Psychopharmacology and Pregnancy: Treatment Efficacy, Risks, and Guidelines 2014

12. Management of Substance Abuse in Pregnancy: Maternal and Neonatal Aspects

Laura Brandt , Anna K. Leifheit , Loretta P. Finnegan2, 3   and Gabriele Fischer 

(1)

Center for Public Health, Medical University of Vienna, Vienna, Austria

(2)

Finnegan Consulting, LLC, Avalon, NJ, USA

(3)

Office of Research on Women’s Health, National Institutes of Health, Bethesda, MD, USA

(4)

Department of Psychiatry and Psychotherapy & Center for Public Health, Medical University of Vienna, Vienna, Austria

Laura Brandt (Corresponding author)

Email: laura.brandt@meduniwien.ac.at

Anna K. Leifheit

Email: anna.leifheit@meduniwien.ac.at

Loretta P. Finnegan

Email: finnegal337@aol.com

Gabriele Fischer

Email: gabriele.fischer@meduniwien.ac.at

12.1 Substance Abuse/Dependence in Pregnant Women

12.1.1 Prevalence of Substance Use Among Pregnant Women

12.1.2 Psychiatric Co-morbidity

12.1.3 Costs

12.1.4 Treatment

12.2 Neonatal Abstinence Syndrome

12.2.1 Aetiology

12.2.2 Symptoms

12.2.3 Assessment

12.2.4 Treatment

12.3 Conclusion

References

Abstract

In Europe, the USA and Australia the prevalence of smoking during pregnancy ranges between 10 and 27 %. Drinking alcohol is reported by 8.5–19.5 % of pregnant women, with a potentially significant number of unreported cases. Additionally, there are as many as 60,000–100,000 pregnant women using illicit drugs per year, with a high percentage of poly-drug users. Substance-dependent women have a high incidence of co-morbid psychiatric disorders, with DSM-IV axis I affective and post-traumatic stress as well as axis II personality disorders being the most frequent co-morbidities. Due to serious consequences of licit and illicit substance use during pregnancy as well as undetected/untreated psychiatric co-morbidities, the primary focus must be on adequate diagnostic assessment. Treatment, tailored individually to the kind of substance dependence and under consideration of evidence-based treatment options available as early as possible during pregnancy, leads to better pregnancy outcomes and fewer birth complications. Neonates born to mothers who are chronic illicit drug users or provided maternal medication-assisted treatment frequently develop a Neonatal Abstinence Syndrome (NAS). Pharmacological NAS treatment should be provided based on principles of accurate assessment and diagnosis, with non-pharmacological measures such as rooming-in being vital supportive interventions. The economic burden of substance dependence during pregnancy and related follow-up costs are significant. To lower societal costs and increase the quality of life of both mothers and children, international treatment standards, building on previous recommendations, must be established and implemented.

Keywords

Substance use disorderPregnancyNeonatal abstinence syndromeOpioidsPsychiatric co-morbidityCostsTreatment

12.1 Substance Abuse/Dependence in Pregnant Women

Since the childbearing ages encompass the years of 15–44, many young women who are misusing substances will become pregnant and deliver a drug-exposed newborn. The stigma of substance use and pregnancy are a combination that is difficult for young women. The result may be avoidance of prenatal care and substance abuse treatment. A healthy mother and baby are more probable when prenatal care is elected providing recognition and treatment of any medical or obstetric complications that may arise during pregnancy. Good prenatal care by physicians knowledgeable in treating high-risk pregnancies can stabilise the pregnant woman and provide appropriate measures for the health of the foetus and newborn. Certain medical conditions in the pregnant woman can influence the infant’s outcome. For example, infection in the mother may cause neonatal infection with pneumonia; hypertension in the mother influences foetal growth; sexually transmitted diseases in the mother can cause infection in the infant; pre-eclampsia in the mother can cause growth restriction, preterm birth or foetal death in the infant; placental abruption or insufficiency in the mother can cause foetal distress, growth restriction or foetal death of the infant; and preterm delivery in the mother will result in an immature low-birth-weight infant who may suffer respiratory distress or intracranial haemorrhage with the potential of long-term developmental problems and disabilities.

Pregnant substance misusing young women may have psychiatric illnesses, histories of physical and/or sexual abuse, family dysfunction and low frustration tolerance coupled with a chaotic lifestyle. These issues predispose the newborn to the potential for serious outcomes including ineffective/poor parenting, failure to thrive, child neglect, child abuse, abandonment and death.

Within the delivery of the necessary services that should be provided to pregnant substance misusing young women, a comprehensive, multidisciplinary approach must be utilised in order to normalise the medical and psychological status of the mother and to ensure a better outcome for the newborn and child.

12.1.1 Prevalence of Substance Use Among Pregnant Women

Many epidemiological studies highlight that smoking tobacco, alcohol consumption and illicit substance abuse are increasing in women of childbearing age (De Santis et al. 2011). Even though consequences of licit drug use during pregnancy can be just as or even more severe than those of illicit drug use, prevalence rates are listed separately. Illicit drug use has special characteristics such as higher stigmatisation and legal consequences that influence the willingness to report use and seek help. Especially for Europe, data on the prevalence of substance use among pregnant women are often derived from isolated studies using various methodologies, and findings are not readily comparable (European Monitoring Centre for Drugs and Drug Addiction 2012). Thus, results have to be considered with caution and cannot simply be generalised.

For Europe, it has been estimated that 10–27 % of pregnant women smoke during pregnancy (European Medicine Agency 2007), whereas in the USA the prevalence was reported as 17.3 % (National Survey on Drug Use and Health 2007). US pregnant women were more likely to have smoked cigarettes during their first trimester (22.9 %) compared to second (14.3 %) and third (15.3 %) trimester (National Survey on Drug Use and Health 2007). According to estimates by the Australian Institute of Health and Welfare 11 % of women smoke during pregnancy. However, the proportion decreases to 7.7 % after women become aware of their pregnancy (National Drug Strategy Household Survey Report 2011).

The 2005 Comparative Risk Assessment Study reported that the pattern of pregnant women’s drinking in Europe is similar to estimates for the USA (Alcohol Consumption, Alcohol Dependence and Attributable Burden of Disease in Europe 2012). In the USA 8.5 % of pregnant women reported current alcohol use, 2.7 % binge drinking and 0.3 % heavy drinking (National Survey on Drug Use and Health 2012). In Australia, 47.3 % of pregnant women drank alcohol prior to the knowledge of their pregnancy and 19.5 % despite knowledge of their pregnancy. The drinking rate, despite knowledge of pregnancy, increases with age and socio-economic status. The majority (over 90 %) of those aged 25 and younger who were drinking prior to knowledge of pregnancy stopped drinking when they became aware of their pregnancy, but only half of those over 36 years of age stopped (National Drug Strategy Household Survey Report 2011).

There is little information on the prevalence of prescription drug use, especially the types of drugs prescribed to pregnant women. Daw et al. (2011) reviewed literature describing patterns of prescription drug use during pregnancy including mainly European studies (12 out of 17). They reported the lowest rates of prescription drug use for Northern European countries ranging from 44.2 to 57 % and the highest rates for the Netherlands (69.2 %), Germany (85.2 %) and France (93 %), excluding vitamins and minerals. However, the authors did not include information on particular therapeutic class. For a German sample of women who gave birth between 2000 and 2001 (n = 41,293), a prevalence of 0.2 % for antidepressant and 0.1 % sedative (benzodiazepines and barbiturates) prescription drug use during pregnancy was reported (Egen-Lappe and Hasford 2004). Based on data of the prospective, population-based Avon Longitudinal Study of Parents and Children (ALSPAC) 39.6 % of pregnant women with a delivery between 1991 and 1992 in Southwest England self-reported analgesic use during pregnancy (Headley et al. 2004). Andrade et al. (2004) provide information on the prevalence of prescription drug use among pregnant women in the USA. Among women who delivered in a hospital between 1996 and 2000 (n = 129,616) 2.8 % were prescribed antidepressants (1st trimester: 2.2 %, 2nd: 1.3 %, 3rd: 1.4 %), 1.3 % sedative hypnotics (1st trimester: 0.5 %, 2nd: 0.3 %, 3rd: 0.7 %) and 14.2 % opioid and non-opioid analgesics (1st trimester: 6.1 %, 2nd: 5.6 %, 3rd: 5.6 %). Information on prescription drug use among Australian pregnant women is limited and based on small sample sizes. Henry and Crowther (2000) reported a prevalence of 97.1 % total (including “over the counter” medication), 2.1 % antidepressant and 50 % analgesic prescription drug use during the first trimester among 140 women delivering at the Women’s and Children’s Hospital in Adelaide in 1999.

The number of European pregnant women using illicit drugs each year is estimated at 60,000 (Gyarmathy et al. 2009). In the USA the use of illicit drugs during pregnancy is known to affect over 100,000 women annually (Benningfield et al. 2010). The National Survey on Drug Use and Health (2013) showed that 5.9 % of US pregnant women aged 15–44 were current illicit substance users based on data averaged across 2011 and 2012, compared to 10.7 % of women in this age group who were not pregnant. For Australia, a prevalence rate of 8 % for illicit substance use among pregnant and breastfeeding women was reported (O’Donnell et al. 2009).

Each year there are as many as 30,000 pregnant women using opioids in Europe (Gyarmathy et al. 2009). For the USA in 2009, the rate of mothers being dependent on, or using opioids at the time of delivery, was 5.6 per 1,000 hospital life births, reflecting an almost fourfold increase compared to 2000 (1.19 per 1,000 hospital 130 births; Patrick et al. 2012). Australian data on opiate use during pregnancy are sparse and mainly reported within the illicit drug category and not listed separately. The prevalence of heroin use increased from 4 % in 1992 to 8 % in 1998 and declined to 2 % in 2001 (O’Donnell et al. 2009). However, it needs to be noted that 2001 is the year of the so-called Australian “heroin shortage” (Degenhardt et al. 2006). A more recent study examining obstetric and perinatal outcomes for women with a drug-related hospital admission during pregnancy in New South Wales (1998–2002) found 1974 records with an opioid ICD-10 diagnosis in a sample of 416,834 women (0.47 %; Burns et al. 2006).

As for the prevalence of cocaine use there are significant differences between countries due to vastly different drug markets. A European multi-centre and multi-modal project illustrated the diverse picture of cocaine use in Europe (Haasen et al. 2004). The 12-month prevalence rate shows an increase from 1990 to 2000/2001 in all studied countries but Sweden. Lifetime prevalence rates show a wide range with the lowest rates in Sweden (1.0 %) and the highest in the UK with 5.6 %. However, not even the highest rates reach anywhere near US rates with a far greater cocaine availability at a higher purity and lower price compared to Europe and Australia (United Nations Office on Drug and Crime 2013). Therefore, the prevalence rates of females aged 18–25 having used cocaine in the past month are higher in the USA with 5.5 % (Department of Health and Human Services 2006) compared to 2.3 % of females aged 20–29 in Australia (Australian Institute of Health and Welfare 2004–2005). For European pregnant women, a prevalence rate of 3.1 % based on meconium analysis is reported from the “Meconium Project” located in Barcelona, Spain. However, the study sample is not representative for the population of European pregnant women since it included mainly women with a low socio-economic status (Pichini et al. 2005). For the USA, the last national survey data were reported in 1992 with an estimated 1.1 % of women using cocaine during pregnancy (US National Institutes of Health 1992). A more recent study, analysing data from the nationally representative epidemiologic 2002 and 2003 National Survey on Drug Use and Health, found that only 0.3 % of pregnant women compared to 1.0 % of non-pregnant women of childbearing age used cocaine (Havens et al. 2009). For Australia, a study examining the consequences of drug use in Western Australian women found only four women reporting cocaine use during pregnancy in a sample of 911 pregnant women (Werler et al. 2003).

In substance use disorder (SUD), frequently, more than one licit or illicit substance is abused. For example, more than 90 % of opioid-dependent women smoke cigarettes (Fischer 2007). Thus, poly-substance use further complicates the adequate study of epidemiology and outcomes of SUD in pregnancy. In the UK, as an example for Europe, 17,856 pregnant women were screened for illicit drug use. Of the 168 (0.9 %) women who were identified to use illicit drugs during pregnancy, 61.3 % showed illicit poly-substance use and almost all women (97 %) used multiple drugs if alcohol and tobacco were included (Goel et al. 2011). In the USA, poly-substance use during pregnancy was reported in 6.1 % of the cases (defined as using at least two drugs including alcohol, cigarettes, marijuana, prescription analgesics, tranquilisers, sedatives, stimulants, cocaine, crack, heroin and methamphetamine; Havens et al. 2009). In South Australia, 89,080 women were screened for substance use in pregnancy and of the 707 (0.9 %) women reporting substance use, 18.8 % showed poly-substance use (including alcohol but not tobacco; Kennare et al. 2005).

In Table 12.1 all prevalence data on substance use in pregnancy for Europe, the USA and Australia are summarised. It is important to note that the table just serves as an overview and results are not readily comparable since methodologies and sample sizes of included studies differ significantly.

Table 12.1

Prevalence of substance use during pregnancy (EU, USA, Australia)

 

Europe

USA

Australia

Nicotine (% of women smoking during pregnancy)

10–27 %

European Medicines Agency (2007)

17.3 %

National Survey on Drug Use and Health (2007)

11 %

National Drug Household Survey Report (2011)

Alcohol (% of pregnant women)

Pattern of drinking was similar to estimates for the US

Comparative Risk Assessment Study (2005)

8.5 % alcohol use

2.7 % binge drinking 0.3 % heavy drinking

National Survey on Drug Use and Health (2012)

19.5 % alcohol use

National Drug Household Survey Report (2011)

Prescription drugs

% of pregnant women using any prescription drug

44.2–93 %

Daw et al. (2011)

97.1 %

Henry and Crowther (2000)

% of pregnant women using antidepressants

0.2 %

Egen-Lappe and Hasford (2004)

2.8 %

Andrade et al. (2004)

2.1 %

Henry and Crowther (2000)

% of pregnant women using sedatives

0.1 %

Egen-Lappe and Hasford (2004)

1.3 %

Andrade et al. (2004)

% of pregnant women using analgesics

39.6 %

Headley et al. (2004)

14.2 %

Andrade et al. (2004)

50 %

Henry and Crowther (2000)

Illicit drugs

Pregnant women using illicit substances per year (n)

% of pregnant women being illicit substance users

60.000

Gyarmathy et al. (2009)

0.9 %

Goel et al. (2011)

100.000

Benningfield et al. (2010)

5.9 %

National Survey on Drug Use and Health (2013)

8 %

O’Donnell et al. (2009)

Opioids

Pregnant women using opioids per year (n)

% of pregnant women using opioids

30.000

Gyarmathy (2009)

23.130a

Patrick et al. (2012)

0.56 %

Patrick et al. (2012)

0.47 %

Burns et al. (2006)

Cocaine (% of pregnant women being cocaine users)

3.1 %

Pichini et al. (2005)

0.3 %

Havens et al. (2009)

0.4 %

Werler et al. (2003)

Polysubstance use (% of pregnant women using ≥2 substances)

0.9 % (licit + illicit)

0.57 % (illicit)

Goel et al. (2011)

6.1 % (licit + illicit)

Havens et al. (2009)

0.15 % (alcohol + illicit)

Kennare et al. (2005)

aOwn calculations based on a total number of births in 2009 of 4,130,665 (Martin et al. 2011)

12.1.2 Psychiatric Co-morbidity

The Epidemiologic Catchment Area study (ECA; Regier et al. 1993), the National Comorbidity Study (NCS; Kessler et al. 1994) and the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Conway et al. 2006) are the most widely cited US studies on co-morbidity between SUD and psychiatric disorders. In the ECA an estimated 72 % of individuals with SUD had at least one co-morbid psychiatric disorder (Regier et al. 1993). Co-morbidity rates are higher in individuals who are dependent on illicit substances compared to alcohol-dependent individuals, while poly-substance use is associated with the highest rates of psychiatric co-morbidity (Kandel et al. 2001). The NCS found an odds ratio (OR) of 2.4 for co-morbidity between any lifetime psychiatric disorder and alcohol or SUD. Half of the NCS respondents with a lifetime alcohol or SUD also met criteria for at least one lifetime psychiatric disorder, while 50.9 % of the NCS respondents with a lifetime psychiatric disorder also had a history of alcohol or substance abuse or SUD (Kessler 2004).

Conway et al. (2006) present nationally representative data from the NESARC sample on DSM-IV lifetime mood and anxiety disorders and co-morbidity with SUDs. The associations between SUDs and psychiatric disorders for women compared to men are displayed in Table 12.2.

Table 12.2

Lifetime odds ratios of mood and anxiety disorders associated with substance use disorders (women compared to men; Conway et al. 2006)

 

Major depression

Mania

Any anxiety disorder

Women

Men

Women

Men

Women

Men

Any drug use disorder

3.6

3.4

6.7

5.6

2.9

3.0

 Abuse

2.6

2.3

4.0a

2.6

2.2

1.9

 Dependence

6.5

5.6

10.7

10.8

5.0

6.1

Opioid use disorder

6.0

4.9

9.5a

5.5

4.2

3.3

 Abuse

4.8

4.3

5.7

3.8

3.1

2.2

 Dependence

10.3

7.6

19.8

12.4

7.8

10.2

Cocaine use disorder

3.2

2.9

6.2

5.5

2.7

3.0

 Abuse

1.9

3.0

3.5

2.8

1.7

2.0

 Dependence

6.1

4.8

10.0

11.4

4.8

5.0

aSignificant gender differences (p < 0.05)

The majority of opioid-dependent women suffers from psychiatric co-morbidities (range between 56 and 73 %), mainly affective disorders, PTSD or personality disorders (Fitzsimons et al. 2007; Martin et al. 2009; Unger et al. 2010). Greenfield et al. (2010) found a 12-month prevalence of 29.7 % for mood and anxiety disorders among women with SUDs, with the most common disorder being major depressive disorder (15.4 %). In a study by Benningfield et al. (2010) 48.6 % of the subjects (n = 174 opioid-dependent women) reported symptoms of a mood disorder and 12.6 % suicidal thinking at some point in the past 30 days. The prevalence rate of depression (33 %) was consistent with results by Fitzsimons et al. (2007).

In the special population of pregnant women, depression is of major concern in clinical research, especially postpartum depression. Postpartum depression rates are reported between 10 and 15 % in the general population (Rogers et al. 2013). Postpartum depressive syndromes lead to the risk of suicide and in severe cases infanticide if not appropriately diagnosed and treated. Women with a history of depression before or during pregnancy and adolescents with a history of substance abuse constitute high-risk groups for postpartum depression (Pajulo et al. 2001). Low income and poor social support are additional risk factors (Clare and Yeh 2012). Mothers of preterm infants are at particular risk for postpartum depression with rates ranging from 14 to 27 % (Rogers et al. 2013). Holbrook and Kaltenbach (2012) analysed in a retrospective chart review 125 pregnant women enrolled in a comprehensive substance abuse treatment program. Almost one-third (30.4 %) of the women screened positive for moderate or severe depression at treatment entry. Nearly half of the sample (43.7 %) exhibited postpartum depression at 6 weeks post-delivery. The demographic variables were not related to the incidence of postnatal depression; only antenatal depression at treatment entry was a significant predictor for postpartum depression. Among opioid-dependent pregnant women, the high rate of unintended pregnancies (between 80 and 90 %; Heil et al. 2011) and socio-economic problems such as unemployment, co-addicted partners, and partner violence (Moore et al. 2011) can increase stress, with a close association between stress and maternal depression (Davis et al. 2007). Clare and Yeh (2012) found that postpartum depression is a challenging diagnosis and difficult to treat.

Selective serotonin reuptake inhibitors (SSRIs) (e.g. fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine) are the most frequently used drugs to treat depression both in the general population and in pregnant women, even though SSRIs and pharmacological interventions in pregnancy are poorly studied due to the problem of entering pregnant women in clinical trials (Nature Editorial 2010). The US Food and Drug Administration issued a warning on SSRIs during pregnancy in 2006 as a single study showed a potential risk of persistent pulmonary hypertension of the newborn (PPHN), a rare heart and lung condition. To date, new studies show conflicting findings, questioning if the use of SSRIs during pregnancy can cause PPHN. Thus, the current FDA advice is not to alter the current clinical practice of treating depression during pregnancy, but to report any adverse events involving SSRIs (FDA Drug Safety Communication 2011). This serves as an example that pharmacological treatment during pregnancy always must be based on a sound risk–benefit assessment. It is however evident that a multidisciplinary approach to depression in pregnant women is necessary to prevent potentially life-threatening consequences in mothers and their children (Clare and Yeh 2012). Furthermore, it is a crucial task of drug regulators to ensure that treating physicians are aware of gender differences in drug reactions and dosages (Nature Editorial 2010).

In addition to affective disorders, epidemiological data indicate that 3–59 % of substance-dependent women meet diagnostic criteria for post-traumatic stress disorder (PTSD) (Najavits et al. 1997). According to El-Bassel et al. (2005), 25–57 % of substance-dependent women are traumatised as victims of intimate partner violence (IPV). Stene et al. (2010) found that women exposed to IPV show higher rates of abusing psychotropic substances, even after adjusting for mental distress. They examined psychotropic substance use (hypnotics, anxiolytics and antidepressants) among women exposed to different forms of IPV (physical, sexual, psychological). Physical and/or sexual IPV was related to increased use of hypnotics, anxiolytics and antidepressants. Psychological IPV alone was associated with increased use of anxiolytics and antidepressants. After adjustments for mental distress the association persisted only for use of antidepressants. As for the substances used, many women suffering from PTSD are poly-drug users, but the most common substance involved in abuse is alcohol (Back et al. 2003). Back et al. (2003) examined the differences between women with co-morbid PTSD and cocaine dependence and women with co-morbid PTSD and alcohol dependence. Women in the alcohol/PTSD group showed higher rates of major depression and social phobia as well as stressful life events. In addition, the rate of avoidance and hyperarousal was higher in the alcohol/PTSD group. Women in the cocaine/PTSD group demonstrated greater occupational and social impairment.

Exploration of the association between SUD and personality disorders revealed that opioid dependence often co-occurs with borderline personality disorder (BPD). A literature review found a mean rate of 27 % of patients with any SUD meeting diagnostic criteria for BPD, with the highest rate for opioid abuse/dependence (18.5 %), followed by cocaine (16.8 %) and alcohol abuse/dependence (14.3 %) (Trull et al. 2000). BPD is diagnosed at higher rates among women compared to men in general clinical samples and among women with SUDs. BPD traits such as impulsivity and risk-taking behaviour may be associated with increased risk of unplanned pregnancies at a very young age, frequently resulting in abortions or miscarriage (De Genna et al. 2011). A study by De Genna et al. (2012) showed that women with BPD often become pregnant during the period when BPD symptoms emerge and intensify. These women are at increased risk of teenage and unintended pregnancies.

Another frequent co-morbid personality disorder in SUD patients is the antisocial personality disorder (ASPD). The prevalence of ASPD among injection drug users (IDU) is up to 75 %, but the majority of IDUs with ASPD are men (Havens et al. 2007). The literature suggests that DSM criteria for ASPD may lead to an underestimation of the prevalence of the disorder in women (Dolan and Vollm 2009). ASPD is associated with risk behaviour such as needle sharing and high-risk sexual behaviour. The consequences are significantly increased transmission rates of HIV, hepatitis C and hepatitis B virus. Emotional instability and impulsivity often occur as a consequence of stressful life events such as childbirth. Thus, pregnant substance-dependent women with ASPD constitute a highly vulnerable group in particular need of support (Havens et al. 2007).

In general, substance-dependent women with co-occurring psychiatric symptoms show poorer treatment outcomes with higher rates of illicit substance abuse (Fitzsimons et al. 2007), highlighting the need for early standardised diagnostic assessment and adequate treatment.

12.1.3 Costs

For Europe, substance dependence is the fifth most expensive disorder of the brain (psychiatric and neurologic disorders; Olesen et al. 2012). The European total annual costs of addiction are displayed in Table 12.3 and compared to other common disorders of the brain. Total European 2010 costs of disorders of the brain were estimated at €798 billion, with €65.7 billion for addictive disorders alone, composed of 37 % direct health-care costs, 23 % direct non-medical costs and 40 % indirect costs.

Table 12.3

European total annual costs of disorders of the brain (Olesen et al. 2012)

Disorder

Annual costs in billion € (2010)

Mood disorders

113.4

Psychotic disorders

93.9

Anxiety disorders

74.4

Stroke

64.1

Addictiona

65.7

aAlcohol and opioid dependence

In Europe, structured data on (long-term) childcare costs related to mothers’ licit and illicit substance use are sparse. Mangham et al. (2009) estimated for the UK costs of early delivery (before the 37th week of gestation), occurring in approximately 15 % of opioid-dependent women, with up to €466.250 per child. In the USA the mean annual costs of health care for children born with foetal alcohol syndrome (FAS) are US$2,842 per child/year. This is US$2,342 more than the annual average costs of care for a child without FAS (US$500). Prevention of FAS in one child would result in savings of US$128,810 in 10 years and US$491,820 in 20 years (Klug and Burd 2003). An investigation measuring trends and costs associated with Neonatal Abstinence Syndrome (NAS) between 2000 and 2009 reported that mean hospital charges per child diagnosed with NAS increased from $39,400 to $53,400 and charges for all other hospital births increased from $6,600 to $9,500 per child (Patrick et al. 2012). The length of hospital stay remained relatively unchanged for NAS during the study period (approximately 16 days) compared with a slightly increased length of stay for all other hospital births of approximately 3 days during the study period. With regard to national estimates, between 2000 and 2009, total hospital charges for NAS are estimated to have increased from $190 million to $720 million adjusted for inflation (Patrick et al. 2012).

12.1.4 Treatment

Treatment as early as possible during pregnancy leads to better pregnancy outcomes and fewer birth complications. Substance-dependent pregnant women are optimally treated in a multi-professional setting with treatment being tailored individually to the kind of substance dependence and under consideration of the evidence-based treatment options available (Metz et al. 2012).

For nicotine dependence, group therapy and cognitive behaviour therapy have shown to be effective in terms of smoking cessation during pregnancy (Windsor et al. 1998). Another psychosocial treatment option, Contingency Management (CM), is based on principles of operant conditioning (i.e. incentives are offered to encourage abstinence) and shows low dropout rates compared with other psychosocial interventions (Dutra et al. 2008). A Cochrane Review reported that CM for pregnant women increases smoking cessation rates significantly compared to other smoking cessation interventions (Lumley et al. 2009). CM interventions also show a positive impact on foetal growth, birth weight and breastfeeding duration (Higgins et al. 2012). Based on these results, pregnant patients with SUD and their offspring could benefit considerably by integration of CM into standard addiction treatment. Contingency Management has been mostly applied in research in the USA and in recent years a growing number of European studies have been published (Winklbaur-Hausknost et al. 2013). As for pharmacological interventions, Brose et al. (2013) examined whether the combination of nicotine replacement therapy (NRT, patch plus a faster acting form) is associated with a higher effect for smoking cessation in pregnancy. Compared with no medication, the use of a combination of nicotine patch and a faster acting form was associated with higher quitting rates, whereas single NRT showed no benefit. However, since NRT is not registered for use in pregnant women it should only be considered under close supervision.

For alcohol, an accurate and early diagnostic assessment not only of addiction, but any consumption during pregnancy, is vital. Alcohol can cause foetal developmental disorders even at the earliest stages of pregnancy while research indicates that binge drinking and regular heavy drinking put a foetus at the greatest risk for Foetal Alcohol Spectrum Disorders (FASD) (US National Institutes of health 1992). Several screening tools for alcohol abuse have been identified and validated for use in prenatal care. The most recently proposed brief and easy to use tool is the T-ACE 3 (Tolerance, Annoyed, Cut down, Eye opener), with high sensitivity and specificity in identifying risk drinking during pregnancy and predicting long-term neurobehavioral outcomes in exposed children. In the treatment of alcohol dependence an appropriate education about consequences of alcohol consumption is recommended (Kraigher et al. 2001). Due to the severe consequences of alcohol consumption on the foetus, abstinence has to be considered a primary goal in pregnant women. In heavy drinking women, detoxification must take place in an inpatient setting under close observation. Concomitant pharmacotherapy should be considered even at early stages of detoxification since elevated stress levels of the mother due to withdrawal pose a significant risk for the foetus. However, a risk–benefit assessment is necessary as pharmacological agents for treating withdrawal symptoms (e.g. benzodiazepines or clomethiazole) are also associated with risks for the foetus. If total abstinence cannot be considered a realistic therapeutic goal, reduction of alcohol intake should be the focus, since any reduction can be beneficial for foetal outcome (Heberlein et al. 2012). Brief interventions (one to three counselling-type sessions providing information and advice to alcohol users), which can be provided by health professionals and nursing staff, have been shown to significantly reduce alcohol consumption during pregnancy (Jones et al. 2013). Brief interventions during pregnancy show the largest effects in women with the highest initial consumption. Furthermore, the effects can be significantly enhanced if the partner is included (Chang et al. 2005).

Opioid maintenance therapy (OMT) is the current standard of care for opioid addiction, with proven efficacy in terms of reducing illegal substance use and increasing treatment retention. The first-line treatment for opioid-dependent pregnant women is OMT with methadone or alternatively with buprenorphine. Winklbaur-Hausknost et al. (2013) compared results of two double-blind, double-dummy, randomised controlled trials on comparison of buprenorphine and methadone [Pilot Study (PS) and European sample of the MOTHER trial (MT)] in opioid-dependent pregnant women. Both groups received vouchers for study attendance and completion of assessments; however, the MT group additionally received a CM intervention following an escalating design for drug-free urine samples. The results demonstrate that earlier treatment enrolment [MT: mean estimated gestational age (EGA) at enrolment week 18.4 vs. PS: mean EGA week 24.3] as well as an escalating incentive structure of CM interventions reduces illicit substance use during pregnancy. The number of opioid- and benzodiazepine-positive urine samples was significantly higher in the PS compared to MT (p = .03 and p < .001, respectively). Furthermore, the rate of preterm deliveries was increased in the PS (36 %) compared to MT (11 %) and similar results were found for dropout rates, with 10 % in MT compared to 22 % in PS. Even though both results were not significant, they are still clinically relevant, especially since the MT preterm delivery rate was very low and almost equal to general population rates of 5–9 % in most developed countries (Goldenberg et al. 2008). Unger et al. (2011) presented a unique case series investigating OMT with buprenorphine compared to methadone in opioid-dependent pregnant women using a within-subjects design. The results confirm effectiveness in terms of relapse prevention and safety of both medications for all three women and in both pregnancies. Treatment with buprenorphine resulted in a trend towards lower expression of NAS.

The importance of considering site-specific factors was highlighted by a study investigating site differences between MOTHER trial centres (Central Europe, rural US and urban US centres). Women in the urban US sites showed higher concomitant substance consumption and dropout rates compared to other centres and furthermore neonatal outcomes differed between sites (Baewert et al. 2012). Thus, it is important to not only consider medication aspects, but also environmental and cultural features in women’s treatment. The final medication decision during pregnancy has to be based on individual benefit ratio decisions, also considering the women’s previous experience, acceptance and tolerance of a particular medication to enhance treatment compliance and retention.

Treatment of opioid dependence with state-of-the-art OMT during pregnancy is associated with better pregnancy outcomes and fewer birth complications, representing an important aspect for long-term health-care system costs (Daley et al. 2001). Even though buprenorphine shows more favourable NAS outcomes, women should not be restricted to one medication, but have the choice between buprenorphine and methadone since both have been shown to be effective and safe treatment options (Unger et al. 2011).

12.2 Neonatal Abstinence Syndrome

Although hospitals around the world are experiencing increases in the number of newborns exposed to substances misused by their mothers, identifying the exact number of neonates born following intrauterine chronic exposure to opioids and other addicting agents has always been a challenging task. Contributing to this imprecision are, as demonstrated above, alterations in drug-taking patterns over time, marked variability in drug use patterns between individual hospitals and health-care facilities in an individual city and across countries and the use of many different agents at the same time, both licit and illicit. A study regarding the current extent of maternal drug abuse and its impact on the number of babies with NAS collected information on 7.4 million discharges from 4,121 hospitals in 44 of the 50 states in the USA between 2000 and 2009 (Patrick et al. 2012). Data from this study compared discharges for NAS versus all other hospital births in 2009. NAS was diagnosed at a rate of 3.39 per 1,000 hospital births per year. The investigators also found that newborns with NAS were 19 % more likely than all other hospital births to have low birth weight and 30 % more likely to have respiratory complications and also had feeding difficulties and seizures more often.

12.2.1 Aetiology

Neonates born to mothers who are chronic illicit opioid users or provided maternal medication-assisted treatment, such as methadone or buprenorphine, are frequently born with a passive dependency to those specific agents. However, many factors have been shown to be associated with the variability in the appearance of this syndrome. Because of their low molecular weight and lipid solubility, all of these drugs easily pass through the placenta from the mother to the foetus, which occurs at varying degrees, depending on the properties of the individual drugs. Once the drugs pass across the placenta and accumulate in the foetus, there is an equilibrium established between maternal and foetal blood. Disruption of the trans-placental passage of drugs at birth, when the umbilical cord is cut, terminates the drug supply to the baby with the potential of resulting in the development of symptoms of withdrawal or abstinence. This constellation of symptoms constitutes a multisystem disorder involving the central nervous system, gastrointestinal system, respiratory system and the autonomic nervous system, which is termed the NAS (Finnegan 1986).

NAS presents as a constellation of behavioural and physiological signs and symptoms that are remarkably similar in spite of marked differences in the properties of the causative agents. Drugs involved include opioids such as heroin, methadone, buprenorphine or prescription drugs (OxyContin, Percodan, Vicodin, Percocet and Dilaudid). Opioids produce the most dramatic effects of abstinence on both the mother and foetus. Other medications that may cause NAS are the sedative-hypnotics such as benzodiazepines (i.e. diazepam) and barbiturates. These agents have a longer half-life, and withdrawal may not start until after the infant has been discharged from hospital. Seligman et al (2008) studied the maternal variables predicting length of treatment for NAS in methadone-exposed newborns. Later gestational age and concomitant maternal benzodiazepine use were associated with longer treatment. This study demonstrates that maternal poly-drug abuse can increase the severity of NAS. SSRIs, alcohol and nicotine have also been implicated in producing symptoms of NAS (Finnegan 1976; Finnegan and Kandall 2004; Weiner and Finnegan 2011).

A newborn can also develop abstinence symptoms at birth if narcotic antagonists are administered in the delivery room. This can be followed by very severe and precipitous symptoms of neonatal abstinence. The type of analgesia and the anaesthesia that the mother receives can also influence the time of onset of NAS. Generally epidural anaesthesia causes fewer problems for the mother and baby (Finnegan and Kandall 2008).

Medications provided for the treatment of opioid dependence in pregnant women (methadone or buprenorphine), although providing many benefits to the maternal–foetal–newborn triad, also have the potential risk of abstinence in the newborn. Between 48 and 94 % of intrauterine opioid-exposed children develop a NAS (Osborn et al. 2010) with a lower incidence in buprenorphine-exposed (47 %) compared to methadone-exposed children (50–81 %; Jones et al. 2010a). Numerous studies have been reported regarding the dose of methadone and its effect on NAS. Some studies found that the greater the dose of methadone, the greater the severity of NAS resulting in physicians lowering the dose in the mother in order to decrease the severity of neonatal symptoms (Arlettaz et al. 2005; Lim et al. 2009; Madden et al. 1977). With inadequate doses of methadone, the women had a significant chance of relapse to heroin use. In contrast, there were an equal number of reports stating that there was no correlation between methadone dose and NAS severity (Dryden et al. 2009; Wouldes and Woodward 2010). This debate was settled when Cleary et al. (2010) did a meta-analysis comparing data from 67 studies (29 of which met the criteria for inclusion) to determine if there was a relationship between maternal methadone dose in pregnancy and the occurrence of NAS or the need for medical treatment in severe cases. From their results, they concluded that the severity of the NAS does not appear to differ according to whether mothers are on high- or low-dose methadone maintenance therapy. In addition, evidence-based studies show no association between NAS severity and trimester of methadone initiation, duration and amount of methadone exposure, duration of maternal drug use prior to pregnancy and no apparent relationship between maternal methadone dose (10–100 mg/day) and frequency or severity of abstinence-associated seizures (Berghella et al. 2003; Cleary et al. 2010; Herzlinger et al. 1977; Kaltenbach et al. 2012; Newman and Gevertz 2011).

For buprenorphine, NAS has been reported in varying degrees of severity and incidence. Many of the studies did not control for the use of other drug abuse concomitant with buprenorphine treatment. NAS occurrence was significant in those studies, which included other drug use; however, studies in Austria and the USA showed minimal abstinence symptoms from buprenorphine alone. A well-controlled clinical trial (The MOTHER Study) compared the differences between the occurrence and severity of NAS from methadone and that from buprenorphine (Jones et al. 2010b). No significant differences between methadone and buprenorphine were found in overall rates of NAS needing treatment, peak NAS scores and head circumference. There was a reduction of severity of NAS in buprenorphine-exposed neonates defined as the total amount of morphine needed in mg, length of hospital stay and number of days for treatment of NAS. These three items are inter-related in that the more morphine that is needed, the longer the days for treatment and the hospital stay (Jones et al 2010b). In addition, differences were found between centres when categorising the sites as urban or rural American and the Central European site showing less differences between the NAS in buprenorphine versus methadone-exposed babies (Baewert et al. 2012).

Wachman et al. (2013) studied the association of OPRM1 and COMT single-nucleotide polymorphisms with length of hospital stay and treatment of NAS in order to determine if there is a link between genetics and the syndrome. Genes tied to addiction in adults may provide future answers for infants with NAS. Certain genes in their common form without variations are associated with a higher risk of opioid addiction in adults. This multi-centre US cohort study (Maine, Massachusetts, Texas & New York) enrolled 86 mother–child pairs exposed to methadone or buprenorphine and analysed their DNA. Infants with variation of the OPRM1 gene were in the hospital 8.5 days less than those without the variation with a higher chance of not needing treatment. With the COMT gene, babies were in the hospital 10.8 fewer days and had less treatment. Concomitant smoking or psychiatric drugs (SSRIs) put babies at greater risk for withdrawal symptoms. The eventual goal of this study is to identify the highest risk babies early, attempt to develop treatment strategies that will prevent some of the NAS and try to get the babies home sooner. The US National Institutes of Health is commencing a larger study regarding genes and their influence on NAS severity.

12.2.2 Symptoms

Smoking cigarettes is common in opioid-dependent women and, dependent on the dose, NAS symptoms can be enhanced by this dual addiction in pregnant women (Winklbaur et al. 2009). Infants who have been exposed to heavy nicotine concentrations in utero have been found to be more excitable and hypertonic and demonstrate more stress and abstinence signs (Neonatal Tobacco Syndrome; Law et al. 2003). Symptoms seen in alcohol-exposed babies are present in the first 24 h of life and are especially reported in those with Foetal Alcohol Syndrome features. The newborns exhibit irritability, tremors, seizures, opisthotonus and abdominal distension.

Antidepressants used in depressed pregnant women predispose their newborns to neurobehavioral symptoms. Central Nervous System signs (e.g. irritability, seizures), motor signs (e.g. agitation, tremors, hypertonia), respiratory symptoms (e.g. increased respiratory rate, nasal congestion) and gastrointestinal signs (e.g. emesis, diarrhoea, feeding difficulty), fever and hypoglycaemia may be manifested by infants exposed to SSRIs during the last trimester of pregnancy (Haddad et al. 2005). The onset of symptoms ranges from several hours to several days after birth and usually resolves by age 2 weeks. Symptoms are more commonly reported with fluoxetine and paroxetine exposure (Lund et al. 2009). A decrease in maternal SSRI use during the third trimester may lower the neonatal risk of developing NAS; however, this needs to be balanced against the harmful effects of depression during pregnancy.

After opioid exposure in utero most infants appear physically and behaviourally normal at birth with symptoms reported to appear shortly after birth and up to 2 weeks of age, but the majority are exhibited within the first 72 h of life (Finnegan 1991; Finnegan and Kandall 2004; Hudak and Tan 2012). Neonatal opioid abstinence is usually apparent within the first 24–72 h of life because most opioids are short-acting and not stored by the foetus in appreciable amounts. Methadone is longer acting and stored in foetal tissues; the occurrence, timing and severity of abstinence signs are therefore more variable. Acute symptoms may persist for several weeks, whereas subacute symptoms may persist for 4 to 6 months (Coyle et al. 2002; Franck and Vilardi 1995).

NAS resulting from opioid exposure in utero is described as a generalised disorder characterized by signs and symptoms of central nervous system hyperirritability, gastrointestinal dysfunction, respiratory and autonomic nervous system symptoms. Descriptions of the four major systems affected are as follows: central nervous system symptoms are most prominent in NAS and are those that bring a great deal of attention because of the considerable irritability seen in the babies. Tremors, those occurring when the infant is disturbed and those that occur when sleeping or in a quiet state, are associated with high-pitched cry, increased muscle tone, irritability, increased deep tendon reflexes and an exaggerated Moro reflex. An exaggerated rooting reflex and a voracious appetite manifested as sucking of fists or thumbs are common. When feedings are administered, the infants may have extreme difficulty because of an ineffectual and uncoordinated sucking and swallowing mechanism, all of which are mediated by the mid-brain (Finnegan 1986). Infants demonstrate gastrointestinal system symptoms with regurgitation, projectile vomiting and loose stools. Dehydration due to poor intake, coupled with increased losses from the gastrointestinal tract, may cause excessive weight loss, electrolyte imbalance, shock, coma and death. Timely and appropriate pharmacological control of abstinence, as well as provision of extra fluids and calories to offset both clinically apparent and insensible losses, is important in the management of these symptoms (Weinberger et al. 1986). Excessive secretions, nasal stuffiness, rapid respirations sometimes accompanied by chest retractions, intermittent cyanosis and apnea constitute the respiratory system symptoms (Finnegan 1980). Infants with acute heroin withdrawal were found to have increased respiratory rates, leading to hypocapnia and an increase in blood pH during the first week of life (Glass et al. 1972). Severe respiratory distress occurs most often when the infant regurgitates, aspirates and develops aspiration pneumonia, which is not often seen in the average NAS. Symptoms related to the autonomic nervous system include spontaneous generalised sweating, sneezing, yawning and skin colour changes (mottling). Increases in temperature and shedding of tears by the baby may occur, both of which increase water loss (Behrendt and Green 1972).

Babies exposed to cocaine in utero do not demonstrate typical abstinence symptoms. Neurobehavioral symptoms in cocaine-exposed babies include tremors, lethargy intermittent with irritability, abnormal cry patterns, poor sucking, hypertonia, abnormal sleep patterns and poor interactions with caretakers. These effects have been described by Askin and Diehl-Jones (2001) as neurotoxicity with under-aroused neurobehavioral function, but not a true NAS. Moreover, symptoms of irritability in these infants are difficult to separate in the context of other factors from which they suffer such as prematurity or prenatal exposure to other drugs concomitantly with cocaine such as heroin, alcohol and nicotine (Askin and Diehl-Jones 2001; Bada et al. 2002).

Maturity of the infant is an important issue when considering the onset of NAS. In full-term infants, the NAS onset is earlier, symptoms are more severe, treatment needs are greater and fewer seizures are observed. Preterm babies have a later onset and less severe symptoms (Doberczak et al. 1991; Doberczak et al. 1993). The reduced severity of abstinence in preterm babies could be due to either developmental immaturity of the central nervous system (immaturity of either dendritic ramifications, specific opiate receptors or neurotransmitter function) or reduced total drug exposure due to the shortened gestation.

There is great variability in the expression of abstinence symptoms in different newborns regarding onsetpattern and duration of symptoms. It has been suggested that the rate of decline in the newborns’ plasma level of the pharmacological agent from day 1 to 4 of life influences the severity of abstinence symptoms (in these studies the pharmacological agent was methadone; Doberczak et al. 1991; Doberczak et al. 1993; Rosen and Pippenger 1976). Basically, the faster a baby excretes the pharmacological agent, the sooner symptoms will occur and they will be more severe.

If not recognised and not treated, NAS can cause death of the infant from excess fluid losses, high temperatures, seizures, respiratory instability, aspiration of fluid into the lungs or cessation of breathing (Jones et al. 2010b). However, with the current medical knowledge concerning drug abuse in pregnancy and the care of the newborn, no infant mortality should occur as a result of NAS.

12.2.3 Assessment

An assessment tool permits an accurate evaluation of the signs and symptoms and the severity, avoids unnecessary treatment of mildly affected infants and provides a methodology for effective dosing and tapering of medications. A number of scoring tools have been developed and reported in the paediatric literature (Finnegan et al. 1975; Finnegan 1986; Green and Suffet 1981; Lipsitz 1975; Zahorodny et al. 1998). Recommended by the American Academy of Paediatrics for assessment of the baby who may develop NAS as a result of in utero exposure to opioids (Hudak and Tan 2012), the Finnegan Neonatal Abstinence Score is administered by the nursing staff to monitor the newborn for the onset, progression and diminution of NAS. The Finnegan Neonatal Abstinence Score rates the individual signs and symptoms assigning each a relative weight based on the relationship to newborn morbidity—the higher score of an item relates to more severe morbidity. Due to the undulating pattern of NAS, babies must be scored throughout the day at regular intervals. With severe symptoms, the infant is evaluated more frequently until stabilisation of the NAS occurs (Finnegan 1986). With the available inter-observer reliability manual and DVD for the Finnegan Neonatal Abstinence Score, a clinician should easily be able to assess opioid-exposed infants for the presence of abstinence signs and symptoms, implement appropriate examination techniques required to evaluate NAS, document clinical signs and symptoms of NAS and achieve a 90 % reliability with other examiners using the score. If individuals are properly trained and inter-rater reliability is achieved, the score becomes a valuable objective measure to assess the onset, progression and diminution of symptoms of abstinence (D’Apoliti and Finnegan 2010).

Assessment for other neonatal conditions should also be considered since the symptoms of NAS can mimic such conditions as septicaemia, encephalitis, meningitis, post-anoxic CNS irritation, hypoglycaemia, hypocalcaemia and cerebral haemorrhage, for all of which the infant born to the substance misusing woman is at risk, especially because of maternal infections and preterm birth.

12.2.4 Treatment

Routine prophylactic pharmacological treatment is not recommended for NAS since not all drug-exposed newborns experience abstinence symptoms; however, it is very important to closely observe the newborns for symptoms that may occur over the first 4–5 days of life. Treatment should be provided based on principles of accurate assessment and diagnosis. The diagnosis should be confirmed by maternal history of opioid use and a urine or meconium toxicology screen.

Routinely in hospital, the opioid-exposed baby is usually separated from the mother, admitted for observation in a quiet, dimly lit environment, or more likely to a Neonatal Intensive Care Unit (NICU) and treated for abstinence, if necessary. Separation from the mother and sensory deprivation have not been studied as independent predictors of improvement in NAS; however, separation may contribute to increased abstinence symptoms, decreased maternal attachment and neonatal abandonment. It has been hypothesised that rooming in might promote more effective mothering and might reduce the prevalence and severity of NAS (Velez and Jansson 2008). Abrahams et al. (2007) studied rooming-in compared with standard care for newborns of mothers using methadone or heroin. Two groups were studied: newborns who roomed in with their mothers and those who received traditional care in the NICU. Results of this study revealed that newborns who roomed-in with their mothers were less likely to require treatment for NAS and more likely to be discharged home with their mothers using weight gain as treatment criteria. Later studies also showed that the incidence of treatment for NAS and the days in hospital were reduced when babies were rooming-in (RI) with their mothers (RI.11 %; NICU.45 %; RI.7 days; NICU.13 days; Hodgson and Abrahams 2012).

Metz et al. (2011) compared maternal and neonatal outcome of women in OMT (buprenorphine or methadone) throughout pregnancy in a randomised double-blind double-dummy clinical trial (CT: daily prenatal visits, assessment of NAS blinded for intrauterine medication exposure and mandatory rooming-in of mother and child after delivery) compared to a group undergoing structured standard protocol (SP: frequency of prenatal visits ranged on average between 2 and 3 per week). Newborns showed significantly better outcomes regarding NAS parameters for buprenorphine in both groups, but a lower total morphine dose administered and shorter length of hospital stay in the CT compared to SP group. These results refer to the benefit of rooming-in with mothers over the total NAS period in CT in addition to the blinded assessment of NAS as the treatment duration was much longer in SD with no significant differences (equivalently low rates) in structured maternal urine toxicology results between the groups.

Provision of supportive interventions, many of which are traditional methods of soothing a newborn infant, is important in the treatment of neonatal abstinence. Some of these supportive interventions include offering a pacifier (Non-Nutritive Sucking), skin to skin contact with the mother, swaddling snugly with hands available for sucking, not overdressing the baby, aspiration of the naso-pharynx, feeding of small amounts frequently (every 2h) if poor feeding persists without overfeeding and finally, positioning baby to right side-lying to reduce aspiration if vomiting or regurgitation is a problem (Weiner and Finnegan 2011). Although there is much that we still need to explore concerning the treatment of NAS, what we do know will provide comfort for the baby and decrease the chances of associated complications such as aspiration pneumonia, dehydration and seizures (Finnegan 1986; Unger et al. 2013). Using supportive care will enhance the baby’s ability to feed normally, gain weight and permit adequate sleep (Finnegan and Kandall 2004).

Another issue that has been explored is whether maternal breast feeding can influence neonatal abstinence expression in view of the fact that very small quantities of methadone and buprenorphine have been detected in breast milk samples (McCarthy and Posey 2000). Methadone is detected in breast milk, but at very low levels. The ratio of breast milk to maternal blood plasma concentrations was found to range from 0.05 to 1.2 (McCarthy and Posey 2000; Wojnar-Horton et al. 1997). Buprenorphine is also detected in breast milk with a maternal blood plasma ratio which approximates one. Buprenorphine is not absorbed well by mouth so the infant is exposed to 1/5 to 1/10 of the total amount available in the breast milk. Absorption of buprenorphine from the breast milk is much less than other opioids (Johnson et al. 2001). Therefore, breast feeding in methadone- or buprenorphine-treated mothers who express an interest in doing so is recommended providing that they are HIV negative, are compliant with their treatment plan and do not use other licit or illicit drugs (Gynaecologists ACoOa Committee Opinion 2012; Paediatrics AAo Policy Statement 2005) since it supports mother–child attachment.

Pharmacological treatment is provided according to the severity of the score which monitors the infant’s clinical response to medication and the amount necessary to control the symptoms, followed by progressive tapering of the dose. Clinicians should provide an opioid medication in the treatment of NAS using a titration method to increase the dose (in mg/kg) according to severity of the scores. Prompt escalation of dose, with aggressive decreases in dose as symptoms abate, are essential principles. Specific medications generally administered for neonatal abstinence from opioids include oral morphine or tincture of opium or methadone according to body weight and score (Osborn et al. 2010). Morphine drops were proven to be superior to other medications (Ebner et al. 2007). Clonidine is used infrequently and is not a first-choice medication. Sublingual administration of buprenorphine has been studied in the treatment of neonatal abstinence and a dose schema has been developed (Anagnostis et al. 2011; Kraft et al. 2011). In the UK 94 % and in the USA 83 % of physicians use morphine or methadone to treat neonatal opioid abstinence (Hudak and Tan 2012). With abstinence syndrome from other substances (e.g. barbiturates, ethanol, sedatives hypnotics), phenobarbital is generally administered.

The development of the infant who has experienced NAS is always of concern. Although many will predict a guarded prognosis for future development of infants who have experienced NAS, it is a transient and treatable condition and, within a stable environment, NAS per se should not influence outcomes. Many wish to implicate the exposure of a particular pharmacological agent, illicit or treatment opioid; however child development is related to multi-factorial issues with the environment in which the child exists and poverty amongst the myriad of influences. Through appropriate recognition, assessment and treatment of NAS coupled with good orientation of the future caretaker, we can better assure a nurturing, healthy environment for the child with a good chance of normal developmental outcomes.

12.3 Conclusion

This chapter provides an overview of the prevalence, consequences and treatment of substance use and related disorders in pregnant women and their neonates. Due to the lack of comparable structured data from Latin America and Africa these regions could not be included, which poses a limitation.

The data and results described above highlight the complexity of substance dependence during pregnancy. Affected women constitute a highly vulnerable group of patients with multiple psychiatric co-morbidities. Co-morbid disorders need to be recognised and treated adequately, since poor prognosis is expected if treatment fails to address both. Optimally managed substance-dependent pregnant women should receive treatment individually tailored to the kind of substance dependence and psychiatric co-morbidity that is being experienced. Initiation of a standardised diagnostic process and treatment of SUD and co-morbidities as early as possible leads to better pregnancy outcomes. Neonates have to be observed closely since between 48 % and 94 % of intrauterine opioid-exposed children develop a NAS. Collective randomised controlled trials, prospective and retrospective data show a less severe NAS for buprenorphine compared to methadone exposure in utero. However, it is of utmost importance that NAS is not used as criteria for selection of OMT. NAS is an easily identifiable and treatable condition that is only one aspect of the complete risk: Benefit ratio decisions have to be considered individually for every patient when making medication decisions during pregnancy. Pharmacological NAS treatment should be provided based on principles of accurate assessment and diagnosis and successful non-pharmacological measures as rooming-in should be considered for integration into standard clinical care. The most important outcome measure for treatment success is the well-being of both mother and child, which can be achieved by a diversification of treatment (i.e. the option of both buprenorphine or methadone for opioid dependence treatment) as well as special treatment options (e.g. CM) and standards of care resulting in superior maternal and neonatal outcomes. Furthermore, all intervention measures that prolong the pregnancy, prevent preterm delivery and shorten the duration of hospital stay also lead to a decrease in societal costs.

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