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Official websites use. Share sensitive information only on official, secure websites. Corresponding author: Sarah H. Heil, Rm. Prospect St. The aim of the present study was to estimate the prevalence of unintended pregnancy and its three subtypes mistimed, unwanted, ambivalent among opioid-abusing women. Interventions are sorely needed to address the extremely high rate of unintended pregnancy among opioid-abusing women. Drug treatment programs are likely to be an important setting for such interventions. Licit and illicit opioid dependence during pregnancy is often complicated by a multitude of other factors, including low socioeconomic status, poor nutrition, lack of prenatal care, family instability, interpersonal violence, homelessness, psychological problems, and other drug use Center for Substance Abuse Treatment, In the perinatal period, these intertwined factors can contribute to a number of adverse maternal and infant outcomes including, but not limited to, premature delivery, low birth weight, and neonatal abstinence syndrome see Kaltenbach et al. In the longer term, bearing a child in such disadvantaged circumstances has been shown to significantly diminish the future wellbeing of both the mother and the child Graham , ; Mishel et al. Further compounding these difficult circumstances, opioid-dependent women become pregnant more often than women in the general population. To our knowledge, there is just one small study estimating unintended pregnancy among opioid-dependent women. As a first step toward developing interventions to reduce unintended pregnancy among opioid-dependent women, the present study sought to estimate the prevalence of unintended pregnancy and its three subtypes mistimed, unwanted, and ambivalent in a much larger sample of pregnant women reporting opioid abuse. This multi-site trial, performed at eight diverse U. Participants who provided informed consent were screened for eligibility either at the time of treatment entry or at the time they considered a change from their established drug treatment program. Interviews were conducted with all potential participants to determine eligibility for the study; at some sites, some information was collected by chart review prior to the interview. Demographic information collected included age, education level, race, and marital status. Drug use and treatment variables assessed included frequency of current opioid and cocaine use and the number and type of prior treatment episodes. Two types of analyses were performed to examine between-group differences. First, analyses examined demographic differences between women with intended pregnancies and women with unintended pregnancies. Statistically significant differences in continuous and dichotomous variables were evaluated using t-tests, and z-tests, respectively. Second, differences between groups on drug use and other factors were evaluated using logistic regression models in which each variable of interest was entered separately into a logit model controlling for age, race and site location. No significant differences were observed on the 5 maternal demographic characteristics compared between women with intended vs. Unintended pregnancy was highly prevalent in this sample; nearly 9 of every 10 women screened reported that the current pregnancy was unintended. This rate is 2—3 times the rate observed in the general population Chandra et al. To our knowledge, this is the first report of the rates of the three subtypes of unintended pregnancy in opioid-abusing pregnant women. The percentage of women reporting mistimed, unwanted or ambivalent pregnancies in the present sample were fairly comparable, with each representing about one-third of the total sample. The percentage of women reporting an unwanted pregnancy was nearly 3 times higher in the present study compared to the general population and the percentage of women reporting ambivalence, more than 4 times higher Mohllajee et al. These figures dramatically underscore the need to develop interventions to bring contraceptive use in line with conception desires among opioid-abusing women. Although there were few differences between women with intended vs. A lower percentage of these women also reported recent cocaine use compared to women with intended pregnancies. Women with ambivalent pregnancies were also more likely to be unemployed and a higher percentage reported prior medication-assisted treatment. Overall, the greatest number of differences was observed between women with ambivalent vs. This is in contrast to the general population literature, where women with ambivalent pregnancies tend to be most similar to women with intended pregnancies in terms of demographic characteristics as well as maternal and infant outcomes Mohlajee et al. Additional studies will be needed to replicate this pattern of results and to determine the implications of such differences. These data suggest that drug abuse treatment programs may be an important setting for interventions to reduce the very high rate of unintended pregnancy in this population. One strategy for doing so involved integrating free family planning services into drug treatment programs. These findings suggest that this is a promising model that should be further developed and rigorously tested as part of efforts to reduce unintended pregnancy among drug-abusing women. The present study has notable strengths. The data were systematically collected across eight diverse U. The study also has limitations. The format of the pregnancy intention question differed from the format used in national surveys e. Also, it is possible that women who were screened for potential study participation may not be representative of the larger population of opioid-dependent women. Nevertheless, the results of the present study clearly document the extremely high rate of unintended pregnancy among a large sample of opioid-abusing women and underscore the need for a greater scientific attention to this serious problem. We thank Laura Garnier for assistance with statistical analyses. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. As a library, NLM provides access to scientific literature. J Subst Abuse Treat. Published in final edited form as: J Subst Abuse Treat. Find articles by Sarah H Heil. Hendree E Jones , Ph. Find articles by Hendree E Jones. Amelia Arria , Ph. Find articles by Amelia Arria. Karol Kaltenbach , Ph. Find articles by Karol Kaltenbach. Mara Coyle , M. Find articles by Mara Coyle. Gabriele Fischer , M. Find articles by Gabriele Fischer. Susan Stine , M. Find articles by Susan Stine. Peter Selby , M. Find articles by Peter Selby. Peter R Martin , M. Find articles by Peter R Martin. Issue date Mar. PMC Copyright notice. The publisher's version of this article is available at J Subst Abuse Treat. Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Mean SD number of times treated for drug abuse in lifetime. Mean SD years of age at 1 st medication-assisted treatment.

Unintended Pregnancy in Opioid-abusing Women

Kaltenbach buy cocaine

Official websites use. Share sensitive information only on official, secure websites. Correspondence: Professor Dr. Marilyn A. To explore methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine EDDP umbilical cord disposition, correlate with maternal methadone dose and neonatal outcomes, and evaluate the window of drug detection in umbilical cord of in utero illicit drug exposure. Subjects, 19 opioid-dependent pregnant women from two clinical studies, one comparing methadone and buprenorphine pharmacotherapy for opioid-dependence treatment, and the second examining monetary reinforcement schedules to maintain drug abstinence. Correlations were calculated for methadone and EDDP umbilical cord concentrations and maternal methadone dose, and neonatal outcomes. Cocaine- and opiate-positive umbilical cord concentrations were compared to those in placenta and meconium, and urine specimens collected throughout gestation. Significant positive correlations were found for umbilical cord methadone concentrations and methadone mean daily dose, mean dose during the 3 rd trimester and methadone cumulative daily dose. Meconium identified many more cocaine and opiate positive specimens than umbilical cord. Umbilical cord methadone concentrations were correlated to methadone doses. Meconium proved to be more suitable than umbilical cord to detect in utero exposure to cocaine and opiates; however, umbilical cord could be useful when meconium is unavailable due to in utero or delayed expulsion. Keywords: methadone, cocaine, opiates, umbilical cord, in utero drug exposure. Illicit drug consumption during pregnancy is an important public health problem. Maternal drug-intake during gestation, in the context of other complex psychosocial stressors, may have negative effects on pregnancy outcomes, and fetal and child development 2 - 7. Methadone-assisted therapy is recommended by the Center for Substance Abuse Treatment and The American Academy of Pediatrics for opioid-dependent pregnant women, reducing fetal exposure to maternal illicit drug use and other maternal risk behaviors, and improving obstetrical care and neonatal outcomes 8 , 9 , 9. However, there are consequences for the infant, with the most serious being neonatal abstinence syndrome NAS. Pharmacokinetics of methadone, heroin and cocaine can be explained, in part, by gene polymorphisms encoding drug-metabolizing enzymes and drug transporters. Methadone is biotransformed in the liver to the inactive metabolites 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine EDDP and 2-ethylmethyl-3,3-diphenylpyrrolidine EMDP , and minor metabolites methadol and normethadol that contribute to methadone's activity to a small extent The main enzymes involved are cytochrome P CYP 3A4, and to a lesser extent, 2B6 14 - 16 , the later enzyme showing stereoselectivity towards the S -enantiomer Genetic polymorphisms of CYP2B6 may be due to ethnic and sex differences 15 , Heroin is rapidly metabolized to 6-acetylmorphine 6AM and morphine by hepatic carboxylesterase-1 hCE-1 , carboxylesterase-2 h C E-2 and plasmatic pseudocholinesterase Morphine is further glucuronidated to morphine and morphineglucuronides by UDP-glucuronyltransferases, mainly UGT2B7, whose genetic polymorphism is implicated in the inter-individual variability in morphine response at a given dose 20 , Genetic polymorphisms of CYP2D6 are responsible for abnormally high concentrations of morphine following codeine administration in some individuals, to low morphine concentrations in others 22 , Other important metabolites include norcocaine, which can follow two metabolic routes catalyzed by CYP3A4 or CYP3A4 and flavin containing monooxygenase, respectively, and cocaethylene, which is formed in the presence of ethanol and hCE-1 In addition to genetic polymorphism in metabolic enzymes, variation in drug transporter activity also could play an important role in drug disposition. P-glycoprotein is a transmembrane efflux transporter for methadone and other opioids including morphine, whose expression and function is influenced by physiological and environmental factors, induction or inhibition by other substrates, as well as genetic polymorphism in the gene encoding this protein, the multidrug resistance 1 ABCB1 gene For safety and ethical reasons, it is difficult to study drug disposition in the maternal-fetal dyad. Controlled methadone administration to opioid-dependent women provides a model for evaluating drug deposition into umbilical cord and other matrices. We prospectively collected urine specimens three times a week throughout pregnancy to monitor relapse to opiates and cocaine, and collected matched meconium, umbilical cord, and placenta at birth. Positive urine test results defined the timing of illicit drug use, and percentage of positive urine specimens provided a relative measure of drug exposure frequency. These unique data defined the window of drug detection of opiates and cocaine in the different biological matrices, and permitted a comparison of the relative efficacy of these matrices for identifying prenatal drug exposure. Detecting in utero drug exposure by testing biological matrices can be an important tool for assisting in the identification of women in need of drug treatment and neonates susceptible to NAS who may require specialized treatment and a longer hospital stay, and for initiating investigations into the welfare of all children in the home. Meconium is the matrix of choice for drug testing due to its easy, non-invasive collection and wide window of drug detection, reflecting prenatal exposure primarily from the 3 rd trimester of pregnancy 26 , However, in some circumstances, meconium collection is difficult, as expulsion can be delayed several days in premature babies and, in cases of fetal distress, discharge may occur before delivery. Umbilical cord was suggested as an alternative to meconium, due to its availability immediately after delivery, and sample amount. Montgomery et al. However, the window of drug detection in umbilical cord has not been adequately evaluated. The aims of this research were to assess the disposition of methadone and its main metabolite, EDDP, in umbilical cord specimens from opioid-dependent pregnant women receiving methadone-assisted therapy, and to evaluate correlations between umbilical cord methadone and EDDP concentrations and methadone maternal dose and neonatal outcomes. In addition, cocaine and opiate results in umbilical cord were compared to those in matched placenta and meconium, and in urine specimens collected throughout pregnancy to evaluate the usefulness of this alternative matrix to detect in utero drug exposure. The aim of study A was to compare different schedules of monetary reinforcement for maintaining cocaine and opioid abstinence in opioid-dependent pregnant women Study B compared methadone and buprenorphine pharmacotherapy for opioid-dependence treatment during pregnancy Patients prescribed methadone generally received 30, 40, 50 and 60 mg on days , respectively. Additional increases of 5 or 10 mg were available based upon clinical indications. Estimated gestational age at birth EGAB , physical birth parameters weight, length and head circumference , Apgar scores at 1 and 5 minutes and NAS scores were collected at birth. NAS was systematically assessed for 10 days using a item modified Finnegan Scale 30 , A score of 4 was selected as the cutoff based on clinical experience and preliminary blinded-condition comparison data from drug-exposed and non-exposed neonates Peak NAS score was defined as the highest score obtained, and time-to-peak h was calculated from time of birth to peak NAS score. Infants were treated with morphine sulfate drops to reduce NAS if modified Finnegan score exceeded 9 on two consecutive measurements. Simultaneous methadone, EDDP, morphine, codeine, 6AM, cocaine and BE quantification in umbilical cord was performed with a fully validated liquid chromatography ion-trap mass spectrometry method The distribution of analytes in umbilical cord at two locations, close to the fetus and close to placenta, was determined in seven placenta specimens prior to analysis of the remaining specimens. Briefly, placenta was homogenized with 0. Depending on the analytical method, meconium was homogenized by ultrasonication with methanol, or simply vortexed with methanol and 0. Thrice-weekly urine specimens were collected throughout pregnancy by CAP staff. All statistical analyses were performed with SPSS The Kolmorogov-Smirnov test was employed to evaluate normal data distribution. Table 1 shows maternal demographic characteristics and methadone dosing information. All were single births for a total of 19 infants. Approximately half Smoking severity might have affected EGAB, but not other measured neonatal parameters. The percentage of preterm newborns was increased to All infants experienced NAS, although only 6 required treatment. Neonatal outcome measures for the 19 in utero methadone-exposed infants. Bolded text indicate below normal parameters. Methadone and EDDP concentrations at the ends of the umbilical cord closest to the placenta UC-placenta and the fetus UC-fetus were quantified in 7 cases to determine if biomarkers were homogenously distributed Table 3. Methadone and EDDP concentrations varied less than As a consequence, one intermediate location was analyzed for the remaining 12 specimens. Methadone and EDDP were measurable in all umbilical cord specimens from participants receiving methadone pharmacotherapy. Methadone concentrations ranged from Table 4 also contains methadone and EDDP concentrations and their ratios in matched placenta and meconium specimens. However, only 17 matched meconium specimens were available, and for two of them participants 6 and 7 the amount of specimen only allowed methadone and EDDP determination Tables 4 and 5. Methadone also was the primary analyte in placenta, while EDDP was present in much higher concentrations than the parent drug in meconium. Matched placenta, meconium and thrice-weekly 2 nd and 3 rd trimester urine specimen results were available for 19, 15 and 17 participants, respectively Table 5. Percentages of positive urine specimens in the 2 nd and 3 rd trimester, and time between the last positive urine specimen and birth also are included in Table 5. Only one matched umbilical cord and placenta specimen participant 16 was positive for cocaine 7. Urine tests were positive for cocaine in the 2 nd or 3 rd trimester in 8 of these women; however, for participant 8, all urine specimens were negative for cocaine. In all matrices, cocaine metabolite concentrations were higher than the parent drug. Opiates were identified in only one umbilical cord and placenta specimen participant 16 by the presence of morphine Eight meconium specimens were positive for morphine, and one also for codeine Table 5. Surprisingly, meconium from the infant with positive umbilical cord and placenta results was negative for opiates. Urine test results confirmed in utero opiate exposure in all cases. Urine test results were negative for opiates and cocaine throughout gestation in one and nine participants, respectively. Seven participants had positive urine specimens for opiates in the 3 rd trimester, and five for cocaine; however, none of the matched umbilical cord specimens verified in utero exposure to these analytes. Umbilical cord from participant 16 confirmed opiate and cocaine exposure during pregnancy, but the window of drug detection could not be determined, as urine data from the 3 rd trimester were not available for this participant. We describe for the first time methadone and EDDP disposition in umbilical cord from opioid-dependent pregnant women receiving methadone-assisted pharmacotherapy. In general, similar concentrations of methadone and EDDP were found in the maternal and fetal ends of the umbilical cords. Methadone concentrations in umbilical cord were positively correlated to methadone mean daily dose, mean dose during the 3 rd trimester and cumulative dose. To our knowledge, dose-concentration relationships for maternal methadone dose and methadone and EDDP umbilical cord concentrations were never reported. However, correlations between maternal methadone dose and methadone concentrations in maternal plasma 37 - 41 and umbilical cord blood 38 , 41 were previously evaluated, reporting discrepant results. As previously described, greater maternal methadone doses were associated with higher umbilical cord methadone and EDDP concentrations. We suggest that the positive correlation between EDDP and neonatal length is reflecting an improvement in neonatal outcome in babies from pregnant women receiving appropriate methadone-assisted therapy, and perhaps lower exposure to illicit drugs. Supporting our hypothesis, neonates from pregnant women receiving methadone-assisted therapy had improved neonatal growth parameters as compared to those whose mothers abused heroin and did not receive this treatment 42 - Almost a third Therefore, it may be possible to predict NAS intensity based on umbilical cord concentrations. Umbilical cord concentrations were not previously correlated to neonatal parameters; however, others investigated correlations between neonatal plasma methadone concentrations and NAS intensity. Mack et al. In contrast, Harper et al. Our results supported findings of others, where NAS intensity associated with lower neonatal methadone plasma concentrations 38 , 45 a higher rate of decline in neonatal methadone levels 37 , or both Methadone and EDDP concentrations in umbilical cord were compared to matched placenta and meconium concentrations. As in umbilical cord, methadone was the predominant placenta analyte; however, mean placenta methadone concentrations were Although methadone metabolism in umbilical cord may have occurred, it is more likely that the much lower umbilical cord methadone concentrations were due to low placental transfer. This also is supported through in vitro experimentation by Nekhayeva et al. As opposed to umbilical cord and placenta, EDDP was the predominant biomarker in meconium. Moreover, concentrations of both analytes in meconium were much higher than those in the other matrices, reflecting meconium accumulation throughout gestation, and subsequent metabolism to the inactive metabolite. Correlations between methadone and EDDP concentrations in matched umbilical cord, placenta and meconium specimens also were evaluated. A statistically significant positive correlation also was found for EDDP umbilical cord concentrations and methadone meconium concentrations. The reason for this correlation is not clear. We hypothesize that higher methadone meconium concentrations result from higher methadone doses and, therefore, higher methadone and EDDP concentrations in umbilical cord. Methadone meconium concentrations were significantly correlated to EDDP, but not to methadone umbilical cord concentrations, most likely due to limited methadone placental transfer. In addition, cocaine and opiate umbilical cord concentrations were determined. BE was found in only one umbilical cord specimen, confirming in utero cocaine exposure. Likewise, Moore et al. Cocaine was not detected in this umbilical cord. Winecker et al. In the present study, similar BE concentrations were observed in matched placenta specimens, but low cocaine concentrations also were noted. Thus, placental cocaine transfer also appeared to be low. Opiate and metabolite disposition in umbilical cord were not previously quantified. We found morphine concentrations 10 times higher than those of codeine in the only positive opiate umbilical cord specimen, at concentrations comparable to those in the matched placenta specimen. To evaluate the usefulness of umbilical cord to detect in utero cocaine and opiate exposure, umbilical cord concentrations were compared to those in matched meconium and urine specimens. Meconium testing identified in utero cocaine exposure in 11 participants, with Although this metabolite was not included in the umbilical cord analytical method, it is unlikely that this analytical difference contributed to fewer umbilical cord positive findings based on Winecker et al. With regard to opiates, morphine was detected in 8 meconium specimens, one also positive for codeine, while none of the matched umbilical cord specimens were positive. Surprisingly, the matched meconium specimen for the only morphine- and codeine-positive umbilical cord specimen participant 16 tested negative for opiates. All participants with the last cocaine or opiate positive urine test in the 3 rd trimester had positive meconium results. The drug detection window in umbilical cord could not be established, as matched urine data from the third trimester were not available for the only cocaine and opiate positive umbilical cord specimen participant Umbilical cord specimens were negative even when the last positive urine test was just 3 or 13 days before delivery participants 9 and 11 , while meconium results participant 11 indicated maternal cocaine and opiate consumption. These results might reflect a shorter window of drug detection in umbilical cord than in meconium. Sensitive umbilical cord analytical LOQs should have compensated for the much lower drug concentrations in this biological matrix. Our results demonstrate that meconium detects more easily in utero drug-exposed neonates than umbilical cord, in contrast to results reported by Montgomery et al. This could be due to a short period of time from last maternal drug consumption to delivery for Montgomery's study participants, higher limits of quantification, or few positive specimens. In addition, the authors did not report any data on metabolites analyzed or measured concentrations in each matrix. Their data supported the efficacy of this alternative matrix for detection of fetal drug exposure; however, data were not available to establish the window of drug detection in umbilical cord. Marin et al. The authors concluded that both specimens could be applied for the detection of in-utero exposure to nicotine in the third trimester; however, concentrations of all analytes were generally greater in meconium and, specifically, nicotine concentrations were 3. These much higher concentrations of parent drug in meconium suggest accumulation of nicotine in this matrix and, therefore, a longer window of detection than in umbilical cord may be expected. These data describe for the first time methadone and EDDP concentrations in umbilical cord specimens from women receiving methadone-assisted therapy, and a statistically significant correlation for methadone umbilical cord concentrations and maternal methadone doses. Finally, our results indicate that meconium is better suited to confirm in utero drug exposure to cocaine and opiates compared to umbilical cord due to the lower concentrations found in this biological matrix and, probably, to its shorter window of drug detection. The authors would like to thank the participants of the clinical studies, and the clinical staff at the Center for Addiction and Pregnancy and Johns Hopkins Bayview Medical Center. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. As a library, NLM provides access to scientific literature. Ther Drug Monit. Published in final edited form as: Ther Drug Monit. Find articles by Ana de Castro. Find articles by Rolley E Johnson. Find articles by Teresa R Gray. Find articles by Diaa M Shakleya. Find articles by Marilyn A Huestis. PMC Copyright notice. The publisher's version of this article is available at Ther Drug Monit. Open in a new tab. A dash indicates that the testing was not done. STT: participant started in 3 rd trimester; AN: always negative. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. 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