To triangulate with our MR estimates, we conducted multivariable regression in 11,745 women from the Avon Longitudinal Study of Parents and Children (ALSPAC), where insomnia was measured in pregnancy for all outcomes except miscarriage and stillbirth for which there were too few cases in the index pregnancy.We used data on up to 356,069 women from UK Biobank (UKB), FinnGen, and 3 birth cohorts and assessed whether genetic susceptibility to insomnia was associated with stillbirth, miscarriage, gestational diabetes (GD), hypertensive disorders of pregnancy (HDP), perinatal depression, preterm birth (PTB), low offspring birthweight (LBW), and high offspring birthweight (HBW) in 2-sample MR.Key limitations are potential horizontal pleiotropy (particularly for perinatal depression) and low statistical power in MR, and residual confounding in multivariable regression. Multivariable regression with miscarriage and stillbirth was not possible due to small numbers in index pregnancies. Multivariable regression showed associations of insomnia at 18 weeks of gestation with perinatal depression (OR 2.96, 95% CI: 2.42, 3.63, p < 0.001), but not with LBW (OR 0.92, 95% CI: 0.69, 1.24, p = 0.60). Results from these sensitivity analyses were directionally consistent with IVW results for all outcomes, with the exception of GD, perinatal depression, and PTB in MR-Egger. Associations of genetic susceptibility to insomnia with miscarriage, perinatal depression, and LBW were not observed in weighted median or MR-Egger analyses. IVW results did not support associations of insomnia with stillbirth, GD, HDP, PTB, and HBW, with wide CIs including the null. We compared MR estimates with multivariable regression of insomnia in pregnancy on outcomes in ALSPAC ( N = 11,745). Main MR analyses used inverse variance weighting (IVW), with weighted median and MR-Egger as sensitivity analyses. ![]() We used data from women of European descent ( N = 356,069, mean ages at delivery 25.5 to 30.0 years) from UK Biobank (UKB), FinnGen, Avon Longitudinal Study of Parents and Children (ALSPAC), Born in Bradford (BiB), and the Norwegian Mother, Father and Child Cohort (MoBa). Our outcomes included ever experiencing stillbirth, ever experiencing miscarriage, GD, HDP, perinatal depression, PTB (gestational age 4,500 grams). ![]() We used 2-sample mendelian randomization (MR) with 81 single-nucleotide polymorphisms (SNPs) instrumenting for a lifelong predisposition to insomnia.
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