PERSPECTIVE For reprint orders, please contact: [email protected]
Care of drug-addicted pregnant women: current concepts and future strategies – an overview Simone M Goettler*1 & Sibil Tschudin1 This review focuses on drug use during pregnancy and the perinatal period, a constellation that is seen more often. Drug use in pregnant women poses an increased risk for adverse health outcomes both for the mother and child. Care is often complicated by social and environmental factors, as well as psychiatric comorbidities. It is, therefore, very important to provide drug-using pregnant women with optimal ante-, peri- and post-natal care. Health professionals should approach them in a nonjudgmental and supportive way, and provide them with the same care and attention as nondrug-using women. Adequate care requires interdisciplinary teams. Ideally, healthcare providers should be specialized in the care of drug-using pregnant women.
Since the 1980s, an increase of drug use in women of childbearing age has been observed [1–7]. The exact number of drug-dependent women is unknown because epidemiological data rely almost exclusively on voluntary patient reports [1,8]. The causes of drug use are likely to be multifactorial including biological, psycho logical, as well as social factors. The care of drugusing women during pregnancy is challenging, as the mother’s and infant’s health might be compromised, and this has to be considered. Furthermore, it is not only the drug itself that harms the pregnant woman and the fetus, but these women may live in difficult social circum stances, and psychiatric comorbidity is frequent. Evidence-based standards of care would thus be beneficial. This review aims to provide an overview of the current literature findings con sidering PubMed listed papers primarily within the time period of 1983–2013. In addition, an established interdisciplinary model of care implemented at a university women’s hospital in Switzerland will be presented and discussed. Vrious effects of drugs in the context of reproduction Drug use & fertility
Impaired fertility associated with heroin use has been previously demonstrated [9], both in men and women [10,11]. Even low doses of narcotics can impair normal ovarian function and ovu lation and therefore reduces the probability of conception. Interestingly, in a longitudinal study on 191 heroin- and cocaine-addicted women, among whom less than a third had a regular cycle, Schmittner et al. demonstrated that the 10.2217/WHE.14.7 © 2014 Future Medicine Ltd
menstrual bleeding pattern began to normalize during methadone maintenance [12]. Even if this was just one of few studies, it leads to the hypo thesis that the stability of methadone mainte nance might interfere less with menstrual func tion than illicit heroin use. Improved fertility, in addition to better medical care as a result of substitution programs, might be possible expla nations for the increase in drug-using pregnant women around the turn of the millennium [12]. Drug effects on mother & child
Substance abuse not only harms the patient her self but also the unborn child [13]. Table 1 shows a summary of the effects of different substances on mother and child. Problems include preterm labor and low birth weight in general [1,27], and special complica tions, such as myocardial infarction, cerebro vascular accidents and placental abruption, in cocaine-using women owing to the vasocon strictive effects of the drug [28]. However, the effects of in utero cocaine exposure are also correlated with other factors, such as prenatal exposure to tobacco use, other drugs and the environment [29]. Examining direct effects of specific drugs is, therefore, challenging since most of the women are poly-drug users [30,31]. The fact that the effects on mother and child are likely to be multifactorial complicates care even more [32–34]. Factors, such as smoking, poor diet, stress and chaotic lifestyle, appear to be the most important etiological factors. Outcomes associated with drug use are, therefore, results of either the effect of the drug itself or of problems related to growth restriction and/or premature Women's Health (2014) 10(2), 167–177
Department of Obstetrics & Gynecology, University Hospital Basel, Basel, Switzerland *Author for correspondence: Tel.: +41 612 659 043 [email protected] 1
Keywords • drug use • interdisciplinary care • pregnancy • psychiatric comorbidity
part of
ISSN 1745-5057
167
perspective – Goettler & Tschudin Table 1. Drug effects on the mother and child. Drug/substance
Effects on mother
Effects on fetus
Ref.
Opiates (heroine, methadone and morphine)
Constipation Vasodilation Drug interactions (pulmonary edema and β2 sympatho-mimetics) Premature contractions Protracted delivery
SGA Prematurity IUGR Intrauterine demise Withdrawal symptoms SIDS Impaired intellectual development
Cocaine
Loss of hunger and sleep Anxiety reduction Increased sympathetic activity Reduced placental perfusion Premature placental abruption Premature contractions Abortion Hypertension Cerebrovascular events Myocardial infarction
SGA IUGR Prematurity Intrauterine demise Malformations (heart, musculoskeletal and urogenital tract) Microcephalus Perinatal cerebral infarction
Cannabis/THC
Increased sympathetic activity (general vasoconstriction) Premature placental abruption Formation of ketone bodies (cave gestational diabetes) Convulsions (cave preeclampsia and premature contractions)
SGA IUGR Prematurity Impaired postnatal intellectual development
[81]
Amphetamines/ ecstasy
Increased sympathetic activity Mental hyperactivity Compulsive chewing Dysfunctional thermoregulation Constriction of placental vessels
Similar to cocaine (placental abruption and fetal distress) IUGR Malformations (heart and skeleton) More male births
[30]
LSD
Increased sympathetic activity Visual hallucination Panic attacks
Chromosomal aberrations Skeletaldysplasias (hands and feet) Ocular dysplasia (suspected)
[16–18]
Alcohol
Gastric hyperacidity Sedation Tocolytic effect
FASD (FAS): facial dysmorphogenesis, cardiac septal effects and joint abnormalities Growth restriction
[19–21]
Tobacco
Vasoconstriction Restriction of placental blood flow and placenta insufficiency Premature contractions Abortion Infertility Ectopic pregnancy
SGA IUGR Prematurity Impaired postnatal development Increased addictive potential, orofacial clefts, SIDS, craniosynostosis, clubfoot, childhood respiratory disease and attention-deficit disorder
[22,81]
Caffeine
More than 200 mg/day may increase risk of miscarriage
No known teratogenic effects
[23,24]
Theobromine (primary Higher maternal serum concentrations of theobromine are not Fetal movements per hour increased methylxanthine associated with reduced occurrence of preeclampsia and sex difference likely alkaloid in chocolate)
[14]
[15,28]
[25,26]
FAS: Fetal alcohol syndrome; FASD: Fetal alcohol spectrum disorders; IUGR: Intrauterine growth retardation; SGA: Small-for-gestational age; SIDS: Sudden infant death syndrome; THC: Tetrahydrocannabinol. Data taken from [27].
delivery. Furthermore, there is a paucity of research regarding newer drugs such as ecstasy, bath salts or synthetic cannabinoids [1,30,35]. In a study on 247 drug-using women and 741 controls conducted over a 4-year period, drug-using women were still at significant risk 168
www.futuremedicine.com
of adverse obstetric and perinatal outcomes, with significantly more preterm births, a higher incidence of low birth weight and intrauterine growth restriction despite coordinated prenatal care. The risk of placental abruption was also higher [36]. future science group
Care of drug-addicted pregnant women: current concepts & future strategies –
The proportion of pregnant women who continue to drink alcohol in pregnancy is noteworthy [37,38]. A large, recent prospective, multicenter cohort study on healthy nulli parous females with singleton pregnancies, with the main aim of developing screening tests to predict adverse outcomes, such as pre eclampsia, small gestational age neonates and spontaneous preterm birth, did not demon strate a strong association between (occasional to heavy amounts of) alcohol consumption in early pregnancy and these outcomes. However, these effects are likely not only dependent on quantity consumed, but also on the timing of exposure. It is also noteworthy, that this study did not investigate the association between alco hol consumption in pregnancy and long-term neurocognitive outcomes of children with fetal exposure to alcohol [39]. Therefore, the authors of this review believe that there is not enough evidence to suggest that any amount of alcohol is safe during pregnancy. Complex psychosocial situation & lack of prenatal care
Drug and alcohol use, and the resulting prob lems mostly precede pregnancy. Likewise, comorbidity can either be a cause or con sequence of drug use. Drug-using women’s reproductive health is affected by many fac tors, such as poor social environment, mal nutrition, inadequate hygiene, sexually trans mitted infections, physical abuse or a history of prostitution [40–43]. It is known that the lack of antenatal care is associated with worse outcomes for mother and child [36]. In a retrospective study on 211 women who came to delivery without any antenatal care, drug abuse was the most preva lent reason for this behavior [44]. Furthermore, in a postpartum cohort of 812 low-income women who delivered at a tertiary care center, cocaine or opiate abuse was predictive of little or no antenatal care [45]. Drug-using pregnant women may not use (and may not have access to) the traditional maternity services the same way nondrug-using women do. They tend to present late, have dif ficulties in attending appointments, and when they present, they might not admit their drug use [46]. Possibly owing to fear of stigmatization or legal consequences, drug-using or alcoholic pregnant, or postpartum women often deny their drug habit, the possible harmful effects and the need to seek appropriate care and, therefore, often receive no care at all [32,47]. future science group
perspective
Psychiatric comorbidity
Clinicians should be aware of psychiatric comor bidities in the population of drug-using women [13,31,48], and both psychiatric comorbidities and the patient’s habit of consuming drugs have to be approached [49]. According to an Australian population-based, retrospective study, depres sion is the most common psychiatric disorder followed by anxiety disorders. Almost half of all drug-using mothers were affected by depression [50]. These mothers had more previ ous pregnancies and suffered more often from domestic violence. Since prenatal care and social outcome may be worse for these mothers and their children, the authors recommend that all pregnant drug-using women should be assessed for psychosocial disorders in order to facilitate timely interventions [50]. Pregnancy care for drug-using women Pregnancy
Even if the risk of each pregnancy of a drugusing woman has to be assessed on an individual basis, some of these pregnancies need to be con sidered as potential high-risk pregnancies, and thus, specialized (obstetrical) interdisciplinary teams should engage in their care [31,48]. An aspect that might be neglected when assessing drug-using women are concomitant factors, such as cigarette smoking, alcohol use and poor social circumstances, which are all common in women using illicit drugs [32]. In a case–control study on 370 full-term gesta tions, the three main risk factors for fetal growth retardation were tobacco, low prepreg nancy weight and low socioeconomic status [51]. Most pregnant women using cocaine and/or heroin appear to be cigarette smokers. In gen eral, babies whose mothers smoked during pregnancy tend to have lower birth weights; an effect that appears to be dose-dependent with a higher number of cigarettes per day related to lower birth weight [52]. It is important to use a consistent, easy-to-use screening tool and a nonjudgmental approach to evaluate patients for possible drug use. There is controversy regarding whether screening should be undertaken systematically in all pregnant women or just in selected patients suspected of drug abuse [53]. The American Congress of Obstetricians and Gynecologists suggest easily applicable screening tests in the form of ques tionnaires [34,54]. In our institution (Univer sity Hospital Basel, Switzerland), screening by means of urine drug tests is performed repeat edly – provided the patient consents – when
Women's Health (2014) 10(2)
169
perspective – Goettler & Tschudin clinically indicated. Furthermore, fetal expo sure to illicit drugs or alcohol in utero can be detected by meconium analysis, reflecting expo sure during the second and third trimester, by means of chromatographic techniques [55–57]. Interdisciplinary approach to care
Neonatal outcomes may be positively influ enced as shown in an interventional study on a large sample of 6774 pregnant women. Rates of assisted ventilation, low birth weight and pre term delivery improved when mothers received substance abuse treatment integrated with pre natal care [58]. Nowadays, most studies suggest that drug-using pregnant women are in need of multidisciplinary antenatal care with medical, social and psychological support [59–61]. Com prehensive, interdisciplinary treatment pro grams are likely to have a positive impact on outcomes [62–67]. The one retrospective study that failed to demonstrate a positive effect was not designed to show an effect of an interdis ciplinary approach. Furthermore, no detailed information on the type of interdisciplinary teamwork is provided [36]. To optimize the ante- and post-natal care for mother and child, an interdisciplinary team, including an obstetrician–gynecologist coor dinating the involved special services, should be developed. As shown in Figure 1, one health professional should be designated as the case manager. In our institution, this is a gynecolo gist and member of our division of social and psychosomatic gynecology. This specialized service is possible, as we are a tertiary care university hospital serving a population of approximately 300,000 people. This service is well accepted and used. Most of the patients are referred by their primary-care providers, in addition to drop-ins at the moment of deliv ery. Divergent from the regular antenatal-care patients, they are seen more frequently – at most every 2–4 weeks. Depending on the individual situation and needs for care, disciplines, such as drug-substi tution centers, social workers, neonatologists, psychiatrists, pediatric psychiatrists, family physicians and child welfare authorities, should be involved. In our setting, it is the obstetri cian–gynecologist who serves as the primary reference point for the patient and takes the lead in the interdisciplinary team, by coordinating and integrating the disciplines that are needed. This process needs to be as easy and comfort able for the patient as possible since compliance is an issue. 170
www.futuremedicine.com
Women who present with a history sugges tive of drug use, should receive the same care as women who do not use drugs, including deter mination of gestational age by ultrasound; keep ing in mind that the population of drug-using women is often underserved. It is advantageous to diagnose pregnancy as timely as possible. To identify women at risk who present in the ante natal phase, the gynecologist has to take the history of past and present drug use, including necessary details, such as participation in sub stitution programs or intravenous application of drugs. Co-ordination and management of the substitution should be performed by the substi tution center. In addition, testing for sexually transmitted diseases and hepatitis C should be undertaken, when considering that, according to a recent study, 41% of drug-using women had evidence of previous exposure to the hepatitis C virus [68]. In our institution, a round table is estab lished during the third trimester, at which the involved disciplines plan postnatal care. This serves as an information platform for the teams, and also establishes contact between the anteand post-natal caretakers and the patient, in order to address their issues and concerns. In this context, the neonatologists have the oppor tunity to inform the patient about postnatal substitution. Admission & delivery
At presentation, for example, admission for delivery, midwives and obstetricians need to be aware of unusual behavior or agitation. Further more, physiological signs of drug abuse, such as dilated or constricted pupils, increased or decreased respirations, bradycardia or tachy cardia, hypotension or hypertension, all depend ing on the substance used, should be registered [8]. These can be both signs of intoxication and withdrawal, and should prompt further testing to confirm drug use and rule out preeclampsia. These symptoms might be harmful for both the mother and child [69]. As substance use and smoking are associated with an increased risk of placental insufficiency, growth restriction and possible fetal distress, monitoring has to be especially thorough; during pregnancy with regular ultrasounds and during labor by con tinuous heart beat monitoring [32]. Neonatal care should be readily available in the mater nity ward. Postnatal care needs to be adjusted to the needs of the patient, for example, with drawal signs or other necessary treatments for the newborn [46,70]. future science group
Care of drug-addicted pregnant women: current concepts & future strategies –
perspective
Division of Gynecological Social Medicine and Psychosomatics Reference person, medical antenatal care, coordination of involved special services
Social services Advice in psychosocial, legal and financial issues. Coordination between mother and child and neonatal care units, organization of the support after hospital dismissal
Drug substitution center Care within the substitution program
Maternity ward/mother–child unit Care during delivery and postpartum
Neonatal care unit During third trimester, information and arrangement of the postnatal proceedings Nurses Instruction and supervision of the mothers in the care of their newborn babies
Pediatric psychiatry Support in establishing the parent–child relationship, mediation between parents and neonatal care unit staff
Child welfare authority Information about assistance in crisis situations. Provision of additional childcare if needed
Psychiatrist Ongoing psychotherapy in case of psychiatric comorbidity
Figure 1. The Basel model of interdisciplinary care of drug-using women.
Breastfeeding
Breastfeeding is beneficial in a number of ways. Apart from its short- and long-term medical and neurodevelopmental benefits [71], it helps bonding between mother and child, which is particularly important when the mother is using drugs. Nevertheless, only approximately 15% of patients were still breastfeeding at discharge in a study from the UK [72]. In methadone-substituted women with no parallel consumption of other drugs, breast feeding is not contraindicated. However, in future science group
a study with small group sizes, fewer infants in the breast-fed group required pharmaco therapy for neonatal abstinence syndrome, an effect that was not statistically significant. Interestingly, this study showed low concen trations of methadone in breast milk, which were not related to maternal intake, supporting the recommendation for breastfeeding among methadone-maintained women [73]. The effect of breastfeeding on severity of neonatal with drawal symptoms has also been reported else where [46,74]. As children of drug-using women
Women's Health (2014) 10(2)
171
perspective – Goettler & Tschudin are often delivered preterm or are small-forgestational age, breastfeeding is particularly useful [75]. Breastfeeding should, therefore, be encouraged in methadone-substituted women [76,77]. Data on breastfeeding are less clear with regard to other drugs, such as cocaine and heroin [78,79], and are often based on case reports or – series [76]. With regard to cocaine, it is crucial for the healthcare provider to counsel patients both on the serious potential risks of cocaine exposure (e.g., potential agi tation, irritability, seizures, hypertension and tachycardia), and on the advantages of breast feeding, to allow for an informed choice [80]. Both cocaine and marijuana are soluble and can potentially become trapped in the breast milk [76]. For cannabis exposure through milk, no increase in neonatal risk has been shown; however, there are no appropriate studies on this, to date [81–83]. Some authors discourage breastfeeding in mothers who regularly use marijuana [76]. Occasional users who are not able to stop, should be evaluated on a case-bycase basis [83]. Cannabis smoke exposure to the child, and breastfeeding during the hours after cannabis use, should be avoided [84]. Buprenorphine might also be safe during breastfeeding and opioid-dependent women can be counseled accordingly [76,77,85,86]. There appears to be no relationship between maternal buprenorphine dose at delivery and the severity of neonatal abstinence syndrome, the amount of morphine needed for treatment and the duration of treatment [87]. The out comes of newborns of pregnant women using methadone and buprenorphine appeared to be similar, with the exception that buprenor phine-exposed infants presented with signifi cantly larger head circumference and tended to have higher weight and length [88]. Accord ing to a recent Cochrane review, the differ ences between methadone and buprenorphine (or slow-release morphine) do not allow for a conclusion that one treatment is superior to another [89]. A very recent retrospective, observational assessment of meconium toxicology performed on samples of a high-risk patient cohort, how ever, demonstrated that, at least a third of pregnant women on methadone-maintenance therapy continue to use at least one additional opioid narcotic [90]. No significant difference was found for opioid or other illicit drug use between the methadone-positive and -negative meconium samples, indicating similar patterns of substance use during late pregnancy. The 172
www.futuremedicine.com
authors of the study speculated that, subthera peutic dosing might have created withdrawal symptoms leading to additional substance use. In addition, these results may be an indica tion of partly inadequate delivery of addiction support services [90]. In our institution, breastfeeding is possible in methadone-substituted women, provided that weekly (but unheralded) urinary toxicology screens are negative for other drugs. Postpartum period
Special attention has to be given to the post partum period [91]. Alcohol withdrawal, for example, generally occurs after 48 h, thus, in the postnatal ward, the woman might appear to be agitated and have problems caring for her baby during this time. Users of cocaine and amphetamines might even be abusive and exhibit strange or inappropriate behavior. Neonatal abstinence syndrome
Opiate-dependent women should be informed that neonates exposed during pregnancy need to be monitored closely for symptoms and signs of neonatal withdrawal [92], as 60–90% of neonates with in utero exposure to opiates suffer from drug withdrawal [86,93]. Withdrawal symptoms typically depend on the substance, and are predominantly autonomic, neurologic or gastrointestinal. They generally occur within 24 h after delivery for heroin and 2–6 days for methadone. This is in contrast to symptoms of benzodiazepine withdrawal, which can be delayed [94,95]. A British study on neonatal abstinence syndrome found great variability in policies for its detection and treatment [96]. Neonatal abstinence syndrome has not been conclusively demonstrated in marijuana- or cocaine-exposed neonates [97,98]. An often unrecognized entity is the neo natal nicotine withdrawal syndrome, albeit its existence is questioned by some authors [99]. Its onset is typically within 12–24 h of life and resolves usually within 36 h, rarely requiring treatment [100,101]. Neonatal nicotine withdrawal syndrome may be misdiagnosed as infant colic when a smoking, breastfeeding mother discontinues breastfeeding [102]. Bonding
Breastfeeding has a positive impact on bond ing; however, as drug-using women often have difficulties in building a relationship with their newborn, additional support by a pediatric psy chiatrist might be helpful [40]. Furthermore, a future science group
Care of drug-addicted pregnant women: current concepts & future strategies –
psychiatrist or psychologist has the skills to provide mediation when conflicts between the patient and staff occurs, and is thus ideally part of the interdisciplinary team. In other settings and depending on local resources, the general practitioner, social worker or addiction coun selor may have a similar role, with the advantage that they continue to follow the woman and her child in the postpartum period. As associated legal and social problems can impede appropriate care, and can impair the ability of the mother to care for her child after birth, well-functioning social services should be involved [32]. Systematic information of the child welfare authority about drug-using mothers allows assistance in crisis situations and provision of help if additional childcare is needed.
use, which had often begun during adolescence. They often had family members with a history of alcohol and drug use. People in their social environment frequently animated their drug use [41].
Attitude towards drug-using pregnant women
Conclusion
Despite the obvious challenges for all disciplines in the care of drug-using women, the impor tance of being supportive and nonjudgmental is underlined in the literature reviewed for this article [103–105]. Care of drug-using women can be a tightrope walk between considerate care and paternalism, as both support and assistance are necessary. The patient–doctor relationship may be difficult, particularly in case of psychiat ric comorbidity (e.g., borderline disorder), and requires patience. It is of utmost importance to work in a constant, transparent fashion in order to gain commitment from the mother’s side by integrating her in the decision-making process. Institutionalized controls of toxicology screen ings are recommended since they are more easily accepted. Long-term outcome & preventive strategies
Although pregnancy might be a ‘window of opportunity’ for drug-using women, many patients do not succeed in maintaining the necessary stability over time [7]. According to several studies, this is only the case in less than half of the families concerned (risk factors: psy chiatric comorbidity, history of prostitution, homelessness, delinquency and a drug-addicted partner) [40,41]. The partner, or the father of the current pregnancy, may also be a drug user. In a sample of 240 pregnant women who voluntarily entered a substance abuse treatment program, most fathers were supportive of seeking treat ment. The majority of these urban, predomi nately African–American, opiate- or cocainedependent women, had long histories of drug future science group
perspective
Birth control
Another important issue is birth control, which may even be discussed during pregnancy so that the patients can choose a method by the time they deliver. Long-acting progestogen devices can be applied early in the postpartum period. In general, a pregnancy should be well planned in these patients and family-planning advice should be given. This allows discussing possible difficulties and preventive strategies in advance. As caring for drug-using pregnant women is challenging, standards of care and an interdisci plinary approach is required. The ultimate aim of these interdisciplinary efforts is to reduce the risk for adverse outcomes for the mother and her baby, both during pregnancy, the neo natal period and in the long term. A well-imple mented standardized approach may also allevi ate the demanding task of health profession als who are engaged in caring for drug-using pregnant women, and could possibly reduce concomitant distress when the patient–doctor relationship is particularly difficult. Future perspective
Early identification of drug-using habits and of the patterns of use by family practitioners, for example, in the preconception period, may provide the opportunity to assist affected women in reducing major health risks [106]. The surrounding social context in which drug use commonly occurs should certainly be taken into account. In order to comprehensively fol low drug-addicted women during pregnancy, thorough knowledge of certain aspects, such as effects of the drugs on the fetus and of breastfeeding on the newborn, are crucial on one hand, but on the other hand, continuous, concise and interdisciplinary care may even be more important. A pregnancy might act as a sentinel event that can help drug-using mothers to start modifying their behavior [107]. This may also have an impact on their children. Further research should focus on assessing and evaluating interdisciplinary strategies to prove their effects and efficacy in the respective settings.
Women's Health (2014) 10(2)
173
perspective – Goettler & Tschudin Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
Executive summary Effects of drugs in the context of reproduction • Impaired fertility was common in heroin-using women in the past, but, nowadays, generally improves in the context of substitution programs. • Drug use in pregnant women poses an increased risk for adverse health outcomes both for the mother and child. • It is difficult to discern direct drug effects from other factors, such as smoking, poor diet, stress and poor social circumstances. • Besides the specific effects of the various substances on the fetus, drugs generally cause preterm labor and low birth weight. Psychosocial situation • Cigarette smoking, alcohol use and poor social circumstances are all common in women using illicit drugs, and are concomitant factors that might be neglected when assessing drug-using women. • Psychiatric comorbidity is frequent in drug-using women (e.g., depression and anxiety disorders). • Psychiatric comorbidity can either be a cause or consequence of drug use. Pregnancy care for drug-using women • It is known that the lack of antenatal care is associated with worse outcomes for mother and child. • Comprehensive, interdisciplinary treatment programs are likely to have a positive impact on outcomes. • Care needs to be as easy and comfortable for the patient as possible since compliance is an issue. • Care of drug-using women can be a tightrope walk between considerate care and paternalism, as both support and assistance are necessary. • During delivery, special attention has to be paid to unusual behavior or physiological signs of drug abuse. • Breastfeeding is possible both in methadone- and buprenorphine-substituted women. • In the postpartum period, withdrawal generally occurs after 48 h for alcohol, after 24 h for heroin and after 2–6 days for methadone, meanwhile benzodiazepine withdrawal can be delayed. • Although pregnancy and consequent motherhood may be a ‘window of opportunity’ for drug-using women, many patients do not succeed in maintaining the necessary stability over time.
References Papers of special note have been highlighted as: • of interest •• of considerable interest 1.
French E. Substance abuse in pregnancy: compassionate and competent care for the patient in labor. Clin. Obstet. Gynecol. 56(1), 173–177 (2013).
2.
Hepburn M. Substance abuse in pregnancy. Curr. Obstet. Gynecol. 14(6), 419–425 (2004).
3.
4.
5.
6.
174
Kuczkowski KM. The effects of drug abuse on pregnancy. Curr. Opin. Obstet. Gynecol. 19(6), 578–585 (2007). Kelly L, Dooley J, Cromarty H et al. Narcotic-exposed neonates in a First Nations population in northwestern Ontario: incidence and implications. Can. Fam. Physician 57(11), e441–e447 (2011). National Survey on Drug Use and Health (NSDUH) (2012). www.samhsa.gov/data/NSDUH.aspx Patrick SW, Schumacher RE, Benneyworth BD, Krans EE, Mcallister JM, Davis MM. Neonatal abstinence syndrome and associated health care expenditures: United States,
2000–2009. JAMA 307(18), 1934–1940 (2012). 7.
8.
9.
Hayatbakhsh MR, Kingsbury AM, Flenady V, Gilshenan KS, Hutchinson DM, Najman JM. Illicit drug use before and during pregnancy at a tertiary maternity hospital 2000–2006. Drug Alcohol. Rev. 30(2), 181–187 (2011). Geary FH Jr, Turnquest Wells MA. Management of the patient in labor who has abused substances. Clin. Obstet. Gynecol. 56(1), 166–172 (2013). Bellati U, Noia G, Conte M, Mazzei R, Tempesta E. Amenorrhea in drug dependence. Minerva Medica 74(16), 865–868 (1983).
10. Singer R, Ben-Bassat M, Malik Z et al.
Oligozoospermia, asthenozoospermia, and sperm abnormalities in ex-addict to heroin, morphine, and hashish. Arch. Androl. 16(2), 167–174 (1986). 11. Ragni G, De Lauretis L, Gambaro V et al.
Semen evaluation in heroin and methadone addicts. Acta Eur. Fertil. 16(4), 245–249 (1985). 12. Schmittner J, Schroeder JR, Epstein DH,
Preston KL. Menstrual cycle length during
www.futuremedicine.com
methadone maintenance. Addiction 100(6), 829–836 (2005). 13. Kashiwagi M, Sieber S, Rechsteiner C,
Lauper U, Zimmermann R, Ehlert U. Psychological mood state of opiate addicted women during pregnancy and postpartum in comparison to non-addicted healthy women. J. Psychosom. Obstet. Gynecol. 28(1), 3–6 (2007). 14. Hulse GK, Milne E, English DR,
Holman CD. The relationship between maternal use of heroin and methadone and infant birth weight. Addiction 92(11), 1571–1579 (1997). 15. Fajemirokun-Odudeyi O, Lindow SW.
Obstetric implications of cocaine use in pregnancy: a literature review. Eur. J. Obstet. Gynecol. Reprod. Biol. 112(1), 2–8 (2004). 16. Cohen MM, Hirschhorn K, Frosch WA.
In vivo and in vitro chromosomal damage induced by LSD-25. N. Engl. J. Med. 277(20), 1043–1049 (1967). 17. Aase JM, Laestadius N, Smith DW. Children
of mothers who took LSD in pregnancy. Lancet 1(7663), 100–101 (1970).
future science group
Care of drug-addicted pregnant women: current concepts & future strategies –
18. Jacobson CB, Berlin CM. Possible
31. Kashiwagi M, Arlettaz R, Lauper U,
reproductive detriment in LSD users. JAMA 222(11), 1367–1373 (1972).
Zimmermann R, Hebisch G. Methadone maintenance program in a Swiss perinatal center: (I): management and outcome of 89 pregnancies. Acta Obstet. Gynecol. Scand. 84(2), 140–144 (2005).
19. Bertrand J, Floyd LL, Weber MK; Fetal
Alcohol Syndrome Prevention Team, Division of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention (CDC). Guidelines for identifying and referring persons with fetal alcohol syndrome. MMWR Recomm. Rep. 54(RR–11), 1–14 (2005).
32. Wright A, Walker J. Management of women
who use drugs during pregnancy. Semin. Fetal Neonatal Med. 12(2), 114–118 (2007). 33. Ludlow J, Christmas T, Paech MJ, Orr B.
Drug abuse and dependency during pregnancy: anaesthetic issues. Anaesth. Intensive Care 35(6), 881–893 (2007).
20. Jones KL, Smith DW, Ulleland CN,
Streissguth P. Pattern of malformation in offspring of chronic alcoholic mothers. Lancet 1(7815), 1267–1271 (1973).
34. Women ACOHCFU, American Society of
Addiction M. ACOG Committee Opinion No. 524: opioid abuse, dependence, and addiction in pregnancy. Obstet. Gynecol. 119(5), 1070–1076 (2012).
21. Mills JL, Graubard BI, Harley EE,
Rhoads GG, Berendes HW. Maternal alcohol consumption and birth weight. How much drinking during pregnancy is safe? JAMA 252(14), 1875–1879 (1984).
35. Oei JL, Kingsbury A, Dhawan A et al.
Amphetamines, the pregnant woman and her children: a review. J. Perinatol. 32(10), 737–747 (2012).
22. Einarson A, Riordan S. Smoking in
pregnancy and lactation: a review of risks and cessation strategies. Eur. J. Clin. Pharmacol. 65(4), 325–330 (2009).
36. Pinto SM, Dodd S, Walkinshaw SA, Siney C,
Kakkar P, Mousa HA. Substance abuse during pregnancy: effect on pregnancy outcomes. Eur. J. Obstet. Gynecol. Reprod. Biol. 150(2), 137–141 (2010).
23. Rosenberg L, Mitchell AA, Shapiro S,
Slone D. Selected birth defects in relation to caffeine-containing beverages. JAMA 247(10), 1429–1432 (1982).
•
24. Weng X, Odouli R, Li DK. Maternal caffeine
consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am. J. Obstet. Gynecol. 198(3), 279.e1–e279.8 (2008). 25. Klebanoff MA, Zhang J, Zhang C,
Levine RJ. Maternal serum theobromine and the development of preeclampsia. Epidemiology 20(5), 727–732 (2009).
37. CDC. Alcohol use and binge drinking among
women of childbearing age – United States, 2006–2010. MMWR. Morbid. Mortal. Wkly Rep. 61(28), 534–538 (2012). 38. CDC. Alcohol use among pregnant and
nonpregnant women of childbearing age – United States, 1991–2005. MMWR. Morbid. Mortal. Wkly Rep. 58(19), 529–532 (2009).
26. Tranquilli AL, Lorenzi S, Buscicchio G,
Di Tommaso M, Mazzanti L, Emanuelli M. Female fetuses are more reactive when mother eats chocolate. J. Matern. Fetal Neona. 27(1), 72–74 (2014).
39. McCarthy FP, O’Keeffe LM, Khashan AS
et al. Association between maternal alcohol consumption in early pregnancy and pregnancy outcomes. Obstet. Gynecol. 122(4), 830–837 (2013).
27. Von Mandach U. Drug use in pregnancy.
Therapeutische Umschau. Revue Therapeutique 62(1), 29–35 (2005). 28. Cain MA, Bornick P, Whiteman V.
The maternal, fetal, and neonatal effects of cocaine exposure in pregnancy. Clin. Obstet. Gynecol. 56(1), 124–132 (2013). 29. Frank DA, Augustyn M, Knight WG, Pell T,
Zuckerman B. Growth, development, and behavior in early childhood following prenatal cocaine exposure: a systematic review. JAMA 285(12), 1613–1625 (2001). 30. Singer LT, Moore DG, Fulton S et al.
Neurobehavioral outcomes of infants exposed to MDMA (ecstasy) and other recreational drugs during pregnancy. Neurotoxicol. Teratol. 34(3), 303–310 (2012).
future science group
Retrospective study on the contribution of drug use to maternal and perinatal complications.
••
Large study investigating the association between alcohol consumption before and during early pregnancy and adverse pregnancy outcomes, which found no association between alcohol consumption before 15 weeks of gestation and small-for-gestational age, reduced birth weight, preeclampsia or spontaneous preterm birth.
40. Gilchrist G, Taylor A. Drug-using mothers:
factors associated with retaining care of their children. Drug Alcohol Rev. 28(2), 175–185 (2009). 41. Kissin WB, Svikis DS, Morgan GD,
Haug NA. Characterizing pregnant
Women's Health (2014) 10(2)
perspective
drug-dependent women in treatment and their children. J. Subst. Abuse Treat. 21(1), 27–34 (2001). 42. Bauer CR, Shankaran S, Bada HS et al.
The Maternal Lifestyle study: drug exposure during pregnancy and short-term maternal outcomes. Am. J. Obstet. Gynecol. 186(3), 487–495 (2002). 43. Schempf AH, Strobino DM. Illicit drug use
and adverse birth outcomes: is it drugs or context? J. Urban Health 85(6), 858–873 (2008). 44. Friedman SH, Heneghan A, Rosenthal M.
Characteristics of women who do not seek prenatal care and implications for prevention. J. Obstet. Gynecol. Neonatal Nurs. 38(2), 174–181 (2009). 45. Schempf AH, Strobino DM. Drug use and
limited prenatal care: an examination of responsible barriers. Am. J. Obstet. Gynecol. 200(4), 412.e1–412.e10 (2009). 46. Berghella V, Lim PJ, Hill MK, Cherpes J,
Chennat J, Kaltenbach K. Maternal methadone dose and neonatal withdrawal. Am. J. Obstet. Gynecol. 189(2), 312–317 (2003). 47. Bolnick JM, Rayburn WF. Substance use
disorders in women: special considerations during pregnancy. Obstet. Gynecol. Clin. North Am. 30(3), 545–558, vii (2003). 48. Gyarmathy VA, Giraudon I, Hedrich D,
Montanari L, Guarita B, Wiessing L. Drug use and pregnancy – challenges for public health. Euro. Surveill. 14(9), 33–36 (2009). 49. Di Forti M, Morrison PD, Butt A,
Murray RM. Cannabis use and psychiatric and cogitive disorders: the chicken or the egg? Curr. Opin. Psych. 20(3), 228–234 (2007). 50. Oei JL, Abdel-Latif ME, Craig F et al.
Short-term outcomes of mothers and newborn infants with comorbid psychiatric disorders and drug dependency. Aust. NZ J. Psychiatry 43(4), 323–331 (2009). 51. Nieto A, Matorras R, Serra M, Valenzuela P,
Molero J. Multivariate analysis of determinants of fetal growth retardation. Eur. J. Obstet. Gynecol. Reprod. Biol. 53(2), 107–113 (1994). 52. Adriaanse HP, Knottnerus JA, Delgado LR,
Cox HH, Essed GG. Smoking in Dutch pregnant women and birth weight. Patient Educ. Couns. 28(1), 25–30 (1996). 53. Roberts SC, Nuru-Jeter A. Women’s
perspectives on screening for alcohol and drug use in prenatal care. Womens Health Issues 20(3), 193–200 (2010). 54. Wong S, Ordean A, Kahan M et al. Substance
use in pregnancy. J. Obstet. Gynecol. Can. 33(4), 367–384 (2011).
175
perspective – Goettler & Tschudin 55. Lozano J, Garcia-Algar O, Vall O, De La
Torre R, Scaravelli G, Pichini S. Biological matrices for the evaluation of in utero exposure to drugs of abuse. Ther. Drug Monit. 29(6), 711–734 (2007). 56. Garcia-Algar O, Vall Combelles O, Puig Sola
C et al. Prenatal exposure to drugs of abuse using meconium analysis in a low socioeconomic population in Barcelona. An. Pediatr. (Barc). 70(2), 151–158 (2009). 57. Garcia-Algar O, Kulaga V, Gareri J et al.
Alarming prevalence of fetal alcohol exposure in a Mediterranean city. Ther. Drug Monit. 30(2), 249–254 (2008). 58. Armstrong MA, Gonzales Osejo V,
Lieberman L, Carpenter DM, Pantoja PM, Escobar GJ. Perinatal substance abuse intervention in obstetric clinics decreases adverse neonatal outcomes. J. Perinatol. 23(1), 3–9 (2003). ••
Evaluation of a managed care organization’s obstetric clinic-based perinatal substance abuse treatment program, demonstrating improved neonatal outcomes.
59. Brulet C, Chanal C, Ravel P, Mazurier E,
Boulot P, Faucherre V. Multidisciplinary monitoring and psychosocial support reduce complications of opiate dependence in pregnant women: 114 pregnancies. Presse Medicale (Paris) 36(11 Pt 1), 1571–1580 (2007). 60. Mayet S, Groshkova T, Morgan L,
MacCormack T, Strang J. Drugs and pregnancy – outcomes of women engaged with a specialist perinatal outreach addictions service. Drug Alcohol Rev. 27(5), 497–503 (2008). •
Study on outcomes of women seen by a specialist perinatal addictions outreach service.
61. Morton J, Konrad SC. Introducing a
caring/relational framework for building relationships with addicted mothers. J. Obstet. Gynecol. Neonatal Nurs. 38(2), 206–213 (2009). •
Integrative, interdisciplinary framework offering guidance in developing relationships that can endure the challenges of substance abuse.
62. Ordean A, Kahan M. Comprehensive
treatment program for pregnant substance users in a family medicine clinic. Can. Fam. Physician 57(11), e430–e435 (2011). •
Comprehensive care in a family medicine setting also leads to positive maternal and infant health outcomes.
63. Corse SJ, Smith M. Reducing substance abuse
during pregnancy. Discriminating among
176
levels of response in a prenatal setting. J. Subst. Abuse Treat. 15(5), 457–467 (1998). 64. Ellwood DA, Sutherland P, Kent C,
O’Connor M. Maternal narcotic addiction: pregnancy outcome in patients managed by a specialized drug-dependency antenatal clinic. Aust. N. Z. J. Obstet. Gynecol. 27(2), 92–98 (1987). 65. Fiocchi FF, Kingree JB. Treatment retention
and birth outcomes of crack users enrolled in a substance abuse treatment program for pregnant women. J. Subst. Abuse Treat. 20(2), 137–142 (2001).
•
77. Shainker SA, Saia K, Lee-Parritz A. Opioid
addiction in pregnancy. Obstet. Gynecol. Survey 67(12), 817–825 (2012). 78. Chasnoff IJ, Lewis DE, Squires L. Cocaine
intoxication in a breast-fed infant. Pediatrics 80(6), 836–838 (1987). 79. Chaney NE, Franke J, Wadlington WB.
Cocaine convulsions in a breast-feeding baby. J. Pediatrics 112(1), 134–135 (1988). 80. Cressman AM, Koren G, Pupco A, Kim E,
Ito S, Bozzo P. Maternal cocaine use during breastfeeding. Can. Fam. Physician 58(11), 1218–1219 (2012).
66. Jansson LM, Svikis D, Lee J, Paluzzi P,
Rutigliano P, Hackerman F. Pregnancy and addiction. A comprehensive care model. J. Subst. Abuse Treat. 13(4), 321–329 (1996).
81. Fried PA, Watkinson B, Gray R. Growth
from birth to early adolescence in offspring prenatally exposed to cigarettes and marijuana. Neurotoxicol. Teratol. 21(5), 513–525 (1999).
67. Whiteside-Mansell L, Crone CC,
Conners NA. The development and evaluation of an alcohol and drug prevention and treatment program for women and children. The AR-CARES program. J. Subst. Abuse Treat. 16(3), 265–275 (1999). 68. Fajemirokun-Odudeyi O, Sinha C, Tutty S
et al. Pregnancy outcome in women who use opiates. Eur. J. Obstet. Gynecol. Reprod. Biol. 126(2), 170–175 (2006). 69. Weaver MF, Jarvis MA, Schnoll SH. Role of
the primary care physician in problems of substance abuse. Arch. Intern. Med. 159(9), 913–924 (1999). 70. Dashe JS, Sheffield JS, Olscher DA, Todd SJ,
Jackson GL, Wendel GD. Relationship between maternal methadone dosage and neonatal withdrawal. Obstet. Gynecol. 100(6), 1244–1249 (2002).
82. Djulus J, Moretti M, Koren G. Marijuana use
and breastfeeding. Can. Fam. Physician 51, 349–350 (2005). 83. Garry A, Rigourd V, Amirouche A,
Fauroux V, Aubry S, Serreau R. Cannabis and breastfeeding. J. Toxicol. 2009, 596149 (2009). 84. Liston J. Breastfeeding and the use of
recreational drugs – alcohol, caffeine, nicotine and marijuana. Breastfeeding Rev. 6(2), 27–30 (1998). 85. Jones HE, Johnson RE, Jasinski DR et al.
Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome. Drug Alcohol Depend. 79(1), 1–10 (2005).
71. Section On Breastfeeding. Breastfeeding and
the use of human milk. Pediatrics 129(3), e827–e841 (2012).
86. Jones HE, Kaltenbach K, Heil SH et al.
Neonatal abstinence syndrome after methadone or buprenorphine exposure. N. Engl. J. Med. 363(24), 2320–2331 (2010).
72. Goel N, Beasley D, Rajkumar V, Banerjee S.
Perinatal outcome of illicit substance use in pregnancy – comparative and contemporary socio-clinical profile in the UK. Eur. J. Pediatrics 170(2), 199–205 (2011).
87. Jones HE, Dengler E, Garrison A et al.
Neonatal outcomes and their relationship to maternal buprenorphine dose during pregnancy. Drug Alcohol Depend. 134, 414–417 (2014).
73. Jansson LM, Choo R, Velez ML et al.
Methadone maintenance and breastfeeding in the neonatal period. Pediatrics 121(1), 106–114 (2008).
88. Welle-Strand GK, Skurtveit S, Jones HE et al.
Neonatal outcomes following in utero exposure to methadone or buprenorphine: a National Cohort Study of opioid-agonist treatment of Pregnant Women in Norway from 1996 to 2009. Drug Alcohol Depend. 127(1–3), 200–206 (2013).
74. Isemann B, Meinzen-Derr J, Akinbi H.
Maternal and neonatal factors impacting response to methadone therapy in infants treated for neonatal abstinence syndrome. J. Perinatol. 31(1), 25–29 (2011). 75. Hilton TC. Breastfeeding considerations of
opioid dependent mothers and infants. MCN Am. J. Matern. Child Nurs. 37(4), 236–240 (2012). 76. D’Apolito K. Breastfeeding and substance
abuse. Clin. Obstet. Gynecol. 56(1), 202–211 (2013).
www.futuremedicine.com
Review on breastfeeding recommendations.
89. Minozzi S, Amato L, Bellisario C, Ferri M,
Davoli M. Maintenance agonist treatments for opiate-dependent pregnant women. Cochrane Database Syst. Rev. 12, CD006318 (2013). ••
Cochrane review did not find sufficient significant differences between methadone
future science group
Care of drug-addicted pregnant women: current concepts & future strategies –
and buprenorphine, or slow-release morphine, regarding efficacy. 90. Delano K, Gareri J, Koren G. Rates of fetal
polydrug exposures in methadone-maintained pregnancies from a high-risk population. PLoS ONE 8(12), e82647 (2013). ••
Analysis of meconium samples demonstrating high rates of additional opioid and other drug use in the methadone maintenance treatment group.
91. Casper T, Arbour MW. Identification of the
pregnant woman who is using drugs: implications for perinatal and neonatal care. J. Midwifery Womens Health 58(6), 697-701 (2013). 92. Wong S, Ordean A, Kahan M. Substance use
in pregnancy. J. Obstet. Gynaecol. Can. 33(4), 367–384 (2011). 93. Ebner N, Rohrmeister K, Winklbaur B et al.
Management of neonatal abstinence syndrome in neonates born to opioid maintained women. Drug Alcohol Depend. 87(2–3), 131–138 (2007). 94. Kraft WK, Van Den Anker JN.
Pharmacologic management of the opioid neonatal abstinence syndrome. Pediatr. Clin. North Am. 59(5), 1147–1165 (2012). 95. Hudak ML, Tan RC; Committee On Drugs,
Committee On Fetus and Newborn,
future science group
American Academy Of Pediatrics. Neonatal drug withdrawal. Pediatrics 129(2), e540–e560 (2012). 96. Sarkar S, Donn SM. Management of neonatal
perspective
and newborn neurobehavior. Pediatrics 111(6 Pt 1), 1318–1323 (2003). 102. Pichini S, Garcia-Algar O. In utero exposure
abstinence syndrome in neonatal intensive care units: a national survey. J. Perinatol. 26(1), 15–17 (2006).
to smoking and newborn neurobehavior: how to assess neonatal withdrawal syndrome? Therap. Drug Monitor. 28(3), 288–290 (2006).
97. Fried PA, Makin JE. Neonatal behavioural
103. Adams ED, Bianchi AL. A practical approach
correlates of prenatal exposure to marihuana, cigarettes and alcohol in a low risk population. Neurotoxicol. Teratol. 9(1), 1–7 (1987). 98. Eyler FD, Behnke M, Garvan CW,
Woods NS, Wobie K, Conlon M. Newborn evaluations of toxicity and withdrawal related to prenatal cocaine exposure. Neurotoxicol. Teratol. 23(5), 399–411 (2001). 99. Behnke M, Smith VC, Committee on
Substance Abuse, Committee On Fetus and Newborn. Prenatal substance abuse: short- and long-term effects on the exposed fetus. Pediatrics 131(3), e1009–e1024 (2013). 100. Godding V, Bonnier C, Fiasse L et al. Does
in utero exposure to heavy maternal smoking induce nicotine withdrawal symptoms in neonates? Pediatric Res. 55(4), 645–651 (2004). 101. Law KL, Stroud LR, Lagasse LL, Niaura R,
to labor support. J. Obstet. Gynecol. Neonatal Nurs. 37(1), 106–115 (2008). 104. Hodnett ED, Lowe NK, Hannah ME et al.
Effectiveness of nurses as providers of birth labor support in North American hospitals: a randomized controlled trial. JAMA 288(11), 1373–1381 (2002). 105. Payant L, Davies B, Graham ID, Peterson
WE, Clinch J. Nurses’ intentions to provide continuous labor support to women. J. Obstet. Gynecol. Neonatal Nurs. 37(4), 405–414 (2008). 106. Floyd RL, Jack BW, Cefalo R et al.
The clinical content of preconception care: alcohol, tobacco, and illicit drug exposures. Am. J. Obstet. Gynecol. 199(6 Suppl. 2), S333–S339 (2008). 107. Keegan J, Parva M, Finnegan M, Gerson A,
Belden M. Addiction in pregnancy. J. Addict. Dis. 29(2), 175–191 (2010).
Liu J, Lester BM. Smoking during pregnancy
Women's Health (2014) 10(2)
177
Care of drug-addicted pregnant women: current concepts and future strategies – an overview Simone M Goettler*1 & Sibil Tschudin1 This review focuses on drug use during pregnancy and the perinatal period, a constellation that is seen more often. Drug use in pregnant women poses an increased risk for adverse health outcomes both for the mother and child. Care is often complicated by social and environmental factors, as well as psychiatric comorbidities. It is, therefore, very important to provide drug-using pregnant women with optimal ante-, peri- and post-natal care. Health professionals should approach them in a nonjudgmental and supportive way, and provide them with the same care and attention as nondrug-using women. Adequate care requires interdisciplinary teams. Ideally, healthcare providers should be specialized in the care of drug-using pregnant women.
Since the 1980s, an increase of drug use in women of childbearing age has been observed [1–7]. The exact number of drug-dependent women is unknown because epidemiological data rely almost exclusively on voluntary patient reports [1,8]. The causes of drug use are likely to be multifactorial including biological, psycho logical, as well as social factors. The care of drugusing women during pregnancy is challenging, as the mother’s and infant’s health might be compromised, and this has to be considered. Furthermore, it is not only the drug itself that harms the pregnant woman and the fetus, but these women may live in difficult social circum stances, and psychiatric comorbidity is frequent. Evidence-based standards of care would thus be beneficial. This review aims to provide an overview of the current literature findings con sidering PubMed listed papers primarily within the time period of 1983–2013. In addition, an established interdisciplinary model of care implemented at a university women’s hospital in Switzerland will be presented and discussed. Vrious effects of drugs in the context of reproduction Drug use & fertility
Impaired fertility associated with heroin use has been previously demonstrated [9], both in men and women [10,11]. Even low doses of narcotics can impair normal ovarian function and ovu lation and therefore reduces the probability of conception. Interestingly, in a longitudinal study on 191 heroin- and cocaine-addicted women, among whom less than a third had a regular cycle, Schmittner et al. demonstrated that the 10.2217/WHE.14.7 © 2014 Future Medicine Ltd
menstrual bleeding pattern began to normalize during methadone maintenance [12]. Even if this was just one of few studies, it leads to the hypo thesis that the stability of methadone mainte nance might interfere less with menstrual func tion than illicit heroin use. Improved fertility, in addition to better medical care as a result of substitution programs, might be possible expla nations for the increase in drug-using pregnant women around the turn of the millennium [12]. Drug effects on mother & child
Substance abuse not only harms the patient her self but also the unborn child [13]. Table 1 shows a summary of the effects of different substances on mother and child. Problems include preterm labor and low birth weight in general [1,27], and special complica tions, such as myocardial infarction, cerebro vascular accidents and placental abruption, in cocaine-using women owing to the vasocon strictive effects of the drug [28]. However, the effects of in utero cocaine exposure are also correlated with other factors, such as prenatal exposure to tobacco use, other drugs and the environment [29]. Examining direct effects of specific drugs is, therefore, challenging since most of the women are poly-drug users [30,31]. The fact that the effects on mother and child are likely to be multifactorial complicates care even more [32–34]. Factors, such as smoking, poor diet, stress and chaotic lifestyle, appear to be the most important etiological factors. Outcomes associated with drug use are, therefore, results of either the effect of the drug itself or of problems related to growth restriction and/or premature Women's Health (2014) 10(2), 167–177
Department of Obstetrics & Gynecology, University Hospital Basel, Basel, Switzerland *Author for correspondence: Tel.: +41 612 659 043 [email protected] 1
Keywords • drug use • interdisciplinary care • pregnancy • psychiatric comorbidity
part of
ISSN 1745-5057
167
perspective – Goettler & Tschudin Table 1. Drug effects on the mother and child. Drug/substance
Effects on mother
Effects on fetus
Ref.
Opiates (heroine, methadone and morphine)
Constipation Vasodilation Drug interactions (pulmonary edema and β2 sympatho-mimetics) Premature contractions Protracted delivery
SGA Prematurity IUGR Intrauterine demise Withdrawal symptoms SIDS Impaired intellectual development
Cocaine
Loss of hunger and sleep Anxiety reduction Increased sympathetic activity Reduced placental perfusion Premature placental abruption Premature contractions Abortion Hypertension Cerebrovascular events Myocardial infarction
SGA IUGR Prematurity Intrauterine demise Malformations (heart, musculoskeletal and urogenital tract) Microcephalus Perinatal cerebral infarction
Cannabis/THC
Increased sympathetic activity (general vasoconstriction) Premature placental abruption Formation of ketone bodies (cave gestational diabetes) Convulsions (cave preeclampsia and premature contractions)
SGA IUGR Prematurity Impaired postnatal intellectual development
[81]
Amphetamines/ ecstasy
Increased sympathetic activity Mental hyperactivity Compulsive chewing Dysfunctional thermoregulation Constriction of placental vessels
Similar to cocaine (placental abruption and fetal distress) IUGR Malformations (heart and skeleton) More male births
[30]
LSD
Increased sympathetic activity Visual hallucination Panic attacks
Chromosomal aberrations Skeletaldysplasias (hands and feet) Ocular dysplasia (suspected)
[16–18]
Alcohol
Gastric hyperacidity Sedation Tocolytic effect
FASD (FAS): facial dysmorphogenesis, cardiac septal effects and joint abnormalities Growth restriction
[19–21]
Tobacco
Vasoconstriction Restriction of placental blood flow and placenta insufficiency Premature contractions Abortion Infertility Ectopic pregnancy
SGA IUGR Prematurity Impaired postnatal development Increased addictive potential, orofacial clefts, SIDS, craniosynostosis, clubfoot, childhood respiratory disease and attention-deficit disorder
[22,81]
Caffeine
More than 200 mg/day may increase risk of miscarriage
No known teratogenic effects
[23,24]
Theobromine (primary Higher maternal serum concentrations of theobromine are not Fetal movements per hour increased methylxanthine associated with reduced occurrence of preeclampsia and sex difference likely alkaloid in chocolate)
[14]
[15,28]
[25,26]
FAS: Fetal alcohol syndrome; FASD: Fetal alcohol spectrum disorders; IUGR: Intrauterine growth retardation; SGA: Small-for-gestational age; SIDS: Sudden infant death syndrome; THC: Tetrahydrocannabinol. Data taken from [27].
delivery. Furthermore, there is a paucity of research regarding newer drugs such as ecstasy, bath salts or synthetic cannabinoids [1,30,35]. In a study on 247 drug-using women and 741 controls conducted over a 4-year period, drug-using women were still at significant risk 168
www.futuremedicine.com
of adverse obstetric and perinatal outcomes, with significantly more preterm births, a higher incidence of low birth weight and intrauterine growth restriction despite coordinated prenatal care. The risk of placental abruption was also higher [36]. future science group
Care of drug-addicted pregnant women: current concepts & future strategies –
The proportion of pregnant women who continue to drink alcohol in pregnancy is noteworthy [37,38]. A large, recent prospective, multicenter cohort study on healthy nulli parous females with singleton pregnancies, with the main aim of developing screening tests to predict adverse outcomes, such as pre eclampsia, small gestational age neonates and spontaneous preterm birth, did not demon strate a strong association between (occasional to heavy amounts of) alcohol consumption in early pregnancy and these outcomes. However, these effects are likely not only dependent on quantity consumed, but also on the timing of exposure. It is also noteworthy, that this study did not investigate the association between alco hol consumption in pregnancy and long-term neurocognitive outcomes of children with fetal exposure to alcohol [39]. Therefore, the authors of this review believe that there is not enough evidence to suggest that any amount of alcohol is safe during pregnancy. Complex psychosocial situation & lack of prenatal care
Drug and alcohol use, and the resulting prob lems mostly precede pregnancy. Likewise, comorbidity can either be a cause or con sequence of drug use. Drug-using women’s reproductive health is affected by many fac tors, such as poor social environment, mal nutrition, inadequate hygiene, sexually trans mitted infections, physical abuse or a history of prostitution [40–43]. It is known that the lack of antenatal care is associated with worse outcomes for mother and child [36]. In a retrospective study on 211 women who came to delivery without any antenatal care, drug abuse was the most preva lent reason for this behavior [44]. Furthermore, in a postpartum cohort of 812 low-income women who delivered at a tertiary care center, cocaine or opiate abuse was predictive of little or no antenatal care [45]. Drug-using pregnant women may not use (and may not have access to) the traditional maternity services the same way nondrug-using women do. They tend to present late, have dif ficulties in attending appointments, and when they present, they might not admit their drug use [46]. Possibly owing to fear of stigmatization or legal consequences, drug-using or alcoholic pregnant, or postpartum women often deny their drug habit, the possible harmful effects and the need to seek appropriate care and, therefore, often receive no care at all [32,47]. future science group
perspective
Psychiatric comorbidity
Clinicians should be aware of psychiatric comor bidities in the population of drug-using women [13,31,48], and both psychiatric comorbidities and the patient’s habit of consuming drugs have to be approached [49]. According to an Australian population-based, retrospective study, depres sion is the most common psychiatric disorder followed by anxiety disorders. Almost half of all drug-using mothers were affected by depression [50]. These mothers had more previ ous pregnancies and suffered more often from domestic violence. Since prenatal care and social outcome may be worse for these mothers and their children, the authors recommend that all pregnant drug-using women should be assessed for psychosocial disorders in order to facilitate timely interventions [50]. Pregnancy care for drug-using women Pregnancy
Even if the risk of each pregnancy of a drugusing woman has to be assessed on an individual basis, some of these pregnancies need to be con sidered as potential high-risk pregnancies, and thus, specialized (obstetrical) interdisciplinary teams should engage in their care [31,48]. An aspect that might be neglected when assessing drug-using women are concomitant factors, such as cigarette smoking, alcohol use and poor social circumstances, which are all common in women using illicit drugs [32]. In a case–control study on 370 full-term gesta tions, the three main risk factors for fetal growth retardation were tobacco, low prepreg nancy weight and low socioeconomic status [51]. Most pregnant women using cocaine and/or heroin appear to be cigarette smokers. In gen eral, babies whose mothers smoked during pregnancy tend to have lower birth weights; an effect that appears to be dose-dependent with a higher number of cigarettes per day related to lower birth weight [52]. It is important to use a consistent, easy-to-use screening tool and a nonjudgmental approach to evaluate patients for possible drug use. There is controversy regarding whether screening should be undertaken systematically in all pregnant women or just in selected patients suspected of drug abuse [53]. The American Congress of Obstetricians and Gynecologists suggest easily applicable screening tests in the form of ques tionnaires [34,54]. In our institution (Univer sity Hospital Basel, Switzerland), screening by means of urine drug tests is performed repeat edly – provided the patient consents – when
Women's Health (2014) 10(2)
169
perspective – Goettler & Tschudin clinically indicated. Furthermore, fetal expo sure to illicit drugs or alcohol in utero can be detected by meconium analysis, reflecting expo sure during the second and third trimester, by means of chromatographic techniques [55–57]. Interdisciplinary approach to care
Neonatal outcomes may be positively influ enced as shown in an interventional study on a large sample of 6774 pregnant women. Rates of assisted ventilation, low birth weight and pre term delivery improved when mothers received substance abuse treatment integrated with pre natal care [58]. Nowadays, most studies suggest that drug-using pregnant women are in need of multidisciplinary antenatal care with medical, social and psychological support [59–61]. Com prehensive, interdisciplinary treatment pro grams are likely to have a positive impact on outcomes [62–67]. The one retrospective study that failed to demonstrate a positive effect was not designed to show an effect of an interdis ciplinary approach. Furthermore, no detailed information on the type of interdisciplinary teamwork is provided [36]. To optimize the ante- and post-natal care for mother and child, an interdisciplinary team, including an obstetrician–gynecologist coor dinating the involved special services, should be developed. As shown in Figure 1, one health professional should be designated as the case manager. In our institution, this is a gynecolo gist and member of our division of social and psychosomatic gynecology. This specialized service is possible, as we are a tertiary care university hospital serving a population of approximately 300,000 people. This service is well accepted and used. Most of the patients are referred by their primary-care providers, in addition to drop-ins at the moment of deliv ery. Divergent from the regular antenatal-care patients, they are seen more frequently – at most every 2–4 weeks. Depending on the individual situation and needs for care, disciplines, such as drug-substi tution centers, social workers, neonatologists, psychiatrists, pediatric psychiatrists, family physicians and child welfare authorities, should be involved. In our setting, it is the obstetri cian–gynecologist who serves as the primary reference point for the patient and takes the lead in the interdisciplinary team, by coordinating and integrating the disciplines that are needed. This process needs to be as easy and comfort able for the patient as possible since compliance is an issue. 170
www.futuremedicine.com
Women who present with a history sugges tive of drug use, should receive the same care as women who do not use drugs, including deter mination of gestational age by ultrasound; keep ing in mind that the population of drug-using women is often underserved. It is advantageous to diagnose pregnancy as timely as possible. To identify women at risk who present in the ante natal phase, the gynecologist has to take the history of past and present drug use, including necessary details, such as participation in sub stitution programs or intravenous application of drugs. Co-ordination and management of the substitution should be performed by the substi tution center. In addition, testing for sexually transmitted diseases and hepatitis C should be undertaken, when considering that, according to a recent study, 41% of drug-using women had evidence of previous exposure to the hepatitis C virus [68]. In our institution, a round table is estab lished during the third trimester, at which the involved disciplines plan postnatal care. This serves as an information platform for the teams, and also establishes contact between the anteand post-natal caretakers and the patient, in order to address their issues and concerns. In this context, the neonatologists have the oppor tunity to inform the patient about postnatal substitution. Admission & delivery
At presentation, for example, admission for delivery, midwives and obstetricians need to be aware of unusual behavior or agitation. Further more, physiological signs of drug abuse, such as dilated or constricted pupils, increased or decreased respirations, bradycardia or tachy cardia, hypotension or hypertension, all depend ing on the substance used, should be registered [8]. These can be both signs of intoxication and withdrawal, and should prompt further testing to confirm drug use and rule out preeclampsia. These symptoms might be harmful for both the mother and child [69]. As substance use and smoking are associated with an increased risk of placental insufficiency, growth restriction and possible fetal distress, monitoring has to be especially thorough; during pregnancy with regular ultrasounds and during labor by con tinuous heart beat monitoring [32]. Neonatal care should be readily available in the mater nity ward. Postnatal care needs to be adjusted to the needs of the patient, for example, with drawal signs or other necessary treatments for the newborn [46,70]. future science group
Care of drug-addicted pregnant women: current concepts & future strategies –
perspective
Division of Gynecological Social Medicine and Psychosomatics Reference person, medical antenatal care, coordination of involved special services
Social services Advice in psychosocial, legal and financial issues. Coordination between mother and child and neonatal care units, organization of the support after hospital dismissal
Drug substitution center Care within the substitution program
Maternity ward/mother–child unit Care during delivery and postpartum
Neonatal care unit During third trimester, information and arrangement of the postnatal proceedings Nurses Instruction and supervision of the mothers in the care of their newborn babies
Pediatric psychiatry Support in establishing the parent–child relationship, mediation between parents and neonatal care unit staff
Child welfare authority Information about assistance in crisis situations. Provision of additional childcare if needed
Psychiatrist Ongoing psychotherapy in case of psychiatric comorbidity
Figure 1. The Basel model of interdisciplinary care of drug-using women.
Breastfeeding
Breastfeeding is beneficial in a number of ways. Apart from its short- and long-term medical and neurodevelopmental benefits [71], it helps bonding between mother and child, which is particularly important when the mother is using drugs. Nevertheless, only approximately 15% of patients were still breastfeeding at discharge in a study from the UK [72]. In methadone-substituted women with no parallel consumption of other drugs, breast feeding is not contraindicated. However, in future science group
a study with small group sizes, fewer infants in the breast-fed group required pharmaco therapy for neonatal abstinence syndrome, an effect that was not statistically significant. Interestingly, this study showed low concen trations of methadone in breast milk, which were not related to maternal intake, supporting the recommendation for breastfeeding among methadone-maintained women [73]. The effect of breastfeeding on severity of neonatal with drawal symptoms has also been reported else where [46,74]. As children of drug-using women
Women's Health (2014) 10(2)
171
perspective – Goettler & Tschudin are often delivered preterm or are small-forgestational age, breastfeeding is particularly useful [75]. Breastfeeding should, therefore, be encouraged in methadone-substituted women [76,77]. Data on breastfeeding are less clear with regard to other drugs, such as cocaine and heroin [78,79], and are often based on case reports or – series [76]. With regard to cocaine, it is crucial for the healthcare provider to counsel patients both on the serious potential risks of cocaine exposure (e.g., potential agi tation, irritability, seizures, hypertension and tachycardia), and on the advantages of breast feeding, to allow for an informed choice [80]. Both cocaine and marijuana are soluble and can potentially become trapped in the breast milk [76]. For cannabis exposure through milk, no increase in neonatal risk has been shown; however, there are no appropriate studies on this, to date [81–83]. Some authors discourage breastfeeding in mothers who regularly use marijuana [76]. Occasional users who are not able to stop, should be evaluated on a case-bycase basis [83]. Cannabis smoke exposure to the child, and breastfeeding during the hours after cannabis use, should be avoided [84]. Buprenorphine might also be safe during breastfeeding and opioid-dependent women can be counseled accordingly [76,77,85,86]. There appears to be no relationship between maternal buprenorphine dose at delivery and the severity of neonatal abstinence syndrome, the amount of morphine needed for treatment and the duration of treatment [87]. The out comes of newborns of pregnant women using methadone and buprenorphine appeared to be similar, with the exception that buprenor phine-exposed infants presented with signifi cantly larger head circumference and tended to have higher weight and length [88]. Accord ing to a recent Cochrane review, the differ ences between methadone and buprenorphine (or slow-release morphine) do not allow for a conclusion that one treatment is superior to another [89]. A very recent retrospective, observational assessment of meconium toxicology performed on samples of a high-risk patient cohort, how ever, demonstrated that, at least a third of pregnant women on methadone-maintenance therapy continue to use at least one additional opioid narcotic [90]. No significant difference was found for opioid or other illicit drug use between the methadone-positive and -negative meconium samples, indicating similar patterns of substance use during late pregnancy. The 172
www.futuremedicine.com
authors of the study speculated that, subthera peutic dosing might have created withdrawal symptoms leading to additional substance use. In addition, these results may be an indica tion of partly inadequate delivery of addiction support services [90]. In our institution, breastfeeding is possible in methadone-substituted women, provided that weekly (but unheralded) urinary toxicology screens are negative for other drugs. Postpartum period
Special attention has to be given to the post partum period [91]. Alcohol withdrawal, for example, generally occurs after 48 h, thus, in the postnatal ward, the woman might appear to be agitated and have problems caring for her baby during this time. Users of cocaine and amphetamines might even be abusive and exhibit strange or inappropriate behavior. Neonatal abstinence syndrome
Opiate-dependent women should be informed that neonates exposed during pregnancy need to be monitored closely for symptoms and signs of neonatal withdrawal [92], as 60–90% of neonates with in utero exposure to opiates suffer from drug withdrawal [86,93]. Withdrawal symptoms typically depend on the substance, and are predominantly autonomic, neurologic or gastrointestinal. They generally occur within 24 h after delivery for heroin and 2–6 days for methadone. This is in contrast to symptoms of benzodiazepine withdrawal, which can be delayed [94,95]. A British study on neonatal abstinence syndrome found great variability in policies for its detection and treatment [96]. Neonatal abstinence syndrome has not been conclusively demonstrated in marijuana- or cocaine-exposed neonates [97,98]. An often unrecognized entity is the neo natal nicotine withdrawal syndrome, albeit its existence is questioned by some authors [99]. Its onset is typically within 12–24 h of life and resolves usually within 36 h, rarely requiring treatment [100,101]. Neonatal nicotine withdrawal syndrome may be misdiagnosed as infant colic when a smoking, breastfeeding mother discontinues breastfeeding [102]. Bonding
Breastfeeding has a positive impact on bond ing; however, as drug-using women often have difficulties in building a relationship with their newborn, additional support by a pediatric psy chiatrist might be helpful [40]. Furthermore, a future science group
Care of drug-addicted pregnant women: current concepts & future strategies –
psychiatrist or psychologist has the skills to provide mediation when conflicts between the patient and staff occurs, and is thus ideally part of the interdisciplinary team. In other settings and depending on local resources, the general practitioner, social worker or addiction coun selor may have a similar role, with the advantage that they continue to follow the woman and her child in the postpartum period. As associated legal and social problems can impede appropriate care, and can impair the ability of the mother to care for her child after birth, well-functioning social services should be involved [32]. Systematic information of the child welfare authority about drug-using mothers allows assistance in crisis situations and provision of help if additional childcare is needed.
use, which had often begun during adolescence. They often had family members with a history of alcohol and drug use. People in their social environment frequently animated their drug use [41].
Attitude towards drug-using pregnant women
Conclusion
Despite the obvious challenges for all disciplines in the care of drug-using women, the impor tance of being supportive and nonjudgmental is underlined in the literature reviewed for this article [103–105]. Care of drug-using women can be a tightrope walk between considerate care and paternalism, as both support and assistance are necessary. The patient–doctor relationship may be difficult, particularly in case of psychiat ric comorbidity (e.g., borderline disorder), and requires patience. It is of utmost importance to work in a constant, transparent fashion in order to gain commitment from the mother’s side by integrating her in the decision-making process. Institutionalized controls of toxicology screen ings are recommended since they are more easily accepted. Long-term outcome & preventive strategies
Although pregnancy might be a ‘window of opportunity’ for drug-using women, many patients do not succeed in maintaining the necessary stability over time [7]. According to several studies, this is only the case in less than half of the families concerned (risk factors: psy chiatric comorbidity, history of prostitution, homelessness, delinquency and a drug-addicted partner) [40,41]. The partner, or the father of the current pregnancy, may also be a drug user. In a sample of 240 pregnant women who voluntarily entered a substance abuse treatment program, most fathers were supportive of seeking treat ment. The majority of these urban, predomi nately African–American, opiate- or cocainedependent women, had long histories of drug future science group
perspective
Birth control
Another important issue is birth control, which may even be discussed during pregnancy so that the patients can choose a method by the time they deliver. Long-acting progestogen devices can be applied early in the postpartum period. In general, a pregnancy should be well planned in these patients and family-planning advice should be given. This allows discussing possible difficulties and preventive strategies in advance. As caring for drug-using pregnant women is challenging, standards of care and an interdisci plinary approach is required. The ultimate aim of these interdisciplinary efforts is to reduce the risk for adverse outcomes for the mother and her baby, both during pregnancy, the neo natal period and in the long term. A well-imple mented standardized approach may also allevi ate the demanding task of health profession als who are engaged in caring for drug-using pregnant women, and could possibly reduce concomitant distress when the patient–doctor relationship is particularly difficult. Future perspective
Early identification of drug-using habits and of the patterns of use by family practitioners, for example, in the preconception period, may provide the opportunity to assist affected women in reducing major health risks [106]. The surrounding social context in which drug use commonly occurs should certainly be taken into account. In order to comprehensively fol low drug-addicted women during pregnancy, thorough knowledge of certain aspects, such as effects of the drugs on the fetus and of breastfeeding on the newborn, are crucial on one hand, but on the other hand, continuous, concise and interdisciplinary care may even be more important. A pregnancy might act as a sentinel event that can help drug-using mothers to start modifying their behavior [107]. This may also have an impact on their children. Further research should focus on assessing and evaluating interdisciplinary strategies to prove their effects and efficacy in the respective settings.
Women's Health (2014) 10(2)
173
perspective – Goettler & Tschudin Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
Executive summary Effects of drugs in the context of reproduction • Impaired fertility was common in heroin-using women in the past, but, nowadays, generally improves in the context of substitution programs. • Drug use in pregnant women poses an increased risk for adverse health outcomes both for the mother and child. • It is difficult to discern direct drug effects from other factors, such as smoking, poor diet, stress and poor social circumstances. • Besides the specific effects of the various substances on the fetus, drugs generally cause preterm labor and low birth weight. Psychosocial situation • Cigarette smoking, alcohol use and poor social circumstances are all common in women using illicit drugs, and are concomitant factors that might be neglected when assessing drug-using women. • Psychiatric comorbidity is frequent in drug-using women (e.g., depression and anxiety disorders). • Psychiatric comorbidity can either be a cause or consequence of drug use. Pregnancy care for drug-using women • It is known that the lack of antenatal care is associated with worse outcomes for mother and child. • Comprehensive, interdisciplinary treatment programs are likely to have a positive impact on outcomes. • Care needs to be as easy and comfortable for the patient as possible since compliance is an issue. • Care of drug-using women can be a tightrope walk between considerate care and paternalism, as both support and assistance are necessary. • During delivery, special attention has to be paid to unusual behavior or physiological signs of drug abuse. • Breastfeeding is possible both in methadone- and buprenorphine-substituted women. • In the postpartum period, withdrawal generally occurs after 48 h for alcohol, after 24 h for heroin and after 2–6 days for methadone, meanwhile benzodiazepine withdrawal can be delayed. • Although pregnancy and consequent motherhood may be a ‘window of opportunity’ for drug-using women, many patients do not succeed in maintaining the necessary stability over time.
References Papers of special note have been highlighted as: • of interest •• of considerable interest 1.
French E. Substance abuse in pregnancy: compassionate and competent care for the patient in labor. Clin. Obstet. Gynecol. 56(1), 173–177 (2013).
2.
Hepburn M. Substance abuse in pregnancy. Curr. Obstet. Gynecol. 14(6), 419–425 (2004).
3.
4.
5.
6.
174
Kuczkowski KM. The effects of drug abuse on pregnancy. Curr. Opin. Obstet. Gynecol. 19(6), 578–585 (2007). Kelly L, Dooley J, Cromarty H et al. Narcotic-exposed neonates in a First Nations population in northwestern Ontario: incidence and implications. Can. Fam. Physician 57(11), e441–e447 (2011). National Survey on Drug Use and Health (NSDUH) (2012). www.samhsa.gov/data/NSDUH.aspx Patrick SW, Schumacher RE, Benneyworth BD, Krans EE, Mcallister JM, Davis MM. Neonatal abstinence syndrome and associated health care expenditures: United States,
2000–2009. JAMA 307(18), 1934–1940 (2012). 7.
8.
9.
Hayatbakhsh MR, Kingsbury AM, Flenady V, Gilshenan KS, Hutchinson DM, Najman JM. Illicit drug use before and during pregnancy at a tertiary maternity hospital 2000–2006. Drug Alcohol. Rev. 30(2), 181–187 (2011). Geary FH Jr, Turnquest Wells MA. Management of the patient in labor who has abused substances. Clin. Obstet. Gynecol. 56(1), 166–172 (2013). Bellati U, Noia G, Conte M, Mazzei R, Tempesta E. Amenorrhea in drug dependence. Minerva Medica 74(16), 865–868 (1983).
10. Singer R, Ben-Bassat M, Malik Z et al.
Oligozoospermia, asthenozoospermia, and sperm abnormalities in ex-addict to heroin, morphine, and hashish. Arch. Androl. 16(2), 167–174 (1986). 11. Ragni G, De Lauretis L, Gambaro V et al.
Semen evaluation in heroin and methadone addicts. Acta Eur. Fertil. 16(4), 245–249 (1985). 12. Schmittner J, Schroeder JR, Epstein DH,
Preston KL. Menstrual cycle length during
www.futuremedicine.com
methadone maintenance. Addiction 100(6), 829–836 (2005). 13. Kashiwagi M, Sieber S, Rechsteiner C,
Lauper U, Zimmermann R, Ehlert U. Psychological mood state of opiate addicted women during pregnancy and postpartum in comparison to non-addicted healthy women. J. Psychosom. Obstet. Gynecol. 28(1), 3–6 (2007). 14. Hulse GK, Milne E, English DR,
Holman CD. The relationship between maternal use of heroin and methadone and infant birth weight. Addiction 92(11), 1571–1579 (1997). 15. Fajemirokun-Odudeyi O, Lindow SW.
Obstetric implications of cocaine use in pregnancy: a literature review. Eur. J. Obstet. Gynecol. Reprod. Biol. 112(1), 2–8 (2004). 16. Cohen MM, Hirschhorn K, Frosch WA.
In vivo and in vitro chromosomal damage induced by LSD-25. N. Engl. J. Med. 277(20), 1043–1049 (1967). 17. Aase JM, Laestadius N, Smith DW. Children
of mothers who took LSD in pregnancy. Lancet 1(7663), 100–101 (1970).
future science group
Care of drug-addicted pregnant women: current concepts & future strategies –
18. Jacobson CB, Berlin CM. Possible
31. Kashiwagi M, Arlettaz R, Lauper U,
reproductive detriment in LSD users. JAMA 222(11), 1367–1373 (1972).
Zimmermann R, Hebisch G. Methadone maintenance program in a Swiss perinatal center: (I): management and outcome of 89 pregnancies. Acta Obstet. Gynecol. Scand. 84(2), 140–144 (2005).
19. Bertrand J, Floyd LL, Weber MK; Fetal
Alcohol Syndrome Prevention Team, Division of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention (CDC). Guidelines for identifying and referring persons with fetal alcohol syndrome. MMWR Recomm. Rep. 54(RR–11), 1–14 (2005).
32. Wright A, Walker J. Management of women
who use drugs during pregnancy. Semin. Fetal Neonatal Med. 12(2), 114–118 (2007). 33. Ludlow J, Christmas T, Paech MJ, Orr B.
Drug abuse and dependency during pregnancy: anaesthetic issues. Anaesth. Intensive Care 35(6), 881–893 (2007).
20. Jones KL, Smith DW, Ulleland CN,
Streissguth P. Pattern of malformation in offspring of chronic alcoholic mothers. Lancet 1(7815), 1267–1271 (1973).
34. Women ACOHCFU, American Society of
Addiction M. ACOG Committee Opinion No. 524: opioid abuse, dependence, and addiction in pregnancy. Obstet. Gynecol. 119(5), 1070–1076 (2012).
21. Mills JL, Graubard BI, Harley EE,
Rhoads GG, Berendes HW. Maternal alcohol consumption and birth weight. How much drinking during pregnancy is safe? JAMA 252(14), 1875–1879 (1984).
35. Oei JL, Kingsbury A, Dhawan A et al.
Amphetamines, the pregnant woman and her children: a review. J. Perinatol. 32(10), 737–747 (2012).
22. Einarson A, Riordan S. Smoking in
pregnancy and lactation: a review of risks and cessation strategies. Eur. J. Clin. Pharmacol. 65(4), 325–330 (2009).
36. Pinto SM, Dodd S, Walkinshaw SA, Siney C,
Kakkar P, Mousa HA. Substance abuse during pregnancy: effect on pregnancy outcomes. Eur. J. Obstet. Gynecol. Reprod. Biol. 150(2), 137–141 (2010).
23. Rosenberg L, Mitchell AA, Shapiro S,
Slone D. Selected birth defects in relation to caffeine-containing beverages. JAMA 247(10), 1429–1432 (1982).
•
24. Weng X, Odouli R, Li DK. Maternal caffeine
consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am. J. Obstet. Gynecol. 198(3), 279.e1–e279.8 (2008). 25. Klebanoff MA, Zhang J, Zhang C,
Levine RJ. Maternal serum theobromine and the development of preeclampsia. Epidemiology 20(5), 727–732 (2009).
37. CDC. Alcohol use and binge drinking among
women of childbearing age – United States, 2006–2010. MMWR. Morbid. Mortal. Wkly Rep. 61(28), 534–538 (2012). 38. CDC. Alcohol use among pregnant and
nonpregnant women of childbearing age – United States, 1991–2005. MMWR. Morbid. Mortal. Wkly Rep. 58(19), 529–532 (2009).
26. Tranquilli AL, Lorenzi S, Buscicchio G,
Di Tommaso M, Mazzanti L, Emanuelli M. Female fetuses are more reactive when mother eats chocolate. J. Matern. Fetal Neona. 27(1), 72–74 (2014).
39. McCarthy FP, O’Keeffe LM, Khashan AS
et al. Association between maternal alcohol consumption in early pregnancy and pregnancy outcomes. Obstet. Gynecol. 122(4), 830–837 (2013).
27. Von Mandach U. Drug use in pregnancy.
Therapeutische Umschau. Revue Therapeutique 62(1), 29–35 (2005). 28. Cain MA, Bornick P, Whiteman V.
The maternal, fetal, and neonatal effects of cocaine exposure in pregnancy. Clin. Obstet. Gynecol. 56(1), 124–132 (2013). 29. Frank DA, Augustyn M, Knight WG, Pell T,
Zuckerman B. Growth, development, and behavior in early childhood following prenatal cocaine exposure: a systematic review. JAMA 285(12), 1613–1625 (2001). 30. Singer LT, Moore DG, Fulton S et al.
Neurobehavioral outcomes of infants exposed to MDMA (ecstasy) and other recreational drugs during pregnancy. Neurotoxicol. Teratol. 34(3), 303–310 (2012).
future science group
Retrospective study on the contribution of drug use to maternal and perinatal complications.
••
Large study investigating the association between alcohol consumption before and during early pregnancy and adverse pregnancy outcomes, which found no association between alcohol consumption before 15 weeks of gestation and small-for-gestational age, reduced birth weight, preeclampsia or spontaneous preterm birth.
40. Gilchrist G, Taylor A. Drug-using mothers:
factors associated with retaining care of their children. Drug Alcohol Rev. 28(2), 175–185 (2009). 41. Kissin WB, Svikis DS, Morgan GD,
Haug NA. Characterizing pregnant
Women's Health (2014) 10(2)
perspective
drug-dependent women in treatment and their children. J. Subst. Abuse Treat. 21(1), 27–34 (2001). 42. Bauer CR, Shankaran S, Bada HS et al.
The Maternal Lifestyle study: drug exposure during pregnancy and short-term maternal outcomes. Am. J. Obstet. Gynecol. 186(3), 487–495 (2002). 43. Schempf AH, Strobino DM. Illicit drug use
and adverse birth outcomes: is it drugs or context? J. Urban Health 85(6), 858–873 (2008). 44. Friedman SH, Heneghan A, Rosenthal M.
Characteristics of women who do not seek prenatal care and implications for prevention. J. Obstet. Gynecol. Neonatal Nurs. 38(2), 174–181 (2009). 45. Schempf AH, Strobino DM. Drug use and
limited prenatal care: an examination of responsible barriers. Am. J. Obstet. Gynecol. 200(4), 412.e1–412.e10 (2009). 46. Berghella V, Lim PJ, Hill MK, Cherpes J,
Chennat J, Kaltenbach K. Maternal methadone dose and neonatal withdrawal. Am. J. Obstet. Gynecol. 189(2), 312–317 (2003). 47. Bolnick JM, Rayburn WF. Substance use
disorders in women: special considerations during pregnancy. Obstet. Gynecol. Clin. North Am. 30(3), 545–558, vii (2003). 48. Gyarmathy VA, Giraudon I, Hedrich D,
Montanari L, Guarita B, Wiessing L. Drug use and pregnancy – challenges for public health. Euro. Surveill. 14(9), 33–36 (2009). 49. Di Forti M, Morrison PD, Butt A,
Murray RM. Cannabis use and psychiatric and cogitive disorders: the chicken or the egg? Curr. Opin. Psych. 20(3), 228–234 (2007). 50. Oei JL, Abdel-Latif ME, Craig F et al.
Short-term outcomes of mothers and newborn infants with comorbid psychiatric disorders and drug dependency. Aust. NZ J. Psychiatry 43(4), 323–331 (2009). 51. Nieto A, Matorras R, Serra M, Valenzuela P,
Molero J. Multivariate analysis of determinants of fetal growth retardation. Eur. J. Obstet. Gynecol. Reprod. Biol. 53(2), 107–113 (1994). 52. Adriaanse HP, Knottnerus JA, Delgado LR,
Cox HH, Essed GG. Smoking in Dutch pregnant women and birth weight. Patient Educ. Couns. 28(1), 25–30 (1996). 53. Roberts SC, Nuru-Jeter A. Women’s
perspectives on screening for alcohol and drug use in prenatal care. Womens Health Issues 20(3), 193–200 (2010). 54. Wong S, Ordean A, Kahan M et al. Substance
use in pregnancy. J. Obstet. Gynecol. Can. 33(4), 367–384 (2011).
175
perspective – Goettler & Tschudin 55. Lozano J, Garcia-Algar O, Vall O, De La
Torre R, Scaravelli G, Pichini S. Biological matrices for the evaluation of in utero exposure to drugs of abuse. Ther. Drug Monit. 29(6), 711–734 (2007). 56. Garcia-Algar O, Vall Combelles O, Puig Sola
C et al. Prenatal exposure to drugs of abuse using meconium analysis in a low socioeconomic population in Barcelona. An. Pediatr. (Barc). 70(2), 151–158 (2009). 57. Garcia-Algar O, Kulaga V, Gareri J et al.
Alarming prevalence of fetal alcohol exposure in a Mediterranean city. Ther. Drug Monit. 30(2), 249–254 (2008). 58. Armstrong MA, Gonzales Osejo V,
Lieberman L, Carpenter DM, Pantoja PM, Escobar GJ. Perinatal substance abuse intervention in obstetric clinics decreases adverse neonatal outcomes. J. Perinatol. 23(1), 3–9 (2003). ••
Evaluation of a managed care organization’s obstetric clinic-based perinatal substance abuse treatment program, demonstrating improved neonatal outcomes.
59. Brulet C, Chanal C, Ravel P, Mazurier E,
Boulot P, Faucherre V. Multidisciplinary monitoring and psychosocial support reduce complications of opiate dependence in pregnant women: 114 pregnancies. Presse Medicale (Paris) 36(11 Pt 1), 1571–1580 (2007). 60. Mayet S, Groshkova T, Morgan L,
MacCormack T, Strang J. Drugs and pregnancy – outcomes of women engaged with a specialist perinatal outreach addictions service. Drug Alcohol Rev. 27(5), 497–503 (2008). •
Study on outcomes of women seen by a specialist perinatal addictions outreach service.
61. Morton J, Konrad SC. Introducing a
caring/relational framework for building relationships with addicted mothers. J. Obstet. Gynecol. Neonatal Nurs. 38(2), 206–213 (2009). •
Integrative, interdisciplinary framework offering guidance in developing relationships that can endure the challenges of substance abuse.
62. Ordean A, Kahan M. Comprehensive
treatment program for pregnant substance users in a family medicine clinic. Can. Fam. Physician 57(11), e430–e435 (2011). •
Comprehensive care in a family medicine setting also leads to positive maternal and infant health outcomes.
63. Corse SJ, Smith M. Reducing substance abuse
during pregnancy. Discriminating among
176
levels of response in a prenatal setting. J. Subst. Abuse Treat. 15(5), 457–467 (1998). 64. Ellwood DA, Sutherland P, Kent C,
O’Connor M. Maternal narcotic addiction: pregnancy outcome in patients managed by a specialized drug-dependency antenatal clinic. Aust. N. Z. J. Obstet. Gynecol. 27(2), 92–98 (1987). 65. Fiocchi FF, Kingree JB. Treatment retention
and birth outcomes of crack users enrolled in a substance abuse treatment program for pregnant women. J. Subst. Abuse Treat. 20(2), 137–142 (2001).
•
77. Shainker SA, Saia K, Lee-Parritz A. Opioid
addiction in pregnancy. Obstet. Gynecol. Survey 67(12), 817–825 (2012). 78. Chasnoff IJ, Lewis DE, Squires L. Cocaine
intoxication in a breast-fed infant. Pediatrics 80(6), 836–838 (1987). 79. Chaney NE, Franke J, Wadlington WB.
Cocaine convulsions in a breast-feeding baby. J. Pediatrics 112(1), 134–135 (1988). 80. Cressman AM, Koren G, Pupco A, Kim E,
Ito S, Bozzo P. Maternal cocaine use during breastfeeding. Can. Fam. Physician 58(11), 1218–1219 (2012).
66. Jansson LM, Svikis D, Lee J, Paluzzi P,
Rutigliano P, Hackerman F. Pregnancy and addiction. A comprehensive care model. J. Subst. Abuse Treat. 13(4), 321–329 (1996).
81. Fried PA, Watkinson B, Gray R. Growth
from birth to early adolescence in offspring prenatally exposed to cigarettes and marijuana. Neurotoxicol. Teratol. 21(5), 513–525 (1999).
67. Whiteside-Mansell L, Crone CC,
Conners NA. The development and evaluation of an alcohol and drug prevention and treatment program for women and children. The AR-CARES program. J. Subst. Abuse Treat. 16(3), 265–275 (1999). 68. Fajemirokun-Odudeyi O, Sinha C, Tutty S
et al. Pregnancy outcome in women who use opiates. Eur. J. Obstet. Gynecol. Reprod. Biol. 126(2), 170–175 (2006). 69. Weaver MF, Jarvis MA, Schnoll SH. Role of
the primary care physician in problems of substance abuse. Arch. Intern. Med. 159(9), 913–924 (1999). 70. Dashe JS, Sheffield JS, Olscher DA, Todd SJ,
Jackson GL, Wendel GD. Relationship between maternal methadone dosage and neonatal withdrawal. Obstet. Gynecol. 100(6), 1244–1249 (2002).
82. Djulus J, Moretti M, Koren G. Marijuana use
and breastfeeding. Can. Fam. Physician 51, 349–350 (2005). 83. Garry A, Rigourd V, Amirouche A,
Fauroux V, Aubry S, Serreau R. Cannabis and breastfeeding. J. Toxicol. 2009, 596149 (2009). 84. Liston J. Breastfeeding and the use of
recreational drugs – alcohol, caffeine, nicotine and marijuana. Breastfeeding Rev. 6(2), 27–30 (1998). 85. Jones HE, Johnson RE, Jasinski DR et al.
Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome. Drug Alcohol Depend. 79(1), 1–10 (2005).
71. Section On Breastfeeding. Breastfeeding and
the use of human milk. Pediatrics 129(3), e827–e841 (2012).
86. Jones HE, Kaltenbach K, Heil SH et al.
Neonatal abstinence syndrome after methadone or buprenorphine exposure. N. Engl. J. Med. 363(24), 2320–2331 (2010).
72. Goel N, Beasley D, Rajkumar V, Banerjee S.
Perinatal outcome of illicit substance use in pregnancy – comparative and contemporary socio-clinical profile in the UK. Eur. J. Pediatrics 170(2), 199–205 (2011).
87. Jones HE, Dengler E, Garrison A et al.
Neonatal outcomes and their relationship to maternal buprenorphine dose during pregnancy. Drug Alcohol Depend. 134, 414–417 (2014).
73. Jansson LM, Choo R, Velez ML et al.
Methadone maintenance and breastfeeding in the neonatal period. Pediatrics 121(1), 106–114 (2008).
88. Welle-Strand GK, Skurtveit S, Jones HE et al.
Neonatal outcomes following in utero exposure to methadone or buprenorphine: a National Cohort Study of opioid-agonist treatment of Pregnant Women in Norway from 1996 to 2009. Drug Alcohol Depend. 127(1–3), 200–206 (2013).
74. Isemann B, Meinzen-Derr J, Akinbi H.
Maternal and neonatal factors impacting response to methadone therapy in infants treated for neonatal abstinence syndrome. J. Perinatol. 31(1), 25–29 (2011). 75. Hilton TC. Breastfeeding considerations of
opioid dependent mothers and infants. MCN Am. J. Matern. Child Nurs. 37(4), 236–240 (2012). 76. D’Apolito K. Breastfeeding and substance
abuse. Clin. Obstet. Gynecol. 56(1), 202–211 (2013).
www.futuremedicine.com
Review on breastfeeding recommendations.
89. Minozzi S, Amato L, Bellisario C, Ferri M,
Davoli M. Maintenance agonist treatments for opiate-dependent pregnant women. Cochrane Database Syst. Rev. 12, CD006318 (2013). ••
Cochrane review did not find sufficient significant differences between methadone
future science group
Care of drug-addicted pregnant women: current concepts & future strategies –
and buprenorphine, or slow-release morphine, regarding efficacy. 90. Delano K, Gareri J, Koren G. Rates of fetal
polydrug exposures in methadone-maintained pregnancies from a high-risk population. PLoS ONE 8(12), e82647 (2013). ••
Analysis of meconium samples demonstrating high rates of additional opioid and other drug use in the methadone maintenance treatment group.
91. Casper T, Arbour MW. Identification of the
pregnant woman who is using drugs: implications for perinatal and neonatal care. J. Midwifery Womens Health 58(6), 697-701 (2013). 92. Wong S, Ordean A, Kahan M. Substance use
in pregnancy. J. Obstet. Gynaecol. Can. 33(4), 367–384 (2011). 93. Ebner N, Rohrmeister K, Winklbaur B et al.
Management of neonatal abstinence syndrome in neonates born to opioid maintained women. Drug Alcohol Depend. 87(2–3), 131–138 (2007). 94. Kraft WK, Van Den Anker JN.
Pharmacologic management of the opioid neonatal abstinence syndrome. Pediatr. Clin. North Am. 59(5), 1147–1165 (2012). 95. Hudak ML, Tan RC; Committee On Drugs,
Committee On Fetus and Newborn,
future science group
American Academy Of Pediatrics. Neonatal drug withdrawal. Pediatrics 129(2), e540–e560 (2012). 96. Sarkar S, Donn SM. Management of neonatal
perspective
and newborn neurobehavior. Pediatrics 111(6 Pt 1), 1318–1323 (2003). 102. Pichini S, Garcia-Algar O. In utero exposure
abstinence syndrome in neonatal intensive care units: a national survey. J. Perinatol. 26(1), 15–17 (2006).
to smoking and newborn neurobehavior: how to assess neonatal withdrawal syndrome? Therap. Drug Monitor. 28(3), 288–290 (2006).
97. Fried PA, Makin JE. Neonatal behavioural
103. Adams ED, Bianchi AL. A practical approach
correlates of prenatal exposure to marihuana, cigarettes and alcohol in a low risk population. Neurotoxicol. Teratol. 9(1), 1–7 (1987). 98. Eyler FD, Behnke M, Garvan CW,
Woods NS, Wobie K, Conlon M. Newborn evaluations of toxicity and withdrawal related to prenatal cocaine exposure. Neurotoxicol. Teratol. 23(5), 399–411 (2001). 99. Behnke M, Smith VC, Committee on
Substance Abuse, Committee On Fetus and Newborn. Prenatal substance abuse: short- and long-term effects on the exposed fetus. Pediatrics 131(3), e1009–e1024 (2013). 100. Godding V, Bonnier C, Fiasse L et al. Does
in utero exposure to heavy maternal smoking induce nicotine withdrawal symptoms in neonates? Pediatric Res. 55(4), 645–651 (2004). 101. Law KL, Stroud LR, Lagasse LL, Niaura R,
to labor support. J. Obstet. Gynecol. Neonatal Nurs. 37(1), 106–115 (2008). 104. Hodnett ED, Lowe NK, Hannah ME et al.
Effectiveness of nurses as providers of birth labor support in North American hospitals: a randomized controlled trial. JAMA 288(11), 1373–1381 (2002). 105. Payant L, Davies B, Graham ID, Peterson
WE, Clinch J. Nurses’ intentions to provide continuous labor support to women. J. Obstet. Gynecol. Neonatal Nurs. 37(4), 405–414 (2008). 106. Floyd RL, Jack BW, Cefalo R et al.
The clinical content of preconception care: alcohol, tobacco, and illicit drug exposures. Am. J. Obstet. Gynecol. 199(6 Suppl. 2), S333–S339 (2008). 107. Keegan J, Parva M, Finnegan M, Gerson A,
Belden M. Addiction in pregnancy. J. Addict. Dis. 29(2), 175–191 (2010).
Liu J, Lester BM. Smoking during pregnancy
Women's Health (2014) 10(2)
177
