Ericksen et al1 have underscored the need for further research on the frequency of prenatal maternal cannabis use, as well as paternal cannabis use during pregnancy. Agrawal et al2 concur with this assessment, highlighting the prevalence of daily prenatal maternal cannabis use and the potential epigenetic and passive exposure effects of paternal cannabis use through their reply in JAMA Pediatrics.

Ericksen et al note that the frequency of cannabis use during pregnancy could affect toxicity. Based on data from 2018, cannabis use during pregnancy is more likely to be occur daily, which would meet criteria for cannabis dependence.3 Furthermore, education on prenatal cannabis use is scarce, which may result in potential fetal harm and missed opportunities to treat dependence. Agrawal et al supplement these concerns with findings from 2015 and 2016 that 21.1% of pregnant black and white women reporting cannabis use in the prior month also reported daily use.2,4 Between 50% and 60% of cannabis use disorder could be due to genetic factors that may be passed onto offspring.5 This could lead to a confound in studies investigating causal relationships between prenatal cannabis exposure and later offspring outcomes.6

Ericksen et al also highlight the possible impact of paternal marijuana use, which can lead to tetrahydrocannabinol accumulations in noncannabis-using partners’ oral secretions, blood, and urine following secondhand smoke exposure.1 It will also be important for studies and clinical procedures to account for the type of intake, including vaping, edibles, or inhalation. Agrawal et al note that paternal cannabis users are just as likely to transmit genetic susceptibilities to offspring as mothers.2 Men who use cannabis regularly may also experience epigenetic changes in sperm cells, though the results of these changes are unknown.7 Infant and childhood exposure to secondhand cannabis smoke poses another threat to offspring well-being. Furthermore, the coaggregation of all these effects serves to confound researchers’ ability to perform causal inference.

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Both groups of authors support further investigation into potential harm resulting from prenatal cannabis use as marijuana is increasingly legalized. As Agrawal et al conclude, “Understanding the factors that might hinder a woman’s ability to quit using substances during pregnancy, be it social or individual specific, is not only likely to identify key sources of conflation in studies of the effects of prenatal exposure but also improve maternal well-being, which has been documented as an independent source of offspring health.”2

Disclosure: Richard A. Grucza, PhD, reported receiving fees from Allergan outside the submitted work.

References

1. Ericksen K, Shah S, Brumberg HL. Public health implications of rising marijuana use in pregnancy in an age of increasing legalization [published online April 8, 2019]. JAMA Pediatr. doi:10.1001/jamapediatrics.2019.0644

2. Agrawal A, Grucza RA, Rogers CE. Public health implications of rising marijuana use in pregnancy in an age of increasing legalization—reply [published online April 8, 2019]. JAMA Pediatr. doi:10.1001/jamapediatrics.2019.0618

3. El Marroun H, Brown QL, Lund IO, et al. An epidemiological, developmental and clinical overview of cannabis use during pregnancy. Prev Med. 2018;116:1-5.

4. Agrawal A, Rogers CE, Lessov-Schlaggar CN, Carter EB, Lenze SN, Grucza RA. Alcohol, cigarette, and cannabis use between 2002 and 2016 in pregnant women from a nationally representative sample. JAMA Pediatr. 2019;173(1):95-96.

5. Agrawal A, Lynskey MT. Cannabis controversies: how genetics can inform the study of comorbidity. Addiction. 2014;109(3):360-370.

6. Agrawal A, Knopik VS, Pergadia ML, et al. Correlates of cigarette smoking during pregnancy and its genetic and environmental overlap with nicotine dependence. Nicotine Tob Res. 2008;10(4):567-578.

7. Murphy SK, Itchon-Ramos N, Visco Z, et al. Cannabinoid exposure and altered DNA methylation in rat and human sperm. Epigenetics. 2018;13(12):1208-1221.