CARING FOR INFANTS WITH
SHORT- AND LONG-TERM
EFFECTS OF IN-UTERO
OPIOID EXPOSURE
Bonny Whalen, MD
Medical Director / Newborn Pediatrician
CHaD/DHMC Newborn Nursery
June 5, 2013
OBJECTIVES

Demonstrate an understanding of short- and long-term
effects of in-utero opioid exposure on the developing
fetus / neonate

Discuss the importance of multi-disciplinary,
family-centered care for these infants in the newborn
period

Help families best prepare for the birth of their at-risk
infant including how to provide calm, nurturing
environments, limiting visitors, etc.
ILLICIT DRUG USE IN U.S. WOMEN

~ 11% illicit drug use in past month in women 15-44 yr


18-25 yr: 16.8%
26-44 yr: 7.6%
4.4% illicit drug use in past month in known pregnancy


15-17 yr: 13%
15-17 yr: 16.2%
18-25 yr: 7.4%
26-44 yr: 1.9%
Most commonly reported illicit drugs used by women:
1.
2.
Marijuana
Psychotherapeutics (e.g., opioids)
2009 & 2010 National Surveys on Drug Use and Health
https://nsduhweb.rti.org/
IN-UTERO OPIATE EXPOSURE AND ITS EFFECTS


Growth restriction
Prematurity
Characteristic
Heroin
MTD
BUP
MTD vs BUP
Delivery < 37 wk (%)
29.8%
26.3%
21.8%*
NS
Birthweight
2601 g
3050 g*
2900 g*
NS
IUGR
27.7%
10.5%*
9.3%*
NS
* P < 0.05 for heroin vs. substitution agent
Binder T and Vavrinkova B. Neuroendocrinol Lett. 2008.

Developmental abnormalities / long-term effects?

Opioid system mediates developmental events



Farid WO, et al. Curr Neuropharmacol. 2008.
Motor delays? Cognitive delays? ADHD?
Review of available studies reveals no adverse effects on development
for opiate-exposed infants

Jones HE, et al. Early Hum Dev. 2009.
NEONATAL ABSTINENCE SYNDROME (NAS)
 CNS
hyperirritability
 Autonomic hyperfunction
 GI dysfunction
CNS HYPERIRRITABILITY
 High-pitched
crying
 Sleeplessness
 Hyperactive
moro reflex
 Tremors
 Increased
muscle tone
 Myoclonic jerks
 Seizures
http://newborns.stanford.edu/PhotoGallery/Jittery3.html
AUTONOMIC HYPERFUNCTION
Metabolic / Vasomotor / Respiratory Disturbances
 Fever
 Sweating
 Yawning
 Mottling
 Nasal
stuffiness
 Sneezing
 Nasal flaring
 Tachypnea
 Retractions
GI DYSFUNCTION
 Excessive
sucking
 Poor feeding
 Regurgitation
 Projectile vomiting
 Loose stools
 Watery stools
NAS: WHAT TO EXPECT


2/3 - 3/4 infants develop some degree of NAS
Symptoms from long-acting opioids start on DOL 2
May see symptoms earlier if:
 Mom missed dose the day prior
 Baby has early rapid withdrawal phase of buprenorphine
 Mom using other substances / meds / nicotine

Symptoms usually peak DOL 3-4


May depend on med, mom’s other meds, baby’s metabolism ...
≥ 1/2 infants require Rx for NAS
 No
relationship b/w dose of substitution agent and NAS
severity or duration of Rx
Lejeune et al. Drug Alcohol Depend. 2006.
Sigman et al. J Peds. 2010
MINIMUM RECOMMEND MONITORING TIMES
FOR OPIOID-EXPOSED INFANTS
2

days
Short-acting opioids

4
e.g., morphine, oxycodone, Percocet
days
Heroin
 Long-acting opioids


e.g., buprenorphine, methadone
METHADONE VS. BUPRENORPHINE
Jones et al. N Engl J Med. 2010; 363:2320-2331.

Multi-center RCT (n = 7) comparing MTD vs. BUP Rx in 175 pregnant
women with opioid dependency (89 MTD, 86 BUP)


Double-blind, double-dummy, flexible-dosing
Comparison of 131 neonates whose mothers were followed to end of pregnancy
Study Outcomes
MTD
BUP
(N = 73)
(N = 58)
57%
47%
0.26
Peak NAS score
12.8±0.6
11.0±0.6
0.04
Total amount of morphine needed for Rx
10.4 mg
1.1 mg
<0.0091
Duration of Rx for NAS
9.9 d
4.1 d
<0.0031
Length of stay
17.5 d
10 d
<0.0091
% infants treated for NAS

P
33% BUP vs. 18% MTD discontinued Rx (P > 0.02) - Most commonly due to
maternal dissatisfaction with Rx

Unclear if pts with more severe dependence more likely to leave BUP group, therefore skewing
towards better outcomes in BUP neonates; however post-hoc analyses remained significant when
excluded moms on ≥ 100 mg methadone
SIGNIFICANT PREDICTORS RELATED TO NAS
Need for Rx for NAS


Maternal cigarette smoking
Higher birthweight
Higher peak NAS score
prior to Rx





Lower maternal weight
Maternal SSRI use
Higher birthweight
Lower gestational age
Vaginal delivery
Longer duration of Rx

Maternal use of SSRIs,
antidepressants, or
antipsychotics
Higher dose of morphine
required for Rx

Maternal use of SSRIs,
antidepressants, or
antipsychotics

SSRIs independently
Lower # days of maternal
receipt of study medication
 Greater # of cigarettes
smoked 24 hr prior to
delivery

Kaltenbach, et al. Addiction. 2012;107:45-52.
SIGNIFICANT DIFFERENCES IN NAS PROFILES
Methadone-exposed

Higher incidence of:
Buprenoropine-exposed

Undisturbed tremors
 Hyperactive Moro



Nasal stuffiness
 Sneezing
 Loose stools

Greater mean severity score:






Total NAS score
Disturbed tremors
Undisturbed tremors
Hyperactive Moro
Excessive irritability
Failure to thrive
Shorter time to Rx initiation

36 hr (compared with 59 hr for
buprenorphine)
Higher incidence of:

Greater mean severity score:

Sneezing
Limitation = Data from neonates requiring
Rx were excluded from analyses once Rx
was initiated → may underestimate
measures of incidence / severity
Gaalema, et al. Addiction. 2012;107:53-62.
HOW TO ASSESS FOR NAS: FINNEGAN SCORING TOOL
Signs / symptoms
DEVELOPMENT OF THE
FINNEGAN SCORING TOOL
• Developed to:
1.monitor full spectrum of abstinence
sx due to narcotic withdrawal
2.monitor response to Rx
• Determined prevalence of 20 most
common sx seen in infants with
narcotic withdrawal
• Ranked sx based on potential for
greatest harm to infant
Finnegan LP, at al. Int J Clin Pharmacol Biopharm. 1975.
Percentage
Tremors
90
Restlessness
85
Hyperactive reflexes
51
Regurgitation
45
Increased muscle tone
45
High pitched cry
33
Sneezing
31
Frantic sucking of fists
25
Inability to sleep
24
Stretching
22
Nasal stuffiness
18
Respiratory distress
12
Vomiting
9
Frequent yawning
9
Sweating
8
Excoriation of knees, toes and nose
7
Mottling
5
Diarrhea
3
Fever
3
Pallor
3
Lacrimation
2
Generalized convulsion
2
•
Assigned score of “5” to sx
with greatest potential to
harm infant and “1” to sx
with least pathological
significance

Scored q 1 hr in 1st 24 hr,
q 2 hr x 24 hr, then
q 4 hr corresponding to
“Nursery feedings”

Good inter-rater reliability
Finnegan LP, et al. Int J Clin
Pharmacol Biopharm. 1975

Modified in 1986
- Score q 4 hr
- Allow to feed q 2-3 hr
LIMITATIONS OF FINNEGAN TOOL
Designed for term infants
At times, difficult to interpret sx of ‘normal newborn’ vs
NAS
 Study


of 102 non-addicted infants
DOL 1-3: Median score = 2
Variability increased on DOL 1-2
th
 DOL 1: 95 percentile = 5.5
th
 DOL 2: 95 percentile = 7
Zimmermann-Baer et al. Addiction. 2010.
Can be prone to subjectivity
Not to be used for a “one point in time” quick assessment
Lacks specificity

DDx: hunger, nicotine or benzo withdrawal,
SSRI toxicity vs withdrawal, hypoglycemia,
infection, CNS injury, hypocalcemia,
hyperthyroidism
CO-MORBIDITIES
 Nicotine

withdrawal
Tobacco use in pregnancy ~85%
Lejeune et al. Drug Alcohol Depend. 2006.
Zimmermann-Baer et al. Addiction. 2010.
 SSRI

withdrawal / toxicity
13% maternal SSRI use in pregnancy
Zimmermann-Baer et al. Addiction. 2010.
 Other

substance / med toxicity
12% benzodiazepine Rx in pregnancy
Zimmermann-Baer et al. Addiction. 2010.
 Difficulties
 Increased
feeding
weight loss
NAS SCORING TIPS

Teach parents how NAS scoring is performed

Teach parents how to help monitor infant

e.g., watch for decreased sleep, yawning, sneezing, excessive sucking

Score within 2 hr of birth, then q 3 - 4 hr

Score baby when awake to elicit reflexes & behaviors
Do not awaken unless asleep for > 3 hr

Allow infant to calm first
e.g., allow infant to feed before scoring, place skin-to-skin with mother
 especially important for muscle tone & RR


Score all symptoms that occur within interval

If score ≥ 8, score NAS q 2 hr until < 8 x 24 hr
SUPPORTIVE CARE FOR NEWBORNS

Rooming-in
Allows family to respond to infant at early feeding / stress cues,
empowers family to care for their infant independently, and
provides opportunity for calmer environment for infant
Decreased need for NAS Rx
 Shorter length of stay
 More likely to be discharged into custody of mother

Abrahams R et al. Can Fam Physician. 2007.
SUPPORTIVE CARE FOR NEWBORNS
 Feed
baby at early feeding cues, till content
 Frequent
 Use







skin-to-skin contact
calming techniques
C-position
Swaddling
Gentle jiggling
Slow, rhythmic up & down movements*
Clap baby’s bottom with cupped hand*
Shooshing
Non-nutritive sucking
*May not work for some babies
SUPPORTIVE CARE FOR NEWBORNS

Provide undisturbed periods of sleep / rest


Decrease environmental stimuli





Cluster care
Low lights
Quiet room
Limit visitors / # caregivers
Avoid “excessive handling” of baby
Introduce stimuli as baby
able to tolerate

Infant touch / massage
BREASTFEEDING AND OPIATE
REPLACEMENT Rx

Methadone and buprenorphine considered safe

Breastfed infants may experience decreased NAS severity
Farid et al. Curr Neuropharmacol. 2008.

Ensure no active illicit drug use - see ABM guidelines

Provide lactation support




Promote calm, organized environment
Frequent, ad lib feedings
Provide emotional support
Teach ways to help baby if NAS present






Skin-to-skin
Hand expression / breast massage during feeding
Organize baby’s suck on finger first if suck disorganized
Feed small amount of colostrum first
C-hold in cross cradle / football positions
May require caloric supplementation for increased
metabolic needs
ABM’S BREASTFEEDING GUIDELINES
Consistent prenatal care
 Abstinent from illicit drug use or licit drug abuse for 90 days
prior to delivery & able to maintain sobriety in outpt setting
 Women engaged in substance abuse Rx who have provided
consent to discuss progress with Rx & postpartum plans with
substance abuse Rx counselor
 Negative urine toxicology testing at delivery
 No medical contraindications


e.g., HIV, contraindicated antipscyh med
The Academy of Breastfeeding Medicine Protocol Committee. ABM Clinical Protocol #21:
Guidelines for breastfeeding and the drug-dependent woman. Breastfeeding Medicine.
2009;4:225-228.
DRUG OF ABUSE SCREENING

Obtain specimens within 24 - 48 hr of delivery to help:



Anticipate timing and type of withdrawal symptoms
Inform DCF / DCYF of exposure, when clinically indicated
Make recommendations re: safety of breastfeeding
Urine drug of abuse screen
 Urine confirmatory testing
 Meconium drug of abuse screen

WHEN TO CONSIDER RX / ICN TRANSFER
Apnea
 Seizures
 3 consecutive scores (or average of) ≥ 8
 2 consecutive scores (or average of) ≥ 12
 Inability to feed orally due to NAS sx

PHARMACOLOGIC RX FOR NAS
Capture Phase


Oral morphine*§ q 4 hr, dose increased until NAS sx controlled
Phenobarbital added if difficult to capture or wean
Maintenance Phase


Find smallest dose that adequately controls baby’s sx
Goal of Rx = NAS scores < 8
Weaning Phase


Begin wean when scores < 8 x 48 hr & baby clinically stable
Wean by 10% daily when following present:


NAS scores < 8
Baby clinically stable
*Agent
of choice at DHMC, alternative agents sometimes preferred at other
institutions (e.g., methadone)
§2010
Cochrane Systematic Review on Opiate Rx for opiate withdrawal in
newborn infants: “There is insufficient data to determine safety or
efficacy of any specific opiate compared to another opiate.”
CARE COORDINATION

Clinical Resource Coordinator

Assist in identifying and arranging postnatal supports
VNA, Good Beginnings, breast pump rental, etc.
 Identify Primary Care Physician (PCP)


Social Worker
Perform initial assessment of mother and newborn
 Assist in identifying and arranging postnatal supports
 Review risk for postpartum depression / stress & identify coping
mechanisms / supports
 Mandated report to DCF/DCYF, when clinically indicated

Consider offering that mother make report herself
 Review how report will help engage parenting/family supports

KEEPING CHILDREN AND FAMILY SAFE ACT

As a condition of federal funds under Child Abuse
Prevention and Treatment Act, each state must develop
policies & procedures to address needs of infants born
and identified as being affected by illegal substance
abuse or withdrawal symptoms resulting from prenatal
drug exposure



Notify CPS of substance-exposed newborns
Develop plan of safe care for infant
Law specifies that reports of prenatal
substance exposure shall not be construed
to be child abuse or require prosecution
for any illegal action
DHMC MANDATED REPORTING GUIDELINES

Mother continuing to use any of following substances
during pregnancy, subsequent to documented teaching on
potential dangers of substance(s) and resources offered
for cessation:
Alcohol
 Controlled medication not prescribed to the mother
 Illicit substance

Mother who admits to prenatal use of illicit substance
and use not previously disclosed
 Baby tests positive for any of above substances
 Baby with Fetal Alcohol Syndrome or Adverse Effects

DISCHARGE READINESS
No apnea or respiratory compromise
 Stable vital signs
 Baby has completed appropriate observation period


No active concerns for significant sx of NAS
Feeding well with appropriate weight pattern
 Parents demonstrate appropriate response to / care of baby
 Home environment assessed as safe
 Referrals to community resources in place

COMMUNITY RESOURCES

Information and Referral











NH Resource 211 802-652-4636
VT Resource 211 866-444-4211
Support/Home-based programs (e.g., VNA, Good Beginnings,
Parenting Programs)
Health and Mental Health / Treatment Programs
Child Protective Services
Domestic/Family Violence
Housing
Emergency Financial Assistance
Legal Assistance
Transportation
Long-term follow-up programs /
interventions (e.g., Early Intervention)
GOING HOME …

Communication with community supports



Update state CPS agency, as clinically indicated





Identify known family challenges (domestic violence, mental
health issues, homelessness)
Identify known family strengths and informal supports
Known family challenges and strengths
Issues in the home which may pose risk for baby
Results of drug of abuse screening
Community supports recommended / accepted
Communication with baby’s PCP & 1st visit made

Update on medical course, social issues,
community resources offered / accepted
PRENATAL PREPARATION
Maintain abstinence
 Engage social supports
 Encourage breastfeeding (with abstinence)
 Decrease / stop smoking
 Educate families regarding what to anticipate

Likelihood of NAS symptoms / what sx look like
 Need to stay in hospital for at least 4 days for monitoring
 Possibility of needing Rx / duration of Rx if needed
 Providing calm environments for baby / calming techniques


Limiting visitors, rooming-in, skin-to-skin, swaddling, etc.
Drug of abuse screening
 Need for mandated reporting / referral to DCF/DCYF

RESOURCES FOR PROVIDERS

“Parenting and Substance Abuse: Developmental
Approaches to Intervention” - Book that explores
issues of the substance exposed dyad pre- and postpartum


Edited by Nancy Suchman, Marjukka Pajulo and Linda
Mayes (Oxford University Press, 2013).
“Highs and Lows” - Book about women and addiction.
http://www.camh.ca/en/education/about/camh_publications/Pag
es/highs_lows.aspx
QUESTIONS?