Neonatal Abstinence Syndrome

Summary
Introduction
Patients Involved in Retrospective Study
Methadone Maintenance & Pregnancy: Counseling and Group Teaching
Results
Conclusion
Relevant, related newer study and letter to the editor [added 7/2016]
Appendix Subjects to be covered in pregnancy groups, as feasible

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 and potentially damaging to the embryo/fetus.

The mother’s stress hormones influence fatal 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:

Neonatal Abstinence Syndrome (NAS) Data – Summary of 13 births 2006-2009
Time in treatment while pregnant Treatment involvement (judged by staff) Daily methadone dose Reported intensity/duration of withdrawal symptoms Gestational age Type of birth Infant descriptive data Comments
 Throughout pregnancy + (minimal counseling) 155mg significant approximately 37 weeks emergency C-section No data  
Throughout pregnancy  ++ (mostly individual;
few groups)
73mg none 40 weeks vaginal birth, induced female; 6lbs., 8oz.  
 Throughout pregnancy + (much stress); groups 140mg few weeks approximately 37 weeks vaginal birth male;
6lbs., 3oz.
 
Throughout pregnancy  ++ (much stress); groups; individual  130mg minor; for a few days 40.5 weeks vaginal birth female; 7lbs., 12 oz.  
Throughout pregnancy  ++ (much stress); groups; individual 60mg none 38 weeks vaginal birth, induced male, 21″, 6lbs., 11oz.  
Throughout pregnancy +  (c/o pain & RLS* while pregnant)  150mg  5-6 weeks  37 weeks vaginal birth no data opiate and benzodiazepine abuse
 2 1/2 weeks + (little time for counseling or groups)  40mg minor; for a few days 38 weeks vaginal birth male;
7lbs., 1 oz.
 
 Throughout pregnancy  + (late few groups)  164mg significant approximately 35 weeks reportedly vaginal birth male;
4lbs., 4oz.
 
 Throughout pregnancy + (counseling crisis-oriented) 114mg few weeks approximately 36 weeks C-section (planned abortion)    
Throughout pregnancy  +++ (stress), pregnancy groups, individual 70mg minor for a few days approximately 36 weeksa vaginal birth, induced male; 18″, 5lbs., 5oz.
 
 Throughout pregnancy +++ (stress), pregnancy groups, individual 100mg noneb 42 weeks vaginal birth female;
8lbs., 8oz.
 
 Throughout pregnancy +++ (stress), pregnancy groups, individual 177mg none 38 weeks vaginal birth female;
7lbs., 13oz.
(breast fed)
 
Throughout pregnancy  +++ (stress), pregnancy groups, individual 22mg nonec possibly 42 weeks vaginal birth male; 20″
7lbs., 2oz.
(jaundice)
 

*  RLS = Restless Leg Syndrome

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

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

Involvement in treatment Neonatal withdrawal Daily methadone dosage Gestational age in weeks Weight
+++ + (minor, few days) 70mg 36 weeksa 5 lbs.
5 oz.
+++ 0 (none?)b 100mg 42 weeks 8 lbs.
8 oz.
+++ 0 (none) 177mg 38 weeks 7 lbs.
13 oz.
+++ 0 (none?)c 22mg 42 weeks(?)
++ 0 (none) 73mg 40 weeks 6 lbs.
8 oz.
++ + (minor, few days) 130mg 40.5 7 lbs.
12 oz.
++ 0 (none) 60mg 38 weeks 6 lbs.
11 oz.


Patients with Low Treatment Participation

Involvement in treatment
Neonatal withdrawal Daily methadone dosage Gestational age in weeks Weight
+ ++
(few weeks)
140mg 37 weeks 7 lbs.
13 oz.
+ ++
(few weeks)
114mg 36 weeks
(+) ++ (significant) 155mg 37 weeks
(+) +++
5-6 weeks
150mg 37 weeks
(+) + (minor,few days) 40mg 38 weeks 7 lbs.
1 oz.
(+) ++ (significant) 164mg 35 weeks 5 lbs.
5 oz.

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 preventive 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”.

Relevant, related newer study
The Christian Science Monitor, cover story of March 13, 2016 “Prescription Contact”
describes how “The infants do better with care in a calm, dark environment – where they are fed on demand and held a lot …” Medication use was decreased from half to a quarter of babies, and hospital stays were decreased from an average of 17 to 12 days
(Study by Dartmouth, NH pediatrics professor Alison Holmes, MD; she had research from Europe and Canada showing that for many of the babies, the less they were medicated and the more they stayed skin-to-skin close to their mother or a primary caregiver, the better they would do)
http://www.csmonitor.com/USA/Society/2016/0313/How-to-save-babies-from-the-opioid-scourge
Letter to the editor (as printed)
Regarding the March 14 cover story, “Prescription: Contact”: I congratulate the Monitor for showing the importance of humane, natural approaches to treat Neonatal Abstinence Syndrome. What is missing are references to the pregnant women’s proper treatment.
Most people do not become addicted when using heroin or pain medications. Women who become addicted usually have significant psychiatric problems, particularly PTSD, panic disorder, depression, etc. These disorders are often ignored and patients may seek tranquilizers and alcohol.
In my experience, pregnant women’s stress is the most important contributor to NAS. These women need support. And we must protect them from people and agencies who berate them.
Heinz Aeschbach, MD, Austin, Texas

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
Meditation: 1. narrow mental focus, e.g. own breathing, clouds, rain, essence of a calm scene; 2. no judgment, i.e. observing sounds, smells and sensations but not trying to explain them and not judging them as desirable or bad. May meditate while walking, dancing or playing instrument with full attention to ‘gestalt’ of artistic expression.
With meditation and Autogenic Training, there are often seemingly paradoxical effects, examples: awareness that one needs to move, intense emotion that was suppressed while preoccupied with other issues and activities, important memory coming to surface, remembering where something last seen before missing it. Accept what comes up, maybe grieve when remembering some loss/anniversary or think shortly of constructive response to what comes up, think “this can wait,” etc., then return to meditation.
May add self-suggestions, with goal to become more accepting of what is perceived as reality; examples: “nothing is important” [except positive directedness]; “I expect nothing” [working towards goal important]; “there is no justice” [good and bad luck are random, many born with “bad” body and into bad environment]; “the past does not define me.”
Goal: being able to meditate at any place at any time, shortly or for extended time. Meditation should get person to neutral pace – getting ready for any task; meditation should not be associated with going to sleep.
Contemplation: while meditative, reviewing data, present, past and in future anticipated, avoiding judgment; when judgmental thoughts come, avoiding rationalizations, trying to let judgmental thoughts go.
Autogenic Training:
The self-suggestions calm physiological systems involved in stress; they lead to felt change as in biofeedback, the suggested feeling coincides with success in calming aspect of stress reaction. 1 addresses muscle tension, readiness for action – relaxation; 2 blood flow directed towards muscles – increase in blood flow into skin and organs; 3 cardiovascular system responding to fear/need for action – calming; 4 breathing fast – let breathing center calm breathing as body calms down; 5 internal (abdominal) organs overreact with nausea, diarrhea, wanting to empty bladder, etc. Solar (or Celiac) plexus consist in ganglia that connect the central nervous system (brain, spinal cord) with systems in the abdominal organs; warmth of upper abdominal skin may calm reactivity of system and generally feels calming; 6 anxiety may lead to ‘stuffy feeling’ in head, coolness of forehead associated with alertness and clarity of mind.
In comfortable position, e.g. sitting upright or lying on back, keep repeatedly thinking self-suggestions that address systems primarily involved in stress reactions, few minutes at a time; at first only first suggestion, later shortly first then going to second, etc. [e.g. while in labor, being able to quickly go through all stages and reach deeply relaxed meditative state between each contraction and stay meditative during contraction and intense pushing.] Generally practicing frequently for one to few minutes, sometimes/later for longer times. Self-suggestions:
1. “My right hand [is or] feels heavy” (dominant hand) – then let heavy feeling spread to other extremities, whole body. [if hand hurting, “my body feels heavy”]
2. “My right hand [is or] feels [comfortably heavy and] warm” – later let lukewarm feeling spread over whole body (not hot like in hot tub)
3. “My heart beats calmly, steadily” – may observe heart beat in chest, neck hands, etc. or hear may it; may observe slight speeding up and slowing down with slow breathing
4. “Breathing calmly, passively – feeling like I am breathed” – effort not to interfere with breathing center by breathing deeply or slowly
5. “Upper abdomen feeling [particularly] warm” – imagining circle between belly button and angle of ribs, considerably warmer than normal body temperature
6. “Forehead cool”
The suggestions may be incorporated in a clam scene on beach: sinking into warm sand, body shaded except sun shining for a while on stomach, breeze over forehead, observing calm ‘automatic’ breathing and heart beat [imagine leotard or thin towel if association with sun burn comes up].
Self-hypnotic techniques:
Self-hypnosis should make goals easier to achieve, but should not be used when not reaching goal would be “unacceptable”
1. Establish clear positive, at least in principle reachable goal. Generally, if self-hypnotic technique not working, will power should be adequate to get through.
2. Learn and use meditative state.
3. Find ways to symbolically move to goal, e.g. in pain relief, may suggest numbing cold or healing warm hand that very slowly “on its own” moves to hurting body part; visualize pain as foreign body that can change or move out of the body. May visualize pain sensation as heat that is uncomfortable, slightly hurting but tolerable (as e.g. when receiving tattoo or dental work). Particularly with pain, always staying in moment, never thinking “I cannot handle that longer than a few more minutes.”
4. May also focus on meaning of sensation (in case of childbirth, contractions “feeling right,” “strenuous ‘labor’ rather than ‘pain,’” etc.
May add other general suggestions: “I am bigger than the pain” or “I trust my resources.”
Gathering more data:
1. OTPs offer pregnancy groups and/or teach the material individually (the subject of the session).
For the study:
2. In the last few months of pregnancy (of all pregnant OTP patients), staff judges
2A. whether patients participated in the sessions and
2B. whether they appear to have practiced what was taught.
3. On follow-up, the new mothers are asked about
3A. the, by mother/parents observed withdrawal symptoms,
3B. the mothers’ ability to closely interact with, hold, breast feed the newborn and protecting him/her from abusive and invasive care in a NICU [Neonatal Intensive Care Unit]
Collected data may then be analayzed.
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.

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