{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:27:26Z","timestamp":1768566446642,"version":"3.49.0"},"posted":{"date-parts":[[2023,6,5]]},"group-title":"Epidemiology","reference-count":51,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>IMPORTANCE<\/jats:title>\n                  <jats:p>Observational studies suggest that chronotype is associated with pregnancy and perinatal outcomes. Whether these associations are causal is unclear.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>To explore associations of a lifetime genetic predisposition to an evening preference chronotype with pregnancy and perinatal outcomes, and explore differences in associations of insomnia and sleep duration with those outcomes between chronotype.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DESIGN, SETTING, AND PARTICIPANTS<\/jats:title>\n                  <jats:p>We conducted two-sample Mendelian randomization (MR) using 105 genetic variants reported in a genome-wide association study (N=248 100) to instrument for lifelong predisposition to evening-versus morning-preference chronotypes. We generated variant-outcome associations in European ancestry women from UK Biobank (UKB, N=176 897), Avon Longitudinal Study of Parents and Children (ALSPAC, N=6826), Born in Bradford (BiB, N=2940) and Norwegian Mother, Father and Child Cohort Study (MoBa, with linked data from the Medical Birth Registry of Norway (MBRN), N=57 430), and extracted equivalent associations from FinnGen (N=190 879). We used inverse variance weighted (IVW) as main analysis, with weighted median and MR-Egger as sensitivity analyses. We also conducted IVW analyses of insomnia and sleep duration on the outcomes stratified by genetically predicted chronotype.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>EXPOSURES<\/jats:title>\n                  <jats:p>Self-reported and genetically predicted chronotype, insomnia and sleep duration.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>MAIN OUTCOMES AND MEASURES<\/jats:title>\n                  <jats:p>Stillbirth, miscarriage, preterm birth, gestational diabetes, hypertensive disorders of pregnancy, perinatal depression, low birthweight and macrosomia.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>In IVW and sensitivity analyses we did not find robust evidence of effects of chronotype on the outcomes. Insomnia was associated with a higher risk of preterm birth among evening preference women (odds ratio 1.61, 95% confidence interval: 1.17, 2.21), but not among morning preference women (odds ratio 0.87, 95% confidence interval: 0.64, 1.18), with an interaction P-value=0.01. There was no evidence of interactions between insomnia and chronotype on other outcomes, or between sleep duration and chronotype on any outcomes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CONCLUSIONS AND RELEVANCE<\/jats:title>\n                  <jats:p>This study raises the possibility of a higher risk of preterm birth among women with insomnia who also have an evening preference chronotype. Our findings warrant replications due to imprecision of the estimates.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Key points<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Question<\/jats:title>\n                    <jats:p>Does an evening preference chronotype adversely affect pregnancy and perinatal outcomes? Is there an interaction between chronotype and either insomnia or sleep duration in relation to those outcomes?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>There was no evidence that evening preference was associated with pregnancy or perinatal outcomes. Women with a genetically predicted insomnia had a higher risk of preterm birth, if they also had a genetically predicted preference for evening chronotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Meaning<\/jats:title>\n                    <jats:p>The suggestive interaction between insomnia and evening preference on preterm birth, if replicated, supports targeting insomnia prevention in women of reproductive age with an evening chronotype.<\/jats:p>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.1101\/2023.06.02.23290898","type":"posted-content","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T14:00:20Z","timestamp":1685973620000},"source":"Crossref","is-referenced-by-count":1,"title":["Evaluating causal associations of chronotype with pregnancy and perinatal outcomes and its interactions with insomnia and sleep duration: a Mendelian randomization study"],"prefix":"10.64898","author":[{"given":"Qian","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria C","family":"Magnus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanny","family":"Kilpi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian","family":"Santorelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2763-4647","authenticated-orcid":false,"given":"Ana Goncalves","family":"Soares","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"West","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Magnus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siri E.","family":"H\u00e5berg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate","family":"Tilling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah A","family":"Lawlor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Carolina","family":"Borges","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5188-5775","authenticated-orcid":false,"given":"Eleanor","family":"Sanderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023060718001674000_2023.06.02.23290898v1.1","doi-asserted-by":"crossref","unstructured":"Neiger R . 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