Level Of Prenatal Cocaine Exposure Research Articles

Neurobehavioral and Developmental Traiectories Associated with Level of Prenatal Cocaine Exposure.

In experimental models, prenatal cocaine exposure has been found to perturb GABA and dopamine development. Clinically, abnormalities in tone, posture and state regulation are noted in early infancy but the evolution of these findings over time is not well described. The current study assesses the longitudinal effects of prenatal cocaine exposure in dose-dependent fashion on developmental & behavioral and neurological trajectories over the first 2 years of life. Three hundred and eighty infants, 113 cocaine-exposed, were enrolled at birth from an urban hospital from 2000 to 2004. Exposure was determined by maternal interview, segmental hair analyses (RIAH™) in all, and meconium and urine in a subset. Developmental, behavioral and neurological assessments were carried out blind to drug exposure at 6, 12 and 24 months of age in the 306 children who returned in follow-up. Mixed-effects linear modeling (developmental growth curve) assessed change in outcome over time. The mental developmental growth curve showed a negative slope (2.2 points) in adjusted analyses among cocaine-exposed children over the first 2 years of life. (p=.04), while the slope of the motor development growth curve did not. Adjusting for microcephaly at 6 months diminished the strength of the association between cocaine exposure and mental developmental growth curve (effect modification). Cocaine exposure was marginally associated with behavioral outcomes in adjusted analyses. Total Behavior scores and Orientation/Engagement scores improved with age. At 1 year of age, prenatal cocaine exposure was significantly associated with lower motor development scores. High rates of hypertonia (global and diparesis) identified at the 6-month visit dropped dramatically in the first 2 years of life: cocaine-exposed children showed a more rapid rate of resolution of hypertonia than unexposed children, with hypertonia improving 2.2 times faster among those with heavy cocaine exposure. We found differences in mental performance over the first 2 years of life associated with prenatal cocaine exposure that was mediated by microcephaly implying that cocaine exerts a sustained teratogenic effect on brain development. Early neurological (hypertonia) and behavioral findings associated with prenatal cocaine exposure improved over time. Hypertonia did not predict long-term development impairments. Conceivably, the transient nature of neurobehavioral manifestations reflects postnatally a tendency towards homeostasis of cocaine-related embryopathic perturbations of GABA and dopaminergic systems.

Adolescents with prenatal cocaine exposure show subtle alterations in striatal surface morphology and frontal cortical volumes

BackgroundPublished structural neuroimaging studies of prenatal cocaine exposure (PCE) in humans have yielded somewhat inconsistent results, with several studies reporting no significant differences in brain structure between exposed subjects and controls. Here, we sought to clarify some of these discrepancies by applying methodologies that allow for the detection of subtle alterations in brain structure.MethodsWe applied surface-based anatomical modeling methods to magnetic resonance imaging (MRI) data to examine regional changes in the shape and volume of the caudate and putamen in adolescents with prenatal cocaine exposure (n = 40, including 28 exposed participants and 12 unexposed controls, age range 14 to 16 years). We also sought to determine whether changes in regional brain volumes in frontal and subcortical regions occurred in adolescents with PCE compared to control participants.ResultsThe overall volumes of the caudate and putamen did not significantly differ between PCE participants and controls. However, we found significant (P <0.05, uncorrected) effects of levels of prenatal exposure to cocaine on regional patterns of striatal morphology. Higher levels of prenatal cocaine exposure were associated with expansion of certain striatal subregions and with contraction in others. Volumetric analyses revealed no significant changes in the volume of any subcortical region of interest, but there were subtle group differences in the volumes of some frontal cortical regions, in particular reduced volumes of caudal middle frontal cortices and left lateral orbitofrontal cortex in exposed participants compared to controls.ConclusionsPrenatal cocaine exposure may lead to subtle and regionally specific patterns of regional dysmorphology in the striatum and volumetric changes in the frontal lobes. The localized and bidirectional nature of effects may explain in part the contradictions in the existing literature.

Estimated effects of in utero cocaine exposure on language development through early adolescence

The potential longitudinal effects of prenatal cocaine exposure (PCE) on language functioning were estimated from early childhood through early adolescence in a large, well-retained urban sample of 451 full-term children (242 cocaine-exposed, 209 non-cocaine-exposed) participating in the Miami Prenatal Cocaine Study (MPCS). The sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview, and toxicology assays of maternal and infant urine, and infant meconium. Age-appropriate versions of the Clinical Evaluation of Language Fundamentals (CELF) were used to measure total, expressive, and receptive language at ages 3, 5, and 12 years. Longitudinal latent growth curve (LLGC) modeling of the data revealed an association between PCE (measured dichotomously as yes/no) and lower functioning in expressive and total language scores, after considering other sources of variation including child's age at testing, sex, prenatal exposure to alcohol, marijuana, and tobacco, and additional medical and social-demographic covariates. Analyses of level of PCE showed a gradient, i.e. dose-dependent, relationship between PCE level and expressive, receptive, and total language scores in the models controlling for age, child's sex, and other prenatal drug exposures. With additional covariate control these findings were most stable for the total language score. The evidence supports an inference about an enduring stable cocaine-specific effect on children's language abilities, with no effect on language growth over time in the longitudinal trajectory of language development.

Preadolescent behavior problems after prenatal cocaine exposure: Relationship between teacher and caretaker ratings (Maternal Lifestyle Study)

Background We previously reported an association between prenatal cocaine exposure (PCE) and childhood behavior problems as observed by the parent or caretaker. However, these behavior problems may not manifest in a structured environment, such as a school setting. Objective We determined whether there is an association between PCE and school behavior problems and whether ratings of behavior problems from the teacher differ from those noted by the parent or caretaker. Methods The Maternal Lifestyle Study, a multicenter study, enrolled 1388 children with and without PCE at one month of age for longitudinal assessment. Teachers masked to prenatal drug exposure status completed the Teacher Report Form (TRF/6–18) when children were 7, 9, and 11 years old. We also administered the Child Behavior Checklist-parent report (CBCL) to the parent/caretaker at same ages and then at 13 years. We performed latent growth curve modeling to determine whether high PCE will predict externalizing, internalizing, total behavior, and attention problems at 7 years of age and whether changes in problems' scores over time differ between those exposed and non-exposed from both teacher and parent report. Besides levels of PCE as predictors, we controlled for the following covariates, namely: site, child characteristics (gender and other prenatal drug exposures), family level influences (maternal age, depression and psychological symptomatology, continuing drug use, exposure to domestic violence, home environment, and socioeconomic status), and community level factors (neighborhood and community violence). Results The mean behavior problem T scores from the teacher report were significantly higher than ratings by the parent or caretaker. Latent growth curve modeling revealed a significant relationship between intercepts of problem T scores from teacher and parent ratings; i.e., children that were rated poorly by teachers were also rated poorly by their parent/caretaker or vice versa. After controlling for covariates, we found high PCE to be a significant predictor of higher externalizing behavior problem T scores from both parent and teacher report at 7 years (p = 0.034 and p = 0.021, respectively) in comparison to non-PCE children. These differences in scores from either teacher or caregiver were stable through subsequent years or did not change significantly over time. Boys had higher T scores than girls on internalizing and total problems by caretaker report; they also had significantly higher T scores for internalizing, total, and attention problems by teacher ratings; the difference was marginally significant for externalizing behavior (p = 0.070). Caretaker postnatal use of tobacco, depression, and community violence were significant predictors of all behavior problems rated by parent/caretaker, while lower scores on the home environment predicted all behavior outcomes by the teacher report. Conclusions Children with high PCE are likely to manifest externalizing behavior problems; their behavior problem scores at 7 years from either report of teacher or parent remained higher than scores of non-exposed children on subsequent years. Screening and identification of behavior problems at earlier ages could make possible initiation of intervention, while considering the likely effects of other confounders.

Estimated Risk of Developing Selected DSM-IV Disorders Among 5-Year-Old Children with Prenatal Cocaine Exposure.

This study estimated childhood risk of developing selected DSM-IV Disorders, including Attention-Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), and Separation Anxiety Disorder (SAD), in children with prenatal cocaine exposure (PCE). Children were enrolled prospectively at birth (n=476) with prenatal drug exposures documented by maternal interview, urine and meconium assays. Study participants included 400 African-American children from the birth cohort, 208 cocaine-exposed (CE) and 192 non-cocaine-exposed (NCE) who attended a 5-year follow-up assessment and whose caregiver completed the Computerized Diagnostic Interview Schedule for Children. Under a generalized linear model (logistic link), Fisher's exact methods were used to estimate the CE-associated relative risk (RR) of these disorders. Results indicated a modest but statistically robust elevation of ADHD risk associated with increasing levels of PCE (p<0.05). Binary comparison of CE versus NCE children indicated no CE-associated RR. Estimated cumulative incidence proportions among CE children were 2.9% for ADHD (vs 3.1% NCE); 1.4% for SAD (vs 1.6% NCE); and 4.3% for ODD (vs 6.8% NCE). Findings offer suggestive evidence of increased risk of ADHD (but not ODD or SAD) in relation to an increasing gradient of PCE during gestation.

Level of prenatal cocaine exposure and 48-month IQ: importance of preschool enrichment

Objective This analysis was designed to determine whether prenatal cocaine exposure is related to children's standardized cognitive test scores at age 4 years after control for relevant covariates. Methods Masked examiners using the WPPSI-R assessed ninety-one 4-year-old children with prenatal cocaine exposure and 79 children of comparable demographic background who were not exposed. Level of cocaine exposure was documented by postpartum interviews of mothers and assays of the infants' meconium. Results Prenatal cocaine exposure, analyzed as exposed/unexposed or as an ordinal dose variable, was not associated in bivariate or multivariate models with decrements in full-scale IQ, performance IQ, verbal IQ, or in any of the subtests. In bivariate analyses, we found significant differences between exposure groups defined as “unexposed”, “lighter”, and “heavier” in mean scores of the WPPSI-R subtests Object Assembly ( P=0.04) and Picture Completion ( P=0.03). For these scores, children with heavier exposure attained higher scaled scores. Birth mother's education and child's experience with preschool enrichment were both associated with higher verbal IQ scores. Conclusion These findings suggest that prenatal cocaine exposure does not exert negative effects on the cognitive competence of preschool-aged children. Children with a history of prenatal cocaine exposure benefit from preschool programs that have been shown to enhance outcomes for other low-income children.

Expressive and receptive language functioning in preschool children with prenatal cocaine exposure.

To estimate the relationship between severity of prenatal cocaine exposure and expressive and receptive language skills in full-term, African American children at age 3 years. Language was assessed at age 3 using the Clinical Evaluation of Language Fundamentals-Preschool (CELF-P). The sample included 424 children (226 cocaine exposed, 198 non-cocaine exposed) who received preschool language assessments at age 3, drawn from a cohort of 476 children enrolled prospectively at birth. Structural equation modeling was used to regress expressive and receptive language as intercorrelated response variables on level of prenatal cocaine exposure, measured by a latent construct including maternal self-report of cocaine use and maternal/infant urine toxicology assays and infant meconium. Results indicated a.168 SD decrease in expressive language functioning for every unit increase in exposure level (95% CI = -.320, -.015; p =.031) after consideration for fetal growth and gestational age as correlated response variables. Receptive language was more modestly related to prenatal cocaine exposure and was not statistically significant. Results for expressive language remained stable with inclusion of the McCarthy general cognitive index as a response variable (expressive language beta = -.173, 95% CI = -.330, -.016; p =.031), and with adjustment for maternal age and prenatal exposures to alcohol, tobacco, and marijuana (expressive language beta = -.175, 95% CI = -.347, -.003; p =.046). Additional child and caregiver environmental variables assessed at age 3 were also evaluated in varying statistical models with similar results. The evidence from this study supports a gradient relationship between increased level of prenatal cocaine exposure and decreased expressive language functioning in preschool-aged cocaine-exposed children.

Neuropathological consequences of prenatal cocaine exposure in the mouse

We have developed an animal model in Swiss Webster mice to identify mechanisms by which prenatal exposure to cocaine results in persistent alterations in brain structure and function. Clinical data suggests that children who demonstrate the largest impairments in prenatal brain growth, which are positively correlated with the highest level of prenatal cocaine exposure, are more likely to demonstrate selective impairment in postnatal brain growth, as well as postnatal impairments in motor function, attention and language skills. We conducted neuroanatomic studies to identify the postnatal evolution of structural changes in the primary somatosensory (SI) cortex of the developing mouse brain following prenatal exposure to cocaine. Our previous work, and that of others, provides evidence that many of the processes underlying corticogenesis are disrupted by gestational exposure of the developing mouse brain to cocaine, and that from the earliest phases of corticogenesis that there is an imprecision in the development of cortical lamination. We performed morphometric comparisons between the brains of animals prenatally exposed to varying amounts of cocaine with vehicle and malnutrition controls on postnatal (P) days P9 and P50. We found that on P50, but not P9, the relative number of cortical neurons in S1 is significantly less in cocaine exposed animals as compared with controls. The significant decrease in the number of cells in cocaine exposed animals on P50 is evident as a decreased density of cells restricted to the infragranular compartment (layers V and VI). Those changes are not seen in malnourished animals.Taken together our findings support the conclusion that cocaine-induced alterations in SI cortical cytoarchitectonics are in part a consequence of altered postnatal survival of infragranular cortical neurons, which are lost during the interval between P9 and P50. Determining whether a similar process is evident in a subset of humans following in utero cocaine exposure is a high priority for future clinical brain imaging studies, because analogous structural changes could impact the brain function and behavioral repertoire of infants and children following significant prenatal exposures.

Severity of Prenatal Cocaine Exposure and Child Language Functioning Through Age Seven Years: A Longitudinal Latent Growth Curve Analysis

The current study estimates the longitudinal effects of severity of prenatal cocaine exposure on language functioning in an urban sample of full-term African-American children (200 cocaine-exposed, 176 noncocaine-exposed) through age 7 years. The Miami Prenatal Cocaine Study sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview and toxicology assays of maternal and infant urine and infant meconium. Language functioning was measured at ages 3 and 5 years using the Clinical Evaluation of Language Fundamentals–Preschool (CELF-P) and at age 7 years using the Core Language Domain of the NEPSY: A Developmental Neuropsychological Assessment. Longitudinal latent growth curve analyses were used to examine two components of language functioning, a more stable aptitude for language performance and a time-varying trajectory of language development, across the three time points and their relationship to varying levels of prenatal cocaine exposure. Severity of prenatal cocaine exposure was characterized using a latent construct combining maternal self-report of cocaine use during pregnancy by trimesters and maternal and infant bioassays, allowing all available information to be taken into account. The association between severity of exposure and language functioning was examined within a model including factors for fetal growth, gestational age, and IQ as intercorrelated response variables and child's age, gender, and prenatal alcohol, tobacco, and marijuana exposure as covariates. Results indicated that greater severity of prenatal cocaine exposure was associated with greater deficits within the more stable aptitude for language performance (D = −0.071, 95% CI = −0.133, −0.009; p = 0.026). There was no relationship between severity of prenatal cocaine exposure and the time-varying trajectory of language development. The observed cocaine-associated deficit was independent of multiple alternative suspected sources of variation in language performance, including other potential responses to prenatal cocaine exposure, such as child's intellectual functioning, and other birth and postnatal influences, including language stimulation in the home environment.

The Maternal Lifestyle Study (MLS): Effects of prenatal cocaine and/or opiate exposure on auditory brain response at one month

Objective To study absolute and interpeak latencies of the auditory brain response in infants exposed to cocaine and/or opiates in utero. Study design The sample included 477 exposed and 554 comparison infants matched for race, sex, and gestational age. Mothers were recruited at 4 urban university-based centers; most were black, receiving public assistance, and had received adequate prenatal care. Exposure was determined by meconium assay and self-report with alcohol, marijuana, and tobacco present in both groups. At 1 month, infants were tested by masked examiners with the auditory brain response. Results Analyses were conducted for exposed and comparison groups and for level of prenatal cocaine exposure with adjustment for covariates (alcohol, marijuana, tobacco, gestational age at birth, social class, and site). Heavy prenatal cocaine exposure (≥3 days per week, first trimester) led to an increase in the I-III, I-V, and III-V interpeak latencies and to a shorter latency to peak I. Infants with prenatal opiate exposure showed a longer latency to peak V and a longer III-V interpeak latency. Conclusions Prenatal cocaine and/or opiate exposure affects neural transmission. Detection of these effects requires a large sample with control for gestational age, other drugs, and level of cocaine use. (J Pediatr 2003;142:279-85)

Level of prenatal cocaine exposure and infant–caregiver attachment behavior

The objective of this longitudinal prospective cohort study was to determine whether level of prenatal cocaine exposure, or the interaction between level of prenatal cocaine exposure and contextual risk variables, was associated with a higher rate of infant–caregiver insecure attachment and disorganized attachment, or with alterations in infant crying or avoidant behavior, after controlling for prenatal exposure to alcohol, tobacco, and marijuana, the quality of the proximal caregiving environment, and other covariates. Subjects were 154 full-term 12-month-old infants (64 unexposed, 61 with lighter cocaine exposure, 29 with heavier cocaine exposure) and their primary caregivers from low-income, urban backgrounds. Exposure status was determined in the maternity ward by biologic assay (infant meconium and/or maternal or infant urine) and maternal self-report. At the 12-month follow-up visit, infants were videotaped with their primary caregiver in Ainsworth's Strange Situation. Reliable coders masked to exposure status scored videotapes for attachment variables, amount of crying, and level of avoidance. Contrary to popular perceptions, level of prenatal cocaine exposure was not significantly related to secure/insecure attachment status, disorganized attachment status, or rated level of felt security. Foster care status also was not associated with attachment status. However, heavier prenatal cocaine exposure, in interaction with maternal contextual variables (public assistance or multiparity) was associated with alterations in infant socio-affective behavior, including a higher level of behavioral disorganization, more avoidance of the caregiver, and less crying.

Longitudinal investigation of task persistence and sustained attention in children with prenatal cocaine exposure

The present study estimates the longitudinal effects of prenatal cocaine exposure on indicators of sustained attention processing at 3, 5 and 7 years of age in an urban sample of full-term African–American children (235 cocaine-exposed, 207 noncocaine-exposed). The sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview, urine and meconium toxicology assays. Sustained attention was measured at age 3 years using a standardized measure of task persistence during a challenging task [G.A. Morgan, N.A. Busch-Rossnagel, C.A. Maslin-Cole and R.J. Harmon, Individualized Assessment of Mastery Motivation: Manual for 15–36 Month Old Children, 1992.], and at ages 5 and 7 years using omission error scores from computerized continuous performance tasks (CPT) [L. Greenberg, R. Leark, T. Dupuy, C. Corman, C. Kindschi, M. Cenedela, Test of Variables of Attention (T.O.V.A. and T.O.V.A.-A.), 22, Universal Attention Disorders, Los Alamitos, CA, 1996; C.K. Conners, Conners' Continuous Performance Test (CPT), second ed., Multi-Health Systems, Canada, 1995.]. Findings from longitudinal GLM/GEE analyses of the three measured time points support a stable influence of prenatal cocaine exposure on indicators of sustained attention, after controlling for prenatal exposure to alcohol, marijuana, tobacco and over 20 additional medical and social–demographic covariates drawn from potentially confounding influences assessed at birth and later assessment visits ( D=0.21; 95% CI=0.04, 0.38; P=.017). This effect was not mediated by fetal growth or gestational age and remained highly stable with increasing levels of covariate control. Separately, using the age 7 data, a structural equations model (SEM) was constructed combining all available self-report and bioassay data to measure magnitude of cocaine exposure in relationship to attention task performance. Results indicated a gradient of influence, with each standard deviation increase in the level of prenatal cocaine exposure relating to a 16% standard deviation increase in omission error scores at age 7. Overall findings support a stable cocaine-specific effect on indicators of sustained attention processing during the early childhood years. Results are discussed within the context of neurobiological and behavioral research linking prenatal cocaine exposure to long-lasting disruption of the brain systems subserving arousal and attention.

Level of in utero cocaine exposure and neonatal ultrasound findings.

To assess whether there is an association between the level of in utero cocaine exposure and findings on neonatal cranial ultrasound, controlling for potentially confounding variables. In a prospective longitudinal study, three cocaine exposure groups were defined by maternal report and infant meconium assay: unexposed, heavier cocaine exposure (>75th percentile self-reported days of use or of meconium benzoylecogonine concentration) or lighter cocaine exposure (all others). Neonatal ultrasounds from 241 well, term infants were read by a single radiologist who was masked to the exposure group. Infants with lighter cocaine exposure did not differ from the unexposed infants on any ultrasound findings. After controlling for infant gender, gestational age, and birth weight z scores and for maternal parity, blood pressure in labor, ethnicity, and use of cigarettes, alcohol, and marijuana during pregnancy, the more heavily cocaine-exposed infants were more likely than the unexposed infants to show subependymal hemorrhage in the caudothalamic groove (covariate adjusted odds ratio: 3.88; 95% confidence interval: 1.45, 10.35). This is the first study to demonstrate that ultrasound findings suggestive of vascular injury to the neonatal central nervous system are related to the level of prenatal cocaine exposure. Inconsistency in previous research in identifying an association between prenatal cocaine exposure and neonatal cranial ultrasound findings may reflect failure to consider dose effects.

Level of Prenatal Cocaine Exposure, Center Based Intervention, and Weschler Pre and Primary School Intelligence Scores (WPPSI-R) at Four Years of Age

Level of Prenatal Cocaine Exposure, Center Based Intervention, and Weschler Pre and Primary School Intelligence Scores (WPPSI-R) at Four Years of Age

Dose-response effect of fetal cocaine exposure on newborn neurologic function.

Studies of fetal cocaine exposure and newborn neurologic function have obtained conflicting results. Although some studies identify abnormalities, others find no differences between cocaine-exposed and cocaine-unexposed infants. To determine the effects of prenatal cocaine exposure on intrauterine growth and neurologic function in infants, we prospectively evaluated 253 infants shortly after birth. Women who delivered a live singleton >36 weeks by dates were eligible for enrollment. Maternal exclusionary criteria were known parenteral drug use, alcoholism, and acquired immunodeficiency syndrome; infant exclusionary criteria were Apgar scores </=4 at 5 minutes, obvious congenital malformations, seizures, or strokes. A total of 98% of infants were evaluated between 1 to 7 days of age. Newborns were assessed with the Neurological Examination for Children (NEC) by a pediatric neurologist (C.A.C.) who was blinded to exposure status. Gestational age was determined by Ballard's examination. Cocaine exposure was determined for the last trimester by radioimmunoassay of maternal hair (RIAH). Exposure values ranged from 2 to 4457 ng/10 mg hair. Infants were excluded if a maternal hair sample was missing (N = 13). The sample comprises 240 woman and infant pairs-104 cocaine-exposed and 136 cocaine-unexposed. Compared with unexposed controls, cocaine-exposed infants exhibited higher rates of intrauterine growth retardation (24% vs 8%), small head circumference ([HC] <10th% percentile) (20% vs 5%) and neurologic abnormalities: global hypertonia (32% vs 11%), coarse tremor (40% vs 15%), and extensor leg posture (20% vs 4%). We found increasing odds (odds ratio) of growth and neurologic impairment with increasing level of cocaine exposure in stratified analyses. The odds ratio associated with three levels of cocaine exposure (no exposure, low exposure = RIAH 2-66 ng/mg; and high exposure = RIAH 81-4457 ng/mg) respectively are: 1.0, 3.3, and 6.1 for small head size (chi2 for trend); 1.0, 3. 3, and 4.3 for global hypertonia (chi2 for trend); 1.0, 3.4, and 7.4 for extensor leg posturing (chi2 for trend); and 1.0, 3.8, and 3.8 for coarse tremor (chi2 for trend). Significant associations between cocaine exposure and neurologic signs were found in logistic regression equations that controlled for 20 or more variables. We conclude that adverse neonatal effects associated with fetal cocaine exposure follow a dose-response relationship: newborns with higher levels of prenatal cocaine exposure show higher rates of impairments in fetal head growth and abnormalities of muscle tone, movements, and posture. Significant relationships between cocaine exposure and these outcomes remain in controlled analyses.

Arousal modulation in cocaine-exposed infants.

The ability to modulate arousal is a critical skill with wide-ranging implications for development. In this study, the authors examined arousal regulation as a function of levels of prenatal cocaine exposure in 107 infants at 4 months of age using a "still-face" procedure. Facial expressions were coded. A greater percentage of heavily cocaine-exposed infants, compared with those who were unexposed to cocaine, showed less enjoyment during en face play with their mothers and continued to show negative expressions during the resumption of play following a period when the interaction was interrupted. This finding was independent of other substance exposure, neonatal medical condition, environmental risk, maternal contingent responsivity, and concurrent maternal sensitivity and vocalizations.