{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T22:46:30Z","timestamp":1757630790552,"version":"3.44.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":240,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Versuss Arthritis","award":["21173","21754","21755"],"award-info":[{"award-number":["21173","21754","21755"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Evidence on the safety of TNF inhibitors (TNFi) for pregnancy-related maternal and foetal outcomes remains limited. While some studies report increased rates of preterm delivery, others have suggested a possible protective role for gestational diabetes. We used population-level data to examine the effect of genetically proxied TNFi on these outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We proxied TNFi using rs1800693, a splicing variant within the TNFRSF1A gene, which is strongly associated with CRP in a genome-wide association study of 575\u2009531 individuals of European ancestry. CRP was selected as the biomarker because TNFi is recognized to suppression CRP. Genetic association data for pregnancy-related outcomes were taken from FinnGen and UK Biobank, including the outcomes of spontaneous abortion, ectopic pregnancy, hyperemesis gravidarum, gestational diabetes, pre-eclampsia or eclampsia, preterm birth and offspring birthweight. Colocalization analysis was used to examine genetic confounding.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found no strong association between genetically proxied TNFi and any adverse pregnancy-related outcome, including spontaneous abortion (odds ratio [OR] 1.07, 95% CI: 0.41, 2.81), preterm birth (OR 0.48, 95% CI 0.14, 1.60), hyperemesis gravidarum (OR 0.20, 95% CI 0.02, 2.57), pre-eclampsia or eclampsia (OR 0.59, 95% CI 0.13, 2.65). Genetically proxied TNFi was associated with lower risk of gestational diabetes (OR 0.16, 95% CI 0.05, 0.52). There was no statistical evidence to suggest genetic confounding through linkage disequilibrium.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This genetic investigation found no evidence linking TNFi to adverse pregnancy-related outcomes. The suggestive association with a reduced risk of gestational diabetes warrants further research and may support its consideration for at-risk pregnant women.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/rap\/rkaf100","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T17:08:18Z","timestamp":1756487298000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetically proxied tumour necrosis factor inhibition and pregnancy-related maternal and foetal outcomes in the general population: a Mendelian randomization study"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3558-7353","authenticated-orcid":false,"given":"Sizheng Steven","family":"Zhao","sequence":"first","affiliation":[{"name":"Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester Academic 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