Maternal tobacco and cannabis use during pregnancy are associated with adverse perinatal outcomes. We hypothesized that maternal tobacco and cannabis use are associated with placental adaptations, which subsequently lead to adverse perinatal outcomes. In a population-based prospective cohort study of 8008 pregnant women, we assessed maternal tobacco and cannabis use by questionnaires. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured in the first and second trimester and at delivery from blood samples. Placental weight and pregnancy complications were obtained from medical records. We observed that tobacco use before and during first-trimester only was not associated with any angiogenic factors. As compared to no tobacco use, continued use during pregnancy was associated with higher PlGF, lower sFlt-1 concentrations, and lower sFlt-1/PlGF ratio in second trimester (all p-values <0.05). Also, compared to no cannabis use, use before and during pregnancy was associated with higher PlGF concentrations and lower sFlt-1/PlGF ratio in first and second trimester (all p-values <0.05). First trimester only cannabis use was associated with higher sFlt-1 concentrations and higher sFlt-1/PlGF ratio at delivery (all p-values <0.05). Compared to non-use, tobacco use before pregnancy was associated with a higher placental weight, whereas continued tobacco use during pregnancy was associated with a lower placental weight. Continued tobacco or cannabis use was related to higher placental weight to birth weight ratio and higher risk of pregnancy complications (all p-values <0.05). These results suggest that maternal tobacco and cannabis use lead to placental vascular maladaptation predisposing to adverse pregnancy outcomes.
Bibliographical noteFunding Information:
This work was supported by European Research Council [Consolidator Grant, ERC-2014-CoG-648916 ]; Stichting Volksbond Rotterdam, the NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation [grant number 27853 ]; the Netherlands Organization for Health Research and Development [Aspasia grant No. 015.016.056 ]; the European Union's Horizon 2020 Research and Innovation Program [LifeCycle, grant agreement 733206 ]; and Peruvian Scholarship [ 547-2018-SERVIR ]. The study sponsors had no role in the study design, collection, analysis and interpretation of data, writing of the report, or in the decision to submit the paper for publication.
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