Association between Cesarean section delivery and increased risk of childhood Kawasaki disease.

AIM: Cesarean section delivery is associated with microbiota disruption and immuno-dysregulation during childhood, but the association with Kawasaki disease remains uncertain. We aimed to evaluate the association between Cesarean section and Kawasaki disease. METHODS: We examined the association between Kawasaki disease between six and eighteen months and Cesarean section within a birth cohort of 15,796 mother-infant pairs in Taiwan. The associations were assessed with Poisson regression in the study population, in the 1:2 propensity score-matched subpopulation, and compared with febrile convulsion, trauma and accidents during the same interval as negative control outcomes. RESULTS: Cesarean section was found to increase the risk of Kawasaki disease among overall population (adjusted relative risk [aRR]: 2.22, 95 % confidence interval (CI): 1.14-4.34) and the matched subpopulation (aRR: 2.29, 95 % CI: 1.14-4.68 in PS-matched subpopulation). Meanwhile, there was no association between Cesarean section and the clinic visits for febrile convulsion, trauma and accidents. CONCLUSION: In conclusion, this study identified a potential association between Cesarean section delivery and a higher risk of Kawasaki disease during six-to eighteen months of the prospective birth cohort in Taiwan.

Fresh Frozen Plasma Transfusion: An Independent Risk Factor for Hemodynamically Significant Patent Ductus Arteriosus in Premature Infants.

OBJECTIVE: The incidence of patent ductus arteriosus (PDA), a major complication of prematurity, may be reduced by restricting fluid administration. Prophylactic fresh frozen plasma (FFP) transfusion may reduce the incidence of intraventricular hemorrhage in these infants, but risks transfusion-related volume overload. We conducted a retrospective study to investigate whether FFP transfusion is a risk factor for hemodynamically significant PDA (hsPDA) in very low birth weight (BW) premature infants. STUDY DESIGN: From January 2009 to December 2014, 102 premature infants with gestational age (GA) less than or equal to 30 weeks were admitted to a level III neonatal intensive care unit, and 88 patients were enrolled. Patients were further divided into non-hsPDA (n = 29) and hsPDA groups (n = 59). We retrospectively reviewed demographic characteristics and various perinatal and postnatal variables. Univariate and multivariable analyses were performed to identify risk factors for hsPDA. RESULTS: Compared with non-hsPDA patients, hsPDA patients had lower mean BW and GA, a higher incidence of severe respiratory distress symptoms, perinatal infection, use of surfactant, and need for FFP transfusion. However, multivariable logistic regression analysis showed that only FFP transfusion remained an independent risk factor for hsPDA (adjusted odds ratio = 3.880, 95% confidence interval: 1.214-12.402, p = 0.022) after adjusting for confounding factors. CONCLUSION: FFP transfusion is a significant risk factor for the subsequent development of hsPDA in our study population. FFP transfusion may complicate the fluid management of premature infants and increase the risk of hsPDA. KEY POINTS: · Hemodynamic significant PDA is an important complication of preterm infant.. · FFP transfusion may complicate the fluid management of premature infants.. · FFP transfusion is an independent risk factor for hsPDA in very low birth weight premature infants..

Associations Between Infant Developmental Delays and Secondhand Smoke Exposure Modified by Maternal Prepregnancy Overweight and Obesity Status.

INTRODUCTION: Secondhand smoke exposure during pregnancy has long been associated with adverse health outcomes in children, but only a few studies have examined its effect modifiers. In this study, we applied effect modification analysis for maternal prepregnancy weight status on detrimental neurodevelopmental effect of secondhand smoke exposure during pregnancy and infancy in a nationwide representative population. AIMS AND METHODS: Term singleton mother-infant pairs with nonsmoking mothers were included for main analysis (N = 15 987) from the Taiwan Birth Cohort Study (TBCS), and were further matched with propensity score (n = 5434). We extracted secondhand smoke exposure during pregnancy and infancy, and eight neurodevelopmental milestones from the responses in the baseline visit at 6 months, and 18-month follow-up of TBCS. The associations between secondhand smoke exposure and neurodevelopmental achievement were analyzed with multivariable logistic regression and Cox model. Propensity score weighting and matching were applied for high-versus-low analysis, and relative excess risk due to interaction were used to estimate effect modification. RESULTS: Higher secondhand smoke exposure was associated with increased likelihood of delayed milestone achievement across gross motor, fine motor, language-related, and social-related domains. The associations in fine motor domains remained observable in propensity score-weighted and -matched models. We identified additive interaction with self-reported maternal overweight and obesity status before pregnancy in milestone development for walking with support, scribbling, and waving goodbye. CONCLUSIONS: Secondhand smoke exposure during pregnancy and infancy were associated with delayed neurodevelopmental milestone achievement at 18 months, and the associations were modified by maternal prepregnancy overweight and obesity status. IMPLICATIONS: The study results suggested the association between maternal secondhand smoke exposure during pregnancy and infancy and delayed fine motor and language-related milestone achievement at 18 months in multivariable, propensity score weighting, and matching populations. The results of positive effect modifications for maternal prepregnancy overweight and obesity status suggested the importance of concurrent interventions on smoke-free environment and maternal health during pregnancy.

Intrauterine exposure to per- and polyfluoroalkyl substances may harm children's lung function development.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA), are common persistent environmental organic pollutants. Animal studies have indicated that PFAS influence inflammatory responses and lung development. However, whether prenatal or childhood PFAS exposure affects children's lung function remains unclear. This study aimed to investigate both in utero exposure and childhood exposure to PFAS and the relationships between them and lung function development in childhood. METHODS: In total, 165 children were recruited from the Taiwan Birth Panel Study (TBPS). Cord blood plasma and children's serum were collected when they were eight years old. PFAS levels were analysed by ultra-high-performance liquid chromatography/tandem mass spectrometry. When these children reached eight years of age, we administered detailed questionnaires and lung function examinations. RESULTS: The mean concentrations of PFOA, PFOS, PFNA and PFUA in cord blood among the 165 study children were 2.4, 6.4, 6.0, and 15.4 ng/mL, respectively. The mean concentrations in serum from eight-year-olds were 2.7, 5.9, 0.6, and 0.3 ng/mL, respectively. At eight years of age, the mean FEV1 (forced expiratory volume per sec), FVC (forced vital capacity), PEF (peak expiratory flow) and FEV1/FVC values were 1679 mL, 1835 mL, 3846 mL/s and 92.0%, respectively. PFOA, PFOS, PFNA and PFUA levels in cord blood were inversely associated with FEV1, FVC and PEF values. The PFOS concentration in cord blood was the most consistently correlated with decreasing lung function before and after adjusting for confounding factors. The PFOS concentration was also significantly inversely correlated with lung function in subgroups with lower birth weight and allergic rhinitis. CONCLUSIONS: Our cohort study revealed that the concentrations of PFOA, PFOS, PFNA and PFUA were higher in cord blood than in serum from eight-year-olds. Some trends were also noted between intrauterine PFOS exposure and children's decreasing FEV1, FVC and PEF, especially in subgroups with lower birth weight and allergic rhinitis. Therefore, intrauterine PFAS exposure, especially PFOS, may play a vital role in lung development.

Associations between household incense burning and delayed motor development among preterm infants modified by gestational age and maternal educational status.

BACKGROUND: Household incense burning is a common ritual behavior in the Asia-Pacific region but has been associated with inferior developmental outcomes in term infants. We aimed to examine these associations among preterm infants. METHODS: Information from 1190 mother-infant pairs during 6- and 18-month follow-up to the Taiwan Birth Cohort Study was examined for associations between household incense burning exposure and infant neurodevelopmental milestone achievement using multivariable Cox proportional hazard model with propensity score weighting, along with stratified, sensitivity, and decomposition analysis. RESULTS: Household incense burning exposure was associated with delayed gross motor milestone achievement among all preterm infants according to the Cox model and after propensity score weighting. Meanwhile, associations for delayed development were found in gross motor domain milestones among late preterm infants, while fine motor domain delay was found among other preterm infants. Furthermore, the associations between household incense burning status and gross motor milestone delays were attenuated by the interaction between higher education level and household incense burning exposure status. CONCLUSIONS: Household incense burning exposure was associated with delays, and the motor domains affected differed according to degree of prematurity. These associations were modified by the attenuation upon higher maternal educational status and exposure status interaction.

The gestational effect of antenatal corticosteroids on respiratory distress syndrome in very low birth weight infants: A population-based study.

BACKGROUND/PURPOSE: The aim of this study was to evaluate the efficacy of antenatal corticosteroids for preventing very low birth weight (VLBW) infants with respiratory distress syndrome (RDS) from surfactant use at different gestational ages (GA). METHODS: We retrospectively analyzed the VLBW preterm infants registered in the Premature Baby Foundation of Taiwan from 1997 through 2014. Infants at 20-37 weeks' gestation were included, and infants with lethal congenital anomaly, chromosomal anomaly, and congenital infection were excluded. Antenatal corticosteroid courses were classified into two groups (<2 doses or ≧2 doses). The beneficial effect of antenatal corticosteroids on preventing VLBW infants with RDS from surfactant use was evaluated according to gestational ages. RESULTS: Total 12,685 VLBW infants were included. For VLBW infants with gestational age 26-33 weeks, antenatal corticosteroid therapy has significantly protective effect (odds ratio 0.43 [95% CI 0.26 to 0.72] - 0.60 [95% CI 0.48 to 0.75], P < 0.05). The effect was not obvious for VLBW infants with gestational age 34 weeks and more (odds ratio 0.32 [95% CI 0.08 to 1.38], P = 0.127). CONCLUSION: For VLBW infants with RDS at 34 weeks' gestation and more, the beneficial effect of antenatal corticosteroids on preventing surfactant use was not evident. In conclusion, completion of two doses or more of antenatal corticosteroids is of great importance for VLBW infants with RDS at gestational age between 26 and 33 weeks on preventing surfactant use.

Critical Trio Exome Benefits In-Time Decision-Making for Pediatric Patients With Severe Illnesses.

OBJECTIVES: Critical illnesses caused by undiagnosed genetic conditions are challenging in PICUs. Whole-exome sequencing is a powerful diagnostic tool but usually costly and often fail to arrive at a final diagnosis in a short period. We assessed the feasibility of our whole-exome sequencing as a tool to improve the efficacy of rare diseases diagnosis for pediatric patients with severe illness. DESIGN: Observational analysis. METHOD: We employed a fast but standard whole-exome sequencing platform together with text mining-assisted variant prioritization in PICU setting over a 1-year period. SETTING: A tertiary referral Children's Hospital in Taiwan. PATIENTS: Critically ill PICU patients suspected of having a genetic disease and newborns who were suspected of having a serious genetic disease after newborn screening were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Around 50,000 to 100,000 variants were obtained for each of the 40 patients in 5 days after blood sampling. Eleven patients were immediately found be affected by previously reported mutations after searching mutation databases. Another seven patients had a diagnosis among the top five in a list ranked by text mining. As a whole, 21 patients (52.5%) obtained a diagnosis in 6.2 ± 1.1 working days (range, 4.3-9 d). Most of the diagnoses were first recognized in Taiwan. Specific medications were recommended for 10 patients (10/21, 47.6%), transplantation was advised for five, and hospice care was suggested for two patients. Overall, clinical management was altered in time for 81.0% of patients who had a molecular diagnosis. CONCLUSIONS: The current whole-exome sequencing algorithm, balanced in cost and speed, uncovers genetic conditions in infants and children in PICU, which helps their managements in time and promotes better utilization of PICU resources.

Concurrent Hearing, Genetic, and Cytomegalovirus Screening in Newborns, Taiwan.

OBJECTIVE: To evaluate the feasibility and potential benefits of incorporating genetic and cytomegalovirus (CMV) screenings into the current newborn hearing screening (NHS) programs. STUDY DESIGN: Newborns were recruited prospectively from a tertiary hospital and a maternity clinic between May 2016 and December 2016 and were subjected to hearing screening, CMV screening, and genetic screening for 4 common mutations in deafness genes (p.V37I and c.235delC of GJB2 gene, c.919-2A>G of SLC26A4 gene, and the mitochondrial m.1555A>G). Infants with homozygous nuclear mutations or homoplasmic/heteroplasmic mitochondrial mutation (referred to as "conclusively positive genotypes") and those who tested positive for CMV received diagnostic audiologic evaluations. RESULTS: Of the total 1716 newborns enrolled, we identified 20 (1.2%) newborns with conclusively positive genotypes on genetic screening, comprising 15 newborns (0.9%) with GJB2 p.V37I/p.V37I and 5 newborns (0.3%) with m.1555A>G. Three (0.2%) newborns tested positive on CMV screening. Twelve of the 20 newborns (60%) with conclusively positive genotypes and all 3 newborns who tested positive for CMV (100%) passed NHS at birth. Diagnostic audiologic evaluations conducted at 3 months confirmed hearing impairment in 6 of the 20 infants (30%) with conclusively positive genotypes. CONCLUSIONS: This study confirms the feasibility of performing hearing, genetic, and CMV screenings concurrently in newborns and provides evidence that the incorporation of these screening tests could potentially identify an additional subgroup of infants with impaired hearing that might not be detected by the NHS programs.

Newborn genetic screening for hearing impairment: a population-based longitudinal study.

PURPOSE: The feasibility of genetic screening for deafness-causing mutations in newborns has been reported in several studies. The aim of this study was to investigate the long-term results in those who screened positive for deafness mutations; these results are crucial to determine the cost-effectiveness to justify population-wide genetic screening. METHODS: We performed simultaneous hearing screening and genetic screening targeting four common deafness mutations (p.V37I and c.235delC of GJB2, c.919-2A>G of SLC26A4, and the mitochondrial m.1555A>G) in 5173 newborns at a tertiary hospital between 2009 and 2015. Serial audiometric results up to 6 years old were then analyzed in children with conclusive genotypes. RESULTS: Newborn genetic screening identified 82 (1.6%) babies with conclusive genotypes, comprising 62 (1.2%) with GJB2 p.V37I/p.V37I, 16 (0.3%) with GJB2 p.V37I/c.235delC, and 4 (0.1%) with m.1555A>G. Of these, 46 (56.1%) passed hearing screening at birth. Long-term follow-up demonstrated progressive hearing loss in children with the GJB2 p.V37I/p.V37I and p.V37I/c.235delC genotypes; this hearing loss deteriorated by approximately 1 decibel hearing level (dBHL) per year. CONCLUSIONS: We delineated the longitudinal auditory features of the highly prevalent GJB2 p.V37I mutation on a general population basis and confirmed the utility of newborn genetic screening in identifying infants with late-onset or progressive hearing impairment undetectable by newborn hearing screening.Genet Med 19 1, 6-12.

Presymptomatic Diagnosis of Spinal Muscular Atrophy Through Newborn Screening.

OBJECTIVE: To demonstrate the feasibility of presymptomatic diagnosis of spinal muscular atrophy (SMA) through newborn screening (NBS). STUDY DESIGN: We performed a screening trial to assess all newborns who underwent routine newborn metabolic screening at the National Taiwan University Hospital newborn screening center between November 2014 and September 2016. A real-time polymerase chain reaction (RT-PCR) genotyping assay for the SMN1/SMN2 intron 7 c.888+100A/G polymorphism was performed to detect homozygous SMN1 deletion using dried blood spot (DBS) samples. Then the exon 7 c.840C>T mutation and SMN2 copy number were determined by both droplet digital PCR (ddPCR) using the original screening DBS and multiplex ligation-dependent probe amplification (MLPA) using a whole blood sample. RESULTS: Of the 120 267 newborns, 15 tested positive according to the RT-PCR assay. The DBS ddPCR assay excluded 8 false-positives, and the other 7 patients were confirmed by the MLPA assay. Inclusion of the second-tier DBS ddPCR screening assay resulted in a positive prediction value of 100%. The incidence of SMA was 1 in 17 181 (95% CI, 1 in 8323 to 1 in 35 468). Two of the 3 patients with 2 copies of SMN2 and all 4 patients with 3 or 4 copies of SMN2 were asymptomatic at the time of diagnosis. Five of the 8 false-positives were caused by intragenic recombination between SMN1 and SMN2. CONCLUSION: Newborn screening can detect patients affected by SMA before symptom onset and enable early therapeutic intervention. A combination of a RT-PCR and a second-tier ddPCR can accurately diagnose SMA from DBS samples with no false-positives. TRIAL REGISTRATION: ClinicalTrials.gov NCT02123186.

Extracorporeal membrane oxygenation for neonatal congenital diaphragmatic hernia: The initial single-center experience in Taiwan.

BACKGROUND/PURPOSE: Extracorporeal membrane oxygenation (ECMO) is a treatment option for stabilizing neonates with congenital diaphragmatic hernia (CDH) in a critical condition when standard therapy fails. However, the use of this approach in Taiwan has not been previously reported. METHODS: The charts of all neonates with CDH treated in our institute during the period 2007-2014 were reviewed. After 2010, patients who could not be stabilized with conventional treatment were candidates for ECMO. We compared the demographic data of patients with and without ECMO support. The clinical course and complications of ECMO were also reviewed. RESULTS: We identified 39 neonates with CDH with a median birth weight of 2696 g (range, 1526-3280 g). Seven (18%) of these patients required ECMO support. The APGAR score at 5 minutes differed significantly between the ECMO and non-ECMO groups. The survival rate was 84.6% (33/39) for all CDH patients and 57.1% (4/7) for the ECMO group. The total ECMO bypass times in the survivors was in the range of 5-36 days, whereas all nonsurvivors received ECMO for at least 36 days (mean duration, 68 days). Surgical bleeding occurred in four of seven patients in the ECMO group. CONCLUSION: The introduction of ECMO rescued some CDH patients who could not have survived by conventional management. Prolonged (i.e., > 36 days) ECMO support had no benefit for survival.

3-O-methyldopa levels in newborns: Result of newborn screening for aromatic l-amino-acid decarboxylase deficiency.

BACKGROUND: The diagnosis of aromatic l-amino-acid decarboxylase (AADC) deficiency is often delayed because a cerebrospinal fluid analysis is required to detect a neurotransmitter deficiency. We here demonstrated that an elevated concentration of l-dopa metabolite 3-O-methyldopa (3-OMD) in dried blood spots could be integrated into newborn screening program to precisely predict AADC deficiency. METHODS: After obtaining parental consent, an additional spot was punched from newborn filter paper, eluted, cleaned, and analyzed by tandem mass spectrometry. Newborns with a 3-OMD concentration exceeding 500ng/mL were referred for confirmatory testing. RESULTS: From September 2013 to December 2015, 127,987 newborns were screened for AADC deficiency. The mean 3-OMD concentration in these newborns was 88.08ng/mL (SD=27.74ng/mL). Four newborns exhibited an elevated 3-OMD concentration (range, 939-3241ng/mL). All four newborns were confirmed to carry two pathologic DDC mutations, indicating an incidence of AADC deficiency of 1:32,000. During the follow-up period, three patients developed typical symptoms of AADC deficiency. Among 16 newborns with mildly elevated 3-OMD levels, six were heterozygous for the DDC IVS6+4A>T mutation. CONCLUSION: Newborn screening of AADC deficiency was achieved with a 100% positive-predictive rate. An association for gestational age could be further elucidated.

Group B streptococcus antimicrobial resistance in neonates born to group B streptococcus-colonized mothers: Single-center survey.

AIM: In this study, we collected group B streptococcus (GBS) screening data and analyzed screening rate, antimicrobial resistance rate, and neonatal observation room (NOR) admission rate due to inadequate chemoprophylaxis. METHODS: The GBS screening data for January 2006-December 2013 were retrospectively collected and analyzed. We also collected data for neonates admitted to NOR due to inadequate chemoprophylaxis during the period 1 April 2010-31 December 2013. RESULTS: A total of 12 200 pregnant women received rectovaginal culture during the 8-year study period. The overall screening rate was 53.8% and maternal colonization rate was 20.7%. The GBS screening rate increased remarkably, from 23.2% in 2006 to 70% in 2013. Antimicrobial resistance was common. The resistance rates for each antimicrobial used in pregnancy were as follows: clindamycin, 49.51%; erythromycin, 49.51%. A total of 297 neonates were admitted to NOR due to inadequate antibiotic prophylaxis during 1 April 2010-31 December 2013. The overall NOR admission rate due to inadequate chemoprophylaxis was 2.67%, and the inadequate chemoprophylaxis rate for those GBS colonized mothers was 19.6%. None of these 297 infants had positive blood culture for GBS sepsis. CONCLUSION: The GBS screening rate increased remarkably, reaching 70% in 2013. The NOR admission rate due to inadequate chemoprophylaxis was 2.67% and there was no early onset GBS disease in a total of 11 123 deliveries in this 4-year cohort study.

Morbidity and mortality of very low birth weight infants in Taiwan-Changes in 15 years: A population based study.

BACKGROUND/PURPOSE: Very low birth weight (VLBW) infants account for over 50% of perinatal deaths in Taiwan. This study aimed to identify changes in parental characteristics, perinatal conditions, mortality, and major neonatal morbidities for VLBW infants in Taiwan, and to highlight the challenges faced by patients, families, and caregivers. METHODS: We conducted a retrospective cohort study to investigate the mortality and morbidity of VLBW infants registered in the Taiwan Premature Infant Follow-up Network from 1997 through 2011. The exclusion criteria included congenital anomalies and chromosome anomalies. Continuous data was represented as mean ± SD, and changes over time in the variables were tested using one-way analysis of variance, with p < 0.05 considered statistically significant. RESULTS: A total of 13,159 VLBW infants were enrolled. We found significant increases over time in the parental age and educational level, in vitro fertilization, first livebirth, multiple births, maternal transfer, cesarean section, and complete antenatal steroid use. Apgar scores at 1 minute and 5 minutes after birth increased, and the intubation rate decreased gradually. Decreasing mortality over time for each successive period was demonstrated. Incidence of some morbidities increased, such as respiratory distress syndrome and patent ductus arteriosus; in contrast, incidence of others decreased, such as sepsis, necrotizing enterocolitis, intraventricular hemorrhage, and chronic lung disease. However, retinopathy of prematurity (ROP) incidence remained constant. CONCLUSION: Although the mortality and most of the morbidity of VLBW infants improved over time, the incidence of ROP remained constant. This requires us to further evaluate our strategy for preventing ROP in the future.

Hypoxic Preconditioning Suppresses Glial Activation and Neuroinflammation in Neonatal Brain Insults.

Perinatal insults and subsequent neuroinflammation are the major mechanisms of neonatal brain injury, but there have been only scarce reports on the associations between hypoxic preconditioning and glial activation. Here we use neonatal hypoxia-ischemia brain injury model in 7-day-old rats and in vitro hypoxia model with primary mixed glial culture and the BV-2 microglial cell line to assess the effects of hypoxia and hypoxic preconditioning on glial activation. Hypoxia-ischemia brain insult induced significant brain weight reduction, profound cell loss, and reactive gliosis in the damaged hemisphere. Hypoxic preconditioning significantly attenuated glial activation and resulted in robust neuroprotection. As early as 2 h after the hypoxia-ischemia insult, proinflammatory gene upregulation was suppressed in the hypoxic preconditioning group. In vitro experiments showed that exposure to 0.5% oxygen for 4 h induced a glial inflammatory response. Exposure to brief hypoxia (0.5 h) 24 h before the hypoxic insult significantly ameliorated this response. In conclusion, hypoxic preconditioning confers strong neuroprotection, possibly through suppression of glial activation and subsequent inflammatory responses after hypoxia-ischemia insults in neonatal rats. This might therefore be a promising therapeutic approach for rescuing neonatal brain injury.

A developmental screening tool for toddlers with multiple domains based on Rasch analysis.

BACKGROUND/PURPOSE: Using multidomain developmental screening tools is a feasible method for pediatric health care professionals to identify children at risk of developmental problems in multiple domains simultaneously. The purpose of this study was to develop a Rasch-based tool for Multidimensional Screening in Child Development (MuSiC) for children aged 0-3 years. METHODS: The MuSic was developed by constructing items bank based on three commonly used screening tools, validating with developmental status (at risk for delay or not) on five developmental domains. Parents of a convenient sample of 632 children (aged 3-35.5 months) with and without developmental delays responded to items from the three screening tools funded by health authorities in Taiwan. Item bank was determined by item fit of Rasch analysis for each of the five developmental domains (cognitive skills, language skills, gross motor skills, fine motor skills, and socioadaptive skills). Children's performance scores in logits derived in Rasch analysis were validated with developmental status for each domain using the area under receiver operating characteristic curves. RESULTS: MuSiC, a 75-item developmental screening tool for five domains, was derived. The diagnostic validity of all five domains was acceptable for all stages of development, except for the infant stage (≤11 months and 15 days). CONCLUSION: MuSiC can be applied simultaneously to well-child care visits as a universal screening tool for children aged 1-3 years on multiple domains. Items with sound validity for infants need to be further developed.

Likelihood ratios of multiple cutoff points of the Taipei City Developmental Checklist for Preschoolers, 2nd version.

BACKGROUND/PURPOSE: This study aimed to examine the reliability and clinical decision validities of the Taipei City Developmental Checklist for Preschoolers, 2nd version (the Taipei II, which was filled out by parents) and the screening procedures conducted in the medical setting. METHODS: Methodology research and case control study designs were adopted. A total of 310 dyads consisting of children who were developing typically and 196 dyads of children with developmental delays and age 5.5 to 35.5 months were recruited for validity test. Among them, 165 mothers filled out the questionnaire twice within 1 week to examine the test-retest reliability of the total score and individual items. Validity indexes of the single cutoff strategy and multiple cutoff strategies were analyzed. With two cutoff point strategies, the likelihood ratios (LR) of the three test results, positive, neutral, and negative, were calculated. RESULTS: The test-retest reliabilities of the total scores of the seven checklists of the Taipei II (rs = 0.54-0.89, p<0.05) and their individual items (agreement 92% to 100%) were acceptable, except for the 30-month checklist and three individual items. The positive LR (LR+) and negative LR (LR-) of the single cutoff strategy were acceptable with most LR+ more than 2, and all LR- less than 0.5. Most of the diagnostic odds ratios of single cutoff strategies were less than 50 and they did not meet the acceptable criteria. When multiple cutoff points were used, all of the LRs with positive test results were equal to infinity that met SpPin criteria, and all of the LRs with negative test results less than 0.5 had at least a small but important diagnostic impact. CONCLUSION: Taipei II with multiple cutoff points could give more useful clinical information than using a single cutoff point. The multiple likelihood ratios of Taipei II for children older than 3 years and in different cultural backgrounds need further study.

Applying the ICF-CY framework to examine biological and environmental factors in early childhood development.

BACKGROUND/PURPOSE: Previous cohort studies for the general pediatric population had a limited focus on either environmental or biological influences, or a specific theoretical framework. The child's development, however, is a composite of physical, mental, social, environmental, and personal factors. The framework of the International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY) provides a comprehensive model for investigating the influential factors of child development within a biopsychosocial perspective. METHODS: A birth cohort study followed up 122 child-parent dyads at birth and when the children were 4 months, 6 months, and 2.5 years old. Structural equation modeling was conducted based on the concept and the definitions of ICF-CY. RESULTS: The path coefficients linking exposures and outcome variables were significant except for the paths from birth weight to general development of infants and toddlers. Home environment explained 59% of variance of infant developmental outcomes. CONCLUSION: The proposed model based on ICF-CY showed acceptable fit to the data and provides support for the importance of the home environment on general development of infants and toddlers.

Adrenal hemorrhage in neonates: Incidence, perinatal characteristics and follow-up outcomes.

BACKGROUND AND OBJECTIVES: Neonatal adrenal hemorrhage (NAH) is relatively uncommon in neonates and it is often noted accidently by abdominal ultrasonogram. Few studies discussed risk factors for and impacts of NAH. This study aimed to assess incidence, perinatal characteristics and follow-up outcomes in neonates with adrenal hemorrhage. METHODS: This was a retrospective cohort study in a single institute from April 2008 to August 2018. All neonates who received abdominal ultrasonogram within seven days-of-life were recruited and divided in to 2 groups according to the presence of NAH. The perinatal characteristics and anthropometric measurements, the follow-up course and the clinical impact of NAH were reviewed in detail. RESULTS: 7217 neonates had received abdominal ultrasonogram within seven days-of-life and 29 of them (0.4%) were diagnosed with NAH. Mean gestation age was 38 ± 1.2 weeks and mean birth weight was 3406 ± 403 g. Most infants (96.6%) had unilateral hemorrhage over the right adrenal gland. Compared with the control group, infants with NAH were significantly heavier (3406 vs. 3094 gm, p < 0.001), longer in body length (50.1 vs. 48.8 cm, p < 0.001) and wider in chest girth (33.2 vs. 32.4 cm, p = 0.006). They also tended to be delivered via vaginal delivery with vacuum-extraction rather than cesarean section. The prevalence of nuchal cord, neonatal jaundice and subgaleal hemorrhage was higher in the NAH group. The hemorrhage area of adrenal gland had a positive correlation with the peak bilirubin level (r = 0.422, p < 0.001) and the days to resolution (r = 0.198, p = 0.033). All infants had resolution of AH before 7 months of age. CONCLUSIONS: NAH occurred more frequently in heavier neonates that were delivered via vaginal delivery with vacuum extraction. The hemorrhage involved mostly over the right adrenal gland. Neonatal jaundice was the major comorbidity. All infants had spontaneous resolution of AH before 7 months of age.