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Neonatal Outcomes after Combined Opioid and Nicotine Exposure in Utero: A Scoping Review.

ABSTRACT: The majority of women who are pregnant with opioid use disorder (OUD) also smoke tobacco but are rarely offered tobacco cessation counseling. While the effects of exposure to opioids and nicotine in utero are well-understood separately, understanding the impact of the combined exposure to these substances on neonatal outcomes is lacking. A scoping review was conducted using PubMed and Scopus databases for studies addressing the combined exposure to opioids and nicotine during pregnancy published between 1 January 1980 and 9 July 2019. A total of 29 papers met the eligibility criteria for inclusion, with nine being identified as clinical trials (three from the MOTHER study) and two as secondary data analysis of clinical trial data. Neonatal outcomes for infants who had a combined exposure to opioids and nicotine in utero indicated a reduction in birth weight and birth length. Findings in infants exposed to both nicotine and opioids were mixed with regard to the duration of neonatal abstinence syndrome (NAS), the likelihood of treatment for NAS, doses of medicine used to treat NAS, and NAS scores when compared with infants who had opioid exposure without nicotine. The combined exposure to nicotine and opioids during pregnancy may lead to a reduction in neonatal birth weight and birth length and more severe NAS signs, compared with opioid use alone, but more research is necessary to identify the minimum dosage and length of nicotine exposure to accurately predict these outcomes.

SUBMITTER: Isaacs KR

PROVIDER: S-EPMC8508043 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Neonatal Outcomes after Combined Opioid and Nicotine Exposure in Utero: A Scoping Review.

Isaacs Krystyna R KR Atreyapurapu Sravanthi S Alyusuf Amal H AH Ledgerwood David M DM Finnegan Loretta P LP Chang Katie H K KHK Ma Tony X TX Washio Yukiko Y

International journal of environmental research and public health 20210928 19

<h4>Background</h4>The majority of women who are pregnant with opioid use disorder (OUD) also smoke tobacco but are rarely offered tobacco cessation counseling. While the effects of exposure to opioids and nicotine in utero are well-understood separately, understanding the impact of the combined exposure to these substances on neonatal outcomes is lacking.<h4>Methods</h4>A scoping review was conducted using PubMed and Scopus databases for studies addressing the combined exposure to opioids and n ...[more]

PMID: 34639512

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Project description:ObjectiveTo provide absolute and relative risk estimates of neonatal abstinence syndrome (NAS) based on duration and timing of prescription opioid use during pregnancy in the presence or absence of additional NAS risk factors of history of opioid misuse or dependence, misuse of other substances, non-opioid psychotropic drug use, and smoking.DesignObservational cohort study.SettingMedicaid data from 46 US states.ParticipantsPregnant women filling at least one prescription for an opioid analgesic at any time during pregnancy for whom opioid exposure characteristics including duration of therapy: short term (<30 days) or long term (≥ 30 days); timing of use: early use (only in the first two trimesters) or late use (extending into the third trimester); and cumulative dose (in morphine equivalent milligrams) were assessed.Main outcome measureDiagnosis of NAS in liveborn infants.Results1705 cases of NAS were identified among 290,605 pregnant women filling opioid prescriptions, corresponding to an absolute risk of 5.9 per 1000 deliveries (95% confidence interval 5.6 to 6.2). Long term opioid use during pregnancy resulted in higher absolute risk of NAS per 1000 deliveries in the presence of additional risk factors of known opioid misuse (220.2 (200.8 to 241.0)), alcohol or other drug misuse (30.8 (26.1 to 36.0)), exposure to other psychotropic medications (13.1 (10.6 to 16.1)), and smoking (6.6 (4.3 to 9.6)) than in the absence of any of these risk factors (4.2 (3.3 to 5.4)). The corresponding risk estimates for short term use were 192.0 (175.8 to 209.3), 7.0 (6.0 to 8.2), 2.0 (1.5 to 2.6), 1.5 (1.0 to 2.0), and 0.7 (0.6 to 0.8) per 1000 deliveries, respectively. In propensity score matched analyses, long term prescription opioid use compared with short term use and late use compared with early use in pregnancy demonstrated greater risk of NAS (risk ratios 2.05 (95% confidence interval 1.81 to 2.33) and 1.24 (1.12 to 1.38), respectively).ConclusionsUse of prescription opioids during pregnancy is associated with a low absolute risk of NAS in the absence of additional risk factors. Long term use compared with short term use and late use compared with early use of prescription opioids are associated with increased NAS risk independent of additional risk factors.

Project description:It is well established that maternal lifestyle during pregnancy and lactation affects the intrauterine programming of F1 offspring. However, despite the co-use of alcohol and nicotine is a common habit, the effects of exposure to both substances on the reproductive system of F1 male offspring and the underlying mechanisms of developmental programming have not been investigated. The present study aimed to examine pre- and postnatal concurrent exposure to these substances on genetic and epigenetic alterations of sperm cells as well as testis properties of F1 offspring compared with exposure to each substance alone. Pregnant dams in the F0 generation randomly received normal saline, nicotine, ethanol, and combinations throughout full gestation and lactation periods. Sperm cells and testes of F1 male offspring were collected at postnatal day 90 for further experiments. High levels of sperm DNA fragmentation were observed in all exposed offspring. Regarding epigenetic alterations, there was a significant increase in the relative transcript abundance of histone deacetylase 1 and 2 in all exposed sperm cells. Moreover, despite a decrease in the expression level of DNA methyltransferase (DNMT) 3A, no marked differences were found in the expression levels of DNMT1 and 3B in any of the exposed sperm cells compared to non-exposed ones. Interestingly, combined exposure had less prominent effects relative to exposure to each substance alone. The changes in the testicular and sperm parameters were compatible with genetic and epigenetic alterations. However, MDA level as an oxidative stress indicator increased in all exposed pups, which may be responsible for such outputs. In conclusion, maternal co-exposure to these substances exhibited epigenotoxicity effects on germline cells of F1 male offspring, although these effects were less marked relative to exposure to each substance alone. These counteracting effects may be explained by cross-tolerance and probably less impairment of the antioxidant defense system.

Project description:IntroductionRates of neonatal opioid withdrawal syndrome (NOWS) have paralleled the rise of opioid use during pregnancy. While short-term phenotypic symptoms of NOWS are well defined, molecular implications and long-term effects are not well understood. Preferred and first-line of treatment for NOWS includes non-pharmacological interventions; however, more than half of the NOWS neonates will need pharmacologics, with opioids as the primary pharmacological treatment. While effective at reducing symptoms, treating NOWS with opioids is paradoxical given that molecular and long-term developmental consequences with such exposure are unknown. There is a pressing need for a synthesis of current and potential/ novel treatment options for NOWS.Methods and analysisFollowing a published framework, a scoping review will be conducted to evaluate NOWS treatment, including established treatment methods and novel methods that may warrant future research and consideration. Using broad search terms, as well as Medical Subject Headings terms, a comprehensive search of PubMed, Cochrane Library, Google Scholar, CINAHL, Web of Science and Scopus, as well as references of selected literature, will take place, followed by a screening procedure to identify included and excluded articles. Included studies must address NOWS treatment, or opioid withdrawal treatment of any age group, that may or may not have been tested in preclinical or clinical models. Results will summarise the current pharmacological and non-pharmacological treatment methods for NOWS, as well as potential novel treatments with a specific interest in non-opioid pharmacological interventions.Ethics and disseminationThis scoping review aims to broadly search preclinical and clinical literature as it relates to treatment of NOWS, including potential novel treatments with a specific interest in non-opioid pharmacological interventions. Given that this study does not directly involve human subjects or animal subjects research, Institutional Review Board (IRB) or Institutional Animal Care and Use Committee (IACUC) approval is not required. Results of this scoping review will be disseminated at conferences and submitted for publication in a peer-reviewed journal.

Project description:Emerging studies find arteriolar dysfunction in offspring with in-utero electronic cigarette (Ecig) exposure, but the long-term effect on offspring's cerebrovascular vascular and neurocognitive health is poorly understood. Ecigs provides a unique opportunity to directly evaluate the contributions of inhaled nicotine from the vehicle e-liquid - which was not possible with traditional cigarettes. Moreover, many Ecigs have variable power settings, which can alter the toxicity of the aerosol cloud produced. We hypothesize maternal vaping at different wattages will have variable effects on cerebrovascular function in the offspring, and that these effects would be independent of nicotine. We used time-mated female Sprague-Dawley rats with Ecig exposure from gestation day (GD)2-21. We studied male and female offspring for vascular and neurocognitive function at 1-, 3-, 6- and 12-months of age. We found that, both sexes, offspring with in-utero exposure (at 5w and 30w Ecig conditions) exhibited impaired middle cerebral artery (MCA) reactivity. While the magnitude of impairment was greater at higher that lower watts, Ecig at 5-watts still exhibited significant impairments in MCA function (suggesting the harm threshold for blood vessels is very low). Vascular dysfunction was evident with or without nicotine in the e-liquid, but nicotine exposure resulted in short-term memory deficits, evidence of neuronal damage, and increased astrocyte interaction with endothelial cells in 6- and 12-month-old offspring. We also observed altered expression of clock genes and antioxidant signaling pathways, along with a decrease in sirtuin-1 expression, decreased ratio of beta-amyloid Aβ 42/40 protein expression, and increased in NOX1, which are consistent with redox imbalance, neuroinflammation, and advancing cellular senescence. These preclinical data provide evidence suggesting that in utero exposure to Ecigs from maternal vaping can be expected to adversely affect the brain health of offspring in their adult life and that neurocognitive outcomes are worsened with exposure to nicotine.

Dataset Information

Neonatal Outcomes after Combined Opioid and Nicotine Exposure in Utero: A Scoping Review.

Publications

Neonatal Outcomes after Combined Opioid and Nicotine Exposure in Utero: A Scoping Review.

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