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EFFECTS ON THE NEWBORN

A pregnant drug-dependent woman puts her developing fetus at risk for a number of diseases, including hepatitis, ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS), tuberculosis, and sexually transmitted diseases (STDs). A number of these diseases may be acquired through needle sharing. Mothers who are infected with these diseases are likely to deliver prematurely.

In pregnant women who inject HEROIN, the placenta, for example, shows microscopic evidence of oxygen deprivation. The infants are small for their gestational age, with all their organs affected. In heroin-dependent women, a significant portion of the medical complications seen in their newborns is due to prematurity and low birthweight. Such complications include immature lungs, difficulties in breathing at birth, brain hemorrhage, low sugar and calcium levels, infections, and jaundice.

Women on METHADONE MAINTENANCE (an oral NARCOTIC used for the treatment of heroin addiction) are likely to give birth to normal- or almost normal-sized babies. Because they are in treatment, the complications in their infants are not as severe and generally reflect: (1) the amount of prenatal care the mother has received; (2) whether the mother has suffered any complications, including hypertension or infection; and (3) most importantly, any multiple drug use that may have produced an unstable intrauterine environment for the fetus, perhaps complicated by WITHDRAWALS and/or OVERDOSE.

Multiple drug use may cause a series of withdrawals, when the pregnant woman cannot obtain the drug she needs. This series of extreme physical conditions in the pregnant woman can severely affect the oxygen and nutrients that feed the developing fetus, causing various birth defects, depending on when in each trimester the withdrawals occur. If the mother overdoses, a decreased oxygen supply to the fetus can cause aspiration pneumonia—if the mother survives the overdose to give birth.

Laboratory and animal studies have shown that narcotics (OPIOIDS) may have an inhibitory effect on enzymes that influence oxygen metabolism. They also alter the passage of oxygen and nutrients to the fetus by constricting the umbilical vessels and decreasing the amount of oxygen delivered to the developing fetal brain. Such metabolic side effects may cause a derangement in the acid/base balance (acidosis). In contrast, increased maturation of organ systems and certain enzymes have been seen in heroin-exposed infants, including maturation of the lungs, tissue-oxygen unloading, sweat glands, and liver enzymes. The stressful life of the pregnant woman probably contributes to this enhanced maturation in heroin-exposed infants.

The genetic risks to the offspring of addicts on heroin and methadone include an increase in the frequency of chromosome abnormalities; infants exposed predominantly to methadone in utero do not. The adverse environmental factors that may contribute to the abnormal findings in heroin-exposed infants may be less prominent in methadone mothers, since drug addiction is compounded by poor maternal nutrition, extreme STRESS, infectious disease, and a lack of early and consistent prenatal care. However, in the absence of specific clinical abnormalities, it is impossible to isolate either methadone or heroin as agents linked to GENETIC damage.

Given the obstetrical and medical complications, the lack of prenatal care, and the prematurity of the infants at delivery, it is not surprising that the death rate for ADDICTED BABIES is higher than for infants born to nonaddicts.

NEONATAL OPIOID WITHDRAWAL SYNDROME

This syndrome is described as a generalized disorder, characterized by signs and symptoms of central nervous system hyperirritability, gastrointestinal dysfunction, respiratory distress, and autonomic nervous system symptoms that include yawning, sneezing, mottling, and fever. At birth, these infants develop tremorous movements, which progress in severity. High-pitched crying, increased muscle tone, irritability, and exaggerated infant reflexes are common. Sucking of fists or thumbs is common, yet when feedings are administered, the infants have extreme difficulty and regurgitate frequently—because of an uncoordinated and ineffectual sucking reflex. The infants may develop loose stools and are therefore susceptible to dehydration and electrolyte imbalance. At birth, the blood levels of the drug(s) used by the mother begin to fall, so the newborn continues to metabolize and excrete the drug, and withdrawal signs occur when critically low levels have been reached.

Whether born to heroin-addicted or methadone-dependent women, most infants seem physically and behaviorally normal. The onset of their withdrawal may begin shortly after birth to two weeks of age, but most develop symptoms within seventy-two hours of birth. If the mother has been on heroin alone, 80 percent of the infants will develop clinical signs of withdrawal between four and twenty-four hours of age. If the mother has been on methadone alone, the baby's symptoms usually appear by forty-eight to seventy-two hours.

In summary, various studies have shown that the time of onset of withdrawal in the individual infant will depend on: the type and amount of drug used by the mother; the timing of her dose before delivery; the character of her labor; the type and amount of anesthesia and pain medication given during labor; and the maturity, nutrition, and presence or absence of systemic diseases in the infant.

Studies indicate that more full-term infants require treatment for withdrawal than do preterm infants. Withdrawal severity appears to correlate with gestational age; less mature infants show fewer symptoms. Decreased symptoms in preterm infants may be due to either (1) developmental immaturity of the preterm nervous system, or (2) reduced total drug exposure because of short gestations.

The most severe withdrawal occurs in infants whose mothers have taken large amounts of drugs for a long time. Usually, the closer to delivery a mother takes heroin, the greater the delay in the onset of withdrawal and the more severe the symptoms in her baby. The duration of symptoms may be anywhere from six days to eight weeks. The maturity of the infant's own metabolic and excretory mechanisms plays an important role. Although the infants are discharged from the hospital after drug therapy is stopped, some symptoms such as irritability, poor feeding, inability to sleep regularly, and sweating may persist for three to four months.

Not all infants born to drug-dependent mothers show withdrawal symptoms, but investigators have reported that between 60 and 90 percent of infants do show symptoms. Since biochemical and physiological processes governing withdrawal are still not fully understood, and since multiple drugs are often used by the mothers in an erratic fashion—with vague or inaccurate maternal histories provided—it is not surprising to find varying descriptions and experiences in reports from different centers. Seizures, a severe outcome in withdrawing infants, are rare in narcotic-exposed infants. One report found that 5.9 percent of 302 newborns exposed to narcotics during pregnancy had seizures that were attributed to withdrawal. Other reports found even rarer occurrences of seizures.

Drug-exposed infants show an uncoordinated and ineffectual sucking reflex as a major manifestation of withdrawal. Regurgitation, projectile vomiting, and loose stools may complicate the illness further. Dehydration, due to poor intake and coupled with excessive losses from the gastrointestinal tract, may occur, causing malnutrition, weight loss, subsequent electrolyte imbalance, shock, coma, and death. Neonatal withdrawal carries a risk of neonatal death when these complications are untreated. The infant's respiratory system is also affected during withdrawal: excessive secretions, nasal stuffiness, and rapid respirations are sometime accompanied by difficulty breathing, blue fingertips and lips, and cessation of breathing. Severe respiratory distress occurs most often when the infant regurgitates, aspirates, and develops aspiration pneumonia.

The increased sensitivity to recognition, the accuracy of clinical and laboratory diagnosis, and treatment have essentially eliminated neonatal mortality attributed to withdrawal per se.

ASSESSMENT AND MANAGEMENT OF NEONATAL OPIOID ABSTINENCE

With proper management, the neonate's prognosis for recovery from the acute phase of withdrawal is good. If symptoms of withdrawal appear, simple nonspecific measures should be instituted, such as gentle, infrequent handling, swaddling, and demand feeding. Careful attention to fluid-electrolyte balance and calorie support is essential in opioid-exposed infants undergoing withdrawal, since they display uncoordinated sucking, feed poorly, often develop vomiting and diarrhea, and have increased water losses due to rapid respirations and sweating.

Indications for specific treatment, dosage schedules, and duration of treatment courses have varied widely. As a general guide, if, in spite of nonspecific measures, babies have difficulty feeding, diarrhea, marked tremors, irritability even when undisturbed, or cry continuously, they should be given medication to relieve discomfort and prevent dehydration and other complications. The dosages must be carefully regulated so that symptoms are minimized without excessive sedation. Several drugs appear to be effective in treating neonatal narcotic withdrawal, but there has been little controlled comparison of their safety and effectiveness. Drugs such as PAREGORIC or tincture of OPIUM are effective in treating narcotic withdrawal symptoms in the infant, and PHENOBARBITAL is useful, but less so when opioid exposure has occurred in high doses.

NEUROBEHAVIOR IN THE NEWBORN

The Brazelton Neonatal Assessment Scale has been used extensively for evaluating newborn behavior. This instrument assesses reaction to stimuli such as a light or a bell, responsivity to animate and inanimate stimuli (face, voice, bell, rattle), state (sleep to alertness to crying), the requirements of state change (such as irritability and consolability), and neurological and motor development. When using this scale in evaluating drug-exposed infants, it was noted that they were less able than nondrug-exposed infants to be maintained in an alert state and less able to orient to auditory and visual stimuli, most pronounced at forty-eight hours of age. Drug-exposed infants were as capable of self-quieting and responding to soothing intervention as normal neonates, although they were substantially more irritable. These findings have important implications for caregivers's perceptions of infants and thus may have long-term impact on the development of infant-caregiver interaction patterns.

Abnormalities in the interaction of drug-dependent mothers and their infants, on measures of social engagement, have been shown. Abnormal interaction was explained by less positive maternal attachment, as well as difficult infant behavior, which impedes social involvement. Many of these interactive abnormalities reverted to normal by four months of age, but the need for "parenting training" is obvious.

OPIOIDS AND SUDDEN INFANT DEATH SYNDROME (CRIB DEATH)

Sudden infant death syndrome (SIDS) is defined as the sudden and unexpected death of an infant between one week and one year of age, whose death remains unexplained after a complete autopsy examination, full history, and a death-site investigation. Compared to an incidence of approximately 1.5 per 1,000 live births in the general population, narcotic-exposed infants appear to have an increased risk of SIDS. Other high-risk factors for SIDS, such as low socioeconomic status, low birth-weight, young maternal age, black racial category, and maternal smoking are all overrepresented in the drug-using groups that are studied. In a most extensive study, New York City SIDS rates were calculated in 1.2 million births from 1979 to 1989. Maternal opiate use, after control for high-risk variables, increased the risk of SIDS by three to four times that of the general population.

LONG-TERM OUTCOME OF CHILDREN WHO HAVE UNDERGONE IN UTERO EXPOSURE TO OPIOIDS

Despite the fact that a drug-exposed newborn may seem free of physical, behavioral, or neurological deficits at the time of birth, the effects of pharmacological agents (used or abused) may not become apparent for many months or years. Although heroin abuse during pregnancy has been recognized for more than forty years, and methadone treatment has been employed for more than twenty years, follow-up of opioid-exposed infants is still fragmentary. The difficulties encountered in long-term follow-up of this population include an inability to fully document a mother's drug intake, separation of the drug effects from high-risk obstetric variables, problems in maintaining a cohesive group of infants for study, and the need to separate drug effects from those of parenting and the home environment.

The easiest part of caring for the neonate is actually over when drug therapy has been discontinued and the infant is physically well. The most difficult parts then begin—the care involved in discharge planning and assuring optimal growth and development throughout infancy and childhood. Because there is no standard for the disposition of these infants, some may be released to their mothers, some to relatives, and others placed in the custody of a state agency. Still others may be voluntarily released by the mother to private agencies for temporary or permanent placement.

In the United States, pressure recommending separation of infants from their addicted mothers has been growing. This solution may not be practical in cities where social services and courts are already understaffed and overworked. Decent foster care is expensive and hard to find. Pediatricians basically feel that the mother-infant association should not be dissolved except in extreme situations. Aside from intensive drug rehabilitation and medical treatment, these women need extensive educational and job training—to become the productive citizens and loving mothers who will positively socialize their children. Supportive therapies such as outpatient care or residential treatment may help eliminate some of the medical and social problems experienced by drug-dependent women and their children.

Most of the children evaluated for long-term development have been exposed to methadone. Evaluations have occurred at various intervals—at six, twelve, eighteen, and twenty-four months; then at three, four, and five years of age. Testing procedures utilized have been the Gesell Developmental Schedule, the Bayley Scales of Infant Development, the McCarthy Scales of Infant Abilities, and the Stanford-Binet and the Wechsler Preschool and Primary Scale of Intelligence. Infants have shown overall developmental scores in the normal range but a decrease in scores at about two years of age—which suggests that environment may confound long-term infant outcome: low socioeconomic groups suffer from this factor particularly, because of poor language stimulation and development.

The developmental scores in these early years, although useful in identifying areas of strength and weakness, may not predict subsequent intellectual achievement. More and more studies have proposed multiple-factor models to assess infant outcome following intrauterine drug exposure. One such postnatal influence involves maternal-infant interaction. Drug-exposed infants are often irritable, have decreased rhythmic movements, and may display increased muscle tone (tensing) when handled. Such behaviors may be interpreted by the mother as "rejecting" behavior, leading to inappropriate maternal caretaking and possible neglect of the infant. Studies of mother—infant interactions show that: (1) infants born to narcotic-addicted women show deficient social responsiveness after birth; (2) this deficient mother—infant interaction persists until the infants' treatment for withdrawal is completed; and (3) maternal drug dosage may affect that interaction.

Based on available data, at five years of age, children born to women maintained on methadone, in contrast to heroin-exposed babies, appear to function within the normal range of their mental development. In addition, no differences in language and perceptual skills were observed between them and children of mothers not involved with drugs and of comparable backgrounds. Difficulty in following large cohorts of drug-exposed infants has led to the study of very limited samples, however.

Positive and reinforcing environmental influences can significantly improve drug-exposed infant development. Women who show a caring concern for their infants are most likely to pursue follow-up pediatric care and cooperate in neurobehavioral follow-up studies. Lacking a large data base, there is an obvious need for comprehensive studies assessing the development of large populations of drug-exposed infants.

COCAINE

The effects of maternal medical and obstetrical complications seen in opioid-exposed infants are similar to those of COCAINE exposure—although cocaine is a stimulant, not a depressant drug (like the opioids). The infants are frequently small in weight, length, and head circumference as a result of preterm birth and/or retardation of fetal growth. The effects of blood-vessel constriction, a characteristic pharmacologic effect of cocaine, is one of the main reasons for adverse effects—since it results in lack of oxygen and nutrients to the fetus. This predisposes the infant to growth problems, brain hemorrhage, abnormal organ development, and crib death.

The many studies on cocaine effects in the newborn need further clarification because of inadequate sample size, research methodology, and actual drug intake; these include studies that have evaluated brain hemorrhage, structural abnormalities, crib death, and long-term development. Although cocaine-exposed infants have been reported to have some irritability and perform poorly on neurobehavioral tests in the first few days of life, no evidence shows that they have a withdrawal syndrome as described previously in infants exposed to opioids. The symptoms have been related to a cocaine toxicity reaction rather than to a withdrawal syndrome. Infants with opioid and cocaine exposure, as compared to opioid exposure alone, have had milder symptoms. This may be a result of interactions between the depressant and stimulant properties of these drugs. No treatment has been found necessary to alleviate the symptoms of infants exposed to cocaine, whereas opioid-exposed infants may need treatment in about 40 to 50 percent of cases.

Although a number of reports in medical literature have described babies who have structural abnormalities related to cocaine exposure, an equal number of studies have found no increased incidence of abnormalities. The abnormalities reported have been those of the urinary tract, intestines, and extremities—all of which are related to the vascular disruption caused by cocaine's ability to constrict blood vessels. The most recent review of the clinical studies describing abnormalities in cocaine-exposed infants shows a very low incidence of occurrence.

Studies evaluating cocaine's effects on the occurrence of SIDS (crib death) have shown diverse results. Although inadequate methodologies and small numbers have accounted for these differences, cocaine-exposed infants have also experienced most of the factors that predispose any child to SIDS. These include low birthweight, POVERTY, neonatal complications, minority ethnicity, low maternal age, and maternal cigarette smoking. When these factors are controlled in the research, cocaine exposure accounts for only a very modest increase in the rate of SIDS.

As with all drugs of abuse, cocaine has properties that permit it to be transmitted through the breast milk. Since a significant portion of drug-using women in the United States may be HIV-positive, until the role of breast feeding in HIV transmission is clarified, breast feeding should be discouraged.

Recent reports indicate that cocaine exposure may even occur in young infants after they leave the hospital. The evidence for the postulated route of cocaine toxicity (passive inhalation of smoked cocaine—"crack") is circumstantial, and the range of occurrences in reported series is 2 to 4 percent. Symptoms involve abnormal neurologic findings, including seizures, drowsiness, and unsteady gait.

Much concern has been voiced regarding the ultimate neurobehavioral outcome of infants following intrauterine exposure to cocaine. Based on multiple-risk factors, it appears reasonable to voice these concerns. Commonly, the parents may be of poor socioeconomic status and culturally deprived. The mother may be poorly nourished, may carry medical and sexually transmitted diseases, including AIDS, and may receive little or no prenatal care. After birth, neurologic and neurobehavioral abnormalities may be present in the infant. Stimulation for intellectual growth may be lacking because of prolonged hospital stays, infrequent and inappropriate parental contact, placement in a group-care facility, or discharge to a home in which intellectual nurturing is lacking.

Follow-up studies of large numbers of cocaine-exposed babies are lacking as of the early 1990s. The lay press has reported anecdotal experiences with the first cohort of three- to five-year-old children born of the crack epidemic. Such cocaine-exposed babies have been characterized as showing significant deficits in environmental interactions during play groups and in nursery schools. These babies have also been described as showing less representational play, decreased fantasy play and curious exploration, and lesser quality of play. Others have described these children as "joyless"—unable to fully participate in either structured or unstructured situations, with attention deficits and flat apathetic moods. Developmental evaluations show, however, that the majority of children who were exposed to cocaine in utero and who now have stable environments score in the normal range.

NICOTINE

Prenatal exposure to smoking has been linked with a number of impairments to the fetus, including impairments to memory, learning, cognition, and perception. Such impairments may result from chronic fetal hypoxia, a loss of oxygen to the cells that may impair normal development of the central nervous system. Maternal smoking during pregnancy also affects the respiratory system of a fetus, and newborns of smokers tend to have reductions in expiratory flows. It may also alter the developing lung and result in respiratory illness in the infant.

Low birth weight is another factor commonly associated with prenatal exposure to smoking, and even passive smoking—that is, from the father or another person in the vicinity of the mother—seems to affect an infant's weight. Some studies have shown an average decrease in birth weight of about 200 grams in newborns whose mothers smoked throughout pregnancy. The risk of a low-birth-weight infant has also been estimated to be two to four times greater for mothers who smoke. In general, women who stop smoking in pregnancy prevent the full effects of low birth weight associated with smoking, and studies have shown that the earlier a woman stops smoking during pregnancy, the lower the risk of a low-birth-weight baby. An infant's birth weight also appears to be "dose dependent," with heavy smokers being at the greatest risk for low-birth-weight babies.

Behavioral studies have also been conducted with children exposed to prenatal smoking. Some research has also shown that a child whose mother smoked during pregnancy is at increased risk of becoming a smoker. Because smoking activates neurotransmitters in the brain, including dopamine, which is involved in reinforcing the effects of addictive drugs, researchers have speculated that nicotine may have an effect on the developing dopamine system of the fetus and put the child at greater risk of addictive behavior in later life.

Prenatal exposure to cigarette smoking may affect a growing fetus in several ways. Carbon monoxide and high doses of nicotine obtained during inhalation of tobacco smoke can interfere with the oxygen supply to the fetus. Nicotine readily crosses the placenta, and it likely causes vasoconstriction of the umbilical arteries and impedes placental blood flow. Carbon monoxide can bind with hemoglobin to reduce the capacity of the blood to transport oxygen. These factors, combined, likely account for the developmental delays commonly seen in the fetuses and infants of smoking mothers.

One of the most striking risks associated with prenatal smoking is that of Sudden Infant Death Syndrome (SIDS). A higher mortality rate exists for infants whose mothers have smoked compared to those who have not. Maternal smoking during pregnancy has also been cited as a major risk factor in almost every epidemiologic study of SIDS. The risk of sudden infant death syndrome is greater among infants exposed to both prenatal and post-natal smoking compared to those only exposed to postnatal smoking. The increase in SIDS risk also appears to be related to the "dose" of passive-smoke exposure—the greater the exposure to smoke both before and after birth, the higher the risk of SIDS. The link between cigarette-smoke exposure and SIDS is not fully understood.

(SEE ALSO: ; Fetal Alcohol Syndrome; Pregnancy and Drug Dependence: Opioids)

LORETTA P. FINNEGAN

MICHAEL P. FINNEGAN

GEORGE A. KANUCK

REVISED BY PATRICIA OHLENROTH