Journal Article

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

Yang, Qian, Wright, John, Håberg, Siri Eldevik, Lawlor, Deborah A., Magnus, Per, Borges, Maria Carolina, Soares, Ana Gonçalves, Tilling, Kate, Sanderson, Eleanor, Kilpi, Fanny, Santorelli, Gillian, Magnus, Maria C., West, Jane

2022

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Biobanks / Biomedicine / Birth Weight / Care and treatment / Child / Cohort Studies / Complications and side effects / Confidence intervals / Diabetes mellitus / Diabetes, Gestational / Disorders / Female / Genetic diversity / Genetic variance / Genomes / Gestational diabetes / Health aspects / Humans / Hypertension / Hypertension in pregnancy / Hypertension, Pregnancy-Induced / Infant, Newborn / Likelihood ratio / Longitudinal Studies / Medicine / Medicine & Public Health / Mendelian randomization / Mendelian Randomization Analysis / Mental depression / Miscarriage / Observational studies / Offspring / Postpartum depression / Pregnancy / Pregnant women / Premature birth / Premature Birth - epidemiology / Premature Birth - genetics / Prenatal depression / Prevention / Randomization / Regression / Research Article / Risk / Risk factors / Sleep / Sleep - genetics / Sleep disorders / Sleep duration / Sleep Wake Disorders / Statistical analysis / Still-birth / Stillbirth / Stillbirth - epidemiology / Stillbirth - genetics / Womens health