Dataset Information

Smoking and infertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study.

ABSTRACT:

Objective

To investigate the association between smoking and infertility.

Design

Prospective study.

Setting

Nationwide cohort.

Patients

28,606 women and 27,096 men with questionnaire and genotype information from the Norwegian Mother, Father, and Child Cohort Study.

Intervention

Self-reported information on smoking (having ever smoked [both sexes], age at initiation [women only], cessation [women only], and cigarettes/week in current smokers [both sexes]) was gathered. Genetically predetermined levels or likelihood of presenting these traits were estimated for Mendelian randomization.

Main outcome measure

Infertility (time-to-pregnancy ≥12 months).

Results

Having ever smoked was unrelated to infertility in women or men. Higher smoking intensity in women was associated with greater infertility odds (+1 standard deviation [SD, 48 cigarettes/week]: odds ratio [OR]_crude, 1.19; 95% confidence interval [CI] 1.11-1.28; OR_adjusted 1.12; 95% CI, 1.03-1.21), also after adjusting for the partner's tobacco use. Later smoking initiation (+1 SD [3.2 years]: OR_crude, 0.94; 95% CI, 0.88-0.99; OR_adjusted 0.89; 95% CI, 0.84-0.95) and smoking cessation (vs. not quitting: OR_crude, 0.83; 95% CI, 0.75-0.91; OR_adjusted, 0.83; 95% CI, 0.75-0.93) were linked to decreased infertility in women. Nevertheless, Mendelian randomization results were not directionally consistent for smoking intensity and cessation and were estimated imprecisely in the 2-sample approach. In men, greater smoking intensity was not robustly associated with infertility in multivariable regression and Mendelian randomization.

Conclusions

We did not find robust evidence of an effect of smoking on infertility. This may be due to a true lack of effect, weak genetic instruments, or other kinds of confounding.

SUBMITTER: Hernaez A

PROVIDER: S-EPMC7612999 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundAlthough observational studies have demonstrated that blood lipids are associated with female infertility, the causality of this association remains unclear. We performed a univariable and multivariable Mendelian randomization (MR) analysis to evaluate the causal relationship between blood lipids and female infertility.MethodsSingle-nucleotide polymorphisms associated with lipid traits in univariate analysis were obtained from the Million Veteran Program (MVP) and Global Lipids Genetics Consortium (GLGC), involving up to 215,551 and 188,577 European individuals, respectively. Blood lipids in multivariate analysis were obtained from the latest genome-wide association study meta-analysis with lipid levels in 73 studies encompassing >300,000 participants. Data on female infertility were obtained from the FinnGen Consortium R6 release, which included 6481 samples and 75,450 controls. Subsequently, MR analysis was performed using inverse variance-weighted (IVW), weighted median, weighted-mode, simple-mode and MR-Egger regression to demonstrate the causal relationship between lipids and female infertility.ResultsAfter controlling confounding factors including body mass index and age at menarche, two-sample MR demonstrated that genetically predicted LDL-C and TC were causally associated with the risk of female infertility (When the genetic instruments come from the MVP database, LDL-C and female infertility, IVW OR: 1.13, 95% CI: 1.001-1.269, p = 0.047; TC and female infertility, IVW OR: 1.16, 95% CI: 1.018-1.317, p = 0.025, and when the genetic instruments came from the GLGC database, LDL-C and female infertility, IVW OR: 1.10, 95% CI: 1.008-1.210, p = 0.033; TC and female infertility, IVW OR: 1.14, 95% CI: 1.024-1.258, p = 0.015). However, the IVW estimate showed that HDL-C was not significantly associated with the risk of female infertility (when the genetic instruments came from the MVP database, IVW OR: 1.00, 95% CI: 0.887-1.128, p = 0.999; when the genetic instruments came from the GLGC database, IVW OR: 1.00, 95% CI: 0.896-1.111, p = 0.968). The multivariable MR analysis also provided evidence that LDL-C (OR: 1.12, 95% CI: 1.006-1.243, p = 0.042) was significantly associated with the risk of female infertility after considering the correlation of all lipid-related traits.ConclusionThese findings support a causal relationship between increased LDL-cholesterol and increased female infertility risk. Furthermore, the association between lipid-related traits and female infertility risk merits more studies.

Project description:BackgroundMore than one third of Norwegian women and men between 20 and 40 years of age have elevated cholesterol concentration. Parental metabolic health around conception or during pregnancy may affect the offspring's cardiovascular disease risk. Lipids are important for fetal development, but the determinants of cord blood lipids have scarcely been studied. We therefore aimed to describe the associations between maternal and paternal peri-pregnancy lipid and metabolic profile and newborn cord blood lipid and metabolic profile.MethodsThis study is based on 710 mother-father-newborn trios from the Norwegian Mother, Father and Child Cohort Study (MoBa) and uses data from the Medical Birth Registry of Norway (MBRN). The sample included in this study consisted of parents with and without self-reported hypercholesterolemia the last 6 months before pregnancy and their partners and newborns. Sixty-four cord blood metabolites detected by nuclear magnetic resonance spectroscopy were analyzed by linear mixed model analyses. The false discovery rate procedure was used to correct for multiple testing.ResultsAmong mothers with hypercholesterolemia, maternal and newborn plasma high-density lipoprotein cholesterol, apolipoprotein A1, linoleic acid, docosahexaenoic acid, alanine, glutamine, isoleucine, leucine, valine, creatinine, and particle concentration of medium high-density lipoprotein were significantly positively associated (0.001 ≤ q ≤ 0.09). Among mothers without hypercholesterolemia, maternal and newborn linoleic acid, valine, tyrosine, citrate, creatinine, high-density lipoprotein size, and particle concentration of small high-density lipoprotein were significantly positively associated (0.02 ≤ q ≤ 0.08). Among fathers with hypercholesterolemia, paternal and newborn ratio of apolipoprotein B to apolipoprotein A1 were significantly positively associated (q = 0.04). Among fathers without hypercholesterolemia, no significant associations were found between paternal and newborn metabolites. Sex differences were found for many cord blood lipids.ConclusionsMaternal and paternal metabolites and newborn sex were associated with several cord blood metabolites. This may potentially affect the offspring's long-term cardiovascular disease risk.

Project description:BackgroundNumerous intrauterine factors may affect the offspring's growth during childhood. We aimed to explore if maternal and paternal prenatal lipid, apolipoprotein (apo)B and apoA1 levels are associated with offspring weight, length, and body mass index from 6 weeks to eight years of age. This has previously been studied to a limited extent.MethodsThis parental negative control study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. We included 713 mothers and fathers with or without self-reported hypercholesterolemia and their offspring. Seven parental metabolites were measured by nuclear magnetic resonance spectroscopy, and offspring weight and length were measured at 12 time points. Data were analyzed by linear spline mixed models, and the results are presented as the interaction between parental metabolite levels and offspring spline (age).ResultsHigher maternal total cholesterol (TC) level was associated with a larger increase in offspring body weight up to 8 years of age (0.03 ≤ Pinteraction ≤ 0.04). Paternal TC level was not associated with change in offspring body weight (0.17 ≤ Pinteraction ≤ 0.25). Higher maternal high-density lipoprotein cholesterol (HDL-C) and apoA1 levels were associated with a lower increase in offspring body weight up to 8 years of age (0.001 ≤ Pinteraction ≤ 0.005). Higher paternal HDL-C and apoA1 levels were associated with a lower increase in offspring body weight up to 5 years of age but a larger increase in offspring body weight from 5 to 8 years of age (0.01 ≤ Pinteraction ≤ 0.03). Parental metabolites were not associated with change in offspring height or body mass index up to 8 years of age (0.07 ≤ Pinteraction ≤ 0.99).ConclusionsMaternal compared to paternal TC, HDL-C, and apoA1 levels were more strongly and consistently associated with offspring body weight during childhood, supporting a direct intrauterine effect.