Clinical epidemiology · 2022
Maternal Cigarette Smoking During Pregnancy and Genital Anomalies in Boys: A Register-Based Cohort and Sibling-Matched Design Study.
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Lindbo Daniel, Arendt Linn Håkonsen, Ernst Andreas, Lunddorf Lea Lykke Harrits, Brix Nis, Ramlau-Hansen Cecilia Høst
Аннотация
PURPOSE: Cryptorchidism and hypospadias share several prenatal risk factors. However, in published studies, boys exposed to cigarette smoking during pregnancy have a higher risk of cryptorchidism and a lower risk of hypospadias. Using Danish register-based data, we revisited these findings with a cohort and sibling-matched design to investigate the potential effect of shared time-stable factors.
PATIENTS AND METHODS: For the cohort study, we included 823,670 live-born, singleton boys born from 1991 to 2016. Crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression models for each genital anomaly according to maternal cigarette smoking during pregnancy. For the sibling-matched design, we included 399,258 brothers and used a stratified Cox regression model creating family-adjusted results.
RESULTS: In the cohort study, we found a higher risk of cryptorchidism (aHR = 1.18, 95% CI: 1.12, 1.24) and a lower risk of hypospadias (aHR = 0.84, 95% CI: 0.76, 0.93) when comparing boys exposed to cigarette smoking with non-exposed, and for increasing numbers of cigarettes smoked. In comparison, the sibling-matched analyses suggested a slightly weaker association for cryptorchidism and an association of similar magnitude for hypospadias, both in the same direction as in the cohort study.
CONCLUSION: Shared, familial confounding does not seem to explain earlier findings of higher risk of cryptorchidism and lower risk of hypospadias.
PATIENTS AND METHODS: For the cohort study, we included 823,670 live-born, singleton boys born from 1991 to 2016. Crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression models for each genital anomaly according to maternal cigarette smoking during pregnancy. For the sibling-matched design, we included 399,258 brothers and used a stratified Cox regression model creating family-adjusted results.
RESULTS: In the cohort study, we found a higher risk of cryptorchidism (aHR = 1.18, 95% CI: 1.12, 1.24) and a lower risk of hypospadias (aHR = 0.84, 95% CI: 0.76, 0.93) when comparing boys exposed to cigarette smoking with non-exposed, and for increasing numbers of cigarettes smoked. In comparison, the sibling-matched analyses suggested a slightly weaker association for cryptorchidism and an association of similar magnitude for hypospadias, both in the same direction as in the cohort study.
CONCLUSION: Shared, familial confounding does not seem to explain earlier findings of higher risk of cryptorchidism and lower risk of hypospadias.