Maternal Cannabis Exposure Linked to Placental Dysfunction-Related Adverse Pregnancy Outcomes

Maternal cannabis use was associated with adverse pregnancy outcomes related to dysfunction of the placenta, including small for gestational age (SGA), preterm birth, stillbirth, and hypertensive disorders of pregnancy, according to findings of a National Institutes of Health-funded study published online in JAMA.

Compared to women who tested negative for cannabis use during pregnancy those who tested positive had a 27% increased risk of any of the complications. Moreover, the risk for an adverse outcome was higher among study participants whose cannabis use continued beyond the first trimester, Torri Metz, MD, MS, associate professor of obstetrics and gynecology maternal-fetal medicine subspecialist and vice chair of Research of Obstetrics and Gynecology at the University of Utah Health, and colleagues wrote. In fact, the study revealed that two-thirds of participants had ongoing cannabis exposure beyond the first 3 months of gestation.

The authors point out that data from past studies suggest use of cannabis by pregnant people is underreported, noting that responses to questionnaires on its use in pregnancy may underestimate actual use by as much as 2- to 3-fold when those results are compared with results of hospital urine screens and tissue samples obtained at admission. Further, “Prior data are limited by confounding because the group of individuals that uses cannabis during pregnancy differs from those who do not use cannabis during pregnancy by a number of characteristics, including nicotine use, that may influence pregnancy outcomes,” Metz and team wrote. “In addition, there are medical conditions, such as anxiety and depression, for which pregnant people may use cannabis; these conditions may also independently affect pregnancy outcomes.”

Compared to women who tested negative for cannabis use during pregnancy those who tested positive had a 27% increased risk of any of the complications...Two-thirds of participants had ongoing cannabis exposure beyond the first 3 months of gestation.

The investigators set out to learn more about the association between maternal cannabis use and adverse pregnancy outcomes specifically related to placental dysfunction, according to the study. They conducted an ancillary analysis of data from participants in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, a multicenter cohort study of 10 038 women who were treated at 8 US medical centers from 2010 to 2013. Participants for the analysis were selected based on availability of stored urine samples and abstracted pregnancy outcome data.

To identify cannabis exposure, Metz and colleagues performed urine immunoassay on frozen stored samples obtained at 3 study visits, during gestational age windows of 6 weeks and 0 days to 13 weeks and 6 days (visit 1); 16 weeks and 0 days to 21 weeks and 6 days (visit 2); and 22 weeks and 0 days to 29 weeks and 6 days (visit 3). Results positive for Δ9-tetrahydrocannabinol (THC) were confirmed with liquid chromatography tandem mass spectrometry. Researchers defined timing of cannabis exposure as only during the first trimester or ongoing beyond the first trimester.

The primary composite outcome included SGA birth, preterm birth, stillbirth, or hypertensive disorders of pregnancy.

FINDINGS

Investigators included 9275 eligible participants for their analysis from the original population. Of the 6.6% of women who had cannabis use during pregnancy, 32.4% used cannabis only during the first trimester; twice that proportion, 67.6%, were found to have had ongoing exposure beyond the first trimester.

In propensity score-weighted analyses adjusted for sociodemographics, body mass index, medical comorbidities, and active nicotine use, Metz et al found that cannabis exposure during any time in pregnancy was associated with at least one of the primary composite outcome complicationsfor 25.9% of participants compared with vs 17.4% of those with no exposure (adjusted relative risk [aRR], 1.27; 95% CI, 1.07-1.49). In a 3-part exposure model (no cannabis exposure, exposure during the first trimester only, or ongoing exposure), researchers observed no association between cannabis use during the first trimester only and the primary composite outcome. Ongoing cannabis use, however, was associated with the primary composite outcome (aRR, 1.32; 95% CI, 1.09-1.6).

“Further evaluation in humans of modes of cannabis consumption that do not require inhalation and frequent co-use or contamination with nicotine products may help provide further insight into the relationship between cannabis, nicotine and fetal growth,” the researchers wrote.

Source: Metz TD, Allshouse AA, McMillin GA, et al. Cannabis exposure and adverse pregnancy outcomes related to placental function. JAMA. 2023;330(22):2191-2199. doi:10.1001/jama.2023.21146