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However, observational associations between maternal gestational lipid concentrations and offspring birth weight (BW) have been inconsistent and ascertaining causality is challenging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used a novel two-sample Mendelian randomization (MR) approach to estimate the causal effect of maternal gestational high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride concentrations on offspring BW. Single nucleotide polymorphisms (SNPs) associated with serum HDL-C, LDL-C and triglyceride concentrations identified in the Global Lipids Genetics Consortium genome-wide association study meta-analysis (n\u2009=\u2009188\u00a0577 European-ancestry individuals; sample 1) were selected as instrumental variables. The effects of these SNPs on offspring BW were estimated using a structural equation model in the UK Biobank and Early Growth Genetics consortium (n\u2009=\u2009230\u00a0069 European-ancestry individuals; sample 2) that enabled partitioning of the genetic associations into maternal- (intrauterine) and fetal-specific effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found no evidence for a causal effect of maternal gestational HDL-C, LDL-C or triglyceride concentrations on offspring BW [standard deviation change in BW per standard deviation higher in HDL-C = \u22120.005 (95% confidence interval: \u22120.039, 0.029), LDL-C\u2009=\u20090.014 (\u22120.017, 0.045), and triglycerides = 0.014 (\u22120.025, 0.052)].<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that maternal gestational HDL-C, LDL-C and triglyceride concentrations play a limited role in determining offspring BW. However, we cannot comment on the impact of these and other lipid fractions on fetal development more generally. Our study illustrates the power and flexibility of two-sample MR in assessing the causal effect of maternal environmental exposures on offspring outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ije\/dyz160","type":"journal-article","created":{"date-parts":[[2019,7,11]],"date-time":"2019-07-11T11:09:46Z","timestamp":1562843386000},"page":"1457-1467","source":"Crossref","is-referenced-by-count":73,"title":["Using a two-sample Mendelian randomization design to investigate a possible causal effect of maternal lipid concentrations on offspring birth weight"],"prefix":"10.1093","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5535-2199","authenticated-orcid":false,"given":"Liang-Dar","family":"Hwang","sequence":"first","affiliation":[{"name":"The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A","family":"Lawlor","sequence":"additional","affiliation":[{"name":"Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M","family":"Freathy","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0663-4621","authenticated-orcid":false,"given":"David M","family":"Evans","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Australia"},{"name":"Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4195-775X","authenticated-orcid":false,"given":"Nicole M","family":"Warrington","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Australia"},{"name":"K.G. 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