Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Human Reproduction |
| Vol/bind | 38 |
| Udgave nummer | 2 |
| Sider (fra-til) | 293-305 |
| Antal sider | 13 |
| ISSN | 0268-1161 |
| DOI | |
| Status | Udgivet - 2023 |
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Selection bias in a male-offspring cohort investigating fecundity : is there reason for concern? / Gaml-Sorensen, Anne; Brix, Nis; Tottenborg, Sandra Sogaard; Hougaard, Karin Sorig; Haervig, Katia Keglberg; Bonde, Jens Peter Ellekilde; Henriksen, Tine Brink; Toft, Gunnar; Ramlau-Hansen, Cecilia Host.
I: Human Reproduction, Bind 38, Nr. 2, 2023, s. 293-305.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Selection bias in a male-offspring cohort investigating fecundity
T2 - is there reason for concern?
AU - Gaml-Sorensen, Anne
AU - Brix, Nis
AU - Tottenborg, Sandra Sogaard
AU - Hougaard, Karin Sorig
AU - Haervig, Katia Keglberg
AU - Bonde, Jens Peter Ellekilde
AU - Henriksen, Tine Brink
AU - Toft, Gunnar
AU - Ramlau-Hansen, Cecilia Host
PY - 2023
Y1 - 2023
N2 - STUDY QUESTION Is there risk of selection bias in etiological studies investigating prenatal risk factors of poor male fecundity in a cohort of young men? SUMMARY ANSWER The risk of selection bias is considered limited despite a low participation rate. WHAT IS KNOWN ALREADY Participation rates in studies relying on volunteers to provide a semen sample are often very low. Many risk factors for poor male fecundity are associated with participation status, and as men with low fecundity may be more inclined to participate in studies of semen quality, a risk of selection bias exists. STUDY DESIGN, SIZE, DURATION A population-based follow-up study of 5697 young men invited to the Fetal Programming of Semen Quality (FEPOS) cohort nested within the Danish National Birth Cohort (DNBC), 1998-2019. PARTICIPANTS/MATERIALS, SETTING, METHODS Young men (age range: 18 years, 9 months to 21 years, 4 months) born 1998-2000 by mothers included in the DNBC were invited to participate in FEPOS. In total, 1173 men answered a survey in FEPOS (n = 115 participated partly); of those, 1058 men participated fully by also providing a semen and a blood sample at a clinical visit. Differential selection according to parental baseline characteristics in the first trimester, the sons' own characteristics from the FEPOS survey, and urogenital malformations and diseases in reproductive organs from the Danish registers were investigated using logistic regression. The influence of inverse probability of selection weights (IPSWs) to investigate potential selection bias was examined using a predefined exposure-outcome association of maternal smoking in the first trimester (yes, no) and total sperm count analysed using adjusted negative binomial regression. A multidimensional bias analysis on the same association was performed using a variety of bias parameters to assess different scenarios of differential selection. MAIN RESULTS AND THE ROLE OF CHANCE Participation differed according to most parental characteristics in first trimester but did not differ according to the prevalence of a urogenital malformation or disease in the reproductive organs. Associations between maternal smoking in the first trimester and male fecundity were similar when the regression models were fitted without and with IPSWs. Adjusting for other potential risk factors for poor male fecundity, maternal smoking was associated with 21% (95% CI: -32% to -9%) lower total sperm count. In the bias analysis, this estimate changed only slightly under realistic scenarios. This may be extrapolated to other exposure-outcome associations. LIMITATIONS, REASONS FOR CAUTION We were unable to directly assess markers of male fecundity for non-participants from, for example an external source and therefore relied on potential proxies of fecundity. We did not have sufficient power to analyse associations between prenatal exposures and urogenital malformations. WIDER IMPLICATIONS OF THE FINDINGS The results are reassuring when using this cohort to identify causes of poor male fecundity. The results may be generalized to other similar cohorts. As the young men grow older, they can be followed in the Danish registers, as an external source, to examine, whether participation is associated with the risk of having an infertility diagnosis.STUDY FUNDING/COMPETING INTEREST(S) The project was funded by the Lundbeck Foundation (R170-2014-855), the Capital Region of Denmark, Medical doctor Sofus Carl Emil Friis and spouse Olga Doris Friis's Grant, Axel Muusfeldt's Foundation (2016-491), AP Moller Foundation (16-37), the Health Foundation, Dagmar Marshall's Fond, Aarhus University and Independent Research Fund Denmark (9039-00128B). The authors declare that they have no conflict of interest.
AB - STUDY QUESTION Is there risk of selection bias in etiological studies investigating prenatal risk factors of poor male fecundity in a cohort of young men? SUMMARY ANSWER The risk of selection bias is considered limited despite a low participation rate. WHAT IS KNOWN ALREADY Participation rates in studies relying on volunteers to provide a semen sample are often very low. Many risk factors for poor male fecundity are associated with participation status, and as men with low fecundity may be more inclined to participate in studies of semen quality, a risk of selection bias exists. STUDY DESIGN, SIZE, DURATION A population-based follow-up study of 5697 young men invited to the Fetal Programming of Semen Quality (FEPOS) cohort nested within the Danish National Birth Cohort (DNBC), 1998-2019. PARTICIPANTS/MATERIALS, SETTING, METHODS Young men (age range: 18 years, 9 months to 21 years, 4 months) born 1998-2000 by mothers included in the DNBC were invited to participate in FEPOS. In total, 1173 men answered a survey in FEPOS (n = 115 participated partly); of those, 1058 men participated fully by also providing a semen and a blood sample at a clinical visit. Differential selection according to parental baseline characteristics in the first trimester, the sons' own characteristics from the FEPOS survey, and urogenital malformations and diseases in reproductive organs from the Danish registers were investigated using logistic regression. The influence of inverse probability of selection weights (IPSWs) to investigate potential selection bias was examined using a predefined exposure-outcome association of maternal smoking in the first trimester (yes, no) and total sperm count analysed using adjusted negative binomial regression. A multidimensional bias analysis on the same association was performed using a variety of bias parameters to assess different scenarios of differential selection. MAIN RESULTS AND THE ROLE OF CHANCE Participation differed according to most parental characteristics in first trimester but did not differ according to the prevalence of a urogenital malformation or disease in the reproductive organs. Associations between maternal smoking in the first trimester and male fecundity were similar when the regression models were fitted without and with IPSWs. Adjusting for other potential risk factors for poor male fecundity, maternal smoking was associated with 21% (95% CI: -32% to -9%) lower total sperm count. In the bias analysis, this estimate changed only slightly under realistic scenarios. This may be extrapolated to other exposure-outcome associations. LIMITATIONS, REASONS FOR CAUTION We were unable to directly assess markers of male fecundity for non-participants from, for example an external source and therefore relied on potential proxies of fecundity. We did not have sufficient power to analyse associations between prenatal exposures and urogenital malformations. WIDER IMPLICATIONS OF THE FINDINGS The results are reassuring when using this cohort to identify causes of poor male fecundity. The results may be generalized to other similar cohorts. As the young men grow older, they can be followed in the Danish registers, as an external source, to examine, whether participation is associated with the risk of having an infertility diagnosis.STUDY FUNDING/COMPETING INTEREST(S) The project was funded by the Lundbeck Foundation (R170-2014-855), the Capital Region of Denmark, Medical doctor Sofus Carl Emil Friis and spouse Olga Doris Friis's Grant, Axel Muusfeldt's Foundation (2016-491), AP Moller Foundation (16-37), the Health Foundation, Dagmar Marshall's Fond, Aarhus University and Independent Research Fund Denmark (9039-00128B). The authors declare that they have no conflict of interest.
KW - selection bias
KW - participation
KW - semen quality
KW - male fecundity
KW - male-offspring cohort
KW - inverse probability of selection weights
KW - bias analysis
KW - SEMEN QUALITY
KW - REPRODUCTIVE HEALTH
KW - BIRTH COHORT
KW - POPULATION
KW - FERTILITY
KW - DISORDERS
KW - PREGNANCY
KW - SMOKING
KW - MARKER
KW - TRENDS
U2 - 10.1093/humrep/deac241
DO - 10.1093/humrep/deac241
M3 - Journal article
C2 - 36370427
VL - 38
SP - 293
EP - 305
JO - Human Reproduction
JF - Human Reproduction
SN - 0268-1161
IS - 2
ER -