Epidemiological studies (human studies with plant cannabinoids)
A systematic review of cohort studies found that cannabis use during pregnancy is associated with clinically unimportant lower birth weights (growth differences of approximately 100 g), but no differences in preterm births or congenital anomalies (Zhang et al., 2017).
In a study of 170 births only 3 (1.9 %) tested positive for cannabis at the time of delivery. Cannabis use was not related to incidence of low birth weight (13.8 % vs 14.0 %, p = 1.00), preterm delivery (17.7 % vs 12.0 %, p = 0.325), or NICU admissions (25.5 % vs 15.8 %, p = 0.139)(Mark et al., 2016).
In a birth cohort study with 3692 participants, maternal cannabis use increased the risk of psychotic-like experiences in the offspring (ORadjusted = 1.38, 95% CI 1.03-1.85). Estimates were comparable for maternal cannabis use exclusively before pregnancy versus continued cannabis use during pregnancy. Paternal cannabis use was similarly associated with offspring psychotic-like experiences (ORadjusted = 1.44, 95% CI 1.14-1.82). Both maternal and paternal cannabis use were associated with more offspring psychotic-like experiences at age ten years. This may suggest that common aetiologies, rather than solely causal intra-uterine mechanisms, underlie the association between parental cannabis use and offspring psychotic-like experiences. These common backgrounds most likely reflect genetic vulnerabilities and shared familial mechanisms, shedding a potential new light on the debated causal path from cannabis use to psychotic-like phenomena (Bolhuis et al., 2018).
In a survey among 3164 black urban women alcohol, cigarette and cocaine, but not cannabis use was found to negatively impact gestational age at delivery. However, alcohol, cigarette and to a lesser extend cannabis (but not cocaine) use negatively affected birth weight. Especially heavy substance use in older women had a strong negative effect on birth weight (Janisse et al., 2014).
In a study among 3207 pregnant women in Colorado (2014-2015) the self-reported prevalence of cannabis use at any time during pregnancy was 5.7 ± 0.5% and the prevalence of early postnatal cannabis use among women who breastfed was 5.0% (95% CI, 4.1%-6.2%). Prenatal cannabis use was associated with a 50% increased likelihood of low birth weight, independent of maternal age, race/ethnicity, level of education, and tobacco use during pregnancy (OR, 1.5; 95% CI, 1.1-2.1; P = .02). Small for gestational age, preterm birth, and neonatal intensive care unit admission were not associated with prenatal cannabis use, independent of prenatal tobacco use (Crume et al., 2018).
A systematic review found that there is insufficient evidence to conclude on any effect on the stillbirth rate. Although there are some reports of a slight increase in the rate of prematurity, most reports do not support this effect. Cannabis does not appear to be a major teratogen; however, a small increased risk for some congenital birth defects may be associated with early pregnancy use (Merlob et al., 2017).
In a cohort study maternal cannabis use was identified in 2.7% (unweighted frequency 48/1610) of live births. Use was self-reported by 1.6% (34/1610) and detected by 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid in cord homogenate for 1.9% (17/897), n = 3 overlapping. Rate of tobacco use was 12.9% (217/1610), with 10.7% (167/1607) by self-report and 9.5% (141/1313) by serum cotinine. The composite adverse pregnancy outcome was not significantly increased in women with cannabis use compared to nonusers (31.2% vs 21.2%; P = .14). After adjustment for tobacco, clinical, and socioeconomic factors, cannabis use was not associated with the composite adverse pregnancy outcome (adjusted odds ratio, 1.29; 95% confidence interval, 0.56-2.96). Similarly, among women with umbilical cord homogenate and serum cotinine data (n = 765), cannabis use was not associated with adverse pregnancy outcomes (adjusted odds ratio, 1.02; 95% confidence interval, 0.18-5.66). Neonatal intensive care unit admission rates were not statistically different between groups (16.9% users vs 9.5% nonusers, P = .12). Composite neonatal morbidity or death was more frequent among neonates of mothers with cannabis use compared to nonusers (14.1% vs 4.5%; P = .002). In univariate comparisons, the components of the composite outcome that were more frequent in neonates of cannabis users were infection morbidity (9.8% vs 2.4%; P < .001) and neurologic morbidity (1.4% vs 0.3%; P = .002). After adjustment for tobacco, race, and other illicit drug use, cannabis use was still associated with composite neonatal morbidity or death (adjusted odds ratio, 3.11; 95% confidence interval, 1.40-6.91). Thus, maternal cannabis use was not associated with a composite of small for gestational age, spontaneous preterm birth, or hypertensive disorders of pregnancy. However, it was associated with an increased risk of neonatal morbidity (Metz et al., 2017).
In a study with 6107 nonusers and 361 cannabis users, after adjustment for maternal age, race, parity, body mass index and no prenatal care, we found higher rates of small for gestational age (aOR 1.30 (95% CI 1.03 to 1.62)) and neonatal intensive care unit admission (aOR 1.54 (1.14 to 2.07)) in women who were not tobacco users. Other obstetrical outcomes including preterm delivery and fetal anomalies were not increased with maternal marijuana use (Warshak et al., 2015).
In a cohort of 661 617 women, the mean gestational age was 39.3 weeks and 51% of infants were male. Mothers had a mean age of 30.4 years and 9427 (1.4%) reported cannabis use during pregnancy. Imbalance in measured maternal obstetrical and sociodemographic characteristics between reported cannabis users and nonusers was attenuated using matching, yielding a sample of 5639 reported users and 92 873 nonusers. The crude rate of preterm birth less than 37 weeks' gestation was 6.1% among women who did not report cannabis use and 12.0% among those reporting use in the unmatched cohort (RD, 5.88% [95% CI, 5.22%-6.54%]). In the matched cohort, reported cannabis exposure was significantly associated with an RD of 2.98% (95% CI, 2.63%-3.34%) and an RR of 1.41 (95% CI, 1.36-1.47) for preterm birth. Compared with no reported use, cannabis exposure was significantly associated with greater frequency of small for gestational age (third percentile, 6.1% vs 4.0%; RR, 1.53 [95% CI, 1.45-1.61]), placental abruption (1.6% vs 0.9%; RR, 1.72 [95% CI, 1.54-1.92]), transfer to neonatal intensive care (19.3% vs 13.8%; RR, 1.40 [95% CI, 1.36-1.44]), and 5-minute Apgar score less than 4 (1.1% vs 0.9%; RR, 1.28 [95% CI, 1.13-1.45])(Corsi et al., 2019).
In a study among 13545 French women, 1.2% of women reported having used cannabis during pregnancy. This percentage was higher among younger women, women living alone, or women who had a low level of education or low income. It was also associated with tobacco use and drinking alcohol. Cannabis users had higher rates of spontaneous preterm births: 6.4 versus 2.8%, for an adjusted odds ratio (aOR) of 2.15 (95% CI 1.10-4.18). The corresponding aOR was 2.64 (95% CI 1.12-6.22) among tobacco smokers and 1.22 (95% CI 0.29-5.06) among non-tobacco smokers (Saurel-Cubizolles et al., 2014).
In a study of 35 pregnancies, infants from cannabis users exhibited significantly more meconium staining (57%, versus 25% in nonusers). Significant differences in duration of labor were also observed (Greenland et al., 1982).
A study among 4077 children found that gestational exposure to cannabis is associated with behavioral problems in early childhood but only in girls and only in the area of increased aggressive behavior (B=2.02; 95% CI: 0.30-3.73; p=0.02) and attention problems (B=1.04; 95% CI: 0.46-1.62; p<0.001). Furthermore, this study showed that long-term (but not short term) tobacco exposure was associated with behavioral problems in girls (B=1.16; 95% CI: 0.20-2.12; p=0.02). There was no association between cannabis use of the father and child behavior problems (El Marroun et al., 2011).
In a systematic review, women who used cannabis during pregnancy had an increase in the odds of anaemia (pooled OR (pOR)=1.36: 95% CI 1.10 to 1.69) compared with women who did not use cannabis during pregnancy. Infants exposed to cannabis in utero had a decrease in birth weight (low birth weight pOR=1.77: 95% CI 1.04 to 3.01; pooled mean difference (pMD) for birth weight=109.42 g: 38.72 to 180.12) compared with infants whose mothers did not use cannabis during pregnancy. Infants exposed to cannabis in utero were also more likely to need placement in the neonatal intensive care unit compared with infants whose mothers did not use cannabis during pregnancy (pOR=2.02: 1.27 to 3.21)(Gunn et al., 2016).
In a cohort study among 344 Aboriginal women 1 in 5 women (20.5%) used cannabis during pregnancy, and 52% smoked cigarettes. Compared with mothers not using cannabis or cigarettes, mothers using cannabis had babies on average 565 g lighter (95% CI -762 to -367), and were more likely to have infants with a low birth weight (OR=6.5, 95% CI 3.0 to 14.3), and small for gestational age (OR=3.8, 95% CI 1.9 to 7.6). Controlling for education and other social characteristics, including stressful events/social health issues did not alter the conclusion that mothers using cannabis experience a higher risk of negative birth outcomes (adjusted OR for odds of low birth weight 3.9, 95% CI 1.4 to 11.2)(Brown et al., 2016).
Bolhuis, K., Kushner, S.A., Yalniz, S., Hillegers, M.H.J., Jaddoe, V.W.V., Tiemeier, H., and El Marroun, H. (2018). Maternal and paternal cannabis use during pregnancy and the risk of psychotic-like experiences in the offspring. Schizophr. Res. 202, 322–327.
Brown, S.J., Mensah, F.K., Ah Kit, J., Stuart-Butler, D., Glover, K., Leane, C., Weetra, D., Gartland, D., Newbury, J., and Yelland, J. (2016). Use of cannabis during pregnancy and birth outcomes in an Aboriginal birth cohort: a cross-sectional, population-based study. BMJ Open 6, e010286.
Corsi, D.J., Walsh, L., Weiss, D., Hsu, H., El-Chaar, D., Hawken, S., Fell, D.B., and Walker, M. (2019). Association Between Self-reported Prenatal Cannabis Use and Maternal, Perinatal, and Neonatal Outcomes. JAMA.
Crume, T.L., Juhl, A.L., Brooks-Russell, A., Hall, K.E., Wymore, E., and Borgelt, L.M. (2018). Cannabis Use During the Perinatal Period in a State With Legalized Recreational and Medical Marijuana: The Association Between Maternal Characteristics, Breastfeeding Patterns, and Neonatal Outcomes. J. Pediatr. 197, 90–96.
El Marroun, H., Hudziak, J.J., Tiemeier, H., Creemers, H., Steegers, E.A.P., Jaddoe, V.W.V., Hofman, A., Verhulst, F.C., van den Brink, W., and Huizink, A.C. (2011). Intrauterine cannabis exposure leads to more aggressive behavior and attention problems in 18-month-old girls. Drug Alcohol Depend. 118, 470–474.
Greenland, S., Staisch, K.J., Brown, N., and Gross, S.J. (1982). Effects of marijuana on human pregnancy, labor, and delivery. Neurobehav. Toxicol. Teratol. 4, 447–450.
Gunn, J.K.L., Rosales, C.B., Center, K.E., Nuñez, A., Gibson, S.J., Christ, C., and Ehiri, J.E. (2016). Prenatal exposure to cannabis and maternal and child health outcomes: a systematic review and meta-analysis. BMJ Open 6, e009986.
Janisse, J.J., Bailey, B.A., Ager, J., and Sokol, R.J. (2014). Alcohol, tobacco, cocaine, and marijuana use: relative contributions to preterm delivery and fetal growth restriction. Subst. Abuse 35, 60–67.
Mark, K., Desai, A., and Terplan, M. (2016). Marijuana use and pregnancy: prevalence, associated characteristics, and birth outcomes. Arch. Womens Ment. Health 19, 105–111.
Merlob, P., Stahl, B., and Klinger, G. (2017). For Debate: Does Cannabis Use by the Pregnant Mother Affect the Fetus and Newborn? Pediatr. Endocrinol. Rev. PER 15, 4–7.
Metz, T.D., Allshouse, A.A., Hogue, C.J., Goldenberg, R.L., Dudley, D.J., Varner, M.W., Conway, D.L., Saade, G.R., and Silver, R.M. (2017). Maternal marijuana use, adverse pregnancy outcomes, and neonatal morbidity. Am. J. Obstet. Gynecol. 217, 478.e1-478.e8.
Saurel-Cubizolles, M.-J., Prunet, C., and Blondel, B. (2014). Cannabis use during pregnancy in France in 2010. BJOG Int. J. Obstet. Gynaecol. 121, 971–977.
Warshak, C.R., Regan, J., Moore, B., Magner, K., Kritzer, S., and Van Hook, J. (2015). Association between marijuana use and adverse obstetrical and neonatal outcomes. J. Perinatol. Off. J. Calif. Perinat. Assoc. 35, 991–995.
Zhang, A., Marshall, R., and Kelsberg, G. (2017). Clinical Inquiry: What effects--if any--does marijuana use during pregnancy have on the fetus or child? J. Fam. Pract. 66, 462–466.