TY - JOUR
T1 - Additive drug-specific and sex-specific risks associated with co-use of marijuana and tobacco during pregnancy
T2 - Evidence from 3 recent developmental cohorts (2003–2015)
AU - Massey, Suena H.
AU - Mroczek, Daniel K.
AU - Reiss, David
AU - Miller, Emily S.
AU - Jakubowski, Jessica A.
AU - Graham, Eileen K.
AU - Shisler, Shannon M.
AU - McCallum, Meaghan
AU - Huestis, Marilyn A.
AU - Ganiban, Jody M.
AU - Shaw, Daniel S.
AU - Leve, Leslie D.
AU - Eiden, Rina D.
AU - Stroud, Laura R.
AU - Neiderhiser, Jenae M.
N1 - Funding Information:
This work was supported by a 2017 Innovation Award (PI Suena Massey) from the Dixon Translational Research Grants Initiative of the Northwestern Memorial Foundation, grants K23DA037913 (PI Suena Massey); R01 DA020585 (PI Jenae Neiderhiser); R01DA019632 (PI Rina Eiden); R01 DA044504, R01 DA031188, and R01DA019558 (PI Laura Stroud); and intramural support (Marilyn Huestis) from the National Institute on Drug Abuse (NIDA); grant R01HD042608 (PI David Reiss Years 1–5; PI Leslie Leve Years 6–10) from the National Institute on Child Health and Human Development; grant R01 MH092118 (Multiple PIs Leslie Leve and Jenae Neiderhiser) from the National Institute of Mental Health (NIMH); grant R01AG018436 (PI Daniel Mroczek) from the National Institute on Aging (NIA); and grant UG3OD023389 (Multiple PIs Leslie Leve, Jenae Neiderhiser, and Jody Ganiban) from the Office of the Director (OD) of the National Institutes of Health (NIH). Responsibility for this work rests solely with the authors. The NIDA (Extramural and Intramural Divisions), NICHD, NIMH, NIA, OD, and NIH had no role in the study design, data collection, analysis or interpretation of the data, or the decision to submit this manuscript for publication.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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.
AB - 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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U2 - 10.1016/j.ntt.2018.06.002
DO - 10.1016/j.ntt.2018.06.002
M3 - Article
C2 - 29886244
AN - SCOPUS:85048995546
SN - 0892-0362
VL - 68
SP - 97
EP - 106
JO - Neurotoxicology and Teratology
JF - Neurotoxicology and Teratology
ER -