Cocaine-exposed Infants Research Articles

Use of fast-scan cyclic voltammetry to assess phasic dopamine release in rat models of early postpartum maternal behavior and neglect.

Maternal behavior (MB) is a complex response to infant cues, orchestrated by postpartum neurophysiology. Although mesolimbic dopamine contributes toward MB, little is known about real-time dopamine fluctuations during the postpartum period. Thus, we used fast-scan cyclic voltammetry to measure individual dopamine transients in the nucleus accumbens of early postpartum rats and compared them with dopamine transients in virgins and in postpartum females exposed to cocaine during pregnancy, which is known to disrupt MB. We hypothesized that dopamine transients are normally enhanced postpartum and support MB. In anesthetized rats, electrically evoked dopamine release was larger and clearance was faster in postpartum females than in virgins and gestational cocaine exposure blocked the change in clearance. In awake rats, control mothers showed more dopamine transients than cocaine-exposed mothers during MB. Salient pup-produced stimuli may contribute toward differences in maternal phasic dopamine by evoking dopamine transients; supporting the feasibility of this hypothesis, urine composition (glucose, ketones, and leukocytes) differed between unexposed and cocaine-exposed infants. These data, resulting from the novel application of fast-scan cyclic voltammetry to models of MB, support the hypothesis that phasic dopamine signaling is enhanced postpartum. Future studies with additional controls can delineate which aspects of gestational cocaine reduce dopamine clearance and transient frequency.

Prenatal cocaine exposure and child outcomes: a conference report based on a prospective study from Cleveland.

The study aims to describe developmental outcomes from a longitudinal prospective cohort (Cleveland study) of prenatally cocaine-exposed (CE) infants. Two hundred eighteen CE and 197 nonexposed infants were enrolled at birth and followed through mid-adolescence. Birth CE status was determined by interview and biologic measures. Multiple demographic, drug, and environmental correlates were controlled. Standardized, normative, reliable measures of fetal growth, intelligence quotient (IQ), behavior, executive function, and language were given at each age and risk for substance misuse assessed in adolescence. A subset of children received volumetric magnetic resonance imaging (MRI) at 7 years and functional MRI at 14 years. The effect of CE was determined through multiple regression analyses controlling for confounders. Cocaine exposed had significant negative effects on fetal growth, attention, executive function, language, and behavior, while overall IQ was not affected. CE had significant negative effects on perceptual reasoning IQ and visual-motor skills and predicted lower volume of corpus callosum and decreased gray matter in the occipital and parietal lobes. CE children had higher risk for substance misuse. Confounding risk factors had additive effects on developmental outcomes. Prenatal exposure to cocaine was related to poorer perceptual organization IQ, visual-spatial information processing, attention, language, executive function, and behavior regulation through early adolescence.

Effects of prenatal substance exposure on infant temperament vary by context.

This was a prospective longitudinal multisite study of the effects of prenatal cocaine and/or opiate exposure on temperament in 4-month-olds of the Maternal Lifestyle Study (N = 958: 366 cocaine exposed, 37 opiate exposed, 33 exposed to both drugs, 522 matched comparison). The study evaluated positivity and negativity during The Behavior Assessment of Infant Temperament (Garcia Coll et al., 1988). Parents rated temperament (Infant Behavior Questionnaire; Rothbart, 1981). Cocaine-exposed infants showed less positivity overall, mainly during activity and threshold items, more negativity during sociability items, and less negativity during irritability and threshold items. Latent profile analysis indicated individual temperament patterns were best described by three groups: low/moderate overall reactivity, high social negative reactivity, and high nonsocial negative reactivity. Infants with heavy cocaine exposure were more likely in high social negative reactivity profile, were less negative during threshold items, and required longer soothing intervention. Cocaine- and opiate-exposed infants scored lower on Infant Behavior Questionnaire smiling and laughter and duration of orienting scales. Opiate-exposed infants were rated as less respondent to soothing. By including a multitask measure of temperament we were able to show context-specific behavioral dysregulation in prenatally cocaine-exposed infants. The findings indicate flatter temperament may be specific to nonsocial contexts, whereas social interactions may be more distressing for cocaine-exposed infants.

Reactivity and regulation of motor responses in cocaine-exposed infants

Effects of prenatal exposure to cocaine on the reactivity and regulation of the motor system of 825 four-month-old infants enrolled in the Maternal Lifestyle Study were examined. Videotaped assessments of 338 cocaine-exposed (CE) infants and 487 non-exposed comparison infants were coded by examiners masked to exposure status. Exposure status was determined by meconium assay and maternal self-report of prenatal cocaine use. Infants were presented with a series of 17 visual, auditory and tactile stimuli for 30-s each. Intensity and latency of limb movement responses on a subset of items were analyzed to test the following hypotheses: CE infants are more active in general; CE infants exhibit increased movement levels for a larger proportion of time in response to stimulation; the motor systems of CE infants are more reactive to stimulation (e.g., shorter latencies to respond); and CE infants are poorer regulators of the motor system. ResultsCE infants were not more active in general and data do not indicate a more highly reactive motor system. However, CE infants exhibited increased movement levels for a larger proportion of time in response to stimulation. Additional analysis of movement exhibited during three tactile items found increased movement lability in CE infants and different patterns of responding, suggesting that the effects of prenatal cocaine exposure on the motor system may vary by context. Covariate effects for tobacco, alcohol, and marijuana are also reported.

Brain Structural Alterations Induced by Fetal Exposure to Cocaine Persist Into Adolescence and Affect Behavior

Thirty years ago, an epidemic of crack cocaine abuse swept the country and had particularly devastating effects on poor individuals andminorities.Thisheavily addictive formof smokedcocaineensnaredmanyyoungwomenwhobecamepregnant.At the time, several clinical reports from small cohorts of cocaine-exposed infants suggestedsevereadverseneurobehavioraloutcomes, leading to the designation“crackbabies.”Nevertheless, thoughtful clinicians raised concerns about facile inferences that cocaine alone caused this phenotype.1,2 They noted a number of other well-established risk factors for these adverse outcomes that could be difficult to disentangle from exposure to cocaine including concurrent use of tobaccoandalcohol, knownbehavioral teratogens,poorperinatal care, and other adverse consequences of poverty such as poor diet. Cocainecauses its rewardingeffectsby inhibitionofthedopaminetransporter, which activates reward circuits in the forebrain.3 However, it is alsoan inhibitorof thenorepinephrine transporter aswell as the serotonintransporter, therebypotentiatingtheeffectsof theseother 2neurotransmitters. These “biogenic amine”neurotransmitter systems, the cell bodies of which are located in the midbrainbrainstem and compose the reticular core, are among the earliest neural systemstodevelop in thebrain.4Preclinical researchhasdemonstrated that during fetal brain development they play important roles inmodulatingneurogenesis, neuronalmigration, neuronal differentiation,andsynaptogenesis.5Thus, it isnotsurprising thatstudies in fetal rodents have demonstrated that cocaine causes a persistentdisruption indopaminesignaling,corticalGABAergic function, and pyramidal neuron dendritic structure in the prefrontal cortex, a dopamine-rich region.6 Other studies have shown that inhibition of serotonin transport in the fetal braindisrupts the formationof the so-called barrel fields in the rodent primary sensory cortex, a cortiJAMAPEDIATRICS

Profiles of reactivity in cocaine-exposed children

This study explored the possibility that specific, theoretically consistent profiles of reactivity could be identified in a sample of cocaine-exposed infants and whether these profiles were associated with a range of infant and/or maternal characteristics. Cluster analysis was used to identify distinct groups of infants based on physiological, behavioral and maternal reported measures of reactivity. Five replicable clusters were identified which corresponded to 1) Dysregulated/High Maternal Report Reactors, 2) Low Behavioral Reactors, 3) High Reactors, 4) Optimal Reactors and 5) Dysregulated/Low Maternal Report Reactors. These clusters were associated with differences in prenatal cocaine exposure status, birthweight, maternal depressive symptoms, and maternal negative affect during mother-infant interactions. These results support the presence of distinct reactivity profiles among high risk infants recruited on the basis of prenatal cocaine exposure and demographically similar control group infants not exposed to cocaine.

Prenatal cocaine exposure and small-for-gestational-age status: Effects on growth at 6 years of age

Objective To evaluate the impact of prenatal cocaine exposure and small-for-gestational-age (SGA) status on childhood growth. Study design Cocaine exposure was defined by history or meconium metabolites. Hierarchical linear modeling was used to examine cocaine exposure and SGA status on growth, while controlling for exposure to other drugs and alcohol use. Results At birth cocaine-exposed infants (n = 364) had significantly lower growth parameters compared to non-exposed children (n = 771). At 6 years, weight was similar between exposed and unexposed children. SGA infants continued to be growth impaired. There was a significant interaction between prenatal cocaine exposure and SGA status at 6 years. The negative effects of cocaine on weight and height were greater among non-SGA than SGA children (432 vs. 280 gm, and 0.7 and 0.5 cm, respectively) while negative effects of SGA status on weight and height were larger in non-cocaine exposed compared to the exposed children (2.3 kg vs.1.6 kg and 2.2 and 1.0 cm). Conclusions Children exposed to prenatal cocaine were similar in weight to non-exposed children at 6 years of age. Cocaine had an unexplained greater detrimental effect on non-SGA than SGA children. SGA status at birth has an independent detrimental effect on childhood growth.

Prenatal Cocaine Exposure and Prolonged Focus Attention

In experimental models, prenatal cocaine exposure has been found to perturb monoaminergic development of systems implicated in modulating attention. To determine whether prenatal cocaine exposure affects infant attention, we assessed visual recognition memory and focused attention during free play. We enrolled at birth 380 infants, 113 cocaine exposed, using multiple biomarkers to assess drug exposure. Behavior was videotaped and coded off-line for sustained looking time (i.e. focused attention), banging and intrusion. Prenatal cocaine exposure was not associated with visual recognition memory, but was significantly associated with longer sustained looking times (average focused attention) at ages 6 months (p = 0.02) and 12 months (p = 0.04) in analyses that adjusted for variables, including maternal intelligence, education, depressive scores and other exposures (alcohol, tobacco and marijuana). Cocaine-exposed infants at age 12 months also spent significantly less time in banging activity (p = 0.02) after adjusting for confounding variables. This finding was not explained through cocaine effects on motor development, neurological findings or time spent in focused attention. Prenatal cocaine exposure was significantly associated with longer periods of sustained looking or focused attention in infancy, a finding that could interpreted as a measure of poor processing efficiency, or alternatively as precocious maturation of attentional systems. Either interpretation has implications for later cognitive development. Lower banging activity among cocaine exposed was not explained through cocaine effects on motor development or neurological findings, suggesting that activity level itself is diminished in these infants. Whether focused attention findings impact long term development awaits further study.

Prenatal cocaine exposure and infant cortisol reactivity.

This study examined the effects of prenatal cocaine exposure on infant hypothalamic-pituitary-adrenal axis activity and reactivity at 7 months of infant age. Participants were 168 caregiver-infant dyads (87 cocaine exposed, 81 not cocaine exposed; 47% boys). Maternal behavior, caregiving instability, and infant growth and behavior were assessed, and children's saliva was sampled before, during, and after standardized procedures designed to elicit emotional arousal. Results revealed cocaine-exposed infants had a high amplitude trajectory of cortisol reactivity compared to non-cocaine-exposed infants. Infant gender and caregiving instability moderated this association. The findings support a dual hazard vulnerability model and have implications for evolutionary-developmental theories of individual differences in biological sensitivity to context.

A Longitudinal Examination of Physiological Regulation in Cocaine-Exposed Infants Across the First 7 Months of Life.

This study examined the association between prenatal exposure to cocaine and physiological regulation across the first 7 months of age. Measures of respiratory sinus arrhythmia (RSA) were obtained from 169 (82 cocaine-exposed and 87 nonexposed) infants during baseline periods at 1 month and 7 months of age and during tasks designed to elicit positive and negative affect at 7 months of age. After controlling for maternal age, gestational age, and obstetrical risk, structural equation modeling indicated that the association between prenatal exposure to cocaine and baseline RSA at 7 months of age was direct even in the presence of an indirect effect through baseline RSA at 1 month of age. There were no indirect effects through maternal affect during mother-infant interactions assessed at 1 month of age. Analyses also indicated a direct association between prenatal exposure to cocaine and RSA regulation to negative affect at 7 months of age.

Cocaine-exposed infant behavior during Still-Face: Risk factor analyses.

Prenatal cocaine exposure and the role of gender were evaluated using risk factor analyses to determine whether 6-month-old cocaine-exposed male infants demonstrated greater disruptions in infant-caregiver socioemotional interactions during a Still-Face test. Overall, non-cocaine-exposed infants spent more time looking at toys, compared with cocaine-exposed infants; nonexposed female infants spent more time scanning the environment, compared with nonexposed male infants. When caregiver behavior during the Still-Face was evaluated, differences emerged in amount of time the caregiver spent vocalizing to the infant. She vocalized more to a cocaine-exposed infant compared with a nonexposed one; she reduced vocalizing more during the test if the cocaine-exposed infant was female. An exposure by gender interaction emerged in the amount of change in caregiver vocalizations; however, the overarching hypothesis that male cocaine-exposed infants are at higher risk than nonexposed male, nonexposed female, and cocaine-exposed female infants was not supported. Because this interaction was evident in this cohort at 24 months, future research is needed to determine at what age an interaction begins to emerge in this cohort.

Physiological responses to social and cognitive challenges in 8‐year olds with a history of prenatal cocaine exposure

Cocaine-exposed infants have been found to have altered arousal responses but little is known about such responses in later childhood. Physiological responses to stressors were used to assess the arousal modulation of school-aged, cocaine-exposed children (n = 73) and two contrast groups, socioeconomically-matched controls (n = 58) and children with behavioral disturbance (n = 35). The behaviorally disturbed group had the highest heart rate across conditions but demonstrated a pattern of hyporesponsiveness to the stressors. They had the smallest decrement in skin conductance response at baseline and the least recovery of skin conductance response following exposure to stressors. Cocaine-exposed children demonstrated greater acceleratory responses to the stressors as indexed by their skin conductance level and were intermediate between the socioeconomically-matched controls and children with behavioral disturbance in recovery of skin conductance response following stressors. Altered arousal responses associated with prenatal cocaine exposure persisted into middle childhood but were different from those found in behaviorally disturbed children.

Prenatal cocaine and other substance exposure: effects on infant autonomic regulation at 7 months of age.

This study examined the association between prenatal exposure to cocaine and autonomic regulation at 7 months of age. Heart rate (HR) and respiratory sinus arrhythmia (RSA) were obtained from 154 (79 exposed, and 75 nonexposed) infants during baseline and tasks designed to elicit positive and negative affect. Cocaine-exposed infants had higher HR during the positive affect task. There was a significant suppression of RSA during the negative affect task for nonexposed infants but not for exposed infants. Fetal growth and maternal caregiving behavior did not mediate or moderate this association. These results provide additional support for an association between prenatal cocaine exposure and dysregulation during infancy.

Pre-natal exposures to cocaine and alcohol and physical growth patterns to age 8 years

Two hundred and two primarily African American/Caribbean children (classified by maternal report and infant meconium as 38 heavier, 74 lighter and 89 not cocaine-exposed) were measured repeatedly from birth to age 8 years to assess whether there is an independent effect of pre-natal cocaine exposure on physical growth patterns. Children with fetal alcohol syndrome identifiable at birth were excluded. At birth, cocaine and alcohol exposures were significantly and independently associated with lower weight, length and head circumference in cross-sectional multiple regression analyses. The relationship over time of pre-natal exposures to weight, height, and head circumference was then examined by multiple linear regression using mixed linear models including covariates: child's gestational age, gender, ethnicity, age at assessment, current caregiver, birth mother's use of alcohol, marijuana and tobacco during the pregnancy and pre-pregnancy weight (for child's weight) and height (for child's height and head circumference). The cocaine effects did not persist beyond infancy in piecewise linear mixed models, but a significant and independent negative effect of pre-natal alcohol exposure persisted for weight, height, and head circumference. Catch-up growth in cocaine-exposed infants occurred primarily by 6 months of age for all growth parameters, with some small fluctuations in growth rates in the preschool age range but no detectable differences between heavier versus unexposed nor lighter versus unexposed thereafter.

Autonomic Alterations in Cocaine-Exposed Neonates Following Orthostatic Stress

We investigated the effects of prenatal cocaine exposure (PCE) on heart rate (HR) and heart rate variability (HRV) in the presence of orthostatic stress among near- and full-term neonates. PCE infants (n = 21) and controls (n = 23) were enrolled within 120 h of birth. ECG was recorded for an hour during quiet sleep, 30 min in supine position and then 30 min in an inclined position. Linear mixed models were used to analyze HR and HRV in the time domain and wavelet and power spectrum analyses in the frequency domain. PCE infants had tachycardia both before (p = 0.091) and after tilting (p = 0.015), but with a clear interaction between PCE and orthostatic stress (p = 0.049). Compared with controls, PCE infants had a delayed and prolonged reaction to orthostatic stress. There was also a pronounced interaction with regard to log-transformed SDDRR, a measure of HRV (p = 0.049). Controls experienced an instantaneous increase in log (SDDRR) followed by a prompt return to normal levels, while PCE infants had a gradual increase that did not dissipate quickly. Frequency-domain analyses also distinguished between the cocaine-exposed infants and the controls. Results suggest that the effects of PCE on the development of sympathetic and parasympathetic systems could lead to altered cardiovascular function.

Prenatal cocaine use and maternal depression: Effects on infant neurobehavior

Objective The present study examined the impact of both perinatal maternal depression and cocaine use on infant neurobehavior at 1 month of age in a large, multi-site study. Methods Infant neurobehavior was examined in 1053 infants at 1 month of age using the NICU Network Neurobehavioral Scale (NNNS). Mothers were interviewed using The Addiction Severity Index to determine present and past psychiatric history. Four groups were derived from the total sample: 385 prenatally cocaine-exposed infants, 76 whose mothers reported current postpartum depression (DEP/COC) and 309 without current postpartum depression (nonDEP/COC); 668 infants were not exposed to cocaine, 104 whose mothers reported current postpartum depression (DEP/nonCOC), 564 without current postpartum depression (nonDEP/nonCOC). A 2 × 2 Analysis of Covariance was used with covariates (birthweight, maternal age, SES, nicotine, alcohol, and research site) to examine infant neurobehavior in these four conditions. Secondary analyses were conducted to examine the effects of amount and timing of prenatal cocaine exposure. Results DEP group by COC exposure status interactions were significant; there was only a DEP effect in the nonCOC infants. Infants in the nonCOC/DEP group had poorer self-regulation and more stress signs, excitability, and arousal than infants in the other groups. Conclusions Postpartum maternal depression has negative effects on infant neurobehavior at 1 month of age. Prenatal cocaine exposure may serve to suppress or buffer the effects of postpartum depression on infant neurobehavior. Maternal mood could explain some of the inconsistencies found in the prenatal cocaine exposure literature.

Prenatal Cocaine Exposure and Child Welfare Outcomes

This study examines the relationship between prenatal cocaine exposure and child welfare outcomes. Seventy-six infants positive for cocaine at birth were matched to 76 negative infants. With prenatal care and maternal use of alcohol and tobacco controlled, cocaine-exposed infants had significant decrements in birth weight, length, head circumference, and depressed 5-min Apgar scores. This confirmed the health risk of prenatal cocaine exposure for the sample. Three-year follow-up data were obtained from the State Central Register and foster care records. Adjusting for prior maternal involvement with child welfare services the study groups did not differ in incidents of child maltreatment or foster care placement. These findings suggest that prenatal cocaine exposure is not a marker for abusive parenting. However, from the perspective of a cumulative risk model, the identification of cocaine-exposed infants at birth can form the starting point for the development of appropriate diagnostic and follow-up services for mother and child.

Maternal cocaine use and caregiving status: Group differences in caregiver and infant risk variables

This study examined differences between cocaine and non-cocaine-using mothers, and between parental and non-parental caregivers of cocaine-exposed infants on caregiver childhood trauma, psychiatric symptoms, demographic, and perinatal risks. Participants included 115 cocaine and 105 non-cocaine mother–infant dyads recruited at delivery. Approximately 19% of cocaine mothers lost custody of their infants by 1 month of infant age compared to 0.02% of non-cocaine mothers. Mothers who used cocaine during pregnancy had higher demographic and obstetric risks. Their infants had higher perinatal risks. Birth mothers who retained custody of their infants had higher demographic risks and perinatal risks, higher childhood trauma, and higher psychiatric symptoms compared to birth mothers who did not use cocaine and non-parental caregivers of cocaine-exposed infants. Results highlight the importance of addressing childhood trauma issues and current psychiatric symptoms in substance abuse treatment with women who engaged in substance use during pregnancy.

Prenatal cocaine exposure and infant sleep at 7 months of age: The influence of the caregiving environment

The primary goal of this study was to examine sleep problems in a sample of cocaine-exposed 7-month-old infants and to determine if maternal psychopathology mediated any existing association between substance exposure and sleep behaviors. We also examined the differences in sleep behaviors of cocaine-exposed infants in parental custody and cocaine-exposed infants in nonparental custody. Participants were 65 cocaine-exposed and 53 nonexposed infants and their primary caregivers who were recruited at delivery and assessed at 7 months of infant age. As expected, women who used cocaine during pregnancy had more psychiatric symptoms than nonusers. Prenatal exposure to heavier amounts of cocaine was significantly related to more severe sleep difficulties, and maternal anxiety mediated this association. Approximately 28% of cocaine mothers lost custody of their infants by 7 months of age. Nonmaternal caregivers had significantly fewer symptoms of psychopathology than the cocaine-using women who retained custody of their children. Infants who were in nonparental care at 7 months of age also had less severe sleep problems than did infants who remained in parental care.

Acute Neonatal Effects of Cocaine Exposure During Pregnancy

To identify associations between cocaine exposure during pregnancy and medical conditions in newborn infants from birth through hospital discharge. Multisite, prospective, randomized study. Brown University, University of Miami, University of Tennessee (Memphis), and Wayne State University. Subjects A total of 717 cocaine-exposed infants and 7442 nonexposed infants. Results of physical examination and conditions observed during hospitalization. Cocaine-exposed infants were about 1.2 weeks younger, weighed 536 g less, measured 2.6 cm shorter, and had head circumference 1.5 cm smaller than nonexposed infants (all P<.001). Results did not confirm previously reported abnormalities. Central and autonomic nervous system symptoms were more frequent in the exposed group: jittery/tremors (adjusted odds ratio, 2.17; 99% confidence interval, 1.44-3.29), high-pitched cry (2.44; 1.06-5.66), irritability (1.81; 1.18-2.80), excessive suck (3.58; 1.63-7.88), hyperalertness (7.78; 1.72-35.06), and autonomic instability (2.64; 1.17-5.95). No differences were detected in organ systems by ultrasound examination. Exposed infants had more infections (3.09; 1.76-5.45), including hepatitis (13.46; 7.46-24.29), syphilis (8.84; 3.74-20.88), and human immunodeficiency virus exposure (12.37; 2.20-69.51); were less often breastfed (0.26; 0.15-0.44); had more child protective services referrals (48.92; 28.77-83.20); and were more often not living with their biological mother (18.70; 10.53-33.20). Central and autonomic nervous system symptoms were more frequent in the exposed cohort and persisted in an adjusted analysis. They were usually transient and may be a true cocaine effect. Abnormal anatomic outcomes previously reported were not confirmed. Increased infections, particularly sexually transmitted diseases, pose a serious public health challenge. Exposure increased involvement of child protective services and out-of-home placement.