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      Cognitive and Motor Outcomes of Children With Prenatal Opioid Exposure : A Systematic Review and Meta-analysis

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      1 , , FRACP, PhD 1 , 2 , 3 , 4 , 5 , , MBBS, FRACP 6 , 7 , , MScMed, PhD 8 , , PhD 7 , 9 , 10 , , MBBS, FRACP, PhD 1 , 10 , , MBBS, FRACP, MD 1 , 11 ,
      JAMA Network Open
      American Medical Association

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          Key Points

          Question

          Is prenatal opioid exposure associated with differences in childhood cognitive and motor development?

          Findings

          In this systematic review and meta-analysis of 26 studies including 1455 children exposed to prenatal opioids compared with unexposed children, prenatal opioid exposure was associated with lower cognitive scores. The largest difference was seen between ages 6 months and 6 years.

          Meaning

          The negative consequences of prenatal opioid exposure on neurocognitive and physical development appear to be present from 6 months and persist beyond school age.

          Abstract

          Importance

          Prenatal opioid exposure (POE) is one of the fastest-growing global health problems, but its association with long-term neurologic and physical development remains unknown.

          Objective

          To assess the association between POE and cognitive and motor development in children from age 6 months to 18 years.

          Data Sources

          Key search terms included prenatal opioid exposure, neonatal abstinence syndrome, and neurocognitive development. Studies were searched using PubMed and Embase, with no publication date restriction, through August 20, 2018.

          Study Selection

          Only published cohort studies comparing the results of age-appropriate standardized cognitive and/or motor tests between children with any POE (aged 0-18 years) with drug-free controls were included. Data that were not convertible to means and SDs were excluded.

          Data Extraction and Synthesis

          This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Data were pooled using a random-effects model.

          Main Outcomes and Measures

          Standardized mean difference of cognitive and motor tests between POE and nonexposed children.

          Results

          Twenty-six peer-reviewed cohort studies were included. Cognitive outcomes were compared for a total of 1455 children with POE and 2982 nonexposed children across 3 age groups (mean [SE] age at cognitive testing was 13 [1.58] months for the toddler group; 4.5 [0.38] years for the preschool group; and 13 [2.36] years for the school-aged group). Motor outcomes were compared for 688 children with POE and 1500 nonexposed children up to age 6 years (mean [SD] age at motor testing, 2 [0.45] years). Standardized mean difference was lower in cognitive tests for children with POE at 0 to 2 years ( d = −0.52; 95% CI, −0.74 to −0.31; P < .001) and 3 to 6 years ( d = −0.38; 95% CI, −0.69 to −0.07; P < .001); the difference was not significant for those aged 7 to 18 years ( d = −0.44; 95% CI, −1.16 to 0.28; P = .23). Motor scores were lower in children with POE ( d = 0.49; 95% CI, 0.23-0.74; P < .001).

          Conclusions and Relevance

          Prenatal opioid exposure appeared to be negatively associated with neurocognitive and physical development from age 6 months, and this association persisted until adolescence. The cause and association of this with POE or other factors (eg, withdrawal treatment) are uncertain but suggest that POE necessitates long-term support and intervention.

          Abstract

          This systematic review and meta-analysis examines the cognitive and motor development of infants and children exposed to opioids prenatally.

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          Most cited references63

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          Systematic reviews in health care: Investigating and dealing with publication and other biases in meta-analysis.

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            Neonatal drug withdrawal.

            Maternal use of certain drugs during pregnancy can result in transient neonatal signs consistent with withdrawal or acute toxicity or cause sustained signs consistent with a lasting drug effect. In addition, hospitalized infants who are treated with opioids or benzodiazepines to provide analgesia or sedation may be at risk for manifesting signs of withdrawal. This statement updates information about the clinical presentation of infants exposed to intrauterine drugs and the therapeutic options for treatment of withdrawal and is expanded to include evidence-based approaches to the management of the hospitalized infant who requires weaning from analgesics or sedatives.
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              The Purdue pegboard; norms and studies of reliability and validity.

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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                12 July 2019
                July 2019
                12 July 2019
                : 2
                : 7
                : e197025
                Affiliations
                [1 ]Medical student, University of New South Wales, Sydney, New South Wales, Australia
                [2 ]Sydney Local Health District, Croydon, New South Wales, Australia
                [3 ]Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia
                [4 ]Sydney Medical School, Faculty of Medicine and Health, Sydney University, Sydney, New South Wales, Australia
                [5 ]Sydney Institute for Women, Children and Their Families, Camperdown, Sydney, New South Wales, Australia
                [6 ]Early Start Research Institute, University of Wollongong, Wollongong, New South Wales, Australia
                [7 ]University of Queensland Centre for Clinical Research, Herston, Queensland, Australia
                [8 ]NHMRC Clinical Trials Centre, Faculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, Australia
                [9 ]Department of Education, University of Oxford, Oxford, United Kingdom
                [10 ]Birkbeck, University of London, London, United Kingdom
                [11 ]Department of Newborn Care, Royal Hospital for Women, Sydney, Australia
                Author notes
                Article Information
                Accepted for Publication: May 21, 2019.
                Published: July 12, 2019. doi:10.1001/jamanetworkopen.2019.7025
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Yeoh SL et al. JAMA Network Open.
                Corresponding Author: Ju Lee Oei, MBBS, FRACP, MD, Department of Newborn Care, The Royal Hospital for Women, Barker Street, Sydney, NSW, 2031 Australia ( j.oei@ 123456unsw.edu.au ).
                Author Contributions: Ms Yeoh and Dr Oei had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Yeoh, Eastwood, Wright, Melhuish, Ward, Oei.
                Acquisition, analysis, or interpretation of data: Yeoh, Morton, Melhuish, Ward, Oei.
                Drafting of the manuscript: Yeoh, Wright, Morton, Oei.
                Critical revision of the manuscript for important intellectual content: All authors.
                Statistical analysis: Yeoh, Melhuish, Oei.
                Obtained funding: Oei.
                Administrative, technical, or material support: Eastwood, Morton, Melhuish, Oei.
                Supervision: Morton, Ward, Oei.
                Conflict of Interest Disclosures: None reported.
                Article
                zoi190285
                10.1001/jamanetworkopen.2019.7025
                6628595
                31298718
                53255269-8cc5-4f80-8606-4d265f638263
                Copyright 2019 Yeoh SL et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 1 March 2019
                : 21 May 2019
                Categories
                Research
                Original Investigation
                Featured
                Online Only
                Pediatrics

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