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There is increasing interest in both the cumulative and long-term impact of early life adversity on brain structure and function, especially as the brain is both highly vulnerable and highly adaptive during childhood. Relationships between SES and neural development have been shown in children older than age 2 years. Less is known regarding the impact of SES on neural development in children before age 2. This paper examines the effect of SES, indexed by income-to-needs (ITN) and maternal education, on cortical gray, deep gray, and white matter volumes in term, healthy, appropriate for gestational age, African-American, female infants. At 5 weeks postnatal age, unsedated infants underwent MRI (3.0T Siemens Verio scanner, 32-channel head coil). Images were segmented based on a locally constructed template. Utilizing hierarchical linear regression, SES effects on MRI volumes were examined. In this cohort of healthy African-American female infants of varying SES, lower SES was associated with smaller cortical gray and deep gray matter volumes. These SES effects on neural outcome at such a young age build on similar studies of older children, suggesting that the biological embedding of adversity may occur very early in development., (© 2015 John Wiley & Sons Ltd.)

Background: Language skills, strongly linked to academic success, are known to differ by socioeconomic status (SES), with lower SES individuals performing less well than higher SES., Aims: To examine the effect of SES on infant language at 7months of age and the relationship between maternal vocabulary skills and infant language function. To determine if the relationships between SES and infant language are mediated by maternal vocabulary skills., Study Design: Longitudinal follow-up of healthy term female African American infants born to mothers in two SES groups: Low SES (income-to-needs≤1, no education beyond high school) and Higher SES (Income-to-Needs >1, at least a high school diploma)., Subjects: 54 infants tested at 7months of age; 54 mothers tested at infant age 7months., Outcome Measures: Preschool Language Scale-5 (PLS-5), Vocabulary and Matrix Reasoning subtests of the Wechsler Adult Intelligence Scale-IV., Results: Low SES infants (n=29) performed less well than Higher SES (n=25) on PLS-5 Total Language, Auditory Comprehension, and Expressive Communication (p≤0.012). Maternal Vocabulary subtest scores were lower in Low SES than Higher SES (p=0.002), but not related to infant PLS Language scores (p≥0.17). Maternal vocabulary did not mediate the relationship between SES and infant language skills at age 7months., Conclusions: In this single sex and race cohort of healthy, term, female infants, lower SES exerted negative effects on infant language by 7months of age. While maternal vocabulary scores showed no relation with infant language skills at 7months, continued study of the relations between SES, infant outcomes and maternal characteristics is needed to determine how low SES conditions impact early language. These findings underscore the importance of early interventions, as well as policies designed to improve socioeconomic conditions for infants and families., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Based on an emerging neuroscience model of addiction, this study examines how an imbalance between two neurobehavioral systems (reward motivation and executive control) can distinguish between early adolescent progressive drug use and mere experimentation with drugs. Data from four annual assessments of a community cohort (N = 382) of 11- to 13-year-olds were analyzed to model heterogeneity in patterns of early drug use. Baseline assessments of working memory (an indicator of the functional integrity of the executive control system) and three dimensions of impulsivity (characterizing the balance between reward seeking and executive control systems) were used to predict heterogeneous latent classes of drug use trajectories from early to midadolescence. Findings revealed that an imbalance resulting from weak executive control and heightened reward seeking was predictive of early progression in drug use, while heightened reward seeking balanced by a strong control system was predictive of occasional experimentation only. Implications of these results are discussed in terms of preventive interventions that can target underlying weaknesses in executive control during younger years, and potentially enable at-risk adolescents to exercise greater self-restraint in the context of rewarding drug-related cues.

This study examined the prospective influence of adolescent working memory (WM) on changes in impulsivity and sexual risk taking and assessed whether this relation could be explained by confounding effects of parental influences. Data from 360 community adolescents (M age  = 13.5 ± 0.95 years; 52% female; 56% non-Hispanic White; low-mid socioeconomic status (SES); recruited from Philadelphia area in 2004-2005) were analyzed using structural equation modeling to predict changes in impulsivity and sexual risk taking over a 2-year follow-up, using baseline assessments of WM, parental monitoring, parental involvement, and SES. Stronger WM predicted reduced involvement in sexual risk taking at follow-up, effects channeled through changes in impulsivity dimensions of "acting without thinking" and "inability to delay gratification." Parental variables had a protective influence on adolescent impulsivity and risk involvement, but the effects of WM operated independently of parental influences., (© 2015 The Authors. Child Development © 2015 Society for Research in Child Development, Inc.)

Working memory (WM) is positively correlated with socioeconomic status (SES). It is not clear, however, if SES predicts the rate of WM development over time or whether SES effects are specific to family rather than neighborhood SES. A community sample of children (n = 316) enrolled between ages 10 and 13 completed four annual assessments of WM. Lower parental education, but not neighborhood disadvantage, was associated with worse WM performance. Neither measure of SES was associated with the rate of developmental change. Consequently, the SES disparity in WM is not a developmental lag that narrows or an accumulating effect that becomes more pronounced. Rather, the relation between family SES and WM originates earlier in childhood and is stable through adolescence., (© 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.)

Background: Independently, both prematurity and low socioeconomic status (SES) compromise language outcome but less is known regarding the effects of low SES on outcome of prior preterm infants at toddler age., Aim: To assess SES effects on the language outcome of prior preterm infants at toddler age., Study Design: Retrospective chart review of infants born at ≤32 weeks, matched for gestational age (GA), birth weight (BW), chronic lung disease (CLD), periventricular leukomalacia (PVL), right and left intraventricular hemorrhage (IVH-R, L), and age at Bayley Scales of Infant Development III (BSID-III) testing., Subjects: Using insurance status as a proxy for SES, 65 children with private insurance (P-Ins) were matched with 65 children with Medicaid-type insurance (M-Ins)., Outcome Measures: Bayley Scales of Infant Development-III Language Composite., Results: M-Ins vs. P-Ins were similar in GA, BW, and age at BSID-III testing (mean 22.6 months adjusted), as well as other matched characteristics (all p ≥ 0.16). BSID-III Language Composite scores were lower in M-Ins than P-Ins (87.9 ± 11.3 vs. 101.9 ± 13.6) with a clinically significant effect size of 0.93 (p < 0.001). Overall, 45% of M-Ins exhibited mild to moderate language delay compared to 8% of P-Ins. Receptive and Expressive subscale scores also were lower in M-Ins than in P-Ins (both p < 0.001)., Conclusions: In this preterm cohort, by toddler age, M-Ins was associated with lower scores on measures of overall language as well as receptive and expressive language skills. Our findings, showing such an early influence of SES on language outcome in a cohort matched for biomedical risk, suggest that very early language interventions may be especially important for low SES preterm toddlers., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Aims: (i) To evaluate the role of pre-existing weakness in working memory ability (WM) as a risk factor for early alcohol use as mediated by different forms of impulsivity and (ii) to assess the adverse effects of progressive alcohol use on variations in WM over time., Design, Setting and Participants: A community sample of 358 adolescents [48% males, mean(age) (baseline) = 11.4 ± 0.87 years] from a longitudinal cohort design, assessed annually over 4 consecutive years with less than 6% attrition., Measurements: Repeated assessments were conducted for the following key variables: WM (based on performance on four separate tasks), frequency of alcohol use (AU) and three forms of impulsivity, namely sensation seeking (SS), acting without thinking (AWT) and delay discounting (DD). Latent growth curve modeling procedures were used to identify individual trajectories of change for all key variables., Findings: Weakness in WM (at baseline) predicted significantly both concurrent alcohol use and increased frequency of use over the four waves (P < 0.05). This effect was entirely mediated by two forms of impulsivity, AWT and DD, both of which were characterized by underlying weakness in WM. No individual variation was observed in the slopes of WM, which suggests that individual variations in alcohol use were not associated with changes in WM in our early adolescent sample., Conclusions: Early adolescent alcohol use may be a consequence of (pre-existing) weaknesses in working memory (WM) rather than a cause of it. Efforts to reduce early alcohol use should consider the distinct roles of different impulsivity dimensions, in addition to WM, as potential targets of intervention., (© 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.)

Research in animals has shown that early life experience, particularly parenting behaviors, influences later-life stress reactivity. Despite the tremendous relevance of this finding to human development and brain function, it has not been tested prospectively in humans. In this study two aspects of parenting were measured at age 4 in a sample of healthy, low socioeconomic status, African American children, and stress reactivity was measured in the same children 11-14 years later using a modified version of the Trier Social Stress Test (n = 55). Salivary cortisol was measured before, during and after the stressor and data were analyzed using piecewise hierarchical linear modeling. Parental responsivity, independent of the use of physical discipline, was positively related to cortisol reactivity. Effects were independent of subjective appraisals of the stressor and were also independent of other environmental risk factors and current psychosocial functioning. Therefore this study demonstrates in a novel and precise fashion that early childhood parental responsivity prospectively and independently predicts stress reactivity in adolescence.

Lower socioeconomic status (SES) is associated with higher levels of life stress, which in turn affect stress physiology. SES is related to basal cortisol and diurnal change, but it is not clear if SES is associated with cortisol reactivity to stress. To address this question, we examined the relationship between two indices of SES, parental education and concentrated neighborhood disadvantage, and the cortisol reactivity of African-American adolescents to a modified version of the Trier Social Stress Test (TSST). We found that concentrated disadvantage was associated with cortisol reactivity and this relationship was moderated by gender, such that higher concentrated disadvantage predicted higher cortisol reactivity and steeper recovery in boys but not in girls. Parental education, alone or as moderated by gender, did not predict reactivity or recovery, while neither education nor concentrated disadvantage predicted estimates of baseline cortisol. This finding is consistent with animal literature showing differential vulnerability, by gender, to the effects of adverse early experience on stress regulation and the differential effects of neighborhood disadvantage in adolescent males and females. This suggests that the mechanisms underlying SES differences in brain development and particularly reactivity to environmental stressors may vary across genders.

Although deficits in working memory ability have been implicated in suboptimal decision making and risk taking among adolescents, its influence on early sexual initiation has so far not been examined. Analyzing 2 waves of panel data from a community sample of adolescents (N = 347; Mean age[baseline] = 13.4 years), assessed 1 year apart, the present study tested the hypothesis that weak working memory ability predicts early sexual initiation and explored whether this relationship is mediated by sensation seeking and 2 forms of impulsivity, namely acting-without-thinking and temporal discounting. The 2 forms of impulsivity were expected to be positively associated with early sexual initiation, whereas sensation seeking was hypothesized to be unrelated or to have a protective influence, due to its positive association with working memory. Results obtained from structural equation modeling procedures supported these predictions and in addition showed that the effects of 3 prominent risk factors (Black racial identity, low socioeconomic background, and early pubertal maturation) on early sexual initiation were entirely mediated by working memory and impulsivity. The findings are discussed in regard to their implications for preventing early sexual onset among adolescents., (PsycINFO Database Record (c) 2012 APA, all rights reserved.)

Our objectives for this report were to identify trajectories of youth gambling behavior, and to examine their relation to executive cognitive function (ECF) and associated problem behaviors. Philadelphia school children, enrolled at ages 10-12 years (n = 387; 49% male), completed three annual assessments of risk behaviors, ECF, impulsivity, problem behaviors and demographics. Across ages 10-15 years, using methods from Nagin et al., two groups were identified: Early Gamblers (n = 111) initiated early and continued in later assessments, and Later Gamblers (n = 276) initiated at later ages and gambled less. Betting money on cards and sports were the most frequently reported gambling behaviors. Using gambling group as outcome, final backward selection logistic regression model showed Early Gamblers are more likely male (P = 0.001), report more active coping (P = 0.042), impulsive behaviors (P ≤ 0.008), and have friends who gamble (P = 0.001). Groups were similar in ECF, parental monitoring, marital status, SES, and race. Early Gamblers had higher incidence of problem behaviors and drug use (all P ≤ 0.006). Two gambling groups were identified in early adolescence with Early Gamblers showing higher levels of impulsivity and comorbid problems but similar levels of ECF compared to Late Gamblers. As more gambling groups are identified through later adolescence, ECF may emerge as a relevant precursor of problem gambling at this later time.

Objective: Research has focused on understanding risk factors associated with suicidal ideation and self-harm behaviors in older youth, but less is known regarding these behaviors in preadolescents. We examined characteristics associated with suicidal ideation and self-harm behavior in youth aged 10-13 years., Design/methods: A community sample of 387 youth was enrolled in a prospective study assessing precursors of risk behaviors. Twenty-three subjects endorsing items regarding suicidal ideation or self-harm behaviors (Achenbach's Youth Self-Report) (endorsers) were matched with 23 non-endorsers. Groups were compared on problem behaviors, impulsivity, neurocognitive function, risk behaviors, and other variables., Results: Endorsers had higher levels of impulsivity, were more likely in borderline/clinical range on 5 of 8 Youth Self-Report Syndrome scales, and reported more risk taking. Endorsers and non-endorsers were similar in neurocognitive function. More non-endorsers were on stimulants, but groups were similar in parental monitoring and parental report of behavioral/emotional issues, socioeconomic status, and marital status., Conclusion: In this study, preadolescent endorsers report significantly more problem behaviors than non-endorsers. However, parental monitoring and parent report of problems were similar between groups. Given these findings, we suggest that at-risk youth may be underrecognized at young ages., (Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Studies of brain development suggest that the increase in risk taking observed during adolescence may be due to insufficient prefrontal executive function compared to a more rapidly developing subcortical motivation system. We examined executive function as assessed by working memory ability in a community sample of youth (n = 387, ages 10 to 12 at baseline) in three annual assessments to determine its relation to two forms of impulsivity (sensation seeking and acting without thinking) and a wide range of risk and externalizing behavior. Using structural equation modeling, we tested a model in which differential activation of the dorsal and ventral striatum produces imbalance in the function of these brain regions. For youth high in sensation seeking, both regions were predicted to develop with age. However, for youth high in the tendency to act without thinking, the ventral striatum was expected to dominate. The model predicted that working memory ability would exhibit (1) early weakness in youth high in acting without thinking but (2) growing strength in those high in sensation seeking. In addition, it predicted that (3) acting without thinking would be more strongly related to risk and externalizing behavior than sensation seeking. Finally, it predicted that (4) controlling for acting without thinking, sensation seeking would predict later increases in risky and externalizing behavior. All four of these predictions were confirmed. The results indicate that the rise in sensation seeking that occurs during adolescence is not accompanied by a deficit in executive function and therefore requires different intervention strategies from those for youth whose impulsivity is characterized by early signs of acting without thinking., (© 2011 Blackwell Publishing Ltd.)

Preclinical studies of gestational cocaine exposure (GCE) show evidence of changes in brain function at the anatomical, physiological, and behavioral levels, to include effects on developing dopaminergic systems. In contrast, human studies have produced less consistent results, with most showing small effects or no effects on developmental outcomes. Important changes in brain structure and function occur through adolescence, therefore it is possible that prenatal cocaine exposure has latent effects on neurocognitive (NC) outcome that do not manifest until adolescence or young adulthood. We examined NC function using a set of 5 tasks designed to tap 4 different systems: inhibitory control, working memory, receptive language, and incidental memory. For each NC task, data were collected longitudinally at ages 12, 14.5 and 17 years and examined using generalized estimating equations. One hundred and nine children completed at least two of the three evaluations. Covariates included in the final model were assessment number, gender, participant age at first assessment, caregiver depression, and two composites from the Home Observation for Measurement of the Environment (HOME), Environmental Stimulation and Parental Nurturance. We found no cocaine effects on inhibitory control, working memory, or receptive language (p=0.18). GCE effects were observed on incidental face memory task (p=0.055), and GCE by assessment number interaction effects were seen on the incidental word memory task (p=0.031). Participant performance on inhibitory control, working memory, and receptive language tasks improved over time. HOME Environmental Stimulation composite was associated with better receptive language functioning. With a larger sample size smaller differences between groups may have been detected. This report shows no evidence of latent effects of GCE on inhibitory control, working memory, or receptive language. GCE effects were observed on the incidental face memory task, and GCE by assessment number interaction effects was seen on the incidental word memory task., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The effects of early life experience on later brain structure and function have been studied extensively in animals, yet the relationship between childhood experience and normal brain development in humans remains largely unknown. Using a unique longitudinal data set including ecologically valid in-home measures of early experience during childhood (at age 4 and 8 years) and high-resolution structural brain imaging during adolescence (mean age 14 years), we examined the effects on later brain morphology of two dimensions of early experience: parental nurturance and environmental stimulation. Parental nurturance at age 4 predicts the volume of the left hippocampus in adolescence, with better nurturance associated with smaller hippocampal volume. In contrast, environmental stimulation did not correlate with hippocampal volume. Moreover, the association between hippocampal volume and parental nurturance disappears at age 8, supporting the existence of a sensitive developmental period for brain maturation. These findings indicate that variation in normal childhood experience is associated with differences in brain morphology, and hippocampal volume is specifically associated with early parental nurturance. Our results provide neuroimaging evidence supporting the important role of warm parental care during early childhood for brain maturation.

Background: Concern for effects of gestational cocaine exposure (GCE) on human neurocognitive (NC) development is based on effects of cocaine on blood flow to the fetus and impact of cocaine on developing monoaminergic systems. GCE has been shown to affect language, attention and perceptual reasoning skills., Objective: Our objective was to investigate effects of GCE on 7 NC systems, assessed behaviorally in middle school-aged, low socioeconomic status subjects followed prospectively since birth., Methods: 55 GCE and 65 non-exposed Control subjects were tested with a battery of 14 tasks adapted from neuroimaging and lesion literature designed to tap 3 frontal systems (Cognitive Control, Working Memory, and Reward Processing) and 4 non-frontal systems (Language, Memory, Spatial Cognition, and Visual Cognition). Using multivariate analysis of covariance, we assessed the relation between NC functioning and GCE status with the following covariates: age at testing; gender; gestational exposure to cigarettes, alcohol and marijuana; foster care placement; caregiver current cocaine use; and two indices of childhood environment., Results: None of the analyses showed an effect of GCE on NC function. In contrast, child characteristics, including age at testing and childhood environment, were associated with NC function., Conclusions: In this cohort there is either no effect of GCE on NC function at middle school age, or that effect is less pronounced than the effect of age or childhood environment.

Initiation of drug use and other risky behavior in preadolescence is associated with poor developmental outcomes. In this research, we examine models that ascribe the trajectory to (a) weak executive cognitive function (ECF), (b) early manifestation of externalizing problems, or (c) heightened levels of trait impulsivity. We test the explanatory power of these factors in a structural equation model with a community sample of 387 preadolescents ages 10-12 years. Participants were tested with a computerized battery of tasks to assess three facets of ECF (working memory, cognitive control, and reward processing) as well as with an audio assisted computerized self-interview to obtain reports of impulsivity and risk behaviors (use of cigarettes and alcohol as well as engaging in fighting and gambling for money) and a self-administered questionnaire to assess externalizing and internalizing problems. The best fitting model explained both early risk taking and externalizing symptoms as the result of individual differences in impulsivity. Although no ECF was directly related to risk taking, working memory and one measure of reward processing performance (reversal learning) were inversely related to impulsivity. The results are discussed in regard to theories of early risk taking with particular focus on the potential relation between ECF and impulsive behavior tendencies and the implications for early intervention to prevent the dysfunctional trajectory associated with early risk behavior.

The effects of environmental stimulation and parental nurturance on brain development have been studied extensively in animals. Much less is known about the relations between childhood experience and cognitive development in humans. Using a longitudinally collected data set with ecologically valid in-home measures of childhood experience and later in-laboratory behavioral measures of cognitive ability, we were able to test hypotheses concerning the effects of environmental stimulation and parental nurturance. A double dissociation was found: On the one hand, there was a selective relation between parental nurturance and memory development, consistent with the animal literature on maternal buffering of stress hormone effects on hippocampal development. On the other hand, there was a selective relation between environmental stimulation and language development. The relevance of these findings to socioeconomic gradients in cognitive ability is discussed.

Gambling has increased in the past decade, with growing opportunities for initiation by adolescents. More limited data, however, are available regarding gambling in preadolescents. In the investigation reported here, gambling for money was the most common risk behavior in 10- to 12-year-olds. Gamblers were more likely to be white, have tried alcohol, have positive affect toward gambling, and have friends who gamble.

Objective: To assess the effect of gestational cocaine exposure on the prefrontal cortex (PFC) with functional magnetic resonance imaging (fMRI)., Study Design: Using an n-back task, we obtained fMRI with a 3T Siemens scanner on 49 adolescents, 25 who were exposed to cocaine and 24 who were not exposed. The primary outcome was PFC activation during task performance. Five functionally derived regions of interest (ROI) were defined; in addition, 2 a priori anatomical ROIs were generated for Brodmann regions 10 and 46., Results: Of the 49 adolescents who underwent imaging, data from 17 who were exposed to cocaine and 17 who were not exposed were in the final analysis. Groups had similar performance on the n-back task (P >/= .4), with both showing a fewer number of correct responses on the 2-back than the 1-back (P < .001), indicating increased demands on working memory with greater task difficulty. In functionally derived ROIs, imaging results showed increased activation for both groups in the 2-back versus the 1-back condition. In anatomical ROIs, both groups showed greater activation in the 2-back versus the 1-back condition, with activation in the non-exposed group proportionally greater for the left prefrontal region (P = .05)., Conclusion: In this sample of adolescents, participants who were exposed to cocaine and participants who were not exposed were similar in performance on an executive function task and in fMRI activation patterns during task performance.

Objective: Comparison of outcomes of infants with respiratory distress syndrome (RDS), post-surfactant, extubated to synchronized nasal intermittent positive pressure ventilation (SNIPPV) or continued on conventional ventilation (CV)., Study Design: Prospective post-surfactant randomized controlled trial of primary mode SNIPPV compared with CV in infants (born from July 2000 to March 2005) with birth weights (BW) of 600 to 1250 g. Primary mode SNIPPV was defined as its use in the acute phase of RDS, following the administration of the first dose of surfactant., Result: There were no significant differences in the maternal demographics, antenatal steroid use, mode of delivery, BW, gestational age, gender or Apgar at 5 min between infants continued on CV (n=21) and those extubated to primary mode SNIPPV (n=20). Significantly, more babies in the CV group had the primary outcome of bronchopulmonary dysplasia (BPD)/death, compared to the SNIPPV group (52 versus 20%, P=0.03). There was no difference in the incidence of other common neonatal morbidities. There were no differences in the Mental or Psychomotor Developmental Index scores on follow-up between the two groups., Conclusion: Infants of BW 600 to 1250 g with RDS receiving surfactant with early extubation to SNIPPV had a significantly lower incidence of BPD/death. Primary mode SNIPPV is a feasible method of ventilation in small premature infants.

Growing up in poverty is associated with reduced cognitive achievement as measured by standardized intelligence tests, but little is known about the underlying neurocognitive systems responsible for this effect. We administered a battery of tasks designed to tax-specific neurocognitive systems to healthy low and middle SES children screened for medical history and matched for age, gender and ethnicity. Higher SES was associated with better performance on the tasks, as expected, but the SES disparity was significantly nonuniform across neurocognitive systems. Pronounced differences were found in Left perisylvian/Language and Medial temporal/Memory systems, along with significant differences in Lateral/Prefrontal/Working memory and Anterior cingulate/Cognitive control and smaller, nonsignificant differences in Occipitotemporal/Pattern vision and Parietal/Spatial cognition.

Hypothesis: Site-specific variables that contribute to the pathogenesis of bronchopulmonary dysplasia (BPD) can be identified., Objectives: To evaluate the demographic, nutrition and growth characteristics of infants at risk for developing BPD at two neonatal intensive care units (NICUs: sites A and O)., Study Design: Records of 306 infants of < or = [corrected] 30 weeks gestational age (GA) who survived to at least 36 weeks postmenstrual age were retrospectively reviewed. Data were obtained for maternal and neonatal demographics, weights, total fluids, calories, carbohydrate, protein and fat intake at birth, 7, 14, 21 and 28 days of life., Results: BPD rates were not different at the two sites. No statistical differences were noted in the incidence of maternal chorioamnionitis, pregnancy-induced hypertension or use of antenatal steroids among infants who developed BPD (n = 169) and those who did not (n = 137). White race, birth weight, respiratory distress syndrome requiring surfactant, sepsis and patent ductus arteriosus were significantly associated (all P < or =0.03) with BPD. After controlling for significant confounding variables, infants who developed BPD had significantly (P < 0.001) less weight gain, received less calories and fat in the first postnatal month. In the 26 to 28 weeks GA group, the odds of getting BPD were 5.4 (95%CI: 1.4 to 21.3) times greater for site A than site O (P = 0.017)., Conclusion: Our analysis suggests that while some decrease in BPD can be achieved by focusing on ventilation/oxygen use, this approach is unlikely to impact on the youngest infants.

Objective: To document school performance (pass/fail, grade point average, reading level, standardized test scores, absences) of cocaine-exposed and control children., Design: A total of 135 children (62 with gestational cocaine exposure and 73 without), who were enrolled at birth, followed prospectively and have completed the fourth grade, were evaluated using report card data, standardized test results, teacher and parent report, and natal and early childhood data. Successful grade progression was defined as completing grades 1 through 4 without being retained., Results: Cocaine-exposed (cocaine-exposed presented first) and control children were similar in school performance: successful grade progression (71% vs. 84%), Grade Point Average (2.4+/-0.8 vs. 2.6+/-0.7), reading below grade level (30% vs. 28%) and standardized test scores below average (reading [32% vs. 35%], math [57% vs. 44%], science [39% vs. 36%]); all p > or = 0.10. Children with successful progression, regardless of cocaine exposure, had higher Full Scale Intelligence Quotient and better home environments., Conclusion: In this inner-city cohort, cocaine-exposed and control children had similar poor school performance. Better home environment and higher Intelligence Quotient conferred an advantage for successful grade progression, regardless of gestational cocaine exposure.

Children with gestational cocaine exposure may be at risk of difficulties in attentional functioning and impulse control. We administered the Gordon Diagnostic System and subtests of the Halstead-Reitan Battery to inner-city children with (COC) and without (CON) gestational cocaine exposure at age 10 years. Subtle differences were found between groups, with differences in Gordon Delay (Efficiency Ratio) and Gordon Distractibility (Total Commissions). With these two exceptions, children had similar performance, with both groups performing poorly. Attentional functioning and impulse control were also assessed in school. Teachers did not distinguish between COC and CON, although both groups presented behavioral problems. We conclude that gestational cocaine exposure may be associated with subtle problems in attention and impulse control, putting exposed children at higher risk of developing significant behavioral problems as cognitive demands increase.

Objective: Although terminal sedation (TS) has generally been seen as legal and ethically acceptable, ethical and moral issues remain. Little is known about the use of TS in general clinical practice and about how TS is viewed by physicians, given moral and ethical concerns. The objectives of this study are (1) to describe attitudes of physicians regarding terminal sedation; (2) to explore demographic characteristics, such as age, gender, subspecialty, and number of years in practice, that might be related to the use of TS; and (3) to compare physicians who have and have not used TS on the degree to which they view TS as moral and consistent with their professional and personal ethics., Methods: An anonymous survey of New Jersey physicians was conducted at the University of Medicine and Dentistry of New Jersey-School of Osteopathic Medicine. A 39-item questionnaire assessing general opinions about, experiences with, and religious, moral, ethical attitudes toward TS and other end-of-life treatments was utilized., Results: A majority of physicians (73%) had used TS for a patient. Most (93%) said there were circumstances under which they would use TS. With regard to questions about whether TS would be "immoral," "would violate my religious beliefs," "would violate my professional ethics" and "is inconsistent with the physician's role of preserving life," approximately 55% of those who have used TS disagreed; for those who have not used TS, approximately 35% disagreed., Significance of Results: Professional education and opportunities for discussion appear necessary to help reconcile the conflicts raised in the use of this end-of-life treatment strategy.

Conventional interval dosing (CID) and extended interval dosing (EID) of gentamicin were compared in preterm infants. Gentamicin peak and trough levels, serum creatinine, urine output, and hearing screens were obtained in 40 preterm infants. Results suggest that EID is safe, provides gentamicin levels in desirable ranges (peak, 5 to 12 microg/mL; trough < 2 microg/mL), and reduces dosage adjustments.

The objective of this study was to analyze if repetitive administration of antenatal steroids (ANS) had an adverse impact on neonatal outcome at hospital discharge in premature infants. We used a retrospective analysis of 306 infants of gestational age (GA) < or = 34 weeks born between January 1997 and June 1999. A detailed review of maternal and neonatal charts was done. Seventy-one percent (216/306) received ANS. While there was no difference in birth weight (1.37 +/- 0.04 versus 1.49 +/- 0.06 kg; p = 0.09), infants receiving ANS were of lesser GA (29.5 +/- 0.2 versus 30.5 +/- 0.4 weeks; p = 0.02). More babies who received ANS had clinical evidence of gastroesophageal reflux (GER) [59/216 (27%) versus 11/90 (12%); p = 0.007]. After correcting for GA, infants receiving ANS were less likely to need surfactant (p = 0.03) and more likely to be diagnosed with clinical GER (p = 0.02). Ninety (29%) infants received no ANS, 47 (15%) received a suboptimal course, 112 (37%) infants received 1 course of ANS, and 57 (19%) infants received > or = 2 courses. There was a significant increase in the incidence of GER with increasing courses of ANS: 0 course 11/90 (12%), suboptimal 12/47 (26%), 1 course 28/112 (25%), 2 or more courses 18/57 (32%); p = 0.006, linear trend. The increased incidence of GER (p = 0.01) still held true among infants who had GER confirmed by a pH-probe study. Use of ANS is associated with a significantly decreased need for surfactant; however, there is an increased incidence of GER.

Background: Late-onset sepsis in the NICU is a major problem associated with high morbidity and mortality., Objective: To determine if clinical characteristics, hematological parameters and serial measurements of serum IL-6 and IL-8 can detect late-onset sepsis in premature neonates prior to positive blood cultures., Design: The study was done in 2 phases. The first phase (S1) was a retrospective evaluation of clinical signs and timing of blood culture positivity in all neonates with late-onset cultures proven sepsis from 1991-1998. The second phase (S2) was a prospective study that enrolled infants > or = 72 hours old, suspected of sepsis based on the presence of criteria identified in S1. At that time (day 0), blood was drawn for a CBC with differential, blood culture, IL-6 and IL-8 levels; cytokine levels were repeated on day 1. Infants with positive cultures were diagnosed as confirmed sepsis; those with negative cultures, as no sepsis., Results: S1: Of the 48 episodes of culture proven, late-onset sepsis, 54% of the blood cultures were positive by 24 hours and 90% by 48 hours. The most common presenting signs were desaturations (50%) and increased gastric residuals (33%); I/T ratio > 0.16 differentiated between gram-positive, negative and fungal infections (p = 0.007). S2: 27 infants were enrolled. Eight (mean [SEM] gestational age of 28.2 [0.94] weeks; birth weight of 1.15 [0.11] kg) had positive blood cultures; 19 (gestational age of 27.7 [0.9] weeks; birth weight of 1.06 [0.13] kg) had no sepsis. Infants with sepsis were more likely to have apnea/bradycardia (p = 0.002); no differences in hematological profile, as compared to those with no sepsis. Seven (88%) infants had positive blood cultures by 48 hours. Median values of IL-6 (pg/ml) were higher in infants with sepsis vs. those with no sepsis on days 0 [40 vs. 13] (p = 0.03) and 1 [24 vs. 9] (p < 0.001). IL-8 levels were not significantly different., Conclusions: In both S1 and S2, a majority of the blood cultures were positive by 48 hours. IL-6 levels on days 0 and 1 were significantly higher in infants with confirmed sepsis, prior to the blood culture being positive. IL-6 levels may be useful in the initiation as well as early termination of antibiotic therapy in late-onset neonatal sepsis.

Background: Inner-city children are frequently exposed to violence; however, there are few data regarding the psychological and academic correlates of such exposure in young children at school entry., Objectives: To document exposure to violence in inner-city children aged 7 years; assess their feelings of distress; and evaluate the relationships of exposure to violence with school performance, behavior, and self-esteem., Setting: A study center in an inner-city hospital., Participants: One hundred nineteen inner-city children evaluated at age 7 years; 119 caregivers (biological and foster)., Design: As part of a longitudinal study, children were administered the following by a masked examiner: Things I Have Seen and Heard (TISH) to assess exposure to violence; Levonn, a cartoon-based interview for assessing children's distress symptoms; and the Culture-Free Self-Esteem Inventory, Second Edition. School performance was assessed by school reports and child behavior by the Child Behavior Checklist (CBCL), the Parent Report Form, and the Teacher Report Form. Caregivers for children were administered the parent report version of the Checklist of Children's Distress Symptoms (CCDS-PRV) as well as the CBCL Parent Report Form., Main Outcome Measures: Exposure to violence (TISH); feelings of distress (Levonn); school performance; behavior (CBCL Parent Report Form and CBCL Teacher Report Form); and self-esteem (Culture-Free Self-Esteem Inventory)., Results: We found that these children were frequently exposed to violence. For example, 75% had heard gun shots, 60% had seen drug deals, 18% had seen a dead body outside, and 10% had seen a shooting or stabbing in the home (TISH). Many showed signs of depression and anxiety; eg, 61% worried some or a lot of the time that they might get killed or die and 19% sometimes wished they were dead (Levonn). Higher exposure to violence (TISH Total Violence score) was correlated with higher Levonn composite scores for depression and anxiety and with lower self-esteem (P< or =.04), and was also associated with lower grade point average and more days of school absence (P< or =.02). Caregiver assessment of child anxiety correlated poorly with child report of anxiety (P =.58)., Conclusions: Young inner-city children have a high exposure to violence by age 7 years; many show signs of distress that frequently are not recognized by caregivers. Further, higher exposure to violence in children correlates with poorer performance in school, symptoms of anxiety and depression, and lower self-esteem.

At age 6 years, a cohort of non-asphyxiated children, 52 with gestational cocaine exposure and 63 control subjects, underwent a neurologic examination. Groups did not differ on any aspect of the examination. This finding, while reassuring, does not exclude the possibility of more subtle deficits.

Children with in utero cocaine exposure may be at risk for adverse neurodevelopmental outcome. To evaluate such outcome in young children, we administered the Battelle Developmental Inventory (BDI) to a group of inner-city children with (COC) and without (CON) in utero cocaine exposure at ages 3 and 5 years. Sixty-five COC and 68 CON, similar at age of testing, were evaluated at both time points by examiners masked to child group status. Both groups scored poorly and worsened over time. Although Total BDI raw scores were lower in the COC group than in the CON group at 3 years, this difference was related to postnatal environmental factors, caregiver (p = .022), and home environment (p = .010), not to in utero cocaine exposure (p = .88). At 5 years, the Total BDI score was related to the home environment (p < .001) but not to the caregiver (p = .36) or in utero cocaine exposure (p = .83). We conclude that inner-city children are at risk for adverse developmental outcome regardless of in utero cocaine exposure.

To evaluate the problem-solving abilities of a cohort of inner-city cocaine-exposed children and controls, children were invited to play with the Goodman Lock Box, a large red and blue box with 10 compartments, each having a different lock and toy. Examiners, blinded to the children's group status, coded the children's activities during the 6.5-minute play period. Nineteen behaviors were collapsed into three outcomes: Aimless Actions, Competence, and Mental Organization. Groups' scores were compared with scores of the Goodman standardization sample of mixed socioeconomic status preschoolers. Seventy-three cocaine-exposed children and 82 controls were evaluated at age 3.5 years; of these, 58 cocaine-exposed and 63 controls were reevaluated at age 4.5 years. The groups' scores did not differ on any outcome at either time point (p > or = .22). However, both groups' Mental Organization scores were consistently lower than the Goodman group at each age (p < .01). This high-risk cohort may experience problems functioning in more complex environments such as the classroom.

Objective: To evaluate the effects of maternal magnesium sulfate treatment on newborn outcome., Methods: Subjects were newborn infants delivered at > or = 34 weeks of gestation whose mothers received a minimum of 12 hours of intravenous MgSO4 therapy before delivery. Control infants were the next born infants of similar gestational age. Outcome recorded at delivery included Apgar scores, whether resuscitation was required, and whether respiratory depression or decreased tone were noted by the physician in attendance. Pneumocardiograms on magnesium-exposed and control infants, obtained within 6 to 18 hours after delivery, were analyzed postdischarge by a single investigator who was blinded to group. The nursery course, feeding patterns, time to first stool, and time to first void were recorded. All patient care decisions, including admission to the neonatal intensive care unit (NICU) or term nursery, were independent of study protocol., Results: A total of 26 magnesium-exposed and 26 control infants were enrolled. The mean total dose of MgSO4 before delivery was 51.2+/-24 gm; the mean duration of therapy was 23.1+/-10 hours. The mean maternal serum magnesium level before delivery was 5.8+/-1.1 mg/dl. The infants' mean cord or initial serum magnesium level was 5.2+/-1.0 mg/dl, which correlated with the maternal magnesium level before delivery (r=0.81, p < 0.001). MgSO4-exposed infants had a higher incidence of hypotonia and lower median Apgar scores than control infants (p < 0.001). However, there was no association between adverse outcomes and maternal serum magnesium concentrations at delivery, duration of treatment, or dose of MgSO4. No difference in dose or length of maternal MgSO4 treatment was noted between infants admitted to term nursery and those admitted to NICU. Pneumocardiogram data were similar between MgSO4-exposed and control infants (all p > or = 0.16). There were no significant differences in number of episodes of feeding intolerance or in time to first stool or void between MgSO4-exposed and control infants (all p > or = 0.31)., Conclusion: Infants born to mothers treated with MgSO4 were more likely to be hypotonic and have lower Apgar scores at birth. Beyond the immediate postdelivery period, there were no additional complications in this cohort attributable to prenatal MgSO4 exposure. We suggest that pediatricians attend deliveries of magnesium-exposed infants.

Objective: To define characteristics that differentiate inner-city children with Average or above-Average Full Scale IQ scores (> or =90) from those with below-Average scores (<90)., Design: As part of a prospective study of children with and without in utero cocaine exposure tested at age 4 years on the Wechsler Preschool and Primary Scales of Intelligence-Revised, we found that, taken together, only 32 (21%) scored at or above 90 whereas 118 (79%) scored below 90. The groups (IQ> or =90 and IQ<90) were compared on prenatal, natal, and postnatal factors., Setting: A study center in an inner-city hospital., Participants: One hundred-fifty children of low socioeconomic status, 34 weeks' gestational age or older, and nonasphyxiated at birth, who had intelligence testing at age 4 years; 150 caregivers (biological and foster)., Main Outcome Measures: Association of Full Scale IQ with prenatal, natal, and postnatal characteristics (including caregiver-child interaction measured by the Parent Caregiver Involvement Scale [PCIS], and home environment measured by the Home Observation for Measurement of the Environment [HOME])., Results: The group of children with IQs at or above 90 (n = 32) did not differ from the group with IQs below 90 (n = 118) in prenatal or natal characteristics (all P> or =.18) or proportion in foster care, attendance at day care or Head Start, continued caregiver cocaine use, or parental IQ. Children with IQs at or above 90 had more developmentally appropriate interaction by caregivers (P=.043) and higher scores on 6 of 8 subscales and Total HOME (P< or =.05) than the group of children with IQs below 90., Conclusions: Two postnatal factors, home environment and caregiver-child interaction, were associated with Full Scale IQ scores at or above 90 whereas prenatal and natal factors were not. These potentially malleable postnatal factors can be targeted for change to improve cognitive outcome of inner-city children.

Objective: To determine if in utero cocaine exposure affects IQ scores in children at age 4 years., Design: A prospective, longitudinal evaluation by blinded examiners of the IQ scores of cocaine-exposed and control children of low socioeconomic status who have been observed since birth., Setting: A study center in an inner-city hospital., Participants: One hundred one children with in utero cocaine exposure and 118 control children, all of whom were 34 weeks' gestational age or older and nonasphyxiated at birth., Main Outcome Measure: Intelligence quotient scores on a standardized intelligence test, the Wechsler preschool and Primary Scale of Intelligence--Revised., Results: Seventy-one cocaine-exposed and 78 control children were administered the Wechsler Preschool and Primary Scale of Intelligence--Revised. Maternal, natal, and 30-month characteristics of the children tested did not differ from those not tested. Groups did not differ on mean Performance (83.2 vs 87.0), Verbal (79.0 vs 80.8), or Full Scale (79.0 vs 81.9) IQ scores (all P > or = .10 [values for cocaine-exposed children given first]). None of these 3 scores was associated with cocaine exposure in multivariate linear regressions. Although cocaine-exposed and control groups did not differ in outcome, 93% of cocaine-exposed and 96% of control children had Full Scale IQ scores below 100, the mean IQ score for the test., Conclusions: In an inner-city cohort, IQ scores did not differ between cocaine-exposed and control children. However, both groups performed poorly.

Objectives: The purpose of this study was to investigate (1) the presence of Clostridium difficile toxin in patients in the newborn intensive care unit and (2) the association of C. difficile toxin with gastrointestinal tract symptoms in this population., Study Design: A prospective, masked study was done in which twice-weekly stool specimens of subjects hospitalized in a newborn intensive care unit during a 4-month period were analyzed for C. difficile toxin A by enzyme immunoassay. Daily data collection included infant clinical status, stool frequency and character, presence of gastrointestinal tract symptoms, and actions taken for gastrointestinal tract symptoms. Infants hospitalized 5 or more days who had at least two stool assays comprised the study population. For data analysis, an infant with C. difficile toxin-positive status was defined as an infant with two or more toxin-positive stools., Results: Of 87 infants who met study criteria, 42 (48%) had toxin-negative and 45 (52%) toxin-positive results on at least one specimen. Of the infants with toxin-positive findings, 27 (31%) had two or more positive stool assays and comprised the comparison group. The infants with toxin-positive results were smaller, less mature, and had a longer hospital stay than infants with toxin-negative results (p < 0.001). Infants with toxin-positive findings had more days per infant with frequent (> 6) stools and abnormal stools (p < 0.001). The total number of symptom days was 8.2 +/- 5.7 in infants in the toxin-positive group versus 2.2 +/- 2.2 in those in the toxin-negative group (p < 0.001). The mean number of times stools were sent for evaluation and culture was greater in infants with toxin-positive findings (p < or = 0.012) whereas there was no difference in the number of times oral feedings were withheld from infants or infants had abdominal films obtained (p > or = 0.18)., Conclusions: Infants hospitalized in our newborn intensive care unit frequently had stools positive for C. difficile toxin A. When compared with infants with toxin-negative findings, infants with colonization had an increased number of days with gastrointestinal tract symptoms.

A cohort of children of low socioeconomic status, 76 with in utero cocaine exposure and 81 control subjects, was assessed for early language development at 2 1/2 years of age by a masked examiner using the Preschool Language Scale. There were no differences between groups in expressive, receptive, or total language score (all p > or = 0.57). Physicians caring for cocaine-exposed children with early language delay should not automatically ascribe the delay to cocaine exposure but should initiate a standard evaluation for language delay.

Play behavior was compared between toddlers with in utero cocaine exposure and controls of similar low socioeconomic status enrolled at birth in a prospective, masked study. At 18 and 24 months, 83 cocaine-exposed and 93 control toddlers were videotaped playing on their own for 15 minutes. An observer who was off-site and unaware of project purpose or drug exposure status of toddlers recorded the most cognitively complex play activity per 15-second interval. In a total of 315 play sessions, the groups did not differ in middle and highest level of play achieved at either 18 or 24 months (p > or = .27). After controlling for confounders, the proportions of play behavior in each of six play categories were similar in the two groups at both 18 and 24 months (p > or = .42). We conclude that in utero cocaine exposure was not associated with differences in play behavior in this cohort of cocaine-exposed and control toddlers.

Objective: To evaluate the effectiveness in low birth weight (LBW) infants of the currently recommended immunization schedule for conjugated Haemophilus influenzae type b (HIB) vaccine., Methods: We quantified antibody responses in 36 preterm infants with a mean birth weight of 1060 g and a mean gestational age of 28 weeks. Infants were immunized with 0.5 mL of HIB vaccine at 2 and 4 months' postnatal age. Specific HIB antibodies were quantified on cord blood, immediately before each immunization and 2 months after the last immunization., Results: Even though the geometric mean titers increased significantly during the study period, they were still markedly lower than values reported in term infants. After the second immunization, only 24 infants (67%) attained antibody concentrations of more than 0.25 micrograms/mL, defined as seropositivity. Also, only 53% of infants achieved antibody concentrations of more than 1.0 micrograms/mL compared with 92% as reported in term infants. Stepwise logistic regression identified gestational age of 27 weeks or less and the amount of intravenous immunoglobulin received as the significant variables influencing the antibody response after the first immunization. The incidence of side effects was negligible., Conclusions: We conclude that LBW infants, and especially those born at 27 or less weeks' gestation, do not respond as effectively to the HIB vaccine. We speculate that reevaluation of the current immunization schedule may be required for very LBW infants.

Cocaine use by pregnant women has increased dramatically in recent years. To assess the effect of maternal cocaine use on infant outcome, we enrolled 224 women (105 cocaine users, 119 control subjects) and their infants (all of 34 weeks or more gestational age and nonasphyxiated) in a prospective, blinded study. Results showed that infants exposed to cocaine were more likely to be admitted to the newborn intensive care unit, be treated for congenital syphilis, have a greater length of stay, and be discharged to a person other than the mother (all p < 0.01). Birth weight and head circumference, adjusted for gestational age, were smaller in the infants exposed to cocaine than in control infants (p < 0.001). After statistically controlling for cigarette use and other confounders, however, the odds of infants exposed to cocaine and control infants having birth weight and head circumferences less than the 25th percentile for gestational age did not differ (both p > 0.80). Infants of cocaine-using mothers and control subjects had a similar incidence of abnormal cranial and renal ultrasonographic findings and abnormal pneumocardiograms (all p > or = 0.32). We conclude that in this cohort of nonasphyxiated infants of 34 weeks or more gestational age, infants exposed to cocaine had more medical and social problems than control infants but did not differ statistically in the incidence of severe growth retardation, abnormal cranial or renal ultrasonographic findings, or abnormal pneumocardiograms. We suggest that natal interventions for the nonasphyxiated term and near-term infant exposed to cocaine should include a careful history and physical examination, follow-up plans, and social service involvement.

This prospective, blinded study evaluates the effect of in utero cocaine exposure on outcome of nonasphyxiated, term and near-term children born to women of low socioeconomic status. Two hundred nineteen children (101 cocaine-exposed and 118 control) with extensive natal evaluations are evaluated at 6-month intervals. We report here growth, performance on the Bayley Scales of Infant Development (BSID) through 30 months of age, and tone and reflexes at 6 and 12 months. To date, subjects have had 816 follow-up visits, with subject retention greater than or equal to 73%. Cocaine-exposed children showed statistically lower mean weights and smaller mean head circumferences than control children over the 30-month follow-up period (p < or = .011). The percentage of children with abnormal tone and reflexes, however, was similar in the two groups at 6 and 12 months (p > or = .34). Mean BSID Mental Development Index (MDI) and Psychomotor Development Index scores did not differ between the two groups (p > or = .16), although both groups' scores decreased over time (p < .001). Of concern, both cocaine-exposed and control groups had lower mean MDI scores than those published for a group of children of higher socioeconomic status. We conclude that, in our cohort of children, low socioeconomic or minority status may have had a substantial influence on BSID scores whereas in utero drug exposure did not.

To determine if there is a specific postnatal (PNA) or postconceptional age (PCA) at which ventilated preterm infants respond to beta-agonists, we evaluated 15 infants with a mean gestational age of 26.5 +/- 1.5 weeks and mean birth weight of 0.89 +/- 0.23 kg who required mechanical ventilation at 10 days of age. Weekly pulmonary function testing (PFT) was performed before and 1 h after administration of albuterol. Taking the group as a whole, as well as individual babies, regression analysis showed no relationship between positive response and either PNA or PCA. Evaluation of individual infants, however, showed that some consistently responded to beta-agonists whereas others did not. We recommend individual PFT to identify those infants who will benefit from use of beta-agonists.

Aspiration is a potential problem in intubated infants who are fed enterally. In this prospective study, intubated preterm infants were fed orogastrically or oroduodenally. Aspiration was assessed by examining endotracheal aspirates for evidence of blue-colored dye. None of the babies had blue-colored endotracheal secretions when fed by either route. Heart and respiratory rates, blood pressure, and transcutaneous oxygen and carbon dioxide measurements were recorded at each interval of the study. There were no significant differences from baseline for these measurements. These findings indicate that there is no significant aspiration in intubated preterm infants who are fed by the orogastric or the oroduodenal route.

Serial serum zinc concentrations were measured in 31 relatively well, growing premature infants during the first 26 weeks of life. Zinc concentrations declined progressively from 17.9 mumol (1.17 mg/l) at birth (normal adult value) to 8.9 mumol (0.58 mg/l) at 6 weeks of age despite a zinc intake of greater than 13.7 mumol (900 micrograms)/kg/day after the second week of life. The serum zinc increased after 16 weeks of age to 10.7 mumol/dl (0.7 mg/l). No infant demonstrated clinical signs of zinc deficiency. This data may serve as a reference against which serum zinc concentrations in other premature infants may be compared in order to help define the deficiency state.

In order to define the range of serum copper concentrations in preterm infants and to determine the effect of growth upon these values, serial serum copper concentrations were measured in 26 preterm infants over their first six weeks of life. Fourteen healthy, growing preterm infants (Group I) had mean serum copper concentrations below 32 microgram/dl throughout the study. Clinical and hematologic signs of copper deficiency which responded promptly to the oral administration of copper sulfate were noted in five of these 14 infants. Twelve ill preterm infants (Group II-A), who received parenteral nutrition without supplemental copper and had slow rates of growth, had mean serum copper concentrations above 50 micrograms/dl after the first week of life. Seven surviving from Group II-A (Group II-B) had a decrease in mean serum copper concentrations to values similar to those in Group I after two weeks of oral feedings and resumption of normal growth. Our findings suggest that preterm infants who have normal growth while receiving oral feedings are at significant risk for developing copper deficiency.