DALLAS (FRONTLINE MEDICAL NEWS) Marijuana use in adolescent mothers was associated with multiple adverse outcomes, including increased risk for stillbirth and preterm birth. Also, hypertensive disorders of pregnancy were higher in marijuana users, according to a study that incorporated universal urine toxicology testing of adolescents.

The study compared maternal and fetal/neonatal outcomes in 211 marijuana-exposed with 995 unexposed pregnancies. Christina Rodriguez, MD, and her coinvestigators found that the risk of a composite adverse pregnancy outcome was higher in marijuana users, occurring in 97/211 marijuana users (46%), and in 337/995 (33.9%) of the non–marijuana users (P less than .001).

Dr. Rodriguez said that since it used biological samples to confirm marijuana exposure, the study helps fill a gap in the literature. She presented the retrospective cohort study at the meeting sponsored by the Society for Maternal-Fetal Medicine.

Previous work, she said, had established that up to 70% of pregnant women who had positive tests for tetrahydrocannabinol also denied marijuana use. “If marijuana use is determined by self-report, some women are misclassified as nonusers,” making it difficult to ascertain the true association between marijuana use during pregnancy and pregnancy outcomes, said Dr. Rodriguez of the University of Colorado, Denver.

Whether marijuana is associated with adverse pregnancy outcomes is an increasingly pressing question given rapidly shifting legislation, said Dr. Rodriguez. “In a state with legal access to marijuana, use is common in adolescent pregnancies,” she said.

Participants who were enrolled in prenatal care through the University of Colorado’s adolescent maternity program, where Dr. Rodriguez is a fellow, and who delivered at the University of Colorado Hospital, Aurora, were eligible to participate; adolescents were excluded for multiple gestation and for known major fetal anomalies or aneuploidy.

In addition to urine toxicology testing, participants also completed a uniformly administered substance use questionnaire. Marijuana exposure was defined as either having a positive urine toxicology result or self-reported marijuana use on the questionnaire (or both). Of the marijuana-exposed pregnancies, 133 (63%) of the adolescents tested positive on urine toxicology, 18 (9%) were positive by self-report, and 60 (28%) had both positive marijuana urine toxicology and positive self-report. Toxicology was available for 91% of participants.

Participants were negative for marijuana exposure if they had a negative toxicology screen, regardless of their response on the substance-use questionnaire.

The study’s primary outcome was a composite of adverse pregnancy outcomes, including stillbirth, defined as Apgar score of 0; any hypertensive disorder of pregnancy, including gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count); preterm birth, defined as spontaneous delivery before 37 weeks gestation; and infants born small for gestational age, defined as a birth weight below the 10th percentile after adjustment for gestational age and sex.

Secondary outcomes included pregnancy outcomes including placental abruption, mode of delivery, and gestational age at delivery. Neonatal outcomes included weight, length, and head circumference at birth, and neonatal intensive care unit admission. An Apgar score less than 7 at 5 minutes was considered an adverse neonatal outcome.

The sample size was determined by an estimate drawn from previous chart abstraction that the composite outcome would be seen in 16% of the clinic’s non–marijuana exposed patients, and 24% of the marijuana-exposed patients. The investigators also factored in that 18% of adolescents in the clinic database were marijuana users.

Dr. Rodriguez and her collaborators used a variety of models for statistical analysis, some of which included self-report alone or in conjunction with urine toxicology. In the end, they found that significant associations between their composite endpoint and marijuana use were seen when patients were dichotomized into those who had at least one positive urine toxicology test, versus those who had no positive toxicology results.

One of the study limitations was that the study didn’t permit investigators to get accurate information about the quantity, timing, or route of marijuana dosing. Also, this methodology may primarily identify heavier marijuana users, said Dr. Rodriguez.

Tobacco use was determined only by self-report, and outcomes were followed over a relatively short period of time.

Still, said Dr. Rodriguez, the study had many strengths, including the use of biological sampling to determine exposure and the near-universal participant urine toxicology testing. The investigators were able to capture and account for many important factors that could confound the results, she said. “Uncertainty regarding the impact of [marijuana] on pregnancy outcomes in the literature may result from incomplete ascertainment of exposure,” she and her coinvestigators wrote in the abstract accompanying the presentation.

SOURCE: Rodriguez C et al. Am J Obstet Gynecol. 2018 Jan;218:S37 .


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