Comparison of the Effect of Human Milk andTopical Hydrocortisone 1% on Diaper

Dermatitis

Leila Amiri Farahani, M.Sc.,* Maryam Ghobadzadeh, M.Sc., Ph.D.,† and Parsa Yousefi, M.D.‡

*Department of Midwifery, School of Nursing and Midwifery, Arak University of Medical Sciences, Arak, Iran,†School of Public Health, University of Minnesota, Minneapolis, Minnesota, ‡Department of Pediatrics, School of

Medicine, Arak University of Medical Sciences, Arak, Iran

Abstract: Diaper dermatitis is one of the most common skin problemsin infants and children, affecting between 7% and 35% of infants. Thisrandomized clinical trial compared the efficacy of hydrocortisone 1%ointment with that of human breast milk in treating acute diaper dermatitisin infants ages 0 to 24 months. Infants with diaper rash were treated witheither hydrocortisone 1% ointment (n = 70) or human breast milk (n = 71)for 7 days. Improvement in the rash from baseline was seen in bothtreatment groups on days 3 and 7; there was no significant difference intotal rash scores on days 3 and 7. Treatment with human breast milk wasas effective as hydrocortisone 1% ointment alone. Human breast milk is aneffective and safe treatment for diaper dermatitis in infants.

Irritant diaper dermatitis is a common form ofirritation and inflammation of those parts of aninfant’s body normally covered by a diaper. Itfrequently occurs also in areas immediately adjacentto the diaper area (1). It is the most commondermatologic disorder of infancy (2,3). It has beensuggested that diaper rash is seen in 20% of pediatricdermatology consultations and that diaper dermatitisis present in 25% of all children presenting to outpa-tient departments (1,3,4). The peak incidence of diaperdermatitis is between 9 and 12 months of age (5).Several factors contribute to recurrent episodes ofdiaper dermatitis, including dietary changes frombreast milk to formula and solid foods during the first

12 months of life (3). Breastfed infants have fewerdiaper rashes than do formula-fed infants (1).

Although diaper dermatitis rarely causes persistingproblems, it can cause significant discomfort toinfants andmight cause considerable parental anxiety.Mild corticosteroids are frequently prescribed to treatdiaper dermatitis. Although certain topical cortico-steroids are approved for use in infants as young as3 months of age, the safety profile of topical corti-costeroids is an important concern in infants, partic-ularly when they are used under occlusion.Uncontrolled topical steroid treatment may haveharmful effects, including cutaneous irritation, burn-ing, and itching; steroid atrophy; steroid acne; and

Address correspondence to Maryam Ghobadzadeh, M.Sc.,Ph.D., University of Minnesota, School of Public Health, Minnea-polis, MN, USA 55455, or e-mail: ghoba001@umn.edu.

DOI: 10.1111/pde.12118

© 2013 Wiley Periodicals, Inc. 725

Pediatric Dermatology Vol. 30 No. 6 725–729, 2013

striae distensae. Long-term exogenous glucocorticoidtherapy can suppress adrenocorticoid hormone syn-thesis and reduce the need for endogenous cortisolproduction (6,7). Misuse or extensive use of topicalhigh-potency corticosteroids can cause Cushingsyndrome (8).

There are multiple lines of evidence supporting theantiinflammatory activity of human breast milk. Theimmunologic components of breast milk help toprotect the mother’s breast and the baby frominfection during feeding, as well as aiding the devel-opment of the baby’s immune system. Antimicrobialproteins naturally present in milk have the ability toinhibit or kill a broad spectrum of bacteria. Some milkcomponents can directly exert an antimicrobial effectagainst pathogens or can indirectly create unfavorableenvironmental conditions for their growth by modi-fying the commensal flora, the pH, or bacterialsubstrates. Immunoglobulin A (IgA) is the predom-inant immunoglobulin in human milk and appears toprotect breastfed infants from a variety of skininfections (9). Human milk also appears to have moregeneral antibacterial and antiviral effects. Humanmilk is a source of two classes of major growthfactors: the transforming growth factors alpha andbeta (TGF-α and TGF-β) and the insulin-like growthfactors 1 and 2 (IGF-1 and IGF-2) (10). These growthfactors promote muscle and cartilage repair and mayhave roles in wound healing (11). TGF-α and TGF-βare involved in normal cell activities such as embry-onic development, cell proliferation, and tissue repair.IGF-1 has pronounced anabolic and wound-healingcharacteristics. It slows catabolism, and it is the onlygrowth factor that can stimulate muscle growth andrepair by itself. Two conditions that can be directlyhealed by the use of breast milk are sore nipples(12–15) and conjunctivitis (15,16). In some regions ofthe world, human milk has been used topically as atreatment for conjunctivitis, and a study by Ramseyet al (17) assessed the antimicrobial capacity of humanmilk against Chlamydia trachomatis, a common agentof ophthalmia neonatorum. The results indicated thattopically applied human milk was effective in theprophylaxis of ophthalmia neonatorum of chlamydialetiology (17). A study by Chaumeil et al (18) revealedthat topically applied human milk alleviates severeeye dryness and problematic eye lesions. Becausehuman milk is free and readily available to mothersworldwide, it is important to explore the possibility ofusing human milk topically to protect infants indeveloping countries from infections. A search of theliterature found no study that compared human milkwith other diaper rash treatments. In an attempt to

find an alternative, this study was designed to com-pare the efficacy of topical hydrocortisone 1%ointment and human breast milk in the treatment ofdiaper rash.

METHODS

This study was conducted at a single center (PediatricsUnit, Amirkabir Hospital, Arak, Iran). The primaryobjective was to compare the efficacy of human breastmilk and hydrocortisone 1% ointment in terms ofseverity scores of dermatitis after 7 days of treatment.The secondary objective was to compare the severityscores after 0, 3, and 7 days.

The Research Consultant Review Committee(Arak, Iran) approved the study protocol. Eachpatientgave written informed consent before undergoing thestudy procedures. Data on demography, mothers’ andinfants’ health, and type and length of time of prenatalbreastfeeding preparation were collected from infor-mation questionnaires that the parents completed.

Infants (ages 0–24 months) with mild to moderatediaper rash were eligible for inclusion in the study.Infants with a history of allergy to hydrocortisone andthose receiving any medication that might affect theresults of the study were excluded. All parentsreceived general advice about diaper rash care,including frequent diaper changes, laying the babyon a towel without a diaper on whenever possible,patting the affected area dry or allowing it to air-dry,and gentle cleansing of the buttocks at each change.All parents were instructed to change their baby’sdiaper often and as soon as possible after the babyurinated or passed stool.

The patients were randomly assigned to receivehydrocortisone 1% in an ointment base or to usehuman breast milk on the affected area for 7 days.Parents were provided with one 28.35-g tube of studymedication and were instructed to apply the medica-tion sparingly to clinically affected areas twice a dayfor 7 days. Parents were asked to bring their childrenfor clinical reassessment on days 3 and 7 aftertreatment was begun.

The mothers assigned to use breast mild were askedto rub the hind milk (the milk at the end of feed thatis higher in fat content) gently on the affected area atthe end of each breastfeeding and let it dry beforerediapering. The presence of diaper rash was noteddaily using a 6-point scale: (0: no erythema; 1: slight,diffuse, or partial erythema; 2: marked, sharplydemarcated erythema; 3: severe erythema withoutinfiltration; 4: severe erythema with infiltration; 5:vesiculation or epidermal defects).

726 Pediatric Dermatology Vol. 30 No. 6 November/December 2013

The severity score was measured before treatmentand on days 3 and 7. Cases with a severity score of 5were excluded from the study. Parents were instructedto cleanse the diaper area of the infants followed bypat-drying. A research assistant who was blind to theintervention used on the affected areas assessed diaperdermatitis on days 0, 3, and 7. Regional skin gradeswere assessed for the anal area, buttocks, genital area,and legs.

Mothers or care providers recorded diary informa-tion daily, including diaper changes, wet diaper, andcleansing of the diaper area.

The efficacy of treatment was defined as thecomplete clearance of lesions. The study medicationand human breast milk were used for the full 7 days.No other topical medication was to be applied to therash area during the study period.

SPSS 18 (SPSS, Inc., Chicago, IL) was used forstatistical analysis. Paired t tests and the Kolmogorov–Smirnov test were used for quantitative variables, andthe chi-square test was used to examine differenceswith categorical variables.

RESULTS

We compared the effects of topical application ofhuman breast milk with those of hydrocortisone 1%ointment in the treatment of diaper rash. The meanage was 4.6 � 12.4 months in the breast milk groupand 4.7 � 11.2 months in the hydrocortisone group.Of the 150 infants enrolled in the study, 75 wererandomly assigned to the hydrocortisone 1% group

and 75 to the human breast milk group; 70 in thehydrocortisone 1% group and 71 in the breast milkgroup were evaluable.

Four of these from the breast milk group and threefrom the hydrocortisone 1% group were excludedbecause other topical drugs were applied to theaffected area (Table 1). Two participants also showedan apparent allergic reaction to hydrocortisone 1%and were therefore excluded from the study. Thenumber of daily applications was two in the hydro-cortisone 1% group and after each diaper change inthe human breast milk group.

Severity scores were not different between thegroups before the application of the topical hydro-cortisone or human breast milk (Table 2). Theprimary efficacy parameter was improvement in theseverity score after 3 days of treatment. The severityscores improved markedly with both treatments. Thisimprovement was highly significant in the within-group comparison (p < 0.001, Wilcoxon signed ranktest) for both treatments and at both time points (3and 7 days). Because the severity score decrease wasnot greater in the hydrocortisone 1% group (Table 3),the hypothesis of the superiority of hydrocortisoneover human breast milk after 3 days of treatmentcould be rejected. The chi-square test confirmed thisfinding (p = 0.95).

The positive findings for both human breast milkand hydrocortisone regarding the secondary efficacyparameter of improvement in the severity score after7 days of treatment were confirmed by statisticaltesting (p < 0.001). The chi-square test could not

TABLE 1. Severity Score Before and 3 Days After Application of Ointment Containing Hydrocortisone 1% or Human BreastMilk

Treatment

Day 3 (after initiation of intervention) Day 0

p (Wilcoxon test)0 1 2 3 1 2 3 4

Human breast milk, n (%) 9 (12.7) 38 (53.5) 20 (28.2) 4 (5.6) 5 (7) 22 (31) 27 (38) 17 (23.9) <0.001Hydrocortisone 1%, n (%) 7 (10) 37 (52.9) 22 (31.4) 4 (5.7) 7 (10) 25 (35.6) 20 (28.6) 18 (25.7) <0.001p (chi-square test) 0.95 0.66

TABLE 2. Severity Score Before and 7 Days After Application of Ointment Containing Hydrocortisone 1% or Human BreastMilk

Treatment

Day 0 Day 7

p (Wilcoxon test)1 2 3 4 0 1

Human breast milk, n (%) 5 (7) 22 (31) 27 (38) 17 (23.9) 70 (98.6) 1 (1.4) <0.001Hydrocortisone 1%, n (%) 7 (10) 25 (35.6) 20 (28.6) 18 (25.7) 70 (100) 0 (0) <0.001p (chi-square test) 0.66 0.32

Farahani et al: Human Breast Milk vs Hydrocortisone 1% 727

reject the hypothesis of no treatment difference(p = 0.32) between the interventions.

Severity scores in the hydrocortisone 1% andbreast milk groups were not significantly differentafter the application of the topical medication on days3 and 7.

DISCUSSION

Diaper dermatitis is the most common dermato-logic disorder of infancy. There have been reports ofinfants who developed iatrogenic Cushing syndromeand prolonged adrenal suppression in the course oftopical glucocorticoid therapy for simple diaperdermatitis (6,7,19). Because of the need for a safeand essentially free treatment for diaper dermatitis,this study was designed to compare the efficacy ofhydrocortisone 1% with that of human breast milk inthe treatment of diaper rash. We provide evidenceshowing that human breast milk is as effective athealing diaper rash as hydrocortisone 1% ointment.The degree of improvement in the dermatitis wassimilar at days 3 and 7 in both groups.

Breast milk had no side effects and was as effectiveas hydrocortisone 1% ointment in decreasing theseverity scores of diaper rash. Our results agree withthe findings of previous studies. Mohammadzadehand colleagues (12) compared the therapeutic effectsof lanolin with those of human breast milk on sorenipples. They recommended that mothers applyexpressed milk to the sore area and allow air-dryingof the areola. Breast milk was found to heal nipplesfaster than using lanolin (12). Hewat et al (13) alsocompared the therapeutic effect of expressed breastmilk or colostrum with that of lanolin in preventingnipple pain and trauma in the first 10 postpartum daysand found that symptom improvement was notsignificantly different between the two groups. Theantibacterial properties of these proteins make themsuitable for use in a variety of applications, includingthe prevention of sore nipples and for healing diaperrash (13). Penjvini et al (20) found that topically

applied human breast milk was effective in recoveryfrom diaper rash. They treated participants with zincoxide or human breast milk and found that there wereno significant differences between the two groups withrespect to lesion size, inflammation, or intense ery-thema. We have replicated this finding in a largercohort of infants. Furthermore, all our samples werehealthy infants, where in the previous study, partic-ipants were hospitalized because of prematurity,sepsis, gastroenteritis, or pneumonia. We have shownthe efficacy of breast milk treatment in otherwisepresumably healthy infants.

The present study found human breast milk to be ahighly effective treatment for diaper rash. Because ofthe safety and convenience of breast milk, we recom-mend its use for the treatment of diaper dermatitis ininfants.

This study was conducted at a single site. For thisreason, the external validity and consequently thegeneralizability of the findings may be decreased, andthe replication of this study with a larger data set isessential. The lack of untreated controls did not allowus to determine the natural history of untreated diaperdermatitis for comparison with both treatment arms.

ACKNOWLEDGMENTS

Special thanks are given to all who participated in thestudy. We would also like to thank the members ofthe scientific board of the Nursing and MidwiferyDepartment of Arak University of Medical Sciencesfor their help in running this study. We thank the staffat the Amirkabir hospitals for their excellent partic-ipation and collaboration.

This study was registered in the Iranian Registryof Clinical Trials (IRCT201102163869N2).

CONTRIBUTORS

LF and MG conceived and designed the study. LFcollected the data. LF and MG analyzed and inter-preted the data.MGdrafted and edited themanuscript.

TABLE 3. Severity Score on Days 3 and 7 After Application of Ointment Containing Hydrocortisone 1% and Human BreastMilk

Treatment

Day 3 (after initiation of intervention) Day 7

p (Wilcoxon test)0 1 2 3 0 1

Human breast milk, n (%) 9 (12.7) 38 (53.5) 20 (28.2) 4 (5.6) 70 (98.6) 1 (1.4) <0.001Hydrocortisone 1%, n (%) 7 (10) 37 (52.9) 22 (31.4) 4 (5.7) 70 (100) 0 (0) <0.001p (chi-square test) 0.95 0.32

728 Pediatric Dermatology Vol. 30 No. 6 November/December 2013

REFERENCES

1. Singalavanija S, Frieden IJ. Diaper dermatitis. PediatrRev 1995;16:142.

2. Weston WL, Lane AT, Weston JA. Diaper dermatitis:current concepts. Pediatrics 1980;66:532.

3. Atherton DJ. The etiology and management of irritantdiaper dermatitis. J Eur Acad Dermatol Venereol2001;15(Suppl 1):1–4.

4. Visscher MO, Chatterjee R, Munson DE et al. Devel-opment of diaper rash in the newborn. Pediatr Derma-tol 2000;17:52–57.

5. Adalt S, Wall D, Goodyea et al. Diaper dermatitis—frequency and contributory factors in hospital attend-ing children. Pediatr Dermatol 2007;24:483–488.

6. Siklar Z, Bostanci I, Atli O et al. An infantile Cushingsyndrome due to misuse of topical steroid. PediatrDermatol 2004;21:561–563.

7. Ozon A, Cetinkaya S, Alikasifoglu A et al. Inappro-priate use of potent topical glucocorticoids in infants.J Pediatric Endocrinol Metab 2007;20:219–225.

8. Hengge UR, Ruzicka T, Schwartz RA et al. Adverseeffects of topical glucocorticosteroids. J Am AcadDermatol 2006;54:1–15; quiz 16-18.

9. KramerMS, Chalmers B, Hodnett ED et al. Promotionof Breastfeeding Intervention Trial (PROBIT): a ran-domized trial in the Republic of Belarus. JAMA2001;285:413–420.

10. Ginjala V, Pakkanen R. Determination of transforminggrowth factor-beta 1 and 2 insulin-like growth factor inbovine colostrum samples. J Immunoassay 1998;19:195–207.

11. Wilson J. Immune system breakthrough: colostrum.J Longevity 1998;4:2.

12. Mohammadzadeh A, Farhat A, Habibolah E. Theeffect of breast milk and lanolin on sore nipples. SaudiMed J 2005;26:1231–1234.

13. Hewat RJ, Ellis D. A comparison of the effectiveness oftwo methods of nipple care. Birth 1987;14:1.

14. Tait P. Nipple pain in breastfeeding women: causes,treatment and prevention strategies. J MidwiferyWomens Health 2000;45:212–215.

15. Pugh LC, Buchko BL, Bishop BA et al. A comparisonof topical agents to relieve nipple pain and enhancebreastfeeding. Birth 1996;23:88–93.

16. Singh M, Sugathan PS, Bhujwala RA. Humancolostrum for prophylaxis against sticky eyes andconjunctivitis in the newborn. J Trop Pediatr1982;28:35–37.

17. Ramsey KH, Poulsen CE, Motiu PP. The in vitroantimicrobial capacity of human colostrum againstChlamydia trachomatis. J Reprod Immunol 1998;38:155–167.

18. Chaumeil C, Loitet S, Kogb O. Treatment of severe eyedryness and problematic eye lesions with enrichedbovine colostrum lactoserum. Adv Exp Med Biol1994;350:595–599.

19. Coureau B, Bussieres J-F, Tremblay S. Cushingsyndrome induced by misuse of moderate to high-potency topical corticosteroid. Ann Pharmacother2008;42:1903–1907.

20. Penjvini S, Shahsavari S, Gazerani F et al. Topical useof human breast milk for diaper rash in infants. IntJ Adv Nurs Stud 2012;1:98–108.

Farahani et al: Human Breast Milk vs Hydrocortisone 1% 729