Maternal methadone therapy increases QTc interval in newborn infants

Parikh, Ravikumar; Hussain, Tarique; Holder, G.; Bhoyar, Abhay; Ewer, Andrew K

doi:10.1136/adc.2009.181701

Cited by 39 publications

(28 citation statements)

References 18 publications

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“…Even though methadone reduces symptoms compared with illicit opiate use, clinical cohorts have demonstrated that prenatal methadone exposure can lead to increased premature birth (Cleary et al, 2012;FajemirokunOdudeyi et al, 2006;Lejeune et al, 2006), decreased birthweight (Cleary et al, 2012;Hulse et al, 1997;Kandall et al, 1976;Sarfi et al, 2009;, and smaller head circumference (Brown et al, 1998;Hans, 1989;Rosen and Johnson, 1985;Welle-Strand et al, 2013;Wilson et al, 1981). Additional reports indicate an increased incidence of respiratory insufficiency at birth (Maas et al, 1990), altered corrected QT interval on electrocardiogram during the first postnatal week (Parikh et al, 2011), postnatal hyperphagia (Martinez et al, 1999), disrupted auditory event related potentials (Paul et al, 2014), and myelination deficits (Walhovd et al, 2012). However, the prevalence of cognitive impairments produced by prenatal methadone has been questioned because some studies have not observed differences in cognitive development (de Cubas and Field, 1993;Hans, 1989;Rosen and Johnson, 1985) or performance (Bauman and Levine, 1986;Soepatmi, 1994;van Baar, 1990;van Baar and de Graaff, 1994;.…”

Section: Methadonementioning

confidence: 99%

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

Ross

Graham

Money

et al. 2014

Neuropsychopharmacol

342

241

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Most drugs of abuse easily cross the placenta and can affect fetal brain development. In utero exposures to drugs thus can have long-lasting implications for brain structure and function. These effects on the developing nervous system, before homeostatic regulatory mechanisms are properly calibrated, often differ from their effects on mature systems. In this review, we describe current knowledge on how alcohol, nicotine, cocaine, amphetamine, Ecstasy, and opiates (among other drugs) produce alterations in neurodevelopmental trajectory. We focus both on animal models and available clinical and imaging data from cross-sectional and longitudinal human studies. Early studies of fetal exposures focused on classic teratological methods that are insufficient for revealing more subtle effects that are nevertheless very behaviorally relevant. Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose-response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures.

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Section: Methadonementioning

confidence: 99%

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

Ross

Graham

Money

et al. 2014

Neuropsychopharmacol

342

241

View full text Add to dashboard Cite

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“…(35, 36, 78–81) These women have high rates of co-occurring mental health disorders – mood disorders, anxiety, and post-traumatic stress disorder,(82) as well as histories of physical and sexual abuse. (83) Polydrug use is common and the impact of other potential drug-drug interactions on the fetus are poorly understood.…”

Section: Prenatal Carementioning

confidence: 99%

Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes

Reddy¹,

Davis²,

Ren³

et al. 2017

Obstetrics &Amp; Gynecology

215

101

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In April 2016, the Eunice Kennedy Shriver National Institute of Child Health and Human Development invited experts to a workshop to address numerous knowledge gaps and to review the evidence for the screening and management of opioid use in pregnancy and neonatal abstinence syndrome. The rising prevalence of opioid use in pregnancy has led to a concomitant dramatic fivefold increase in neonatal abstinence syndrome over the past decade. Experts from diverse disciplines addressed research gaps in the following areas: 1) optimal screening for opioid use in pregnancy; 2) complications of pregnancy associated with opioid use; 3) appropriate treatments for pregnant women with opioid use disorders; 4) the best approaches for detecting, treating, and managing newborns with neonatal abstinence syndrome; and 5) the long-term effects of prenatal opioid exposure on children. Workshop participants identified key scientific opportunities to advance the understanding of opioid use disorders in pregnancy and to improve outcomes for affected women, their children, and their families. This article provides a summary of the workshop presentations and discussions.

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“…Among reports of 27 newborns with in utero exposure to methadone, 1 developed bradycardia and 4 transiently developed QTc intervals greater than 460 msec. 5,6 In a study of intravenous methadone in 7 neonates between 33 and 45 weeks postmenstrual age, the maximum QTc interval prolongation was 10.4 msec; however, all QTc intervals remained within the normal range. 12 In 2 pediatric patients (ages 11 and 17 years) receiving methadone for chronic pain, 1 had no change in QTc interval and the other had QTc prolongation in the setting of concomitant QTc-prolonging drugs.…”

Section: Discussionmentioning

confidence: 99%

“…3 Existing evaluations of the QTc-prolonging effects of methadone in children are limited to very small studies and case reports (73 total children) that reach varying conclusions regarding the degree of QTc prolongation induced by methadone. [4][5][6][7][8] Notably, existing studies have largely excluded critically ill children, including those with underlying cardiac disease. Critically ill children are among the most frequent recipients of methadone therapy.…”

Section: Introductionmentioning

confidence: 99%

Effects of Methadone on Corrected Q-T Interval Prolongation in Critically Ill Children

Heath

Greenberg

Hupp

et al. 2018

The Journal of Pediatric Pharmacology and Therapeutics

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OBJECTIVESThis study aimed to determine the association between methadone use and corrected Q-T interval (QTc) prolongation in critically ill children METHODS A retrospective cohort study of critically ill children receiving methadone at a tertiary care pediatric hospital was conducted. Patients younger than 19 years who had been admitted to the intensive care unit between January 1, 2009, and June 21, 2013, who had received methadone while inpatients, and who had had electrocardiograms (ECGs) performed within 30 days before and after methadone initiation were included. The primary outcome was the net change in QTc interval between baseline and postmethadone ECGs. Secondary outcomes included percent change in QTc interval and the proportion of patients whose QTc intervals changed from normal to prolonged following methadone initiation. We also evaluated potential predictors of QTc interval prolongation, including age, sex, admission diagnosis category, exposure to other QTc-prolonging medications, presence of congenital heart disease or known arrhythmias, and methadone daily dose and route of administration.RESULTS Sixty-four patients met the inclusion criteria. The median (25th, 75th percentiles) change in QTc interval following methadone initiation was −8 msec (−34, 13.5 msec; p = 0.19). Five patients (8%) had a baseline normal QTc interval that became prolonged after methadone initiation. We identified no statistically significant predictors of QTc prolongation after methadone initiation.CONCLUSIONS In this dedicated pediatric safety study, methadone initiation did not result in prolongation of the QTc interval. Although these findings suggest methadone initiation may not have a substantial effect of QTc prolongation in critically ill children, a controlled, prospective evaluation in this population remains warranted.

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Maternal methadone therapy increases QTc interval in newborn infants

Cited by 39 publications

References 18 publications

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes

Effects of Methadone on Corrected Q-T Interval Prolongation in Critically Ill Children

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