Prenatal exposure to cannabis and child growth: Examining angiogenic and adipogenic pathways in perinatal tissues

About This Grant

PROJECT SUMMARY Cannabis use in pregnancy is becoming increasingly common, with up to 23% of pregnant people testing positive for delta 9-tetrahydrocannabinol (Δ9-THC; the most common cannabinoid) at delivery. Prenatal exposure to cannabis has been linked to low birthweight. Our pilot data further suggests that prenatal cannabis is associated with rapid infant growth followed by higher adiposity and glucose at 5 years. While compelling, the epidemiologic data is often limited by self-report of whole cannabis use or bioanalytic testing of Δ9-THC. As such, there is a paucity of data on the potential health effects of cannabidiol (CBD). Emerging evidence suggests that one in five pregnant people use CBD products, yet we know shockingly little about its health impacts in pregnancy. Furthermore, human studies may be confounded by socioeconomic status, polysubstance use, and other lifestyle factors, which limits our ability to establish causality. Therefore, exploring the direct effects of prenatal exposure to cannabis on perinatal tissues may help to provide evidence of a causal relationship. Both Δ9-THC and CBD interact with receptors in the endocannabinoid system, as well as non-canonical metabolic receptors like peroxisome proliferator-activated receptor (PPAR)-γ. These pathways are relevant to two perinatal tissue types: placental microvascular endothelial cells (ECs) and umbilical cord tissue-derived mesenchymal stem cells (MSCs). To address these gaps in knowledge, we have designed a translational study that will combine large-scale epidemiologic investigation with in vitro experiments. We will leverage two ongoing racially and ethnically diverse Colorado-based cohorts: Healthy Start and Mile High ECHO. Our overarching goal is to assess the impact of in utero and in vitro exposure to Δ9-THC and CBD on angiogenic and adipogenic pathways in primary placenta EC and MSC cell lines derived from our participants. We will also explore the extent to which these phenotypes mediate the associations between prenatal exposure to cannabis and child adiposity and metabolic health. Finally, we will explore whether other individual-level factors (diet, tobacco) alter risk, and whether there are prenatal windows of heightened suscepticilty. Drs. Moore (contact MPI; environmental epidemiologist with established expertise on health effects of prenatal cannabis exposure) and Boyle (MPI; basic scientist with a strong focus on molecular metabolism and stem cell biology) will carry out this research. They will lead a talented, multidisciplinary team of investigators with complementary and integrated research expertise with expertise in molecular mechanisms underlying placental insufficiency (Dr. Su), cannabinoid exposure assessment (Dr. Klawitter), and community- based dissemination (Dr. Rinehart). The findings have great potential to identify biological pathways and will support a community-based dissemination plan that is designed to educate providers and empower pregnant people about the potential health risks and legal consequences of cannabis use.