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      Early life opioid exposure and potential long-term effects

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          Abstract

          The long-term consequences of perinatal opioid exposure and subsequent development of neonatal opioid withdrawal syndrome is largely unknown and likely dependent on a multitude of factors, including co-morbid drug use, pre- and post-natal care, and individual factors including the maternal-infant relationship and home environment. This review summarizes the current literature from clinical and preclinical studies on perinatal opioid exposure, focusing on the consequences in the offspring. Although a large number of preclinical studies have been conducted examining the impact of prenatal opioid exposure, the models employed are not necessarily representative of clinical use patterns, making it challenging to translate these results to the impacted population. Use of more clinically-relevant models of perinatal opioid exposure are requisite for the development of improved pharmacological and behavioral treatment strategies to improve quality of life for this vulnerable population.

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          Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009.

          Stephen W Patrick, Robert E Schumacher, Brian Benneyworth … (2012)
          Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal syndrome primarily caused by maternal opiate use. No national estimates are available for the incidence of maternal opiate use at the time of delivery or NAS. To determine the national incidence of NAS and antepartum maternal opiate use and to characterize trends in national health care expenditures associated with NAS between 2000 and 2009. A retrospective, serial, cross-sectional analysis of a nationally representative sample of newborns with NAS. The Kids' Inpatient Database (KID) was used to identify newborns with NAS by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code. The Nationwide Inpatient Sample (NIS) was used to identify mothers using diagnosis related groups for vaginal and cesarean deliveries. Clinical conditions were identified using ICD-9-CM diagnosis codes. NAS and maternal opiate use were described as an annual frequency per 1000 hospital births. Missing hospital charges (<5% of cases) were estimated using multiple imputation. Trends in health care utilization outcomes over time were evaluated using variance-weighted regression. All hospital charges were adjusted for inflation to 2009 US dollars. Incidence of NAS and maternal opiate use, and related hospital charges. The separate years (2000, 2003, 2006, and 2009) of national discharge data included 2920 to 9674 unweighted discharges with NAS and 987 to 4563 unweighted discharges for mothers diagnosed with antepartum opiate use, within data sets including 784,191 to 1.1 million discharges for children (KID) and 816,554 to 879,910 discharges for all ages of delivering mothers (NIS). Between 2000 and 2009, the incidence of NAS among newborns increased from 1.20 (95% CI, 1.04-1.37) to 3.39 (95% CI, 3.12-3.67) per 1000 hospital births per year (P for trend < .001). Antepartum maternal opiate use also increased from 1.19 (95% CI, 1.01-1.35) to 5.63 (95% CI, 4.40-6.71) per 1000 hospital births per year (P for trend < .001). In 2009, newborns with NAS were more likely than all other hospital births to have low birthweight (19.1%; SE, 0.5%; vs 7.0%; SE, 0.2%), have respiratory complications (30.9%; SE, 0.7%; vs 8.9%; SE, 0.1%), and be covered by Medicaid (78.1%; SE, 0.8%; vs 45.5%; SE, 0.7%; all P < .001). Mean hospital charges for discharges with NAS increased from $39,400 (95% CI, $33,400-$45,400) in 2000 to $53,400 (95% CI, $49,000-$57,700) in 2009 (P for trend < .001). By 2009, 77.6% of charges for NAS were attributed to state Medicaid programs. Between 2000 and 2009, a substantial increase in the incidence of NAS and maternal opiate use in the United States was observed, as well as hospital charges related to NAS.
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            Incidence of Neonatal Abstinence Syndrome — 28 States, 1999–2013

            Jean Y. Ko, Stephen W Patrick, Van Tong … (2016)
            Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal syndrome that occurs primarily among opioid-exposed infants shortly after birth, often manifested by central nervous system irritability, autonomic overreactivity, and gastrointestinal tract dysfunction (1). During 2000-2012, the incidence of NAS in the United States significantly increased (2,3). Several recent publications have provided national estimates of NAS (2,3); however, data describing incidence at the state level are limited. CDC examined state trends in NAS incidence using all-payer, hospital inpatient delivery discharges compiled in the State Inpatient Databases of the Healthcare Cost and Utilization Project (HCUP) during 1999-2013. Among 28 states with publicly available data in HCUP during 1999-2013, the overall NAS incidence increased 300%, from 1.5 per 1,000 hospital births in 1999, to 6.0 per 1,000 hospital births in 2013. During the study period, significant increases in NAS incidence occurred in 25 of 27 states with at least 3 years of data, with annual incidence rate changes ranging from 0.05 (Hawaii) to 3.6 (Vermont) per 1,000 births. In 2013, NAS incidence ranged from 0.7 cases per 1,000 hospital births (Hawaii) to 33.4 cases per 1,000 hospital births (West Virginia). The findings underscore the importance of state-based public health programs to prevent unnecessary opioid use and to treat substance use disorders during pregnancy, as well as decrease the incidence of NAS.
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              Adverse neurodevelopmental outcome of infants exposed to opiate in-utero.

              Rod Hunt, Dimitra Tzioumi, Edith Collins … (2008)
              In-utero drug exposure is associated with increased risks of perinatal morbidity and mortality, however longer term neurodevelopmental outcome of survivors is poorly described. The aims of this paper are: (1) to review the published literature which examines neurodevelopmental outcome in infants with Neonatal Abstinence Syndrome (NAS) and (2) to report developmental follow-up data from a case-control study of babies exposed to opiate in-utero. This study was conducted at Royal Prince Alfred Hospital in Sydney, NSW, through the multidisciplinary NAS service. Literature was reviewed after searching MEDLINE for relevant studies. Our own case-control study was conducted to examine neurodevelopmental outcome. A number of standardized neuropsychological tools were employed to assess these infants. Results from previously published studies on outcome of infants with NAS were not reassuring as to reported 'normal development'. In our own case-control study, opiate-exposed infants were significantly more likely to have neurodevelopmental impairment compared to healthy control infants, when assessed at 18 months and 3 years of age. Infants exposed to opiates in-utero are at increased risk of neurodevelopmental problems throughout early childhood.
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                Author and article information

                Contributors
                Anne Z. Murphy
                Journal
                Journal ID (nlm-ta): Neurobiol Stress
                Journal ID (iso-abbrev): Neurobiol Stress
                Title: Neurobiology of Stress
                Publisher: Elsevier
                ISSN (Electronic): 2352-2895
                Publication date PMC-release: 13 March 2019
                Publication date Collection: February 2019
                Publication date (Electronic): 13 March 2019
                Volume: 10
                Electronic Location Identifier: 100156
                Affiliations
                [1]Neuroscience Institute, Georgia State University, Atlanta, GA, 30308, USA
                Author notes
                [∗ ]Corresponding author. Neuroscience Institute, Georgia State University, PO Box 4010, Atlanta, GA, 30302-4010, USA. amurphy@ 123456gsu.edu
                Article
                Publisher ID: S2352-2895(18)30080-8 Publisher ID: 100156
                DOI: 10.1016/j.ynstr.2019.100156
                PMC ID: 6629922
                PubMed ID: 31338390
                SO-VID: f0cfcecf-46e8-4d7a-b735-d61315cded89
                Copyright © © 2019 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 2 October 2018
                Date revision received : 13 January 2019
                Date accepted : 8 March 2019
                Categories
                Subject: Articles from the Special Issue on Stress and substance abuse throughout development; Edited by Roger Sorensen, Da-Yu Wu, Karen Sirocco, Cora lee Wetherington and Rita Valentino

                Keywords: neonatal opioid withdrawal syndrome,stress,morphine,endogenous opioid tone
                Data availability:
                Keywords: neonatal opioid withdrawal syndrome, stress, morphine, endogenous opioid tone

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