Drugs And Pregnancy Part 37

PSILOCYBIN.

Psilocybin is a naturally occurring hallucinogenic alkaloid present in several species of psychedelic mushrooms belonging to the genus Psilocin. Psilocin mexicana Psilocin mexicana is the cla.s.sic source of the drug and is known as the magic mushroom. It is most commonly found in Mexico, particularly in the Valley of Oaxaca. However, other species occur north of Mexico in the southern USA and elsewhere. Psilocybin typically grows in highly organic is the cla.s.sic source of the drug and is known as the magic mushroom. It is most commonly found in Mexico, particularly in the Valley of Oaxaca. However, other species occur north of Mexico in the southern USA and elsewhere. Psilocybin typically grows in highly organic Opiate abuse during pregnancy Opiate abuse during pregnancy 321.

media, such as cow feces (cow patties) and usually in the springtime. Psilocybin mushrooms are eaten as an illegal recreational drug. The hallucinogenic effects usually last 68 h. Ingestion of these hallucinogenic mushrooms has become a popular form of substance abuse among some adolescents and young adults (Schwartz and Smith, 1988). The effects of psilocybin ingestion include hallucinogenic visions, altered states of consciousness, and a p.r.o.nounced pyrogenic effect. Several surveys have indicated that mushroom use is more prevalent among high school and college students than is the use of LSD.

The frequency of congenital anomalies in the offspring of mothers who ingested psilocybin during pregnancy has not been published for human studies or animal experiments.

Summary of hallucinogens Hallucinogen use during pregnancy is not well studied and unknown risks may exist.

The purported a.s.sociation of LSD with limb defects found in the offspring of LSD-using women is very probably not causal. The pyrogenic effects of hallucinogens and nonmedical use of other substances may be cause for concern. However, any concern is based upon theoretical grounds and not published information.

OPIATE ABUSE DURING PREGNANCY.

Opiates are a cla.s.s of drugs with sedative and a.n.a.lgesic effects derived from white, milky secretions of the flower bud of the opium poppy plant ( Papaver somniferum Papaver somniferum). Synthetic opi-ods are also available (e.g., meperidine). Opiates (natural and synthetic) are pharmacological narcotics, not to be confused with the legally defined narcotic cla.s.s which includes such drugs as marijuana, amphetamines, and methamphetamines. Opiates are used medically to treat moderate to severe pain. Narcotics include opium, morphine, the codeines (hydrocodeine, oxycodeine, and codeine), meperidine, paperavine, thebaine, and heroin.

Opiates act on opioid receptors to produce a.n.a.lgesia and euphoria. A severe opiate withdrawal syndrome occurs after discontinuation of chronic use, medical or illicit. Importantly, withdrawal occurs among both adults and neonates chronically exposed to these drugs. An increasingly more common source of opiates for abuse is prescription drugs such as oxycodone (Percocet) and hydrocodone (Vicodin), obtained either legally or illegally.

Methadone is a synthetic opioid a.n.a.log and is used as an alternative to heroin.

Heroin Heroin is a narcotic a.n.a.lgesic available in many countries (e.g., UK). However, in the USA it is a schedule I drug (no medically beneficial use) and cannot be prescribed for medical treatment. Heroin abuse occurs worldwide. Most population studies report the prevalence of illicit heroin use to be from 2 to 5 percent. In Amsterdam, The Netherlands, however, where illegal drug use is tolerated, an estimated 20 percent of adults use heroin. Among pregnant women in Dallas at a large public hospital, 2.5 percent reported using heroin (unpublished data).

Studies of heroin use during pregnancy are of illicit use only. The health effects of heroin use are confounded and probably compounded because often users abuse other 322 322 Substance abuse during pregnancy drugs (alcohol, cocaine), use tobacco, and have poor health and nutritional status.

Importantly, heroin dose, frequency, duration, and trimesters of use are usually unknown.

Numerous investigators have reported that the frequency of congenital anomalies was not increased among infants born to heroin-addicted mothers compared to the rate expected among infants born in the general population (Kandall et al et al., 1977; Little et et al al., 1990e; Naeye et al et al., 1973; Stimmel and Adamsons, 1976; Stone et al et al., 1971). No pattern of congenital anomalies that would comprise a syndrome was found among infants born to heroin users (Rothstein and Gould, 1974). One cohort study (830 heroin-exposed infants) suggested that heroin was a.s.sociated with an increased frequency of congenital anomalies (3.5 percent) compared to controls (2.4 percent) (Ostrea and Chavez, 1979). However, this was because of a nonrepresentative, unrealistically low frequency of congenital anomalies among control group infants (0.5 percent).

Recall from Chapter 1 that the background rate is 3.55 percent in human populations.

Frequencies of acquired chromosomal aberrations in peripheral blood lymphocytes were elevated above background frequency in narcotic addicts (Amarose and Norusis, 1976; Kushnick et al et al., 1972). These findings were replicated in infants of narcotic-addicted women in one study (Amarose and Norusis, 1976), but not in another (Kushnick et al et al., 1972). Aberrations in somatic cells and risks to reproduction are not related.

Severe infections correlated with IVDA [hepat.i.tis B and C, syphilis, human immunodeficiency virus (HIV), gonorrhea] occur with increased frequency among pregnant heroin addicts and infants (Perez-Bescos et al et al., 1993). Birth weight and other fetal growth measures (head circ.u.mference, birth length) are consistently decreased among infants born to heroin addicts compared to drug-free controls (Fricker and Segal, 1978; Kandall et al et al., 1977; Lam et al et al., 1992; Lifschitz et al et al., 1983; Little et al et al., 1990a, 1990e; Oleske, 1977; Zelson et al et al., 1971). Miscarriages, perinatal death, and a variety of other perinatal complications were increased in frequency among heroin-exposed children (Fricker and Segal, 1978; Kandall et al et al., 1977; Lifschitz et al et al., 1983; Little et al et al., 1990e; Oleske, 1977, Zelson et al et al., 1971). Fetal exposure to heroin is confounded by the generally poor health status of heroin-using mothers.

Postnatal growth of children exposed to heroin prenatally seems normal compared to controls and reference data (Little et al et al., 1991a). However, head circ.u.mference was smaller than that of children not exposed to heroin prenatally in several studies (Chasnoff et al et al., 1986; Lifschitz et al et al., 1985). As noted for all substances of abuse discussed in this chapter, heroin crosses the placenta freely. If the mother is addicted to heroin, her infant is also addicted because the drug rapidly enters fetal circulation.

Accordingly, neonatal withdrawal symptoms (tremors, irritability, jitteriness, diarrhea, seizures, poor feeding, high-pitched, shrill cry, irregular sleep patterns, sneezing, respiratory distress, fever, vomiting) occur among 4080 percent of infants born to heroin-using gravidas (Alroomi et al et al., 1988; Fricker and Segal, 1978; Kandall et al et al., 1977; Rothstein and Gould, 1974). Withdrawal symptoms may appear shortly after birth or take from 6 to 10 days to develop, depending upon the time needed for the infant to metabolize heroin at birth. These symptoms can be of prolonged duration, usually persisting for less than 3 weeks. Treatment is often with tincture of opium (paregoric) in downward tapering doses.

Opiate abuse during pregnancy 323.

Ultimately, the postnatal environment of infants exposed prenatally to heroin seems to primarily determine developmental status (Ornoy et al et al., 1996; van Baar and de Graff, 1994; van Baar et al et al., 1994). This seems to be true for most substances of abuse, except alcohol and perhaps cocaine.

Methadone Methadone is a synthetic opiate narcotic structurally similar to propoxyphene. The princ.i.p.al medical use of methadone is as a maintenance therapy for heroin addiction, but it is used illegally as a subst.i.tute for heroin. Published studies reported include only pregnant women on regimented-dose maintenance therapy who took methadone of known pharmacological purity.

Congenital anomalies were not increased in frequency compared to the background rate among infants born to heroin-addicted women treated with methadone during pregnancy (Fundaro et al et al., 1994; Kempley, 1995; Soepatmi, 1994; Stimmel and Adamsons, 1976; van Baar et al et al., 1994; Vering et al et al., 1992). However, withdrawal symptoms occurred frequently (up to 80 percent) and birth weights were significantly lower (2600 g) among methadone-exposed infants ( n n = 278) (Connaughton = 278) (Connaughton et al et al., 1977). Neonatal complications occur at a high rate, and include asphyxia neonatorum, transient tachypnea, aspiration pneumonia, congenital syphilis, jaundice, meconium staining, and neonatal death. Adverse maternal effects include prolonged rupture of membranes, breech presentation, abruptio placentae, preeclampsia, and postpartum hemorrhage (Naeye et al et al., 1973). An unusually high frequency of sudden infant death syndrome (SIDS) (17) occurred among infants in a group of 688 drug-using mothers followed by Chavez and a.s.sociates (1979). Of the 17 infants, 14 were born to mothers who were enrolled in a methadone treatment program, but who continued to use other drugs as well. Review of effects of methadone maintenance during pregnancy on neonatal outcome showed two consistent findings across studies: withdrawal symptoms (7090 percent) and lowered gestational age and birth weight of infants in the drug-exposed group compared to a control group (Behnke and Eyler, 1993).

Developmental outcomes of heroin- and/or methadone-exposed children children Several researchers have been following, a.s.sessing, and reporting on the progress of children born to heroin- and methadone-using mothers. Overall, heroin- and methadone-exposed children obtained lower scores than comparison groups in the domains of motor coordination, attention and focus, activity level and behavior, emotional disturbances, and behavioral problems (aggression, anxiety, and rejection) (Behnke and Eyler, 1993; Davis and Templer, 1988; de Cubas and Field, 1993; Deren, 1986; Kaltenbach and Finnegan, 1984; Wilson et al et al., 1979).

Summary of opiates during pregnancy Chronic use/abuse of opiates during pregnancy does not significantly increase the risk of congenital anomalies. Adverse pregnancy outcomes are increased in frequency: abruptio 324 324 Substance abuse during pregnancy placentae, neonatal withdrawal, preterm birth, and fetal growth r.e.t.a.r.dation. Some differences were found in cognitive abilities, motor development and behavior between opiate-exposed children and nondrug-exposed children, but the postnatal environment with a drug-abusing mother must be considered because it is an important factor.

Maternal personality traits, degrees of life stress, the quality of the motherchild relations.h.i.+p, and a.s.sessment of the environment must be considered.

INHALANT (ORGANIC SOLVENT) ABUSE DURING PREGNANCY.

Epidemiology Use of inhalants during pregnancy is 1 percent, somewhat lower than other substances of abuse (for example, cocaine, marijuana, and tobacco). In Dallas, it was estimated that 1 percent of women used inhalants during pregnancy, including toluene, spray paint, gasoline, freon, and other substances (Madry et al et al., 1991). Women who use inhalants during pregnancy are primarily Hispanic or American Indian, with an age range of 2029 years (Goodwin, 1988; Wilkins-Haug and Gabow, 1991). In Dallas, the majority of women using inhalants during pregnancy are young, 1520 years of age, and usually Hispanic.

Fetal solvent syndrome A collection of dysmorphic features called the 'fetal solvent syndrome' was observed among infants born to women who 'huffed' or 'sniffed' toluene, gasoline, benzene, and other aromatic liquids during pregnancy. The syndrome is characterized by prenatal growth r.e.t.a.r.dation (low birth weight, microcephaly), dysmorphic facial features (facies) that resemble FAS, and digital malformations (short phalanges, nail hypoplasia).

Investigators have noted that these features are reminiscent of FAS. Importantly, women who use a substance of abuse, including inhalants, during pregnancy frequently use other substances, including alcohol. Nonetheless, data from case reports seem to support the notion that inhalants such as toluene or gasoline, independently of concurrent use of other substances of abuse, may be a.s.sociated with congenital anomalies consistently described as the fetal solvent syndrome. Anecdotal evidence suggests that the fetal solvent syndrome is a.s.sociated with significant mental r.e.t.a.r.dation. It is important to note that usual occupational exposure to organic solvents cannot be compared to inhalant abuse.

The doses encountered in occupational exposure are of a lower magnitude.

Animal studies The frequency of congenital anomalies was not increased among rats whose mothers were exposed to high levels of toluene, but growth r.e.t.a.r.dation was observed (Gospe et et al al., 1994; Ono et al et al., 1995).

Specific inhalants GASOLINE.

Gasoline is a fuel mixture of volatile hydrocarbon and aromatic compounds possibly containing tetraethyl lead, methanol, and other agents. Gasoline is sometimes 'sniffed'

Inhalant (organic solvent) abuse during pregnancy 325.

by inhalant abusers to produce a euphoric effect. Acute poisoning by gasoline is a.s.sociated with pneumonitis, shock, cardiac arrhythmias, convulsions, coma, and death.

A case report was published of two infants with profound mental r.e.t.a.r.dation, neurological dysfunction, and minor dysmorphic features ('fetal gasoline syndrome') born to women who had abused gasoline by inhalation throughout pregnancy (Hunter et al et al., 1979). It has not been possible to a.s.sess a causal relations.h.i.+p based upon two children in a case report.

TOLUENE.

Toluene is an aromatic organic solvent used in paint thinner, in printing, and in adhesives. It is a substance of abuse used by 'huffing' or 'sniffing' for its euphoric effect. It has caused organic brain syndrome in adults and is a.s.sociated with cerebral atrophy (Allison and Jerrom, 1984; Cooper et al et al., 1985; Filley et al et al., 1990; King, 1982; La.r.s.en and Leira, 1988; Lowenstein, 1985; Pearson et al et al., 1994). Adult brain damage suggests the same damage may be caused by toluene exposure in utero in utero.

Unusual dysmorphic features suggestive of a toluene embryopathy were described in three children who were born to women who frequently inhaled large amounts of toluene throughout pregnancy (Hersh, 1989; Hersch et al et al, 1985) and these are strikingly similar to FAS (Pearson et al et al., 1994). Among 35 infants with the toluene embryopathy phenotype, 42 percent were premature, 52 percent had low birth weight, and 32 percent were microcephalic. Postnatally, they were below the fifth percentile for all measures, including neurodevelopment and had dysmorphic facies (Arnold et al et al., 1994). Preterm delivery, perinatal death, and prenatal growth r.e.t.a.r.dation are a.s.sociated with toluene use during pregnancy (Wilkins-Haug and Gabow, 1991). Two cases of renal tubular dysfunction and metabolic acidosis (including hyperchloremic acidosis and amnioaciduria) were recently reported in infants whose mothers chronically abused inhalants containing toluene (Lindemann, 1991). Early childhood growth and development were also significantly delayed among toluene-exposed infants (Wilkins-Haug and Gabow, 1991).

They had the typical syndrome stigma of the toluene embryopathy at follow up (Arnold et al et al., 1994). Four of five neonates born to women who abused toluene during pregnancy had low birth weight (< 2500="" g),="" but="" only="" one="" had="" a="" congenital="" anomaly="" (goodwin,="">

Summary of solvents during pregnancy Solvent abuse during pregnancy poses significant risks to the pregnancy, endangering both the mother and the fetus. A fetal solvent syndrome probably exists and consists of dysmorphic facial features and severe growth and developmental delay (below 5th percentile).

Distal renal tubular acidosis and hyperchloremic metabolic acidosis should be expected in solvent using pregnant women and it may precipitate labor. Premature labor should be antic.i.p.ated and will usually follow toluene toxicity. Fetal/neonatal metabolic acidosis (arterial pH less than or equal to 7.0), respiratory difficulties, and renal function abnormalities have been observed, in addition to the usual complications of prematurity.

326.

Substance abuse during pregnancy TOBACCO USE IN PREGNANCY.

Native Americans grew and smoked tobacco in pre-Columbian times. However, tobacco native to North America is not the tobacco used today because it was too bitter to be smoked or chewed alone, and was mixed with a variety of other substances for use, including willow bark, mushrooms, and wild lettuce. The tobacco, Nicotiana tabac.u.m Nicotiana tabac.u.m, is widely used by smoking, chewing, or dipping, and is a hybrid of South and North American species. Tobacco smoke comprises several-hundred different chemicals, including nicotine and carbon monoxide in greatest abundance. There are several-thousands of publications on the risks of tobacco use during pregnancy, including extensive reviews (Fredricsson and Gilljam, 1992; Landesman-Dwyer and Emanuel, 1979; McIntosh, 1984a,b; Nash and Persaud, 1988; Rosenberg, 1987; Stillman et al et al., 1986; Streissguth, 1986; Surgeon General, 1979).

Approximately 20 percent of pregnant women smoke tobacco in some studies (Rantakallio et al et al., 1995; Vega et al et al., 1993), and in Dallas the rate was 15 percent. The ear-liest finding was increased frequencies of prematurity (estimated by lowered birth weight) among smokers (Simpson, 1957), which was later confirmed (Herriot et al et al., 1962; Lowe, 1959; Ravenholt and Lerinski, 1965). It later became apparent that lowered birth weight was not due to prematurity, but was in fact intrauterine growth r.e.t.a.r.dation (Rubin et al et al., 1986).

Low birth weight Several-hundred thousand women who smoked during pregnancy have been studied (Anonymous, 1993; Cnattingius et al et al., 1993; Fox et al et al., 1994; Hjortdal et al et al., 1989; McIntosh, 1984a; Stillman et al et al., 1986) and lowered birth weight was definitely a.s.sociated with maternal tobacco smoking during pregnancy. Smoking more heavily during pregnancy results in infants that are more growth r.e.t.a.r.ded. In addition, pa.s.sive exposure to smoke was also related to reduced birth weight (Bardy et al et al., 1993; Fortier et al et al., 1994; Haddow et al et al., 1989, 1993; Martinez et al et al., 1994; Mathai et al et al., 1992; Ogawa et et al al., 1991; Rebagliato et al et al., 1995; Seidman and Mas.h.i.+ach, 1991). However, growth is apparently not delayed when there is exposure to tobacco smoke postnatally (Day et al et al., 1994; Jacobson et al et al., 1994). Importantly, birth weight was unaffected in infants whose mothers ceased smoking early in pregnancy (i.e., during the early second trimester) (Ahlsten et al et al., 1993; Li et al et al., 1993; Olsen, 1992).

Intellectual development and behavior Very mild, insignificant reductions in IQ (15 points) were found among children whose mothers smoked during pregnancy (Davie et al et al., 1972; Dunn et al et al., 1977; Fried, 1989, 1992, 1993; Fried et al et al., 1992; Olds et al et al., 1994; Rush and Callahan, 1989). However, socioeconomic status (SES) and maternal education were lower among women who smoked.

Birth defects The purported teratogenic relations.h.i.+p between smoking or use of tobacco during pregnancy is unlikely, but, if it does exist, is very small (1 percent or less). The possibility Tobacco use in pregnancy Tobacco use in pregnancy 327.

that tobacco is a teratogen has been a.n.a.lyzed in dozens of epidemiological studies, involving over 100 000 children (McIntosh 1984a; Stillman et al et al., 1986). The frequency of major congenital anomalies is generally not increased among mothers who smoke tobacco during pregnancy (Andrews and McGarry, 1972; Christianson, 1980; Erickson, 1991; Evans et al et al., 1979; Hemminki et al et al., 1983; Kullander and Kallen, 1976; Malloy et al et al., 1989; Pradat, 1992; Seidman et al et al., 1990; s.h.i.+ono et al et al., 1986; Tikkanen and Heinonen, 1991, 1992, 1993; Van Den Eeden et al et al., 1990; Werler et al et al., 1990, 1992).

Some investigators found significant a.s.sociations between cigarette smoking and birth defects, such as craniosynostosis (Alderman et al et al., 1994). A nonspecific collection of birth defects (gastroschisis, limb reduction defects, strabismus, and congenital heart disease) have been reported to be increased in frequency among infants born to smokers (Aro, 1983; Christianson, 1980; Czeizel et al et al., 1994; Fedrick et al et al., 1971; Goldbaum et et al al., 1990; Haddow et al et al., 1993; Hakim and Tielsch, 1992; Himmelberger et al et al., 1978).

Cleft palate and orofacial clefts have been reported to be increased in frequency (Andrews and McGarry, 1972; Ericson et al et al., 1979; Hw.a.n.g et al et al., 1995; Khoury et al et al., 1989; Shaw et al et al., 1996). The a.s.sociation of tobacco with clefting remains controversial because other large studies found no such a.s.sociation (Frazier et al et al., 1961; Lowe, 1959; Underwood et al et al., 1965; Yerushalmy 1964). For example, in one study no a.s.sociation was found with maternal tobacco smoking among 288 067 infants, of whom 10 223 had congenital anomalies (Malloy et al et al., 1989). In a cohort of 67 609 pregnancies, an increased frequency of anencephalic infants was found among progeny of women who smoked heavily during gestation (greater than 20 cigarettes per day) (Evans et al et al., 1979).

Notably, smoking is more prevalent in the lower social cla.s.ses, as is the incidence of anencephaly. White cigarette smokers gave birth to anecephalics at 1.72 per 1000, while White nonsmokers had a rate of 1.0 per 1000 (Naeye, 1978). A similar trend was not found among Black women, who have a lower rate of anencephaly than White women, and no trend with smoking was found for smoking and anencephaly for this ethnic group. If the risk of congenital anomalies is increased above the background rate among infants whose mothers smoke tobacco during pregnancy it is very small at 1 percent or less.

Childhood cancer Very weak evidence suggests that cancer during childhood is a.s.sociated with in utero in utero exposure to tobacco smoke (McKinney exposure to tobacco smoke (McKinney et al et al., 1986; Schwartzbaum, 1992; Stjernfeldt et et al al., 1986). These a.s.sociations are equivocal and contradicted by other studies (Gold et al et al., 1993; John et al et al., 1991; McCredie et al et al., 1994; Pers.h.a.gen, 1989; Pers.h.a.gen et al et al., 1992).

Pregnancy complications An increased frequency of premature rupture of membranes (Underwood et al et al., 1965), abruptio placentae, placenta previa, and amniotic infections occurs among gravidas who are heavy smokers (Naeye, 1979). Smoking was reported to be a risk factor for gynecological diseases, ovarian cycle disturbance, spontaneous abortion, pregnancy toxicosis, premature delivery, and chronic fetal hypoxia (Sheveleva et al et al., 1986). Preterm delivery, placenta previa, perinatal mortality, and other complications of pregnancy have shown 328 328 Substance abuse during pregnancy an increase among women who smoke (Anonymous, 1993; English and Eskenzai, 1992; Guinn et al et al., 1994; Handler et al et al., 1994; Little and Weinberg, 1993; McIntosh, 1984b; Meis et al et al., 1995; Raymond and Mills, 1993; Stillman et al et al., 1986; Wilc.o.x 1993).

Animal studies Nicotine and cigarette smoking in animals has also been studied and reduced fetal weight was found. Notably, a very early study showed that rabbits exposed to the equivalent of 20 cigarettes per day gave birth to fetuses that were 7 percent lighter than controls (Schoeneck, 1941).

Summary of tobacco during pregnancy Tobacco smoke adversely affects pregnancy. Pa.s.sive tobacco smoke exposure negatively affects fetal growth. However, catch-up growth in the neonatal period fully compensates for fetal growth r.e.t.a.r.dation for active smokers.

PHENCYCLIDINE USE IN PREGNANCY.

Phencyclidine (PCP) is used as a recreational drug and is taken orally, intravenously, intranasally, or smoked. Phencyclidine is no longer available as a pharmaceutical preparation, but was formerly used as an anesthetic and a.n.a.lgesic in human but mainly vet-erinary medicine. Ketamine is a more predictable and effective medicine that is used in its place.

Among 57 infants whose mothers took PCP throughout pregnancy, including the first trimester, the frequency of congenital anomalies was not increased above background risk (3.55 percent) for human populations (Wachsman et al et al., 1989). The frequency of congenital anomalies in two studies with control groups was not increased among 131 infants exposed to PCP during gestation (Golden et al et al., 1987; Tabor et al et al., 1990). A case report was published of an infant with intracerebral abnormalities who was exposed to PCP during gestation (Michael et al et al., 1982), but this has no causal meaning. Birth weights and head circ.u.mferences were depressed in another report, with more than 40 percent of PCP-exposed infants falling below the tenth percentile for reference data (Lubchenco et al et al., 1966). Postnatal follow-up at age 1 year for 36 infants exposed to PCP in utero in utero found slight growth delays, with 24 percent below the tenth percentile (Wachsman found slight growth delays, with 24 percent below the tenth percentile (Wachsman et al et al., 1989).

An increased frequency of low birth weight and microcephaly was found among 505 infants exposed to cocaine and PCP during gestation (Rahbar et al et al., 1993).

Withdrawal symptoms (tremors, jitteriness, irritability) were observed among about 50 percent of infants exposed prenatally to PCP (Wachsman et al et al., 1989), but in none of seven infants in another case series (Chasnoff et al et al., 1983a).

Summary of PCP in pregnancy Phencyclidine is a.s.sociated with fetal growth r.e.t.a.r.dation and withdrawal symptoms. It does not seem to be a strong cause of birth defects.

Use of Ts and blues in pregnancy 329.

USE OF TS AND BLUES IN PREGNANCY.

Used as a subst.i.tute for heroin, 'Ts and blues' is a street mixture of the narcotic a.n.a.lgesic pentazocine (Talwin) and the over-the-counter antihistamine tripelennamine (pyribenzamine). Pentazocine is a synthetic narcotic a.n.a.lgesic given medically by parenteral, oral, or rectal routes to relieve moderate to severe pain. In the early 1970s it was in wide use in Chicago, and popular among inner-city drug users as a 'high' less expensive than, but similar to, heroin (Senay, 1985).

Ts and blues abuse during pregnancy has not been well studied. Data are available for 86 infants born to women who used Ts and blues during pregnancy ( n n = 13, 50, and 23, respectively) (Chasnoff = 13, 50, and 23, respectively) (Chasnoff et al et al., 1983b; Little et al et al., 1990f; von Almen and Miller, 1984).

Infants born to Ts and blues abusers have fetal growth r.e.t.a.r.dation and suffer from perinatal complications more frequently than controls (Chasnoff et al et al., 1983b; Little et al et al., 1990f; von Almen and Miller, 1984). The frequency of congenital anomalies was not increased among these 86 infants (Chasnoff et al et al., 1983b; Little et al et al., 1990f; von Almen and Miller, 1984).

The effect of the use of pentazocine during pregnancy on development of 39 infants whose mothers took the drug showed 21 percent were premature, 31 percent were growth r.e.t.a.r.ded, 11 percent (four children) had congenital anomalies, and 28 percent had withdrawal symptoms (DeBooy et al et al., 1993). At 68 months of age, five of 19 had failure to thrive, and eight were removed from birth mothers and placed in foster care because of abuse and neglect. Twenty-one children were tested and 81 percent (17) scored within the normal range (85 or more) and four children received scores in the subnormal (70 to 84) range. No children received scores below 70. These types of findings are difficult to a.s.sess because of other factors in the drug abusers' life style (poor diet, lack of prenatal care, and concomitant use of other substances of abuse, especially alcohol) contributed to low birth weight and other untoward outcomes among infants born to Ts and blues abusers.

Transient neonatal withdrawal symptoms were observed by several investigators in infants born to women who chronically took pentazocine in a medically supervised environment late in pregnancy (Goetz and Bain, 1974; Kopelman, 1975; Scanlon, 1974).

The symptoms resembled those seen in neonatal withdrawal from other narcotics: irritability, hyperactivity, vomiting, high-pitched cry, fever, and diarrhea.

Another Ts and blues combination is also used, Alwin (pentazocine) and Ritalin (methylphenidate) (Carter and Watson, 1994), and was anecdotally a.s.sociated with fetal growth r.e.t.a.r.dation, but not birth defects (Debooy et al et al., 1993). As with the other Ts and blues mixture, alcohol abuse is highly prevalent.

Ts and blues summary Although Ts and blues use during pregnancy is a.s.sociated with fetal growth r.e.t.a.r.dation and withdrawal symptoms, maternal complications such as pulmonary thromboembolic disease and placental infarcts may occur secondary to intravenous injection of tablet vehicle (microcrystalline cellulose). Infants born to Ts and blues users are at increased risk for fetal alcohol syndrome because most users of this drug combination drink alcohol in abusive amounts (more than six drinks per day).

330.

Substance abuse during pregnancy POLYDRUG USE DURING PREGNANCY.

Pregnant women who use a substance of abuse usually use more than one substance. We conducted a study to a.n.a.lyze patterns of substance abuse and polydrug use during pregnancy at one of the largest obstetric services in the USA, providing medical care for a primarily indigent (less than 5 percent pay for their health care) patient population. The substances that were a.n.a.lyzed included methamphetamine, cocaine, heroin, and Ts and blues.

Among 174 pregnant women who abused drugs during their pregnancies, 83 percent had some prenatal care. Heroin users were significantly older (28.3 years) than cocaine users (24.8 years) or methamphetamine users (23.4 years) (Little et al et al., 1990e).

Over 90 percent of gravid methamphetamine abusers were White and used tobacco (54 percent), marijuana (37 percent), and cocaine (12 percent). About one-half (55 percent) of pregnant cocaine users were Black and they also used tobacco (53 percent), alcohol (11 percent), heroin (8 percent), and marijuana (8 percent). Among White women who used cocaine, the substances they used most frequently were tobacco (46 percent), methamphetamine (42 percent), marijuana (35 percent), and alcohol (27 percent). Pregnant Black and White women heroin abusers (respectively) also used cocaine (62 and 25 percent), alcohol (38 and 25 percent), methadone (8 and 63 percent), and tobacco (62 and 35 percent). Approximately 94 percent Ts and blues users were Black and they also used alcohol (53 percent), cocaine (12 percent), marijuana (12 percent), and methamphetamine (6 percent) (Little et al et al., 1990c).

Polydrug use (more than one drug) was reported by 130 (75 percent) of pregnant women studied. Other than tobacco, alcohol, and cocaine were the most frequently used secondary and tertiary drugs. Alcohol and/or cocaine use during pregnancy differed considerably by primary drug of abuse. Heroin and Ts and blues users drank alcohol 5.2-and 14.2-fold more often, respectively, than gravidas who abused methamphetamine.

Heroin abusers used cocaine 8.9 times more frequently than abusers of methamphetamine or Ts and blues. Heroin abusers used alcohol and cocaine 5.2- and 5.2-fold, respectively, more frequently than methamphetamine abusers (Little et al et al., 1990e).

Concomitant use of several substances of abuse that have teratogenic potential has serious implications for substance abuse during pregnancy because of the risks for mother and fetus. Growth r.e.t.a.r.dation appears to be more severe, and the frequency of congenital anomalies seems to be increased in the offspring of mothers who abuse multiple substances (Oro and Dixon, 1987). The primarily intravenous use of these drugs increases the risk of maternal HIV infection and vertical transmission.

Ts and blues, heroin, and cocaine users are at greatest risk for birth defects attributable to alcohol abuse. Heroin abusers used cocaine significantly more frequently than abusers of any other drug, probably because of the popularity of a mixture called 'speedball' (cocaine and heroin, and occasionally methamphetamine). Because of polydrug use, infants born to heroin abusers are at 8.9 times greater risk for cocaine-induced damage than those born to abusers of other drugs, except for those born to cocaine abusers alone. Infants born to Ts and blues abusers are at a three to 14 times greater risk of alcohol-induced damage to the embryo or fetus than infants born to abusers of other drugs (Little et al et al., 1990f).

It is widely known that alcohol is a leading cause of birth defects (Abel and Sokol, 1987; Jones et al et al., 1973) and cocaine is very likely a teratogen (Chasnoff et al et al., 1988; Key references Key references 331.

Little and Snell, 1991b; Little et al et al., 1989b; Little and VanBeveren, 1996; VanBeveren et et al al., 2000). Infants born to heroin abusers are exposed to cocaine and alcohol five times more often than those born to methamphetamine abusers. It is clear that alcohol is a major contributor to the risk of congenital anomalies and growth r.e.t.a.r.dation in infants born to drug abusers, particularly those who abuse Ts and blues or heroin. Importantly, multiple substance use increases the possibility of drugdrug and drugalcohol interac-tions. Whether or not alcohol and cocaine interact to increase the severity of damage to the conceptus is not known, but this seems likely (Hofkosh et al et al., 1995).

Cocaine and heroin increase the risk for abruptio placentae and premature birth for women who use cocaine (Acker et al et al., 1983; Chasnoff et al et al., 1985). Alcohol is used frequently by those who abuse cocaine, heroin, and Ts and blues, and may cause such pregnancy complications as premature labor (NIAAA, 1983).

Summary of substance abuse during pregnancy The risk for morbidity increases with the number of substances used and the frequency of their use. Not all substances of abuse cause congenital anomalies, but most substance use is a.s.sociated with the use of alcohol and/or cocaine, generally acknowledged to cause birth defects. Abuse of any substance during pregnancy is a.s.sociated with fetal growth r.e.t.a.r.dation and possibly with neurological dysfunction. a.s.sociated risks include s.e.xually transmitted diseases, hepat.i.tis, and undernutrition.

Key references Arria AM, Derauf C, Laga.s.se LL et al. Methamphetamine and other substance use during pregnancy. Preliminary estimates from the infant development, environment, and lifestyle (IDEAL) study. Matern Child Health J 2006; 5 5: 1.

Chomchai C, Na Manorom N, Watanarungsan P, Yossuck P, Chomchai S. Methamphetamine abuse during pregnancy and its health impact on neonates born at Siriraj Hospital, Bangkok, Thailand. Southeast Asian J Trop Med Public Health 2004; 35 35: 228.

Dashe JS, Sheffield JS, Olscher DA, Todd SJ, Jackson GL, Wendel GD. Relations.h.i.+p between maternal methadone dosage and neonatal withdrawal. Obstet Gynecol 2002; 100 100: 1244.

Frank DA, Rose-Jacobs R, Beeghly M, Wilbur M, Bellinger D, Cabral H. Level of prenatal cocaine exposure and 48-month IQ. importance of preschool enrichment. Neurotoxicol Teratol 2005; 27 27: 15.

Hurt H, Brodsky NL, Roth H, Malmud E, Giannetta JM. School performance of children with gestational cocaine exposure. Neurotoxicol Teratol 2005; 27 27: 203.

Kuczkowski KM. Peripartum care of the cocaine-abusing parturient. Are we ready? Acta Obstet Gynecol Scand 2005; 84 84: 108.

Lewis BA, Singer LT, Short EJ et al. Four-year language outcomes of children exposed to cocaine in utero. Neurotoxicol Teratol 2004a; 26 26: 617.

Lewis MW, Misra S, Johnson HL, Rosen TS. Neurological and developmental outcomes of prenatally cocaine-exposed offspring from 12 to 36 months. Am J Drug Alcohol Abuse 2004b; 30 30: 299.

Little BB, Snell LM, VanBeveren TT, Crowell RB, Trayler S, Johnston WL. Treatment of substance abuse during pregnancy and infant outcome. Am J Perinatol 2003; 20 20: 255.

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Substance abuse during pregnancy Wolfe EL, Davis T, Guydish J, Delucchi KL. Mortality risk a.s.sociated with perinatal drug and alcohol use in California. J Perinatol 2005; 25 25: 93.