Safety of Petroleum-Based Emollients in Pediatric Atopic Dermatitis

Introduction

Atopic dermatitis (AD) is a chronic, relapsing, pruritic skin condition characterized by a complex interplay of genetic, immunological, and environmental factors. It typically presents with erythema and pruritus, which can lead to excoriation and lichenification of the skin. Atopic dermatitis represents the primary non-lethal health burden associated with skin disorders. ¹ The condition usually begins in childhood with 15%–20% of children affected globally and persists throughout life in up to 60% of cases of moderate to severe childhood eczema, significantly impacting quality of life.^1-3

For all age groups with AD, fundamental care includes avoiding irritants, managing acute symptoms, and using emollients. ⁴ Emollients alleviate skin dryness associated with impaired barrier function and inflammation in AD. ⁵ One such emollient is petrolatum, often referred to as petroleum jelly or Vaseline (Unilever; London, United Kingdom) which is a white petrolatum substance that undergoes a proprietary triple purification process to remove impurities. ⁶ Other popular choices include Aquaphor and Eucerin petroleum jelly products (Beiersdorf; Hamburg, Germany) which are comprised of 40% to 45% petrolatum and other inactive ingredients. The purification process employed by these brands of petrolatum is not well disclosed.

Petrolatum has gained prominence in the pharmaceutical and skincare sectors, initially as a carrier to safely dilute essential oils and now as a highly effective moisturizing ingredient. ⁷ This review seeks to explore the efficacy of petrolatum in managing pediatric AD and addressing safety-related apprehensions stemming from information on mobile applications.

Production

Petrolatum is a semi-solid blend of branched and cyclic saturated hydrocarbons of varying lengths greater than 25, with the general chemical formula C_nH_2n+2. ⁸ Petrolatum is derived from naturally occurring petroleum during the refining process. ⁹ Initially, petroleum undergoes distillation at high temperatures to vaporize fuels like gasoline or kerosene. Subsequently, the product undergoes deasphalting followed by dewaxing to remove additional unwanted components.

There are 2 forms of natural petrolatum: white and yellow. White petrolatum, commonly found in consumer products, is a highly refined variant processed to remove impurities, including polycyclic aromatic hydrocarbons (PAH). ¹⁰ Polycyclic aromatic hydrocarbons have garnered significant attention due to apprehensions related to allergenicity and carcinogenicity. Petrolatum also consists of mineral oil-saturated hydrocarbons (MOSH) and traces of mineral oil aromatic hydrocarbons (MOAH) both of which have raised concerns as potential carcinogens.

Skin Barrier Benefits of Petrolatum-Based Emollients

Petrolatum remains the gold standard for ingredients that aid in barrier repair due to its similarity to natural intercellular lipids and its ability to penetrate intercellular spaces. ¹¹ At a minimum concentration of 5%, petrolatum reduces transepidermal water loss (TEWL) by over 98%, while substances like lanolin, mineral oil, and silicones decrease TEWL by 20% to 30%. ¹² Petrolatum-occluded skin has been shown to have significant upregulations of antimicrobial peptides and innate immune genes with comparable properties to topical antibiotics in the prevention of infections following cutaneous procedures.^13-18 In addition, petrolatum use promotes the expression of crucial markers for skin barrier differentiation, such as filaggrin and loricrin. ¹⁴ This results in an increased thickness of the stratum corneum and a significant reduction in T-cell infiltrates in cases of non-lesional AD skin. ¹³

The hydrocarbon component of petrolatum creates an oily barrier over the skin surface, reducing TEWL in both healthy ¹⁹ and irritated human skin.^20,21 The temporary trapping of moisture within the stratum corneum, helps alleviate the dryness commonly seen in AD, reducing inflammation. ²² Studies have indicated that the application of preservative-free petrolatum-based emollients in preterm infants, who have an underdeveloped epidermal barrier function, leads to a decrease in TEWL. ²³ Similar studies in atopic infants with pure petrolatum compared to oil-in-water creams containing humectants were both shown to significantly increase skin capacitance; ²⁴ however, pure petrolatum was found to be effective across all body sites, while the impact of oil-in-water creams with humectants was less pronounced on cheek sites.

Carcinogenicity and Side Effects

Polycyclic aromatic hydrocarbons are a group of organic compounds composed of multiple fused aromatic rings found in tobacco smoke and particulate matter associated with lung and colorectal cancers.^25,26 However, PAHs are present in negligible concentrations in petrolatum due to elimination during the refinement process.^27,28 The Food and Drug Administration (FDA) refrains from specifying a limit for PAH concentration in cosmetic products, ²⁷ but purification standards are established for petrolatum directly added to food.^28-31 The European Union (EU) requires a PAH content of less than 0.005%, ³² and Health Canada has verified the absence of PAH or the presence of only traces (<0.00001%) in a range of topical products containing petrolatum. ³³

Mineral oil-saturated hydrocarbon comprises 2 distinct categories: paraffins and naphthenes. ³⁴ Possible routes of contamination include air inhalation, food intake, and dermal absorption. A correlation was found between MOSH contamination in human fat tissue and milk samples, and factors such as age, body mass index, country of residence, and the use of certain cosmetic products. ³⁵ MOSH are present in crude mineral oil, but also in highly refined mineral oil products such as white petrolatum depending on the source and refining process. ³⁶

Conversely, MOAHs of higher molecular weights have been linked to the carcinogenic potential of unrefined mineral oil. ³⁷ The refining process targets the removal of these hazardous MOAHs, resulting in petroleum jelly products with an average MOAH content <1.0%. ³⁶ Murine studies report that MOAH levels of ≤1.0% are the standard for ensuring that base oils do not possess carcinogenic potential. ³⁸

Allergenicity

Petrolatum is considered inert and therefore cannot bind to proteins or undergo chemical changes when applied topically. ²⁵ Furthermore, it is not absorbed through unharmed or wounded skin. ²⁶ Although there are recorded instances of allergic contact dermatitis linked to petrolatum, such reported occurrences are rare and have largely been observed in adults.^48-55 Chromatographic and spectrometric testing has identified residual PAH as the suspected allergen. ¹⁰ The rarity of allergic contact dermatitis to petrolatum emphasizes the effectiveness of the purification process in eliminating PAH. In a retrospective study involving 80,000 patch-test patients using white petrolatum, the occurrence of positive reactions was 0.03%. ⁵³ A randomized controlled trial with patients receiving postoperative wound care showed that none developed allergic contact dermatitis to petrolatum, compared to 0.9% of patients who used bacitracin (P = .12). ¹⁸

Safety in Infants and Children

Preterm infants constitute a unique population in which the use of petrolatum requires careful consideration. Several studies have emphasized the benefits of petrolatum in neonates, demonstrating reduced TEWL and dermatitis.^56,57 However, recent investigations have raised concerns linked to petrolatum use in premature infants (Table 1).

OPEN IN VIEWER

Table 1.

Petrolatum-Based Emollient Outcomes in Premature Infants.

Authors	Mean gestational age	Mean birthweight	Pattern of petrolatum usage	Outcomes
Campbell JR, 2000	<26 weeks	<1000 g	Incorporation of petrolatum into standard skincare	Rise in systemic candidiasis
Edwards WH, 2004	26.2 weeks	770 g treatment group 778 g control group	Twice-daily petrolatum use for 2 weeks	Higher incidence of nosocomial bacterial sepsis with Coagulase-negative Staphylococci
AlKharfy T, 2014	27 weeks	874 g treatment group 858 g control group	Twice-daily therapy of 2 g/kg petroleum jelly for 2 weeks	Improved skin condition, fluid balance, temperature control, and a higher rate of sepsis
Nopper AJ, 1996	29.3 weeks treatment group 29.1 weeks control group	1237 g treatment group 1231 g control group	Twice daily therapy with petrolatum products for 2 weeks	Significant decrease in TEWL and significantly superior skin condition scores with significantly less bacterial colonization
Lane AT, 1993	32.3 weeks treatment group 32.5 weeks control group	1584g treatment group 1725 control group	Twice-daily treatment with a water-in-oil emollient cream (petrolatum USP, mineral oil, mineral wax)	Less dermatitis and equivalent fungal cultures and quantitative bacterial cultures as compared to the control group

Abbreviation: TEWL, Transepidermal water loss.

A retrospective study of 40 low-birth-weight neonates (<1000 g) under 26 weeks gestational age revealed that incorporating petrolatum into their standard skincare routine led to a rise in systemic candidiasis from 5.9 to 17.4%. ⁵⁸ Discontinuation of petrolatum usage resulted in a return to baseline incidence levels. In a multicenter trial involving 1191 neonates with a mean gestational age of 26.2 weeks and a mean birthweight between 770 and 780 g, prophylactic twice-daily petrolatum use for 14 days did not significantly affect mortality but was associated with a higher incidence of nosocomial bacterial sepsis with coagulase-negative Staphylococci (25.8%) compared to the control group (20.4%) (P = .03). ⁵⁹ Similarly, infants with a mean gestational age of 29 weeks and a mean birthweight of 865 g received twice-daily topical therapy with 2 g/kg petroleum jelly until 34 weeks of gestation. ⁶⁰ Despite better skin condition, fluid balance, and temperature control, the intervention group exhibited a higher rate of sepsis (54% compared to 41% in the control group); however, this did not reach statistical significance. The cause of increased sepsis in petrolatum treated low-birthweight or preterm infants is not fully understood. While contamination during the application process and a common source outbreak could account for this finding, ⁵⁸ another explanation is that emollients create a conducive environment for bacterial pathogens to grow when applied to the delicate skin of preterm infants. ⁶¹

Other investigations have reported no increased risk of infection in infants treated with petrolatum. Sixty infants with a mean gestational age of 29 weeks and a mean birthweight of 1235 g received therapy for 2 weeks with petrolatum products. ⁵⁷ Those in the treatment group showed a significant decrease in TEWL (P = .001) and significantly superior skin condition scores (P ≤ .001). Quantitative bacterial cultures also indicated less colonization compared to the control group (P = .04). The incidence of positive findings in blood and/or cerebrospinal fluid cultures was 3.3% in the treatment group versus 26.7% in the control group (P = .02). In a similar study, 34 neonates with an average gestational age of 32 weeks, received twice-daily treatment with a water-in-oil emollient cream. ⁶² The emollient cream was an over-the-counter preparation that consisted of 45% hydrocarbons (petrolatum USP, mineral oil, mineral wax). The neonates treated with emollient cream demonstrated significantly less dermatitis (P values ranged from 1.1% to 14.2%) and equivalent fungal and bacterial cultures to the control group.

Product Safety Mobile Applications

Mobile applications analyzing cosmetics have provided users with tools to assess product safety; however, there is concern that they may present information in a manner that lacks context leading to confusion. Herein we explore data from such applications scanning products with 100% white petrolatum.

Conclusion

This review highlights petrolatum-based emollients as a promising treatment for AD in children, offering skin barrier benefits by reducing TEWL. Safety assessments suggest these products are suitable for neonates older than 29 weeks gestational age, with a mean birthweight exceeding 1230 g. However, further research and larger-scale studies are warranted to validate these observations. Overall, properly refined petrolatum is deemed non-toxic, with no evidence of systemic health risks.

Author Contributions

The conceptualization of the manuscript was developed by H.G., A.K., and S.E.A. The original draft was prepared by H.G. and A.K., and the review and editing were carried out by A.K. and S.E.A.