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Marijuana Use in Pregnancy and While Breastfeeding

Metz, Torri D., MD, MS; Borgelt, Laura M., PharmD

doi: 10.1097/AOG.0000000000002878
Contents: Substance Use Disorder: Clinical Expert Series
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The prevalence and perceived safety of marijuana use in pregnancy are increasing with expanding legalization. Marijuana crosses the placenta and passes into breast milk, resulting in fetal and neonatal exposure. Many women cite medical reasons for prenatal marijuana use such as nausea and vomiting of pregnancy, anxiety, and chronic pain. The scientific literature regarding marijuana in pregnancy is mixed, resulting in confusion among practitioners as to how to counsel women about risks of use. In addition, there is a paucity of literature related to marijuana use and breastfeeding. Existing pregnancy studies are predominantly retrospective cohorts with a reliance on self-report for ascertainment of exposure, which underestimates use. Many studies fail to adjust for important confounding factors such as tobacco use and sociodemographic differences. Despite the limitations of the existing evidence, there are animal and human data suggesting potential harm of cannabis use. The harms are biologically plausible given the role of the endocannabinoid system in pregnancy implantation, placentation, and fetal neurologic development. Two recent systematic reviews and meta-analyses found an association between marijuana use and adverse perinatal outcomes, especially with heavy marijuana use. In addition, three longitudinal cohort studies demonstrate a possible effect of prenatal marijuana exposure on long-term neurobehavioral outcomes. Marijuana use may be associated with growth restriction, stillbirth, spontaneous preterm birth, and neonatal intensive care unit admission. Therefore, women should be advised to refrain from using marijuana during pregnancy and lactation.

Based on available animal and human data demonstrating the potential for maternal and fetal harm, pregnant and breastfeeding women should refrain from using marijuana.

Denver Health and Hospital Authority, Denver, and the University of Colorado School of Medicine and the University of Colorado Skaggs School of Pharmacy, Aurora, Colorado.

Corresponding author: Torri D. Metz, MD, MS, 30 North 1900 East, 2B200, Salt Lake City, UT 84132; email: torri.metz@hsc.utah.edu.

Dr. Metz was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development under award number 5K12HD001271-18. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Financial Disclosure Dr. Borgelt received grant funding from the Colorado Department of Public Health and Environment (CDPHE) for a study evaluating the use of cannabidiol for the treatment of refractory pediatric epilepsy. Additionally, she has provided continuing education for pharmacists through PharmCon, Inc and served on seven different working groups for the Colorado Department of Revenue and CDPHE regarding use of cannabis and patient safety. Dr. Metz did not report any potential conflicts of interest.

Continuing medical education for this article is available at http://links.lww.com/AOG/B149.

The authors thank Amanda Allshouse for creating Figure 3. Ms. Allshouse is supported by the Department of Obstetrics and Gynecology at Denver Health and Hospital Authority.

Each author has indicated that she has met the journal's requirements for authorship.

Cannabis (or marijuana) contains more than 400 chemical entities and is consumed through different modalities including vaping, dabbing, smoking, and eating. Marijuana is now legalized for medicinal use in 29 states plus Washington, DC, and for recreational use in eight states plus Washington, DC. In addition to the psychoactive component, delta-9-tetrahydrocannabinol, there are other components of cannabis that have generated interest for potential therapeutic properties. Women report using marijuana in pregnancy for treatment of nausea, anxiety, and pain1; however, marijuana crosses the placenta and may have adverse effects on the developing fetus.2,3

As legalization expands, there is renewed interest in the health effects of marijuana, yet there remains uncertainty regarding maternal and neonatal outcomes with prenatal marijuana use. The confusion surrounding the effect of marijuana on perinatal outcomes does not stem from a lack of available literature. Instead, the lack of clarity regarding anticipated outcomes is a result of the heterogeneity of findings for the association between marijuana use and adverse pregnancy outcomes. There is, however, an almost complete lack of data regarding marijuana use and breastfeeding.

Two recent systematic reviews and meta-analyses provide a comprehensive review of the human literature related to marijuana and pregnancy outcomes.4,5 Given the recent publication of these articles, we did not pursue further meta-analysis. Rather we hope to provide evidence-based information regarding the biological plausibility of existing findings and expand on outcomes not addressed in the meta-analyses to provide a practical review of the available literature.

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PREVALENCE OF MARIJUANA USE IN PREGNANCY AND PERCEIVED SAFETY

The proportion of women using marijuana during pregnancy increased from 2.37% (95% CI 1.85–3.04) in 2002 to 3.85% (95% CI 2.87–5.18) in 2014 based on self-reported data from the National Surveys of Drug Use and Health.6 However, self-report likely underestimated the prevalence of use. In a Kaiser population with universal self-report and urine toxicology screening, the rate of use was 7.1% (95% CI 6.7–7.5%) in 2016, and more than half of the women using marijuana were identified only by toxicology testing.

There is also an increasing perception of safety. Jarlenski et al7 published a research letter using data from the National Surveys of Drug Use and Health from 2005 to 2012. Survey respondents were asked, “How much do people risk harming themselves physically and in other ways when they smoke marijuana once or twice per week?” The proportion of pregnant women without use in the past 30 days who reported “no risk” of harm increased from 3.5% to 16.5% over the study time period. The proportion of pregnant women with recent use who reported “no risk” of harm was even higher increasing from 25.8% to 65.4%.7

Anecdotally, women report ongoing use in pregnancy to relieve nausea, decrease pain, and for psychiatric disorders such as anxiety and depression. In a cross-sectional survey (N=1,749), the majority of women reported use to help with depression and anxiety (63%) followed by help with pain (60%).1 Only 39% of the women with current use reported using marijuana for fun or recreation. Given that women perceive medical benefits of marijuana use, there is an opportunity for health care providers to query women as to the reasons for use and discuss alternative therapies.

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PHARMACOLOGY OF CANNABIS

Cannabis plants produce more than 400 chemical entities and more than 60 cannabinoids, which can have both physical and mental effects when consumed.8 The main psychoactive component of cannabis, delta-9-tetrahydrocannabinol, acts on type 1 (CB1) and type 2 (CB2) cannabinoid receptors that are expressed throughout the central nervous system and peripheral tissues.9

Our contemporary understanding of the effects of exogenous cannabinoids (eg, delta-9-tetrahydrocannabinol) on humans stems predominantly from studying endogenous CB1 receptor agonists such as anandamide and 2-arachidonoyl glycerol. Unlike typical transmitters, anandamide and 2-arachidonoyl glycerol are produced only when and where they are needed. Their action is presynaptic (in a retrograde manner) rather than postsynaptic, which makes inhibition of various excitatory or inhibitory neurotransmitter systems possible.8

The effects of endocannabinoids are dependent on the rate of synthesis, cellular uptake, and degradation. Endocannabinoids are rapidly removed by a membrane transport process, whereas exogenous cannabinoids such as delta-9-tetrahydrocannabinol are metabolized by the liver and stored in peripheral tissues as stable metabolites (Fig. 1).8 The metabolites are then excreted by the kidney over time.

Fig. 1.

Fig. 1.

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POTENTIAL THERAPEUTIC USES FOR CANNABIS

There is growing evidence that the endocannabinoid system plays a role in a variety of medical conditions. Exogenous cannabinoids such as delta-9-tetrahydrocannabinol and cannabidiol may function at cannabinoid and other receptors to improve symptoms of conditions with a relative endocannabinoid deficiency such as migraines, fibromyalgia, and irritable bowel syndrome.10

Cannabinoid receptors represent potential treatment targets for several neurologic disorders. Seizures trigger homeostatic changes in CB1 receptors found in the hippocampus.11 Animal models demonstrate that activation of CB1 receptors reduces seizure severity. In addition, patients with temporal lobe epilepsy have decreased levels of anandamide in cerebrospinal fluid samples compared with healthy patients.12 However, efficacy of exogenous cannabinoids for treatment of epilepsy in children has been inconsistent across randomized clinical trials and notably ineffective in adults.13

Cannabis has been found to relieve some symptoms related to cancer or cancer treatment including antiemetic effects, appetite stimulation, pain relief, and improved sleep.13 Preclinical studies utilizing delta-9-tetrahydrocannabinol and cannabidiol have demonstrated antitumor effects in glioma, melanoma and pancreatic and hepatic cancer cells by inducing cancer cell death and inhibiting angiogenesis and metastasis while protecting healthy tissue from cell death.14

CB1 receptors in the basal ganglia affect mechanisms of muscle spasticity.15 Several randomized controlled trials demonstrate that oral cannabis extracts significantly improve mobility and perceptions of muscle spasticity and pain in patients with multiple sclerosis.16 A cannabinoid-based product is now available in 30 countries for treatment of spasticity related to multiple sclerosis.

Severe or intractable nausea is a qualifying condition in most states where medical cannabis laws are enacted. Cannabinoids can block acute, delayed, and potentially anticipatory nausea and vomiting.17 Cannabis-based treatments had superior efficacy to prochlorperazine and similar efficacy to ondansetron in randomized controlled trials of patients with cancer.18,19 However, there are no data to support the efficacy of marijuana for nausea and vomiting of pregnancy, and given the potential harmful effects for the fetus, cannabis should not be recommended as a treatment for pregnant women.

Cannabis is being investigated as a therapy for posttraumatic stress disorder. Patients with posttraumatic stress disorder have lower peripheral anandamide levels and increased CB1 receptors in the brain compared with those without posttraumatic stress disorder.20 Studies have demonstrated significant decreases in nightmare occurrence and severity as well as subjective improvement in sleep time, quality, flashbacks, and night sweats in patients with posttraumatic stress disorder treated with cannabis.21

In summary, exogenous cannabinoids (eg, delta-9-tetrahydrocannabinol and cannabidiol) have potential therapeutic effectiveness for conditions in which there is a relative endocannabinoid deficiency or hypofunction. However, more research is needed to provide adequate support for expanded medical cannabis use because the available body of evidence is insufficient and often conflicting.

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IMPORTANCE OF THE ENDOCANNABINOID SYSTEM IN PREGNANCY

The endocannabinoid system plays an important role in implantation and pregnancy maintenance. The pregnancy implantation site expresses low levels of anandamide, whereas adjacent sites express higher levels of anandamide to assure highly synchronized communication between the embryo and the endometrium.9 Maintaining a balance of anandamide synthesis and degradation is required for successful embryonic passage through the oviduct and implantation (Fig. 2).9

Fig. 2.

Fig. 2.

On implantation, activated blastocysts have higher expression of CB1 receptors than dormant blastocysts and anandamide levels remain tightly regulated without variation in the first and second trimesters of pregnancy.9 Plasma anandamide levels are elevated in women with nonviable first-trimester pregnancies compared with those with viable pregnancies.9 Furthermore, higher anandamide levels are associated with miscarriage and low levels of progesterone in some studies.9 However, one prospective study found no difference between plasma levels of anandamide in asymptomatic women sampled at 6–10 weeks of gestation who miscarried compared with those who did not.22 Several studies in humans and mice have provided evidence that CB1 and CB2 receptors are expressed in the decidualization process of differentiation and remodeling.9

During fetal life, the CB1 receptor plays a major role in brain development by regulating neural progenitor differentiation into neurons and glia and guiding axonal migration and synaptogenesis. By 2 weeks of gestation in mice and 19 weeks of gestation in humans, the fetus has the complete array of cannabinoid receptors.9,23 However, in both rats and humans, the number of CB1 receptors is substantially higher in fetal brains compared with adult brains.23,24 The increased concentration of CB1 receptors in the fetus has been attributed to key developmental events including cell proliferation and migration and axonal elongation with eventual synaptogenesis and myelogenesis.

Rats exposed to cannabinoids during pregnancy or lactation demonstrate motor hyperactivity in infancy and adolescence, but not adulthood.25 When rats were exposed prenatally to low or moderate levels of delta-9-tetrahydrocannabinol, cognitive impairments were induced with long-term memory impairment and short-term olfactory memory.26 These impairments were associated with long-lasting changes in the expression of genes related to glutamatergic neurotransmission. In addition, long-lasting changes in emotional reactivity of offspring have been observed with less social interaction and social play at adolescence.27

Additional insights regarding the effect of cannabis on the developing fetal human brain suggest critical interruptions in the endocannabinoid system are possible. For example, repeated delta-9-tetrahydrocannabinol exposure disrupts endocannabinoid signaling, particularly with the CB1 cannabinoid receptor, resulting in a “rewiring” of the fetal cortical circuitry.28

In summary, both animal and human studies demonstrate the importance of appropriate endocannabinoid signaling for normal fetal development. The endocannabinoid system also plays an active role in pregnancy implantation and placental development. With a clear understanding of the role of the endocannabinoid system, one can see how manipulating it with prenatal administration of exogenous cannabis could have subtle but significant effects on human offspring.

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MARIJUANA AND ADVERSE PREGNANCY OUTCOMES

Human evidence regarding the association between prenatal marijuana use and adverse pregnancy outcomes is mixed. Practitioners should be aware that there are significant limitations to the existing literature. Marijuana use is often not quantified and studies are limited by ascertainment of marijuana exposure through self-report, which underestimates the prevalence of use.2 Biological sampling should be used to accurately determine the effects of prenatal marijuana use on maternal and neonatal outcomes. Important confounders such as education level and concurrent tobacco use will need to be measured thoughtfully and prospectively to evaluate the independent role of marijuana use in pregnancy outcomes.

The National Academy of Sciences published a consensus document in 2017 detailing the evidence related to the health effects of cannabis and cannabinoids.13 The committee reported that smoking cannabis during pregnancy was linked to lower birth weight in offspring. They also concluded that there is limited evidence of a statistical association between prenatal marijuana use and both maternal pregnancy complications and neonatal intensive care unit (NICU) admission. The committee found insufficient evidence to support or refute associations between marijuana and later outcomes in the offspring such as cognition and academic achievement. The lack of conclusive evidence regarding later childhood outcomes is predominantly a result of mixed findings as well as difficulty in attributing any observed differences to prenatal exposure rather than subtle differences in the environment throughout childhood and adolescence that could not be measured.

Two recent systematic reviews and meta-analyses provide a comprehensive review of the literature, which can be translated into guidance for practitioners to counsel women regarding marijuana use in pregnancy. One of these5 was published before the National Academy of Sciences report and was drawn on heavily in the committee's evaluation of the existing literature. Gunn et al5 identified 6,854 articles, fully screened 881 articles, and included 24 articles (one cross-sectional, one case–control, and 22 cohort studies) in a systematic review. The authors created a comprehensive list of maternal and neonatal outcomes of interest and completed a meta-analysis for any outcomes assessed in three or more studies.

They found an association between prenatal marijuana use and anemia (pooled odds ratio [OR] from six studies 1.36, 95% CI 1.10–1.69), low birth weight less than 2,500 g (pooled OR from seven studies 1.77, 95% CI 1.04–3.01 with a mean pooled birth weight difference of 109 g), and higher odds of NICU admission (pooled OR from four studies 2.02, 95% CI 1.27–3.21). They did not detect an association with preterm birth (pooled OR from nine studies 1.29, 95% CI 0.80–2.08). These authors concluded that further study is needed, especially for maternal outcomes, and were concerned about the associations between marijuana use and both low birth weight and NICU admission (Fig. 3).

Fig. 3.

Fig. 3.

In a second meta-analysis, Conner et al4 evaluated the association between marijuana use and low birth weight or preterm birth at less than 37 weeks of gestation. The authors identified 4,875 studies and ultimately included 31 studies in the meta-analysis. In initial pooled estimates, there was an association with low birth weight and preterm birth. However, after adjustment for confounding factors such as tobacco use, there was no association between any marijuana use and low birth weight (adjusted pooled relative risk [RR] 1.16, 95% CI 0.98–1.37) or preterm birth (adjusted pooled RR 1.08, 95% CI 0.82–1.43) (Fig. 3). In a planned subanalysis of women reporting moderate to heavy marijuana use (at least once per week), there was an association with both low birth weight (RR 1.90, 95% CI 1.44–2.45) and preterm birth (RR 2.04, 95% CI 1.32–3.17).

There are some studies included in each meta-analysis that are not included in the other. This discrepancy is in part a result of a focus on neonatal outcomes in the Conner et al4 meta-analysis and both maternal and neonatal outcomes in the Gunn et al5 meta-analysis. Differences in results may also be the result of adjustment for confounding factors in the Conner et al4 analysis. A summary of the ORs and RRs for adverse outcomes in these meta-analyses are depicted in Figure 3.

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Fetal Growth

Recent meta-analyses demonstrate an association between marijuana use and low birth weight as noted previously.4,5 Importantly, Conner et al4 only observed this association with heavy marijuana use. A relationship between aberrant fetal growth and prenatal marijuana use was also recognized in the National Academy of Sciences report.13 This association is biologically plausible given the importance of the endocannabinoid system in pregnancy implantation and placental formation.

Essentially all of the studies that evaluate the relationship between marijuana use and fetal growth use a primary endpoint of birth weight, low birth weight (less than 2,500 g), or small for gestational age (less than 10% birth weight for gestational age and sex). Only the Generation R study evaluated fetal growth prospectively in a population of women with marijuana use.29 In this study, the investigators demonstrated a relative “dose–response” effect of marijuana on fetal growth with greater growth decrements demonstrated with increasing use. Fetuses exposed to marijuana in early pregnancy (n=214) grew 11.2 g (−15.3 to −7.1 g) per week less than those not exposed; those with ongoing exposure grew 14.4 g (−22.9 to −5.9 g) per week less than those not exposed. However, given the limited evidence for antenatally detected abnormal growth, Doppler studies and serial growth ultrasonograms are not recommended strictly for the indication of marijuana use in the absence of clinical concern for growth restriction.

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Preterm Birth

Preterm birth at less than 37 weeks of gestation is commonly evaluated in the marijuana and pregnancy literature. However, data are inconsistent for this outcome.1 Odds ratios from meta-analyses for the association between marijuana use and preterm birth are presented in Figure 3. Although Conner et al4 found no association between any marijuana use and preterm birth, there was an association between heavy marijuana use and preterm birth. Of note, the majority of the studies included in the meta-analyses did not classify preterm birth into spontaneous or iatrogenic.

There are three recent studies demonstrating an association between marijuana use and spontaneous preterm birth. The first is an observational study of nulliparous women (N=3,184) by Dekker et al30 in which women who used marijuana prepregnancy had increased odds of spontaneous preterm birth with intact membranes (adjusted OR 2.34, 95% CI 1.22–4.52). Similarly, in a secondary analysis of a prospectively collected cohort, Saurel-Cubizolles et al31 found an increased risk of spontaneous preterm birth among women with marijuana use compared with nonusers (OR 2.15, 95% CI 1.10–4.18). However, this association was no longer significant when evaluating women with only marijuana use and no tobacco use. Finally, Leemaqz et al32 found an increased risk of spontaneous preterm birth after adjustment for tobacco exposure (adjusted OR 2.28, 95% CI 1.45–3.59). Future research efforts need to classify women as having either iatrogenic or spontaneous preterm birth to better elucidate the role of marijuana use (if any) in this important perinatal outcome.

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Stillbirth

There is a relative paucity of evidence related to stillbirth and prenatal marijuana use. This is predominantly a result of stillbirth being excluded from many existing studies. Stillbirth and perinatal death were included as secondary outcomes in the Conner et al4 meta-analysis with only two available studies for stillbirth and three for perinatal death. Marijuana use was associated with stillbirth (pooled OR 1.74, 95% CI 1.03–2.93) but not perinatal death (pooled RR 1.09, 95% CI 0.62–1.91). Gunn et al5 also found no association with perinatal mortality.

Varner et al33 completed a secondary analysis of Eunice Kennedy Shriver National Institute of Child Health and Human Development Stillbirth Collaborative Research Network data including 1,468 women with umbilical cord specimens available. Of these, 3.9% of stillbirths and 1.7% of live births had cord homogenate positive for tetrahydrocannabinol metabolites. Marijuana use as measured by cord homogenate assays was associated with stillbirth (OR 2.34, 95% CI 1.13–4.81), and this association persisted after adjustment for tobacco use with serum cotinine.

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Congenital Anomalies

There is insufficient evidence to support an association between marijuana use and any specific congenital abnormality.2 Many studies evaluating the effect of marijuana on embryogenesis do not specify whether use was during the critical period of development. In addition, the majority are subject to recall bias with marijuana use ascertained by self-report in the postpartum period. The Gunn et al5 meta-analysis found no association between marijuana use and congenital birth defects.

In a review of the available scientific evidence, the Retail Marijuana Public Health Advisory Committee for the Colorado Department of Public Health and Environment found limited evidence for an association between marijuana use and isolated ventricular septal defects based on a single study of 122 cases of isolated simple ventricular septal defect and 3,029 controls.34 After adjustment for maternal age, race, overt diabetes, and multivitamin use, periconceptional marijuana use as ascertained by maternal self-report was associated with ventricular septal defect (OR 1.90, 95% CI 1.29–2.81). This work has not been replicated. At this time, women should be counseled that there is no consistent association between marijuana and congenital birth defects; however, there is also insufficient evidence to demonstrate safety.

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Neonatal Morbidity and Neonatal Intensive Care Unit Admission

Marijuana use was associated with NICU admission in the Gunn et al meta-analysis (pooled OR 2.02, 95% CI 1.27–3.21) but not in the Conner et al meta-analysis (pooled RR 1.41, 95% CI 0.99–2.0).4,5 Despite these differential findings, there is an increasing body of evidence indicating that marijuana use may be associated with neonatal morbidity.

Warshak et al35 demonstrated an increased risk of NICU admission among marijuana users compared with nonusers in a single-center retrospective cohort study (17.2% compared with 12.5%, adjusted OR 1.54, 95% CI 1.14–2.07). Metz et al36 found similar rates of NICU admission between marijuana-exposed (16.9%) and marijuana-nonexposed (9.5%) groups among the live births in the Stillbirth Collaborative Research Network database. However, this difference was not significant in the setting of a smaller sample size. There was, however, an increased risk of composite neonatal morbidity consisting of respiratory, neurologic, infection, and hematologic morbidity or death before hospital discharge (adjusted OR 3.11, 95% CI 1.40–6.91).

Neonatal withdrawal syndrome from marijuana is not well described. A few articles report increased tremor, irritability, hand-to-mouth activity, and startle response among exposed neonates.5 However, others demonstrate no difference on neonatal behavioral assessment scales.5 It is unclear what factors and neonatal diagnoses drive the observed increase in NICU admission.

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Long-term Adverse Neurologic Events

None of the existing meta-analyses address the effects of prenatal marijuana use on neurobehavioral outcomes in the offspring. Evidence related to neurodevelopmental outcomes comes predominantly from three longitudinal human studies: the Ottawa Prenatal Prospective Study, Maternal Health Practices and Child Development, and Generation R (Table 1). For all of these studies, marijuana use was ascertained by maternal self-report.

Table 1.

Table 1.

The National Academy of Sciences report found insufficient evidence to support or refute an association between maternal marijuana use and later childhood outcomes such as cognition and academic achievement.13 Considering the findings from the longitudinal human studies, the animal data related to neurodevelopment, and one human study demonstrating decreased dopamine receptors in 18- to 22-week fetuses after pregnancy termination who were exposed to cannabis in utero compared with those who were not,37 we conclude that there remain concerns related to neurologic development with prenatal marijuana use. The authors recognize that it is difficult to complete longitudinal studies that adequately control for the childhood environment to evaluate the independent effects of in utero exposure. It should also be noted that these longitudinal studies may not reflect the effects of contemporary products with higher concentrations of delta-9-tetrahydrocannabinol.

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BREASTFEEDING

A survey of lactation consultants in New England demonstrates the spectrum of opinions of lactation professionals regarding breastfeeding in the setting of marijuana use. Of the 74 lactation professionals surveyed, 41% reported their recommendation would depend on the amount of marijuana use, 44% would recommend breastfeeding despite marijuana use given the other known benefits of breastfeeding, and 15% would recommend not breastfeeding with marijuana use.38

A difference in opinion regarding breastfeeding and marijuana use likely stems from a paucity of data. Using samples from two patients, Reyes-Perez et al39 demonstrated excretion of tetrahydrocannabinol into the breast milk with a relative infant dose of 0.8%, which means approximate consumption by the infant is 0.8% of its mother's dose per kilogram. Baker et al studied transfer of delta-9-tetrahydrocannabinol into the breast milk of eight women after consumption of a cannabis product with known concentration of delta-9-tetrahydrocannabinol. Delta-9-tetrahydrocannabinol was detected in pumped breast milk at an estimated mean of 2.5% (range 0.4–8.7%) of the maternal dose, and the average absolute infant dose was estimated at 8 micrograms per kilogram per day. The mean concentrations of delta-9-tetrahydrocannabinol in the breast milk from 20 minutes to 4 hours postinhalation are depicted in Figure 4. Although this study has significant limitations as a result of sampling of breast milk in an uncontrolled environment, and small sample size, it provides preliminary data supporting transfer of delta-9-tetrahydrocannabinol into breast milk.40

Fig. 4.

Fig. 4.

Cannabis concentration in the breast milk is likely related to maternal dose, frequency of dosing, simple diffusion, and trapping within the breast milk as a result of lipophilicity. The bioavailability of marijuana metabolites ingested by neonates in the breast milk is largely unknown. In one chronic, heavy user, the milk:plasma ratio was noted at 8:1 and detectable metabolites were found in the neonate's feces.41 Baker et al did not measure a milk/plasma ratio nor obtain neonatal samples.

There are conflicting data regarding outcomes of infants exposed to cannabis during breastfeeding. In one study, 136 breastfed infants were assessed at 1 year for motor and mental development.42 The 68 infants exposed to cannabis during the first month postpartum showed an association of decreased motor development at 1 year compared with matched infants in a control group. Specifically, there was a 14±5-point decrease in the Bayley index of infant motor development. However, the authors believed that marijuana use during pregnancy confounded the association.

Another study compared 27 breastfed infants exposed to cannabis with 35 unexposed breastfed infants.43 At 1 year, no differences were noted for motor and mental skills using the Bayley Scales of Infant Development. The authors noted that statistical analyses were limited as a result of a small sample size and lack of comparability regarding dose and duration of exposure.

The paucity of clinical evidence has made it difficult for organizations to make definitive recommendations regarding cannabis use during lactation. Both the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics recommend that women refrain from using cannabis while lactating.3,44 The Academy of Breastfeeding Medicine states breastfeeding mothers “should be counseled to reduce or eliminate their use of cannabis to avoid exposing their infants and advised of the possible long-term neurobehavioral effects from continued use.”45 They ask clinicians to consider the wide range of occasional, regular medical, and heavy exposure to cannabis and urge caution when breastfeeding occurs with cannabis use.

The authors believe that discontinuation of cannabis provides the least risk and highest safety profile for the mother and infant. If discontinuation is not possible, women should be encouraged to limit use as much as they can. For women who use cannabis for medical indications, alternative therapies with more safety data during breastfeeding should be considered. If women continue to use cannabis while breastfeeding after counseling, it is reasonable to provide lactation support per standard of care at the birthing facility given the limited data regarding passage of cannabis into the breast milk and the many known benefits of breastfeeding for both the mother and neonate. Recommendations regarding breastfeeding will evolve as more evidence becomes available. In the meantime, the lack of data should not be interpreted as an endorsement of safety.

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COUNSELING PATIENTS REGARDING MARIJUANA USE IN PREGNANCY AND WHEN BREASFEEDING

All women should be verbally screened for drug use during the course of standard prenatal care. Screening for drug use should be completed with the goal of providing counseling regarding potential adverse effects and referral to resources to assist with cessation when needed. Some practitioners use biological sampling to confirm self-report. The utility of this is unknown because women who self-report are likely using marijuana and would be candidates for intervention with or without a positive urine test.

Holland et al46 recorded 468 patient interactions during which 90 pregnant patients disclosed marijuana use to 47 different health care providers. The health care providers responded to the disclosure only 48% of the time. When health care providers did respond to the disclosure, they discussed implications of exposure such as referral to social services rather than investigating why patients were using and educating them about possible risks. There are clearly opportunities for improvement in how health care providers counsel women regarding use.

Women also seek information regarding perinatal marijuana use from other sources. In qualitative work by Jarlenski et al,47 women were unlikely to obtain information about marijuana use from their health care providers. Instead, women relied on anecdotal experiences, advice from friends and family, and internet searching. It is unclear from this study whether women intentionally do not seek information from health care workers or whether the information that we provide is not perceived as valuable or helpful. In addition, women may seek advice directly from dispensary employees. In a cross-sectional study of randomly selected dispensaries in Colorado, 69% recommended cannabis products to a woman posing as pregnant with nausea in the first trimester.48 Many endorsed safety and few recommended consultation with a health care provider without prompting.48

With the time pressures of obstetric practice, clinicians need resources to provide information regarding prenatal marijuana use to patients in an efficient way. After the legalization of marijuana in Colorado, the Colorado Department of Public Health and Environment assembled a task force to review the scientific literature regarding the health effects of marijuana on mothers and neonates (Fig. 5). After this review, the task force translated their findings into documents that can be used by clinicians to assist with responding to patient concerns and questions regarding marijuana use in pregnancy. This guidance and resources for distribution to patients can be found at the following web address: https://www.colorado.gov/pacific/cdphe/marijuana-clinical-guidelines and as Appendix 1, available online at http://links.lww.com/AOG/B150. Additionally, ACOG recently published “Marijuana and Pregnancy: Frequently Asked Questions” with patient information that may help health care providers in answering questions and having conversations about marijuana use. The ACOG resource is available online at https://www.acog.org/Patients/FAQs/Marijuana-and-Pregnancy. Women may or may not opt to cease using marijuana, but health care providers should be informing pregnant women of possible risks.

Fig. 5.

Fig. 5.

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SUMMARY OF CLINICAL RECOMMENDATIONS

The heterogeneity of findings in the scientific literature leads to uncertainty in counseling women regarding marijuana use in pregnancy. Although more evidence is needed for informed decision-making, it seems reasonable to follow ACOG guidelines recommending that women be discouraged from using marijuana during pregnancy and lactation.3 The rationale to follow these recommendations stems from a growing body of studies showing potential harm to fetuses with evidence of decreased growth (in particular with heavy use) and concern from longitudinal studies for long-term neurologic effects. Marijuana use may be associated with spontaneous preterm birth, stillbirth, and NICU admission. The health effects on the mother remain largely unknown.13

We recognize that there is still uncertainty regarding the effects of prenatal marijuana use and even more so for marijuana use while breastfeeding. As practitioners, we can be honest with women regarding the uncertain effects of marijuana but still express concern for fetal harm based on the available evidence. A better understanding of why women are using marijuana during pregnancy may enable a conversation of alternative therapies for which we have extensive safety and efficacy data. Further evidence to guide counseling of women as to the anticipated effects of prenatal marijuana use will allow for informed decision-making and help promote appropriate public health policies as legalization expands.

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REFERENCES

1. Retail Marijuana Public Health Advisory Committee. Monitoring health concerns related to marijuana in Colorado: 2014. Available at: http://dhss.alaska.gov/dph/Director/Documents/marijuana/Monitoring_Health_Concerns_Related_to_Marijuana_in_Colorado_2014.pdf. Retrieved February 13, 2018.
2. Metz TD, Stickrath EH. Marijuana use in pregnancy and lactation: a review of the evidence. Am J Obstet Gynecol 2015;213:761–78.
3. Marijuana use during pregnancy and lactation. Committee Opinion No. 722. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;130:e205–9.
4. Conner SN, Bedell V, Lipsey K, Macones GA, Cahill AG, Tuuli MG. Maternal marijuana use and adverse neonatal outcomes: a systematic review and meta-analysis. Obstet Gynecol 2016;128:713–23.
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