Summary
   The literature indicates that most neonates born to mothers in methadone maintenance treatment will have withdrawal symptoms and are likely to need medical intervention. However, studies are contradictory:  frequency of needed treatment varies widely between studies. Some indicate that withdrawal is dose-related, others that it is not -- not even if the mother is on a very high dosage of methadone. These findings do not make sense. A more or less linear correlation between maternal methadone dosage and likelihood of significant withdrawal would be expected.
   There are indications that other factors are more important than methadone dosage. For instance, there appears to be a correlation between NAS and other drug use, particularly benzodiazepines and nicotine, and there is a correlation with gestational age with premature babies having fewer withdrawal symptoms.
   My retrospective study (exclusively based on the mother's reports) seems to show that the neonatal abstinence syndrome is most closely related to maternal stress due to uncertainties and fears. Mothers who participated well in offered services, who handled general stress and the stress of anticipated childbirth well, were likely to have a baby with only minor or no appreciable neonatal withdrawal symptoms.

Introduction 
1.  Medication withdrawal
   Opioid withdrawal is primarily a stress syndrome. Medication withdrawal is generally not correlated to blood levels but to the mind's expectation of relief from stress. Opiate, tranquilizer and alcohol addicts get, thanks to the drug use, regularly relief from stress. The mind, i.e. the central nervous system (CNS), develops a tolerance, allowing essentially normal functioning with the drug, but the CNS also expects the relaxing drug action and develops rhythms that incorporate the drug action at specific receptor sites. When the expected relief does not come, increasing stress symptoms occur; however these are typically vacillating. The worst withdrawal typically occurs long after the medication has become undetectable in blood level measurements. Alcohol addicts may work regularly while sober during the day but go into mild withdrawal if there is no new alcohol intake in the evening. Withdrawal is much worse on the second evening without alcohol. Opioid maintenance patients who previously used drugs mainly in the evening usually suffer most craving and withdrawal-like symptoms in the evening while in treatment with a long-acting opioid medication.
   Usually, these drug withdrawal symptoms are easily influenced. Placebo drugs and false beliefs can greatly increase or decrease withdrawal symptoms. When patients believe their methadone dosage has been decreased, they may go into withdrawal, while forgetting the medication altogether is easily tolerated, e.g. during vacation in unfamiliar settings. When introduced, it was thought that heroin, as compared to morphine, has only minimal or no withdrawal symptoms. The same was thought of benzodiazepines, as compared to barbiturates, oral methadone, as compared to heroin and opioid pain medications, and most recently, the same myth applied to sublingual buprenorphine.
   Drugs suppressing the stress reaction of the CNS, such as clonidine, propanolol and amitriptyline, or a slow taper of an opioid medication, considerably reduce opiate withdrawal symptoms. Placebo drugs and meditation/prayer may also work.

2.  Pregnancy and stress
   During pregnancy, stress may be significant. The mother's stress hormones influence fetal development. For instance, in the late first trimester, when the male fetal brain is supposed to be 'masculinized', the mother's stress hormones may interfere with this process, leading in a male fetus to a person with male body but essentially female brain and later development of primary homosexuality (births during World War II; rat studies¹).
   Many more recent studies indicate that major stress in the pregnant women may have adverse effects on the fetus, including stress reactivity in the newborn and insomnia².

3. Neonatal withdrawal syndrome
   The literature indicates that withdrawal symptoms in infants born to mothers on methadone maintenance are the rule rather than the exception (up to 90% with 50-75% needing treatment³, 62-74% with length of treatment ranging from 7-49 days. These results are reportedly comparable with results reported at other institutions⁴). In addition, there is an association between maternal methadone use, pre-term births and small infants. In accordance with some studies, the frequency of neonatal withdrawal symptoms from methadone correlates poorly with methadone dosage at all dosage levels⁵. My observation was that at least in lower dosage range, neonatal abstinence symptoms were unpredictable while high dosage maintenance had a much higher rate of withdrawal.  Some studies indicate that likelihood of withdrawal is closely related with maternal methadone dosage⁶. However, one study indicates that even in high dosage methadone maintenance, there is no correlation between dosage and observed withdrawal symptoms in the newborn. These findings do not make sense:  a more or less linear correlation between maternal methadone dosage and likelihood of significant withdrawal would be expected. One study indicated that later gestational age (37 weeks or more) and concomitant benzodiazepine use were associated with the need for longer treatment of neonatal withdrawal symptoms⁶.  A Swiss study showed the detrimental effect of polydrug use while pregnant and on methadone maintenance⁷.  In my retrospective study, I did not look closely at nicotine and other drug use; however, there appeared to be a correlation between other drug use, including nicotine, non-participation in our services and withdrawal in the newborn.

Patients Involved in Retrospective Study 
   All births to patients at this clinic in the years 2006-2009 are included. All patients were in methadone treatment either when they became pregnant or they started treatment in early pregnancy (one patient diagnosed to be pregnant on admission; one transferred to our clinic very late in pregnancy).  To our knowledge, none of the pregnancies were planned.  There were eleven Anglo women and one Latin woman who had two children during this time. All but one were in their late twenties and thirties, and most had given birth previously. Regarding outcomes, no significant difference between primipara and multipara were observed, however the youngest patient did most poorly. To my knowledge, most patients planned to breastfeed, but hospital routines, CPS involvement, etc. created too much stress during the postnatal period for most to do this. Almost all bottle fed their newborns mostly or exclusively. All patients had ready access to individual counseling. A few did not take advantage of what the clinic offered, and for a few of the patients counseling was primarily crisis-oriented (involvement with Child Protective Services, family conflicts, legal problems, and one case with a short jail stay and temporary homelessness). The youngest women had ongoing complaints about aches, pains, painful restless leg syndrome, and panic attack. The two women who had most problems had relapses:  temporarily or intermittent severe drug abuse. Several patients had lapses (on one or few occasions impulsive one-time use) and/or some continued smoking.  One baby was shortly icteric. Otherwise we have no information about any baby having abnormalities or needing treatment other than for NAS.

Methadone Maintenance & Pregnancy:  Counseling & Group Teaching 
   Pregnancies in methadone maintenance patients are usually stressful. They are rarely planned even though often welcomed.  However, often there is then the consequent fears of disapproval by relatives and friends, of intervention by Child Protective Services and the fear of childbirth itself. Patients on methadone maintenance are usually more sensitive to pain than average, and opioid pain medications have little effect unless given in much larger dosage than usual (this is rarely understood by physicians). In addition, clinics for indigent obstetric patients are rarely conducive to making women feel cared for. Obviously, the high level of stress often leads to lapsing thoughts and behaviors and the fear of relapse is in itself a stress factor.
   In counseling pregnant methadone maintenance patients, our goal has been to minimize stress during pregnancies in order to improve our patients' birth experiences while decreasing the rate of complications. To improve these services, I started to facilitate educational pregnancy groups. Patients were encouraged to start in the first trimester. Group teaching included autogenic training (AT), specific self-hypnotic techniques, education about childbirth, education regarding breast-feeding and discussions about dealing with institutions (hospitals, child protective services). Most important was the practice of AT which has been much used in Europe for many conditions, and techniques to raise pain tolerance and modify/decrease pain perception. AT is used to go very quickly into a deeply relaxed state, starting with comfortable heaviness and warmth in dominant hand and letting the feeling quickly spread over the whole body. Then AT steps three to five may be utilized and self-hypnotic suggestions may be added. Patients are also taught that it is always important to stay in the present, to go into meditative state between contractions, and focus on the moment during contractions.    

Results
Benefits of counseling and group teaching
   The result of this study indicates mothers who were most involved in offered services reported relatively good birth experiences (all participating patients who had given birth previously reported  the present birth experience was better than the previous one(s) and that the techniques acquired were helpful). In this sense the counseling and groups fulfilled their originally intended purpose. However, we were not very successful in our encouragements to breastfeed their infants. Regarding the neonatal abstinence syndrome:  in our small group, newborns of patients who participated in our childbirth preparation counseling and learned relaxation/meditation techniques had much less neonatal abstinence symptoms than statistically expected. In addition, the only premature baby (<37weeks) in that group was induced due to maternal increase in blood pressure (two 42 weeks, two 40 weeks, two 38 weeks, one 36 weeks.)

Data:

Number of patients by treatment involvement (as judged by staff):               4 +++          3 ++          2 +          4 (+)
Number of patients by mother's dosage of methadone (at time of birth):      6 >120mg     5  60-120mg     2 <60mg
Number of patients by, by mother reported, withdrawal symptoms (NAS):   5 none      3 minor     4 few wks    1 >1mo

Patients with Good Treatment Participation

a = Induced, maternal increase in blood pressure
b = The mother reports that the baby was kept a few weeks in hospital for observation but did not need treatment
c = Newborn had mild jaundice. It was reportedly given small dosages of methadone preventively for four weeks even though no withdrawal symptoms were observed/reported

Conclusions
Pregnancy counseling at the clinic started to improve our patients' birth experiences. This indicates that good childbirth preparation and learning stress/pain management techniques improved outcomes for the neonates. There were much fewer neonatal withdrawal symptoms, generally shorter hospital stays, and less premature births. However, this was neither a blind nor prospective study and the numbers are small. It may be considered "good anecdotal evidence".

Appendix
Subjects to be covered in pregnancy groups, as feasible:
- methadone (or buprenorphine) o. k (generally: do not switch from one to the other during pregnancy).; how to talk to family 
- ask for TH dose if too nauseated to take dose and/or stay here after taking it 
- dose decreases mid trimester o.k.
- abortion o.k. (particularly if malformation) 
- smoking/nicotine (stop or at least decrease) 
- benzodiazepine use (decrease and stop) 
- antidepressant/mood stabilizer use
- measures and medications for nausea
- CPS issues
- Urine drug screens (refuse if using and discuss lapse with case manager)
- circumcision (not recommended)
- healthy lifestyle, diet, walking after carbohydrate meal (diabetes prevention)
- stress management, cognitive (What am I afraid of? What are conflicts about? Is it my problem? How much time do I have to decide? What is the worst case scenario? "I'm bigger than the problem.")
- autogenic training (AT) 
- pain in general: pain stimuli reach brain, mind "screams no" or accepts sensation (sometimes welcomes it, e.g. in masochism, when self-injecting drug, in self-injurious behaviors to relieve mental pain); sensitization (increased fear after painful experience, "was much worse than expected" "I'd rather die than live through such pain again") and desensitization (more self-confidence, "I lived through it", "I'm proud of how I handled that pain", often "the result was worth the pain", etc.) 
- self-hypnotic techniques
- birth process; physiology and anatomy; stages; relaxing between contractions; always staying in moment - content of our "surgery letter": for pain, considerably more methadone best, dosing every 8-12 hours; no agonist-antagonist medications (Nubain, Stadol, Talwin, Buprenex, etc.)
- epidural
- emergency and planned C-section
- withdrawal symptoms in newborn, mangment
- breast feeding; as much physical contact with newborn as possible 

References
1  Irenäus Eible-Eibeseldt:  Die Biologie des menschlichen Verhaltens, 4. Auflage 1997, p.358f 
2  
a) http://cpj.sagepub.com/content/49/2/158.abstract CLIN PEDIATR February 2010 vol. 49 no. 2 158-165 Perceived Maternal Stress During Pregnancy and Its Relation to Infant Stress Reactivity at 2 Days and 10 Months of Postnatal Life Eman Leung et al. [Conclusion. These preliminary findings suggest that maternal stress during pregnancy may negatively affect neonatal stress reactivity within 24 to 48 hours after birth, and these influences may persist through the first year of postnatal life.]
b)  www.womensmentalhealth.org/.../maternal-stress-during-pregnancy-linked-to-infant-sleep-problems MGH Center for Women’s Mental Health Maternal Stress During Pregnancy Linked to Infant Sleep Problems Published: July 26, 2008
c)  J Psychiatry Neurosci. 2008 January; 33(1): 10–16. Relation of maternal stress during pregnancy to symptom severity and response to treatment in children with ADHD Natalie Grizenko, et al 
d)  http://www.sciencedaily.com/releases/2008/08/080820194845.htm Science Daily (Aug. 21, 2008) Acute Maternal Stress During Pregnancy Linked To Development Of Schizophrenia 
e)  http://www.guardian.co.uk/science/2007/may/31/childrensservices.medicineandhealth "Mother's stress harms foetus, research shows - Brain development may suffer as early as 17 weeks · Charity urges supportive environment in pregnancy," Lucy Ward, social affairs correspondent The Guardian, Thursday 31 May 2007 
f)  http://www.jhsph.edu/publichealthnews/press_releases/2006/dipietro_stress.html May 17, 2006 Mild Maternal Stress May Actually Help Children Mature 
3  www.bsuh.nhs.uk/EasySiteWeb/GatewayLink.aspx?alId=52020 TMBU PROTOCOL – August 2006 NEONATAL DRUG WITHDRAWAL 
4  American journal of obstetrics and gynecology “Predicting length of treatment for neonatal abstinence syndrome in methadone exposed neonates.” Volume 199, Issue 4, October 2008, Pages 396.e1-396.e7 DOI: 10.1016/j.ajog.2008.06.088 Neil S SELIGMAN, et al 
5  a) American Journal of Obstetrics and Gynecology (2005) 193, 606-10 "High-dose methadone maintenance in pregnancy: Maternal and neonatal outcomes," John J. McCarthy, et al 
b)  The Journal of Pediatrics, "Relationship between Maternal Methadone Dose at Delivery and Neonatal Abstinence Syndrome," Neil S. Seligman, et al Available online 15 May 2010 
6  Obstetrics & Gynecology: December 2002 - Volume 100 - Issue 6 - p 1244-1249 "Original Research Relationship Between Maternal Methadone Dosage and Neonatal Withdrawal" Dashe, Jodi S., et al 
7 Acta Obstet Gynecol Scand 2005: 84: 145--150 "Methadone maintenance program in pregnancy in a Swiss perinatal center (II): neonatal outcome and social resources" ROMAINE ARLETTAZ, et al From the Clinic of Neonatology and Department of Obstetrics and Gynecology, Zurich University Hospital, Switzerland.