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Sarojini S. Budden, MD, Oregon Health Sciences University, Pediatric Development Program at Legacy Emanuel Children's Hospital in Portland, Ore.

Medscape General Medicine 1(1), 1999. © 1999 Medscape

Posted 10/01/1996

The increasing use of drugs and alcohol by pregnant women has resulted in a population of children with unique neurodevelopmental behaviors. Of 223 children evaluated in a multidisciplinary child-development program in Portland, Oregon, 188 required long-term follow-up because of neurodevelopmental and/or behavioral problems; 153 had been polydrug-exposed in utero and 35 were born with fetal alcohol syndrome (FAS). Evaluations of the polydrug-exposed children revealed that 13% had severe speech and language disorders, 10% had significant cognitive deficits, and 81% had behavior problems after the age of 3 years. These deficits could not be attributed to social/environmental factors alone and probably reflect the effect of toxins on the developing brain. While polydrug-exposed children had learning problems related to impaired neurodevelopment and attention deficits, their IQs were normal. Among children with FAS, however, 67% had some degree of mental retardation.

Over the past 15-20 years, increasing numbers of women in their reproductive years are using drugs while pregnant.^[1] The U.S. General Accounting Office, in a report to the Senate, estimated that 5 million or more women have used nicotine, alcohol, or illicit drugs during pregnancy^[2]. According to the National Institute on Drug Abuse, 5.5% of women used an illicit drug during pregnancy--2.9% used marijuana, 1.1% cocaine, and 1.5% an unprescribed psychotherapeutic agent. In addition, 18.8% used alcohol and 20.4% smoked cigarettes.^[2,3] What long-term effect does the use of such substances have on children?

Several studies^[4-7] have shown that children prenatally exposed to drugs are more likely to manifest problems in physical growth, emotional development, and behavior than their peers who were not exposed to drugs in utero (Table I).

Defining the biological effects of specific drugs such as cocaine is a challenge because of the pervasiveness of polydrug use and because many of the drugs used are adulterated with other substances. Furthermore, there is a significant variation in the amounts consumed, the combination of drugs used, and the route of administration. In addition, the individual genetic and metabolic makeup of the fetus, as well as the timing of drug use during pregnancy, may influence the phases of fetal development and growth. Other confounding variables in trying to identify the effect of drugs on the fetus are the mother's nutritional status, exercise, rest, and presence or absence of other medical problems. In addition, a variety of environmental and social factors greatly influence children's development and behavior, including poverty, level of education, inadequate and unsafe housing, coping mechanisms, inconsistencies in caregiving, and run-ins with social agencies and the legal system.Women who are addicted to drugs often lead chaotic lives. They exhibit low tolerance for frustration, have little capacity to delay gratification, and experience anxiety and depression, which limits their ability to nurture.^[8-11] They are seldom prepared for an unwanted or unplanned pregnancy and often overlook the consequences of their addictive behavior on the outcome.

In some states, children born with drugs in their urine are removed from their biological homes and placed in foster homes while their mothers go through rehabilitative programs. Children with drug-dependent parents often are moved from home to home or placed for adoption or in permanent foster care. In recent years, grandparents have come forward to offer support and nurturing to their offspring and grandchildren. However, tense family relationships often interfere with their ability to raise their grandchildren.

Over a period of 8 years, from 1985 to 1993, the number of drug-exposed children evaluated in the Pediatric Development Program at Legacy Emanuel Children's Hospital in Portland, Oregon, and then placed into foster homes and the number adopted both increased. In the first year of the program, 1985, of the 22 drug-exposed children evaluated, 5 (23%) were placed in foster homes, 1 (5%) was adopted, and 16 (72%) remained with their biological mothers; at the end of 1993, of 223 children evaluated, 169 (76%) were placed in foster care, 47 (21%) were adopted, and only 7 (3%) children were living with their biological mothers. It was impossible to identify any continued relationship with biological fathers. All the disruptions associated with drug addiction can have an adverse impact on toddlers and preschoolers and are not conducive to their mental health. Such psychosocial aspects further complicate attempts to identify the long-term consequences of in utero exposure to drugs.

Despite the limitations I have just outlined, the Pediatric Development Program at Legacy Emanuel decided to collect data on the neurodevelopmental and behavioral outcomes of children exposed to intrauterine drugs and alcohol. The program has a multidisciplinary pediatric staff that offers diagnostic assessments for children with an array of developmental and behavioral problems, follows the developmental progress of high-risk infants discharged from a level 3 nursery, and provides direct treatment and intervention.

Since 1985, increasing numbers of children exposed to intrauterine drugs and alcohol have been referred to this program by their physicians, health departments, social service agencies, early-intervention programs, and schools. Each year the referral rate of children drug-exposed in utero had nearly doubled, increasing by more than 80% a year. Simultaneously, the numbers of women using drugs and known to social agencies and legal systems in Oregon increased, reflecting the increase in drug use nationwide.^[12-13]

A total of 223 children were evaluated between 1985 and 1993. Of these, 188 were followed: 153 had been polydrug-exposed in utero, and 35 children had been diagnosed with fetal alcohol syndrome (FAS).

The demographic profile of mothers whose children were referred to the program is documented in Figure 1. These data were obtained from a review of medical records and information from Services to Children and Families (SCF) of Oregon, along with interviews conducted by the pediatric development program staff. The overall population of blacks and Hispanics in the State of Oregon is just 2%, and this is reflected in the population of women in this program: 60% were white. Also, these women were mostly single (85%), school dropouts (78%), had more than 1 child (92%), and were in drug treatment programs (52%).

Figure 1. The pregnant women whose children were followed were mostly white, single, school drop outs, and had more than 1 child.

Review of mothers' medical records and neonatal urine toxicology shows a changing pattern of drug use over 5 years (Fig. 2). Nearly all--92%--of the women smoked cigarettes all through pregnancy and continued to smoke while they were in drug treatment programs. At least 40% had tried IV drug use, but it could not be determined how far into their pregnancies this use continued. Just 11% claimed to have used only 1 illicit drug, mainly cocaine in the form of crack. The other 89% of women said they used more than 2 substances during pregnancy--most commonly cocaine in combination with other substances. Amounts of drugs used and period of gestation when they were used were impossible to document. Women using drugs are often poor historians. They tend not to be aware of their cycles of menstruation, much less which drugs they are using, when, and in what amounts. Some said they were into their seventh month of pregnancy before they recognized that they had conceived.

Figure 2. The changing pattern of drug use in 5 years shows a rise in cocaine and alcohol.

Psychiatric problems were documented in the medical records of about 10% of the mothers of polydrug-exposed infants. Diagnoses included mild/borderline mental retardation (8), schizophrenia (7), personality disorders (2), and manic depression (1). The most frequent medical diagnoses were sexually transmitted disease (7) and hepatitis (4). The relatively high incidence of mental health problems may indicate pre-existing psychosocial problems that may be linked to the use of drugs and alcohol. Most mothers had no work skills. On the Hudson scale, which measures parent attitude and self-esteem,^[14] the majority were identified as having poor self-image. Women documented as having limited cognitive skills or known learning disabilities were thoroughly evaluated by a psychologist and a psychiatrist, because genetic factors have a powerful influence on children's development and can compound the effects of drugs on their developmental deficits.

Of the 153 children followed, 116 (76%) were full-term babies with birth weights ranging from 2400 to 3800g (mean, 2640g). Most were in the low percentile for weight; only 5 were identified as being small for gestational age. Of the 37 (24%) premature infants, most were born between 30 and 37 weeks. Only 6 infants were born before 29 weeks; these ranged in birth weight from 980 to 1460g. The smallest baby was born weighing 980g at 25 weeks. Chasnoff^[15] reported a higher incidence of premature and small-for-gestational-age (SGA) infants than we found in our experience.

Urine toxicology was negative for all drugs in 41 (27%) of the newborns, although all the mothers had used drugs at some point in their pregnancy. In 112 (73%) of the infants, urine tested positive for cocaine. Neonatal abstinence scores^[16] over 15, a measure of withdrawal symptoms in newborns, were documented in 90 of these children.

Table II lists the most common reasons for referral to the Pediatric Development Program. Most frequently seen were delayed development (75%) and increased tone (50%). At the time of referral, 42 (28%) of the newborns had seizures; by 1 year of age, the number who continued to have seizures had declined to 12%; by 2 years, 8% were still having seizures; and by 3 years of age, 5% still had seizures. Most (72%) of the neonates had been discharged on monitors and remained on an apnea monitor for a mean of 7.8 months; this was twice as long as the mean 3.8 months noted in a comparison group followed in the clinic of 50 high-risk infants born prematurely between 30 and 35 weeks of age to women who did not use drugs during pregnancy and also used the monitor. While others have reported an increase in apnea and sudden infant death syndrome (SIDS) among neonates exposed to intrauterine cocaine, which impedes CNS maturation,^[17] none of the drug-exposed children in this study experienced SIDS.

Medical problems diagnosed in these children are documented in Table III. Of particular interest, 1 child was identified as having fragile X syndrome, a genetic disorder that has been linked to mental retardation. All 4 autistic children had been exposed to cocaine and alcohol. Davis and associates^[18]reported an 11.4% rate of autism among children exposed to cocaine in utero; these researchers noted that such a high rate of autistic disorders has not been identified in children exposed to either opioids or alcohol.

Researchers also have linked prenatal cocaine exposure to cerebral infarctions. In fact, 5 of the 153 children in this study were recognized to have sustained cerebral infarcts, and all 5 were diagnosed to have cerebral palsy (CP): Just 1 newborn was diagnosed to have CP; the others were diagnosed 3 to 9 months after birth. One child who had sustained multiple cerebral infarcts had asymmetric spastic diplegia. The other 4 children had mild hemiparesis, secondary to unilateral infarcts. Microphthalmia and optic atrophy, along with other ocular abnormalities, have been described by Dominguez and colleagues as outcomes of fetal cerebral infarcts possibly induced by cocaine-associated vasoconstriction.^[19] Two children in this sample suffered optic changes, specifically optic-nerve hypoplasia, possibly linked to cocaine exposure.

As many as 73% of children we saw at Emanuel were diagnosed to have asthma, for which they continued to require treatment even after they were placed in homes where there was no evidence of smoking. Whether this is due to an abnormal immunologic response is not clear. Opioids are known to affect the body's immunologic responses.^[20] It is possible that some women using cocaine were also using opioids.

Developmental evaluation of children referred to us included neurodevelopmental and pediatric examinations. All children had audiologic evaluations, and 70% had ophthalmologic evaluations. All children younger than 3 years were given Bayley Scales of Infant Development; those between 3 and 6 years old were evaluated with the Peabody Motor Score, Sensorimotor Integration Test, ELM (Early Language Milestone), Preschool Language Scale, (PLS III), Peabody Picture Vocabulary Test (PPVT), Receptive Expressive Emerging Language (REEL), and tests for articulation. Cognitive evaluations included the Bayley Scales, the Stanford-Binet Intelligence Scale, and the Weschler Preschool and Primary Scale of Intelligence (WPPSI), where indicated.

Motor development. At the time of referral, 75% of children presented with motor delays. The children had rigidity as well as significant delays in the emergence of their equilibrium reactions and acquisition of their transitional motor skills. Dystonia without primitive reflexes but with associated hyper-reflexia, clonus, and positive Babinski responses were observed in a significant number of children who had had severe withdrawal symptoms and positive urine toxicology. Dystonia resolved in most children between 8 and 10 months; in 23%, however, dystonia persisted, lasting 18 to 24 months. Several studies that have evaluated developmental outcomes using the Bayley Scales suggest that, by 2-3 years of age, most cocaine-exposed children scored within the normal range.^[5,6,8,9,21] These studies did not attempt to describe the quality of motor skills or whether earlier neuromotor dysfunctions had any impact on motor performance later. In our sample (Table IV), most of the 80 children between the ages of 3 and 6 years showed improved motor skills; only 3 children, all of whom had CP, continued to show a significant motor disorder.

Language development. Language is a highly developed complex skill that is a unique human trait and a function of neurologic development. A close observation of infants exposed to intrauterine cocaine reveals an interesting profile.

Below the age of 12 months, 78% of the infants in this sample lacked spontaneous vocalization and babbling, and demonstrated a lack of imitative vocal play as documented on the ELM screening tool. This a powerful sign of interactive communication and development of central language as well as personal social interactions, which begin at birth and continue to expand exponentially. Although none of the children evaluated had any sensorineural hearing deficits, it was strikingly noticeable that more than 50% of them showed a lack of auditory responsiveness, with some being referred as possibly hearing impaired. The Auditory Brainstem Response (ABR) audiometry test evoked responses in all these children proved to be normal. Whether both these factors influence normal language development has not been reported, but this would seem a likely possibility.

Environmental influences are known to have a substantial impact on language development. But in these children, deficits in speech and language development persisted in spite of early diagnosis and intervention and the move to nurturing foster homes for 76% and adoptive families for 21%. There were 54 children under the age of 2 years who were screened for speech and language development using the ELM screening tool and the REEL test: 58% scored +1SD and 14% scored +2SD. Among 75 children ages 2 to 5 years tested on the PLS III (Table V), 13% continued to show significant speech and language problems, while 62% tested in the mild-to-borderline range, and 25% were within the normal range.

Cognitive development. Several studies^[22-24] have reported on the long-term cognitive deficits in children exposed to alcohol, but fewer discuss the long-term effects of cognitive delays in children who are cocaine-exposed. Using the Bayley Scales and the Stanford-Binet Intelligence Scale (Table VI), 20%-28% of this group had normal IQs. However, 6%-10% had IQs below 50, leaving more than half with at least mild delays. Yet these children are most likely to be found in regular classrooms, where it is impossible for them to meet normal expectations for academic performance, and they experience repeated failures and secondary emotional and psychological problems.

Motor deficits. As children enter preschool and elementary school, a critical review of their motor development reveals characteristics of motor deficits that include difficulty with motor planning, a function of the central nervous system that allows the individual to initiate a motor activity, sequence the moves in an activity, coordinate bilateral movement, and rapidly alternate movements. Among the everyday activities that require motor planning skills are walking and speaking. Motor planning deficits can affect gross and fine motor function as well as the oral motor skills needed in speaking. In our study, children with impaired motor planning demonstrated a lack of coordination and showed persistent fine tremors. Although the child may be able to accomplish certain motor tasks, the quality and precision of movement is affected, reflecting a neuromaturational lag. Hence, functional skills such as buttoning clothes, tying shoe laces, using scissors, and completing paper-and-pencil tasks are difficult--reflecting weakness in sensorimotor integration, spatial awareness, orientation, directionality, and left-right discrimination. This is a subjective evaluation of neurological function and is best measured with the Peabody Motor Score or the Bayley Scale.

Communication disorders. Communicative skills often reflect cognitive abilities. To what extent attention deficits interfere with language development and vice versa is not clear, but a large majority of polydrug-exposed preschool and kindergarten children are overwhelmed with auditory stimuli and become frustrated due to their lack of ability to express themselves clearly. Younger preschool children with problems articulating their needs may have learning disabilities in the language or verbal areas. Continuing identified problems are in the quality of speech; articulation is affected and may be further distorted by the presence of oral dyspraxia. In children polydrug-exposed in utero, speech is often telegraphic in nature--for example, normally a child unable to find a lost toy might say "lost doll," while in telegraphic speech, the communication would be reduced to unconnected single words like "Toy?" and "Find!" Such a child's efforts at communication may also lack appropriate vocabulary, grammar, syntax, and meaning; as a result, the child may suffer from misarticulation, saying "puc" when cup is meant. The child also may stutter and slur words.

Frequently, children have difficulty following directions; when further analyzed, there appears to be a weakness in short-term auditory memory and auditory sequencing. Tests for auditory language processing show deficiencies that underlie basic language development. For example, in the Token Test used to assess auditory language processing in 41 children, 28 were found to have a mean of 2 SD below their expected ages.

Cognitive deficits. Parents and teachers consistently report that children exposed to intrauterine drugs have peculiarities in their learning styles. For example, some have excellent long-term memories, but cannot generalize and apply information to daily problem-solving. Their work appears incomplete, disorganized, and lacking in content. Visual motor integration tasks and visual perceptual skills are weak, and visual sequencing may be impaired. On the Beery Visual Motor Integration Test, 18 of 41 children drug-exposed in utero were found to be an average of 2 SD below their expected ages, and to have communication disorders. Mild cognitive deficits are often associated with attention-deficit hyperactivity disorder (ADHD). It is also well recognized that cognitive deficits are commonly associated with microcephaly,^[25] which was present in 35 (15%) of the children we examined. Minor or major weakness associated with language or cognitive deficits can compound academic performance.

Play skills. Published studies^[26] on play skills in children exposed to intrauterine drugs refer to the lack of imitative play and late emergence of symbolic play. Such children lack curiosity, have difficulty initiating play, do not demonstrate interactive behavior during play, and often use toys inappropriately or randomly; they tend to move from one activity to another without careful reflection and without gaining experiential learning. During play and other activities, children have major difficulties making transitions, showing limited emotional expression and lack of attachment. In general, they make poor judgments, are concrete and unable to generalize skills they have already mastered to use in new situations, and have limited executive functions. Mood swings are common, and emotional lability is evident.

Neurobehaviorial characteristics. Neurobehavioral disruption commonly identified during an infant's drug withdrawal in the neonatal period is a consequence of underlying neurologic dysfunction.^[27] With neuromaturation, many of these behaviors resolve. However, a great many children continue to demonstrate distractibility, unfocused play, inattention, impulsivity, and in some cases, frank hyperactivity. Using the Auchenbach behavior checklist in children over 3 years of age, we identified 81% as having behaviors that were consistent with the Diagnostic & Statistical Manual, 3rd edition,^[24] criteria for the diagnosis of ADHD. These behaviors were noted by their preschool and elementary school teachers as well as their parents. Van Dyke^[28] and Scott^[29] described the long-term effects of drugs on academic achievement and performance of children exposed to drugs in utero. The longer each child is followed into his/her early school years, the clearer it becomes that, although IQ scores may be within the normal range, many children continue to demonstrate learning and behavior difficulties that interfere with achievements.

The cognitive skills in 35 children with FAS were compared with those in the children who were exposed to drugs, mainly cocaine. It was not surprising that 15% of children with FAS had moderate mental retardation, and 52% showed mild to borderline retardation. As a group, they scored lower on the Bailey Mental Development Index (MDI) and Stanford-Binet Intelligence Scale and seemed to have more difficulty academically than the cocaine-exposed children.

To provide appropriate intervention strategies for children exposed to drugs in utero, the Pediatric Development Program of Legacy Emanuel tested a 1-year pilot project entitled "Good Start" in 1987. The primary goals of this project were to educate drug-addicted women with young infants about the effects of drugs on infant development and behavior, and to provide them with parent training and support in caring for their infants. While in the program, the women were required to remain drug-free; in return, they were assured access to safe housing, child care, transportation, health care, and meals. The success of this pilot study led to the initiation in 1989 of Project Network, a federally funded project to keep mothers and infants together and to maintain the family structure while offering inpatient treatment, outpatient drug rehabilitation, safe housing, residential facilities, child care, transportation, meals, developmental and behavioral interventions, drug counseling, and work skills. Drug-addicted women who are pregnant are enrolled into the program and provided close prenatal monitoring. After the women deliver, health care is provided for mother and infant. Over 175 women have been through the program in the first 5 years, and it is now in its second 5-year phase. Preliminary data clearly show that babies born in controlled environments are of higher birth weight and require shorter stays in the hospital nursery, and fewer show withdrawal symptoms. Developmentally, they appear to be doing well, although follow-up until school age is necessary.

Intervention for infants. Intervention for infants experiencing withdrawal must include treatment for withdrawal, seizures, apnea, and malnutrition. Infants who manifest oral motor incoordination and dysfunction resulting in feeding problems experience weight loss; this may be further compounded by diarrhea, high temperature, hyperventilation, and excessive sweating--all of which contribute to dehydration. Many children demonstrate marked dystonia; excessive extensor tone and truncal retractions can interfere with movement, feeding, and motor development. Therapists with expertise in neurodevelopmental therapy can treat children and demonstrate effective changes. The neurodevelopmental approach to therapy is based on the premise that therapeutic intervention should take into account the child's present neurodevelopmental and functional skills and build on these, rather than intervene at the skill level expected for the child's chronological age. For example, if a 15-month-old child, who should be starting to walk, can only roll and sit, the intervention includes passive and strengthening exercises designed to promote crawling and pulling to stand. Neurodevelopmental therapy uses strategies for sensory-motor integration, inhibition of primitive reflexes, and facilitation of normal balance and equilibrium. Simultaneous support for adult family members in the form of education, health care, parent training, respite care, and access to social services is also necessary.

Intervention for toddlers and preschool children. As children exposed prenatally to drugs move into their preschool years, the frequency of visits to the physician decreases, but there is an increase in rehabilitation services needed from speech-and-language and occupational therapists. Special education and remedial services for learning problems need to be addressed. Behavior management can be provided by a psychologist in coordination with the child's physician. The psychologist must also teach parents and teachers how to use behavior management strategies consistently and effectively to prevent and correct behavior problems. Nursing services are important in coordinating care among teachers and health care providers.

Although exact figures are not available, there is a consensus in elementary schools that special education services and resources are being overstretched to meet the needs of increasing numbers of children exposed to drugs in utero, who are now entering the educational system. Some children remain in chaotic home environments where they may be exposed to secondary effects of drugs.

The care of newborns exposed to drugs and alcohol can be costly. At Legacy Emanuel Children's Hospital, Calhoun and Watson^[30] compared the delivery-and-newborn costs of 91 mother-infant pairs who tested positive for cocaine with matched controls of drug-free pairs. Because cocaine-positive women were more likely to deliver premature, low-birth-weight, growth-retarded babies with Apgar scores under 7 at 5 minutes, the hospital costs for mother and baby were significantly higher than for the drug-free controls. The labor, delivery, and postpartum care of cocaine-positive mothers averaged $3608, whereas maternal control charges averaged $3147 (P<.05). Neonatal charges from the cocaine-positive group averaged $13,222, whereas, neonatal control charges averaged $1297 (P<.03).

In 1990, the Services for Children and Families Program of Oregon estimated that it cost $8000 to $10,000 to care for a drug-exposed child in the first year of life. That estimate did not calculate the added costs associated with neurodevelopmental therapy, special education services, or other intervention services.

A small study done at Legacy Emanuel Children's Hospital^[31] showed that comprehensive prenatal treatment and support for drug-dependent pregnant women not only decreased the cost of neonatal care, but also resulted in overall benefits in the children's social and educational outcomes. This finding is consistent with that of other studies that have shown that prenatal care can improve the outcomes for both mother and newborn.^[32-34]

In spite of the studies^[15] that have carefully tried to analyze the major factors that have an impact on children's development when they are exposed to intrauterine drugs, the specific effects of each drug on neurodevelopment and behavior can only be understood when an animal model is used. Effects of polydrug use, alcohol, poor nutrition, maternal medical problems, and underlying genetic factors on children are not easy to measure. Nevertheless, we need to look upon prenatal drug use as a very high-risk factor affecting the long-term development, behavior, and academic achievement of the generations to come.

The author would like to thank Maxine Heard for typing and preparing this manuscript.

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Dr. Budden is Associate Professor of Pediatrics at the Oregon Health Sciences University and the Medical Director of the Pediatric Development Program at Legacy Emanuel Children's Hospital in Portland, Ore. Address correspondence to: Sarojini Budden, MD, Associate Professor of Pediatrics, Child Development and Rehabilitation Center/OHSU, P.O. Box 574, Portland, OR 97207.

Budden SS. Intrauterine Exposure to Drugs and Alcohol: How Do the Children Fare? MedGenMed 1(1), 1999. [formerly published in Medscape Women's Health eJournal 1(5), 1996]. Available at: http://www.medscape.com/viewarticle/408822.