Neonatal abstinence syndrome

The neonatal abstinence syndrome occurs in 30-80% of infants whose mothers have taken opiates during pregnancy. The incidence is higher in those whose mothers have a history of opioid dependence and are taking methadone maintenance than in those who are taking methadone for chronic pain (39). The methadone blood concentration may be a useful predictor of the likelihood of severe withdrawal requiring treatment, but clinical assessment by a standardized scoring system is still required to determine the need to treat the neonatal abstinence syndrome (40). 

Methadone is extensively used in opioid withdrawal and maintenance programs (see Drug tolerance in this monograph), and has been safely used for this purpose in pregnancy, with only mild effects on the offspring (41). However, fetal exposure to methadone in utero can cause a neonatal abstinence syndrome after delivery. 

Kuschel CA, Austerberry L, Cornwell M, Couch R, Rowley RSH. Can methadone concentrations predict the severity of withdrawal in infants at risk of neonatal abstinence syndrome Arch Dis Child Fetal Neonatal Ed 2004 89 F390-F393. 

Paregoric affects the gastrointestinal tract by inhibiting motility and propulsion and increasing smooth muscle tone. Thus, it has been used to treat diarrhea, opioid addiction, and neonatal abstinence syndrome. 

Theis JG, Selby P, Ikizler Y, and Keren G (1997) Current management of the neonatal abstinence syndrome A critical analysis of the evidence. Biology of the Neonate 71(6) 345-356. 

Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Arria AM, O Grady KE, Selby P, Martin PR, Fischer G. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med 2010 363 2320-31. 

Observational studies Tincture of opium is a preparation of powdered opium, which contains morphine, codeine, papaverine, and alcohol. It is used as an antidiarrheal agent, to treat neonatal abstinence syndrome, in the management of pain, and traditionally for the management of opioid dependency in some Asian countries. In an open study, opium-dependent subjects were allocated to three different doses of tincture of opium twice a day 10 ml (6.66 mg morphine equivalents n = 13), 20 ml (13.3 mg morphine equivalents n = 8), and 30 ml (20 mg morphine equivalents n = 11) [1 j. In all the subjects tincture of opium effectively suppressed withdrawal symptoms without causing significant adverse effects. 

Fetotoxicity Exposure to opioids in utero can lead to the development of the neonatal abstinence syndrome, especially in infants born to mothers who have misused these drugs. Neonatal abstinence syndrome in neonates bom to mothers taking treatment has been investigated in 68 neonates. Pre-delivery higher doses of maternal methadone were associated with an increased incidence of treatment for withdrawal and with longer episodes of neonatal abstinence syndrome. There was a dose-response relationship— for every 1 mg increase in last maternal methadone dosage before delivery, an extra 0.18 days of infant treatment for neonatal abstinence syndrome were required furthermore, breastfeeding reduced the duration of neonatal abstinence syndrome by 7.76 days [261. 

In a similar study, involving 450 singleton pregnancies in drug misusing women taking methadone, 46% of the neonates developed the neonatal abstinence syndrome [27 1. Breastfeeding was associated with amelioration of symptoms. Admissions to... 

In a prospective study, the neonatal abstinence syndrome has also been described in 58 infants who had been exposed to buprenorphine in utero. There was neonatal abstinence syndrome in 38 infants, most of whom had been hospitalized for around 28 days. There was a positive correlation between urinary norbu-prenorphine concentrations over the first 3 days of life and the duration of morphine treatment and length of hospital stay. The authors also studied social problems, which were evident in all infants and contributed to the length of hospital stay [28 ]. 

Sublingual buprenorphine has been proposed as an effective and well-tolerated treatment for neonatal abstinence syndrome. In a randomized trial, infants with neonatal abstinence syndrome, who had been born to mothers taking maintenance methadone, were randomized to either sublingual buprenorphine 13-39 micrograms/ kg per day ( = 13) or standard-of-care oral neonatal opium solution ( = 13) [29 ]. Buprenorphine administration was associated with a 31% reduction in length of treatment and a 29% reduction in the length of hospital stay. One infant had seizures after buprenorphine, but it was not clear whether buprenorphine was causal. 

Lim S, Prasad MR, Samuels P, Gardner DK, Cordero L. High-dose methadone in pregnant women and its effect on duration of neonatal abstinence syndrome. Am J Obstet Gynecol 2009 200(1) 70.el-5. 

Dryden C, Young D, Hepburn M, MacTier H. Maternal methadone use in pregnancy factors associated with the development of neonatal abstinence syndrome and imphcations for healthcare resources. BJOG 2009 116(5) 665-71. 

Kraft WK, Gibson E, Dysart K, Damle VS, Larusso JL, Greenspan JS, Moody DE, Kaltenbach K, Ehrlich ME. Subhngual buprenorphine for treatment of neonatal abstinence syndrome a randomized trial. Pediatrics 2008 122(3) e601-7. 

In this preterm infant, the initial clinical impairment was the result of neonatal abstinence syndrome consequent upon sertraline exposure in utero not being maintained at the same level after delivery. As sertraline is not contraindicated diuing lactation, breastfeeding was continued, ultimately resulting in serotonergic overstimulation in this preterm infant. On day 9, the breast milk was substituted with formula due to further clinical impairment. As serum levels of sertraline and desmethylserfraline decreased, the infant s condition improved. 

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