Cannabis pregnancy and maternity. For obvious reasons, this is not an easy topic to deal with. Consuming medications of any kind during pregnancy and lactation always raises serious concerns. Since cannabis freely crosses the placenta, and is found in breast milk, It's used by pregnant, or breastfeeding women is obviously a topic of great interest. When examining evidence concerning the use of cannabis by pregnant and breastfeeding women, we need to distinguish between medical cannabis and cannabis-related drugs. Let's begin with the later, the FDA has classified the potential for birth defects for drugs used during pregnancy into five categories: A, B, C, D, and X. These categories are determined by two factors, whether or not adequate controlled trials have been conducted, envisaged of conducted trials. Category A, for example, includes medication for which there exist adequate and well-controlled studies which have failed to demonstrate a risk to the fetus. In other words, safe medications. Category B includes those medications for which adequate studies in animals have failed to demonstrate a risk to the fetus, but for which there are no adequate and well-controlled studies in pregnant women. Drugs in this class are likely safe. Category C is reserved for those drugs for which potential benefits may warrant use during pregnancy despite potential risks, but because of lack of certitude, caregivers must be careful. Category D suggests positive evidence of human fetal risk, and drugs in this category are generally not recommended for use. Category X includes studies in animals and humans having demonstrated fetal abnormalities, and the risks involved in use of these drugs in pregnant women clearly outweigh potential benefits. These categories by the way, apply to labor and child delivery as well. The Hale's Lactation Risk Categories, a complementary set of categories, refers to the use of medications during breastfeeding. It is also divided into five categories, labeled L1 through L5. L1 indicates no risk, L2, a drug appears safe, L3, a drug is moderately safe, L4, the drug is potentially risky, L5, contraindicated. This label indicates that the drug should not be used no matter the circumstances. As we've discussed previously, three cannabinoid-based drugs have been approved, and are available for human consumption in different parts of the world. One is the oromucosal spray name Sativex and the two other out-world drugs. So, how safe are these drugs? Side effects should not be use during pregnancy, unless the potential risk to the fetus or embryo are overweighted by the benefit of treatment. The patient information leaflet specifically indicates, whether male or female, you must use a reliable contraceptive method while using this medicine. Keep using it for at least three months after your treatment has stopped. Furthermore, it is contraindicated that women who are breastfeeding. In other words, it appears to suggest category D for pregnancy, and L4 for breastfeeding women. The oral medication Nabilone showed those dependent developmental toxicity during pregnancy and afterbirth in rats and rabbits. In the absence of adequate and well-controlled studies in pregnant women, and since animal studies cannot rule out the possibility of harm, Nabilone should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. This places Nabilone in category C. It is not known whether Nabilone is excreted in breast milk. Since cannabinoids are generally excreted in breast milk, Nabilone use is not recommended for nursing mothers. It should be considered a health category L4. And finally, Maronil, our third cannabinoid drug is labeled similarly. In mice and rats, it decrease maternal weight gain, and number of viable pups while increasing fetal mortality and earlier resorption. It should therefore be used only if the potential benefit justifies the risk to the fetus. It is not recommended in nursing mothers since it is concentrated and secreted in human breast milk. Hence, it is regarded as category C and L4 respectively. Taking together, the use of official cannabinoid-related drugs during pregnancy and breastfeeding can not be regarded as safe. We will now attempt to examine the use of medical herbal cannabis on pregnancy and maternity. This is a complicated task since most available data on the safety of smoked cannabis during pregnancy and breastfeeding is drawn from studies on recreational cannabis users which are often difficult to understand. Numerous recreational cannabis users smoked tobacco, and some used additional substances and drugs, and there is no accurate data on the quantity or quality of the smoked cannabis. Isolating the effect of cannabis may require some statistical maneuvering and careful evaluation. And as we have already seen, studies on medical cannabis often yield conflicting results, and a firm overall conclusion cannot always be drawn, unless a meta-analysis is conducted. So let's jump into the water. I'll begin with an optimistic example, a 2015 study conducted by the University of Washington aimed at determining the prevalence and the risk factors for cannabis use during pregnancy. Investigators were interested in evaluating if cannabis use is associated with poor pregnancy outcomes. Poor pregnancy outcomes include low birth weight, under 2.5 kilograms, admission to neonatal intensive care, and apgar score under seven, five minutes after delivery, and low umbilical artery blood acidity which is an indicator of fetal distress. This retrospective study undertaking a four year period examined only full term deliveries without accounting for known pre-delivery fetal anomalies. Women were divided into two groups, those having consumed cannabis during pregnancy, either by self-report or positive urine drug screen, and those who did not use cannabis. Results show that 8.4% of women, some six hundred eighty of over 8,000 women in the cohort, used cannabis during pregnancy. Cannabis users were younger, predominantly of African-American origin, had inadequate prenatal care, and use tobacco, alcohol, and other drugs. Since all of these factors could influence pregnancy outcomes, investigators had to adjust for confounding factors, such as tobacco smoking, alcohol consumption, and other drugs. Adjustment are statistical methods which allow to control for specific factors and isolate the effect of the investigated factor or drug. Interestingly, all investigated marker of poor neonatal outcome were the same for women having consumed cannabis and for those who hadn't. The study concluded that although cannabis use is common during pregnancy, it is not necessarily an independent risk factor for poor neonatal outcomes. Importantly, the study was published in high impact journal of Obstetrics and Gynecology and its results are regarded as trustworthy. One year later, another retrospective study was published in the very same journal. Although this study included just over 12,000 participants, marijuana smoking was remarked in only 106 women. This is approximately 0.9%, roughly one tenth of the results found in the previous study. Since 48 of the 106 women were using cigarettes and cannabis concurrently, investigators compared outcomes in cannabis and tobacco smokers against exclusive smokers of cannabis and against non smokers. Results are consistent with those of the previous study, and show that cannabis use alone is not associated with any significant adverse pregnancy outcomes. In contrast, cannabis use in combination with cigarette smoking significantly increases the risk for multiple unfavorable outcome for both mothers and their babies. In mothers, the risk of asthma in preeclampsia was shown to increase by approximately 250%. In newborns, investigators remarked it two to three hundred percent increase in pre-term birth risk, decreased the head size, and decreased birth weight. Nonetheless, the study concludes that cannabis exposure alone is not associated with significant prenatal adverse outcomes. Another recent study included nearly 350 Australian Aboriginal women who were interviewed and completed a questionnaire between four months and one year after childbirth. Fifty two percent of women smoked cigarettes and 20% use cannabis. Of the 56 women who smoke cannabis only, 12 use it alone, while the rest use both tobacco and cannabis. Compared with non-smoker's, those who smoke cannabis delivered babies weighing half a kilogram less on the average. The likelihood of having an infant with low birth weight was shown to be 6.5 times higher. Put differently, 39% of mothers who used cannabis had infants that were small for their gestational age, versus 23% of mothers who smoke cigarettes only, and 14% of mother who did not smoke or use cannabis. Although this study includes just a small number of participants and does not document self-report of outcomes, it paints the use of cannabis during pregnancy in somewhat darker colors. Similar resides were report in a French studies surveying some 13.5 thousand women. 1.2% reported using cannabis once a month or more during pregnancy. The percentage was higher among women who were younger, leaving alone, or had a low level of education or income. As in other studies, cannabis use was also associated with tobacco use or alcohol consumption. Cannabis users and tobacco smokers showed a two-fold increase in the rates of spontaneous pre-term or early birth as compared to non-tobacco smokers. A related, yet separate topic, is late developmental effects of using cannabis during pregnancy and during lactation. As many studies on the topic have been published over the years, I will summarize by quoting a few recently published reviews. A review published in the American Journal of Obstetrics and Gynecology claims that evidence suggests that marijuana may cause problems with neurological development, resulting in hyperactivity and poor cognitive function. Not only that, but contemporary marijuana products have higher concentrations of DNC than those used in the 80s when much of the marijuana research was completed. The effects on pregnancy and on the fetus may therefore be different than those previously seen. The authors of the review admit that further research is needed, but in the meanwhile, women are advised not to use marijuana in pregnancy or while lactating. A second review states that cannabis used in pregnancy is also associated with adverse effects on fetal and adolescent brain growth, poorer attention and executive function skills, lower academic achievements, and increased behavioral problems. It goes on to say that prenatal cannabis was associated with lower levels of education and employment, as well as with more substance abuse and depressive symptoms. A third perhaps more cautious reviews summarizes by saying, current basic and clinical findings can be organized into a logical hypothesis, predicting narrow vulnerability to and attenuated adaptation to world environmental challenges, such as stress and drug exposure in children affected by in uterus cannabinoid exposure. Yet, the authors continue and say, "We warned that the lack of critical data from longitudinal follow-up studies precludes valid conclusions on such possible delayed adverse effects." I would suggest that this should also be the summary of this lesson.
