Teens with heavy prenatal cocaine exposure respond to experimental social provocation with escape not aggression.

Preclinical data show that, compared to no exposure, prenatal cocaine exposure (PCE) has age-dependent effects on social interaction and aggression. The aim of this clinical study was to determine how heavy/persistent PCE--after controlling for other prenatal drug exposures, sex and postnatal factors--predicts behavioral sensitivity to provocation (i.e., reactive aggression) using a well-validated human laboratory model of aggression. African American teens (mean=14.2 years old) with histories of heavy/persistent PCE (maternal cocaine use ≥ 2 times/week during pregnancy, or positive maternal or infant urine/meconium test at delivery; n=86) or none/some exposure (NON: maternal cocaine use < 2 times/week during pregnancy; n=330) completed the Point Subtraction Aggression Paradigm. In this task, teens competed in a computer game against a fictitious opponent. There were three possible responses: (a) earn points, to exchange for money later; or (b) "aggress" against the fictitious opponent by subtracting their points; or (c) escape temporarily from point subtraction perpetrated by the fictitious opponent. The PCE group responded significantly more frequently on the escape option than the NON group, but did not differ in aggressive or money-earning responses. These data indicate that PCE-teens provoked with a social stressor exhibit a behavioral preference for escape (negative reinforcement) than for aggressive (retaliatory) or appetitive (point- or money-reinforced) responses. These findings are consistent with preclinical data showing that social provocation of adolescent or young adult offspring after PCE is associated with greater escape behavior, inferring greater submission, social withdrawal, or anxiety, as opposed to aggressive behavior.

PGE2/TXB2 imbalance in neonatal hypoxemic respiratory failure.

BACKGROUND: An imbalance of vaso-constrictor and -dilator mediators has been implicated in the pathogenesis of the pulmonary hypertension accompanying neonatal hypoxemic respiratory failure (NHRF). AIM: To characterize plasma PGE2, TXB2 and their ratio in normal newborns and in those with NHRF. METHODS: Twenty newborns with NHRF received inhaled PGE1 (IPGE1) by jet nebulizer in doses of 25, 50, 150 and 300 ng/kg/min followed by weaning. Blood for PGE2 and TXB2 assay using EIA was available in 8 neonates with NHRF prior to IPGE1. Umbilical cord arterial samples were also obtained at delivery from 10 normal newborns to serve as controls. RESULTS: Compared to normal newborns, those with NHRF had significantly lower PGE2/TXB2 ratios after controlling for preterm gestation (< 37 weeks) and postnatal age (p < 0.05). Notably, all subjects except one in the NHRF group had a value of < 1.0 (range 0.1-1.2) compared to a value of > 1.0 in all subjects in the Control group (range 1.1-5.2). CONCLUSIONS: Lower PGE2/TXB2 ratio in subjects with NHRF compared with controls reflects a predominance of vaso-constrictor activity in these patients as the basis of pulmonary hypertension. Plasma PGE2/TXB2 ratio may have important implications for the diagnosis and treatment of NHRF.

Prenatal alcohol exposure and childhood behavior at age 6 to 7 years: I. dose-response effect.

OBJECTIVE: Moderate to heavy levels of prenatal alcohol exposure have been associated with alterations in child behavior, but limited data are available on adverse effects after low levels of exposure. The objective of this study was to evaluate the dose-response effect of prenatal alcohol exposure for adverse child behavior outcomes at 6 to 7 years of age. METHODS: Beginning in 1986, women attending the urban university-based maternity clinic were routinely screened at their first prenatal visit for alcohol and drug use by trained research assistants from the Fetal Alcohol Research Center. All women reporting alcohol consumption at conception of at least 0.5 oz absolute alcohol/day and a 5% random sample of lower level drinkers and abstainers were invited to participate to be able to identify the associations between alcohol intake and child development. Maternal alcohol, cigarette, and illicit drug use were prospectively assessed during pregnancy and postnatally. The independent variable in this study, prenatal alcohol exposure, was computed as the average absolute alcohol intake (oz) per day across pregnancy. At each prenatal visit, mothers were interviewed about alcohol use during the previous 2 weeks. Quantities and types of alcohol consumed were converted to fluid ounces of absolute alcohol and averaged across visits to generate a summary measure of alcohol exposure throughout pregnancy. Alcohol was initially used as a dichotomous variable comparing children with no prenatal alcohol exposure to children with any exposure. To evaluate the effects of different levels of exposure, the average absolute alcohol intake was relatively arbitrarily categorized into no, low (>0 but <0.3 fl oz of absolute alcohol/day), and moderate/heavy (>/=0.3 fl oz of absolute alcohol/day) for the purpose of this study. Six years later, 665 families were contacted. Ninety-four percent agreed to testing. Exclusions included children who missed multiple test appointments, had major congenital malformations (other than fetal alcohol syndrome), possessed an IQ >2 standard deviations from the sample mean, or had incomplete data. The Achenbach Child Behavior Checklist (CBCL) was used to assess child behavior. The CBCL is a parent questionnaire applicable to children ages 4 to 16 years. It is widely used in the clinical assessment of children's behavior problems and has been extensively used in research. Eight syndrome scales are further grouped into Externalizing or undercontrolled (Aggressive and Delinquent) behavior and Internalizing or overcontrolled (Anxious/Depressed, Somatic Complaints, and Withdrawn) behaviors. Three syndromes (Social, Thought, and Attention Problems) fit neither group. Higher scores are associated with more problem behaviors. Research assistants who were trained and blinded to exposure status independently interviewed the child and caretaker. Data were collected on a broad range of control variables known to influence childhood behavior and/or to be associated with prenatal alcohol exposure. These included perinatal factors of maternal age, education, cigarette, cocaine, and other substances of abuse and the gestational age of the baby. Postnatal factors studied included maternal psychopathology, continuing alcohol and drug use, family structure, socioeconomic status, children's whole blood lead level, and exposure to violence. Data were collected only from black women as there was inadequate representation of other racial groups. STATISTICAL ANALYSES: Statistical analyses were performed using the SPSS statistical package. Frequency distribution, cross-tabulation, odds ratio, and chi(2) tests were used for analyzing categorical data. Continuous data were analyzed using t tests, analyses of variance (ANOVAs) with posthoc tests, and regression analysis. RESULTS: Testing was available for 501 parent-children dyads. Almost one fourth of the women denied alcohol use during pregnancy. Low levels of alcohol use were reported in 63.8% and moderate/heavy use in 13% of pregnancies. Increasing prenatal alcohol exposure was associated with lower birth weight and gestational age, higher lead levels, higher maternal age, and lower education level, prenatal exposure to cocaine and smoking, custody changes, lower socioeconomic status, and paternal drinking and drug use at the time of pregnancy. Children with any prenatal alcohol exposure were more likely to have higher CBCL scores on Externalizing (Aggressive and Delinquent) and Internalizing (Anxious/Depressed and Withdrawn) syndrome scales and the Total Problem Score. The odds ratio of scoring in the clinical range for Delinquent behavior was 3.2 (1.3-7.6) in children with any prenatal exposure to alcohol compared with nonexposed controls. The threshold dose was evaluated with the 3 prenatal alcohol exposure groups. One-way ANOVA revealed a significant between group difference for Externalizing (Aggressive and Delinquent) and the Total Problem Score. (ABSTRACT TRUNCATED)

Neurodevelopmental outcome after congenital diaphragmatic hernia: Extracorporeal membrane oxygenation before and after surgery.

BACKGROUND/PURPOSE: Extracorporeal membrane oxygenation (ECMO) as a treatment of last resort for neonates with persistent pulmonary hypertension of the newborn (PPHN) caused by congenital diaphragmatic hernia (CDH) may be used for preoperative stabilization or postoperative rescue. The aim of this study was to examine the acute and long-term morbidity associated with pre- and postoperative ECMO. METHODS: Neonates born with CDH and needing ECMO were classified into 2 groups. Group 1 consisted of neonates placed on ECMO after CDH surgery. Patients in group 2 underwent preoperative ECMO stabilization. Medical records after birth were evaluated. Growth, neuromotor and cognitive development, hearing, and behavior were evaluated. Student t test and chi(2) were used to determine statistical significance between groups. RESULTS: Subjects in group 2 had significantly more days on ECMO and loop diuretics. Alkalosis was induced for a longer duration in group 2. At follow-up 3 to 9 years later, no differences were found between the 2 groups in growth parameters, neuromotor outcome, or behavior. However, in group 1, 2 of 9 children had significant hearing impairment necessitating amplification compared with 6 of 6 subjects in group 2. CONCLUSIONS: Neonates with CDH first stabilized on ECMO (group 2) had a higher incidence of hearing loss compared with those needing ECMO postrepair (group 1). The etiology of this finding is not clear. This may be secondary to the prolonged period of hyperventilation or general intensive care that is part of the protocol for neonates who are electively stabilized on ECMO preoperatively. J Pediatr Surg 36:539-544.

Teacher-assessed behavior of children prenatally exposed to cocaine.

OBJECTIVE: Prenatal cocaine exposure has been associated with alterations in neonatal behavior and more recently a dose-response relationship has been identified. However, few data are available to address the long-term behavioral effects of prenatal exposures in humans. The specific aim of this report is to evaluate the school-age behavior of children prenatally exposed to cocaine. METHODS: All black non-human immunodeficiency virus-positive participants in a larger pregnancy outcomes study who delivered singleton live born infants between September 1, 1989 and August 31, 1991 were eligible for study participation. Staff members of the larger study extensively screened study participants during pregnancy for cocaine, alcohol, cigarettes, and other illicit drugs. Prenatal drug exposure was defined by maternal history elicited by structured interviews with maternal and infant drug testing as clinically indicated. Cocaine exposure was considered positive if either history or laboratory results were positive. Six years later, 665 families were contacted; 94% agreed to participate. The child, primary caretaker (parent), and, when available, the biologic mothers were tested in our research facilities. Permission was elicited to obtain blinded teacher assessments of child behavior with the Achenbach Teacher's Report Form (TRF). Drug use since the child's birth was assessed by trained researchers using a structured interview. RESULTS: Complete laboratory and teacher data were available for 499 parent-child dyads, with a final sample size for all analyses of 471 (201 cocaine-exposed) after the elimination of mentally retarded subjects. A comparison of relative Externalizing (Aggressive, Delinquent) to Internalizing (Anxious/Depressed, Withdrawn, Somatic Complaints) behaviors of the offspring was computed for the TRF by taking the difference between the 2 subscales to create an Externalizing-Internalizing Difference (T. M. Achenbach, personal communication, 1998). Univariate comparisons revealed that boys were significantly more likely to score in the clinically significant range on total TRF, Externalizing-Internalizing, and Aggressive Behaviors than were girls. Children prenatally exposed to cocaine had higher Externalizing-Internalizing Differences compared with controls but did not have significantly higher scores on any of the other TRF variables. Additionally, boys prenatally exposed to cocaine were twice as likely as controls to have clinically significant scores for externalizing (25% vs 13%) and delinquent behavior (22% vs 11%). Gender, prenatal exposures (cocaine and alcohol), and postnatal risk factors (custody changes, current drug use in the home, child's report of violence exposure) were all related to problem behaviors. Even after controlling for gender, other prenatal substance exposures, and home environment variables, cocaine-exposed children had higher Externalizing-Internalizing Difference scores. Prenatal exposure to alcohol was associated with higher total score, increased attention problems, and more delinquent behaviors. Prenatal exposure to cigarettes was not significantly related to the total TRF score or any of the TRF subscales. Postnatal factors associated with problem behaviors included both changes in custody status and current drug use in the home. Change in custody status of the cocaine-exposed children, but not of the controls, was related to higher total scores on the TRF and more externalizing and aggressive behaviors. Current drug use in the home was associated with higher scores on the externalizing and aggressive subscales. CONCLUSIONS: Results of this study suggest gender-specific behavioral effects related to prenatal cocaine exposure. Prenatal alcohol exposure also had a significant impact on the TRF. Postnatal exposures, including current drug use in the home and the child's report of violence exposure, had an independent effect on teacher-assessed child behavioral problems. (ABSTRACT TRUNCATE

Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993-1994.

OBJECTIVES: The purposes of this study were to report the neurodevelopmental, neurosensory, and functional outcomes of 1151 extremely low birth weight (401-1000 g) survivors cared for in the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network, and to identify medical, social, and environmental factors associated with these outcomes. STUDY DESIGN: A multicenter cohort study in which surviving extremely low birth weight infants born in 1993 and 1994 underwent neurodevelopmental, neurosensory, and functional assessment at 18 to 22 months' corrected age. Data regarding pregnancy and neonatal outcome were collected prospectively. Socioeconomic status and a detailed interim medical history were obtained at the time of the assessment. Logistic regression models were used to identify maternal and neonatal risk factors for poor neurodevelopmental outcome. RESULTS: Of the 1480 infants alive at 18 months of age, 1151 (78%) were evaluated. Study characteristics included a mean birth weight of 796 +/- 135 g, mean gestation (best obstetric dates) 26 +/- 2 weeks, and 47% male. Birth weight distributions of infants included 15 infants at 401 to 500 g; 94 at 501 to 600 g; 208 at 601 to 700 g; 237 at 701 to 800 g; 290 at 801 to 900 g; and 307 at 901 to 1000 g. Twenty-five percent of the children had an abnormal neurologic examination, 37% had a Bayley II Mental Developmental Index <70, 29% had a Psychomotor Developmental Index <70, 9% had vision impairment, and 11% had hearing impairment. Neurologic, developmental, neurosensory, and functional morbidities increased with decreasing birth weight. Factors significantly associated with increased neurodevelopmental morbidity included chronic lung disease, grades 3 to 4 intraventricular hemorrhage/periventricular leukomalacia, steroids for chronic lung disease, necrotizing enterocolitis, and male gender. Factors significantly associated with decreased morbidity included increased birth weight, female gender, higher maternal education, and white race. CONCLUSION: ELBW infants are at significant risk of neurologic abnormalities, developmental delays, and functional delays at 18 to 22 months' corrected age.

Expressive language development of children exposed to cocaine prenatally: literature review and report of a prospective cohort study.

It was hypothesized that prenatal exposure to cocaine and other substances would be related to delayed expressive language development. Speech and language data were available for 458 6-year olds (204 were exposed to cocaine). No significant univariate or multivariate differences by cocaine exposure group were observed. Classification and regression tree modeling was then used to identify language variable composites predictive of cocaine exposure status. Meaningful cut points for two language measures were identified and validated. Children with a type token ratio of less than 0.42 and with fewer than 97 word types were classified into a low language group. Low language children (n = 57) were more likely to be cocaine exposed (63.1%), with cocaine-exposed children 2.4 times more likely to be in the low language group compared with control children after adjustment for covariates. Prenatal cigarette, but not alcohol exposure, was also significantly related to expressive language delays.

EEG abnormalities in survivors of neonatal ECMO: its role as a predictor of neurodevelopmental outcome.

The incidence and site of electroencephalogram (EEG) abnormalities and the efficacy of post-ECMO EEG as a predictor of neurodevelopmental outcome was evaluated in survivors of neonatal extracorporeal membrane oxygenation (ECMO). All survivors of neonatal ECMO with an EEG performed prior to their discharge were included if they had at least 12 months of follow-up. The neurodevelopmental outcome was reported as normal, suspect, and abnormal on the basis of neurological examination and the scores on Bayley Scales of Infant Development or McCarthy Scale of Children's Abilities. EEG abnormalities were noted in 31 (70%) of 44 infants. The distribution of EEG abnormalities was not significantly different for right and left hemispheres. The incidence of abnormal neurodevelopmental outcome was similar in infants with a normal or an abnormal EEG (3 of 13 vs. 7 of 31; p = 0.8). EEG abnormalities had no correlation with neurodevelopmental outcome. We conclude that the high incidence of EEG abnormalities and their lack of correlation with neurodevelopmental outcome would suggest that these abnormalities do not represent permanent brain injury and a single EEG performed after decannulation from ECMO is not helpful in identifying infants at risk of subsequent abnormal neurodevelopmental outcome.

Identifying at risk infants following neonatal extracorporeal membrane oxygenation.

OBJECTIVE: To identify infants at risk of death and abnormal neurodevelopmental outcome following extracorporeal membrane oxygenation (ECMO) in the neonatal period. METHODS: The medical records of 82 neonates treated with ECMO were reviewed to evaluate risk of death. All survivors were followed by neurologic examinations and tested using the Bayley Scales of Infant Development or McCarthy Scale of Children's Abilities, and risk for abnormal neurodevelopmental outcome was assessed. RESULTS: The overall survival was 91% (75 of 82). The mean gestational age and birth weight of nonsurvivors were lower than those of survivors (37 +/- 1 weeks vs 40 +/- 0 weeks; 2734 +/- 230 vs 3325 +/- 69 gm, p < 0.05). Infants who were lost to follow-up (16%) did not differ from those with follow-up in demographic variables or clinical indicators of illness severity. Thirty-five of 63 infants (56%) with follow-up had normal neurodevelopmental outcome. Risk of abnormal outcome was higher in infants requiring assisted ventilation for > or = 15 days (relative risk [RR] 5.5; 95% confidence interval [CI] 2.0 to 14.8), supplemental oxygenation for > or = 22 days (RR 3.1; 95% CI 1.3 to 7.6), and black race (RR 8.9; 95% CI 1.3 to 62.9). None of the neuroimaging studies accurately predicted the neurodevelopmental outcome of these infants. CONCLUSION: We conclude that ECMO in critically ill infants is associated with good survival. The need for prolonged respiratory support may help in identifying infants at risk for abnormal neurodevelopmental outcome.

Prenatal cocaine exposure and child behavior.

OBJECTIVE: The aim of this study was to evaluate previous teacher reports that children exposed to cocaine prenatally have more problem behaviors. METHODS: A historical, prospective design was used. Maternal subjects (n = 116) of 6-year-old singleton, term (>/=36 weeks) children, and the children's first-grade teachers (n = 102) agreed to participate. The child's first-grade teacher, blinded to study design and exposure status, rated the child's behavior with the Conners' Teacher Rating Scales (CTRS) and an investigator-developed scale, the Problem Behavior Scale (PROBS 14), measuring behaviors reported by educators to be specific to cocaine exposure. Mothers were interviewed by telephone regarding demographic and socioeconomic factors. RESULTS: Although the cocaine-exposed group had higher (more problem behaviors) for each of the CTRS subscales, the overall multivariate analysis of variance for the CTRS was not significant. Children exposed to cocaine prenatally had higher scores (more problem behaviors) for 11 of the 14 PROBS items and the overall multivariate analysis of variance relating prenatal cocaine exposure to the PROBS was significant (Wilkes' lambda =.775), even after controlling for gender and prenatal exposure to alcohol and cigarettes. CONCLUSIONS: This pilot study supports that teachers blinded to exposure status of early elementary students did rate the cocaine-exposed group as demonstrating significantly more problem behaviors than control children. Although an important first step, postnatal factors that also may influence behavior were not evaluated; hence, causation is not addressed.

Prenatal coke: what's behind the smoke? Prenatal cocaine/alcohol exposure and school-age outcomes: the SCHOO-BE experience.

Despite media reports and educators' concerns, little substantive data have been published to document or refute the emerging reports that children prenatally exposed to cocaine have serious behavioral problems in school. Recent pilot data from this institution have indeed demonstrated teacher-reported problem behaviors following prenatal cocaine exposure after controlling for the effects of prenatal alcohol use and cigarette exposure. Imperative in the study of prenatal exposure and child outcome is an acknowledgement of the influence of other control factors such as postnatal environment, secondary exposures, and parenting issues. We report preliminary evaluation from a large ongoing historical prospective study of prenatal cocaine exposure on school-age outcomes. The primary aim of this NIDA-funded study is to determine if a relationship exists between prenatal cocaine/alcohol exposures and school behavior and, if so, to determine if the relationship is characterized by a dose-response relationship. A secondary aim evaluates the relationship between prenatal cocaine/alcohol exposures and school achievement. Both relationships will be assessed in a black, urban sample of first grade students using multivariate statistical techniques for confounding as well as mediating and moderating prenatal and postnatal variables. A third aim is to evaluate the relationship between a general standardized classroom behavioral measure and a tool designed to tap the effects thought to be specific to prenatal cocaine exposure. This interdisciplinary research team can address these aims because of the existence of a unique, prospectively collected perinatal Database, funded in part by NIAAA and NICHD. The database includes repeated measures of cocaine, alcohol, and other substances for over 3,500 births since 1986. Information from this database is combined with information from the database of one of the largest public school systems in the nation. The final sample will be composed of over 600 first grade students for whom the independent variables, prenatal cocaine/alcohol exposures, were prospectively assessed and quantified at the university maternity center. After informed consent, the primary dependent variable, school behavior, is assessed, using the PROBS-14 (a teacher consensus developed instrument), the Child Behavior Check List, and the Conners' Teacher Rating Scale. The secondary dependent measure, school achievement, is measured by the Metropolitan Achievement Text and the Test of Early Reading Ability. Control variables, such as the environment and parenting, are measured by several instruments aimed at capturing the child and family ecology since birth. All analyses will be adjusted as appropriate for prospectively gathered control variables such as perinatal risk, neonatal risk, and other prenatal drug and cigarette exposures. Further adjustment will be made for postnatal social risk factors which may influence outcome. Of particular concern are characteristics of the home (adaptation of HOME), parent (depression, stress), and neighborhood (violence exposure). Finally, postnatal exposure to lead and other drugs is being considered.

Meconium does not guarantee fetal lung maturity.

OBJECTIVE: In utero passage of meconium may represent a response to hypoxic stress or a normal maturational event. When found during the third trimester, one may be tempted to use its presence as prima facie evidence of fetal lung maturity. The purpose of our study was to determine the frequency of meconium-stained fluid in the third trimester and the incidence of biochemical and physiologic lung immaturity in these fetuses. METHODS: Amniotic fluid specimens obtained at our institution from 1991 through 1993 (n = 2,377) were analyzed for maturity and visually inspected for meconium. Perinatal outcome was obtained for intramural deliveries occurring within 3 days of amniotic fluid collection (n = 905). Gestational age was defined as the best obstetric estimate based on menstrual dates, clinical examination, and ultrasound results. RESULTS: Meconium staining was present in 2.7% (n = 64) of specimens. Although meconium-stained specimens were more likely to have mature lecithin-sphingomyelin (L:S) ratios (OR 2.1, 95% confidence interval [CI] = 1.2-3.6) and phosphatidylglycerol (PG) concentrations (OR 3.8, CI 2.2-6.7), 17.2% were immature for both L:S and PG (n = 11, CI = 9.9-28.2%). When analysis was limited to fetuses delivering intramurally within 3 days of amniotic fluid collection, respiratory distress syndrome occurred in 3.0% (CI = 0.5-15%) with meconium-stained fluid. CONCLUSIONS: The presence of meconium in amniotic fluid does not guarantee lung maturity. The same consideration of the risks of prematurity must be given to the fetus with meconium-stained fluid as given to the fetus with clear fluid.

Prenatal cocaine and neonatal outcome: evaluation of dose-response relationship.

OBJECTIVE: The aim of this study was to evaluate the hypothesis that prenatal cocaine exposure would negatively affect newborn behavior. METHODS: A prospective observational study of term infants recruited from the low-risk nursery used a structured, standardized interview to obtain maternal data. Cocaine exposure was determined by radioimmunoassay of the infant's meconium stool. An examiner blinded to the infant's cocaine status administered the Brazelton Neonatal Behavioral Assessment Scales. RESULTS: The sample was composed of 23 exposed and 29 nonexposed infants. On six of the seven Brazelton Neonatal Behavioral Assessment Scale clusters, cocaine-exposed infants performed less well than control infants, with significant differences observed for autonomic stability. In addition, a dose-response relationship was suggested. Significant negative, within-group relationships were evident in the exposed group, indicating poorer performance with increasing meconium cocaine concentration for orientation (r = -.40) and regulation of state (r = -.40). Regression model testing of the influence of meconium cocaine concentration on neurobehavioral outcomes, after controlling for significant confounders, identified a significant independent, negative effect of meconium cocaine concentration on two clusters-motor and regulation of state. CONCLUSION: In otherwise healthy full-term infants, prenatal cocaine exposure identified by quantitative analysis of cocaine concentration in meconium had a significant, independent negative association with motor and regulation of state that remained after controlling for other significant confounders. A dose-response relationship was evident.

Lung maturity tests. Relation to source, clarity, gestational age and neonatal outcome.

OBJECTIVE: To determine whether gestational age is a significant determinant of neonatal outcome, irrespective of biochemical lung maturity. The effects of specimen source and clarity on the reliability of biochemical tests for predicting respiratory distress syndrome are also evaluated. STUDY DESIGN: Perinatal outcome was analyzed for 904 neonates undergoing amniotic fluid maturity studies within three days of delivery from 1991 to 1993. The relationships of gestational age and biochemical maturity to neonatal outcome were examined using multivariate analysis of covariance. Test reliability was evaluated using log-linear analysis of multiway frequency tables. RESULTS: Gestational age was a better predictor of neonatal outcome than biochemical lung maturity. Gestational age significantly correlated with every measure of outcome except intraventricular hemorrhage and jaundice. Test reliability was not significantly influenced by specimen source or clarity. CONCLUSION: Results obtained using contaminated amniotic fluid are reliable when the proper technique is used. Irrespective of biochemical maturity, neonatal outcome is significantly related to gestational age. Gestational age, and not just biochemical maturity, should be considered when timing delivery.

Antenatal phenobarbital therapy and neonatal outcome. II: Neurodevelopmental outcome at 36 months.

OBJECTIVE: To evaluate the effect of antenatal phenobarbital (PB) therapy on neurodevelopmental outcome at 36 months. DESIGN: Prospective, randomized, controlled trial. SETTING: Single-institution study. SUBJECT AND INTERVENTIONS: Children born to women who participated in the study evaluating the effect of antenatal phenobarbital (PB) on neonatal intracranial hemorrhage were prospectively followed to 3 years of age. OUTCOME MEASURES: Physical growth, neurologic examinations, and developmental testing (McCarthy Scales of Children's Abilities). Comparisons between groups were made on all children and those born to multiple gestations. RESULTS: Forty-one children born to women who received 10 mg/kg PB before delivery and 55 children in the control group were evaluated. Three children, all in the control group, had growth parameters (height, weight, and head circumference) below the fifth percentile. The McCarthy General Cognitive Index (standard, 100 +/- 16) was 93 +/- 20 in the PB group and 85 +/- 18 in the control group. The subscores tended to be higher in the PB group than in the control group, with higher quantitative scores in the PB group (44 +/- 11 vs 39 +/- 8). Neurologic deficits were noted in 2 of 41 in the PB group and in 6 of 55 in the control group. CONCLUSIONS: Infants born to women who received antenatal PB therapy had similar neurodevelopmental outcomes as infants born to women who did not receive PB. No adverse effects of PB exposure were detected.

History of in utero cocaine exposure in language-delayed children.

To determine whether children with language delays are more likely to have been exposed to cocaine in utero than children with normal language development, a case-control study was undertaken. Based on routine office screening in our primary-care clinic over a 1-year period, we identified 29 consecutive children, aged 24 to 48 months, as language-delayed. They were compared with an approximate 2:1 match of children without language delay who had been seen in the clinic on the same days and who were of similar age. There was more reported cocaine use during pregnancy (six of 29, 21%) among the language-delayed children than among the controls (five of 71, 7%). This difference is statistically significant (P < 0.05, chi 2 = 3.92; odds ratio = 3.4 +/- 2.2). Discriminant analysis revealed that both cocaine and nicotine exposure were associated with delayed language development--with an unexpected negative, i.e., an antagonistic, protective, interactive effect (F[3,96] = 4.66, R2 = 12.7%, P < .005); neither gender nor caretaker contributed to language development in this sample. These results suggest that children with language delay detected in a clinical setting are more likely to have been exposed in utero to cocaine than children with normal language development. Prenatal cocaine exposure should be a risk factor in monitoring development in children.

Post extracorporeal membrane oxygenation single photon emission computed tomography (SPECT) as a predictor of neurodevelopmental outcome.

OBJECTIVE: To determine the incidence and site of single photon emission computed tomography scan (SPECT) abnormalities in survivors of neonatal extracorporeal membrane oxygenation and to evaluate the efficacy of SPECT scan as a predictor of neurodevelopmental outcome in these infants. SETTING: Tertiary care neonatal intensive care unit in Detroit, MI. PATIENT POPULATION: Survivors of neonatal extracorporeal membrane oxygenation who had a SPECT scan of the brain performed after decannulation and before their discharge from the neonatal intensive care unit were included if they had at least 12 months of follow-up in our developmental assessment clinic. OUTCOME MEASURES: The neurological outcome was reported as normal, suspect, and abnormal on the basis of neurological examination and developmental milestones. The developmental outcome was assessed by Bayley mental development index or McCarthy general cognitive index scores. RESULTS: A total of 59 patients met study criteria. SPECT scan abnormalities were noted in 45 (76%) infants. Global hypoperfusion was the most frequent abnormality followed closely by bilateral focal perfusion defects. The distribution of perfusion abnormalities was not significantly different for right and left hemispheres. Among 14 infants with normal SPECT scans, 13 infants had normal neurological outcome and all had a normal developmental outcome. Of the 45 infants with an abnormal SPECT scan, 7 infants had an abnormal neurological outcomes and 4 infants had an abnormal developmental outcome. SPECT scan abnormalities had no significant correlation with neurodevelopmental outcome of these infants. CONCLUSION: Although a normal SPECT scan was more likely to predict a normal neurodevelopmental outcome, an abnormal SPECT scan did not predict an abnormal outcome in these infants.

Feasibility of invasive monitoring of intracranial pressure in term neonates.

Seven term neonates with encephalopathy resulting from asphyxia and/or intracranial hemorrhage underwent invasive monitoring of intracranial pressure through the epidural or intracerebral space. The average age (in hours) at insertion of the monitor was 27 h in the 3 neonates with asphyxia and 70 h in the 4 neonates with hemorrhage. Intracranial hypertension was noted in 6 neonates. The management of the hypertension included hyperventilation followed by mannitol for pressures that were sustained above 20 mmHg and pentobarbital for pressures above 30 mmHg. The duration of the hypertension varied in 5 neonates from 4 to 72 h, while in the remaining neonates, the pressure remained elevated until death at 70 h. All 4 survivors with intracranial hemorrhage have minimal neuromotor deficits on follow up and 2 survivors with asphyxia have cognitive deficits and are microcephalic. From this small series, it appears that in the management of term neonates with intracranial hemorrhage, monitoring of intracranial pressure should be considered.

Hydrops fetalis, polyhydramnios, pulmonary hypoplasia, and Down syndrome.

A complex case of trisomy 21-related pulmonary hypoplasia with polyhydramnios and hydrops fetalis is described. The value of antenatal surveillance and genetic counselling is emphasized.