Maternal Drug Use, Infant Exposure, and Neonatal Abstinence Syndrome
Maternal Drug Use, Infant Exposure, and Neonatal Abstinence Syndrome
Stephen W. Patrick
KEY POINTS
An estimated 440,000 substance-exposed infants are born each year.
Verbal screening for substance use should occur in every pregnancy.
Opioid use in pregnancy is increasingly common and can result in drug withdrawal.
Every birth hospital should have a protocol in place to screen, evaluate, and treat substance-exposed infants.
An opioid (morphine or methadone) should be the first choice for opioid withdrawal if pharmacotherapy is required.
I. MATERNAL DRUG USE
A. Use of illicit substances. Data from the National Survey of Drug Use and Health (NSDUH) suggest that at least 5.4% of pregnant women use illicit drugs in pregnancy. Illicit drug use is highest among younger women, with the highest rate (14.6%) in 15- to 17-year-old girls. Overall, the rate of illicit drug use in pregnant women is nearly half that of the general population (11.4%), and women are less likely to use in the third trimester (2.4%). This suggests that, although illicit drug use in pregnancy is common, becoming pregnant may motivate some women to engage in treatment of substance use disorders. NSDUH reports the most common illicit drugs used as a percentage of the U.S. population >12 years old in the United States are marijuana (7.5%), psychotherapeutics used illicitly (2.5%), cocaine (0.6%), hallucinogens (0.5%), inhalants (0.2%), heroin (0.1%).
B. Maternal use and misuse of legal substances. The use of prescription medicines in pregnancy grew by nearly 70% over the last three decades. Pregnant women use an average of 1.8 prescription medications, and data on risk of fetal effects are limited for many. Prescribed medications include atypical antipsychotics (e.g., risperidone), antidepressants (e.g., sertraline), and opioid (e.g., hydrocodone). In addition, NSDUH reports high use by pregnant women of alcohol (9.4%) and cigarettes (15.4%). The Centers for Disease Control and Prevention website Treating for Two (http://www.cdc.gov/pregnancy/meds/treatingfortwo/) provides information to support safer medication use in pregnancy.
II. DIAGNOSIS OF DRUG USE IN PREGNANCY. A comprehensive medical and social history should be obtained from the mother with every newborn evaluation and should include use of illicit drugs, prescription drugs, tobacco, and alcohol. The American College of Obstetricians and Gynecologists recommends use of a validated screening tool for drug use such as the 4 P s or CRAFFT (Table 12.1). This history can be augmented by communication with obstetric providers and, when available, the state’s prescription drug monitoring program database.
Table 12.1. Clinical Screening Tools for Prenatal Substance Use and Abuse
4 P’s
Parents: Did any of your parents have a problem with alcohol or other drug use?
Partner: Does your partner have a problem with alcohol or drug use?
Past: In the past, have you had difficulties in your life because of alcohol or other drugs, including prescription medications?
Present: In the past month have you drunk any alcohol or used other drugs?
Scoring: Any “yes” should trigger further questions.
Ewing H. A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics: theoretical framework, brief screening tool, key interview questions, and strategies for referral to recovery resources. Martinez (CA): The Born Free Project, Contra Costa County Department of Health Services; 1990.
CRAFFT—Substance Abuse Screen for Adolescents and Young Adults
C Have you ever ridden in a CAR driven by someone (including yourself) who was high or had been using alcohol or drugs?
R Do you ever use alcohol or drugs to RELAX, feel better about yourself, or fit in?
A Do you ever use alcohol or drugs while you are by yourself or ALONE?
F Do you ever FORGET things you did while using alcohol or drugs?
F Do your FAMILY or friends ever tell you that you should cut down on your drinking or drug use?
T Have you ever gotten in TROUBLE while you were using alcohol or drugs?
Scoring: Two or more positive items indicate the need for further assessment.
Source: American College of Obstetricians and Gynecologists Committee Opinion No. 524: opioid abuse, dependence, and addition in pregnancy. Obstet Gynecol 2012;119(5):1070-1076.
A. Accurate information regarding illicit drug use may be difficult to obtain. Nonspecific maternal and infant associations with illicit drug use include the following:
1. Maternal
a. Poor or no prenatal care
b. Preterm labor
c. Placental abruption
d. Precipitous delivery
2. Infant
a. Small for gestational age
b. Intrauterine growth restriction
c. Microcephaly
d. Neonatal stroke
B. Diagnostic testing can be useful to supplement standardized verbal screening tools. Testing should be considered in infants with signs consistent with neonatal abstinence, severe intrauterine growth restriction without an identified etiology, intracranial hemorrhage or stroke, or placental abruption. It is important to know state, local, and institutional reporting requirements to child welfare agencies for positive test results as laws may be interpreted differently among jurisdictions.
1. Urine testing is a quick, noninvasive way to test for recent drug exposure in the neonate. For example, cocaine will appear in the urine up to 3 days after the most recent use, marijuana for 7 to 30 days, methamphetamine for 3 to 5 days, and opiates (including methadone) 3 to 5 days. Drugs administered during labor may cause difficulty in interpreting results.
2. Meconium testing provides information about drug use for a longer period in pregnancy. However, collection is time intensive for nursing staff, stools can be missed, and specimens can be contaminated.
3. Umbilical cord testing may provide similar data to meconium, although collection and storage of the umbilical cord at birth can be resource intensive.
C. Risk of infection. Illicit drug use increases the risk of infections in the pregnant woman and her infant, especially when associated with intravenous drug use or other high-risk behaviors (e.g., prostitution). The mother’s HIV, hepatitis B, hepatitis C, and syphilis status should be determined, and the infant should be managed accordingly (see Chapters 48 and 51).
III. NONOPIOID SUBSTANCE EXPOSURE. Substance use in pregnancy may result in abnormal psychomotor behavior in the newborn that is consistent with toxicity or withdrawal, as summarized in Table 12.2.
IV. NEONATAL ABSTINENCE SYNDROME FOLLOWING OPIOID EXPOSURE IN PREGNANCY
A. Because of the high prevalence of opioid use during pregnancy, the American Academy of Pediatrics (AAP) recommends that all hospitals that care for infants at risk for withdrawal have policies in place for screening and treatment. Adherence to such protocols appears to impact clinical outcomes more than pharmacotherapy. Neonatal abstinence syndrome (NAS) can result from a variety of opioids including prescription opioids (e.g., hydrocodone), illicit opioids (e.g., heroin), or medication-assisted treatment (e.g., methadone). Although medication-assisted treatment increases an infant’s risk of NAS, the infant’s risk of being born preterm or low birth weight is less than with continued heroin use. As a result, the American College of Obstetrics and Gynecologists recommends medication-assisted treatment.
Table 12.2. Onset and Duration of Clinical Signs Consistent with Neonatal Withdrawal after Intrauterine Substance Exposure (Excluding Narcotics)
Hyperactivity, crying, irritability, poor suck, tremors, seizures; onset of signs at birth, poor sleeping pattern, hyperphagia, diaphoresis
3-12 h
18 mo
Barbiturates
Irritability, severe tremors, hyperacusis, excessive crying, vasomotor instability, diarrhea, restlessness, increased tone, hyperphagia, vomiting, disturbed sleep; onset first 24 h of life or as late as 10-14 d of age
a Prescription indicates the infant was treated with pharmacologic agents, and the natural course of the signs may have been shortened.
Source: Hudak ML, Tan RC. Neonatal drug withdrawal. Pediatrics 2012;129:e540-e560.
B. An infant’s risk of drug withdrawal and its severity varies by opioid type and the presence of additional exposures. Methadone has the greatest risk, which becomes less with buprenorphine, followed by a long-acting opioid (MS Contin, morphine sulfate extended release), and then a short-acting opioid (hydrocodone). Adjunctive use of tobacco, selective serotonin reuptake inhibitors, atypical antipsychotics, and benzodiazepines increase the likelihood of NAS or make it more severe.
C. Timing of presentation. The initial presentation of NAS depends on when the drug was last used in pregnancy, infant metabolism, and half-life of the opioid used. In addition, for reasons that are uncertain, not all infants develop withdrawal. As a result, the AAP recommends that all opioid-exposed infants be observed in the hospital for signs of withdrawal for 4 to 7 days after birth.
D. Site of care. There is increasing evidence that processes of care that keep mother and infant together (e.g., rooming in), promote bonding, breastfeeding, and may reduce infant symptomatology and decrease NAS severity. Where possible, infants should not be separated from their mothers.
E. Assessment. Infants at risk for drug withdrawal should be assessed for drug withdrawal using an available scoring tool. We use the modified Finnegan Neonatal Abstinence Score Tool (NAST) (see Table 12.2). Scoring should begin soon after admission and continue every 3 to 4 hours, reflecting the preceding period and depending on the frequency of feedings, taking of vital signs, and provision of care. If infants appear hungry, we provide half of the feeding volume and then complete scoring. Infants are scored for a total of 4 days if pharmacologic intervention is not required. We continue to score infants who require pharmacologic therapy for the duration of therapy and for 48 to 72 hours after drug is discontinued to ensure that symptoms do not redevelop. We typically score infants who do not require pharmacologic intervention for a total of 4 days.
1. Signs of withdrawal include the following:
a. Central nervous system/neurologic excitability: tremors, irritability, increased wakefulness/sleep disturbance, frequent yawning and sneezing, high-pitched cry, increased muscle tone, hyperactive reflexes (e.g., Moro), seizures
b. Gastrointestinal dysfunction: poor feeding, uncoordinated and constant sucking, vomiting, diarrhea, dehydration, and poor weight gain
c. Autonomic signs: sweating, nasal stuffiness, fever/temperature instability, and mottling
F. Management. Infants with signs of withdrawal are treated based on NAST scores. Treatment begins with nonpharmacologic measures. Infants with severe withdrawal are treated with an opioid (morphine or methadone) as a first-line agent. Examples of treatment protocols using morphine (Vanderbilt University School of Medicine) and methadone (University of Michigan) are shown in the text and Figure 12.1.
1. Nonpharmacologic interventions are implemented for NAST scores <8.
a. Decrease stimulation by reducing lights, noise, and touch.
b. Promote infant self-regulation by encouraging pacifier use, nonnutritive sucking, and swaddling.
c. Room in with mother if possible.
d. Encourage holding, especially skin-to-skin.
e. Encourage breastfeeding.
2. Pharmacologic interventions are implemented for NAST scores ≥8, whereas nonpharmacologic interventions are continued. Infants treated with an opioid should be on a cardiac and respiratory monitor, particularly in the initial period, to ensure there are no clinical signs of respiratory depression.
a. We use morphine as the first-line drug, although methadone is an appropriate alternative. We use a dosing interval of 3 hours although, depending on feeding schedule, some infants benefit from alternative dosing intervals to provide the same 24-hour total dose (e.g., a baby feeding every 4 hours could be dosed every 4 hours).
Figure 12.1. Neonatal abstinence syndrome treatment protocol used at University of Michigan (methadone for pharmacologic treatment). NICU, neonatal intensive care unit; PO, orally; IV, intravenous; D/C, discontinue.
i. Morphine dose is adjusted based on the NAST score as shown in Table 12.3.
ii. One rescue dose of oral morphine 0.05 mg/kg is available for each infant until appropriate dosing changes are made. It may only be given once and must then be reordered by the clinician after reassessment of the maintenance dose. If scores are ≥8 following weaning, one rescue dose can be considered with return to the previous dose/dosing level. One rescue dose may be considered before adding clonidine.
b. Adjunct management
i. We reevaluate infants who reach level 4 and continue to score ≥8 and consider addition of clonidine, as shown in Table 12.4.
ii. If we are unable to wean morphine after 3 weeks of treatment, we consider adjunct management with oral phenobarbital.
c. Weaning begins when the average daily score is <8 without a single score of ≥14. Morphine is typically weaned by dose, not interval. If treatment includes clonidine, we wean the morphine first.
i. If the NAST score remains <8 for 48 hours, we wean morphine by 10% of the maximum dose every 48 hours if the average score continues to remain <8. We consider a faster wean after 24 hours if the NAST score remains <8.
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