Effect of Sunscreen and Clothing on the Number of Melanocytic Nevi in 1,812 German Children Attending Day Care

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1 American Journal of Epidemiology Copyright ª 2005 by the Johns Hopkins Bloomberg School of Public Health All rights reserved Vol. 161, No. 7 Printed in U.S.A. DOI: /aje/kwi086 Effect of Sunscreen and Clothing on the Number of Melanocytic Nevi in 1,812 German Children Attending Day Care Jürgen Bauer 1, Petra Büttner 2, Tine Sander Wiecker 1, Heike Luther 3, and Claus Garbe 1,2 1 Department of Dermatology, Faculty of Medicine, Eberhard-Karls-University, Tübingen, Germany. 2 Skin Cancer Research Group, School of Public Health and Tropical Medicine, James Cook University, Townsville, Australia. 3 Department of Dermatology, Faculty of Medicine, Ruhr-University, Bochum, Germany. Received for publication May 4, 2004; accepted for publication November 11, The number of melanocytic nevi is the most important risk factor for cutaneous melanoma. This 1998 crosssectional study of 1,812 children aged 2 7 years from 78 day-care centers in Germany analyzed the protective effect of sunscreen and clothing on the number of melanocytic nevi. Total body nevi were counted, and pigmentary features were assessed. Parents underwent a standardized interview concerning their children s sun exposure and sun-protective behavior. Almost 95% of the children had used sunscreen previously. Children who used sunscreen and wore more clothing spent significantly longer periods on holidays in sunny climates (p < and p , respectively) and had a higher outdoor activity score at home (p < and p , respectively). Multivariate analysis adjusted for confounders showed no significant protective effects of applying sunscreen. Examination of the potential protective effect of clothing revealed an inverse dose-response correlation between the number of clothes worn at the beach or outdoor swimming pool and the number of melanocytic nevi (p < 0.001, adjusted for confounding). Randomized controlled trials are needed to confirm these results. Meanwhile, public education should aim to protect children primarily by sun avoidance and protective clothing, while sunscreen should also be used. child; clothing; health behavior; melanoma; nevus, pigmented; sunlight; sunscreening agents Abbreviations: CI, confidence interval; IQR, interquartile range; SPF, sun-protection factor. Numerous studies have investigated host factors such as the number of melanocytic nevi, skin type, and freckling (1 4), as well as environmental factors (5 8), with regard to their impact on the risk of developing cutaneous melanoma. Exposure to ultraviolet light in childhood and during adulthood was found to be the central environmental risk factor for cutaneous melanoma (9 11). Sun-protective behavior such as the use of sunscreen is intended to avoid sunburn and reduce cutaneous melanoma risk. However, it is unclear whether sunscreen use is indeed protective. Case-control studies focusing on the effect of sunscreen use on the risk of cutaneous melanoma have reported contrasting results ranging from a reduced risk (12 15), to an unchanged risk (16), to an increased risk for persons using sunscreen (8, 17 21). Most of these case-control studies were hospital based and may not have been comprehensively controlled for exposure to sunlight. In addition, these studies could have been biased by lack of control for skin type and were most likely influenced by recall bias. Recently published meta-analyses of studies on the relation between sunscreen use and the risk of cutaneous melanoma did not establish any association (22 25). The number of melanocytic nevi is known to be the strongest risk factor for cutaneous melanoma, and melanocytic nevi are direct precursor lesions of a substantial proportion (varying between 20 percent and 60 percent) of cutaneous melanoma (1). Humans develop melanocytic nevi from an early age onward, and numerous studies have investigated the Correspondence to Dr. Jürgen Bauer, Department of Dermatology, University of Tübingen, Liebermeisterstr. 25, Tübingen, Germany ( mail@j-bauer.de). 620

2 Impact of Sun Protection on Young German Children 621 development of melanocytic nevi in children (9, 26 33). There are advantages to studying the sun-protective behavior of children and its relation to melanocytic nevi because recall bias should be reduced. To date, investigations of sunprotective behavior in children have been unable to convincingly conclude whether sunscreen has a harmful (34, 35), protective (36), or no effect. In view of these contradictory results, more studies on the association between sun-protective behavior and the development of melanocytic nevi and cutaneous melanoma seem warranted. Results of the present risk factor study of 1,812 German children attending day care that investigated the effects of sun exposure and host factors on the development of melanocytic nevi have been reported previously (30). The present analysis focused on the associations of the use of sunscreen and protective clothing with the number of melanocytic nevi in German children 2 7 years of age. MATERIALS AND METHODS Participants From March to October 1998, baseline assessment for a randomized controlled trial investigating the impact of sunscreens on incident melanocytic nevi in German children aged 2 7 years was conducted. At study initiation, 2,440 children from 81 day-care centers were eligible. Three daycare centers (81 children) declined participation. Children were recruited from 49 day-care centers in Stuttgart and 29 in Bochum, and the day-care centers were randomly selected from different suburbs of the two cities. Some children were excluded from this study for various reasons. For example, parents of 436 children did not give their written consent to the study. Thirty-six children were ill or on holidays at baseline examination, or their parents did not attend the educational session. No physical examination was available for 31 children. Children with skin types V and VI (37) (non-caucasian; 40 children) and for whom information on age (four children) was missing were also excluded from the analysis. Thus, the present cross-sectional analysis was based on a total of 1,812 children (overall response rate, 74.3 percent). Standardized interviews of parents Before the physical examinations of the children were conducted, the parents who were present (most frequently the mothers) were given a questionnaire. Information was obtained about the residential history of the child, the ethnic origins of the parents, possible family history of cutaneous melanoma, the highest level of education of the parents, and the current occupation of the parents. Patterns of sun exposure of the child from birth to the present were assessed, including usual activities during the summer at home, history of vacations, and history and severity of sunburns. Parents were asked about the sun-protection practices used for their child regarding items of clothing worn at the beach or outdoor swimming pool, the pattern of sunscreen use, and the sun-protection factor (SPF) of the sunscreen applied. The following scores were calculated: 1. A summary score for the extent (face, anterior trunk, shoulders and back, upper extremities, and lower extremities) and frequency (never 5 0, sometimes 5 1, or almost always 5 2) of sunscreen use. The resulting score ranged between 0 (no use of sunscreen) and 10 (highest sunscreen use). 2. A summary score for clothing worn at the beach or outdoor swimming pool (swimsuit/trunks, T-shirt, and shorts) ranging between 0 (no clothes worn) to 3 (swimsuit/trunks, T-shirt, and shorts). Two-piece bathing suits were classified as 1. Frequency of use was not incorporated into the clothing score. 3. A score combining sunscreen use (never/yes) and clothing worn at the beach or outdoor swimming pool (none/swimsuit/t-shirt/shorts) was defined, ranging from 0 (no sun protection) to 7 (sunscreen, swimsuit, T-shirt, and shorts). 4. A home activity score was calculated by considering the following activities during summer: playing ball, sunbathing, swimming outdoors, playing outdoors, walking, cycling, and being outdoors in general. Each activity was scored 0 for less than once per week and 1 for once per week or more often. These scores were added to gain an overall home activity score ranging from 0 to 7. Nevus counts on arms of parents Efforts were undertaken to count melanocytic nevi on the arms of mothers and fathers. For about 20 percent of all children, both parents were present, and melanocytic nevi were counted by the examiners. If only one parent was seen, the examiner instructed this parent to count the melanocytic nevi on the arms of the second parent. Multiple linear regression analysis was used to estimate the missing values for the numbers of melanocytic nevi on the fathers arms (n 5 107), as described elsewhere (30). Nevus counts and assessment of pigmentary features The physical examination was conducted by two dermatologists. Evaluation of the reliability of melanocytic nevi counts for 49 Australian children showed a very high concordance between one of the authors (J. B.) and an expert in assessing melanocytic nevi in children who did not participate in the present study (Dr. Simone Harrison, Townsville, Australia). The concordance correlation coefficient was 0.97 (95 percent confidence interval (CI): 0.95, 0.98) (unpublished data). Children were examined while wearing only underpants in a well-illuminated room. A standard protocol was used to define and count melanocytic nevi (38). Melanocytic nevi were defined as brown-to-black pigmented macules or papules of any size, darker than the surrounding skin, excluding lesions with the clinical characteristics of freckles, solar lentigines, or café-au-lait spots. No attempt was made to differentiate lentigo simplex from junctional melanocytic nevi. Halo nevi, nevi spili,

3 622 Bauer et al. congenital nevi, and blue nevi were counted separately and were included in the total count of melanocytic nevi. The severity and distribution of freckling was recorded separately. Skin type was assessed according to Fitzpatrick (37). Hair color and eye color were assessed by comparison with 10 standard hair samples and 10 iris-color prints. Freckling was assessed semiquantitatively on the face, both arms, and shoulders by using drawings developed by Dubin et al. (39). Further details on the methodology of the study have been published previously (30). Statistical evaluation The distributions of the newly calculated sunscreen score and the total number of melanocytic nevi on the children s bodies were skewed and were therefore summarized by using the median and interquartile range (IQR). Bivariate associations between sun-protective behaviors, sun exposure, and host factors were assessed by using t tests, chi-square tests, the Spearman s rank correlation coefficient, and the nonparametric Wilcoxon test, as appropriate. The following characteristics were considered as potential confounders for the associations between different sunprotective practices and the number of melanocytic nevi: age, gender, skin type according to Fitzpatrick (37), hair color, eye color, facial freckling, country of birth (Germany, not in Germany), lived abroad (yes, no), ethnicity of parents (both parents, one parent, or no parent of German descent), highest level of education of the parents (combined for father and mother), number of moles on the mother s arms, number of moles on the father s arms, family history of melanoma, weeks spent during previous holidays in sunny climates, score for activities at home during summer, number of previously experienced sunburns, and effect of the participating day-care center. The target variable, number of melanocytic nevi, was logarithmically transformed for use in multiple linear regression analyses. Confounding was assessed by using multiple linear regression analyses, comparing the effect measure (i.e., regression coefficient) in the model with and without the potential confounder (excluding all missing values). An absolute difference of 10 percent or more in the effect measure before and after adjustment was considered confounding. Potential confounders were initially considered separately and were then combined. Results of linear regression analyses were presented by means of regression coefficients (r) with 95 percent confidence intervals and p values. RESULTS A total of 1,812 children participated in the study (52.9 percent boys). Overall, 98.1 percent of participating children presented with melanocytic nevi. Total melanocytic nevi counts increased progressively with age (age 2 years: median, 3; IQR 5 2 5; age 3 years: median, 5; IQR 5 3 7; age 4 years: median, 8; IQR ; age 5 years: median, 10; IQR ; age 6 years: median, 14; IQR ; age 7 years: median, 19; IQR ), with no differences between the genders. The distribution of melanocytic nevi was positively skewed, with few children having very high melanocytic nevi counts. Participants general characteristics have been described in detail previously (30). Sun-protective behavior Overall, 94.4 percent of parents reported that their child had used sunscreens previously, with no significant differences between the genders (p ) or with age (p ). Use of sunscreens with an SPF value of 20 or higher was reported by 51.1 percent of the parents. On average, sunscreens with higher SPF values were applied to girls (p ) and younger children (p ). The median age at which children used sunscreen for the first time was 1 year (range, 0 6 years); 15.1 percent of children were 6 months or younger at the first use. When asked how often sunscreen was used during sun exposure, 76.2 percent of parents answered almost always, while 12.8 percent reported that they applied sunscreen only every now and then or less often. A majority of parents said that they almost always applied sunscreen to the face (81.7 percent) and to the upper extremities (78.3 percent) of their child; 56.5 percent of the parents almost always applied sunscreen to the child s entire body. The median score calculated for the frequency and extent of application of sunscreen to different body sites was 9 (IQR 5 8, 10), with no significant differences between the genders (p ) or with age of the child (p ). At the beach or outdoor swimming pool, swimsuits or trunks were usually worn by 93.3 percent of the boys and 96.7 percent of the girls (p ), while 73.0 percent of the children wore T-shirts and 17.1 percent shorts. According to the combined clothing score, 14.8 percent of children usually wore three pieces of clothing (swimsuit/trunks, T-shirt, and shorts), 57.1 percent wore two pieces, and 26.1 percent wore one piece. The younger the child, the more likely that more clothing was worn (p ). Sun-protective behavior and exposure to sunlight Of the children who had previously spent holidays in sunny climates, 81.4 percent almost always used sunscreen compared with 64.3 percent of the children who had not previously spent holidays in sunny climates (p <0.0001). The median score calculated for the application of sunscreen on different body sites was 10 (IQR 5 8, 10) for children who previously spent holidays in sunny climates compared with 8 (IQR 5 5, 10) for those who had not (p <0.0001). Overall, 31.7 percent of children who had not spent any holidays in sunny climates, 27.1 percent of children who had spent 1 or 2 weeks on holidays, 26.3 percent who had spent 3 or 4 weeks, and 26.6 percent who had spent 5 or more weeks of holidays in sunny climates usually wore no or only one piece of clothing (swimsuit/trunks, T-shirt, or shorts) at the beach or outdoor swimming pool (p ). For children who had used sunscreen, the median activity score at home was 5 (IQR 5 4, 6); for children who had never used sunscreen, the median activity score was 4 (IQR 5 0, 5) (p <0.0001). Children who reportedly wore more pieces of clothing (swimsuit/trunks, T-shirt, shirts) at the

4 Impact of Sun Protection on Young German Children 623 TABLE 1. Bivariate associations of sun-protective behavior with melanocytic nevi in 1,812 German children aged 2 7 years, 1998 Melanocytic nevi (no.) % Median IQR* Range Use of sunscreen Ever used sunscreen No , Yes , Frequency of sunscreen use during sun exposure Never , Rarely , Now and then , Beginning of summer , Almost always , Application of sunscreen on the entire body Never , Sometimes , Almost always , Sun-protection factor of the sunscreen applied , , , Clothing worn at the beach or outdoor swimming pool Swimsuit or trunks No , Yes , T-shirt No , Yes , Shorts No , Yes , Combined clothingy None , One , Two , All three , Combined clothing and sunscreen score None , Sunscreen only , One piece of clothing , One piece of clothing and sunscreen , Two pieces of clothing , Two pieces of clothing and sunscreen , Three pieces of clothing , Three pieces of clothing and sunscreen , * IQR, interquartile range. y Swimsuit or trunks, T-shirt, and shorts.

5 624 Bauer et al. TABLE 2. Results, based on data for 1,812 German children aged 2 7 years, of multiple linear regression analyses assessing the associations between different sun-protective behaviors and the logarithmic-transformed number of melanocytic nevi, adjusted for confounding,* 1998 Behavior Regression coefficient 95% confidence interval beach or outdoor swimming pool were less likely to have a high activity score at home (p ), were more likely to have a sensitive skin type (p <0.0001), and were more likely to have parents with a higher level of education (p ). Sun-protective behavior and melanocytic nevi p value Use of sunscreen Ever used sunscreen , Frequency of sunscreen use during sun exposure , Sunscreen score , Application of sunscreen on the entire body , Sun-protection factor of the sunscreen applied , Clothing worn at the beach or outdoor swimming pool Swimsuit or trunks , T-shirt , Shorts , <0.001 Combined clothing score , <0.001 Combined clothing and sunscreen score , <0.001 * The models were adjusted for the confounding effects of age, skin type, facial freckling, weeks spent on holidays in sunny climates, activity score at home during the summer, ethnicity of parents, number of moles on the mother s arms, and number of previously experienced sunburns. Bivariate analysis analysis not adjusted for confounders such as skin type showed that children who had never used sunscreen had fewer melanocytic nevi compared with children who had previously used sunscreen (table 1). Children who wore all three clothing items (swimsuit/trunks, T-shirt, and shorts) at the beach or outdoor swimming pool had a lower median count of melanocytic nevi compared with children who wore fewer items of clothing. Analysis of the score combining clothing and sunscreen use showed that children who used sunscreen had higher melanocytic nevi counts than children who were wearing the same number of clothes but had not used sunscreen. Results of multiple linear regression analyses showed that none of the different measures of sunscreen application investigated was statistically significantly related to the number of melanocytic nevi (table 2). Wearing shorts (p < 0.001) and the combined clothing score (p <0.001) had the strongest protective effects on the number of melanocytic nevi (table 2). A dose-response relation was found between the number of items of clothing worn at the beach or outdoor swimming pool and the number of nevi (baseline 5 no clothes; one piece of clothing: r , 95 percent CI: 20.42, 0.04, p ; two pieces of clothing: r , 95 percent CI: 20.45, 0.00, p ; three pieces of clothing: r , 95 percent CI: 20.62, 20.15, p adjusted for the confounding effects of age, activity score at home, and ethnicity of parents). A doseresponse relation between frequency of sunscreen application and the number of nevi was not established (baseline 5 never or rarely; sometimes: r , 95 percent CI: 20.25, 0.06, p ; at the beginning of summer: r , 95 percent CI: 20.21, 0.13, p ; almost always: r , 95 percent CI: 20.24, 0.01, p adjusted for the confounding effects of ethnicity of the parents, skin type, facial freckling, weeks on holidays in sunny climates, activity score at home, and number of moles on the mother s arms), nor was there a significant linear trend for the sunscreen score (p ) (table 2). DISCUSSION A cross-sectional risk factor study that included 1,812 German children attending day care was conducted. The impact of sun exposure and host factors on melanocytic nevi counts has been reported previously (30). The present study analyzed the relation between sun-protective behaviors and the number of melanocytic nevi. After adjustment for all confounders, multivariate linear regression analyses showed no statistically significant effects between the measures of sunscreen practices considered and the number of melanocytic nevi, although the calculated regression coefficients suggested protective effects. Thus, the apparent association of sunscreen use with higher nevus counts, as seen in the bivariate analysis, was due to confounding. In contrast, wearing clothes at the beach or outdoor swimming pool showed a dose-response relation to the number of melanocytic nevi, implying that children who wore more items of clothing had a significantly lower number of melanocytic nevi. Immediate analysis of the combined score for clothing and sunscreen use consistently resulted in higher median melanocytic nevi counts in children using only sunscreen or sunscreen and clothing compared with children who were protected by clothing only. In the present study, all variables for sunscreen use and protective clothing considered were significantly positively correlated with holidays spent in sunny climates and sun exposure of children at home; that is, increased sun protection was associated with increased sun exposure. This result was reported previously by several other investigators,

6 Impact of Sun Protection on Young German Children 625 who found that the use of sunscreen and the application of higher SPF sunscreen was associated with an increased duration of recreational sun exposure and an increased number of sunburns (40 43). The results of these studies imply that people with high levels of sun exposure are more likely to use sun protection. These results also suggest that studies investigating the effect of sun protection on nevus counts are, among other things, potentially confounded by sun exposure and that multivariate analysis should in general be applied to allow for the necessary adjustments. Moreover, research on the impact of sunscreen use should consider that results are most likely influenced by inappropriate application of sunscreen. It is known that sunscreen is washed off during swimming and when sweating, while reapplication has been shown to increase the protective efficacy (44 46). However, studies have also revealed that sunscreens were often applied too sparingly to reach the indicated SPF value (47, 48) and were usually not reapplied (43, 49). Those human failures could well imply that people who apply sunscreen consider themselves sun protected while in reality they are not. Thus, overall, studies on the effectiveness of sunscreen in humans can be considered prone to misclassification bias. In the present cross-sectional study, this potential misclassification was most likely nondifferential, leading to an underestimation of the protective effect of sunscreen use. Conflicting results have been reported regarding the impact of sunscreen use on the number of melanocytic nevi in children. Sunscreen use was found to be associated with higher melanocytic nevi counts in 631 children from four European cities (34) and in 974 children from Israel (35). However, an interventional study of 458 schoolchildren from Vancouver, Canada, found a protective effect for sunscreens (SPF 30), especially in freckled children (36). Another longitudinal study of melanocytic nevi in children found a higher number of incident melanocytic nevi to be associated with frequent sunscreen use (33). The authors attributed this effect to undetected confounding. It seems likely that the contradictory results of the effect of sunscreen use might be caused by incomplete control of confounders. The present study found, for example, a positive association between the use of sunscreen and higher nevus counts in the bivariate analysis that was reversed and nonsignificant when adjusted for confounding. An 85 percent polyester, child-size, short-sleeved T-shirt provides the same protection against ultraviolet light as an SPF 5 10 sunscreen does (50). Photoprotection of a fabric depends on various factors such as the type of fabric, porosity, dyes, and ultraviolet radiation absorbers (51, 52), and studies have found that the use of ultraviolet-radiationblocking clothes can provide excellent protection against the hazards of sunlight (53). The present study revealed a doseresponse relation between the number of clothes worn at the beach or outdoor swimming pool and the number of melanocytic nevi in children: the more clothes, the fewer melanocytic nevi. Hence, the present analysis suggests that the protective effect of clothing should be promoted more widely. These results agree with data from Autier et al. (34), who found significantly lower nevus counts for the highest level of wearing clothes while in the sun. In Germany, special ultraviolet-light-protective clothing is still uncommon; thus, the protective effect shown in the present study was most likely due to wearing normal clothing. However, because of the cross-sectional nature of the present study, the results have to be interpreted with caution. The present study suggested a protective effect of clothing and should be considered as hypothesis-generating for respective randomized controlled intervention studies. In addition, it could be argued that parents who agreed to participate in the present study were on average more conscious about sun exposure and sun-protective behavior. This seemingly unavoidable selection bias might have resulted in a sample that was more homogenous with respect to sun-protective behavior, thereby decreasing the likelihood of finding significant results. This selection bias in combination with the probability of nondifferential misclassification bias might have led to an underestimation of the protective effect of sunscreen use. If our future randomized controlled trial of sunscreen use shows an effect in this homogenous population, then such results should translate to populations with greater variation. In conclusion, multivariate analysis adjusted for confounding variables revealed that the use of sunscreen by young German children was not associated with an increased number of prevalent melanocytic nevi, a finding in contrast to other studies of children. However, the present study was also unable to confirm a significant protective effect of sunscreen despite the sufficiently large sample size. In contrast, more clothing was related to lower numbers of melanocytic nevi. Randomized controlled trials will be necessary to confirm these findings. Meanwhile, it is recommended that public health education messages should focus on avoiding sun exposure and using clothing as the primary means of sun protection. 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