This study was conducted to evaluate whether an association exists between cannabis use during pregnancy and neonatal outcomes given the growing acceptance and subsequent use of cannabis, particularly amongst pregnant individuals and those of childbearing age. Based on adjusted findings, our results reaffirm the association of cannabis use during pregnancy with significant adverse neonatal outcomes, specifically a more than sixfold elevated risk for fetal death and nearly a twofold increased risk for low birth weight.

The association between cannabis use and fetal death observed in our study is consistent with some of the existing literature suggesting detrimental effects of cannabis on fetal outcomes [5, 6, 12]. Even after adjusting for modifiable (nicotine use, marital status) and non-modifiable covariates (maternal age and race), the risk associated with cannabis use remained markedly elevated. These findings may relate to the integral role of endocannabinoids and endocannabinoid signaling in the modulation of gestational events. For example, the tight regulation of the endocannabinoid ligand anandamide (AEA) is known to be necessary for successful embryo implantation [9]. Moreover, when levels of AEA are impaired, a spontaneous abortion or ectopic pregnancy may result [9, 18,19,20,21]. AEA can also have disruptive effects on decidualization, which is important for normal embryo and placental development [9, 22]. AEA mediates its actions at cannabinoid receptors the same target for Δ9 tetrahydrocannabinol (THC), the main psychoactive component of cannabis, which is known to disrupt AEA levels [9]. Our findings would thus be in line with the crucial role that the endocannabinoid system plays in normal gestational development.

Cannabis use during pregnancy has often been shown to be associated with an increased risk for low birth weight [2, 4, 6, 13,14,15]. Although we did not find a significant increase in the risk of low birth weight, preterm birth, or NICU admission in our unadjusted models evaluating cannabis use, there was a significant risk for low birth weight when cannabis use was factored in along with other predictor variables. Therefore, this finding indicates that there may be a more complex relationship between cannabis use during pregnancy and low birth weight. Given the strong association between low birth weight on offspring morbidity, these results may have implications for not only fetal but also subsequent infant/early child health and development.

Contrary to reported associations in the literature, our analysis did not find alcohol use during pregnancy to be associated with adverse effects [23,24,25]. Our findings may reflect differences in patterns of use or population characteristics, leading to these unanticipated results.

While our study provides valuable insights into the impact of prenatal cannabis use on neonatal outcomes, we recognize its limitations. First, characterization of substance use is lacking, without detailed description of substance mode, exact timing (including gestation), duration, or amount. Second, our data does not include toxicology testing to serve as corroboration of interview-derived substance use history. Third, our findings are limited to pregnant individuals seeking prenatal care at urban settings thus restricting the generalizability. Despite these limitations, our study did replicate other findings in the literature and a notable strength of our study is the longitudinal nature of the data.

In summary, our findings highlight a significant association between prenatal cannabis use and adverse neonatal outcomes, i.e., fetal death and low birth weight. The noted association between fetal death and cannabis use during pregnancy emphasizes the need for larger studies that evaluate individuals’ substance use throughout the gestational period, beginning either pre-pregnancy or early pregnancy, to better determine whether there may be particularly sensitive windows in fetal development. In addition, identifying potential mechanistic underpinnings that specifically link cannabis use with fetal death would be important. Overall, our findings illuminate the need for interventions aimed at educating individuals of childbearing age about the potential risks associated with cannabis use during pregnancy. Given the increasing acceptance and use of cannabis, along with greater THC potency [26], it is crucial to expand research in this field to ensure the health and safety of both pregnant parents and neonates.