2017 July-December; 5(3-4): 99–106. ISSN: 2282-4103
Published online 2018 March 23. doi: 10.11138/cderm/2017.5.3.99.

Comparison of two skincare regimens in healthy newborns during the first six weeks of life

Jennifer Theunis,corresponding author1 Cecile Villeneuve,1 Pascale Bianchi,1 Adeline Bacquey,1 Christiane Casas,1 Valérie Mengeaud,1 Varvara Kanti,2 Anne-Marie Schmitt,1 Ulrike Blume-Peytavi,2 and Natalie Garcia Bartels2

1Pierre Fabre Dermo-Cosmétique Research Centre, Toulouse, France
2Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science, Charité-Universitätsmedizin and Skin Science, Berlin, Germany

corresponding authorCorresponding author.

Address for correspondence : Jennifer Theunis, Pierre Fabre Dermo-Cosmétique Research Centre, Toulouse, France, E-mail : jennifer.theunis@pierre-fabre.com

Summary

Background/objectives
The fragile skin of full-term newborns has not yet acquired all the qualities of adult skin and requires special attention. This study examines how two skincare regimens specifically designed for healthy newborns affect the development of normal skin barrier function and microflora.

Methods
In this open-label trial, healthy newborns aged <4 days were randomized 1:1 to apply a skin care oil, a cleansing oil, and a no-rinse cleansing oil (group 1) or only the cleansing oil and the no-rinse cleansing oil (group 2). Transepidermal water loss, skin hydration, skin pH, skin lipid index, and clinical skin condition were assessed at baseline and at weeks 3 and 6. Skin was swabbed at baseline and week 6 to assess microflora.

Results
Sixty newborns were included (n=30 per group) in the study. In both groups, skin lipid index and transepidermal water loss did not change from baseline, whereas pH significantly decreased and skin hydration significantly increased. At week 6, clinical skin condition, especially xerosis, was significantly better in the skincare group. Candida albicans was not detected in either group at baseline or week 6. Staphylococcus aureus, Staphylococcus epidermidis, and Malassezia global counts did not significantly differ at week 6 vs baseline.

Conclusion
This study showed that application of a skincare oil designed for newborn skin significantly improved skin condition in full-term healthy newborns. In addition, the two skincare regimens did not differ significantly in their effects on the physiological course of skin barrier maturation, skin pH changes, or the development of the microflora.

Keywords: skin barrier, neonate, dermatitiseczemas NOS

Introduction

Neonatal skin is frequently dry and has low lipid and sebum content, high pH, and a weak barrier function, which can leave newborns susceptible to chemicals and microbes, as well as to the development of skin diseases such as atopic dermatitis (1). During the first few days and weeks after birth, pH decreases and skin hydration, transepidermal water loss, and sebum secretion increase as the skin barrier matures (1). In addition, the skin is gradually colonized by a commensal microbiota, which may require more than a year to establish (2). The commensal microbiota contributes to cutaneous homeostasis, modulates skin inflammation and immunity, and prevents colonization by harmful microbes, but under certain conditions, it can be the source of harmful or life-threatening infections or can contribute to skin diseases like atopic dermatitis (2).

Moisturizers can improve barrier function and prevent the development of atopic dermatitis in newborns (35). The role of cleansing practices in protecting or damaging the skin of newborns is less clear, and there is generally little data on the effects of skincare regimens on skin properties in newborns, but the consensus is that skincare and cleaning products for newborns should not be aggressive, should contain minimal preservatives and fragrances, and should not irritate the skin (68).

A line of fragrance- and preservative-free skincare products (Primalba®, Pierre Fabre) has been available in France since 2012. These include a skincare oil, a cleansing oil, and a no-rinse cleansing oil, all based on only 11 ingredients including 4 alimentary oils. In this study, we compared two skincare regimens based on these products in healthy full-term newborns, with the aim of showing that they do not interfere with the physiological or microbiological maturation of the skin.

Materials and methods

This was a randomized, open-label, parallel-group study comparing two skincare regimens in healthy full-term newborns conducted at the Charité - Universitätsmedizin (Berlin, Germany) between August 10, 2012 and June 5, 2013. The trial was conducted according to Good Clinical Practice (9) and the Declaration of Helsinki, and the study was approved by the local ethics committee of Charité – Universitätsmedizin, Berlin, Germany (Votum No. EA2/068 / 1 2). Signed informed consent was provided by parents or guardians of all infants participating in the study.

Subjects included in the study had to be < 4 days of age, at least 37 weeks of gestation, and have an Apgar score > 7. Newborns were excluded if one or both parents were allergic or intolerant to any of the ingredients, if they had a disease or were receiving a treatment that could have affected the observations, or if both parents had atopic dermatitis.

Subjects were randomized 1:1 to 6-week treatment with skincare oil on the face and body + cleansing oil on the hair and body + no-rinse cleansing oil on the buttocks (group 1) or to cleansing oil + no-rinse cleansing oil only (group 2) (Figure 1). All products used in this study were from the Primalba® product line (Pierre Fabre, Toulouse, France). During the study, the protocol was amended to remove the no-rinse cleansing oil due to diaper rashes considered probably related to the product.

Figure 1Figure 1
Study design and subject disposition. (A) Treatments applied. Subjects were randomized 1:1 to treatment with skincare oil + cleansing oil + no-rinse cleansing oil (group 1) or to cleansing oil + no-rinse cleansing oil (group 2). Original image obtained (more ...)

The primary objective was to assess the non-inferiority of the two skincare regimens in terms of transepidermal water loss (TEWL) on the right upper leg after 6 weeks of treatment (Tewameter TM300, Courage+ Khazaka, Cologne, Germany). Secondary objectives were to compare TEWL on the buttocks; skin hydration on the right upper leg and buttocks (Corneometer, Courage+Khazaka); pH on right upper leg and buttocks (pH-meter, Courage+Khazaka); skin lipid index on the forehead (Sebumeter, Courage+ Khazaka); Staphylococcus aureus, Malassezia Spp, and Candida albicans densities of the right axillary fold, volar aspect of the right forearm, and forehead measured by real-time PCR (10); microbiological species cartography (Genoscreen, Lille, France); investigator-assessed skin condition on the whole body assessed by Neonatal Skin Condition Score (NSCS) (11); and adverse events (AEs) recorded according to Good Clinical Practice guidelines (9). Density of Staphylococcus epidermidis of the right axillary fold, volar aspect of the right forearm, and forehead were also examined as a post-hoc assessment.

The funders of this clinical trial subcontracted and funded the data treatment and the statistical analysis of the study. The study design was approved by a dermatologist with significant experience in the field of newborns clinical trials who signed a contract with the funders to conduct the study.

Statistical analysis
Statistical analysis was performed using SAS version 9.3 (SAS Institute, Cary, NC). For the primary outcome measure, TEWL on the upper thigh at week 6, the 95% confidence interval (CI) of the difference between groups was calculated for the subjects completing the study according to protocol using an analysis of covariance model with product as fixed factor and baseline score as covariate. Group 1 was considered non-inferior to group 2 if the upper limit of the 95% CI was > 3 g/m2/h. Secondary endpoints were analysed in the full analysis set, which included all treated subjects. Appropriate contrasts on product-by-visit interaction were performed to test the null hypothesis that the differences between application groups on the score changes from baseline at each concerned visit were equal. Microbial counts were compared using Student’s t-test. Visual and clinical evaluations of skin were compared using a chi square test. A p-value < 0.05 was considered statistically significant.

Results

Sixty newborns < 4 days of age were enrolled and treated with skincare oil + cleansing oil + no-rinse cleansing oil (group 1; n=30) or cleansing oil + no-rinse cleansing oil (group 2; n=30) (Figure 1). For both groups, subjects were on average 2 days of age, and characteristics at enrolment were similar (Table 1). Of the 60 enrolled subjects, 57 completed the study.

Table 1Table 1
Subject baseline characteristics.

Skin barrier
During the 6 weeks of the study, skin hydration on the upper leg and buttocks increased in both groups (Table 2). The increase in hydration on the buttocks was significantly greater in group 1 than group 2 at week 6 (p=0.0263) but this was not found at week 3. The increase in skin hydration on the upper leg, however, did not differ between groups at 3 or 6 weeks. Skin pH decreased to a similar extent between enrolment and week 3 on both the upper leg and buttocks (from 5.5–5.6 to 4.7–4.8 on the upper leg and from 5.4–5.5 to 5.0–5.2 on the buttocks), after which it did not appear to change further. In contrast to hydration and pH, TEWL on the upper leg did not change in either group, and differences from baseline were non-inferior in group 1 vs group 2 at week 3 and week 6 (upper limit of the 95% CI of the difference < 3 g/m2/h). On the buttocks, TEWL was unchanged at week 3, but at week 6, it was significantly increased in group 2 (p=0.0318) but not group 1. The skin lipid index on the forehead did not change in either group.
Table 2Table 2
Functional parameters.

According to investigators, erythema (Figure 2B) and excoriation (Figure 2C) did not differ between groups at the end of the study (week 6). However, xerosis (p=0.0391) (Figure 2A) and overall skin condition (p=0.0244) (Figure 2D) were lower in group 1 than in group 2 (p=0.0391). This was associated with significant decreases from baseline in group 1 (p=0.0007 for xerosis and p=0.0002 for NSCS).

Figure 2Figure 2
Clinical assessments: NSCS and subscores. Xerosis (A), erythema (B), and excoriation (C) were scored at enrolment (day 1), week 3, and study end (week 6) by investigators on a 3-point scale where 1 was the least severe and 3 was the most severe. The NSCS (more ...)

Microbiological colonization
Densities of S. aureus, S. epidermidis, and Malassezia spp on the forearm, forehead, or axillary area at the end of the study did not differ between the two groups (Table 3). C. albicans was not detected in the children at any time (data not shown). Microbiological species cartography also revealed no major differences at the end of the study in either group (Figure 3).
Table 3Table 3
Mean cell counts ± standard deviation of Staphylococcus aureus, Malassezia Spp, and Staphylococcus epidermidis on the forearm, forehead, and axillary fold.
Figure 3Figure 3
Bacterial species cartography at enrolment (week 0) and end of the study (week 6). Microflora samples from the axillary fold, forearm, and forehead were taken for the first 15 subjects in each group using cotton swabs gently applied to the skin with rubbing (more ...)

Safety and tolerability of the treatments
AEs considered related or possibly related to the investigational products were reported by 11 subjects in group 1 and 10 subjects in group 2. Most of these were diaper rash, nearly all of which (4/5 cases in group 1, 8/8 cases in group 2) were considered to be related to the no-rinse cleansing oil. The remaining possibly related AEs all occurred outside the diaper area and included mild erythema (2 subjects in group 1, 1 subject in group 2), mild dry skin (2 subjects in group 1, 2 subjects in group 1), and mild seborrheic dermatitis (2 subjects in group 2). No SAEs related to the investigational products were reported.

Discussion

Few controlled clinical trials have assessed the effect of skincare and hygiene products on skin function and properties in newborns. Here, we compared the effects of two related skincare regimens on skin condition in full-term healthy newborns. One regimen included cleansing oil applied to the hair and body at least twice weekly combined with no-rinse cleansing oil applied to the buttocks at each diaper change; the other was the same base regimen plus a skincare oil applied to the face and body once daily. Overall effects on functional skin properties were similar for the two regimens; however, xerosis and overall skin condition, measured using a validated scoring system (NSCS) (11), improved with the regimen including the skincare oil but not with the base regimen alone. During the first few weeks of life, skin properties change significantly (1214). Hydration of the stratum corneum increases during the first few days of life, and pH decreases gradually over the first several weeks. In this study, hydration increased equally in the two treatment groups, whereas TEWL values, which remained below 10 g/m2/h, did not change, in agreement with previous reports for full-term infants (12, 13). Although xerosis, according to clinical assessment, was significantly reduced when the treatment regimen included the skincare oil, TEWL changes in this study were non-inferior between the two treatment regimens and skin hydration as assessed by corneometer was similar, suggesting that the improvement in xerosis may have been unrelated to maturation of the barrier function or improvement in hydration. Skin pH changed as expected (13, 15), decreasing from around 5.5 at baseline and decreased to around 4.7–5.0 by week 3. Although sebum levels are reported to increase during the first few weeks of life (14, 16), we did not detect any changes in forehead sebum levels, probably because the first post-baseline assessment was at week 3, after most of the changes would have already occurred.

Establishment of a specific skin microflora is considered to be essential for maintaining immune tolerance and preventing colonization by potentially harmful microbes (2). Colonization of the skin begins immediately after birth and is dominated by staphylococci but continues to evolve over at least the first year of life. In the current study, we did not detect any differences between the groups in colonization by S. aureus, S. epidermidis, or Malassezia spp, and we did not detect C. albicans. We also did not observe any obvious differences in overall microfloral profiles. Thus, the products do not appear to affect the development of a normal skin microflora in healthy newborns and, importantly, did not appear to put the children at risk for skin infections.

The cleansing oil and skincare oil appeared safe and well tolerated. During the study, however, the no-rinse cleansing oil, used on the buttocks only, was stopped because of diaper rashes that appeared to be associated with its use. This should not have affected the main results of the study, which focused on skin properties and condition on non-diaper areas of the body. These results agree with a study by Garcia Bartels et al. (7) showing that bathing with a wash gel combined with application of a cream or application of a cream alone reduced TEWL on the front, abdomen, and upper leg and improved stratum corneum hydration on the front and abdomen compared to bathing with water, while bathing with the wash gel alone decreased pH on all sites compared to bathing with water alone. No differences in sebum level, microbiologic colonization, or skin condition score were found. The Authors concluded that the skincare regimens did not affect the physiologic neonatal skin barrier adaptation within the first 8 weeks of life.

In conclusion, the combination of skincare and cleansing oils studied here does not appear to interfere with the normal physiological development of skin properties or skin microflora in healthy full-term newborns. This combination also improves xerosis and overall skin condition compared to the cleansing oil alone. The combination of the skincare and cleansing oils should therefore provide optimal protection against skin damage and dryness in healthy full-term newborns.

Acknowledgements

Medical writing was provided by Dr. Phillip Leventhal (4Clinics, Paris, France). Medical writing and the study were funded by Pierre-Fabre Dermo-Cosmétique.

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