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      Prenatal exposure to opioid maintenance treatment and neonatal outcomes: Nationwide registry studies from the Czech Republic and Norway

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          Abstract

          There is lack of knowledge about the safety of treatment with methadone and buprenorphine as part of opioid maintenance treatment (OMT) during pregnancy. The purpose of this study was to examine neonatal outcomes concerning the use of OMT during pregnancy. We used nationwide registry linkages from the Czech Republic (2000‐2014) and Norway (2004‐2013). We compared prenatally OMT–exposed newborns with (a) newborns of women hospitalized with opioid use disorder during pregnancy in the Czech sample and (b) newborns with neonatal abstinence syndrome (NAS) in Norway. We performed multivariate linear and binary logistic regression exploring the associations between OMT and neonatal outcomes (growth parameters, gestational age, fetal death, small for gestational age, Apgar score, and NAS). Regression coefficients ( b) and odds ratios (ORs) were estimated. The cohorts consisted of 333 Czech, and 235 Norwegian OMT–exposed newborns, and 106 and 294 newborns in the comparison groups, respectively. In both countries, the neonatal growth parameters were similar in the OMT and the comparison groups. In Norway, OMT exposure prolonged gestational age (adjusted b = 0.96 weeks, 95% confidence interval [CI] =0.39‐1.53) while the odds of preterm birth and Apgar score at 5 minutes were lower than in the comparison group (adjusted OR = 0.35, 0.16‐0.75 and aOR = 0.21, 0.06‐0.78, respectively). Newborns of women in OMT had similar growth parameters as newborns of women with opioid use disorders who were not in OMT during pregnancy. Overall, our findings do not suggest that OMT results in worse neonatal outcomes.

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          Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence.

          Methadone maintenance was the first widely used opioid replacement therapy to treat heroin dependence, and it remains the best-researched treatment for this problem. Despite the widespread use of methadone in maintenance treatment for opioid dependence in many countries, it is a controversial treatment whose effectiveness has been disputed. To evaluate the effects of methadone maintenance treatment (MMT) compared with treatments that did not involve opioid replacement therapy (i.e., detoxification, offer of drug-free rehabilitation, placebo medication, wait-list controls) for opioid dependence. We searched the following databases up to Dec 2008: the Cochrane Controlled Trials Register, EMBASE, PubMED, CINAHL, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF-VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews; authors of identified RCTs were asked about other published or unpublished relevant RCTs. All randomised controlled clinical trials of methadone maintenance therapy compared with either placebo maintenance or other non-pharmacological therapy for the treatment of opioid dependence. Reviewers evaluated the papers separately and independently, rating methodological quality of sequence generation, concealment of allocation and bias. Data were extracted independently for meta-analysis and double-entered. Eleven studies met the criteria for inclusion in this review, all were randomised clinical trials, two were double-blind. There were a total number of 1969 participants. The sequence generation was inadequate in one study, adequate in five studies and unclear in the remaining studies. The allocation of concealment was adequate in three studies and unclear in the remaining studies. Methadone appeared statistically significantly more effective than non-pharmacological approaches in retaining patients in treatment and in the suppression of heroin use as measured by self report and urine/hair analysis (6 RCTs, RR = 0.66 95% CI 0.56-0.78), but not statistically different in criminal activity (3 RCTs, RR=0.39; 95%CI: 0.12-1.25) or mortality (4 RCTs, RR=0.48; 95%CI: 0.10-2.39). Methadone is an effective maintenance therapy intervention for the treatment of heroin dependence as it retains patients in treatment and decreases heroin use better than treatments that do not utilise opioid replacement therapy. It does not show a statistically significant superior effect on criminal activity or mortality.
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            Intrauterine growth curves based on ultrasonically estimated foetal weights.

            Available standard intrauterine growth curves based on birthweights underestimate foetal growth in preterm period. New growth curves are presented based on data from four Scandinavian centres for 759 ultrasonically estimated foetal weights in 86 uncomplicated pregnancies. Mean weight of boys exceeded that of girls by 2-3%. A uniform SD value of 12% of the mean weight was adopted for the standard curves as the true SD varied non-systematically between 9.1 and 12.4%. Applied to an unselected population of 8663 singleton births, before 210 days of gestation, 32% of birthweights were classified as small-for-gestational age (SGA; i.e. below mean - 2 SD); the corresponding figures were 11.1% for gestational ages between 210 and 258 days, and 2.6% for ages of 259 days or longer. The new growth curves reveal better the true distribution of SGA foetuses and neonates, and are suggested for use in perinatological practice.
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              The effects of nicotine on human fetal development.

              Maternal smoking during pregnancy continues to represent a major public health concern. Nicotine is extremely harmful to the developing fetus through many different mechanisms, and the harms increase with later gestational age at exposure. Pregnancies complicated by maternal nicotine use are more likely to have significant adverse outcomes. Nicotine-exposed children tend to have several health problems throughout their lives, including impaired function of the endocrine, reproductive, respiratory, cardiovascular, and neurologic systems. Poor academic performance and significant behavioral disruptions are also common, including ADHD, aggressive behaviors, and future substance abuse. To diminish the adverse effects from cigarette smoking, some women are turning to electronic cigarettes, a new trend that is increasing in popularity worldwide. They are largely perceived as being safer to use in pregnancy than traditional cigarettes, although there is not adequate evidence to support this claim. At this time, electronic cigarette use during pregnancy cannot be recommended. Birth Defects Research (Part C) 108:181-192, 2016. © 2016 Wiley Periodicals, Inc.
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                Author and article information

                Contributors
                marte.handal@fhi.no
                Journal
                Pharmacol Res Perspect
                Pharmacol Res Perspect
                10.1002/(ISSN)2052-1707
                PRP2
                Pharmacology Research & Perspectives
                John Wiley and Sons Inc. (Hoboken )
                2052-1707
                14 August 2019
                October 2019
                : 7
                : 5 ( doiID: 10.1002/prp2.2019.7.issue-5 )
                : e00501
                Affiliations
                [ 1 ] Department of Mental Disorders Norwegian Institute of Public Health Oslo Norway
                [ 2 ] Department of Addictology, First Faculty of Medicine Charles University Prague Czech Republic
                [ 3 ] Institute of Health Information and Statistics of the Czech Republic Prague Czech Republic
                [ 4 ] Norwegian Centre for Addiction Research at the University of Oslo Oslo Norway
                [ 5 ] Department of Chronic Diseases and Ageing Norwegian Institute of Public Health Oslo Norway
                [ 6 ] Department of Global Public Health and Primary Care University of Bergen Bergen Norway
                [ 7 ] National Monitoring Centre for Drugs and Addiction Office of the Government of the Czech Republic Prague Czech Republic
                Author notes
                [*] [* ] Correspondence

                Marte Handal, Norwegian Institute of Public Health, Department of Mental Disorders, PO Box 222 Skøyen, N‐0213 Oslo, Norway.

                Email: marte.handal@ 123456fhi.no

                Author information
                https://orcid.org/0000-0003-1773-0184
                Article
                PRP2501
                10.1002/prp2.501
                6694203
                e9358e7b-dcdf-4c17-a80b-8cf5180cc68e
                © 2019 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 March 2019
                : 14 June 2019
                : 16 June 2019
                Page count
                Figures: 0, Tables: 4, Pages: 10, Words: 12985
                Funding
                Funded by: Norges Forskningsråd
                Award ID: 240197/H10.
                Funded by: Ministerstvo Zdravotnictví Ceské Republiky
                Award ID: PRVOUK-P03/LF1/9
                Funded by: Ministry of Health
                Award ID: 16-28157A
                Award ID: LF1
                Award ID: 9
                Funded by: Norwegian Research Council
                Award ID: 240197
                Award ID: H10
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                prp2501
                October 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.7 mode:remove_FC converted:15.08.2019

                buprenorphine,methadone,neonate,opioid maintenance treatment,prenatal exposure

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