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.

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.

Association Between Serum Glycated Hemoglobin Levels at Early Gestation and the Risk of Subsequent Pregnancy Loss in Pregnant Women Without Diabetes Mellitus: Prospective Cohort Study.

BACKGROUND: As a severe morbidity during pregnancy, the etiology of spontaneous pregnancy loss (SPL) remains largely unknown. Serum glycated hemoglobin (HbA1c) level is an established predictor of SPL risk among women with diabetes, but little is known about whether such an association exists among pregnant women without diabetes when glycemic levels are within the normal range. OBJECTIVE: This study aimed to quantify the association between maternal HbA1c levels in early pregnancy and subsequent SPL risk in a cohort of pregnant women without diabetes. METHODS: This prospective cohort study involved 10,773 pregnant women without diabetes enrolled at their first antenatal care visit at a hospital's early pregnancy clinic from March 2016 to December 2018 in Shanghai, China. HbA1c and fasting blood glucose (FBG) levels were examined at enrollment. Participants with diabetes before or pregnancy or those diagnosed with gestational diabetes were excluded. Diagnosis of SPL, defined as fetal death occurring before 28 gestational weeks, was derived from medical records and confirmed via telephone interviews. We used generalized linear models to quantify the associations of continuous and dichotomized maternal HbA1c levels with SPL risk and reported crude and adjusted risk ratios (RRs) and 95% CIs. A restricted cubic spline (RCS) regression model was used to assess the potential nonlinear dose-response relationship. Adjusted covariates included maternal age, education level, preconception BMI, gestational weeks, gravidity, history of adverse pregnancy outcomes, family history of diabetes, folic acid supplementation, and smoking and drinking during the periconception period. RESULTS: In total, 273 (2.5%) SPL cases occurred. Every 0.5% increase in HbA1c levels was linearly associated with a 23% increase in SPL risk (adjusted RR [aRR] 1.23; 95% CI 1.01-1.50). The RCS model revealed that this association was linear (P=.77 for the nonlinearity test). Analyses based on dichotomized HbA1c levels showed a significantly increased risk of SPL when HbA1c levels were ≥5.9% (aRR 1.67; 95% CI 0.67-3.67), and the significance threshold was ≥5.6% (aRR 1.60; 95% CI 1.01-2.54). Sensitivity analyses showed similar results when including the participants with missing SPL records or HbA1c data. Linear associations of HbA1c levels remained significant even in the subgroups without overweight, alcohol consumption, and a family history of diabetes and adverse pregnancy outcomes. Every 1 mmol/L increment in maternal FBG levels was associated with a >2-fold higher risk of SPL (aRR 2.12; 95% CI 1.61-2.80; P<.001). CONCLUSIONS: Higher HbA1c levels in early pregnant women without diabetes are associated with an increased SPL risk in a dose-response manner. Pregnant women with an HbA1c level above 5.6% at early gestation need attention for its potentially increased risk for SPL. Our findings support the need to monitor HbA1c levels to identify individuals at high risk of subsequent SPL in the general population of pregnant women. TRIAL REGISTRATION: ClinicalTrials.gov NCT02737644; https://clinicaltrials.gov/study/NCT02737644.

Intermittent dietary carbohydrate restriction versus calorie restriction and cardiometabolic profiles: A randomized trial.

OBJECTIVE: The aim of this study was to investigate the effectiveness of an intermittent low-carbohydrate diet (ILCD) versus calorie restriction (ICR) in young populations and potential mechanisms. METHODS: Thirty-four participants aged 9 to 30 years with cardiometabolic risk were randomized to receive a self-administered 2-week ILCD (carbohydrate intake ≤ 50 g/d on seven nonconsecutive days) or ICR (500-600 kcal/d for two consecutive days per week). Differences in changes in obesity measures, glycemic and lipid profiles, gut microbiota composition, and three serum biomarkers were compared. RESULTS: The ILCD and ICR similarly reduced body weight, waist circumference, fasting glucose, insulin, postprandial glucose variation, monocyte chemoattractant protein-1, free fatty acid, and fibroblast growth factor 21, whereas ILCD produced significantly different alterations in the following outcomes compared with ICR: greater increases in low-density lipoprotein cholesterol and total cholesterol (-0.36 mmol/L, 95% CI: -0.68 to -0.04; -0.40 mmol/L, 95% CI: -0.73 to -0.06) and greater decrease in triglyceride (0.20 mmol/L, 95% CI: 0.04 to 0.37). Actinobacteria and Bifidobacterium reduced after ILCD but not ICR; and the reductions strongly correlated with changes in fasting glucose (both r = 0.84) and low-density lipoprotein cholesterol (r = -0.81 and -0.72). CONCLUSIONS: This study found no evidence of differences in changes from baseline in obesity measures, glucose regulation, and inflammation between ILCD and ICR, despite trends in reduction in those parameters. However, there seemed to be some differences in responses in lipids and gut microbiota.

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.

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.

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.

High-normal liver enzyme levels in early pregnancy predispose the risk of gestational hypertension and preeclampsia: A prospective cohort study.

Background: Gestational hypertension (GH) and preeclampsia (PE) are severe adverse gestational complications. Previous studies supported potential link between elevated liver enzyme levels and GH and PE. However, given the transient physiological reduction of liver enzyme levels in pregnancy, little is known whether the associations of the high-normal liver enzyme levels in early pregnancy with GH and PE exist in pregnant women. Methods: Pregnant women in this study came from a sub-cohort of Shanghai Preconception Cohort, who were with four liver enzyme levels examined at 9-13 gestational weeks and without established liver diseases, hypertension and preeclampsia. After exclusion of pregnant women with clinically-abnormal liver enzyme levels in the current pregnancy, associations of liver enzyme levels, including alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT), with GH and PE status were assessed by multivariable log-binomial regression. Population attributable fraction was measured to estimate the fractions of GH and PE that were attributable to the high-normal liver enzyme levels. Results: Among 5,685 pregnant women 160 (2.8%) and 244 (4.3%) developed GH and PE, respectively. After adjustment for potential covariates, higher ALP, ALT and GGT levels were significantly associated with the risk of GH (adjusted risk ratio (aRR):1.21 [95% confidence interval, 1.05-1.38]; 1.21 [1.05-1.38]; and 1.23 [1.09-1.39]), as well as the risk of PE(1.21 [1.13-1.29]; 1.15 [1.03-1.28]; 1.28 [1.16-1.41]), respectively. The cumulative population attributable fraction of carrying one or more high-normal liver enzyme levels (at 80th percentile or over) was 31.4% for GH and 23.2% for PE, respectively. Conclusion: Higher ALT, ALP and GGT levels within the normal range in early pregnancy are associated with increased risk of GH and PE. The documented associations provide new insight to the role of hepatobiliary function in GH and PE pathogenesis.

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.

Aetiology and outcomes of prolonged neonatal jaundice in tertiary centres: data from the China Neonatal Genome Project.

OBJECTIVE: To investigate the distribution of aetiologies and outcomes in neonates with prolonged neonatal jaundice. DESIGN: An observational study. SETTING: Multiple tertiary centres from the China Neonatal Genome Project. PATIENTS: Term infants with jaundice lasting more than 14 days or preterm infants with jaundice lasting more than 21 days were recruited between 1 June 2016 and 30 June 2020. MAIN OUTCOME MEASURES: Aetiology and outcomes were recorded from neonates with prolonged unconjugated hyperbilirubinaemia (PUCHB) and prolonged conjugated hyperbilirubinaemia (PCHB). RESULTS: A total of 939 neonates were enrolled, and known aetiologies were identified in 84.1% of neonates (790 of 939). Among 411 neonates with PCHB, genetic disorders (27.2%, 112 of 411) were the leading aetiologies. There were 8 deceased neonates, 19 neonates with liver failure and 12 with neurodevelopmental delay. Among 528 neonates with PUCHB, a genetic aetiology was identified in 2 of 219 neonates (0.9%) who showed disappearance of jaundice within 4 weeks of age and in 32 of 309 neonates (10.4%) with persistent jaundice after 4 weeks of age. A total of 96 of 181 neonates (53.0%) who received genetic diagnoses had their clinical diagnosis modified as a result of the genetic diagnoses. CONCLUSION: Known aetiologies were identified in approximately 80% of neonates in our cohort, and their overall outcomes were favourable. Genetic aetiology should be considered a priority in neonates with PCHB or the persistence of jaundice after 4 weeks of age. Moreover, genetic data can modify the clinical diagnosis and guide disease management, potentially improving outcomes.

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.

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.

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 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.

Associations of early nutrition with growth and body composition in very preterm infants: a prospective cohort study.

BACKGROUND/OBJECTIVE: To investigate impacts of early postnatal macronutrient intakes on growth and body composition of preterm infants within the first 6 months. SUBJECTS/METHODS: One hundred and thirty-three very preterm (VPT) and/or very low birth weight (VLBW) infants were consecutively included. Enteral and parenteral macronutrient intakes during the first 28 days were recorded and average daily intakes were calculated. Growth was measured at birth, term age, and 6 months of corrected age (CA). Body composition was examined by air displacement plethysmograph at term age and 6 months of CA. Associations of nutrient intakes with growth and body composition over time were analyzed using generalized estimating equation. RESULTS: After adjusting for covariates, higher daily protein, lipid, and energy intake during the first 28 days was associated with higher weight at term age for every 1 g/kg/day increment of protein and lipid intake, and every 10 kcal/kg/day increment of energy intake was associated with 0.50 (95% CI 0.04, 0.96), 0.29 (95% CI 0.07, 0.51), and 0.27 (95% CI 0.10, 0.44) higher weight z-score, respectively. Higher protein intake was associated with lower z-score of fat mass (FM, ß = -1.88, 95% CI -3.53, -0.23) and percentage of body fat (PBF, ß = -2.18, 95% CI -3.98, -0.39) at 6 months of CA, but higher lipid and carbohydrate intake was associated with higher FM and PBF z-scores at 6 months of CA. CONCLUSIONS: Macronutrient intakes during the first month of life have impacts on growth and body composition before 6 months of age. Higher daily protein intake is associated with a better growth and healthier body composition for VPT/VLBW infants.

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.

Higher Serum Bilirubin Levels in Response to Higher Carbohydrate Intake During Early Pregnancy and Lower Gestational Diabetes Mellitus Occurrence in Overweight and Obese Gravidae.

Background and Aim: Serum bilirubin levels are recently shown to be a novel protector of gestational diabetes mellitus (GDM), yet whether they could be affected by carbohydrate quality is unclear. We aimed to examine the associations between dietary carbohydrate parameters and serum bilirubin levels during early pregnancy, with further exploration on a potential mediating role of serum bilirubin levels on carbohydrate parameters-GDM pathways. Methods: 260 healthy but overweight or obese gravidae (BMI ≥24 kg/m2) derived from a historical cohort in two hospitals in China were included. The associations between carbohydrate parameters (total carbohydrate intake, glycemic index GI, fiber intake, glycemic load GL) and serum bilirubin levels (total bilirubin, TB and direct bilirubin, DB) and GDM were evaluated by multivariable regression analysis. Generalized structural equation modeling was then applied to perform adjusted mediation analysis. Results: Increased serum bilirubin levels (mmol/L) and decreased GDM occurrence were observed following dietary carbohydrate intake (%E) and GL (g/1,000 kcal) in highest tertile compared to the lowest tertile [carbohydrate: TB: ß = 0.926 (95%CI: 0.069, 1.782), DB: ß = 0.554 (95%CI: 0.192, 0.916);GL:TB: ß = 1.170 (95%CI: 0.339, 2.001); DB: ß = 0.369 (95%CI: 0.016, 0.700); carbohydrate: adjusted OR = 0.43 (95%CI:0.19-0.99); GL: adjusted OR = 0.36 (95%CI:0.16, 0.84)]. The mediating effect of carbohydrate intake and GL on GDM through bilirubin levels was evaluated as modest (carbohydrate: 6.2% for TB, 1.3% for DB; GL: 8.7% for TB, 2.3% for DB). No association was observed regarding GI and fiber. Conclusions: Mildly elevated serum bilirubin levels appeared to be in response to higher energies consumed from carbohydrate during early pregnancy in healthy overweight or obese gravidae. However, the mediating effect of bilirubin levels on carbohydrate-GDM pathways is not evident. Larger investigation is further needed for solid evidence.

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.

Dynamic trends in skin barrier function from birth to age 6 months and infantile atopic dermatitis: A Chinese prospective cohort study.

BACKGROUND: Skin barrier functions develop after birth and may be related to skin disorders in infants. We aimed to assess associations between dynamic trends of four skin barrier functional parameters in early life with infant atopic dermatitis (AD). METHODS: Based on the prospective cohort MKNFOAD (NCT02889081), we examined transepidermal water loss (TEWL), stratum corneum hydration (SCH), skin pH, and sebum content at five anatomical sites (cheek, forehead, forearm, abdomen, and lower leg) in 418 term infants at birth, 42 days, and 6 months. Trend differences by sex and association with AD at age 1 year were tested using variance analyses. Associations of the parameters with AD risk were tested using discrete time survival analysis, adjusting extensive covariates including parental history of allergy, infant's sex, birth weight (kg), and delivery mode. Odds ratios (ORs) and 95% confidence interval (CIs) were reported. RESULTS: Overall TEWL and SCH appeared trends of increase while skin surface pH and sebum content showed trends of decrease within the first six postnatal months. Sex differences were significant for sebum content only (p < 0.001). After adjustment for parental and children covariates, cheek TEWL at birth (OR = 1.26, 95% CI 1.00-1.57, p = 0.045) and 42 days (OR = 1.52, 95% CI 1.17-1.97, p = 0.002) were significantly associated with increased AD risk. Associations were not observed between SCH, skin pH, and sebum content at birth or 42 days with AD. CONCLUSIONS: Skin barrier functions of Chinese term infants varied nonlinearly after birth. Higher postnatal TEWL levels in early life indicate higher risk of early-onset AD.