Changes in skin barrier over the first four days of life: a cross-sectional study.

BACKGROUND: We aimed to evaluate the trajectory of skin barrier properties in full-term newborns during the first four days after birth. METHODS: Based on the MKNFOAD cohort (NCT02889081), transepidermal water loss (TEWL), stratum corneum hydration (SCH), skin pH, and sebum content at five anatomical sites (cheek, forehead, volar forearm, abdomen, and dorsal lower leg) were examined once within 96 h after birth in 384 full-term infants. Multivariable linear regression analysis was performed to assess variations in these skin barrier parameters with age adjusted for gestational age, neonate's sex, parents' allergy history, delivery mode, amniotic fluid characteristics, and birth weight. The regression coefficient (ß) and 95% confidence interval were reported. RESULTS: We analyzed a total of 384 neonates including 198 (51.6%) boys. TEWL values remained stable and showed no significant association with age (days). pH values exhibited a declining trend with age (p for trend <0.001). Both SCH values and sebum content grew with age (p for trend <0.001). CONCLUSION: During the first four days after birth, the skin TEWL remained stable, pH decreased, and the SCH and sebum content increased over time. These findings provide insights into the neonatal skin physiological development at the beginning of life. IMPACT: From birth to 96 h, TEWL was stable, pH showed a steep decline, SCH and sebum content increased. This study provides the first evidence of skin adaptation in the newborn due to changes in utero to after birth in the first 4 days of life in an Asian population. These findings will provide a new theoretical basis for neonatal skin physiology and clinical strategies for guiding newborn skin care.

Dietary folic acid intake, 13 genetic variants and other factors with red blood cell folate concentration in pregnancy-preparing population.

PURPOSE: This study aims to evaluate a combined effect of dietary folic acid intake, multiple genetic polymorphisms in folate metabolism, and other environmental factors on red blood cell (RBC) folate concentration in pregnancy-preparing population. METHODS: 519 pregnancy-preparing subjects (260 couples) were investigated. Dietary intake was measured by 3-day dietary recalls. 13 Single Nucleotide polymorphisms (SNPs) reported in association with one-carbon metabolism including the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were genotyped. RBC folate concentration was measured using chemiluminescence assay. Hierarchical regression was applied for covariate selection. Factors showed significance(p < 0.0125) on RBC folate level was included for prediction model construction and R2 estimation. Validation cohort analysis was performed as post-hoc analysis if applicable. RESULTS: The median RBC folate was 212.8 ng/ml. Only 10% took folic acid supplementation within three months. Based on hierarchical selection, folic acid supplementation, genetic polymorphism (especially TT genotype of MTHFR C677T), serum folate level were determinants of the variance of RBC folate concentrations, with adjusted R2 of 0.178-0.242. MTHFR A1298C polymorphism, sex difference with other socio-demographic and lifestyle factors (age, BMI, alcohol drinking, smoking, education, occupation) explained little to change in RBC folate level. Validation in another sub-cohort(n = 8105) had adjusted R2 of 0.273. CONCLUSION: In pregnancy-preparing subjects, folic acid supplementation, serum folate level and TT allele of MTHFR C677T polymorphism were determinants of the total variance of RBC folate level, which explained 19.8% variance in our subjects and 27.3% in the validation cohort. Food folate intake, sex and other environmental factors explained little to RBC folate level.

Peripheral perfusion index in well newborns at 6 to 72 h of life at different altitudes: a multi-center study in China.

The purpose of this study is to obtain the reference range of peripheral perfusion index (PPI) of asymptomatic well newborns at 6 to 72 h of life at different altitudes. A population-based prospective cohort study was conducted in cities at different altitudes in China. Asymptomatic well newborns were enrolled consecutively from six hospitals with an altitude of 4 to 4200 m between February 1, 2020, and April 15, 2021. PPI was measured at 6, 12, 24, 48, and 72 h after birth on the right hand (pre-ductal) and either foot (post-ductal) using a Masimo SET Radical-7 oximeter. Fiftieth percentile reference curves of the pre- and post-ductal PPI values at 6-72 h after birth were generated using the Lambda Mu Sigma method. Linear mixed-effects regression was performed to determine the influence of different altitude levels on PPI values over different measurement time points. A total of 4257 asymptomatic well newborns were recruited for analysis. The median and quartile pre- and post-ductal PPI values at 6-72 h of life at different altitudes were 1.70 (1.20, 2.60) and 1.70 (1.10, 2.70) for all infants, 1.30 (1.10, 1.90) and 1.10 (0.88, 1.80) for infants at low altitude, 1.40 (1.00, 2.00) and 1.30 (0.99, 2.00) at mild altitudes, 1.90 (1.30, 2.50) and 1.80 (1.20, 2.70) at moderate altitudes, 1.80 (1.40, 3.50) and 2.20 (1.60, 4.30) for high altitudes, 3.20 (2.70, 3.70), and 3.10 (2.10, 3.30) for higher altitudes, respectively. Overall, both pre- and post-ductal PPI increased with altitude. The 50th percentile curves of pre- and post-ductal PPI values in well newborns at mild, low, moderate, and high altitudes were relatively similar, while the difference between the PPI curves of infants at higher altitudes and other altitudes was significantly different.  Conclusions: With the increase of altitude, pre- and post-ductal PPI of newborns increases. Our study obtained the PPI reference values of asymptomatic well newborns at 6 to 72 h after birth at different altitudes from 4 to ≥ 4000 m. What is Known: • Monitoring hemodynamics is very important to neonates. As an accurate and reliable hemodynamic monitoring index, PPI can detect irreversible damage caused by insufficient tissue perfusion and oxygenation early, directly, noninvasively, and continuously. What is New: • Our study obtained the PPI reference values of asymptomatic well newborns at 6 to 72 h after birth at different altitudes from 4 to ≥ 4000 m. With the increase of altitude, pre- and post-ductal PPI of newborns increase with statistical significance. Therefore, the values and disease thresholds of PPI for asymptomatic neonates should be modified according to altitudes.

The clinical experience of early skin-to-skin contact combined with non-nutritive comfort sucking in mothers of preterm infants: a qualitative study.

BACKGROUND: In most areas of China, mothers typically do not participate in early care of preterm infants in NICU. This study aims to examine the early experience of mothers of preterm infants participating in skin-to-skin contact combined with non-nutritive comfort sucking in China. METHODS: This qualitative research study used one-on-one, face-to-face, semi-structured in-depth interviews. Eighteen mothers who participated in early skin-to-skin contact combined with non-nutritive comfort sucking were interviewed in the NICU of a tertiary children's hospital in Shanghai between July and December 2020. Their experiences were analyzed using the inductive topic analysis method. RESULTS: Five themes about skin-to-skin contact combined with non-nutritive comfort sucking were identified, including alleviation of maternal anxiety and fear during mother infant separation, reshaping the maternal role, promotion of active breast pumping, enhances the mother's willingness to actively breast feed and building the maternal confidence in baby care. CONCLUSION: Skin-to-skin contact combined with non-nutritive comfort sucking in the NICU can not only enhance the identity and responsibility of the mother's role, but also provide non-nutritive sucking experience for promoting the establishment of oral feeding in preterm infants.

Periconception Red Blood Cell Folate and Offspring Congenital Heart Disease : Nested Case-Control and Mendelian Randomization Studies.

BACKGROUND: Periconception folic acid supplementation has been suggested to protect against congenital heart disease (CHD), but the association between maternal red blood cell (RBC) folate, the gold-standard biomarker of folate exposure, and subsequent offspring CHD risk is lacking. OBJECTIVE: To quantify the association between periconception maternal RBC folate and offspring CHD risk. DESIGN: Prospective, nested, case-control study and 1-sample Mendelian randomization. (ClinicalTrials.gov: NCT02737644). SETTING: 29 maternity institutions in 12 districts of Greater Shanghai, China. PARTICIPANTS: All 197 mothers of offspring with CHD and 788 individually matched mothers of unaffected offspring from the SPCC (Shanghai Preconception Cohort). MEASUREMENTS: Maternal RBC folate was measured before or at early pregnancy. Odds ratios [ORs] were estimated using conditional logistic regression after adjustment for covariates. Mendelian randomization was done using the methylenetetrahydrofolate reductase (MTHFR) C677T as the genetic instrument. RESULTS: Case patients had lower median maternal RBC folate concentrations than control participants (714 nmol/L [interquartile range, 482 to 1008 nmol/L] vs. 788 nmol/L [557 to 1094 nmol/L]). Maternal RBC folate concentrations were inversely associated with offspring CHD (adjusted OR per 100 nmol/L, 0.93 [95% CI, 0.89 to 0.99]). The adjusted OR for mothers with periconception RBC folate of 906 nmol/L or more (vs. <906 nmol/L) was 0.61 (CI, 0.40 to 0.93). Mendelian randomization showed that each 100-nmol increase in maternal RBC folate concentrations was significantly associated with reduced offspring CHD risk (OR, 0.75 [CI, 0.61 to 0.92]). LIMITATION: Potential confounding due to unmeasured covariates in the nested case-control study. CONCLUSION: Higher maternal RBC folate is associated with reduced offspring CHD risk. For primary CHD prevention, higher target RBC folate levels than currently recommended for neural tube defect prevention may be needed and warrant further study. PRIMARY FUNDING SOURCE: National Key Research and Development Program of China, National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.

RBC Folate and Serum Folate, Vitamin B-12, and Homocysteine in Chinese Couples Prepregnancy in the Shanghai Preconception Cohort.

BACKGROUND: The protective effects of maternal folate on neural tube defects are well-established. Emerging evidence has shown paternal folate also is related to pregnancy outcome and offspring health. OBJECTIVES: This study aimed to assess the status of red blood cell (RBC) folate and serum folate, vitamin B-12, and homocysteine (Hcy) and their associated factors in a cohort of pregnancy-preparing couples. METHODS: This was a cross-sectional study involving 14,178 participants from the extension of the Shanghai Preconception Cohort conducted in 2018-2021. Circulating biomarker concentrations were measured, and the prevalence of abnormal status was reported. Linear and logistic regression analyses were conducted to examine associations of demographic factors (age, education, and income), lifestyle factors (smoking, drinking, and folic acid supplement use), and BMI with concentrations of the folate-related biomarkers, abnormal status of folate (deficiency and insufficiency) and vitamin B-12 (deficiency and marginal deficiency), and hyperhomocysteinemia. RESULTS: The geometric mean (95% CI) concentrations of RBC folate, serum folate, vitamin B-12, and Hcy were 490 nmol/L (485, 496 nmol/L), 20.1 nmol/L (19.8, 20.3 nmol/L), 353 pmol/L (350, 357 pmol/L), and 7.54 µmol/L (7.48, 7.60 µmol/L) in females, respectively, and 405 nmol/L (401, 409 nmol/L), 13.5 nmol/L (13.4, 13.7 nmol/L), 277 pmol/L (274, 279 pmol/L), and 12.0 µmol/L (11.9, 12.2 µmol/L) in males, respectively. Prevalence of abnormal status was higher in males than females for the 4 folate-related biomarkers: RBC folate deficiency (<340 nmol/L, 32.2% compared with 18.9%), serum folate deficiency (<10.0 nmol/L, 26.5% compared with 7.3%), RBC folate insufficiency (<906 nmol/L, 96.6% compared with 90.1%), serum folate insufficiency (<15.9 nmol/L, 65.5% compared with 31.4%), vitamin B-12 marginal deficiency (148-221 pmol/L, 21.4% compared with 8.8%), and hyperhomocysteinemia (>15.0 µmol/L, 22.1% compared with 2.5%). CONCLUSIONS: Most pregnancy-preparing couples failed to achieve the optimal RBC folate status (>906 nmol/L) as recommended by the WHO. These findings call for attention to the insufficiency status of folate and promising strategies to improve the folate status of the pregnancy-preparing population not exposed to folic acid fortification.

Maternal liver dysfunction in early pregnancy predisposes to gestational diabetes mellitus independent of preconception overweight: A prospective cohort study.

OBJECTIVE: To evaluate whether the associations of maternal liver dysfunction and liver function biomarkers (LFBs) with gestational diabetes mellitus (GDM) are independent of overweight. DESIGN: Prospective cohort study. METHODS: A sub-cohort of pregnant women with seven LFBs examined at 9-13 weeks of gestation and with complete GDM evaluation at mid-gestation were extracted from the prospective Shanghai Preconception Cohort Study. Associations of liver dysfunction, defined as having any elevated LFB levels, and individual LFB levels with GDM incidence were assessed by adjusting body mass index and other covariates in the multivariable logistic regression model. Odds ratios (ORs) and 95% CI were reported. MAIN OUTCOME MEASURES: Incident GDM. RESULTS: Among 6211 pregnant women, 975 (15.7%) developed GDM. Liver dysfunction was associated with increased odds of GDM (OR 1.63; 95% CI 1.38-1.92). This association persisted after adjustment for BMI (adjusted OR [aOR] 1.37; 95% CI 1.15-1.63). Higher γ-glutamyl transferase, alanine aminotransferase, alkaline phosphatase, and albumin levels were also linked with GDM (aOR per 1 SD: 1.15, 95% CI 1.08-1.23; 1.10, 1.03-1.17; 1.21, 1.13-1.29 and 1.19, 1.11-1.27, respectively). Similar magnitudes of associations were observed between normal weight and overweight pregnant women. CONCLUSION: Maternal liver dysfunction in early pregnancy predisposes women to subsequent GDM, and this association is independent of being overweight preconception. Our findings of an increased risk even in normal-weight pregnant women adds new mechanistic insights about the pathophysiological role of liver function in GDM aetiology. TWEETABLE ABSTRACT: Maternal liver dysfunction in early pregnancy is associated with GDM incidence independent of preconception overweight.

Multiple non-invasive peripheral vascular function parameters with obesity and cardiometabolic risk indicators in school-aged children.

BACKGROUND: The Peripheral Arterial Tonometry (PAT) technique measured by Endo-PAT™, is recently introduced for peripheral vascular assessment in youth, primarily benefits from its easy and non-invasive operation. However, the value of Endo-PAT as early indicator of obesity-related cardiometabolic risk factors remains unclear, with few studies focusing solely on Reactive Hyperemia Index (RHI). A wider coverage of Endo-PAT algorithms is recommended to be applied simultaneously in youth. We evaluated the value of multiple Endo-PAT parameters on obesity and cardiometabolic risk indication in school-aged children, in comparison with another non-invasive Brachial-ankle Pulse Wave Velocity (BaPWV) method. METHODS: This cross-sectional sample included 545 youth (80 with overweight and 73 with obesity) aged 7-17 years. RHI, Framingham-Reactive Hyperemia Index (F-RHI), peak response and Augmentation Index normalized to Heart Rate 75 bpm (AIx75) were measured by Endo-PAT™ 2000 device. Spearman correlations of abovementioned Endo-PAT parameters and BaPWV, with adiposity (weight, waist circumference, BMI, body fat mass) and cardiometabolic indicators (glycemic response, blood pressure, lipid profiles) were calculated with non-linear adjustment on age, height, gender and baseline pulse-wave amplitude (PWA) using fractional polynomials. Analysis was repeated in students with obesity only [median BMI z score: 3.0 (2.5,3.5)] for sensitivity analysis. RESULTS: The correlations of Endo-PAT parameters with adiposity measures and cardiometabolic indicators were overall mixed and weak (DBP: r ranged from - 0.20 to - 0.13, others: |r| < 0.1) after adjustment. Except that body fat mass (AIx75: r = 0.52 p < 0.01) and triglyceride level (RHI: r = - 0.32 p < 0.01, F-RHI: r = - 0.21 p > 0.05) was moderately reversed in students with obesity. In contrast, BaPWV showed consistently moderate correlations (|r| ranged from 0.123 to 0.322, p < 0.05) with almost all adiposity measures and cardiometabolic indicators regardless of obesity status. CONCLUSION: Contrary to previous suggestion, various Endo-PAT parameters performed similarly weak for early cardiometabolic risk indication in school-aged children, and less preferable than that by another non-invasive BaPWV method. Despite further investigation is needed to improve certainty of relevant research evidence, innovative technology and algorithms taking into account specifics of young population are worthy of consideration.

Care practices and short-term clinical outcomes of very low birth weight infants in Yangtze River Delta in China.

BACKGROUND: Intensive care is of great significance for very low birth weight infants (VLBWI). The Yangtze River Delta is the most ecomonically developed area in China. However, there are few data on the care practices and survival of VLBWI in this region. OBJECTIVES: To investigate the prevalence, care practices and motality of VLBWI in Yangtze River Delta in China. METHODS: A multi-center retrospective investigation study was conducted at five tertiary hospitals within the Yangtze River Delta in China from January to December 2017. Clinical data included the general characteristics of the infants and the mothers, clinical prognosis, care practices in NICUs was collected by trained research members. RESULTS: During the study period, 1059 VLBWIs were included. Infants with birth weight < 750 g, 750-1000 g, 1000-1250 g and 1250-1500 g accounted for 2.3, 14.9, 34.8 and 47.8%, respectively. Premature rupture of membranes (17.8%) was the main cause of premature delivery. The catheterization rates of umbilical vein catheterization (UVC) and peripherally inserted central catheter (PICC) were 25.0 and 64.4%, respectively. The duration of parenteral nutrition was 27.0 ± 19.5 d, the meantime of feeding tube indwelling was 36.2 ± 24.2 d. The corrected gestational age of the infants who reached full oral feeding was 35.8 ± 2.7 weeks. The breast feeding rate in the investigated infants was 61.9%. The mortality rate of preterm infants was 3.4%. The incidence of main complications BPD, PDA, ROP, NEC and sepsis were 24.9, 29.9, 21.7, 9.4 and 13.3% respectively. CONCLUSIONS: Maternal and infant care practices need to be improved in the very preterm births. This study provides a baseline for the improvement in the further study.

Evaluation of the clinical effect of an artificial intelligence-assisted diagnosis and treatment system for neonatal seizures in the real world: a multicenter clinical study protocol. / æ–°ç”Ÿå„¿æƒŠåŽ¥æ™ºèƒ½è¯Šç–—ç³»ç»ŸçœŸå®žåœºæ™¯ä¸´åºŠå®žæ–½æ•ˆæžœç»¼åˆè¯„ä»·çš„å¤šä¸­å¿ƒä¸´åºŠç ”ç©¶æ–¹æ¡ˆ.

Neonatal seizures are the most common clinical manifestations of critically ill neonates and often suggest serious diseases and complicated etiologies. The precise diagnosis of this disease can optimize the use of anti-seizure medication, reduce hospital costs, and improve the long-term neurodevelopmental outcomes. Currently, a few artificial intelligence-assisted diagnosis and treatment systems have been developed for neonatal seizures, but there is still a lack of high-level evidence for the diagnosis and treatment value in the real world. Based on an artificial intelligence-assisted diagnosis and treatment systems that has been developed for neonatal seizures, this study plans to recruit 370 neonates at a high risk of seizures from 6 neonatal intensive care units (NICUs) in China, in order to evaluate the effect of the system on the diagnosis, treatment, and prognosis of neonatal seizures in neonates with different gestational ages in the NICU. In this study, a diagnostic study protocol is used to evaluate the diagnostic value of the system, and a randomized parallel-controlled trial is designed to evaluate the effect of the system on the treatment and prognosis of neonates at a high risk of seizures. This multicenter prospective study will provide high-level evidence for the clinical application of artificial intelligence-assisted diagnosis and treatment systems for neonatal seizures in the real world.

Maternal serum 25-hydroxyvitamin D levels and infant atopic dermatitis: A prospective cohort study.

BACKGROUND: Maternal vitamin D status during pregnancy has been linked with the risk of atopic dermatitis (AD) in children, while the results were inconsistent. The objective of this study was to assess the potential association. METHODS: Serum 25-hydroxyvitamin D (25(OH)D) levels were measured in pregnant women from the birth cohort MKFOAD. Infant AD was diagnosed according to Williams' criteria. Multivariate logistic regression model was used to examine the association of maternal serum 25(OH)D levels in the first, second, and third trimester of gestation with the risk of infant AD at first year of age. RESULTS: In total, 121 (26.5%) of 456 infants developed AD prior to 1 year of age. In general, higher maternal serum 25(OH)D levels throughout pregnancy were associated with increased risks of AD in infants prior to 1 year of age in multivariate logistic regression models, with borderline statistical significance in the first (per ln unit increase: adjusted OR = 1.93, 95% CI: 0.96, 3.88) and second (per ln unit increase: adjusted OR = 1.72, 95% CI: 0.93, 3.19) trimester. Multivariate logistic regression models using categorical variables of maternal 25(OH)D levels by tertiles showed similar results: Infants born to mothers with serum 25(OH)D levels in the highest tertile had higher risk of AD than those with 25(OH)D in the lowest tertile. CONCLUSIONS: The present study found some evidence supporting that higher maternal 25(OH)D levels during pregnancy increased the risk of infant AD. However, the clinical implication of the findings should be limited for those with blood levels over the recommendations.

Maternal periconceptional folate status and infant atopic dermatitis: A prospective cohort study.

BACKGROUND: Maternal folate status is linked with the risk of allergic disorders including atopic dermatitis (AD) in children, but findings remain inconclusive. We aim to assess the relationship between maternal folate status in early gestation and early-onset infant AD, based on a prospective mother-child cohort study. METHODS: Pregnant women were recruited at 12-14 weeks of gestation. Red blood cell folate (RBC folate) and serum folate concentrations were examined at enrollment. Periconceptional folic acid supplementation was investigated through a self-administered questionnaire. The primary outcome was AD incidence before 6 months of age, diagnosed according to Williams' criteria. Multivariate logistic regression was used to evaluate associations of maternal folate status with infant AD by adjusting parental and child covariates. RESULTS: In total, 107 (23.4%) of 458 infants developed AD before 6 months, with more male infants affected (P = .002). Higher maternal RBC folate levels (per 100 ng/mL) were associated with an increased risk of AD (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.04-1.31). An RBC folate level ≥620 ng/mL was associated with increased infant AD by 91% (aOR 1.91, 95% CI 1.09-3.36). However, associations were not observed for maternal serum folate at early gestation or periconceptional folic acid supplement intakes. CONCLUSIONS: We provide the first evidence that higher maternal RBC folate concentrations during early gestation are associated with increased early-onset infant AD. Our findings support the importance of maintaining appropriate folate levels during the periconceptional period to reduce the risk of AD in infants.

Inpatient medical cost of status epilepticus in children: A national-wide, multicenter study from China.

OBJECTIVES: To describe the inpatient medical cost during hospitalization in children with status epilepticus (SE) and identify factors associated with the cost by a nationwide, multicenter study in China. MATERIALS & METHODS: We retrospectively identified pediatric inpatients with SE form Hospital Information System (HIS) of 44 hospitals in 27 provinces in China between 2013 and 2015. Inpatient medical cost and factors associated with the cost were analyzed. RESULTS: A total of 4041 children diagnosed with SE with inpatient medical cost were enrolled in the present study. The median age at admission was 2.9 (range 0.1-18) years, and 2271 patients were male (56.2%). The median inpatient medical cost of children with SE was $1175.5 (665.1-2320.6). The median inpatient medical cost was $3865.6 (1837.4-8210.4) in children with SRSE and $1048.6 (619.8-1865.4) in those with N-SRSE (p < 0.0001). Children with length of hospital stay (LOS) > 7 showed a much higher inpatient medical cost than those with LOS ≤ 7 day ($2300.7 vs. $767.2, p < 0.0001). Regarding different etiologies, children with acute symptomatic etiology showed the highest median inpatient medical cost of $1681.1 (901.0-3699.6), in which children with central nervous system (CNS) infection reported $2606.0 (1380.0-5016.1) and prolonged febrile seizures (PFS) reported $909.8 (649.3-1322.0). Additionally, children with idiopathic/cryptogenic etiology reported a medical cost of $923.2 (548.9-1534.5). Multiple linear regression analysis of cost-driving factors revealed LOS > 7, examinations, treatment equipment and procedures, and treatment medicines were independently associated with a higher inpatient medical cost (R2 = 60.91). In addition, PFS and idiopathic/cryptogenic epilepsy etiology were independently associated with a lower cost. CONCLUSIONS: SE in children was a cost intensive disease in China with a median inpatient medical cost of $1175.5. LOS, etiology and examinations, treatment equipment and procedures, and treatment medicines were significantly associated with inpatient medical cost.

Early initial video-electro-encephalography combined with variant location predict prognosis of KCNQ2-related disorder.

BACKGROUND: The clinical features of KCNQ2-related disorders range from benign familial neonatal seizures 1 to early infantile epileptic encephalopathy 7. The genotype-phenotypic association is difficult to establish. OBJECTIVE: To explore potential factors in neonatal period that can predict the prognosis of neonates with KCNQ2-related disorder. METHODS: Infants with KCNQ2-related disorder were retrospectively enrolled in our study in Children's Hospital of Fudan University in China from Jan 2015 to Mar 2020. All infants were older than age of 12 months at time of follow-up, and assessed by Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III) or Wechsler preschool and primary scale of intelligence-fourth edition (WPPSI-IV), then divided into three groups based on scores of BSID-III or WPPSI-IV: normal group, mild impairment group, encephalopathy group. We collected demographic variables, clinical characteristics, neuroimaging data. Considered variables include gender, gestational age, birth weight, age of the initial seizures, early interictal VEEG, variant location, delivery type. Variables predicting prognosis were identified using multivariate ordinal logistic regression analysis. RESULTS: A total of 52 infants were selected in this study. Early interictal video-electro-encephalography (VEEG) (ß = 2.77, 1.20 to 4.34, P = 0.001), and variant location (ß = 2.77, 0.03 to 5.5, P = 0.048) were independent risk factors for prognosis. The worse the early interictal VEEG, the worse the prognosis. Patients with variants located in the pore-lining domain or S4 segment are more likely to have a poor prognosis. CONCLUSIONS: The integration of early initial VEEG and variant location can predict prognosis. An individual whose KCNQ2 variant located in voltage sensor, the pore domain, with worse early initial VEEG background, often had an adverse outcome.

Effectiveness of community-based folate-oriented tertiary interventions on incidence of fetus and birth defects: a protocol for a single-blind cluster randomized controlled trial.

BACKGROUND: Birth defects are the main cause of fetal death, infant mortality and morbidity worldwide. However, the etiology of birth defects remains largely unknown. Maternal folate status during periconception plays an important role in organogenesis and folic acid supplement reduces the risk of neural tube defects, congenital heart diseases, and several other birth defects. This trial seeks to evaluate the effectiveness of folate-oriented tertiary interventions during periconception on the incidence of fetus and birth defects. METHODS: This is a single-blind, two-arm cluster randomized controlled trial in Shanghai, China. Eligible women from 22 clusters are recruited at pre-pregnancy physical examinations clinical settings. Compared to the routine perinatal care group (control arm), folate-oriented tertiary interventions will be provided to the intervention arm. The core interventions consist of assessments of folate status and metabolism, folate intake guidance, and re-evaluation of folate status to ensure red blood cell folate level above 400 ng/ml (906 nmol/L) before pregnancy. Screening and consulting of fetus and birth defects, and treatments of birth defects during pregnancy and afterward will be provided to both arms. The primary outcome is a composite incidence of fetus defects, stillbirth, and neonatal birth defects identified from the confirmation of pregnancy to 28 days after birth. Secondary outcomes include maternal and offspring adverse complications and cost-effectiveness of folate-oriented tertiary interventions. This protocol adheres to the SPIRIT Checklist. DISCUSSION: To achieve the recommended folate status before or during pregnancy is still a challenge worldwide. This community-based cluster-randomized controlled intervention trial will evaluate the effectiveness of a package of interventions aiming at achieving recommended maternal folate status covering pre- and during pregnancy in reducing fetus and birth defects. Our study has the potential to improve the community-based practice of reducing modifiable risk factors of disease and improving primary prevention of the defects in China. The procedures would formulate the policy on folic acid supplementation during periconception against birth defects in primary care settings. TRIAL REGISTRATION: Clinical Trial Registry, NCT03725878 . Prospectively registered on 31 October 2018.

Waist-to-height ratio remains an accurate and practical way of identifying cardiometabolic risks in children and adolescents.

AIM: We evaluated how effectively the waist-to-height ratio (WHtR) identified cardiometabolic risk (CMR) in children and adolescents, compared with the tri-ponderal mass index, percentage of body fat and other obesity indexes. METHODS: Eligible subjects were recruited from three metropolitan regions of China from May 2013 to June 2014. Subjects with at least three of the following abnormalities - hypertension, dyslipidemia, elevated fasting blood glucose and central obesity - were defined as CMR1 and children with at least two were defined as CMR2. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare how effectively obesity indexes predicted CMR. RESULTS: We recruited 3556 subjects aged 7-18 years. All five obesity indexes showed good, comparable performances in identifying CMR and the AUCs ranged from 0.89 to 0.90 for CMR1 and 0.83 to 0.85 for CMR2. The cut-off of 0.467 for WHtR achieved a sensitivity of 0.91 and specificity of 0.80 for predicting CMR1, with the best cut-offs being 0.463 for boys and 0.469 for girls. CONCLUSION: The WHtR was a superior and practical screening tool for detecting CMR in this paediatric population, as it provided comparable accuracy to other methods and just required a simple calculation.

[Association between copy number variations and risk of overweight/obesity among Han, Uyghur, and Kazak children].

OBJECTIVE: To study the association between the prevalence of overweight/obesity and copy number variations (CNVs) among Han, Uyghur, and Kazak children in Xinjiang, China. METHODS: The kindergartens in Ili, Altay, and Karamay in Xinjiang were selected as research sites, and stratified cluster sampling was used to select the children aged 3-7 years. Body height and body weight were measured, and exfoliated buccal mucosa cells were collected. CNVplex® was used to measure the CNVs of FTO_1, IRX3_1, IRX3_2, MC4R_1, and MC4R_2. RESULTS: A total of 603 children were surveyed (307 boys and 296 girls). There were 261 Han children, 194 Uyghur children, and 148 Kazak children. The overweight/obesity rates in Han, Uyghur, and Kazak children were 28.3%, 10.3%, and 31.1%, respectively (P<0.001). In Kazak children, the CNVs of IRX3_1 and MC4R_2 were associated with overweight/obesity (P<0.05). The multivariate logistic regression analysis showed that the risk of overweight/obesity in Han and Kazak children was 3.443 times (95%CI: 2.016-5.880) and 3.924 times (95%CI: 2.199-7.001), respectively, that in Uyghur children. The CNV of IRX3_1 was a risk factor for overweight/obesity (P=0.028, OR=2.251, 95%CI: 1.418-5.651). CONCLUSIONS: The CNV of IRX3_1 is associated with overweight/obesity in Han, Uyghur, and Kazak children, and the association between the CNV of IRX3_1 and overweight/obesity in Kazak children should be taken seriously.

Early Rituximab as an Add-On Therapy in Children With the Initial Episode of Nephrotic Syndrome.

Introduction: The approximately 70% 12-month relapse in children experiencing the initial episode of steroid-sensitive nephrotic syndrome (SSNS) is a significant concern, with over 50% developing frequent relapses or steroid-dependent nephrotic syndrome (FRNS/SDNS). There is a lack of strategies to reduce relapse after the onset. Whether early administration of rituximab, which effectively reduces relapses in FRNS/SDNS, may be a solution has not been evaluated. Methods: A prospective, multicenter, open-label, single-arm trial was conducted in China, with a 12-month follow-up. Children aged 1 to 18 years with the first episode of nephrotic syndrome (NS) were screened for eligibility. Proteinuria was evaluated daily using dipsticks. A dose of 375 mg/m2 of rituximab was intravenously infused within 1 week after achieving corticosteroid-induced remission. The main outcome was 12-month relapse-free survival. Results: Out of the initially 66 children screened, 44 were enrolled and received rituximab, with all but 1 participant completing the 12-month follow-up. The median age at diagnosis was 4.3 years (interquartile range [IQR]: 3.4-5.9), and 33 (77%) of the participants were male. In the rituximab group, the 12-month relapse-free survival was significantly higher compared to historical controls (32 of 43 [74.4%] vs. 10 of 33 [30.3%]; P < 0.001; hazard ratio [HR], 3.76; 95% confidence interval [CI], 1.80-7.81). The post hoc analysis revealed a higher 24-month relapse-free survival and a lower incidence of FRNS/SDNS at the 12-month follow-up. Treatment with rituximab was well-tolerated. Conclusion: Our findings support that early administration of rituximab may be associated with a higher 12-month relapse-free survival and a reduced incidence of FRNS/SDNS in children experiencing the initial episode of SSNS.

The effect of developmental care on the length of hospital stay and family centered care practice for very low birth weight infants in neonatal intensive care units: A cluster randomized controlled trial.

BACKGROUND: Despite previous studies suggesting that developmental care can provide benign stimulation to promote neural development of newborns, more evidence is needed regarding the other clinical benefits of developmental care. OBJECTIVE: To evaluate the effect of implementing developmental care on the length of hospital stay, the improvement of care practice in neonatal intensive care units, as well as the short-term outcome of very low birth weight infants. DESIGN: Cluster-randomized controlled trial. SETTING(S) AND PARTICIPANTS: From March 1, 2021 to March 1, 2022, 1400 very low birth weight infants were recruited from 14 tertiary neonatal intensive care units in China. METHODS: We assigned 14 neonatal intensive care units to either developmental care or standard care. The length of hospital stay of the infants was the primary outcome analyzed at the individual level. Secondary outcomes were family centered care practice including parental involvement, the skin to skin care, exclusive breast milk, oral immune therapy and breastfeeding. The environmental management (noise and light) and the short-term outcomes were also evaluated. RESULTS: The length of hospital stay for the developmental care group was 65 % as long as that for the control group (HR: 0.65, 95 % CI, 0.451-0936, p = 0.021). After controlling the covariables, the adjusted HR = 0.755 (95 % CI, 0.515 to 1.107, p = 0.150). When compared to the control group, the developmental care group had greater access to SSC, with 22 infants (3.8 %) in the developmental care group compared to 13 infants (1.7 %) in the standard care group (p = 0.013). A greater proportion of infants in the developmental care group were fed at the breast, than those in the standard care group (136 [23.6 %] vs 9 [1.1 %]; p = 0.029). Compared to the control group, exclusively breast milk was significantly more favorable in the developmental care group (435 [75.6 %] vs 114 [15.0 %]; p = 0.001). The difference remained significant even after adjusting for covariates. However, the rate of oral immune therapy and parental involvement was similar in the two groups. The average noise and light levels in the developmental care group were significantly lower than those in the standard care group. After adjusting for confounders, the difference remained significant. There were no significant differences among groups in the mortality and major morbidity. CONCLUSIONS: Developmental care might have developed an accumulated effect over time on the length of hospital stay among very low birth weight infants. The implementation of developmental care can greatly improve family centered care practices and the neonatal intensive care unit environment. REGISTRATION: ClinicalTrials.govNCT05166720. Registration date: 1 March, 2021.