Cannabis use during pregnancy and breastfeeding
Cannabis sativa is the most commonly used drug during pregnancy. The self-reported prevalence of cannabis use during pregnancy is between 2 and 5% in most studies, but in reality it is likely to be much higher. For young, urban and socioeconomically disadvantaged women, the proportion rises to between 15 and 28 %.
Interviewing women at the time of delivery shows a higher rate of use than prenatal visits because some users do not seek prenatal care. It is notable that 34-60% of female cannabis users continue to use cannabis during pregnancy, many of whom think that it is relatively safe and also cheaper than tobacco use during pregnancy. A recent study reported that 18.1% of pregnant women who admitted to using cannabis in the last year met the criteria for cannabis abuse, dependence or even both.
As more and more states legalise the use of cannabis for medicinal or recreational purposes, its use by pregnant women could become even more common. Given the fears and uncertainties surrounding the impairment of neurological development of the fetus and the exposure of mother and fetus to the adverse effects of smoking, pregnant women or women considering pregnancy are often advised to stop using cannabis. Gynaecologists should not prescribe or suggest the use of cannabis for medicinal purposes in the period before conception, during pregnancy and during breastfeeding. Pregnant women or women considering pregnancy are usually advised to discontinue the use of cannabis for medicinal purposes in favour of another treatment for which there are better safety data in relation to pregnancy. Insufficient data are available to evaluate the effects of cannabis use on infants during lactation and breastfeeding and, in the absence of such data, cannabis use is not routinely recommended.
The medicinal and psychoactive effects of cannabis are caused by compounds called cannabinoids which are absorbed into the body from the lungs when smoked and from the digestive tract when ingested. Tetrahydrocannabinol (THC) is a small and highly lipophilic molecule that is rapidly distributed to the brain and fat. It is metabolised in the liver, the half-life of THC ranges from 20-36 hours for occasional users to 4-5 days for heavy users, and up to 30 days may be required for complete elimination. In animal models, THC crossed the placenta and after acute exposure produced fetal plasma levels that were approximately 10 % of maternal levels. Significantly higher concentrations were observed in the fetus after repeated exposures. Some findings in humans suggest that THC also appears in breast milk.
There is a lack of information on the specific effects of cannabis on pregnancy and the developing foetus, partly because users often use other drugs, including tobacco, alcohol or illicit drugs, and partly because of the potential confounding effects of other substances. Cannabis smoke contains many of the same respiratory and carcinogenic toxins as tobacco smoke, often at concentrations several times higher than tobacco smoke. Adverse socio-economic conditions such as poverty and malnutrition may contribute to effects otherwise attributed to cannabis. For example, one population-based study reported that pregnant cannabis users were more likely to be underweight and have lower levels of education, lower household income and less frequent use of folic acid supplements than women who did not use cannabis. Another study found that women exposed to marijuana were more likely to experience intimate partner violence, another risk factor for adverse pregnancy outcomes. Studies evaluating marijuana use during pregnancy often account for these confounding factors using social stratification of data or multivariate analysis. Studies of cannabis exposure during pregnancy are potentially burdened by reporting and recall bias because they often rely on self-reported habits, including frequency of use, timing of use, and amount of cannabis used. Other misleading issues may arise due to the potency of the herb, which generally increases with time.
Effect of cannabis use on pregnancy
Cannabinoids, whether endogenous or plant-derived, act on the central nervous system via the type 1 cannabinoid receptor. Animal models have shown that endocannabinoids play a key role in normal fetal brain development, including neurotransmitter systems and neuronal proliferation, migration, differentiation and survival. Human fetuses have developed a type 1 cannabinoid receptor for the central nervous system as early as 14 weeks gestation, with receptor density increasing with increasing gestational age, suggesting a role endocannabinoids in normal human brain development.
Studies in laboratory animals show that exposure to exogenous cannabinoids in utero can disrupt normal brain development and function. Manifestations of in utero exposure include impaired cognition and increased sensitivity to the drug of abuse. Of further concern is that supraphysiological exposure of the fetus to cannabinoids may induce brain sensitivity to the apoptotic effects of ethanol, raising concerns about substance abuse and suggesting that exposure to exogenous cannabinoids could adversely affect brain development. Studies have noted that children who were exposed to cannabis in utero performed worse on tests of visual problem solving, visual-motor coordination and visual analysis than children who were not exposed to cannabis in utero. In addition, prenatal exposure to cannabis is associated with reduced attention span and behavioural problems and is an independent predictor of marijuana use at age 14 years. The effects of prenatal cannabis exposure on school performance are less well known. Although one study found no significant effect on several measures of cognition and school performance in children aged 5-12 years from predominantly middle socioeconomic class backgrounds, another investigation of children from predominantly lower socioeconomic urban areas observed poorer reading and spelling scores and lower teacher-perceived school performance.
The available evidence does not suggest that cannabis causes structural anatomical defects in humans. In one large study, female cannabis users who had newborns with severe birth defects were not statistically significantly more likely to have this possibility. However, the study did not address the timing of cannabis exposure during pregnancy. A later study looked at cases of cannabis use during the month before pregnancy or during the first three months of pregnancy, with non-users serving as a control group. There were no significant differences in the likelihood of occurrence for the 20 major anomalies examined between users and non-users.
However, when the analysis was restricted to cannabis use in the first month of pregnancy, the chance of anencephaly in the offspring of users increased significantly to 2.5 (95% confidence interval [CI]). However, this finding may be confounded by the independent fact that female cannabis users are less likely to take supplemental folic acid than non-users, as well as the aforementioned problem of multiple comparisons and the possibility of a type I error (incorrect rejection of the null hypothesis).
Current evidence does not suggest an association between marijuana use in pregnancy and perinatal mortality, although the risk of stillbirth may be slightly increased. A meta-analysis of 31 observational and case-control studies evaluating neonatal outcomes in female marijuana users versus non-users examined perinatal death and stillbirth as secondary outcomes. Compared with nonusers, cannabis users had similar rates of perinatal death (relative risk [RR], 1.09; 95% CI, 0.62-1.91) but somewhat higher rates of stillbirth (RR, 1.74; 95% CI, 1.03-2.93). The latter findings should be interpreted with caution because these results could not be adjusted for tobacco use, and in this study, the significant associations between marijuana use and other adverse outcomes tended to become statistically insignificant when the adjusted estimates were pooled. Support for this interpretive approach is provided by a report included in the meta-analysis that found THC to be significantly associated with stillbirth at or after 20 weeks' gestation, although this finding remains somewhat confounded by the effect of cigarette smoking 33. In this context, it should be noted that THC is significantly associated with stillbirth during or after pregnancy, although this finding is confounded by the effects of cigarette smoking.
Several studies have evaluated neonatal birth weight and a number of other biometric parameters after in utero exposure to marijuana. The primary outcome of this analysis was birth weight less than 2 500 g. Cannabis use alone was not associated with an increased risk of birth weight less than 2 500 g. However, when cannabis use alone was assessed by frequency of use, women who used cannabis less than once a week were not at increased risk of delivering a newborn weighing less than 2 500 g (8.8% versus 6.7%). However, women who used cannabis at least once a week during pregnancy were significantly more likely to give birth to a newborn weighing less than 2 500 g (11.2% versus 6.7%). A recent retrospective cohort study, which was not considered in the meta-analysis, found a slightly increased risk of birth weight below the 10th percentile among cannabis users after adjustment for confounders among non-tobacco users (16.3% versus 9.6%) and tobacco users (20.2% versus 14.8%). Several studies reported statistically significantly smaller birth length and head circumference as well as lower birth weight in exposed offspring. These findings were more pronounced in women who used more cannabis, especially in the first and second trimesters. However, the clinical relevance of these observations remains uncertain.
Another primary outcome of the above cited meta-analysis was preterm birth before 37 weeks of gestation. Compared with women using cannabis less frequently, those using it at least once a week had an increased risk of preterm birth (10.4% versus 5.7%). When assessing cannabis use with concurrent tobacco use, cannabis use alone was not associated with an increased risk of preterm birth, but use of both substances together was associated compared with women who used neither substance (11.4% versus 5.7%). Where women used cannabis, the risk of preterm birth was higher than for women who did not use either substance. Similarly, a retrospective cohort study published at the same time as the meta-analysis also found that the risk of preterm birth in cannabis users was only observed in women who also used tobacco. Concomitant tobacco use may therefore be an important mediator of some adverse pregnancy outcomes in cannabis users. It is worth noting that in another report, no increase in the likelihood of preterm birth was observed in cannabis users regardless of reported tobacco use.
Although the data on cannabis use during pregnancy have limitations - animals are often poor surrogates and human studies are often heavily influenced by multiple substance use and lifestyle issues - some worrying findings are emerging. Given the risk of impaired neurodevelopment and exposure of mother and foetus to the adverse effects of smoking, pregnant women or women considering pregnancy should discontinue marijuana use. As the effects of cannabis use can be as severe as those of cigarette smoking or alcohol consumption, it should be avoided during pregnancy. All women should be asked about their use of tobacco, alcohol and other drugs, including cannabis and non-medical drugs, before becoming pregnant and early in pregnancy. Women who report using cannabis should be advised of the dangers of the possible adverse health consequences of use during pregnancy. Patients should be informed that the purpose of screening is to enable a woman to receive treatment, not to punish or prosecute her. However, patients should also be informed of the possible consequences of a positive screening result, including any mandatory reporting. Seeking obstetric-gynaecological care should not expose a woman to criminal or civil penalties for cannabis use, such as incarceration, involuntary commitment of a child to foster care or loss of housing. Addiction is a chronic, relapsing biological and behavioral disorder with genetic components, and cannabis use can be addictive for some individuals.
Effect of marijuana use on breastfeeding
More data are needed to assess the effect of cannabis use on infants during lactation and breastfeeding. In the absence of such data, the use of cannabis during breastfeeding is not recommended. Breastfeeding women should be aware that the potential risks of exposure to cannabis metabolites are unknown. Therefore, they should discontinue use.
Medical cannabis
There are currently no officially approved indications, contraindications, precautions or recommendations for the use of cannabis during pregnancy and breastfeeding. Similarly, there are no standardised formulations, dosages or routes of administration. Smoking, which is the most common method of cannabis use, cannot be medically recommended during pregnancy and breastfeeding. Women who are pregnant or considering pregnancy should also discontinue the use of cannabis for medical reasons and try treatments for which there is better evidence of safety during pregnancy. High-quality studies on the effects of cannabis and cannabis products on pregnancy and breastfeeding need to be conducted.
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