Kyoto Scale Of Psychological Development Research Articles

Predictability of the neurodevelopmental assessment based on the Kyoto Scale of Psychological Development 2001 at 18–24 months of corrected age and 3 years of age in identifying cognitive impairment at 6 years of age in very preterm infants: A retrospective study at a Japanese tertiary center

BackgroundIt is unknown how accurately the current Japanese classification system for neurodevelopmental delay based on the assessment with the Kyoto Scale of Psychological Development (KSPD) at toddlerhood and pre-school periods predicts cognitive impairment at school age. MethodsThis single-center retrospective cohort study enrolled infants born at 22–29 weeks of gestational age. At 18–24 months of corrected age and 3 years of age, the patients were categorized according to the current Japanese criteria for neurodevelopmental delay based on their overall developmental quotient calculated using the KSPD-2001. Cognitive impairment at 6 years of age was classified according to the calculated or estimated full-scale intelligence quotient. The predictability of the current Japanese classification of neurodevelopmental delay for cognitive impairment at 6 years of age was investigated. ResultsOf 566 eligible patients, 364 (64 %) completed the protocol. The current classification for the neurodevelopmental delay showed significant agreement with the severity of cognitive impairment at 6 years of age. The sensitivity and specificity of the KSPD-2001-based assessment for any cognitive impairment at 6 years of age were 0.64 and 0.74 at 18–24 months of corrected age and 0.83 and 0.70 at 3 years of age. The corresponding sensitivity and specificity for moderate/severe cognitive impairment were 0.51 and 0.96 at 18–24 months of corrected age and 0.68 and 0.95 at 3 years of age. ConclusionThe KSPD-2001 is a useful tool to predict the severity of cognitive impairment at school age.

Maternal prenatal and postnatal psychological distress trajectories and impact on cognitive development in 4-year-old children: the Japan Environment and Children's Study.

Maternal prenatal and postnatal psychological distress, including depression and anxiety, may affect children's cognitive development. However, the findings have been inconsistent. We aimed to use the dataset from the Japan Environment and Children's Study, a nationwide prospective birth cohort study, to examine this association. We evaluated the relationship between the maternal six-item version of the Kessler Psychological Distress Scale (K6) scores and cognitive development among children aged 4 years. K6 was administered twice during pregnancy (M-T1; first half of pregnancy, M-T2; second half of pregnancy) and 1 year postpartum (C-1y). Cognitive development was assessed by trained testers, using the Kyoto Scale of Psychological Development 2001. Multiple regression analysis was performed with the group with a K6 score ≤ 4 for both M-T1 and M-T2 and C-1y as a reference. Records from 1,630 boys and 1,657 girls were analyzed. In the group with K6 scores ≥ 5 in both M-T1 and M-T2 and C-1Y groups, boys had significantly lower developmental quotients (DQ) in the language-social developmental (L-S) area (partial regression coefficient: -4.09, 95% confidence interval: -6.88 - -1.31), while girls did not differ significantly in DQ for the L-S area. Among boys and girls, those with K6 scores ≤ 4 at any one or two periods during M-T1, M-T2, or C-1y did not have significantly lower DQ for the L-S area. Persistent maternal psychological distress from the first half of pregnancy to 1 year postpartum had a disadvantageous association with verbal cognitive development in boys, but not in girls aged 4 years.

Vitamin D deficiency associated with neurodevelopmental problems in 2-year-old Japanese boys.

While associations between vitamin D deficiency and neurodevelopmental disorders have been found, large studies on child vitamin D, neurodevelopment, and sex differences among the general population are lacking. This study aimed to investigate the association between child serum 25-hydroxyvitamin D (25(OH)D)) levels and neurodevelopmental problems (NDPs). Serum 25(OH)D and NDPs were measured at age two among the subcohort study of the Japan Environment and Children's Study. NDPs were assessed with the Kyoto Scale of Psychological Development 2001 (Kyoto scale). Adjusted odds ratios (aORs) for the Kyoto-scale developmental quotient scores <70 were calculated, for postural-motor, cognitive-adaptive, and language-social domains and overall scores, adjusted for test month, latitude, small for gestational age, maternal age, and daycare attendance. Among 2363 boys and 2290 girls, boys had higher 25(OH)D levels, but scored lower in the Kyoto scale. For boys in the vitamin D deficiency (<20 ng/mL) group, aORs of scoring the Kyoto-scale DQs <70 were 2.33 (p = 0.006) for overall DQs, 1.91 (p = 0.037) for cognitive-adaptive, and 1.69 (p = 0.024) for language-social domains. For girls, results were inconclusive. Only boys showed a clear and cross-modal association between vitamin D deficiency and NDPs.

Intracerebroventricular enzyme replacement therapy in patients with neuronopathic mucopolysaccharidosis type II: Final report of 5-year results from a Japanese open-label phase 1/2 study

Intravenous idursulfase is standard treatment for mucopolysaccharidosis II (MPS II) in Japan. In the interim analysis of this open-label, phase 1/2 study (Center for Clinical Trials, Japan Medical Association: JMA-IIA00350), intracerebroventricular (ICV) idursulfase beta was well tolerated, suppressed cerebrospinal fluid (CSF) heparan sulfate (HS) levels, and stabilized developmental decline over 100 weeks in Japanese children with MPS II. Here, we report the final study results, representing 5 years of ICV idursulfase beta treatment. Six male patients with MPS II and developmental delay were enrolled starting in June 2016 and followed until March 2021. Patients received up to 30 mg ICV idursulfase beta every 4 weeks. Outcomes included CSF HS levels, developmental age (DA) (assessed by the Kyoto Scale of Psychological Development), and safety (adverse events). Monitoring by laboratory biochemistry tests, urinary uronic tests, immunogenicity tests, and head computed tomography or magnetic resonance imaging were also conducted regularly. Following ICV idursulfase beta administration, mean CSF HS concentrations decreased from 7.75 μg/mL at baseline to 2.15 μg/mL at final injection (72.3% reduction). Mean DA increased from 23.2 months at screening to 36.0 months at final observation. In five patients with null mutations, mean DA at the final observation was higher than or did not regress compared with that of historical controls receiving intravenous idursulfase only, and the change in DA was greater in patients who started administration aged ≤3 years than in those aged >3 years (+28.7 vs −6.5 months). The difference in DA change versus historical controls in individual patients was +39.5, +40.8, +17.8, +10.5, +7.6 and − 4.5 (mean + 18.6). Common ICV idursulfase beta-related adverse events were vomiting, pyrexia, gastroenteritis, and upper respiratory tract infection (most mild/moderate). These results suggest that long-term ICV idursulfase beta treatment improved neurological symptoms in Japanese children with neuronopathic MPS II.

Prenatal folic acid supplement/dietary folate and cognitive development in 4-year-old offspring from the Japan Environment and Children’s Study

We evaluated the association between maternal prenatal folic acid supplement use/dietary folate intake and cognitive development in 4-year-old offspring (N = 3445) using data from the Japan Environment and Children’s Study. Cognitive development was evaluated using the Kyoto Scale of Psychological Development 2001. Multiple regression analysis revealed that offspring of mothers who started using folic acid supplements pre-conception had a significantly higher language-social developmental quotient (DQ) (partial regression coefficient 1.981, 95% confidence interval 0.091 to 3.872) than offspring of mothers who did not use such supplements at any time throughout their pregnancy (non-users). Offspring of mothers who started using folic acid supplements within 12 weeks of gestation had a significantly higher cognitive-adaptive (1.489, 0.312 to 2.667) and language-social (1.873, 0.586 to 3.159) DQ than offspring of non-users. Regarding daily dietary folate intake from preconception to early pregnancy, multiple regression analysis revealed that there was no significant association with any DQ area in the 200 to < 400 µg and the ≥ 400 µg groups compared with the < 200 µg group. Maternal prenatal folic acid supplementation starting within 12 weeks of gestation (but not adequate dietary folate intake from preconception to early pregnancy) is positively associated with cognitive development in 4-year-old offspring.

Fetal Biometric Assessment and Infant Developmental Prognosis of the Tadalafil Treatment for Fetal Growth Restriction.

Background and Objectives: Tadalafil is expected to treat fetal growth restriction (FGR), a risk factor for stillbirth and neonatal morbidity. This study aimed to evaluate the fetal biometric growth pattern of fetuses with FGR treated with tadalafil by ultrasonographic assessment. Materials and Methods: This was a retrospective study. Fifty fetuses diagnosed with FGR and treated by maternal administration of tadalafil and ten controls who received conventional treatment at Mie University Hospital from 2015 to 2019 were assessed. Fetal biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW) at the start of treatment and at two weeks and four weeks of treatment were mainly assessed by ultrasound examination. The Wilcoxon signed-rank test was used to assess the measures. The Kyoto Scale of Psychological Development (KSPD) was used to assess the developmental prognosis on tadalafil-treated children at 1.5 years of corrected age (CA) and 3 years old. Results: The median gestational age at the start of treatment was 30 and 31 weeks in the tadalafil and control groups, respectively, and the median gestational age at delivery was 37 weeks in both groups. The Z-score of HC was significantly increased at 4 weeks of treatment (p = 0.005), and the umbilical artery resistance index was significantly decreased (p = 0.049), while no significant difference was observed in the control group. The number of cases with an abnormal score of less than 70 on the KSPD test was 19% for P-M, 8% for C-A, 19% for L-S, and 11% for total area at 1.5 years CA. At 3 years old, the respective scores were 16%, 21%, 16%, and 16%. Conclusions: Tadalafil treatment for FGR may maintain fetal HC growth and infants' neuro-developmental prognosis.

Association between cerebrospinal fluid parameters and developmental and neurological status in glucose transporter 1 deficiency syndrome.

In glucose transporter 1 deficiency syndrome (Glut1DS), cerebrospinal fluid glucose (CSFG) and CSFG to blood glucose ratio (CBGR) show significant differences among groups classified by phenotype or genotype. The purpose of this study was to investigate the association between these biochemical parameters and Glut1DS severity. The medical records of 45 patients who visited Osaka University Hospital between March 2004 and December 2021 were retrospectively examined. Neurological status was determined using the developmental quotient (DQ), assessed using the Kyoto Scale of Psychological Development 2001, and the Scale for the Assessment and Rating of Ataxia (SARA). CSF parameters included CSFG, CBGR, and CSF lactate (CSFL). CSF was collected from 41 patients, and DQ and SARA were assessed in 24 and 27 patients, respectively. Simple regression analysis showed moderate associations between neurological status and biochemical parameters. CSFG resulted in a higher R2 than CBGR in these analyses. CSF parameters acquired during the first year of life were not comparable to those acquired later. CSFL was measured in 16 patients (DQ and SARA in 11 and 14 patients, respectively). Although simple regression analysis also showed moderate associations between neurological status and CSFG and CSFL, the multiple regression analysis for DQ and SARA resulted in strong associations through the use of a combination of CSFG and CSFL as explanatory variables. The severity of Glut1DS can be predicted from CSF parameters. Glucose and lactate are independent contributors to the developmental and neurological status in Glut1DS.

Maternal prenatal psychological distress and motor/cognitive development in two-year-old offspring: The Japan Environment and Children's Study.

Maternal prenatal psychological distress, including depression and anxiety, may affect offspring's motor/cognitive development. However, research findings have been inconsistent. We used a dataset from the Japan Environment and Children's Study to evaluate associations between maternal six-item Kessler Psychological Distress Scale (K6) scores and motor/cognitive development among offspring at two years of age. Their offspring's motor/cognitive development was assessed using the Kyoto Scale of Psychological Development 2001. Records for 1859 male and 1817 female offspring were analyzed. The maternal K6 was administered twice during pregnancy: at a median of 14.6 weeks (M-T1) and 27.3 weeks (M-T2) of gestation. Multiple regression analysis was performed with the group with K6 scores ≤4 at both M-T1 and M-T2 as a reference. In the group with K6 scores ≥5 at both M-T1 and M-T2, male offspring had significantly lower developmental quotients (DQ) in the posture-motor area (partial regression coefficient [B]: -3.68, 95% confidence interval [CI]: -5.92 to -1.44) and language-social area (B: -1.93; 95%CI: -3.73 to -0.12), while female offspring had a lower DQ for the language-social area (B: -1.95; 95%CI: -3.73 to -0.17). In those with K6 scores ≥5 only at M-T1 or M-T2, male and female offspring did not differ significantly in DQ for any area. Continuous maternal psychological distress from the first to the second half of pregnancy was associated with lower motor and verbal cognitive development in male offspring and lower verbal cognitive development in female offspring at 2 years compared with the group without persistent maternal prenatal psychological distress.

Limitation of developmental test to measure functional independence of children: Relationship between the Japanese version of WeeFIM II® and KSPD.

The purpose of the study was to explore whether a developmental test provides enough information to estimate a child's functional independence. The strength of the relationship between developmental level and functional independence of different skills was investigated. The participants were 397 children (age 0-7 years) who were referred to NCCHD for suspected developmental delay. The participants' developmental level was measured with the Kyoto Scale of Psychological Development (KSPD) and their functional independence was assessed through a Japanese version of the WeeFIM II®. To calculate the strengths of the relationship between developmental age (DA) in different domains of the KSPD and WeeFIM II item scores, partial correlation analyses were conducted, controlling for chronological age. Partial correlation coefficients between the score of each of the 18 WeeFIM II items and each of the three KSPD domain DAs (controlling chronological age) fell in the ranges of r = 0.169-0.581 (Posture-Motor; P-M), r = 0.377-0.627 (Cognitive-Adaptive; C-A), and r = 0.332-0.655 (Language-Social; L-S). When the participants were divided into three age groups, the correlations ranged from -0.095 to 0.552 for the youngest group (mean age = 14.21 months), from 0.283 to 0.653 for the middle group (mean age = 32.98 months), and from 0.345-0.692 for the oldest group (mean age = 57.48 months), depending on the combinations of the WeeFIM II items/developmental domains of the KSPD. The results indicated that for most of the daily living skills, its functional independence was only partially explained by the scores of a developmental test, once chronological age was controlled. This study showed the limitation of a developmental test as a tool to measure the functional independence of children and the necessity of using an independent tool, such as WeeFIM II, to evaluate the level of required support for each daily living skill.

Safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (SHIELD trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial

IntroductionNeonatal hypoxic-ischaemic encephalopathy (HIE) is an important illness associated with death or cerebral palsy. This study aims to assess the safety and tolerability of the allogenic human multilineage-differentiating stress-enduring cell...

Maternal folic acid supplement use/dietary folate intake from preconception to early pregnancy and neurodevelopment in 2-year-old offspring: the Japan Environment and Children's Study.

We evaluated the association between maternal prenatal folic acid supplementation/dietary folate intake and motor and cognitive development in 2-year-old offspring using data from the Japan Environment and Children's Study database. Neurodevelopment of 2-year-old offspring were evaluated using the Kyoto Scale of Psychological Development 2001. In total, data of 3839 offspring were analysed. For folic acid supplementation, a multiple regression analysis showed that offspring of mothers who started using folic acid supplements before conception had a significantly lower developmental quotient (DQ) in the postural-motor DQ area than offspring of mothers who did not use them at any time throughout their pregnancy (partial regression coefficient (B) -2·596, 95 % CI -4·738, -0·455). Regarding daily dietary folate intake from preconception to early pregnancy, a multiple regression analysis showed that the group with ≥ 200 µg had a significantly higher DQ in the language-social area than the group with <200 µg. The DQ was higher in the ≥ 400 µg group (B 2·532, 95 % CI 0·201, 4·863) than the 200 to <400 µg group (B 1·437, 95 % CI 0·215, 2·660). In conclusion, our study showed that maternal adequate dietary folate intake from preconception to early pregnancy has a beneficial association with verbal cognition development in 2-year-old offspring. On the other hand, mothers who started using folic acid supplements before conception had an inverse association with motor development in 2-year-old offspring. There were no details on the amount of folic acid in the supplements used and frequency of use. Therefore, further studies are required.

Clinical Features of Neurodevelopmental Outcomes in Children with Preterm Severe Fetal Growth Restriction: A Retrospective Observational Study.

Introduction: Fetal growth restriction (FGR) is a clinical condition wherein a fetus fails to achieve the expected growth potential. Although FGR is the leading cause of perinatal morbidity and mortality, there is a lack of knowledge about the long-term developmental outcomes of children who had FGR in Japan. Here, we sought to clarify the features of neurodevelopmental outcomes in preterm-born children with severe FGR (sFGR) and identify associated clinical factors. Methods: The clinical data of 26 preterm sFGR cases and 26 preterm appropriate for gestational age (AGA) cases with a similar gestational age distribution were reviewed retrospectively. Developmental quotient (DQ) scores assessed during the 1- and 2-year corrected ages using the Kyoto Scale of Psychological Development were analyzed. Results: sFGR was diagnosed at 26 (18-34) weeks of gestation, and the gestational age at delivery was 31 (25-36) weeks. The overall DQ scores of children in the sFGR group were significantly lower than those in the AGA group (80 vs. 90.5, P = 0.0127). Of the three areas that comprise the DQ (Postural-Motor, Cognitive-Adaptive, and Language-Social), the sFGR group only showed significantly lower DQ scores (72.5 vs. 88, P = 0.0255) in the Language-Social area. Both fetal body weight and fetal body weight Z score at birth significantly correlated with the DQ scores (r = 0.4912, P = 0.0108, and r = 0.5621, P = 0.0028), whereas neither the duration of fetal growth arrest nor the gestational age at birth correlated with the DQ scores (r = 0.3598, P = 0.0842, and r = 0.3522, P = 0.0776). Conclusions: Our results indicate that preterm-born children with sFGR have greater neurodevelopmental impairment than preterm-born children without FGR, specifically in terms of the DQ scores for the Language-Social area. It is imperative to encourage continuous long-term follow-up and appropriate interventions after birth.

Association of prenatal exposure to cadmium with neurodevelopment in children at 2years of age: The Japan Environment and Children's Study.

Prenatal cadmium exposure has been associated with adverse neurodevelopmental outcomes. However, previous findings are contradictory, and little is known about the potential modifiers of the cadmium-related neurodevelopmental risk. We investigated the associations between prenatal cadmium exposure and neurodevelopment in 2-year-old children and examined the influence of mother/child characteristics. We recruited 3545 mother-child pairs from the Japan Environment and Children's Study. We collected maternal blood during mid/late pregnancy and cord blood at delivery, and measured cadmium concentrations using inductively coupled plasma mass spectrometry. Neurodevelopment was assessed using the Kyoto Scale of Psychological Development (KSPD), which includes cognitive-adaptive (C-A), language-social (L-S), postural-motor (P-M) and developmental quotient (DQ) domains. Associations between cadmium and KSPD scores were tested using multivariable models after controlling for confounders. Median levels (interquartile ranges) of cadmium in maternal and cord blood were 0.70 (0.52-0.95) and 0.04 (0.03-0.06) μg/L, respectively. Maternal blood cadmium concentrations were inversely associated with P-M scores in boys (β=-1.4, 95% confidence interval (CI): -2.7, -0.038), DQ in children of mothers who smoked during pregnancy (β=-2.9, 95% CI: -5.7, -0.12), P-M (β=-5.4, 95% CI: -10, -0.67), C-A (β=-6.1, 95% CI: -11, -1.8), L-S (β=-9.0, 95% CI: -13, -4.8) and DQ scores (β=-6.4, 95% CI: -9.6, -3.1) in children born to mothers with gestational diabetes. Cord blood cadmium concentrations were negatively associated with L-S scores (β=-6.0., 95% CI: -11, -0.91) in children born to mothers with gestational diabetes. Prenatal cadmium exposure was negatively associated with neurodevelopment in boys, in children whose mothers smoked, and in children born to mothers with gestational diabetes. Further studies in other populations are needed to confirm our findings.

23 Pulmonary Hypertension Associated with Bronchopulmonary Dysplasia and Neurodevelopmental Outcomes: A Systematic Review and Meta-Analysis

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Pulmonary Hypertension (PH) is estimated to occur in 1 in 4 infants with Bronchopulmonary Dysplasia (BPD). The impact of PH in infants with BPD on their neurodevelopmental (ND) outcomes is uncertain. Objectives This systematic review aims to evaluate whether PH in infants with BPD is associated with ND delay. Design/Methods A systematic literature search was performed to identify studies that reported ND outcomes of infants with BPD (based on NIH definition) and PH (based on echocardiographic findings of PH at 36 weeks PMA). The primary outcome was ND delay in infants with pulmonary hypertension associated with BPD compared with BPD alone. Standardized developmental tests evaluated ND outcomes at 18-24 months corrected age (CA) and three years of age. Quality assessment of the studies was done using the Newcastle-Ottawa Quality Assessment for Cohort studies. Results Three retrospective cohort studies met the inclusion criteria. Two studies reported ND outcomes based on Bayley Scales of Infant and Toddler Development-III Edition in cognitive, language, and motor domains at 18-24 months CA (Table 1 and Figure 1). One study reported outcomes at 3 years, including overall developmental delay (Kyoto Scale of Psychological Development [KSPD] scores &amp;lt; 70) and cerebral palsy. The quality of all 3 studies was rated between good, fair, and poor. Pooled data from the 2 studies reporting outcomes at 18-24 months showed no difference between the 2 infant groups for Bayley cognitive score &amp;lt; 85 (Odds ratio [OR]: 3.78; 95% CI 0.87-16.52), Bayley language score &amp;lt; 85 (OR: 1.19; 95% CI0.57-2.49), and Bayley motor score &amp;lt; 85 (OR: 2.04; 95% CI 0.89-4.67). At 3 years of age, children in the BPD-PH group had an increased risk of developmental delay (DQ &amp;lt; 70 in all areas) compared with the BPD group (OR: 4.37; 95% CI 1.16-16.46), but no difference in the risk of cerebral palsy (OR: 0.57; 95%0.03-12.39). Conclusion PH in BPD is not associated with a developmental delay compared to BPD alone at 18-24 months CA. However, a single study showed infants in BPD-PH had delayed development at 3 years of age. A large prospective cohort study with longer multidisciplinary follow-up is required to confirm this.

6.22 The Combination of Kampo and Western Antipsychotic Drugs Were Effective for 20 Cases in Child Psychiatric Outpatients

Kampo is the Japanese herbal traditional medicine formula, with a root from ancient China, that is used for irritation, mood swing, and agitation in Japan. Ninety percent of Japanese doctors have an experience of prescribing Kampo, and 80% of doctors have combined Kampo and a Western antipsychotic drug (WAD). The indication of atypical WAD is for the irritability and agitation with autism spectrum disorder (ASD), and Kampo is used for peripheral symptoms in the child and adolescent psychiatric patient. For now, risperidone and aripiprazole are the only choices under the Japanese health insurance system to treat children with ASD. This retrospective case series report was conducted in 20 children who received Kampo and a WAD, from April 1, 2017 to December 31, 2020, at our child and adolescent psychiatric outpatient clinic. Their ages ranged from 7 to 19 years. Their age, gender, IQ test (Wechsler Intelligence Scale for Children–Fourth Edition [WISC-4], Tanaka-Binet-5 test, Kyoto Scale of Psychological Development), the severity that DSM-5 defines on the initial examination and the end of this research (none = Level 0, mild = Level 1, moderate = Level 2, severe = Level 3), dropouts, side effects, and the number of medications were surveyed. The average age was 12.2 years (7-19). The ratio of males to females was 19:1. The average IQ was 69.4 (22-143). There were no side effects from Kampo. Seven children had a blood test, and their average serum potassium level was 4.0 mEq/l (3.5-4.4). In addition, 0.5 (25%) of them had any type of drug and food allergies, 6 (30%) had febrile convulsion, abnormality of EEG, and epilepsy, and 3 (15%) had any severe physical disabilities. The initial diagnosis (maximum 2) was 11 (55%) with pervasive developmental disorder and ASD, 9 (45%) with ADHD, 2 (10%) with ODD, 12 (60%) with intellectual disability containing below average IQ (BAIQ), 14 (70%) had continued combined medicine, 5 (25%) had dropped out of the child and adolescent psychiatric outpatient clinic, 6 (30%) had taken multiple WADs. The average Kampo dose per day was 4.6 g (1 package is 2.5 g). The average administration duration was 14.4 month (2-41). The price of a risperidone tablet (2 mg) is $0.40 USD, aripiprazole (3 mg) is $0.60 USD, and Kampo is $0.34 to $0.16 USD per 1 package. The average severity level according to the DSM-5 on the initial examination was 1.95 (1-3). The average severity at the end of this research was 1.17 (0-3). The combination of Kampo and WADs might alleviate the severity of children in the child and adolescent psychiatric outpatient.

Sleep maturation influences cognitive development of preterm toddlers

Our recent study on full-term toddlers demonstrated that daytime nap properties affect the distribution ratio between nap and nighttime sleep duration in total sleep time but does not affect the overall total amount of daily sleep time. However, there is still no clear scientific consensus as to whether the ratio between naps and nighttime sleep or just daily total sleep duration itself is more important for healthy child development. In the current study, to gain an answer to this question, we examined the relationship between the sleep properties and the cognitive development of toddlers born prematurely using actigraphy and the Kyoto scale of psychological development (KSPD) test. 101 premature toddlers of approximately 1.5 years of age were recruited for the study. Actigraphy units were attached to their waist with an adjustable elastic belt for 7 consecutive days and a child sleep diary was completed by their parents. In the study, we found no significant correlation between either nap or nighttime sleep duration and cognitive development of the preterm toddlers. In contrast, we found that stable daily wake time was significantly associated with better cognitive development, suggesting that sleep regulation may contribute to the brain maturation of preterm toddlers.

Outcomes in symptomatic preterm infants with postnatal cytomegalovirus infection.

ABSTRACTPremature infants are at risk for developing symptomatic postnatal cytomegalovirus (CMV) disease, including sepsis-like syndrome. We performed a retrospective case–control study including infants born before 32 weeks of gestation and diagnosed with symptomatic postnatal CMV infection during the neonatal period. Neurodevelopmental outcome was evaluated using the Kyoto Scale of Psychological Development 2001 at 18 months of corrected age and at 3 years of age. Twenty-four infants were diagnosed with postnatal CMV infection; of them, 14 had sepsis-like symptoms and 10 had laboratory test abnormalities only. Home oxygen therapy was used significantly higher in the CMV-positive group compared with the control group at hospital discharge (52% vs 21%, P=0.032). The incidence of neurodevelopmental impairment was not significantly different between the two groups at 18 months of corrected age (29% vs 17%, P=0.48) and at 3 years of age (43% vs 29%, P=0.34). Postnatal CMV infection did not have a significant influence on neurodevelopmental outcomes of symptomatic preterm infants, although those in the CMV-positive group appeared worse. Larger studies with long-term follow-up are needed for a better understanding of continued neurodevelopmental outcomes in preterm infants with postnatal CMV infection.

Pre-eclampsia Complicated With Maternal Renal Dysfunction Is Associated With Poor Neurological Development at 3 Years Old in Children Born Before 34 Weeks of Gestation.

Objective: The purpose of this study was to investigate perinatal factors associated with a poor neurodevelopmental outcome in preterm infants.Methods: A retrospective study was conducted by searching our clinical database between January 2006 and December 2016. A total of 165 singleton children who were born between 23 and 33 weeks of gestation were included. We defined poor neurological development outcomes as follows: cerebral palsy; intellectual disability; developmental disorder including autism and attention-deficit/hyperactivity disorder; low score (<85 points) on Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III); or low score of Kyoto Scale of Psychological Development corrected at 3 years old. We diagnosed maternal renal dysfunction according to the Clinical Practice Guideline for chronic kidney disease 2018 and the Best Practice Guide 2015 for Care and Treatment of Hypertension in Pregnancy.Results: The rate of poor neurological development was 25/165 (15.2%): cerebral palsy (n = 1), intellectual disability (n = 1), developmental disorder (n = 2), low score of Bayley-III (n = 20), and low score of Kyoto Scale of Psychological Development (n = 1). Preeclampsia complicated with maternal renal dysfunction (P = 0.045) and delivery at <30 weeks of gestation (P = 0.007) were independent risk factors for poor neurological development.Conclusions: In addition to previous risk factors such as delivery at <30 weeks of gestation, preeclampsia complicated with renal dysfunction was also associated with poor neurodevelopmental outcomes corrected at 3 years old.

Factors affecting psychosocial development of very low birth weight infants at 18 and 36 months of age.

To identify relationships between neonatal factors including conditions and treatments, nurturing environment, and psychosocial development of children born at very low birth weight (VLBW). In this longitudinal study, the medical records of 113 VLBW infants were examined, and the children were then followed up at 18 and 36 months of age. Their developmental quotient (DQ) was assessed using the Kyoto Scale of Psychological Development (KSPD), and their parents were asked about their own health, financial situation, education, and family support. Pearson's correlation and stepwise multiple regression analyses were used to explore relationships between DQ, potentially significant predictors on the KSPD, and nurturing environment. DQ at 18 months was associated with the following neonatal factors: mechanical ventilation days (β = -.241, p = .020), Apgar score at 5 min (β = .278, p = .005), periventricular leukomalacia (β = -.218, p = .006), and treatment for retinopathy of prematurity (β = -.171, p = .048) (adjusted R2 = .32). DQ at 36 months was associated with the following neonatal and parenting factors: mechanical ventilation days (β = -.354, p < .001), periventricular leukomalacia (β = -.207, p = .009), sex (β = -.199, p = .011), mother's educational background (β = -.304, p < .001), mother's health status (β = -.159, p = .042) (adjusted R2 = .35). These findings suggest that in addition to neonatal clinical parameters including conditions and treatments, the nurturing environment after discharge from the neonatal intensive care unit influences the psychosocial development of VLBW infants.

Impact of intracerebroventricular enzyme replacement therapy in patients with neuronopathic mucopolysaccharidosis type II

This open-label, phase 1/2 study (JMACCT CTR JMA-IIA00350) evaluated the efficacy and safety of intracerebroventricular idursulfase beta in patients with mucopolysaccharidosis II (MPS II). Herein, we report the 100-week results. Six patients with severe MPS II aged 23–65 months were enrolled. Idursulfase beta (increasing from 1 to 30 mg between weeks 0 and 24, followed by a 30-mg final dose) was administered intracerebroventricularly once every 4 weeks using an implanted cerebrospinal fluid (CSF) reservoir; intravenous administration of idursulfase was also continued throughout the study. Efficacy endpoints included developmental age by the Kyoto Scale of Psychological Development 2001 and heparan sulfate (HS) concentration in CSF (primary outcome). In all six patients, HS concentrations decreased (40%–80%) from baseline to week 100. For overall developmental age, the difference in change from baseline to week 100 in each patient compared with patients treated by intravenous idursulfase administration (n = 13) was +8.0, +14.5, +4.5, +3.7, +8.2, and –8.3 months (mean, +5.1 months). Idursulfase beta was well tolerated. The most common adverse events were pyrexia, upper respiratory tract infection, and vomiting. The results suggest that intracerebroventricular idursulfase beta is well tolerated and can be effective at preventing and stabilizing developmental decline in patients with neuronopathic MPS II.