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However, current evidence was insufficient for mechanistic pathways. We aim to use two\u2010sample Mendelian randomization (MR) to obtain a comprehensive understanding of the causal association and mediation pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Genetic variants of fasting glucose (FG), insulin sensitivity index (ISI), glycated haemoglobin (HbA1c), gestational diabetes mellitus (GDM) and type 2 diabetes (T2D) were used as instruments (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200950\u2009404\u2013898\u2009130). The associations with offspring birthweight, gestational duration, spontaneous preterm and post\u2010term birth were assessed by the inverse\u2010variance weighted method, using summary statistics of European genome\u2010wide association studies (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009131\u2009279\u2013210\u2009248). Sensitivity analyses, including multivariable MR removing pleiotropic effect from maternal body mass index (BMI), assessed the robustness. Mediation via placental weight and maternal hypertension were assessed via a two\u2010step MR design.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>FG (0.46 SD per mmol\/L, 95% confidence interval [95% CI]: 0.32, 0.61) and GDM liability (0.18 SD per log odds, 95% CI: 0.08, 0.18) were positively associated with birthweight, with consistent findings for HbA1c, T2D liability and ISI. These associations were mediated by placental weight (proportion mediated: 32.8% to 77.7%). Higher HbA1c, GDM and T2D liability were associated with preterm birth (odds ratios for GDM: 1.07, 95% CI: 1.01, 1.14) and shorter gestational duration, whilst the association for T2D attenuated after adjusted for maternal BMI and gestational hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Maternal hyperglycemia is associated with higher birthweight (possibly indicating macrosomia), mediated via increased placental growth. GDM and T2D liability are related to preterm birth, whilst the association for T2D liability is driven by maternal adiposity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.16045","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T04:18:23Z","timestamp":1730866703000},"page":"529-538","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Association and mediation pathways of maternal hyperglycaemia and liability to gestational diabetes with neonatal outcomes: A two\u2010sample Mendelian randomization study"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9976-7775","authenticated-orcid":false,"given":"Baoting","family":"He","sequence":"first","affiliation":[{"name":"School of Public Health, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh Simon","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Faculty of Medicine The Chinese University of Hong Kong  Hong Kong SAR People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou People's Republic of China"},{"name":"Department of Women's Health, Guangdong Provincial Key Clinical Specialty of Woman and Child Health, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songying","family":"Shen","sequence":"additional","affiliation":[{"name":"Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Public Health, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A. 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