Diagnostic Overshadowing: Insidious Neuroregression Mimicking Presentation of Autism Spectrum Disorder.

CASE: Zac is a 13-year-old boy who presented with his parents to developmental-behavioral pediatrics seeking diagnostic clarity. He was born by vaginal delivery at full term after an uncomplicated pregnancy. Developmental milestones were met at typical ages until he was noted to have language delay and to be hyperactive and impulsive on entering preschool at age 4 years. Although he used some phrases in speech, he often used physical force to take toys from other children, rather than using words.On entering preschool at age 4 years, he was noted to have language delay (i.e., continued use of phrase speech only) and to be hyperactive and impulsive. An evaluation to determine eligibility for an Individualized Education Program (IEP) was completed and found him to have delays in cognition, receptive language, expressive language, social-emotional, and adaptive skills. His fine motor skills were in the low average range, and his gross motor skills were in the average range. He was admitted into an early childhood special education program, and aggressive behavior and hyperactivity decreased in the structured classroom.At age 7 years, Zac was re-evaluated by the school district and found to have moderate intellectual disability (ID). Chromosomal microarray analysis and testing for Fragile X syndrome were normal. He was noted to enjoy interacting with other children and adults, but his play was very immature (e.g., preference for cause/effect toys). He was able to respond appropriately when asked his name and age, but he also frequently demonstrated echolalia. He was also evaluated by his primary care physician and found to meet the criteria for attention-deficit/hyperactivity disorder, combined presentation (ADHD). Treatment with methylphenidate was initiated but discontinued after a brief time because of increased aggressive behaviors.Owing to continued significant tantrums, aggressive tendencies, and inability to communicate his basic needs, Zac was evaluated at a local Regional Center (statewide system for resources and access to services for individuals with developmental disabilities) at age 10 years and found to meet the criteria for autism spectrum disorder (ASD), and previous diagnosis of ID was confirmed. Zac received applied behavior analysis (ABA), but this was discontinued after 1 year because of a combination of a change in the insurance provider and parental perception that the therapy had not been beneficial.Zac became less hyperactive and energetic as he grew older. By the time Zac presented to the developmental-behavioral clinic at age 13 years, he was consistently using approximately 30 single words and was no longer combining words into phrases. He had a long latency in responding to verbal and nonverbal cues and seemed to be quite withdrawn. Physical examination revealed scoliosis and hand tremors while executing fine motor tasks. Seizures were not reported, but neuromotor regression was apparent from the examination and history. Laboratory studies including thyroid-stimulating hormone, free T4, creatine kinase, very-long-chain fatty acids, lactate, pyruvate, urine organic acids, and plasma amino acids were normal. Cranial magnetic resonance imaging demonstrated abnormal T2 hyperintensities in the periventricular and deep cerebral white matter and peridentate cerebellar white matter, consistent with a "tigroid" pattern seen in metachromatic leukodystrophy (MLD) and other white matter neurodegenerative diseases. Arylsulfatase A mutation was detected with an expanded ID/ASD panel, and leukocyte arylsulfatase activity was low, confirming the diagnosis of juvenile-onset MLD.Are there behavioral markers and/or historical caveats that clinicians can use to distinguish between ASD/ID with coexisting ADHD and a neurodegenerative disorder with an insidious onset of regression?

Effects of prenatal exposure to pyrethroid pesticides on neurodevelopment of 1-year- old children: A birth cohort study in China.

Pregnant women have been ubiquitously exposed to pyrethroid pesticides. Previous studies, mainly based on third trimester measurements of maternal urinary pyrethroid metabolites, have reported inconsistent findings in the effects of prenatal pyrethroid exposure on children's neurodevelopmental outcomes. The purpose of this study was to clarify if pyrethroid exposure during the entire three trimesters of pregnancy may be associated with deleterious effects on infant neurodevelopmental status, particularly at a high dosage of exposure. We measured maternal urinary concentrations of pyrethroid metabolites in all trimesters of pregnancy and assessed children's neurodevelopment at one year of age using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Multiple linear regression models were used to estimate the effects of metabolites (3-PBA, 4 F-3-PBA, cis-DBCA) in each trimester on BSID-III composite scores. Logistic regression analyses were applied to predict developmental delay vs non-delayed status (cut-off composite score of below 80 for developmental delay) based on the maternal levels of pyrethroid metabolites. In the first, second and third trimesters of pregnancy, the detection rates of pyrethroid metabolites were 94.7%, 90.7%, and 89.0%; the 50th percentiles of exposure level were 0.24 µg/g, 0.24 µg/g and 0.21 µg/g for 3-PBA, 0.14 µg/g, 0.17 µg/g and 0.15 µg/g for 4 F-3PBA, 0.21 µg/g, 0.25 µg/g and 0.19 µg/g for cis-DBCA respectively. In the second trimester, 3-PBA was inversely associated with Cognition and Language scores [ß = -3.34 (95% CI = -6.11, -0.57) and ß = -2.90 (95% CI = -5.20, -0.61), respectively], and significantly increased the risk of Cognition and Language developmental delay [OR= 1.64 (95% CI = 1.03, 2.62) and OR = 1.52 (95% CI = 1.06, 2.19), respectively]; cis-DBCA was inversely associated with Adaptive Behavior scores [ß = -0.73 (95% CI = -1.27, -0.19)], and significantly increased the risk of Adaptive Behavior developmental delay [OR= 1.11 (95% CI = 1.02, 1.21)]. When the maternal levels of pyrethroid metabolites were stratified into the regression models according to the 90th percentile of exposure, in the first trimester, Cognition and Motor scores were inversely associated with higher cis-DBCA [ß = -7.19 (95% CI = -12.97, -1.41) and ß = -8.20 (95% CI = -13.35, -3.05), respectively], Language scores were inversely associated with higher 3-PBA [ß = -6.01 (95% CI = -10.96, -1.06)]; in the second trimester, Cognition scores were inversely associated with higher cis-DBCA [ß = -6.64 (95% CI = -12.51, -0.76)], Language scores were inversely associated with higher 3-PBA [ß = -5.17 (95% CI = -10.07, -0.27)] and cis-DBCA [ß = -5.40 (95% CI = -10.28, -0.52)]. We concluded that pyrethroid exposure in the first and second trimesters was associated with poorer infants neurodevelopmental outcomes at one year of age, and these effects were particularly pronounced at high levels of pyrethroid exposure.

Neurodevelopmental outcomes in young children born to HIV-positive mothers in rural Yunnan, China.

BACKGROUND: Children born to HIV-infected mothers are at risk for neurodevelopmental delay. Little is known about the neurodevelopmental outcomes of infants and toddlers born to HIV-positive mothers but who were not themselves infected by HIV, especially in poor rural areas. This study was conducted to compare developmental outcomes between young children who were HIV exposed but uninfected (HEU), and their HIV unexposed and uninfected (HUU) peers in rural Yunnan, China. METHODS: A total of 250 HEU children aged 6-36 months and 250 HUU children matched for age, gender and residency were recruited from rural Yunnan, China. Neurodevelopmental outcomes were measured using Bayley Scales of Infant and Toddler Development-Third Edition (Bayley III). Multivariate analysis was performed to adjust for potential confounding effects of caregiver demographic data, maternal health status, birth outcome and children's health status. RESULTS: HIV exposed but uninfected children had significantly lower composite scores in Bayley III assessment than HUU children (in the cognitive domain: 90.34 vs 92.75, P<0.05; in the adaptive behavior domain: 77.04 vs 80.80, P< 0.05). On stepwise logistic regression analysis, HIV exposure (OR, 1.45; 95%CI: 1.04-1.98) and child malnutrition (OR, 1.67; 95%CI: 1.09-2.23) were risk factors for below-average cognition development. Mother's low education and child anemia were significant risk factors for below-average motor and adaptive behavior development. CONCLUSION: Perinatal HIV infection may have a negative impact on neurodevelopment in young children. Other factors such as mother's education and child nutrition status may play important roles in child neurodevelopment, especially in resource-poor areas. Further studies are needed to examine the long-term effect of perinatal HIV infection on later childhood neurodevelopment.

Effect of therapeutic touch on brain activation of preterm infants in response to sensory punctate stimulus: a near-infrared spectroscopy-based study.

OBJECTIVE: The purpose of this study was to determine whether therapeutic touch in preterm infants can ameliorate their sensory punctate stimulus response in terms of brain activation measured by near-infrared spectroscopy. METHODS: The study included 10 preterm infants at 34-40 weeks' corrected age. Oxyhaemoglobin (Oxy-Hb) concentration, heart rate (HR), arterial oxygen saturation (SaO2) and body movements were recorded during low-intensity sensory punctate stimulation for 1 s with and without therapeutic touch by a neonatal development specialist nurse. Each stimulation was followed by a resting phase of 30 s. All measurements were performed with the infants asleep in the prone position. RESULTS: sensory punctate stimulus exposure significantly increased the oxy-Hb concentration but did not affect HR, SaO2 and body movements. The infants receiving therapeutic touch had significantly decreased oxy-Hb concentrations over time. CONCLUSIONS: Therapeutic touch in preterm infants can ameliorate their sensory punctate stimulus response in terms of brain activation, indicated by increased cerebral oxygenation. Therefore, therapeutic touch may have a protective effect on the autoregulation of cerebral blood flow during sensory punctate stimulus in neonates.

Prenatal anxiety associated with male child preference among expectant mothers at 10-20 weeks of pregnancy in Xiangyun County, China.

OBJECTIVE: To examine the relationship between male child preference and maternal prenatal psychological distress among expectant mothers from Xiangyun County, Yunnan Province, China. METHODS: Child gender preference, state-trait anxiety and depression, relationships with the husband and mother-in-law, and self-esteem were measured in a sample of 198 women between 10 and 20 weeks of pregnancy. Multivariate logistic regression analysis was used to identify risk factors for prenatal anxiety. RESULTS: Prenatal anxiety was correlated with male child preference (r=0.15, P<0.05), maternal age (r=-0.17, P<0.05), level of education (r=-0.23, P<0.01), self-esteem (r=-0.36, P<0.01), relationship with mother-in-law (r=-0.34, P<0.01), and relationship with husband (r=-0.35, P<0.01). Significant relationships were maintained in multivariate analysis that included gender preference, maternal education, pregnancy anxiety, self-esteem, number of people in the household, and relationship with husband as predictors (adjusted r(2)=0.28, P<0.001). CONCLUSION: Male child preference was associated with prenatal anxiety in this sample. Younger maternal age, lower self-esteem, lower level of education, worse relationship with husband, and less family cohesiveness were also related to prenatal anxiety. Expectant mothers experienced prenatal anxiety when there was strong family preference for sons.

Procedural challenges in international collaborative research.

OBJECTIVE: Knowledge of the procedural requirements for international research is not widely disseminated to investigators involved in the administration of a federal grant with a foreign component. The purpose of this article is to highlight the major challenges in administrative, procedural, and equipment management aspects of grant implementation when federal funding is involved in international collaborative research. METHODS: The author describes the procedural requirements for international research from the time of priority score receipt to the implementation of the grant. RESULTS: There is tremendous promise for rewarding experiences in international research projects due to the collaboration, mutual learning, and cultural bridging that intrinsically occur. However, there are also inherent cross-national procedural requirements that can be demanding in time and effort for the investigator and other stakeholders of the grant. CONCLUSIONS: It is hoped that awareness of these difficulties and demystification of the process for future investigators can minimize the potential encumbrances in such international research.

Dreams of tigers and flowers: child gender predictions and preference in an urban mainland Chinese sample during pregnancy.

In an urban, mainland Chinese sample, we investigated expectant mothers' stated gender preference for a boy or girl child, their conjectures on the fetal gender, the culture-specific beliefs for making their predictions, and their relations to sociodemographic variables. A total of 174 women were interviewed at 12-19 weeks gestation. Among 84 women who made a prediction on gender, 56 (67%) thought they were carrying a boy, and 28 (33%) expected a girl. The most frequent reasons cited for their speculation were personal feelings (36%), food/taste preference (13%), feedback from others (13%), somatic responses (13%), and dreams (7%). Out of 63 women who stated a wish for a boy or girl child, 45 (71%) wished for a girl and 18 (29%) wished for a boy. Women with undergraduate or graduate degrees were more likely to indicate a preference for boys. Older expectant mothers were more likely to report that they thought they were carrying boys. In conclusion, the majority of the women did not state a distinct choice for gender of the child. When they expressed a gender preference, more mothers expressed a desire to have a girl. However, boy child conjectures were more frequent than girl child conjectures. Greater boy child preference and prediction among the most highly educated and older expectant mothers might be reflective of implicit social status in having sons in urban China.

Time series analysis of spontaneous upper-extremity movements of premature infants with brain injuries.

BACKGROUND AND PURPOSE: Comparisons of spontaneous movements of premature infants with brain injuries and those without brain injuries can provide insights into normal and abnormal processes in the ontogeny of motor development. In this study, the characteristics of spontaneous upper-extremity movements of premature infants with brain injuries and those without brain injuries were examined with time series analysis. SUBJECTS: Participants were 7 premature infants with brain injuries and 7 matched, low-risk, premature infants at the age of 1 month after term. METHODS: A triaxial accelerometer was used to measure upper-extremity limb acceleration in 3-dimensional space. Acceleration signals were recorded from the right wrist when the infant was in an active, alert state and lying in the supine position. The recording time was 200 seconds. The acceleration signal was sampled at a rate of 200 Hz. The acceleration time series data were analyzed by nonlinear analysis as well as linear analysis. RESULTS: The nonlinear time series analysis indicated that spontaneous movements of premature infants have nonlinear, chaotic, dynamic characteristics. The movements of the infants with brain injuries were characterized by larger dimensionality, and they were more unstable and unpredictable than those of infants without brain injuries. DISCUSSION AND CONCLUSION: As determined by nonlinear analysis, the spontaneous movements of the premature infants with brain injuries had the characteristics of increased disorganization compared with those of the infants without brain injuries. Infants with brain injuries may manifest problems with self-organization as a function of the coordination of subsystems. Physical therapists should be able to support interactions among the subsystems and promote self-organization of motor learning through the individualized provision of various sensorimotor experiences for infants.

A dynamical systems analysis of spontaneous movements in newborn infants.

The authors evaluated the characteristics of infants' spontaneous movements by using dynamical systems analysis. Participants were 6 healthy 1-month-old full-term newborn infants (3 males, 3 females). They used a triaxial accelerometer to measure limb acceleration in 3-dimensional space. Acceleration signals were recorded during 200 s from the right wrist when the infant was in an active alert state and lying supine (sampling rate 200 Hz). and was stored in the system's memory. Digitized data were transferred to a PC for subsequent processing with analysis software. The acceleration time series data were analyzed linearly and nonlinearly. Nonlinear time series analysis suggested that the infants' spontaneous movements are characterized by a nonlinear chaotic dynamics with 5 or 6 embedding dimensions. The production of infants'spontaneous movements involves chaotic dynamic systems that are capable of generating voluntary skill movements.

Maternal confidence in China: association with infant neurobehaviors but not sociodemographic variables.

OBJECTIVE: To examine the relations of sociodemographic factors and infant neurobehaviors to maternal confidence in China. METHODS: The Brazelton Neonatal Behavioral Assessment Scale, Family APGAR, and Maternal Confidence in Caring for the Newborn scales were administered to 40 healthy, full-term neonates. RESULTS: Range and regulation of state, autonomic stability, and reflex cluster scores were positively correlated; the autonomic stability cluster score was negatively correlated with maternal confidence in meeting the infant's social and instrumental needs. Educational level, age, income, satisfaction with family conditions, and infant sex were not associated with maternal confidence. Range of state and autonomic stability cluster scores predicted maternal confidence. CONCLUSIONS: The infant's abilities to tolerate stimuli, and to be consoled, were associated with maternal confidence. Also, maternal confidence was related to the recognition of infant autonomic cues. Family and sociodemographic variables were not associated with maternal confidence. The sex of the newborn did not affect maternal confidence.

Neurobehaviors of Japanese newborns in relation to the characteristics of early mother-infant interaction.

The authors examined the relationship between newborn neurobehavioral profiles and the characteristics of early mother-infant interaction in Nagasaki, Japan. The authors administered the Brazelton Neonatal Behavioral Assessment Scale (NBAS; T. B. Brazelton & J. K. Nugent, 1995) in the newborn period and the Nursing Child Assessment Teaching Scale at 1 month (NCATS; G. Sumner & A. Spietz, 1994). They administered the Perceived Stress Scale (S. Cohen, T. Kamarck, & R. Mermelstein, 1983) as an index of maternal stress experienced over the past month. Lower irritability, higher stability in skin coloration, and lower tremulousness in the neonatal period were correlated with higher levels of maternal nurturing behaviors at 1 month. Birth weight and 2 NBAS range-of-state items (peak of excitement, irritability) predicted 31% of the variance in NCATS caregiver subscale score. The NBAS autonomic stability items (tremulousness, startles, lability of skin color) predicted 31% of the variance in the NCATS child subscale score. Perceived stress and maternal sociodemographic variables (education, income, age, parity) were not associated with child, caregiver, and total scores on the NCATS. The results suggested that lack of autonomic stability in Japanese neonates might serve as an early indicator of infant frailty, negative behavioral cues, and decreased maternal responsiveness.

Cross-cultural comparison of the neurobehavioral characteristics of Chinese and Japanese neonates.

BACKGROUND: Similarities and differences in the neurobehavioral repertoire of neonates from different cultures have been noted using the Brazelton Neonatal Behavioral Assessment Scale (NBAS). By identifying the behavioral attributes of newborns that are seen more universally versus those that are culture-specific, comparative studies increase understanding of the roles of cultural factors in shaping the behavioral trajectory of infants. This study compared the neurobehavioral characteristics of neonates in Chengdu, China and Nagasaki, Japan. METHODS: The Brazelton NBAS was administered within the first week of life to 40 Chinese and 62 Japanese healthy, full-term neonates in Chengdu and Nagasaki. RESULTS: The two groups differed significantly in birthweight, gender, age at time of exam, mode of delivery, and gestational age. When these variables, in addition to group status (Chinese or Japanese), were entered into multiple linear analyses with NBAS cluster scores as dependent variables, group status independently predicted Range of State and Habituation scores. The group status did not predict Orientation, Motor, Regulation of States, Autonomic Stability, and Abnormal Reflexes cluster scores. CONCLUSION: These results suggest that Japanese newborns habituated more readily to stimuli, and were less irritable than newborns in the Chinese sample. The infants in the two groups shared many similar neurobehavioral characteristics as well. The implications of these similarities and differences were discussed.

Using knowledge to cope with stress in the NICU: how parents integrate learning to read the physiologic and behavioral cues of the infant.

Parental stress in the NICU has at least a short-term impact on the establishment of the parent-child relationship and potential repercussions on long-term child development outcomes. One way to help parents mitigate stress is to help them learn what they need to know about their infant's condition and care. In this article, we examine how learning to read the infant's physiologic and behavioral cues helps parents cope with stress. We view parental learning as a process in which parents target specific domains of information for learning according to the temporal relevance of the domain to their concerns. It is important that we recognize the fluidity of the process and anticipate what parents need to learn at different times during hospitalization. The NICU staff assumes a crucial role in reducing parental stress by delivering information that is relevant to the parents' needs and by helping parents understand this information.