Cannabis use during pregnancy has been increasing in the US.^1,2 A growing number of states across the US have legalized cannabis³ and studies have documented an increase in accessibility and acceptance of use.⁴ Thus, understanding how exposure during pregnancy affects child development is important.

A growing body of literature has documented associations between maternal prenatal cannabis use and adverse birth outcomes, including preterm birth and low birthweight.^5,6 Additionally, cannabinoids can cross the placenta and enter the fetal bloodstream potentially disrupting fetal neurodevelopment. However, there has been little research assessing the association of maternal prenatal cannabis use and childhood developmental outcomes, specifically early developmental delays such as speech and language disorders, motor delays, and global delays.⁷ Studies evaluating speech and language outcomes report conflicting results with a study reporting worse verbal ability⁸ and others documenting no association with language and verbal ability.^8,9,10 Similarly, inconsistent findings have been reported for motor skills. One study reported superior motor performance,⁸ another found worse processing speed and interhemispheric coordination on fine motor tasks,¹¹ and others documented no association with motor ability or performance^9,11,12 or psychomotor speed or eye-hand coordination.¹³ To our knowledge, global delays, such as delayed milestones, have not been evaluated in the context of maternal prenatal cannabis use. Furthermore, nearly all prior studies rely solely on self-reported cannabis use, which may underestimate the true prevalence of use during pregnancy and parent-reported developmental outcomes or the use of screeners rather than clinical diagnoses which may result in misclassification.¹⁴ This study evaluated the association between maternal cannabis use during early pregnancy and delays diagnosed in early childhood (speech and language, motor, and global) in a population universally screened for maternal prenatal cannabis use and early childhood developmental delays.

The cohort included 119 976 pregnancies (among 106 240 unique pregnant individuals). The sample included 32 793 Asian or Pacific Islander pregnancies (27.3%), 29 543 Hispanic pregnancies (24.6%), 6567 non-Hispanic Black pregnancies (5.5%), and 46 823 non-Hispanic White pregnancies (39.0%); 12 837 pregnancies (10.7%) were to individuals aged 24 years or less; 25 568 (21.3%) had at least 2 previous live births, and 10 365 (8.6%) were insured by Medicaid (Table 1). Maternal prenatal cannabis use was identified (via self-report or urine toxicology) for 6778 (5.6%) pregnancies. Of those, 1785 (26.3%) were positive by both self-report and toxicology results, 3821 (56.4%) by toxicology test only, and 1172 (17.3%) by self-report only. A total of 618 pregnancies (0.5%) identified with maternal prenatal cannabis use were to individuals who reported daily use, 722 (0.6%) who reported weekly use, and 1617 (1.3%) who reported monthly or less use. Urine toxicology tests were conducted at mean (SD) of 9.4 (3.6) weeks’ gestation; 5606 pregnant individuals (4.7%) tested positive for THC. Overall, 115 363 pregnancies (96.2%) were screened in the first trimester. Maternal sociodemographic and clinical characteristics by prenatal cannabis use are shown in Table 1 and eTable 1 in Supplement 1.

The median (IQR) age of follow-up was 39 (26-46) months (39 [26-47] months for children not exposed to maternal prenatal cannabis use and 29 [15-42] months for those exposed). The cumulative incidence of speech and language disorders among children up to age 5.5 years was 11.1% (95% CI, 10.9%-11.4%), with a first diagnosis or therapy session at mean (SD) age of 25 (9) months. The cumulative incidence of global developmental delay was 0.5% (95% CI, 0.5%-0.6%) among children up to age 5.5 years, with a first diagnosis at mean (SD) age of 23 (11) months. The cumulative incidence of motor delay up to age 5.5 years was 2.2% (95% CI, 2.1%-2.3%), with a first diagnosis at mean (SD) age of 13 (11) months. Cumulative incidences by prenatal cannabis use are presented in Table 2.

Maternal prenatal cannabis use was not associated with speech and language disorders in model 1 (hazard ratio [HR]: 1.01; 95% CI, 0.91-1.10) (Table 2). Results were similar as covariates were added in models 2 to 5 (model 5: HR, 0.93, 95% CI, 0.84-1.03). Self-reported frequency of maternal prenatal cannabis use was not associated with speech and language disorders (Figure). The sensitivity analysis defining prenatal cannabis use with only self-report data produced results similar to the main analysis (eTable 2 in Supplement 1). The sensitivity analysis defining prenatal cannabis use with only urine toxicology test data produced a modest inverse association with speech and language disorders (HR, 0.88; 95% CI, 0.78-0.99) (eTable 3 in Supplement 1). The sensitivity analysis restricted to pregnancies with no noncannabis substance use produced an inverse association with self-reported monthly or less cannabis use and speech and language disorders (HR, 0.68; 95% CI, 0.46-1.00) (eFigure 3 in Supplement 1).

Although a suggestive increased risk of global developmental delay was found with any prenatal cannabis use in model 1 (HR, 1.38; 95% CI, 0.94-2.03), after adjusting for maternal demographic characteristics the association was attenuated and remained not statistically significant (model 2: HR, 1.08; 95% CI, 0.71-1.64). Adjustment for all potential confounders also demonstrated no statistically significant association (model 5: HR, 1.04; 95% CI, 0.68-1.59) (Table 2). There was no association between self-reported frequency of cannabis use and global developmental delay (Figure). Similarly, no significant associations were observed for global developmental delay in sensitivity analyses defining prenatal cannabis use by self-report data only and by urine toxicology test data only (eTables 2 and 3 in Supplement 1) and in the sensitivity analysis restricting to pregnancies with no noncannabis substance use (eFigure 3 in Supplement 1).

Although a suggestive decreased risk of motor delay was found with any maternal prenatal cannabis use in model 1 (HR, 0.84; 95% CI, 0.69-1.00), after adjustment for all potential confounders the association was not statistically significant (model 5: HR, 0.86; 95% CI, 0.69-1.06) (Table 2). There was no association between self-reported frequency of cannabis use and motor delay (Figure). No statistically significant associations were observed for motor delay in the sensitivity analyses (eTables 2 and 3 and eFigure 3 in Supplement 1). The sensitivity analysis with no continuous enrollment requirement in the year prior to or during pregnancy produced results generally similar to the main analyses (eFigures 4 and 5 in Supplement 1).

In this large, population-based longitudinal birth cohort study, maternal cannabis use during early pregnancy was not associated with speech and language disorders, global delay, or motor delay. These associations were relatively stable across multiple sets of adjustment for potential confounders. Sensitivity analyses also largely support findings from the main analyses, except for a suggested modest inverse association with speech and language disorders when defining cannabis use based only on the urine toxicology results. Understanding the associations between maternal prenatal cannabis use and these early developmental outcomes is important because they may be early indicators of other salient developmental outcomes including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability.^23,24,25

Our findings are consistent with the majority of previous studies evaluating maternal prenatal cannabis use and various characteristics of speech and language development.^8,9,10 The previous research evaluating speech and language outcomes was based on data from the Ottawa Prenatal Prospective Study (OPPS) which ascertained prenatal cannabis use from maternal self-report. The study population was recruited in 1978 representing a time of lower potency cannabis products and the largest analytic sample evaluating speech and language disorders included 272 parent-child dyads.⁹ Maternal prenatal cannabis use was not associated with several speech and language outcomes (eg, verbal ability, language ability) at age 12 and 24 months,¹⁰ and 3,⁸ 4,⁸ or 5 to 6 years.⁹ Contrary to our findings, an association between heavy cannabis use and poor verbal ability at 4 years of age was documented in an analysis.⁸

An association between maternal prenatal cannabis use and superior motor performance in children aged 3 years was documented in an OPPS analysis,⁸ in contrast with the majority of the research evaluating motor developmental outcomes, including ours, which did not find an association. Four analyses conducted on data from the OPPS and the Maternal Health Practices and Child Development (MHPCD) studies found no association between maternal prenatal cannabis use and various motor skill traits including fine motor skills,¹¹ psychomotor speed and eye-hand coordination,¹³ and motor ability.^8,12 In contrast, an analysis from the MHPCD study reported worse interhemispheric coordination on fine motor tasks. This study evaluated outcomes at age 16 years, suggesting poorer motor outcomes may not arise until adolescence.¹¹

Future research is needed to understand the inverse association with speech and language disorders that emerged with a positive urine toxicology test. Our dose-response analyses of self-report data and speech and language disorders showed null associations, and the estimate for self-reported daily use was in the positive direction, contrasting the urine toxicology findings. Because our routine toxicology screening only documents yes or no use rather than concentration of THC, we were unable to investigate the dose-response association of toxicology results. Our prior study comparing self-report and toxicology results found that toxicology screening detected 65.8% of women who self-reported cannabis use, with greater detection by toxicology for self-reported daily (83.9%) and weekly (77.4%) than monthly or less use (54.1%).¹⁴ Future studies with more detailed data on frequency and duration of use and concentration of THC may be able to determine whether there is any association or whether the association is null.

Maternal prenatal cannabis use has been associated with adverse neonatal outcomes^26,27,28 and increased child psychopathology.^29,30 Furthermore, the underlying neurobiology and animal models suggest potential health risks. Animal models indicate that THC exposure may disrupt normal brain development and function by interfering with the endocannabinoid system³¹ resulting in long-lasting neurodevelopmental and behavioral abnormalities.^32,33,34,35 Epidemiologic research has documented changes to brain structure and function with prenatal cannabis exposure.^36,37,38 Despite our findings of no increased risks for early developmental delays, past evidence for adverse fetal and neonatal outcomes indicate that American College of Obstetrics and Gynecology and American Academy of Pediatrics recommendations for pregnant individuals and those considering pregnancy to discontinue cannabis use should be followed.³⁹

We note several strengths. This study included the largest number of pregnancies exposed to maternal cannabis use, and 1 of the largest cohorts to evaluate the association between maternal prenatal cannabis use and early developmental delays. The population of pregnant individuals was universally screened for cannabis use at entrance to prenatal care via urine toxicology and self-report, and children were routinely screened at multiple time points for developmental delays reducing recall bias and misclassification. Our study used diagnosis codes prospectively recorded in electronic medical records to identify early developmental delays. Diagnoses codes represent a more rigorous assessment of delay than used in previous research, which has relied on developmental screeners and parental report which are less accurate and informative for clinical care. To our knowledge, this analysis is among the first to assess infant global delay in relation to maternal prenatal cannabis use. We used rigorous methods through the development of a DAG to reduce potential bias and residual confounding and included many potential confounders captured through EHR data. We conducted sensitivity analyses to address variance in exposure classification by self-report and urine toxicology and confounding by cooccurrence of other maternal prenatal substance use which all produced similar results. Finally, we highlight the study sample was racially, ethnically, and geographically diverse.

This study did not find evidence of an association between maternal cannabis use in early pregnancy and child developmental delays up to age 5.5 years. Additional studies are needed to evaluate cannabis use throughout pregnancy, mode of administration and product strength, as well as potential factors that may mitigate adverse associations and neurodevelopmental outcomes that may emerge later in childhood. Given the association with other adverse neonatal outcomes and documented changes to brain structure and function, pregnant individuals and those considering pregnancy should be educated on the risks of prenatal cannabis use.