We included 169 girls aged 5 to 16 years (mean, 11.3; SD, 1.8) who underwent 202 pelvic ultrasound examinations with Doppler assessment (Fig. 1). Twenty-seven girls underwent pelvic ultrasound in more than 1 of the 3 pubertal stages.
The study flowchart is presented in Fig. 2. Mean ages of thelarche, pubarche, and menarche were 10.1 (SD, 1.2), 10.2 (SD, 1.2), and 12.1 (SD, 1.2) years, respectively. Table 1 summarizes the clinical characteristics of the participants.
Table 1
Clinical characteristics and ultrasound measurements of the participants according to pubertal stage.
Characteristic | Prepuberty (N = 39) | Initial puberty (N = 92) | Late puberty (N = 71) | P* |
Clinical characteristics Age at pelvic US (years) | 9.3 ± 1.3 | 11.0 ± 1.4 | 12.7 ± 1.4 | < 0.001 |
Age of thelarche (years) | - | 10.2 ± 1.2 | 10.0 ± 0.9 | 0.077 |
Age of pubarche (years) | 10.2 ± 1.3 | 10.3 ± 1.4 | 10.2 ± 0.9 | 0.836 |
Age of menarche (years) | - | - | 12.1 ± 1.2 | 0.196 |
Age of maternal menarche (years) | 12.4 ± 2.7 | 12.9 ± 1.4 | 12.7 ± 1.6 | 0.440 |
Prematurity, % | 6 (15) | 13 (14) | 10 (14) | 0.400 |
Weight (kg) | 32.0 ± 5.0 | 39.8 ± 9.0 | 48.9 ± 12.1 | NA |
Height (cm) | 133.6 ± 7.2 | 143.8 ± 8.9 | 154.0 ± 7.7 | NA |
Height-for-age z-score | -0.12 (-1.14; 0.56) | -0.06 (-0.87; 0.58) | -0.24 (-0.43; 0.48) | 0.524 |
BMI (kg/m2) | 17.9 ± 2.4 | 19.2 ± 3.5 | 20.6 ± 4.5 | NA |
BMI z-score | 0.60 (-0.50; 1.30) | 0.61 (-0.50; 1.20) | 0.64 (-0.60 to 1.20) | 0.935 |
Overweight | 11 (28) | 26 (28) | 17 (24) | 0.212 |
Obesity | 0 | 3 (3,2) | 2 (2,8) | 0.134 |
Target height (cm) Ultrasound measurements | 162.0 ± 4.4 | 162.7 ± 5.7 | 161.0 ± 6.0 | 0.206 |
Pulsatility index | 6.70 ± 2.15 | 4.14 ± 1.55 | 2.81 ± 1.05 | < 0.001 |
Uterine volume (cm3) | 2.60 (2.2; 3.6) | 6.30 (4.4; 12.45) | 34.3 (22.8; 47.6) | < 0.001 |
Uterine longitudinal diameter (cm) | 3.35 ± 0.47 | 4.30 ± 0.83 | 6.24 ± 1.0 | < 0.001 |
Endometrial thickness (mm) | 0 (0; 1.3) | 2.2 (1.2; 3.4) | 6.0 (3.8; 9.1) | < 0.001 |
Right ovarian volume (cm3) | 1.64 ± 0.79 | 3.55 ± 1.98 | 7.16 ± 4.54 | < 0.001 |
Left ovarian volume (cm3) | 1.62 ± 0.85 | 3.30 ± 1.82 | 6.03 ± 4.40 | < 0.001 |
Mean ovarian volume (cm3) | 1.64 ± 0.77 | 3.43 ± 1.77 | 6.55 ± 3.76 | < 0.001 |
Data are presented as mean ± SD, median (IQR) or number of cases (%). |
BMI: body mass index; NA: not applicable; US: ultrasound. |
*P for comparison between the three groups. |
Figure 3 shows the mean PI according to Tanner stage (panel A) and to study group (panel B). No differences were observed in mean PI measurements between Tanner 2 and 3 (P = 0.939) or between Tanner 4 and 5 (P = 0.833), and, therefore, the girls were grouped in 3 categories: prepubertal, initial and late puberty. Prepubertal girls had a significantly higher mean PI (mean, 6.70; SD, 2.15) than girls in initial puberty (mean, 4.14; SD, 1.55) and in late puberty (mean, 2.81; SD, 1.05) (P < 0.001 for all comparisons).
Table 1 shows the other ultrasound measurements of the participants according to pubertal stage. The uterine volume and longitudinal diameter, endometrial thickness, and ovarian volumes of prepubertal girls were significantly different from those of girls in initial and late puberty. Additionally, these measurements were also different between girls in initial puberty and those in late puberty.
ROC curve analysis showed that the PI was able to identify the onset of puberty with a mean AUC of 0.838 (SD, 0.04) (P < 0.001), which was comparable to the AUC of other ultrasound parameters (Fig. 4).
Table 2 shows the AUC, cutoff, sensitivity, specificity, PPV, NPV, LR+, LR−, and accuracy of PI and other pelvic ultrasound parameters. The PI cutoff point of 5.05 had a sensitivity of 77%, specificity of 85%, PPV of 92%, NPV of 61%, and accuracy of 79% to detect initial puberty. The combination of PI < 5.05 plus uterine volume > 3.75 cm³ increased the specificity (95%) and PPV (97%). The addition of ovarian volume > 2.15 cm³ decreased the sensitivity and did not increase the specificity or PPV.
Table 2
Diagnostic value of pulsatility index and ultrasound measurements for the diagnosis of pubertal onset.
Parameter | AUC | Cutoff | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) | LR+ | LR− | Accuracy (%) |
Pulsatility index | 0.838 | 5.05 | 77 | 85 | 92 | 61 | 5.13 | 0.27 | 79 |
Uterine volume | 0.897 | 3.75 cm3 | 81 | 79 | 90 | 65 | 3.86 | 0.24 | 80 |
Uterine longitudinal diameter | 0.837 | 3.55 cm | 84 | 68 | 86 | 63 | 2.63 | 0.24 | 79 |
Right ovarian volume | 0.811 | 2.15 cm3 | 78 | 77 | 89 | 60 | 3.39 | 0.29 | 78 |
Left ovarian volume | 0.802 | 2.15 cm3 | 76 | 77 | 89 | 58 | 3.30 | 0.31 | 76 |
Endometrial thickness | 0.809 | 1.35 mm | 75 | 79 | 90 | 57 | 3.57 | 0.32 | 76 |
PI and UV combined | 0.866 | PI 5.05; UV 3.75 cm3 | 73 | 95 | 97 | 60 | 14.6 | 0.28 | 79 |
PI, UV, and OV combined | 0.886 | PI 5.05; UV 3.75 cm3; OV 2.15 cm3 | 66 | 95 | 97 | 54 | 13 | 0.36 | 75 |
AUC: area under the curve; LR+: positive likelihood ratio; LR−: negative likelihood ratio; OV: ovarian volume; PI: pulsatility index; PPV: positive predictive value; NPV: negative predictive value; UV: uterine volume. |
We found a strong negative correlation of PI with uterine volume (rs = − 0.72, P < 0.001) and a moderate negative correlation with endometrial thickness (rs = − 0.68, P < 0.001), uterine longitudinal diameter (rs = − 0.68, P < 0.001), and right (rs = − 0.60, P < 0.0001) and left (rs = − 0.59, P < 0.001) ovarian volumes.
The intraclass correlation coefficient for intraobserver agreement of the PI was 0.967 (95% confidence interval, 0.782–0.998; P < 0.001), indicating excellent reliability. The coefficient of variation was 12%.