Cannabis Use During Pregnancy Rising, but Likely Unsafe

Tara Haelle

June 18, 2019

Self-reported cannabis use has risen considerably among pregnant women in the United States even as Canadian research reveals that such use comes with greater risk of preterm birth and several other poor perinatal and neonatal outcomes, two new studies suggest. On the other hand, a slight protective effect from cannabis use appeared to exist for preeclampsia and gestational diabetes.

The study and research letter on cannabis use during pregnancy were published online today in JAMA.

"These two studies send a straightforward message: cannabis use in pregnancy is likely unsafe; with an increasing prevalence of use (presumably related to growing social acceptability and legalization in many states), its potential for harm may represent a public health problem," write Michael Silverstein, MD, MPH, of Boston University School of Medicine, and two colleagues in an accompanying editorial.

"This message is based on the sound, if imperfect, epidemiology of these two studies and is heightened by a misperception that marijuana is safe, as evidenced by its direct marketing to pregnant women for morning sickness despite accumulating evidence of harm," they continue.

In a research letter on US prevalence, Nora D. Volkow, MD, of the National Institute on Drug Abuse in Bethesda, Maryland, and colleagues analyzed data from women aged 12 to 44 years who participated in the 2002-2017 National Surveys on Drug Use and Health (NSDUH), which had an annual mean response rate of 63.6%. They adjusted findings on the frequency and type of cannabis use in the past month for age, race/ethnicity, and family income.

Among 467,100 pregnant and nonpregnant respondents, prevalence of daily and past-month cannabis use and total days of use increased from 2002-2017. The proportion of pregnant women who used cannabis in the past month doubled from 3.4% in 2002-2003 to 7% in 2016-2017. First trimester use was more common than use in the second and third trimesters and more than doubled from 5.7% to 12.1% during that time.

Prevalence tripled for pregnant women's use of daily or near-daily cannabis use in the past month, from 0.9% to 3.4%. Substantial increases in daily use occurred across all three trimesters: from 1.8% to 5.3% in the first trimester, from 0.6% to 2.5% in the second, and from 0.5% to 2.5% in the third.

The average number of days pregnant women used cannabis in the past month rose from 0.4 days to 1.1 days, with increases in all three trimesters. Only 0.5% of both pregnant and nonpregnant women reported using cannabis only for doctor-recommended medical reasons in the previous month between 2013-2017.

Outcomes Data Suggest Risk

In the second study, which focused on outcomes associated with cannabis use during pregnancy, Daniel J. Corsi, PhD, of Ottawa Hospital Research Institute in Ontario, Canada, and colleagues analyzed data from live births and stillbirths among women at least 15 years old in Ontario from April 2012 to December 2017.

"The risk of preterm birth associated with cannabis exposure was statistically significant in subgroups of women who only used cannabis and no other substances, and among women using tobacco," they report.

Though preterm birth was the primary outcome, the authors also investigated 10 other maternal, perinatal, and neonatal outcomes among the 661,617 mothers in the study, 1.4% of whom reported cannabis use during pregnancy.

Before adjustment, the rate of preterm births (< 37 weeks) was 12% among cannabis users and 6.1% in nonusers. Yet significant differences existed between users and nonusers in terms of maternal age, parity, income, pre-pregnancy body mass index, maternal smoking, alcohol use, opioid use, psychiatric disorders, prenatal care, and birth year.

After the authors matched 5639 women who used cannabis to 92,873 nonusers to address the population differences, the risk difference (RD) of overall preterm birth was 2.98% (10.2% vs 7.2%) among those exposed to cannabis (relative risk [RR], 1.41; 95% confidence interval [CI], 1.36 - 1.47).

The RR for progressively earlier preterm birth was greater for prenatal cannabis exposure even as the absolute RD decreased. A decreasing number of cases for earlier preterm birth likely accounted for this divergence. For example, the RR of preterm birth at 34 to 36 6/7 weeks was 1.86, while the absolute RD was 4%. But the RR at 32 to 33 6/7 weeks and 28 to 31 6/7 weeks was 2.4 and 3.09, respectively, with absolute RD of 0.9 and 1, respectively.

Infants born small for gestational age, defined as those in the third percentile or lower, were also significantly more frequent among mothers in the matched cohort who used cannabis (6.1%) compared with those who didn't (4.0%; RR, 1.53). Other significant associations with cannabis use included placental abruption (1.6% in users vs 0.9% in nonusers; RR, 1.72), need for NICU (19.3% vs 13.8%; RR 1.40), and 5-minute Apgar scores below 4 (1.1% vs 0.9%; RR, 1.28).

Meanwhile, preeclampsia risk in the matched cohort was 10% lower (RR, 0.90; RD, –0.46%) and unadjusted gestational diabetes risk 9% lower (RR, 0.91; RD, –0.41%) with cannabis use relative to nonuse.

Context Key, Experts Say

Though these findings effectively illuminate the prevalence of cannabis use during pregnancy and the risks associated with it, the results must be considered within the greater context of understanding the limitations of this type of research and the lessons learned from previous research into alcohol and cocaine use during pregnancy, the editorialists write.

In addition to the usual confounding risks of epidemiological cohort studies, the Canadian outcomes study is "further limited by use of registry data, derived primarily from clinical encounters, to assess cannabis exposure," they write. The study lacked data on when cannabis was used during pregnancy, birthweight data, and any data for assessing a dose-response relationship.

"One lesson of the current alcohol debate — which is often couched in terms of women's ability to enjoy wine with dinner and thus assumes the perception of an issue that predominantly affects the privileged — is that two reasonable perspectives can be applied to the same body of literature and reach opposing, nonstigmatizing conclusions," write Silverstein and his colleagues. "In other words, the issue is not the data but the values that individuals bring to the data and to whom the data are thought to be most relevant."

Considering this with the cannabis use findings, some may perceive "41% increased relative risk of preterm birth as unacceptably high" while others may see the absolute increased risk of 2.98% a worthwhile tradeoff if cannabis use enhances relaxation or improves morning sickness during pregnancy.

Or, the findings may have greater relevance at the population level rather than an individual level, with implications more closely linked to the 1980s' "fundamentally flawed" studies on cocaine use during pregnancy than to alcohol use findings, the editorial authors write. Those studies led to alarmism and exaggeration of perinatal and neonatal risks of prenatal cocaine exposure given that later research found long-term outcomes among these predominantly minority children to be similar to unexposed, demographically similar children. Exacerbated by stereotype, stigma, judgment and use of terms like "cocaine mother" and "crack baby," "the exaggerated dialogue on cocaine did little to shed light on the sequelae of urban poverty and legacy of racism in the United States," they write.

Yet the editorial authors acknowledge that neither comparison, with alcohol or cocaine, is perfectly analogous. Whereas the cocaine research led to hyperbole, a "false perception of safety" has infused discussion of cannabis.

Still, "it is impossible to separate data from the values that individuals bring to those data, no group is immune to the judgment of others, and women and minority groups (particularly pregnant women of color) tend to bear the greatest burden of many of these judgments," Silverstein and his colleagues write. Epidemiological research findings will not solve those problems or combat the implicit biases that infect interpretation of the findings.

"The current data reported by Corsi et al and Volkow et al should spark genuine concern about the association of cannabis use in pregnancy with preterm birth," the editorial authors concluded. "However, there should be additional concern about whether such findings may ripple through society and re-create some of the mistakes of the past."

The research letter on self-reported cannabis use was funded by the National Institute on Drug Abuse and the Substance Abuse and Mental Health Services Administration of the US Department of Health and Human Services. One author has stock ownership in General Electric Co, 3M Co, and Pfizer Inc. The outcomes study was funded by the Canadian Institutes of Health Research. The letter, study, and editorial authors disclosed no relevant financial relationships.

JAMA. Published online June 18, 2019. Abstract, Letter, Editorial

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