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Clitoral size in term newborns in Kumasi, Ghana Asafo-Agyei, Serwah B; Ameyaw, Emmanuel; Chanoine, Jean-Pierre; Zacharin, Margaret; Nguah, Samuel B Jun 6, 2017

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RESEARCH Open AccessClitoral size in term newborns in Kumasi,GhanaSerwah Bonsu Asafo-Agyei1*, Emmanuel Ameyaw1, Jean-Pierre Chanoine2, Margaret Zacharin3and Samuel Blay Nguah1AbstractBackground: Data on normative clitoral sizes in newborns is relatively sparse and racial/ethnic differences have alsobeen reported. This study was performed to establish norms for clitoral size in term Ghanaian female newborns.Methods: This was a cross-sectional study of all apparently well full-term newborns of postnatal age < 48 h andbirth weight between 2.5 and 4.0 kg delivered at Komfo Anokye Teaching Hospital between May and September,2014. Anthropometric and genital parameters were documented for study subjects as well as parental socio-demographic indices.Results: In 612 newborn females studied, the mean (±SD) clitoral length (MCL) and the mean (±SD) clitoralwidth (MCW) were 4.13 ± 1.6 mm and 4.21 ± 1.1 mm, respectively. MCL was inversely related to birth weight(r = −0.62; p < 0.001) while MCW was inversely related to both gestational age (r = −0.1; p = 0.02) and birthweight (r = −0.54; p < 0.001). Babies with a clitoris that was completely covered by the labia majora hadrelatively lower clitoral sizes (p < 0.001) than those who had a partially covered or prominent clitoris. NeitherMCL nor MCW differed significantly by birth length or maternal tribe.Conclusions: Clitoral size varies with birth weight and gestational age. Babies with a completely coveredclitoris are unlikely to warrant detailed clitoral measurements for clitoromegaly.Keywords: Clitoral length, Clitoral width, Clitoral size, Ghana, Newborns, ClitoromegalyBackgroundEarly detection of genital anomalies in the female infant iscrucial. Significant clitoromegaly at birth usually reflectsvirilization and suggests that the female foetus has beenexposed to androgens during the intrauterine period [1].Congenital adrenal hyperplasia (CAH) is the most com-mon cause of virilization of a female foetus. Failure toidentify and treat this disorder results in potentially fataladrenal crisis, an avoidable outcome if the endocrineemergency is correctly diagnosed and treated [2]. Sincethe technique of analyzing 17-hydroxyprogesterone(17-OHP) in filter paper blood samples was developedby Pang et al. [3] in 1977, the utility of newborn screeningfor CAH has been amply demonstrated and several devel-oped countries have established a newborn screeningprogramme [4–7]. Unfortunately, newborn screening isstill not available in most developing countries includingGhana. Thus, until routine newborn CAH screeningis commenced, comprehensive clinical assessment in-cluding genital examination remains the simplest andmost cost-effective option of circumventing the chal-lenges imposed by financial and diagnostic restraintsin resource limited settings.Propitiously, females with classical CAH usually haveambiguous genitalia or clitoromegaly which may be readilydetected by genital examination [2]. Hospital statistics atthe study site indicate that about 9000 - 12,000 babies aredelivered annually in the hospital, with about 16 - 18% ofthese being preterms. Newborn screening for congenitaladrenal adrenal hyperplasia is not carried out in the hos-pital but between May 2014 and April 2015 we diagnosed4 females with CAH in a cohort of 9255 neonates throughsystematic newborn examination (unpublished data). Al-though it has been reported that clinical examination may* Correspondence: sbasafoagyei@gmail.com1Department of Child Health, Komfo Anokye Teaching Hospital, Kumasi,GhanaFull list of author information is available at the end of the article© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Asafo-Agyei et al. International Journal of Pediatric Endocrinology  (2017) 2017:6 DOI 10.1186/s13633-017-0045-ymiss some cases of non-classical and even classicalCAH [5, 8, 9], detailed genital examination still hasdistinct benefits over a cursory look at the genitalia andmay even help prevent extremely virilized females frombeing labelled as “males”.Conversely, the clitoris may seem prominent in somehealthy newborns, leading to many unnecessary investi-gations [10]. Clitoral size measurements permit accurateclitoral assessment and avoid over- or misdiagnosis ofabnormalities based on clinical impression alone, thusminimizing unnecessary cost and psychological traumato the parents [11].Normative clitoral anthropometric data for healthynewborns has been reported but is sparse and mainlyderived from Caucasian and Asian infants. However, ra-cial/ethnic differences in newborn clitoral sizes havebeen reported [12, 13] and existing data may thereforenot be applicable to our population in Ghana, for whichno published data exist.Aim: To establish reference ranges for clitoral sizes inapparently healthy term newborns in Ghana.MethodsThis cross-sectional study was conducted in KomfoAnokye Teaching Hospital (KATH) between May 2014and September 2014. KATH is a tertiary care teachinghospital in Kumasi, the second largest city in Ghana. Itserves as a referral centre for the Kumasi Metropolisand the whole northern half of Ghana.A complete antenatal history was obtained from themother and from the hospital records, including a his-tory of ingestion of herbal medicine or prescribed medi-cations. The gestational age was determined by using thelast menstrual period and early ultrasound results andconfirmed if necessary with Dubowitz/Ballard score [14].Physical examination of both mother and newborn wasdone. All apparently well female term newborns with agestational age of 40 ± 2 weeks and birth weight between2.5 and 4.0 kg were considered for recruitment into thestudy. Exclusion criteria for newborns included majorcongenital anomalies/dysmorphism, apparent disorders ofsexual development, breech presentation and twins of dif-ferent gender. Maternal exclusion criteria were pregnancyhistory of hormonal drug intake, signs of virilization dur-ing pregnancy, pre-eclampsia and diabetes mellitus.Anthropometric measurements of newborns were takenwithin 48 h after delivery. A nurse attached to the paediat-ric endocrine unit was trained to assist the principalinvestigator with the genital and anthropometric measure-ments. Two research assistants were also trained to assistthe two examiners with positioning of the newborns andwith data entry. In a warm environment, the newbornswere put in the supine position and the perineum was ad-equately exposed. It was noted on inspection whether theclitoris was visible or completely covered by the labiamajora. The baby was then placed in a frog-like positionand the position secured by an assistant. The labia majorawere separated and the prepuce of the clitoris gentlyretracted. Clitoral size was measured as described byVerkauf et al. [15], with clitoral length measured as thedistance from the crura insertion at the pubis symphysisto the tip of the glans and clitoral width measured in thegreatest transverse diameter (Fig. 1). Both the clitorallength and width were measured twice using digital Verniercalipers (Resolution 0.01 mm, Accuracy +/−0.02 mm) andtheir respective means were recorded. The weight was mea-sured to the nearest 10 g with a Salter scale (Model 180,Salter Brecknell, England) and the length was measured tothe nearest centimetre with an infantometer (Seca 416Mobile infantometer, Seca GmbH & Co. KG, Germany).All anthropometric measurements were done by a 2-member team, with one person taking the measurementswhile the other positioned the baby and helped enter thedata onto the Case report form. Majority (72.1%) of themeasurements were done by the principal investigator.Inter-observer variability for genital measurements waschecked on a 2-weekly basis throughout the study on 5randomly selected newborns and it remained insignificant.The standard deviations for inter-observer variation were0.05 mm and 0.09 mm and 95% of paired measurementswere within range of 0.09 mm and 0.03 mm for clitorallength and clitoral width respectively.The data was analyzed using R statistical software ver-sion 3.1.2. Continuous variables were presented as meanswith standard deviation as well as median with theircorresponding ranges. Single categorical variables weretabulated and expressed as percentages. The relationshipsbetween genital measurements and various categoricalvariables were determined using an analysis of variance,correcting for possible confounders and reporting theFig. 1 Schematic diagram of clitoris and surrounding structures showingthe anatomic landmarks utilized for clitoral length measurementAsafo-Agyei et al. International Journal of Pediatric Endocrinology  (2017) 2017:6 Page 2 of 5respective p-values as appropriate. Relationships betweengenital measurement and other continuous variables weredetermined using linear regression. These analyses werepresented as their regression coefficient (r) with their 95%confidence intervals. For all analysis a two sided p-value of<0.05 was considered statistically significant. This studywas approved by the Committee on Human Research,Publications and Ethics of KATH/Kwame NkrumahUniversity of Science and Technology, Kumasi. Writteninformed consent was received from the parents prior toenrollment.ResultsA total of 612 female infants were studied including oneset of identical twins. One mother/baby pair was excludedbecause of maternal virilization. A descriptive data ofstudy subjects is shown in Table 1. The distribution of ma-ternal tribe is shown in Fig. 2. Genital measurements fromstudy subjects were used to construct clitoral size percent-ile charts (Table 2). The mean (±SD) clitoral length[MCL] was 4.13 ± 1.6 mm and the mean (±SD) clitoralwidth [MCW] was 4.21 ± 1.1 mm. There were 3/612 fe-males (0.49%) with a clitoral length ≥ 1 cm and 31/612 fe-male newborns (5.1%) with a clitoral width greater than6 mm. Using the 97th percentile, a newborn will be con-sidered to have clitoromegaly if clitoral length is greaterthan 7.5 mm and/or clitoral width is greater than 6.2 mm.No correlation was seen between genital size and ma-ternal herbal intake or mode of delivery. Seventy-nine(12.9%) mothers took herbs at varying periods duringtheir pregnancy. There was also no significant differencein genital measurements done in the first 24 h of postna-tal life and those done from 24 h up to 48 h. Aftercorrecting for confounders, there was no significantdifference in MCL or MCW by tribe. Table 3 shows thecorrelation between clitoral size and gestational age,birth weight and birth length. There was a strong nega-tive correlation between clitoral size and birth weight.Both clitoral length and width varied significantlywith appearance of the clitoris (Table 4). A com-pletely covered clitoris was significantly smaller thana partially covered one, which was in turn smallerthan a prominent clitoris.DiscussionThis is the first description of the characteristics and sizeof the clitoris in Ghana and the largest cohort of new-born clitoral sizes in published literature. Traditionally,normal clitoral length is accepted as < 1.0 cm, althoughrare variations exist [16]. In our study, only 3/612females (0.49%) had a clitoral length ≥ 1 cm. Thesepatients were followed up for a year and their clitoralsize did not increase with time, nor did they develop anyclinical features suggestive of CAH. Studies in newbornsfrom different parts of the world have reported MCLranging from 3.1–7.7 mm [10, 13, 17–21]. Most pub-lished studies done in newborns did not elaborate onhow the clitoral measurements were done. Amongststudies with similar inclusion criteria, our MCL of 4.13± 1.60 mm was comparable to the 4.0 ± 1.24 mm re-ported by Oberfield et al. [17] in United States and the4.93 ± 1.61 mm reported by Kutlu et al. [10] in Turkey.Our MCL was also similar to that of other studies thatinvolved preterms, including the 3.66 ± 0.13 mm re-ported by Riley and Rosenbloom [13] in black term andpreterm newborns in United States. Mondal et al. [20]also reported a comparable albeit slightly lower MCL of3.1 ± 1.54 mm in India and Jarrett et al. [19] reported arelatively higher MCL of 7.7 ± 1.37 mm in 244 term andpreterm newborns in Nigeria.A clitoral width > 6 mm has been said to suggestvirilization [22], probably based on earlier studies byTable 1 Descriptive characteristics of study subjectsMean SD Median Minimum MaximumGestational age (weeks) 40.0 1.1 40.0 38.0 42.0aPost-natal age (hours) 10.1 7.8 8.0 1 47Birth weight (kgs) 3.1 0.4 3.1 2.5 4.0Length (cm) 48.1 2.1 48.2 37.6 53.6Clitoral Length (mm) 4.1 1.6 3.7 1.1 10.8Clitoral Width (mm) 4.2 1.1 4.3 1.3 8.8aAge in hours at which anthropometric measurements were doneFig. 2 Distribution of maternal tribe in study subjectsTable 2 Clitoral size percentilesPercentile Clitoral Length (mm) Clitoral Width (mm)3 1.6 2.210 2.3 2.850 3.9 4.390 6.3 5.697 7.5 6.299 8.6 6.8Asafo-Agyei et al. International Journal of Pediatric Endocrinology  (2017) 2017:6 Page 3 of 5Riley and Rosenbloom (1980) [13] and Oberfield et al.(1989) [17]; who both reported an upper limit of 6 mmfor clitoral width range in newborns. However, the rangefor clitoral width is not well established as fewer studieshave reported clitoral width. In this study, as many as 31/ 612 newborns (5.1%) had a clitoral width greater than6 mm. These patients were followed up and theyremained healthy. Jarrett et al. [19] also reported a clit-oral width range of 1–7 mm, and so regional differencesin clitoral size may exist. More African data will beneeded to clarify this. Our MCW of 4.21 ± 1.1 mm wassimilar to reports from Jarrett et al. [19] and Yokoya etal. [21] of 4.4 ± 0.89 mm and 4.4 ± 1.2 mm respectively.Oberfield et al. [17] reported a relatively lower meanclitoral width (MCW) of 3.32 ± 0.78 mm in NorthAmerican term newborns.Factors that may be responsible for the reportedvariation in clitoral sizes include differences in studypopulation. Some studies included preterms [13, 19, 20]whereas this study recruited only term newborns.Clitoral size has also been reported to correlate with an-thropometric parameters of the study population [10].Furthermore, differences in tools and techniques ofmeasurement as well as inter observer variability mayplay a role. This study utilized calipers in the meas-urement of clitoral length and width while other stud-ies utilized tumorimeters or rulers [19, 23]. MCLhave also been reported to vary with ethnicity/race,which may also partly account for the differences inreported values [12, 13].Only MCW but not MCL in our study was negligiblyassociated, though inversely, with gestational age. Thelack of significant association was not unexpected as allthe newborns were full term. The analysis for correlationbetween maternal herbal intake and clitoral size wasdone to evaluate for possible hormonal effects of theingested herbal medicines, since their constituents werelargely unknown. There was no significant difference ingenital measurements done in the first 24 h and thosedone afterwards. Oberfield et al. [17] also noted no dif-ference in clitoral sizes when they compared measure-ments done before and after 24 h in order to evaluatefor possible variation from swelling of the genital areadue to birth trauma.Birth weight was inversely associated with both MCLand MCW, implying newborns with a lower birth weighthad larger clitoral sizes and vice versa. Similarly, Kutluand Akbiyik [10] also found a negative correlation be-tween MCL with birth weight. However, unlike this studythey also reported a negative correlation between MCLand birth length. Oberfield et al. [17] found no correlationbetween clitoral size and birth weight or length.Kutlu and Akbiyik [10] reported that the clitorallength was < 5 mm when it appeared to be covered bythe labia majora and concluded that no extra clitoralmeasurement was clinically indicated in such cases. Inour study, the highest recorded MCL and MCW in new-borns with completely covered clitoris was 8.3 mm and6.22 mm respectively. Overall, newborns whose clitoriswas completely covered by the labia majora had the low-est mean clitoral size (p < 0.001) and indeed furtherclitoral measurements may not be indicated in suchnewborns; as suggested by Kutlu and Akbiyik [10].One limitation of our study is that measurements weredone by two examiners and could have introduced anerror due to inter-observer variability. However, an exten-sive training was done and a subset of study subjects wasexamined by both 2 examiners to evaluate and control forvariability, which remained insignificant throughout thestudy.Table 3 Association of clitoral size with gestational age, birth weight and birth lengthGestational Age (weeks) Birth Weight (kgs) Birth Length (cm)r (95% CI) p-value r (95% CI) p-value r (95% CI) p-valueMCL (mm) −0.06 (−0.17 to 0.06) 0.330 −0.62 (−0.96 to −0.29) <0.001 −0.03 (−0.09 to 0.03) 0.390MCW (mm) −0.1 (−0.17 to −0.02) 0.020 −0.54 (−0.78 to −0.31) <0.001 −0.04 (−0.08 to 0) 0.070Linear regression utilized for analysis; r: Coefficient of linear regressionSignificant p-values are in bold italicsTable 4 Correlation between clitoral appearance and sizeaClitoris Completely coverednumber =132 (21.6%)Partially showingnumber =188 (30.7%)Prominentnumber = 278 (45.4%)p-valueMean (SD) Median (range) Mean (SD) Median (range) Mean (SD) Median (range)CL (mm) 3.3 (1.2) 3.3 (1.1–8.3) 3.8 (1.4) 3.8 (1.4–10.8) 4.8 (1.6) 4.8 (1.2–10.6) <0.001CW (mm) 3.5 (1.0) 3.5 (1.3–6.2) 3.8 (0.9) 3.8 (1.8–6.1) 4.8 (1.1) 4.8 (2.0–8.82) <0.001Analysis of variance utilized for analysis; Significant p-values are in bold italicsaFourteen missing dataAsafo-Agyei et al. International Journal of Pediatric Endocrinology  (2017) 2017:6 Page 4 of 5ConclusionsOur study suggests that the mean clitoral size of Ghanaiannewborns is similar to results reported by others butregional differences may exist in clitoral size range. Ourdata will be useful for the assessment of female neonatesin Ghana by establishing the norm and thus help promoteearly recognition of deviation from the norm; such asgenital abnormalities in female neonates.AbbreviationsCAH: Congenital Adrenal Hyperplasia; CI: Confidence Interval; KATH: KomfoAnokye Teaching Hospital; MPL: Mean Penile length; MPW: Mean PenileWidth; r: Coefficient of linear regression; SPL: Stretched penile lengthAcknowledgementsThe authors will like to acknowledge Mr Isaac Appiah, the research team, thestaff of KATH Obstetrics and Gynaecology department and the co-ordinatorsand fellows of the PETCWA programme. This research was jointly funded byGlobal Pediatric Endocrinology and Diabetes (GPED) and the EuropeanSociety for Paediatric Endocrinology (ESPE).FundingThis research was jointly funded by Global Paediatric Endocrinology andDiabetes and the European Society for Paediatric Endocrinology.Availability of data and materialsThe dataset (Clitoral size Ghana.txt) analysed during this study has beenadded as an additional file.Authors’ contributionsSBAA participated in the study design, data collection and entry andmanuscript writing. EA sought for ethical clearance, participated in the studydesign, data collection and entry and supervision and completion of finalmanuscript. JPC and MZ participated in the study design, supervision andcompletion of final manuscript. SBN participated in the study design,statistical analysis and completion of final manuscript. All authors read andapproved the final manuscript.Competing interestsThe authors declare that they have no competing interests.Consent for publicationNot applicable.Ethics approval and consent to participateEthical approval was obtained from the Committee on Human Research,Publications and Ethics of KATH/Kwame Nkrumah University of Science andTechnology, Kumasi, Ghana. A written informed consent was obtained fromall parent(s) of study subjects.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.Author details1Department of Child Health, Komfo Anokye Teaching Hospital, Kumasi,Ghana. 2Endocrinology and Diabetes Unit, British Columbia Children’sHospital, University of British Columbia, Vancouver, BC, Canada. 3The RoyalChildren’s Hospital, Murdoch Children’s Research Institute and University ofMelbourne, Melbourne, Australia.Received: 28 December 2016 Accepted: 17 May 2017References1. Kaiser GL. 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