Comparing Neonatal Abstinence Syndrome and its Management in Babies Prenatally Exposed to Opioids and Methamphetamines

Comparing Neonatal Abstinence Syndrome and its Management in Babies Prenatally Exposed to Opioids and Methamphetamines | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparing Neonatal Abstinence Syndrome and its Management in Babies Prenatally Exposed to Opioids and Methamphetamines Reza Behmadi, Zahra Vahedi, Reza Marzban, Camellia Akhgarjand, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4235596/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The increasing prevalence of methamphetamine use during pregnancy has raised concerns about its impact on neonatal outcomes, including neonatal abstinence syndrome (NAS). This retrospective cohort study aimed to examine the severity of NAS and associated clinical outcomes in neonates based on the type of prenatal substance exposure (opioids, methamphetamines, or a combination). Material and Methods The study population included 80 term neonates born to mothers with documented substance use, stratified into three cohorts: opioid-only exposure, stimulant-only exposure, and combined opioid and stimulant exposure. Data on birth weight, gestational age, gender, route of delivery, length of hospital stay, and treatment requirements were extracted from medical records. Results Significant differences were observed in birth weight, with infants in the opioid-only group being heavier compared to the other two groups. The rates of small for gestational age (SGA) were 0%, 12.5%, and 21.4% in the opioid, methamphetamine, and Opioid + Methamphetamine groups, respectively. However, gestational age and the need for cesarean delivery did not differ significantly across the groups. Regarding treatment requirements, there were no statistically significant differences among the groups in the need for pharmacological or non-pharmacological interventions, nor in the duration of hospitalization. Conclusions Contrary to previous findings, this study suggests that neonates prenatally exposed to methamphetamines may exhibit NAS severity and treatment requirements comparable to those exposed to opioids. These findings challenge the long-held notion that opioid withdrawal universally eclipses the severity of methamphetamine withdrawal in newborns. Further research is needed to elucidate the potential mediating variables that may contribute to the observed equivalency in NAS susceptibility across different drug classes. Neonatal Abstinence Syndrome Opioids Metamfetamine Introduction The use of methamphetamine has increased dramatically in recent decades, including in women of childbearing age. Misuse of methamphetamine during pregnancy can have serious adverse effects on the developing fetus and newborn. Prenatal methamphetamine exposure is associated with an increased risk of premature delivery, placental abruption, fetal distress, and intrauterine growth restriction [1–4]. Newborns prenatally exposed to methamphetamine are also at risk of neonatal abstinence syndrome (NAS), a complex condition involving neurobehavioral dysregulation [5]. Although NAS is most commonly linked to opioid exposure, methamphetamine and other stimulant substances can also induce withdrawal symptoms in infants and that methamphetamine abuse during pregnancy may have a milder withdrawal syndrome and less need for pharmacological therapy in newborns than opioids [6]. In our center the first line of treatment for all cases of NAS infants with symptoms is nonpharmacologic support, including swaddling, placing the infant in a dark and quiet environment, holding and Kangaroo care, and reducing stimulation [5]. If despite these measures, the severity of withdrawal symptoms is high (as Finnegan score 8 or above, in three consecutive assessments), pharmacologic treatment is added. Due to the changing trends in illicit drug use during pregnancy, with more women misusing methamphetamine and other stimulants, we conducted this study to examine the impact of prenatal exposure to these drugs on newborns, including withdrawal symptoms and the potential need for pharmacological treatment. Material and Methods Study design This retrospective cohort study was approved by Research Ethics Committee of Iran University of Medical Sciences (approval code: IUMS.REC.1398.425). The study population was identified by reviewing medical records of all live births at Firoozabadi Teaching Hospital Tehran, Iran, between April 2019 to April 2022. Inclusion criteria were term neonates who were exposed to illicit substances in utero as documented by urine toxicology screening on mothers (according to our center policy with informed constant of mothers). The files of these mothers and babies of them, which include an informed consent form regarding the use of information from the file for research purposes, were examined and the design questionnaire including the investigated variables was completed by the researchers. Eligible neonates were stratified into three cohorts based on type of illicit substance exposure: opioid-only exposure; stimulant-only exposure; and combined opioid and stimulant exposure. Exclusion Criteria were neonates who was preterm birth (< 37 weeks gestation); had major congenital anomalies; had early-onset sepsis upon admission workup; were multiple gestation; or in case of incomplete medical records after telephone follow-up using parental contact information. Gestational age was calculated using the mother’s last menstrual period and early obstetric ultrasonography when available. Data Collection The following neonatal outcomes were abstracted from the medical records: birth weight, gestational age, gender, route of delivery, length of neonatal hospital stay and type of treatment (pharmacologic or non-pharmacologic). The appropriate sample size was calculated at least 73 based on the prevalence reported in the study by Wendell AD (7) suggest that about 5 percent of pregnant women use one or more addictive substances and the following formula, where alpha was taken as 0.05 and d as 0.1. n = (z^2 * p * (1 - p)) / d^2 Urine Toxicology Screening Urine toxicology immunoassays were performed on mothers according to our center policy to confirm exposure to illicit substances such as morphine, methadone, amphetamine, metamphetamine, cannabionols, cocaine, barbiturates, teramadol, benzodiazepines and tricyclic antidepressants (TCAs). Neonatal urine toxicology was also reviewed when available. But the inclusion criteria were only when maternal test was positive. Assessment of Neonatal Abstinence Syndrome Neonates with in utero illicit drug exposure were assessed for neonatal abstinence syndrome every 4 hours starting at 2 hours of life using a Finnegan scoring system. Infants with scores ≥ 8 on three consecutive assessments were determined to have neonatal abstinence syndrome which need pharmacological treatment and were started on treatment with morphine, phenobarbital or clonidine. Statistical analysis The results were described by frequency (percentage) and mean ± standard deviation (SD). The qualitative variables were tested using chi-square test, and the quantitative variables were tested using one-way ANOVA. For the statistical analysis, the statistical software SPSS version 24 (IBM Crop, Armonk, NY, USA) was used. P values of 0.05 or less were considered statistically significant. Results In this retrospective cohort study, we evaluated 80 neonates born to mothers with substance addiction to determine the severity of neonatal abstinence syndrome (NAS) and associated clinical outcomes based on the type of substance used. The infants were stratified into three groups: those born to mothers who used opioids (n = 26), amphetamines (MA, n = 40), and a combination of opioids and amphetamines (Opioid + MA, n = 14). Demographic and Clinical Characteristics The gender distribution did not differ significantly across the study groups (p = 0.462) (Table 1 ). Table 1 Demographic characteristics Opioid group MA group Opioid + MA group p-value Gender Male 15 (57.7) 16 (40.0) 11 (78.6) 0.462 a Female 11 (42.3) 24 (60.0) 3 (21.4) Birth weight, g 2749 ± 149 2599 ± 199 2551 ± 254 0.047 b Gestational age, wk 38.8 ± 1.5 38.0 ± 1.4 37.8 ± 1.7 0.092 b Route of delivery Vaginal 14 (53.8) 22 (55.0) 9 (64.3) 0.648 a C/S 12 (46.2) 18 (45.0) 5 (35.7) Total 26 (32.5) 40 (50.0) 14 (17.5) a Results of chi-square test. b Results of one-way ANOVA. Methamphetamine (MA), Cesarean section (C/S). Data are presented as number (%) or mean ± SD. Birth weight varied significantly among the groups (p = 0.047) (Table 1 ). Infants in the Opioid group were, on average, heavier compared to the other two groups. The gestational age at birth showed no significant difference among the groups (p = 0.092) (Table 1 ). With regard to the route of delivery, The differences between groups were not statistically significant (p = 0.648) (Table 1 ). Treatment Requirement and Hospitalization The mean days of hospitalization was not significantly different between the three groups (p = 0.23) (Table 2 ). The rate of small for gestational age (SGA) was 0%, 12.5% and 21.4% in the opioid, MA, and opioid + MA groups, respectively (p = 0.68) (Table 2 ). Table 2 Treatment Requirement and Hospitalization Opioid group MA group Opioid + MA group p-value Duration of hospitalization, days 4.6 ± 1.2 4.4 ± 1.1 6.75 ± 2.3 0.23 a SGA 0 (0.0) 5 (12.5) 3 (21.4) 0.68 b Treatment Requirement None 10 (38.5) 16 (40.0) 6 (42.9) 0.76 b Non-pharmacological 6 (23.1) 10 (25.0) 2 (14.3) Pharmacological 10 (38.5) 14 (35.0) 6 (42.9) a Results of one-way ANOVA. b Results of chi-square test. Small for gestational age (SGA) Among the opioid group, 10 infants (38.5%) did not require any treatment, 6 (23.1%) needed non-pharmacological treatment, and 10 (38.5%) required pharmacological treatment for their withdrawal symptoms. For the MA group, the corresponding numbers were 16 (40%), 10 (25%), and 14 (35%). In the opioid + MA group, 6 infants (42.9%) did not need treatment, 2 (14.3%) required non-pharmacological, and 6 (42.9%) needed pharmacological treatment. There was no significant difference in treatment requirements between the groups (p = 0.76) (Table 2 ). Discussion Birth weight Both opioid misuse and methamphetamine misuse during pregnancy have been associated with adverse effects on the birth weight of newborns. Research indicates that opioid use during pregnancy can lead to low birth weight and other complications for the newborn [3]. Opioid use disorder among pregnant women is a significant concern, and efforts are made to prevent adverse outcomes for both the mother and the child [8]. Similarly, methamphetamine use during pregnancy has been linked to an increased risk of low birth weight. Stopping methamphetamine use at any time during pregnancy has been shown to improve birth outcomes, emphasizing the importance of timely interventions [9]. While specific studies comparing the birth weight of opiate users and methamphetamine users during pregnancy have not be done specifically, the information highlights potential adverse effects associated with both substances [10]. In our study Birth weight varied significantly among the groups (p = 0.047) Infants in the Opioid group were, on average, heavier compared to the other two groups. This differences can be due to different cultural and Socioeconomical status of mothers who use opiates as old and Traditional drugs versus methamphetamines as new and synthetic drugs. The positive effect of methadone replacement therapy by health care providers can be another probable cause [11]. Further Research on Substance-Specific Outcomes Should be considered. Gestational Age, SGA This finding along with another finding of our research that the length of pregnancy and gestational age in these babies are normal led to another finding of our research that ). The rate of small for gestational age (SGA) was 0%, 12.5% and 21.4% in the opioid, MA, and opioid + MA groups, respectively (p = 0.68) Research suggests that opioid misuse during pregnancy is associated with an increased risk of preterm birth and low birth weight [12].On the other hand, methamphetamine use in pregnancy is linked to an increased risk of low birth weight and small for gestational age babies [13]. Although The effect of drug abuse on gestational age was not confirmed by our results but the risk of being small for gestational age for infants of drug misusing mothers was evident in our results. Route of Delivery Although methamphetamine use during pregnancy has been associated with an increased risk of adverse outcomes, and addressing potential complications may involve decisions about the method of delivery [7]. There is limited direct information available on the specific comparison between opioid and methamphetamine misuse during pregnancy in terms of the need for caesarian section for newborns. In our study, we did not find a significant difference in the need for cesarean delivery in the two groups which can indicate that there is no clear difference in the birth complications of these groups, However, more dedicated studies in the future seem necessary in this field. Need To Admission and Duration of Admission Researches indicate that both opioid misuse and methamphetamine misuse during pregnancy can contribute to prolonged hospital admissions for newborns, but the specific duration may vary based on individual cases and circumstances. Opioid misuse during pregnancy, especially if it leads to Neonatal Abstinence Syndrome (NAS), is associated with an increased likelihood of extended hospital stays for affected newborns. Similarly, infants born to mothers who misuse methamphetamine may also face prolonged hospital admissions due to the potential health complications associated with methamphetamine exposure during pregnancy [14,15]. In our study, there was no significant difference in the need for hospitalization of the newborn and the duration of hospitalization of the newborn in the three groups which can indicate that between three groups in the field of the severity of withdrawal symptoms, overall health of the infant, and the effectiveness of medical interventions The differences are not significant . Need for pharmacological treatment and hospitalization duration Past literature demonstrates that neonates born to mothers with opioid use disorders during pregnancy have historically displayed more severe neonatal abstinence syndrome (NAS) Symptomatology and required pharmacological treatment more frequently compared to neonates with in utero methamphetamine exposure [7]. For example, Smith et al. ( 2003 ), infant withdrawal signs from methamphetamine withdrawal only need pharmacologic therapy in 4% of cases [6]. However, intriguingly, our recent retrospective data challenges these long-held notions .Upon dividing our maternal-infant cohort into three distinct groups - opiate misuse, methamphetamine misuse, and multi-drug misuse during gestation - we found no statistically significant differences between groups in regards to NAS diagnosis rates using similar scoring methods to Smith et al. or infant hospital lengths of stay. Therefore, the notion that opioid withdrawal universally eclipses methamphetamine severity may require re-evaluation through rigorous designed study to elucidate the potential mediating variables resulting in equivalently increased NAS susceptibly in our sample across differing drug classes. Practical application of these findings could inform clinical screening and monitoring practices. Declarations Acknowledgements We express our sincere gratitude to our colleagues and the dedicated staff of the Neonatal Intensive Care Unit (NICU) at Firoozabadi Hospital for their invaluable support throughout the duration of this study. Author contributions RB conceived and implemented the study idea; wrote the first draft. RM conceived and implemented the study idea. HH conducted statistical data analysis. CA and ZV analyzed the first draft. All authors reviewed and approved the final manuscript. Funding No financial support was provided in any way for this research. Data availability The datasets generated and/or analyzed during the current study are not publicly available, but are available from the corresponding author at reasonable request. Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics approval and consent to participate The study was performed by the ethical standards promoted by the 1964 Declaration of Helsinki and its later amendments, and the Ethical Committee approved its protocol of Iran University of Medical Sciences (approval code: IUMS.REC.1398.425). The study population was identified by reviewing medical records of all live births at Firoozabadi Teaching Hospital Tehran, Iran, between April 2019 to April 2022. Consent for publication Not applicable. Competing interests The authors declare no competing interests. References Han B, Compton WM, Jones CM, Einstein EB, Volkow ND. Methamphetamine use, methamphetamine use disorder, and associated overdose deaths among US adults. JAMA psychiatry. 2021 Dec 1;78(12):1329-42. Harst L, Deckert S, Haarig F, Reichert J, Dinger J, Hellmund P, Schmitt J, Rüdiger M. Prenatal Methamphetamine Exposure: Effects on Child Development: A Systematic Review. Deutsches Ärzteblatt International. 2021 May;118(18):313. Wright TE, Schuetter R, Tellei J, Sauvage L. Methamphetamines and pregnancy outcomes. Journal of addiction medicine. 2015 Mar;9(2):111. Motlagh PD, Kachuei M, Noormohamadi A, Falahi S, Alaei H. Evaluation of Medical Prefrontal Cortex (mPFC) Stimulation and Destruction Effects on Addiction to Morphine. Journal of Isfahan Medical School. 2013 Jun 8;31(232). Kocherlakota P. Neonatal abstinence syndrome. Pediatrics. 2014 Aug 1;134(2):e547-61. Smith L, Yonekura ML, Wallace T, Berman N, Kuo J, Berkowitz C. Effects of prenatal methamphetamine exposure on fetal growth and drug withdrawal symptoms in infants born at term. Journal of Developmental & Behavioral Pediatrics. 2003 Feb 1;24(1):17-23. Wendell AD. Overview and epidemiology of substance abuse in pregnancy. Clin Obstet Gynecol. 2013;56(1):91-96. doi:10.1097/GRF.0b013e31827feeb9 Kalaitzopoulos DR, Chatzistergiou K, Amylidi AL, Kokkinidis DG, Goulis DG. Effect of methamphetamine hydrochloride on pregnancy outcome: a systematic review and meta-analysis. Journal of addiction medicine. 2018 May 1;12(3):220-6. Wright TE, Schuetter R, Tellei J, Sauvage L. Methamphetamines and pregnancy outcomes. Journal of addiction medicine. 2015 Mar;9(2):111. Wachman EM, Schiff DM, Silverstein M. Neonatal abstinence syndrome: advances in diagnosis and treatment. Jama. 2018 Apr 3;319(13):1362-74. Aklin WM, Herrmann ES. National Institute on Drug Abuse (NIDA) research priorities to support the development of incentive-based treatments for substance use disorders. Preventive Medicine. 2023 Nov 1;176:107650.12. PubMed - Opioid use during pregnancy: a population-based study Arria AM, Derauf C, LaGasse LL, Grant P, Shah R, Smith L, Haning W, Huestis M, Strauss A, Grotta SD, Liu J. Methamphetamine and other substance use during pregnancy: preliminary estimates from the Infant Development, Environment, and Lifestyle (IDEAL) study. Maternal and child health journal. 2006 May;10:293-302. Han B, Compton WM, Jones CM, Einstein EB, Volkow ND. Methamphetamine use, methamphetamine use disorder, and associated overdose deaths among US adults. JAMA psychiatry. 2021 Dec 1;78(12):1329-42. Batra K, Cruz P, Cross CL, Bhandari N, Abdulla F, Pharr JR, Buttner MP. Incidence of neonatal abstinence syndrome epidemic and associated predictors in Nevada: A statewide audit, 2016–2018. International journal of environmental research and public health. 2021 Jan;18(1):232. Chasnoff IJ, Gardner S. Neonatal abstinence syndrome: a policy perspective. Journal of Perinatology. 2015 Aug;35(8):539-41. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4235596","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":290608272,"identity":"7b456672-cea1-4f0a-9fdf-419a484d0ffa","order_by":0,"name":"Reza Behmadi","email":"","orcid":"","institution":"Iran University of Medical Sciences (IUMS)","correspondingAuthor":false,"prefix":"","firstName":"Reza","middleName":"","lastName":"Behmadi","suffix":""},{"id":290608273,"identity":"a46126e7-c382-4eb4-ac01-b949a0fed08c","order_by":1,"name":"Zahra Vahedi","email":"","orcid":"","institution":"Iran University of Medical Sciences (IUMS)","correspondingAuthor":false,"prefix":"","firstName":"Zahra","middleName":"","lastName":"Vahedi","suffix":""},{"id":290608274,"identity":"08a208da-698e-4379-b869-17f63325965b","order_by":2,"name":"Reza Marzban","email":"","orcid":"","institution":"Iran University of Medical Sciences (IUMS)","correspondingAuthor":false,"prefix":"","firstName":"Reza","middleName":"","lastName":"Marzban","suffix":""},{"id":290608275,"identity":"3a1dc48c-ab2a-4a1a-920c-efdcf0247735","order_by":3,"name":"Camellia Akhgarjand","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Camellia","middleName":"","lastName":"Akhgarjand","suffix":""},{"id":290608276,"identity":"ae903951-1db4-45ea-9223-080a243cbcdc","order_by":4,"name":"Hirad Houjaghani","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+UlEQVRIiWNgGAWjYDCCAwxsQBKIJYBUQgWQYGZuIEXLGZAWRqK0MEC0MLaBWAS08N0+wPbgYxufvHx087MHD+fVRvO3A7X8qNiGU4vkuQR2w5ltbIYb7xwzN0jcdjx3xmHGBsaeM7dxajE4w8AmzdvGxrhxRoKZROK2Y7kNQC3MjG2EtdhvnJH+TSJxzrHc+cRqSZwvkQO0paEmdwMhLZJnGNskZ5xjS94gkVMmkXDsQO5GoJaD+PzCd4b5mMSHsmO282ekb5P8UVOXO+/84YMPflTg1gKNhWMMBgfAvMNg8gAe9TBQwyDfAGbUEaF4FIyCUTAKRhoAAHrNW9kuRmzPAAAAAElFTkSuQmCC","orcid":"","institution":"Iran University of Medical Sciences (IUMS)","correspondingAuthor":true,"prefix":"","firstName":"Hirad","middleName":"","lastName":"Houjaghani","suffix":""}],"badges":[],"createdAt":"2024-04-08 10:18:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4235596/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4235596/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86269555,"identity":"eccb466f-aeb4-4f66-b037-de76d59b2096","added_by":"auto","created_at":"2025-07-08 16:46:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":567600,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4235596/v1/eda6bf4c-b127-4a7a-8de7-a8eb7e1cfff9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparing Neonatal Abstinence Syndrome and its Management in Babies Prenatally Exposed to Opioids and Methamphetamines","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe use of methamphetamine has increased dramatically in recent decades, including in women of childbearing age. Misuse of methamphetamine during pregnancy can have serious adverse effects on the developing fetus and newborn. Prenatal methamphetamine exposure is associated with an increased risk of premature delivery, placental abruption, fetal distress, and intrauterine growth restriction [1\u0026ndash;4]. Newborns prenatally exposed to methamphetamine are also at risk of neonatal abstinence syndrome (NAS), a complex condition involving neurobehavioral dysregulation [5]. Although NAS is most commonly linked to opioid exposure, methamphetamine and other stimulant substances can also induce withdrawal symptoms in infants and that methamphetamine abuse during pregnancy may have a milder withdrawal syndrome and less need for pharmacological therapy in newborns than opioids [6].\u003c/p\u003e \u003cp\u003eIn our center the first line of treatment for all cases of NAS infants with symptoms is nonpharmacologic support, including swaddling, placing the infant in a dark and quiet environment, holding and Kangaroo care, and reducing stimulation [5]. If despite these measures, the severity of withdrawal symptoms is high (as Finnegan score 8 or above, in three consecutive assessments), pharmacologic treatment is added.\u003c/p\u003e \u003cp\u003eDue to the changing trends in illicit drug use during pregnancy, with more women misusing methamphetamine and other stimulants, we conducted this study to examine the impact of prenatal exposure to these drugs on newborns, including withdrawal symptoms and the potential need for pharmacological treatment.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003e This retrospective cohort study was approved by Research Ethics Committee of Iran University of Medical Sciences (approval code: IUMS.REC.1398.425). The study population was identified by reviewing medical records of all live births at Firoozabadi Teaching Hospital Tehran, Iran, between April 2019 to April 2022.\u003c/p\u003e \u003cp\u003eInclusion criteria were term neonates who were exposed to illicit substances in utero as documented by urine toxicology screening on mothers (according to our center policy with informed constant of mothers). The files of these mothers and babies of them, which include an informed consent form regarding the use of information from the file for research purposes, were examined and the design questionnaire including the investigated variables was completed by the researchers. Eligible neonates were stratified into three cohorts based on type of illicit substance exposure: opioid-only exposure; stimulant-only exposure; and combined opioid and stimulant exposure.\u003c/p\u003e \u003cp\u003eExclusion Criteria were neonates who was preterm birth (\u0026lt;\u0026thinsp;37 weeks gestation); had major congenital anomalies; had early-onset sepsis upon admission workup; were multiple gestation; or in case of incomplete medical records after telephone follow-up using parental contact information. Gestational age was calculated using the mother\u0026rsquo;s last menstrual period and early obstetric ultrasonography when available.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData Collection\u003c/h2\u003e \u003cp\u003eThe following neonatal outcomes were abstracted from the medical records: birth weight, gestational age, gender, route of delivery, length of neonatal hospital stay and type of treatment (pharmacologic or non-pharmacologic).\u003c/p\u003e \u003cp\u003eThe appropriate sample size was calculated at least 73 based on the prevalence reported in the study by Wendell AD (7) suggest that about 5 percent of pregnant women use one or more addictive substances and the following formula, where alpha was taken as 0.05 and d as 0.1.\u003c/p\u003e \u003cp\u003en = (z^2 * p * (1 - p)) / d^2\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eUrine Toxicology Screening\u003c/h2\u003e \u003cp\u003eUrine toxicology immunoassays were performed on mothers according to our center policy to confirm exposure to illicit substances such as morphine, methadone, amphetamine, metamphetamine, cannabionols, cocaine, barbiturates, teramadol, benzodiazepines and tricyclic antidepressants (TCAs). Neonatal urine toxicology was also reviewed when available. But the inclusion criteria were only when maternal test was positive.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eAssessment of Neonatal Abstinence Syndrome\u003c/h2\u003e \u003cp\u003eNeonates with in utero illicit drug exposure were assessed for neonatal abstinence syndrome every 4 hours starting at 2 hours of life using a Finnegan scoring system. Infants with scores\u0026thinsp;\u0026ge;\u0026thinsp;8 on three consecutive assessments were determined to have neonatal abstinence syndrome which need pharmacological treatment and were started on treatment with morphine, phenobarbital or clonidine.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe results were described by frequency (percentage) and mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). The qualitative variables were tested using chi-square test, and the quantitative variables were tested using one-way ANOVA. For the statistical analysis, the statistical software SPSS version 24 (IBM Crop, Armonk, NY, USA) was used. P values of 0.05 or less were considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn this retrospective cohort study, we evaluated 80 neonates born to mothers with substance addiction to determine the severity of neonatal abstinence syndrome (NAS) and associated clinical outcomes based on the type of substance used. The infants were stratified into three groups: those born to mothers who used opioids (n\u0026thinsp;=\u0026thinsp;26), amphetamines (MA, n\u0026thinsp;=\u0026thinsp;40), and a combination of opioids and amphetamines (Opioid\u0026thinsp;+\u0026thinsp;MA, n\u0026thinsp;=\u0026thinsp;14).\u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eDemographic and Clinical Characteristics\u003c/h2\u003e \u003cp\u003eThe gender distribution did not differ significantly across the study groups (p\u0026thinsp;=\u0026thinsp;0.462) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOpioid group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMA group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOpioid\u0026thinsp;+\u0026thinsp;MA group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (57.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 (78.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.462\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (42.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (21.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBirth weight, g\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2749\u0026thinsp;\u0026plusmn;\u0026thinsp;149\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2599\u0026thinsp;\u0026plusmn;\u0026thinsp;199\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2551\u0026thinsp;\u0026plusmn;\u0026thinsp;254\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.047\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGestational age, wk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.092\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eRoute of delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVaginal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (53.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (55.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (64.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.648\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC/S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (45.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (35.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (32.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14 (17.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003e Results of chi-square test. \u003csup\u003eb\u003c/sup\u003eResults of one-way ANOVA. Methamphetamine (MA), Cesarean section (C/S). Data are presented as number (%) or mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBirth weight varied significantly among the groups (p\u0026thinsp;=\u0026thinsp;0.047) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Infants in the Opioid group were, on average, heavier compared to the other two groups.\u003c/p\u003e \u003cp\u003eThe gestational age at birth showed no significant difference among the groups (p\u0026thinsp;=\u0026thinsp;0.092) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). With regard to the route of delivery, The differences between groups were not statistically significant (p\u0026thinsp;=\u0026thinsp;0.648) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eTreatment Requirement and Hospitalization\u003c/h2\u003e \u003cp\u003eThe mean days of hospitalization was not significantly different between the three groups (p\u0026thinsp;=\u0026thinsp;0.23) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The rate of small for gestational age (SGA) was 0%, 12.5% and 21.4% in the opioid, MA, and opioid\u0026thinsp;+\u0026thinsp;MA groups, respectively (p\u0026thinsp;=\u0026thinsp;0.68) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTreatment Requirement and Hospitalization\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOpioid group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMA group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOpioid\u0026thinsp;+\u0026thinsp;MA group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDuration of hospitalization, days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.75\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.23\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.68\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eTreatment Requirement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (38.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.76\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-pharmacological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (23.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (14.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePharmacological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (38.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (35.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (42.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003e Results of one-way ANOVA. \u003csup\u003eb\u003c/sup\u003eResults of chi-square test. Small for gestational age (SGA)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong the opioid group, 10 infants (38.5%) did not require any treatment, 6 (23.1%) needed non-pharmacological treatment, and 10 (38.5%) required pharmacological treatment for their withdrawal symptoms. For the MA group, the corresponding numbers were 16 (40%), 10 (25%), and 14 (35%). In the opioid\u0026thinsp;+\u0026thinsp;MA group, 6 infants (42.9%) did not need treatment, 2 (14.3%) required non-pharmacological, and 6 (42.9%) needed pharmacological treatment. There was no significant difference in treatment requirements between the groups (p\u0026thinsp;=\u0026thinsp;0.76) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eBirth weight\u003c/p\u003e \u003cp\u003eBoth opioid misuse and methamphetamine misuse during pregnancy have been associated with adverse effects on the birth weight of newborns.\u003c/p\u003e \u003cp\u003eResearch indicates that opioid use during pregnancy can lead to low birth weight and other complications for the newborn [3]. Opioid use disorder among pregnant women is a significant concern, and efforts are made to prevent adverse outcomes for both the mother and the child [8].\u003c/p\u003e \u003cp\u003eSimilarly, methamphetamine use during pregnancy has been linked to an increased risk of low birth weight. Stopping methamphetamine use at any time during pregnancy has been shown to improve birth outcomes, emphasizing the importance of timely interventions [9].\u003c/p\u003e \u003cp\u003eWhile specific studies comparing the birth weight of opiate users and methamphetamine users during pregnancy have not be done specifically, the information highlights potential adverse effects associated with both substances [10]. In our study Birth weight varied significantly among the groups (p\u0026thinsp;=\u0026thinsp;0.047) Infants in the Opioid group were, on average, heavier compared to the other two groups.\u003c/p\u003e \u003cp\u003eThis differences can be due to different cultural and Socioeconomical status of mothers who use opiates as old and Traditional drugs versus methamphetamines as new and synthetic drugs. The positive effect of methadone replacement therapy by health care providers can be another probable cause [11]. Further Research on Substance-Specific Outcomes Should be considered.\u003c/p\u003e \u003cp\u003eGestational Age, SGA\u003c/p\u003e \u003cp\u003eThis finding along with another finding of our research that the length of pregnancy and gestational age in these babies are normal led to another finding of our research that ). The rate of small for gestational age (SGA) was 0%, 12.5% and 21.4% in the opioid, MA, and opioid\u0026thinsp;+\u0026thinsp;MA groups, respectively (p\u0026thinsp;=\u0026thinsp;0.68)\u003c/p\u003e \u003cp\u003eResearch suggests that opioid misuse during pregnancy is associated with an increased risk of preterm birth and low birth weight [12].On the other hand, methamphetamine use in pregnancy is linked to an increased risk of low birth weight and small for gestational age babies [13].\u003c/p\u003e \u003cp\u003eAlthough The effect of drug abuse on gestational age was not confirmed by our results but the risk of being small for gestational age for infants of drug misusing mothers was evident in our results.\u003c/p\u003e \u003cp\u003eRoute of Delivery\u003c/p\u003e \u003cp\u003eAlthough methamphetamine use during pregnancy has been associated with an increased risk of adverse outcomes, and addressing potential complications may involve decisions about the method of delivery [7]. There is limited direct information available on the specific comparison between opioid and methamphetamine misuse during pregnancy in terms of the need for caesarian section for newborns.\u003c/p\u003e \u003cp\u003eIn our study, we did not find a significant difference in the need for cesarean delivery in the two groups which can indicate that there is no clear difference in the birth complications of these groups, However, more dedicated studies in the future seem necessary in this field.\u003c/p\u003e \u003cp\u003eNeed To Admission and Duration of Admission\u003c/p\u003e \u003cp\u003eResearches indicate that both opioid misuse and methamphetamine misuse during pregnancy can contribute to prolonged hospital admissions for newborns, but the specific duration may vary based on individual cases and circumstances.\u003c/p\u003e \u003cp\u003eOpioid misuse during pregnancy, especially if it leads to Neonatal Abstinence Syndrome (NAS), is associated with an increased likelihood of extended hospital stays for affected newborns.\u003c/p\u003e \u003cp\u003eSimilarly, infants born to mothers who misuse methamphetamine may also face prolonged hospital admissions due to the potential health complications associated with methamphetamine exposure during pregnancy [14,15].\u003c/p\u003e \u003cp\u003eIn our study, there was no significant difference in the need for hospitalization of the newborn and the duration of hospitalization of the newborn in the three groups which can indicate that between three groups in the field of the severity of withdrawal symptoms, overall health of the infant, and the effectiveness of medical interventions The differences are not significant .\u003c/p\u003e \u003cp\u003eNeed for pharmacological treatment and hospitalization duration\u003c/p\u003e \u003cp\u003ePast literature demonstrates that neonates born to mothers with opioid use disorders during pregnancy have historically displayed more severe neonatal abstinence syndrome (NAS) Symptomatology and required pharmacological treatment more frequently compared to neonates with in utero methamphetamine exposure [7]. For example, Smith et al. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2003\u003c/span\u003e), infant withdrawal signs from methamphetamine withdrawal only need pharmacologic therapy in 4% of cases [6]. However, intriguingly, our recent retrospective data challenges these long-held notions .Upon dividing our maternal-infant cohort into three distinct groups - opiate misuse, methamphetamine misuse, and multi-drug misuse during gestation - we found no statistically significant differences between groups in regards to NAS diagnosis rates using similar scoring methods to Smith et al. or infant hospital lengths of stay. Therefore, the notion that opioid withdrawal universally eclipses methamphetamine severity may require re-evaluation through rigorous designed study to elucidate the potential mediating variables resulting in equivalently increased NAS susceptibly in our sample across differing drug classes. Practical application of these findings could inform clinical screening and monitoring practices.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe express our sincere gratitude to our colleagues and the dedicated staff of the Neonatal Intensive Care Unit (NICU) at Firoozabadi Hospital for their invaluable support throughout the duration of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRB conceived and implemented the study idea; wrote the first draft. RM conceived and implemented the study idea. HH conducted statistical data analysis. CA and ZV analyzed the first draft. All authors reviewed and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo financial support was provided in any way for this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available, but are available from the corresponding author at reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u0026nbsp;\u003c/strong\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was performed by the ethical standards promoted by the 1964 Declaration of Helsinki and its later amendments, and the Ethical Committee approved its protocol of\u0026nbsp;Iran University of Medical Sciences (approval code: IUMS.REC.1398.425). The study population was identified by reviewing medical records of all live births at Firoozabadi Teaching Hospital Tehran, Iran, between April 2019 to April 2022.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eHan B, Compton WM, Jones CM, Einstein EB, Volkow ND. Methamphetamine use, methamphetamine use disorder, and associated overdose deaths among US adults. JAMA psychiatry. 2021 Dec 1;78(12):1329-42.\u003c/li\u003e\n \u003cli\u003eHarst L, Deckert S, Haarig F, Reichert J, Dinger J, Hellmund P, Schmitt J, R\u0026uuml;diger M. Prenatal Methamphetamine Exposure: Effects on Child Development: A Systematic Review. Deutsches \u0026Auml;rzteblatt International. 2021 May;118(18):313.\u003c/li\u003e\n \u003cli\u003eWright TE, Schuetter R, Tellei J, Sauvage L. Methamphetamines and pregnancy outcomes. Journal of addiction medicine. 2015 Mar;9(2):111.\u003c/li\u003e\n \u003cli\u003eMotlagh PD, Kachuei M, Noormohamadi A, Falahi S, Alaei H. Evaluation of Medical Prefrontal Cortex (mPFC) Stimulation and Destruction Effects on Addiction to Morphine. Journal of Isfahan Medical School. 2013 Jun 8;31(232).\u003c/li\u003e\n \u003cli\u003eKocherlakota P. Neonatal abstinence syndrome.\u0026nbsp;Pediatrics. 2014 Aug 1;134(2):e547-61.\u003c/li\u003e\n \u003cli\u003eSmith L, Yonekura ML, Wallace T, Berman N, Kuo J, Berkowitz C. Effects of prenatal methamphetamine exposure on fetal growth and drug withdrawal symptoms in infants born at term. Journal of Developmental \u0026amp; Behavioral Pediatrics. 2003 Feb 1;24(1):17-23.\u003c/li\u003e\n \u003cli\u003eWendell AD. Overview and epidemiology of substance abuse in pregnancy. Clin Obstet Gynecol. 2013;56(1):91-96. doi:10.1097/GRF.0b013e31827feeb9\u003c/li\u003e\n \u003cli\u003eKalaitzopoulos DR, Chatzistergiou K, Amylidi AL, Kokkinidis DG, Goulis DG. Effect of methamphetamine hydrochloride on pregnancy outcome: a systematic review and meta-analysis. Journal of addiction medicine. 2018 May 1;12(3):220-6.\u003c/li\u003e\n \u003cli\u003eWright TE, Schuetter R, Tellei J, Sauvage L. Methamphetamines and pregnancy outcomes. Journal of addiction medicine. 2015 Mar;9(2):111.\u003c/li\u003e\n \u003cli\u003eWachman EM, Schiff DM, Silverstein M. Neonatal abstinence syndrome: advances in diagnosis and treatment. Jama. 2018 Apr 3;319(13):1362-74.\u003c/li\u003e\n \u003cli\u003eAklin WM, Herrmann ES. National Institute on Drug Abuse (NIDA) research priorities to support the development of incentive-based treatments for substance use disorders. Preventive Medicine. 2023 Nov 1;176:107650.12.\u0026nbsp;\u0026nbsp;PubMed - Opioid use during pregnancy: a population-based study\u003c/li\u003e\n \u003cli\u003eArria AM, Derauf C, LaGasse LL, Grant P, Shah R, Smith L, Haning W, Huestis M, Strauss A, Grotta SD, Liu J. Methamphetamine and other substance use during pregnancy: preliminary estimates from the Infant Development, Environment, and Lifestyle (IDEAL) study. Maternal and child health journal. 2006 May;10:293-302.\u003c/li\u003e\n \u003cli\u003eHan B, Compton WM, Jones CM, Einstein EB, Volkow ND. Methamphetamine use, methamphetamine use disorder, and associated overdose deaths among US adults. JAMA psychiatry. 2021 Dec 1;78(12):1329-42.\u003c/li\u003e\n \u003cli\u003eBatra K, Cruz P, Cross CL, Bhandari N, Abdulla F, Pharr JR, Buttner MP. Incidence of neonatal abstinence syndrome epidemic and associated predictors in Nevada: A statewide audit, 2016\u0026ndash;2018. International journal of environmental research and public health. 2021 Jan;18(1):232.\u003c/li\u003e\n \u003cli\u003eChasnoff IJ, Gardner S. Neonatal abstinence syndrome: a policy perspective. Journal of Perinatology. 2015 Aug;35(8):539-41.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Neonatal Abstinence Syndrome, Opioids, Metamfetamine","lastPublishedDoi":"10.21203/rs.3.rs-4235596/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4235596/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe increasing prevalence of methamphetamine use during pregnancy has raised concerns about its impact on neonatal outcomes, including neonatal abstinence syndrome (NAS). This retrospective cohort study aimed to examine the severity of NAS and associated clinical outcomes in neonates based on the type of prenatal substance exposure (opioids, methamphetamines, or a combination).\u003c/p\u003e\u003ch2\u003eMaterial and Methods\u003c/h2\u003e \u003cp\u003eThe study population included 80 term neonates born to mothers with documented substance use, stratified into three cohorts: opioid-only exposure, stimulant-only exposure, and combined opioid and stimulant exposure. Data on birth weight, gestational age, gender, route of delivery, length of hospital stay, and treatment requirements were extracted from medical records.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSignificant differences were observed in birth weight, with infants in the opioid-only group being heavier compared to the other two groups. The rates of small for gestational age (SGA) were 0%, 12.5%, and 21.4% in the opioid, methamphetamine, and Opioid\u0026thinsp;+\u0026thinsp;Methamphetamine groups, respectively. However, gestational age and the need for cesarean delivery did not differ significantly across the groups. Regarding treatment requirements, there were no statistically significant differences among the groups in the need for pharmacological or non-pharmacological interventions, nor in the duration of hospitalization.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eContrary to previous findings, this study suggests that neonates prenatally exposed to methamphetamines may exhibit NAS severity and treatment requirements comparable to those exposed to opioids. These findings challenge the long-held notion that opioid withdrawal universally eclipses the severity of methamphetamine withdrawal in newborns. Further research is needed to elucidate the potential mediating variables that may contribute to the observed equivalency in NAS susceptibility across different drug classes.\u003c/p\u003e","manuscriptTitle":"Comparing Neonatal Abstinence Syndrome and its Management in Babies Prenatally Exposed to Opioids and Methamphetamines","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-15 08:38:07","doi":"10.21203/rs.3.rs-4235596/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"de959080-3216-4228-ac0f-853d91d97b11","owner":[],"postedDate":"April 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-08T16:38:40+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-15 08:38:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4235596","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4235596","identity":"rs-4235596","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}