Correlation between anogenital distance and severity of hypospadias in male children

Abstract

Background

Previous studies have shown an association between anogenital distance (AGD) and types of hypospadias. This study aims to determine whether AGD can be used to predict the severity of hypospadias in male children.

Methods

We used a cross-sectional study design to evaluate (43) children with hypospadias. The severity of hypospadias based on the meatal position before surgery was classified using the meatal score of the glans-urethral meatal-shaft (GMS) classification into four groups of M1–M4. Three AGD parameters viz: ano-scrotal distance (ASD), the ano-penal distance 1 (APD1) and the ano-penal distance 2 (APD2) were measured using a digital calliper. The glanulomeatal distance 1 (GMD1) before and the glanulomeatal distance 2 (GMD2) after chordee correction were calculated for any change in the position of the meatus. Data were collected over 18 months and analysed using Statistical Package for Social Sciences (IBM SPSS) version 25 software. A P-value of < 0.05 was considered to be statistically significant.

Results

The mean ano-scrotal distance (ASD), ano-penile distance 1 (APD1) and ano-penile distance 2 (APD2) were 35.0 ± 7.11 mm, 66.0 ± 13.0 mm and 82.05 ± 14.0 mm, respectively. The parameters of AGD and AGD index progressively decreased with increasing meatal score but these decreases were not statistically significant across the four categories of meatal score. Statistically significant, moderately negative correlations were observed between GMD2 and mean ASD (R = − 0.394, P ≤ 0.009), APD1 (R = − 0.308, P ≤ 0.045) and APD2 (R = − 0.391, P ≤ 0.010). There were also statistically significant predictive relationships between GMD2 (intra-operative meatal position) with ASD (R² = 0.155, P ≤ 0.009), APD1 (R² = 0.095, P ≤ 0.045) and APD2 (R² = 0.153, P ≤ 0.010).

Conclusion

The study demonstrated a significant relationship between the AGD and meatal position. Therefore, AGD may be used to predict the intra-operative meatal position and hence, the severity of hypospadias before surgery.

1 Background

In children with hypospadias, the position of the meatus on the ventral surface of the penis is the most common way to classify the severity of hypospadias [1,2,3]. This pre-operative classification may differ from intra-operative findings after correction of chordee or release of peno-scrotal transposition, as the meatus may become significantly more proximal or distal [1, 2, 4]. Such intra-operative observations may result in a change of planned repair technique to a more complex one and sometimes the conversion of one-stage surgery to a two-stage procedure [1] that both the surgeons and caregivers may not have prepared for.

Previous studies on hypospadias and anogenital distance (AGD) have indicated that the preoperative location of the meatus correlates with AGD with the more proximal meatal location associated with shorter AGD [4,5,6]. These prior studies, however, have not determined the utility of AGD in predicting the eventual severity of hypospadias after excision of abnormal fibrotic urethral tissue, the release of chordee, and or release of peno-scrotal transposition. Preoperative determination of the ultimate meatal location and hence severity of hypospadias might be invaluable in planning for the repair of hypospadias. The objective of this study was to determine if AGD can be used to preoperatively predict the actual severity of hypospadias.

2 Methods

2.1 Study design

This was a prospective cross-sectional study of children with hypospadias managed at the Alex Ekwueme Federal University Teaching Hospital, Abakaliki (AEFUTHA) from February 2019 to July 2020. Ethical clearance for the study with reference number FETHA/REC/VOL2/2018/146 was obtained from the Hospital’s Research and Ethics Committee (HREC). Informed consent was obtained from the participant's parents or guardians.

2.2 Sample size calculation

The sample size was determined using the formula for a single proportion [7]:

$$n = Zpq/d^{2} ,$$

where Z = 2.0 (standard normal deviation corresponding to the probability of type I error).

P = 0.208 (prevalence of severe hypospadias) [8]:

$$q = 1{-}p = 0.792,$$

$$d = 0.{13 }\left( {\text{degree of accuracy}} \right),$$

$$n = \left( {2^{2} \times 0.208 \times 0.792} \right)/0.13^{2} ,$$

$$n = 39.$$

Assuming 10% non-response or attrition rate = 10/100 × 39 = 3.9 = 4.

Then, n = 39 + 4 = 43.

For this study, the minimum sample size was 43.

2.3 Procedure

Before the operative intervention, all the children were evaluated clinically and the severity of hypospadias based on the meatal position before surgery was noted and classified into (a) glanular, (b) coronal, (c) distal penile, (d) mid-penile, (e)proximal penile, (f) peno-scrotal, (g) scrotal or (h) perineal. This was further grouped into four classes using Meatal Score of Glans-Urethral Meatus-Shaft Score (GMS) hypospadias classification [9] into glandular—M1, coronal sulcus—M2, distal or middle penile—M3, proximal shaft, peno-scrotal, scrotal or perineal—M4.

Using a digital calliper (Stainless steel electronic digital calliper, Original Equipment Manufacturer (OEM), Hong Kong) that reads in increments of 0.01 mm, and with the patients in supine and frog-leg position under general anaesthesia, the AGD was measured. Three AGD parameters (Fig. 1) were measured viz: Anoscrotal Distance (ASD distance from the centre of the anus to the junction between the smooth perineal skin and the rugated skin of the scrotum), Anopenile Distance 1 (APD1; distance from the centre of the anus to the posterior border of the base of the penis), and Anopenile Distance 2 (APD2 distance from the centre of the anus to the anterior border of the base of the penis).

Fig. 1

Parameters of male angenital distance

For those that had chordee, a gentle downward pressure was applied at the penopubic junction, and the degree of chordee was measured with a protractor and classified using the Shaft Score of Glans-Urethral Meatus-Shaft Score (GMS) hypospadias classification into no chordee(S1), mild—less than 30° (S2), moderate—30° to 60° (S3) and severe—greater than 60° (S4) [9]. The distance from the tip of the glans to the abnormally located external urethral meatus (glanulomeatal distance 1—GMD1) was measured before degloving the penis.

After degloving, an artificial erection test as described by Gittes and McLaughlin [10] was done. The degree of chordee was measured with a protractor and graded into: no chordee (S1), mild—less than 30° (S2), moderate—30° to 60° (S3) and severe—greater than 60° (S4). Subsequently, an artificial erection test was used to monitor the adequacy of chordee correction. After adequate chordee correction, the GMD2 was measured using a separate digital calliper and if there was any change in meatal position, the intra-operative severity of the hypospadias based on the new meatal position after correction of chordee was also re-graded using the Meatal Score into glandular—M1, coronal sulcus—M2, distal or middle penile—M3, proximal shaft, penoscrotal, scrotal or perineal—M4 [9]. To mitigate observer error, two researchers took the same measurements and the average for each measurement was calculated and used for analysis. Anogenital index (AGI), which is AGD/patient’s weight (mm/kg) was calculated to control any effect of variation in body size on AGD.

2.4 Data collection

A well-structured proforma was used for data collection. Data collected included biodata, weight (kg), height (mm), diagnosis, AGD (mm), AGI—AGD/patient’s weight (mm/kg), degree of chordee, pre-operative and intra-operative meatal position/score.

2.5 Statistical analysis

Data entry and analyses were done using the Statistical Package for Social Sciences (IBM; SPSS, Chicago, IL, USA) version 25 software). Descriptive statistics of socio-demographic and other background characteristics were presented. Categorical variables were summarized with frequencies and proportions, while continuous variables were presented as means and standard deviations.

The relationship between the GMD1, GMD2, and AGD was analysed using Pearson correlation, and the predictive equations were obtained using regression analysis. The level of significance was set at a P < 0.05. The degree of correlation was set to be perfect if the correlation coefficient is ± 1, strong if the value is between ± 0.5 and ± 1, moderate if the value is ± 0.3 and 0.49, weak if the value is < ± 0.29 and no correlation if the value is zero.

3 Results

Overall, 43 participants were studied, with a mean age of 2.5 ± 1.67 years (0.5–7.0 years). The mean height, weight and BMI were 1.0 ± 0.19 m, 13.1 ± 4.97 kg and 13.6 ± 2.38 kg/m², respectively.

3.1 Pre-operative severity of hypospadias based on the position of the external urethral meatus

Assessment of pre-operative severity of hypospadias based on the position of external urethral meatus showed that 6 (14.0%) participants had glanular, 9 (20.9%) coronal, 12 (27.9%) distal penile, 4 (9.3%) mid-penile, 5 (11.6%) proximal penile, 5 (11.6%) peno-scrotal and 2 (4.7%) perineal hypospadias.

3.2 Severity of hypospadias based on meatal score

Using meatal score to assess the severity of hypospadias, 6 patients had an M score of 1, 9 had an M score of 2, 16 had an M score of 3 and 12 had an M score of 4 (Fig. 2).

Fig. 2

Pie chart showing the severity of the hypospadias based on meatal Score

Twenty-three (53.5%) participants had chordee. Fourteen (32.6%) of the patients had the severity of their hypospadias re-classified based on the more proximal position of the urethral opening after correcting chordee.

3.3 Comparison of anthropometric characteristics of participants with meatal score

The mean ages for participants in M1, M2, M3 and M4 were 2.2 ± 2.42 years, 2.2 ± 1.33 years, 2.6 ± 1.78 years and 2.8 ± 1.48 years, respectively, with P-value = 0.830. The mean BMI for the participants in M1, M2, M3 and M4 were 13.0 ± 2.43 kg/m², 13.9 ± 2.86 kg/m², 13.1 ± 2.25 kg/m² and 13.1 ± 2.25 kg/m², respectively, with P-value = 0.534. There was no statistically significant difference in mean age and BMI in the 4 groups of hypospadias severity.

3.4 Comparison of parameters of anogenital distance with the meatal score

In comparing the parameters of anogenital distance with the meatal score, the ano-scrotal distance (ASD) ranged from 18.5 to 50.4 mm with a mean of 35.0 ± 7.1 mm. The mean APD1 was 66.0 ± 13.04 mm (range: 44.0–95.0 mm) while the mean APD2 was 82.1 ± 13.99 mm (range: 60.0–112.0 mm). The mean ASD, ano-penal distance 1 (APD1) and ano-penal distance 2 (APD2) decreased with increasing meatal (M) score. However, the difference in mean ASD, APD1 and APD2 for participants in groups M1, M2, M3 and M4 were not statistically significant, as shown in Table 1.

Table 1 Comparison of anogenital distance with meatal score

3.5 Comparison of parameters of anogenital distance index with meatal score

In the 4 groups of hypospadias severity (M1–M4), the mean ano-scrotal index (ASDI), ano-penal distance 1 index (APD1I) and ano-penal distance 2 index (APD2I) decreased with increase in meatal score. These decreases in mean ASDI, APD1I and APD2I were not statistically significant as shown in Table 2.

Table 2 Comparison of parameters of anogenital distance index with meatal score

3.6 Parameters of glanulomeatal distance

The distance from the tip of the glans to the abnormally located external urethral meatus (glanulomeatal distance 1—GMD1) was measured before degloving the penis and it ranged from 5.0 to 20.0 mm with a mean of 12.8 ± 3.56 mm. The distance from the tip of the glans to the external urethral meatus after correction of chordee (glanulomeatal distance 2—GMD2) was measured, and it ranged from 5.0 to 56.0 mm with a mean of 26.0 ± 16.1 mm.

3.7 Comparison of GMD1 and GMD2 with meatal score

Comparing the GMD1 and GMD2 with the meatal score revealed that the mean glanulomeatal distance 1 (GMD1) did not show a regular pattern of increment across the four groups of the meatal score (M1–M4). However, the difference in mean GMD1 was statistically significant with a P-value of 0.001. There was a progressive increase in mean glanulomeatal distance 2 (GMD2) with an increase in Meatal Score. This was statistically significant with a P-value = 0.000 as shown in Table 3.

Table 3 Comparison of GMD1 and GMD2 with meatal score

3.8 Correlation between AGD parameters and pre-operative meatal position

There was no statistically significant correlation between ASD, APD1 and APD2 and glanulomeatal meatal distance 1 (GMD1) as shown in Table 4.

Table 4 Correlation between AGD parameters and GMD1

3.9 Correlation between AGD parameters and GMD2

Statistical analysis with Pearson correlation showed significant, moderately negative correlations between ASD, APD1 and APD2 with glanulomeatal meatal distance 2 (GMD2—meatal position after correction of chordee) as shown in Table 5 and Figs. 3, 4 and 5. This implied that an increase in ASD, APD1 and APD2 was associated with a decrease in GMD2 and hence, the more distal the hypospadias would be.

Table 5 Correlation between GMD2 and AGD parameters

Fig. 3

Scatter plot showing the correlation between GDM2 and ASD

Fig. 4

Scatter plot showing the correlation between GDM2 and APD1

Fig. 5

Scatter plot showing the correlation between GDM2 and APD2

3.10 Prediction of the intra-operative meatal position with AGD parameters

Statistically significant regression equations were found between the meatal position after the correction of chordee and anogenital distance parameters. Such equations can use AGD parameters to predict the intra-operative meatal position. ASD predicted GMD2 (meatal position) using the regression equation, GMD2 (mm) = 57.114–0.890(ASD). APD1 predicted GMD2 using the regression equation, GMD2 (mm) = 50.978–0.379(APD1) and APD2 predicted GMD2 using the regression equation, GMD (mm) = 62.794–0.449(APD2). This means that every 1 mm increase in ASD resulted in a decrease in GMD2 by 0.89 mm. Every 1 mm increase in APD1 was associated with a 0.38 mm decrease in GMD2. Also, every 1 mm increase in APD2 was associated with a 0.45 mm decrease in GMD2 as shown in Table 6.

Table 6 Prediction of intra-operative meatal position with AGD

4 Discussion

The mean anogenital distance parameters obtained in this study fell within the range of values reported by earlier researchers [4, 5, 11, 12, 16, 18]. The mean ASD obtained in this study was longer than the values reported in previous studies on male children under 2 years old with hypospadias [5, 11, 12]. The participants in their study were younger than those seen in ours. The differences observed in the mean ASD in these reports may be due to variations in the age, and weight of participants [5, 13] and differences in tools used for the measurement of AGD [12]. Longer perineal length in older children may be responsible for the longer ASD obtained in this study as anogenital distance has been reported to grow with the external genitalia from birth through puberty [14, 15].

On the other hand, some studies [4, 6, 16] reported higher ASD when compared with the value obtained in this work. Singal et al. [6] in the USA used participants with similar mean age, weight, and height characteristics as in this present study. Twenty-seven percent of their patients had posterior hypospadias which is similar to what was recorded in our study. The value of ASD they obtained was longer than that obtained in the current study. This might be attributed to their use of vernier callipers (instead of digital callipers) in their measurements.

In the United Kingdom, Cox et al. [4] used a digital calliper to study hypospadiac children with a smaller mean age and weight. They obtained a longer mean ASD. The higher value of ASD found in their study may be due to the smaller percentage (16.9%) of participants with posterior hypospadias compared with 27.9% recorded in this study. More severe types of hypospadias have been reported to be associated with shorter AGD [4, 6, 16, 17]. Abdelhalim et al. [16] in Egypt studied patients with similar age and weight distribution with 21.1% of them having severe hypospadias. They also reported a higher value of ASD. However, they used a ruler as the measuring instrument. The higher mean ASD obtained by them may be related to a difference in the measuring instrument and a smaller percentage of patients with severe hypospadias.

The APD1 obtained in our study varied from that reported in some other studies. Hsieh et al. [12, 18] in two separate studies conducted in the United States used two different measuring instruments; a flexible surgical tape [12] and sutures, and then measured the marked suture against vernier callipers [18]. They obtained longer APD1 in both studies. The longer mean APD1 in these studies may be explained by the difference in the instruments used for the measurement of AGD. The differences in the age and weight of the participants may also have played a role. Singal et al. [6] also obtained longer APD1. They, however, used vernier callipers in their measurements which may account for the difference in value of APD1 seen in their study. Cox et al. [4] in their study equally obtained a longer APD1 when compared with the value recorded in our study. This may be due to the smaller group of patients with severe hypospadias in their study. In a study [6] on APD2 in boys with hypospadias using vernier callipers, the authors recorded a shorter APD2 of 79.30 mm compared with our value of 82.05 mm. The difference in values may again be due to the difference in the instruments used in the studies.

In this current work, the mean ASD, APD1 and APD2 showed a progressive decrease with increasing severity of hypospadias based on pre-operative meatal position. The participants with milder forms of hypospadias had longer AGD. The differences in AGD parameters among the four groups of severity of hypospadias persisted even after adjustment for weight (AGD/Wt). However, this decrease was not statistically significant. This may be because of the small sample size of patients used in this study. This agrees with the findings in a study by Thankamony et al. [13] using vernier callipers. In another study [6] with a similar age and weight distribution to our study, the authors demonstrated progressively shorter AGD parameters with an increase in the severity of hypospadias. The differences in ASD and APD1 across the three groups of hypospadias severity used in their study were statistically significant. This indicates that patients with more severe forms of hypospadias had significantly shorter ASD and APD1 when compared with those having milder forms of hypospadias. The statistically significant difference observed in that study may be ascribed to the larger sample size of 180 male children with hypospadias used. It may also be due to their use of three classes of hypospadias severity instead of the four groups used in this study. Also, Cox et al. [4] demonstrated a progressive decrease in mean ASD and APD1 with an increase in the severity of hypospadias. The decrease showed only a statistically significant difference with mean APD1 across two groups of hypospadias severity used in their work. This may be because the distance from the anus to the posterior border of the base of the penis (APD1) is longer and can easily be measured with less error when compared with the shorter distance from the anus and the junction between the smooth perineal skin and ruggated skin of the scrotum (ASD). The decrease in mean ASD and AGD index were not statistically significant. Their report that the difference in mean AGD index was not statically significant is keeping with the finding in this present study. This may indicate that patients’ weight has little or no effect on AGD. Therefore, dividing AGD with weight may not improve the reliability of AGD as has been observed by some authors [19].

There was no significant correlation between the position of the external urethral meatus before correction of chordee (glanulomeatal distance 1—GMD1) and AGD parameters in this study. This may be attributed to the smaller number of patients that were pre-operatively diagnosed with posterior hypospadias in the study based on the apparent position of the meatus before correction of chordee. There was a progressive statistically significant increase in glanulomeatal distance 2 (GMD2) with an increase in the severity of hypospadias (meatal score). This indicates that longer GMD2 is associated with more proximal hypospadias. Also, a moderate negative correlation between GMD2 and AGD parameters was observed. This means that as the GMD2 increases (more proximal hypospadias) the AGD reduces. This may be because 33% of the participants acquired more proximal meatal location with increased glanulomeatal distance after correction of chordee. A similar observation was also reported by Cox et al. [4] who re-classified the severity of hypospadias in 7 (11.8%) of their patients after chordee correction. Presently, we could not access any published study on the relationship between glanulomeatal distance and AGD parameters in boys with hypospadias for comparison of results.

There was a significant predictive relationship between GMD2 (intra-operative meatal position) and AGD parameters in this study. This implies that AGD can be used to determine the severity of hypospadias based on the actual position of the meatal opening. No previous study was found that used AGD parameters to predict the severity of hypospadias for comparison of results.

4.1 Limitations of the study

The present report is limited by the small sample size which did not provide adequate power to the study. Another limitation was that different authors used different instruments for the measurement of AGD. This made comparison of data difficult.

5 Conclusion

This study has shown that AGD parameters progressively decreased with increasing severity of hypospadias with a significant relationship between the AGD and meatal position. This correlation between AGD and the severity of hypospadias and AGD may be used to predict the intra-operative meatal position and provide a guide in preoperative planning and counselling of parents of children with hypospadias.