children with soft signs were noted to have a birth weight
<1500 g. Of these children (n Z 110), more than two soft
signs were seen in 53% of cocaine-exposed and 27% of non-
cocaine-exposed children (OR 3.0; 95% CI 1.4e6.7), in 71%
of high-alcohol-exposed and 28% no or low-alcohol-exposed
children (OR 6.4; 2.5e16.6) and in 67% of children exposed
to alcohol binging and 36% who were not exposed to binging
(OR 3.6; 1.0e12.8). The effect of cocaine use and alcohol
use on soft neurological signs persisted after controlling
for other substance use, birth weight, site, infant sex
Current research suggests that although there are effects
of cocaine on child development, these effects are in-
consistent and subtle and need to be understood in the
context of polydrug use and the caregiving environment. At
1 month of age, the NICU Network Neurobehavioral Scale
demonstrated that cocaine exposure was related to lower
arousal, poorer quality of movement and self-regulation,
higher excitability, more hypertonia and more non-optimal
reﬂexes, with most effects maintained after adjustment
for covariates. This was also noted in the MLS study, in 658
exposed and 730 comparison infants matched for race, sex
and gestational age.
Some of the effects were associated
with heavy cocaine exposure but effects were also found for
opiates, alcohol, marijuana and birth weight. Acoustic cry
characteristics that reﬂect reactivity, respiratory and neu-
ral control of the cry sound were also compromised by pre-
natal drug exposure, including cocaine, opiates, alcohol and
marijuana; they were also affected by birth weight. Fewer
cry effects remained after adjustment for covariates.
Prenatal cocaine and/or opiate exposure also affects
neural transmission when examined on auditory brain re-
sponse at 1 month of age.
The MLS found that heavy pre-
natal cocaine exposure led to an increase in the IeIII, IeV
and IIIeV interpeak latencies and to a shorter latency to
peak I. Infants with prenatal opiate exposure showed a lon-
ger latency to peak V and a longer IIIeV interpeak latency.
The MLS measured the direct effects of prenatal cocaine
exposure and prenatal opiate exposure on infant mental
motor and behavioral outcomes. Outcomes were evaluated
longitudinally between 1 and 3 years of age.
were evaluated at 1, 2 and 3 years of age by the Bayley
Scales of Infant Development, which were administered to
1227 infants who had been exposed to cocaine (n Z 474),
opiates (n Z 50), cocaine plus opiates (n Z 48) and neither
substance (n Z 655). Overall, mental developmental index
points were 1.6 below in the cocaine-exposed infants
compared with infants who were not exposed to cocaine.
Opiate-exposed infants scored 3.8 psychomotor develop-
mental index points below infants who were not exposed
to opiates. Neither the cocaine nor the opiate effect re-
mained signiﬁcant after controlling for covariates. Neither
the cocaine nor opiate exposure was associated with the
Bayley behavioral record score during the examination.
Low birth weight and indices of non-optimal caregiving
were associated with lower Mental Developmental Index
(MDI), Psychomotor Developmental Index (PDI) and behav-
ioral record scores among all groups of infants.
The MLS has also carried out the largest study to date
evaluating the effect of prenatal cocaine exposure on
childhood behavior problems. A total of 1056 children was
followed using the childhood behavior checklist at ages 3, 5
Longitudinal, hierarchical, linear models were used
to determine the effects of prenatal cocaine exposure on
behavior-problem trajectories while controlling for other
prenatal exposures and for time-varying covariates (includ-
ing ongoing caretaker level of use of legal and illegal
substances, demographic factors, family violence and
caretaker psychological distress). After controlling for
confounders (including other drug use), the internalizing,
externalizing and total behavior-problem scores were
higher for high prenatal cocaine exposure than for some
or no cocaine use during pregnancy. Signiﬁcant effects per-
sisted to age 7 years. Additional factors (including other
drug use) also had signiﬁcant effects on childhood behavior
problems. Prenatal tobacco and alcohol exposure were sig-
niﬁcantly associated with total behavior-problem trajecto-
ries until the age of 7, with a signiﬁcant doseeresponse
relationship, i.e. higher behavior-problem scores were as-
sociated with a greater average number of cigarettes/day
and a greater average volume of alcohol/day. Moreover, on-
going tobacco and alcohol exposure signiﬁcantly affected
externalizing and total behavior problems. Caretaker re-
port of physical or sexual abuse and caretaker depression
were signiﬁcantly associated with all behavior problems.
Mediation analysis revealed that the child’s living situation
was a signiﬁcant mediator for the relationship between pre-
natal cocaine exposure and behavior outcomes.
In another analysis of behavior problems, structural
equation modeling was used to describe developmental
pathways from birth to predict Child Behavior Check List
(CBLL) scores at age 7.
Prenatal drug exposure was related
to poor neurobehavioral scores at 1 month. The children
who showed poor neurobehavioral scores had a more difﬁ-
cult temperament at 4 months. Children with difﬁcult tem-
perament had behavior problems on the CBCL at age 3 and
also at age 7. This model was able to explain 52% of the var-
iance in 7-year CBCL scores (all paths P < 0.05). The study of
developmental pathways might be particularly useful for
identifying ‘touch-points’ for intervention.
When evaluated up to 36 months in MLS, the attachment
status in children exposed prenatally to cocaine and other
substances showed that those children exposed to cocaine
and opiates were more likely to be insecurely attached.
The type of insecurity was more likely to be ambivalent
Continued postnatal alcohol use was asso-
ciated with higher rates of insecurity and disorganization at
18dbut not 36dmonths of age. Stability of attachment
across the 18-month period was barely above chance ex-
pectation. Attachment status at 18 months was associated
with child temperament and caregiver child interaction;
at 36 months attachment was associated with child temper-
ament, child behavioral problems and the caregiver’s par-
enting and self-esteem.
In a longitudinal analysis of the trajectory of mental
development at ages 1, 2, 3, 4.5 and 7 years, the MLS
looked at 1270 subjects. After adjustment for covariates,
the effects of cocaine on IQ were 1.45 points up to age 3;
this increased to 4.4 points between 4.5 and 7 years of
age (P Z 0.003).
In addition, cocaine-exposed children
were more likely (OR Z 1.56; P Z 0.03) to be referred for
special education services in school than unexposed chil-
dren. It was estimated that the additional cost to society
for this cocaine effect alone is US$25,248,384 per year.
Impact of maternal substance use 147