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. 2021 Mar 1;27(4):747–770. doi: 10.1093/humupd/dmaa063

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© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com

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Figure 3. — Four directed acyclic graphs to guide the analysis of first trimester teratogens, biomarkers and child outcomes. (A) The directed acyclic graph for direct effects. (X: prenatal exposure, Y: foetal outcome, C: set of confounders). (B) The directed acyclic graph for placental molecular mediation (indirect effects). (X: prenatal exposure, M: placental mediator/biomarker, Y: foetal outcome, C_1,2,3: set of confounders). (C) The directed acyclic graph for pre-placental embryonic teratogenicity. (X: pre-conception/prenatal exposure, Y_e: embryo outcome, Yp: extraembryonic/placental outcome, C: set of confounders, M_p: extraembryonic/placental secreted biomarker, M_e: embryonic secreted biomarker). (D) The directed acyclic graph for multi-step mediation. (X: prenatal exposure, M_1…x: mediator/biomarker, Y: foetal outcome, C_1…X+1: set of confounders).