August 27, 2018
Clinicians should counsel women who are considering becoming pregnant or are of childbearing age about the potential negative effects of maternal marijuana use on pregnancy outcomes, as well as on fetal, infant, and child neurodevelopment, according to a clinical report from the American Academy of Pediatrics (AAP).
Prompted in part by the increasing prevalence of marijuana use among reproductive-aged women, the guidance is informed by a small but growing body of data showing that cannabis compounds quickly cross the placenta and can be transferred through breast milk. Those data suggest marijuana use can potentially influence obstetrical outcomes and embryonic development, write Sheryl A. Ryan, MD, from the Department of Pediatrics at Penn State Health Milton S. Hershey Medical Center in Pennsylvania, and colleagues write in the report, published online today in Pediatrics.
To help clinicians address the issue with their patients, the clinical report provides specific recommendations and summarizes available data on the pharmacokinetics of cannabinoids during pregnancy and lactation. Data link maternal marijuana use to a range of adverse pregnancy outcomes, including low birth weight, premature birth, small head circumference, small length, and stillbirth, as well as to poor pediatric outcomes, such as trouble with memory, attention, impulse control, and school performance.
While Ryan and colleagues acknowledge that the evidence for adverse effects of marijuana are limited — particularly because women who use marijuana are also more likely to use substances such as alcohol, tobacco, and other drugs — "the evidence from the available research studies indicates reason for concern, particularly in fetal growth and early neonatal behaviors."
Cannabinoids in Breast Milk
A study published in the same issue of Pediatrics, quantifying cannabinoid concentrations in breast milk, validates the concern and supports the recommendation that clinicians advise mothers to abstain from marijuana use while breastfeeding.
In the study, Kerri A. Bertrand, MPH, from the Department of Pediatrics at the University of California, San Diego, and colleagues, analyzed breast milk samples from 50 women who reported using marijuana while breastfeeding between 2014 and 2017. The investigators used mass spectrometry to identify concentrations of several cannabinoids, including Δ-9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive ingredient in marijuana, and 11-hydroxy-Δ-9-tetrahydrocannabinol, cannabidiol, and cannabinol.
Of 54 samples analyzed (four women provided samples at two time points), Δ9-THC, 11-OH-THC, and cannabidiol were detected at 1 ng/mL or higher in at least one sample, and Δ9-THC was detected in 34 (63%) samples, the authors report. Significant predictors of Δ9-THC concentrations included the number of times a women used marijuana per day, as well as hours since last use.
"[W]e estimated the mean infant plasma concentration of Δ9-THC obtained from breastfeeding to be ~1000 times lower than the concentration in an adult after a single dose of 10 mg of Δ9-THC," the authors state. "If a child is exposed to low levels of Δ9-THC in milk daily, there is a concern for accumulation of the various cannabinoids in the nursing infant because of slow elimination from body fat stores and continuous daily exposure.?"
This exposure, they hypothesize, may alter brain development because the brain develops rapidly during the first 2 years of life — the period when infants' main source of nutrition is likely human milk.
The findings by Bertrand and colleagues are "extremely important in documenting the ability of cannabinoids, including cannabidiol, which is increasingly being used for medicinal purposes, to be transferred from a cannabis-using lactating mother into her breast milk," Ryan writes in an accompanying commentary.
Ryan suggests that legalization has led people to think marijuana is safe, despite accumulating evidence that its use has harmful side effects. "Up to 36% of women report having used marijuana at some point in their pregnancy, and 18% report having used it while breastfeeding," she explains. "These high rates of reported use raise important issues for those medical providers who provide care to infants and children or who may be asked by parents about the safety of marijuana use during lactation."
Ryan notes that more context is needed to fully understand the implications of the findings from Bertrand and colleagues. For example, it's not clear yet how or how quickly the compounds are metabolized or what the short- and long-term developmental effects are.
Acknowledging limitations, the study authors call for further research into the oral absorption of cannabinoids in breastfeeding infants as well as metabolic and accumulation patterns and pharmacologic effects on neurodevelopment. "Because marijuana is the most commonly used recreational drug among breastfeeding women, information regarding risks to breastfeeding infants is urgently needed," they write.
Some of this research has already begun, according to Christina D. Chambers, PhD, MPH, professor and director of clinical research in the Department of Pediatrics at the University of California in San Diego, senior author on the breastfeeding study. "We have in process collection of long term follow up data for the mothers and children enrolled in this study, including growth and neurodevelopmental testing, and we continue to enroll new mothers in the UCSD Human Milk Biorepository," she said in an interview with Medscape Medical News. "While this work will help answer the key question of whether or not the exposure does affect infant brain development, additional work is also needed to determine the actual dose of cannabis the breastfed infant is receiving."
Limitations notwithstanding, the AAP urges clinicians to discuss what is currently known about adverse consequences of marijuana use during pregnancy and breastfeeding at prenatal visits to promote optimal health outcomes for mother and child.
"Legalization of marijuana may give the false impression that marijuana is safe," the authors write in the AAP clinical report. Although ethical concerns preclude randomized controlled studies to definitively prove otherwise, the current pool of data provides "theoretical justification" for this conclusion.
Whether legalization of marijuana has led to its increased use among pregnant/lactating women or whether it is a function of the increasingly common perception that the substance's medicinal properties are benign "is hard for me to say," Chambers said. "But recent national survey data do suggest that a high proportion of women think that occasional use is harmless." For this reason, she stressed, the AAP's clinical guidance is timely and necessary.
Bertrand et al and the authors of the AAP clinical report have disclosed no relevant financial relationships.