Cannabis use in pregnancy: Clinical and policy implications NATIONAL MATERNAL AND INFANT NUTRITION INTENSIVE COURSE Marian Jarlenski, PhD, MPH August

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1 Cannabis use in pregnancy: Clinical and policy implications NATIONAL MATERNAL AND INFANT NUTRITION INTENSIVE COURSE Marian Jarlenski, PhD, MPH August 16, 2017

2 Conflict of Interest Disclosure I have no relationships, financial or otherwise, with any manufacturer or provider of any commercial product or service that relates to the topic of this presentation. Cannabis use in pregnancy 2

3 Outline 1. What is cannabis? 2. What is the epidemiology of cannabis use in pregnant and reproductive-aged women? 3. What are hypothesized risks of cannabis use in pregnancy? 4. Does cannabis use cause adverse perinatal or child outcomes? 5. What are the policy implications of cannabis use in pregnancy? 6. How can we deliver high-quality prenatal and postpartum care to women who use cannabis amid scientific uncertainty? Cannabis use in pregnancy 3

4 1. What is cannabis? Cannabis use in pregnancy 4

5 Cannabis Cannabis sativa plant contains cannabinoids, some of which have psychoactive properties Marijuana: American term for dried flowers and leaves of the plant Hashish: Resin product made by extracting cannabinoid-rich structures from the plant Cannabis use in pregnancy 5

6 Psychoactive properties of cannabis - THC Delta-9-tetrahydrocannainol (THC) is the primary psychoactive component (and best-understood cannabinoid) THC interacts with receptors CB1 and CB2 Receptors are activated with exogenous cannabinoids (THC) and endogenous cannabinoids (anandamide) Experience of intoxication may include increased focus on sensory experience, reduced short-term memory, increased appetite Cannabis use in pregnancy 6

7 Other properties of cannabis - CBD Cannabidiol (CBD) is a second compound in cannabis CBD is not an intoxicant but may interact with THC CBD is hypothesized to have anti-psychotic effects Recent trial published in NEJM showed CBD to reduce convulsive seizures in children with Dravet syndrome, relative to placebo Cannabis use in pregnancy 7

8 2. What is the epidemiology of cannabis use in pregnant and reproductive-aged women? Cannabis use in pregnancy 8

9 Cannabis use in pregnancy 9

10 Year-to-Year Prevalence of Past-Month Marijuana Use Among Pregnant and Nonpregnant Women, Overall and by Age, From: Trends in Marijuana Use Among Pregnant and Nonpregnant Reproductive-Aged Women, JAMA. 2017;317(2): doi: /jama Cannabis use in pregnancy 10

11 Marijuana use across trimesters of pregnancy Volkow et al, Ann Intern Med

12 Cannabis use is much higher in certain subgroups Maryland: 29% of 369 pregnant patients self-disclosed or tested positive for marijuana use (Mark et al, 2016) Pittsburgh: 27% of 422 pregnant patients self-disclosed or tested positive for marijuana use (Chang et al, 2017) Among women with opioid use disorders, 32.4% of reproductive-aged women and 35.1% of pregnant women report past-month marijuana use (Jarlenski et al, 2017) Cannabis use in pregnancy 12

13 0 Proportion Time trends in perception of risk of cannabis use among reproductive-aged women From the NSDUH, women ages 18-44y. How much do people risk harming themselves physically and in other ways when they smoke marijuana once or twice a week? No Risk 400% Slight Risk 67% Great Risk 37% year No Risk Moderate Risk Slight Risk Great Risk Cannabis use in pregnancy 13

14 % Reporting "No Risk" 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% Pregnant, no marijuana use Non-pregnant, no marijuana use Pregnant, marijuana use Non-pregnant, marijuana use Times trends in perception of no risk of using marijuana once or twice a week, among women y. Adjusted for age, race/ethnicity, and educational attainment. From the NSDUH.

15 Mode of cannabis consumption Possible mode of consumption: Smoking (combustible inhalation) Vaping (non-combustible inhalation) Edible products Transdermal products No published research to date on mode of consumption in pregnant women Cannabis use in pregnancy 15

16 Why do pregnant women use cannabis? Cannabis use in pregnancy 16

17 3. What are hypothesized risks of cannabis use in pregnancy? Cannabis use in pregnancy 17

18 THC rapidly crosses the placenta Animal models show: THC rapidly crosses the placenta after dosing Fetal clearance of THC is slow Prolonged fetal exposure This THC exposure may affect fetal development Baily et al, Toxicol Appl Pharmcaol, 1987 Khare et al, Mol Hum Reprod, 2006 Wu et al, Future Neurol, 2011 Cannabis use in pregnancy 18

19 Friedrich et al, BMC Pharmacol Toxicol, 2016 Cannabis use in pregnancy 19

20 THC concentration in marijuana is increasing Cannabis use in pregnancy 20

21 4. Does cannabis use cause adverse perinatal or child outcomes? Cannabis use in pregnancy 21

22 Cannabis use and links with adverse health outcomes Outcome Quality of data in humans Strength of evidence for association Marijuana dependence High High Fetal growth effects Medium, but variable by study Medium Spontaneous preterm birth Low? Breastfeeding Low? Child cognitive function Medium, but variable by study Medium Cannabis use in pregnancy 22

23 Marijuana dependence An estimated 25%-30% of U.S. women who use marijuana meet criteria for abuse or dependence (similar estimates in men) Dependence estimates among users appear stable over time (Hasin et al, JAMA Psychiatry, 2015) 18.1% of U.S. pregnant women who use marijuana meet criteria for abuse or dependence (Ko et al, AJOG, 2015) Cannabis use in pregnancy 23

24 Women may progress more rapidly to cannabis dependence, relative to men Hernandez-Avila et al. Drug Alcohol Depend, Cannabis use in pregnancy 24

25 Marijuana use is increasing in substance use treatment admissions among pregnant women Martin et al. J Addict Med, Cannabis use in pregnancy 25

26 Cannabis exposure and fetal growth El Marroun et al. J Acad Child Adolesc Psychiatry, Cannabis use in pregnancy 26

27 Cannabis exposure and neurobehavioral and cognitive effects 2 longitudinal studies in humans: Ottawa Prenatal Prospective Study (1978) Maternal Health Practices and Child Development Study (1982) Cannabis use in pregnancy 27

28 Cannabis exposure and neonatal and postneonatal neurobehavior Neonates may have: sleep disturbances, altered responses to stimuli, tremors (Fried and Smith, Neurotoxicol Teratol, 2001) Children exposed to marijuana in the third trimester had decreased cognitive scores at 9 months of age, but no significant differences at 19 months of age (Richardson et al, Neurotoxicol Teratol, 1995) Cannabis use in pregnancy 28

29 Prenatal cannabis exposure independently predicts academic achievement at age 10 Goldschmidt et al. Neurotoxicology and Teratology, Cannabis use in pregnancy 29

30 Relationship of prenatal marijuana exposure and maladjustment to adult roles may be mediated by early onset of marijuana use Goldschmidt et al. Neurotoxicology and Teratology, Cannabis use in pregnancy 30

31 Cannabis use and spontaneous preterm birth Most prospective research has not found any association between cannabis exposure and spontaneous preterm birth However, most studies relied on self-report of marijuana use (Metz, Am J Obstet Gynecol, 2015) Cannabis use in pregnancy 31

32 Cannabis use while breastfeeding THC can be passed via breastmilk to infants Scarce data on effects of THC in breastmilk on child health Cannabis use in pregnancy 32

33 Limitations to drawing causal inference Not able to randomize women to cannabis exposure (selection bias) Imperfect measurement of THC exposure (misclassification) Cannabis is not a standardized product (imprecision) Cannabis use in pregnancy 33

34 5. What are the policy implications of cannabis use during pregnancy? Cannabis use in pregnancy 34

35 WA OR NV CA ID AZ UT MT WY CO NM ND SD NE KS OK MN WI IA IL MO AR MS MI OH IN KY TN AL VT NY PA WV VA NC SC GA ME NH MA CT RI NJ DE MD DC TX LA AK HI FL No law (43% of births) Medical use (36% of births) Medical and recreational use (21% of births) 57% of births are in states permitting medical or recreational marijuana use. Proportion of births calculated from 2014 vital statistics data. State law data from the National Conference on State Legislatures.

36 Mandatory reporting and legal consequences Federal law requires states to have mandatory reporting policies and procedures to: Require health care providers to report to child protective services infants born with and identified as being affected by substance abuse or withdrawal symptoms resulting from prenatal drug exposure, or a Fetal Alcohol Spectrum Disorder Develop a plan of safe care for such infants, including health and substance use disorder treatment needs of the infant and affected family or caregiver 42 USC 5106a Cannabis use in pregnancy 36

37 Example: Minnesota law Cannabis use in pregnancy 37

38 Criminal prosecution for prenatal cannabis use varies Cannabis use in pregnancy 38

39 The use of the legal system to address perinatal alcohol and substance abuse is inappropriate. [Providers] should be aware of the reporting requirements within their states. They are encouraged to work with state legislators to retract legislation that punishes women for substance abuse during pregnancy. ACOG Committee Opinion #473, 2011 Cannabis use in pregnancy 39

40 6. How can we deliver high-quality prenatal and postpartum care to women who use cannabis? Cannabis use in pregnancy 40

41 What happens in prenatal care for women who use cannabis? 48% of prenatal visits with patient disclosure had no counseling Holland et al., Obstet Gynecol, Cannabis use in pregnancy 41

42 Perspectives from physicians, nurse midwives, and nurse practitioners We always talk about methadone and problems with [opiate] use in pregnancy.i mean, outcomes [for marijuana use during pregnancy] are not as important. There are no syndromes caused by marijuana that we know of. It doesn t affect the pregnancy, health outcomes the same way [as other drugs]. [Using marijuana during pregnancy] is particularly bad for you socially because now that we know [about your use], you definitely have to get a urine drug test when you deliver your baby. If you test positive, then social services has to get involved and talk to you about the safety of your baby at home. So it is really important that you know that this is going to happen. I don t think we really know what marijuana does in pregnancy. So I think that s a harder one to counsel people about. Holland et al. Pat Educ Counsel, 2016 Cannabis use in pregnancy 42

43 Clinical Guidelines: ACOG Before pregnancy and in early pregnancy, all women should be asked about their use of tobacco, alcohol, and other drugs, including marijuana and other medications used for nonmedical reasons. Women reporting marijuana use should be counseled about concerns regarding potential adverse health consequences of continued use during pregnancy. Women who are pregnant or contemplating pregnancy should be encouraged to discontinue marijuana use. Pregnant women or women contemplating pregnancy should be encouraged to discontinue use of marijuana for medicinal purposes in favor of an alternative therapy for which there are better pregnancyspecific safety data. Cannabis use in pregnancy 43

44 Disagreement about universal screening Obstet Gynecol, 2015 Cannabis use in pregnancy 44

45 Treatment for marijuana dependence Treatment of co-occurring psychiatric disorder Cognitive behavioral therapy Motivational enhancement therapy Contingency management No medications currently approved for use to treat marijuana dependence NIDA, Marijuana Research Report Series, April Cannabis use in pregnancy 45

46 Breastfeeding Guidelines American Academy of Pediatrics: [C]annabis can be detected in human milk, and use by breastfeeding mothers is of concern, particularly with regard to the infant s long-term neurobehavioral development and thus [is] contraindicated. Academy of Breastfeeding Medicine: At this time, although the data are not strong enough to recommend not breastfeeding with any marijuana use, we urge caution A recommendation of abstaining from any marijuana use is warranted. Cannabis use in pregnancy 46

47 Considerations for screening in prenatal care Universal screening for marijuana and/or other substances? If yes, urine toxicology or questionnaire? Informed consent process for urine toxicology? What treatment resources are available for women with dependence? What are state legal requirements or hospital protocols? Cannabis use in pregnancy 47

48 Few public health departments publish information about cannabis use in pregnancy Jarlenski et al. Subst Abuse, 2016 Cannabis use in pregnancy 48

49 Communications from Colorado and CDC Cannabis use in pregnancy 49

50 Summary Cannabis use is not rare and is increasing among reproductive-aged and pregnant U.S. women One-third of women who use cannabis have dependence Cannabis exposure is associated with restricted fetal growth Cannabis exposure is associated with neurobehavioral effects in children Little is known about effects of cannabis use while breastfeeding Screening for cannabis use and dependence should be informed by treatment options and knowledge of legal consequences Cannabis use in pregnancy

51 Thank you! NATIONAL MATERNAL AND INFANT NUTRITION INTENSIVE COURSE Marian Jarlenski, PhD, MPH August 16, 2017

52 NATIONAL MATERNAL AND INFANT NUTRITION INTENSIVE COURSE References to accompany: Cannabis use in pregnancy: Clinical and policy implications. Jarlenski, August 16, 2017, 1 PM Recommended Summary Readings: Caulkins, J. P. (2016). Marijuana legalization : What everyone needs to know. 2 nd Edition. New York: Oxford University Press. National Academy of Medicine Committee on the Health Effects of Marijuana. (2017). The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. National Institute on Drug Abuse (NIDA). (April 2017). Marijuana Research Reports. Retrieved from: Selected Clinical Guidelines: American Academy of Pediatrics Section on Breastfeeding. (2012). Breastfeeding and the use of human milk. Pediatrics, 129(3), e doi: /peds American College of Obstetricians and Gynecologists Committee on Obstetrc Practice. (2015). Committee Opinion No. 637: Marijuana Use During Pregnancy and Lactation. Obstet Gynecol, 126(1), doi: /01.aog a6 American College of Obstetricians Gynecologists Committee on Health Care for Underserved Women. (2011). AGOG Committee Opinion No. 473: substance abuse reporting and pregnancy: the role of the obstetrician-gynecologist. Obstet Gynecol, 117(1), doi: /aog.0b013e31820a6216 Reece-Stremtan, S., & Marinelli, K. A. (2015). ABM clinical protocol #21: guidelines for breastfeeding and substance use or substance use disorder, revised Breastfeed Med, 10(3), doi: /bfm Recent Literature Reviews and Systematic Reviews: 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. Obstetrics and gynecology. 2016;128(4): Gunn JK, Rosales CB, Center KE, et al. Prenatal exposure to cannabis and maternal and child health outcomes: a systematic review and meta-analysis. BMJ Open. 2016;6(4):e Jaques SC, Kingsbury A, Henshcke P, et al. Cannabis, the pregnant woman and her child: weeding out the myths. J Perinatol. 2014;34(6): Metz TD, Stickrath EH. Marijuana use in pregnancy and lactation: a review of the evidence. American journal of obstetrics and gynecology. 2015;213(6): Cannabis in Pregnancy, Reference List 1

53 Other peer-reviewed studies: Bailey, J. R., Cunny, H. C., Paule, M. G., & Slikker, W., Jr. (1987). Fetal disposition of delta 9- tetrahydrocannabinol (THC) during late pregnancy in the rhesus monkey. Toxicol Appl Pharmacol, 90(2), Brown, Q. L., Sarvet, A. L., Shmulewitz, D., Martins, S. S., Wall, M. M., & Hasin, D. S. (2016). Trends in Marijuana Use Among Pregnant and Nonpregnant Reproductive-Aged Women, JAMA. doi: /jama Chang, J. C., Holland, C. L., Tarr, J. A., Rubio, D., Rodriguez, K. L., Kraemer, K. L.,... Arnold, R. M. (2017). Perinatal Illicit Drug and Marijuana Use. Am J Health Promot, 31(1), doi: /ajhp qual-625 Devinsky, O., Cross, J. H., Laux, L., Marsh, E., Miller, I., Nabbout, R.,... Cannabidiol in Dravet Syndrome Study, G. (2017). Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med, 376(21), doi: /nejmoa El Marroun, H., Tiemeier, H., Steegers, E. A., Jaddoe, V. W., Hofman, A., Verhulst, F. C.,... Huizink, A. C. (2009). Intrauterine cannabis exposure affects fetal growth trajectories: the Generation R Study. J Am Acad Child Adolesc Psychiatry, 48(12), doi: /chi.0b013e3181bfa8ee Fried, P. A., & Smith, A. M. (2001). A literature review of the consequences of prenatal marihuana exposure. An emerging theme of a deficiency in aspects of executive function. Neurotoxicol Teratol, 23(1), Friedrich, J., Khatib, D., Parsa, K., Santopietro, A., & Gallicano, G. I. (2016). The grass isn't always greener: The effects of cannabis on embryological development. BMC Pharmacol Toxicol, 17(1), 45. doi: /s Goldschmidt, L., Richardson, G. A., Cornelius, M. D., & Day, N. L. (2004). Prenatal marijuana and alcohol exposure and academic achievement at age 10. Neurotoxicol Teratol, 26(4), doi: /j.ntt Goldschmidt, L., Richardson, G. A., Larkby, C., & Day, N. L. (2016). Early marijuana initiation: The link between prenatal marijuana exposure, early childhood behavior, and negative adult roles. Neurotoxicol Teratol, 58, doi: /j.ntt Hasin, D. S., Saha, T. D., Kerridge, B. T., Goldstein, R. B., Chou, S. P., Zhang, H.,... Grant, B. F. (2015). Prevalence of Marijuana Use Disorders in the United States Between and JAMA Psychiatry, 72(12), doi: /jamapsychiatry Hernandez-Avila, C. A., Rounsaville, B. J., & Kranzler, H. R. (2004). Opioid-, cannabis- and alcoholdependent women show more rapid progression to substance abuse treatment. Drug Alcohol Depend, 74(3), doi: /j.drugalcdep Holland, C. L., Nkumsah, M. A., Morrison, P., Tarr, J. A., Rubio, D., Rodriguez, K. L.,... Chang, J. C. (2016). "Anything above marijuana takes priority": Obstetric providers' attitudes and counseling strategies regarding perinatal marijuana use. Patient Educ Couns. doi: /j.pec Holland, C. L., Rubio, D., Rodriguez, K. L., Kraemer, K. L., Day, N., Arnold, R. M.,... Chang, J. C. (2016). Obstetric Health Care Providers' Counseling Responses to Pregnant Patient Disclosures of Marijuana Use. Obstet Gynecol, 127(4), doi: /aog Jarlenski, M., Barry, C. L., Gollust, S., Graves, A. J., Kennedy-Hendricks, A., & Kozhimannil, K. (2017). Polysubstance Use Among US Women of Reproductive Age Who Use Opioids for Nonmedical Reasons. Am J Public Health, e1-e3. doi: /ajph Jarlenski, M., Hogan, C., Bogen, D. L., Chang, J. C., Bodnar, L. M., & Van Nostrand, E. (2017). Characterization of U.S. State Laws Requiring Health Care Provider Reporting of Perinatal Substance Use. Womens Health Issues. doi: /j.whi Cannabis in Pregnancy, Reference List 2

54 Jarlenski, M., Zank, J., Tarr, J., & Chang, J. C. (2016). Public health messages about perinatal marijuana use in an evolving policy context. Subst Abus, 0. doi: / Khare, M., Taylor, A. H., Konje, J. C., & Bell, S. C. (2006). Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod, 12(5), doi: /molehr/gal036 Ko, J. Y., Farr, S. L., Tong, V. T., Creanga, A. A., & Callaghan, W. M. (2015). Prevalence and Patterns of Marijuana Use among Pregnant and Non-Pregnant Women of Reproductive Age. Am J Obstet Gynecol. doi: /j.ajog Mark, K., Desai, A., & Terplan, M. (2016). Marijuana use and pregnancy: prevalence, associated characteristics, and birth outcomes. Arch Womens Ment Health, 19(1), doi: /s Martin, C. E., Longinaker, N., Mark, K., Chisolm, M. S., & Terplan, M. (2014). Recent Trends in Treatment Admissions for Marijuana Use During Pregnancy. J Addict Med. doi: /adm Mehmedic, Z., Chandra, S., Slade, D., Denham, H., Foster, S., Patel, A. S.,... ElSohly, M. A. (2010). Potency trends of Delta9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to J Forensic Sci, 55(5), doi: /j x Metz, T. D., & Stickrath, E. H. (2015). Marijuana use in pregnancy and lactation: a review of the evidence. Am J Obstet Gynecol, 213(6), doi: /j.ajog Richardson, G. A., Day, N. L., & Goldschmidt, L. (1995). Prenatal alcohol, marijuana, and tobacco use: infant mental and motor development. Neurotoxicol Teratol, 17(4), Volkow, N. D., Compton, W. M., & Wargo, E. M. (2016). The Risks of Marijuana Use During Pregnancy. JAMA. doi: /jama Volkow, N. D., Han, B., Compton, W. M., & Blanco, C. (2017). Marijuana Use During Stages of Pregnancy in the United States. Ann Intern Med, 166(10), doi: /l Wu, C. S., Jew, C. P., & Lu, H. C. (2011). Lasting impacts of prenatal cannabis exposure and the role of endogenous cannabinoids in the developing brain. Future Neurol, 6(4), Cannabis in Pregnancy, Reference List 3