Continuing Education Activity

Substance use and substance use disorders in pregnancy are common and linked with multiple obstetric and neonatal adverse outcomes. Ideally, all pregnant women should be screened, and those with positive screens should be promptly diagnosed and treated to avoid the morbidity and mortality associated with continued substance use during pregnancy. This activity reviews the adverse outcomes associated with the most commonly used substances and the need to collaborate with an interprofessional team to counsel, appropriately treat, and support women during their pregnancies for better outcomes.

Objectives:

• Identify the common adverse outcomes associated with the most commonly used substances during pregnancy.

• Review the use of validated screening instruments to better identify substance use in pregnancy.

• Implement the recommended treatments for substance use disorders in pregnancy.

• Collaborate with an interprofessional team to counsel and support women during treatment for substance use during pregnancy for better outcomes.

Introduction

Perinatal substance use is a significant public health issue in the United States (US) and worldwide. In the US, 40% of persons with a lifetime drug use disorder and 26% with a combined alcohol and drug use disorder during the prior year are women. They are at the highest risk for substance use disorder during their reproductive years, and substance use during pregnancy is prevalent. The most frequently used substances in pregnancy are tobacco, alcohol, and marijuana, followed by cocaine and opioids. Use in pregnancy is associated with multiple adverse outcomes for the mother and their child.

Universal screening is recommended, with access to effective interventions if indicated. However, pregnant women who use substances often feel stigmatized, and barriers to evidence-based treatments exist. This activity will include a discussion of legal and psychosocial issues and the importance of the interprofessional team in ensuring healthy outcomes for women who use substances during pregnancy and their children. 

Etiology

Most women who use substances decrease their use during pregnancy. In general, women do not choose to begin using any potentially toxic substances once they know they are pregnant. Those who can quit on their own usually do so, which is the distinguishing factor between substance use and substance use disorder (SUD).

The etiology of SUD is multifactorial, and pregnant women are no different than the general population. Many genetic, environmental, psychological, biological, and socioeconomic factors contribute to individual susceptibility.[1] Tobacco and alcohol are often readily available and perceived as safe because they are legal. Prescription opioids, including those prescribed after delivery, contribute to opioid use disorder (OUD) by exposing women to addictive medications and making available leftover pills that can be misused or diverted.[2] 

Other prescribed controlled substances like amphetamines and barbiturates can also lead to dependence. Illicit drugs such as heroin may be easy to obtain by those with SUD and drug-seeking behaviors. Other conditions such as poor nutrition, needle sharing, lack of safe housing, poverty, low educational level, and intimate partner violence are associated with the diagnosis of SUD. Patient-report surveys investigating the influence of the environment demonstrate increased levels of alcohol and drug use in urban locales and communities with higher proportions of adolescents, young adults, and immigrants.[1][3]

Epidemiology

Between 2005 and 2014, 11.5% of adolescent and 8.7% of adult pregnant women reported drinking alcohol, and 23% of adolescent and 14.9% of adult women reported using tobacco.[4] A US national survey in 2012 showed that 5.9% of pregnant women reported using illicit drugs, 8.5% reported drinking alcohol, and 15.9% reported smoking cigarettes during pregnancy. Similar use and fetal exposure to these substances have been reported in Europe and Australia.[5]

Retrospective reviews demonstrate that 2.5% of all pregnant women and about 20% of those with US Medicaid insurance received at least one prescription for an opioid during pregnancy.[6] Most pregnancies in mothers with OUD are unplanned.[7] Polysubstance use is frequent during pregnancy, similar to the general population. 

There is a documented decrease in cigarette, alcohol, marijuana, and cocaine use during pregnancy, with most women quitting or cutting back.[8] 

SUD is rarely an isolated diagnosis. It is associated with increased rates of psychiatric conditions, including major depressive, bipolar, posttraumatic stress, and panic disorder.[9] Comorbid human immunodeficiency virus (HIV), hepatitis B and C, tuberculosis, and sexually transmitted infections occur due to an association with multiple sex partners, sharing drug paraphernalia, homelessness, and increased incarceration rates.[10][11]

Pathophysiology

Substance use and SUD in pregnancy are associated with significant maternal, fetal, and neonatal pathology, depending on the substances involved. Explaining the pathophysiological consequences of each substance is beyond the scope of this activity.

History and Physical

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) combined the substance abuse and dependence criteria to diagnose SUD.[12] The presence of two or more in the preceding 12 months is diagnostic of SUD: 

• hazardous use
• social/interpersonal problems due to using
• neglect of expected roles
• withdrawal
• tolerance
• using more or for longer than intended
• repeated attempts to quit
• related physical/psychological problems
• craving
• use preferred over other activities

A comprehensive medical history and a complete physical examination are the first steps in establishing the diagnosis of SUD. Some pregnant women readily admit to substance use, but others may be reluctant to disclose this sensitive information due to fear of repercussions, judgmental treatment, and social services involvement. When a stated history of substance use is absent, other features of the medical history can point to possible SUD, including a history of endocarditis, HIV, hepatitis C, sexual and/or physical abuse, and psychiatric conditions. A pregnant woman with late or no prenatal care may have avoided appointments due to concerns about revealing her substance use and the perceived adverse consequences. Many fear arrest, prosecution, and loss of child custody.

Physical examination begins with vital signs, with hypertension being a clue for possible cocaine or amphetamine use. Nasal septal perforation may be an additional clue for cocaine use. An underweight patient may be malnourished due to drugs or alcohol. Clinical staff, including medical assistants, nurses, nurse practitioners, physician assistants, and physicians, should observe the patient's general appearance. Women who are obtunded, agitated, or sleepy may be under the influence of substances. Dilated or constricted pupils and injection marks on the skin suggest possible opioid use. Bruises should elicit questions about maltreatment. If a pregnant woman smells strongly of tobacco, alcohol, or marijuana, she should be asked specifically about these substances in a confidential setting. Another frequent but nonspecific physical finding is poor dentition. 

Evaluation

Substance use in pregnancy is a common condition with substantial complications. A thorough medical history and physical examination will often lead to a diagnosis of SUD or reveal concerning substance use that does not meet the DSM-5 criteria for SUD. However, many women will not disclose sensitive information about their substance use, so clinicians must rely on other methods to identify those at risk.

The American College of Obstetricians and Gynecologists (ACOG) recommends early, universal screening for substance use as part of comprehensive prenatal care in partnership with pregnant women.[13] In fact, most developed countries advocate for universal screening.[14] If women are screened only when a medical provider suspects drug or alcohol use, many patients will be missed. A validated screening instrument that is easy to administer, acceptable, and economical should be used. Barriers exist, including the perception that screening will offend women and insufficient time during an office visit to counsel and refer those whose screen is positive. In general, no screening instrument is superior; three free and easy-to-use screens are the NIDA Quick Screen, 4 Ps, and CRAFFT (for women younger than 27).[15] The T-ACE and T-ACER 3 screens are specific for alcohol use in pregnancy.[16] These validated screening instruments are readily available online. Trained clinical staff, including medical assistants and nurses, can administer the selected screening instrument. ACOG recommends an initial screening at the first prenatal visit, and many practitioners repeat screening at designated intervals during subsequent visits. 

A positive screen cannot be considered diagnostic of SUD in pregnancy. False positive and false negative results occur, and screening may reveal occasional substance use rather than SUD. The clinician's next step is a conversation regarding the frequency of substance use and whether there is any current use. It is essential to counsel pregnant women about the risks to themselves and their children and discourage further use. When SUD is suspected or confirmed, it is essential to provide information about local resources for counseling and treatment in a nonjudgmental manner. Medical providers should never assume family members or significant others know about a woman's substance use, and respecting patient confidentiality is of utmost importance. Clinicians should also be knowledgeable about local and state reporting requirements. SUD is a medical condition, not a moral failing, and punitive attitudes can negatively impact maternal and neonatal outcomes. Women with SUD who feel stigmatized may avoid continuing essential prenatal care.

Screening is often confused with drug or alcohol testing. Universal screening, but not routine drug or alcohol toxicology testing, is recommended in pregnant women. Screening is a test used for at-risk populations, including those without symptoms. However, testing for biological markers of substance use may be indicated in specific situations, especially when objective or specific information about multiple substances is required. Urine, hair, and meconium samples have shown adequate sensitivity as biological markers of substance use. Urine drug screening mainly detects recent use.[17] Neonatal hair and meconium testing can reveal intrauterine use in the second and third trimesters.[18] Maternal consent, except in life-threatening situations, is required before performing drug testing during pregnancy.[18] 

Mandated biological testing may be required for women in treatment programs or involved with the legal system. Drug testing does not distinguish between regular and occasional substance use and should be based on medical criteria rather than demographic profiling. Testing in the hospital during labor and delivery must occur before administering prescription medications that may produce a positive result. Each community has trends in drug use, which should be reflected in local and hospital laboratories' testing panels. False-positive test results have been linked to ingesting poppy seeds and dextromethorphan.[19][20] False-negative results occur when patients substitute someone else's urine for their own. An astute laboratory technician or nurse may notice that the sample provided by the patient is cool or at room temperature rather than body temperature and question the specimen's origin.

Treatment / Management

The optimal management strategy for pregnant women with substance use or SUD begins with comprehensive prenatal care. The next step is counseling and educating them about the consequences of tobacco, alcohol, and drug use related to themself and their unborn child and encouraging them to discontinue or reduce usage. Motivational interviewing and brief intervention rather than a judgmental or punitive approach are more likely to produce positive behavioral change. All women with SUD should be referred to the appropriate provider without delay for comprehensive behavioral and medical treatment.

Treatment of all types of SUD reduces the risk of relapse and improves pregnancy outcomes. ACOG recommends that pregnant women who smoke or use nicotine and tobacco products quit. Babies born to women who abstain by 15 weeks of gestation benefit the most. When behavioral counseling does not result in smoking cessation, varenicline, bupropion, and nicotine replacement can be considered, but these treatments lack safety data for use in pregnancy. Varenicline and bupropion are both FDA category C medications. Nicotine replacement during pregnancy has not been proven to result in long-term smoking cessation.[21] 

Patients with alcohol or benzodiazepine use disorder can be managed with detoxification using a diazepam or lorazepam taper.[18] Approved medications for alcohol use disorder include naltrexone, disulfiram, and acamprosate. However, they are category C medications with no human data to support safety during pregnancy, and animal studies show adverse and possible teratogenic effects.[22] Alcohol withdrawal syndrome is dangerous and potentially life-threatening, resulting in seizures and delirium tremens, and patients with withdrawal should receive inpatient detoxification.[23] 

Medication-assisted treatment is the standard of care for pregnant women with OUD. Although some women choose medically supervised withdrawal, current guidelines recommend treatment with methadone or buprenorphine. There is a higher rate of relapse during pregnancy in women who elect detoxification rather than medication-assisted treatment.[24] Naltrexone, an opioid receptor antagonist, is also approved for OUD, but insufficient data exist to recommend initiating the medication during pregnancy. However, when a pregnant woman is already treated with naltrexone, she may elect to continue it after reviewing potential risks and benefits with her clinician and with close medical supervision.[25]

Medication-assisted treatment suppresses cravings and withdrawal symptoms, and patients are less likely to use illicit substances when enrolled in a treatment program. Pregnant women better adhere to prenatal care recommendations and experience fewer complications associated with intravenous drug use, such as overdose and infection. However, many pregnant women with OUD struggle to access medication-assisted treatment compared to their non-pregnant peers, especially those living in rural areas, non-English speakers, and those not covered by health insurance.[24][26][27]

The decision to prescribe either buprenorphine or methadone depends on many factors, including the availability of treatment programs and whether the patient prefers daily supervised medication appointments or a prescription to be taken at home.[28][29] Methadone is a long-acting, full mu-receptor agonist and, in the US, must be dispensed at a federally accredited opioid treatment program under direct supervision. Patients require access to a local program and reliable transportation. Methadone reduces HIV risks and fetal mortality and increases birth weight and adherence to prenatal care. Buprenorphine is a partial mu-receptor agonist and can be prescribed in office-based settings. Patients may take oral or sublingual buprenorphine at home, with regular follow-up office visits. They do not need daily transportation to a treatment facility, but there is a risk of medication diversion and non-compliance. Prescribers must know about local resources and patient-specific factors to determine the best treatment plan for each patient. 

Mainstreaming Addiction Treatment (MAT) Act

The Mainstreaming Addiction Treatment (MAT) Act provision updates federal guidelines to expand the availability of evidence-based treatment to address the opioid epidemic. The MAT Act empowers all health care providers with a standard controlled substance license to prescribe buprenorphine for opioid use disorder (OUD), just as they prescribe other essential medications. The MAT Act is intended to help destigmatize a standard of care for OUD and will integrate substance use disorder treatment across healthcare settings. 

As of December 2022, the MAT Act has eliminated the DATA-Waiver (X-Waiver) program. All DEA-registered practitioners with Schedule III authority may now prescribe buprenorphine for OUD in their practice if permitted by applicable state law, and SAMHSA encourages them to do so. Prescribers who were registered as DATA-Waiver prescribers will receive a new DEA registration certificate reflecting this change; no action is needed on the part of registrants.

There are no longer any limits on the number of patients with OUD that a practitioner may treat with buprenorphine. Separate tracking of patients treated with buprenorphine or prescriptions written is no longer required. 

Pharmacy staff can now fill buprenorphine prescriptions using the prescribing authority's DEA number and does not need a DATA 2000 waiver from the prescriber. However, depending on the pharmacy, the dispensing software may still require the X-Waiver information in order to proceed. Practitioners are still required to comply with any applicable state limits regarding the treatment of patients with OUD.  Contact information for State Opioid Treatment Authorities can be found here: https://www.samhsa.gov/medicationassisted-treatment/sota.  

Neonatal opioid withdrawal syndrome (NOWS)

Neonatal opioid withdrawal syndrome (NOWS), previously referred to as neonatal abstinence syndrome (NAS), is an expected and manageable condition in newborns with prenatal opioid exposure. Treatment with methadone and buprenorphine during pregnancy can decrease the severity of NOWS. Some studies demonstrate that newborns exposed to prenatal buprenorphine require less medication and have a shorter hospital stay than those exposed to methadone.[30] They may also have a slightly improved birth weight and gestational age.[31] 

Medication-assisted treatment has not been associated with congenital malformations, and studies show minimal to no long-term neurodevelopmental adverse outcomes in exposed infants.[32][33] Symptom onset often occurs within 12 to 24 hours with heroin exposure but between 48 and 72 hours with medication-assisted treatment. Occasionally, infants do not exhibit symptoms until aged 5 to 7 days. Some studies correlate the dose of medication-assisted treatment with the severity and incidence of NOWS, but others find no association.[34][35] 

Women who begin medication-assisted treatment before or early in pregnancy are more likely to receive comprehensive prenatal care, follow medical recommendations, and deliver healthier babies. They are also less likely to relapse or acquire sexually transmitted infections. Medication-assisted treatment should be readily available to all pregnant women identified with OUD to improve maternal and infant outcomes.

Breastfeeding

Women who breastfeed and "room-in" with their newborns require less pain medication after delivery. Breastfeeding is associated with a decreased severity of NOWS symptoms and a decreased need for pharmacotherapy for affected newborns.[36][37] However, it is not recommended when women use illicit substances, including marijuana, because traces can be found in breast milk. Few controlled studies exist on marijuana in breastfeeding women, and it is difficult to separate prenatal from breast milk exposure. Without data supporting its safety, ACOG and the American Academy of Pediatrics (AAP) regard abstaining as prudent.[38]

Women with hepatitis C should breastfeed unless they have cracked or bleeding nipples, but it is generally contraindicated for mothers with HIV.[39][40] However, the World Health Organization recommends that mothers infected with HIV in developing countries who are treated with combined antiretroviral therapy (cART) should breastfeed their infants because breast milk is likely more nutritious than available alternatives.

Occasionally, a new mother will feel uncomfortable breastfeeding, especially if she has a history of intimate partner violence. Clinicians should respect and support her decision to nourish her baby with formula. 

Differential Diagnosis

The differential diagnosis is based on the particular substance(s) being used during the pregnancy.

If the medical history, physical examination, validated screening, or biological testing reveals substance use, the next step is to distinguish between occasional or prescription usage and SUD. If a woman is diagnosed with SUD, she should be evaluated for single versus polysubstance use because the consequences and treatment differ, depending on the substances involved. The clinician must search for common comorbid conditions related to SUD, including sexually transmitted infections such as HIV. Individuals with SUD also have higher rates of mental health disorders than the general population. Diagnosing psychiatric conditions may be difficult before initiating SUD treatment due to overlapping symptoms. In addition, poor nutrition and dental hygiene often accompany SUD.

Clinicians who listen carefully, perform a complete physical examination, and screen with a validated instrument are more likely to diagnose SUD early and initiate appropriate treatment. Pregnant women with SUD must be evaluated for coexisting conditions that can adversely impact the pregnancy if not diagnosed and promptly managed. A high index of suspicion for SUD will lead to early treatment and improved outcomes for both mother and her child.

Prognosis

Abstinence and medication-assisted treatment improve outcomes for pregnant women and their children. Pregnancy is a strong motivator for abstinence, and most women refrain from or decrease their use of tobacco, alcohol, marijuana, and cocaine by the second trimester. Those with OUD receiving medication-assisted treatment, enrolled in a comprehensive program with behavioral counseling and psychosocial support, usually maintain sobriety until delivery. However, postpartum relapse is frequent, especially for tobacco, marijuana, and alcohol, with rates as high as 80% in the first year after giving birth.[8] Following delivery, a combination of sleep deprivation, hormonal shifts, and caring for an infant causes stress, making ongoing recovery challenging. Postpartum unintentional overdoses contribute to maternal mortality, and women should be followed closely during the first postpartum year.[41]

Complications

Tobacco use increases the risk of stillbirth, fetal growth restriction, decreased birth weight, prematurity, and sudden unexplained infant death.[42][43] Smoking is associated with attention deficit/hyperactivity disorder in childhood, but studies confirming causation are lacking.[44]

No amount of alcohol is deemed safe during pregnancy, and drinking may result in fetal alcohol syndrome (FAS) and congenital malformations. Like tobacco, alcohol may be perceived as safe and socially acceptable because it is legal. As many as 13.5% of pregnant women have consumed alcohol in the previous month, according to the Centers for Disease Control. Alcohol is a known teratogen, and FAS is the leading cause of preventable intellectual disability in the US.[22] 

Marijuana is a federally banned substance in the US, but legal in many states. Randomized, controlled studies during pregnancy are lacking, but there is evidence of an association with stillbirth, decreased birth weight, and preterm birth.[45][46] Direct causal evidence is lacking, but there is a concern about poorer cognitive outcomes in school-aged children.[38] One study reported that maternal marijuana use during pregnancy did not predict adverse neonatal outcomes after adjusting for concomitant tobacco use and other confounding factors.[47] However, a recent review and meta-analysis reported increased adverse outcomes in neonates exposed to marijuana in-utero.[48] These included a birth weight under 2500 grams, decreased mean birth weight, small for gestational age, prematurity, lower Apgar score at 1 minute, and smaller mean head circumference.[48] ACOG and the AAP advise avoiding marijuana due to the possible neurodevelopmental impact on the developing fetus.[49]

Cocaine use is associated with maternal hypertension and placental abruption and may result in low birth weight, small for gestational age, and prematurity in neonates.[50][51] Researchers have established a link between cocaine use and growth deceleration involving all parameters, with a more pronounced effect in late gestation.[52] 

Amphetamines are associated with increased maternal and fetal morbidity and mortality, including maternal hypertension, preeclampsia, placental abruption, fetal demise, and neonatal death.[53]

Opioids, both illicit and prescribed, can cause NOWS, which affects the newborn's central nervous, autonomic, respiratory, and gastrointestinal systems and may lead to prolonged hospitalization.[54] Early signs and symptoms include irritability, poor feeding, temperature instability, and difficulty sleeping. Prenatal opioid use also increases the risk of low birth weight and neonates who are small for gestational age.[55][56][57]

Legal issues can also occur with substance use during pregnancy. Eighteen states in the US define substance use as child abuse, and three consider it grounds for commitment. Many women fear arrest, prosecution, and loss of custody and therefore avoid prenatal care or do not disclose their substance use to their medical providers. Some states mandate reporting all illicit or prescribed substance use, including marijuana and medication-assisted treatment, to Child Protective Services. Clinicians must know their local testing and reporting requirements and share this information with their pregnant patients while advocating for holistic and comprehensive care. Criminalizing substance use will not lead to improved clinical outcomes for mothers or their children. 

Deterrence and Patient Education

Patient education regarding maternal and neonatal complications of substance use in pregnancy is essential. Comprehensive prenatal and postnatal care, including behavioral counseling and psychosocial support, improves clinical outcomes.[14] Childbearing-aged women should receive information about the dangers of prenatal substance use, including alcohol, tobacco, and marijuana because many pregnancies are unplanned. For women with OUD, initiating medication-assisted treatment before pregnancy is a recommended public health approach. 

Women whose newborns are at risk for NOWS benefit from learning what to expect after delivery. Nurses and other clinicians can discuss newborn withdrawal symptoms, comfort measures, breastfeeding, pharmacotherapy options, and the need for close observation. Many labor and delivery units offer prenatal tours to mothers with OUD to prepare them for their perinatal experience. 

Patient education, counseling, and monitoring do not end with delivery. Women with SUD are at high risk for postpartum relapse and must be educated about the dangers of resuming substance use after delivery. They should be screened and closely monitored, especially during the first postpartum year. Continued medication-assisted treatment and consultation with substance use specialists and behavior therapists will help achieve optimal outcomes.[8] Broadly defined, patient education includes information and access to resources for transportation, safe housing, food security, childcare, and contraception. Trauma-informed counseling and peer recovery support groups can also improve the chances of sobriety following delivery.[58] 

Enhancing Healthcare Team Outcomes

Caring for women with substance use during pregnancy can be rewarding, challenging, complex, and time-consuming. A holistic approach to comprehensive care requires an interprofessional team. Nurses, nurse practitioners, physician assistants, physicians, midwives, social workers, pharmacists, and mental health and addiction medicine specialists who work together as a cohesive interprofessional team can improve outcomes for mothers and their children. Prenatal screening for substance use can be performed by nursing staff in the office setting. Nurses can also educate pregnant women about substance use, medication-assisted treatment, NOWS, and the advantages of breastfeeding. 

Many hospitals employ the LDRP model, where the same nurses care for the mother during labor, delivery, recovery, and postpartum. Nurses are often the first to notice a new mother having difficulty caring for her newborn, especially if experiencing side effects of medication-assisted treatment, such as falling asleep while holding her child. Pregnant women, due to a greater volume of distribution and rate of metabolism, often require more methadone during pregnancy, and the dose might need adjustment after delivery.[32] An astute nurse observes maternal medication side effects and early signs of neonatal withdrawal. Everyone who cares for the mother-infant dyad is part of the team.

Many programs conduct multidisciplinary rounds regularly, with professionals from obstetrics, pediatrics, pharmacy, and social work discussing the care of all mothers and their newborns. Social workers assist with assessing the social determinants of health, including housing, food insecurity, and transportation, and preparing mothers for the possible involvement of Child Protective Services. 

A model perinatal program at the Dartmouth-Hitchcock Medical Center combines midwifery services and addiction treatment. This model provides specialized care for women during pregnancy and the postpartum year and recognizes this population's unique and challenging needs. The program has led to better access to prenatal care, continuity of care, and family planning services.[59] 

The interprofessional healthcare team can improve care for pregnant women with substance use and SUD. SUD is a complex medical condition requiring empathy, knowledge, and skills from a team of caregivers working together. Implementing universal screening, overcoming barriers to treatment, addressing psychosocial needs, establishing an early diagnosis, and initiating medication-assisted treatment when appropriate will result in healthier outcomes for mothers and their children.