A C TA Obstetricia et Gynecologica
AOGS S H O R T RE S E A R CH RE P OR T
Prevalence of substance abuse in pregnancy among Danish women NETE L.K. RAUSGAARD, INGE O. IBSEN, JAN S. JØRGENSEN, RONALD F. LAMONT & PERNILLE RAVN Department of Gynecology and Obstetrics, University of Southern Denmark, Odense University Hospital, Odense, Denmark
Key words Amphetamine, benzodiazepines, cannabis, cocaine, methadone, methamphetamine, opiates, pregnancy, prevalence, substance abuse Correspondence Pernille Ravn, Department of Gynecology and Obstetrics, OUH - Odense University Hospital, Sdr. Boulevard 29, Indgang 55, 5000 Odense C, Denmark. E-mail: [email protected] Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
Abstract There are few recent data on the prevalence of substance abuse among Danish pregnant women. During 2013, in the Region of Southern Denmark, a crosssectional, anonymous, screening-based study was conducted among pregnant women attending for routine ultrasound scan at 12 weeks gestation. The women submitted a urine sample and completed a short questionnaire. Urine samples were tested for opiates, cannabis, benzodiazepines, cocaine, methadone, amphetamine and methamphetamine. Positive samples underwent repeat analysis for confirmation. Of 690 pregnant women, 88.1% participated. Overall, 3.6% of women had a positive urine sample confirmed by repeated analysis. The age distribution in women with positive samples did not differ from the entire cohort. Our findings indicate a larger prevalence than anticipated, and that a substantial number of pregnant women with substance abuse are not appropriately referred to the focused specialist center for such women at risk.
Please cite this article as: Rausgaard NLK, Ibsen IO, Jørgensen JS, Lamont RF, Ravn P. Prevalence of substance abuse in pregnancy among Danish women. Acta Obstet Gynecol Scand 2015; 94: 215–219. Received: 18 July 2014 Accepted: 13 October 2014 DOI: 10.1111/aogs.12528
Introduction Substance exposure can cause malformations as well as more subtle damage and development of functional central nervous system disorders (1–5). However, it is difficult to determine the exact causal relation between prenatal substance exposure and perinatal outcomes. The interaction of different risk factors is often complex, making analysis of individual risk factors very difficult and leaving ample room for residual confounding, even when attempts are made to adjust for confounding. The effects may be the result of concomitant abuse of other substances such as tobacco and alcohol, genetics, inadequate antenatal care, malnutrition and infection. Worldwide,
there is a paucity of information on the prevalence of substance abuse among pregnant women. Existing studies including a Danish study conducted in 1998 are based on self-reported substance abuse (6), and the true prevalence remains unknown. The Pompidou Group has estimated the prevalence of substance abuse among pregnant women in Europe to be approximately 4% (7). In the USA, the Substance Abuse and Mental Health Services Administration and the National Institute on Drug Abuse found that self-reported prevalence rates of substance abuse among pregnant women was 4–5% overall and 20.9% among 15–17-year-olds (1,2,8–10). The Danish Health and Medicines Authority recommends complete avoidance of alcohol during pregnancy. Denmark has an
ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 94 (2015) 215–219
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efficient, free health-care system with a very high participation rate in antenatal care that offers an open atmosphere with an inclusive approach to substance abuse without reprisal. Accordingly, the majority of pregnant women who engage in substance abuse should be identified. The Family Center of Denmark was established to focus obstetric care on women with substance abuse during pregnancy (prescribed or illegal) and arranges followup of affected children until school age. Due to the lack of information on the prevalence, the assumptions which contributed to the setting up of the Family Center of Denmark were that 1–3% of pregnant women in the region would need support because of substance abuse by pregnant women or their partners. With respect to illegal substances, all pregnant women with present or previous abuse (in the last 2 years) are referred to the Family Center. As regards alcohol, pregnant women are referred if they have had two or more episodes of binge drinking, or consume more than three alcoholic drinks/week during their pregnancy (15 mL or 12 g of pure alcohol). In this context, use of addictive substances or alcohol according to these definitions is considered a possible abuse. The aim of the study was to establish the prevalence and age distribution of substance abuse during pregnancy and whether our base estimates for the Family Center of Denmark were accurate.
Material and methods Urinary screening for substance abuse took place at haphazardly chosen dates between January and May 2013, at the time of the 12-week ultrasound scan, voluntarily and anonymously, in eight hospital antenatal clinics in the Region of Southern Denmark (Odense, Svendborg, Kolding, Esbjerg, Sønderborg, Haderslev, Vejle and Fredericia). Three of the centers joined towards the end of the study. The survey was anonymous to ensure a high participation rate. However, the anonymity meant that we could not analyze reasons for participation refusals. Over time, recruitment practice changed as we gained experience and modified our approach to recruitment. Urine samples were analyzed for the following substances: opiates, cannabis, benzodiazepines, amphetamine, methamphetamine, cocaine and methadone. The urine samples were screened using AccuSign-DOA7 (urine stick analysis; Ferle Produkter Aps, Hellebæk, Denmark). AccuSignDOA7 is an immunochromatographic test for the rapid detection of substances and/or their metabolites. Positive AccuSign samples were sent for diagnostic confirmation by gas chromatography/mass spectrometry (or liquid chromatography/mass spectrometry in the case of benzodiazepines) to confirm that the tested substance was the cause of the positive result (Instruments: Waters and
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Figure 1. Distribution of substances in screen positive samples.
Agilent, Trollh€atten, Sweden). Self-reported data on medication use were used to explain cross-reacting substances. EXCEL (Microsoft Corp., Redmond, WA, USA) was used for data analysis and statistical evaluation. The twotailed t-test was used to test mean values with different variances to compare the age of pregnant women with confirmed samples compared with the mean age of the total cohort. Results were presented as the mean of the difference with standard deviations and p-value. The age distribution was presented with standard error or confidence interval. Statistical significance was set at p < 0.05. Ethical approval was granted by the Local Ethics
Figure 2. Distribution of substances in confirmed positive samples.
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Figure 3. Age distribution of all women included (n = 609) and of pregnant women with confirmed positive samples (n = 21) as a percentage. Error bars show standard error of the proportion. There was no reported age on one pregnant woman with a sample confirmed positive for morphine. It should be noted that the number of included women in the calculation of the age distribution does not match the number of those included in the calculation of the prevalence (609 vs. 608). Some submitted a urine sample but did not fill in questionnaires, or vice versa. If a urine sample was submitted, this was included in the calculation of prevalence despite the lack of completed questionnaire. If age was reported, this was included in the calculation of age distribution despite the lack of a urine sample.
Committee (21 December 2012), who characterized the study as a quality control project and therefore not requiring notification to the Data Protection Agency.
Results Of 690 pregnant women who attended for ultrasound scan, 608 (88.1%) provided a urine sample. A total of 42 urine samples were positive on AccuSign (33 for opiates; four for cannabis; two for benzodiazepines; two for amphetamine; and one for methamphetamine) (Figure 1). No one tested positive for more than one substance. Of screened samples positive for opiates and cannabis, 19 of 33 were subsequently diagnosed as positive for opiates and three of four for cannabis (Figure 2). The 19 screening samples confirmed positive for opiates contained morphine rather than codeine. The remaining 20 samples positive at screening but not confirmed as positive, can only be explained by ingestion of unknown or not reported cross-reacting substances. None of the screening tests positive for benzodiazepines, amphetamine or methamphetamine was confirmed positive, and no urine samples were positive for cocaine or methadone. Accordingly, the 22 urine samples confirmed as positive corresponded to a prevalence of 3.6%. Only two of the pregnant women with positive AccuSign-DOA7 samples reported medication use. One had a positive AccuSign-DOA7 for benzodiazepines, which was
not confirmed; she reported the use of antidepressants, migraine medications, and sleeping pills. This suggests that the positive test result was due to cross-reaction with the self-reported medication. The other woman had a positive AccuSign-DOA7 for opiates, which was confirmed positive for morphine. She reported the use of lamotrigine, but this cannot explain the result, as lamotrigine is not a cross-reacting substance. Maternal age was normally distributed (Figure 3). The mean age of pregnant women with confirmed positive samples was not significantly different from the mean age of all included women [29.5 (SD = 5.6) years vs. 29.8 (SD = 5.2) years, respectively, p = 0.83]. However, pregnant women with confirmed positive samples accounted for 8.7% of all pregnant women aged 40–42 years, and there were no pregnant women with confirmed positive samples in the age groups 16–18 years, 34–36 years or 43–44 years (data not shown).
Discussion This study, which we look upon as a pilot study, found (i) an overall prevalence of substance abuse among pregnant women of 3.6% and (ii) that the age of pregnant women with confirmed positive samples was not significantly different from the age of the entire cohort. This indicates that substance abuse is evenly distributed across age groups. Our study did not include tobacco or alcohol, which are the most commonly abused substances in Denmark. Accordingly, the true prevalence of substance abuse among pregnant women is probably higher. The overall prevalence found in this study of 3.6% was above the anticipated 1–3% estimated for the Family Center. The prevalence of cannabis abuse was lower than self-reported in the Danish study from 1998 (0.5 vs. 1.2%), but the prevalence of abuse of other substances was much higher (3.1 vs. 0.0%) (6). The results are not easily comparable, as we used objective measurements and only took seven substances into account, whereas the 1998 study used self-report by interview and took an unspecified number of substances into account. However, the comparison indicates that substance abuse is underreported by self-reporting, apart from cannabis abuse, which we found to be lower in our study. Another explanation for the difference in prevalences could be that there has been a change in the abuse of substances between 1998 and 2013. Although throughout the study we use the term substance abuse rather than the more adequate term substance use, many pregnant women may use substances (such as painkillers) that can be harmful to the fetus without their use being defined as substance abuse. The term abuse is predominantly used in larger studies and
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has technical implications in the published literature. However, the term use is preferred in Danish clinical practice as a means of preventing stigmatization of pregnant women. Accordingly, we recommend an increased focus on the use of the words use and abuse. Women were invited to participate at the time of their 12-week ultrasound scan. Accordingly, our data provided a snapshot of self-reported substance abuse at that time, and did not reflect what may have happened later in pregnancy. Three of the centers joined the study towards the end of the study period, and from lessons learned in the earlier part of the study, the rate of participation increased across all centers in the latter part of the study period, and the rate of positive samples rose from 3.0 to 5.1% (data not shown). Had we employed the same recruitment practices across the cohort, we were likely to have found an even higher prevalence than 3.6%. The possible influence of seasonal variation remains undetermined. The survey was anonymized to maximize the participation rate, which hindered analyses of reasons for refusals. However, we consider that there is a significant risk that pregnant women who practice substance abuse, those with pregnancy complications, or those lacking confidence in anonymity might refuse to participate in the screening process due to fear of consequences. Our results do not include pregnant women who do not attend antenatal care or who have already been referred to the Family Center. Thus, our results may underestimate the true prevalence of substance abuse. Although in an anonymous survey, we would not expect tampering (dilution or exchange of urine samples), we did measure concentrations of creatinine in the samples to control for dilution, and found that all urine samples were reliable. The AccuSign-DOA7 is a preliminary and qualitative test with specificities of 98.6–99.9% for the respective groups of substances. Accordingly, in accordance with the Danish Association of Clinical Biochemistry [Dansk Selskab for Klinisk Biokemi (DSKB)] guidelines, only positive samples were submitted for confirmation and quantitative analysis by the gas chromatography/mass spectrometry or liquid chromatography/mass spectrometry. The average confirmation rate in our study was 52.4% (data not shown), which is much lower than the reported sensitivity of 98% by the manufacturer. Only one sample was excluded due to an insufficient amount of urine for confirmation. The reason for the low confirmation rate remains unexplained, but based on our results, we must question the sensitivity and specificity of AccuSignDOA7. Currently, there is no consensus with respect to the method for urine screening for substance abuse in
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Denmark and in the Family Centers. We recommend that future studies screening for substance abuse should use consistently validated methods for urine analysis. The analgesic drug Kodimagnyl, which is not recommended for use during pregnancy, can be purchased over the counter in Denmark. Although its use cannot explain all the opiate cases, Kodimagnyl is a combination of aspirin and codeine, which can result in the degradation product morphine in urine when codeine is no longer measurable. Accordingly, it is possible that consumption of Kodimagnyl may have caused confirmed samples to test opiate-positive. According to the Statens Serum Institut (SSI, Copenhagen) Birth Statistics, the Family Center in Odense supported 0.8% of the pregnant population who gave birth in Odense (28 of 3520 mother and baby pairs) during 2012. However, this constitutes only 22% of the detected prevalence of 3.6%, which suggests that the current antenatal care system overlooks almost 80% of women with substance abuse in pregnancy. This was highly unanticipated due to our antenatal care system, where pregnant women with substance abuse should feel that they can get support and not reprisals by coming to light. US data indicate a prevalence of 4–5% (3–5,11) but these data are based on self-reported substance abuse, and the genuine prevalence is probably underestimated. Accordingly, we would encourage an increased focus on substance abuse particularly among pregnant women without apparent indicators of abuse. A recent review from our group demonstrated that no biological sample has the ability to identify all substance users, and each sample has different advantages and disadvantages. Accordingly, we concluded that continuous maternal selfreporting of abuse and repeated urine testing during pregnancy provides the most accurate record of substance abuse (Rausgaard NLK, Ibsen IO, Jørgensen JS, Lamont RF, Ravn P, in preparation). The implementation of such a strategy during antenatal care might help to break the habit of substance abuse. Unfortunately, screening may, in addition to ethical challenges, also cause a lower participation rate in antenatal care. Pregnant women who practice substance abuse may avoid antenatal care in general practice but are likely to attend for ultrasound scanning. Accordingly, we suggest that urine screening and maternal self-reporting of substance abuse should be implemented at the time of nuchal translucency ultrasound scanning at 12 weeks’ gestation. However, screening requires consistently validated urine test kits with high sensitivity. We recommend that the choice of substances for testing be considered. Pregnant women identified as substance abusers should be offered additional antenatal care and fetal monitoring to minimize maternofetal complications. When urine screening during preg-
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nancy is not available, other biological specimens from the mother, fetus or both can help to identify exposure (Rausgaard NLK, Ibsen IO, Jørgensen JS, Lamont RF, Ravn P, in preparation). Furthermore, increased surveillance, observation and specific treatment for exposed newborns are required, and family support should be optimized. Our study indicates that screening identifies more pregnant women with evidence of substance abuse than the existing focused, intermittent method of identification.
Funding Funding was through the Danish Foundation “Trygfonden”, J.nr. 3-12-0359 (foundation to increase safety, security and health in Denmark). References 1. Irner TB. Substance exposure in utero and developmental consequences in adolescence: a systematic review. Child Neuropsychol. 2012;18:521–49. 2. Keegan J, Parva M, Finnegan M, Gerson A, Belden M. Addiction in pregnancy. J Addict Dis. 2010;29:175–91. 3. Shankaran S, Lester BM, Das A, Bauer CR, Bada HS, Lagasse L, et al. Impact of maternel substance use during pregnancy on childhood outcome. Semin Fetal Neonatal Med. 2007;12:143–50.
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4. Bandstra ES, Morrow CE, Mansoor E, Accornero VH. Prenatal drug exposure: infant and toddler outcomes. J Addict Dis. 2010;29:245–58. 5. 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. 2013;131:e1009–24. 6. Kesmodel U, Kesmodel PS, Larsen A, Secher NJ. Use of alcohol and illicit drugs among pregnant Danish women, 1998. Scand J Public Health. 2003;31:5–11. 7. Brule C. The role of the Pompidou Group of the Council of Europe in combating drug abuse and illicit drug trafficking. Bull Narc. 1983;35:73–7. 8. Wong S, Ordean A, Kahan M. Substance use in pregnancy. J Obstet Gynaecol Can. 2011;33:367–84. 9. Hudak ML, Tan RC. Neonatal drug withdrawal. Pediatrics. 2012;129:540–60. 10. Minozzi S, Amato L, Vecchi S, Davoli M. Maintenance agonist treatments for opiate dependent pregnant women. Cochrane Database Syst Rev. 2008;16: CD006318. 11. ACOG Committee on Health Care for Underserved Women; American Society of Addiction Medicine. ACOG Committee Opinion No. 524: Opioid abuse, dependence, and addiction in pregnancy. Obstet Gynecol. 2012;119:1070–6.
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Prevalence of substance abuse in pregnancy among Danish women NETE L.K. RAUSGAARD, INGE O. IBSEN, JAN S. JØRGENSEN, RONALD F. LAMONT & PERNILLE RAVN Department of Gynecology and Obstetrics, University of Southern Denmark, Odense University Hospital, Odense, Denmark
Key words Amphetamine, benzodiazepines, cannabis, cocaine, methadone, methamphetamine, opiates, pregnancy, prevalence, substance abuse Correspondence Pernille Ravn, Department of Gynecology and Obstetrics, OUH - Odense University Hospital, Sdr. Boulevard 29, Indgang 55, 5000 Odense C, Denmark. E-mail: [email protected] Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
Abstract There are few recent data on the prevalence of substance abuse among Danish pregnant women. During 2013, in the Region of Southern Denmark, a crosssectional, anonymous, screening-based study was conducted among pregnant women attending for routine ultrasound scan at 12 weeks gestation. The women submitted a urine sample and completed a short questionnaire. Urine samples were tested for opiates, cannabis, benzodiazepines, cocaine, methadone, amphetamine and methamphetamine. Positive samples underwent repeat analysis for confirmation. Of 690 pregnant women, 88.1% participated. Overall, 3.6% of women had a positive urine sample confirmed by repeated analysis. The age distribution in women with positive samples did not differ from the entire cohort. Our findings indicate a larger prevalence than anticipated, and that a substantial number of pregnant women with substance abuse are not appropriately referred to the focused specialist center for such women at risk.
Please cite this article as: Rausgaard NLK, Ibsen IO, Jørgensen JS, Lamont RF, Ravn P. Prevalence of substance abuse in pregnancy among Danish women. Acta Obstet Gynecol Scand 2015; 94: 215–219. Received: 18 July 2014 Accepted: 13 October 2014 DOI: 10.1111/aogs.12528
Introduction Substance exposure can cause malformations as well as more subtle damage and development of functional central nervous system disorders (1–5). However, it is difficult to determine the exact causal relation between prenatal substance exposure and perinatal outcomes. The interaction of different risk factors is often complex, making analysis of individual risk factors very difficult and leaving ample room for residual confounding, even when attempts are made to adjust for confounding. The effects may be the result of concomitant abuse of other substances such as tobacco and alcohol, genetics, inadequate antenatal care, malnutrition and infection. Worldwide,
there is a paucity of information on the prevalence of substance abuse among pregnant women. Existing studies including a Danish study conducted in 1998 are based on self-reported substance abuse (6), and the true prevalence remains unknown. The Pompidou Group has estimated the prevalence of substance abuse among pregnant women in Europe to be approximately 4% (7). In the USA, the Substance Abuse and Mental Health Services Administration and the National Institute on Drug Abuse found that self-reported prevalence rates of substance abuse among pregnant women was 4–5% overall and 20.9% among 15–17-year-olds (1,2,8–10). The Danish Health and Medicines Authority recommends complete avoidance of alcohol during pregnancy. Denmark has an
ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 94 (2015) 215–219
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efficient, free health-care system with a very high participation rate in antenatal care that offers an open atmosphere with an inclusive approach to substance abuse without reprisal. Accordingly, the majority of pregnant women who engage in substance abuse should be identified. The Family Center of Denmark was established to focus obstetric care on women with substance abuse during pregnancy (prescribed or illegal) and arranges followup of affected children until school age. Due to the lack of information on the prevalence, the assumptions which contributed to the setting up of the Family Center of Denmark were that 1–3% of pregnant women in the region would need support because of substance abuse by pregnant women or their partners. With respect to illegal substances, all pregnant women with present or previous abuse (in the last 2 years) are referred to the Family Center. As regards alcohol, pregnant women are referred if they have had two or more episodes of binge drinking, or consume more than three alcoholic drinks/week during their pregnancy (15 mL or 12 g of pure alcohol). In this context, use of addictive substances or alcohol according to these definitions is considered a possible abuse. The aim of the study was to establish the prevalence and age distribution of substance abuse during pregnancy and whether our base estimates for the Family Center of Denmark were accurate.
Material and methods Urinary screening for substance abuse took place at haphazardly chosen dates between January and May 2013, at the time of the 12-week ultrasound scan, voluntarily and anonymously, in eight hospital antenatal clinics in the Region of Southern Denmark (Odense, Svendborg, Kolding, Esbjerg, Sønderborg, Haderslev, Vejle and Fredericia). Three of the centers joined towards the end of the study. The survey was anonymous to ensure a high participation rate. However, the anonymity meant that we could not analyze reasons for participation refusals. Over time, recruitment practice changed as we gained experience and modified our approach to recruitment. Urine samples were analyzed for the following substances: opiates, cannabis, benzodiazepines, amphetamine, methamphetamine, cocaine and methadone. The urine samples were screened using AccuSign-DOA7 (urine stick analysis; Ferle Produkter Aps, Hellebæk, Denmark). AccuSignDOA7 is an immunochromatographic test for the rapid detection of substances and/or their metabolites. Positive AccuSign samples were sent for diagnostic confirmation by gas chromatography/mass spectrometry (or liquid chromatography/mass spectrometry in the case of benzodiazepines) to confirm that the tested substance was the cause of the positive result (Instruments: Waters and
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Figure 1. Distribution of substances in screen positive samples.
Agilent, Trollh€atten, Sweden). Self-reported data on medication use were used to explain cross-reacting substances. EXCEL (Microsoft Corp., Redmond, WA, USA) was used for data analysis and statistical evaluation. The twotailed t-test was used to test mean values with different variances to compare the age of pregnant women with confirmed samples compared with the mean age of the total cohort. Results were presented as the mean of the difference with standard deviations and p-value. The age distribution was presented with standard error or confidence interval. Statistical significance was set at p < 0.05. Ethical approval was granted by the Local Ethics
Figure 2. Distribution of substances in confirmed positive samples.
ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 94 (2015) 215–219
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Figure 3. Age distribution of all women included (n = 609) and of pregnant women with confirmed positive samples (n = 21) as a percentage. Error bars show standard error of the proportion. There was no reported age on one pregnant woman with a sample confirmed positive for morphine. It should be noted that the number of included women in the calculation of the age distribution does not match the number of those included in the calculation of the prevalence (609 vs. 608). Some submitted a urine sample but did not fill in questionnaires, or vice versa. If a urine sample was submitted, this was included in the calculation of prevalence despite the lack of completed questionnaire. If age was reported, this was included in the calculation of age distribution despite the lack of a urine sample.
Committee (21 December 2012), who characterized the study as a quality control project and therefore not requiring notification to the Data Protection Agency.
Results Of 690 pregnant women who attended for ultrasound scan, 608 (88.1%) provided a urine sample. A total of 42 urine samples were positive on AccuSign (33 for opiates; four for cannabis; two for benzodiazepines; two for amphetamine; and one for methamphetamine) (Figure 1). No one tested positive for more than one substance. Of screened samples positive for opiates and cannabis, 19 of 33 were subsequently diagnosed as positive for opiates and three of four for cannabis (Figure 2). The 19 screening samples confirmed positive for opiates contained morphine rather than codeine. The remaining 20 samples positive at screening but not confirmed as positive, can only be explained by ingestion of unknown or not reported cross-reacting substances. None of the screening tests positive for benzodiazepines, amphetamine or methamphetamine was confirmed positive, and no urine samples were positive for cocaine or methadone. Accordingly, the 22 urine samples confirmed as positive corresponded to a prevalence of 3.6%. Only two of the pregnant women with positive AccuSign-DOA7 samples reported medication use. One had a positive AccuSign-DOA7 for benzodiazepines, which was
not confirmed; she reported the use of antidepressants, migraine medications, and sleeping pills. This suggests that the positive test result was due to cross-reaction with the self-reported medication. The other woman had a positive AccuSign-DOA7 for opiates, which was confirmed positive for morphine. She reported the use of lamotrigine, but this cannot explain the result, as lamotrigine is not a cross-reacting substance. Maternal age was normally distributed (Figure 3). The mean age of pregnant women with confirmed positive samples was not significantly different from the mean age of all included women [29.5 (SD = 5.6) years vs. 29.8 (SD = 5.2) years, respectively, p = 0.83]. However, pregnant women with confirmed positive samples accounted for 8.7% of all pregnant women aged 40–42 years, and there were no pregnant women with confirmed positive samples in the age groups 16–18 years, 34–36 years or 43–44 years (data not shown).
Discussion This study, which we look upon as a pilot study, found (i) an overall prevalence of substance abuse among pregnant women of 3.6% and (ii) that the age of pregnant women with confirmed positive samples was not significantly different from the age of the entire cohort. This indicates that substance abuse is evenly distributed across age groups. Our study did not include tobacco or alcohol, which are the most commonly abused substances in Denmark. Accordingly, the true prevalence of substance abuse among pregnant women is probably higher. The overall prevalence found in this study of 3.6% was above the anticipated 1–3% estimated for the Family Center. The prevalence of cannabis abuse was lower than self-reported in the Danish study from 1998 (0.5 vs. 1.2%), but the prevalence of abuse of other substances was much higher (3.1 vs. 0.0%) (6). The results are not easily comparable, as we used objective measurements and only took seven substances into account, whereas the 1998 study used self-report by interview and took an unspecified number of substances into account. However, the comparison indicates that substance abuse is underreported by self-reporting, apart from cannabis abuse, which we found to be lower in our study. Another explanation for the difference in prevalences could be that there has been a change in the abuse of substances between 1998 and 2013. Although throughout the study we use the term substance abuse rather than the more adequate term substance use, many pregnant women may use substances (such as painkillers) that can be harmful to the fetus without their use being defined as substance abuse. The term abuse is predominantly used in larger studies and
ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 94 (2015) 215–219
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has technical implications in the published literature. However, the term use is preferred in Danish clinical practice as a means of preventing stigmatization of pregnant women. Accordingly, we recommend an increased focus on the use of the words use and abuse. Women were invited to participate at the time of their 12-week ultrasound scan. Accordingly, our data provided a snapshot of self-reported substance abuse at that time, and did not reflect what may have happened later in pregnancy. Three of the centers joined the study towards the end of the study period, and from lessons learned in the earlier part of the study, the rate of participation increased across all centers in the latter part of the study period, and the rate of positive samples rose from 3.0 to 5.1% (data not shown). Had we employed the same recruitment practices across the cohort, we were likely to have found an even higher prevalence than 3.6%. The possible influence of seasonal variation remains undetermined. The survey was anonymized to maximize the participation rate, which hindered analyses of reasons for refusals. However, we consider that there is a significant risk that pregnant women who practice substance abuse, those with pregnancy complications, or those lacking confidence in anonymity might refuse to participate in the screening process due to fear of consequences. Our results do not include pregnant women who do not attend antenatal care or who have already been referred to the Family Center. Thus, our results may underestimate the true prevalence of substance abuse. Although in an anonymous survey, we would not expect tampering (dilution or exchange of urine samples), we did measure concentrations of creatinine in the samples to control for dilution, and found that all urine samples were reliable. The AccuSign-DOA7 is a preliminary and qualitative test with specificities of 98.6–99.9% for the respective groups of substances. Accordingly, in accordance with the Danish Association of Clinical Biochemistry [Dansk Selskab for Klinisk Biokemi (DSKB)] guidelines, only positive samples were submitted for confirmation and quantitative analysis by the gas chromatography/mass spectrometry or liquid chromatography/mass spectrometry. The average confirmation rate in our study was 52.4% (data not shown), which is much lower than the reported sensitivity of 98% by the manufacturer. Only one sample was excluded due to an insufficient amount of urine for confirmation. The reason for the low confirmation rate remains unexplained, but based on our results, we must question the sensitivity and specificity of AccuSignDOA7. Currently, there is no consensus with respect to the method for urine screening for substance abuse in
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Denmark and in the Family Centers. We recommend that future studies screening for substance abuse should use consistently validated methods for urine analysis. The analgesic drug Kodimagnyl, which is not recommended for use during pregnancy, can be purchased over the counter in Denmark. Although its use cannot explain all the opiate cases, Kodimagnyl is a combination of aspirin and codeine, which can result in the degradation product morphine in urine when codeine is no longer measurable. Accordingly, it is possible that consumption of Kodimagnyl may have caused confirmed samples to test opiate-positive. According to the Statens Serum Institut (SSI, Copenhagen) Birth Statistics, the Family Center in Odense supported 0.8% of the pregnant population who gave birth in Odense (28 of 3520 mother and baby pairs) during 2012. However, this constitutes only 22% of the detected prevalence of 3.6%, which suggests that the current antenatal care system overlooks almost 80% of women with substance abuse in pregnancy. This was highly unanticipated due to our antenatal care system, where pregnant women with substance abuse should feel that they can get support and not reprisals by coming to light. US data indicate a prevalence of 4–5% (3–5,11) but these data are based on self-reported substance abuse, and the genuine prevalence is probably underestimated. Accordingly, we would encourage an increased focus on substance abuse particularly among pregnant women without apparent indicators of abuse. A recent review from our group demonstrated that no biological sample has the ability to identify all substance users, and each sample has different advantages and disadvantages. Accordingly, we concluded that continuous maternal selfreporting of abuse and repeated urine testing during pregnancy provides the most accurate record of substance abuse (Rausgaard NLK, Ibsen IO, Jørgensen JS, Lamont RF, Ravn P, in preparation). The implementation of such a strategy during antenatal care might help to break the habit of substance abuse. Unfortunately, screening may, in addition to ethical challenges, also cause a lower participation rate in antenatal care. Pregnant women who practice substance abuse may avoid antenatal care in general practice but are likely to attend for ultrasound scanning. Accordingly, we suggest that urine screening and maternal self-reporting of substance abuse should be implemented at the time of nuchal translucency ultrasound scanning at 12 weeks’ gestation. However, screening requires consistently validated urine test kits with high sensitivity. We recommend that the choice of substances for testing be considered. Pregnant women identified as substance abusers should be offered additional antenatal care and fetal monitoring to minimize maternofetal complications. When urine screening during preg-
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nancy is not available, other biological specimens from the mother, fetus or both can help to identify exposure (Rausgaard NLK, Ibsen IO, Jørgensen JS, Lamont RF, Ravn P, in preparation). Furthermore, increased surveillance, observation and specific treatment for exposed newborns are required, and family support should be optimized. Our study indicates that screening identifies more pregnant women with evidence of substance abuse than the existing focused, intermittent method of identification.
Funding Funding was through the Danish Foundation “Trygfonden”, J.nr. 3-12-0359 (foundation to increase safety, security and health in Denmark). References 1. Irner TB. Substance exposure in utero and developmental consequences in adolescence: a systematic review. Child Neuropsychol. 2012;18:521–49. 2. Keegan J, Parva M, Finnegan M, Gerson A, Belden M. Addiction in pregnancy. J Addict Dis. 2010;29:175–91. 3. Shankaran S, Lester BM, Das A, Bauer CR, Bada HS, Lagasse L, et al. Impact of maternel substance use during pregnancy on childhood outcome. Semin Fetal Neonatal Med. 2007;12:143–50.
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4. Bandstra ES, Morrow CE, Mansoor E, Accornero VH. Prenatal drug exposure: infant and toddler outcomes. J Addict Dis. 2010;29:245–58. 5. 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. 2013;131:e1009–24. 6. Kesmodel U, Kesmodel PS, Larsen A, Secher NJ. Use of alcohol and illicit drugs among pregnant Danish women, 1998. Scand J Public Health. 2003;31:5–11. 7. Brule C. The role of the Pompidou Group of the Council of Europe in combating drug abuse and illicit drug trafficking. Bull Narc. 1983;35:73–7. 8. Wong S, Ordean A, Kahan M. Substance use in pregnancy. J Obstet Gynaecol Can. 2011;33:367–84. 9. Hudak ML, Tan RC. Neonatal drug withdrawal. Pediatrics. 2012;129:540–60. 10. Minozzi S, Amato L, Vecchi S, Davoli M. Maintenance agonist treatments for opiate dependent pregnant women. Cochrane Database Syst Rev. 2008;16: CD006318. 11. ACOG Committee on Health Care for Underserved Women; American Society of Addiction Medicine. ACOG Committee Opinion No. 524: Opioid abuse, dependence, and addiction in pregnancy. Obstet Gynecol. 2012;119:1070–6.
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