TY - JOUR
T1 - Associations between health behaviours, fertility and reproductive outcomes
T2 - triangulation of evidence in the Norwegian Mother, Father and Child Cohort Study (MoBa)
AU - Wootton, Robyn E.
AU - Lawn, Rebecca B.
AU - Magnus, Maria C.
AU - Treur, Jorien L.
AU - Corfield, Elizabeth C.
AU - Njølstad, P. l R.
AU - Andreassen, Ole A.
AU - Lawlor, Deborah A.
AU - Munafò, Marcus R.
AU - Håberg, Siri E.
AU - Davey Smith, George
AU - Reichborn-Kjennerud, Ted
AU - Magnus, Per
AU - Havdahl, Alexandra
N1 - Funding Information: This study includes data from the Norwegian Mother, Father and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. We are grateful to all the participating families in Norway who take part in this ongoing cohort study. We thank the Norwegian Institute of Public Health (NIPH) for generating high-quality genomic data. Funding Information: The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. This research is part of the HARVEST collaboration, supported by the Research Council of Norway (#229,624). For providing genotype data we thank deCODE Genetics, and the NORMENT Centre for providing genotype data, funded by the Research Council of Norway (#223,273), South-East Norway Health Authority and KG Jebsen Stiftelsen. We further thank the Center for Diabetes Research, the University of Bergen for providing genotype data and performing quality control and imputation of the data funded by the ERC AdG project SELECTionPREDISPOSED, Stiftelsen Kristian Gerhard Jebsen, Trond Mohn Foundation, the Research Council of Norway, the Novo Nordisk Foundation, the University of Bergen, and the Western Norway health Authorities (Helse Vest). This research was also supported by the Research Council of Norway through its Centres of Excellence funding scheme (project No 262700). Funding Information: Open access funding provided by Norwegian Institute of Public Health (FHI). This work was partly supported by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. REW is currently funded by a postdoctoral fellowship from the South-Eastern Norway Regional Health Authority (2020024). AH was supported by a career grant from the South-Eastern Norway Regional Health Authority (2020022) and by the Research Council of Norway (300668, 288083, 274611). TRK was supported by the Research Council of Norway (274611). PM and SEH were partly funded by the Research Council of Norway (262700 and 320656). GDS, MRM and DAL are supported by the Medical Research Council Integrative Epidemiology Unit at the University of Bristol (MM_UU_00011/1, MM_UU_00011/6, and MM_UU_00011/7). JLT was supported by a Veni grant from the Netherlands Organization for Scientific Research (NWO: grant number 016.Veni.195.016) and by the Foundation Volksbond Rotterdam. MCM has funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 947684). DAL’s contribution is supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 101021566). This project was conducted using Sigma2 (NS9791S). Publisher Copyright: © 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - BACKGROUND: Guidance to improve fertility includes reducing alcohol and caffeine consumption, achieving healthy weight-range and stopping smoking. Advice is informed by observational evidence, which is often biased by confounding. METHODS: This study primarily used data from a pregnancy cohort, the Norwegian Mother, Father and Child Cohort Study. First, we conducted multivariable regression of health behaviours (alcohol and caffeine consumption, body-mass index (BMI), and smoking) on fertility outcomes (e.g. time to conception) and reproductive outcomes (e.g. age at first birth) (n = 84,075 females, 68,002 males), adjusting for birth year, education and attention-deficit and hyperactive-impulsive (ADHD) traits. Second, we used individual-level Mendelian randomisation (MR) to explore possible causal effects of health behaviours on fertility/reproductive outcomes (n = 63,376 females, 45,460 males). Finally, we performed summary-level MR for available outcomes in UK Biobank (n = 91,462-1,232,091) and controlled for education and ADHD liability using multivariable MR. RESULTS: In multivariable regression analyses, higher BMI associated with fertility (longer time to conception, increased odds of infertility treatment and miscarriage), and smoking was associated with longer time to conception. In individual-level MR analyses, there was strong evidence for effects of smoking initiation and higher BMI on younger age at first birth, of higher BMI on increased time to conception, and weak evidence for effects of smoking initiation on increased time to conception. Age at first birth associations were replicated in summary-level MR analysis; however, effects attenuated using multivariable MR. CONCLUSIONS: Smoking behaviour and BMI showed the most consistent associations for increased time to conception and a younger age at first birth. Given that age at first birth and time to conception are positively correlated, this suggests that the mechanisms for reproductive outcomes are distinct to the mechanisms acting on fertility outcomes. Multivariable MR suggested that effects on age at first birth might be explained by underlying liability to ADHD and education.
AB - BACKGROUND: Guidance to improve fertility includes reducing alcohol and caffeine consumption, achieving healthy weight-range and stopping smoking. Advice is informed by observational evidence, which is often biased by confounding. METHODS: This study primarily used data from a pregnancy cohort, the Norwegian Mother, Father and Child Cohort Study. First, we conducted multivariable regression of health behaviours (alcohol and caffeine consumption, body-mass index (BMI), and smoking) on fertility outcomes (e.g. time to conception) and reproductive outcomes (e.g. age at first birth) (n = 84,075 females, 68,002 males), adjusting for birth year, education and attention-deficit and hyperactive-impulsive (ADHD) traits. Second, we used individual-level Mendelian randomisation (MR) to explore possible causal effects of health behaviours on fertility/reproductive outcomes (n = 63,376 females, 45,460 males). Finally, we performed summary-level MR for available outcomes in UK Biobank (n = 91,462-1,232,091) and controlled for education and ADHD liability using multivariable MR. RESULTS: In multivariable regression analyses, higher BMI associated with fertility (longer time to conception, increased odds of infertility treatment and miscarriage), and smoking was associated with longer time to conception. In individual-level MR analyses, there was strong evidence for effects of smoking initiation and higher BMI on younger age at first birth, of higher BMI on increased time to conception, and weak evidence for effects of smoking initiation on increased time to conception. Age at first birth associations were replicated in summary-level MR analysis; however, effects attenuated using multivariable MR. CONCLUSIONS: Smoking behaviour and BMI showed the most consistent associations for increased time to conception and a younger age at first birth. Given that age at first birth and time to conception are positively correlated, this suggests that the mechanisms for reproductive outcomes are distinct to the mechanisms acting on fertility outcomes. Multivariable MR suggested that effects on age at first birth might be explained by underlying liability to ADHD and education.
KW - Alcohol
KW - BMI
KW - Caffeine
KW - Fertility
KW - MBRN
KW - Mendelian randomisation
KW - MoBa
KW - Reproductive outcomes
KW - Smoking
UR - http://www.scopus.com/inward/record.url?scp=85151752948&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s12916-023-02831-9
DO - https://doi.org/10.1186/s12916-023-02831-9
M3 - Article
C2 - 37013617
SN - 1464-2662
VL - 21
SP - 125
JO - BMC medicine
JF - BMC medicine
IS - 1
M1 - 125
ER -