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Neurotoxicol Teratol. 2018 Jul - Aug;68:97-106. doi: 10.1016/j.ntt.2018.06.002. Epub 2018 Jun 7.

Additive drug-specific and sex-specific risks associated with co-use of marijuana and tobacco during pregnancy: Evidence from 3 recent developmental cohorts (2003-2015).

Author information

1
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Suite 1000, Chicago, IL 60611, USA; Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, 633 N Saint Clair, 19th Floor, Chicago, IL 60611, USA. Electronic address: suena.massey@northwestern.edu.
2
Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, 633 N Saint Clair, 19th Floor, Chicago, IL 60611, USA. Electronic address: daniel.mroczek@northwestern.edu.
3
Yale Child Study Center, Yale University, 230 South Frontage Rd., New Haven, CT 06519, USA. Electronic address: david.reiss@yale.edu.
4
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Suite 1000, Chicago, IL 60611, USA; Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Northwestern University Feinberg School of Medicine, 250 E. Superior Street, 05-2175, Chicago, IL 60611, USA. Electronic address: emily-miller-1@northwestern.edu.
5
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 676 N Saint Clair, Suite 1000, Chicago, IL 60611, USA. Electronic address: j-jakubowkski@northwestern.edu.
6
Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, 633 N Saint Clair, 19th Floor, Chicago, IL 60611, USA. Electronic address: eileen.graham@northwestern.edu.
7
Research Institute on Addictions, University at Buffalo, State University of New York, 1021 Main Street, Buffalo, NY 14203-1016, USA. Electronic address: sshisler@ria.buffalo.edu.
8
Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Box G-A1, Providence, RI 02912, USA. Electronic address: meaghan.mccallum@lifespan.org.
9
Institute for Emerging Health Professions, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: marilyn.huestis@gmail.com.
10
George Washington University Columbian College of Arts and Sciences, 2125 G Street, NW, Room 308, Washington, DC 20052, USA. Electronic address: ganiban@gwu.edu.
11
Department of Psychology, University of Pittsburgh, 4101 Sennott Square, 3rd Floor, Pittsburgh, PA 15260, USA. Electronic address: casey@pitt.edu.
12
Department of Counseling Psychology and Human Services, College of Education 6217, University of Oregon, Eugene, OR 97403, USA. Electronic address: leve@uoregon.edu.
13
Research Institute on Addictions, University at Buffalo, State University of New York, 1021 Main Street, Buffalo, NY 14203-1016, USA. Electronic address: eiden@ria.buffalo.edu.
14
Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Box G-A1, Providence, RI 02912, USA; The Miriam Hospital Centers for Behavioral and Preventive Medicine, Coro West, 164 Summit Ave, Suite 309, Providence, RI 02906, USA. Electronic address: laura_stroud@brown.edu.
15
Department of Psychology, The Pennsylvania State University, 411 Moore Building, University Park, PA 16801, USA. Electronic address: jenaemn@psu.edu.

Abstract

BACKGROUND:

Methodologic challenges related to the concomitant use (co-use) of substances and changes in policy and potency of marijuana contribute to ongoing uncertainty about risks to fetal neurodevelopment associated with prenatal marijuana use. In this study, we examined two biomarkers of fetal neurodevelopmental risk-birth weight and length of gestation-associated with prenatal marijuana use, independent of tobacco (TOB), alcohol (ALC), other drug use (OTH), and socioeconomic risk (SES), in a pooled sample (N = 1191) derived from 3 recent developmental cohorts (2003-2015) with state-of-the-art substance use measures. We examined differential associations by infant sex, and multiplicative effects associated with co-use of MJ and TOB.

METHODS:

Participants were mother-infant dyads with complete data on all study variables derived from Growing Up Healthy (n = 251), Behavior and Mood in Babies and Mothers (Cohorts 1 and 2; n = 315), and the Early Growth and Development Study (N = 625). We estimated direct effects on birth weight and length of gestation associated with MJ, TOB, and co-use (MJ x TOB), using linear regression analysis in the full sample, and in male (n = 654) and female (n = 537) infants, separately.

RESULTS:

Mean birth weight and length of gestation were 3277 g (SD = 543) and 37.8 weeks (SD = 2.0), respectively. Rates of prenatal use were as follows: any use, n = 748 (62.8%); MJ use, n = 273 (22.9%); TOB use, n = 608 (51.0%); co-use of MJ and TOB, n = 230 (19.3%); ALC use, n = 464 (39.0%); and OTH use n = 115 (9.7%.) For all infants, unique effects on birth weight were observed for any MJ use [B(SE) = -84.367(38.271), 95% C.I. -159.453 to -9.281, p = .028], any TOB use [B(SE) = -0.99.416(34.418), 95% C.I. -166.942 to -31.889, p = .004], and each cigarette/day in mean TOB use [B(SE) = -12.233(3.427), 95% C.I. -18.995 to -5.510, p < .001]. Additional effects of co-use on birth weight, beyond these drug-specific effects, were not supported. In analyses stratified by sex, while TOB use was associated with lower birth weight in both sexes, MJ use during pregnancy was associated with lower birth weight of male infants [B(SE) = -153.1 (54.20); 95% C.I. -259.5 to -46.7, p = .005], but not female infants [B(SE) = 8.3(53.1), 95% C.I. -96.024 to 112.551, p = .876]. TOB, MJ, and their co-use were not associated with length of gestation.

CONCLUSIONS:

In this sample, intrauterine co-exposure to MJ and TOB was associated with an estimated 18% reduction in birth weight not attributable to earlier delivery, exposure to ALC or OTH drugs, nor to maternal SES. We found evidence for greater susceptibility of male fetuses to any prenatal MJ exposure. Examination of dose-dependence in relationships found in this study, using continuous measures of exposure, is an important next step. Finally, we underscore the need to consider (a) the potential moderating influence of fetal sex on exposure-related neurodevelopmental risks; and (b) the importance of quantifying expressions of risk through subtle alterations, rather than dichotomous outcomes.

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