Prenatal Substance Abuse: Short- and Long-term Effects on the Exposed Fetus

abstract Prenatal substance abuse continues to be a significant problem in this country and poses important health risks for the developing fetus. The primary care pediatrician’s role in addressing prenatal substance exposure includes prevention, identification of exposure, recognition of medical issues for the exposed newborn infant, protection of the infant, and follow-up of the exposed infant. This report will provide information for the most common drugs involved in prenatal expo- sure: nicotine, alcohol, marijuana, opiates, cocaine, and methamphet- amine. Pediatrics 2013;131:e1009–e1024

Substance abuse has been a worldwide problem at all levels of society since ancient times. Attention has been directed toward the use of legal and illegal substances by pregnant women over the past several decades. Almost all drugs are known to cross the placenta and have some effect on the fetus. The effects on the human fetus of prenatal cigarette use have been identified and studied since the 1960s,1 the effects of alcohol and opiate use have been studied since the 1970s,2–4

and the effects a variety of other illicit drugs have been studied since the 1980s.5–7 This report reviews data regarding the prevalence of exposure and available technologies for identifying exposure as well as current information regarding short- and long-term outcomes of exposed infants, with the aim of facilitating pediatricians in fulfilling their role in the promotion and maintenance of infant and child health.

PREVALENCE

Prevalence estimates for prenatal substance use vary widely and have been difficult to establish. Differences are likely attributable to such things as the use of different sampling methods and drug-detection methods, screening women in different settings, and obtaining data at different points in time. For example, prevalence will vary depending on whether history or testing of biological specimens is used; whether the biological specimen is hair, urine, or meconium; and whether the specimens are merely screened for drugs or screened and confirmed with additional testing. There also will be differences depending on whether the sample being investigated is a community sample or a targeted sample, such as women who are in drug treatment or are incarcerated. Lastly, prevalence must be interpreted in light of the fact

Marylou Behnke, MD, Vincent C. Smith, MD, COMMITTEE ON SUBSTANCE ABUSE, and COMMITTEE ON FETUS AND NEWBORN

KEY WORDS prenatal drug exposure, alcohol, nicotine, marijuana, cocaine, methamphetamine, growth and development

ABBREVIATIONS AAP—American Academy of Pediatrics THC—tetrahydrocannabinol

This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication.

The guidance in this report does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate.

All technical reports from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time.

www.pediatrics.org/cgi/doi/10.1542/peds.2012-3931

doi:10.1542/peds.2012-3931

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2013 by the American Academy of Pediatrics

PEDIATRICS Volume 131, Number 3, March 2013 e1009

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that the use of specific drugs waxes and wanes over time nationwide as the popularity of certain substances changes.

Although a variety of prevalence studies have been conducted over the past 2 decades, there is 1 national survey that regularly provides in- formation on trends in substance abuse among pregnant women. The National Survey on Drug Use and Health (formerly called the National Household Survey on Drug Abuse), sponsored by the Substance Abuse and Mental Health Services Adminis- tration (http://www.oas.samhsa.gov/ nhsda.htm), is an annual survey pro- viding national and state level in- formation on the use of alcohol, tobacco, and illicit drugs in a sample of more than 67 000 noninstitu- tionalized people older than 12 years. Data are combined into 2-year epochs and include reported drug use for pregnant women between the ages of 15 and 44 years. Current illegal drug use among pregnant women re- mained relatively stable from 2007– 2008 (5.1%) to 2009–2010 (4.4%). These average prevalence rates are significantly lower than reported current illicit drug use rates for non- pregnant women (10.9%). Importantly, the rate of current drug use among the youngest and possibly the most vulnerable pregnant women was highest (16.2% for 15- to 17-year-olds, compared with 7.4% among 18- to 25- year-olds and 1.9% among 26- to 44- year-olds). Table 1 summarizes these data along with information regarding current alcohol use, binge drinking,

and cigarette use by pregnant and nonpregnant women. An additional important finding from this survey was that the rate of cigarette smoking for those 15 to 17 years of age actually was higher for pregnant women than for nonpregnant women (22.7% vs 13.4%, respectively). This report details many sociodemographic variables re- lated to drug use in the American population, and the reader is referred to the Substance Abuse and Mental Health Services Administration Web site for the full report (http://www.oas. samhsa.gov/nhsda.htm).

IDENTIFICATION OF PRENATAL EXPOSURE

Two basic methods are used to identify drug users: self-report or biological specimens. Although no single ap- proach can accurately determine the presence or amount of drug used during pregnancy, it is more likely that fetal exposure will be identified if a biological specimen is collected along with a structured interview.8

Self-reported history is an inexpensive and practical method for identifying prenatal drug exposure and is the only method available in which information can be obtained regarding the timing of the drug use during pregnancy and the amount used. Unfortunately, self- report suffers from problems with the veracity of the informant and recall accuracy.9,10 Histories obtained by trusted, nonjudgmental individuals or via computerized survey forms; ques- tions referring back to the previous trimester or prepregnancy usage, not current use; and pregnancy calendars used to assist recollection each im- prove the accuracy of the information obtained.11–13

Several biological specimens can be used to screen for drug exposure. Each specimen has its own individual var- iations with regard to the window of detection, the specific drug metabolites

used for identification, methods of adulteration of the sample, and ana- lytical techniques, thus altering the sensitivity and specificity for each drug of interest. The most common analyt- ical method used for screening bi- ological specimens is an immunoassay designed to screen out drug-free samples. Threshold values generally are set high to minimize false-positive test results but may be too high to detect low-dose or remote exposure. Because immunoassay is a relatively nonspecific test, positive results re- quire confirmation by using gas chromatography/mass spectrometry. In addition, confirmation of the presence of a drug is not always associated with drug abuse. Alternative explanations in- clude passive exposure to the drug, in- gestion of other products contaminated with the drug, or use of prescription medications that either contain the drug or are metabolized to the drug.14 Thus, careful patient histories remain essen- tial to the process of identification.

The 3 most commonly used specimens to establish drug exposure during the prenatal and perinatal period are urine, meconium, and hair; however, none is accepted as a “gold standard.” Urine has been the most frequently tested biological specimen because of its ease of collection. Urine testing identifies only recent drug use, be- cause threshold levels of drug metabolites generally can be detected in urine only for several days. A no- table exception to this is marijuana, the metabolites of which can be ex- creted for as long as 10 days in the urine of regular users15 or up to 30 days in chronic, heavy users. Urine is a good medium as well for the de- tection of nicotine, opiate, cocaine, and amphetamine exposure.16,17

Meconium is also easy to collect noninvasively. It is hypothesized that drugs accumulate in meconium through- out pregnancy, and thus, meconium is

TABLE 1 Comparison of Drug Use Among Women 15 to 44 Years of Age by Pregnancy Status: 2009–2010

Pregnant Women, %

Nonpregnant Women, %

Illicit drug use 4.4 10.9 Alcohol use 10.8 54.7 Binge drinking 3.7 24.6 Cigarette use 16.3 26.7

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thought to reflect exposure during the second and third trimester of preg- nancy when meconium forms. How- ever, use of meconium to determine the timing or extent of exposure during pregnancy is controversial18 because of a lack of studies regarding the effects of the timing and quantity of the post- partum specimen collection as well as the effects of urine or transitional stool contamination of the meconium samples.19 Meconium has been used for the detection of nicotine, alcohol, marijuana, opiate, cocaine, and am- phetamine exposure.16,20

Hair is easy to collect, although some people decline this sampling method because of cosmetic concerns and societal taboos. Drugs become trapped within the hair and, thus, can reflect drug use over a long period of time. Unfortunately, using hair to determine timing and quantity of exposure also is controversial. In addition, envi- ronmental contamination, natural hair colors and textures, cosmetic hair processing, and volume of the hair sample available all affect the rational interpretation of the results.21–24

Hair is useful for the detection of nic- otine, opiate, cocaine, and amphetamine exposure.16,25

Other biological specimens have been studied for use in the detection of in utero drug exposure but are not commonly used in the clinical setting. These include such specimens as cord blood, human milk, amniotic fluid, and umbilical cord tissue.8,19,26 In the case of umbilical cord tissue, drug class- specific immunoassays for amphet- amines, opiates, cocaine, and canna- binoids appear to be as reliable as meconium testing, with the additional benefit of availability of the tissue at the time of birth.27

Beginning in the early 1980s, states began to enact legislation in response to the increasingly popular use of “crack” cocaine in our society. Such

laws required the reporting of women who used drugs during pregnancy to the legal system through states’ child abuse statutes. In 2003, the Keeping Children and Families Safe Act (Public Law 108-36) was passed by Congress, requiring physicians to notify their state child protective services agency of any infant identified as affected by illegal substances at birth or experi- encing drug withdrawal. Currently, issues of whether to use biological specimens to screen for drug abuse; whether to screen the mother, her infant, or both; and which women and infants to screen are issues compli- cated by legal, ethical, social, and scientific concerns. Each of these concerns must be taken into account as obstetricians, neonatologists, and pediatricians work to develop proto- cols for identifying prenatal drug exposure. For example, there is no biological specimen that, when ob- tained randomly, identifies prenatal drug use with 100% accuracy; hence, a negative drug screening result does not ensure that the pregnancy was drug free. Targeted screening of high- risk women is problematic, because it can be biased toward women of racial or ethnic minorities and those who are economically disadvantaged or socially disenfranchised. Universal screening of pregnant women is im- practical and not cost-effective.28–30

Finally, testing of biological specimens when the maternal history is positive for drug use increases medical costs and does not necessarily provide in- formation that guides the medical care of the infant.31