Longitudinal investigation of task persistence and sustained attention in children with prenatal cocaine exposure

The present study estimates the longitudinal effects of prenatal cocaine exposure on indicators of sustained attention processing at 3, 5 and 7 years of age in an urban sample of full-term African–American children (235 cocaine-exposed, 207 noncocaine-exposed). The sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview, urine and meconium toxicology assays. Sustained attention was measured at age 3 years using a standardized measure of task persistence during a challenging task [G.A. Morgan, N.A. Busch-Rossnagel, C.A. Maslin-Cole and R.J. Harmon, Individualized Assessment of Mastery Motivation: Manual for 15–36 Month Old Children, 1992.], and at ages 5 and 7 years using omission error scores from computerized continuous performance tasks (CPT) [L. Greenberg, R. Leark, T. Dupuy, C. Corman, C. Kindschi, M. Cenedela, Test of Variables of Attention (T.O.V.A. and T.O.V.A.-A.), 22, Universal Attention Disorders, Los Alamitos, CA, 1996; C.K. Conners, Conners' Continuous Performance Test (CPT), second ed., Multi-Health Systems, Canada, 1995.]. Findings from longitudinal GLM/GEE analyses of the three measured time points support a stable influence of prenatal cocaine exposure on indicators of sustained attention, after controlling for prenatal exposure to alcohol, marijuana, tobacco and over 20 additional medical and social–demographic covariates drawn from potentially confounding influences assessed at birth and later assessment visits (D=0.21; 95% CI=0.04, 0.38; P=.017). This effect was not mediated by fetal growth or gestational age and remained highly stable with increasing levels of covariate control. Separately, using the age 7 data, a structural equations model (SEM) was constructed combining all available self-report and bioassay data to measure magnitude of cocaine exposure in relationship to attention task performance. Results indicated a gradient of influence, with each standard deviation increase in the level of prenatal cocaine exposure relating to a 16% standard deviation increase in omission error scores at age 7. Overall findings support a stable cocaine-specific effect on indicators of sustained attention processing during the early childhood years. Results are discussed within the context of neurobiological and behavioral research linking prenatal cocaine exposure to long-lasting disruption of the brain systems subserving arousal and attention.     

The effects of prenatal cocaine exposure and gender on inhibitory control and attention

Children exposed prenatally to cocaine show deficits in emotion regulation and inhibitory control. While controlling for the measures of medical complication in the perinatal period, environmental risk, and prenatal polydrug exposure (alcohol, tobacco, and marijuana), we examined the effects of prenatal cocaine exposure and gender on attention and inhibitory control in 203 children at ages 6, 9, and 11. Cocaine exposure affected the performance of males, but not females. Heavily exposed males showed deficits in the attention and the inhibition tasks. In addition, a significantly greater proportion of heavily exposed males (21%) than unexposed males (7%) or heavily exposed females (7%) failed to complete the task (p < 0.01). Even without those poorest performing subjects, the overall accuracy for heavily exposed males (81%) was significantly reduced (p < 0.05) compared to lightly exposed males (87%) and unexposed males (89%). The findings highlight the importance of considering gender specificity in cocaine exposure effects. Processes by which cocaine effects may be specific to males are discussed.     

Prenatal cocaine exposure: Effects on mother- and teacher-rated behavior problems and growth in school-age children

In this longitudinal study of prenatal cocaine exposure (PCE), school-age physical and cognitive development and behavioral characteristics were examined, while controlling for other factors that affect child development. At this follow-up phase, children were on average 7.2 years old, and their caregivers were 33.7 years old, had 12.5 years of education, and 48% were African American. During the first trimester, 20% of the women were frequent cocaine users (≥1 line/day). First trimester cocaine exposure predicted decreased weight and height at 7 years. There was no significant relationship between PCE and the cognitive and neuropsychological measures. Third trimester cocaine use predicted more total and externalizing behavior problems on the Child Behavior Checklist (Achenbach, 1991 [3]) and the Teacher Report Form (Achenbach, 1991 [4]), and increased activity, inattention, and impulsivity on the Routh Activity (Routh et al., 1974 [67]) and SNAP scales (Pelham and Bender, 1982 [55]). Children who were exposed to cocaine throughout pregnancy had more mother- and teacher-rated behavior problems compared to children of women who stopped using early in pregnancy or who never used cocaine prenatally. These detrimental effects of PCE on behavior are consistent with other reports in the literature and with the hypothesis that PCE affects development through changes in neurotransmitter systems. These school-age behaviors may be precursors of later adolescent behavior problems.     

Estimated effect of prenatal cocaine exposure on examiner-rated behavior at age 7 years

Prenatal cocaine exposure has been linked to increased child behavior difficulties in some studies but not others.

Objective

The primary aim was to estimate the relationship between in utero cocaine exposure and child behavioral functioning at age 7 years with ratings made by blinded examiners during a structured testing session. A second aim was to examine whether caregiver drug use and psychological problems might mediate suspected relationships between prenatal cocaine exposure and aspects of examiner-rated behavior.

Methods

407 children (212 cocaine-exposed, 195 non-exposed) participating in the longitudinal Miami Prenatal Cocaine Study (MPCS) were rated with regard to their behavior during a neuropsychological assessment conducted at age 7 years. Raters were trained research psychometricians blinded to drug exposure status. Individual behavioral items were summarized and the cocaine-behavior relationship was estimated within the context of latent variable modeling, using Mplus software.

Results

Two latent variables, Behavioral Regulation and Sociability, were derived via exploratory latent structure analysis with promax rotation. Prenatal cocaine exposure, statistically controlling for child sex, test age, and prenatal exposure to alcohol, tobacco, and marijuana, was associated with Behavioral Regulation (estimated slope ß = − 0.25; 95% CI = − 0.48, − 0.02; p = 0.04) but not Sociability (estimated slope ß = − 0.03; 95% CI = − 0.26, 0.20; p = 0.79). Neither postnatal drug use by caregivers nor the severity of their psychological problems at age 5 follow-up predicted levels of child Behavioral Regulation or Sociability at age 7 years (p > 0.10).

Conclusions

Examiner ratings of child behavior at age 7 revealed less optimal behavioral regulation for prenatally cocaine-exposed compared to non-exposed children, in contrast with what had been previously found from parent-report data. This evidence highlights the potential value of trained observers in assessing behavioral outcomes of children exposed in utero to drugs and other toxicants.     

Neurobehavioral study of prenatal exposure to hyperthermia combined with irradiation in mice

Thirty-two pregnant adult LACA mice were randomly assigned to one of five exposure groups: control, 38 °C, 42 °C. irradiation, and 42 °C + irradiation. Animals were exposed on gestation day 9 to either 38 °C waterbath for 5 min, 42 °C waterbath for 5 min, treatment with 0.5 Gy of ⁶⁰Co_γ irradiation, or pretreatment at 42 °C waterbath for 5 min following by 0.5 Gy of ⁶⁰Co_γ irradiation. On postnatal day 7, litters were reduced to a maximum of eight pups per litter, with equal members of male and female offspring whenever possible. A total of 216 pups were observed for the age of acquisition of four physiological landmarks (pinna detachment, incisor eruption, eye opening, testes descent), six developmental reflexes (surface righting, cliff avoidance, auditory startle, air righting, visual placing, hindlimb splaying), and examination of learning and memory function. These studies, at threshold exposure levels to hyperthermia and ionizing radiation, indicate there is no consistent significant additional postnatal effect when pregnant mice are exposed to both of these agents. These studies are important for our understanding of the relative long-range effects of prenatal exposure to hyperthermia and acute dose irradiation early in gestation on neurobehavioral teratogenesis.     

Behavioral and developmental changes in rats with prenatal exposure of mirtazapine

Mirtazapine is an often used antidepressant drug; however insufficient information is available regarding its safety during pregnancy. Therefore, this work was initiated to study the effect of prenatal exposure of mirtazapine on postnatal developments of rats. The study was conducted on pregnant rats to observe the safety profile of mirtazapine in comparison to control. The percentage weight gain, gestation period and litter size of the rats treated with double therapeutic dose (DTD) was significantly lower than the rats treated with therapeutic dose (TD) and rats of control group. However the litter size of the TD treated rats was also found smaller than the control. The offspring were examined through battery of test in order to evaluate their developmental neurotoxicity. The test includes the assessment of postnatal growth, reflex ontogeny, neuromotor abilities, activity level, emotional reactivity and learning ability. The DTD exposure negatively affected on overall growth of pups in comparison to TD exposed pups and control group. Further, the amine concentration in brain was also found significantly lower in DTD exposed pups. Therefore, this study reveals that the treatment of pregnant rats with TD and DTD decreases their litter size. In addition the prenatal exposure of DTD of mirtazapine negatively affects on neurodevelopment of rats.     

Relations among parental substance use, violence exposure and mental health: the national survey of adolescents

OBJECTIVE: To study the relations among parental substance use, violence exposure and psychopathology in a nationally representative sample of adolescents. METHOD: Random digit dialing methodology was used to obtain a nationally representative sample of 4023 adolescents, ages 12-17. Telephone surveys, conducted in 1995, assessed demographics, parental substance use, violence exposure, and three psychiatric disorders: major depressive disorder (MDE), posttraumatic stress disorder (PTSD), and substance abuse/dependence (SA/D). RESULTS: Obtained prevalence rates included: 8.2% for sexual assault, 22.5% for physical assault, and 39.7% for witnessing violence at home or in the community. Substance use by a family member was reported by 18.4% (n=721) of adolescents, with 50.6% reporting parental alcohol use and 19.1% (n=138) reporting parental drug use. Consistent with hypotheses, violence exposure and parental substance use, particularly parental alcohol abuse, were independently associated with outcomes. Additionally, parental substance use emerged as a moderator for MDE, PTSD, and SA/D; however, the moderating relations varied according to the outcome variable investigated. CONCLUSIONS: Violence-exposed adolescents reporting parental alcohol or drug use had the highest rates of psychiatric diagnoses.     

A longitudinal analysis of prenatal exposure to methylmercury and fatty acids in the Seychelles

Background

Maternal fish consumption during pregnancy exposes the fetus simultaneously to methylmercury (MeHg) and long chain polyunsaturated fatty acids (LCPUFA). Data from the Seychelles Child Development Nutrition Study (SCDNS) showed a negative association of MeHg with child development when children were 30 months of age, only when controlling for LCPUFA. Concomitantly, n − 3 LCPUFA were found to have a significant positive association only at 9 months. These findings suggest that the effects of MeHg and LCPUFA may vary with age over the first few years of life. We address this by including outcomes at two ages and adjusting for the child's age at testing.

Methods

A longitudinal analysis utilizing linear mixed models was performed to assess the associations of maternal hair total mercury (THg, a biomarker for MeHg) and maternal LCPUFA with children's Bayley Scales of Infant Development Psychomotor Developmental Index (BSID-II PDI) at 9 and 30 months of age, and to determine whether these associations change over time. Data from 228 children were included.

Results

Maternal hair MeHg had a negative effect on BSID PDI, while maternal n − 3 LCPUFA had a positive effect. These effects did not change significantly from 9 to 30 months in this analysis.

Conclusions

The longitudinal analysis provides increased power for estimating the relationships of prenatal MeHg and LCPUFA exposures during child development. Significant associations of these exposures in opposite directions confirm the importance of LCPUFA in development and the need to adjust for maternal nutrition when studying prenatal MeHg exposure.     

Gender differences in physical and mental health outcomes among an aging cohort of individuals with a history of heroin dependence

Background

This paper examines the health status and functioning of an aging cohort of individuals with a history of heroin dependence with a focus on gender differences.

Method

Study subjects were originally sampled from methadone maintenance clinics in California in the 1970s and completed follow-up interviews in 2005-09. Out of the original study sample (N = 914), 343 participants (44.3% female) were interviewed (70.6% of those not deceased). Bivariate analyses examined gender differences in participants' overall health status and physical and mental health problems. Scores on SF-36 scales were compared with general population norms by gender and age, as well as between participants in the study sample who did and did not report past-year drug use.

Results

Average age of the study sample was 58.3 (SD = 4.9) years for males and 55.0 (SD = 4.1) years for females. There were no significant gender differences in past-year drug use (38% of sample) or injection drug use (19%). Women reported significantly more chronic health problems and psychological distress compared with men, and overall poorer health and functioning compared with general population norms. Men under 65 had poorer physical health and social functioning compared with population norms. Men in the study sample reporting past-year substance use had poorer physical functioning, but less bodily pain, than non-users, whereas women with past-year substance use had poorer mental health than other women.

Conclusion

Individuals with a history of heroin dependence have poorer health and functioning than their counterparts in the general population. At a younger age, women reported poorer overall health status and more chronic health and mental health problems than men. Study findings may inform interventions for this population, particularly related to gender-specific treatment needs.     

Association of prenatal and early life exposure to tetrachloroethylene (PCE) with polycystic ovary syndrome and other reproductive disorders in the cape cod health study: A retrospective cohort study

BackgroundTetrachloroethylene (PCE) is an organic lipophilic solvent with possible neuroendocrine toxicity. The objective of this study was to determine the association of prenatal and early childhood exposure to PCE-contaminated drinking water and development of adult-onset Polycystic Ovary Syndrome (PCOS), endometriosis, difficulty conceiving and miscarriage.MethodsFive-hundred exposed and 331 unexposed female participants born between 1969 and 1983 completed questionnaires on demographic and lifestyle characteristics, and reproductive disorders. Residential locations from the prenatal period through five years of age were used to estimate early life PCE exposure with water modeling software.ResultsFor any early life exposure to PCE, the adjusted risk ratio for PCOS was 0.9 (95% CI: 0.5-1.6). No statistically significant associations were observed for increasing levels of exposure with PCOS or the other reproductive disorders.ConclusionNo meaningful associations were found among adult women with early life exposure to PCE-contaminated drinking water and adult-onset reproductive disorders.     

Systematic review of biomonitoring studies to determine the association between exposure to organophosphorus and pyrethroid insecticides and human health outcomes

For the appropriate protection of human health it is necessary to accurately estimate the health effects of human exposure to toxic compounds. In the present review, epidemiological studies on the health effects of human exposure to organophosphorus (OP) and pyrethroid (PYR) insecticides have been critically assessed. This review is focused on studies where the exposure assessment was based on quantification of specific biomarkers in urine or plasma. The 49 studies reviewed used different epidemiological approaches and analytical methods as well as different exposure assessment methodologies. With regard to OP pesticides, the studies reviewed suggested negative effects of prenatal exposure to these pesticides on neurodevelopment and male reproduction. Neurologic effects on adults, DNA damage and adverse birth outcomes were also associated with exposure to OP pesticides. With regard to exposure to PYR pesticides, there are currently few studies investigating the adverse health outcomes due to these pesticides. The effects studied in relation to PYR exposure were mainly male reproductive effects (sperm quality, sperm DNA damage and reproductive hormone disorders). Studies' findings provided evidence to support the hypothesis that PYR exposure is adversely associated with effects on the male reproductive system. The validity of these epidemiological studies is strongly enhanced by exposure assessment based on biomarker quantification. However, for valid and reliable results and conclusions, attention should also be focused on the validity of the analytical methods used, study designs and the measured toxicants characteristics.