Pain Reactivity and Plasma β-Endorphin in Children and Adolescents with Autistic Disorder

Background

Reports of reduced pain sensitivity in autism have prompted opioid theories of autism and have practical care ramifications. Our objective was to examine behavioral and physiological pain responses, plasma β-endorphin levels and their relationship in a large group of individuals with autism.

Methodology/Principal Findings

The study was conducted on 73 children and adolescents with autism and 115 normal individuals matched for age, sex and pubertal stage. Behavioral pain reactivity of individuals with autism was assessed in three observational situations (parents at home, two caregivers at day-care, a nurse and child psychiatrist during blood drawing), and compared to controls during venepuncture. Plasma β-endorphin concentrations were measured by radioimmunoassay. A high proportion of individuals with autism displayed absent or reduced behavioral pain reactivity at home (68.6%), at day-care (34.2%) and during venepuncture (55.6%). Despite their high rate of absent behavioral pain reactivity during venepuncture (41.3 vs. 8.7% of controls, P<0.0001), individuals with autism displayed a significantly increased heart rate in response to venepuncture (P<0.05). Moreover, this response (Δ heart rate) was significantly greater than for controls (mean±SEM; 6.4±2.5 vs. 1.3±0.8 beats/min, P<0.05). Plasma β-endorphin levels were higher in the autistic group (P<0.001) and were positively associated with autism severity (P<0.001) and heart rate before or after venepuncture (P<0.05), but not with behavioral pain reactivity.

Conclusions/Significance

The greater heart rate response to venepuncture and the elevated plasma β-endorphin found in individuals with autism reflect enhanced physiological and biological stress responses that are dissociated from observable emotional and behavioral reactions. The results suggest strongly that prior reports of reduced pain sensitivity in autism are related to a different mode of pain expression rather than to an insensitivity or endogenous analgesia, and do not support opioid theories of autism. Clinical care practice and hypotheses regarding underlying mechanisms need to assume that children with autism are sensitive to pain.     

Children Love Their Pets: Do Relationships between Children and Pets Co-vary with Taxonomic Order,Gender, and Age?

Generally, children love their pets. However, a deeper insight into the beneficial effects of pets on the physical, psychological, and social wellbeing and development of children is needed. This study investigated whether children have more intense relationships with animals which are behaviorally similar to humans (according to the scala naturae), and whether the relationship patterns between 11- to 14-year-old children (n = 72) and their pets differ from those in prepubescent children, between 6 and 10 years of age (n = 84). We also investigated whether pet-relationship quality is associated with children’s age, gender, and number of siblings. Data about individual bonding type and attachment quality between the children and their pet were collected using a questionnaire. The results indicate that the younger children’s relationships clearly co-varied with taxonomic order of the pet. In contrast, 11- to 14-year-old children reported similarly high scores of attachment with their mouse or iguana as with their dog or cat, and the relationship patterns did not co-vary with taxonomic order. Gender effects on relationship quality were found in both age groups; especially girls reported intense relationships with their pets. In addition to gender, children without siblings had stronger attachment to their pet than children who had siblings. Our data suggest that young children develop high-quality relationships with pets, particularly those which are taxonomically closely related, such as dogs and cats, and less so with other pet species, such as birds or fish. Older children were also able to strongly attach to other pet species. We argue that mental relationship representations change during puberty and that older (11- to 14-year-old) children may no longer make attachments to pets based on them being behaviorally similar to people.     

Hair Mineral and Trace Element Content in Children with Down’s Syndrome

Biological Trace Element Research - Chronic exposure to lead causes disruption to energy production mechanisms and tissue damage, in particular through its binding to thiol groups and competition...     

Background Values for Essential and Toxic Elements in Children’s Nails and Correlation with Hair Levels

Human nails are an attractive matrix for assessing environmental exposures to toxic elements as well as the deficiency of essential elements since it is noninvasively collected and can be stored at room temperature. However, reference or baseline levels in nonexposed and healthy populations are not yet established. Then, the aims of this study were (a) to estimate background values for essential and toxic elements in nails from a healthy young population in southern Brazil and (b) to evaluate possible correlations between essential and toxic elements in nails. Furthermore, this report took part of a recent study of background values in the hair of a young population. Thus, correlations between chemical elements in nails and hair were also evaluated. Nails were collected from healthy children (n?=?126), and element concentrations were determined by inductively coupled plasma mass spectrometry. This study provides new and reliable reference concentrations for toxic and essential elements in children's nails. The results can be used as reference values for epidemiological or clinical investigations based on trace elements in nails. Additionally, we also showed weak to strong correlations between Cu, Mg, Mn, Se, and Zn levels in nails and hair.     

Evaluation of Status of Zinc, Copper, and Iron Levels in Biological Samples of Normal Children and Children with Night Blindness with Age Groups of 3–7 and 8–12 Years

The causes of night blindness in children are multifactorial, and particular consideration has been given to childhood nutritional deficiency, which is the most common problem found in underdeveloped countries. Such deficiency can result in physiological and pathological processes that in turn influence hair composition. This study was designed to compare the levels of zinc (Zn), copper (Cu), and iron (Fe) in scalp hair, blood, and urine of both genders of children with night blindness with age range of 3–7 and 8–12 years, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure was developed as a sample pretreatment, for the determination of zinc, copper, and iron in biological samples of children with night blindness. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood, and urine. The digests of all biological samples were analyzed for Cu, Fe, and Zn by flame atomic absorption spectrometry using an air/acetylene flame. The results indicated significantly lower levels of Fe, Cu, and Zn in the biological samples (blood and scalp hair) of male and female children with night blindness, compared with control subjects of both genders. These data present guidance to clinicians and other professionals investigating the deficiency of essential trace metals in biological samples (scalp hair and blood) of children with night blindness.     

Do Children with Uncomplicated Severe Acute Malnutrition Need Antibiotics? A Systematic Review and Meta-Analysis

Background

Current (1999) World Health Organization guidelines recommend giving routine antibiotics (AB) for all children with severe acute malnutrition (SAM), even if they have uncomplicated disease with no clinically obvious infections. We examined the evidence behind this recommendation.

Methods and Findings

OVID-MEDLINE, EMBASE, COCHRANE, GLOBAL-HEALTH, CINAHL, POPLINE, AFRICA-WIDE-NiPAD, and LILACS were searched for AB efficacy, bacterial resistance, and infection rates in SAM. Following PRISMA guidelines, a systematic review and meta-analysis were performed. Three randomised controlled trials (RCT), five Cochrane reviews, and 37 observational studies were identified. One cohort-study showed no increase in nutritional-cure and mortality in uncomplicated SAM where no AB were used. (p>0.05). However, an unpublished RCT in this setting did show mortality benefits. Another RCT did not show superiority of ceftriaxone over amoxicilllin for these same outcomes, but adressed SAM children with and without complications (p = 0.27). Another RCT showed no difference between amoxicillin and cotrimoxazole efficacies for pneumonia in underweight, but not SAM. Our meta-analysis of 12 pooled susceptibility-studies for all types of bacterial isolates, including 2767 stricly SAM children, favoured amoxicillin over cotrimoxazole for susceptibility medians: 42% (IQR 27–55%) vs 22% (IQR 17–23%) and population-weighted-means 52.9% (range 23–57%) vs 35.4% (range 6.7–42%). Susceptibilities to second-line AB were better, above 80%. Prevalence of serious infections in SAM, pooled from 24 studies, ranged from 17% to 35.2%. No study infered any association of infection prevalence with AB regimens in SAM.

Conclusions

The evidence underlying current antibiotic recommendations for uncomplicated SAM is weak. Susceptibility-studies favour amoxicillin over cotrimoxazole. However, given that these antibiotics have side-effects, costs, and risks as well as benefits, their routine use needs urgent testing. With reliable monitoring, we believe that there is sufficient equipoise for placebo controlled RCTs, the only robust way to demonstrate true efficacy.     

Facial Mimicry in 6–7 Year Old Children with Disruptive Behavior Disorder and ADHD

Background

Impairments in facial mimicry are considered a proxy for deficits in affective empathy and have been demonstrated in 10 year old children and in adolescents with disruptive behavior disorder (DBD). However, it is not known whether these impairments are already present at an earlier age. Emotional deficits have also been shown in children with attention-deficit/hyperactivity disorder (ADHD).

Aims

To examine facial mimicry in younger, 6–7 year old children with DBD and with ADHD.

Methods

Electromyographic (EMG) activity in response to emotional facial expressions was recorded in 47 children with DBD, 18 children with ADHD and 35 healthy developing children.

Results

All groups displayed significant facial mimicry to the emotional expressions of other children. No group differences between children with DBD, children with ADHD and healthy developing children were found. In addition, no differences in facial mimicry were found between the clinical group (i.e., all children with a diagnosis) and the typically developing group in an analysis with ADHD symptoms as a covariate, and no differences were found between the clinical children and the typically developing children with DBD symptoms as a covariate.

Conclusion

Facial mimicry in children with DBD and ADHD throughout the first primary school years was unimpaired, in line with studies on empathy using other paradigms.     

Detection of Heart Sounds in Children with and without Pulmonary Arterial Hypertension―Daubechies Wavelets Approach

Background

Automatic detection of the 1^st (S1) and 2^nd (S2) heart sounds is difficult, and existing algorithms are imprecise. We sought to develop a wavelet-based algorithm for the detection of S1 and S2 in children with and without pulmonary arterial hypertension (PAH).

Method

Heart sounds were recorded at the second left intercostal space and the cardiac apex with a digital stethoscope simultaneously with pulmonary arterial pressure (PAP). We developed a Daubechies wavelet algorithm for the automatic detection of S1 and S2 using the wavelet coefficient ‘D ₆’ based on power spectral analysis. We compared our algorithm with four other Daubechies wavelet-based algorithms published by Liang, Kumar, Wang, and Zhong. We annotated S1 and S2 from an audiovisual examination of the phonocardiographic tracing by two trained cardiologists and the observation that in all subjects systole was shorter than diastole.

Results

We studied 22 subjects (9 males and 13 females, median age 6 years, range 0.25–19). Eleven subjects had a mean PAP < 25 mmHg. Eleven subjects had PAH with a mean PAP ≥ 25 mmHg. All subjects had a pulmonary artery wedge pressure ≤ 15 mmHg. The sensitivity (SE) and positive predictivity (+P) of our algorithm were 70% and 68%, respectively. In comparison, the SE and +P of Liang were 59% and 42%, Kumar 19% and 12%, Wang 50% and 45%, and Zhong 43% and 53%, respectively. Our algorithm demonstrated robustness and outperformed the other methods up to a signal-to-noise ratio (SNR) of 10 dB. For all algorithms, detection errors arose from low-amplitude peaks, fast heart rates, low signal-to-noise ratio, and fixed thresholds.

Conclusion

Our algorithm for the detection of S1 and S2 improves the performance of existing Daubechies-based algorithms and justifies the use of the wavelet coefficient ‘D ₆’ through power spectral analysis. Also, the robustness despite ambient noise may improve real world clinical performance.     

Is He Being Bad? Social and Language Brain Networks during Social Judgment in Children with Autism

Individuals with autism often violate social rules and have lower accuracy in identifying and explaining inappropriate social behavior. Twelve children with autism (AD) and thirteen children with typical development (TD) participated in this fMRI study of the neurofunctional basis of social judgment. Participants indicated in which of two pictures a boy was being bad (Social condition) or which of two pictures was outdoors (Physical condition). In the within-group Social–Physical comparison, TD children used components of mentalizing and language networks [bilateral inferior frontal gyrus (IFG), bilateral medial prefrontal cortex (mPFC), and bilateral posterior superior temporal sulcus (pSTS)], whereas AD children used a network that was primarily right IFG and bilateral pSTS, suggesting reduced use of social and language networks during this social judgment task. A direct group comparison on the Social–Physical contrast showed that the TD group had greater mPFC, bilateral IFG, and left superior temporal pole activity than the AD group. No regions were more active in the AD group than in the group with TD in this comparison. Both groups successfully performed the task, which required minimal language. The groups also performed similarly on eyetracking measures, indicating that the activation results probably reflect the use of a more basic strategy by the autism group rather than performance disparities. Even though language was unnecessary, the children with TD recruited language areas during the social task, suggesting automatic encoding of their knowledge into language; however, this was not the case for the children with autism. These findings support behavioral research indicating that, whereas children with autism may recognize socially inappropriate behavior, they have difficulty using spoken language to explain why it is inappropriate. The fMRI results indicate that AD children may not automatically use language to encode their social understanding, making expression and generalization of this knowledge more difficult.     

In Sync with the Family: Children and Partners Influence the Sleep‐Wake Circadian Rhythm and Social Habits of Women

Different factors have been proposed to influence morningness‐eveningness, biological rhythms, and sleep‐wake cycles, but few studies focused on the influence of social habits. Here, we focus on the influence of children and partners on the social habits of women at different stages of their lives and on synchronization within the family. One hundred and seventy‐nine women participated in the study and were allocated into four groups: women without children, pregnant women without children, pregnant women with children, and non‐pregnant mothers. Morningness was predicted by the presence of children, and earlier chronotype was predicted by the presence of children, pregnancy, and age. Average sleep duration was longest in pregnant women. The presence of children was responsible for a difference in rise times of approximately 1.5 h on the weekend. Subjective sleep‐onset latencies were shortest in women with children. The synchrony between partners (husband/wife) was 0.46 in women without children, 0.79 in pregnant women, 0.40 in women with children, and 0.56 between mother and child. Partners’ chronotypes were highly correlated, as were those of mother and child. This study suggests children have a strong influence on their mother's lifestyle and sleep‐wake rhythm, far beyond the first months of life, and that children are a more important social factor than the male partner.     

Serum 8,12-iso-iPF2α-VI Isoprostane Marker of Oxidative Damage and Cognition Deficits in Children with Konzo

We sought to determine whether motor and cognitive deficits associated with cassava (food) cyanogenic poisoning were associated with high concentrations of F2-isoprostanes, well-established indicators of oxidative damage. Concentrations of serum F2-isoprostanes were quantified by LC-MS/MS and anchored to measures of motor proficiency and cognitive performance, which were respectively assessed through BOT-2 (Bruininks/Oseretsky Test, 2^nd Edition) and KABC-II (Kaufman Assessment Battery for Children, 2^nd edition) testing of 40 Congolese children (21 with konzo and 19 presumably healthy controls, overall mean age (SD): 9.3 (3.2) years). Exposure to cyanide was ascertained by concentrations of its main metabolite thiocyanate (SCN) in plasma and urine. Overall, SCN concentrations ranged from 91 to 325 and 172 to 1032 µmol/l in plasma and urine, respectively. Serum isoprostanes ranged from 0.1 to 0.8 (Isoprostane-III), 0.8 to 8.3 (total Isoprostane-III), 0.1 to 1.5 (Isoprostane-VI), 2.0 to 9.0 (total Isoprostane-VI), or 0.2 to 1.3 ng/ml (8,12-iso-iPF2α-VI isoprostane). Children with konzo poorly performed at the BOT-2 and KABC-II testing relative to presumably healthy children (p<0.01). Within regression models adjusting for age, gender, motor proficiency, and other biochemical variables, 8,12-iso-iPF2α-VI isoprostane was significantly associated with the overall cognitive performance (β = −32.36 (95% CI: −51.59 to −13.03; P<0.001). This model explained over 85% of variation of the KABC-II score in children with konzo, but was not significant in explaining the motor proficiency impairment. These findings suggest that cognitive deficits and, possibly, brain injury associated with cassava poisoning is mediated in part by oxidative damage in children with konzo. 8,12-iso-iPF2α-VI isoprostane appears to be a good marker of the neuropathogenic mechanisms of konzo and may be used to monitor the impact of interventional trials to prevent the neurotoxic effects of cassava cyanogenic poisoning.     

Associations of Children’s Appetitive Traits with Weight and Dietary Behaviours in the Context of General Parenting

Background

Individual variations in child weight can be explained by genetic and behavioural susceptibility to obesity. Behavioural susceptibility can be expressed in appetite-related traits, e.g. food responsiveness. Research into such behavioural factors is important, as it can provide starting points for (preventive) interventions.

Objectives

To examine associations of children’s appetitive traits with weight and with fruit, snack and sugar-sweetened beverage intake, and to examine whether parenting style interacts with appetite in determining child weight/intake.

Methods

Data were used from 1275 children participating in the INPACT study in 2009–2010, with a mean age of 9 years in 2009. Their height and weight were measured to calculate body mass index (BMI). Parents completed a questionnaire to measure children’s appetitive traits, children’s dietary intake and parenting style. Child BMI z-scores, fruit, snack and sugar-sweetened beverage intake were regressed on appetitive traits. Moderation by parenting style was tested by adding interaction terms to the regression analyses.

Results

Food-approaching appetitive traits were positively, and food-avoidant appetitive traits were negatively related to child BMI z-scores and to child fruit intake. There were no or less consistent associations for snack and sugar-sweetened beverage intake. Authoritative parenting voided the negative association between food fussiness and fruit intake, while neglecting parenting strengthened the positive association between food-approaching appetitive traits and weight.

Conclusions

Early assessment of appetitive traits could be used to identify children at risk for overweight. As parenting style can moderate the associations between appetitive traits and weight/intake in a favourable way, parents are a promising target group for preventive interventions aimed at influencing the effect of appetitive traits on children.     

Associations of Physical Activity and Sedentary Behavior with Academic Skills – A Follow-Up Study among Primary School Children

Background

There are no prospective studies that would have compared the relationships of different types of physical activity (PA) and sedentary behavior (SB) with academic skills among children. We therefore investigated the associations of different types of PA and SB with reading and arithmetic skills in a follow-up study among children.

Methods

The participants were 186 children (107 boys, 79 girls, 6–8 yr) who were followed-up in Grades 1–3. PA and SB were assessed using a questionnaire in Grade 1. Reading fluency, reading comprehension and arithmetic skills were assessed using standardized tests at the end of Grades 1–3.

Results

Among all children more recess PA and more time spent in SB related to academic skills were associated with a better reading fluency across Grades 1–3. In boys, higher levels of total PA, physically active school transportation and more time spent in SB related to academic skills were associated with a better reading fluency across the Grades 1–3. Among girls, higher levels of total PA were related to worse arithmetic skills across Grades 1–3. Moreover, total PA was directly associated with reading fluency and arithmetic skills in Grades 1–3 among girls whose parents had a university degree, whereas these relationships were inverse in girls of less educated parents.

Conclusions

Total PA, physically active school transportation and SB related to academic skills may be beneficial for the development of reading skills in boys, whereas factors that are independent of PA or SB may be more important for academic skills in girls.

Trial Registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01803776","term_id":"NCT01803776"}}NCT01803776     

Comorbidities in Children and Adolescents with AIDS Acquired by HIV Vertical Transmission in Vitória,Brazil

Background

Studying diseases associated with AIDS is essential for establishing intervention strategies because comorbidities can lead to death. The objectives were to describe the frequency of comorbidities and verify their distribution according to demographic, epidemiological and clinical data as well as to classify diseases in children and adolescents with AIDS in Vitória, Brazil.

Methods

A retrospective cohort study was conducted among children with AIDS, as defined according to the criteria established by the Ministry of Health, who acquired HIV via vertical transmission, were aged 0 to 18 years, and were monitored at a referral hospital from January 2001 to December 2011.

Results

A total of 177 patients were included, of whom 97 were female (55%). There were 60 patients (34%) <1 year old, 67 patients (38%) between the ages of 1 and 5, and 50 patients (28%) ≥6 years of age included at the time of admission to the Infectious Diseases Ward. Regarding clinical-immunological classification, 146 patients (82.5%) showed moderate/severe forms of the disease at the time of admission into the Ward, and 26 patients (14.7%) died during the study. The most common clinical signs were hepatomegaly (81.62%), splenomegaly (63.8%), lymphadenopathy (68.4%) and persistent fever (32.8%). The most common comorbidities were anaemia (67.2%), pneumonia/septicaemia/acute bacterial meningitis (ABM) (64.2%), acute otitis media (AOM)/recurrent sinusitis (55.4%), recurrent severe bacterial infections (47.4%) and dermatitis (43.1%). An association between severe clinical-immunological classification and admission to the Ward for children aged less than one year old was found for several comorbidities (p<0.001).

Conclusion

Delayed diagnosis was observed because the majority of patients were admitted to the Infectious Diseases Ward at ≥1 year of age and were already presenting with serious diseases. The general paediatrician should be alert to this possibility to make an early diagnosis in children infected with HIV.     

“Vision for Action” in Young Children Aligning Multi-Featured Objects: Development and Comparison with Nonhuman Primates

Effective vision for action and effective management of concurrent spatial relations underlie skillful manipulation of objects, including hand tools, in humans. Children’s performance in object insertion tasks (fitting tasks) provides one index of the striking changes in the development of vision for action in early life. Fitting tasks also tap children’s ability to work with more than one feature of an object concurrently. We examine young children’s performance on fitting tasks in two and three dimensions and compare their performance with the previously reported performance of adult individuals of two species of nonhuman primates on similar tasks. Two, three, and four year-old children routinely aligned a bar-shaped stick and a cross-shaped stick but had difficulty aligning a tomahawk-shaped stick to a matching cut-out. Two year-olds were especially challenged by the tomahawk. Three and four year-olds occasionally held the stick several inches above the surface, comparing the stick to the surface visually, while trying to align it. The findings suggest asynchronous development in the ability to use vision to achieve alignment and to work with two and three spatial features concurrently. Using vision to align objects precisely to other objects and managing more than one spatial relation between an object and a surface are already more elaborated in two year-old humans than in other primates. The human advantage in using hand tools derives in part from this fundamental difference in the relation between vision and action between humans and other primates.     

Fluoride and Children’s Intelligence: A Meta-analysis

This paper presents a systematic review of the literature concerning fluoride that was carried out to investigate whether fluoride exposure increases the risk of low intelligence quotient (IQ) in China over the past 20 years. MEDLINE, SCI, and CNKI search were organized for all documents published, in English and Chinese, between 1988 and 2008 using the following keywords: fluorosis, fluoride, intelligence, and IQ. Further search was undertaken in the website www.fluorideresearch.org because this is a professional website concerning research on fluoride. Sixteen case-control studies that assessed the development of low IQ in children who had been exposed to fluoride earlier in their life were included in this review. A qualitative review of the studies found a consistent and strong association between the exposure to fluoride and low IQ. The meta-analyses of the case-control studies estimated that the odds ratio of IQ in endemic fluoride areas compared with nonfluoride areas or slight fluoride areas. The summarized weighted mean difference is -4.97 (95%confidence interval [CI] = -5.58 to -4.36; p < 0.01) using a fixed-effect model and -5.03 (95%CI = -6.51 to 3.55; p < 0.01) using a random-effect model, which means that children who live in a fluorosis area have five times higher odds of developing low IQ than those who live in a nonfluorosis area or a slight fluorosis area.     

Grandmothers and Children’s Schooling in Sub-Saharan Africa

Under poor circumstances, co-residence of a grandmother is generally considered to be beneficial for (grand)children. Empirical evidence does not unequivocally support this expectation and suggests that the grandmother’s importance depends on the family’s circumstances. We study the relationship between grandmother’s co-residence and children’s schooling in sub-Saharan Africa under a broad range of circumstances. Results make clear that the effect of a co-residing grandmother varies but is almost always positive. Grandmothers over age 60 are most effective in helping their (grand)children. They are particularly important for girls, and when the mother is deceased or not living in the household. Grandmothers are less effective in situations with few opportunities, as in very poor regions or in communities with few schooling opportunities. Our findings indicate that providing support to grandmothers should not be overlooked when designing policies aimed at strengthening the position of women and children in the sub-Saharan African context.     

Too Materialistic to Get Married and Have Children?

We developed new materials to induce a luxury mindset and activate materialistic values, and examined materialism’s relationship to attitudes toward marriage and having children in Singapore. Path analyses indicated that materialistic values led to more negative attitudes toward marriage, which led to more negative attitudes toward children, which in turn led to a decreased number of children desired. Results across two studies highlight, at the individual level, the tradeoff between materialistic values and attitudes toward marriage and procreation and suggest that a consideration of psychological variables such as materialistic values may allow for a better understanding of larger-scale socioeconomic issues including low fertility rates among developed countries. We discuss implications and describe how psychological factors relating to low fertility fit within evolutionary mismatch and life history theory frameworks.