Methadone dose and neonatal abstinence syndrome-systematic review and meta-analysis
Coombe Women and Infants University Hospital, Dublin 8, Ireland School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland. Addiction
(Impact Factor: 4.74).
12/2010; 105(12):2071-84. DOI: 10.1111/j.1360-0443.2010.03120.x
To determine if there is a relationship between maternal methadone dose in pregnancy and the diagnosis or medical treatment of neonatal abstinence syndrome (NAS).
PubMed, EMBASE, the Cochrane Library and PsychINFO were searched for studies reporting on methadone use in pregnancy and NAS (1966-2009). The relative risk (RR) of NAS was compared for methadone doses above versus below a range of cut-off points. Summary RRs and 95% confidence intervals (CI) were estimated using random effects meta-analysis. Sensitivity analyses explored the impact of limiting meta-analyses to prospective studies or studies using an objective scoring system to diagnose NAS.
A total of 67 studies met inclusion criteria for the systematic review; 29 were included in the meta-analysis. Any differences in the incidence of NAS in infants of women on higher compared with lower doses were statistically non-significant in analyses restricted to prospective studies or to those using an objective scoring system to diagnose NAS.
Severity of the neonatal abstinence syndrome does not appear to differ according to whether mothers are on high- or low-dose methadone maintenance therapy.
Available from: Lorna Leal
- "Not only 4-methylethcathinone but also methadone and its metabolite were present in both maternal and neonatal matrices. Whereas there is literature describing neonatal withdrawal syndrome following maternal methadone use of opioid-dependency treatment   , recent systematic review, meta-analysis and cohort study showed that severity of the neonatal abstinence syndrome does not appear to differ according to whether mothers are on high-or low-dose methadone maintenance therapy and that incidence and duration of the neonatal abstinence syndrome is not associated with maternal methadone dose, but maternal opiate, benzodiazepine or cocaine use is associated with longer neonatal hospitalization  . This latter evidence agreed with a case report observed by our study group where a late-onset neonatal abstinence syndrome in a newborn of methadone treated mother has been proved to be not associated with maternal methadone use, but with concomitant drugs of abuse consumption as tobacco, opiate, benzodiazepines or cocaine . "
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ABSTRACT: Synthetic cathinones have been markedly present in the Spanish drug market in recent years. These substances can be easily obtained in "smart shops", smoke shops, gas stations and web sites where they can be bought and received anonymously avoiding normal law controls. For the first time we present a case of a neonatal withdrawal syndrome in a baby born to a woman who was a chronic consumer of 4-methylethcathinone. The newborn presented with increased jitteriness and irritability, highpitched cry, hypertonia in the limbs and brisk tendon reflexes. 4-Methylethcathinone was identified and quantified by liquid chromatography tandem mass spectrometry in the four subsequent 3cm segments of maternal hair (4.3, 4.0, 4.0 and 3.9ng/mg hair starting from most proximal segment) accounting for maternal consumption during the whole pregnancy and before and in neonatal meconium (0.7ng/g) confirming fetal exposure during intrauterine life. Methadone and its metabolite were also measured in maternal and neonatal matrices. Counseling pregnant women and women who may become pregnant on the consequences of fetal drug exposure to new designer drugs like 4-methylethcathinone is critical to preventing poor neonatal outcomes. This case report is informative to those studying designer drugs and those clinically involved with pregnant women abusing psychoactive substances.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Available from: Ann Kelly
- "Methadone-exposed babies have demonstrated reduced birth weight and head circumference, prematurity,  and rates of neonatal withdrawal syndrome ranging from 46%  to 97% [12,23]. A dose–response relationship between methadone and neonatal abstinence syndrome (NAS) has been reported in a large series of 618 women  but a meta-analysis by the same author  and others  did not confirm these findings. A recent prospective study by this group concluded that neonates exposed to methadone doses ≥ 80 mg required higher cumulative doses of morphine treatment for NAS but attributed this to concomitant use of other drugs . "
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The prevalence of maternal drug use during pregnancy in North America has been estimated to be as high as 6-10%. The consequences for the newborn include increased risk for perinatal mortality and ongoing physical, neurobehavioral, and psychosocial problems. Methadone is frequently used to wean women off street drugs but is implicated as a cause of adverse fetal/neonatal outcomes itself. The purpose of our study was to test the ability of maternal acupuncture treatment among mothers who use illicit drugs to reduce the frequency and severity of withdrawal symptoms among their newborns.
We randomly assigned chemically dependent pregnant women at BC Women's Hospital in Vancouver, British Columbia to daily acupuncture treatments versus usual care. By necessity, neither our participants nor acupuncturists were blinded as to treatment allocation. Our primary outcome was days of neonatal morphine treatment for symptoms of neonatal withdrawal. Secondary neonatal outcomes included admission to a neonatal ICU and transfer to foster care.
We randomized 50 women to acupuncture and 39 to standard care. When analyzed by randomized groups, we did not find benefit of acupuncture; the average length of treatment with morphine for newborns in the acupuncture group was 2.7 (6.3) compared to 2.8 (7.0) in the control group. Among newborns of women who were compliant with the acupuncture regime, we observed a reduction of 2.1 and 1.5 days in length of treatment for neonatal abstinence syndrome compared to the non-compliant and control groups, respectively. These differences were not statistically significant.
Acupuncture may be a safe and feasible treatment to assist mothers to reduce their dosage of methadone. Our results should encourage ongoing studies to test the ability of acupuncture to mitigate the severity of neonatal abstinence syndrome among their newborns.
Available from: Gabrielle Welle-Strand
- "NAS is observed in 40–90% of neonates prenatally exposed to methadone or buprenorphine, and is characterized by symptoms of hyperirritability of the central-nervous, the gastrointestinal, the respiratory and the autonomic nervous systems (Finnegan et al., 1975; Fischer et al., 1998b). In a recent review of the relationship between the maternal dose of methadone and NAS in 67 studies, Cleary concludes that the severity of NAS does not appear to differ whether the woman is on low or high dose of methadone at delivery (Cleary et al., 2010). The use of illicit drugs in addition to MMT is associated with a greater likelihood of needing NAStreatment (Jansson et al., 2012) and a longer duration of treatment for NAS (Seligman et al., 2008) than for the use of methadone alone. "
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In Norway, most opioid-dependent women are in opioid maintenance treatment (OMT) with either methadone or buprenorphine throughout pregnancy. The inclusion criteria for both medications are the same and both medications are provided by the same health professionals in any part of the country. International studies comparing methadone and buprenorphine in pregnancy have shown differing neonatal outcomes for the two medications.
This study compared the neonatal outcomes following prenatal exposure to either methadone or buprenorphine in a national clinical cohort of 139 women/neonates from 1996 to 2009.
After adjusting for relevant covariates, buprenorphine-exposed newborns had larger head circumferences and tended to be heavier and longer than methadone-exposed newborns. The incidence of neonatal abstinence syndrome (NAS) and length of treatment of NAS did not differ between methadone- and buprenorphine-exposed newborns. There was little use of illegal drugs and benzodiazepines during the pregnancies. However, the use of any drugs or benzodiazepines during pregnancy was associated with longer lasting NAS-treatment of the neonates.
The clinical relevance of these findings is that both methadone and buprenorphine are acceptable medications for the use in pregnancy, in line with previous studies. If starting OMT in pregnancy, buprenorphine should be considered as the drug of choice, due to more favorable neonatal growth parameters. Early confirmation of the pregnancy and systematic follow-up throughout the pregnancy are of importance to encourage the women in OMT to abstain from the use of tobacco, alcohol, illegal drugs or misuse of prescribed drugs.
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