Effects of Vitamin D Supplementation on Children with Autism Spectrum Disorder: A Systematic Review and Meta-analysis

The effect of vitamin D supplementation on individuals with autism spectrum disorder (ASD) is inconclusive. We aimed to conduct a meta-analysis of the available randomized controlled trials (RCTs) to explore whether vitamin D supplementation can improve core symptoms and coexisting conditions in children with ASD. Data were obtained by searching the PubMed, Embase, Web of Science, CINAHL and Cochrane Library databases up to February 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using a random-effects model, mean differences with 95% confidence intervals (CIs) were calculated through a meta-analysis. There were eight RCTs with 266 children with ASD in the present review, among which six RCTs were included in the meta-analysis.Children who received vitamin D supplementation showed a significant improvement in stereotypical behavior scores (pooled mean difference (MD): −1.39; 95% CI: −2.7, −0.07; p = 0.04) with low heterogeneity (I2 = 34%), and there was a trend toward decreased total scores on the Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS, p = 0.05); however, there were no other significant differences in the core symptoms of ASD and coexisting conditions between groups as measured by the Aberrant Behavior Checklist (ABC). Vitamin D supplementation appears to improve stereotypical behaviors but does not improve other core symptoms and coexisting conditions. Further randomized controlled trials with large sample sizes and individualized doses are needed.

Impacts of pre-pregnancy body mass index, gestational diabetes mellitus and gestational weight gain on perinatal outcomes and mode of delivery / 中国新生儿科杂志

Objective:To study the impacts of pre-pregnancy body mass index (BMI), gestational diabetes mellitus (GDM) and gestational weight gain (GWG) on perinatal outcomes and mode of delivery.Methods:From November 2016 to December 2017, single-pregnancy women in early pregnancy (<13 weeks) regularly checked-up at our hospital were enrolled in this prospective cohort study and followed up until delivery. They were assigned into four groups according to pre-pregnancy BMI: obese group (≥28.0 kg/m 2), overweight group(24.0-<28.0 kg/m 2), normal group (18.5-<24.0 kg/m 2) and underweight group(<18.5 kg/m 2). A 75-g oral glucose tolerance test was performed at 24-28 weeks of pregnancy to screen for GDM. The optimal GWG was 11.0-16.0 kg for underweight group, 8.0-14.0 kg for normal group, 7.0-11.0 kg for overweight group and 5.0-9.0 kg for obesity group. The effects of pre-pregnancy BMI, GDM and GWG on perinatal outcomes and delivery mode were evaluated using multivariate logistic regression methods. Results:A total of 802 pregnant women were included. The incidences of pre-pregnancy overweight and obesity were 21.8% and 8.9%, respectively. The incidence of GDM was 14.1%. 57.2% of the participants experienced excessive GWG. The incidences of macrosomia, low birth weight and premature birth were 7.1%, 2.7% and 2.2%, respectively. The incidence of Cesarean delivery (C-section) was 37.7%. Pre-pregnancy obesity [adjusted odds ratio ( AOR)=4.355, 95% confidence interval ( CI) 1.900-9.980] and excessive GWG ( AOR=3.799, 95% CI 1.796-8.034) were independent risk factors for macrosomia. Excessive GWG was a protective factor for low birth weight ( AOR=0.279, 95% CI 0.084-0.928) and inadequate GWG was a risk factor for low birth weight ( AOR=10.954, 95% CI 3.594-33.382) and premature birth ( AOR=8.796, 95% CI 2.628-29.438). Compared with the normal group, overweight group had an increased risk of C-section ( AOR=1.817, 95% CI 1.119-2.949). Compared with pregnant women without pre-pregnancy overweight/obesity, GDM nor excessive GWG, any combination of two of the above-mentioned three factors increased the risks of macrosomia ( AOR=3.908, 95% CI 1.630-9.370) and C-section ( AOR=2.269, 95% CI 1.325-3.886). The risks of macrosomia and C-section were the highest when all three factors existed. Conclusions:Pre-pregnancy obesity and excessive GWG are independent risk factors for macrosomia and pre-pregnancy overweight is a risk factor of C-section. Exposure to any two of the three factors (pre-pregnancy overweight/obesity, GDM and excessive GWG) increases risks of macrosomia and C-section and the highest risk is observed when all three factors are present.

Advances in research related to severe pertussis in infants and young children / 中华实用儿科临床杂志

Pertussis is a highly contagious respiratory disease.Although widespread vaccination has greatly reduced the incidence of pertussis, there was a " recurrence of pertussis" in the past 30 years, and pertussis outbreaks occurred in some areas.Infants who have not been vaccinated or have not completed the full course of immunization suffer from more severe pertussis infections.Because of the atypical symptoms of young infants, missed diagnosis and misdiagnosis often occur, and pertussis cannot be diagnosed and treated in time.As a result, they can easily develop into severe pertussis or even die.In this article, recently published research on severe pertussis are summarized, so as to provide guidance for the clinical diagnosis, treatment, prevention and basic scientific research of severe pertussis.

Serum Presepsin in the diagnosis and assessment of sepsis in children / 中国小儿急救医学

Objective:To investigate clinical significance of Presepsin(soluble CD14 subtype) in the diagnosis and condition assessment of sepsis in children compared with traditional biomarkers.Methods:For the prospective study, 102 children with sepsis admitted to the PICU of the Children′s Hospital of the Capital Institute of Pediatrics from January 2017 to December 2018 were selected, including 57 cases in the sepsis group, 45 cases in the severe sepsis/septic shock group and 25 cases in the non-infectious systemic inflammatory response syndrome(SIRS group), and 35 children with healthy physical examination during the same period as the control group.The sepsis group was further divided into the survival group( n=86)and the death group( n=16)based on the 28-day mortality.The data collected included serum Presepsin, procalcitonin(PCT), C-reaction protein(CRP) and interleukin(IL)-6 levels on days 1, 3 and 7 of admission, and compared with paediatric critical case scores. Results:(1)The levels of serum Presepsin [12.43(7.21, 15.07) ng/mL], PCT [23.00(5.70, 87.00) ng/mL], CRP [160.0(105.5, 200.0) mg/L], IL-6 [1 000.0(125.0, 1, 000.0) pg/mL] were significantly higher than those in the sepsis, SIRS and control groups( P<0.001). (2) The area under the ROC curve(AUC) values for Presepsin, PCT, and IL-6 subjects on day 1 of admission were 0.856, 0.812, and 0.516, respectively.The sensitivity of Presepsin at a cut-off value of 4.40 ng/mL for the diagnosis of sepsis was 81.1% and the specificity was 72.3%, which would significantly higher diagnostic efficacy of the combination of Presepsin, PCT and IL-6.(3) There was a significant difference between the survival and death groups in Presepsin( P<0.001), and Presepsin was significantly higher in the death group on days 3 and 7 than those in the survival group(both P<0.001); IL-6 was significantly higher in the death group on day 3 than that in the survival group( P=0.04); the differences in PCT and CRP between the death and survival groups at all time points were not statistically significant(both P>0.05 ). (4) The AUCs of inflammatory factors on days 1, 3 and 7 to predict sepsis outcome were 0.597, 0.656 and 0.951 for Presepsin, 0.576, 0.613 and 0.655 for PCT and 0.726, 0.786 and 0.664 for IL-6, respectively.The diagnostic values of Presepsin on day 7 and IL-6 on days 1 and 3 were higher.The combination of Presepsin, PCT and IL-6 significantly improved the prognostic judgment of sepsis.(5) The difference between sepsis-related acute kidney injury(AKI) and non-AKI was not statistically significant when comparing Presepsin on day 1 and 3(all P>0.05). Presepsin levels on day 7 were significantly higher in children with sepsis-associated AKI than in those without AKI( P<0.001). Conclusion:Presepsin is a good biomarker for sepsis diagnosis in children, which is equivalent to PCT in the diagnosis of sepsis, superior to IL-6 and superior to PCT in the prognosis evaluation.Combined testing of Presepsin, PCT and IL-6 may improve the diagnosis of sepsis and the assessment of the condition in children.

The differential expression of ATPase-related genes and associated long non-coding RNAs in peripheral blood of children with sepsis / 中国小儿急救医学

Objective:To screen and identify differentially expressed long non-coding RNA (lncRNAs) in peripheral blood of children with sepsis, and to explore the role of lncRNAs in the pathogenesis of sepsis in children.Methods:The peripheral blood samples of 3 children with sepsis admitted to the ICU of Children′s Hospital of Capital Institute of Pediatrics from January to December 2016 and 3 healthy children who underwent physical examination in our hospital during the same period were selected, and the differential expression profiles of lncRNAs and mRNAs were screened by lncRNAs sequencing technology.The target genes of differentially expressed lncRNAs were predicted and the relationship pairs of lncRNA-mRNA related to F 1F O-ATPase activity were constructed according to the results of GO analysis.Further increasing the sample size, we verified the expression of some F 1F O-ATPase activity-related mRNAs and lncRNAs which were differentially expressed in the screening results by real-time fluorescent quantitative polymerase chain reaction(qRT-PCR). Results:Sequencing results showed that there were 252 lncRNAs with significant differential expression in peripheral blood of children with sepsis compared with healthy children, of which 86 were up-regulated and 166 were down-regulated; meanwhile, there were 2 652 mRNAs with significant differential expression, of which 955 were up-regulated and 1 697 were down-regulated.The results of qRT-PCR showed that the expression of lncRNA ENST00000621933.1, ENST00000616950.1 and ENST00000595748.1 in peripheral blood of children with sepsis increased( P<0.05), while the expression of MT-ATP8, ATP5E and ENST00000624705.1, ENST00000615535.1 in peripheral blood of children with sepsis decreased( P<0.05), which was consistent with the sequencing results. Conclusion:lncRNAs are differentially expressed in peripheral blood of children with sepsis compared with healthy children.The expression levels of lncRNA ENST00000621933.1, ENST00000616950.1, ENST00000595748.1, ENST00000624705.1 and ENST00000615535.1 which their target genes are MT-ATP8 and ATP5E may be related to the development of sepsis in children.

Pertussis antibody titers in pregnant women's venous blood and cord blood—a survey from three women and children's hospitals in Beijing / 中国新生儿科杂志

Objective To study the levels of antibodies against bordetella pertussis among pregnant women and neonates in Beijing. Method From December 2016 to March 2017, pregnant women and their newborns from three women and children′s hospitals in Beijing were enrolled in this study. 3 ml of venous blood from the mothers and 3 ml of umbilical cord blood from neonates were drawn.Pertussis bacillus IgG antibody (PER-IgG) and pertussis toxin IgG antibody (PT-IgG) were tested using enzyme-linked immunosorbent assay. χ2 test was used to compare the positive rate of pertussis IgG antibodies in maternal and cord blood in the three hospitals. Correlational analyses of the antibodies levels in each hospital were conducted. The demographic characteristics, history of cough during pregnancy and history of DTaP vaccination of the mothers were collected via questionnaires. Result A total of 612 pairs of venous blood and cord blood samples were collected, including 4 mothers delivered twins and 616 cases of cord blood sample were collected. No history of pertussis were found in the 612 mothers. Among the 616 cases of umbilical cord blood, positive rate of PER-IgG was 13.3％ (82/616), positive rate of PT-IgG was 0.5％ (3/616). Among 612 cases of venous blood from the mothers, positive rate of PER-IgG was 7.7％ (47/612), positive rate of PT-IgG was 0.3％ (2/612). Positive rates of PER-IgG and PT-IgG in the mothers′ venous blood were not correlated with their residences (P=0.676 and 0.544). Positive rates of PER-IgG (r=0.842, P<0.001) and PT-IgG (r=0.619, P<0.001) in the mothers′ blood were positively correlated with the positive rate in umbilical cord blood. Conclusion This study shows that the positive rate of PER-IgG is very low in the maternal and umbilical cord blood in Beijing. Positive correlations of PER-IgG and PT-IgG between mother and umbilical cord blood were existed. Most mothers and their newborns do not have enough protection against pertussis.

The detection rate of pertussis in children and infants with persistent cough in Beijing during 2011-2016 / 中华传染病杂志

Objective To investigate the prevalence of pertussis in infants and children with persistent cough in Beijing during 2011-2016.Methods The eligible infants and children from over ten hospitals who were suspected to have pertussis from 2011 to 2016 were enrolled for detection.Nasopharyngeal secretions and blood samples were collected.Multiplex-PCR was performed for Bordetella pertussis and real-time PCR was performed for nucleic acid of Bordetella pertussis.Results A total of 1 318 eligible cases were enrolled,including 820 males and 498 females.Pertussis was detected positive in 534 cases,including 81.3％ (434/534) of B.pertussis positive cases and 31.8％ (170/534) of IgG positive cases.There were 13.1 ％ (70/534) had double positive for bacteria and antibodies.From 2011 to 2016,the enrolled patients were increased from 103 cases per year to 460 cases per year,and the test positive patients were increased from 29 cases to 194 cases.Among the pertussis patients,466 (87.3 ％) cases were younger than one year old.From the first quarter to the fourth quarter of the year,There were 65 cases,151 cases,205 cases,and 113 cases,respectively.In further analysis of the 268 cases from Children's Hospital affiliated to Capital Institute of Pediatrics,90.7％ of the patients who had whooping cough were scattered children;185 cases (69.0％) of the patients had not begun programmed immunization,71 cases (26.5％) did not complete programmed immunization and 12 cases (4.5％)completed the programmed immunization.Of all the inpatients,21.6％ were critical ill,0.8％ (2 cases) dead,and the remaining patients were recovered and discharged.Conclusions The prevalence of pertussis is increasing,especially in summer.Infants are the most susceptible population.Bordetella pertussis is one of the most important pathogen that can induce persistent and chronic cough.

Bordetella pertussis infection in infants less than three months: analysis of 59 cases from 2011 to 2015 in a single center / 中华围产医学杂志

Objective To study the epidemiological and clinical characteristics ofpertussis in infants younger than three months.Methods Infants younger than three months were enrolled from January 1,2011 to December 31,2015 with one or more of the following symptoms:persistent cough,spasmic cough,cyanosis of unknown causes,asphyxia and apnea.Multiplex polymerase chain reaction(PCR) assay was performed to identify Bordetella pertussis and enzyme-linked immunosorbent assay was used to detect antibody to pertussis toxin.Clinical features,complications,treatments and prognosis of the infants confirmed with pertussis were analyzed.Results Altogether 202 cases were enrolled in the five years,and 59 (29.2％) of which were positive for pertussis confirmed by multiplex PCR.Among the 59 cases,37 were boys and 22 were girls.The youngest baby was 13 days and the oldest one was 85 days.Length of stay ranged from 7 to 21 days.Twelve cases had a contact history with family members having chronic cough.Symptoms occurred in spring or summer in 46 cases (78.0％),and in autumn or winter in 13 (22.0％) cases.Symptoms of spasmic cough,cyanosis after coughing,vomiting after coughing and conjunctival hemorrhage were respectively found in 41 (69.5％),36 (61.0％),39 (66.1％)and 33 (55.9％) cases,while only six (10.2％) presented with inspiratory whooping sound on coughing.Fortynine cases (83.1％) showed increased lymphocyte count (≥ 10 × 109/L).Twenty-eight cases (47.5％) developed severe pertussis.Complications including apnea and bradycardia after coughing,respiratory failure and heart failure,pertussis encephalopathy as well as highly increased leucocyte count (≥ 60× 109/L) occurred in 23 (39.0％),18 (30.5％),five (8.5％) and four (6.8％) cases,respectively.Twenty-four cases with severe pertussis required respiratory support,of which six received invasive ventilation and 18 received non-invasive ventilation.Fifty-eight infants were recovered and discharged,while one baby died.Conclusions Bordetella pertussis infection is an important cause of persistent cough in unimmunized infants under three months of age.The symptoms of pertussis in infants are untypical,but the incidence of severe pertussis is high.Thus early diagnosis and timely treatment are necessary.

Effect of sulfur dioxide on endoplasmic reticulum stress protein expression in myocardial tissue of rats with left to right shunt / 中华实用儿科临床杂志

Objective To explore the possible role of sulfur dioxide (SO2) in endoplasmic reticulum stress (ERS) protein expression in myocardial tissue of rats with left to right shunt.Methods A total of 24 male Sprague Dawley rats were randomly divided into sham group(n =8),shunt group(n =8)and shunt plus SO2 donor group (n =8).The rats of shunt group and shunt plus SO2 donor group,an abdominal aorta and inferior vena cava shunting was created.Na2SO3/NaHSO3 was administrated intra-peritoneally in rats of shunt plus SO2 donor group.Eight weeks later,the ratio of quantity of pulmonary to quantity of system (Qp/Qs) was measured ; Heart weight/body weight (HW/BW) and right ventricle/left ventricle + ventricular septum [RV/(LV + SP)] were detected;Expressions of collagen type Ⅰ in right ventricle myocardial tissue was measured by enzyme linked immunosorbent assay (ELISA) ;High performance liquid chromatography was used to measure SO2 content in right ventricle myocardial tissue.Glucose regulated protein 78 (GRP78),c-jun N-terminal kinase(JNK) and phosphorylation-c-jun N-termina kinase(p-JNK) mRNA and protein expressions in RV myocardial tissue were detected by Western blot and real time-polymerase chain reaction(RT-PCR).Results After 8-weeks shunting,Qp/Qs in the shunt and shunt plus SO2 groups were higher significantly than those of the sham group(all P ＜ 0.05).Compared with sham group,HW/BW,RV/LV + SP and expressions of collagen type Ⅰ in the shunt group were significantly higher(all P ＜ 0.05).Treatment of SO2,HW/BW and RV/LV + SP and collagen type Ⅰ in the shunt group were lower significantly(all P ＜ 0.05).The level of SO2 of RV in shunt group increased significantly compared with sham group (all P ＜ O.05),but significantly lower than that of shunt plus SO2 donor group (P ＜ 0.05).Compared with sham group,the expressions of GRP78,JNK and p-JNK mRNA and protein in RV increased significantly in shunt group(P ＜ 0.05).After treatment with SO2,the expressions of GRP78,JNK and p-JNK mRNA and protein decreased significantly (P ＜ 0.05).Conclusion SO2 might protect RV myocardial tissue of the rats with left-right shunt by regulating the expressions of ERS.

Protective effect of anti-inflammatory peptides on LPS-induced acute lung injury of mouse / 中国小儿急救医学

Objective To explore the anti-inflammatory effect of antiflammin-2 (AF2) and recombinant peptide sequence 2(R2) on acute lung injury of mouse. To observe the expression of clara cell 16000 protein (CC16) and surfactant protein A (SP-A) in the lung of mouse inoculated with lipopolysaccharide (LPS) and the impact of AF2,R2,and glucocorticoids(hydrocortisone,HC) may have on the expression of the CC16 and SP-A in the lung of mice with acute lung injury. Methods Balb/c mice were inoculated with LPS (5 mg/kg) by intraperitoneal injection to set up ALI mice model. Mice weighed from 15 g to 16 g were grouped into control group, model group and treated groups respectively treated with AF2, R2 or HC. Mice in the control group were injected with physiological saline solution, while mice in the other four groups were inoculated with LPS to induce acute lung injury. Then animals in the treated groups were treated with AF2, R2 or HC each on a dose of 2 mg/kg also through intraperitoneal injection,while those of the control group and the model group, were given equivalent physiological saline solution as a placebo. The respiratory rate of all of these animals were recorded 6 hours after the injection. And at the time point of 12 hour,all the mice were sacrificed for a preparation of the whole lung tissue for the sake of a pathological investigation ,or for extractions of RNA for a semiquantitative analysis of the expression of CC16 and SP-A within the lungs. Results (1) An obvious attenuation of the respiratory rates of the three treated groups were observed when comparing with that of the mice in the model group without any anti-inflammatory treatment. (2) Remarkable extenuation of the extent of intra-alveolar and intersticial hemorrhage and infiltration of inflammatory cells were observed within the treated groups comparing with that of the model group. (3) An attenuate expressions of CC16 or SP-A were observed in the model group,while obvious uptrend of CC16 expression was observed in AF2 treated groups and increase of SP-A expressions were found in R2 and HC treated groups. Conclusion The anti-inflammatory effect of the peptide, AF-2 or R2, has been conformed on ALI mice model induced by LPS.

Adrenal dysfunction in rats with pulmonary acute lung injury / 临床儿科杂志

Objective To study the adrenal function in rats with pulmonary acute lung injury (ALI) induced by Escherichia coli (0111B4) . Methods ALI rat model was induced by intratracheal injection of E.coli (3 ml/kg,0111B4,(4.4-5.6) x 10~(12) CFU/L).ALI rats were then randomly divided into three groups,and each group had 10 rats.Mechanical ventilation was applied at three time points,6 hours,24 hours,and 36 hours after injection At each time point 8 rats were used as control with saline administered intratracheally.The plasma ACTH and corticosterone levels were measured after stimulated by 100 μg porcine ACTH.Results Compared with control group,the model group had a higher level of plasma ACTH at each time point (P < 0.01).The plasma ACTH level reached the peak at 24 hours.The model group had a higher level of plasma corticosterone at 6 hours (P < 0.01) and 24 hours (P <0.05),but had a lower level of plasma corticosterone at 36 hours (P < 0.05).The plasma corticosterone level reached the peak at 6 hours in model group,which was higher than 24 hours (P < 0.05).After stimulated by ACTH,the increased levels of corticosterone were lower in model group than those in control group (6 hours,P < 0.05; 24 hours and 36 hours,P < 0.01).Conclusions Adrenal dysfunction may occur at early stage of ALI in rats.With the disease developed,adrenal response to ACTH decreased.Low dose corticotrophin-stimulated test could evaluate adrenal function in rats with pulmonary ALI induced by Escherichia coli (O111B4).

The establishment of pulmonary acute lung injury model in rats / 中国小儿急救医学

Objective To establish pulmonary acute lung injury(ALI)model in rats.Methods ALI model was induced in rats by intratracheal Escherichia coli injection[3 ml/kg,O111B4,(4.0～6.0)×1012 CFU/L].Mechanical ventilation was applied 12,24,36,48 and 72 h after Escherichia coli injection,PaO_2/FiO_2 and dynamic compliance were recorded,and the normal control group was also subjected to mechanical ventilation.After the experiment,lungs were fixed with formalin to perform pathological examination.Results At 12,24,36,48 and 72 h,the PaO_2/FiO_2 were(30.71±7.95)kPa,(21.66±5.34)kPa,(21.09±4.75)kPa,(25.01±8.78)kPa and(33.82±8.02)kPa,respectively,which were significantly lower than that in the normal control group(63.82±3.03)kPa(P＜0.01).At 12,24,36,48 and 72 h,the Cdyn were(4.23±0.13)ml/(kg·kPa),(4.19±0.96)ml/(kg·kPa),(4.28±0.69)ml/(kg·kPa),(4.44±0.62)ml/(kg·kPa)and(4.58±0.35)ml/(kg·kPa)respectively,which were significantly lower than that in the normal control group(8.16±0.78)mL/(kg·kPa)(P＜0.01).At 12,24,36,48 and 72,the percentage of ALI was 71.4%,100.0%,100.0%,83.3%and 57.1%respectively,and the percentage of ARDS was 28.6%,85.7%,83.3%,66.7%,14.3%respectively.As for pathological examinations,predominance of alveolar collapse,fibrinous exudates,alveolar wall edema and neutrophil recruitment into the alveolar space was observed.Hyaline membrane formation was found.At 72 h,inflammation was relieved.Conclusion We successfully established pulmonary ALI/ARDS model in rats induced by intratracheal Escherichia coli injection,and acquired some useful information by observing the lung function and morphological changes at different time points.