Five-year follow-up of a clinic-based sleep intervention for paediatric epilepsy: A randomized clinical trial.

Sleep disturbances in children with epilepsy are prevalent, and are associated with substantial adverse medical and psychosocial consequences. This study is a 5-year follow-up of a clinic-based sleep intervention study that randomized 100 toddlers and preschool-age children with epilepsy to a usual care group or a sleep intervention group. The intervention group received standard paediatric neurology care plus three education sessions during the child's routine clinic visit. The outcomes measured were: (1) child sleep by actigraphy and parental report; and (2) maternal sleep and depression. We aimed to evaluate the long-term benefits of a clinic-based sleep intervention for paediatric epilepsy. In total, 42 families (42.0%) participated. The average child's age at follow-up was 9.55 years. Thirty-eight (90.5%) children were not obtaining sufficient sleep at baseline, and 40 (95.2%) at the 5-year follow-up. The numbers of children with clinically significant sleep disturbances were 40 (95.2%) at baseline and 36 (85.7%) at the 5-year follow-up. Fourteen mothers (33.3%) had poor sleep quality and high depressive symptoms at both assessment time points. There were no differences (P > 0.05) in the child and maternal outcomes between the two trial arms. Overall, there was no evidence that a clinic-based sleep intervention that effectively improved multiple aspects of sleep in toddlers and preschool-age children with epilepsy had long-lasting beneficial effects. Our findings suggest that sleep interventions for families of children with epilepsy require ongoing reinforcement and monitoring during routine paediatric neurology care to prevent sleep problems from persisting or recurring.

Screen Time Exposure and Altered Sleep in Young Children With Epilepsy.

PURPOSE: 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. DESIGN: A cross-sectional actigraphic sleep study. METHODS: 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. FINDINGS: Mean minutes per day of screen time exposure was 89.79 ± 83.94 min, with 62 parents (44.0%) reporting their child having >1 hr of screen time daily. Mean daily sleep duration was 9.26 ± 1.01 hr, with 106 children (93.0%) sleeping <10 hr in a 24-hr period. In multivariate regression models, daily screen time exposure of >1 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). CONCLUSIONS: 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. CLINICAL RELEVANCE: 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 to <1 hr per day for their toddlers and preschool-age children with epilepsy.

Sleep in mothers of children with epilepsy and its relation to their children's sleep.

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 (ß = 0.14; p < .01) and higher sleep disturbance scores in children (ß = 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.

Agreement Between Actigraphy and Diary-Recorded Measures of Sleep in Children With Epilepsy.

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.

Application of Artificial Intelligence in Infant Movement Classification: A Reliability and Validity Study in Infants Who Were Full-Term and Preterm.

OBJECTIVE: Preterm infants are at high risk of neuromotor disorders. Recent advances in digital technology and machine learning algorithms have enabled the tracking and recognition of anatomical key points of the human body. It remains unclear whether the proposed pose estimation model and the skeleton-based action recognition model for adult movement classification are applicable and accurate for infant motor assessment. Therefore, this study aimed to develop and validate an artificial intelligence (AI) model framework for movement recognition in full-term and preterm infants. METHODS: This observational study prospectively assessed 30 full-term infants and 54 preterm infants using the Alberta Infant Motor Scale (58 movements) from 4 to 18 months of age with their movements recorded by 5 video cameras simultaneously in a standardized clinical setup. The movement videos were annotated for the start/end times and presence of movements by 3 pediatric physical therapists. The annotated videos were used for the development and testing of an AI algorithm that consisted of a 17-point human pose estimation model and a skeleton-based action recognition model. RESULTS: The infants contributed 153 sessions of Alberta Infant Motor Scale assessment that yielded 13,139 videos of movements for data processing. The intra and interrater reliabilities for movement annotation of videos by the therapists showed high agreements (88%-100%). Thirty-one of the 58 movements were selected for machine learning because of sufficient data samples and developmental significance. Using the annotated results as the standards, the AI algorithm showed satisfactory agreement in classifying the 31 movements (accuracy = 0.91, recall = 0.91, precision = 0.91, and F1 score = 0.91). CONCLUSION: The AI algorithm was accurate in classifying 31 movements in full-term and preterm infants from 4 to 18 months of age in a standardized clinical setup. IMPACT: The findings provide the basis for future refinement and validation of the algorithm on home videos to be a remote infant movement assessment.

Perfluorinated compound levels in cord blood and neurodevelopment at 2 years of age.

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.

In utero exposure to environmental lead and manganese and neurodevelopment at 2 years of age.

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 (ß=-7.03, SE=2.65, P=0.0085), cognitive (ß=-8.19, SE=3.17, P=0.0105), and language quotients (ß=-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.

Cognitive and motor development in preterm children from 6 to 36 months of age: Trajectories, risk factors and predictability.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION AND IMPLICATIONS: Preterm children born VLBW display heterogeneous trajectories in early cognitive and motor development that predict subsequent developmental and behavioral outcomes.

GSTM1 modifies the effect of maternal exposure to environmental tobacco smoke on neonatal primitive reflexes.

OBJECTIVE: The aim of this study was to examine whether infant metabolic gene polymorphisms modify the effect of maternal environmental tobacco smoke (ETS) on neonatal neurobehavior. METHODS: We conducted a birth cohort study of 87 nonsmoking women who delivered single births of normal birth weight. We enrolled the women before delivery, interviewed them using a structured questionnaire, and collected umbilical cord blood. Umbilical cord cotinine, a blood indicator of prenatal ETS exposure, was analyzed. The Neonatal Neurobehavioral Examination-Chinese Version (NNE-C) was administrated within 5 days after delivery to examine neonatal neurobehavior. Four infant metabolic genes, CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1, and GSTM1, were identified. RESULTS: Maternal ETS exposure during pregnancy was not related to neonatal neurobehavior when infant genetic polymorphisms were not considered. However, maternal ETS exposure did cause adverse effects in neonates with the absent type of GSTM1. Adverse effects were seen on the total NNE-C (ß = -2.55; p = .02) and on primitive reflexes (ß = -1.70; p = .004), especially in grasp reflexes (ß = -.36; p = .011) and tonic neck reflexes (ß = -.36; p = .049). In addition, there was a significant interaction between maternal ETS exposure and infant GSTM1 genotype on neonate grasp reflexes (p for interaction = .019). CONCLUSIONS: These data indicate that weaker responses in neonatal primitive reflexes in infants with the absent type GSTM1 were related to maternal ETS exposure during pregnancy.

Maternal psychosocial factors around delivery on development of 2-year-old children: A prospective cohort study.

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.

Serial measurements of serum alkaline phosphatase for early prediction of osteopaenia in preterm infants.

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 (R(2) = 0.93, P < 0.001). Infants who had osteopaenia showed a higher level of ALP and BALP after 3 weeks post-natal age than those who had no osteopaenia. ALP concentration exceeding 700 IU/L at 3 weeks post-natal age was predictive of osteopaenia at term age (sensitivity 73% and specificity 73%) and so did for the predictive value of BALP concentration exceeding 95 ug/L (sensitivity 73% and specificity 80%). BALP measures provided no greater benefit of diagnostic performance than ALP in early detection of osteopaenia. Furthermore, premature infants with osteopaenia showed similar levels of calcium and inorganic phosphatase concentration compared with those without. CONCLUSION: Serum ALP concentration exceeding 700 IU/L at 3 weeks post-natal age can predict the risk of osteopaenia in preterm infants.

International comparisons of behavioral and emotional problems in preschool children: parents' reports from 24 societies.

International comparisons were conducted of preschool children's behavioral and emotional problems as reported on the Child Behavior Checklist for Ages 1½-5 by parents in 24 societies (N = 19,850). Item ratings were aggregated into scores on syndromes; Diagnostic and Statistical Manual of Mental Disorders-oriented scales; a Stress Problems scale; and Internalizing, Externalizing, and Total Problems scales. Effect sizes for scale score differences among the 24 societies ranged from small to medium (3-12%). Although societies differed greatly in language, culture, and other characteristics, Total Problems scores for 18 of the 24 societies were within 7.1 points of the omnicultural mean of 33.3 (on a scale of 0-198). Gender and age differences, as well as gender and age interactions with society, were all very small (effect sizes < 1%). Across all pairs of societies, correlations between mean item ratings averaged .78, and correlations between internal consistency alphas for the scales averaged .92, indicating that the rank orders of mean item ratings and internal consistencies of scales were very similar across diverse societies.

Maternal psychosocial factors around delivery, and the behavior of 2-year-old children.

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.

CYP1A1 modifies the effect of maternal exposure to environmental tobacco smoke on child behavior.

INTRODUCTION: Maternal environmental tobacco smoke (ETS) has been identified as a key risk factor for problem behavior in children, but the role of genetic susceptibility is not clear. The purpose of this study was to examine the metabolic genetic modification effect of exposure to ETS in nonsmoking mothers on child behavior at 2 years of age. METHODS: A prospective cohort study was conducted among 191 mothers who gave births between 2004 and 2005 and their infants in Taiwan. The mothers completed a questionnaire before delivery in which they provided information on exposure to ETS during pregnancy. Four metabolic genes, CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1, and GSTM1 were isolated from both maternal and infant DNA samples. Children's behavior problems at 2 years of age were reported by their mothers using the Child Behavior Checklist/1.5-5. Multiple linear models were used to estimate the effects of ETS and genotype on child behavior. RESULTS: Maternal ETS exposure was associated with the anxious score. The ETS-exposed group with both the CYP1A1 MspI and the CYP1A1 Ile462Val variants had higher scores, as reflected in total CBCL score as well as scores on the internalizing scale and its emotional subdomain, the anxious scale, and the externalizing scale and its aggressive subdomain. CONCLUSIONS: Child behavioral problems may be associated with prenatal ETS exposure, and this effect may be modified by infant CYP1A1 MspI and CYP1A1 Ile462Val genes.

Collaborative Home-Visit Program for Young Children With Motor Delays in Rural Taiwan: A Pilot Randomized Controlled Trial.

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.

Behavioral-educational sleep interventions for pediatric epilepsy: a randomized controlled trial.

STUDY OBJECTIVES: To 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. METHODS: A 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. RESULTS: Sleep 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. CONCLUSION: Sleep 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 TRIAL: This trial has been registered at www.clinicaltrials.gov (trial name: Sleep Intervention for Pediatric Epilepsy; registration number: NCT02514291).

Interaction Between Prematurity and the MAOA Gene on Mental Development in Children: A Longitudinal View.

This study aimed to examine the association of dopamine-related genes with mental and motor development and the gene-environment interaction in preterm and term children. A total of 201 preterm and 111 term children were examined for their development at 6, 12, 18, 24, and 36 months and were genotyped for 15 single-nucleotide polymorphisms (SNPs) in dopamine-related genes (DRD2, DRD3, DAT1, COMT, and MAOA). An independent sample of 256 preterm children was used for replication. Since the developmental age trends of preterm children differed from those of term children, the analyses were stratified by prematurity. Among the 8 SNPs on the MAOA gene examined in the whole learning sample, the results of linkage disequilibrium analysis indicated that they were located in one block (all D' > 0.9), and rs2239448 was chosen as the tag (r2 > 0.85). In the analysis of individual SNPs in each dopamine-related gene, the tag SNP (rs2239448) in MAOA remained significantly associated with the mental scores of preterm children for the interaction with age trend (p < 0.0001; largest effect size of 0.65 at 24 months) after Bonferroni correction for multiple testing. Similar findings for rs2239448 were replicated in the independent sample (p = 0.026). However, none of the SNPs were associated with the motor scores of preterm children, and none were related to the mental or motor scores of term children. The genetic variants of the MAOA gene exert influence on mental development throughout early childhood for preterm, but not term, children.

Impact of delivery mode and gestational age on haematological parameters in Taiwanese preterm infants.

AIM: Reference ranges of haematological parameters in preterm infants are limited. The aim of this study is to determine the reference values of haematological parameters in preterm infants in Taiwan, and to assess the impact of gestational age and mode of delivery on these parameters. METHOD: Medical records were retrospectively reviewed in preterm infants admitted to National Taiwan University Hospital from January 2001 to December 2004. The inclusion criteria included infants with <37 weeks of gestation who had blood sampling within 24 h of birth. The exclusion criteria included those with maternal history of antepartum haemorrhage, chorioamnionitis, fever, sepsis, preeclampsia and hypertension; and perinatal history of twin-to-twin transfusion syndrome, feto-maternal transfusion, injury and infection. RESULTS: Of 568 preterm infants with blood cell counts, 337 were available for analysis. There were trends of increase in red blood cell counts, haemoglobin levels and haematocrit values as gestation increased up to 34 weeks. In contrast, a trend of decrease was noted in mean corpuscular volume values. There was an initial trend of decrease in white blood cell counts and then increased after 31 weeks gestation. The platelet counts were essentially unchanged. Infants born by vaginal delivery generally had higher haematological parameters than those born by Caesarean section at different gestational ages except for mean corpuscular volume values. CONCLUSIONS: We established the reference ranges of haematological parameters in Taiwanese preterm infants. Health-care professionals must be cautious in clinical application of the haematological values because of varying antenatal and perinatal risk factors.

Sleep and Behavior Problems in Children With Epilepsy.

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.

Neonatal respiratory status predicts longitudinal respiratory health outcomes in preterm infants.

OBJECTIVES: To examine the relationship between neonatal respiratory status and longitudinal respiratory health outcomes in preterm infants with very low birth weight (VLBW, birth weight <1500 g). METHODS: A total of 109 VLBW preterm infants were prospectively assessed for respiratory status using the Toce clinical and radiographic scoring method on a postnatal day 28, and severity of bronchopulmonary dysplasia (BPD) at 36-weeks postmenstrual age (PMA), respiratory morbidity within 1 year of corrected age (CA), pulmonary function test, and six-minute walk test at 4 years of age. RESULTS: A high Toce clinical score on day 28 was associated with the occurrence of respiratory morbidity within 1 year of CA and poor pulmonary function and functional exercise performance at 4 years of age in VLBW preterm infants (all P < 0.05). BPD at 36-weeks PMA was associated with an increased risk of respiratory morbidity within 1 year of CA and its negative impact on pulmonary function and functional exercise performance at 4 years of age was most pronounced in the severe form (all P < 0.05). CONCLUSIONS: Early assessments of neonatal respiratory status including Toce clinical score and the severity of BPD are valid to identify VLBW preterm infants who are at risk of adverse longitudinal respiratory health outcomes.