product is occlusive, like petrolatum, c) the skin and its moisture, due to TEWL, contains microorganisms that are multiplying and trapped between the occlusive barrier and the skin, d) the skin care product on the skin is not preserved and now, e) a microorganism-rich moisture is being added. What are the consequences? Is there a systemic link and what is the potential sequela?
Toxins will be introduced to the neonate’s environment. They will come from mother’s milk, linens, clothing, human contact and a myriad of other sources. Careful consideration must always be given to the source of toxins and how multiple sources of them will impact the neonate. Product preservatives and fragrance are but two of these sources. The protection against e-TEWL and reducing the risks of systemic infections are worth considering when making neonate skin care choices.
Nutrashield from Medline Industries, Inc. is a semipermeable emollient barrier cream that:
• has excellent wash-off characteristics
• may reduce the incidence of colony forming microorganisms in the neonate population associated with petrolatum
• offers excellent aesthetic benefits including spreadability.
Additional creams and lotions in the REMEDY product line provide semipermeable barriers and nourish the skin37. Further research is necessary to confirm the product’s suitability in NICUs.
Article by Darlene McCord, Ph.D.
Lillis
