Running Head: RISK OF DEVELOPMENTAL DELAYS

Risk of Developmental Delays related to infants born with Neonatal Abstinence Syndrome
Kara Whitman, Celeste Cavanaugh, Kristy Farkas, Josh DeSalvo, Adeyemi Shodipo
04/05/2017
NURS 3947: Nursing Research
Dr. Patricia Hoyson and Ms. Nicole Kent-Strollo
RISK OF DEVELOPMENTAL DELAYS 1

Abstract
The purpose of this research was to look at the relationship between neonatal abstinence

syndrome (NAS) and its effect on child development. The prevalence of NAS along with the its

link to cognitive, motor, behavior, and speech/language development was examined. This

research was conducted by looking at a mixture of eighteen articles and literature reviews.

Research suggests that there is likely a correlation between NAS and developmental delays;

however, there is not enough concrete evidence to fully support that claim. Overall, the research

presented within this paper shows the connections we already know and discusses the need for

further exploration of this topic.

RISK OF DEVELOPMENTAL DELAYS 2

Neonatal abstinence syndrome is a syndrome that goes beyond the few weeks an infant

will likely spend in the neonatal ICU (NICU). It is becoming a problem that needs to be

addressed. The number of NAS cases within the United States is on the rise. There is limited

research on the long-term effects NAS has on infants. This presents an issue in the nursing

community due to the fact that nurses are caring for more of these children than ever before. It is

difficult to treat an infant with a drug withdrawal without knowing what the outcome will be.

The drugs themselves along with the process of withdrawal can create a delay in child

development. Therefore, the following research question was addressed: Are infants with NAS at

an increased risk for developmental delays compared to healthy infants?

Literature Review

Introduction

Information on this research was obtained via an OhioLINK database, specifically

Academic Search Complete, as well as Google Scholar. From these search engines, eighteen

articles were used to analyze the effect of NAS on child development. Cognitive, motor,

behavioral, and speech/language development in children that had NAS will be discussed.

Incidence of NAS will also be discussed.

NAS

Neonatal Abstinence Syndrome (NAS) is a group of problems in a newborn as a result of

exposure to addictive, illicit or prescription drugs while in a mother’s womb. It is a term given to

infants that are suffering from drug withdrawal. It most often manifests after exposure to opioids

but can also be seen with exposure to methadone, buprenorphine, antidepressants and

benzodiazepines. Symptoms of NAS are typically characterized by tremors, irritability, excessive

RISK OF DEVELOPMENTAL DELAYS 3

crying, poor feeding, vomiting, diarrhea, slow weight gain (or impaired) and sometimes seizures

(Jean Y. Ko, Stephen W. Patrick, Van T. Tong, Roshni Patel, Jennifer Lind, Wanda D. Barfield,

2016). Newborns with NAS have also been known to have respiratory complications and some

even face death due to the effects of withdrawal. The onset of the withdrawal symptoms can

range anywhere from minutes to two weeks after birth and can last for six days to eight weeks.

However, symptoms or irritability may continue for more than three months (Hutchings, DE.,

1982).

The prevalence of NAS has increased since 1999. While looking at NAS cases from 28

states, Ko et al., (2016) found that reported NAS cases increased by 300% between 1999 and

2013. “In 1999 (the first year), 2,419 NAS cases were identified among 1,610,733 births in 14

reporting states (1.5 per 1,000 births). In 2013, 8,270 NAS cases were identified among

1,385,371 births in 21 states (6.0 per 1,000 births)” (Ko et al., 2016). In a study conducted by

Veeral N. Tolia, Stephen W. Patrick, Monica M. Bennett, Karna Murthy, John Sousa, P. Brian

Smith, Reese H. Clark, Alan R. Spitzer (2015), there was an increase in number of NAS cases,

length of stay in the NICU, and number of NICU days where NAS was the prominent diagnosis.

At two out of the 157 centers involved in the study, more than 40% of the NICU days were

related to NAS babies (Tolia et al., 2015). A surprising ten percent of the clinical centers

reported having more than 10% of their NICUs day attributed to NAS infants. Although it may

not seem like a significant number, it is much higher than previous records. Tolia et al., (2015),

believe that their study was actually under representative of NAS cases. They did not include

infants that had suspected cases of NAS or infants that were admitted to the NICU after initial

discharge from the hospital. Infants that are less severely impacted by NAS may be treated in

settings other than the NICU which also lead them to believe that their reports were
RISK OF DEVELOPMENTAL DELAYS 4

underestimates. With that being said, NAS is a fast-growing medical problem. It is a problem

that extends beyond the first couple weeks of life. To explore the effects of NAS on a growing

child, this paper is going to give a brief insight into potential developmental delays related to

NAS.

Cognitive Development

Newborns are not fully developed upon birth and must go through many changes to

become the person that they will eventually grow into. Some changes a newborn is going

through may be easier to see than some other changes may be. A physical change a newborn is

going through, for example, may be easier to notice because it can be observed; a cognitive

change, however, may be impossible to observe and can easily be missed. “Children prenatally

exposed to opioids and polysubstances are at increased risk for neuropsychological dysfunction”

(Nygaard, Moe, Slinning, Walhovd, 2015, p. 330). Whereas newborns born to healthy mothers

have milestones that they achieve at a certain age, a newborn with NAS will most likely be

preterm with a low birth weight and be at a serious disadvantage to perform these milestones

from the get go.

The research that is available about the cognitive differences of children that had

previously been prenatally exposed to opioids and polysubastances as compared to those who

had no prenatal exposure are very limited. According to Nygaard, Moe, Slinning, and Walhovd

(2015), there is a consensus that children born to addicted mothers definitely have lower

cognitive ability than children born to healthy mothers (p. 330). Also, found by these

researchers, was that boys’ cognitive development was delayed on all assessments from age 1 to

age 8 ½; whereas the girls’ cognitive development was not noticeably different until the last

assessment at 8 ½ years of age (p. 331). The only explanation against why boys have more
RISK OF DEVELOPMENTAL DELAYS 5

cognitive deficits than girls is that they may be more susceptible to the effects of the opioids and

polysubstances that their mothers are ingesting than girls are (p. 333). These researchers have

hypothesized that girls are more susceptible to cognitive effects at a later age, 8 ½, than boys are

because, “Girls’ general preponderance for emotional problems arising in adolescence may also

begin to interact with the vulnerability of the exposed girls at an even earlier age” (p. 333).

Another set of researchers has broken up their research based on the differences between

prenatally exposed infants to drugs and infants not prenatally exposed to drugs. The difference

with this research is that it is broken into each specific drug and what effects each drug has on a

fetus and the delays the drugs may cause. Ross, Graham, Money, and Stanwood (2015) state

“Given the crucial roles for the major protein targets of drugs of abuse in shaping brain

development, it should not be surprising that fetal drug exposures have been linked to a wide

variety of brain deficits” (p. 1).

A common drug consumed during pregnancy, per Ross, Graham, Money, and Stanwood

(2015), is cocaine (p.7). Infants prenatally exposed to cocaine can have an array of problems

after birth and even into later childhood and adolescence. Research has shown that there are

effects on a child’s executive function from those who were born to mothers addicted to cocaine.

“Executive function is a set of mental processes for the management of cognitive operations that

include attention, behavior, cognition, working memory, and information/problem solving”

(Ross, Graham, Money, and Stanwood, 2015, p. 8). These effects on executive function may last

until adolescence and there may be differences based on gender. “Females had greater problems

with initiation activities, working memory, and organization” (p. 8), whereas males had problems

with attention and inhibitory control performance (p. 8).

RISK OF DEVELOPMENTAL DELAYS 6

Overall, the research has shown that there are longitudinal and long-term cognitive

effects on babies with Neonatal Abstinence Syndrome, NAS, as compares to babies born to a

healthy mother, not addicted to drugs. Although there is not an immense amount of research on

this topic, the research that is out there has come to the same conclusion about the effects on the

children and how the effects are different based on gender.

Motor Delays

Short and long term motor delays associated with NAS can vary with the majority of

motor delays occurring from the use of opiates and methadone. The length of time and degree of

fetal exposure to such drugs in-utero can be the determining factors in whether or not motor

abilities are affected. According to Logan (2013), “Methadone-exposed infants have been found

to exhibit increased motor rigidity, dysregulated motor patterns and decreased activity by

observation and maternal report on the Bayley Infant Behavior Record”. The Bayley Infant

Behavior Record (BSID-III) is used to assess developmental functioning in infants and young

children between the age of 1 month and 42 months of age with applications in cognition,

language and motor development making this scale an important assessment tool for NAS.

Logan’s (2013) study of 200 methadone and non-methadone participating families found

the following: At 9 months of age, 37.5 % of our sample of methadone exposed infants

showed clinically significant motor delays using the BSID-III compared to low but

typical development in the comparison group. Motor deficits were most prominent in the

milestones of sitting independently and crawling (pg 4).

RISK OF DEVELOPMENTAL DELAYS 7

The motor deficits found in the first study of methadone exposed infants are focused on gross

motor skills which are movements associated with large muscle groups and whole body

movement and develop in a head-to-toe order.

In the second study of opiate exposed infants the findings are directed more toward

psychomotor delays. Psychomotor refers to the relationship between cognitive functions and

physical movement. Psychomotor skills are physical skills such as movement, coordination,

manipulation, dexterity, strength, and speed all of which demonstrate the fine motor skills. 133

infants from opiate dependent moms and 103 healthy infants were tested with psychomotor

deficits being evident among the opiate exposed infants compared to the control group of healthy

infants. According to Hunt (2007), “Despite no differences being detected in psychomotor

development at 18 months, there was a significantly lower score on the McCarthy Motor Scale at

3 years of age for opiate-exposed children”. Hunt also states that, “Many investigators have been

less than willing than us to attribute significance to their finding because the opiate-exposed

infants had psychometric scores that fell within range. We challenge this premise and argue that

despite the small numbers studied, there are still clear differences in development between

opiate-exposed infants and controls. To clarify, findings for this study were based on the

Psychomotor Development Index pertaining to the Bayley Scales which tested both groups on

their level of psychomotor development by age and although the opiate-exposed infants were

technically within range, their scores were significantly lower than those of the control group

leading the researchers to believe that opiate exposed infants in fact have these delays due to

their exposure in-utero.

As mentioned above, many past researchers have failed to find the link between motor

delays and NAS because not meeting the age appropriate developmental milestones in motor
RISK OF DEVELOPMENTAL DELAYS 8

coordination can also be contributed to other factors such as; environment, parental involvement,

and genetic influences. Another big factor is that children all have their own unique pattern of

meeting milestones within a certain time frame. All of this considered, it has made it hard for

researchers to pinpoint motor delays strictly to NAS because most NAS infants fall into the

normal range. This range however, has been significantly lower than that of the control groups.

According to Logan (2013), “Few studies have used both biological and clinical measures to

evaluate developmental delays”. This can very well be part of the reason why the majority of

other studies done on developmental delays of NAS have limited information on motor deficits.

Not to mention, that most of the studies performed have had a hard time keeping participation

levels high (as was the case for Hunt), leaving them with a consistently low number of

participants over 42 months of age to assess for motor delays, which in turn has led to very

mixed findings. With all that being said, there is an extreme need for further research to

investigate short and long term motor delays seen with NAS as well as a need for more long term

participation.

Behavioral

Obstetrical complications have been found in connection with heroin addiction. These

complications include abortion, intrauterine growth, retardation, placental insufficiency,

polyglycolic and pulmonary hemorrhage. Factors contributing to this failure to take care of their

health may include financial difficulty, lack of health insurance, lack of education,

unemployment, home issues, poor diet, and the difficult lifestyle of the addicts such as being a

heavy smoker and various illegal activities/ crimes carried out to get money.

The two articles used for the research studied mostly methamphetamine (MA) as the drug

of use because methamphetamine is a worldwide problem with more users than cocaine and
RISK OF DEVELOPMENTAL DELAYS 9

opiates combined. MA users comprise mostly of women as first time users, as a result there is

increasing concern about the effect of prenatal use on women and newborns. According to the

Substance Abuse and Mental Health administration; in 2009, 6.7% of those seeking treatment of

MA abuse in the United States were pregnant women (Substance Abuse and Mental Health

Services Administration. Treatment Episode Data Set, 2011)

Though the research on cocaine addicted pregnant women is illuminating because both

MA and cocaine are sympathomimetic agents, nevertheless MA’s Neurotoxicity outcome may

have a larger adverse effect than cocaine due to its longer half-life and multiplied effect (Mayes,

LC. 2002), MA has vasoconstrictive effects, resulting in decreased uteroplacental blood flow and

fetal hypoxia (Stek AM, Fisher BK, Baker RS, Lang U, Tseng CY, Clark KE, 1993).

Toddlers

According to Linda. L.L. Lagrasse et al (2012), their study found that developmental

changes in children exposed to MA at more externalizing ages as well as ADHD problems at 5

years but not at 3 years however internalizing behaviors and syndrome scores for withdrawal

behavior and somatic complaints were found to increase from 3 years to 5 which may be

unrelated to MA because it is consistent with normal development trajectories but both ages are

characterized by higher emotional reactivity and anxiety and depression problems than compared

age groups.

Toddlers of Opiate-Addicted mothers have been found to be highly energetic, talkative,

and easily distracted with brief attention spans. Their goal directedness has been found to be

brief (Bauman P. S., Levine S. A., 1986). It has been suggested by some studies that these

toddlers may have immature object manipulation, especially with regard to fine motor skills,

cognitive, speech and perceptual disturbances and sleep disturbances. These characteristics may
RISK OF DEVELOPMENTAL DELAYS 10

put these children at high risk for child abuse because their mothers may become frustrated with

what they perceive as negative attributes.

Preschool

According to Bauman and Levine (1986), the children of methadone maintained mothers

have increased incidences of adverse behaviors such as yelling, whining, and physical abuse of

their children in comparison to children of non-addicted mothers. These attributes may be due to

drug addicted mothers’ tendency to yell, command and disapproval of their children. Ramon et al

also suggested that these children showed lower intelligence quotient scores than children of

non-addicted mothers based on the Stanford-Binet intelligence scale. This may be due to the

children not receiving adequate intellectual stimulation at home because the mothers themselves

may have low average intelligence scores. Furthermore, these children may have lower levels of

learning and adapting to new situations at home. Bauman and Levine suggested that there may

be an intergenerational cycle of addiction.

Speech and Language

Due to research still being in its early stages pertaining to the long-term

developmental effects of neonatal abstinence syndrome, research for language development had

to be more so directed at teratogen exposure, in particular, cocaine exposure in utero. The major

difference being evident in the fact that neonatal abstinence syndrome is characterized by

withdrawals and the only research available deals with exposure alone. Although more research

is available with a focus on prenatal cocaine exposure and future language deficits, studies have

found mixed results. Studies have looked to see the effects of cocaine exposure on the

monoaminergic neurotransmitter systems with emphasis on dopamine levels. According to

Bandstra, Morrow, Accornero, Mansoor, Xue, and Anthony (2011), “The effect of prenatal
RISK OF DEVELOPMENTAL DELAYS 11

cocaine exposure(PCE) on the arousal and attention regulating systems of the brain may be

associated with poorer auditory discrimination, language-based attention processing, and

memory” (p. 25). In order to truly understand the effects of gestational cocaine exposure,

research must be conducted and analyzed.

In continuation, links have been drawn to prenatal cocaine exposure and language

deficits. As pointed out by Bandstara et al. (2011) they found that infants exposed to higher

doses of cocaine compared to lighter doses or non-exposure, presented with lower auditory

comprehension and lower total language scores on the Preschool Language Scale-3 (p. 25-26).

Although, there has not been consensus concerning this research. Betancourt, Yang, Brodsky,

Gallagher, Malmud, Gianeetta, Farah, and Hurt (2011) contributed that, “Our group found no

gestational cocaine exposure (GCE) effects on language functioning assessed using the

Preschool Language scale at age 2.5 years and the Battelle Developmental Inventory

Communication Subscale at ages 3 and 5 years” (p. 2). Much of the research that has been

conducted has been primarily interested on the deficits observed in infant, preschool, and early

school aged children without observing the more long-term effects of pre-adolescents and

adolescent children.

To elaborate, Bandstra et al. (2011) pointed out, “Only a few studies, including our own,

have evaluated language abilities in school-aged or preadolescent children” (p.26). In their study,

The Miami Prenatal Cocaine study, they looked to determine the effect of cocaine exposure in

utero on language development in children 3, 5, and 12. Included in the sample were a total of

451 children in which 242 were cocaine exposed and 209 who were not exposed in utero. Of

particular interest were areas of expressive, receptive, and total language measures where

measures evaluated word structure, ability to formulate sentences, ability to recall sentences,
RISK OF DEVELOPMENTAL DELAYS 12

sentence assembly, word association, semantic relationships, and ability to listen and discern

paragraphs (Bandstra et al., 2011, p. 27). Results of the Bandstra et. al (2011) study indicated

that for receptive, expressive, and total language, “…analyses did not indicate a deficit in the

developmental trajectory of receptive language over time” and later went on to conclude, “…the

observed PCE-related difference between prenatally cocaine exposed and non-cocaine exposed

children in language function from early childhood into early adolescence is approximately 3

standard units in total and expressive language scores” (p.32-35). This identifies that with

expressive and total language measures, there has been observed developmental delays in

language for 3, 5, and 12-year-old children compared to their non-exposed peers. Another study

was conducted by Betancourt et al. in which a similar population of urban, African-American

women of low SES and their children were observed. The sample included 120 participants, of

which, 60 were exposed to cocaine in utero and 60 who were not. The children were then

observed at 12, 14.5, and 17 years of age. The study looked to observe measures in inhibitory

control, working memory, receptive language, and incidental memory. According to the study

conducted by Betancourt et al. (2011) pertaining to inhibitory control, working memory, and

receptive language tasks, “The targeted study design revealed little evidence of latent effects of

GCE in this sample of low SES adolescents” (p. 9). Although the studies did not find repeating

results for their research, both of the studies mentioned in this section state subtle deficits

attributed to prenatal cocaine exposure have potential for negative outcomes in the future,

according to Bandstra et al. (2011), “Research suggests that there is strong continuity between

early language delay in children and later reading and literacy difficulties” (p. 31). Betancourt et

al. (2011) backed this view as well, making the statement, “There is accumulating evidence for
RISK OF DEVELOPMENTAL DELAYS 13

the existence of subtle effects of GCE and their impact on the individual and society may be

significant” (p. 11).

Analysis

When examining the effect of NAS on child development, studies showed mixed results.

Studies showed that it is likely that NAS can lead to developmental delays but NAS cannot be

assumed as the only factor (as of research now). Factors such as socioeconomic status,

environment, as well as genetics can affect child development. Overall, there is a great need for

further research into the question of whether there is a connection between NAS and

developmental delays.

Conclusion

Educating pregnant women about the effects of potentially harmful drugs during

pregnancy is a key in preventing NAS. With further research, we would be able to teach mothers

about the possibility of developmental delays in their children. By reducing the prevalence of

prenatal drug use, infants could be spared from a life of difficulty.

RISK OF DEVELOPMENTAL DELAYS 14

References

Bandstra, E. S., Morrow, C. E., Accornero, V. H., Mansoor, E., Xue, L., & Anthony, J. C.

(2011). Estimated effects of in utero cocaine exposure on language development through

early adolescence. Neurotoxicology and Teratology, 33 (1). Retrieved from

http://www.sciencedirect.com/science/article/pii/S0892036210001406

Betancourt, L. M., Yang, W., Brodsky, N. L., Gallagher, P. R., Malmud, E. K., Gianetta, J. M.,

Farah, M. J., & Hurt, H. (2011). Adolescents with and without gestational cocaine

exposure: longitudinal analysis of inhibitory control, memory and receptive language.

NIH Public Access, 33 (1). Retrieved from

http://www.sciencedirect.com/science/article/pii/S0892036210001613

Bauman P. S., Levine S. A., The development of children of drug addicts. Int J Addict. 1986

Aug;21(8):849–863

Bongers I. L., Koot H. M., van der Ende J, Verhulst F. C. (2003) The normative development of

child and adolescent problem behavior. J Abnorm Psychol. 112(2):179–

192pmid:12784827

Early Childhood Physical Development: Gross and Fine Motor Development. (n.d). Retrieved

March 3, 2017, from http://gracepointwellness.org/462-child-development-parenting-

early-3-7/article/12755 early-childhood-physical-development-gross-and-fine-motor-

development

Finnegan P. (1984). Effects of maternal opiate abuse on the newborn. Symposium, Drug Toxicity

in the Newborn

Hunt, R. W., Tzioumi, D., Collins, E., &Jeffery, H.E. (2008). Adverse neurodevelopmental
RISK OF DEVELOPMENTAL DELAYS 15

outcome of infants exposed to opiate in-utero. Early Human Development, 84(1), 29-35.

doi:10.1016/j.earlhumdev.2007.01.013

Hutchings D. E. (1982). Methadone and heroin during pregnancy: a review of behavioral effects

in human and animal offspring. Neurobehav Toxicol Teratol 4(4):429–434. [PubMed]

Ko, J. Y., Patrick, S. W., Tong, V. T., Patel, R., Lind, J. N., & Barfield, W. D. (2016). Incidence

of Neonatal Abstinence Syndrome — 28 States, 1999–2013. MMWR. Morbidity and

Mortality Weekly Report, 65(31), 799-802. doi:10.15585/mmwr.mm6531a2

LaGasse, L. L., Derauf, C., Smith, L. M., Newman, E., Shah, R., Neal, C., & ... Lester, B. M.

(2012). Prenatal Methamphetamine Exposure and Childhood Behavior Problems at 3 and

5 Years of Age. Pediatrics, 129(4), 681-688. doi:10.1542/peds.2011-2209

Logan, B. A., Brown, M. S., & Hayes, M. J. (2013). Neonatal Abstinence Syndrome. Clinical

Obstetrics and Gynecology, 56(1), 186-192. doi:10.1097/grf.0b013e31827feea4

Mayes LC. A behavioral teratogenic model of the impact of prenatal cocaine exposure on arousal

regulatory systems. Neurotoxicol Teratol. 2002;24(3):385–395pmid:12009493

Nygaar, E., Moe, V., Slinning, K., Walhovd, K. B. (2015). Longitudinal cognitive development

of children born to mothers with opioid and polysubstance abuse. Pediatric research,

78, 330-335.

Ross, E. J., Graham, D. L., Money, K. M., Stanwood, G. D. (2014). Developmental

consequences of fetal exposure to drugs: what we know and what we still must learn.

Neuropsychopharmacology, 1-21
RISK OF DEVELOPMENTAL DELAYS 16

Stek AM, Fisher BK, Baker RS, Lang U, Tseng CY, Clark KE. Maternal and fetal cardiovascular

responses to methamphetamine in the pregnant sheep. Am J Obstet Gynecol.

1993;169(4):888–897pmid:8238145

Substance Abuse and Mental Health Services Administration. Treatment Episode Data Set

(TEDS). 1999 - 2009. National Admissions to Substance Abuse Treatment Services,

DASIS Series: S-56, HHS Publication No. (SMA) 11-4646. Rockville, MD: Substance

Abuse and Mental Health Services Administration; 2011

Tolia, V. N., Patrick, S. W., Bennett, M. M., Murthy, K., Sousa, J., Smith, P., Spitzer, A. R.

(2016). Increasing Incidence of the Neonatal Abstinence Syndrome in US Neonatal

ICUs. Obstetric Anesthesia Digest, 36(1). doi:10.1097/01.aoa.0000479516.96285.5d

United National Office on Drugs and Crime. World Drug Report, Analysis. Vol. 1. Vienna,
Austria: United Nations Publication; 2004

Wilson GS, Desmond MM, Verniaud WM. Early development of infants of heroin-addicted
mothers. Am J Dis Child. 1973 Oct;126(4):457–462.