Running head: INTEGRATIVE REVIEW 1

Interventions for Neonatal Abstinence Syndrome

Ashley B. Butchello

Bon Secours Memorial College of Nursing

Arlene Holowaychuk, MSN

Nursing Research 4122

October 30, 2017

“I pledge”
INTEGRATIVE REVIEW 2

Abstract

The purpose of this integrative review is to appraise literature pertaining to the effects of non-

pharmacological and pharmacological treatments on the signs and symptoms of withdrawal in

infants diagnosed with Neonatal Abstinence Syndrome (NAS). NAS results from opioid

exposure in utero and then the abrupt cessation of drug transfer from mother to fetus after

delivery. Symptoms of NAS experienced by infants include hyperirritability, high-pitched

crying, seizures, poor feeding, irregular patterns in breathing and heart rate, and temperature

instability (Zuzarte et al., 2017). The database EBSCO Discovery Services was utilized to locate

research articles. The search yielded over 2,000 results; however, only five academic journal

articles satisfied the specific research criteria set for this topic. The results of these five articles

included how non-pharmacological and pharmacological treatments affected the length of

hospital stay and symptom management in newborns with NAS. Due to the researcher’s limited

background pertaining to the research and the lack of research articles available specifically

focusing on non-pharmacological treatments for NAS, there are limitations to this review.

Additional research should focus more on alternative therapies for the treatment of NAS so that

there is a decrease in the number of infants who need further opioid management to reduce

withdrawal symptoms after birth.

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Interventions for Neonatal Abstinence Syndrome

The purpose of this integrative review is to review the literature based on the

researcher’s PICOT question. Drug withdrawal in newborns from opioid exposure during

pregnancy has become a growing problem that healthcare facilities have had to endure in the past

decade. As a result, more and more newborns have been diagnosed with Neonatal Abstinence

Syndrome (NAS). “NAS is a disorder characterized by both behavioral and physiological signs

and symptoms observed in neonates delivered to women dependent on addictive substances

during pregnancy” (Young, Hager, & Spurlock, 2015). Symptoms of NAS that newborns

experience include hyperirritability, poor feeding, seizures, high-pitched crying, irregular

breathing and heart rate patterns, and poor thermoregulation (Zuzarte et al., 2017). Addressing

the effects of the opioid epidemic on neonates born to mothers who suffer from substance abuse

is necessary to not only promote awareness of the issue, but to find better interventions to treat

NAS. The researcher chose the following PICOT question: In neonates, what is the effect of

non-pharmacological treatments on opioid withdrawal symptoms caused by NAS and hospital

length of stay compared with pharmacological treatments?

Design/Research Methods

The research design is an integrative review. The database, EBSCO Discovery Services,

was used to search for research articles relevant to the PICOT question. The search terms

included, ‘neonatal abstinence syndrome’, ‘treatments’, ‘non-pharmacological therapy’, and

‘pharmacological therapy’. The search yielded over 2,000 articles, indicating a great deal of

literature on the topic. To ensure the credibility of the articles, the search was limited to peer-

reviewed qualitative and quantitative academic journal articles, published in English, and written

within the last five years. The articles pertained to the researcher’s PICOT question, “In
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neonates, what is the effect of non-pharmacological treatments on opioid withdrawal symptoms

caused by NAS compared with pharmacological treatments?” The articles were then selected

based on the following inclusion criteria: neonatal abstinence syndrome, non-pharmacological

treatment, and pharmacological treatment. The research articles were screened based on

inclusion criteria and PICOT question significance. Articles that did not meet criteria were

excluded from the review. The screening produced five articles published between 2015-2017

and included three quantitative and two qualitative research studies.

Findings/Results

The result findings of the five research articles clearly identify non-pharmacological and

pharmacological treatments that lead to a decrease in withdrawal symptoms and hospital length

of stay in neonates diagnosed with NAS (Chisamore, Labana, Blitz, & Ordean, 2016; Lee,

Hulman, Musci, & Stang, 2015; Newman et al., 2015; Young, Hager, & Spurlock, 2015; Zuzarte

et al., 2017). Overall, oral morphine sulfate as a pharmacological treatment deemed to be most

effective in subsiding symptoms of withdrawal and decreasing the length of stay newborns had

to reside in the hospital. A summary of the research articles is located in Table 1. This review is

structured based on the following categories: non-pharmacological interventions and

pharmacological interventions.

Non-Pharmacological Interventions

The two qualitative research studies used alternative therapies as an approach to reduce

withdrawal symptoms in neonates with NAS, as well as decrease the length of hospital stay

(Newman et al., 2015; Zuzarte et al., 2017). In the evaluation conducted by Newman et al.

(2015), a rooming-in program was implemented to support close uninterrupted contact between

mother and infants in order to decrease the need for pharmacotherapy, lessen the severity of NAS
INTEGRATIVE REVIEW 5

scores, and shorten hospital stays. 21 mother-infant dyads were included in the program and the

results revealed that neonates who roomed-in with their mothers required significantly lower oral

morphine therapy than those directly admitted to the NICU. Along with this, the average length

of stay was shorter among the rooming-in cohort as well.

The alternative therapy of stochastic vibrotactile stimulation (SVS) was implemented in

the study by Zuzarte et al. (2017) where the researchers hypothesized that SVS would reduce

symptoms of NAS and transform destabilized central and autonomic function. This single-

session, within-subjects design was conducted in 26 full term infants documented with fetal

opioid exposure that were being pharmacologically treated for NAS to compare the effects of

SVS to no stimulation. A specially-constructed mattress delivered low-level SVS in alternating

30-minute intervals of continuous vibration (ON) and no vibration (OFF) over a six to eight-hour

session. The data collected was recorded and stored on a hard disk for offline analysis and

included physiological, behavioral, and environmental signals and analog output to the mattress.

For the infants that revealed having multiple paired ON/OFF trials, a single mean was calculated

for both the ON and OFF conditions so that subjects in each analysis were equally weighted.

The results exposed a 35% reduction in movement activity, along with significantly reduced

incidents of increased respiratory rate and heart rate with SVS.

Pharmacological Interventions

The other three research articles included quantitative studies that addressed the effects of

morphine and methadone on the length of treatment, symptom management, and length of

hospital stay in newborns with NAS (Chisamore et al., 2016; Lee et al. 2015; Young et al.. 2015).

Chisamore et al. performed a retrospective chart audit to compare NAS outcomes consisting of

morphine doses and length of stay for the weight-based model and symptom-based model of
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morphine delivery. The study was conducted at St. Joseph’s Health Centre and a total number of

146 newborns’ charts were audited. Data was collected from hospital discharge face sheets that

disclosed information regarding the infants’ length of stay. In addition, the researcher’s

handwritten NAS scoring records and the newborn’s medical administration record were used to

obtain the peak NAS score and total amount of morphine administered to each newborn. After

the data was analyzed, results showed that infants in the symptom-based model had higher

median NAS scores and were more likely to receive morphine when compared to infants in the

weight-based model. However, there was no significant difference between the length of stay

and total amount of morphine administered between the symptom-based and weight-based

morphine delivery models.

Young et al. (2015) also conducted a retrospective chart review to determine whether oral

morphine sulfate or oral methadone for the treatment of NAS led to a decreased length of

hospital and NICU stay for neonates. Through the use of the health system’s pharmacy

computer system, 13 neonates were identified as receiving oral morphine sulfate and 13 neonates

were identified as receiving oral methadone for the treatment of NAS over a six-month period.

Maternal information, neonatal birth parameters, and neonatal treatment information were all

used in the data collection to identify potential study candidates. Neonates in each group were

evaluated every four hours to determine if pharmacologic treatment needed to be initiated when

NAS scores were eight or greater, two consecutive times. The group treated with oral morphine

sulfate was evaluated using the Finnegan scoring tool, while the group treated with oral

methadone was evaluated using the Neonatal Withdrawal Inventory (NWI) to obtain NAS

scores. Results concluded that neonates treated with oral morphine sulfate had reduced hospital

and NICU lengths of stay when compared to neonates treated with oral methadone.
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Furthermore, the length of treatment was significantly decreased for the neonates given oral

morphine sulfate.

A retrospective data analysis was implemented by Lee et al. (2015) to examine the

average length of stay of infants treated with methadone for NAS by ProgenyHealth from 2007-

2013. Through a search of ProgenyHealth’s NICU database, 139 cases were identified from 22

hospitals that fit the criteria of required pharmacologic intervention due to the diagnosis of NAS

at a gestational age of 35 weeks or greater. A regression analysis was used to look for a

correlation between average length of stay and number of NAS cases a hospital manages. Study

data showed that there is a significantly shorter average length of stay when neonates are treated

with methadone alone compared to other treatment regimens.

Discussion/Implications

The results of the research articles discussed in this review identify positive results from

both pharmacological and non-pharmacological treatment options in newborns diagnosed with

NAS (Chisamore et al., 2016; Lee et al., 2015; Newman et al., 2015; Young et al., 2015; Zuzarte

et al., 2017). Neonates treated with alternative therapies were shown to have better outcomes

and symptom relief, but there was not a great deal of information on length of hospital stay. In

comparison, the research articles that discussed medication use for therapy focused more on

length of treatment and hospital stay rather than symptom management. Although there were not

distinct commonalities among pharmacological and non-pharmacological treatment methods,

there were commonalities among the impact these interventions had on newborns with NAS.

Overall, the research included in this review supports the PICOT question set by the researcher.

Implications for practice based on these studies include finding a sole pharmacological

treatment that is shown to be most effective for treating NAS (Young et al., 2015). It is also
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pertinent to address how well these medications improved symptom management and what the

side effects were, if any, on neonates. In addition, more education and resources are needed for

mothers who are opioid dependent so that healthcare facilities can see a reduction in the number

of infants born with NAS. For this to happen, there needs to be an increased awareness of NAS

throughout society and healthcare providers, themselves, need to be further educated on the

issue.

Future research on this topic should address more non-pharmacological strategies that

can be used in practice to treat NAS. These could include minimizing environmental stimuli,

improving caloric intake, swaddling, and positioning (Zuzarte et al., 2017). By promoting these

alternative therapies, there may be less requirements for pharmacotherapy and better long-term

outcomes for neonates, as well.

Limitations/Conclusions

There were multiple limitations that should be noted in regard to the studies conducted.

All three of the quantitative studies were retrospective, meaning they could not be blinded or

randomized. Much of the data collected among each of the five research articles was procured

through a database, which relied on accuracy of data entry. Moreover, the small sample sizes

from a few of the research studies may have limited the generalization of the findings. Another

limitation of this review is the researcher’s lack of experience analyzing studies and completing

an integrative review.

Overall, there is an agreement within all five studies that both non-pharmacological and

pharmacological interventions can be used to promote better well-being in newborns diagnosed

with NAS. There is evidence that suggests alternative therapies reduce withdrawal symptoms

suffered by infants exposed to opioids in utero. However, there is little information about how
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these complementary therapies influence the length of hospital stay for infants diagnosed with

NAS. Pharmacological therapies seem to have the most profound effect on symptom

management and the resulting length of hospital stay, but there are still debates on what

medication is most beneficial in treating NAS. Therefore, further research needs to be performed

in relation to both treatment options to decide if one therapy is better than the other or if a

combination therapy is best practice.

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References

Chisamore, B., Labana, S., Blitz, S., & Ordean, A. (2016). A comparison of morphine delivery in

neonatal opioid withdrawal. Substance Abuse: Research and Treatment, 10(Suppl 1), 49-

54.

Lee, J., Hulman, S., Musci, M. J., & Stang, E. (2015). Neonatal abstinence syndrome: Influence

of a combined inpatient/outpatient methadone treatment regimen on the average length of

stay of a medicaid NICU population. Population Health Management, 18(5), 392-397.

doi:10.1089/pop.2014.0134

Newman, A., Davies, G. A., Dow, K., Holmes, B., Macdonald, J., McKnight, S., & Newton, L.

(2015). Rooming-in care for infants of opioid-dependent mothers: Implementation and

evaluation at a tertiary care hospital. Canadian Family Physician Medecin De Fammille

Canadien, 61(12), e555-e561.

Young, M. E., Hager, S. J., & Spurlock Jr., D. (2015). Retrospective chart review comparing

morphine and methadone in neonates treated for neonatal abstinence syndrome.

American Journal of Health-System Pharmacy, 72S162-S167. doi: 10.2146/sp150025

Zuzarte, I., Indic, P., Barton, B., Paydarfar, D., Bednarek, F., & Bloch-Salisbury, E. (2017).

Vibrotactile stimulation: A non-pharmacological intervention for opioid-exposed

newborns. Plos ONE, 12(4), 1-15. doi:10.1371/journal.pone.0175981

INTEGRATIVE REVIEW 11

Table 1: Qualitative and Quantitative Research Articles Summary

Reference (APA) Chisamore, B., Labana, S., Blitz, S., & Ordean, A. (2016). A comparison of morphine delivery in
neonatal opioid withdrawal. Substance Abuse: Research and Treatment, 10(Suppl 1), 49-54.

Author (2016) Chisamore, B. & Labana, S. – Department of Paediatrics, St. Joseph’s Health Centre
Blitz, S. – University Health Network
(Year)/Qualifications Ordean, A. – Department of Family and Community Medicine, St. Joseph’s Health Centre
The authors are qualified.

Introduction/Abstr Introduction: There are two different strategies for evaluation and treatment of NAS: a weight-
based scale, in which medication is dispensed on a milligram per kilogram basis, and a symptom-based
act/ scale, in which medication dose is determined by NAS score. No standardized approach has been
determined due to lack of comparative studies. Limited studies providing evidence for morphine dose
Background/Probl used in either model.
Abstract: Includes background, introduction, methods, results, and conclusion
em Statement Background: The incidence of neonatal abstinence syndrome (NAS) secondary to opioid
withdrawal is more than 4 cases per 1000 deliveries in Canada and US. Study done at St. Joseph’s
Health Centre. Protocol of NAS opioid withdrawal treatment, whether weight based or symptom only,
used a monotherapy of morphine sulfate 0.5 mg/mL.
Problem Statement/Purpose: The objective of this study was to compare NAS outcomes
consisting of morphine doses and length of stay (LOS) for the two models of morphine delivery.

Conceptual/ There was no conceptual/theoretical framework identified.

Theoretical

Framework

Design/Research Design: Retrospective chart audit

Research Methods: All newborns born in hospital from January 1, 2000, to December 31, 2014,
Methods/Sample/ inclusive, and whose chart was coded with an ICD10 of P96.1 were identified. Those infants exposed to
maternal opioids through confirmed drug screen and or self-admitted use were included in audit.
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Setting/Ethical Maternal use of other drugs and antidepressants use during pregnancy were captured by either self-
report and/or by positive maternal or infant toxicology testing.
Considerations/ Setting: St. Joseph’s Health Centre
Sample: Total number of newborns’ charts audited was 146
Major Variable Ethical Considerations: The research was approved by the Research Ethics Board of St. Joseph’s
Health Centre.
Studied/ Major Variable Studied: Length of stay and total accumulative morphine dose used for each
newborn
Measurement Data Collection Tool: Information for infants’ LOS was derived from hospital discharge face
sheets. Two parts of a newborn’s flagged chart were used to obtain the peak NAS score and the total
Tool/Data Collection accumulative morphine dose: the baby’s medical administration record and our handwritten NAS
scoring records. Each morphine dose from the newborn’s medication administration record was added
Tool/Data Analysis to create a total accumulated morphine dose.
Data Analysis: Categorical descriptive variables are summarized using counts and percentages,
and group comparisons were carried out using a chi-square test. Continuous variables are summarized
using medians and interquartile ranges; groups were compared using a Wilcoxon signed-rank test.

Findings/Results The symptom-only model was associated with a greater proportion of babies assessed as
requiring morphine initiation. There was no statistically significant difference in the timing of morphine
initiation between the two models in those babies who received morphine. Babies in the symptom-only
group were more likely to receive morphine. Those infants who received morphine in the symptom-only
model, did so at a similar onset of time, and required as much morphine as those who received morphine
in the weight-based model, and had similar lengths of stay. Some babies in the symptom-only model
received prompt morphine at a dose lower than the lowest dose in the weight-based model and were
weaned and discharged on par with regular NICU benchmark parameters. The symptom-only cohort had
a significantly higher median NAS score than that of the weight-based model.

Discussion/ Audit reveals that length of stay and total accumulative morphine might be affected by the
choice of morphine delivery model. The symptom-only model did not demonstrate any advantages with
Implications respect to LOS or morphine dose, which would not inspire a center to spend resources in converting
from a weight-based to a symptom-based model.
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Limitations/ Conclusions: The result of the audit does not indicate a need to discontinue the current model of
symptom-based morphine delivery. Comparing only those infants who did receive morphine, the
Conclusions comparative total accumulative dose of morphine and LOS were not significantly different between the
weight-based and symptom-only morphine delivery models.
Limitations: Could not control for timely discharges of mothers before the desired duration of
neonatal observation was completed. Did not record the temporal dispersion of the babies’ hospital
admissions. Given the propensity for a mother in the symptom-only group to have her baby need
morphine, it is possible that not being able to house all mothers with their withdrawing newborns might
be cause of that group’s inflated NAS scores.

Appraisal/Worth Audit has motivated two movements in the organization. The first is a low cost but anticipated
long-term gain in creating a system that can better collect and connect neonatal outcomes paired with
to practice their corresponding maternal demographics. The second initiative is one toward a structured sharing of
resource intensity of NAS with an inpatient pediatric ward.
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Reference (APA) Lee, J., Hulman, S., Musci, M. J., & Stang, E. (2015). Neonatal abstinence syndrome: Influence
of a
combined inpatient/outpatient methadone treatment regimen on the average length of stay of a
medicaid NICU population. Population Health Management, 18(5), 392-397.
doi:10.1089/pop.2014.0134

Author (2015) Lee, J. MD; Hulman, S. MD, MBA; Musci, M. DO, MBA; Stang, E. MD
The authors are qualified.
(Year)/Qualifications

Introduction/Abstr Introduction: In the neonate, the predominant signs and symptoms of acute opioid withdrawal
involve central nervous system irritability, gastrointestinal tract dysfunction, and autonomic overactivity.
act/ This syndrome can present as tremors, irritability, high-pitched crying, increased muscle tone, frequent
yawning and sneezing, seizures, poor feeding, vomiting, diarrhea, dehydration, failure to thrive,
Background/Probl sweating, nasal congestion, and temperature instability. A neonate with in utero drug exposure who
exhibits any signs of NAS should, at minimum, receive non-pharmacologica treatment for comfort,
em Statement which includes swaddling, rocking, therapeutic sucking, and minimization of sensory or environmental
stimulation. To determine if infant requires pharmacologic intervention, a scoring scale is implemented
to assess the severity of NAS. The mainstay of pharmacologic NAS treatment is oral opioid therapy.
Abstract: Includes some background information, objective, results, and conclusions.
Background: It has been estimated that illicit drug use occurs in 4.4% of pregnant women,
16.2% among pregnant teens, and 7.4% among pregnant women aged 18-25 years. As can be expected
with the increasing use of prescription drugs, the incidence of neonatal abstinence syndrome (NAS) will
increase and remain an ongoing problem in the neonatal population. These infants often require costly,
prolonged stays in the neonatal intensive care unit (NICU) for drug withdrawal treatment.
Problem Statement/Purpose: Goal is to examine all of AmeriHealth Caritas Pennsylvania’s
members with NAS managed by ProgenyHealth from 2007-2013. The primary outcome of the study is
the average length of stay (ALOS) of this cohort. The secondary outcomes are differences in ALOS
between individual hospitals and possible contributing variables, such as hospital experience, type of in
utero drug exposure, and treatment regimen.
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Conceptual/ There was no mention of a conceptual/theoretical framework.

Theoretical

Framework

Design/Research Design: Retrospective data analysis

Sample: 139 cases from 22 hospitals
Methods/Sample/ Research Methods: A search of ProgenyHealth’s NICU database was performed for all ACP
members born between January 1, 2007, and December 31, 2013, who fit the following criteria: >/= 35
Setting/Ethical weeks gestational age with diagnosis of NAS and required pharmacologic intervention.
Data Collection Tool: admission date, discharge date, length of stay, maternal age, maternal
Considerations/ opioid used during pregnancy, hospital where treatment occurred, primary medication used to treat NAS
(including whether the treatment was completed in the hospital or as an outpatient), and any adjunctive
Major Variable medications used
Data Analysis: Welch’s t test for independent samples was used to compare the methadone-only
Studied/ treatment group to all-others treatment group, and also used to compare the methadone-exposed group
to the buprenorphine-exposed group. Regression analysis was used to look for correlation between
Measurement number of NAS cases a hospital manages and ALOS.
Ethical Considerations: N/A
Tool/Data Collection

Tool/Data Analysis

Findings/Results Study data shows that neonates treated with methadone alone have a significantly shorter ALOS
of 11.4 +/- 4.8 days versus an ALOS of 25.1 +/- 12.3 days for all other treatment regimens. Of the 41
infants treated with methadone alone, all but 4 were discharged home to complete outpatient medication
wean. There is wide variability of ALOS within the subset of individual hospitals, and there appears to
be a weak, but significant correlation between number of NAS cases a hospital manages and ALOS. Of
139 cases in the study cohort, there were 12 discrete patient readmissions in the first year of life. Ten of
the 12 readmissions were not directly related to the initial NAS diagnosis.
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Discussion/ Results of retrospective study confirm that ACP admissions for NAS have been increasing
steadily, mirroring the national trend. The overall ALOS of 21.1 days for the current study population
Implications compares favorably to a consensus duration of approximately 30 days reported by Kraft and Seligman.
When ALOS was evaluated further by treatment regimen, it can be seen that infants who begin their
treatment in the hospital with methadone were discharged home to complete outpatient treatment had an
ALOS of 11.4 days versus 25.1 days for infants who completed their entire treatment in the hospital. In
the data analysis, there was 1 treatment failure requiring readmission for exacerbation of NAS
symptoms as a result of missed methadone doses from a caregiver unable to obtain additional outpatient
methadone.

Limitations/ Limitations: Include retrospective nature and small sample size. Procurement of cases from a
database, which relies on accuracy of data entry. Lack of access to data sets containing other potential
Conclusions confounding variables influencing length of stay, such as family/social issues, staff training, and
breastfeeding rates.
Conclusion: The authors believe that this study provides further evidence that a combined
inpatient/outpatient NAS treatment regimen with methadone can significantly decrease length of stay
and associated health care expenditures without increased adverse outcomes. Development of successful
combined inpatient/outpatient management programs for NAS warrants further discussion.

Appraisal/Worth The fact that methadone treatment significantly decreased the length of stay for newborns
without increased adverse outcomes proves to be an effective pharmacological intervention.
to practice
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Reference (APA) Newman, A., Davies, G. A., Dow, K., Holmes, B., Macdonald, J., McKnight, S., & Newton, L.
(2015). Rooming-in care for infants of opioid-dependent mothers: Implementation and evaluation at a
tertiary care hospital. Canadian Family Physician Medecin De Fammille Canadien, 61(12), e555-e561.

Author (2015)
Newman MD, CCFP FCFP; Davies MD FRCSC FABOG; Dow MD FRCPC; Holmes MSW
(Year)/Qualifications RSW; McKnight MD; Newton RN(EC) Med IBCLC
The authors are qualified.

Introduction/ Introduction: Infants born to opioid-dependent women are admitted to intensive care units for
management of neonatal abstinence syndrome (NAS), serious morbidity, and prevention of mortality;
Background/Probl however, the disadvantages of this approach include infants experiencing more severe NAS and
exhibiting a greater need for pharmacotherapy owing to the interference with mother-infant bonding.
em Statement Abstract: Includes problem addressed, objective of program, program description, and
conclusion.
Background: Across Ontario there has been increasing attention in the academic press and lay
media to the rising incidence of opioid dependence in the population, which has resulted in a marked
increase in pregnant women presenting for prenatal care who disclose a history of opioid dependence.
Problem Statement/Purpose: To implement a rooming-in program to support close uninterrupted
contact between opioid-dependent women and their infants in order to decrease the severity of NAS
scores, lessen the need for pharmacotherapy, and shorten hospital stays.

Conceptual/ There was no conceptual/theoretical framework identified.

Theoretical

Framework

Design/Research Opioid-dependent pregnant women were assessed antenatally by a multidisciplinary team and
provided with education and support. Psychosocial issues were addressed in collaboration with a
Methods/Sample/ community program developed to support addicted mothers. The mother-infant dyad was admitted
postpartum to a private room and attended by nurses trained in Finnegan scoring. Infants remained with
INTEGRATIVE REVIEW 18

Setting/Ethical their mothers unless persistently elevated scores made transfer to neonatal intensive care units necessary
for initiation of pharmacotherapy.
Considerations/ Sample: 21 mother-infant dyads

Major Variable

Studied/

Measurement

Tool/Data Collection

Tool/Data Analysis

Findings/Results During the 13 months subsequent to the implementation of the rooming-in program, 21 women
taking opioid therapy gave birth to full-term infants and were admitted to a private room in the
pediatrics unit with their babies. The requirement for oral morphine therapy for the neonates in the
rooming-in cohort was significantly lower than those admitted directly to the NICU. The mean LOS was
also significantly shorter among the rooming-in cohort.

Discussion/ The cohort study demonstrates a statistically significant decreased need for pharmacotherapy and
hospital LOS. Opioid-dependent pregnant women were seen at least once in our multidisciplinary clinic
Implications where they were educated about NAS and the rooming-in goals and where staff could identify and
address social risk factors before admission for labor and delivery. All women had access to a
community-based primary care worker who supported them at home and accompanied them to their
clinic appoints and reinforced the rooming-in goals.

Limitations/ Limitations: Adoption of a more “low tech” approach has achieved better outcomes for infants,
their mothers, and the hospital. The NAS scoring tool was used to quantify withdrawal severity relies to
Conclusions some extent on subjective judgment and might therefore be a possible source of bias. Sought to
minimize this by using the same tool in both cohorts, and maintaining the same criteria for initiating
pharmacotherapy before and after implementation of rooming-in.
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Conclusions: With the rooming-in program, the proportion of infants requiring pharmacotherapy
decreased from 83.3% to 14.3% and the average length of stay decreased from 25 days to 8 days. The
rooming-in experience was rated favourably by participating mothers.

Appraisal/Worth A decrease in NICU admissions leaving more room for other infants requiring NICU care. The
rooming-in program seems to have a positive effect on mothers and their infants, with mothers finding
to practice an overall satisfaction with the program.
INTEGRATIVE REVIEW 20

Reference (APA) Young, M. E., Hager, S. J., & Spurlock Jr., D. (2015). Retrospective chart review comparing
morphine and methadone in neonates treated for neonatal abstinence syndrome. American Journal of
Health-System Pharmacy, 72S162-S167. doi: 10.2146/sp150025

Author (2015) Young, M. E. Pharm.D., BCPS; Hager, S. J. Pharm.D., BCNSP; Spurlock Jr., D. PH.D.,
RN
(Year)/Qualifications The authors are qualified.

Introduction/ Introduction: Neonatal tolerance or addiction is due to passage of the substance across the
placental barrier. These substances tend to accumulate in the fetus due to immature renal function and
Background/Probl metabolic enzymes. Once the fetus is born and no longer receiving the substance from the mother,
withdrawal occurs. Symptoms occur in approximately 55-94% of neonates exposed to opiates in utero.
em Statement NAS frequently involves multiple body systems, including gastrointestinal, central nervous, autonomic,
and respiratory systems. Onset of withdrawal symptoms varies depending upon the maternal substance
used. Substances with longer half-lives cause withdrawal symptoms later than those with shorter half-
lives.
Abstract: Includes objective, methods, results, and conclusion.
Background: In 2009-2010, the National Survey on Drug Use and Health (NSDUH) found that
4.4% of pregnant women ages 15-44 years reported using illicit drugs. Neonatal abstinence syndrome
(NAS) is a disorder characterized by both behavioral and physiological signs and symptoms observed in
neonates delivered to women dependent on addictive substances during pregnancy.
Problem Statement/Purpose: The primary objective was to determine whether oral morphine
sulfate has a decreased neonatal length of stay, both in the hospital and NICU, when compared to oral
methadone for the treatment of NAS.

Conceptual/ There was no conceptual/theoretical framework mentioned.

Theoretical

Framework
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Design/Research Design: Single-site, retrospective chart review conducted between September 2010 and March
2011
Methods/Sample/ Sample: 26 patient retrospective chart review
Setting: Study took place in a 500 bed adult teaching hospital with a 19 bed NICU
Setting/Ethical Ethical Considerations: Institutional Review Board approval was obtained from the hospital
system. All data were recorded without identifiers to maintain patient confidentiality.
Considerations/ Major Variable Studied: Oral methadone as treatment for NAS versus oral morphine sulfate
Research Methods: The health system’s pharmacy computer system was used to retrospectively
Major Variable identify consecutive neonates who received oral morphine sulfate as treatment for NAS for six months
after the change in practice. Same system used to identify an equal number of consecutive neonates who
Studied/ received NAS treatment with oral methadone. Inclusion criteria included in utero exposure to opioids as
determined by maternal history, toxicology reports, reports during pregnancy or at the time of delivery,
Measurement or infant urine toxicology reports; and symptoms of NAS requiring pharmacological treatment.
Data Collection Tool: Maternal information (prenatal care, polysubstance abuse, toxicology
Tool/Data Collection screen results), neonatal birth parameters (gender, head circumference, birth weight, gestational age,
length, delivery location), and neonatal treatment information (toxicology screen results, NAS scores,
Tool/Data Analysis hospital length of stay, NICU length of stay, maximum opioid dose, adjuvant therapy, duration of
treatment, cost of treatment)
Data Analysis: Neonates were divided into two treatment groups, those treated with oral
morphine sulfate and those treated with oral methadone. Group one neonates were evaluated every 4
hours using the Finnegan scoring tool. Pharmacologic treatment was initiated after two consecutive
NAS cores of eight or greater. Initial dose of oral morphine sulfate for was based upon most recent NAS
score. Re-evaluation of NAS scores continued every four hours, and the same dose adjustment protocol
was used. Group two included neonates treated with oral methadone and they were evaluated using the
Neonatal Withdrawal Inventory (NWI). Treatment started when the neonate had two consecutive NAS
scores of eight or greater.

Findings/Results A statistically significant difference in the length of stay, both in the hospital as well as the NICU
was found. The average length of hospital stay for neonates was lower in the oral morphine sulfate
group versus the oral methadone study group. The average length of NICU stay for neonates was lower
in the oral morphine sulfate group compared to the oral methadone study group. There was also a
significant decrease in length of treatment in the oral morphine sulfate group when compared to the oral
methadone group.
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Discussion/ Due to the long half-life of oral methadone, obtaining initial control of NAS symptoms and
weaning took much longer. Oral morphine sulfate has a much shorter half-life and therefore NAS
Implications symptoms were controlled much quicker than with the methadone. This also allowed the oral morphine
sulfate to be weaned off more rapidly, as nurses were able to decrease the oral morphine sulfate dose
every four hours. Different scoring tools were used in each group; however, both tools were guided by
symptom measurement and they evaluated similar signs/symptoms.

Limitations/ Limitations: The small sample size may limit the generalization of the findings. Another
limitation is that the oral methadone group was not treated with a standardized protocol. A final
Conclusions limitation was that because this was retrospective, it could not be blinded or randomized.
Conclusions: The neonatal intensive care unit length of stay was reduced by 32 days and the
hospital length of stay was decreased by 30 days in infants treated with morphine sulfate. The length of
treatment was reduced in the oral morphine sulfate group by approximately 32 days.

Appraisal/Worth The retrospective chart review supports the use of oral morphine sulfate instead of oral
methadone in the treatment of NAS.
to practice
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Reference (APA) Zuzarte, I., Indic, P., Barton, B., Paydarfar, D., Bednarek, F., & Bloch-Salisbury, E. (2017).
Vibrotactile stimulation: A non-pharmacological intervention for opioid-exposed newborns. Plos
ONE, 12(4), 1-15. doi:10.1371/journal.pone.0175981

Author (2017) Zuzarte, I., Indic, P., Paydarfur, D. – Department of Neurology, University of
Massachusetts Medical School
(Year)/Qualifications Barton, B. – Department of Quantitative Health Sciences, University of Massachusetts Medical
School
Paydarfur, D. – Wyss Institute for Biologically Inspired Engineering; Harvard University
Bednarek, F., Bloch-Salisbury, E. – Department of Pediatrics, University of Massachusetts
Medical School

The authors are qualified.

Introduction/ Introduction: Infants exposed to drugs in utero develop physical tolerance and dependence
through placental transfer. NAS refers to physiological adaptation that occurs from prenatal drug
Background/Probl exposure and to the physical disturbance when the drug is terminated at birth. The abrupt cessation of
drug transfer that occurs when the infant’s blood supply is severed from their mother’s at delivery
em Statement results in dysregulation of central and autonomic function, which can be life-threatening. Clinically
significant physiological signs of NAS include hyperirritability defined by increased movement, as well
as seizures, irregular patterns in breathing and heart rate, and problems with thermoregulation and
feeding. Non-pharmacologic strategies such as minimizing environmental stimuli, swaddling and
position, and improving caloric intake are considered first-line treatment of infants with NAS, and there
is some recent evidence that parental rooming-in models may reduce withdrawal symptoms, facilitate
weaning, decrease length of stay and reduce pharmacotherapy requirement.
Abstract: Includes objective, study design, results, and conclusions.
Background: Drug withdrawal in newborn infants from drug exposure during pregnancy is a
growing and costly public health problem due in large part to unprecedented maternal use and addiction
to opioids. Over last decade, there has been 5-fold increase in rate of hospital admissions nationwide for
neonatal drug withdrawal, with recent estimates of ~6 per 1000 hospital births.
Problem Statement/Purpose: To assess the therapeutic potential of stochastic (random),
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vibrotactile stimulation (SVS) using a uniquely-constructed crib mattress as a complementary

intervention for NAS in newborn infants exposed to opioids in utero. It was hypothesized that SVS
would transform destabilized central and autonomic function and reduce symptoms of NAS.

Conceptual/ There was no conceptual/theoretical framework discussed.

Theoretical

Framework

Design/Research Design: Prospective, within-subjects single-center study conducted in 26 opioid-exposed

newborns hospitalized since birth and treated pharmacologically for Neonatal Abstinence Syndrome
Methods/Sample/ Sample: 26 full term infants documented with fetal opioid exposure were identified to study
investigators by attending physician
Setting/Ethical Setting: University of Massachusetts Memorial Medical Center Neonatal Intensive Care Unit
and Newborn Nursery, Worchester MA
Considerations/ Major Variable Studied: Movement, heart rate, respiratory rate, axillary temperature, and
arterial-blood oxygen saturation were calculated separately for ON and OFF
Major Variable Research Methods: Specially-constructed mattress delivered low-level SVS, alternated in 30-min
intervals between continuous vibration (ON) and no vibration (OFF) over a 6-8 hr session
Studied/ Data Collection Tool: All physiological, behavioral, and environmental signals and analog output
to the mattress were recorded and displayed during the environments and stored on hard disk for offline
Measurement analysis; overt behavioral data recorded with video camera within the infant’s crib area were
synchronized with the physiological, audiometry and light signals.
Tool/Data Collection Ethical Considerations: Written informed consent was obtained from the biological mother of
each infant enrolled. Study was approved by University of Massachusetts Medical School Institutional
Tool/Data Analysis Review Board for Human Subjects.
Data Analysis: The number of paired ON/OFF trials varied among subjects due to factors
beyond study control: inter-feed durations (infants were on-demand feed), continual touching by parent,
or excessive irritability during 30-min post feed interval wherein infant did not settle and was placed by
nurse in prone position, in alternative hospital-issued vacillating seat, or held by caregiver. Conditions
that did not have matched ON/OFF pairing were excluded. For subjects having multiple paired ON/OFF
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trials, a single mean was calculated for the ON conditions and for the OFF conditions so that subjects
were equally weighted for each analysis.

Findings/Results 35% reduction in movement activity with SVS, with significantly fewer movement periods >30
sec duration for ON than OFF. Incidents of tachypneic breaths and tachycardic heart beats were each
significantly reduced with SVS, whereas incidents of eupneic breaths and eucardic heart beats each
significantly increased with SVS. Infants maintained body temperature and arterial-blood oxygen level
independent of stimulation condition.

Discussion/ Novel finding is that SVS reduced prolonged movement activity and improved cardiac and
respiratory function in opioid-exposed newborns diagnosed with NAS. Findings suggest SVS may help
Implications regulate autonomic function by stimulating pressure receptors, specifically slowly-adapting pulmonary
stretch receptors, to increase vagal tone. Prolonged movement periods were significantly reduced with
SVS, indicating that SVS may reduce arousals and improve sleep duration and organization. No adverse
effects associated with SVS in current study. Nurses and parents reported anecdotally that infants
seemed “less irritable”, “calmer”, and “slept better” during periods of SVS. Infants in this study were all
being treated with morphine to help manage withdrawal symptoms, yet continued to present with
dysregulated behaviors during the study day despite pharmacological management. Study demonstrated
that brief intervals of whole-body SVS reduced cardiac and respiratory instabilities commonly observed
in pharmacologically-managed opioid exposed newborns. Because intervention was set at 30 min
intervals, could not assess the direct effect of SVS on Finnegan withdrawal scores since these
assessments were performed over the procedural 3-4 hour period.

Limitations/ Limitations: Full-polysomnography was not used to assess sleep states. Single session study in a
small group of infants with various drugs of exposure, who presented with mild to severe withdrawal at
Conclusions the time of the study session and were studied at varying post-conceptual ages.
Conclusions: SVS reduced hyperirritability and pathophysiological instabilities commonly
observed in pharmacologically-managed opioid-exposed newborns. SVS may provide an effective
complementary therapeutic intervention for improving autonomic function in newborns with Neonatal
Abstinence Syndrome.
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Appraisal/Worth Utilizing non-pharmacological therapies to reduce withdrawal symptoms in newborns with

Neonatal Abstinence Syndrome may prove to be safer than pharmacological therapies.
to practice