Prenatal exposure to methadone and buprenorphine: A review of the potential effects on cognitive development

The amount of opioid users receiving opioid maintenance therapy has increased significantly over the last few years. As a result, an increasing number of children are prenatally exposed to long-lasting opioids such as methadone and buprenorphine. This article reviews the literature on the cognitive development of children born to mothers in opioid maintenance therapy. Topics discussed are the effects of prenatal exposure on prematurity, somatic growth, brain volume, myelination, and the endocrine and neurotransmitter system. Social-environmental factors, including parental functioning, as well as genetic factors are also described. Areas requiring further research are identified.     

Effects of cocaine exposure on infant development: A review

We review the effects of maternal cocaine use on the developing human fetus and infant in terms of methodological problems; the physiological action of cocaine on adults and on the developing fetus; the epidemiology of cocaine use; effects on fetal and infant mortality; growth of cocaine-exposed fetuses and infants; physical anomalies; evidence for and against infant withdrawal from cocaine; neurological effects; behavioral effects as shown by the NBAS; findings related to mother-infant interaction and emotional development; and parenting by cocaine-using mothers. Findings in most areas should be considered preliminary due to methodological problems. Published studies of long-term development are not yet available. In general, deleterious consequences of prenatal cocaine exposure are found for some portion of prenatally exposed infants. However, many findings of no difference are also available in methodologically well-controlled studies.     

Prenatal depression effects on early development: A review

This review of recent research on prenatal depression suggests that it is a strong predictor of postpartum depression and is more common than postpartum depression. Prenatal depression has been associated with excessive activity and growth delays in the fetus as well as prematurity, low birthweight, disorganized sleep and less responsiveness to stimulation in the neonate. Infants of depressed mothers have difficult temperament, and later in development attentional, emotional and behavioral problems have been noted during childhood and adolescence, as well as chronic illnesses in adulthood. Several variables have confounded the effects of prenatal depression including comorbid anxiety and anger as well as stressful life events. Potential mediating variables are low prenatal maternal dopamine and serotonin levels and elevated cortisol and norepinephrine. The associated intrauterine artery resistance may limit blood flow, oxygen and nutrients to the fetus. Some studies also suggest the heritability of developmental problems for the children of prenatally depressed mothers, including ADHD and antisocial behavior. Multivariate, longitudinal research is needed to disentangle these confounding and mediating variables.     

The Inconsolable Doll Task: Prenatal coparenting behavioral dynamics under stress predicting child cognitive development at 18 months

Studies have demonstrated that coparenting can be assessed prenatally through playful observational conditions, including simulated baby enactments. Regrettably, there is a lack of empirical research examining how prenatal coparenting under the emotional stress elicited by the distress of a simulated infant predicts children’s cognitive development. The current longitudinal study introduces a novel procedure—the Inconsolable Doll Task—to assess prenatal coparenting behavioral dynamics under the stress of a non-responsive doll simulator, and examines the extent to which prenatal interaction patterns predict the child’s cognitive development at 18 months. The sample consists of 105 community-based, co-living, expectant fathers and mothers. Data were collected prenatally, at three, six, and 18 months in home and lab visits. Results indicate that the prenatal coparenting dynamic of negative escalation explains a unique variance in children’s cognitive development at 18 months. This effect is evident even when accounting for both prenatal and postnatal assessments of low-stress coparenting behavioral patterns or self-reported coparenting perceptions, and when controlling for parental education. These findings are discussed in terms of their methodical, empirical, and clinical implications.     

Hemispheric specialization for emotional word processing is a function of SSRI responsiveness

Vulnerability to depression and non-response to Selective Serotonin Reuptake Inhibitors (SSRIs) are associated with specific neurophysiological characteristics including greater right hemisphere (RH) relative to left hemisphere (LH) activity. The present study investigated the relationship between hemispheric specialization and processing of emotional words using a divided visual field paradigm administered to never-depressed and previously-depressed individuals, who were subdivided into SSRI responders and non-responders. SSRI responders and never-depressed participants were similar in their left hemispheric lateralization for evaluating emotional words. In contrast, SSRI non-responders showed a relative shift towards RH processing of negative words, and a strong bias toward negative evaluation of words presented to the RH. The results are discussed within the context of a biological-cognitive model of vulnerability to depression.     

Fetal SSRI antidepressant exposure and infant sleep: Findings from the MPEWS pregnancy cohort study

This longitudinal study examines the association between fetal Selective Serotonergic Reuptake Inhibitor antidepressant exposure and infant sleep behaviours at six and 12 months of age and focus on three of the most commonly prescribed antidepressants in pregnancy.This study utilises data on 698 women recruited at less than 20 weeks of pregnancy and are followed up at six and 12 months postpartum. Women were recruited into one of three groups: those taking either sertraline, citalopram or escitalopram antidepressants in pregnancy (n = 85); women with a depressive disorder who were not taking antidepressants (non-medicated depressed, NMD; n = 82); and, and a control group of women (n = 531). At six and 12 months, data were collected on breastfeeding and sleep location and infant sleep was measured using the Brief Infant Sleep Questionnaire. Antidepressants sertraline, escitalopram and citalopram were not associated with increased infant waking or time awake. However, sertraline was associated with longer time for an infant to go to sleep.This study provides reassurance that SSRI antidepressants and, in particular, sertraline, escitalopram and citalopram are not associated with infant sleep behaviours that are commonly regarded as problematic including night waking. Further replication of these findings, including with direct measures of infant sleep, are recommended.     

Prenatal predictors of maternal and newborn EEG

Ninety-two mothers were recruited at a prenatal ultrasound clinic at which time they were given the CES-D for depression and the State-Trait Anxiety Inventory, and their urines were assayed for cortisol, norepinephrine, epinephrine, dopamine, and serotonin. At the neonatal period the mothers and neonates were assessed on frontal EEG asymmetry. Correlation analyses revealed the following: (1) the mothers’ frontal asymmetry was negatively related to prenatal depression (CES-D) symptoms, negatively related to prenatal norepinephrine levels and positively related to prenatal serotonin levels; (2) the frontal asymmetry of the newborn was positively correlated with the mothers’ frontal asymmetry and negatively correlated with the mothers’ prenatal depression (CES-D) symptoms and negatively correlated with the mothers’ prenatal state anxiety scores. The neonates’ EEG frontal asymmetry was also, like the mother's, negatively related to prenatal maternal norepinephrine and positively related to prenatal maternal serotonin.     

Estimated Risk of Developing Selected DSM-IV Disorders Among 5-Year-Old Children with Prenatal Cocaine Exposure

We estimated childhood risk of developing selected DSM-IV Disorders, including Attention-Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), and Separation Anxiety Disorder (SAD), in children with prenatal cocaine exposure (PCE). Children were enrolled prospectively at birth (n = 476) with prenatal drug exposures documented by maternal interview, urine and meconium assays. Study participants included 400 African-American children from the birth cohort, 208 cocaine-exposed (CE) and 192 non-cocaine-exposed (NCE), who attended a 5-year follow-up assessment and whose caregiver completed the Computerized Diagnostic Interview Schedule for Children. Under a generalized linear model (logistic link), Fisher’s exact methods were used to estimate the PCE-associated relative risk (RR) of these disorders. Our results indicated a modest but statistically robust elevation of ADHD risk associated with increasing levels of PCE (p < 0.05). Binary comparison of CE versus NCE children indicated no PCE-associated RR. Estimated cumulative incidence proportions among CE children were 2.9% for ADHD (vs 3.1% NCE); 1.4% for SAD (vs 1.6% NCE); and 4.3% for ODD (vs 6.8% NCE). Our findings suggest evidence of increased risk of ADHD (but not ODD or SAD) in relation to an increasing gradient of PCE during gestation.     

Prenatal dysthymia versus major depression effects on the neonate

Depressed pregnant women were classified as dysthymic or major depression disorder based on the Structured Clinical Interview for Depression and followed to the newborn period. The newborns of dysthymic versus major depression disorder mothers had a significantly shorter gestational age, a lower birthweight, shorter birth length and less optimal obstetric complications scores. The neonates of dysthymic mothers also had lower orientation and motor scores and more depressive symptoms on the Brazelton Neonatal Behavioral Assessment Scale. These findings were not surprising given the elevated cortisol levels and the inferior fetal measures including lower fetal weight, fetal length, femur length and abdominal circumference noted in our earlier study on fetuses of dysthymic pregnant women.     

Postnatal exposure to methyl mercury and neuropsychological development in 7-year-old urban inner-city children exposed to lead in the United States

Background: The most common route for general population exposure to methyl mercury (MeHg) is fish consumption. Recommendations to pregnant women about consuming fish contaminated with MeHg are also applied to children, but there are few studies available about the effects of low-level postnatal MeHg exposure in them.

Objectives: To investigate the association between postnatal methyl mercury exposure and neuropsychological development in a study of children also exposed to lead, both measured at 7 years.

Methods: We measured MeHg concentrations in blood samples from the Treatment of Lead-Exposed Children (TLC) trial in which 780 children with elevated concentrations of lead in blood were followed with neuropsychological tests from ages 12–33 months through 7 years. Here we examine blood MeHg concentration and neuropsychological test scores, both measured at age 7 years. We used a maximum likelihood method to estimate geometric mean MeHg concentration and generalized linear regression models to analyze MeHg and neuropsychological test scores.

Results: Geometric mean MeHg concentration was 0.56 (95% confidence interval: 0.52, 0.59) μg/L. A 1 μg/L increase in MeHg was associated with a 2.1 (95% confidence interval: 0.4, 3.8) point increase in Full-Scale IQ and 0.2 (95% confidence interval: 0.02, 0.4) point increase in Learning Slopeindex T-score on a test of verbal memory.

Conclusions: Our results suggest that the relatively low MeHg exposure in US school-aged children from this population has no detectable adverse effect on neuropsychological development. The positive associations observed between MeHg and neurodevelopment may indirectly reflect consumption of beneficial polyunsaturated fatty acids from seafood.     

Social Information Processing Skills in Children with Histories of Heavy Prenatal Alcohol Exposure

Based on caregiver report, children with prenatal alcohol exposure have difficulty with social functioning, but little is known about their social cognition. The current study assessed the social information processing patterns of school-age children with heavy prenatal alcohol exposure using a paradigm based on Crick and Dodge’s reformulated six-stage model. Fifty-two children (aged 7–11) with and without heavy prenatal alcohol exposure were tested using a structured interview measure of social information processing involving 18 videotaped vignettes of children in group entry and provocation situations. Alcohol-exposed children displayed maladaptive processing patterns on the goal, response generation, and response evaluation steps in group entry situations, and encoding, attribution, response evaluation, and enactment steps during provocation situations. Children with heavy prenatal alcohol exposure also had difficulty on the Test of Problem Solving, and performance correlated with social information processing measures. Such difficulties may lead to problems in social functioning and warrant early intervention.     

Facial memory deficits in children with fetal alcohol spectrum disorders

Prenatal exposure to alcohol may lead to a range of neurobehavioral effects, including impaired learning and memory. Although children with fetal alcohol spectrum disorders (FASD) exhibit both verbal and nonverbal memory impairments, their memory for faces has not been as thoroughly investigated and the extent literature provides inconsistent results. The aim of the current study was to determine whether difficulties in face memory exist in children with FASD and whether the difficulties are mediated by task demands. To address this, we used two measures of immediate and delayed facial recognition memory, the Children's Memory Scale (CMS) and Test of Memory and Learning (TOMAL). Compared to typically developing controls, children with FASD showed memory deficits on all tests and were more likely to perform in a clinically significant range. As well, children performed more poorly on the CMS compared to TOMAL, a finding consistent with the greater difficulty of the CMS task. Our results are consistent with our hypothesis that children with FASD show impairment in facial memory, particularly on demanding memory tasks.     

Effects of television exposure on developmental skills among young children

BackgroundLiterature addressing the effects of television exposure on developmental skills of young children less than 36 months of age is scarce. This study explored how much time young children spend viewing television and investigated its effects on cognitive, language, and motor developmental skills.MethodsData were collected from the Pediatric Clinics at University Medical Center in Southern Taiwan. The participants comprised 75 children who were frequently exposed to television and 75 children who were not or infrequently exposed to television between 15 and 35 months old. The age and sex were matched in the two groups. The Bayley Scales of Infant Development-second edition and Peabody Developmental Motor Scales-second edition were used to identify developmental skills. Independent t-tests, χ² tests, and logistic regression models were conducted.ResultsAmong 75 children who were frequently exposed to television, young children watched a daily average of 67.4 min of television before age 2, which was excessive according to the American Academy of Pediatrics. Viewing television increased the risk of delayed cognitive, language, and motor development in children who were frequently exposed to television. Cognitive, language, and motor delays in young children were significantly associated with how much time they spent viewing television. The type of care providers was critical in determining the television-viewing time of children.ConclusionWe recommend that pediatric practitioners explain the impacts of television exposure to parents and caregivers to ensure cognitive, language, and motor development in young children. Advocacy efforts must address the fact that allowing young children to spend excessive time viewing television can be developmentally detrimental.     

Prenatal cocaine exposure and neurobehavioral development: How subjects lost to follow-up bias study results

Ninety-four prenatally cocaine-exposed and 50 non-cocaine-exposed infants were enrolled at birth and seen at 3,6, and 12 months. Applying a recently developed model (Cicchetti&Nelson, 1994) produced four independent groups: those infants assessed at birth only (n=61), those returning for at least one (n=29) or two (n=15) assessments after birth, and those returning for all three (n=35). Among those infants having all follow-up assessments, cocaine-exposed infants showed significantly lower psychomotor performance on the Bayley Scales of Infant Development (BSID) than did non-exposed infants. Results approached statistical significance for mental development. Except for birthweight (cocaine-exposed infants weighed significantly less), none of a wide range of maternal, perinatal, or neurobehavioral demographic variables biased study results or the generalization of findings to the total sample from those who returned for all visits.     

Prenatal depression effects and interventions: A review

This review covers research on the negative effects of prenatal depression and cortisol on fetal growth, prematurity and low birthweight. Although prenatal depression and cortisol were typically measured at around 20 weeks gestation, other research suggests the stability of depression and cortisol levels across pregnancy. Women with Dysthymia as compared to Major Depression Disorder had higher cortisol levels, and their newborns had lower gestational age and birthweight. The cortisol effects in these studies were unfortunately confounded by low serotonin and low dopamine levels which in themselves could contribute to non-optimal pregnancy outcomes. The negative effects of depression and cortisol were also potentially confounded by comorbid anxiety, by demographic factors including younger age, less education and lower SES of the mothers and by the absence of a partner or a partner who was unhappy about the pregnancy or a partner who was depressed. Substance use (especially caffeine use) was still another risk factor. All of these problems including prenatal depression, elevated cortisol, prematurity and low birthweight and even postpartum depression have been reduced by prenatal massage therapy provided by the women's partners. Massage therapy combined with group interpersonal psychotherapy was also effective for reducing depression and cortisol levels. Several limitations of these studies were noted and suggestions for future research included exploring other predictor variables like progesterone/estriol ratios, immune factors and genetic determinants. Further research is needed both on the potential use of cortisol as a screening measure and the use of other therapies that might reduce prenatal depression and cortisol in the women and prematurity and low birthweight in their infants.     

Attentional blink for acronyms: Effects of familiarity and pre‐exposure

Seventy‐two university students participated in one of two experiments in the rapid serial visual presentation (RSVP) task. Distractors were four‐letter non‐words, the first target (T1) was a four‐letter word, and the second target (T2) was a two‐four‐letter acronym that followed T1 at lags of 2, 3 and 5 items (Experiment 1) or lags of 3 and 5 items (Experiment 2). Familiar acronyms were identified better than unfamiliar acronyms. One pre‐exposure of acronyms in a rating task improved RSVP accuracy for familiar acronyms only (Experiments 1 and 2), whereas three pre‐exposures produced a benefit for unfamiliar acronyms and no significant additional benefit for familiar acronyms (Experiment 2). Thus a pre‐existing unitised memory representation, and a relatively recent access of this representation, enhanced target identification. The effects of pre‐exposure were more consistent with resource depletion than attentional filtering accounts of the attentional blink.     

Effects of prior hypoxia exposure on visual target detection during later more severe hypoxia.

Three groups of 15 subjects each were exposed to 3 different combinations of intermediate (staging) altitudes and exposure times, and were then tested for visual target detection capability at a final altitude of 4300 m. All groups with staging exposure performed better at altitude and had fewer symptoms of acute mountain sickness than a fourth group which went directly to 4300 m altitude from sea level. The data showed that task factors of both viewing distance and degree of peripheral placement of the target significantly influenced detection time within all groups regardless of variations in exposure to altitude.     

Poly I:C母体免疫刺激诱导的子代精神分裂症神经发育动物模型研究

精神分裂症是一组病因未明的重性精神障碍,其病理生理学机制极其复杂,建立能够确切模拟精神分裂症的动物模型对于其发病机制的研究及抗精神分裂症药物的研发具有十分重要的意义。本文意在介绍产前母体免疫刺激（聚肌胞苷酸聚肌苷酸-聚胞苷酸,poly-I:C）诱导子代出现精神分裂症样的神经发育动物模型,以及该模型对精神分裂症的病因研究、生物学机制及其治疗和药物研发的重要意义。