Vagal tone as a resilience factor in children with prenatal cocaine exposure

Studies have investigated the potential effects of prenatal cocaine exposure (CE) on children's development. However, few studies have examined predictors of resilient outcomes in this population. We examined vagal tone (VT) as a resilience factor in prenatal CE. Utilizing data from the Maternal Lifestyle Study, a cumulative risk index was derived for children with and without prenatal CE. Presence of CE and other prenatal drugs was summed with postnatal risks in infancy to yield a 15-item risk index. Preschool cognitive outcomes, problem behaviors, and adaptive behaviors were measured. VT was assessed during an infant exam at 1 month and toy exploration at 36 months. We included children with complete physiologic data (217 CE, 333 non-CE). Children were classified as having consistently high, consistently low, or fluctuating VT at 1 and 36 months. Children were also classified as high versus low risk. High-risk children had lower IQ scores, more problem behaviors, and lower ratings of adaptive behaviors than low-risk children. A significant risk by VT-stability interaction indicated that for high-risk children, those with stable low VT had higher ratings of adaptive behaviors at 36 months. This is consistent with theory linking reduced VT during tasks to adaptive regulation and indicates that such regulatory functioning may serve as a protective factor in prenatal CE.     

Focused and shifting attention in children with heavy prenatal alcohol exposure

Attention deficits are a hallmark of the teratogenic effects of alcohol. However, characterization of these deficits remains inconclusive. Children with heavy prenatal alcohol exposure and nonexposed controls were evaluated using a paradigm consisting of three conditions: visual focus, auditory focus, and auditory-visual shift of attention. For the focus conditions, participants responded manually to visual or auditory targets. For the shift condition, participants alternated responses between visual targets and auditory targets. For the visual focus condition, alcohol-exposed children had lower accuracy and slower reaction time for all intertarget intervals (ITIs), while on the auditory focus condition, alcohol-exposed children were less accurate but displayed slower reaction time only on the longest ITI. Finally, for the shift condition, the alcohol-exposed group was accurate but had slowed reaction times. These results indicate that children with heavy prenatal alcohol exposure have pervasive deficits in visual focused attention and deficits in maintaining auditory attention over time. However, no deficits were noted in the ability to disengage and reengage attention when required to shift attention between visual and auditory stimuli, although reaction times to shift were slower.     

Expressive and receptive language functioning in preschool children with prenatal cocaine exposure

OBJECTIVE: To estimate the relationship between severity of prenatal cocaine exposure and expressive and receptive language skills in full-term, African American children at age 3 years. METHODS: Language was assessed at age 3 using the Clinical Evaluation of Language Fundamentals-Preschool (CELF-P). The sample included 424 children (226 cocaine exposed, 198 non-cocaine exposed) who received preschool language assessments at age 3, drawn from a cohort of 476 children enrolled prospectively at birth. RESULTS: Structural equation modeling was used to regress expressive and receptive language as intercorrelated response variables on level of prenatal cocaine exposure, measured by a latent construct including maternal self-report of cocaine use and maternal/infant urine toxicology assays and infant meconium. Results indicated a.168 SD decrease in expressive language functioning for every unit increase in exposure level (95% CI = -.320, -.015; p =.031) after consideration for fetal growth and gestational age as correlated response variables. Receptive language was more modestly related to prenatal cocaine exposure and was not statistically significant. Results for expressive language remained stable with inclusion of the McCarthy general cognitive index as a response variable (expressive language beta = -.173, 95% CI = -.330, -.016; p =.031), and with adjustment for maternal age and prenatal exposures to alcohol, tobacco, and marijuana (expressive language beta = -.175, 95% CI = -.347, -.003; p =.046). Additional child and caregiver environmental variables assessed at age 3 were also evaluated in varying statistical models with similar results. CONCLUSION: The evidence from this study supports a gradient relationship between increased level of prenatal cocaine exposure and decreased expressive language functioning in preschool-aged cocaine-exposed children.     

Learning disabilities and intellectual functioning in school-aged children with prenatal cocaine exposure

Risk for developing a learning disability (LD) or impaired intellectual functioning by age 7 was assessed in full-term children with prenatal cocaine exposure drawn from a cohort of 476 children born full term and enrolled prospectively at birth. Intellectual functioning was assessed using the Wechsler Intelligence Scale for Children-Third Edition (Wechsler, 1991) short form, and academic functioning was assessed using the Wechsler Individual Achievement Test (WIAT; Wechsler, 1993) Screener by examiners blind to exposure status. LDs were categorized based on ability-achievement discrepancy scores, using the regression-based predicted achievement method described in the WIAT manual. The sample in this report included 409 children (212 cocaine-exposed, 197 non-cocaine-exposed) from the birth cohort with available data. Cumulative incidence proportions and relative risk values were estimated using STATA software (Statacorp, 2003). No differences were found in the estimate of relative risk for impaired intellectual functioning (IQ below 70) between children with and without prenatal cocaine exposure (estimated relative risk = .95; 95% confidence interval [CI] = 0.65, 1.39; p = .79). The cocaine-exposed children had 2.8 times greater risk of developing a LD by age 7 than non-cocaine-exposed children (95% CI = 1.05, 7.67; p = .038; IQ ≥ 70 cutoff). Results remained stable with adjustment for multiple child and caregiver covariates, suggesting that children with prenatal cocaine exposure are at increased risk for developing a learning disability by age 7 when compared to their non-cocaine-exposed peers.     

Topical phenytoin in diabetic ulcers: a double blind controlled trial

Data of 57 patients who completed the trial and 13 who did not, were analysed. With phenytoin, there was a marginal: increase in the reduction of mean ulcer area and acceleration of effect 3rd on 4th week. With control: the number completing the trial was larger: response to treatment was better in grade II ulcers, Table IV. This study has the hall marks of a real clinical trial, has raised the possibility of wound healing properties of phenytoin and confirms the results of others.     

Association between a marker for prenatal testosterone exposure and externalizing behavior problems in children

Prenatal androgen exposure has been associated with aggressive behavior in adults. It is less clear whether this association holds for childhood externalizing behavior. This study tests the hypothesis that increased prenatal androgen exposure is associated with aggressive behavior and attention problems in childhood. The ratio of the length of the second finger digit relative to the fourth digit, which is a marker for prenatal testosterone exposure, was assessed in 239 male and female fifth grade schoolchildren from Jintan, China, together with parent and teacher ratings of aggression and attention problems. Increased aggression and attention problems were both significantly associated with a lower ratio of the length of the second finger digit relative to the fourth digit ratios in boys but not girls. The effects remained significant after controlling for early adversity. These findings are the first to establish a relationship between an indirect indicator of fetal androgen exposure and any child psychopathology in Chinese children, and the observed effect size in boys was stronger than in male adults in Western studies. The results provide limited cross-cultural support for the importance of prenatal androgen exposure in contributing to the development of externalizing behavior problems in children, and they suggest that such effects may be specific to boys who may be relatively more vulnerable to early prenatal influences.     

Discordant noninvasive prenatal testing and cytogenetic results: a study of 109 consecutive cases

PurposeRecent published studies have demonstrated the incremental value of the use of cell-free DNA for noninvasive prenatal testing with 100% sensitivity for trisomies 21 and 18 and a specificity of ≥99.7% for both. Data presented by two independent groups suggesting positive results by noninvasive prenatal testing were not confirmed by cytogenetic studies.MethodsConcordance of results among cases with noninvasive prenatal testing referred for cytogenetic prenatal and/or postnatal studies by karyotyping, fluorescence in situ hybridization, and/or oligo–single-nucleotide polymorphism microarray was evaluated for 109 consecutive specimens.ResultsCytogenetic results were positive for trisomy 21 in 38 of the 41 noninvasive prenatal testing–positive cases (true-positive rate: 93%) and for trisomy 18 in 16 of the 25 noninvasive prenatal testing–positive cases (true-positive rate: 64%). The true-positive rate was only 44% (7/16 cases) for trisomy 13 and 38% (6/16 cases) for sex chromosome aneuploidy.ConclusionThese findings raise concerns about the limitations of noninvasive prenatal testing and the need for analysis of a larger number of false-positive cases to provide true positive predictive values for noninvasive testing and to search for potential biological or technical causes. Our data suggest the need for a careful interpretation of noninvasive prenatal testing results and cautious transmission of the same to providers and patients.     

Patterns of prenatal alcohol exposure and associated non-characteristic minor structural malformations: a prospective study

The characteristic facial features of the more severe end of Fetal Alcohol Spectrum Disorders (FASD) include smooth philtrum, thin vermillion of the upper lip, and short palpebral fissures. A systematic evaluation of a comprehensive list of minor structural defects in association with varying patterns of prenatal exposure to alcohol has not been performed. We examined the patterns and timing of prenatal alcohol exposure to minor structural malformations occurring in at least 5% of the sample. Patterns of drinking were evaluated by drinks per day, number of binge episodes, and maximum number of drinks. Timing of exposure was evaluated 0-6 weeks post-conception, 6-12 weeks post-conception, first trimester, second trimester, and third trimester. Naevus flammeus neonatorum is significantly associated with various patterns of drinking during the second half of the first trimester (RR 1.14, 95% CI 1.04, 1.24 for average number of drinks per day; RR 1.04, 95% CI 1.02, 1.07 for number of binge episodes; RR 1.08, 95% CI 1.01, 1.15 for maximum number of drinks in one episode) and similar for number of binge episodes in all categories of timing of exposure and in the second trimester for average number of drinks per day. Other minor malformations occurring in at least 5% of the sample were not found to be significantly associated with prenatal alcohol exposure. Expected minor malformations were not found to be significantly associated with prenatal alcohol exposure. Naevus flammeus neonatorum appears to be part of the spectrum of features associated with prenatal alcohol exposure.     

School-aged children of depressed parents: a blind and controlled study

This study examines the prevalence of psychiatric dysfunction in the children of parents diagnosed with affective disorders. Sixty children from 37 proband families were compared to 43 children from 26 families obtained from matched controls as well as 20 children from 13 medically ill families. Group differences in diagnosable childhood disorders and familial characteristics are investigated. Significantly more disorders and symptoms were noted in the children with psychiatrically ill parents as compared to children from matched controls and medically ill parents. Using logistic and Cox survival analyses, correlates for the risk of affective disorder, attention deficit and conduct disorder in the children were examined. Maternal depression and paternal alcoholism were related to the risk for depression in the child. The child's sex and the presence of affective disorders in the father were significantly related to the risk for attention deficit disorder. Maternal alcoholism, parental divorce and the type of subject (proband or control family) were significantly related to the risk for conduct disorder. The findings are discussed relative to results from earlier studies on rates of disorder in the offspring of depressed parents.     

Isolation of enterotoxigenic Bacteroides fragilis from Bangladeshi children with diarrhea: a controlled study.

We undertook a controlled study of children younger than 5 years in Bangladesh to determine whether enterotoxigenic Bacteroides fragilis (ETBF) was associated with diarrhea in this population. ETBF was isolated from 22 (6.1%) of 358 patients and 5 (1.2%) of 425 controls (P = 0.0001). In children younger than 1 year, however, low isolation rates (2 to 3%) were found in both patients and controls. In children older than 1 year, the rates were significantly higher in children with diarrhea (16 [9%] of 177) than in controls (2 [1%] of 264; P = 0.00001). When children with mixed infections with other known diarrheal pathogens were removed, the differences in children older than 1 year were still significant (7 [4%] of 177 versus 2 [1%] of 264; P = 0.033). The syndrome associated with ETBF was secretory in nature, with watery diarrhea, and of mild severity. These epidemiological and clinical findings are similar to those from a previous study of White Mountain Apaches in the United States and are the first to suggest that ETBF may also be an important diarrheal pathogen in other geographic areas and in the developing world where diarrhea is highly endemic.     

Pulmonary hypoplasia in babies with severe rhesus isoimmunisation: a quantitative study.

Analysis of lung weights of 96 infants dying with rhesus isoimmunisation has shown that the lung is considerably retarded in its growth. Detailed analysis of the lungs of six babies after pulmonary artery injection showed in all a reduction in airway number and thus acinar and artery number, suggesting arrest in growth before the 16th week of gestation. The alveoli were also of either abnormal number, size or maturity, suggesting a continuing effect in later foetal life. Total lung volume varied from the normal value in one case to one-quarter normal in the smallest lung.     

Cue exposure therapy for the treatment of opiate addiction: results of a randomized controlled clinical trial

BACKGROUND: Persistent cue reactivity to drug-related stimuli is a well-known phenomenon among abstinent drug users and has been found to be a predictor of relapse. Cue exposure therapy (CET) aims to reduce this cue reactivity by exposing abstinent drug users to conditioned drug-related stimuli while preventing their habitual response, i.e. drug use. METHODS: 127 abstinent heroin-dependent Dutch inpatients were randomized to CET (n = 65; 55 completers) and placebo psychotherapy treatment (PPT) (n = 62; 59 completers). It was examined whether CET would lead to a decrease in drug-related cue reactivity (using mixed-design ANOVA) and subsequently to lower dropout and relapse rates (using logistic regression) compared to PPT. RESULTS: Both groups responded with a similar decrease in self-reported cue reactivity (craving, mood). The CET group did show a significant decrease in physiological reactivity (skin conductance) compared to PPT. However, dropout and relapse rates were, contrary to our expectations, significantly higher in the CET group. CONCLUSIONS: This is the first randomized controlled trial showing that CET, compared to a non-specific psychotherapy, might increase dropout and relapse rates among abstinent heroin-dependent clients in a drug-free setting. Caution is warranted when applying CET in this specific context.     

Early endotoxin exposure and atopy development in infants: results of a birth cohort study

BACKGROUND: Exposure to endotoxin in childhood is currently discussed to protect from the development of allergic diseases. OBJECTIVE: To study the effect of early endotoxin exposure on incidence of atopic sensitization, atopic dermatitis and wheezing until the age of 2 years in infants with different risk status in terms of parental atopy. METHODS: Data of 1942 infants of an ongoing birth cohort study were analysed by logistic regression. Endotoxin was measured in settled dust of the mothers' mattresses at infants' age of 3 months. Data on allergic symptoms and physicians' diagnoses were gathered by questionnaire. Sensitization to common food and inhalant allergens was assessed by specific serum IgE. RESULTS: High endotoxin levels increased the risk of repeated wheeze [adjusted odds ratio (OR) for 4th exposure quartile (Q4) 1.52, 95% confidence interval (CI) 1.08-2.14], but were associated with neither sensitization to food allergens nor atopic dermatitis. Stratification by parental atopy showed that there was an association of endotoxin exposure with incidence of repeated wheeze as well as with sensitization to inhalant allergens (P for trend = 0.008 and 0.044, respectively) only in infants with parental atopy, with the highest risk in the 4th exposure quartile (repeated wheeze: ORQ4 1.77, 95% CI 1.14-2.73; sensitization to inhalant allergens: ORQ4 1.69, 95% CI 0.70-4.11). CONCLUSION: Early endotoxin exposure in terms of mattress dust endotoxin levels seemed to increase the risk of atopic reactions to inhalant allergens at the age of 2 years, especially in infants at risk due to parental atopy. Our data disagree with an early protective effect of endotoxin on atopy development until the age of 2 years.     

A possible link between prenatal exposure to famine and breast cancer: a preliminary study.

In a study of 475 women born around the 1944-1945 Dutch famine, women exposed to prenatal famine more often reported a history of breast cancer than nonexposed women (hazard ratio, 2.6; 95% confidence interval, 0.9-7.7). They also had alterations in reproductive risk factors. Prenatal famine may increase breast cancer incidence.     

Effects of a mindfulness-based intervention during pregnancy on prenatal stress and mood: results of a pilot study

Summary Stress and negative mood during pregnancy increase risk for poor childbirth outcomes and postnatal mood problems and may interfere with mother–infant attachment and child development. However, relatively little research has focused on the efficacy of psychosocial interventions to reduce stress and negative mood during pregnancy. In this study, we developed and pilot tested an eight-week mindfulness-based intervention directed toward reducing stress and improving mood in pregnancy and early postpartum. We then conducted a small randomized trial (n = 31) comparing women who received the intervention during the last half of their pregnancy to a wait-list control group. Measures of perceived stress, positive and negative affect, depressed and anxious mood, and affect regulation were collected prior to, immediately following, and three months after the intervention (postpartum). Mothers who received the intervention showed significantly reduced anxiety (effect size, 0.89; p < 0.05) and negative affect (effect size, 0.83; p < 0.05) during the third trimester in comparison to those who did not receive the intervention. The brief and nonpharmaceutical nature of this intervention makes it a promising candidate for use during pregnancy. Correspondence: C. Vieten, California Pacific Medical Center Research Institute, Rm. 514, 2200 Webster Street, San Francisco, CA 94115, U.S.A.     

Choanal atresia associated with prenatal methimazole exposure: three new patients

We report three patients with bilateral choanal atresia in children prenatally exposed to methimazole (MMI) in order to define a MMI embryopathy clinical pattern. The combination of choanal atresia and other specific malformations strongly resembles previously reported patients exposed to MMI in utero. At present, propylthiouracil is considered the best treatment in pregnancies. However in Argentina and some other countries MMI is the only antithyroid drug, possibly posing a significant risk to the unborn fetus.