PEDIATRICS Vol. 113 No. 3 March 2004, pp. 668-675
Summary Statistics of Neonatal Intensive Care Unit Network Neurobehavioral Scale Scores From the Maternal Lifestyle Study: A Quasinormative Sample
Barry M. Lester, PhD*,
Edward Z. Tronick, PhD
,
Linda LaGasse, PhD*,
Ronald Seifer, PhD
,
Charles R. Bauer, MD||,
Seetha Shankaran, MD¶,
Henrietta S. Bada, MD#,
Linda L. Wright, MD**,
Vincent L. Smeriglio, PhD and
Jing Lu, PhD*
* Brown Medical School, Infant Development Center, Women and Infants Hospital and Bradley Hospital, Providence, Rhode Island
Child Development Unit, Children’s Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
Brown Medical School and Bradley Hospital, Providence, Rhode Island
|| University of Miami School of Medicine, Miami, Florida
¶ Wayne State University School of Medicine, Detroit, Michigan
# University of Tennessee at Memphis, School of Medicine, Memphis, Tennessee
** National Institute of Child Health and Human Development, Bethesda, Maryland
National Institute on Drug Abuse, Bethesda, Maryland
 |
ABSTRACT
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Descriptive statistics for the Neonatal Intensive Care Unit
Network Neurobehavioral Scale summary scores are provided based
on data from 1388 1-month-old infants in the Maternal Lifestyle
Study (MLS) of prenatal drug exposure and child outcome. The
multisite MLS is described, followed by tables with descriptive
statistics and percentile for the Neonatal Intensive Care Unit
Network Neurobehavioral Scale summary scores. The tables include
data for the entire MLS sample as well as tables by drug exposure
status, gestational age, poverty status, sex, race and ethnicity,
and MLS study site. These tables can be used as quasinorms for
comparison with other infants of this age.
Key Words: MLS • multisite • NNNS • neurobehavioral • norms • prenatal dry exposure • summary scores
Abbreviations: NNNS, Neonatal Intensive Care Unit Network Neurobehavioral Scale • MLS, Maternal Lifestyle Study • NICHD, National Institute of Child Health and Human Development • MISU, Maternal Interview of Substance Use
The purpose of this article is to provide descriptive statistics for the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) scores from a large, prospective, longitudinal study of prenatal drug exposure and child outcome: the Maternal Lifestyle Study (MLS). The MLS started as an interagency collaborative effort involving the National Institute of Child Health and Human Development (NICHD); the National Institute on Drug Abuse; the Administration on Children, Youth and Families; and the Center for Substance Abuse Treatment. The MLS is the largest clinical, prospective, longitudinal study to date of acute neonatal events and long-term health and developmental outcomes associated with cocaine use during pregnancy. The MLS was developed with the recognition that cocaine use by pregnant women is a marker variable for 2 critical factors that can affect child outcome in addition to prenatal cocaine exposure: use of drugs other than cocaine and an inadequate caregiving environment.1–3 The MLS was designed to address many of the methodologic issues in the field. They include, in addition to polydrug use and the role of the caregiving environment, sample size, methods of drug detection, prematurity, other confounding variables (eg, medical factors, interventions, protective services), and neurodevelopmental assessments such as the NNNS that are sensitive to putative drug effects.
The NNNS was developed for MLS as part of a separate contract (N01-HD-2-3159) from the NICHD and National Institute on Drug Abuse because of concern that existing instruments were not sensitive to the neurobehavioral effects of prenatal drug exposure and infants at risk. The contract supported the development of a neurodevelopmental assessment battery specifically designed to tap hypothesized mechanisms of action of the effects of cocaine on the "four A’s of infant behavior": arousal, attention, affect (including social interaction), and action (motor patterning).3,4
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SAMPLE
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The sample included 1211 infants who were enrolled in the longitudinal
phase of the MLS. The MLS is conducted at 4 NICHD Neonatal Research
Network sites (Brown University, Providence, RI; University
of Miami, Miami, FL; Wayne State University, Detroit, MI; and
the University of Tennessee at Memphis, Memphis, TN). The study
was conducted in 2 phases: acute outcome and longitudinal outcome.
Subjects in the longitudinal phase were drawn from the 11 811
mothers who consented to participate in the acute phase.
5 Maternal
exclusion criteria for the acute phase were age <18 years,
identified psychosis or history of institutionalization for
mental retardation or emotional problems, and language barriers
that prevented her from giving informed consent or understanding
the study. Infant exclusion criteria were outborn birth; multiple
gestation; birth weight <501 g; gestational age >42 weeks;
and if, in the judgment of the attending physician, the infant
was unlikely to survive. Meconium samples were collected in
the nursery and shipped to a central laboratory for analysis
of metabolites of illicit drugs.
6,7 The assay consisted of an
enzyme multiplied immunoassay technique screen for cocaine,
opiates, THC, amphetamines, and PCP followed by gas chromatography/mass
spectroscopy confirmation for presumptive positive screens.
A history of maternal alcohol, marijuana, and nicotine use during
the pregnancy was recorded during a hospital interview with
the mother.
Infants were selected for the longitudinal phase to be in the exposed group or the comparison group. Exposed infants were defined by maternal admission of cocaine or opiate use during the pregnancy based on the hospital interview or positive gas chromatography/mass spectroscopy confirmation of cocaine or opiate metabolites. Comparison infants were defined by maternal denial of cocaine or opiate use during the pregnancy and a negative enzyme multiplied immunoassay technique screen for cocaine and opiate metabolites. Uses of alcohol, marijuana, or tobacco were allowed in the comparison group.
Infants were excluded from the longitudinal phase when they had a chromosomal abnormality or toxoplasmosis, rubella cytomegalovirus, herpes, and syphilis infection or when the mother planned to move out of the catchment area. A list of possible comparison infants from the "unexposed" group within each center that matched an infant in the exposed group on race, sex, and gestational age was sent by the data center to each study site. Mothers on the list were called in sequence to confirm consent for phase II and to schedule the 1-month visit. When an infant in the comparison group did not attend the 1-month visit, another match was generated for each exposed infant until a comparison infant was successfully enrolled or the recruitment period ended. This procedure resulted in 2 groups that were matched on race, sex, and gestational age. The 1388 mother-infant dyads (658 in the exposed group and 730 in the comparison group) that came to the 1-month visit were enrolled in the longitudinal study.
The longitudinal phase began at the infant’s first follow-up visit at 1 month (age corrected for prematurity). Information about the frequency and the quantity of substance use for each trimester during this pregnancy was collected from the Maternal Interview of Substance Use (MISU) administered to the biological mothers only. The MISU was completed by 1255 biological mothers who brought their infants to the 1-month visit within the 2-week time frame.
The NNNS was completed on 1211 of these infants. All infants were examined between 42 and 44 weeks’ postconceptional age by psychometrists certified on the examination and masked as to infant exposure status.
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NNNS SUMMARY SCORES
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Summary scores for the NNNS were developed using an approach
that combined conceptual and statistical (coefficient
) aggregation
of items and scores. The summary scores were first developed
on a random selection of one half of the sample and then "replicated"
on the second half of the sample. The 13 summary scores (see
Appendix 2 later in this issue) described previously in the
volume include habituation, attention, handling, quality of
movement, regulation, nonoptimal reflexes, asymmetric reflexes,
stress/abstinence, arousal, hypertonia, hypotonia, excitability,
and lethargy. A higher score on each scale means a higher level
of the construct. For example, a high score on hypertonia means
that the infant was more hypertonic; a high score on hypotonia
means that the infant was more hypotonic. The
coefficients
for the summary scores based on the 1211 scores from the MLS
data are shown in Table
1.
Medical and Maternal Characteristics
Medical characteristics of the infants are presented in Table
2. Preterm infants (<38 weeks) accounted for 41% (
N = 270)
of the cocaine/opiate-exposed group and 43% (
N = 314) of the
comparison group. The percentages of preterm infants born at
<33 weeks were 10.8% (
N = 71) in the cocaine/opiate-exposed
group and 12.5% (
N = 91) in the comparison group. Demographic
information on the mothers is presented in Table
3. Mothers
in the cocaine/opiate-exposed group were more likely to be older,
not married, on Medicaid and not private insurance, less educated,
and less likely to receive prenatal care than mothers in the
comparison group.
Maternal Drug Use
On the basis of the hospital interview, more mothers in the
exposed group used alcohol during pregnancy (
N = 461; 70.3%)
than in the comparison group (
N = 361; 49.5%). Similarly, more
mothers in the exposed group used tobacco (
N = 535; 81.6%) than
in the comparison group (
N = 211; 28.9%), and more mothers in
the exposed group used marijuana (
N = 253; 38.6%) than in the
comparison group (
N = 71; 9.7%). On the basis of the MISU interview,
Table
4 describes patterns of cocaine use for admitted users.
As expected, cocaine use declined over the 3 trimesters. For
example, the percentage of women who reported daily use decreased
from 17% in the first trimester to 7% in the third trimester
with a corresponding increase in the percentage of women who
were not using from 16% in the first trimester to 33% in the
third trimester.
Tables
5 to
18 show the means, standard deviations, minimum
and maximum scores, and percentiles for the 13 NNNS summary
scale scores. The tables are as follows: Table
5 shows the NNNS
scores for the entire MLS sample.
Table
6 shows the NNNS scores for the exposed and comparison
groups.
Tables
7 to
9 show the scores by gestational age using best obstetrical estimate divided in 3 categories (24–32 weeks, 33–37 weeks, and 
38 weeks).
Table
10 shows the NNNS scores by poverty status (above and
below the federal poverty line).
Table
11 shows the NNNS scores by sex.
Tables
12 to
14 show the NNNS scores by race and ethnicity
(black, white, and Hispanic).
Tables
15 to
18 show the NNNS scores by site (Detroit, Memphis,
Miami, and Providence).
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DISCUSSION
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MLS is the largest prospective study reported to date on the
effects of prenatal cocaine/opiate exposure on neurobehavioral
outcome in early infancy. Results from the MLS on the NNNS showed
that prenatal cocaine exposure was related to lower arousal,
poorer quality of movement and regulation, higher excitability,
more hypertonia, and more nonoptimal reflexes with most effects
remaining after adjustment for covariates.
8 There were also
effects of heavy cocaine exposure and separate effects for opiates,
alcohol, marijuana, tobacco, and birth weight. The NNNS has
also been used in 4 other studies. In 1 study,
9 infants with
cocaine and alcohol exposure were compared with infants with
alcohol exposure alone and those without prenatal drug exposure.
Differences were found between the cocaine/alcohol and alcohol
group as well as between these groups and the unexposed group.
In another study, infants who were treated with diluted tincture
of opium and phenobarbital were more alert and interactive with
their environment, had smoother movements, were physically easier
to handle, and were less stressed during the first 3 weeks than
infants who were treated with diluted tincture of opium alone
(M. Coyle, MD, A. Ferguson, OTR/L, L. LaGasse, PhD, E. Liu,
PhD, and B. Lester, PhD, unpublished data, 2000). Johnson et
al
10 used the NNNS to show that buprenorphine may be more beneficial
than methadone for pregnant, heroin-addicted women by reducing
withdrawal in the infant. Finally, in a study of the effects
of cigarette smoking during pregnancy, tobacco-exposed infants
were more excitable and hypertonic, required more handling,
and showed more stress/abstinence signs.
11 There were also dose-response
relationships: higher levels of maternal salivary cotinine (metabolite
of nicotine) and the number of cigarettes per day that the mother
smoked during pregnancy were related to the number of stress/abstinence
signs on the NNNS.
The advantages of the MLS data set include the large sample size, the use of the meconium assay to detect prenatal drug exposure along with maternal report, the multisite design that allows for geographic diversity, and the inclusion of preterm infants. The values in Tables 5 to 18 can be used to compare with other samples and can serve as quasinorms for the 1-month-old infant.
The limitations of this sample are that the values are not truly norms because the sampling plan was not designed to collect normative data. The data are also limited to 1-month-old infants, and there is no true unexposed group as the comparison group included exposure to alcohol, marijuana, and tobacco. This is best thought of as a sample of infants at varying degrees of biological and/or social risk. The data set provided by Tronick et al (see "Normative Neurobehavioral Performance of Healthy Infants on the Neonatal Intensive Care Unit Network Neurobehavioral Scale" later in this issue) do include healthy newborn infants, and the Tronick study is also collecting data on preterm infants that will provide additional information. Finally, the MLS data are limited to the population studied and may not represent all drug-exposed infants. Most of the pregnant women who use cocaine and most of the subjects in research studies, including ours, are referred to as "recreational users" rather than "hard-core addicts." Even our "heavy users" were rarely daily users, and use at all levels decreased over the 3 trimesters.
Despite these limitations, this is the largest database available as a reference on the neurobehavioral organization of drug-exposed infants and should be useful for researchers and clinicians as we learn more about these infants and develop appropriate treatment programs.
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ACKNOWLEDGMENTS
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This study was supported by the National Institute of Child
Health and Human Development through cooperative agreements
U10 HD 27904 (to B.M.L. and J.L.), U10 HD 21397 (to C.R.B.),
U10 HD 21385 (to S.S.), and U10 HD 27856 (to H.S.B.) and contract
N01-HD-2-3159 (to B.M.L. and J.L) and intra-agency agreements
with the National Institute on Drug Abuse, the Administration
on Children, Youth, and Families, and the Center for Substance
Abuse Treatment.
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FOOTNOTES
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Received for publication Apr 28, 2003; Accepted Oct 8, 2003.
Reprint requests to (B.M.L.) Infant Development Center, Women and Infants Hospital, 79 Plain St, 2nd Fl, Providence, RI 02903. E-mail: barry_lester{at}brown.edu
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REFERENCES
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- Lester BM, LaGasse L, Brunner S. Data base of studies on prenatal cocaine exposure and child outcome. J Drug Issues. 1997;27:487–499
- Lester BM, Tronick EZ, Mayes L, et al. Neurodevelopmental consortium, the NICHD Neonatal research network. A neurodevelopmental follow-up battery for substance exposed infants. Pediatr Res. 1994;35:23A
- Bauer CR, Shankaran S, Bada H, et al. The Maternal Lifestyle Study: drug exposure during pregnancy and short-term maternal outcomes. Am J Obstet Gynecol. 2002;186:487–495[CrossRef][Web of Science][Medline]
- elSohly MA, Stanford DF, Murphy TP, et al. Immunoassay and GC-MS procedures for the analysis of drugs of abuse in meconium. J Anal Toxicol. 1999;23:436–445[Web of Science][Medline]
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PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics
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