Approximately one in five people use alcohol, tobacco, marijuana, or other illicit substances during pregnancy in the United States (U.S. Department of Health and Human Services, 2023). Nationally, tobacco products are the most commonly used substances during pregnancy (10.8% of people who are pregnant), followed by alcohol (9.8%) and marijuana (7.7%) (U.S. Department of Health and Human Services, 2023). Nearly 8% of women who are pregnant have a substance use disorder (SUD) or need SUD treatment (Martin et al., 2020). Substance use during pregnancy can lead to miscarriage, stillbirth, preterm birth, low birthweight, neonatal abstinence syndrome or neonatal opioid withdrawal syndrome, and fetal alcohol spectrum disorders (Smid and Terplan, 2022).

While the prevalence of using individual substances during pregnancy is well-documented (Creanga et al., 2012; Handmaker et al., 2006; Ko et al., 2020a, 2020b; Luke et al., 2019; Smid and Terplan, 2022; Substance Abuse and Mental Health Services Administration, 2009), less is known about polysubstance use. Use of multiple substances during pregnancy may exacerbate adverse health outcomes for the person who is pregnant and the infant over single substance use. For example, compared with infants of people who used only marijuana or tobacco during pregnancy, neonates of mothers who reported co-use of marijuana and tobacco during pregnancy had higher odds of cardiac, musculoskeletal, and gastrointestinal birth defects, small head circumference, and poor infant self-soothing (Coleman-Cowger et al., 2018; De Genna et al., 2019). A recent study found that 38.2% of women who are pregnant who drank alcohol in the past 30 days also reported use of another substance, most commonly tobacco or marijuana (England et al., 2020). Another found that approximately half of women who were pregnant and reported nonmedical opioid use also reported having more than five alcoholic drinks in one day in the past month; 42.1% reported cigarette use and 35.1% reported marijuana use (Jarlenski et al., 2017). These studies suggest that among people who are pregnant and use at least one substance, polysubstance use is common.

Overdose is a leading cause of pregnancy-associated death (Campbell et al., 2021), with mortality rates increasing approximately 81% from 2017 to 2020 (Bruzelius and Martins, 2022). Polysubstance use was involved in a majority (83%) of drug-induced deaths among women who were pregnant or postpartum in one study (Smid et al., 2019); in another, nearly half (48.9%) of people with pregnancy-related overdose deaths were diagnosed with depression (Kountanis et al., 2023). Access to substance use and mental health screening and treatment, including medications for opioid use disorder (MOUD), is a critical component of efforts to reduce harmful substance use and overdose during pregnancy (Smid and Terplan, 2022; Campbell et al., 2021). Unfortunately, SUD treatment services remain limited for people who are pregnant; only about 13% of women who were pregnant with a past-year need for SUD treatment actually received it (Martin et al., 2020).

In addition to adverse pregnancy, birth, and infant outcomes linked with substance use, polysubstance use, and overdose, some prescription medications may also be associated with birth defects or may have interaction effects with certain substances if taken during pregnancy. An estimated seven in ten women take at least one prescription medication during pregnancy (Mitchell et al., 2011). In 2019, 6.6% of women took prescription opioids during pregnancy, and approximately one in five of these women reported prescription opioid misuse (Ko et al., 2020b). Prescription stimulant use has risen among young adult women, and prescription stimulant use during pregnancy has been linked to birth defects including gastroschisis, omphalocele, and transverse limb deficiency (Anderson et al., 2020). Prescription benzodiazepine use during pregnancy may also be associated with birth defects such as Dandy-Walker malformation, anophthalmia or microphthalmia, gastroschisis, esophageal atresia or stenosis, and pulmonary valve stenosis, although additional research is needed (Tinker et al., 2019). It is important that patients take medications as prescribed and do not start or stop using prescribed medications during pregnancy unless advised to do so by a physician (Centers for Disease Control and Prevention, 2022; March of Dimes, 2022; Food and Drug Administration, 2019). Patient and clinician communication is important to ensure patients understand the risks involved in stopping medications or taking medications along with certain substances during pregnancy (Lynch et al., 2018) and that patients are screened for substance use and referred as indicated for treatment. Comprehensive information surrounding medication and substance use during pregnancy is lacking (Franks et al., 2020; McCance-Katz, 2011; Widnes et al., 2017); enhancing knowledge can inform clinical practice and messaging to improve health outcomes without stigmatizing people who take medications or use substances.

This study estimates the prevalence and patterns of substance use, polysubstance use, and use of select prescription medications during pregnancy. A secondary aim of this study was to estimate the prevalence of respondent-reported clinician screening for alcohol, tobacco, and other substance use during pregnancy. Understanding these patterns can inform public health actions and clinical care, reduce the potential for harmful interactions between prescription medications and substances, improve overall family health, and prevent adverse infant developmental outcomes related to substance use. Additionally, understanding polysubstance use during pregnancy can inform evidence-based interventions, and the role of harm reduction in addressing associated health risks.

In this large, population-based sample of individuals with a recent live birth, approximately one in five persons reporting substance use during pregnancy engaged in polysubstance use. Cigarettes, alcohol, and cannabis were the most frequently reported single substances used during pregnancy, and polysubstance use varied by substance type. These findings underscore the importance of messaging about the risks of polysubstance use during pregnancy and screening for multiple substances, followed by linkage to substance use treatment and harm reduction services.

Our results are consistent with other reports (Kar et al., 2021; Qato et al., 2020). However, our findings fill important gaps by examining any use of prescription medications with other substances and multiple combinations of polysubstance use across legal and illicit substances during pregnancy. Use of other substances with alcohol during pregnancy was higher in the National Survey on Drug Use and Health (NSDUH; 38.2% (England et al., 2020)) than in our study; however, NSDUH captures alcohol use at any time during pregnancy, while PRAMS only captures use in the last three months of pregnancy.

Our findings of demographic differences in substance use can inform clinical practice, not by singling out specific subpopulations to receive greater scrutiny, but by illustrating the importance of considering social determinants of health, community environment, and the broader social and systemic context (including the impact of structural racism and bias) in providing holistic and comprehensive care to all persons who are pregnant. In this analysis, people aged 20–24 years more frequently reported cigarette and cannabis use during pregnancy, while people aged 35 years or older more frequently reported alcohol use during the last three months of pregnancy. Such age-related differences have been described in other studies (Cheng et al., 2011; Houston-Ludlam et al., 2019; Luke et al., 2019; Thompson et al., 2021). We also observed differences in substance use by race/ethnicity, with American Indian/Alaska Native persons reporting the highest prevalence of substance use during pregnancy, followed by non-Hispanic White persons. The higher prevalence of substance use among American Indian/Alaska Native persons must be understood within the context of historical and contemporary trauma, colonization, discrimination, and oppression (Gonzales et al., 2021; Morgan and Freeman, 2009; Szlemko et al., 2006), as well as barriers to culturally competent, inclusive, and non-stigmatizing treatment and prevention services (Gonzales et al., 2021; Szlemko et al., 2006). Additionally, factors such as systemic racism and bias may lead to inequities for persons from racial and ethnic minority groups compared to persons who are White, including higher rates of child services reporting and removal among prenatally substance-exposed infants (Chasnoff et al., 1990; Roberts and Nuru-Jeter, 2011).

We also observed higher prevalence of substance use among individuals who reported having depression or taking antidepressants during pregnancy. Co-occurrence of mental health conditions and substance use during pregnancy, particularly depression, has been identified in prior research (Brown et al., 2019). In addition, the use of medications such as opioids and benzodiazepines may be more common among people with certain mental health conditions (e.g. mood disorders, anxiety) (Sujan et al., 2021) and the convergence of mental health concerns, prescription medication use, and substance use may play a role in adverse pregnancy and birth outcomes (Viswanathan et al., 2021; Zhao et al., 2017). These findings indicate the need for screening for depression and substance use throughout pregnancy, and providing resources and treatment as indicated.

Although the overall prevalence of illicit opioid and stimulant use was low, use of illicit stimulants frequently occurred among respondents who reported use of illicit opioids, and vice versa. As illicit opioid and stimulant co-use has increased in the general population, so have overdoses involving both substances (Ciccarone, 2021; O’Donnell et al., 2020). Many of these deaths are attributable to the presence of synthetic opioids such as illicitly manufactured fentanyl, due to both substances being in the same product or co-use (Centers for Disease Control and Prevention, 2020; Ciccarone, 2021). Drug overdose is a leading cause of pregnancy-associated death, and overdose mortality among people who are pregnant has been increasing in recent years (Campbell et al., 2021; Bruzelius and Martins, 2022).

It is recommended that people who are pregnant with opioid use disorder (OUD) be initiated on MOUD (American College of Obstetricians and Gynecologists, 2017). MOUD during pregnancy is associated with improved pregnancy, birth, and infant outcomes, including reductions in overdose, preterm birth, and low birthweight compared with people with OUD who did not take MOUD during pregnancy (Krans et al., 2021). Over two-thirds of respondents who reported heroin use also took MOUD during pregnancy, indicating potentially successful linkages to treatment, though the available data cannot confirm that they were receiving MOUD from a clinician or using it as provided, or whether they stopped misusing opioids with a transition to MOUD. Patients receiving MOUD may also have frequent touchpoints with the healthcare system, which can improve health outcomes and provide additional opportunities to address substance use. Nevertheless, there are multiple barriers to accessing MOUD and other forms of substance use treatment during pregnancy, including transportation and geographic barriers, childcare barriers, stigma, and fear of child welfare services involvement (Choi et al., 2022; Frazer et al., 2019); as a result, many persons who are pregnant with a SUD are unable to access treatment (Martin et al., 2020). Integrated behavioral health, SUD treatment, and prenatal and postpartum care services paired with social service support, harm reduction, and care coordination may reduce these barriers and improve overall health and wellbeing (Ellis et al., 2023).

The U.S. Preventive Services Task Force recommends screening all adults aged 18 and older, including people who are pregnant, for alcohol, tobacco, and unhealthy drug use (Curry et al., 2018; Krist et al., 2020, 2021). Patterns of demographic differences in alcohol use in this analysis differed from those observed for other substances, particularly with regard to age, race/ethnicity, and educational status, which reinforces the need for universal screening for alcohol and other substances during pregnancy. However, the prevalence of respondent-reported clinician screening for cannabis and other drug use during pregnancy was lower than the prevalence of asking about alcohol and cigarette use. Barriers to clinician screening for substance use during pregnancy may include time constraints, competing priorities, and concerns about mandatory reporting laws, and persons who use substances during pregnancy may face additional trauma, stress, and stigma that interferes with prenatal care access and screening (Dozet et al., 2023). Adopting a trauma-informed and culturally sensitive therapeutic approach may help to reduce barriers to screening and treatment during pregnancy (Raffi et al., 2021). Additionally, findings of prescription medication use among persons who reported substance use during pregnancy, and vice versa, highlight the importance of ongoing discussions throughout pregnancy regarding potentially harmful interaction effects between medications and substances, such as co-use of alcohol with benzodiazepines or opioids.

Some people may not be able to achieve abstinence from substance use during pregnancy, or may not want to (Academy of Perinatal Harm Reduction, 2020). For these individuals, harm reduction strategies can be employed to reduce risks associated with substance use and promote health, worth, and dignity. Specific strategies include reducing the frequency of substance use, switching to a safer form of use (e.g. oral vs. injection), planning ways to stay safe before using substances (including not using alone, access to naloxone, and use of fentanyl test strips), and reducing the risk of skin bacterial and bloodborne infections if injecting substances by using sterilized injection supplies (Academy of Perinatal Harm Reduction, 2020). One pilot harm reduction program found that 96% of participants who were pregnant had negative urine toxicology screens at delivery and their infants had similar rates of prematurity as the state and national population, despite experiencing additional risk factors for prematurity (Wright et al., 2012).

Many factors can impact pregnancy and birth outcomes in addition to substance use (Academy of Perinatal Harm Reduction, 2020; Viteri et al., 2015), and it can be challenging to identify the causes of adverse health impacts, particularly when use of multiple substances are involved. Furthermore, there are no standardized definitions of polysubstance use during pregnancy. Previous studies have defined polysubstance use as co-occurring use or substance use disorders (Jarlenski et al., 2020; Hardt et al., 2013), use within the past 30 days (Coleman-Cowger et al., 2017; Jarlenski et al., 2017), or use at any time point during pregnancy (Nguyen et al., 2023). Additionally, polysubstance use in some studies may include nonmedical prescription medication use (Jarlenski et al., 2017) or any prescription medication use (Nguyen et al., 2023). This lack of consistency in defining and reporting on polysubstance use during pregnancy may inhibit conversations with patients around the potential health impacts of substance use individually, in combination, and in conjunction with prescription medications.

This analysis was subject to several limitations. First, findings may not be generalizable beyond the included jurisdictions. Additionally, only 11 of the 25 jurisdictions asked respondents about alcohol use, limiting our sample size for reporting on use of alcohol with other substances. Individuals’ responses to the survey may have been impacted by recall and social desirability biases. Sample sizes were small for some illicit substances and demographic groups and prevalence estimates with wide confidence intervals should be interpreted with caution. Due to question wording, we were only able to examine e-cigarette and alcohol use during the last three months of pregnancy. Due to high rates of reducing or quitting alcohol use once pregnancy is recognized (England et al., 2020; Handmaker et al., 2006), our results may under-estimate alcohol use prior to the last three months of pregnancy, and do not allow for distinction between the characteristics and behaviors of those who quit early and those who did not. PRAMS also does not collect information on substance use or medication frequency, duration, and dose. Additionally, our data were from the 2019 PRAMS survey and do not reflect changes in substance use that may have occurred during the COVID-19 pandemic. For example, one study found that cannabis use during pregnancy in Northern California increased by 25% during the pandemic compared to the 15 months prior (Young-Wolff et al., 2021). Finally, we only had information on selected prescription medications, and did not have complete information about patterns of use as prescribed or misuse, with the exception of prescription opioids.

Polysubstance use was common in this sample among individuals who reported use of any substance during pregnancy. The frequency of polysubstance use during pregnancy demonstrates the importance of understanding substance use epidemiology and implementing screening, prevention, patient and clinician education, and intervention efforts, including overdose prevention and harm reduction services, for people who use substances while pregnant. Furthering understanding around substance use while also taking prescription medications is also important. Additional data and research may help to better understand polysubstance use throughout pregnancy, including patterns of use by pregnancy trimester and other factors that may be associated with polysubstance use, including social determinants of health. Importantly, clinicians and public health practitioners can engage people who are pregnant in conversations around the risks of substance use during pregnancy, especially polysubstance use, emphasizing respect and dignity through the lens of a harm reduction approach. Substance use during pregnancy is complex and requires a thoughtful, well-resourced, multi-layered approach to effect change and improve the lives of people who are pregnant and their families.