Investigating causal relations between sleep duration and risks of adverse pregnancy and perinatal outcomes: linear and nonlinear Mendelian randomization analyses

Background Observational studies have reported maternal short/long sleep duration to be associated with adverse pregnancy and perinatal outcomes. However, it remains unclear whether there are nonlinear causal effects. Our aim was to use Mendelian randomization (MR) and multivariable regression to examine nonlinear effects of sleep duration on stillbirth (MR only), miscarriage (MR only), gestational diabetes, hypertensive disorders of pregnancy, perinatal depression, preterm birth and low/high offspring birthweight. Methods We used data from European women in UK Biobank ( N =176,897), FinnGen ( N =~123,579), Avon Longitudinal Study of Parents and Children ( N =6826), Born in Bradford ( N =2940) and Norwegian Mother, Father and Child Cohort Study (MoBa, N =14,584). We used 78 previously identified genetic variants as instruments for sleep duration and investigated its effects using two-sample, and one-sample nonlinear (UK Biobank only), MR. We compared MR findings with multivariable regression in MoBa ( N =76,669), where maternal sleep duration was measured at 30 weeks. Results In UK Biobank, MR provided evidence of nonlinear effects of sleep duration on stillbirth, perinatal depression and low offspring birthweight. Shorter and longer duration increased stillbirth and low offspring birthweight; shorter duration increased perinatal depression. For example, longer sleep duration was related to lower risk of low offspring birthweight (odds ratio 0.79 per 1 h/day (95% confidence interval: 0.67, 0.93)) in the shortest duration group and higher risk (odds ratio 1.40 (95% confidence interval: 1.06, 1.84)) in the longest duration group, suggesting shorter and longer duration increased the risk. These were supported by the lack of evidence of a linear effect of sleep duration on any outcome using two-sample MR. In multivariable regression, risks of all outcomes were higher in the women reporting <5 and ≥10 h/day sleep compared with the reference category of 8–9 h/day, despite some wide confidence intervals. Nonlinear models fitted the data better than linear models for most outcomes (likelihood ratio P -value=0.02 to 3.2×10 −52 ), except for gestational diabetes. Conclusions Our results show shorter and longer sleep duration potentially causing higher risks of stillbirth, perinatal depression and low offspring birthweight. Larger studies with more cases are needed to detect potential nonlinear effects on hypertensive disorders of pregnancy, preterm birth and high offspring birthweight.

Abstract licence: CC BY-NC-ND

1. 2.

   Trajectories of maternal sleep problems before and after childbirth: a longitudinal population-based study · 2015

2. 9.

   Genome-wide association of sleep and circadian phenotypes · 2007

3. 14.

   Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression · 2015

4. 17.

   A review of instrumental variable estimators for Mendelian randomization · 2015

5. 26.

   Combining information on multiple instrumental variables in Mendelian randomization: comparison of allele score and summarized data methods · 2015

6. 28.

   Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator · 2016

7. 30.

   Commentary: Two-sample Mendelian randomization: opportunities and challenges · 2016

8. 31.

   Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci · 2016

9. 32.

   Bias due to participant overlap in two‐sample Mendelian randomization · 2016

10. 33.

    Hyperglycaemia and risk of adverse perinatal outcomes: systematic review and meta-analysis · 2016

11. 35.

    Collider scope: when selection bias can substantially influence observed associations · 2017

12. 37.

    Triangulation in aetiological epidemiology · 2017

13. 39.

    Using Mendelian randomization to determine causal effects of maternal pregnancy (intrauterine) exposures on offspring outcomes: Sources of bias and methods for assessing them · 2017

14. 40.

    Comparison of Sociodemographic and Health-Related Characteristics of UK Biobank Participants With Those of the General Population · 2017

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