Relationship of prenatal cocaine exposure and maternal postpartum psychological distress to child developmental outcome

Maternal cocaine use during pregnancy can affect the infant directly through toxic effects or indirectly through cocaine's influence on maternal psychological status. We followed 160 cocaine exposed and 56 nonexposed infants and their mothers identified at birth through interview and/or urine screen. Although cocaine exposure defined the groups, infant exposure to alcohol, marijuana, and tobacco was allowed to vary. Infants were 99% African American and poor. All mothers completed the Brief Symptom Inventory (BSI) and infants were given the Bayley Scales of Mental (MDI) and Motor (PDI) Development at a mean corrected age of 17 +/- 8 months. Both MDIs (94 +/- 17 vs. 103 +/- 16) and PDIs (101 +/- 16 vs. 108 +/- 12) were lower for cocaine exposed infants. Psychological distress was greater in cocaine using mothers. Hierarchical multiple regression was used to assess the relative effects of gestational age, maternal psychological distress, and cocaine and polydrug exposure on infant outcomes. Both psychological distress and cocaine and alcohol exposure predicted lower MDIs after controlling for prematurity. Neither psychological distress nor alcohol exposure predicted motor outcome, while cocaine had a significant effect. Tobacco and marijuana exposure were unrelated to outcome. These findings provide further support for direct effects of cocaine and alcohol on infant development as well as highlight the need for studies to document maternal psychological factors, which may increase child risk for poorer outcomes.     

Interactive effects of prenatal cocaine and nicotine exposure on maternal toxicity, postnatal development and behavior in the rat

Two experiments were performed to investigate the interactive effects of prenatal coadministration of cocaine hydrochloride (C) and nicotine tartrate (N). Experiment I was designed to determine doses of C and N that could be coadministered without altering maternal gestational parameters and/or fetal viability. Exposure of Sprague-Dawley rats to combined high-dose C (20 mg/kg) and high-dose N (5.0 mg/kg) on gestation days 8-21 was not more toxic to dam or fetus that that of exposure to C alone. Experiment II investigated pregnancy outcome, postnatal development, and behavior of the offspring following drug exposure to either high-dose cocaine (20 mg/kg: CS), high-dose nicotine (5.0 mg/kg: NS), or both (NC) on gestation days 8-21. N was administered by osmotic minipump and C by sc injection. Saline-injected dams, fitted with saline-fitted pumps (SS), and untreated dams, pair-fed (PF) to NC females, served as controls. Alterations in maternal variables were limited to a 10-15% decrease in food consumption in NC and CS groups. Pregnancy outcome and birth statistics were unaffected by prenatal treatment, as was offspring body weight during the first four postnatal weeks. However, the development of surface righting was delayed inC CS pups, and only CS offspring were underresponsive to the stimulatory effects of dopamine agonists on activity and stereotypy. Behavioral responses to N challenge were similar in all groups. In addition, only CS offspring showed altered behavioral responses in a spontaneous alternation task. Treatment effects on dopamine D1 and D2 binding in the caudate nucleus were not observed. The combination of N and C did not exacerbate any of the behavioral changes seen in CS offspring. These results support the hypothesis that C is a behavioral teratogen in rodents, and suggest that in the present model, nicotine can mitigate some of the consequences of in utero exposure to cocaine.     

Behavioral and neuroanatomical effects of prenatal, postnatal, or combined exposure to ethanol in weanling rats.

Separate and combined effects of prenatal and postnatal exposure to ethanol on activity, emotionality, learning, and hippocampal neuroanatomy were examined in infant rats. Neonatal rats from mothers that were fed either a liquid ethanol (E) or control (C) diet were artificially reared on either 3% ethanol (E) or isocaloric maltose/dextrin (C). Pups in 4 treatment groups (EE, EC, CE, and CC) were compared. Differences in activity and emotionality were slight. Ethanol affected both the partial reinforcement acquisition effect and the partial reinforcement extinction effect. Hippocampal cell density (compared with Group CC) showed a 12% reduction in CA1 pyramidal cells and an 11% reduction in mature granule cells in Groups EC and EE; the CA4 area (compared with Group CC) was significantly larger after postnatal exposure (Groups CE and EE). Significant positive correlations were found between rate of extinction after partial reinforcement (PRF) training and CA1 pyramidal cell density in Groups CC and CE. A significant negative correlation was found between extinction rate after PRF training and CA4 area in Group EE. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The prevalence, stability and significance of developmental language delay in preschool children

A sample of 937 children in Dunedin, New Zealand, was assessed at ages three and five years in order to estimate the nature, prevalence, stability and significance of developmental language delays in three-year-olds. Assessments included language development, intelligence, and fine and gross motor-co-ordination. Detailed results are given which described three types of language delay at age three: delayed verbal comprehension only, delayed verbal expression only, and delayed development in both aspects of language. Follow-up testing at age five indicated that the specific language delays were not highly stable, whereas delays in both aspects were highly stable. A large proportion of the latter children gained very low scores on the measures at age five, and they accounted for 84 per cent of all children with very low intelligence. The implications of the results for a screening programme to identify three-year-old children at high risk of later developmental delays are considered.     

Alterations in the reinforcing efficacy of cocaine in adult rats following prenatal exposure to cocaine.

Adult male rats gestationally exposed to cocaine and nonexposed control offspring were examined for differences in operant responding for cocaine and sucrose reinforcement. Offspring were derived from dams that had received subcutaneous injections of 40 mg/kg/3cc cocaine hydrochloride daily on gestational Days 8–20 and nontreated control dams. Although no prenatal treatment differences were seen when the animals lever pressed for sucrose pellets on a progressive-ratio (PR) schedule, adult offspring prenatally exposed to cocaine were observed to exhibit an enhanced rate of cocaine intravenous self-administration on a fixed-ratio 5 (FR-5) schedule along with a marked decrease in break point on the PR reinforcement schedule. These results suggest that the reinforcing efficacy of cocaine may be reduced in animals with a prenatal history of cocaine exposure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of cocaine administration during early organogenesis on prenatal development and postnatal growth in mice

Cocaine use has been associated with adverse developmental effects in humans. However, clinical reports both confirm and deny an association between cocaine use and malformations. Similarly, differences in species and strain, as well as route and timing of cocaine administration, have added to the difficulties in determining the teratogenicity of cocaine in animal models. This study was undertaken to compare the effects of dose, route, and timing of cocaine administration in ICR mice during early organogenesis. A single intraperitoneal (ip) administration of cocaine ( > or = 60 mg/kg) on Day 9 of gestation (plug day = 1) produced maternal lethality. The predominant developmental effect of cocaine administration was an increase in the percentage of litters exhibiting an enlarged renal pelvis. Despite a high incidence of affected pups at these doses, the enlargement was not severe. These results, in agreement with previous reports, provide further evidence that the developing urogenital system is sensitive to cocaine administration. When cocaine was administered using a subcutaneous route, pup weights were greater and the incidence of enlarged renal pelvis was lower than when an ip route was used. To better mimic human binge cocaine abuse, the toxicity of a "split dose" was determined. A 60 mg/kg dose was administered using one administration of 60 mg/kg, two treatments of 30 mg/kg, or three administrations of 20 mg/kg with 1 hr separating the treatments. The incidence of enlarged renal pelvis was similar when cocaine was administered as one or two but was decreased when cocaine was administered as three treatments. Both the route and split-dose studies suggest that high-peak serum concentrations are required to perturb development. There were no differences in the incidence or severity of enlarged renal pelvis when cocaine was administered on Day 8, 9, or 10 or on all 3 days of gestation. This suggested that the increase in enlarged renal pelvis may not be a specific teratogenic effect of cocaine administration but may be a delay of normal development induced by cocaine exposure during this early period of organogenesis. To address this hypothesis, cocaine was administered on Day 9 using an ip route and the pups were allowed to be naturally born. In pups whose mothers received cocaine there was an increase in postnatal deaths and a trend toward a reduction in pup body weight/litter at Postnatal Day 21. However, when renal morphology was assessed on Postnatal Day 21 no abnormal kidneys were seen. This supports the hypothesis that enlarged renal pelvis produced by cocaine administration during early organogenesis represents a developmental delay and not a persistent teratogenic defect. These studies suggest that high peak cocaine concentrations are required to delay normal kidney morphogenesis in mice.     

Effects of prenatal exposure to N-methylpyrrolidone on postnatal development and behavior in rats

Pregnant rats (Mol:WIST) were exposed to 150 ppm N-methylpyrrolidone for 6 hours per day on gestation days 7-20. The dose level was selected so as not to induce maternal toxicity or decrease viability of offspring. In the preweaning period, the exposed offspring had a lower body weight and their physical development was delayed. Neurobehavioral evaluation of the male pups revealed no effects on basal functions of the central nervous system. The animals appeared normal and motor function (rotarod), activity level (open field), and performance in learning tasks with a low grade of complexity were similar in the two groups. However, in more difficult tasks such as the reversal procedure in Morris water maze and operant delayed spatial alternation (Skinner boxes), performance was impaired in exposed offspring.     

Enduring effects of prenatal cocaine exposure on attention and reaction to errors.

Rats exposed to cocaine prenatally were administered a series of 3-choice visual attention tasks, with the most pronounced deficits seen in a task in which the onset time, location, and duration of a visual cue varied unpredictably between trials. The cocaine-exposed rats were less accurate than controls but did not differ in the rate of premature responses or omission errors. The pattern of errors, coupled with response latency data, implicated deficits in the ability to rapidly engage attention and maintain a high level of alertness to the task. The cocaine-exposed rats also exhibited a blunted reaction to an error on the previous trial, possibly reflecting an alteration in emotional regulation and/or error monitoring. Implications for underlying neuropathology are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Becoming a parent: The relation between prenatal expectations and postnatal experience.

The relationship between individuals' prenatal expectations about parenthood and their postnatal experience of parenthood was examined. Seventy-three primiparous couples were interviewed during the 3rd trimester of pregnancy and asked open-ended questions regarding their expectations. A content analysis of these expectations identified several themes. A cluster analysis, using these themes as variables, identified 3 clusters of women labeled prepared, fearful, and complacent and 4 clusters of men labeled prepared, fearful, complacent, and mixed. Postnatal comparisons indicated that women and men in the prepared cluster generally demonstrated better adjustment than did individuals in the other clusters. Results are discussed in terms of the content of expectations about parenthood, gender differences in these expectations, and the association between prenatal expectations and postnatal experiences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of prenatal exposure to cocaine on conditional discrimination learning in adult rats.

Adult male rats that were gestationally exposed to cocaine and control offspring were trained on an instrumental conditioning task for assessment of the acquisition and reversal of an appetitive conditional discrimination based on olfactory cues. Offspring were derived from Sprague-Dawley dams that had received subcutaneous/ly (sc) injections of 40 mg/kg/3 cc cocaine hydrochloride (C40) daily on Gestational Days 8–20, pair-fed (PF) dams that were injected with saline, nutritional control dams (NC) that received saline injections, and nontreated control dams (LC). There were no differences among the prenatal treatment groups in acquisition of the barpress response or response rate throughout all phases of training. All prenatal treatment groups required approximately the same number of sessions to criterion on the initial odor discrimination. In contrast, adult C40 offspring required more sessions to acquire the reversal of the conditional discrimination than did animals from the other treatment groups (PF, NC, and LC). In addition, even at criterion performance for acquisition of the reversal discrimination, C40 animals exhibited lower accuracy on the 1st 10 responses and made significantly more errors before the 1st reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of increasing resource demand on vigilance performance in adults with schizophrenia or developmental attentional/learning disorders: a preliminary study

Rab proteins form the largest branch of the Ras superfamily of GTPases. They are localized to the cytoplasmic face of organelles and vesicles involved in the biosynthetic/secretory and endocytic pathways in eukaryotic cells. It is now well established that Rab proteins play an essential role in the processes that underlie the targeting and fusion of transport vesicles with their appropriate acceptor membranes. However, the recent discovery of several putative Rab effectors, which are not related to each other and which fulfil diverse functions, suggests a more complex role for Rab proteins. At least two Rab proteins act at the level of the Golgi apparatus. Rab1 and its yeast counterpart Ypt1 control transport events through early Golgi compartments. Work from our laboratory points out a role for Rab6 in intra-Golgi transport, likely in a retrograde direction.     

A review of the neurobehavioral deficits in children with fetal alcohol syndrome or prenatal exposure to alcohol

HeLa cells and HeLa cells expressing the HIV-1 regulatory protein Rev were immunostained for Rev and pre-mRNA processing factors and examined histographically by confocal laser scanning microscopy. Following short pulse-labelling with bromouridine tri-phosphate nascent RNA gave a granular nucleoplasmic staining increasing somewhat towards the periphery as did also the heterogeneous ribonucleoproteins (hnRNPs) A1 and particularly C1/C2, a distribution pattern which has not been described. The sm-antigen of the small ribonucleoprotein particle (snRNP) proteins U1, U2, U4/U6 and U5 stained the nucleoplasm diffusely in addition to speckles which co-localised with speckles of the non-snRNP splicing factor SC-35. Brominated RNA and the hnRNPs A1 and C1/C2 were to varying degrees excluded from the speckles. Rev concentrated in the nucleolus and often as a perinucleolar ring/zone. Rev also stained the nucleoplasm and cytoplasm without co-localising with the above-mentioned proteins or brominated RNA and was not enriched or excluded in SC-35 speckles. The nucleolar proteins B23 and C23, like Rev, gave primarily a perinucleolar ring and stained the nucleoplasm but did not otherwise co-localise with Rev or with nuclear proteins. Histographic recording of immunofluorescence images proved to be a valuable tool in the study of localisation of HIV-1 Rev and cellular components and of possible co-localisations. A parallel comparison of the subcellular patterns of pre-mRNA processing factors versus major nucleolar antigens is new and suggests that the factors are not strictly separated in the nucleoplasm.     

Iron staining of the acquired enamel pellicle after exposure to tannic acid or chlorhexidine: preliminary report

Extrinsic discoloration of teeth following a large consumption of tannin-containing beverages or a prolonged use of chlorhexidine mouthrinses is a well known observation. Tannins as well as chlorhexidine are denaturing agents. Based on preliminary studies revealing the presence of iron in chlorhexidine discolored pellicle material, the ability of iron to stain the integument after pretreatment with the two denaturants was studied in a human model. The denaturing effect of an acidic environment was also included. Enamel slabs fixed to acrylic appliances were carried in the oral cavity and alternately exposed to the test solutions in different sequences in vitro. Pretreatment with chlorhexidine or tannic acid led to marked discoloration upon iron application during 5-d tests, whereas the compounds individually had no such effect. A large content of the metal was found in the stained material. Stannous fluoride appeared to reduce the formation of the pigments, and strong oxidation completely bleached the established color. Possible mechanisms underlying the phenomena observed are discussed.     

Effects of prenatal exposure to cocaine on Morris water maze performance in adult rats.

The spatial memory of adult rats prenatally exposed to cocaine and that of control offspring was assessed using the Morris water maze. Offspring were derived from Sprague Dawley dams that received subcutaneous injection of 40 mg/kg/3 cc cocaine hydrochloride (C40) daily on gestational Days 8-20, pair-fed dams injected with saline, or nontreated control dams. After acquisition, the platform was moved to a new location (reversal phase). Probe trials were conducted at the end of acquisition and reversal training. On the 1st acquisition day, adult male and female offspring prenatally exposed to cocaine required significantly more time and traversed a greater distance to find the hidden platform than did control offspring. Despite these initial differences observed in C40 offspring performance, all of the rats were performing at equivalent levels at the time probe trials were conducted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interactive effects of cocaine and gender on thymocytes: a study of in vivo repeated cocaine exposure

This study used a mouse model including both sexes to assess the impact of repeat cocaine exposure on the differentiation and function of T cell in thymus. Cocaine hydrochloride in 0.9% saline, 5 mg or 40 mg/kg, was administrated by i.p. injection to C57BL/6 mice for 10 days. Thymocytes were obtained 24 h after the 10th injection. Repeat in vivo cocaine exposure inhibited the proliferation of T lymphocytes in response to Con-A and Con-A plus anti-CD28. The proliferation induced by IL-2 in the Con-A stimulated T blasts was attenuated in cocaine treated mice. These effects were seen at a lower cocaine dose in female mice. The total number of thymocytes was reduced. Although the percentage of mature thymocytes (CD4+ CD8- and CD4- CD8+ cells) was not altered, the absolute cell numbers were attenuated. Both percentage and absolute cell number of immature thymocytes (CD4+ CD8+) decreased and the pre-mature (CD4- CD8-) cells increased. CD28 and CD25 expression were attenuated in Con-A stimulated thymocytes of mice treated with cocaine at 40 mg/kg. Interleukin 2 production was not significantly altered, however, gamma-IFN production was decreased by cocaine exposure at 40 mg/kg. In conclusion, cocaine exerts inhibitory effects on the function of mature thymocytes, and on the differentiation of thymocytes. A gender difference in response to cocaine was noted in that female mice were more sensitive to lower dose of cocaine exposure.     

Risk factors in the relationship between gender and crack/cocaine.

Female inner-city substance users evidence greater crack/cocaine use and are more likely to be dependent on this drug than on any other drug. Additionally, female inner-city substance users evidence greater crack/cocaine use and are more likely to be dependent on this drug than their male counterparts, despite no consistent difference demonstrated in use and dependence across other drugs. Because no published work has empirically examined the factors underlying this link between females and crack/cocaine, the current study examined the role of theoretically relevant personality and environmental variables. Among 152 (37% female) individuals in a residential substance-use treatment program, females evidenced greater use of crack/cocaine (current and lifetime heaviest) and were significantly more likely to evidence crack/cocaine dependence than their male counterparts. In contrast, no gender differences were found for any other substance across alcohol, cannabis, and hallucinogens (including PCP). Surprisingly, females were more impulsive than their male counterparts, with impulsivity serving as a risk factor in the relationship between gender and crack/cocaine dependence and lifetime heaviest use. Females also evidenced higher levels of negative emotionality and childhood abuse, but neither variable served as a risk factor in the relationship between gender and crack/cocaine dependence or use. Limitations and future directions are discussed, including the need for further exploration of impulsivity across its various dimensions as well as the inclusion of additional variables such as social context variables to account more fully for this complex link between gender and crack/cocaine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Therapeutic motor training increases parallel fiber synapse number per Purkinje neuron in cerebellar cortex of rats given postnatal binge alcohol exposure: preliminary report

Because therapeutic approaches to fetal alcohol effects in humans have been rare, this study explored the rehabilitative effect of complex motor training on an animal model of binge drinking in the third trimester of human pregnancy. Neonatal alcohol exposure induces significant and permanent reductions in Purkinje and granule cell number accompanied by impaired motor behavior in rats. The purpose of this study was to determine: (1) whether the motor skill impairment caused by exposure to alcohol in the early postnatal period could be ameliorated by the learning of a set of complex motor tasks that had been demonstrated to cause synaptogenesis in the cerebellar cortex; and (2) the extent to which cerebellar neurons in alcohol-exposed (AE) rats exhibit synaptic plasticity. The AE group was given 4.5 g/kg/day of ethanol from postnatal days 4 to 9 via an artificial rearing procedure producing a mean peak blood alcohol level of 257 mg/dl. Control groups consisted of a gastrostomy control (GC) group, that received an isocaloric mixture of maltose/dextrin instead of ethanol, and a suckle control (SC) group, that was reared normally by dams. At approximately 6 months of age, animals from the three groups were assigned either to a rehabilitation condition (RC; that received 10 days of training on the motor tasks) or to an inactive condition (IC; where rats stayed in isolation in their cages). Although SC rats were significantly faster to complete the course in the first 5 days of training, there were no differences in ability to perform among animals from all three groups-SC, GC, and AE--at the end of the training period. Unbiased stereological techniques were used to obtain estimates of the number of parallel fiber synapses/Purkinje cell within the cerebellar paramedian lobule. Results showed that the RC rats from the SC and AE groups had significantly more synapses/Purkinje cell than corresponding IC animals. These data demonstrate that rehabilitative intervention (complex motor training) can improve motor performance impaired by postnatal alcohol exposure and that surviving Purkinje neurons retain the capacity for synaptic plasticity.     

Case-control study of prenatal ultrasonography exposure in children with delayed speech

OBJECTIVE: To determine whether there is an association between prenatal ultrasound exposure and delayed speech in children. DESIGN: Case-control study. SETTING: Network of community physicians affiliated with the Primary Care Research Unit, University of Calgary. SUBJECTS: Thirty-four practitioners identified 72 children aged 24 to 100 months who had undergone a formal speech-language evaluation and were found to have delayed speech of unknown cause by a speech-language pathologist. For each case subject the practitioners found two control subjects matched for sex, date of birth, sibling birth order and associated health problems. MAIN OUTCOME MEASURES: Rates of prenatal ultrasound exposure and delayed speech. RESULTS: The children with delayed speech had a higher rate of ultrasound exposure than the control subjects. The findings suggest that a child with delayed speech is about twice as likely as a child without delayed speech to have been exposed to prenatal ultrasound waves (odds ratio 2.8, 95% confidence limit 1.5 to 5.3; p = 0.001). CONCLUSION: An association between prenatal ultrasonography exposure and delayed speech was found. If there is no obvious clinical indication for diagnostic in-utero ultrasonography, physicians might be wise to caution their patients about the vulnerability of the fetus to noxious agents.