Developmental outcomes and environmental correlates of very low birthweight, cocaine-exposed infants.

Fetal cocaine exposure may have differentially adverse effects on developmental outcomes of very low birthweight (VLBW) infants. As part of a longitudinal study, 31 cocaine-positive very low birthweight infants, and age, race and socioeconomic status matched VLBW controls enrolled at birth were followed. Neonatal maternal-child interactions, concurrent maternal psychological characteristics and environmental factors conceptualized as important for child outcome were assessed as well as standard developmental outcomes at 3 years.In the neonatal period, cocaine-exposed VLBW infants who remained in maternal custody tended to be rated as less responsive and their mothers as less nurturing, less emotionally available and with a tendency to use more maladaptive coping mechanisms than nonexposed VLBW infants. At follow-up, cocaine-exposed VLBW children were delayed in cognitive, motor and language development compared to controls. Almost half (45%) of the exposed children scored in the range of mental retardation compared to 16% of the comparison VLBW children.The persistent cognitive, motor and language delays of the cocaine-exposed VLBW children, combined with the poorer behavioral interactions of cocaine-using women with their infants in the neonatal period, indicate a need for increased developmental surveillance of cocaine-exposed VLBW infants with a focus on maternal drug treatment and parenting interventions.     

Cocaine and development: mechanisms of fetal toxicity and neonatal consequences of prenatal cocaine exposure.

As cocaine use during pregnancy has become increasingly recognized, there also has been increased concern about the toxic and teratogenic properties of cocaine on the fetus. A significant literature exists describing the adverse fetal and neonatal outcomes associated with in utero cocaine exposure. However, specific causality by cocaine on outcome in the human is difficult to ascertain because of multiple confounding variables associated with substance abuse including social factors and polydrug use as well as difficulty in confirming timing, dose and frequency of cocaine exposure. Most literature suggests that prenatal cocaine exposure is associated with developmental risk to the fetus. What is currently unknown is the extent of risk, the additive and/or synergistic factors contributing to cocaine's toxicity and the reversibility of the injury. In this paper we review the pharmacologic properties of cocaine as related to a model of mechanisms for developmental injury secondary to cocaine exposure and the published literature on the adverse fetal and neonatal outcomes associated with cocaine use during pregnancy. Specific attention has been focused on the structural, neurobehavioral and respiratory control teratogenesis.     

Thirty-six-month outcome of prenatal cocaine exposure for term or near-term infants: impact of early case management

Gestational cocaine use is associated with serious pregnancy complications having fetal and neonatal implications. However, many cocaine-abusing women deliver uneventfully at term. The purpose of this study was to assess the neurodevelopmental outcome for term or near-term infants after prenatal cocaine exposure and to determine whether that outcome would be modified by early, intensive family case management. Cocaine-exposed infants identified after delivery at an urban hospital were alternately assigned to receive case management (n = 70) or routine follow-up (n = 48). A matched, non-drug-exposed group of infants was identified for comparison (n = 41). Infants aged up to 36 months were serially evaluated in a multidisciplinary clinic with cognitive, psychomotor, and language testing. Group comparisons were performed using one-way analysis of variance. There were no statistical differences in mean cognitive, psychomotor, or language quotients between cocaine-exposed and non-drug-exposed infant groups aged up to 36 months. At 6 months of age, case-managed cocaine-exposed infants had a significantly higher mean Bayley Mental Developmental Index score than those who were routinely managed. However, no differences were present at subsequent assessments. Among cocaine-exposed infants who remained with their mothers at 36 months, verbal scores were significantly higher for case-managed compared with routine-managed infants. The negative effects of urban, low socioeconomic status may overshadow the impact of prenatal cocaine exposure on early childhood outcome for those infants born without prenatal complications.     

Measurement of gestational cocaine exposure: sensitivity of infants' hair, meconium, and urine.

We studied the sensitivity of testing the newborn infant's hair, meconium, and urine in detecting gestational cocaine exposure. The infants were born to 59 women who were interviewed to determine their use of cocaine during pregnancy and whose hair was analyzed for the presence of cocaine. Regression analysis was used to evaluate the relationship between cocaine in newborn hair and in maternal hair. Radioimmunoassay of infants' hair and gas chromatography-mass spectrometry of meconium were more sensitive than immunoassay of urine (p less than 0.02), which failed to identify 60% of cocaine-exposed infants. The quantity of benzoylecgonine in the newborn infant's hair correlated best with the proximal-segment maternal hair, representing the last 12 weeks of antepartum hair growth (R = less than R less than 0.83). Approximately half (52%) of the variation in infants' hair was explained by variation in the proximal maternal hair segment. Correlation (R = 0.77) and explained variation (59%) improved slightly when premature infants (n = 9) were excluded. We conclude that analysis of the newborn infant's hair by radioimmunoassay or of meconium by gas chromatography-mass spectrometry is more sensitive than analysis by immunoassay of urine, and can detect fetal cocaine exposure that occurred during the last two trimesters of pregnancy.     

Maternal cocaine use during pregnancy: effect on the newborn infant

The newborn infants of 56 mothers who used cocaine were prospectively studied in to determine the effects of cocaine. There were no differences with respect to maternal preeclampsia or cesarean section rate. Meconium-stained amniotic fluid was increased (10 of 56 cases [17.8%]) compared with the control group (3 of 56 cases [5.3%]) (X2 = 4.2, P less than .05). Fetal distress recorded with fetal monitoring and Apgar scores at 1 and 5 minutes were similar. The weight, length, and head circumference growth curves of the infants born to cocaine-using mothers were shifted below the 25th percentile. Microcephaly was present in 12 of 56 (21.4%) infants whose mothers used cocaine during pregnancy (X2 = 5.96, P less than .01), and 15 of 56 (26.7%) had intrauterine growth retardation (X2 = 9.53, P less than .01) compared with the control infants (2 of 5 [3.5%] and 3 of 56 [5.3%], respectively). There was no increase in teratogenicity. Neither narcotic withdrawal symptoms nor illness could distinguish the infants born of cocaine-using mothers from the control infants. In conclusion, cocaine use during pregnancy results in newborn infants with growth retardation and microcephaly.     

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.     

Prenatal cocaine exposure and prematurity: neurodevelopmental growth

The consequences of prematurity and prenatal cocaine exposure on early neurobehavior and physical growth were examined longitudinally in a sample of 20 cocaine-exposed and 20 non-exposed preterm neonates. The magnitude of the difference in physical growth acceleration related to prenatal cocaine exposure increased with increasing birth gestational age, whereas growth rate differences in irritability decreased. In contrast, prenatal cocaine exposure, independent of prematurity, was related to reduced attention skills at 36 weeks conceptional age and increased rates of neurobehavioral change. The effects of prenatal cocaine exposure differed with respect to the degree of prematurity, depending on the nature of the outcome examined, suggesting differing windows of vulnerability for different outcome domains. The usefulness of a developmental growth perspective was demonstrated.     

Influence of prenatal cocaine exposure on early language development: longitudinal findings from four months to three years of age

The influence of prenatal cocaine exposure on children's language functioning was evaluated longitudinally at six time points from 4 months to 3 years of age. The Miami Prenatal Cocaine Study prospectively enrolled 476 full-term African-American infants at birth, categorized as cocaine-exposed (n = 253) or non-cocaine-exposed (n = 223) by maternal self-report and bioassays (maternal/infant urine, meconium). The Bayley Scales of Infant Development, scored using the Kent Scoring Adaptation for language, was administered at 4, 8, 12, 18, and 24 months. The Clinical Evaluation of Language Fundamentals-Preschool was administered at 3 years. In longitudinal analyses using Generalized Estimating Equations, cocaine-exposed children had lower overall language skills than non-cocaine-exposed children (D = -0.151; 95% CI = -0.269, -0.033; p =.012). Longitudinal findings remained stable after evaluation of potential confounding influences including other prenatal substance exposures and sociodemographic factors. Preliminary evidence also indicated possible mediation through an intermediary effect involving cocaine-associated deficits in fetal growth.     

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

BACKGROUND: 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. METHODS: 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 相似文献   

Prenatal cocaine and neuromotor outcome at four months: effect of duration of exposure.

The effect of prenatal cocaine exposure on the motor development of full-term infants was examined in a prospective study, controlling for maternal characteristics and exposure to other substances. Intrauterine cocaine exposure was determined at birth by maternal self-report and was verified by hair analysis. At 4 months, 120 cocaine-exposed (COC) and 186 non-cocaine-exposed (NON-COC) infants were assessed by blinded examiners using a standard evaluation of neuromotor function, the Movement Assessment of Infants (MAI). Relative to NON-COC infants, COC infants had significantly higher full-scale MAI total risk scores after adjusting for covariates (p = .05). Infants exposed through the third trimester of pregnancy (n = 48) had higher MAI scores for both total risk (p = .02) and Volitional Movement (p = .01), and when compared with infants exposed only within the first two trimesters (n = 72), they had significantly more deficits in Volitional Movement (p = .03). Although MAI scores for the majority of exposed infants were within the normal range, infants exposed through the third trimester were at significantly increased risk for motor dysfunction (relative risk = 1.6; 95% confidence interval = 1.1, 2.8). Intrauterine cocaine exposure had an adverse effect on infant motor development after the neonatal period; this association was related to the timing and duration of gestational exposure. Further study is needed to evaluate the long-term clinical implications of neuromotor abnormalities in prenatally exposed infants.     

Prenatal cocaine exposure is associated with respiratory pattern abnormalities

As retrospectively determined, the rate of sudden infant death syndrome in 66 infants prenatally exposed to cocaine was 15%, compared with only 4% among infants exposed to opiates. This prospective evaluation of cardiorespiratory pattern in 32 cocaine-exposed and 18 methadone-exposed infants was therefore performed to further evaluate the effects of intrauterine exposure. The two groups were similar in maternal age, race, and cigarette, alcohol, and marijuana use and in gestational age, sex, and birth weight. Apnea density and episodes of periodic breathing exceeded the 95th percentile for normal infants in 12 (38%) of 32 of cocaine-exposed infants vs only 1 (6%) of 18 opiate-exposed infants. Five cocaine-exposed but no opiate-exposed infants had apnea of infancy, and all 5 of these infants had an abnormal cardiorespiratory pattern. In all 13 infants with an abnormal cardiorespiratory pattern, theophylline treatment resulted in normalization of the respiratory pattern and was associated with absence of any (further) clinical events. In summary, infants prenatally exposed to cocaine have a higher incidence of cardiorespiratory pattern abnormalities than do infants with methadone or no prenatal drug exposure.     

A preliminary report of prenatal cocaine exposure and respiratory distress syndrome in premature infants

A prospective study of maternal drug use during pregnancy and newborn outcomes provided us with an opportunity to assess the relationship between prenatal cocaine use and respiratory distress syndrome among premature infants. Women were consecutively recruited from the prenatal clinics at Boston (Mass) City Hospital between 1984 and 1988 and were interviewed during the prenatal and postpartum period by trained bilingual interviewers. Urine specimens were collected at the time of each interview and were analyzed for marijuana and cocaine metabolites. Following delivery, one of five pediatricians who were "blinded" to the mothers' prenatal and drug history performed a physical examination and abstracted medical information, including the diagnosis of respiratory distress syndrome from the medical record. The study sample consisted of 33 infants born at 34 weeks' or less gestation who were appropriate for gestational age and not exposed to heroin or methadone prenatally. Eight of the mothers of these 33 infants used cocaine prenatally. One (12%) of eight cocaine-exposed infants was diagnosed as having respiratory distress syndrome compared with 13 infants (56%) not exposed to cocaine prenatally. Infants not exposed had an odds ratio of 8.9 (95% confidence interval: 0.9, 83.5) for respiratory distress syndrome compared with infants exposed to cocaine prenatally. When the analysis was controlled for prolonged rupture of membranes, black race, infant gender, or gestational age, the adjusted odds ratio was essentially unchanged. This preliminary observation of a decreased incidence of respiratory distress syndrome among premature infants prenatally exposed to cocaine appears to be biologically plausible and needs to be confirmed in future studies with larger numbers of subjects to control for potentially confounding variables.     

Children prenatally exposed to cocaine: developmental outcomes and environmental risks at seven years of age

Data are equivocal regarding the long-term consequences of prenatal exposure to cocaine on school-aged children. We compared 101 children exposed prenatally to cocaine with 130 unexposed children on measures of intelligence, visual motor, and motor abilities at age 7 years. Bivariate analyses revealed that cocaine-exposed children scored significantly lower than comparison children on the abbreviated Wechsler Intelligence Scale for Children-Third Edition Verbal and Full Scale IQ scores, the Visual Motor Integration and Motor Coordination standardized scores, and the Bruininks-Oseretsky Fine Motor Composite score. Regression analyses indicated that the biological mother's vocabulary and home environment assessed at the same 7-year visit were stronger predictors of developmental outcome than prenatal drug exposure. Level of cocaine exposure, however, predicted visual motor and motor skills. The results indicate that although prenatal cocaine exposure may confer some degree of developmental disadvantage in the visual motor domain, it frequently occurs in the context of an inadequate rearing environment, which may be a stronger determinant than prenatal cocaine exposure of children's outcome.     

Neonatal body proportionality and body composition after in utero exposure to cocaine and marijuana

The relationship of maternal use of marijuana and cocaine during pregnancy to measures of neonatal body proportionality and body composition was assessed in a multiethnic sample of 1082 newborn infants. Maternal use of marijuana and cocaine during pregnancy was ascertained by self-report and by an enzyme-multiplied immunoassay technique for screening of urine samples obtained prenatally and again post partum. After each substance was analytically controlled for use of the other and for other potentially confounding variables, detection of marijuana metabolites in maternal urine was associated (p less than 0.05) with depressed mean arm muscle circumference and nonfat area of the arm but not with any measure of neonatal fatness. In contrast, detection of cocaine in maternal urine was associated (p less than 0.05) with decrements of subscapular fat folds and of the fat and nonfat areas of the arm. Although both substances were associated with depressed birth weight, there was no decrement of neonatal ponderal index or of the arm circumference/head circumference ratio in association with exposure to either substance. We conclude that both marijuana exposure and cocaine exposure during pregnancy are associated with symmetric intrauterine growth retardation, but that deficits are in differing compartments of intrauterine growth. These findings suggest that marijuana may retard fetal growth through maternal-fetal hypoxia, whereas cocaine may alter nutrient transfer to the fetus and fetal metabolism.     

Cocaine toxicity in the newborn. Detection and prevalence

The neonatal effects of fetal cocaine exposure are not completely known. Serious adverse effects have been described in several series of women consuming pure cocaine, but in recent years articles questioning some of the damaging effects of cocaine on the fetus and newborn have been published. The use of cocaine is currently increasing both in Spain and in many other countries and this will in turn lead to an increase in the incidence of fetal and neonatal adverse effects. We review the possible effects of cocaine exposure in utero, and place particular emphasis on neurobehavioral abnormalities, which are present even when exposure is limited to the first trimester of pregnancy. We also analyze various biomarkers for cocaine detection in newborns and their mothers and, finally, we review pharmacogenetic and dose-response relation susceptibility factors.     

Neuromotor Outcomes of Infants Exposed Prenatally to Cocaine:

The effect of prenatal cocaine exposure on the neuromotor outcome of infants has been investigated through animal research, neurophysiological studies of neonates, and longitudinal follow-up of exposed infants. The inconsistency in reported findings may reflect methodological problems as well as variations among study populations and individual infants. Several studies using the Movement Assessment of Infants (MAI) have reported significant differences in motor performance at four months of age in infants who were cocaine-exposed prenatally, but specific clinical findings vary. A review of relevant work is presented here with a discussion of issues and variables which must be considered in an evaluation of the neuromotor consequences of intrauterine cocaine exposure for the developing infant.     

Prenatal cocaine exposure and fetal vascular disruption

The question of the potential teratogenicity of cocaine has been raised by the increasing frequency of its abuse in the United States. In previous studies, an increased incidence has been documented of spontaneous abortion, placental abruption, prematurity, intrauterine growth retardation, and neurologic deficits in the infants of women who abused cocaine. More recently, it has been suggested in studies that fetal vascular disruption accompanying maternal cocaine abuse may lead to cavitary central nervous system lesions and genitourinary anomalies. In this article, 10 children born of women who abused cocaine are described, 9 of whom have congenital limb reduction defects and/or intestinal atresia or infarction. The spectrum of anomalies associated with embryonic and fetal vascular disruption accompanying maternal cocaine abuse is thus enlarged. The specific risk for congenital anomalies accompanying maternal cocaine abuse during an individual pregnancy is unknown. However, data from these patients and the available literature suggest that counseling pregnant women concerning cocaine use should incorporate warnings about the possibility of associated embryonic or fetal vascular disruption.     

Do "we just know"? Masked assessors' ability to accurately identify children with prenatal cocaine exposure

This study evaluated perceptions of masked assessors to determine whether there are subtle differences in cocaine-exposed and unexposed children who might be identified by those interacting with children. As part of a longitudinal study, developmental assessors were masked to 163 4-year-old children's actual in utero cocaine exposure status and developmental history. After each battery, assessors documented their guesses of the child's cocaine exposure. Thirty-seven percent of the children who were exposed were misclassified as unexposed, whereas 74% of those unexposed were incorrectly classified as exposed. Although the sample did not differ on assessment scores when results were analyzed by actual cocaine exposure status ( >.3), children who did less well on assessments were more likely to be labeled by assessors as cocaine-exposed ( <.001). Results highlight the potential of stereotyping and negative attributions that might distort observations, both in unmasked studies of prenatal cocaine exposure and in clinical settings.     

Cocaine/polydrug use in pregnancy: two-year follow-up.

The impact of cocaine on pregnancy and neonatal outcome has been well documented over the past few years, but little information regarding long-term outcome of the passively exposed infants has been available. In the present study, the 2-year growth and developmental outcome for three groups of infants is presented: group 1 infants exposed to cocaine and usually marijuana and/or alcohol (n = 106), group 2 infants exposed to marijuana and/or alcohol but no cocaine (n = 45), and group 3 infants exposed to no drugs during pregnancy. All three groups were similar in racial and demographic characteristics and received prenatal care through a comprehensive drug treatment and follow-up program for addicted pregnant women and their infants. The group 1 infants demonstrated significant decreases in birth weight, length, and head circumference, but by a year of age had caught up in mean length and weight compared with control infants. The group 2 infants exhibited only decreased head circumference at birth. Head size in the two drug-exposed groups remained significantly smaller than in control infants through 2 years of age. On the Bayley Scales of Infant Development, mean developmental scores of the two groups of drug-exposed infants did not vary significantly from the control group, although an increased proportion of group 1 and 2 infants scored greater than two standard deviations below the standardized mean score on both the Mental Developmental Index and the Psychomotor Developmental Index compared with the control infants. Cocaine exposure was found to be the single best predictor of head circumference.(ABSTRACT TRUNCATED AT 250 WORDS)     

Motor development of cocaine-exposed children at age two years

OBJECTIVE: This article was designed to investigate effects of prenatal cocaine exposure on motor development of young children from a predominately underprivileged, urban population. METHODOLOGY: A total of 260 infants and young children were initially recruited from either the newborn nursery or the at-risk pediatric clinic of an urban teaching hospital. Prenatal history and birth outcomes were collected from medical records. Demographic characteristics and additional drug histories were obtained from the mothers. The 199 subjects (98 cocaine-exposed and 101 unexposed) who returned at age 2 years were assessed by examiners blinded to drug exposure status using the Peabody Developmental Motor Scales. RESULTS: Compared with control subjects, the cocaine-exposed group performed significantly less well on both the fine and the gross motor development indices. Mean scores for both groups were within the average range on the gross motor index, but greater than 1 standard deviation below average on the fine motor index. Differences were significant on the balance and the receipt and propulsion subscales of the gross motor scale, and on the hand use and the eye-hand coordination subscales of the fine motor scale. Cocaine status independently predicted poorer hand use and eye-hand coordination scores. There also was an effect of alcohol exposure on the receipt and propulsion subscale. CONCLUSIONS: Findings indicate that deficiencies in motor development remain detectable at 2 years of age in children exposed to drugs prenatally. Although other environmental variables may influence motor development, children exposed to cocaine and to alcohol in utero may encounter developmental challenges that impede later achievement.