Opioid Dependence and Methadone Maintenance Treatment during Pregnancy

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0PIOID DEPENDENCE AND METHADONE MAINTENANCE TREATMENT DURING PREGNANCY Dat,id V. Caloia, BSc, Medical Student, Unit,ersity of Toronto ABSTRACT

The usc of methadone maintenance treatment for the care of opioid-depcndcnt individnaL1 is well established. However, pregnant women who either arc currentl:v ahusin?, ojJioid.1 ur are maintained on methadone jJYesent particular challen?,es to the obstetrician. As the outcomes of methadone-maintained preRYJLlncie.\ arc comistently better than those of untreated opioid abusers, the recognition of dependence and the provision of appropriate prenatal and post-natal care arc t•ital to the future health of both the hahy and its mother. The literature is reviewed to provide an introduction to the abuse of heroin and its treatment with methadone. An overview of the medical mana?,ement of the pre?,nant methadone-maintained woman is ?,iven, includin?, care of the infant under?,oin?, neonatal abstinence syndrome. RESUME

Lc traitcment de substitution a Ia methadone des jJer.\rmncs qui dejJendcnt des ojJiace.\ est utilise courammcnt. Lcs femmes enceintes qui consomment iKtuellement de.1 opiaces ou qui suit•ent un traitement de substitution aIa methadone nc posent toutefoi.\ aucun prohleme particulier a l' ohstetricien. Puisque l' issue de Ia ?,YOS.\esse des femmes traitees aIa methadone est comtamment mcilleurc que celle des toxicomanes non traitees, le dia!',!lostic de dependance et Ia jJYestation de soins prenatals et postnatals apjJYopries sont essentiels aIa sante ulterieure du hebe et de sa mere. La litteraturc est analysee en ?,Uise d'introduction al'heroi'rwmanie eta son traitement aIa methadone. On donne un apcn,;u du traitemcnt medical de Ia femme enceinte qui suit un traitement de substitution a Ia methadone' y comjms les soim du nourrisson en jJYoic au syndrome de sevra?,e neonatal.

J SOGC 1997;19:257-71

KEY WORDS Diacetylmorphine, narcotic dependence, methadone maintenance treatment, jJYcgnancy. Received on June 11th, 1996. Revised and accepted on Octohcr 9th, 1996.

While the use of heroin remains low among mainstream populations (at approximately 1 to 2%), of concern is the age distribution. Between 1993 and 1994, the percentage of Addiction Research Foundation attendees seeking treatment for abuse of this narcotic increased from six to almost ten percent, with the greatest noticeable increase among those under the age of 26. 1 Heroin abuse among street youth is higher than in the general populace, and national data demonstrate that the

INTRODUCTION

The abuse of heroin is a growing problem in many Canadian urban centres. Recent seizures show sizeable increases in both Metropolitan Toronto 1 and Canada.' Average purity rose from 20 to 30 percent ten years ago to almost 70 percent in 1994, the most recent year for which data were available. With availability and purity at record highs, the price has been dropping.'

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' ' ' common, and use of multiple drugs may compound adverse effects. 7 The impurity of street drugs and the possibility of the heroin being "cut" with a known teratogen such as quinine pose a greater risk for the pregnant opioid user. 8 The user is also less likely to receive adequate prenatal care, a factor related directly to infant morbidity. 9 Prenatal opioid exposure can lead to intra-uterine growth restriction, increased numbers of stillbirths, sudden infant death syndrome (SIDS), and neonatal abstinence syndrome (NAS). 9' 11 Transient periods of fetal depression alternate with abstinence as the fetus is exposed to varying levels of opioids. Uterine contractions during maternal withdrawal cause an intermittent obstruction to placental perfusion, which results in intermittent fetal hypoxiaY In addition, more than seventy percent of paediatric AIDS cases occur in children born to drug-using women, or women who are having sexual relations with drug-using men.ll Children raised in an environment of drug abuse are at greater risk of showing impaired mental development.14 Neglect, abuse, and abandonment are common outcomes for the infant of the opioid-dependent woman, even when there is vigilant monitoring. 8 Opioid dependence clearly increases maternal and neonatal morbidity and mortality significantly, although there is a lack of hard evidence due to the problem of separating drug use from its correlates of social disadvantage, poor health, and multiple substance abuse. The only medication currently approved for the treatment of the pregnant opioiddependent woman is methadone, established as the standard of care by studies from the late 1960s and early 1970s. 11

majority of the users are under 34Y These statistics are of special interest to obstetricians and gynaecologists as most of the female heroin abusers are in the reproductive age group. This article will introduce the medical aspects of opioid abuse and the foundations of methadone maintenance treatment (MMT), and will review the pertinent literature on the obstetrical aspects of this therapy. OPIOID DEPENDENCE

Heroin-dependent individuals are constantly trying for their next "fix." They are chasing the sensations of analgesia, sedation, and euphoria that are steadily and inevitably requiring higher doses to attain. Eventually they become physically dependent, and abstention from opiates results in a syndrome of withdrawal. Unable to function without their drug, opioid-dependent individuals require diacetylmorphine in order to "feel normal." Their pursuit of heroin becomes all-consuming and is associated with increased use of social welfare, increased illegal activity and incarceration, and increased use of the health care system. A heroin abuser may use one to two grams a day, each costing anywhere from $120 to $300; being employed is not worth the time. Many abusers are on social assistance, and when this does not suffice they borrow from friends and family. Requiring more money, they sell or pawn their possessions, and typically resort to criminal activity. While some progress no further than to petty theft, many move on to prostitution, assault, auto theft, and robbery. If they are arrested, there are the associated costs of the court proceedings and, potentially, incarceration. When released, few resist falling back into their former habits. Should they want to change their way of life, opioid-dependent individuals face further challenges. Many heroin users have tried drug detoxification, outpatient treatment, residential therapeutic communities, or combinations of all three. Rarely are these options successful in caring for chronic opioid abuse. 3 Opioid addiction is not a choice, but a well-established psychological and physiological process of tolerance and dependence.4 The incurable, chronic, and progressive disease of opioid addiction has several associated health risks. Within Toronto, drug-factor deaths where there are positive findings for heroin have been rising steadily, and abusers are prone to such diseases as syphilis, endocarditis, abscesses, hepatitis, tuberculosis, and acquired immunodeficiency syndrome (AIDS). 15 '6 Polydrug use is

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METHADONE MAINTENANCE TREATMENT

Methadone maintenance treatment (MMT) is generally recognized as the most rigorously studied method of treatment for opioid dependence and has had the most consistently positive results. 1' 16'17 Because most of the negative consequences of opioid dependence are related to illicit drug use and its complications and not to the opioid itself, methadone maintenance is a tool for patients having trouble in achieving and maintaining abstinence. Since Dole, Nyswander, and Warner's first assessment in 1968, study after study has linked methadone maintenance treatment with increased socio-economic status and level of employment and decreased mortality, criminal behaviour, and illicit drug use. 18' 22 Randomized clinical trials and complementary studies demonstrate

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' ' ' involved in affording and obtaining heroin and has the potential for complete detoxification." 7 In caring for the heroin-dependent individual, it must be remembered that rehabilitation not abstinence is the primary goal of

that, on average, people dependent on opioids have significantly better long-term outcomes on MMT than if they are detoxified and released, or if the dose is tapered 1 and then terminated at the patient's requestY ' 24 Once adjusted, the dose produces neither subjective intoxication nor clinically detectable behavioural impairment.1'w There are no toxic effects, and minimal side effectsY' The most common persistent side effects are increased sweating and decreased libido ( 48 and 22%, respectively). Some individuals also experience constipation (17'X)) or insomnia (16%). 2" As for the control and prevention of human immunodeficiency virus (HIV) infection in intravenous drug abusers, current literature advocates MMT as one of the safest and most helpful means of reducing risk, and recommends that 2711 Glantz programmes should be available on demand. and Woods summarize its clinical advantages: "Methadone has the advantage of oral rather than intravenous administration, known doses and purity, and lower cost. It does not require the maladaptive behaviors

this treatment. Methadone maintenance treatment for the pregnant opioid-dependent woman serves several purposes. It provides an opportunity for women to remove themselves from the drug-seeking environment, reduces concomitant illicit behaviour, and prevents the peaks and troughs in the maternal drug levels that may occur throughout the day." While the outcomes are not equivalent to that of a drug-free pregnancy, mothers in methadone maintenance programmes receive more prenatal care, have fewer obstetrical complications, and have longer gestations and larger babies than untreated abusers.' 2 "' 12 There does not seem to be an increase in the rate of congenital anomalies with opiate abuse.'' The incidences of haemorrhage and abruptio placentae are no greater than in the general obstetrical population and should be treated in the

Once you prescribe Triphasil, you'll find that most patients get into a very !'omfortable rhythm. Triphasil offers excellent cycle control with a low in!'idence of side effects and our unique Cyclette packaging helps make compliance easy and rPcluces errors.'' As well, only Triphasil has thP Pill Passport

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' ' ' same way. 34 The mothers who accept methadone are often more amenable to prenatal care and psychosocial rehabilitation. With intensive prenatal care for pregnant opioid-dependent women, methadone maintenance treatment can also improve maternal nutrition, and reduce the incidence of HIV infection, intra-uterine death, neonatal death, and prematurity. The pharmacology of methadone has been well studied. It is widely distributed throughout the body after oral ingestion, with extensive non-specific tissue binding. This creates a reservoirs that releases unchanged methadone back into the blood and contributes to its long duration of action. 11 With a half-life of 24 to 36 hours, methadone avoids the acute peaks and valleys of intravenous heroin use. In the pregnant woman, methadone readily crosses the placenta, and has been identified in amniotic fluid, cord blood, and neonatal urine. It is metabolized in the fetal liver and excreted in fetal urine and faeces. Drug clearance undergoes several changes throughout pregnancy. The non-specific tissue binding, combined with an increased fluid space and an increased drug metabolism by both the placenta and the fetus, leads to the development of a significant reservoir in the fetal environment. 36 Despite this reservoir, decreased plasma protein binding, increased tissue binding, and an increased metabolism secondary to higher levels of progestin, cause a decline in steady-state maternal methadone levels late in human gestation." Thus, the half-life of methadone is shorter in the third trimester than at any other time during pregnancy. This is relevant to clinical management and will be addressed later. The dangers of methadone to the infant include prematurity and an increased percentage of breech presentations, though the latter is generally ascribed to the former. 7·14 The most widely documented post-natal problem associated with MMT is the neonatal abstinence syndrome. Early neurobehavioural abnormalities, however, do not persist and the syndrome is easily resolved when managed properly. 10·' 7 While separating the environmental and drug-exposure factors that result in a poor outcome is difficult, follow-up studies to preschool age have not found serious or consistent cognitive impairments or deficits in IQ. 9 •14 ' 18 Jarvis and Schnall, in an excellent review, state that "The clinical studies available demonstrate that methadone maintenance at an appropriate dose, when combined with prenatal care and a comprehensive program of support for the pregnant

JOURNAL SOGC

opioid-dependent woman, can significantly improve fetal and neonatal outcome." 11 It must be noted that in Canada methadone is a controlled substance. Prescription of this drug requires authorization and, until recently, this function was administered by Health Canada's Bureau of Drug Surveillance (BDS). In November of 1995, an agreement was reached between the College of Physicians and Surgeons of British Columbia and Health Canada, transferring the administrative duties of the methadone programme of that province to the College. As of May 1996, the College of Physicians and Surgeons of Ontario has also accepted responsibility for tracking patients who are receiving methadone for narcotic dependence. In addition to transferring much of its authority to provincial medical regulators, the BDS has resolved that access to MMT should be facilitated so that more patients can benefit from the treatment. The BDS also indicated that there should be a liberalization of the requirements to permit greater access. Provincial medical regulators are developing guidelines pursuant to these goals. CLINICAL MANAGEMENT OF THE METHADON E-M AI NT AI NED PREGNANT WOMAN RECOGNITION OF HEROIN DEPENDENCE

A physician taking a detailed history of any pregnant woman should include tactful questions regarding substance abuse. A positive family history of alcohol or drug abuse, drug-seeking behaviour, or legal problems may raise concern. A history of hepatitis, unexplained bacterial endocarditis, or multiple episodes of cellulitis, pneumonia or sexually transmitted diseases are also a cause for alarm. Low birth weight babies, premature birth or fetal demise may have complicated past pregnancies. Poor attendance during prenatal care may arouse additional concern. Physical clues to addiction include such dermatologic signs as the presence of track marks, thrombotic veins or subcutaneous abscesses. The appearance of hepatomegaly adds further suspicion. The drug abuser may also present with signs of intoxication which include drowsiness, euphoria, constipation, and miosis (pupillary constriction). Alternatively, she may present with hyperventilation, yawning, perspiration, lacrimation, and rhinorrhoea-all signs of early withdrawal. Other symptoms include mydriasis, piloerection, tremors,

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' ' ' muscle spasms, chills, flushing, vomiting, diarrhoea, abdominal cramping, and anorexia. Frequently the opioid abuser escapes diagnosis during pregnancy. Up to fifty percent of pregnant street addicts first present in labour. 8 Any woman presenting for delivery who has had no prenatal care should alert the physician to the possibility of substance abuse. Failure to diagnose maternal dependence leaves the newborn vulnerable to NAS, a potentially fatal but treatable condition. Neonatal problems may, thus, provide the first clue to maternal dependence. 19

in the number of cocaine-using individuals over the past several years. 12 This is important, as cocaine abuse concomitant with MMT increases the number of medical and obstetric complications, particularly the frequency of premature delivery. 7'8 Cocaine itself leads to various prenatal complications including placental abruption, precipitous labour, and fetal distress, which lead to an increased need for emergency Caesarean sections.11 Noting any alcohol use is also prudent, as this potent teratogen is commonly used when illicit drugs are unavailable. Complete abstinence from alcohol should be encouraged even if historically this drug has presented no apparent problem to the woman. 8 The pregnant heroin user may be a challenge to manage psychologically, and trust may be difficult to establish. She may demonstrate impulsive, demanding or provocative behaviour, arriving late or missing appointments.7 It is vital to try and understand the patient's emotional state and to be supportive of positive behaviours. It would be wise to avoid displays of disappointment

ANTEPARTUM ASSESSMENT AND MANAGEMENT

Following recognition of the opioid-dependent woman, a complete and comprehensive medical and drug abuse history should be taken. The method of drug administration is important, as needle sharing may put the woman at risk for hepatitis or AIDS. Of special importance is any history of polydrug abuse. Many treatment centres have experienced a marked increase

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' ' ' when the patient inevitably fails to meet expectations. Psychiatric illnesses common to pregnant drug abusers include personality disorders, maladies that are difficult to diagnose and have no specific treatments available. Recognizing the presence of these disorders is important as they frequently interfere with management, and lead to conflicts with health care personnel. Screening for other psychiatric illnesses is important, as depression is common in pregnant abusers. Women who have been stable may find the physiological or emotional stress of pregnancy overwhelming, and should be encouraged to bring depressive or suicidal thoughts to the attention of their physicians. Denial of feelings, moods, and above all drug use is a part of addiction that needs to be recognized. In general, all pregnant substance abusers are considered to be in a higher than normal risk category. This should be reflected in the obstetrical work-up. Careful dating of the pregnancy is required, as well as a nutritional assessment. Heroin users frequently are poorly nourished, with iron, folic acid, and vitamin (primarily C and the B complexes) deficiencies. It is important to screen for infection. The initial work-up should include a Pap. test and cultures for gonococcus and chL!mydia, as well as a wet prep. for trichomonas.' Serological testing for syphilis should be ordered, keeping in mind the high incidence of false-positive serological results in both active and former heroin abusers."' T repone mal specific tests should, therefore, be used to confirm the diagnosis. Given the high risk of infection with syphilis, treatment is indicated if the diagnosis is unclear but suspected." These women should be asked if they would be willing to undergo an assay for HIV, as early recognition of HIV seropositivity appears to be correlated with an improved clinical course. 41 This test is important not only for management of the woman during pregnancy but also for management of the newborn. Twenty-five percent of HIV-positive women deliver infants who will be HIV positive due to active infectionY Another twenty-five percent of their newborns will test positive for HIV due to passive immunity from the mother, but will usually revert to a negative status within fifteen months ofbirth. 41 A recent clinical trial demonstrated that, in women with mildly symptomatic HIV disease and no prior treatment with antiretrovirals during pregnancy, zidovudine (AZT) reduced the risk of vertical transmission by almost twothirds.44 Therapy was administered during pregnancy and delivery, and to the infant in the first six weeks of life.

JOURNAL SOGC

There were no significant adverse effects observed in either the mother or the infant. Pretest and post-test counselling is essential, and should emphasize ways to cope with the disease and prevent further transmission. Liver function testing and a hepatitis panel for acute and chronic disease are necessary. It should be noted that up to sixty percent of heroin abusers in treatment have persistent abnormalities in liver function tests due to chronic liver disease. 41 While the appearance of these abnormalities is usually caused by chronic hepatitis or cirrhosis, alcohol abuse is also implicated.' Hepatitis screening should be included because more than twelve percent of heroin abusers and former heroin users are chronic carriers of the hepatitis B antigen. 1 ~ 4 Treatment of the neonate with hepatitis B immunoglobulin and vaccine should be initiated if the mother is a carrier of this antigen. A current tuberculin skin test should be carried out, and a urine culture performed to rule out urinary tract infections. The skin should be inspected for signs of injection-induced cellulitis , remembering that an abuser has available expanded sites including the abdomen and breast.' Ultrasound is useful in evaluating gestational age, as opioid-dependent women are often unsure of their last normal menstrual period. If pregnancy occurs while the woman is already in a methadone maintenance programme, then the use of methadone should be continued throughout the pregnancy.'2·11 Altering the dose further on in the pregnancy may be necessary as described later. If a dependent woman who has not been on methadone presents for care, a physician authorized to prescribe that drug must determine the appropriate dose required to block withdrawal and reduce craving. This can often be a difficult process, and it may take several weeks before the correct dose is established. In the ambulatory setting, documentation of opioid addiction by noting withdrawal signs and interpreting urine screens is recommended!" Hoegerman and Schnoll feel that most pregnant opioid abusers can be started safely on 15 mg of methadone in the morning, then observed carefully over several hours for signs of intoxication.' The patient can return in the afternoon to be assessed for either withdrawal or intoxication and then medicated appropriately. If, on the days that follow, she is still exhibiting withdrawal signs, her total daily dose may be increased by 10 mg of methadone per day until stabilized.

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' ' ' Daily urine toxicology testing would be helpful, as the absence of intoxication with the presence of illicit opioid in the urine may be evidence that more methadone is necessary. 8 If admitting the patient for a brief time is possible, the dose of methadone can be established more rapidly. 15 The heroin-dependent patient is initially evaluated for signs and symptoms of withdrawal. Finnegan recommends 10 mg of methadone if evidence of withdrawal is present, with additional five milligram doses given every four to six hours as neededY On the next day, the previous day's total dose is administered as the maintenance dose. The patient is evaluated for withdrawal, as before, and supplemental doses are given as needed. Alternatively, Jarvis and Schnall provide a scoring system to determine dosage, based on the presence of opioid withdrawal signs. 15 Once the amount of methadone required to block withdrawal is determined (generally 20 to 35 mg), it can be increased to the full (euphoria) blocking dose. It should be emphasized that the magnitude of this increase is dependent on the con-

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comitant use of other drugs and continued use of heroin, and should take into account potential changes in the third trimester. These changes are due to altered methadone pharmacokinetics, and may require a dosage increase to produce the required steady-state plasma levels. 12 Alternatively, a split-dose schedule may be attempted. Recent evidence has shown that splitting the dose of methadone into twice-daily dosing has produced better results by reducing fetal stress and increasing the comfort of the pregnant woman. 47 The most recent Canadian recommendations regarding dose scheduling state that no carry privileges should be provided during pregnancy, except in an emergency or when the patient has no easy access to a distribution centre, and public health services cannot provide a daily supply.46 A second issue that must be addressed in methadone maintenance is the treatment of drug-using partners. Failure to provide methadone to a partner may lead to significant conflict between the two individuals. Ideally, the partner should also enter an MMT programme.

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' ' ' overdose is not definitely established. Repeat doses can be given every five minutes until the patient regains consciousness, though dosages should not be so great as to precipitate withdrawal.' Naloxone has a duration of action of only two to three hours, whereas most shortacting opioids have a six- to eight-hour duration, and methadone has a 12- to 48-hour action. Thus, once the patient has regained consciousness and respiration has returned to normal, close observation is vital. Symptoms may be expected to recur within three hours, and should be treated as required with further doses of naloxone.'· 1' In the pregnant drug abuser, acute withdrawal symptoms may be hazardous for the fetus. Naloxone should be titrated against clinical symptoms, and a short-acting opioid should be available to reverse any potentially dangerous symptoms. It should be noted that the use of naloxone in a pregnant heroin abuser, for any other treatment, is contra-indicated.>~ 12 Gastric lavage may be helpful when an oral drug has been ingested within one to three hours before presentation, but the protein binding of narcotics in the plasma makes dialysis ineffective.' After the initial assessment and methadone dose stabilization are complete, prenatal visits should follow every two weeks. Weight, blood pressure, and fundal height should be assessed, as well as the patient's ongoing ability to comply with the treatment regimen. Urinalysis for drug concentration should be performed at random twice a week,4" although it should be noted that relapse is extremely common. A finding of "dirty urine" should not be seen as a reason for ending treatment. It may suggest the need for further assessment and the possibility of increasing the methadone dosage. Due to their high risk, female abusers should have frequent screening for sexually transmitted diseases and urinary tract infections, even if the initial work-up was negative. Liver function and HIV serological testing can be repeated as deemed appropriate. Hoegerman and Schnoll advocate a weekly nonstress test late in the pregnancy.s Long-term methadone exposure, however, can affect fetal performance on the nonstress test, increasing the incidence of nonreactive assessments. 404" While a biophysical profile may be similarly altered, a contraction stress test should not be affected and may be used as a follow-up to a nonreactive NST.' Prenatal courses and substance abuse counselling are an integral part of the woman's progress towards acquiring not only baby care skills but also new living habits.

Several treatment centres have attempted to withdraw pregnant women from opioids prior to delivery. Infants of women who withdrew successfully did not experience neonatal withdrawal, and also gained the benefits ascribed to methadone maintenance. No obstetrical complications were reported. 11 But while any treatment of opioid-dependent women can positively influence the pregnancy outcome, and while some motivated women are capable of abstinence, most opioid abusers cannot remain drug-free after withdrawal. Not only does withdrawal resubject the woman to all of the attendant complications of illicit heroin use, but the serum-drug cycling of withdrawing and then placing the pregnant opioid abuser back on treatment may be more detrimental than either maintaining her in a steadystate of methadone or keeping her drug-free. 11 Thus, the recommended therapy is that methadone should be maintained throughout the pregnancy.w· 11 Should withdrawal be necessary (for example, if the patient requests withdrawal from methadone, or is so disruptive as to jeopardize the care of other patients), the risks and consequences should be carefully explained. The patient should sign a release form stating that detoxification is performed against medical advice. 46 Intensive psychosocial support is essential, and withdrawal should proceed at no more than five to ten mg per week. 12 · 11 While conventional wisdom held that withdrawal during the first trimester would result in spontaneous abortion, and withdrawal in the third trimester could result in premature delivery, there are no reports in the literature to support these beliefs. 11 Withdrawal can be initiated at any time during the pregnancy if carried out in a controlled, patient-blinded fashion. Some researchers advocate a weekly nonstress test (NST) if the pregnancy is close to completion.' An overdose is also a danger. When an overdose is due to an intravenous injection of heroin, symptoms may occur within seconds. When excess methadone is taken orally, symptoms may not appear for one to three hours, and may progress over a three- to six-hour period with effects lasting for more than 24 hours. 12 Respiratory depression, apnoea, obtundation, pulmonary oedema, and coma may result. Treatment involves airway and ventilatory support, intravenous access, and administration of naloxone. This narcotic antagonist is safe to use, at a dose of 0.01 mg/kg intravenously, even if the diagnosis of an opioid

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' ' ' respiratory distress, poor sucking reflex, tremors, hypertonicity, and high-pitched crying." 50 This constellation of symptoms is generally evident within 24 hours after birth if heroin was the last narcotic used. Due to the drug's longer half-life, methadone abstinence begins three to five days after birth, although it may not appear for as long as ten days. 1111 This is especially important to consider given the recent routine discharge of mothers 24 to 48 hours after delivery. Severe abstinence also may result in seizures. More seizures occur with methadone use ( 7.8%) than with heroin use ( 1.2%), with generalized motor seizures and myoclonic jerks being the predominant convulsive manifestations. The mean age of seizure onset in neonates is reported to be 10 days and extends to over one month, reinforcing the need for prolonged observation. 52 The course of abstinence is most often mild and transient, lasting for less than two weeks. It may, however, follow an intermittent pattern, or one that is biphasic, with acute withdrawal followed by improvement and then the onset of subacute withdrawal. Some infants show mild signs for as long as six months. 11 ·46·" The severity, timing of onset, and duration of the NAS have been difficult to correlate with maternal dosages. At methadone doses of less than 20 mg per day, little or no neonatal abstinence is seen. 54 Several studies have shown the degree of NAS to be correlated with the daily methadone dose and maternal serum methadone level at delivery. Also implicated is the total methadone intake in the 12 weeks before delivery, and the rate of decline of the methadone level in the fetal blood. 1517 Other studies, however, have shown no relationship between the severity of withdrawal and the maternal dose. 1"·1" Treatment of the neonate should begin with supportive care. Swaddling will decrease sensory stimulation, as will ensuring that lights and noise are kept low. Observation of sleeping habits, temperature, weight loss or gain, or change in symptomatology may suggest another disease process. 51 Excess weight loss is common in these infants, and may represent inadequate provision of calories rather than the need for pharmacologic therapy.'4·'' It has been shown that infants withdrawing from maternal narcotics have an increased oxygen consumption at the tissue level. 60 Thus, caloric intake should be calculated to provide the 150 to 250 calories per kg per 24 hours necessary for proper growth. 11 Supportive care in the form of intravenous fluids and replacement electrolytes may be enough to stabilize the

As noted by Finnegan, the most effective treatments and best outcomes for drug-dependent pregnant women are delivered in well coordinated, multidisciplinary treatment settings that allow for the provision and monitoring of methadone, offer high levels of psychosocial support, and provide good obstetrical and medical care. 12 ·11 INTRAPARTUM CARE

Intrapartum management of the narcotic user does not differ greatly from that of the non-user. At the time of admission, urine drug screening should be performed. 46 On the day of delivery, the women should have their total oral daily dosages so as to prevent withdrawal. An intramuscular injection of methadone can be given if oral methadone is not tolerated,' although at present parenteral methadone is not available in Canada. Methadone does not provide adequate pain control, and analgesics may be required more frequently than in a non-drug user. Analgesia with meperidine, or epidural or local anaesthesia, may be given. Such agonist-antagonists as butorphanol, nalbuphine or pentazocine are unpredictable in patients receiving pure agonist drugs, and may cause acute withdrawal.4Narcotic antagonists (e.g. naloxone) should not be given to the mother or newborn except in the case of a massive narcotic overdose. Opioid withdrawal is thought to result in increased oxygen consumption, and superimposed on variable uterine blood flow in labour, may result in fetal hypoxia and compromise." Throughout the intrapartum period, careful observation for signs of narcotic withdrawal or overdose is necessary. Glantz and Woods examined labour outcomes in a comparison of several controlled and uncontrolled studies. There appears to be no difference in the incidence of meconium in the pregnancies of the MMT population compared with those of untreated heroin abusers. Low five-minute Apgar scores are not more frequent in infants of narcotic users compared with controls, and there does not appear to be an increase in fetal deaths in pregnancies complicated by narcotic use. 7 POST-PARTUM MANAGEMENT OF THE MOTHER AND THE NEONATE

The use of methadone to suppress maternal craving and withdrawal can cause neonatal abstinence syndrome. This combines the symptoms of central nervous system ( CNS) hyper-irritability, gastro-intestinal dysfunction,

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' ' ' infant's condition in the acute phase without the need for pharmacologic intervention. It is necessary to rule out other causes for the symptoms ofNAS and these may include infection, hypoglycaemia, hypocalcaemia, hypomagnesaemia, hyperthyroidism, CNS haemorrhage, and anoxia. 51

Clonidine, an a-2 adrenergic agonist, has been shown to reduce withdrawal symptoms in adult opiate abusers. It has been administered to two neonates withdrawing from maternal methadone and appeared to reduce NAS symptoms without side effects. 5163 Further studies are necessary to define the role of clonidine in the treatment of neonatal withdrawal. 51 When pharmacotherapeutic intervention is required, scoring is continued at two-hour intervals. The dosage is increased if the average of three consecutive scores is eight or higher. After a stabilizing dose is attained, the drug dose should be maintained so that the infant sleeps well, eats effectively, and gains weight over three to five days. The dose may then be tapered if scores stay below eight and appropriate weight gain continues. It should be noted that substantial changes in the infant's weight may occur, and a recalculation of the dose may be required. Irritability and tremors should not be used as criteria for continued drug administration because subacute symptoms may last until age six months. Once therapy is ended, scoring is continued for three to five days to ensure that symptoms do not reappear. Physicians must be able to explain the course, as well as the treatment, of NAS to expectant mothers and involved health care personnel. Given their CNS hyperirritability, neonates often display vague autonomic symptoms including sweating, tearing, yawning, sneezing, mottling, and fever. While having an uncoordinated and ineffectual sucking reflex, they may suck frantically on their fists or thumbs. The tremors are initially mild and occur only when the infant is disturbed, but may progress to the point where they occur spontaneously. The combination of increased muscle tone and highpitched crying may further concern those involved. Neonates born to methadone-dependent women have also been found to be more irritable and less cuddly. 12 These early neurobehavioural characteristics have important implications for mother-infant interaction. Infants born to methadone-maintained women have been found to be deficient in their capacity for attention and social responsiveness during the first few days of life, whether or not the NAS was severe enough to require treatment. 64 Infants and their mothers appear to experience a difficult early period during which they are less socially involved with each other. 1265 While there do not appear to be any long term cognitive deficits, behavioural abnormalities may persist into the school years. 66

Should pharmacologic intervention be required, Finnegan's abstinence scoring system can be used to monitor the onset and progression of symptoms, as well as the infant's response. 61 The score includes 21 symptoms that are usually evaluated dynamically, that is, all of the signs and symptoms observed during the four-hour interval are point-totalled for that interval. If, at any time, the score is eight or greater, two-hour scoring will be instituted. When the score is eight or higher for three consecutive screenings, intervention is recommended. Pharmacotherapy traditionally used to control NAS symptoms includes paregoric (anhydrous morphine), phenobarbital, and diazepam. 51 Paregoric has been preferred by many physicians for several reasons. It can be administered orally, has no known adverse effects, and can provide a level of sedation that inhibits bowel motility, decreasing the loose stools frequently accompanying abstinence." Phenobarbitol addresses the symptoms of CNS irritability and insomnia, but does not prevent loose stools, while diazepam causes infants to become severely obtunded and diminishes their sucking reflex. Sucking behaviour has been found to be much closer to normal among paregoric-treated infants than among those treated with phenobarbital or diazepam."' For these reasons, paregoric has been considered by some to be the drug of choice for the control of symptoms due exclusively to narcotic use. 11 Doses for a full-term infant are 0.2 to 0. 5 mL orally every three to four hours until the symptoms of withdrawal are controlled. The disadvantages of paregoric are that large doses are often necessary, and the duration of treatment can be longer with this drug than with other drugs. 11 Concerns have arisen regarding the content of paregoric. In addition to morphine and opium alkaloids, it contains camphor (a CNS stimulant that is eliminated from the body slowly), a high concentration of alcohol ( 44 to 46% ), anise oil, and benzoic acid. An oral preparation of morphine (2 and 4 mg/mL) which contains no additives and less alcohol (10%) is now available. Oral morphine doses should be calculated to deliver the same quantity of morphine equivalent usually supplied in paregoric. 51

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' ' ' cern, but may not be used regularly or properly. Progestin implants do not require compliance after insertion, but offer no protection against STDs. Sterilization is an option if the woman has completed child-bearing. 7 Appropriate post-discharge support is vital. Methadone maintenance treatment requires a multidisciplinary team capable of providing comprehensive medical, psychiatric, and psychosocial care. Should the woman relapse, not only will she be once again at risk of the myriad complications of heroin dependence, but the newborn may suffer from neglect when finances intended for food, clothing, and shelter are diverted to pay for alcohol and drugs. Children may be left alone or abandoned at acquaintances' homes. The mother's depressive, withdrawn or agitated moods, experienced after major drug use, may further endanger her children."' Thus, ongoing substance abuse treatment, psychosocial services, and community outreach play critical roles in the care of the opioid-dependent woman and her child.

This emphasizes the need for appropriate interdisciplinary post-natal counselling. While drugs of abuse are contra-indicated during breastfeeding, appropriately prescribed narcotics are not. 67 Recommendations to reduce infant drug exposure include taking the medication just after completion of nursing or just before an anticipated long sleep period. Methadone in human breast milk, as compared with maternal serum levels, peaks two to four hours after a single oral dose. 68 Methadone is felt to be compatible with breastfeeding if the mother receives no more than 20 mg per 24-hour period. 6' Due to the risk to the infant, it is not recommended that breastfeeding be undertaken by an HIV-positive mother, or one who is still abusing illicit drugs. Good contraceptive options for the methadonemaintained woman are limited. Poor compliance may hinder the use of oral contraceptives, and the high risk of sexually transmitted disease makes the use of intra-uterine devices unsafe. Barrier methods address the latter con-

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' ' ' patients. 11 Thus, both the obstetrician and the obstetrically-trained family physician may provide care to a methadone-maintained woman during her pregnancy. The opportunity to help to break the cycle of heroin abuse and dependence must be of primary concern to the physician presented with an opioid-abusing woman.

CONCLUSIONS

The interplay between heroin addiction, methadone maintenance treatment, and the associated individual and social concerns is an issue that has been dogged by controversy since methadone was first used almost fifty years ago. This having been said, methadone, when combined with psychosocial counselling and medical support, is currently considered one of the safest and most effective means of treating chronic opioid abuse. For those women who are motivated to provide proper prenatal care and optimize the health of their pregnancies, methadone can provide the stability required to regain a normal and productive life. Given proper education and support, general medical practice (i.e. the family physician) has been successful in administering methadone treatment. 10 While usually more expensive than large treatment facilities, family practice or community health centres, with their emphasis on individual care, are preferred by MMT

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