We established normative data which will aid the identification and further evaluation of newborn females with abnormal clitoral sizes and ano-genital distances for the possible aetiology, as well as management in Southwest of Nigeria.
An abnormally-sized clitoris may either be enlarged or small and defined as clitoromegaly or microclitoris respectively, with the former discussed far more than the latter in the literature. Using the definition of mean + 2 SD, we define clitoromegaly as a clitoris greater than 9.9 mm in length. In many neonates, no cause is found (idiopathic clitoromegaly) [15] but, it can also reflect exposure of the fetus to fetal or maternal androgens. Congenital adrenal hyperplasia is the commonest cause of pathological clitoromegaly in the newborn [6]. Other causes of clitoromegaly include conditions such as fetal aromatase deficiency [16] maternal and placental factors such as luteoma of pregnancy, ovarian tumors and placental aromatase deficiency [17].
In the absence of systematic neonatal CAH screening, identification of clitoromegaly (of genital ambiguity) may be the earliest sign of CAH at birth. This is a reminder of the importance of careful examination of the genitalia in the neonate, which is not routinely performed in many parts of Africa. It provides a unique opportunity to identify clitoromegaly and to perform an early diagnosis of CAH in affected infants [2]. Clitoromegaly may also be part of complex disorders, including Russell-Silver Syndrome, Beckwith-Wiedemann Syndrome and Fraser syndrome [15].
On the other hand, microclitoris is more difficult to recognize because the low end of the normal spectrum (3rd percentile) is already very small (3.6 mm). Using the definition of mean – 2SD, we define microclitoris as a clitoris less than 3.2 mm in length. Aetiology of microclitoris in the newborn include Prader-Willi syndrome [18].
The conventional ano-genital ratio, which corresponds to the AF/AC ratio is considered as a marker for the degree of virilization. A value greater than 0.5 suggests posterior labial fusion and virilization [16]. Consistent with this data, the ratio observed in this study was 0.48, slightly higher than the ratio observed in American (0.37 ± 0.07) [14] and Indian infants (0.34 ± 0.07) [19].
The effects of environmental endocrine disrupting chemicals on the developing genitalia in newborn females have been observed. Shorter ano-genital distances (AGD) were documented in infants of mothers with high bisphenol A in early trimester [20] while longer AGD was reported in those with maternal polycystic ovarian syndrome (PCOS) [21]. Therefore, the evaluation for abnormal clitoral sizes and AGD in the newborn requires detailed maternal history.
There was no significant correlation between clitoral length, width and the anthropometric measurements in the present study. These findings are in agreement with some [4] but not all reports [3]. Only the ACD and AFD were positively correlated with anthropometric parameters, contrasting with findings by Ozkan et al [22] who found that all three ano-genital measurements increased as the weight, length and head circumference increased.
The mean clitoral length in the present study is higher than documented in some countries [3, 4, 8, 10]. Similarly, the AFD was higher than previously reported [8, 10, 23, 24]. The same observation was reported in male newborns in the same location [25]. Although these various observations suggest that newborn clitoral length and anogenital distances may differ according to ethnicity, they may also reflect differences in the methodology.
A strength of our study is that we ensured that all participants belonged to a Nigerian tribe, meaning that our results only reflect the characteristics of this part of Africa. Our study also has limitations. First, all measurements were performed by one investigator. Therefore, we cannot provide any information on interobserver variability which may affect the interpretation of measurements performed by other clinicians. Second, the investigator only assessed whether mothers were taking androgenic substances through history and could not verify through chart review. It is possible that the mother did not report all substances consumed.