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Volume 68, Number 10 OBSTETRICAL AND GYNECOLOGICAL SURVEY Copyright * 2013 by Lippincott Williams & Wilkins
CHIEF EDITOR’S NOTE: This article is part of a series of continuing education activities in this Journal through which a total of 36 AMA PRA Category 1 CreditsTM can be earned in 2013. Instructions for how CME credits can be earned appear on the last page of the Table of Contents.
Pregnancy, Breast-feeding, and Marijuana: A Review Article Meg Hill, MBBS,* and Kathryn Reed, MD† *Fellow, Maternal Fetal Medicine, and †Professor and Head, Department of Obstetrics and Gynecology, The University of Arizona, Tucson, AZ Marijuana is a commonly used drug. At present, it remains an illegal substance in most areas of the United States. Recent controversy regarding the perceived harms of this drug has resulted in debate in both legal and medical circles. This review examines evidence regarding the effects of marijuana exposure during pregnancy and breast-feeding. We examined studies pertaining to fetal growth, pregnancy outcomes, neonatal findings, and continued development of fetuses and neonates exposed to marijuana through adolescence. In addition, the legal implications for women using marijuana in pregnancy are discussed with recommendations for the care of these patients. The current evidence suggests subtle effects of heavy marijuana use on developmental outcomes of children. However, these effects are not sufficient to warrant concerns above those associated with tobacco use. Marijuana is the most commonly used illicit substance in the United States. It is predominantly used for its pleasurable physical and psychotropic effects. With the recent changes to legislature in Colorado and Washington State making the recreational use of marijuana legal, marijuana has gained national attention. This raises the question: If it is legal for a woman to consume marijuana, what is the safety of this activity in pregnancy and breast-feeding? Moreover, do the harms of marijuana use on the fetus or infant justify the mandatory reporting laws in some states? Target Audience: Obstetricians and gynecologists, family physicians Learning Objectives: After completing this CME activity, physicians should be better able to assess the prevalence of marijuana use in the general obstetric population, evaluate the fetal, neonatal and childhood outcomes associated with marijuana use during pregnancy and breastfeeding, and care for pregnant women who are faced with the possible legal implications of screening for drug use.
Cannabis the Drug Cannabis sativa is grown in many temperate climates.1 Historically, the plant has been used for its fiber in the fabric industry.1,2 However, the sap from the plant, which the plant produces in copious All authors and staff in a position to control the content of this CME activity and their spouses/life partners (if any) have disclosed that they have no financial relationships with, or financial interests in, any commercial organizations pertaining to this educational activity. Correspondence requests to: Meg Hill, MBBS, Department of Obstetrics and Gynecology, The University of Arizona, 1501 N Campbell Ave, 8th Floor Tucson, AZ 85724. E-mail: meghanhill@ obgyn.arizona.edu.
amounts in hot climates, can be made into hashish.3 The foliage produced can be smoked or cooked and ingested.3 In the United States, the most common form of ingestion is via smoke inhalation either through rolled cigarettes referred to as joints or through glass or plastic containers used to concentrate the drug for delivery.3 Although farming of the C. sativa plant is either discouraged or illegal in most of the United States, the plant is commonly found growing in other regions of the world. Testing of human subjects in Asia where the plant is encountered shows that Delta 9 Tetrahydrocannabinol (THC) is found in human urine after ingestion of milk from buffalo that have been feeding
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on the plants.4 This exposure of humans to the plant dates back thousands of years. Many cultures have commonplace uses for the plant in regions where marijuana has been a part of the local culture for generations.5 Incidence of Use Marijuana is commonly used by pregnant women in the United States.6 However, it is not a legal drug in the majority of states in America. It can be smoked or consumed in the form of liquid or solid preparations.3 Studies regarding marijuana use in pregnancy and during lactation can be confounded by recall and reporting bias as well as the differing baseline characteristics of those who use and abstain from marijuana use. Rates of use are higher in younger cohorts, with the rates of usage decreasing as women age.7Y9 Women do use marijuana during their fertile years.8 Cannabis users are also more likely to be nonHispanic black and be having their first child and are less likely to have used folic acid supplementation during their pregnancy.9 There is evidence to suggest that patients in urban areas, from lower socioeconomic status groups, and from single-parent households have higher rates of use.7,9Y11 Four percent of doctors self-reported marijuana use in California recently, indicating that marijuana use is not limited to these groups and is simply more often utilized among them.12 Use in Pregnancy Pregnant women use marijuana at a higher rate during the first trimester, with many reporting a cessation of use or decreased use by the third trimester.11 Many women report use of the drug in the months preceding a pregnancy with cessation on discovery of the pregnancy, often in the first or early second trimester.11 Physiologic and Psychological Effects of Marijuana The pleasurable effects of marijuana are usually described as a feeling of elation or amusement. This is followed by a sense of calm, an increase in appetite, and relaxation. Medicinal marijuana is frequently used in adjunctive treatments for AIDS and cancer patients. Animal studies reflect various effects on appetite and food intake when the endocannabinoid system is manipulated.13Y15 Negative experiences have been reported, including palpitations, anxiety, and sedation. Rare complications can occur such
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as cannabinoid hyperemesis syndrome, which occurs only with long-term, heavy use of the drug.16,17 The syndrome is alleviated by abstinence.16,17 Long-term effects of marijuana can be assessed in both current and previous users. Current, heavy users do have a decreased cognitive ability, spatial reasoning, and decision making. This reflects acute intoxication.18 Some studies show a persistence of these effects in abstinent heavy users for several weeks to months after use.18,19 These effects dissipate with time, and no consistent effects can be demonstrated in most studies after a period of months to years.18,19 Use of marijuana in young people has been associated with anxiety and depression.20,21 It is unclear whether this is related to the demographic reporting heavy use or to the substance itself. Some evidence suggests that heavy marijuana use in the teen years can be related to schizophrenia in later life.22 Whether this is due the drug or whether the drug is used as a form of self-medication in these patients is unclear. Effects in Women Hormones of women have been studied while they inhale marijuana at both the follicular and luteal phase of the menstrual cycle.23 In a placebo-controlled, crossover trial, women who smoked marijuana during the luteal phase of the menstrual cycle had a depression of prolactin levels, whereas those inhaling a placebo did not.23 Similar effects were not seen during the follicular phase of the menstrual cycle.23 This effect has not been investigated in lactating women and cannot be extrapolated to this population. The Pregnant Patient General Approach to Pregnant Women Using Illicit Substances Before initiating a discussion or performing a screening drug test on a pregnant woman, the provider should be aware of the reporting laws in the state in which they practice. Women should be made aware of any mandatory reporting laws that exist in the state in which they reside. Likewise, they should refuse screening if they wish without undue pressure from their provider.24 Some states have punitive laws in place that can result in imprisonment or loss of custody for women using drugs.24Y26 These laws have consistently been found to decrease compliance with prenatal care and increase the perinatal mortality rate.25,27 They cast doctors in an adversarial position with the patient and create a dynamic of distrust.25 Doctors should use their best judgment in
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documenting drug use in their patients and should do so only with the understanding of the patient.24 Creating a disclosure in the chart without the patient’s knowledge may undermine the doctor-patient relationship when evidence of this surfaces later, especially if the disclosure is based on the physician’s interpretation or assumptions and not on the facts related by the patient.24 The states that currently have laws enabling criminal charges for child abuse to be brought against a woman for use of drugs while pregnant are Arkansas, Colorado, Florida, Illinois, Indiana, Iowa, Louisiana, Minnesota, Nevada, Oklahoma, Rhode Island, South Carolina, South Dakota, Tennessee, Texas, Virginia, and Wisconsin.28 Involuntary commitment to a drug treatment program can be instituted for use of drugs while pregnant in Minnesota, South Dakota, and Wisconsin.28 Interestingly Arizona, Georgia, Kansas, Maryland, Missouri, Oklahoma, Tennessee, Texas, Utah and Wisconsin are the only states that have expedited drug treatment available for pregnant women.28 This punitive approach creates a climate in which women are afraid to seek care.25,27 Considering the measures in place to make women subject to charges of child endangerment without realistic hope of treatment in many states as well as legal precedent including arrest and prolonged incarceration in South Carolina, it is not surprising that many women are not forthcoming regarding drug use during pregnancy.28 The approach to the pregnant patient who discloses illicit drug use should be impartial and focus on the health and well-being of both the woman and fetus. Type, amount, and frequency of the drug used should be ascertained through either a thorough face-to-face history or through a screening tool. Providers should be aware that the context in which they view drug use during pregnancy may not be the same as that of the patient. Although marijuana use has historically been considered an unacceptable behavior, the beliefs of the general public and policy makers in some states do not reflect this view. The provider should be aware that many women view marijuana as a harmless substance that is not associated with significant negative effects. If the patient sees no detriment from the use of the drug, she is unlikely to stop, and the provider’s opinion regarding cessation of use may not be a powerful motivator to the patient. Providers should also recognize that patients may choose to wean marijuana use during pregnancy and increase their use again following delivery.29 Women should be asked if they feel that their use is ‘‘out of their control’’ or if they are experiencing negative life effects because of marijuana use. These
patients fall into a group that should be offered additional counseling and referral to a substance abuse program as would be offered with other legal drugs that can be abused, such as alcohol. Levels Transferred via the Placenta and Breast Milk Marijuana enters the bloodstream within seconds and the brain within minutes when inhaled.30 A longer time generally elapses before effects when marijuana is ingested orally. It is a highly lipophilic substance and hence can be bound to fat stores throughout the body,31 with a tissue half-life of 7 days.30 The active drug is metabolized by the liver.30,31 It is not unusual for heavy chronic users (defined in most studies as 95 joints smoked per week) to have urine toxicology screens that are intermittently positive for several months after their last use. Complete elimination after a single exposure to the drug may take a month.30 Light users have the substance detected in their urine for days to weeks after use. Placental transfer to the fetus does occur,30,32 and this results in detectable cord blood levels of the drug.32 Levels detected in the cord blood indicate that the fetus receives a proportionately smaller dose than does the mother.32 Neonates have tested positive for marijuana in urine.33 Analysis of breast milk reveals the presence of marijuana in recent users,33 where it is bound to proteins.34 However, seeing that the concentration of protein in breast milk is less than 1%,34 the transfer of the drug is likely commensurate to this protein level. One study calculated exposure to the neonate to be 0.8% that of the mother’s exposure.31 Effects of Use on Fetal Outcomes There are few studies that assess the isolated effects of marijuana on the developing fetus. The confounding introduced by polydrug use makes interpretation difficult.35Y39 The most common concurrently used drugs are cigarettes, alcohol, and cocaine.35,36,39 Tobacco is an important confounder as the use of tobacco is highly associated with the use of marijuana in most studies, and tobacco by itself is associated with effects on growth.38,40 Studies have reported varying associations including growth restriction, shortening of gestation, and neonatal withdrawal symptoms.37,38,40Y42 Another study reported on altered mRNA expression in the fetal brain.43 These findings have not been reproduced in well-designed, rigorously performed studies. In addition, marijuana is not associated with birth defects in humans.44 One cohort of 756 pregnant women was followed up in Colorado.32 Subjects were approached for
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information on drug use in pregnancy. When asked, 34% affirmed that they had used marijuana during pregnancy. When controlling for cigarette use, there were no detrimental effects noted on fetal growth or fetal neurodevelopmental outcomes when infants were examined at 24 to 72 hours after birth. There were also no differences in length or growth when adjusting for cigarette use, nor was there an increase in anomalies. The mothers who used marijuana had a statistically significant higher weight gain during pregnancy in this cohort.32 Interestingly, this study did report a statistically significant increased rate of male births in marijuana users. This effect has been noted in trends in other studies and may be related to the effects of marijuana on sperm.40,39 Many of the women using marijuana had male partners who also used marijuana. When the Colorado cohort was followed up at 1 year of age, 62 of the infants were reported to have been breast-fed. Again, differences were not found between groups. In addition, there was no difference in age at weaning, suggesting that marijuana was not detrimental to the suckling behavior of infants or the maternal production of milk.32 A second cohort of women in Jamaica were followed up during pregnancy and after their deliveries.45 In the cultural context of the region, marijuana is seen as a medicinal substance. Most women smoked or drank tea with marijuana contained in it.45 Following birth, 24 babies of subjects using marijuana and 20 babies of women abstaining from use were examined. Neonatal outcomes were equivalent in the first week after delivery in this cohort. At follow-up 30 days after delivery, no detrimental effects of marijuana use were documented.45 The women who were habitual marijuana users rated their experience of motherhood as more fulfilling than those who were not. These children were again examined at age 5 years, and no deleterious effects were noted.46 Confounders in this study were the different economic statuses between groups, with the marijuana users on average having a larger amount of control over the household income.45 The MHPCD (Maternal Health Practices and Child Development Study)47 and OPPS (Ottawa Prenatal Prospective Study) were large prospective cohort studies carried out in Pittsburg and Ottawa, respectively. These studies aimed to include as many pregnant women as possible and assess drug use and effects of different ingested substances on pregnancy and childhood outcomes. They relied on maternal reports of marijuana use both during and after pregnancy. The MHPCD study was carried out in a higher-risk,
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lower-socioeconomic-status group of women than the OPPS cohort of women. These studies did not find an association between marijuana use in pregnancy and immediate pregnancy outcomes such as miscarriage rates, rates of anomalies, mode of delivery, Apgar scores, or meconium-stained fluid.8 Fried,39 an author particularly interested in the effects of marijuana on offspring, was involved in the OPPS cohort. However, before completing this work, he originally published a study claiming that marijuana causes a neonatal abstinence syndrome, not unlike that of narcotic withdrawal, which results in neonates exhibiting high-pitched cries and startles and poor visual habituation, which resolved within a few days of birth.39,41 This study relied on maternal report of marijuana use, and there was no mention of testing for use of additional drugs such as heroin or prescription narcotics. In both of the studies from Jamaica and Colorado, the cohorts were specifically examined for these same signs and symptoms in neonates of mothers who used marijuana. These findings could not be reproduced, with no apparent withdrawal effects in neonates. This seems congruent with the adult response to marijuana, which does not seem to cause a significant withdrawal phenomenon. Effects of Use on Childhood Outcomes The MHPCD and OPPS cohorts of children were reexamined regularly during their childhood.36,47Y49 A battery of psychological tests was carried out on these children addressing broad areas such as global intelligence quotient and specific neurologic functions pertaining to auditory processing, spatial reasoning, and accuracy. The problems encountered in these cohorts were the small numbers of ‘‘heavy’’ marijuana users and the confounding introduced by the social determinants of health and use of other drugs concurrently with marijuana.36,48 Neither study demonstrated a convincing difference in global IQ of offspring at any age when taking light or moderate use into account.49 Many associations that were statistically significant ceased to be so when confounding factors were adjusted for.36,48 Subtle effects were suggested in the ability of children to comprehend language at age 2 years. However, after adjustments were made for other determinants of outcomes such as specific aspects of the home environment, this finding did not persist.49 At this age, the children of moderate users actually performed better at motor tasks.50 Some testing showed decreased ability of children to analyze visual stimuli.49 This area requires more study as effects noted in these studies were subtle. These studies also noted
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differences in functioning in children exposed to prenatal cigarette smoking as it related to visual analytic function.49 The findings were in a different facet of function but did nonetheless confound the findings related to marijuana, as in North America, marijuana is generally mixed with tobacco and then smoked. Heavy use of marijuana (95 joints per week) during pregnancy was associated with an increase in omission errors in offspring, highlighting the fact that significant use may be required to produce a cognitive effect.49 Additional findings were that teachers rated children of marijuana users as more impulsive, and parents rated the children as being less attentive. Interpretation of this finding is difficult because marijuana users had a lower average income, were more likely to be single parents, and were more likely to use both alcohol and cigarettes.47,49 The context of this use was also in locations were marijuana is illegal and associated with risk to the parents of these children should they be found to be using marijuana, which could in turn affect the home environment. When growth trajectories were assessed in the OPPS cohort, the infants prenatally exposed to marijuana did not have an altered growth pattern when compared with control subjects after adjusting for confounding variables.51 There was a smaller head circumference noted in children of mothers who used marijuana while pregnant at age 12 years. However, this finding is based on 19 children of ‘‘heavy’’ users compared with 93 control subjects and 23 ‘‘light’’ users.51 This finding again ceased to be statistically significant by midadolescence.8 The Jamaican cohort was also followed to age 5 years with no differences in children of mothers who continued to use marijuana to those who never used the substance. The Colorado cohort did not show any deleterious effects of marijuana use through pregnancy and breast-feeding, although this cohort was not followed up past 12 months of age. One report focused on the effect of prenatal marijuana exposure on the incidence of childhood leukemia.52 There was an increase in this disease in exposed offspring. However, they also noted an increase in leukemia in offspring of pregnancies treated with antinausea medication. The authors supplant that the use of pesticides on the marijuana inhaled by study subjects may have been related to the increased risk of leukemia.52 Certainly, recall bias is also a consideration in this retrospective cohort. Effects on Adolescent Outcomes The OPPS and MHPCD cohorts were followed by researchers from infancy into late childhood, and
Fried et al53Y55 continued to publish the findings of research with the OPPS cohort into the children’s teens. The findings from the OPPS cohort suggested that growth and specifically head circumference were not statistically significantly different between groups: nonusers, light, moderate, and heavy users throughout early childhood. However, at follow-up at age 12 years, the difference in head circumference reached statistical significance for the maternal ‘‘heavy marijuana use’’ group. This could reflect a true causeand-effect relationship, or it could reflect the higher levels of alcohol and tobacco use in women who admitted to heavy use of marijuana.11 In addition, the number of patients followed up was small, only 20 and 19 in the moderate and heavy use groups, respectively. Another study assessed the adolescent brain with the utilization of magnetic resonance imaging. Findings suggested that as the mother accrued illicit substance use in pregnancy, the brain volume of the offspring was found to be decreased in adolescence. However, this study focused on cocaine use with or without concomitant use of other drugs, including marijuana.56 On cognitive testing, the OPPS and MHPCD cohorts were found to have differences noted in early adolescence. Executive function seemed affected with omission errors more common in the group of children with heavy exposure to maternal marijuana.54 IQ was not affected, however.53 This is in stark contrast to the findings in the same study of a comparison group: the children of cigarette smokers. The children of heavy tobacco smokers had more prominent effects, including differences in perception and statistically significant lower global intelligence scores.53 Effects of Marijuana During Breast-feeding There is inadequate evidence to make a statement about the isolated use of marijuana in breast-feeding mothers. The studies that address this issue are confounded by the fact that few women have isolated use during breast-feeding in the absence of additional prenatal use of marijuana. The OPPS, MHPCD, and Jamaican and Colorado cohorts followed up women and children exposed to marijuana in pregnancy and breast milk, with the results discussed above. Several articles have been published outlining the risks of marijuana and breast-feeding and defining use as a contraindication to breast-feeding. The concern is that marijuana causes an immediate threat to the health and safety of the child either through sedation of the child if breast-fed while the mother is using marijuana or through negligent behavior by the
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mother who uses marijuana.57,58 It should be noted that these articles are based on opinion and not on any scientific evidence. An extensive literature review was unable to yield a single case report of a neonatal death from exposure to marijuana. One study did find an effect of marijuana on isolated motor, but not mental, development at age 1 year in infants exposed during breast-feeding. The 10 infants in this cohort exposed only prenatally did not have any motor deficits when compared with control subjects. This study was confounded by socioeconomic factors and included only 14 women who were using marijuana while breast-feeding but not while pregnant.59 Cigarette smoking can be used as a surrogate for marijuana smoking in some respects, although there is an association with maternal cigarette smoking and sudden infant death syndrome, where one does not exist for maternal marijuana use.60,61 A concerning feature of advising women to ‘‘protect’’ their child by not breast-feeding is the continued environmental exposure to marijuana and tobacco smoke in the home without the protective effects of breast-feeding. There is evidence that women who use recreational drugs are less likely to breast-feed,10 although this has not been seen in all cohorts, with women in the OPPS with little effect of marijuana on the method or duration of breast-feeding.51 It may be that women are reliant on the advice of physicians, nurses, and lactation consultants to guide their decisions regarding method of feeding for their infants. These conflicting results may reflect different comfort levels with breast-feeding in the setting of marijuana use. Several publications have recommended that patients not smoke tobacco while they are pregnant or breast-feeding.60,62Y64 The basis for this is evidence that cotinine and nicotine (contained in cigarette smoke) can be detected in breast milk and in the urine of newborn babies who breast-feed from mothers who smoke.65,66 Bottle-fed children of mothers who smoke also have cotinine detected in their urine.65 However, if patients do smoke tobacco, it is recommended that they should continue to provide the protection of breast-feeding to their children because of the multiple health benefits to the child.60,64,67 The benefits of breast-feeding mitigate some of the risks associated with neonatal exposure to passive cigarette smoke, such as sudden infant death syndrome, ear infections, abnormal weight gain, and hospitalization for bacterial and viral infections.60,64,67 If a mother chooses to use marijuana, it may be advisable for her to breast-feed to mitigate some of the effects of passive smoke exposure. This becomes especially important advice in the setting of escalating use, as there is
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evidence that tapered use tends to increase again after delivery.7,29 It is prudent to advise women that if they choose to smoke marijuana; they do so away from their children (preferably outside the house) and change their clothing after use, so as to not expose their children to smoke particles in clothing. This advice is in line with what is recommended to mothers who smoke tobacco. There is no adequate evidence to address whether orally ingesting marijuana may be safer for the neonate, although this would certainly eliminate the concern regarding inhalation of smoke particles. Legal Implications Mandatory reporting of drug use in pregnancy is a reality that persists in many states. The American College of Obstetricians and Gynecologists has made it clear that women should not be tested without their consent and that punitive measures dissuade patients from prenatal care and actually increase perinatal mortality.27 Women have been prosecuted for the use of marijuana and other illicit substances.8,26,27 The treatment of a woman as a child abuser in this circumstance reduces her status to that of a carrier, existing only to house the fetus without the right to make her own decisions as an entity with separate rights.27 Physicians should be cognizant of the laws in their state of practice and consider the screening methods used in their institutions. Common indications for drug testing in pregnant women are preterm labor, hypertension in pregnancy, and placental abruption. Marijuana use has not been associated with any of these complications in the large cohorts discussed in this article; hence, the indication for toxicology for THC is not indicated in this setting. It may be wise to omit THC testing in the setting of medical complications and restrict testing to cocaine and methamphetamine if symptoms suggest their use, as these drugs can be associated with pregnancy complications such as placental abruption and acute hypertensive episodes. Many physicians order this test without the patient’s knowledge in the setting of poor compliance with prenatal care. These patients are often in disadvantaged economic groups and are more frequently African American patients.25 Indeed, the disproportionate pursuit of legal action against African American patients for drug use has been noted.26 As previously discussed, testing patients for drug use without their knowledge, consent, or medical indication only serves to strain the physician-patient relationship and dissuade the patient from prenatal care.25,27
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In the newborn period, positive toxicology may also present challenges in the new family when there are differing opinions as to whether marijuana is contraindicated in breast-feeding. Other substances found in breast milk with moderate use such as cotinine, caffeine, and alcohol are generally not seen as a contraindication to breast-feeding.68 However, marijuana is more controversial, probably because it remains an illicit substance in most states. For this reason, the author suggests that physicians consider whether screening for marijuana use is indicated in the setting in which they practice. If a positive screen is present in a mother who wishes to breast-feed, she should be made aware that there is no consistent evidence of severe, ill effects with marijuana and breast-feeding, but that long-term neurodevelopmental outcomes are not fully investigated, and there may be an association with harm in women who smoke 5 or more joints per week both while pregnant and during breast-feeding. The best advice is to abstain from marijuana completely seeing that it seems to have similar effects to cigarettes, but that breastfeeding is an option. Least preferable is continuation of marijuana use in conjunction with bottle-feeding. This results in passive smoke exposure without the benefits of breast milk. As mentioned above, the effects of heavy tobacco use are more striking than those of marijuana use, and tobacco remains a legal drug. SUMMARY Marijuana may be inhaled or ingested and is primarily used by pregnant women for recreational purposes, although it does have medicinal properties. Marijuana does cross the placenta and can be detected in newborn infants. It can also be detected in breast milk after recent maternal use. Although some studies report specific effects of marijuana on the developing brain of the fetus and neonate, these effects are not reproducible. Heavy marijuana smokers do have babies who are smaller than those of nonusers. This finding is confounded by the concurrent use of cigarettes and other illicit substances in most studies reporting this effect and consistent with the evidence that heavy tobacco use also results in a lower average birth weight. Patients should be cautioned that inhaled marijuana may have effects on fetal growth similar to those of cigarette use. Neurodevelopmental outcomes seem similar between babies of nonusers and users with no resultant effects on global intelligence quotient. There may be some effects on visuoperceptual ability, reasoning and attention noted in older children. These findings have been
reproduced in 2 large cohorts, and the association was statistically significant only with prolonged, heavy maternal use (95 joints per week throughout pregnancy and breast-feeding). If these effects do exist with light, moderate, or sporadic use, they are sufficiently subtle as to not be consistently demonstrated between studies. The effects of marijuana on the developing fetus and child are subtly different from, but not evidenced to be more severe than, those of heavy cigarette consumption by the mother during pregnancy and early childhood. Based on these findings, mandatory reporting of marijuana use during pregnancy and punitive measures related to the use of this drug during pregnancy or breast-feeding do not seem medically warranted. A consistent message of ‘‘breast is best’’ seems appropriate for mothers who continue to use marijuana while breast-feeding.
REFERENCES 1. Rawson JM. Hemp as an Agricultural Commodity, 2011. Congressional Research Service, The Library of Congress: Diane Publishing; 2011. 2. Ranalli P, Venturi G. Hemp as a raw material for industrial applications. Euphytica. 2004;140:1Y6. 3. NIH, DrugFacts. Available at: http://www.drugabuse.gov/ publications/drugfacts/marijuana. Accessed June 2013. 4. Ahmad GR, Ahmad N. Passive consumption of marijuana through milk: a low level chronic exposure to delta-9tetrahydrocannabinol. Clin Toxicol. 1990;28:255Y260. 5. Morningstar PJ. Thandai and chilam: traditional Hindu beliefs about the proper uses of Cannabis. J Psychoactive Drugs. 1985;17:141Y165. 6. Jutras-Aswad D, DiNieri JA, Harkany T, et al. Neurobiological consequences of maternal Cannabis on human fetal development and its neuropsychiatric outcome. Eur Arch Psychiatry Clin Neurosci. 2009;259:395Y412. 7. Fried PA. Prenatal exposure to marihuana and tobacco during infancy, early and middle childhood: effects and an attempt at synthesis. Arch Toxicol Suppl. 1995;17:233Y260. 8. Fried PA. Cannabis use during pregnancy: its effects on offspring from birth to young adulthood. In: Preece PM, Riley EP, eds. Alcohol, Drugs and Medication in Pregnancy: The Long Term Outcome for the Child. London: Mac Keith Press; 2011:P153YP168. 9. van Gelder MMHJ, Reefhuis J, Caton AR, et al. Characteristics of pregnant illicit drug users and associations between Cannabis use and perinatal outcome in a population-based study. Drug Alcohol Depend. 2010;109:243Y247. 10. Goel N, Beasley D, Rajkumar V, et al. Perinatal outcome of illicit substance use in pregnancy Y comparative and contemporary socio-clinical profile in the UK. Eur J Pediatr. 2011;170:199Y205. 11. Fried PA, Watkinson B, Grant A, et al. Changing patterns of soft drug use prior to and during pregnancy: a prospective study. Drug Alcohol Depend. 1980;6:323Y343. 12. Bazargan M, Makar M, Bazargan-Hejazi S, et al. Preventive, lifestyle, and personal health behaviors among physicians. Acad Psychiatry. 2009;33:289Y295. 13. Fride E, Bregman T, Kirkham TC. Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood. Exp Biol Med. 2005;230:225Y234.
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Pregnancy, Breast-feeding, Marijuana 14. Fride E. Review article: multiple roles for the endocannabinoid system during the earliest stages of life: pre- and postnatal development. J Neuroendocrinol. 2008;20(suppl 1):75Y81. 15. Fride E, Foox A, Rosenberg E, et al. Milk intake and survival in newborn cannabinoid CB1 receptor knockout mice: evidence for a ‘‘CB3’’ receptor. Eur J Pharmacol. 2003;461:27Y34. 16. Price SL, Fisher C, Kumar R, et al. Cannabinoid hyperemesis syndrome as the underlying cause of intractable nausea and vomiting. JAOA. 2011;111:166Y169. 17. Budhraja V, Narang T, Azeez S. Cannabinoid hyperemesis syndrome: cyclic vomiting, chronic Cannabis use, and compulsive bathing. Pract Gastroenterol. 2008;32:79Y80. 18. Gonzalez R. Acute and non-acute effects of Cannabis on brain functioning and neuropsychological performance. Neuropsychol Rev. 2007;17:347Y361. 19. Fried PA, Watkinson B, Gray R. Neurocognitive consequences of marihuanaVa comparison with pre-drug performance. Neurotoxicol Teratol. 2005;27:231Y239. 20. Patton GC, Coffey C, Carlin JB, et al. Cannabis use and mental health in young people: cohort study. BMJ. 2002;325: 1195Y1198. 21. Bovasso GB. Cannabis abuse as a risk factor for depressive symptoms. Am J Psychiatry. 2001;158:2033Y2037. 22. Zammit S, Allebeck P, Andreasson S, et al. Self reported Cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ. 2002;325:1199. 23. Mendelson JH, Mello NK, Ellingboe J. Acute effects of marijuana smoking on prolactin levels in human females. J Pharmacol Exp Ther. 1985;232:220Y222. 24. At-risk drinking and illicit drug use: ethical issues in obstetric and gynecologic practice, ACOG committee opinion no. 422. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2008;112:1449Y1460. 25. Substance abuse reporting and pregnancy: the role of the obstetrician-gynecologist, ACOG Committee opinion no. 473. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2011;117:200Y201. 26. Ferguson v City of Charleston: Social and Legal Contexts, e-reference, Available at: http://www.aclu.org/reproductivefreedom/ferguson-v-city-charleston-social-and-legal-contexts. Accessed June 2013. 27. Maternal decision making, ethics and the law, ACOG committee opinion no. 321, American College of Obstetricians and Gynecologists. Obstet Gynecol. 2005;106:1127Y1137. 28. Guttmacher Institute, Substance abuse during pregnancy State Policies in Brief, New York (NY). Available at: http://www. guttmacher.org/statecenter.spibs/spib_SADP.pdf. Accessed September 2013. 29. Bartu A, Sharp J, Ludlow J, et al. Postnatal home visiting for illicit drug-using mothers and their infants: a 21andomized controlled trial. Aust N Z J Obstet Gynaecol. 2006;46:419Y426. 30. Brown HL, Graves CR. Smoking and marijuana use in pregnancy. Clin Obstet Gynecol. 2013;56:107Y113. 31. Djulus J, Moretti M, Koren G. Marijuana use and breastfeeding. Can Fam Phys. 2005;51:349Y350. 32. Tennes K, Avitable N, Blackard C, et al. Marijuana: prenatal and postnatal exposure in the human. NIDA Res Monogr Ser. 1985;59:48Y60. 33. Alapiti S, Hale TW. Effects of marijuana on the fetus and breastfeeding infants. September 18, 2012. Available at: http://www.infantrisk.com/content/effects-marijuana-fetus-andbreastfeeding-infants. Accessed June 2013. 34. D’Apolito K. Breastfeeding and substance abuse. Clin Obstet Gynecol. 2013;56:202Y211. 35. Noland JS, Singer LT, Short EJ, et al. Prenatal drug exposure and selective attention in preschoolers. Neuortoxicol Teratol. 2005;27:429Y438.
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36. Goldschmidt L, Richardson GA, Willford J, et al. Prenatal marijuana exposure and intelligence test performance at age 6. J Am Acad Child Adolesc Psychiatry. 2008;47:254Y263. 37. Kline J, Stein Z, Hutzler M. Cigarettes, alcohol and marijuana: varying associations with birthweight. Int J Epidemiol. 1987; 16:44Y51. 38. Hurd YL, Wang X, Anderson V, et al. Marijuana impairs growth in mid-gestation fetuses. Neurotoxicol Teratol. 2005;27:221Y229. 39. Fried PA. Marijuana use by pregnant women and effects on offspring: an update. Neurobehav Toxicol Teratol. 1982;4: 451Y454. 40. El Marroun H, Tiemeier H, Steegers EAP, et al. Intrauterine Cannabis exposure affects fetal growth trajectories: the generation R study. J Am Acad Child Adolesc Psychiatry. 2009; 48:1173Y1181. 41. Fried PA, Makin JE. Neonatal behavioural correlates of prenatal exposure to marijuana, cigarettes and alcohol in a low risk population. Neurotoxicol Teratol. 1987;9:1Y7. 42. Zuckerman B, Frank DA, Hingson R, et al. Effects of maternal marijuana and cocaine use on fetal growth. N Engl J Med. 1989;320:762Y768. 43. Wang X, Dow-Edwards D, Anderson V, et al. In utero marijuana exposure associated with abnormal amygdala dopamine D2 gene expression in the human fetus. Biol Psychiatry. 2004;56: 909Y915. 44. Behnke M, Eyler FD. The consequences of prenatal substance use for the developing fetus. Newborn Young Child. 1993;28: 1341Y1391. 45. Dreher MC, Nugent K, Hudgins R. Prenatal marijuana exposure and neonatal outcomes in Jamaica: an ethnographic study. Pediatrics. 1994;93:254Y260. 46. Hayes JS, Lampart R, Dreher MC, et al. Five-year follow-up of rural Jamaican children whose mothers used marijuana during pregnancy. W I Med J. 1991;40:120Y123. 47. Day NL, Richardson GA, Geva D, et al. Alcohol, marijuana, and tobacco: effects of prenatal exposure on offspring growth and morphology at age six. Alcohol Clin Exp Res. 1994;18:786Y794. 48. Goldschmidt L, Richardson GA, Cornelius MD, et al. Prenatal marijuana and alcohol exposure and academic achievement at age 10. Neurotoxicol Teratol. 2004;26:521Y532. 49. Fried PA, Smith AM. A literature review of the consequences of prenatal marijuana exposure. An emerging theme of a deficiency in aspects of executive function. Neurotoxicol Teratol. 2001;23:1Y11. 50. Fried PA, Watkinson B. 36- And 48-month neurobehavioral follow-up of children prenatally exposed to marijuana, cigarettes, and alcohol. J DEV Behav Pediatr. 1990;11:49Y58. 51. Fried PA, Watkinson B, Gray R. Growth from birth to early adolescence in offspring prenatally exposed to cigarettes and marijuana. Neurotoxicol Teratol. 1999;21:513Y525. 52. Robison LL, Buckley JD, Daigle AE, et al. Maternal drug use and risk of childhood nonlymphoblastic leukemia among offspring. Cancer. 1989;63:1904Y1911. 53. Fried PA, Watkinson B, Gray R. Differential effects on cognitive functioning in 9- to 12- year olds prenatally exposed to cigarettes and marihuana. Neurotoxicol Teratol. 1998;20: 293Y306. 54. Fried PA, Watkinson B. Differential effects on facets of attention in adolescents prenatally exposed to cigarettes and marihuana. Neurotoxicol Teratol. 2001;23:421Y430. 55. Fried PA, Watkinson B. 12 And 24 month neurobehavioural follow-up of children prenatally exposed to marihuana cigarettes and alcohol. Neurotoxicol Teratol. 1988;10:305Y313. 56. Rivkin MJ, Davis PE, Lemaster JL, et al. Volumetric MRI study of brain in children with intrauterine exposure to cocaine, alcohol, tobacco and marijuana. Pediatrics. 2008;121: 741Y750. 57. Liston J. Breastfeeding and the use of recreational drugsV alcohol, caffeine, nicotine and marijuana. Breastfeed Review. 1998;6:27Y30.
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58. Garry A, Rigourd V, Amirouche A, et al. Review article: Cannabis and breastfeeding. J Toxicol. 2009;1Y5. 59. Astley SJ, Little RE. Maternal marijuana use during lactation and infant development at one year. Neurotoxicol Teratol. 1990;12:161Y168. 60. Hauck FR, Thompson JMD, Tanabe KO, et al. Breastfeeding and reduced risk of sudden infant death syndrome: a metaanalysis. Pediatrics. 2011;128:1Y8. 61. Klonoff-Cohen H, Lam-Kruglick P. Maternal and paternal recreational drug use and sudden infant death syndrome. Arch Pediatr Adolesc Med. 2001;155:765Y770. 62. Schoendorf KC, Kiely JL. Relationship of sudden infant death syndrome to maternal smoking during and after pregnancy. Pediatrics. 1992;90:905Y908. 63. Breastfeeding and smoking: Australian Breastfeeding Association. Available at: https://www.breastfeeding.asn.au/bfinfo/ breastfeeding-and-smoking. Accessed June 2013. 64. Dorea JG. Maternal Smoking and Infant Feeding: Breastfeeding is better and safer. Matern Child Health J. 2007;11:287Y291.
65. Schulte-Hobein B, Schwartz-Bickenbach D, Abt S, et al. Cigarette smoke exposure and the development of infants throughout the first year of life: influence of passive smoking and nursing on cotinine levels in breast milk and infant’s urine. Acta Paediatr. 1992;81:550Y557. 66. American Academy of Pediatrics Committee on Drugs. The transfer of drugs and other chemicals into human milk. Pediatrics. 2001;108:776Y789. 67. Ip S, Chung M, Raman G, et al. Breastfeeding and Maternal and Infant Health Outcomes in Developed Countries. Evidence Report/Technology Assessment No. 153 (Prepared by TuftsNew England Medical Center Evidence-Based Practice Center, Under Contract No. 290-02-0022). AHRQ Publication 07-E007. Rockville, MD: Agency for Healthcare Research and Quality; 2007. 68. Catz CS, Giacola GP. Drugs and breast milk. Pediatr Clin North Am. 1972;19:151Y166.
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Volume 68, Number 10 OBSTETRICAL AND GYNECOLOGICAL SURVEY Copyright * 2013 by Lippincott Williams & Wilkins
CHIEF EDITOR’S NOTE: This article is part of a series of continuing education activities in this Journal through which a total of 36 AMA PRA Category 1 CreditsTM can be earned in 2013. Instructions for how CME credits can be earned appear on the last page of the Table of Contents.
Pregnancy, Breast-feeding, and Marijuana: A Review Article Meg Hill, MBBS,* and Kathryn Reed, MD† *Fellow, Maternal Fetal Medicine, and †Professor and Head, Department of Obstetrics and Gynecology, The University of Arizona, Tucson, AZ Marijuana is a commonly used drug. At present, it remains an illegal substance in most areas of the United States. Recent controversy regarding the perceived harms of this drug has resulted in debate in both legal and medical circles. This review examines evidence regarding the effects of marijuana exposure during pregnancy and breast-feeding. We examined studies pertaining to fetal growth, pregnancy outcomes, neonatal findings, and continued development of fetuses and neonates exposed to marijuana through adolescence. In addition, the legal implications for women using marijuana in pregnancy are discussed with recommendations for the care of these patients. The current evidence suggests subtle effects of heavy marijuana use on developmental outcomes of children. However, these effects are not sufficient to warrant concerns above those associated with tobacco use. Marijuana is the most commonly used illicit substance in the United States. It is predominantly used for its pleasurable physical and psychotropic effects. With the recent changes to legislature in Colorado and Washington State making the recreational use of marijuana legal, marijuana has gained national attention. This raises the question: If it is legal for a woman to consume marijuana, what is the safety of this activity in pregnancy and breast-feeding? Moreover, do the harms of marijuana use on the fetus or infant justify the mandatory reporting laws in some states? Target Audience: Obstetricians and gynecologists, family physicians Learning Objectives: After completing this CME activity, physicians should be better able to assess the prevalence of marijuana use in the general obstetric population, evaluate the fetal, neonatal and childhood outcomes associated with marijuana use during pregnancy and breastfeeding, and care for pregnant women who are faced with the possible legal implications of screening for drug use.
Cannabis the Drug Cannabis sativa is grown in many temperate climates.1 Historically, the plant has been used for its fiber in the fabric industry.1,2 However, the sap from the plant, which the plant produces in copious All authors and staff in a position to control the content of this CME activity and their spouses/life partners (if any) have disclosed that they have no financial relationships with, or financial interests in, any commercial organizations pertaining to this educational activity. Correspondence requests to: Meg Hill, MBBS, Department of Obstetrics and Gynecology, The University of Arizona, 1501 N Campbell Ave, 8th Floor Tucson, AZ 85724. E-mail: meghanhill@ obgyn.arizona.edu.
amounts in hot climates, can be made into hashish.3 The foliage produced can be smoked or cooked and ingested.3 In the United States, the most common form of ingestion is via smoke inhalation either through rolled cigarettes referred to as joints or through glass or plastic containers used to concentrate the drug for delivery.3 Although farming of the C. sativa plant is either discouraged or illegal in most of the United States, the plant is commonly found growing in other regions of the world. Testing of human subjects in Asia where the plant is encountered shows that Delta 9 Tetrahydrocannabinol (THC) is found in human urine after ingestion of milk from buffalo that have been feeding
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on the plants.4 This exposure of humans to the plant dates back thousands of years. Many cultures have commonplace uses for the plant in regions where marijuana has been a part of the local culture for generations.5 Incidence of Use Marijuana is commonly used by pregnant women in the United States.6 However, it is not a legal drug in the majority of states in America. It can be smoked or consumed in the form of liquid or solid preparations.3 Studies regarding marijuana use in pregnancy and during lactation can be confounded by recall and reporting bias as well as the differing baseline characteristics of those who use and abstain from marijuana use. Rates of use are higher in younger cohorts, with the rates of usage decreasing as women age.7Y9 Women do use marijuana during their fertile years.8 Cannabis users are also more likely to be nonHispanic black and be having their first child and are less likely to have used folic acid supplementation during their pregnancy.9 There is evidence to suggest that patients in urban areas, from lower socioeconomic status groups, and from single-parent households have higher rates of use.7,9Y11 Four percent of doctors self-reported marijuana use in California recently, indicating that marijuana use is not limited to these groups and is simply more often utilized among them.12 Use in Pregnancy Pregnant women use marijuana at a higher rate during the first trimester, with many reporting a cessation of use or decreased use by the third trimester.11 Many women report use of the drug in the months preceding a pregnancy with cessation on discovery of the pregnancy, often in the first or early second trimester.11 Physiologic and Psychological Effects of Marijuana The pleasurable effects of marijuana are usually described as a feeling of elation or amusement. This is followed by a sense of calm, an increase in appetite, and relaxation. Medicinal marijuana is frequently used in adjunctive treatments for AIDS and cancer patients. Animal studies reflect various effects on appetite and food intake when the endocannabinoid system is manipulated.13Y15 Negative experiences have been reported, including palpitations, anxiety, and sedation. Rare complications can occur such
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as cannabinoid hyperemesis syndrome, which occurs only with long-term, heavy use of the drug.16,17 The syndrome is alleviated by abstinence.16,17 Long-term effects of marijuana can be assessed in both current and previous users. Current, heavy users do have a decreased cognitive ability, spatial reasoning, and decision making. This reflects acute intoxication.18 Some studies show a persistence of these effects in abstinent heavy users for several weeks to months after use.18,19 These effects dissipate with time, and no consistent effects can be demonstrated in most studies after a period of months to years.18,19 Use of marijuana in young people has been associated with anxiety and depression.20,21 It is unclear whether this is related to the demographic reporting heavy use or to the substance itself. Some evidence suggests that heavy marijuana use in the teen years can be related to schizophrenia in later life.22 Whether this is due the drug or whether the drug is used as a form of self-medication in these patients is unclear. Effects in Women Hormones of women have been studied while they inhale marijuana at both the follicular and luteal phase of the menstrual cycle.23 In a placebo-controlled, crossover trial, women who smoked marijuana during the luteal phase of the menstrual cycle had a depression of prolactin levels, whereas those inhaling a placebo did not.23 Similar effects were not seen during the follicular phase of the menstrual cycle.23 This effect has not been investigated in lactating women and cannot be extrapolated to this population. The Pregnant Patient General Approach to Pregnant Women Using Illicit Substances Before initiating a discussion or performing a screening drug test on a pregnant woman, the provider should be aware of the reporting laws in the state in which they practice. Women should be made aware of any mandatory reporting laws that exist in the state in which they reside. Likewise, they should refuse screening if they wish without undue pressure from their provider.24 Some states have punitive laws in place that can result in imprisonment or loss of custody for women using drugs.24Y26 These laws have consistently been found to decrease compliance with prenatal care and increase the perinatal mortality rate.25,27 They cast doctors in an adversarial position with the patient and create a dynamic of distrust.25 Doctors should use their best judgment in
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documenting drug use in their patients and should do so only with the understanding of the patient.24 Creating a disclosure in the chart without the patient’s knowledge may undermine the doctor-patient relationship when evidence of this surfaces later, especially if the disclosure is based on the physician’s interpretation or assumptions and not on the facts related by the patient.24 The states that currently have laws enabling criminal charges for child abuse to be brought against a woman for use of drugs while pregnant are Arkansas, Colorado, Florida, Illinois, Indiana, Iowa, Louisiana, Minnesota, Nevada, Oklahoma, Rhode Island, South Carolina, South Dakota, Tennessee, Texas, Virginia, and Wisconsin.28 Involuntary commitment to a drug treatment program can be instituted for use of drugs while pregnant in Minnesota, South Dakota, and Wisconsin.28 Interestingly Arizona, Georgia, Kansas, Maryland, Missouri, Oklahoma, Tennessee, Texas, Utah and Wisconsin are the only states that have expedited drug treatment available for pregnant women.28 This punitive approach creates a climate in which women are afraid to seek care.25,27 Considering the measures in place to make women subject to charges of child endangerment without realistic hope of treatment in many states as well as legal precedent including arrest and prolonged incarceration in South Carolina, it is not surprising that many women are not forthcoming regarding drug use during pregnancy.28 The approach to the pregnant patient who discloses illicit drug use should be impartial and focus on the health and well-being of both the woman and fetus. Type, amount, and frequency of the drug used should be ascertained through either a thorough face-to-face history or through a screening tool. Providers should be aware that the context in which they view drug use during pregnancy may not be the same as that of the patient. Although marijuana use has historically been considered an unacceptable behavior, the beliefs of the general public and policy makers in some states do not reflect this view. The provider should be aware that many women view marijuana as a harmless substance that is not associated with significant negative effects. If the patient sees no detriment from the use of the drug, she is unlikely to stop, and the provider’s opinion regarding cessation of use may not be a powerful motivator to the patient. Providers should also recognize that patients may choose to wean marijuana use during pregnancy and increase their use again following delivery.29 Women should be asked if they feel that their use is ‘‘out of their control’’ or if they are experiencing negative life effects because of marijuana use. These
patients fall into a group that should be offered additional counseling and referral to a substance abuse program as would be offered with other legal drugs that can be abused, such as alcohol. Levels Transferred via the Placenta and Breast Milk Marijuana enters the bloodstream within seconds and the brain within minutes when inhaled.30 A longer time generally elapses before effects when marijuana is ingested orally. It is a highly lipophilic substance and hence can be bound to fat stores throughout the body,31 with a tissue half-life of 7 days.30 The active drug is metabolized by the liver.30,31 It is not unusual for heavy chronic users (defined in most studies as 95 joints smoked per week) to have urine toxicology screens that are intermittently positive for several months after their last use. Complete elimination after a single exposure to the drug may take a month.30 Light users have the substance detected in their urine for days to weeks after use. Placental transfer to the fetus does occur,30,32 and this results in detectable cord blood levels of the drug.32 Levels detected in the cord blood indicate that the fetus receives a proportionately smaller dose than does the mother.32 Neonates have tested positive for marijuana in urine.33 Analysis of breast milk reveals the presence of marijuana in recent users,33 where it is bound to proteins.34 However, seeing that the concentration of protein in breast milk is less than 1%,34 the transfer of the drug is likely commensurate to this protein level. One study calculated exposure to the neonate to be 0.8% that of the mother’s exposure.31 Effects of Use on Fetal Outcomes There are few studies that assess the isolated effects of marijuana on the developing fetus. The confounding introduced by polydrug use makes interpretation difficult.35Y39 The most common concurrently used drugs are cigarettes, alcohol, and cocaine.35,36,39 Tobacco is an important confounder as the use of tobacco is highly associated with the use of marijuana in most studies, and tobacco by itself is associated with effects on growth.38,40 Studies have reported varying associations including growth restriction, shortening of gestation, and neonatal withdrawal symptoms.37,38,40Y42 Another study reported on altered mRNA expression in the fetal brain.43 These findings have not been reproduced in well-designed, rigorously performed studies. In addition, marijuana is not associated with birth defects in humans.44 One cohort of 756 pregnant women was followed up in Colorado.32 Subjects were approached for
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information on drug use in pregnancy. When asked, 34% affirmed that they had used marijuana during pregnancy. When controlling for cigarette use, there were no detrimental effects noted on fetal growth or fetal neurodevelopmental outcomes when infants were examined at 24 to 72 hours after birth. There were also no differences in length or growth when adjusting for cigarette use, nor was there an increase in anomalies. The mothers who used marijuana had a statistically significant higher weight gain during pregnancy in this cohort.32 Interestingly, this study did report a statistically significant increased rate of male births in marijuana users. This effect has been noted in trends in other studies and may be related to the effects of marijuana on sperm.40,39 Many of the women using marijuana had male partners who also used marijuana. When the Colorado cohort was followed up at 1 year of age, 62 of the infants were reported to have been breast-fed. Again, differences were not found between groups. In addition, there was no difference in age at weaning, suggesting that marijuana was not detrimental to the suckling behavior of infants or the maternal production of milk.32 A second cohort of women in Jamaica were followed up during pregnancy and after their deliveries.45 In the cultural context of the region, marijuana is seen as a medicinal substance. Most women smoked or drank tea with marijuana contained in it.45 Following birth, 24 babies of subjects using marijuana and 20 babies of women abstaining from use were examined. Neonatal outcomes were equivalent in the first week after delivery in this cohort. At follow-up 30 days after delivery, no detrimental effects of marijuana use were documented.45 The women who were habitual marijuana users rated their experience of motherhood as more fulfilling than those who were not. These children were again examined at age 5 years, and no deleterious effects were noted.46 Confounders in this study were the different economic statuses between groups, with the marijuana users on average having a larger amount of control over the household income.45 The MHPCD (Maternal Health Practices and Child Development Study)47 and OPPS (Ottawa Prenatal Prospective Study) were large prospective cohort studies carried out in Pittsburg and Ottawa, respectively. These studies aimed to include as many pregnant women as possible and assess drug use and effects of different ingested substances on pregnancy and childhood outcomes. They relied on maternal reports of marijuana use both during and after pregnancy. The MHPCD study was carried out in a higher-risk,
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lower-socioeconomic-status group of women than the OPPS cohort of women. These studies did not find an association between marijuana use in pregnancy and immediate pregnancy outcomes such as miscarriage rates, rates of anomalies, mode of delivery, Apgar scores, or meconium-stained fluid.8 Fried,39 an author particularly interested in the effects of marijuana on offspring, was involved in the OPPS cohort. However, before completing this work, he originally published a study claiming that marijuana causes a neonatal abstinence syndrome, not unlike that of narcotic withdrawal, which results in neonates exhibiting high-pitched cries and startles and poor visual habituation, which resolved within a few days of birth.39,41 This study relied on maternal report of marijuana use, and there was no mention of testing for use of additional drugs such as heroin or prescription narcotics. In both of the studies from Jamaica and Colorado, the cohorts were specifically examined for these same signs and symptoms in neonates of mothers who used marijuana. These findings could not be reproduced, with no apparent withdrawal effects in neonates. This seems congruent with the adult response to marijuana, which does not seem to cause a significant withdrawal phenomenon. Effects of Use on Childhood Outcomes The MHPCD and OPPS cohorts of children were reexamined regularly during their childhood.36,47Y49 A battery of psychological tests was carried out on these children addressing broad areas such as global intelligence quotient and specific neurologic functions pertaining to auditory processing, spatial reasoning, and accuracy. The problems encountered in these cohorts were the small numbers of ‘‘heavy’’ marijuana users and the confounding introduced by the social determinants of health and use of other drugs concurrently with marijuana.36,48 Neither study demonstrated a convincing difference in global IQ of offspring at any age when taking light or moderate use into account.49 Many associations that were statistically significant ceased to be so when confounding factors were adjusted for.36,48 Subtle effects were suggested in the ability of children to comprehend language at age 2 years. However, after adjustments were made for other determinants of outcomes such as specific aspects of the home environment, this finding did not persist.49 At this age, the children of moderate users actually performed better at motor tasks.50 Some testing showed decreased ability of children to analyze visual stimuli.49 This area requires more study as effects noted in these studies were subtle. These studies also noted
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differences in functioning in children exposed to prenatal cigarette smoking as it related to visual analytic function.49 The findings were in a different facet of function but did nonetheless confound the findings related to marijuana, as in North America, marijuana is generally mixed with tobacco and then smoked. Heavy use of marijuana (95 joints per week) during pregnancy was associated with an increase in omission errors in offspring, highlighting the fact that significant use may be required to produce a cognitive effect.49 Additional findings were that teachers rated children of marijuana users as more impulsive, and parents rated the children as being less attentive. Interpretation of this finding is difficult because marijuana users had a lower average income, were more likely to be single parents, and were more likely to use both alcohol and cigarettes.47,49 The context of this use was also in locations were marijuana is illegal and associated with risk to the parents of these children should they be found to be using marijuana, which could in turn affect the home environment. When growth trajectories were assessed in the OPPS cohort, the infants prenatally exposed to marijuana did not have an altered growth pattern when compared with control subjects after adjusting for confounding variables.51 There was a smaller head circumference noted in children of mothers who used marijuana while pregnant at age 12 years. However, this finding is based on 19 children of ‘‘heavy’’ users compared with 93 control subjects and 23 ‘‘light’’ users.51 This finding again ceased to be statistically significant by midadolescence.8 The Jamaican cohort was also followed to age 5 years with no differences in children of mothers who continued to use marijuana to those who never used the substance. The Colorado cohort did not show any deleterious effects of marijuana use through pregnancy and breast-feeding, although this cohort was not followed up past 12 months of age. One report focused on the effect of prenatal marijuana exposure on the incidence of childhood leukemia.52 There was an increase in this disease in exposed offspring. However, they also noted an increase in leukemia in offspring of pregnancies treated with antinausea medication. The authors supplant that the use of pesticides on the marijuana inhaled by study subjects may have been related to the increased risk of leukemia.52 Certainly, recall bias is also a consideration in this retrospective cohort. Effects on Adolescent Outcomes The OPPS and MHPCD cohorts were followed by researchers from infancy into late childhood, and
Fried et al53Y55 continued to publish the findings of research with the OPPS cohort into the children’s teens. The findings from the OPPS cohort suggested that growth and specifically head circumference were not statistically significantly different between groups: nonusers, light, moderate, and heavy users throughout early childhood. However, at follow-up at age 12 years, the difference in head circumference reached statistical significance for the maternal ‘‘heavy marijuana use’’ group. This could reflect a true causeand-effect relationship, or it could reflect the higher levels of alcohol and tobacco use in women who admitted to heavy use of marijuana.11 In addition, the number of patients followed up was small, only 20 and 19 in the moderate and heavy use groups, respectively. Another study assessed the adolescent brain with the utilization of magnetic resonance imaging. Findings suggested that as the mother accrued illicit substance use in pregnancy, the brain volume of the offspring was found to be decreased in adolescence. However, this study focused on cocaine use with or without concomitant use of other drugs, including marijuana.56 On cognitive testing, the OPPS and MHPCD cohorts were found to have differences noted in early adolescence. Executive function seemed affected with omission errors more common in the group of children with heavy exposure to maternal marijuana.54 IQ was not affected, however.53 This is in stark contrast to the findings in the same study of a comparison group: the children of cigarette smokers. The children of heavy tobacco smokers had more prominent effects, including differences in perception and statistically significant lower global intelligence scores.53 Effects of Marijuana During Breast-feeding There is inadequate evidence to make a statement about the isolated use of marijuana in breast-feeding mothers. The studies that address this issue are confounded by the fact that few women have isolated use during breast-feeding in the absence of additional prenatal use of marijuana. The OPPS, MHPCD, and Jamaican and Colorado cohorts followed up women and children exposed to marijuana in pregnancy and breast milk, with the results discussed above. Several articles have been published outlining the risks of marijuana and breast-feeding and defining use as a contraindication to breast-feeding. The concern is that marijuana causes an immediate threat to the health and safety of the child either through sedation of the child if breast-fed while the mother is using marijuana or through negligent behavior by the
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Pregnancy, Breast-feeding, Marijuana
mother who uses marijuana.57,58 It should be noted that these articles are based on opinion and not on any scientific evidence. An extensive literature review was unable to yield a single case report of a neonatal death from exposure to marijuana. One study did find an effect of marijuana on isolated motor, but not mental, development at age 1 year in infants exposed during breast-feeding. The 10 infants in this cohort exposed only prenatally did not have any motor deficits when compared with control subjects. This study was confounded by socioeconomic factors and included only 14 women who were using marijuana while breast-feeding but not while pregnant.59 Cigarette smoking can be used as a surrogate for marijuana smoking in some respects, although there is an association with maternal cigarette smoking and sudden infant death syndrome, where one does not exist for maternal marijuana use.60,61 A concerning feature of advising women to ‘‘protect’’ their child by not breast-feeding is the continued environmental exposure to marijuana and tobacco smoke in the home without the protective effects of breast-feeding. There is evidence that women who use recreational drugs are less likely to breast-feed,10 although this has not been seen in all cohorts, with women in the OPPS with little effect of marijuana on the method or duration of breast-feeding.51 It may be that women are reliant on the advice of physicians, nurses, and lactation consultants to guide their decisions regarding method of feeding for their infants. These conflicting results may reflect different comfort levels with breast-feeding in the setting of marijuana use. Several publications have recommended that patients not smoke tobacco while they are pregnant or breast-feeding.60,62Y64 The basis for this is evidence that cotinine and nicotine (contained in cigarette smoke) can be detected in breast milk and in the urine of newborn babies who breast-feed from mothers who smoke.65,66 Bottle-fed children of mothers who smoke also have cotinine detected in their urine.65 However, if patients do smoke tobacco, it is recommended that they should continue to provide the protection of breast-feeding to their children because of the multiple health benefits to the child.60,64,67 The benefits of breast-feeding mitigate some of the risks associated with neonatal exposure to passive cigarette smoke, such as sudden infant death syndrome, ear infections, abnormal weight gain, and hospitalization for bacterial and viral infections.60,64,67 If a mother chooses to use marijuana, it may be advisable for her to breast-feed to mitigate some of the effects of passive smoke exposure. This becomes especially important advice in the setting of escalating use, as there is
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evidence that tapered use tends to increase again after delivery.7,29 It is prudent to advise women that if they choose to smoke marijuana; they do so away from their children (preferably outside the house) and change their clothing after use, so as to not expose their children to smoke particles in clothing. This advice is in line with what is recommended to mothers who smoke tobacco. There is no adequate evidence to address whether orally ingesting marijuana may be safer for the neonate, although this would certainly eliminate the concern regarding inhalation of smoke particles. Legal Implications Mandatory reporting of drug use in pregnancy is a reality that persists in many states. The American College of Obstetricians and Gynecologists has made it clear that women should not be tested without their consent and that punitive measures dissuade patients from prenatal care and actually increase perinatal mortality.27 Women have been prosecuted for the use of marijuana and other illicit substances.8,26,27 The treatment of a woman as a child abuser in this circumstance reduces her status to that of a carrier, existing only to house the fetus without the right to make her own decisions as an entity with separate rights.27 Physicians should be cognizant of the laws in their state of practice and consider the screening methods used in their institutions. Common indications for drug testing in pregnant women are preterm labor, hypertension in pregnancy, and placental abruption. Marijuana use has not been associated with any of these complications in the large cohorts discussed in this article; hence, the indication for toxicology for THC is not indicated in this setting. It may be wise to omit THC testing in the setting of medical complications and restrict testing to cocaine and methamphetamine if symptoms suggest their use, as these drugs can be associated with pregnancy complications such as placental abruption and acute hypertensive episodes. Many physicians order this test without the patient’s knowledge in the setting of poor compliance with prenatal care. These patients are often in disadvantaged economic groups and are more frequently African American patients.25 Indeed, the disproportionate pursuit of legal action against African American patients for drug use has been noted.26 As previously discussed, testing patients for drug use without their knowledge, consent, or medical indication only serves to strain the physician-patient relationship and dissuade the patient from prenatal care.25,27
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In the newborn period, positive toxicology may also present challenges in the new family when there are differing opinions as to whether marijuana is contraindicated in breast-feeding. Other substances found in breast milk with moderate use such as cotinine, caffeine, and alcohol are generally not seen as a contraindication to breast-feeding.68 However, marijuana is more controversial, probably because it remains an illicit substance in most states. For this reason, the author suggests that physicians consider whether screening for marijuana use is indicated in the setting in which they practice. If a positive screen is present in a mother who wishes to breast-feed, she should be made aware that there is no consistent evidence of severe, ill effects with marijuana and breast-feeding, but that long-term neurodevelopmental outcomes are not fully investigated, and there may be an association with harm in women who smoke 5 or more joints per week both while pregnant and during breast-feeding. The best advice is to abstain from marijuana completely seeing that it seems to have similar effects to cigarettes, but that breastfeeding is an option. Least preferable is continuation of marijuana use in conjunction with bottle-feeding. This results in passive smoke exposure without the benefits of breast milk. As mentioned above, the effects of heavy tobacco use are more striking than those of marijuana use, and tobacco remains a legal drug. SUMMARY Marijuana may be inhaled or ingested and is primarily used by pregnant women for recreational purposes, although it does have medicinal properties. Marijuana does cross the placenta and can be detected in newborn infants. It can also be detected in breast milk after recent maternal use. Although some studies report specific effects of marijuana on the developing brain of the fetus and neonate, these effects are not reproducible. Heavy marijuana smokers do have babies who are smaller than those of nonusers. This finding is confounded by the concurrent use of cigarettes and other illicit substances in most studies reporting this effect and consistent with the evidence that heavy tobacco use also results in a lower average birth weight. Patients should be cautioned that inhaled marijuana may have effects on fetal growth similar to those of cigarette use. Neurodevelopmental outcomes seem similar between babies of nonusers and users with no resultant effects on global intelligence quotient. There may be some effects on visuoperceptual ability, reasoning and attention noted in older children. These findings have been
reproduced in 2 large cohorts, and the association was statistically significant only with prolonged, heavy maternal use (95 joints per week throughout pregnancy and breast-feeding). If these effects do exist with light, moderate, or sporadic use, they are sufficiently subtle as to not be consistently demonstrated between studies. The effects of marijuana on the developing fetus and child are subtly different from, but not evidenced to be more severe than, those of heavy cigarette consumption by the mother during pregnancy and early childhood. Based on these findings, mandatory reporting of marijuana use during pregnancy and punitive measures related to the use of this drug during pregnancy or breast-feeding do not seem medically warranted. A consistent message of ‘‘breast is best’’ seems appropriate for mothers who continue to use marijuana while breast-feeding.
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