Over the past decade, cannabis use among women of reproductive age has increased significantly as more states have legalized the recreational and medical use of cannabis. Despite declining rates of alcohol and tobacco use during pregnancy, Cannabis use during pregnancy is on the rise. IIn a large study involving more than 9,000 pregnant women from across the US, researchers examined the effects of cannabis exposure during pregnancy.
This multicenter observational cohort study was an ancillary analysis of the Null Pregnancy Outcomes Study: Maternal Follow-up (nuMoM2b) in which participants were recruited during the first trimester of pregnancy from eight US medical centers and followed longitudinally throughout pregnancy until delivery. Instead of asking about cannabis use during pregnancy, cannabis exposures were ascertained using a urine drug test of frozen samples collected during routine obstetric visits. In addition, exposure to nicotine and other drugs was measured using urine immunoassays.
The researchers assessed several different adverse pregnancy outcomes, including small-for-gestational-age delivery, preterm delivery, stillbirth, and hypertensive disorders of pregnancy.
Cannabis exposure and adverse pregnancy outcomes
Of the 10,038 participants, 9,257 were eligible for this analysis. Of the 610 participants (6.6%) with cannabis use, 32.4% (n?=?197) had exposure only in the first trimester and 67.6% (n?=?413) had exposure beyond from the first trimester.
Adverse pregnancy outcomes were more common in cannabis-exposed pregnancies (25.9%) compared to unexposed pregnancies (17.4%). The risk for adverse outcomes was higher among those who continued to use cannabis after the first trimester (26.7%) compared to those who had exposure only during the first trimester (24.1%).
Cannabis exposure at any time during pregnancy was associated with small-for-gestational-age delivery (adjusted RR, 1.52; 95% CI, 1.08-2.14). Cannabis exposure was also associated with stillbirth in unadjusted models. However, this finding was no longer significant after adjustment for potential confounders. Cannabis exposure was not significantly associated with neonatal morbidity or mortality.
The researchers also measured the amount of cannabis metabolites (THC-COOH) in urine samples. Higher THC-COOH levels during the first trimester, as well as higher cumulative estimated cannabis exposure during pregnancy, were associated with a higher likelihood of adverse pregnancy outcomes.
Signs of placental insufficiency
In this multicenter cohort with prospective collection of clinical data, urine samples, and validated survey instruments, cannabis exposure was associated with an increased risk of adverse pregnancy outcomes, with the highest risk occurring in pregnancies exposed to cannabis beyond the first trimester. This association remained after adjustment for a number of clinical and sociodemographic factors and when using different modeling approaches. Additionally, a dose response was observed where higher cumulative amounts of cannabis metabolites in urine samples during pregnancy were associated with a higher risk of adverse pregnancy outcomes.
While previous studies have shown a link between cannabis use during pregnancy and an increased risk of adverse pregnancy outcomes, it has been difficult to assess the contribution of other factors. More specifically, it was difficult to determine whether concurrent nicotine use (rather than cannabis exposure) contributed to or led to risk for adverse outcomes. One of the many strengths of this large prospective study is that it was able to control for a wide range of potential confounders, including exposure to nicotine and other substances. The use of urinalysis to document and quantify exposure to cannabis and other substances, including nicotine metabolites, also eliminated the potential for underreporting drug and nicotine exposure.
This study more definitively links cannabis exposure to adverse pregnancy outcomes. The authors speculate that, given the pattern of adverse outcomes seen with cannabis exposure, cannabis may exert its negative effects by compromising placental function, an explanation that is biologically plausible. The endocannabinoid system is active during early pregnancy and is responsible for regulating placental implantation. Although no studies have specifically examined the effect of cannabis on placental function in humans, chronic cannabis exposure in a nonhuman primate model was associated with visible changes in the placenta consistent with placental infarct and insufficiency. One of the most consistently reported outcomes in cannabis-exposed human pregnancies was suboptimal fetal growth, a finding consistent with placental insufficiency.
While many studies have raised concerns about cannabis use during pregnancy, the prevalence of cannabis use among pregnant women continues to rise. The legalization of recreational and medical cannabis in many states has been coupled with the perception that cannabis is relatively safe.
Given concerns about the known and unknown risks associated with cannabis exposure during pregnancy, professional organizations, including American College of Obstetricians and Gynecologists (ACOG), have called for greater vigilance, emphasizing the importance of screening for cannabis use and educating patients about the risks of cannabis use in women of childbearing age. If cannabis does in fact affect placental implantation and function, women should be advised to abstain from cannabis before conception to avoid exposure to cannabis and its metabolites during the early stages of pregnancy.
Ruta Nonacs, MD PhD
bibliographical references
Metz TD, Allshouse AA, McMillin GA, Greene T, Chung JH, Grobman WA, Haas DM, Mercer BM, Parry S, Reddy UM, Saade GR, Simhan HN, Silver RM. Cannabis exposure and adverse pregnancy outcomes related to placental function. GLASS. 2023 Dec 12;330(22):2191-2199.
