Pediatric Dermatology Vol. 31 No. 6 683–691, 2014
Effect of Diaper Cream and Wet Wipes on Skin Barrier Properties in Infants: A Prospective Randomized Controlled Trial Natalie Garcia Bartels, M.D.,*,1 Lena L€ unnemann, M.D.,*,1 Andrea Stroux, Dipl.-Math.,† Jan Kottner, Ph.D.,* Jose Serrano, B.S.,‡ and Ulrike Blume-Peytavi, M.D.* *Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charit eUniversit€ atsmedizin Berlin, Berlin, Germany, †Department of Medical Statistics and Clinical Epidemiology, Charit e-Universit€ atsmedizin Berlin, Berlin, Germany, ‡Research and Development, Johnson & Johnson, Issy-Les-Moulineaux, France
Abstract: The effect of different diaper care procedures on skin barrier function in infants has been minimally investigated and may be assessed using objective methods. In a single-center, prospective trial, 89 healthy 9-month-old infants (8 wks) were randomly assigned to three diaper care regimens: group I used water-moistened washcloths at diaper changes (n = 30), group II additionally applied diaper cream twice daily (n = 28), and group III used wet wipes and diaper cream twice daily (n = 31). Transepidermal water loss (TEWL), skin hydration (SCH), skin pH, interleukin 1a (IL-1a) levels, and microbiologic colonization were measured in diapered skin (upper outer quadrant of the buttocks), nondiapered skin (upper leg), and if diaper dermatitis (DD) occurred, using the most affected skin area at day 1 and weeks 4 and 8. Skin condition was assessed utilizing a neonatal skin condition score and diaper rash grade. On diapered skin, SCH decreased in groups II and III, whereas TEWL values were reduced in group II only. Skin pH increased in groups II and III. In general, SCH, skin pH, and IL-1a levels were higher in healthy diapered skin than in nondiapered skin. The incidence and course of DD was comparable in all groups. Areas with DD had greater TEWL and skin pH than unaffected skin areas. Infants who received diaper cream had lower SCH and TEWL and higher pH levels in the diapered area than on nondiapered skin. No correlation with the occurrence of DD was found.
Address correspondence to N. Garcia Bartels, M.D., Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science, Chariteplatz 1, Charite-Universit€atsmedizin Berlin, 10117 Berlin, or e-mail: [email protected]. 1 These authors contributed equally to the manuscript. DOI: 10.1111/pde.12370
© 2014 Wiley Periodicals, Inc.
683
684 Pediatric Dermatology Vol. 31 No. 6 November/December 2014
When evaluating the effectiveness of daily skin care in young infants, objective and noninvasive methods are useful to characterize the distinct influences of products on barrier function and clinical course (1–5). Limited scientific data are available regarding the effect of currently available diaper care products on infants with regards to skin barrier function and condition (4–6). Because maturation of the epidermal barrier continues beyond the neonatal period and varies by body site, diapered and nondiapered skin may be evaluated in parallel to understand the specific effects of diaper care products (2,7–9). Skin barrier maturation is reflected by changes in skin functional parameters such as transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin surface pH (2,3,8,10,11). A disturbed balance of these parameters seems to influence the development of inflammatory skin reactions and may result in diaper dermatitis (DD) (12,13), thus diaper care procedures should aim at supporting skin barrier function (2,11). Recently, research in diaper technology has been aimed at increased skin surface dryness for prevention of DD (13). Evidence-based cleansing procedures with disposable wipes or a washcloth have been recommended as skin barrier maturation remained physiological (6,10,14), but little is known about the effect of diaper creams or wet wipes with creams on skin barrier function in infants (13). In this trial we investigated the skin barrier function of diapered and nondiapered skin and areas irritated by DD in healthy infants using three standardized diaper care regimens including wet wipes and diaper cream.
METHODS Aim of the Study and Outcome Variables The trial investigated the use of daily wet wipes or water-moistened washcloths and diaper cream in the diaper area. The primary outcome variable was TEWL. Secondary outcome variables were pH, SCH, interleukin 1a (IL-1a) level, neonatal skin condition score (NSCS), and diaper rash grade (DRG) (1–3,11,14). Nondiapered skin was measured to evaluate the effect of a standardized twice-weekly skin care regimen. Study Site and Population A single-center, prospective, randomized trial was conducted from November 2010 to April 2012 at the Clinical Research Center for Hair and Skin Science (CRC), Charite-Universit€ atsmedizin Berlin. The local
ethics committee approved the trial. Healthy infants ages 9 months (8 wks) were enrolled. Immunocompromised infants and infants with severe illness, congenital disorders, contagious or irritated skin affecting measurements, current or previous atopic dermatitis (AD) in both parents, or acute or chronic illness with high or low body temperature and those participating in another study were excluded. Clinical Procedures A physician enrolled eligible infants after obtaining informed consent from both guardians and randomly assigned them to three diaper care regimens: group I (n = 30) received cleansing with water-moistened washcloths at each diaper change, group II (n = 28) received cleansing like group I and diaper cream twice per day, and group III (n = 31) received cleansing with wet wipes at each diaper change and diaper cream like group II. Parents were advised to wash the watermoistened washcloths at 60°C in the washing machine without using any fabric softener. Wet wipes (Penaten Baby-Lotiont€ ucher, Johnson & Johnson, Neuss, Germany) and cotton washcloths were used. All participants were supplied with the same diapers (Pampers, Procter & Gamble, Euskirchen, Germany) in the appropriate size. The trial statistician generated block randomization. To avoid concealment bias, sealed, opaque envelopes were used for group assignment. Participating parents and physicians were aware of the allocated study arm, whereas outcome assessors and data analysts were blinded to allocation, not knowing skin care regimens according to group. In addition to group-specific diaper care, the twice-weekly skin care (2,15) for all groups included bathing with a baby cleanser (Penaten Baby Bad & Shampoo, Johnson & Johnson) and applying baby lotion after bathing (Penaten Baby Intensiv Lotion, Johnson & Johnson) except for the diaper region. If DD occurred, zinc paste or Candio-Hermal paste (Allmirall Hermal, Reinbeck, Germany) was provided. For ingredients, see Appendix 1. Clinical Evaluations Clinical measurements were performed at inclusion (week 0 [W0]), week 4 (W4), and week 8 (W8) at the CRC. Diapers were removed 10 minutes before measurements. The minimum duration between last diaper change and measurements was 1 hour; bathing or skin care was allowed 12 hours before measurements. A minimum of four diaper changes every 24 hours was required, and if DD occurred, a topical
Bartels et al: Effect of Diaper Care on Infantile Skin Barrier 685
therapy was allowed on the affected areas as needed. Ambient conditions were standardized (temperature 22°C–26°C, relative humidity 40%–60%). During the study period, DD occurred in the perianal and genital area but not in the investigational areas, that is, the outer upper quadrant of the buttock (diapered area) and the upper leg (nondiapered area). When DD occurred, extra measurements were made in the affected area. Skin condition was evaluated using a modified NSCS (2,3,11) and in the diaper area using a modified DRG (1) (7-point scale; none = 0, severe = 3). Clinically relevant DD was defined as a DRG of 1.5 or greater. Parents were advised to document in a diary any changes in skin care and the health status of the infant, which they were given and was explained at the inclusion visit. The investigator verified diary entries at each visit. TEWL, SCH, and skin pH were measured using a Tewameter TM 300, a Corneometer CM 825, and a skin pH meter PH 905, respectively (Courage & Khazaka, Cologne, Germany), according to standardized protocols (2,14). IL-1a was determined using a modified Sebutape extraction method (CuDerm, Dallas, TX) (14,16). Cytokine levels were expressed as picograms of IL-1a per microgram of total protein load on the tapes (pg IL-1a/lg TP). Microbiologic swabs were taken on perianal and umbilical areas (W0– W8). Candida and bacteria were recorded as positive or negative colonization without subspecies identification (2,14). Statistical Methods For data description, absolute and relative frequencies were presented for categorial variables and means, standard deviations, medians, and ranges for quantitative measurements. Depending on the scaling structure, univariate group comparisons were performed using the chi-square test, Mann–Whitney U test, or Kruskal–Wallis test for overall comparisons. Differences between visits or different body regions were analyzed using the McNemar test or Wilcoxon signed-rank test. Correlation analyses were performed using Spearman correlation coefficients. Hypotheses were tested on a two-sided a level of 0.05; no Bonferroni correction was applied. Statistical calculations were performed using SPSS version 20.0 (SPSS, Chicago, IL). Sample size calculation was based on the mean differences of the primary endpoint TEWL; with 26 infants per group and a power of 80%, a difference in means of 4 (SD = 5) can be
shown on a two-sided significance level of a = 0.05. Assuming a dropout rate of 10% to 15%, a sample size of 90 (30 per group) infants was deemed necessary. Sample size calculation was performed using the commercially available software nQuery 6.0 (Statistical Solutions, Cork, Ireland).
RESULTS Participants Eighty-nine infants with comparable characteristics (Table 1), functional parameters, IL-1a levels, microbiologic colonization, and clinical scores at baseline were enrolled. Six dropouts occurred after the first visit because of nonadherence and AD, leaving 83 participants, who did not differ from those who dropped out in terms of age, birth age, and sex (Fig. 1). Age and birth age did not differ significantly between the study groups or between infants with and without DD. No correlation was found between age and birth age and skin functional parameters. Functional skin parameters developed differently in healthy diapered skin depending on the applied diaper care regimen. Areas with DD had high DRGs and impaired skin barrier function (Table 2). Functional Parameters in Healthy Diapered and Nondiapered Skin In group II, TEWL decreased significantly in diapered areas with healthy skin between W0 and W8 (Fig. 2) and remained stable in groups I and III. Significantly lower TEWL was found in diapered skin than in nondiapered skin after 8 weeks for the entire sample (Fig. 2, Table 2). In nondiapered skin, TEWL remained stable in groups I and III and decreased significantly in group II from W0 to W4 and W8 (Fig. 3). SCH decreased significantly (p < 0.03) in groups II and III on healthy, diapered skin between W0 and W8, whereas in group I a trend of SCH decrease (p = 0.06) was observed (Fig. 4). In nondiapered skin, SCH values remained stable in all groups (Table 2). At all visits, significantly higher SCH was found in healthy diapered areas than in nondiapered areas (Table 2). In groups II and III, skin pH increased significantly in diapered skin from W0 to W4 and W8 and remained stable in group I (Fig. 5). Skin pH at W4 and W8 was significantly higher in diapered skin than in nondiapered skin, which remained stable in all groups (Table 2).
686 Pediatric Dermatology Vol. 31 No. 6 November/December 2014
TABLE 1. Baseline Characteristics of Enrolled Infants (n = 89) in Diaper Care Groups Characteristic
I (n = 30)
II (n = 28)
III (n = 31)
Female, n (%) Age at birth, weeks of pregnancy, mean (range) Birthweight, g, mean (range) Body length at birth, cm, mean (range) Head circumference at birth, cm, mean (range) Spontaneous delivery, n (%) Caesarean section, (%) Fitzpatrick skin type, n (%) I II III IV V Parents Caucasian, n (%) Both One Neither Atopic dermatitis mother, n (%) Atopic dermatitis father, n (%) Allergic rhinitis mother, n (%) Allergic rhinitis father, n (%) Asthma mother, n (%) Asthma father, n (%) Breastfeeding and mash, n (%) Mash only, n (%) Mash, solid food, and milk, n (%) Milk and mash, n (%)
18 (60) 39 (35–42) 3,442 (2,460–4,068) 51 (46–55) 35 (33–37) 22 (73.3) 8 (26.7)
17 (60.7) 39 (35–41) 3,433 (2,200–4,320) 52 (45–55) 35 (30–38) 21 (75.0) 7 (25.5)
16 (51.6) 39 (38–42) 3,370 (2,460–4,090) 52 (47–55) 35 (32.5–38) 21 (67.7) 10 (32.3)
6 (20) 14 (46.7) 9 (30) 1 (3.3) 0 (0)
5 (17.9) 16 (57.1) 6 (21.4) 0 (0) 1 (3.6)
5 (16.1) 15 (48.4) 9 (29) 2 (6.5) 0 (0)
24 (80.0) 4 (13.3) 2 (6.7) 4 (13.3) 2 (6.7) 8 (26.7) 5 (16.7) 1 (3.3) 0 (0) 23 (76.7) 0 (0) 5 (16.7) 2 (6.7)
25 (89.3) 3 (10.7) 0 (0) 4 (14.3) 0 (0) 9 (32.1) 6 (21.4) 2 (7.1) 1 (3.6) 18 (64.3) 1 (3.6) 7 (25) 2 (7.1)
26 (83.9) 4 (13.3) 0 (0) 2 (6.5) 2 (6.5) 10 (32.3) 8 (25.8) 1 (3.2) 4 (12.9) 15 (48.4) 2 (6.5) 5 (16.1) 9 (29.0)
Group I: cleansing with water-moistened washcloths; group II: cleansing with water-moistened washcloths and application of diaper cream twice daily; group III: cleansing with wet wipes and application of diaper cream twice daily.
During the study, the area with DD was too small to reach the investigational areas (diapered or nondiapered areas). Therefore no DD was found on the upper quadrant of the buttock (diapered skin) or the leg (nondiapered skin), as reflected by physiologic NSCS values in these areas (3.1 0.1; 3.0 0.3). DD and Corresponding Skin Parameters DD occurred only in the perianal and genital areas during the study period. This investigational area was called the “affected area” because it was not located on the defined areas for diapered or nondiapered skin, which remained unaffected during the study. TEWL and pH were significantly higher in areas with DD than in unaffected skin in all groups at W4 and W8 (Table 2); SCH levels were not significantly higher (Table 2). A DRG of 1.5 or greater was present in six infants at W0, seven at W4, and eight at W8. One infant had a DRG of 1.5 twice, at W4 and W8 (group III). Another child in group III had a DRG of 1.5 at W4 and W8. IL-1a measurements were assessed in selected DD cases (n = 12) and were comparable with those in unaffected areas (Fig. 6).
Stratum Corneum Levels of IL-1a IL-1a was significantly higher in diapered than nondiapered skin (Fig. 6). All groups had comparable IL-1a levels in nondiapered areas. Diapered skin revealed stable levels of IL-1a until W8 in groups II and III; a decrease occurred in group I between W0 and W4 (p = 0.02) and then remained unchanged until W8 (Fig. 6). Microbiologic Colonization Bacterial colonization was present in the perianal region (90–96%) and umbilicus (59–65%), with no differences between groups. Candida colonization of the perianal area was rarely present (W0, n = 1; W4, n = 2; W8, n = 3). DISCUSSION Quantification of clinical signs and monitoring of skin barrier function is helpful to understanding the effect of diaper care in infants (5). Several factors may cause barrier compromise in diapered skin, which may result in DD (17–19). Skin barrier function has been
Bartels et al: Effect of Diaper Care on Infantile Skin Barrier 687
Figure 1. Flow diagram.
TABLE 2. Skin Physiologic Measurements in Diapered Areas and Nondiapered Areas (n = 83) and Diaper Dermatitis Affected Areas Week 0
*n = 6. †n = 7. ‡n = 8.
Week 8
Mean standard deviation (range)
Body Area Transepidermal water loss, g/m2/h Diapered Nondiapered p-value diapered vs nondiapered Affected p-value affected vs diapered p-value affected vs nondiapered Stratum corneum hydration, U Diapered Nondiapered p-value diapered vs nondiapered Affected p-value affected vs diapered p-value affected vs nondiapered pH, U Diapered Nondiapered p-value diapered vs nondiapered Affected p-value affected vs diapered p-value affected vs nondiapered
Week 4
12.0 8.1 (4.0–75.2) 11.8 4.0 (5.9–29.0) 0.52 25.6 16.7 (5.7–51.0)* 0.12 0.12
10.3 4.0 (4.8–25.0) 10.3 2.6 (4.8–18.1) 0.26 33.3 9.2 (22.6–43.7)† 0.02 0.02
9.5 2.2 (4.0–16.1) 10.5 3.1 (5.8–23.5) 0.02 34.0 15.7 (19.2–67.4)‡ 0.008 0.008
44.6 12.2 (21.1–85.7) 34.5 9.4 (12.0–47.7)
Effect of Diaper Cream and Wet Wipes on Skin Barrier Properties in Infants: A Prospective Randomized Controlled Trial Natalie Garcia Bartels, M.D.,*,1 Lena L€ unnemann, M.D.,*,1 Andrea Stroux, Dipl.-Math.,† Jan Kottner, Ph.D.,* Jose Serrano, B.S.,‡ and Ulrike Blume-Peytavi, M.D.* *Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charit eUniversit€ atsmedizin Berlin, Berlin, Germany, †Department of Medical Statistics and Clinical Epidemiology, Charit e-Universit€ atsmedizin Berlin, Berlin, Germany, ‡Research and Development, Johnson & Johnson, Issy-Les-Moulineaux, France
Abstract: The effect of different diaper care procedures on skin barrier function in infants has been minimally investigated and may be assessed using objective methods. In a single-center, prospective trial, 89 healthy 9-month-old infants (8 wks) were randomly assigned to three diaper care regimens: group I used water-moistened washcloths at diaper changes (n = 30), group II additionally applied diaper cream twice daily (n = 28), and group III used wet wipes and diaper cream twice daily (n = 31). Transepidermal water loss (TEWL), skin hydration (SCH), skin pH, interleukin 1a (IL-1a) levels, and microbiologic colonization were measured in diapered skin (upper outer quadrant of the buttocks), nondiapered skin (upper leg), and if diaper dermatitis (DD) occurred, using the most affected skin area at day 1 and weeks 4 and 8. Skin condition was assessed utilizing a neonatal skin condition score and diaper rash grade. On diapered skin, SCH decreased in groups II and III, whereas TEWL values were reduced in group II only. Skin pH increased in groups II and III. In general, SCH, skin pH, and IL-1a levels were higher in healthy diapered skin than in nondiapered skin. The incidence and course of DD was comparable in all groups. Areas with DD had greater TEWL and skin pH than unaffected skin areas. Infants who received diaper cream had lower SCH and TEWL and higher pH levels in the diapered area than on nondiapered skin. No correlation with the occurrence of DD was found.
Address correspondence to N. Garcia Bartels, M.D., Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science, Chariteplatz 1, Charite-Universit€atsmedizin Berlin, 10117 Berlin, or e-mail: [email protected]. 1 These authors contributed equally to the manuscript. DOI: 10.1111/pde.12370
© 2014 Wiley Periodicals, Inc.
683
684 Pediatric Dermatology Vol. 31 No. 6 November/December 2014
When evaluating the effectiveness of daily skin care in young infants, objective and noninvasive methods are useful to characterize the distinct influences of products on barrier function and clinical course (1–5). Limited scientific data are available regarding the effect of currently available diaper care products on infants with regards to skin barrier function and condition (4–6). Because maturation of the epidermal barrier continues beyond the neonatal period and varies by body site, diapered and nondiapered skin may be evaluated in parallel to understand the specific effects of diaper care products (2,7–9). Skin barrier maturation is reflected by changes in skin functional parameters such as transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin surface pH (2,3,8,10,11). A disturbed balance of these parameters seems to influence the development of inflammatory skin reactions and may result in diaper dermatitis (DD) (12,13), thus diaper care procedures should aim at supporting skin barrier function (2,11). Recently, research in diaper technology has been aimed at increased skin surface dryness for prevention of DD (13). Evidence-based cleansing procedures with disposable wipes or a washcloth have been recommended as skin barrier maturation remained physiological (6,10,14), but little is known about the effect of diaper creams or wet wipes with creams on skin barrier function in infants (13). In this trial we investigated the skin barrier function of diapered and nondiapered skin and areas irritated by DD in healthy infants using three standardized diaper care regimens including wet wipes and diaper cream.
METHODS Aim of the Study and Outcome Variables The trial investigated the use of daily wet wipes or water-moistened washcloths and diaper cream in the diaper area. The primary outcome variable was TEWL. Secondary outcome variables were pH, SCH, interleukin 1a (IL-1a) level, neonatal skin condition score (NSCS), and diaper rash grade (DRG) (1–3,11,14). Nondiapered skin was measured to evaluate the effect of a standardized twice-weekly skin care regimen. Study Site and Population A single-center, prospective, randomized trial was conducted from November 2010 to April 2012 at the Clinical Research Center for Hair and Skin Science (CRC), Charite-Universit€ atsmedizin Berlin. The local
ethics committee approved the trial. Healthy infants ages 9 months (8 wks) were enrolled. Immunocompromised infants and infants with severe illness, congenital disorders, contagious or irritated skin affecting measurements, current or previous atopic dermatitis (AD) in both parents, or acute or chronic illness with high or low body temperature and those participating in another study were excluded. Clinical Procedures A physician enrolled eligible infants after obtaining informed consent from both guardians and randomly assigned them to three diaper care regimens: group I (n = 30) received cleansing with water-moistened washcloths at each diaper change, group II (n = 28) received cleansing like group I and diaper cream twice per day, and group III (n = 31) received cleansing with wet wipes at each diaper change and diaper cream like group II. Parents were advised to wash the watermoistened washcloths at 60°C in the washing machine without using any fabric softener. Wet wipes (Penaten Baby-Lotiont€ ucher, Johnson & Johnson, Neuss, Germany) and cotton washcloths were used. All participants were supplied with the same diapers (Pampers, Procter & Gamble, Euskirchen, Germany) in the appropriate size. The trial statistician generated block randomization. To avoid concealment bias, sealed, opaque envelopes were used for group assignment. Participating parents and physicians were aware of the allocated study arm, whereas outcome assessors and data analysts were blinded to allocation, not knowing skin care regimens according to group. In addition to group-specific diaper care, the twice-weekly skin care (2,15) for all groups included bathing with a baby cleanser (Penaten Baby Bad & Shampoo, Johnson & Johnson) and applying baby lotion after bathing (Penaten Baby Intensiv Lotion, Johnson & Johnson) except for the diaper region. If DD occurred, zinc paste or Candio-Hermal paste (Allmirall Hermal, Reinbeck, Germany) was provided. For ingredients, see Appendix 1. Clinical Evaluations Clinical measurements were performed at inclusion (week 0 [W0]), week 4 (W4), and week 8 (W8) at the CRC. Diapers were removed 10 minutes before measurements. The minimum duration between last diaper change and measurements was 1 hour; bathing or skin care was allowed 12 hours before measurements. A minimum of four diaper changes every 24 hours was required, and if DD occurred, a topical
Bartels et al: Effect of Diaper Care on Infantile Skin Barrier 685
therapy was allowed on the affected areas as needed. Ambient conditions were standardized (temperature 22°C–26°C, relative humidity 40%–60%). During the study period, DD occurred in the perianal and genital area but not in the investigational areas, that is, the outer upper quadrant of the buttock (diapered area) and the upper leg (nondiapered area). When DD occurred, extra measurements were made in the affected area. Skin condition was evaluated using a modified NSCS (2,3,11) and in the diaper area using a modified DRG (1) (7-point scale; none = 0, severe = 3). Clinically relevant DD was defined as a DRG of 1.5 or greater. Parents were advised to document in a diary any changes in skin care and the health status of the infant, which they were given and was explained at the inclusion visit. The investigator verified diary entries at each visit. TEWL, SCH, and skin pH were measured using a Tewameter TM 300, a Corneometer CM 825, and a skin pH meter PH 905, respectively (Courage & Khazaka, Cologne, Germany), according to standardized protocols (2,14). IL-1a was determined using a modified Sebutape extraction method (CuDerm, Dallas, TX) (14,16). Cytokine levels were expressed as picograms of IL-1a per microgram of total protein load on the tapes (pg IL-1a/lg TP). Microbiologic swabs were taken on perianal and umbilical areas (W0– W8). Candida and bacteria were recorded as positive or negative colonization without subspecies identification (2,14). Statistical Methods For data description, absolute and relative frequencies were presented for categorial variables and means, standard deviations, medians, and ranges for quantitative measurements. Depending on the scaling structure, univariate group comparisons were performed using the chi-square test, Mann–Whitney U test, or Kruskal–Wallis test for overall comparisons. Differences between visits or different body regions were analyzed using the McNemar test or Wilcoxon signed-rank test. Correlation analyses were performed using Spearman correlation coefficients. Hypotheses were tested on a two-sided a level of 0.05; no Bonferroni correction was applied. Statistical calculations were performed using SPSS version 20.0 (SPSS, Chicago, IL). Sample size calculation was based on the mean differences of the primary endpoint TEWL; with 26 infants per group and a power of 80%, a difference in means of 4 (SD = 5) can be
shown on a two-sided significance level of a = 0.05. Assuming a dropout rate of 10% to 15%, a sample size of 90 (30 per group) infants was deemed necessary. Sample size calculation was performed using the commercially available software nQuery 6.0 (Statistical Solutions, Cork, Ireland).
RESULTS Participants Eighty-nine infants with comparable characteristics (Table 1), functional parameters, IL-1a levels, microbiologic colonization, and clinical scores at baseline were enrolled. Six dropouts occurred after the first visit because of nonadherence and AD, leaving 83 participants, who did not differ from those who dropped out in terms of age, birth age, and sex (Fig. 1). Age and birth age did not differ significantly between the study groups or between infants with and without DD. No correlation was found between age and birth age and skin functional parameters. Functional skin parameters developed differently in healthy diapered skin depending on the applied diaper care regimen. Areas with DD had high DRGs and impaired skin barrier function (Table 2). Functional Parameters in Healthy Diapered and Nondiapered Skin In group II, TEWL decreased significantly in diapered areas with healthy skin between W0 and W8 (Fig. 2) and remained stable in groups I and III. Significantly lower TEWL was found in diapered skin than in nondiapered skin after 8 weeks for the entire sample (Fig. 2, Table 2). In nondiapered skin, TEWL remained stable in groups I and III and decreased significantly in group II from W0 to W4 and W8 (Fig. 3). SCH decreased significantly (p < 0.03) in groups II and III on healthy, diapered skin between W0 and W8, whereas in group I a trend of SCH decrease (p = 0.06) was observed (Fig. 4). In nondiapered skin, SCH values remained stable in all groups (Table 2). At all visits, significantly higher SCH was found in healthy diapered areas than in nondiapered areas (Table 2). In groups II and III, skin pH increased significantly in diapered skin from W0 to W4 and W8 and remained stable in group I (Fig. 5). Skin pH at W4 and W8 was significantly higher in diapered skin than in nondiapered skin, which remained stable in all groups (Table 2).
686 Pediatric Dermatology Vol. 31 No. 6 November/December 2014
TABLE 1. Baseline Characteristics of Enrolled Infants (n = 89) in Diaper Care Groups Characteristic
I (n = 30)
II (n = 28)
III (n = 31)
Female, n (%) Age at birth, weeks of pregnancy, mean (range) Birthweight, g, mean (range) Body length at birth, cm, mean (range) Head circumference at birth, cm, mean (range) Spontaneous delivery, n (%) Caesarean section, (%) Fitzpatrick skin type, n (%) I II III IV V Parents Caucasian, n (%) Both One Neither Atopic dermatitis mother, n (%) Atopic dermatitis father, n (%) Allergic rhinitis mother, n (%) Allergic rhinitis father, n (%) Asthma mother, n (%) Asthma father, n (%) Breastfeeding and mash, n (%) Mash only, n (%) Mash, solid food, and milk, n (%) Milk and mash, n (%)
18 (60) 39 (35–42) 3,442 (2,460–4,068) 51 (46–55) 35 (33–37) 22 (73.3) 8 (26.7)
17 (60.7) 39 (35–41) 3,433 (2,200–4,320) 52 (45–55) 35 (30–38) 21 (75.0) 7 (25.5)
16 (51.6) 39 (38–42) 3,370 (2,460–4,090) 52 (47–55) 35 (32.5–38) 21 (67.7) 10 (32.3)
6 (20) 14 (46.7) 9 (30) 1 (3.3) 0 (0)
5 (17.9) 16 (57.1) 6 (21.4) 0 (0) 1 (3.6)
5 (16.1) 15 (48.4) 9 (29) 2 (6.5) 0 (0)
24 (80.0) 4 (13.3) 2 (6.7) 4 (13.3) 2 (6.7) 8 (26.7) 5 (16.7) 1 (3.3) 0 (0) 23 (76.7) 0 (0) 5 (16.7) 2 (6.7)
25 (89.3) 3 (10.7) 0 (0) 4 (14.3) 0 (0) 9 (32.1) 6 (21.4) 2 (7.1) 1 (3.6) 18 (64.3) 1 (3.6) 7 (25) 2 (7.1)
26 (83.9) 4 (13.3) 0 (0) 2 (6.5) 2 (6.5) 10 (32.3) 8 (25.8) 1 (3.2) 4 (12.9) 15 (48.4) 2 (6.5) 5 (16.1) 9 (29.0)
Group I: cleansing with water-moistened washcloths; group II: cleansing with water-moistened washcloths and application of diaper cream twice daily; group III: cleansing with wet wipes and application of diaper cream twice daily.
During the study, the area with DD was too small to reach the investigational areas (diapered or nondiapered areas). Therefore no DD was found on the upper quadrant of the buttock (diapered skin) or the leg (nondiapered skin), as reflected by physiologic NSCS values in these areas (3.1 0.1; 3.0 0.3). DD and Corresponding Skin Parameters DD occurred only in the perianal and genital areas during the study period. This investigational area was called the “affected area” because it was not located on the defined areas for diapered or nondiapered skin, which remained unaffected during the study. TEWL and pH were significantly higher in areas with DD than in unaffected skin in all groups at W4 and W8 (Table 2); SCH levels were not significantly higher (Table 2). A DRG of 1.5 or greater was present in six infants at W0, seven at W4, and eight at W8. One infant had a DRG of 1.5 twice, at W4 and W8 (group III). Another child in group III had a DRG of 1.5 at W4 and W8. IL-1a measurements were assessed in selected DD cases (n = 12) and were comparable with those in unaffected areas (Fig. 6).
Stratum Corneum Levels of IL-1a IL-1a was significantly higher in diapered than nondiapered skin (Fig. 6). All groups had comparable IL-1a levels in nondiapered areas. Diapered skin revealed stable levels of IL-1a until W8 in groups II and III; a decrease occurred in group I between W0 and W4 (p = 0.02) and then remained unchanged until W8 (Fig. 6). Microbiologic Colonization Bacterial colonization was present in the perianal region (90–96%) and umbilicus (59–65%), with no differences between groups. Candida colonization of the perianal area was rarely present (W0, n = 1; W4, n = 2; W8, n = 3). DISCUSSION Quantification of clinical signs and monitoring of skin barrier function is helpful to understanding the effect of diaper care in infants (5). Several factors may cause barrier compromise in diapered skin, which may result in DD (17–19). Skin barrier function has been
Bartels et al: Effect of Diaper Care on Infantile Skin Barrier 687
Figure 1. Flow diagram.
TABLE 2. Skin Physiologic Measurements in Diapered Areas and Nondiapered Areas (n = 83) and Diaper Dermatitis Affected Areas Week 0
*n = 6. †n = 7. ‡n = 8.
Week 8
Mean standard deviation (range)
Body Area Transepidermal water loss, g/m2/h Diapered Nondiapered p-value diapered vs nondiapered Affected p-value affected vs diapered p-value affected vs nondiapered Stratum corneum hydration, U Diapered Nondiapered p-value diapered vs nondiapered Affected p-value affected vs diapered p-value affected vs nondiapered pH, U Diapered Nondiapered p-value diapered vs nondiapered Affected p-value affected vs diapered p-value affected vs nondiapered
Week 4
12.0 8.1 (4.0–75.2) 11.8 4.0 (5.9–29.0) 0.52 25.6 16.7 (5.7–51.0)* 0.12 0.12
10.3 4.0 (4.8–25.0) 10.3 2.6 (4.8–18.1) 0.26 33.3 9.2 (22.6–43.7)† 0.02 0.02
9.5 2.2 (4.0–16.1) 10.5 3.1 (5.8–23.5) 0.02 34.0 15.7 (19.2–67.4)‡ 0.008 0.008
44.6 12.2 (21.1–85.7) 34.5 9.4 (12.0–47.7)
