Exposure to Cannabis during Pregnancy Associated with Risk to Unborn Child

Written by Joyce Smith, BS. △9–tetrahydrocannabinol (Δ9-THC), the main psychoactive component in cannabis, significantly impacts placental and fetal development when used during pregnancy. 

The use of cannabis in the United States has increased 6 to 22% among pregnant women with some of them reporting daily use ¹. Cannabis use is more prevalent among young, urban, socially disadvantaged women ² who have no knowledge of its risk to an unborn child ³. Clinical studies have suggested that, Δ9-THC, the psychoactive ingredient in cannabis, when used during pregnancy causes fetal growth restriction and low birth weight babies, although the mechanisms involved are not fully understood. To address the intrinsic limitations of those clinical studies, animal experiments have demonstrated that exposure of pregnant rodent dams to Δ9-THC leads to placental dysfunction and low birth weight offspring ⁴. This is alarming as the concentration of Δ9-THC in cannabis has steadily increased (from 3 to 22%) over the last two decades, and animal studies indicate that Δ9-THC crosses the placenta with 10 to 28% of maternal concentrations detected in the fetal plasma, and 2 to 5 times higher concentrations found in fetal tissues ⁵. Impaired placental development is associated with intrauterine growth restriction (IUGR) which not only restricts fetal growth ⁶ but may subsequently lead to the development of type 2 diabetes, obesity⁷, and even metabolic syndrome (MetS) ⁷. The postnatal catch-up growth period that follows fetal growth restriction can significantly increases the risk of MetS in adulthood ⁸, although IUGR is more often the result of genetic causes, intrauterine infections and maternal alcohol use ⁹.

Natale and team⁹ sought to prove that maternal exposure of THC during pregnancy has a measurable impact on both the development of fetal organs and gene expression essential to placental function. Using a rat model, they demonstrated that compromising the development of fetal-placental circulation could affect maternal-fetal exchange of oxygen and nutrients from mother to fetus, and consequently affect fetal growth. Dams were given a daily intraperitoneal injection (i.p.) of vehicle control or Δ9-THC (3 mg/kg) from embryonic day (E)6.5 through E22, and were allowed to deliver normally to measure pregnancy and neonatal outcomes. A subset of dams were sacrificed at E19.5 for placenta assessment using immunohistochemistry and gene expression using polymerized chain reaction (PCR).

△9–THC exposure in rats during pregnancy did not affect maternal weight or food intake, nor did it alter gestational length, litter size or live birth. It did, however, affect the pups who were born with symmetrical fetal growth restriction, with catch-up growth by postnatal day (PND)21. Compared to control pups, Δ9-THC pups had reduced birth weight and a 25% decrease in liver to bodyweight ratio and brain to body weight ratios (p<0.01).

The research team also characterized how THC prevents oxygen and nutrients from crossing the placenta into the developing fetus. By studying human placental cells, the researchers found that exposure to THC caused a decrease in a glucose transporter called GLUT-1 which when coupled with reduced placental vasculature, as seen in the rat model, strongly suggests impaired nutrient transfer from mother to fetus and growth restriction of offspring. This is the first study to definitively support the fact that THC alone has a direct impact on placental and fetal Growth.

Given the strong links between placental-insufficiency, induced fetal growth restriction and metabolic disease risk, more studies examining the effects of gestational Δ9-THC exposure on the fetus, placenta, and offspring are required. Furthermore, the perception by pregnant women that cannabis use poses no risk to the fetus ⁹ calls for the education of cannabis use during pregnancy among young women, particularly those who are socioeconomically disadvantaged.

Source: Natale, Bryony V., Katarina N. Gustin, Kendrick Lee, Alison C. Holloway, Steven R. Laviolette, David RC Natale, and Daniel B. Hardy. “Δ9-tetrahydrocannabinol exposure during rat pregnancy leads to symmetrical fetal growth restriction and labyrinth-specific vascular defects in the placenta.” Scientific Reports 10, no. 1 (2020): 1-15.

© The Author(s) 2020.  This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/.

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Posted February 25, 2020.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

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