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. Author manuscript; available in PMC: 2026 Jan 1.
Published in final edited form as: J Dev Behav Pediatr. 2024 Oct 15;46(1):e25–e32. doi: 10.1097/DBP.0000000000001323

Prenatal Cannabis Use and Offspring Attention Deficit Hyperactivity Disorder and Disruptive Behavior Disorders: A Retrospective Cohort Study

Kelly C Young-Wolff 1,2, Kevin Kong 1, Stacey E Alexeeff 1, Lisa A Croen 1, Nina Oberman 1, Harshal Kirane 3, Deborah Ansley 4, Meghan Davignon 4, Sara R Adams 1, Lyndsay A Avalos 1
PMCID: PMC11832326  NIHMSID: NIHMS2021051  PMID: 39400201

Abstract

Objective:

To examine whether maternal cannabis use during early pregnancy is associated with offspring attention deficit hyperactivity disorder (ADHD) and disruptive behavior disorders (DBD).

Methods:

We conducted a population-based retrospective birth cohort study of children (N=141,570) born between 2011–2018 to pregnant individuals (N=117,130) in Kaiser Permanente Northern California universally screened for any prenatal cannabis use at entrance to prenatal care (at ~8–10 weeks gestation). Prenatal cannabis use was defined as 1) self-reported use and/or a positive toxicology test, 2) self-reported use, 3) a positive toxicology test, and 4) self-reported use frequency. Cox proportional hazards regression models adjusting for maternal characteristics (socio-demographics, other substance use and substance use disorders, prenatal care initiation, comorbidities) examined associations between prenatal cannabis use and offspring ADHD and DBD diagnosed by age 11.

Results:

The sample of pregnant individuals was 27.2% Asian/Pacific Islander, 5.7% Black, 24.5% Hispanic, 38.8% non-Hispanic White, , with a mean (SD) age of 30.9 (5.2) years; 4.6% screened positive for any cannabis use (0.4% daily, 0.5% weekly, 1.1% monthly or less, 2.7% unknown frequency); 3.92% had a positive toxicology test and 1.8% self-reported use; 7.7% of offspring had ADHD and 6.8% had DBD. Maternal prenatal cannabis use was not associated with ADHD (aHR:0.84, 95%CI: 0.70–1.01), and there was an inverse association with DBD (aHR:0.83, 95%CI: 0.71–0.97), which remained when cannabis was defined by toxicology testing but not by self-report. Frequency of use was not associated with outcomes.

Conclusions:

Maternal prenatal cannabis use was not associated with an increased risk of offspring ADHD or DBD.

Keywords: Marijuana, pregnancy, child, ADHD, conduct disorder, oppositional defiant disorder, impulse control disorder

INTRODUCTION

Cannabis use during pregnancy is common, with 7.0% of pregnant individuals in the US reporting past-month cannabis use in 2017.1 Pregnant individuals report using cannabis during pregnancy to self-medicate issues with mood, anxiety, sleep, and pregnancy-related conditions, and many believe that cannabis is safe for use during pregnancy.2–4 However, cannabis can freely cross the placenta and blood-brain barrier,5,6 and there is growing evidence for an association between prenatal cannabis use and adverse fetal and neonatal outcomes (e.g., lower birthweight, neonatal intensive care unit admission).7–9

The endocannabinoid system is critical for neurodevelopment,10 and maternal prenatal cannabis use could affect offspring neurodevelopment and behavioral problems via interactions with the endocannabinoid system in the placenta and developing fetus.11 Animal studies have found that cannabis exposure in utero is associated with increased conflict behavior and adverse cognitive and developmental outcomes.12–15 Similarly, neuroimaging studies have found long-term, subtle effects of maternal prenatal cannabis use on offspring neural circuitry supporting cognitive functions, such as response inhibition and visual-spatial working memory.16

Studies examining longer-term offspring neurodevelopmental and psychiatric outcomes have come primarily from a few longitudinal cohorts with prenatal cannabis use assessed during the 1980s to early 2000s.17 Some have found an association between maternal prenatal cannabis use and increased offspring externalizing behaviors (e.g., delinquency, aggression, impulsivity), hyperactivity, and attention problems from early childhood into adolescence, although results are mixed.11,17–20 A study using data from the Adolescent Brain and Cognitive Development (ABCD) found that maternal retrospective self-report of prenatal cannabis use that continued after knowledge of pregnancy was associated with parent and teacher measures of externalizing symptoms and attention problems in offspring (born 2005–2009) at ages 9–10.21,22 Further, a study of pregnant individuals between 2006–2009 found that prenatal cannabis use measured via urine toxicology testing was associated with worse offspring attention at 48 months.23

Despite evidence of an association between maternal prenatal cannabis use and offspring difficulties with behavior, attention, and hyperactivity, less is known about the association with offspring diagnoses of attention deficit hyperactivity disorder (ADHD), a neurodevelopmental disorder marked by patterns of inattention and/or hyperactivity/impulsivity that interfere with functioning, or diagnoses of disruptive behavior disorders (DBD; including conduct disorder, impulse control disorders, and oppositional defiant disorder), characterized by ongoing patterns of disruptive or defiant behavior. To our knowledge, no prior studies have examined prenatal cannabis use and offspring DBD, and limited studies on offspring ADHD find no association.24–26 Existing studies relied on self-reporting of prenatal cannabis use, which can underestimate true exposure rates.27 Furthermore, given the rapid increases in cannabis potency in recent years,28 findings from older studies may not generalize to more contemporary products.19,29,30

Identifying modifiable prenatal risk factors for ADHD and DBD, which are conditions commonly diagnosed in childhood,31 is critical for improved detection of at-risk individuals and the development of targeted prevention efforts. In contrast to studies of attention and behavioral difficulties, our study includes diagnosed ADHD and DBD, which reflects outcomes that were clinically significant enough to come to the attention of the healthcare system. In this large, retrospective cohort study, we address gaps in the literature by examining the association between maternal prenatal cannabis use and offspring ADHD and DBD using data from pregnant individuals universally screened for prenatal cannabis use and their offspring born 2011–2018.

Methods

Setting

Kaiser Permanente Northern California (KPNC) is an integrated healthcare delivery system that provides healthcare to ~4.6 million patients, with a sociodemographic profile generally similar to the local and statewide California population.32 IRB approval was obtained from KPNC and the state of California (governing the use of birth certificate data) with a waiver of consent. This study followed the STROBE reporting guideline.

Cohort

We conducted a retrospective longitudinal cohort study of mothers with singleton pregnancies and their children born between January 1, 2011, and December 31, 2018. Eligibility criteria for the pregnant individual included KPNC membership one year before pregnancy through pregnancy end (allowing 3-month gaps), ≥1 KPNC prenatal care visit, a response to the self-reported question about prenatal cannabis use, and a urine toxicology test. Exclusion criteria included a maternal prescription fill for a teratogenic, antineoplastic, or antiepileptic drug during pregnancy; missing data on parity or address; child death <1 month of age; or child not enrolled in KPNC at age 4 (eMethods). Children were followed to the end of the study period (12/31/2022) or the maximum follow-up age of 11 years. Pregnant individuals with >1 pregnancy during the study could contribute >1 child to the analysis.

Measures

Data come from the electronic health record (EHR) unless otherwise specified.

Outcomes

ADHD was defined based on ICD-9-CM/ICD-10-CM diagnostic codes and/or ADHD medication fills, and DBD was defined based on ICD-9-CM/ICD-10-CM diagnostic codes, when the child was ≥4 years old between January 2015 (when the oldest children in the cohort turned 4) and December 2022 (study end; see eMethods). DBD included diagnoses of conduct disorders, oppositional defiant disorders, and impulse control disorders (see eMethods).

Prenatal Cannabis Use

KPNC pregnant individuals are universally screened for cannabis use at entrance to prenatal care (typically at ~8–10 weeks gestation) via a self-administered questionnaire that assesses frequency of prenatal use since pregnancy (with mutually exclusive categories of “none,” “monthly or less,” “weekly,” and “daily”) and a urine toxicology test (UDAP) to which they consent.33 Prenatal cannabis use was defined four ways: (1) any self-reported use since pregnancy and/or a positive UDAP, (2) any self-reported use since pregnancy, (3) a positive UDAP, and (4) frequency of use (with a category of “unknown” for individuals who did not self-report use but had a positive UDAP; eMethods).

Socio-Demographics

We extracted data on maternal age, self-reported race and ethnicity (Asian/Pacific Islander, Black, Hispanic, non-Hispanic White, and Other/Unknown), maternal insurance (Medicaid vs. commercial/self-insured), parity (0, 1, 2+), maternal neighborhood deprivation index (NDI; categorized into quartiles),34 maternal education (≤12th grade, some college/technical school, college graduation, graduate school, and missing), and child sex and birth year. Maternal race/ethnicity, parity, and education were supplemented with birth certificate data.

Other Prenatal Substance Use

Maternal non-cannabis prenatal substance use was assessed at entrance to prenatal care and defined as any use of: alcohol, nicotine, opioids, stimulants, or anxiety/sleep medications (see eMethods).

Prenatal Care Initiation

Prenatal care initiation was based on the Kotelchuck Month of Initiation Index35 and categorized as inadequate (initiated prenatal care at month 7+), intermediate (initiated prenatal care at month 5–6), adequate (initiated prenatal care at month 3–4), and adequate plus (initiated prenatal care at month 1–2).

Maternal Comorbidities

Asthma, chronic pain, non-cannabis substance use disorders, ADHD, anemia, depressive, bipolar, anxiety, thyroid, and hypertension disorders were identified based on ICD-9/ICD-10 diagnosis codes during the year prior to last menstrual period through the first prenatal visit. Maternal body mass index (BMI) at entrance to prenatal care was categorized as underweight (<18.5 kg/m2), normal (18.5 to <23.0 kg/m2), overweight (23.0 to <27.5 kg/m2), or obese (≥27.5 kg/m2). Diabetes mellitus was categorized based on clinical diagnosis by ICD-9/ICD-10 codes during the 2 years prior to pregnancy onset. Antidepressant use was identified based on ≥1 prescription dispensed from last menstrual period through the first prenatal visit, or before pregnancy with supply lasting into pregnancy onset. Nausea or vomiting during pregnancy was identified by ICD-9/ICD-10 diagnosis codes from last menstrual period through the first prenatal visit.

Statistical Analysis

We fit Cox proportional hazards regression to model the association of prenatal cannabis use with ADHD and DBD. Follow-up time began when offspring were 48 months old, with the age of the child in months as the time scale. Children were followed until the earliest of outcome occurrence, end of KPNC health plan membership (allowing for ≤3-month membership gaps), no pediatric or mental health department visit within 2-year intervals, death, or end of the study. Pediatric or mental health department visits were required within 2-year intervals to ensure an opportunity for clinicians to recognize potential behavior issues.

Offspring health care utilization was required for follow-up to ensure that children had the opportunity to receive an ADHD or DBD diagnosis. To account for the potential impact of informative censoring (e.g., due to any differences in healthcare visits or membership loss among children of mothers with vs. without prenatal cannabis use) we fit Cox models with inverse probability of censoring weights.36 Time-varying stabilized weights were generated for each 2-year time interval (months 48–71, 72–95, 96–119, and 120–132).

Marginal Cox models with a cluster term at the maternal level and robust standard errors were used to account for correlated observations (i.e., multiple pregnancies nested within individuals). ADHD and DBD were modeled separately, with increasing levels of covariate adjustment to understand the role of potential confounders on our associations. The first series of analyses included the exposure of any prenatal cannabis use (by self-report or toxicology testing). Model 1 was unadjusted, Model 2 adjusted for maternal sociodemographics, Model 3 additionally adjusted for other non-cannabis substance use, Model 4 additionally adjusted for prenatal care initiation, and Model 5 additionally adjusted for maternal comorbidities. Next, analyses were repeated with prenatal cannabis use based on 1) any self-reported use, 2) a positive toxicology test, and 3) use frequency. All models adjusted for child age by using child age as the time scale of the Cox model. We conducted a sensitivity analysis limited to children born to mothers who did not screen positive for any non-cannabis prenatal substance use.

Analyses were conducted using SAS 9.4 and R 4.0.2. Two-sided P values <.05 were considered statistically significant.

RESULTS

The sample of 141,570 pregnancies (from 117,130 unique individuals) was 27.2% Asian/Pacific Islander, 5.7% Black, 24.5% Hispanic, 38.8% non-Hispanic White, 11.5% were ≤24 years old, and 4.6% were insured by Medicaid (Table 1). Overall, 4.6% screened positive for any cannabis use (0.4% daily, 0.5% weekly, 1.1% monthly or less, 2.7% unknown frequency [i.e., positive toxicology test but no self-reported use]); 2.0% self-reported use (1.1% monthly or less, 0.5% weekly, 0.4% daily) and 3.9% had a positive toxicology test; 0.7% were positive by self-report only, 2.7% were positive by urine toxicology testing only, and 1.2% were positive by self-report and urine toxicology testing. The median (SD) weeks gestation of the prenatal substance use screening was 8.0 (2.8). Children of mothers with vs. without prenatal cannabis use had slightly fewer membership years (mean [SD] 2.09 [1.99] vs. 2.63 [2.11]) and pediatric visits overall (mean [SD] 7.36 [9.08] vs. 8.58 [9.64]), but slightly more visits per membership year (mean [SD] 3.74 [6.45] vs. 3.49 [5.44]). Mothers with any vs. no prenatal cannabis use were younger, less likely to be Asian and more likely to be Black, with less education, lower parity, greater neighborhood deprivation and Medicaid, greater prenatal use of other substances and greater comorbidities (Table 1). Socio-demographic and clinical characteristics were generally similar among those who self-reported cannabis use and those with a positive UDAP (eTable 1). Among those who screened positive, compared to those with monthly or less, weekly or daily prenatal cannabis use, those with unknown frequency had lower parity, lower prenatal use of other substances, and were more likely to be obese (eTable 2).

Table 1.

Characteristics of 141,570 Pregnancies at Kaiser Permanente Northern California, Overall and by Any Prenatal Cannabis Use (by Self-Report and/or Urine Toxicology Testing)

Prenatal Cannabis Use
Characteristic Overall, N = 141,570 No, N = 134,992 Yes, N = 6,578
Maternal sociodemographic characteristics
Age at pregnancy onset
 <18 1,068 (0.8) 862 (0.6) 206 (3.1)
 18–24 15,131 (10.7) 12,823 (9.5) 2,308 (35.1)
 25–30 46,455 (32.8) 44,484 (33.0) 1,971 (30.0)
 31–35 52,778 (37.3) 51,289 (38.0) 1,489 (22.6)
 36+ 26,138 (18.5) 25,534 (18.9) 604 (9.2)
Race/ethnicity
 Asian/Pacific Islander 38,469 (27.2) 38,055 (28.2) 414 (6.3)
 Hispanic 34,689 (24.5) 32,941 (24.4) 1,748 (26.6)
 Non-Hispanic Black 8,030 (5.7) 6,539 (4.8) 1,491 (22.7)
 Non-Hispanic White 54,889 (38.8) 52,385 (38.8) 2,504 (38.1)
 Other/Unknown 5,493 (3.9) 5,072 (3.8) 421 (6.4)
Education level
 High School or Less 21,209 (15.0) 19,046 (14.1) 2,163 (32.9)
 Some College 40,953 (28.9) 38,101 (28.2) 2,852 (43.4)
 College Graduate 47,316 (33.4) 46,283 (34.3) 1,033 (15.7)
 Graduate School 29,065 (20.5) 28,716 (21.3) 349 (5.3)
 Unknown 3,027 (2.1) 2,846 (2.1) 181 (2.8)
Parity category
 0 57,618 (40.7) 54,023 (40.0) 3,595 (54.7)
 1 52,966 (37.4) 51,159 (37.9) 1,807 (27.5)
 2+ 30,957 (21.9) 29,786 (22.1) 1,171 (17.8)
Neighborhood Deprivation Index
 Q1 - Least deprived 37,112 (26.2) 36,223 (26.8) 889 (13.5)
 Q2 36,572 (25.8) 35,201 (26.1) 1,371 (20.8)
 Q3 35,312 (24.9) 33,536 (24.8) 1,776 (27.0)
 Q4 - Most deprived 32,544 (23.0) 30,003 (22.2) 2,541 (38.6)
Insurance Status
  Medicaid 6,515 (4.6) 5,240 (3.9) 1,275 (19.4)
  Other 135,055 (95.4) 129,752 (96.1) 5,303 (80.6)
Other (non-cannabis) maternal substance use
 Prenatal Alcohol use 13,379 (9.5) 11,993 (8.9) 1,386 (21.1)
 Prenatal Nicotine use 5,661 (4.0) 4,086 (3.0) 1,575 (23.9)
 Prenatal Anxiety/Sleep medication use 3,914 (2.8) 3,465 (2.6) 449 (6.8)
 Prenatal Stimulant use 837 (0.6) 615 (0.5) 222 (3.4)
 Prenatal Opioid use 3,971 (2.8) 3,478 (2.6) 493 (7.5)
Prenatal care initiation
 Adequate Plus (Month 1–2) 95,237 (67.3) 91,036 (67.4) 4,201 (63.9)
 Adequate (Month 3–4) 44,207 (31.2) 42,059 (31.2) 2,148 (32.7)
 Intermediate (Month 5–6) 1,593 (1.1) 1,430 (1.1) 163 (2.5)
 Inadequate (Month 7+) 533 (0.4) 467 (0.3) 66 (1.0)
Maternal comorbidities
Maternal pre-existing asthma 14,383 (10.2) 13,179 (9.8) 1,204 (18.3)
Maternal pre-existing diabetes (Type I or II) 1,992 (1.4) 1,909 (1.4) 83 (1.3)
Pre-pregnancy BMI Category
 Obese 33,301 (23.5) 31,098 (23.0) 2,203 (33.5)
 Overweight 38,760 (27.4) 37,015 (27.4) 1,745 (26.5)
 Normal 63,953 (45.2) 61,618 (45.6) 2,335 (35.5)
 Underweight 3,738 (2.6) 3,549 (2.6) 189 (2.9)
 Unknown 1,818 (1.3) 1,712 (1.3) 106 (1.6)
Nausea/vomiting during pregnancy 15,035 (10.6) 13,534 (10.0) 1,501 (22.8)
Antidepressant use during pregnancy 6,218 (4.4) 5,642 (4.2) 576 (8.8)
Maternal pre-existing chronic pain 4,617 (3.3) 4,152 (3.1) 465 (7.1)
Maternal pre-existing substance use disorder (excluding cannabis-related disorders) 4,504 (3.2) 3,366 (2.5) 1,138 (17.3)
Maternal pre-existing ADHD 842 (0.6) 711 (0.5) 131 (2.0)
Maternal pre-existing Anemia 7,004 (4.9) 6,657 (4.9) 347 (5.3)
Maternal pre-existing mood or other psychiatric disorder, except ADHD 16,396 (11.6) 14,840 (11.0) 1,556 (23.7)
Maternal pre-existing thyroid disorder 8,327 (5.9) 8,100 (6.0) 227 (3.5)
Maternal pre-existing hypertension disorder 1,075 (0.8) 993 (0.7) 82 (1.2)
Child Sex
 Female 69,069 (48.8) 65,838 (48.8) 3,231 (49.1)
 Male 72,501 (51.2) 69,154 (51.2) 3,347 (50.9)
Frequency of cannabis use
 None 134,992 (95.4) 134,992 (100.0) 0 (0.0)
 Monthly or less 1,520 (1.1) 0 (0.0) 1,520 (23.1)
 Weekly 717 (0.5) 0 (0.0) 717 (10.9)
 Daily 562 (0.4) 0 (0.0) 562 (8.5)
 Unknown 3,779 (2.7) 0 (0.0) 3,779 (57.4)
Offspring outcomes
 ADHD 3,709 (2.6) 3,548 (2.6) 161 (2.4)
 DBD 4,360 (3.1) 4,168 (3.1) 192 (2.9)
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Note. Unknown frequency = Positive toxicology test but self-reported no use. ADHD = attention deficit hyperactivity disorder. DBD = Disruptive behavior disorders.

Of the 141,570 children in the cohort (69,069 girls [48.8%] and 72,501 boys [51.2%]; median age, 6 years, maximum age=11 years [IQR 5–8 years]); 7.7% had ADHD, with a median (SD) first recorded diagnosis at 6.9 (1.6) years, and 6.8% had DBD, with a median (SD) recorded diagnosis at 5.7 (1.6) years.

ADHD Outcome

Any Maternal Prenatal Cannabis Use

Any prenatal cannabis use was positively associated with offspring ADHD in Model 1 (hazard ratio [HR]):1.27, 95%CI:1.09–1.49) (Table 2). After adjustment for sociodemographic characteristics, non-cannabis substance use, prenatal care utilization, and maternal comorbidities (Model 5), there was a suggestive inverse association between any use and offspring ADHD that did not meet statistical significance (adjusted HR [aHR]:0.84, 95%CI: 0.70–1.01) (Table 2, Figure). Maternal prenatal cannabis use was not significantly associated with offspring ADHD when defined by self-report (aHR:0.98, 95%CI: 0.76–1.26), but there was a non-significant inverse association when defined by a toxicology test (aHR:0.82, 95%CI:0.67–1.01) (Figure).

Table 2.

Stepwise Adjusted Hazard Ratios for Associations Between Maternal Cannabis Use and Offspring Attention Deficit Hyperactivity Disorder (ADHD) and Disruptive Behavior Disorders (DBD), Overall and Stratified by Frequency of Maternal Cannabis Use (N = 141,570).

ADHD
Maternal Prenatal Cannabis Use Model 1 Model 2 Model 3 Model 4 Model 5
ADHD, % Crude +Socio-demographics +Other prenatal substance use +Month of prenatal care initiation +Maternal comorbidities
Any Use
  No 8.9 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
  Yes 7.7 1.27 (1.09 – 1.49) 0.98 (0.82 – 1.16) 0.88 (0.73 – 1.06) 0.86 (0.72 – 1.03) 0.84 (0.70 – 1.01)
Frequency of Use
 None 7.7 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
 Monthly or less 9.1 1.45 (1.05 – 2.01) 1.12 (0.81 – 1.56) 0.94 (0.67 – 1.32) 0.96 (0.68 – 1.34) 0.95 (0.68 – 1.34)
 Weekly 9.4 1.48 (0.94 – 2.32) 1.05 (0.66 – 1.67) 0.88 (0.55 – 1.41) 0.89 (0.55 – 1.42) 0.83 (0.52 – 1.33)
 Daily 18.0 2.00 (1.24 – 3.23) 1.44 (0.88 – 2.35) 1.18 (0.71 – 1.95) 1.17 (0.71 – 1.94) 1.1 (0.66 – 1.85)
Unknown 7.4 0.10 (0.04 – 0.30) 0.85 (0.67 – 1.08) 0.82 (0.64 – 1.04) 0.82 (0.65 – 1.05) 0.77 (0.60 – 0.98)
DBD
Maternal Prenatal Cannabis Use Model 1 Model 2 Model 3 Model 4 Model 5
DBD, % Crude +Socio-demographics +Other prenatal substance use +Month of prenatal care initiation +Maternal comorbidities
Any Use
 No 6.8 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
 Yes 7.8 1.23 (1.06 – 1.42) 0.96 (0.82 – 1.13) 0.87 (0.74 – 1.02) 0.89 (0.74 – 1.06) 0.83 (0.71 – 0.97)
Frequency of Use
  None 6.8 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
  Monthly or less 7.9 1.45 (1.07 – 1.97) 1.14 (0.84 – 1.54) 0.98 (0.72 – 1.33) 1 (0.73 – 1.36) 0.97 (0.71 – 1.32)
  Weekly 9.6 1.47 (0.98 – 2.21) 1.09 (0.72 – 1.64) 0.91 (0.60 – 1.38) 0.92 (0.61 – 1.39) 0.85 (0.56 – 1.29)
  Daily 10.9 1.38 (0.83 – 2.29) 1.01 (0.61 – 1.69) 0.84 (0.50 – 1.41) 0.83 (0.49 – 1.40) 0.77 (0.46 – 1.31)
  Unknown 6.9 0.59 (0.36 – 0.94) 0.87 (0.70 – 1.07) 0.83 (0.67 – 1.02) 0.83 (0.67 – 1.02) 0.78 (0.63 – 0.96)
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Note: Bold values denote statistical significance at the p < 0.05 level; HR=Hazard Ratio; aHR= Adjusted Hazard Ratio; CI= Confidence Interval. Unknown frequency = positive toxicology test but self-reported no use.

Model 1: Unadjusted Cox proportional hazards model with inverse-probability of censoring weights and maternal-level cluster term.

Model 2: Adjusted for sociodemographic characteristics (age at pregnancy onset, race/ethnicity, education, Neighborhood Deprivation Index (NDI), parity, Medicaid status, birth year, infant sex).

Model 3: Adjusted for all covariates in Model 2 plus other non-cannabis prenatal substance use (alcohol, nicotine, opioids, anxiety/sleep medication, and stimulants).

Model 4: Adjusted for all covariates in Model 3 plus month of prenatal care initiation.

Model 5: Adjusted for all covariates in Model 4, plus maternal medical and mental health comorbidities (asthma, diabetes mellitus, nausea/vomiting during pregnancy, mood/anxiety disorders, other psychiatric disorders, substance use disorders, antidepressant use, chronic pain, ADHD, anemia, thyroid disorders, hypertension).

Figure.

Figure.

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Adjusted Hazard Ratios for Associations Between Maternal Cannabis Use and Attention Deficit Hyperactivity Disorder (ADHD) and Disruptive Behavior Disorders (DBD)

Notes. UDAP = Urine toxicology test. All models adjusted for socio-demographics, other substance use during first trimester (alcohol, nicotine, opioids, anxiety/sleep medication, and stimulants), prenatal care utilization (Kotelchuck month of initiation index), medical and mental health comorbidities (asthma, diabetes mellitus, nausea/vomiting during pregnancy, mood/anxiety disorders, other psychiatric disorders, substance use disorders, antidepressant use, chronic pain) before or on date of first prenatal visit, inverse probability of censoring weights applied, maternal-level cluster term included.

Frequency of Maternal Prenatal Cannabis Use

In Model 1, relative to no prenatal cannabis use, monthly or less use (HR:1.45, 95%CI:1.05–2.01) and daily use (HR:2.0, 95%CI:1.24–3.23) were positively associated with offspring ADHD (Table 2). In model 5, compared to no use, monthly or less (aHR:0.95, 95%CI:0.68–1.34), weekly (aHR:0.83, 95%CI:0.52–1.33), and daily (aHR:1.11, 95%CI:0.66–1.85) use were not associated with offspring ADHD. However, unknown frequency was inversely associated with offspring ADHD (aHR:0.77, 95%CI:0.60–0.98) (Table 2, Figure).

DBD Outcome

Any Maternal Prenatal Cannabis Use

Any prenatal cannabis use was positively associated with offspring DBD in Model 1 (HR:1.23, 95%CI:1.06–1.42) (Table 2). In the fully adjusted model 5, any use was inversely associated with DBD (aHR:0.83, 95%CI:0.71–0.97) (Table 2; Figure). Prenatal cannabis use was not associated with offspring DBD when defined by self-report (aHR:0.92, 95%CI: 0.73–1.16), and was inversely associated with offspring DBD when defined by UDAP (aHR:0.78, 95%CI:0.65–0.94).

Frequency of Use

In Model 1, relative to no prenatal cannabis use, monthly or less use (HR:1.45, 95%CI: 1.07–1.97) was positively associated with offspring DBD (Table 2). In the fully adjusted model, frequency of cannabis use was not associated with DBD, with the exception that unknown frequency of use was inversely associated with DBD (aHR:0.78, 95%CI:0.63–0.96) (Table 2, Figure).

Sensitivity Analyses

Similar results for each outcome were found for all exposure definitions in the subset of pregnant individuals who did not screen positive for any non-cannabis substance use, but there was no longer a significant inverse association between unknown use frequency (versus no use) and DBD (eFigure).

DISCUSSION

This large, retrospective cohort study found that prenatal cannabis use based on universal screening via self-report and urine toxicology testing during standard prenatal care was not associated with increased risk of offspring ADHD or DBD. The lack of increased risk for offspring ADHD associated with prenatal cannabis is consistent with the limited studies to date that have found no association between maternal self-reported prenatal cannabis use and offspring ADHD,24–26 but differ from some prior studies that have found a positive association between prenatal cannabis use and attention and behavior difficulties based on developmental testing23 or parental/teacher report.21,22 Notably, we found a suggestive inverse association between any maternal prenatal cannabis use and offspring ADHD, and a statistically significant inverse association with offspring DBD, which appeared to be driven by those with a positive cannabis toxicology test.

Further, while there was no association between maternal daily, weekly, or monthly or less cannabis use (versus no use) and offspring ADHD or DBD, those with unknown frequency (i.e., had a positive toxicology test but did not disclose prenatal cannabis use) had significantly lower risk of both outcomes. Results were similar in sensitivity analyses that limited the sample to mother-child dyads with no evidence of any non-cannabis maternal substance use during pregnancy, indicating that findings are not attributable to other prenatal substance use.

Further research using urine toxicology testing is needed to better assess the relationship between a positive UDAP and offspring outcomes. ADHD and DBD are not universally screened for in KPNC, and typically, parents need to approach KPNC clinicians with concerns about their child to get an assessment. The finding of lower risk of DBD (and suggestive lower risk of ADHD) associated with maternal prenatal cannabis use, as well as unknown use frequency, could be driven by residual confounding, for example, if individuals with prenatal cannabis use (or those who choose not to disclose and have a positive toxicology test) are less likely to notice symptoms in their children, or less likely to bring their child in to see their doctor for assessment. However, the number of visits was slightly higher per membership year among children of mothers with vs. without prenatal cannabis use. Other unmeasured factors such as maternal and child socio-demographics, nutrition, social support, or genetic factors might explain inverse findings. Importantly, the data reflect offspring population-level outcomes and do not predict the outcome for any individual. Additional research is needed to tease apart the mechanisms underlying the inverse association between prenatal cannabis use and risk of ADHD and DBD.

Strengths and Limitations

A unique strength of our study is the inclusion of a large, diverse cohort of pregnant individuals and their offspring within a closed healthcare system followed from maternal prenatal substance use screening up to their offspring’s 11th birthday. Our prenatal cannabis use exposures were based on universal screening during prenatal care, and included maternal self-report of cannabis use, frequency of use, and biochemically verified use via UDAP. We adjusted for a range of covariates, and we conducted a sensitivity analysis limited to offspring of pregnant individuals without any use of non-cannabis substances during pregnancy.

However, our study also has several limitations. Our sample was limited to individuals seeking prenatal care in KPNC who were screened for prenatal substance use, and findings may not generalize to uninsured populations, pregnant individuals not screened for substance use, children who did not come in for care, or those outside of KPNC. We examined cannabis use at a snapshot in time at entrance to prenatal care (typically at 8–10 weeks gestation), and we did not have data on continued cannabis use throughout pregnancy, mode of use, or potency. Different modes (e.g., smoking, edibles) or trimesters of exposure may have different health impacts, and there may be greater risks associated with more potent products.29,30 Additional studies are needed that account for these important aspects of cannabis use. We limited the cohort to children who were KPNC members at age 4, and children at risk for poorer outcomes may have been more likely to leave KPNC before age 4. It is also possible that some pregnancies of individuals with the heaviest prenatal cannabis use and potentially greatest risk of adverse offspring outcomes did not end in a live birth, and survivor bias may affect our results.

While we have done our best to account for offspring healthcare utilization, we were unable to adjust for postpartum maternal substance use; however, we note that postpartum substance use might be a mediator rather than a confounder,19 in which case it would not be appropriate to adjust for it. Our outcomes were limited to data available in the EHR rather than conducting a complete diagnostic assessment of each child, and some children in our cohort may have been misclassified. Clinician diagnoses of ADHD and DBD likely underestimate the true prevalence of these conditions and some children who would have been identified with a diagnostic interview may not have been identified in our EHR data. We note that the children in our cohort were still young and may go on to receive a diagnosis of ADHD or DBD. Additional research is needed to follow these children into adolescence. Given these limitations, our results should be interpreted with caution.

Conclusions

Using a large sample with universal screening for maternal prenatal cannabis use, prenatal cannabis use was not associated with an increased risk of ADHD or DBD. Additional research that accounts for the timing, duration, and modes of use is needed. Prenatal cannabis use is a risk factor for adverse fetal and neonatal outcomes,9 and there are many important reasons for quitting cannabis use when pregnant. Clinicians should continue to educate patients about the potential health risks and provide patient-centered support to help patients make informed decisions about prenatal cannabis use.

Supplementary Material

supplemental digital content

Acknowledgments

A portion of the data was obtained through the Kaiser Permanente Northern California Division of Research’s Perinatal Research Unit’s Perinatal Obstetric Database. Kevin Kong conducted the data analysis for this study. Dr. Young-Wolff had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Funding/Support:

This study was supported by grant R01DA048033 and co-funded by National Institute on Drug Abuse (NIDA) and Office of the Director, NIH (OD), R01DA047405 and K01DA043604 funded by NIDA.

Role of Funder/Sponsor:

The NIH had no role in the design or conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Footnotes

Conflict of Interest Disclosures: The authors declare no conflicts of interest.

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