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Cross-Sectional Observational Study of Nipple and Areola Changes During Acta Biomed 2016; Vol. 87, N. 2: 177-183 © Mattioli 1885 Original article Cross-sectional observational study of nipple and areola changes during pubertal development and after menarche in 313 Italian girls Vincenzo De Sanctis1, Ihab Zaki Elhakim2, Ashraf T. Soliman3, Heba Elsedfy2, Nada Soliman4, Rania Elalaily5 1 Pediatric and Adolescent Outpatient Clinic Quisisana Hospital, Ferrara, Italy; 2 Department of Pediatrics, Ain Shams Univer- sity, Cairo, Egypt; 3 Department of Pediatrics, Division of Endocrinology, Alexandria University Children’s Hospital, Alexan- dria, Egypt; 4 Ministry of Health, Alexandria, Egypt; 5 Department of Primary Health Care, Abu Nakhla Hospital, Doha, Qatar Summary. Obiective: To describe the characteristics of nipple development during puberty in Italian females. In addition this is compared with Tanner criteria for breast and pubic hair development at different stages and correlated with body mass index (BMI) and the menstrual age. Design: Cross-sectional observational study. Setting: Italian children and adolescents consecutively assessed at the Endocrine and Adolescent Outpatient Clinic of Private Accredited Quisisana Hospital of Ferrara. Partecipants: Healthy females 2-20 years, belong- ing to Italian middle socio-economic class. Study duration: This study was conducted for a total period of 39 months from September 2012 to December 2015. Methods: Demographic characteristics, age at menarche and menstrual duration, anthropometry (weight, height, BMI) and pubertal status (breast and pubic hair) were evaluated. The greatest diameters of the erect nipple and areola sizes were measured in all subjects in supine position using a plastic template with graduated circular cut-outs or a transparent graduated ruler. Results: Significant increments in nipple diameter were noted between Tanner’s stages B1, B2, B3, B4 and B5 but the differences between stages B1 vs B2, B3 vs B4, B4 were more significant (p<0.001) than the difference between B4 vs B5 (p<0.004).The same statistical pattern was documented between Tanner’s stage PH1 and PH2, PH2 and PH3 and PH4 and PH5. The nipple diameter increased significantly in relation to BMI in all Tanner’s stage groups (p: 0.021 for B1 vs B2; and p<0.001 for B3 vs B4 and B4 vs B5) but one (B2 vs B3=p: 0.518).A significant correlation was observed between duration of menses, nipple and areola sizes (r: 0.490; p=<0.001 and r: 0.252; p=0.012, respectively). Conclusions: The assessment of sexual maturation is important in population studies as well as for daily clinical encounter. In our subjects the mean age of onset of secondary sexual characteristics was 10.3±1.4 years and mean age at menarche was 12.02±1.5 years. The study provides the normative data for nipple and areola sizes in Italian girls. Change in nipple and areola sizes may represent an early marker for transition to puberty. (www.actabiomedica.it) Key words: puberty, breast development, nipple size, areola size, Body Mass Index Introduction nied by a marked increase in skeletal mass, and chang- es in body composition. A myriad of biological changes occur during pu- Development of breast tissue is the first clinical berty including sexual maturation, increases in height sign of the onset of central puberty (CP) in girls (1-4). and weight, completion of skeletal growth accompa- Whilst in boys, the first physical indication is enlarge- 178 V. De Sanctis, I.Z. Elhakim, A.T. Soliman, et al. ment of the testis and reddening of the scrotal skin Inclusion criteria (1,2). While the first menstruation is the most com- 1. Italian children and adolescents consecutively monly assessed pubertal marker in large-scale epide- assessed at the Endocrine and Adolescent Outpa- miological studies, it is a rather late event in puberty. It tient Clinic of Private Accredited Quisisana Hospital occurs on average 2 years after the onset of breast de- of Ferrara were enrolled; 2. Children and adolescent velopment, and its timing varies between populations whose consent was obtained. and ethnic groups (1,2). Sexual Maturity Rating (SMR), also known as Exclusion criteria Tanner Staging, is based on an assessment scale of 1. Subjects with history of endocrine and growth development of secondary sexual characteristics. This disorders; 2. Subjects with physical disability, which helps health professionals to gauge the degree of pu- prevented accurate anthropometric measurements; bertal maturation that has occurred among adoles- 3. Subjects with dysmorphic features suggestive of cents, regardless of chronological age. SMR is based syndromic diseases or bone dysplasia known to af- on the appearance of pubic hair, the development of fect height of the child and/or sexual maturation; 4. breasts, and the occurrence of menarche in females. Subjects with congenital and acquired pediatric breast However, difficulties exist in determining breast stage anomalies (13-15); 5. Unwillingness of the parent or development in the obese children (4). In teens self re- guardian to participate in the study; 6. Obese children porting of breast stage, using this method, is associated and adolescents with BMI >30 Kg/m2. with considerable inaccuracies (5-7). The availability of an easy, cost-effective, reliable, Clinical data collection non-invasive method to assess the onset of puberty is Demographic characteristics, age at menarche and useful in both clinical and research settings. Very lit- menstrual duration, anthropometry (weight, height, tle attention has been paid to development of nipple BMI) and pubertal status (breast and pubic hair) were and areola maturation characteristics during pubertal evaluated. development and after menarche (8-11). The primary purpose of this project was to de- Anthropometry and definitions scribe the characteristics of nipple development during Height and weight were measured according to puberty in Italian females. In addition this is compared international recommendations (16,17). Body weight with Tanner criteria for breast and pubic hair develop- was measured, wearing minimal underclothes, to the ment at different stages and correlated with body mass nearest 100 g on properly calibrated scales. Body mass index (BMI) and the menstrual age. index (BMI) was calculated (weight in Kg/height in m2). A subject was considered overweight when the BMI was between 25 and 30 and obese above 30 (18). Subjects and Methods Assessment of pubertal stage Target population A pediatric endocrinologist (VDS) assessed breast This cross-sectional observational study was con- development (inspection and palpation) and pubic hair ducted on children and adolescents correlating the using SMR described by Tanner et al as following: nipple and areola diameters with the SMR stages described by Tanner et al. Our target population was Sexual Maturity Rating (SMR) healthy females 2-20 years, belonging to Italian mid- I. Preadolescent; elevation of papilla only; II. dle socio-economic class (12). Breast bud stage; elevation of breast and papilla as a small mound and/or enlargement of areola diameter; Study duration III. Further enlargement of breast and areola, with no This study was conducted for a total period of 39 separation of their contours; IV. Projection of areola months from September 2012 to December 2015. and papilla to form a secondary mound above the level Cross-sectional observational study of nipple and areola changes during pubertal development 179 of the breast; and V. Mature stage; projection of papilla pressed as mean ± standard deviation (SD). Compari- only, owing to recession of the areola to the general son of different variables in the two groups was made contour of the breast. using unpaired - Student t-test and Mann-Whitney Onset of puberty was defined as Tanner’s breast test for normal and nonparametric variables respec- stage 2. tively. Kruskal-Wallis and McNemar-Bowker tests were used to study correlations between variables with Techniques for nipple and areola size measurements parametric and non-parametric distributions . p < 0.05 The greatest diameters of the erect nipple and was considered as significant. areola sizes were measured in all subjects in supine position using a plastic template with graduated circu- lar cut-outs (8) or a transparent graduated ruler (11). Results When the areola diameter was greater than the gradu- ated circular cut-outs of plastic template, the greater There were 313 eligible girls for this study. Table 1 horizontal or vertical midpoint diameter of areola was shows the age and auxological parameters of our chil- recorded to the nearest millimetre with the transparent dren and adolescents in relation to their breast Tanner ruler pressing it against each areola until the areolar stage. The youngest subject was 2 years old and the margin contacted the ruler. oldest 20 years old. The mean age of onset of secondary sexual characteristics was 10.3±1.4 years and mean age Ethical Approval at menarche was 12.02±1.5 years. Informed verbal consent was taken from the per- A statistical chronological age difference was ob- son or the guardian for each study subject. All proce- served in the five studied groups (p<0.001 for Tanner’s dures were carried out with the adequate understanding stage B1 vs B2; B3 vs B4 and B4 vs B5 and a p value and consent of parents or patients in accordance with <0.015 for Tanner’s stage B2 vs B3). the Declaration of Helsinki (http://www.wma.net). Significant increments in nipple diameter were noted between Tanner’s stages B1, B2, B3, B4 and B5 Statistical analysis but the differences between stages B1 vs B2, B3 vs B4, Standard computer program SPSS for Windows, B4 were more significant (p<0.001) than the difference release 13.0 (SPSS Inc, Tulsa, IL, USA) was used for between B4 vs B5 (p<0.004).The same statistical pat- data entry and analysis. All numeric variables were ex- tern was documented between Tanner’s stage PH1 and Table 1. Auxological parameters in 313 girls in relation to breast stage development (Tanner’s stage 1-5) Variables expressed as mean and Tanner’s Tanner’s Tanner’s Tanner’s Tanner’s standard deviation stage 1 stage 2 stage 3 stage 4 stage 5 (n.
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