Background
Methods
Data and study design
Male hypospadias
Placental perfusion measurement and definition
Covariates
Data analysis
Results
Basic characteristics of the study participants
Prevalence of male hypospadias
Characteristics | Male Hypospadias (n = 21,447, cases = 43) | ||||
---|---|---|---|---|---|
Total no. of infants | No. of cases | Prevalence per 1000 infants (95% CI) | P value | ||
Placental perfusiona | .03 | ||||
Normal | 14,186 | 24 | 1.7 (1.0–2.4) | ||
Abnormal | 1861 | 9 | 4.8 (1.7–8.0) | .01b | |
NA | 5400 | 10 | 1.9 (0.7–3.0) | .81 | |
Preeclampsia | .001 | ||||
No | 20,275 | 36 | 1.8 (1.2–2.4) | ||
Yes | Mild | 960 | 3 | 3.1 (0.0–6.7) | .26b |
Severe | 212 | 4 | 18.9 (0.4–37.3) | .001b | |
Any | 1172 | 7 | 6.0 (1.6–10.4) | .008b | |
Maternal age at delivery (year) | .34b | ||||
≥ 35 | 2145 | 5 | 2.3 (0.3–4.4) | ||
25–34 | 18,224 | 38 | 2.1 (1.4–2.7) | ||
< 25 | 1078 | 0 | 0 | ||
Residence | .59 | ||||
Shanghai | 16,536 | 35 | 2.1 (1.4–2.8) | ||
Other provinces | 4884 | 8 | 1.6 (0.5–2.8) | ||
Parity | .14 | ||||
Nulliparous | 18,099 | 40 | 2.2 (1.5–2.9) | ||
Multiparous | 3348 | 3 | 0.9 (0.0–1.9) | ||
Gestational diabetes mellitus | >.99b | ||||
No | 19,616 | 40 | 2.0 (1.4–2.7) | ||
Yes | 1831 | 3 | 1.6 (0.0–3.5) | ||
Assisted conception | .18b | ||||
No | 21,061 | 41 | 1.9 (1.4–2.5) | ||
Yes | 386 | 2 | 5.2 (0.0–12.3) |
Association between APP and male hypospadias
Characteristics | Male hypospadias | ||
---|---|---|---|
Crude odds ratio (95% CI) | Adjusted odds ratio (95% CI) | ||
Placental perfusion | |||
Normal | 1.00 | 1.00 | |
Abnormal a | 2.87 (1.33–6.18) | 2.40 (1.09–5.29) | |
NA | 1.10 (0.52–2.29) | 1.12 (0.53–2.37) | |
Preeclampsia | |||
No | 1.00 | 1.00 | |
Yes | Mild | 1.76 (0.54–5.73) | 1.56 (0.47–5.11) |
Severe | 10.81 (3.82–30.66) | 7.75 (2.62–22.89) | |
Maternal age at delivery (years) | |||
≥ 35 | 1.00 | 1.00 | |
25–34 | 0.89 (0.35–2.27) | 0.74 (0.27–1.99) | |
< 25 | – | – | |
Residence | |||
Shanghai | 1.00 | 1.00 | |
Other provinces | 0.78 (0.36–1.67) | 0.90 (0.41–1.96) | |
Parity | |||
Nulliparous | 1.00 | 1.00 | |
Multiparous | 0.41 (0.13–1.31) | 0.39 (0.11–1.33) | |
Gestational diabetes mellitus | |||
No | 1.00 | 1.00 | |
Yes | 0.80 (0.25–2.60) | 0.68 (0.21–2.23) | |
Assisted conception | |||
No | 1.00 | 1.00 | |
Yes | 2.66 (0.64–11.02) | 1.96 (0.45–8.55) |
Variant of abnormal placental perfusion | Male hypospadias | |||
---|---|---|---|---|
No. of infants | No. of cases | Adjusted odds ratio (95% CI) | ||
Right uterine artery | ||||
PI | Normal (≤P95) | 15,244 | 28 | 1.00 |
High (>P95) | 835 | 5 | 2.60 (0.97–6.98) | |
RI | Normal (≤P95) | 15,348 | 29 | 1.00 |
High (>P95) | 731 | 4 | 2.34 (0.80–6.85) | |
EDN | No | 15,942 | 32 | 1.00 |
Yes | 144 | 1 | 2.27 (0.29–17.65) | |
Left uterine artery | ||||
PI | Normal (≤P95) | 15,218 | 28 | 1.00 |
High (>P95) | 839 | 4 | 2.03 (0.68–5.99) | |
RI | Normal (≤P95) | 15,267 | 27 | 1.00 |
High (>P95) | 790 | 5 | 2.86 (1.06–7.70) | |
EDN | No | 15,859 | 30 | 1.00 |
Yes | 226 | 3 | 5.33 (1.56–18.26) | |
No. of insufficient markers | ||||
0 | 14,186 | 24 | 1.00 | |
1 | 663 | 3 | 2.50 (0.75–8.34) | |
2 | 872 | 3 | 1.79 (0.53–6.04) | |
3 and above | 326 | 3 | 3.59 (0.99–12.95) | |
Left uterine artery RI and EDN | ||||
Normal RI and without EDN | 15,112 | 26 | 1.00 | |
High RI or with EDN | 866 | 6 | 3.35 (1.34–8.38) | |
High RI and with EDN | 75 | 1 | 6.33 (0.68–41.70) | |
Any of high RI and/or with EDN | 941 | 7 | 3.53 (1.48–8.41) |
Effect of APP on the risk of male hypospadias
No. of population | Direct factor (causal chainb) | Total effect | The effect of abnormal placental perfusion | |||||
---|---|---|---|---|---|---|---|---|
Coef. | Standard Error | P value | Coef. | Standard Error | P value | Size of the total effect (%) | ||
Infants (16051), any PE (874), APP (1861), anomalies (33) | Any PE (1) | 1.30 | 0.49 | .007 | 0.15 | 0.06 | .009 | 11.54 |
APP (2) | 1.06 | 0.36 | .003 | 0.95 | 0.34 | .006 | 89.62 | |
Total (3) | 2.36 | 1.10 | 46.61 | |||||
Infants (15903), mild PE (726), APP (1792), anomalies (29) | Mild PE (1) | 0.36 | 0.60 | .54 | 0.04 | 0.05 | .37 | 11.11 |
APP (2) | 0.50 | 0.56 | .38 | 0.49 | 0.55 | .37 | 98.00 | |
Total (3) | 0.86 | 0.53 | 61.63 | |||||
Infants (15325), severe PE (148), APP (1730), anomalies (31) | Severe PE (1) | 2.68 | 0.60 | <.001 | 0.30 | 0.16 | .07 | 11.19 |
APP (2) | 1.01 | 0.35 | .004 | 0.74 | 0.31 | .02 | 73.27 | |
Total (3) | 3.69 | 1.04 | 28.18 |