Cocaine exposure is associated with subtle compromises of infants' and mothers' social-emotional behavior and dyadic features of their interaction in the face-to-face still-face paradigm.

Prenatal cocaine and opiate exposure are thought to subtly compromise social and emotional development. The authors observed a large sample of 236 cocaine-exposed and 459 nonexposed infants (49 were opiate exposed and 646 nonexposed) with their mothers in the face-to-face still-face paradigm. Infant and maternal behaviors were microanalytically coded. No opiate-exposure effects were detected. However, mothers of cocaine-exposed infants showed more negative engagement than other mothers. The cocaine-exposed dyads also showed higher overall levels of mismatched engagement states than other dyads, including more negative engagement when the infants were in states of neutral engagement. Infants exposed to heavier levels of cocaine showed more passive-withdrawn negative engagement and engaged in more negative affective matching with their mothers than other infants. Although effect sizes were small, cocaine exposure, especially heavy cocaine exposure, was associated with subtly negative interchanges, which may have a cumulative impact on infants' later development and their relationships with their mothers.

Developmental outcome prediction from acoustic cry analysis in term and preterm infants.

It has been suggested that the cry may reflect the neurophysiologic integrity of the infant and relate to later developmental outcome. In this study, the cry was recorded at term conceptional age in 18 preterm and 13 term infants using a standardized procedure and analyzed by high-speed computer. At 18 months of age, a significant number of infants were correctly classified as scoring high or low on the Bayley Scales of Infant Development based on the mean and variability in the fundamental frequency, variability in the first formant, and the amplitude of the cry. At 5 years of age, a significant number of infants were correctly classified on the McCarthy General Cognitive Index and on the verbal, perceptual-performance, and quantitative subscales based on the variability of the fundamental frequency, variability of the first formant, and amplitude and duration of the cry. Although preliminary, this study supports the potential use of the cry as a noninvasive measure to detect developmental outcome in the infant at risk.

A comparative study of the behavior of Greek neonates.

Three groups of 30 Greek neonates each (an adoptive group from the Metera orphanage, a lower-class group, and a middle-class group) were evaluated at days 1, 5, and 10 after birth using a behavioral scale of 21 items and a neurologic evaluation of 16 items. Behaviors were examined for group differences and group-by-age recovery curves were determined during the first ten days. Significant differences were found in the separate items and items grouped to reflect interactive, motor, and state behavioral dimensions. The adoptive babies at the Metera orphanage generally performed the most poorly. This difference seems not only to reflect intrauterine differences, especially in regard to nutrition, but to point to the likelihood of eliciting less than optimal responses from future environments. The middle-class group had the worst scores on physiologic items and were similar to the Metera babies in having initially depressed interactive, motor, and state behavior. Improvement in these areas over ten days suggested that temporary effects of maternal medication caused the poor scores. The recovery curves of the infants pointed to the important effects of such perinatal variables as maternal medication on early neonatal behavior.

Effects of in utero substance exposure on infant neurobehavior.

OBJECTIVE: This study had two objectives: (1) to assess infant behavior by using the NICU Network Neurobehavioral Scale (NNNS), an assessment designed specifically for prenatally drug-exposed infants; and (2) to control for the effects of polydrug use involving alcohol, marijuana, and cigarettes on the neurobehavioral status of the newborn infant. METHODS: The subjects and controls in this study were full-term infants of appropriate gestational age with no medical problems. At 1 to 2 days of age, 20 infants exposed to cocaine, alcohol, marijuana, and cigarettes; 17 infants exposed to alcohol and/or marijuana and cigarettes; and 20 drug-free infants were evaluated by using the Neonatal Intensive Care Unit Network Neurobehavioral Scale. The data were reduced to reflect clinically defined categories of neurobehavioral function and were analyzed by using analysis of variance and chi 2 statistics. RESULTS: Cocaine-exposed infants showed increased tone and motor activity, more jerky movements, startles, tremors, back arching, and signs of central nervous system and visual stress than unexposed infants. They also showed poorer visual and auditory following. There were no differences in how the examination was administered to cocaine-exposed and nonexposed infants. Reduced birth weight and length were also observed in cocaine-exposed infants. CONCLUSION: Differences attributable to cocaine-exposed infants were related to muscle tone and motor performance, following during orientation, and signs of stress. However, cocaine-exposed infants were not more difficult to test, nor did they require an alteration in the examination. Both neurobehavioral patterns of excitability and lethargy were observed. Findings may have been due to the synergistic effects of cocaine with alcohol and marijuana.

Newborn acoustic cry characteristics of infants subsequently dying of sudden infant death syndrome.

OBJECTIVE: To test the hypothesis that the occurrence of a neonatal cry exhibiting a high first formant is a risk factor for sudden infant death syndrome (SIDS) and to evaluate the association between SIDS and other acoustic cry variables. METHOD: We recorded cries and obtained medical and demographic data for 21,880 apparently healthy term newborns. Two cries were recorded between days 2 and 7 of life, after a painful stimulus at the time of routine blood drawing. Acoustic variables were measured with an automated computer-based analysis system. Twelve infants died of SIDS. Age at death ranged from 19 days to 6.5 months. Autopsies were performed in all cases. At least one cry was analyzed for all 12 infants who died of SIDS and 20,167 infants without SIDS. Two cries were analyzed for 9 infants who died of SIDS and 14,235 infants without SIDS. RESULTS: Newborns whose first cries exhibited a high first formant were more likely to die of SIDS than infants whose first cries did not have this characteristic (relative risk, 3.5; 95% confidence interval [CI], 1.1 to 12). The relative risk for SIDS increased to 8.8 (95% CI, 2.2 to 35) for newborns whose second cries showed that this characteristic persisted. Newborns with the combination of both a high first formant and a high number of mode changes on both of two cries had a relative risk of 32 (95% CI, 8.7 to 120). CONCLUSIONS: We have shown an association between alterations in neonatal cry acoustics and SIDS. Cry analysis represents a potentially important research tool that, when studied in relation to other physiologic measures, may lead to an improved understanding of SIDS.

Effects of in utero cocaine exposure on newborn acoustical cry characteristics.

As part of a large, multicenter study of newborn cry analysis and Sudden Infant Death Syndrome, we examined the effects of in utero cocaine exposure on ten acoustical cry characteristics. Newborn cry recording and medical record review was performed for 23,948 newborns. Cocaine use during pregnancy (determined by record review) was identified in 438 (1.8%) women (310 by self-report only; 128 newborns also had positive urine assay). A demographically similar group of 373 newborns, selected from the 23,510 newborns without known cocaine exposure, made up the comparison group. Cry analysis was technically possible for 768 recordings: 404 cocaine-exposed and 364 non-exposed controls. Comparison of cocaine-exposed vs control newborns, after adjustment for potential confounding variables, found significant differences including: fewer cry utterances (P = .001), more short cries (P = .02), and less crying in the hyperphonation mode (P = .01), for the cocaine-exposed neonates. As reported in other studies, cocaine-exposed newborns also were significantly lower in birth weight, length, and head circumference. Newborns who had positive urine tests for cocaine suffered the greatest effects on both cry and growth parameters. These findings suggest a pattern of underaroused neurobehavioral function and are consistent with the emerging picture of the adverse neurobehavioral effects of cocaine. Developmental outcome studies are in progress to determine if acoustical analysis of the newborn cry can be used to identify cocaine-exposed newborns who are at highest risk for poor outcome.

Developmental outcome as a function of the goodness of fit between the infant's cry characteristics and the mother's perception of her infant's cry.

OBJECTIVE: To determine whether the "goodness of fit" between infant cry characteristics and the mother's perception of the cry is related to developmental outcome at 18 months of age. DESIGN: This was a prospective, longitudinal study from birth to 18 months performed in a blinded manner. SETTING: The study was conducted in a maternity hospital, including normal and special care nurseries and a laboratory for developmental follow-up. PATIENTS: The 121 term and preterm infants and their mothers were selected to meet medical criteria. MEASUREMENT: Acoustic analysis of 1-month infant cry and the mother's perception of the same cry was used to divide subjects into four groups representing matches and mismatches between infant cry characteristics and maternal cry perception. Primary outcome measures of cognitive, language, motor, and neurologic outcome were administered at 18 months. Caretaking environment measures were also recorded. RESULTS: Statistically significant (P < .05) findings showed that matched groups scored higher on measures of language and cognitive performance than infants in the mismatch groups, with a particular advantage for infants in the matched group in which mothers accurately perceived the higher-pitched cries of their infants. There were no differences between the groups in biologic or sociodemographic factors. Group differences were observed in social support and maternal self-esteem. CONCLUSIONS: Matches and mismatches between infant cry characteristics at 1 month and the mother's perception of the cry are related to cognitive and language outcome at 18 months in term and preterm infants. This relation is probably due to transactional processes in which developmental outcome is affected by the clarity of the infants' signals and by the ability of the mother to accurately perceive her infant's signals. The mother's ability to read her infant's cues may be affected by factors such as social support and self-esteem.

Family-based intervention improves maternal psychological well-being and feeding interaction of preterm infants.

OBJECTIVE: To determine the efficacy of an individualized, family-based intervention with preterm infants and their families. DESIGN: Randomized, repeated measures intervention outcome study. SETTING: Level III neonatal intensive care nursery. PATIENTS: Random sample of 34 preterm infants < or = 1500 g and their families. INTERVENTIONS: Individualized, family-based intervention during the hospitalization and transition to home addressed problems identified by parents in four domains including: infant behavior and characteristics, family organization and functioning, caregiving environment, and home discharge and community resources. MEASUREMENTS AND MAIN RESULTS: Standardized questionnaires were administered at baseline and discharge to mothers, and predischarge bottle-feeding interactions were videotaped and coded by two blinded observers. Results were in favor of intervention (Int) versus control (Con) mothers (baseline; discharge) (P < .05) on the Parental Stressor Scale Sights and Sounds subscale (Int 2.4 +/- 1.0; 2.0 +/- 0.8 vs Con 2.4 +/- 0.9; 2.6 +/- 0.8); Child's Appearance and Behavior subscale (Int 2.8 +/- 1.0; 2.5 +/- 1.1 vs Con 2.8 +/- 0.8; 3.1 +/- 0.6); and Total Stressor Score (Int 93.9 +/- 36.6; 72.3 +/- 41.8 vs Con 87.5 +/- 26.7; 87.8 +/- 26.2). On the Beck Depression Inventory, intervention mothers had significant decreases in depressive symptoms (39%; 11%) vs control mothers (31%; 44%). Maternal self-esteem in both groups improved over time. There were no significant group differences in family environment. During feeding interactions, intervention infants grimaced (P < .001) and gagged (P < .05) less than controls. Intervention mothers less frequently interrupted feedings (P < .001); less frequently stimulated infant sucking (P < .01); smiled more (P < .001); vocalized more (P < .01); demonstrated greater sensitivity to infant behavior (P < .001), better quality of physical contact (P < .001), and more positive affect (P < .01). CONCLUSIONS: Individualized, family-based intervention appears to reduce maternal stress and depression, and to enhance early mother-infant feeding interactions. Further research is needed to determine whether these short-term beneficial effects persist beyond the newborn period.

Possible association between fluoxetine hydrochloride and colic in an infant.

This is a case study of a 6-week-old infant referred for colic whose mother was using fluoxetine hydrochloride and breast feeding the infant. The mother switched to a commercial formula and reported a dramatic decrease in the infant's crying. We asked the mother to feed the infant breast milk from a bottle and she agreed. Throughout the study the mother kept a daily diary of her infant's crying, sleeping, stooling patterns, and feeding problems. Analysis of the mother's breast milk showed concentrations of 69 ng/mL for fluoxetine and 90 ng/mL for norfluoxetine. Infant blood serum/plasma level was analyzed for fluoxetine hydrochloride following return to breast milk. The concentrations were 340 ng/mL for fluoxetine and 208 ng/mL for norfluoxetine. The diary records showed increased crying, decreased sleep, increased vomiting, and watery stools when fluoxetine hydrochloride was transmitted through breast feeding or breast milk in bottle. These symptoms were reduced when the infant was formula fed. We suggest a possible relationship between colic and associated symptoms and fluoxetine hydrochloride in maternal breast milk.

Buprenorphine treatment of pregnant opioid--dependent women: maternal and neonatal outcomes.

This open-label prospective study examined maternal and neonatal safety and efficacy outcome measures during and following prenatal buprenorphine exposure. Three opioid-dependent pregnant women received 8 or 12 mg sublingual buprenorphine tablets daily for 15-16 weeks prior to delivery. Results showed that buprenorphine in combination with comprehensive prenatal care was safe and effective in these women. Prenatal exposure to buprenorphine resulted in normal birth outcomes, a mean of 4.33 days (minimum possible=4) hospitalization, and a 'relatively mild' neonatal abstinence syndrome comprised primarily of tremors (disturbed), hyperactive moro and shortened sleep after feeding. The infants required no pharmacological treatment. Onset of neonatal abstinence signs occurred within the first 12 h after birth, peaked by 72 h and returned to below pre-12 h levels by 120 h. It is concluded that buprenorphine has potential utility for the treatment of pregnant opioid-dependent women.

The effects of maternal depression on fetal heart rate response to vibroacoustic stimulation.

To better understand the effects of untreated maternal depression on the fetus, this study examined fetal heart rate (FHR) and FHR reactivity to vibroacoustic stimulation in pregnant women with untreated depression. The 20 participants were 32- to 36-week pregnant women divided into groups with depression (N = 10) and without depression (N = 10) based on the Beck Depression Inventory (BDI; Beck, 1977; Beck & Steer, 1987). Participants were attached to a fetal heart monitor, and 10 min of baseline FHR were recorded. A vibroacoustic stimulus (VAS) was presented, and an additional 10 min of FHR were recorded. Fetuses of mothers with depression had an elevated baseline FHR and a 3.5-fold delay in return to baseline FHR after VAS presentation. Additionally, mothers with depression had significantly higher anxiety levels and took fewer prenatal vitamins during pregnancy. Delayed habituation of FHR in the fetuses of mothers with depression may be due to alterations in the internal hormonal environment and could have implications for postnatal information processing.

Prenatal drug exposure and maternal and infant feeding behaviour.

OBJECTIVE: To evaluate feeding difficulties and maternal behaviour during a feeding session with 1 month old infants prenatally exposed to cocaine and/or opiates. METHODS: The study is part of the maternal lifestyle study, which recruited 11 811 subjects at four urban hospitals, then followed 1388 from 1 to 36 months of age. Exposure to cocaine and opiates was determined by maternal interview and meconium assay. At the 1 month clinic visit, biological mothers were videotaped while bottle feeding their infants. This sample included 364 exposed to cocaine, 45 exposed to opiates, 31 exposed to both drugs, and 588 matched comparison infants. Mothers were mostly black, high school educated, and on public assistance. Videotapes were coded without knowledge of exposure status for frequency, duration and quality of infant sucking, arousal, feeding problems, and maternal feeding activity and interaction. RESULTS: No cocaine effects were found on infant feeding measures, but cocaine-using mothers were less flexible (6.29 v 6.50), less engaged (5.77 v 6.22), and had shorter feeding sessions (638 v 683 seconds). Opiate exposed infants showed prolonged sucking bursts (29 v 20 seconds), fewer pauses (1.6 v 2.2 per minute), more feeding problems (0.55 v 0.38), and increased arousal (2.59 v 2.39). Their mothers showed increased activity (30 v 22), independent of their infants' feeding problems. CONCLUSIONS: Previous concerns about feeding behaviour in cocaine exposed infants may reflect the quality of the feeding interaction rather than infant feeding problems related to prenatal exposure. However, opiate exposed infants and their mothers both contributed to increased arousal and heightened feeding behaviour.

Behavioral intervention and post-natal growth in full-term intrauterine growth retarded (IUGR) infants.

The purpose of this study was twofold: (1) to describe the patterns of post-natal growth in full-term infants as a function of IUGR and (2) to assess the impact of an individualized behavioral feeding intervention with the mothers on these patterns of infant growth. Eighty-eight (88) full-term infants, including 54 with IUGR, half of whom received behavioral intervention were included. Weight, length, skinfold thickness, head circumference and Ponderal Index were measured at birth and at 1, 4, 8, 12, and 18 months. Results show positive intervention effects between birth and 1 month in weight, length, skinfold thickness, and Ponderal Index. However, there were no intervention effects at subsequent ages. No evidence was found for catch-up growth in full-term IUGR infants in weight, length, and head circumference. We conclude that an individualized behavioral feeding intervention can accelerate early growth in IUGR infants, but the positive effects on growth are only seen while the intervention lasts (between birth and 1 month). On most parameters of physical growth, there is no lasting catch-up growth over the first 18 months in IUGR full-term infants.

The NICU Network Neurobehavioral Scale. Clinical use with drug exposed infants and their mothers.

The NNNS provides a comprehensive assessment of the at-risk and drug-exposed infant. The examination was developed for research and has now been extended to clinical practice. It is routinely used in our hospital in several clinical programs. In this article we detailed how the examination is used with substance-involved mothers and their infants. As we continue to develop assessment procedures based on understanding the capacities of the infant and understanding the parenting capacities of mothers, we will improve our ability to secure the welfare of drug-exposed infants.

Biology versus environment in the extremely low-birth weight infant.

This article examines the role of biologic and environmental factors in determining the long-term outcomes of extremely low-birth weight infants. Research focusing on follow-up to at least 4 years of age is reviewed. Methodologic issues related to sampling, the use of control groups, and diagnostic criteria are also discussed. The use of cumulative models of risk for examining the relative contribution of environmental and biologic factors is presented.

Interpreting research on prenatal substance exposure in the context of multiple confounding factors.

Fetal exposure to specific drugs often occurs in the context of polydrug use, medical complications, and social/environmental risks. Early reports of severe developmental consequences of fetal exposure to illicit drugs, for example, cocaine, have largely been unsupported by recent studies that take these factors into account. Using a database of published studies on cocaine exposure, this article examines how confounding factors are controlled by recruitment and statistical strategies. Rather than attempting to reduce the impact of these factors, it is suggested that multiple risks in children's lives should be included in models of developmental outcomes along with drug exposure. Understanding the complexity of multiple risks in the child's environment and the subtlety of drug exposure effects can guide the choice of clinical treatment and intervention.

Behavioral and psychophysiologic assessment of the preterm infant.

Cardiorespiratory activity was recorded during attentional responsivity on the Brazelton scale in term and preterm infants. Preterm infants showed less heart rate deceleration, less heart rate variance and less power in the ECG spectrum at frequencies associated with respiratory sinus arrhythmia and oscillations in blood pressure: A lower threshold for attentional stimulation in the preterm infant may trigger a CNS mechanism that protects the infant from stimulus overload. Study of the coordination between behavioral and physiological reactivity provides an understanding of the role of the CNS in mediating information processing.

Immunoassay and GC-MS procedures for the analysis of drugs of abuse in meconium.

The analysis of meconium specimens for metabolites of substances of abuse is a relatively accurate method for the detection of fetal exposure to drugs. Most of the methods reported in the literature before the early 1990s relied on radioimmunoassays. The purpose of this study was to develop and validate methods for meconium sample preparation for the screening and gas chromatography-mass spectrometry (GC-MS) confirmation of meconium extracts for cannabinoids, cocaine, opiates, amphetamines, and phencyclidine. EMIT and TDx immunoassays were evaluated as screening methods. The sample preparation method developed for screening included extraction and purification prior to analysis. Cutoff levels were administratively set at 20 ng/g for 11-nor-delta9-THC-9-COOH (THCCOOH) and phencyclidine and at 200 ng/g for benzoylecgonine, morphine, and amphetamines, although lower levels could be detected in meconium using the EMIT-ETS system. Ninety-five meconium specimens were subjected to the screening procedure with GC-MS confirmation of presumptive positives. In addition, 30 (40 for cocaine) meconium specimens were subjected to GC-MS analysis for all analytes regardless of the screening results to determine the false-negative rate, if any, of the immunoassay. Although there were no false negatives detected, the GC-MS confirmation rate for the immunoassay-positive specimens was generally low, ranging from 0% for amphetamines to 75% for opiates. The lowest rate of confirmed positives was found with the cannabinoids, suggesting that tetrahydrocannabinol (THC) metabolites other than free 11-nor-9-carboxy-delta9-THC may be major contributors to the immunoassay response in meconium.

Prenatal cocaine exposure and child outcome: a model for the study of the infant at risk.

The problem of cocaine use by pregnant women and the effects on the developing child has become major focus of research, treatment and public policy in the United States. The purpose of this article is to summarize our knowledge base in this area including methodological issues, discuss the drug exposed infant as a prototype of the infant at risk, and to consider issues that impact on public policy and treatment.