Prenatal cannabis exposure and childhood outcomes: Results from the ABCD study (original) (raw)
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Associations Between Prenatal Cannabis Exposure and Childhood Outcomes
JAMA Psychiatry
In light of increasing cannabis use among pregnant women, the US Surgeon General recently issued an advisory against the use of marijuana during pregnancy. OBJECTIVE To evaluate whether cannabis use during pregnancy is associated with adverse outcomes among offspring. DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, data were obtained from the baseline session of the ongoing longitudinal Adolescent Brain and Cognitive Development Study, which recruited 11 875 children aged 9 to 11 years, as well as a parent or caregiver, from 22 sites across the United States between June 1, 2016, and October 15, 2018. EXPOSURE Prenatal cannabis exposure prior to and after maternal knowledge of pregnancy. MAIN OUTCOMES AND MEASURES Symptoms of psychopathology in children (ie, psychotic-like experiences [PLEs] and internalizing, externalizing, attention, thought, and social problems), cognition, sleep, birth weight, gestational age at birth, body mass index, and brain structure (ie, total intracranial volume, white matter volume, and gray matter volume). Covariates included familial (eg, income and familial psychopathology), pregnancy (eg, prenatal exposure to alcohol and tobacco), and child (eg, substance use) variables. RESULTS Among 11 489 children (5997 boys [52.2%]; mean [SD] age, 9.9 [0.6] years) with nonmissing prenatal cannabis exposure data, 655 (5.7%) were exposed to cannabis prenatally. Relative to no exposure, cannabis exposure only before (413 [3.6%]) and after (242 [2.1%]) maternal knowledge of pregnancy were associated with greater offspring psychopathology characteristics (ie, PLEs and internalizing, externalizing, attention, thought and, social problems), sleep problems, and body mass index, as well as lower cognition and gray matter volume (all |β| > 0.02; all false discovery rate [FDR]-corrected P < .03). Only exposure after knowledge of pregnancy was associated with lower birth weight as well as total intracranial volume and white matter volumes relative to no exposure and exposure only before knowledge (all |β| > 0.02; all FDR-corrected P < .04). When including potentially confounding covariates, exposure after maternal knowledge of pregnancy remained associated with greater PLEs and externalizing, attention, thought, and social problems (all β > 0.02; FDR-corrected P < .02). Exposure only prior to maternal knowledge of pregnancy did not differ from no exposure on any outcomes when considering potentially confounding variables (all |β| < 0.02; FDR-corrected P > .70). CONCLUSIONS AND RELEVANCE This study suggests that prenatal cannabis exposure and its correlated factors are associated with greater risk for psychopathology during middle childhood. Cannabis use during pregnancy should be discouraged.
Maternal cannabis use in pregnancy and child neurodevelopmental outcomes
Nature Medicine, 2020
Cannabis use in pregnancy has increased 1,2 , and many women continue to use it throughout pregnancy 3. With the legalization of recreational cannabis in many jurisdictions, there is concern about potentially adverse childhood outcomes related to prenatal exposure 4. Using the provincial birth registry containing information on cannabis use during pregnancy, we perform a retrospective analysis of all live births in Ontario, Canada, between 1 April 2007 and 31 March 2012. We link pregnancy and birth data to provincial health administrative databases to ascertain child neurodevelopmental outcomes. We use matching techniques to control for confounding and Cox proportional hazards regression models to examine associations between prenatal cannabis use and child neurodevelopment. We find an association between maternal cannabis use in pregnancy and the incidence of autism spectrum disorder in the offspring. The incidence of autism spectrum disorder diagnosis was 4.00 per 1,000 person-years among children with exposure compared to 2.42 among unexposed children, and the fully adjusted hazard ratio was 1.51 (95% confidence interval: 1.17-1.96) in the matched cohort. The incidence of intellectual disability and learning disorders was higher among offspring of mothers who use cannabis in pregnancy, although less statistically robust. We emphasize a cautious interpretation of these findings given the likelihood of residual confounding. Cannabinoids, including tetrahydrocannabinol, readily cross the placenta and can enter the fetal bloodstream 5. Exposure to cannabinoids while in utero can disrupt the fetal endogenous cannabinoid signaling system, which has several roles in embryo development 5. Human and animal studies suggest that disruption of endocannabinoid signaling may lead to defects in neuronal wiring, and have implications for fetal neurodevelopment 6,7. Data on long-term follow-up of children with exposure to cannabis in utero are currently limited 8,9. Previous studies indicate decreases in concentration and attention among offspring of mothers with cannabis use in pregnancy compared to those without 9. There is a need for larger studies that can adequately control for confounding in cannabis-outcome associations 10. Here we aimed to assess whether there is an association between cannabis exposure in pregnancy and neurodevelopmental outcomes in childhood using the birth registry (BORN) from Ontario, Canada with nearly complete capture of every pregnancy and birth. A total of 689,071 births in Ontario were registered by BORN between 1 April 2007 and 31 March 2012. Following exclusions, the final cohort was based on 508,025 births. Children who lost Ontario Health Insurance eligibility or died before 18 months (n = 4,960) or 4 years (n = 10,204) of age were excluded from the primary analyses of autism spectrum disorder (ASD) and secondary analyses of neurodevelopmental outcomes, yielding analytical cohorts of 503,065 and 497,821, respectively (Supplementary Table 1). The mean age of mothers was 30.1 years (s.d. = 5.6), the mean gestational age at delivery was 38.9 weeks (s.d. = 1.7) and 51.4% of children were male. The rate of reported cannabis use in pregnancy was 0.6%. An analysis comparing excluded records to the analytical cohort indicated some modest differences by maternal age, area-level income, parity, maternal health conditions, rural residence and drug and medication use in pregnancy (Supplementary Table 2). An analysis by year of birth indicates that the rates of exclusion were lower among the cohort born after 2010 (Supplementary Table 3). Maternal cannabis use was lower among excluded records (0.3%). The first prenatal consultation, where cannabis use information is collected, occurred at a median of the 79th gestational day (11 weeks and 2 d) overall, and the 94th day (13 weeks and 3 d) among women with reported cannabis use. Significant imbalance in covariates was identified between cannabis users and nonusers. The L 1 statistic, a global measure of imbalance, was 0.77 in the unmatched cohort, but this was reduced to 0.02 following coarsened exact matching (CEM). Imbalance in the distribution of baseline covariates was reduced in the matched cohort (standardized mean difference (SMD) < 1% for all covariates except placental abruption (SMD = 5.4%)). The matched analytical cohort comprised 173,035 records, of which 2,364 were cannabis users and 170,671 were cannabis nonusers (Table 1). The sample distribution was similar in the 4-year analytical cohort (Supplementary Table 4). Association between prenatal cannabis use and ASD. In the 18-month cohort, 7,125 (1.4%) children were diagnosed with ASD by the end of follow-up (median length of follow-up, 7.4 years). The rate of ASD diagnosis was 2.2% among children with in utero cannabis exposure. The incidence of ASD diagnosis was 4.00 per 1,000 person-years (95% confidence interval (CI): 3.65-4.38) among children exposed to cannabis compared to 2.42 (95% CI: 2.39-2.44) among unexposed children, and the crude hazard ratio (HR) was 1.63 (95% CI: 1.29-2.06). In the CEM-matched cohort, the HR for ASD associated with cannabis exposure was 1.53 (95% CI: 1.18-1.98), and 1.51 (95% CI: 1.17-1.96) in unadjusted and fully adjusted models (Table 2). Association between prenatal cannabis use and neurodevelopmental disorders. In the 4-year cohort, the rates of secondary
2020
Cannabis use in pregnancy has increased, and many women continue to use it throughout pregnancy. With the legalization of recreational cannabis in many jurisdictions, there is concern about potentially adverse childhood outcomes related to prenatal exposure.4 Using the provincial birth registry containing information on cannabis use during pregnancy, we will assemble a large, population-based cohort of children born to mothers in Ontario, with and without prenatal exposure to cannabis from birth to 10 years of age. A series of investigations will examine the health effects of prenatal cannabis exposure on child outcomes using novel methods to address confounding. We will link pregnancy and birth data to provincial health administrative databases to ascertain child neurodevelopmental outcomes. The unique aspect of our proposed research is that we plan to utilize an existing population-based perinatal registry combined with administrative datasets for long-term follow up of children u...
JAMA Psychiatry, 2019
Mirroring increases in the general population, the prevalence of past-month marijuana use among pregnant mothers in the United States increased by 75% between 2002 (2.85%) and 2016 (4.98%). 1 Although cannabis use has been linked to psychosis, little is known about prenatal exposure. 2,3 Unprecedented increases in marijuana use during pregnancy, alongside evidence that cannabis use is correlated with psychosis and that endocannabinoids play an important role in neurodevelopment, highlight the importance of evaluating potential long-term consequences of prenatal exposure. 4 Methods | We used data from the ongoing Adolescent Brain Cognitive Development (ABCD) study (data release 1.0; https://abcdstudy.org/) to test whether maternal report of cannabis use during pregnancy is associated with psychosis proneness (Prodromal Questionnaire-Brief Child Version total score) among 4361 children aged 8.9 to 11.0 years who were born between 2005 and 2008 to 3774 mothers through 3926 pregnancies (Table). All parents provided written informed consent, and all children provided assent to a research protocol approved by the institutional review board at each data collection site (https://abcdstudy.org/sites/abcdsites.html). The Prodromal Questionnaire-Brief Child version
Reproductive Health
Introduction This study analyze factors associated to cannabis use in pregnant women, its perceived availability, its risk perception and the relationship between prenatal exposure to cannabis and developmental and mental disorders. Objectives We present a review of the literature on cannabis use among pregnant women. The objective is to analyze factors associated to cannabis use during pregnancy and assess the potential effects of prenatal exposure to cannabis on the development of the fetus and the mental health of those exposed. Methods Systematic review of studies on the maternal use of cannabis and the relationship between early exposure and the development of psychiatric disorders in the PubMed database until July 2018 in English and Spanish with the following keywords: Marijuana, Cannabinoids, Mental disorders, Pregnancy, Prenatal Cannabis Exposure, Risk factors. Results The use of cannabis among pregnant women is frequent but it has not been extensively researched. Prenatal ...
JAMA, 2019
IMPORTANCE Recent evidence suggests that cannabis use during pregnancy is increasing, although population-based data about perinatal outcomes following in utero exposure remain limited. OBJECTIVE To assess whether there are associations between self-reported prenatal cannabis use and adverse maternal and perinatal outcomes. DESIGN, SETTING, AND PARTICIPANTS Population-based retrospective cohort study covering live births and stillbirths among women aged 15 years and older in Ontario, Canada, between April 2012 and December 2017. EXPOSURES Self-reported cannabis exposure in pregnancy was ascertained through routine perinatal care. MAIN OUTCOMES AND MEASURES The primary outcome was preterm birth before 37 weeks' gestation. Indicators were defined for birth occurring at 34 to 36 6/7 weeks' gestation (late preterm), 32 to 33 6/7 weeks' gestation, 28 to 31 6/7 weeks' gestation, and less than 28 weeks' gestation (very preterm birth). Ten secondary outcomes were examined including small for gestational age, placental abruption, transfer to neonatal intensive care, and 5-minute Apgar score. Coarsened exact matching techniques and Poisson regression models were used to estimate the risk difference (RD) and relative risk (RR) of outcomes associated with cannabis exposure and control for confounding. RESULTS 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]). CONCLUSIONS AND RELEVANCE Among pregnant women in Ontario, Canada, reported cannabis use was significantly associated with an increased risk of preterm birth. Findings may be limited by residual confounding.
European Journal of Midwifery
INTRODUCTION Cannabis and its derivatives are becoming increasingly popular in women's preferences during pregnancy in order to relieve nausea. The present study examines cannabis use during pregnancy and its effects on the fetus, newborn and later childhood. METHODS All primary studies were searched in the databases: PubMed, Scopus, Medline during the period June 2019 to August 2020. The keywords used were 'pregnancy', 'pregnant women', 'cannabis', 'marijuana', 'fetus', 'newborn', 'childhood', and combined with 'AND' and 'OR' Boolean operators. Inclusion criteria were: pregnant users of cannabis as the study group and pregnant non-users of cannabis as the control group; the articles could be in English or in Greek. The exclusion criteria were: unpublished studies, reviews, presentations at conferences, and animal studies. RESULTS From the systematic review of the literature, the study included 13 primary research studies in which it was found that the children of mother-user faced: disorders in the sleep cycle, memory problems, hyperactivity, increased chances of low birth weight, prematurity with lower Apgar score in the 1st and 5th minutes and hospitalization in an NICU, DNA methylation at the position CpG.32, and modifications in the brain, especially in the amygdala. In addition, girls had more aggressive behavior at the age of 18 months, shorter breastfeeding period, and neonatal death. CONCLUSIONS The use of cannabis during the gestation period by the mother, aggravates the physical and mental development of the fetus, the newborn and the later childhood.
Neurotoxicology and teratology
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. 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 dir...
Exposure to marijuana during pregnancy alters neurobehavior in the early neonatal period
The Journal of Pediatrics, 2006
Objective To assess the neurobehavior of full-term neonates of adolescent mothers exposed to marijuana during pregnancy. Study design This prospective cross-sectional study included full-term infants within 24 to 72 hours of life born to adolescent mothers at a single center in Brazil. Data on sociodemographic and obstetrical and neonatal characteristics were collected. The mothers underwent the Composite International Diagnostic Interview, and the infants were assessed with the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS). Maternal hair and neonatal meconium were analyzed. Neonates exposed in utero to tobacco, alcohol, cocaine, and/or any other drugs except marijuana were excluded. Results Of 3685 infants born in the study hospital, 928 (25%) were born to adolescent mothers. Of these, 561 infants met the inclusion criteria and were studied. Marijuana exposure was detected in 26 infants (4.6%). Infants exposed (E) or not exposed (NE) to marijuana differed in the following NNNS variables: arousal (E, 4.05 ؎ 1.19 vs NE, 3.68 ؎ 0.70), regulation (E, 5.75 ؎ 0.62 vs NE, 6.04 ؎ 0.72), and excitability (E, 3.27 ؎ 1.40 vs NE, 2.40 ؎ 1.57). After controlling for confounding variables, the effect of marijuana exposure on these scores remained significant. Conclusions Marijuana exposure during pregnancy alters the neurobehavioral performance of term newborn infants of adolescent mothers.