Prenatal Substance Exposure

After completing this article, readers should be able to: Over the past 2 decades, neonatologists have cared for growing numbers of infants who were exposed passively in utero to a variety of licit and illicit drugs consumed by their mothers (Table 1). These infants present a complex web of medical and social problems. Information from the recently published National Household Survey on Drug Abuse: 1996 to 1998 indicated that 45% of women of childbearing age in the United States had used an illegal drug over their lifetime. Within a subsample of 1,249 pregnant women, 3% currently were using an illicit substance, and 54% currently were using alcohol, tobacco, or both.Substances that act on the central nervous system usually are highly lipophilic and of relatively low molecular weight (<1,000 g/mol). These characteristics facilitate crossing from maternal to fetal circulation, and there is rapid equilibration of free drug between mother and fetus. Once drugs cross the placenta, they tend to accumulate in the fetus. Most studied drugs have a longer half-life in the fetus than in the adult because the enzymes involved in the metabolic process of glucuronidation and oxidation are not fully developed in the fetus. In addition, the immature renal function of the fetus may delay the excretion of drugs that have been metabolized to an excretable form.Neonates passively exposed to maternal substances of abuse demonstrate both physical and neurobehavioral difficulties. There is an increased rate of intrauterine growth retardation and microencephaly. Interacting with the direct effects of alcohol and illicit drugs is the greater likelihood of drug- or alcohol-using women to smoke cigarettes, have infections complicating their pregnancy, and have inadequate prenatal care. In addition, cocaine and amphetamines have a direct effect on the uterus, causing contractions. Thus, it is not surprising that there is a high rate of prematurity among prenatally exposed infants.In addition, children who have been exposed prenatally to substances of abuse may suffer a range of physical problems, often based on the direct toxic effect of the substance (such as alcohol) or the interruption of adequate blood flow to developing organs caused by substances such as cocaine or amphetamines. Alcohol can produce structural changes in the face and head; cocaine or methamphetamine use during pregnancy can result in limb reduction deformities. Prenatal exposure to alcohol or other drugs also may interfere with neonatal neurobehavior, especially in the arenas of motor functioning, orientation (affecting the newborn’s ability to respond to auditory and visual stimuli), and state regulation (state changes tend to be abrupt and inappropriate).Over the long term, children who have fetal alcohol syndrome (FAS) have intelligence quotients (IQs) that range from approximately 20 to 105, with a mean of 68, and many alcohol-exposed children who do not have the characteristic FAS features have consistently lower IQ scores than nonexposed children. Importantly, even alcohol-exposed children who have “normal” IQs demonstrate difficulty with behavioral regulation, impulsivity, social deficits, and poor judgment, causing difficulties in day-to-day management in the classroom and home. Although some deficits seen in alcohol-exposed children may stem from the family environment, human studies have demonstrated that prenatal alcohol exposure can produce a broad spectrum of significant abnormalities of various brain structures, including the frontal lobes, limbic system, hippocampus, amygdala, basal ganglia, and corpus callosum as well as ventricular and cerebellar anomalies. These abnormalities translate into significant neurocognitive deficits in the older child.It has been more difficult to discern the exact impact of prenatal exposure to illicit drugs on long-term development of the child. However, biochemical research has begun to gather evidence of possible linkages between behavior regulation problems and prenatal exposure to cocaine, heroin, amphetamines, and other illicit drugs. For example, cocaine blocks the reuptake of the biogenic amines serotonin, dopamine, and norepinephrine, thereby increasing the availability of these transmitters at the receptor sites and producing the cocaine “high” by increasing neuronal excitability. With chronic exposure, a dampening effect may be produced by downregulation of the postsynaptic dopaminergic receptors in the brain. Many of the common illicit substances have an impact on the dopamine system. Thus, children exposed to marijuana, cocaine, heroin, or other illicit substances may suffer a wide range of mild-to-severe physical and neurobehavioral problems.Most importantly, there is clear evidence that recognizing the substance-exposed infant and implementing early intervention services for the child and mother are keys to minimizing the acute and long-term effects of prenatal substance exposure. Thus, even if the infant exhibits no clinically significant difficulties in the neonatal period, identification of the substance-exposed infant can improve his or her long-term outcome.Several studies have explored the barriers to screening for substance use in pregnant and parenting women. When screening for alcohol or drug use is implemented in clinical practice, it often focuses on targeted populations rather than the general population. Clinicians often state that they can “tell” who is an alcoholic or drug user by looking at the person. A 1990 study of substance use in pregnancy in Pinellas County, Florida, revealed that although the overall use of licit and illicit substances was approximately 15% in African-American and Caucasian women within the population, urine toxicology screening or intensive evaluation for substance use was ten times more likely ordered for African-American than Caucasian women. This study showed that physicians’ perception of women at high risk for substance use in pregnancy was based on two factors: race and social class. More recent similar studies have documented these same biased selection criteria driving screening and assessment for alcohol and illicit drug use in pregnancy in North Carolina, Illinois, and Iowa.Universal screening of the postpartum woman for substance use serves a first-level function within the clinical setting of the nursery or neonatal intensive care unit by identifying the presence or absence of risk for the neonate due to prenatal substance exposure. The purpose of screening a newborn’s mother is identification of risk, not diagnosis. Screening is initiated by the clinician rather than by the patient. A good screening strategy serves as an initial process that leads to fuller assessment and perhaps diagnosis of a new mother’s substance use problem.Full clinical assessment of the mother’s substance use serves a second- or third-level function, with patient evaluation and diagnosis leading to treatment. In practical terms, most assessment for substance abuse is performed outside the pediatrician’s or neonatologist’s immediate direction by a team trained to provide an in-depth evaluation. Most clinical assessments use a multiproblem approach to substance use evaluation. An assessment not only evaluates the woman’s substance use, but it also examines the personal and psychosocial issues affecting the woman and her ability to care for her new infant. For postpartum women, the clinical assessment should address comprehensive support services needed to intervene successfully on behalf of the woman, the family, and the child.The role of the neonatologist or pediatrician, therefore, becomes one of screening postpartum women for substance use. Results of the subsequent assessment on a targeted population of at-risk women can be used to guide early intervention efforts for the child as well as referrals for treatment for the mother. Such a universal screening and assessment strategy focuses on a public health model and moves a community away from the punitive approach taken in some states.Many of the commonly recognized screening instruments are not useful for pregnant or postpartum women. The CAGE, although easy to administer and having very good validity, sensitivity, and specificity, primarily targets heavy alcoholic use and does not provide a method for identifying newborns at lower exposure levels for early intervention. Nor does the CAGE address illicit drug use. The NET is similar to the CAGE in that it targets only heavy alcohol use. It may not identify early-stage at-risk drinkers or users of illicit substances. The T-ACE was designed specifically for office detection of risk drinking among obstetric patients. It has been validated as a reliable screening instrument for obstetric practice, and the tolerance question helps sidestep the denial often found in alcohol users. Again, however, heavy drinkers are the primary targets of the T-ACE, and it may not identify more moderate drinkers in a prenatal care setting.The TWEAK was developed to screen for risky drinking during pregnancy and has demonstrated moderately high sensitivity (79%) and specificity (83%) in a sample of pregnant women when detecting consumption of at least 1 oz/d of absolute alcohol and had high sensitivity and relatively high specificity when used to identify DSM-III Alcohol Use Disorder among a population of pregnant women. However, the TWEAK does not identify risk for the use of illicit drugs.The 4P’s, as cited by Morse and associates, is a four-question screen specifically designed to identify quickly obstetric patients in need of in-depth assessment or follow-up monitoring for alcohol or illicit drug use. It can be integrated easily into the initial prenatal visit and used for follow-up screening through the pregnancy. The four questions are broad-based and highly sensitive, requiring only yes or no answers from the patient regarding her alcohol or drug use problems during the current pregnancy, in the past, in her partner, and in her parents. One positive answer to any question is considered a positive screening result and indicates that the patient requires more in-depth evaluation. The questions can be reworded to address specifically alcohol or any illicit drugs. The high sensitivity of this instrument makes it likely that false-positive screening results will occur. The 4P’s never has been evaluated for validity, sensitivity, or specificity, but clinical use of the instrument in a general obstetric clinic did not appear to screen successfully for substance use.Over the past 10 years, studies have been conducted to develop the 4P’s Plus, a five-question screen specifically designed to identify quickly obstetric patients in need of in-depth assessment or follow-up monitoring (Table 2). Taking less than 1 minute to perform, it also has been found to be successful in the immediate postpartum period. The five questions are broad-based and highly sensitive. The predictive validity of the 4P’s Plus was evaluated on a sample of 2,000 Medicaid-eligible women. If a woman has used any alcohol or any tobacco in the month before she knew she was pregnant, she had a 34% risk of having used alcohol or illicit drugs during the pregnancy.Based on this research, a positive response to the first P, for Parents, does not predict substance use by the woman during the pregnancy. However, most clinicians are comfortable initiating the 4P’s Plus as an extension of the family history. The second P, for Partner, is similar to the first P, in that a positive response does not predict the woman’s use of alcohol or other drugs in pregnancy. However, this is a good screening question for domestic violence, given the close link between substance abuse and violence in the home. A positive response to the third P, for Past, places the woman at 10% (low) risk for alcohol use during pregnancy, an indication for the institution of prevention services for the mother as part of the child’s intervention plan, especially if the mother plans on breastfeeding. The two questions related to the fourth P, for Present Pregnancy, are open-ended. Any use of tobacco or alcohol in the month before the woman knew she was pregnant places the woman at 34% risk for using or having used alcohol and illicit drugs during pregnancy. This is considered high risk and an indication for referral of the new mother to a social worker or substance abuse specialist for further assessment of maternal substance use.The 4P’s Plus has been field tested in a variety of settings and communities involving more than 10,000 pregnant and postpartum women. For example, in 2002, 5,082 women were screened in Fresno, California, by their primary care physicians with the 4P’s Plus through a universal screening program. Among these women, 18% had a positive screening result for risk of alcohol or illicit drug use, and 10% were found to need substance abuse treatment. Further, among women who had positive responses to the second P regarding the Partner having a problem with alcohol or drugs, 65% were found to need drug treatment.The research, development, and clinical experience with the 4P’s Plus has shown it to be a viable procedure for instituting universal substance use screening in pregnant women. Although experience with the postpartum woman in the month following delivery is more limited, the instrument appears to be a viable methodology for identifying neonates at high risk for prenatal substance exposure. Such early identification is necessary to enhance the institution of the early intervention services that have been shown to improve significantly the long-term outcome of alcohol- and drug-exposed children.Despite the fact that maternal use of alcohol, tobacco, and other drugs during pregnancy has been shown to cross all social, economic, and racial barriers, clinicians often are reluctant to address this issue within the context of primary care. A 2000 survey of 600 obstetricians conducted by the American College of Obstetrics and Gynecology documented that few obstetricians formally screen pregnant women for substance use. In fact, the survey found that 80% of obstetricians tell their patients that “small amounts” of alcohol are safe to drink during pregnancy. Unfortunately, the obstetricians’ definitions of “small amounts” covered a wide range, with 4% stating that eight drinks or more per week are safe for the fetus. In contrast, a recent study documented that more than one drink per week places the child at increased risk for delinquent behavior and overall problem behavior, one drink per week places the child at increased risk for hyperactive and aggressive behaviors, and any alcohol use in pregnancy places the child at more than three times increased risk for delinquent behavior.Many prenatal and neonatal care clinicians hesitate to implement formal interview procedures because they assume urine toxicologies to be the most appropriate methodology for screening. However, the use of urine toxicologies at one point in time to identify women or infants who have had prenatal exposure limits identification to those infants whose mothers used substances in only the approximately 48 hours prior to delivery. In addition, urine toxicologies measure the concentration of the substance in the urine. With the delayed ability of the neonatal renal system to concentrate urine, the concentration of the substance in the urine of the newborn often falls below federally established thresholds for detection. Thus, more often than not, the urine toxicology report is negative, even though the infant was exposed to significant amounts of a drug.Testing the neonate’s meconium for alcohol or illicit drug exposure during gestation has become more popular over the past few years. The advantage of meconium testing is that this approach can identify substances the mother used throughout the third trimester of pregnancy. However, such testing is expensive, and it usually requires several days to obtain results, often after the child has been discharged from the hospital.There are specific clinical conditions for which urine or meconium toxicology testing is indicated (Table 3). Commonly accepted indications for toxicology analysis include no prenatal care or intrauterine growth retardation, preterm delivery, abruptio placentae, or cardiovascular accidents in mother or child, especially in those cases in which there are no other reasons for the poor outcome.The earliest studies of infants affected by prenatal exposure focused on those neonates whose mothers used narcotics, usually either heroin or methadone, during pregnancy. Narcotic-exposed infants demonstrate a high rate of perinatal morbidity and mortality, with increased rates of prematurity, intrauterine growth retardation, and microcephaly. Neurologically, the infants exhibit signs and symptoms similar to adults going through heroin withdrawal. The most significant features of the neonatal abstinence syndrome are a high-pitched cry, sweating, tremulousness, excoriation of the extremities, vomiting, and diarrhea (Table 4). Symptoms of neonatal withdrawal from narcotics may be present at birth but may not reach a peak until 3 to 4 days after delivery. However, onset of withdrawal depends on many factors, and symptoms may not appear until 10 to 14 days. Withdrawal from opiates persists in a subacute form for 4 to 6 months after birth, with a peak in symptoms at about 6 weeks of age. Neurologic irritability due to intrauterine opiate exposure has been noted, with abnormalities of the Moro reaction documented through as late as 7 to 8 months of age.Infants exposed to nonopiate drugs, such as cocaine and methamphetamines, exhibit a high rate of prematurity, intrauterine growth retardation, and asphyxia related to abruptio placentae at the time of delivery. However, these infants must be evaluated within the context of polydrug abuse because almost all women who are using drugs are using multiple substances, including tobacco and alcohol. Thus, the child’s presentation in the neonatal nursery can vary across a wide spectrum from subtle to marked and In addition, affected infants can exhibit significant and and to and diagnosis for infants who have signs of neonatal abstinence or neurobehavioral difficulties with exposure to perinatal and The diagnosis the child’s evaluation. studies should be used as In addition, based on clinical can identify or and renal can possible renal which appear to at an increased rate in exposed However, the to these procedures should be based on clinical presentation rather than an response to the treatment of neonatal symptoms related to prenatal substance exposure should be because can and the infant to that often are not low and of abrupt changes in the can be are and should provide to per hours for growth of the infant to the child’s neurobehavioral especially to and visual should be and treatment of neonatal abstinence syndrome should be based on developed through the use of one of the various abstinence weight or due to and of the infant to or to or are the most common clinical indications for treatment. It should be that the developed for the of neonatal abstinence are specific to withdrawal and are not to infants exposed to such as cocaine or regarding the treatment of neonates affected by prenatal exposure is based on experience from the of withdrawal. is there a need to provide such treatment to the infant who has been prenatally exposed to nonopiate drugs. form the for of neonatal withdrawal from opiate such as methadone, and primary advantage of is of In addition, infants with have and more behavior and exhibit weight than infants with or The of to an infant for treatment of abstinence symptoms from to 3 to 4 hours until the symptoms of withdrawal are at an initial of 1 to 2 is an for neonatal withdrawal. A neonatal abstinence is for the of or methadone, and the should be after symptoms have been for 4 to days. A about the use of opiate in neonates is the marked has been used by some clinicians in a of 1 to 2 8 to withdrawal symptoms in the but the newborn has a to the and may to 1 alcohol and which may for and should not be used in an or preterm infant. Use of can be with of the neonatal and have in neonates after of the infant who is neonatal but it does for the of a marked effect on the central nervous system of the infant and A neonatal of per with of 2 to 8 per hours to has been to withdrawal levels of should be and to the symptoms and the abstinence After the symptoms have the should be to the drug to by 10% to per infants who have neurobehavioral difficulties related to prenatal exposure to if an affected infant does as for opiate is the of appears that the and of the problem of drug abuse in pregnancy has not over the past years. Although the specific drugs with in and infants to be exposed prenatally to substances. are with a of infants should be screened for substance in the exposed infant are affected there for the fetus or the are the subtle effects that with maternal characteristics to such complex as an infant from the effects of illicit substance use by his or her mother the effects of only one of a system. It is the system, not the drug use that must be in any