1.  John McCarthy, M.D.  Executive/Medical Director, Bi-Valley Medical Clinic, Sacramento

2.  Women are often given inaccurate and conflicting advice and information relative to the effect of methadone on the fetus.  They are often told that methadone will harm the baby and given advice to taper off methadone to ‘protect the baby’.  This misinformation often extends to issues around breastfeeding.

3.  URL:http://.atwatchdog.org/stories/stories_ my babysstory.html (Addiction Treatment Watchdog) URL:http://.atwatchdog.org/stories/stories_ my babysstory.html  Angel conceives on 90mg while tapering. She’s unaware she’s pregnant until she’s at 76mg. Then she asks her counselor about whether tapering is safe and is told, ‘without hesitation’, “it wouldn’t harm the baby”.  Her OB tells her ‘how awful it would be for the baby to be born on methadone’ and advises 5-10mg week taper.

4.  Angel pursues 5mg week taper with no apparent problems, but her baby “kicked all of the time”.  At about 47mg she finds her own information on the risks of withdrawal, including fetal death.  She tells her counselor who informs the clinic doctor (for the first time) who confirms the risks and advises that the baby is probably in active withdrawal because of the rapid taper.  She goes back to the OB who is ‘enraged’ at the clinic telling her tapering was unsafe and writes a prescription to the clinic for 5-10mg/wk taper.  Angel tapers from 47mg to 7mg in 4 weeks.

5.  At 7mg she is physically shaking from withdrawal and the baby’s movements “became very frantic’” The OB suggests an increase to 11mg.  She finds the AT Forum website & CSAT’s TIP 2.  She requests a dose increase but the clinic doctor is reluctant to do this without the OB approval.  She is finally approval to increase to 40mg and finishes the pregnancy in mild chronic withdrawal. At birth her baby is treated for NAS.

6.  Prescription drug abuse is increasing among pregnant patients, while heroin use is going down.  Vicodin (hydrocodone) and Oxycontin (oxycodone) are the most common prescription drugs abused.  Half of the patients on methadone in a suburban methadone clinic are prescription abusers.  Virtually all patients in a private buprenorphine program are pill users.

7.  Pregnant women forced to maintain on low doses to “protect the baby from methadone”  Dosing regimen for pregnancy has not followed the increase in dose seen in non- pregnant patients  Higher doses have been presumed to result in more severe neonatal abstinence syndrome.  Research is confusing with 8 studies showing a correlation and 8 not.

8.  Specialized drug treatment counselor with training in interfacing with the obstetrical care system and CPS  Coordination with OB and hospital  Pregnancy group: supportive, educational  Psychiatric assessment, supportive psychotherapy, meds as needed  Random weekly toxicology screens

9.  Required weekly during pregnancy and early post-partum  Mutual support and sharing of pregnancy and birth experiences  Education re: methadone dosing, serum levels, metabolism, NAS, nursing, psychiatric, drug use effects on fetus, pain management, SIDS, Hep C, CPS  Nubain – an absolute contraindication

10.  Avoid maternal and intrauterine fetal withdrawal.  Individualize dose, no arbitrary limits.  Split dose all patients, BID, at times TID  Use serum levels to monitor maternal methadone metabolism and fetal exposure

11.  Are higher methadone doses associated with more severe NAS or other adverse events?  Are higher doses associated with better drug treatment outcomes?

12.  94 admissions between 2/99-5/03.  13 pregnancies were excluded:  4 miscariages  3 TAB  2 AMA  2 tapered off methadone in 3 rd trimester  2 no information on infant, CPS hold  81 women, 81 infants  8 women had 2 pregnancies,  25 conceived on methadone

13.  Ethnicity: White 64%, Hispanic 25%, African American 6%, Asian 4%, other 1%  Age 32 (range 20-46).  Age at first opiate use: 22, range 12-38  Years of addiction 10 (range 1-28)  38% report polydrug abuse, 78% are nicotine dependent on admission

14.  Average dose 101mg/day (range 14-190)  Average serum level 146ng/ml (r 20-478)  78% negative urine toxicology during pregnancy (N=1188/1528)

15.  Mean length of Rx: 24 weeks, (r 2-41)  Gestational age: 37.3 weeks  Birth weight: 2792 gram (6.2 lbs)  46% of mothers breastfed for some period  82% (66/81) of hospital toxicology screens negative for illicit drugs

16.  46% (N=37) of neonates required meds for NAS  Median length of stay in hospital: 10 days  Treated babies: median 25, r 8-105  Not Treated: median 3, r 1-44  Neonates were treated with: paregoric (N=20), phenobarb (N=10), Both (N=4), methadone (N=1), ativan (N=1), paregoric and ativan (N=1)

17.  Cohort divided into high dose (132mg/d, N=45) and low dose (62mg/d, N=36) groups to assess effect of dose on outcomes and NAS  There were 2 differences between the groups: ◦ The high dose group had less drug use at delivery than the low dose group: 11% vs 27% (p=.05). ◦ The high dose group had greater number of years of addiction (11.6 vs 7.8. p=.05). ◦ There was no difference in treatable NAS or days in hospital between high dose and low dose groups

18. Figure 1. Number of infants treated for NAS, by maternal dose range

19.  American Association of Pediatrics 2002 guidelines now lists methadone as “usually compatible with nursing” without dose restrictions or other guidelines. (see Jansen et al, J of human Lactation for review of this topic)  This replaced the 1978 guideline that restricted nursing to patients on <20mg  Nursing is the ideal method and milk is the ideal medium to deliver methadone to the neonate to alleviate NAS (Ballard).

20.  Rate of decline in infant methadone serum levels, i.e rate of metabolism and excretion (Kandell)  Individual infant responses to birth and withdrawal  Polydrug exposure: nicotine, illicit opiates, stimulants, benzodiazepines  Possible infant sensitization to repeated episodes of intra-uterine withdrawal, prior to methadone or secondary to inadequate methadone dose or too long a dosing interval

21.  This study confirms other studies showing no correlation between methadone dose and need for treatment for NAS, reporting on the highest average dose studied: 101mg/day  It reports a dose range of safety to 190mg/day and serum level to 478ng/ml  Confirms relationship between adequate, individualized methadone dose and recovery from drug abuse for a pregnant population .