Population-specific reference values for clitoral dimensions and anogenital distance among healthy term female neonates in Ethiopia: a Cross-Sectional Study

Technical Summary: Population-Specific Reference Values for Clitoral Dimensions and Anogenital Distance in Ethiopian Female Neonates

Problem Statement
The assessment of external genitalia at birth is a critical component of newborn care, serving as the primary clinical indicator for Disorders of Sex Development (DSD), including Congenital Adrenal Hyperplasia (CAH). In low-resource settings like Ethiopia, where newborn screening programs, hormonal assays, and genetic testing are often unavailable, clinical examination remains the sole mechanism for identifying infants requiring urgent evaluation. Currently, healthcare providers in Ethiopia lack population-specific reference data for clitoral dimensions and anogenital distance (AGD). Consequently, clinicians must rely on reference values derived from other populations (e.g., European, Asian, or other African cohorts). The paper argues that significant variability exists between populations due to genetic background, fetal growth patterns, and environmental factors; applying foreign standards may lead to inaccurate interpretations, resulting in either unnecessary investigations or the failure to recognize clinically significant abnormalities.

Methodology
This study employed a hospital-based cross-sectional design conducted at Saint Paul's Hospital Millennium Medical College (SPHMMC) in Addis Ababa, Ethiopia, between July and August 2021.

• Participants: The study enrolled 284 healthy term female neonates (gestational age ≥37 weeks). Exclusion criteria included ambiguous genitalia, major congenital malformations, severe neonatal illness, preterm birth, or incomplete data.
• Data Collection: Measurements were taken within the first 72 hours of life by two trained physicians using calibrated digital vernier calipers.
• Parameters Measured:
  • Clitoral Length (CL): Distance from the pubic ramus to the tip of the glans clitoris.
  • Clitoral Width (CW): Maximum transverse diameter of the clitoral glans.
  • Anus–Fourchette Distance (AFD): Distance from the center of the anus to the posterior fourchette.
  • Anus–Clitoris Distance (ACD): Distance from the center of the anus to the base of the clitoris.
• Statistical Analysis: Reference intervals were calculated using the mean ± 2 standard deviations (SD). Gestational age-specific reference curves (nomograms) were developed for the 37–42 week range. Pearson correlation analysis was used to evaluate associations between genital measurements and neonatal anthropometric characteristics (birth weight, length, head circumference).

Key Results

• Demographics: The mean gestational age was 38.95 ± 1.21 weeks. The mean birth weight was 3074.44 ± 482.45 g.
• Reference Intervals: The study established the following population-specific reference intervals (mean ± 2 SD) for healthy term Ethiopian female neonates:
  • Clitoral Length (CL): 6.06 – 12.47 mm (Mean: 9.27 ± 1.60 mm).
  • Clitoral Width (CW): 2.17 – 6.05 mm (Mean: 4.11 ± 0.97 mm).
  • Anus–Fourchette Distance (AFD): 7.44 – 13.76 mm (Mean: 10.60 ± 1.58 mm).
  • Anus–Clitoris Distance (ACD): 23.29 – 39.73 mm (Mean: 31.51 ± 4.11 mm).
• Correlations: A significant positive correlation was observed between ACD and both birth weight (r = 0.218, p < 0.001) and birth length (r = 0.222, p < 0.001). No significant associations were found between clitoral dimensions (CL or CW) and neonatal anthropometric characteristics.
• Gestational Age Trends: Within the term range (37–42 weeks), mean values for all measurements showed modest variation with overlapping distributions, indicating that a single cutoff value is insufficient for clinical assessment across the term spectrum.

Significance and Claims
The paper claims to provide the first population-specific normative reference values and gestational age-specific nomograms for clitoral dimensions and AGD among healthy term female neonates in Ethiopia. The authors emphasize that these findings offer a clinically relevant tool to support newborn genital assessment, particularly in resource-limited settings where biochemical and genetic confirmations are delayed or inaccessible.

The study highlights that Ethiopian neonates exhibit a mean clitoral length (9.27 mm) that is higher than values reported in Turkish and Iranian populations but comparable to Nigerian cohorts. The authors assert that these differences underscore the necessity of locally derived standards to distinguish normal variation from genital atypia. By providing these reference intervals, the study aims to facilitate the early recognition of infants who may require evaluation for DSD, thereby reducing reliance on potentially inappropriate international cutoff values.

Limitations
The authors acknowledge several limitations: the study was conducted at a single tertiary hospital, which may limit generalizability to diverse Ethiopian ethnic and geographic populations; preterm infants and those with congenital anomalies were excluded; and maternal hormonal status, prenatal medication exposure, and environmental endocrine disruptors were not assessed. The paper concludes that further multicenter studies across diverse Ethiopian populations are needed to validate and refine these reference standards.