Author:
Wootton Robyn E.,Lawn Rebecca B.,Magnus Maria C.,Treur Jorien L.,Corfield Elizabeth C.,Njølstad Pål R.,Andreassen Ole A.,Lawlor Deborah A.,Munafò Marcus R.,Håberg Siri E.,Davey Smith George,Reichborn-Kjennerud Ted,Magnus Per,Havdahl Alexandra
Abstract
Abstract
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.
Funder
Helse Sør-Øst RHF
Norges Forskningsråd
Medical Research Council
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
National Institute of Mental Health and Neurosciences
HORIZON EUROPE European Research Council
Horizon 2020 Framework Programme
Norwegian Institute of Public Health
Publisher
Springer Science and Business Media LLC
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