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To examine the association between daily screen time exposure and both sleep patterns (sleep onset, sleep offset, and nighttime, and daily sleep durations) and sleep disturbances among a clinical sample of children with epilepsy.A cross-sectional actigraphic sleep study.A convenience sample of 141 children with epilepsy (1.5-6 years of age) was recruited from an outpatient pediatric neurology clinic of a university-affiliated children's hospital in northern Taiwan. Participating families completed questionnaires and reported children's screen time use, with children wearing an actigraphy monitor for 7 days to assess sleep patterns. Multivariable linear regression analyses were conducted to examine the association of screen time exposure with the child's sleep patterns and sleep disturbance scores.Mean minutes per day of screen time exposure was 89.79 ± 83.94 min, with 62 parents (44.0%) reporting their child having1 hr of screen time daily. Mean daily sleep duration was 9.26 ± 1.01 hr, with 106 children (93.0%) sleeping10 hr in a 24-hr period. In multivariate regression models, daily screen time exposure of1 hour was associated with 23.4-min later sleep onset (b = 0.39, p = .02), 20.4-min later sleep offset (b = 0.34, p = .04), and more severe sleep disturbances (b = 2.42, p = .04).In toddlers and preschool-age children with epilepsy, daily screen time exposure is greater and sleep duration is shorter than the recommended amount, with increased screen time exposure associated with disturbed sleep.Parents need to be informed about the possible adverse impact of screen time exposure on children's sleep and health as well as the importance of limiting screen time exposure to1 hr per day for their toddlers and preschool-age children with epilepsy.

Background Caregiver engagement and collaborative team early childhood intervention (ECI) services are international trends; however, relevant evidence of collaborative home-visiting ECI in rural areas is as yet undetermined. Objective The study aimed to investigate the effectiveness of a collaborative ECI program in a rural area of Taiwan. Design The study was a pilot randomized control led trial. Methods Children aged 6 to 33 months experiencing motor delays and their caregivers were enrolled in Taitung, Taiwan. Using stratified randomization, 24 participants were allocated to either experimental or control groups, and both received 5 home visits within 3 months. The experimental group received ECI services based on the International Classification of Functioning, Disability and Health framework and family-centered approaches. The control group received regular home visits by local social workers. Child outcomes included Pediatric Evaluation of Disability Inventory Chinese Version and Peabody Developmental Motor Scale, 2nd edition. Family outcomes included the Disability-Adapted Infant–Toddler version of Home Observation for Measurement, and Chinese versions of the Knowledge of Infant Development Inventory and Parental Stress Index-Short Form. A tester blinded to the study conducted assessments at baseline, postintervention, and 3-month follow-up. Two-way mixed analysis of variance was used with α = .05 (2-tailed). Results The experimental group improved scores on the Disability-Adapted Infant–Toddler version of Home Observation for Measurement significantly more than the control group with an effect size of 0.64 at follow-up. In other outcomes, both groups showed no significant differences. The follow-up rate was 69%, and adherence to the ECI program was acceptable. Limitations A limitation of the study was the heterogeneity of the sample. Conclusions This pilot study revealed possible effectiveness in implementing collaborative ECI programs based on family-centered approaches and the International Classification of Functioning, Disability and Health in rural areas. Larger field studies are needed to confirm our findings.

Although numerous studies have examined the development of preterm children born very low birth weight (VLBW, birth body weight 1500 g), variations of developmental progress within individuals have rarely been explored. The aim of this research was to examine the cognitive and motor trajectories in preterm children born VLBW at early ages and to assess the risk factors and predictability of these trajectories.Five hundred and eighty preterm infants born VLBW from three cohort studies (2003 to 2014) were prospectively assessed their mental and motor development using the Bayley Scales at 6, 12, 24, and 36 months, and cognitive, motor and behavioral outcomes using the Movement Assessment Battery for Children and the Child Behavior Checklist for Ages 1.5-5 at 4 years of age.Preterm children born VLBW manifested three cognitive patterns (stably normal [64.0 %], deteriorating [31.4 %], and persistently delayed [4.6 %]) and four motor patterns (above average [6.3 %], stably normal [60.0 %], deteriorating [28.5 %], and persistently delayed [5.2 %]) during 6-36 months. Low birth body weight, stage III-IV retinopathy of prematurity and low parental socio-economic status were associated with the deteriorating patterns; prolonged hospitalization and major brain damage were additionally associated with the persistently delayed patterns. Furthermore, the cognitive and motor deteriorating pattern was each predictive of cognitive and motor impairment at 4 years of age; whereas, the persistently delayed patterns were predictive of multiple impairments.Preterm children born VLBW display heterogeneous trajectories in early cognitive and motor development that predict subsequent developmental and behavioral outcomes.

Background Few studies have investigated multidimensional developments and free-play movement performance in toddlers with an early diagnosis of autism spectrum disorder (ASD). Objective This study compared cognitive, motor, and behavioral developments and free-play movement performance in toddlers with ASD who were full term (FT-ASD), toddlers who were full term and are typically developing (FT-TD), and toddlers who were born preterm and had a very low birth weight (VLBW-PT). Design This was a prospective cross-sectional study. Methods Forty-five 30- to 36-month-old age-matched toddlers were recruited and divided into FT-ASD, FT-TD, and VLBW-PT groups. Their developments were examined using the Mullen Scales of Early Learning; the Peabody Developmental Motor Scales, Second Edition; the Child Behavior Checklist for Ages 1.5 to 5; and the Repetitive Behavior Scale-Revised. In addition, the toddlers’ free-play movements were tracked in laboratory settings using an automatic movement tracking system. Results Toddlers with FT-ASD exhibited lower cognitive and motor scores and a higher degree of behavioral problems compared with toddlers with FT-TD or VLBW-PT. Furthermore, the movement tracking data in a free-play setting revealed that toddlers with FT-ASD displayed a higher degree of turning velocity, a higher moving time, and a higher frequency of moving toward the peripheral region compared with toddlers with FT-TD or VLBW-PT. Moreover, several motor developmental and movement-tracking indicators were found to correlate with behavioral problems and cognitive scores in toddlers with FT-ASD. Limitations The study results may have been affected by the small sample size, the cross-sectional design, and tracking only the whole body without subtle movements or segmental motions. Conclusions The findings suggest varied aspects of co-occurring developmental conditions and movement-based problems in toddlers with FT-ASD. Using standardized and sensitive measures for the early assessment of perceptuo-motor impairments is necessary for timely early intervention for such toddlers.

Background The Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M−CHAT-R/F) is a two-stage screening scale for determining the risk of autism spectrum disorder (ASD) in toddlers. However, the validity of the M−CHAT-R/F for Asian populations has not yet been established. Aims This study investigated the psychometric properties of the M−CHAT-R/F, Taiwan version (M−CHAT-R/F–T), among low- and high-risk Taiwanese toddlers aged 16–30 months. The associations among M−CHAT-R/F−T scores, developmental performance at 24 and 30 months, and ASD diagnosis prediction at 36 months were examined. Methods and Procedures A two-stage screening of the M−CHAT-R/F−T was applied to a study sample comprising 25 toddlers with ASD and 71 atypically developing (ATD) and 221 typically developing (TD) toddlers. Outcomes and Results The M−CHAT-R/F–T exhibited acceptable internal consistency and test–retest reliability. The M−CHAT-R/F–T scores were significantly correlated with several syndrome scores of the Child Behavior Checklist for Ages 1.5–5 and were significantly higher among toddlers with ASD than among ATD or TD toddlers. Furthermore, M−CHAT-R/F–T scores were negatively correlated with developmental scores in the Mullen Scales of Early Learning at 24 and 30 months. Moreover, the screening exhibited acceptable predictive validity (sensitivity = 0.86; specificity = 0.96) for ASD diagnosis at 36 months. Conclusions and Implications The findings indicate that the M−CHAT-R/F–T is a valid and reliable tool for the developmental screening of low- and high-risk Taiwanese toddlers in community and clinical settings.

Purpose To describe sleep patterns in young children with epilepsy and to examine levels of agreement between measurements derived from actigraphy and diary recordings. Design Cross-sectional study. Methods Eighty-nine toddlers and preschool-aged children with epilepsy wore an actigraph on their wrists for 7 consecutive days. Parents and caregivers maintained a concurrent sleep diary while the child was wearing the monitor. Levels of agreement between actigraphy and diary recordings were examined using the Bland and Altman method separately for all recording days, weekdays, and weekends. Findings Discrepancies between actigraphy-derived and diary-documented sleep onset, sleep offset, actual sleep at night, wake after sleep onset, and daytime sleep were ±35, ±15, ±82, ±70, and ±29 min, respectively. Differences between actigraphy and diary-derived sleep variables were consistently greater for weekends than for weekdays. Discrepancies between actigraphy and diary-derived actual sleep at night were significantly greater for children who slept alone than for those who co-slept with a parent. Conclusions Our study demonstrates an acceptable agreement between actigraphy and diary recordings for sleep onset, sleep offset, and daytime sleep, but insufficient agreement for actual sleep at night and wake after sleep onset, with parents of children sleeping alone more likely to misestimate child sleep behaviors. Deviation of weekend sleep from weekdays further decreased the accuracy of parental sleep estimates and increased the discrepancies between actigraphy and diary. Clinical relevance Sleep in children with epilepsy assessed using diary recordings alone could be misleading, and actigraphy should be preferred over diaries when resources are available.

Background Family-centered care for preterm infants in Western societies has yielded short- to medium-term benefits. However, the intervention effects have rarely been validated in Eastern societies. Objective The aim of this study was to examine whether a family-centered intervention program (FCIP) could improve the short-term medical and neurobehavioral outcomes in preterm infants with very low birth weight (VLBW; a birth weight of Design This was a multicenter, single-blind, randomized controlled trial study. Setting Three medical centers in northern and southern Taiwan were the locations for the study. Participants The participants were 251 VLBW preterm infants without severe perinatal complications. Intervention The infants were randomly assigned to receive the FCIP or the UCP during hospitalization. Measurements Infant morbidities, feeding, growth, and neurobehavioral performance were evaluated during the neonatal period. Parental adherence to interventions was measured in the FCIP group. Results The FCIP promoted earlier full enteral feeding (β = –1.1 weeks; 95% CI = –1.9 to –0.2 weeks) and hospital discharge (β = –0.6 week; 95% CI = –1.1 to –0.1 weeks), greater weight gain (β = 3.3 g/d; 95% CI = 0.1 to 6.6 g/d), and better neurobehavioral performance than the UCP (β = 1.2 points; 95% CI = 0.2 to 2.3 points). Furthermore, a higher degree of parental motivation in interventions, goal attainment, and comprehensiveness of home activities was significantly associated with greater effects in infants’ neurobehavioral performance and weight gain (r = .20–.31; all Ps Limitations The findings may not be generalized to preterm infants with severe perinatal diseases and parents with a low level of interest in interventions. Conclusions Family-centered care facilitated short-term medical and neurobehavioral outcomes in VLBW preterm infants in Taiwan; the effects were likely achieved through parental adherence to interventions. The designated strategies may be considered in a future launch of family-centered care in Taiwan.

Background Early identification of motor dysfunction in preterm infants with very low birth weight (VLBW) is important in order to provide early intervention. Objective This study was to examine the motor trajectories of preterm infants with VLBW during their first year of life and to investigate the predictive ability and influencing factors of the trajectories. Design and Methods A total of 342 preterm infants with VLBW were prospectively assessed for motor development by the Alberta Infant Motor Scales at 4, 6, 9, and 12 months and for developmental outcomes using the Bayley Scales of Infant and Toddler Development, second edition, at 24 months. Perinatal and socio-environmental factors were collected at baseline. Growth mixture modeling was used to explore the patterns of infants’ motor trajectories during their first year of life. Logistic regression analyses were applied to examine the influencing factors associated with motor trajectories and their predictability of 24-month developmental outcomes. Results Preterm infants with VLBW showed 3 distinct motor trajectories: stably normal (55%), deteriorating (32%), and persistently delayed (13%). Furthermore, the motor trajectories were predictive of 24-month cognitive and motor outcomes. Perinatal factors including lower birth weight, male gender, moderate to severe bronchopulmonary dysplasia, stage III to IV retinopathy of prematurity, and major brain damage were associated with a risk of deteriorating and persistently delayed trajectories (all P < .05). Socio-environmental factors had no association with motor trajectories. Limitations The small sample size of the infants with a persistently delayed trajectory may have limited the assessment of some influencing factors. Conclusion The identified early motor trajectories, predictive values, and influencing factors provide insightful implications for early detection and prevention of motor -disorders in preterm infants with VLBW.

Background Family-centered intervention for preterm infants has shown short- to medium-term developmental benefits; however, the neurological effects of intervention have rarely been explored. Objective The objectives of this study were to examine the effect of a family-centered intervention program (FCIP) on neurophysiological functions in preterm infants with very low birth weight (VLBW; birth weight of Design This was a multicenter, single-blind randomized controlled trial. Setting The study took place in 3 medical centers in northern and southern Taiwan. Participants Two hundred fifty-one preterm infants with VLBW were included. Intervention The FCIP group received a family-centered intervention and the UCP group received standard care during hospitalization. Measurements Infants were assessed in terms of neurobehavioral performance using the Neonatal Neurobehavioral Examination–Chinese version, and their neurophysiological function was assessed using electroencephalography/event-related potentials during sleep and during an auditory oddball task during the neonatal period. Results The FCIP promoted more mature neurophysiological function than the UCP, including greater negative mean amplitudes of mismatch negativities in the left frontal region in the oddball task in all infants, lower intrahemispheric prefrontal-central coherence during sleep in infants who were small for gestational age, and higher interhemispheric frontal coherence during sleep in those who were appropriate for gestational age. Furthermore, interhemispheric coherence was positively associated with the total neurobehavioral score in preterm infants who were appropriate for gestational age (r = 0.20). Limitations The fact that more parental adherence strategies were used in the FCIP group than in the UCP group might have favored the intervention effect in this study. Conclusions Family-centered intervention facilitates short-term neurophysiological maturation in preterm infants with VLBW in Taiwan.

We conducted a cross-sectional study to examine sleep in mothers of children with epilepsy and its relation to their children's sleep. A total of 133 dyads of mothers and children with epilepsy aged 1.5-6 years were recruited between 2015 and 2018 from a children's hospital in northern Taiwan. Participating families provided demographic and health information, with children wearing an actigraphy monitor for 7 days and mothers completing sleep and depressive mood questionnaires. We found that 76 (57.1%) of the mothers had poor sleep quality, with 65 (48.9%) mothers having a clinically significant depressive symptom score. Mean actigraphic wake after sleep onset in children was 1.42 (standard deviation = 0.51) hours, with 126 (94.7%) of the children having a clinically significant sleep disturbance score. Multivariate regression analyses showed that higher depressive symptom scores in mothers (β = 0.14; p < .01) and higher sleep disturbance scores in children (β = 0.07; p = .04) were associated with poorer maternal sleep quality, even when maternal demographic characteristics and the child's clinical and epilepsy variables were considered. Findings from our study suggest that sleep disturbances are a shared problem for mothers and their children with epilepsy. Sleep in both mothers and their children with epilepsy should be evaluated in pediatric neurologic practices, with maternal depressive symptoms screened concurrently. Future pediatric epilepsy studies are warranted to examine whether a family-based intervention program would be effective to improve sleep in mother-child dyads and to promote better health and functioning of the entire family.

Study ObjectivesTo evaluate the effect of a clinic-based, behavioral-educational sleep intervention on sleep of children with epilepsy, maternal knowledge about childhood sleep, and maternal sleep quality.MethodsA total of 100 toddlers and preschool-age children with epilepsy (1.5–6 years, 55% boys) and their parents were randomized to receive sleep intervention (n = 50) or usual care with attention (n = 50). Outcomes were assessed at baseline, 3, 6, and 12 months after intervention with the use of objective actigraphy, Children’s Sleep Habits Questionnaire, Parents’ Sleep Knowledge Inventory, and Pittsburgh Sleep Quality Index. Intervention effects were examined using general linear models for repeated measurements to compare the mean change in outcomes from baseline to 12 months post-intervention between the two groups.ResultsSleep intervention resulted in children having greater sleep efficiency by 2.03% compared with the usual care group (95% CI = 0.20% to 3.86%; p = .03). Children in the intervention group also had significantly longer total nighttime sleep as objectively assessed by actigraphy than did those in the usual care group, with an adjusted mean difference of 16.13 minutes (95% CI = 0.24% to 32.03%; p = .04). No intervention effects were observed for maternal knowledge about childhood sleep, and maternal sleep quality.ConclusionSleep intervention provided during routine neurologic visits results in significant, measurable, and sustained benefits in sleep quality and quantity in children with epilepsy. Future trials are warranted to evaluate whether improvements in sleep could impact health-related quality of life or other aspects of functioning in children with epilepsy.Clinical TrialThis trial has been registered at www.clinicaltrials.gov (trial name: Sleep Intervention for Pediatric Epilepsy; registration number: NCT02514291).

Study objectives To examine maternal knowledge of childhood sleep and its relation to sleep quantity, quality, and variability in a clinic sample of mothers of toddlers and preschool-age children with epilepsy. Methods A total of 112 epileptic children wore a wrist actigraphy to objectively assess daily sleep duration and its variability across 7 days. Mothers completed the Parents' Sleep Knowledge Inventory and Children's Sleep Habits Questionnaire (CSHQ). Multivariate linear regression models were performed to predict CSHQ sleep disturbance scores, daily sleep duration, and daily sleep duration variability in children with epilepsy. Results On average, mothers answered 30.5 per cent of the questions correctly about normal childhood sleep patterns. Only six (5.3%) of the mothers answered half or more of the questions correctly. Mothers more frequently answered "don't know" to questions about dreams, symptoms of sleep-disordered breathing, and adequate amounts of sleep required by children and adolescents. After adjusting for the child's age, gender, bed-sharing, and relevant clinical and epilepsy variables, poorer maternal sleep knowledge was the independent predictor of higher CSHQ sleep disturbance scores and greater intraindividual variability of daily sleep duration in epileptic children (p Conclusions Maternal knowledge about childhood sleep is inadequate and decreased maternal sleep knowledge is associated with poorer and more variable sleep in children with epilepsy. Findings from this study document the need to provide parental education about childhood sleep, particularly emphasizing the recommended sleep duration for children across different developmental stages and addressing the symptoms of sleep disorders commonly comorbid with epilepsy. Trial registration This trial has been registered at www.clinicaltrials.gov (trial name: Sleep Intervention for Pediatric Epilepsy; registration number: NCT02514291).

Background Increasing evidence shows common motor deficits associated with autism spectrum disorder (ASD) that can relate to impaired planning and control processes of the sensorimotor system. Catching is a fundamental motor skill that requires coordination between vision, posture, and arm movements. Although postural control and ball catching have been shown to be impaired in children with ASD, previous studies have not investigated how these components are integrated. Objective The objective of this study was to investigate the sensorimotor control of arm movements and postural adjustments during ball catching in children with and without ASD. Design This study employed a cross-sectional design. Methods Fifteen children with ASD (mean [SD] age = 8.8 [1.2] years; 12 boys) and 15 age- and sex-matched typically developing children participated in this study. Children were asked to catch a ball rolling down a ramp in 6 test conditions in which visual inputs and ramp direction were manipulated to provide different sensory conditions and postural demands. Results Compared with their typically developing peers, children with ASD had increased difficulties catching balls, especially those from lateral directions. They less often used visual information to plan for catching motion, demonstrated fewer and delayed anticipatory postural adjustments, and exhibited increased corrective control. Limitations The sample excluded children with intellectual disability and attention deficit and hyperactivity disorders that might reduce the generalizability to the whole ASD population. Conclusions Our results suggest that motor difficulties present in children with ASD can result from compromised sensorimotor integration in planning and control of movements.

We designed a cross-sectional study to examine the association between sleep and behavior problems in toddlers and preschool-age children with epilepsy. We found that 71 (78.9%) children slept less than 10 hours in a 24-hour period according to the actigraphy, with 75 (83.3%) children waking for more than an hour during nocturnal sleep. Twenty-five (27.8%) children usually or sometimes had an inconsistent bedtime, and 24 (26.7%) did not sleep the same amount each day. Twenty-nine (32.2%) and 18 (20.0%) children had an internalizing and externalizing problem in clinical range, respectively. Sleep anxiety was significantly (p < .01) associated with increased internalizing and externalizing problems, even after the relevant epilepsy variables were controlled for. Findings from our study suggest that screening of sleep and behavior problems should be part of routine epilepsy care to identify children with problematic sleep and unrecognized sleep disorders and those at risk of behavioral dysfunction.

Background Nationwide birth weight norms for twins have been reported in several countries across different ethnicities, but such data have not been established in Taiwan. The purpose of this study was to develop reference growth charts that are population-based and contain the information of birth weight percentiles by gestational age for twin neonates in Taiwan. Methods In this study, we collected nationwide birth weight data for twins by sex and gestational age through the Taiwan Birth Registry. Percentiles, means, and standard deviations of birth weight for each 1-week increment of gestational age from 21 weeks of gestation were estimated and smoothed using weighted polynomial models. Results The 10 th , 50 th , and 90 th percentiles of birth weight born at the 37 th gestational week were 2174 g, 2580 g, and 3125 g for male twins, respectively, and they were 2100 g, 2500 g, and 3000 g for female twins, respectively. The 10 th , 50 th , and 90 th percentiles of birth weight born at the 40 th gestational week were 2326, 3285, and 3790 g for male twins, respectively, and they were 2200 g, 2770 g, and 3690 g for female twins, respectively. Conclusion This is the first nationwide birth weight norm for twins in Taiwan, which is particularly useful for investigation into the predictors and outcomes of altered fetal growth through twin studies in the Taiwanese population.

BackgroundThere are limited nationwide data relating to neonatal mortality rate in Taiwan. This study aims to provide updated national birth weight/gestational age-specific neonatal mortality reference rates.MethodsWe abstracted the birth registration database from the Ministry of Interior in Taiwan from 1998 to 2002 and linked the data to the death registration database from the Ministry of Health and Welfare in Taiwan between 1998 and 2003. We included 1,331,785 infants born between 20 weeks and 44 weeks of gestation and weighing within the median ± 2 interquartile ranges in their age group in this study. We calculated the birth weight/gestational age-specific neonatal mortality rates of different genders by birth weight increments of 250 g and at gestational age intervals of 1 week. A Poisson regression model was used in modeling the mortality data.ResultsA total of 4,169 deaths occurred within 28 days of life out of a total of 1,331,785 live births between 20 weeks and 44 weeks of gestation, giving a neonatal mortality rate (0–27 days) of 3.39 per 1000 live births for males and 2.80 per 1000 for females. The infant mortality rate remained higher in the male (5.91 per 1000) than the female (5.10 per 1000) population within the 1st year of life. Birth weight/gestational age-specific neonatal mortality rates were plotted with curves representing the 10th and 90th birth weight percentiles. The risk of an early neonatal death (0–6 days) does not exceed 50% except for female neonates

To describe sleep patterns in young children with epilepsy and to examine levels of agreement between measurements derived from actigraphy and diary recordings.Cross-sectional study.Eighty-nine toddlers and preschool-aged children with epilepsy wore an actigraph on their wrists for 7 consecutive days. Parents and caregivers maintained a concurrent sleep diary while the child was wearing the monitor. Levels of agreement between actigraphy and diary recordings were examined using the Bland and Altman method separately for all recording days, weekdays, and weekends.Discrepancies between actigraphy-derived and diary-documented sleep onset, sleep offset, actual sleep at night, wake after sleep onset, and daytime sleep were ±35, ±15, ±82, ±70, and ±29 min, respectively. Differences between actigraphy and diary-derived sleep variables were consistently greater for weekends than for weekdays. Discrepancies between actigraphy and diary-derived actual sleep at night were significantly greater for children who slept alone than for those who co-slept with a parent.Our study demonstrates an acceptable agreement between actigraphy and diary recordings for sleep onset, sleep offset, and daytime sleep, but insufficient agreement for actual sleep at night and wake after sleep onset, with parents of children sleeping alone more likely to misestimate child sleep behaviors. Deviation of weekend sleep from weekdays further decreased the accuracy of parental sleep estimates and increased the discrepancies between actigraphy and diary.Sleep in children with epilepsy assessed using diary recordings alone could be misleading, and actigraphy should be preferred over diaries when resources are available.

This study examined the effects and mediators of a clinic-based intervention program (CBIP) and a home-based intervention program (HBIP) compared with usual care in very-low-birth-weight (VLBW) preterm infants on developmental and behavioral outcomes at 24 months of age (corrected for prematurity). In this randomized controlled trial, VLBW preterm infants received either CBIP (n=57), HBIP (n=63), or usual care (n=58) from hospitalization to 12 months. At 12 months, infant emotional regulation was assessed using the toy-behind-barrier procedure and dyadic interaction was observed during free play. At 24 months, infant developmental and behavioral outcomes were assessed using the Bayley Scales of Infant and Toddler Development- 3rd edition and the Child Behavior Checklist for Ages 1.5-5, respectively. Compared with infants under usual care, the CBIP-group infants showed higher cognitive composite scores (difference, 95% confidence interval (CI)=4.4, 0.8-7.9) and a lower rate of motor delay (odds ratio (OR), 95% CI=0.29, 0.08-0.99); the HBIP-group infants had lower sleep problem scores (difference, 95% CI=-1.4, -2.5 to -0.3) and a lower rate of internalizing problems at 24 months (OR, 95% CI=0.51, 0.28-0.93) (all p

Summary Accumulating evidence suggests a role for microRNAs (miRNAs) in regulating various processes of mammalian postnatal development and aging. To investigate the changes in blood-based miRNA expression from preterm infants to adulthood, we compared 365 miRNA expression profiles in a screening set of preterm infants and adults. Approximately one-third of the miRNAs were constantly expressed from postnatal development to adulthood, another one-third were differentially expressed between preterm infants and adults, and the remaining one-third were not detectable in these two groups. Based on their expression in infants and adults, the miRNAs were categorized into five classes, and six of the seven miRNAs chosen from each class except one with age-constant expression were confirmed in a validation set containing infants, children, and adults. Comparing the chromosomal locations of the different miRNA classes revealed two hot spots: the miRNA cluster on 14q32.31 exhibited age-constant expression, and the one on 9q22.21 exhibited up-regulation in adults. Furthermore, six miRNAs detectable in adults were down-regulated in older adults, and four chosen for individual quantification were verified in the validation set. Analysis of the network functions revealed that differentially regulated miRNAs between infants and adults and miRNAs that decreased during aging shared two network functions: inflammatory disease and inflammatory response. Four expression patterns existed in the 11 miRNAs from infancy to adulthood, with a significant transition in ages 9–20 years. Our results provide an overview on the regulation pattern of blood miRNAs throughout life and the possible biological functions performed by different classes of miRNAs.

Background Epidemiologic data regarding the potential neurotoxicity of perfluorinated compounds (PFCs) are inconclusive. We investigated the associations between in utero exposure to perfluorooctanoic acid (PFOA) and perfluorooctyl sulfonate (PFOS) and early childhood neurodevelopment. Methods We recruited 239 mother-infant pairs in northern Taiwan from the Taiwan Birth Panel Study, which was established in 2004. We examined the association between PFCs in cord blood and children's neurodevelopment at 2 years of age, using the Comprehensive Developmental Inventory for Infants and Toddlers. This tool contains cognitive, language, motor, social, and self-help domains; test scores were further transformed into developmental quotients according to standardized norms. All multivariate regression models were adjusted for infant sex and gestational age, maternal education, family income, cord blood cotinine levels, postnatal environmental tobacco smoke exposure, and breastfeeding. Results Prenatal PFOS concentrations in both untransformed and natural log (Ln)-transformed values were associated with adverse performance on the whole test and the domains related to development. A dose-response relationship was observed when PFOS levels were categorized into four groups. This association was most obvious in relation to the gross-motor subdomain. Across the PFOS interquartile range, the quotients of the gross-motor subdomain decreased by 3.7 points (95% confidence interval [CI] = -6.0 to -1.5), with an increasing odds ratio of poor performance (2.4; 95% CI = 1.3 to 4.2). In contrast, measures of association between PFOA concentrations and test scores were close to null. Conclusions Prenatal exposure to PFOS, but not PFOA, may affect children's development, especially gross-motor development at 2 years of age.

This study investigated the effect of still-face interaction on the affect, behavior, and perception in mothers of term and low-birth-weight preterm (gestational age

Introduction Intervention studies of developmental care for preterm infants in Western societies have shown early but unsustainable effects on child outcomes, however only a limited of studies have examined if developmental care interventions produce similar effects in Eastern cultural contexts. Aims To examine the effectiveness of in-hospital developmental care on neonatal morbidity, growth and development of preterm infants with very low birth weight (VLBW; birth weight Methods One hundred and seventy-eight VLBW preterm infants were randomly assigned to the clinical trial during hospitalization at three hospitals in Taiwan; the control group received five sessions of standard child-focused developmental care and the intervention group received five sessions of child- and parent-focused developmental care. Sixty-two normal term infants were also included as a comparison group. Infants were examined for morbidity, growth and developmental outcomes at term age. Results At study entry, more infants in the intervention group were twins or multiples than those in the control group (29% vs. 16%, p = 0.05). After adjusting for birth set, the intervention group had lower incidences of stage II–III retinopathy (odds ratio [OR] = 0.34 [95% confidence interval (CI): 0.15–0.79]; p = 0.01) and feeding desaturation (OR = 0.32 [95% CI: 0.10–1.00]; p = 0.05) and had greater daily weight gains (difference = 2.0 g/day [95% CI: 0–4.0 g/day]; p = 0.05) as compared with the control group. However, the intervention and control groups did not differ in any of the neurodevelopmental measures. Conclusions In-hospital developmental care has short-term benefits for Taiwanese VLBW preterm infants in reducing the risk of retinopathy and feeding desaturation as well as in enhancing weight gains at term age.

The objective of this study was to examine the relationships of Doppler cerebral blood flow velocity (CBFV) asymmetry measures with developmental outcomes in term infants. Doppler CBFV parameters (peak systolic velocity [PSV] and mean velocity [MV]) of the bilateral middle cerebral arteries of 52 healthy term infants were prospectively examined on postnatal days 1-5, and then their motor, cognitive and language development was evaluated with the Bayley Scales of Infant and Toddler Development, Third Edition, at 6, 12, 18 and 24 months of age. The left CBFV asymmetry measure (PSV or MV) was calculated by subtracting the right-side value from the left-side value. Left CBFV asymmetry measures were significantly positively related to motor scores at 6 (r = 0.3-0.32, p0.05) and 12 (r = 0.35, p0.05) months of age, but were not related to cognitive or language outcome. Thus, the leftward hemodynamic status of the middle cerebral arteries, as measured by cranial Doppler ultrasound in the neonatal period, predicts early motor outcome in term infants.

Background and objective Manganese, lead, arsenic and mercury are common neurotoxic metals in the environment. Nonetheless, the relationship between prenatal exposure to low doses of neurotoxic metals and neurodevelopment in children is not clear. The objective of this study was to explore the relationship between in utero exposure to environmental neurotoxic metals and neurodevelopment at 2 years of age. Methods The population of this study came from the Taiwan Birth Panel Study. We included 230 pairs of non-smoking mothers without any occupational exposure and their singleton full-term children. The information about exposure during pregnancy was obtained using a structured questionnaire, and the manganese, lead, arsenic and mercury levels in umbilical cord blood samples were analyzed using inductively coupled plasma mass spectrometry. We used the Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) to evaluate the developmental status of each child at 2 years of age, and we examined the association of in utero exposure to environmental metals and neurodevelopment using linear regression models. Results The median concentrations of manganese, lead, arsenic and mercury in the cord blood samples in this study were 47.90 µg/L (range, 17.88–106.85 µg/L), 11.41 µg/L (range 0.16–43.22 µg/L), 4.05 µg/L (range, 1.50–12.88 µg/L) and 12.17 µg/L (range, 1.53–64.87 µg/L), respectively. After adjusting for maternal age, infant gender, environmental tobacco smoke during pregnancy and after delivery, Home Observation for Measurement of the Environment Inventory results, and arsenic and mercury levels in cord blood, we found that manganese and lead levels above the 75th percentile had a significant adverse association with the overall (β=−7.03, SE=2.65, P=0.0085), cognitive (β=−8.19, SE=3.17, P=0.0105), and language quotients (β=−6.81, SE=2.73, P=0.0133) of the CDIIT. Conclusions In utero exposure to environmental manganese and lead may have an adverse association with neurodevelopment at 2 years of age, and there is an interaction effect between the manganese and lead levels in the cord blood that could aggravate the effect.

Background This study aimed to investigate the association between cord blood cotinine levels and birth outcome, and to determine whether fetal metabolic gene polymorphisms of glutathione-S-transferase (GST) modulate the effect of environmental tobacco smoke exposure during pregnancy. Methods This study included 328 maternal and neonatal pairs. Maternal and cord blood cotinine levels were measured using high performance liquid chromatography. The GST T1 ( GSTT1 ) and GST M1 ( GSTM1 ) polymorphisms were examined using the polymerase chain reaction method. The birth outcomes included birth weight, length, and head circumference, and the risks of having low birth weight and being small for gestational age (SGA). Results Cord cotinine level had a dose-dependent impact on the reduction of birth weight, length, and head circumference in newborns. Elevation of cord blood cotinine concentration increased the rate of SGA and low birth weight. The neonates who had GSTT1 or GSTM1 polymorphism were associated with an increased risk of being SGA. A combination of the GSTT1 and GSTM1 null genotype exacerbated the effect of maternal environmental tobacco smoke exposure on SGA more than the presence of either genotype alone (odds ratio=8.90, 95% confidence interval=1.00–79.5). Conclusion Cord blood cotinine adversely affects birth outcomes. GSTT1 and GSTM1 null genotype may modify the effect of cord blood cotinine on birth outcomes.

Objective The purpose of this study was to evaluate the nationwide stillbirth rate and explore the potential risk factors associated with stillbirths. Patients and methods Data from vital registrations during the time period from January 1, 2001 through to December 31, 2004 in Taiwan were used. Stillbirth was defined as fetal death with more than 20 completed weeks’ gestational age (GA) or with birth weight more than 500 g if the GA was not known. Results There were a total of 8481 stillbirths identified nationwide between January 1, 2001 and December 31, 2004. The stillbirth rate was nine per 1000 total births in the study period, and the proportionate decline was nearly 48.8% in the most recent decade. There was a significant increase in average maternal age during this period. Advanced maternal age and teenage pregnancy were independent significant risk factors for stillbirths even after accounting for the effects of medical conditions that were more likely to occur among these particular age groups. Those fetuses that had been exposed to cord prolapse, maternal cervical incompetence and oligohydramnios/polyhydramnios were especially vulnerable. By contrast, women who had foreign nationality, fetal ultrasound surveys, fetal heart beat monitoring and hastened parturition were less likely to have stillbirth. Conclusion The stillbirth rate in Taiwan has remained high despite advancements in medical care. Prenatal evaluation of high risk women may decrease the adverse fetal outcomes.

Background: The objectives of the present study were to explore whether maternal psychosocial factors, mental health and work stress around delivery, are related to the behavior of 2-year-old children. Methods: In a prospective cohort study design, pregnant women attending the National Taiwan University Hospital for delivery and post-partum care from April 2004 to January 2005 were recruited and their children were observed at 24 months. A total of 186 mother–term-born child dyads completed the measurement. The five-item Mental Health Index (MHI-5) self-report data of maternal psychosocial factors were selected from the Taiwanese version of the short form 36 (SF-36). The Child Behavior Checklist for age 1½–5 (CBCL/1½-5) was completed by the parents when the child was 2 years old. Results: The mean score of mental health around delivery was 68.11. The proportion of mothers with work stress seldom and always was 61.8% and 24.7%, respectively. The mean of the total CBCL score, and internalizing, externalizing behavior and sleep problems scores was 45.95, 11.89, 15.59 and 4.23, respectively. After adjusting for the potential confounders, maternal work stress around delivery was found to have a significant effect on the total CBCL and externalizing, attention and aggressive, behavioral problems of 2-year old children. Maternal mental health around delivery, however, did not show significant effects on child behavior. Conclusions: Work stress around delivery seems to aggravate children's externalizing behavior problems at 2 years old. It is therefore important to improve the psychosocial health and reduce the stress of pregnant women.

Although racial/ethnic disparities in neonatal and infant health are well known, positive associations between migration and perinatal health exist among immigrant mothers in western countries. There are unique marriage migration, East Asia culture, universal national health insurance system, and adequate social support in Taiwan that may differ from the situation in western countries. We aimed to assess the neonatal outcomes among live births to married immigrant mothers in recent years in Taiwan.We conducted a population-based analysis among all the live births in Taiwan during the period 1998-2003 to assess neonatal outcomes, including incidence of low birth weight and preterm birth and of early and late neonatal mortality, according to maternal nationality. Logistic regression was used to estimate the odds ratios (ORs) associated with low birth weight and preterm birth, and Cox proportional hazards were used to estimate the relative risks (RRs) associated with mortality in the neonatal period.There were a total of 1,405,931 single live births, including 6.6% born to immigrant mothers and 93.4% born to Taiwanese mothers. Disparities existed among the intercultural couples, including paternal age, parental educational level, and residential distribution. Fewer low birth weight and fewer preterm babies were born to immigrant mothers than to Taiwanese mothers. In addition, babies born to immigrant mothers had lower early neonatal and neonatal mortalities than those born to Taiwanese mothers. There were lower risks of having a low birth weight (adjusted OR [AOR] 0.73, 95% confidence interval [CI] 0.70-0.75) or preterm (AOR 0.72, 95% CI 0.69-0.74) baby and lower hazard ratios (HRs) of having an early neonatal death (adjusted HR [AHR] 0.68, 95% CI 0.56-0.82) or neonatal death (AHR 0.74, 95% CI 0.64-0.87) in babies born to immigrant mothers. There is a gradual increase in the risks of adverse neonatal outcomes associated with increases in length of residence.Evidence of a healthy immigrant mother effect on neonatal health is clear. Despite lower parental education, advancing paternal age, and spatial distribution disparity, babies born to married immigrant mothers in Taiwan had favorable neonatal outcomes.

BackgroundArterial blood gas analysis is the gold standard for assessing the adequacy of ventilation. However, arterial blood sampling may be associated with serious complications in neonates. The aim of the study was to utilize the side-stream capnometry measurement of end-tidal carbon dioxide (PetCO2) via nasal cannula circuits and to verify the reliability of PetCO2 in reflecting the arterial blood carbon dioxide (PaCO2) level in nonintubated neonates.MethodsA retrospective medical record review analysis was performed in nonintubated neonates admitted to the neonatal ward in a medical center. Simultaneous arterial PaCO2 and PetCO2 levels were evaluated. PaCO2 and PetCO2 levels were compared by paired t test and were correlated using Pearson's correlation. The PetCO2 bias was defined as the difference between PaCO2 and PetCO2, and was assessed by Bland-Altman plot analysis.ResultsA total of 34 neonates were recruited, and data of 54 pairs of PaCO2 and PetCO2 levels were available for comparison. The average (mean ± SD) gestational age was 32.5 ± 4.2 weeks, and the average birth weight was 1881 ± 1077 g. There was a good correlation between PetCO2 and PaCO2 levels among all paired samples (r = 0.809, p < 0.001). When the data were divided into those with respiratory disease (n = 34) and those without (n = 20), significant correlation between PetCO2 and PaCO2 levels were both noted in the former group (r = 0.823, p < 0.001) and the latter group (r = 0.770, p < 0.001). The overall average mean value of PetCO2 was lower than that of PaCO2 (39.4 ± 8.8 mmHg vs. 41.3 ± 9.2 mmHg, p = 0.014). The difference between PetCO2 and PaCO2 levels was significant only among those with respiratory disease (38.8 ± 9.8 mmHg vs. 41.2 ± 10.3 mmHg, p = 0.027), but not among those without (40.5 ± 7.0 mmHg vs. 41.6 ± 7.2 mmHg, p = 0.289).ConclusionsEnd-tidal CO2 measurement by side-stream capnometry through nasal cannula could provide an accurate and noninvasive estimate of PaCO2 levels in nonintubated neonates.

Objective: To test the fit of a seven-syndrome model to ratings of preschoolers' problems by parents in very diverse societies. Method: Parents of 19,106 children 18 to 71 months of age from 23 societies in Asia, Australasia, Europe, the Middle East, and South America completed the Child Behavior Checklist for Ages 1.5-5 (CBCL/1.5-5). Confirmatory factor analyses were used to test the seven-syndrome model separately for each society. Results: The primary model fit index, the root mean square error of approximation (RMSEA), indicated acceptable to good fit for each society. Although a six-syndrome model combining the Emotionally Reactive and Anxious/Depressed syndromes also fit the data for nine societies, it fit less well than the seven-syndrome model for seven of the nine societies. Other fit indices yielded less consistent results than the RMSEA. Conclusions: The seven-syndrome model provides one way to capture patterns of children's problems that are manifested in ratings by parents from many societies. Clinicians working with preschoolers from these societies can thus assess and describe parents' ratings of behavioral, emotional, and social problems in terms of the seven syndromes. The results illustrate possibilities for culture general taxonomic constructs of preschool psychopathology. Problems not captured by the CBCL/1.5-5 may form additional syndromes, and other syndrome models may also fit the data., Dr. Ivanovo receives research and salary support from the Research Center for Children, Youth, and Families, which publishes the Child Behavior Checklist [CBCL]. Dr. Achenbach is President of the Research Center for Children, Youth, and Families, and receives remuneration. Dr. Rescorla receives remuneration from the Research Center for Children, Youth, and Families. Dr. Harder previously held a University of Vermont Postdoctoral Fellowship funding by the Research Center for Children, Youth, and Families. Drs. Bjarnadottir, Gudmundsson, Leung, Verhulst, and Mr. Gudmundsson, receive research support from the sole of the CBCL. Dr. Bilenberg has received honoraria from Eli Lilly and Co., Novartis, Neuroscience, and Janseen Cilag. He has received research support from the Danish Research Foundation, the Lundbeck Foundation, Hermansens Mindelegat, and Mods Clausen Fond. Dr. Rapes has received research support from the Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences. Dr. Jusiene has received research support from the Lithuanian Science and Studies Foundation. Drs. Ang, Capron, Dias, Dobrean, Doepfner, Duyme, Erol, Esmaeili, Ezpeleta, Frigerio, Goncalves, Jung, Kim, Liu, Oh, Plueck, Pomo limo, Shahini, Silva, Simsek, Souronder, Valverde, Van Leeuwen, and Zubrick, Ms. De Paw, Ms. Kristensen, Mr. Lecannelier, Ms. Montirosso, Ms. Jetishi, Ms. Woo, and Ms. Wu report no biomedical financial interests or potential conflicts of interest., info:eu-repo/semantics/publishedVersion

Aim: Osteopaenia commonly occurs in preterm infants; however, its diagnosis is often delayed when based on radiological findings. The aim of this study was to examine whether serial measurements of bone turnover markers are useful for early prediction of osteopaenia in preterm infants. Methods: Premature infants of ≤34 weeks gestation were enrolled. Serum alkaline phosphatase (ALP), bone form ALP (BALP), calcium and inorganic phosphate were concurrently measured biweekly from 3 weeks post-natal age until 40 weeks post-conceptional age. Radiographic examination of the forearm was performed at term age. Osteopaenia was defined as positive radiographic findings according to Koo's criteria. Results: Of the 46 premature infants completing the follow-up study at term age, 18 showed osteopaenia in radiographic examination. Serum ALP was highly correlated with BALP (R2 = 0.93, P

Aim: To explore whether maternal psychosocial factors around delivery are related to development of 2-year-old children. Methods: Pregnant women going to the hospital for delivery were recruited, and their children were observed at 24 months. A total of 186 mother–child dyads completed the measurement. Self-report data of maternal psychosocial factors around delivery were selected from the Taiwanese version of the short-form 36. The Comprehensive Developmental Inventory for Infants and Toddlers was completed by interviewers and the main care givers for the child at 2 years old. Results: Using the multiple linear regression analysis and adjusting for potential confounders, maternal vitality around delivery was found to have a significantly positive relationship with the whole Comprehensive Developmental Inventory for Infants and Toddlers (P = 0.005) and self-help development (P = 0.001), but work stress had a significantly negative relationship with motor development (seldom, P = 0.050; always, P = 0.048). Conclusions: Maternal vitality around delivery was beneficial to a child's self-help development, while work stress seemed to be an adverse effect on child's motor development in later life. It is important to improve the psychosocial health of pregnant women.

Purpose: The objectives of this study were to translate and modify the Assessment of Mother–Infant Sensitivity scale into a Chinese version (modified AMIS-C) and to examine its reliability with preterm and term Taiwanese mother–infant dyads. Method: A total of 241 mother–infant pairs (179 preterm dyads and 62 term dyads) were prospectively recorded and their behaviour in feeding assessed using the modified AMIS-C when infants were at 4 and 6 months corrected age. A subset of the sample was used for interrater reliability testing, and the whole sample was used for assessment of internal consistency. Results: Interrater reliability was high for the modified AMIS-C section and total scores (intra-class correlation coefficients=0.91–0.99). Internal consistency was good to excellent for the maternal section and total score (α=0.71–0.86) and was fair to good for the infant and dyadic section score (α=0.44–0.75). Conclusions: The modified AMIS-C scale is a clinically feasible and reliable instrument for assessing mother–infant interaction of preterm and term dyads during early infancy.

Oral feeding has been reported to compromise breathing among preterm infants with bronchopulmonary dysplasia (BPD) during hospitalization or shortly after discharge. However, limited information was available concerning whether preterm infants with BPD remain vulnerable to feeding and growth insufficiency after a longer term of follow-up. The purpose of this study was therefore to examine the effect of severity of BPD on pulse oxygen saturation (SpO(2)) during feeding and growth in very low birth weight (VLBW) preterm infants during infancy. Seventy-two preterm infants with VLBW and 15 term infants were prospectively examined their growth and SpO(2) during feeding at 2, 4, and 6 months of corrected age. The severity of BPD was graded in VLBW infants according to the American National Institutes of Health consensus definition. In comparison to VLBW infants with mild BPD and term infants, VLBW infants with severe BPD showed significantly lower mean levels of SpO(2) during feeding at 2-6 months corrected age (P < 0.05). Those with severe BPD further exhibited higher rates of growth delay (weight < 10th percentile) throughout the study period. Among VLBW infants, severe BPD had an adverse relation with subsequent weight measures after adjustment for medical and demographic confounding variables (beta = -904 g, P = 0.03). The consensus BPD definition is useful to identify those preterm infants who are at greater risk of feeding desaturation and growth delay during infancy and close monitoring of SpO(2) during feeding should be advised.

Background/PurposeAll children should have some developmental screening periodically throughout childhood, especially those who were born prematurely. There is limited information about the development of children with very low birth weight (VLBW; birth weight < 1500 g) beyond the preschool age in Taiwan. We evaluated intelligence quotient (IQ) and cognitive ability of prematurely born school-aged children in Taiwan.MethodsThis was a multicenter study of VLBW and full-term children born between 1995 and 1997 at four hospitals in northern Taiwan. We used the Wechsler Intelligence Scale for Children, 3rd Edition (WISC-III), to assess these children. Demographic data were recorded including maternal and paternal age, education, birth weight, gestational age, and gender.ResultsA total of 189 children (130 with VLBW born prematurely and 59 born at full term) were recruited. There were significant differences in performance IQ (PIQ; 90.16 ± 17.05 vs. 108.51 ± 15.65, p < 0.001), verbal IQ (VIQ; 97.43 ± 15.62 vs. 111.78 ± 13.65, p < 0.001), full-scale IQ (FSIQ; 93.14 ± 16.33 vs. 111.05 ± 14.81, p < 0.001), verbal comprehension index score (VCIS; 98.06 ± 15.53 vs. 112.47 ± 13.74, p < 0.001), perceptional organization index score (POIS; 92.39 ± 17.13 vs. 109.42 ± 14.87, p < 0.001) and freedom from distractibility index score (FDIS; 98.34 ± 17.71 vs. 110.53 ± 10.94, p = 0.008). There was no correlation between perinatal outcomes and FSIQ.ConclusionOur results suggest that VLBW children have significantly lower PIQ, VIQ, FSIQ, VCIS, POIS and FDIS at primary school compared with full-term children.

Pneumomediastinum usually occurs after assisted ventilation. Spontaneous pneumomediastinum without preceding assisted ventilation, and presenting as a huge cystic mass in a term newborn infant has rarely been reported. We report a term baby who developed respiratory distress at 2 days of age. A huge cystic tumor of the thymus or a congenital mediastinal cystic tumor was initially suggested by chest radiography and computed tomography. Follow-up chest film revealed a “spinnaker sail sign” which is a typical radiographic presentation of pneumomediastinum.