The association of 25(OH)D, interleukin-4, interleukin-5, and interleukin-13 levels with the burden of soil-transmitted helminth infection in stunted children aged 24-59 months.

Soil-transmitted helminth (STH) among children aged 24-59 months is one cause of chronic infection that could lead to stunting. The association of 25(OH)D and immune responses during chronic infection in stunted populations has not yet been well established. An association study of case-control data was conducted in Bandung district from October 2019 to January 2023. Sociodemographic factors, stool samples, and serum levels of 25(OH)D, interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) were assessed. Statistical analysis was performed to evaluate the prevalence and association of 25(OH)D, IL-4, IL-5, and IL-13 with the burden of STH infection in stunted children. In total, 401 stunted children were recruited. A higher burden of STH infection was found for lower levels of IL-5 (r = -0.477; p = 0.004) and IL-13 (r = -0.433; p = 0.028). Thus, 25(OH)D, IL-4, IL-5, and IL-13 play a role in the burden of STH infection.

Surveillance of Soil-Transmitted Helminth Infection in Preschool Child Population: Do Changes in Behavior and Immunological Responses Affect Prevalence?

Soil-transmitted helminths (STHs) persist as a significant global public health issue among neglected tropical diseases (NTDs), particularly in children. STH infection can induce immune responses that affect the course of the disease; if treatment fails, chronic infection can lead to stunting, especially among children aged 24-59 months, which is a vulnerable period for growth and development. We conducted a correlational, cross-sectional data collection study to evaluate the characteristics and association of 25(OH)D, interleukin-5 (IL-5), and interleukin-13 (IL-13) with the prevalence of STH infection in children aged 24-59 months in Bandung District, Indonesia, in October 2019-January 2023. We recruited 694 subjects (401 stunted and 293 normal-height children). The prevalence of STH infection among the stunted and normal-height groups was 5.7% (95% CI: 3.85-8.46%) and 3.4% (95% CI; 1.86-6.17%) (p = 0.156), respectively. The probability of the prevalence of STH infection in children with levels of 25(OH)D, IL-5, and IL-13 below the cut-off point was 6,93 to 16.71 times higher. We found a relationship between IL-5, IL-13, and environmental factors and the prevalence of STH infection in stunted children.

A Meta-Analysis of Atrial Septal Defect Closure in Patients With Severe Pulmonary Hypertension: Is There a Room for Poking Holes Amid Debate?

Severe pulmonary arterial hypertension (PAH) associated with atrial septal defect (ASD) poses a challenge to a closure of ASD, particularly severe PAH that persists even after pharmacological therapeutic strategy. Our study was aimed to evaluate this matter. A systematic literature search from several databases was conducted up until August 1st, 2023. A meta-analysis was undertaken on studies that reported hemodynamic measurements in ASD patients with severe PAH before and after closure. The primary objectives were the extent of improvement in all hemodynamic parameters following closure, and the secondary outcomes were major adverse cardiac events (MACEs) during follow-up. Our study comprised 10 studies with a total of 207 participants. Patients were divided into treat-and-repair and straight-to-repair groups based on the therapeutic strategy. Meta-analysis of all studies demonstrated significant improvement in mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), pulmonary vascular resistance index (PVRI), 6-minutes walking distance (6MWD), and lower prevalence of World Health Organization functional classes (WHO fc), particularly in the treat-and-repair strategy subgroup. Additionally, merely 4 of the 156 individuals died from cardiac causes, and only 1 required rehospitalization, indicating a low likelihood of MACEs arising. Our new findings support the notion that effective shunt closure can improve various hemodynamic parameters in carefully chosen patients with noncorrectable ASD-PAH. Further large and prospective observational studies are still warranted to validate these findings.

Correlation Between Vitamin D Status and HBsAg Antibody Levels in Indonesian Adolescents Immunised Against Hepatitis B.

Introduction: Hepatitis B virus (HBV) infection is a global health problem. Anti-hepatitis B surface antigen (HBsAg) levels increase along with vitamin D levels in adults. However, few studies have examined this relationship in adolescents. Few studies have examined the relationship between vitamin D and HBsAg antibody levels, especially in Indonesia. Methods: This cross-sectional study examined vitamin D and anti-HBsAg levels before and after hepatitis B immunisation. All subjects blood was taken to check for vitamin D level. This study was part of the Safety and Preliminary of Immunogenicity Following Recombinant Hepatitis B (Bio Farma) Vaccine in Adults and Children Phase I trial. Results: This study found that 25-hydroxyvitamin D [25(OH)D] status was primarily deficient based on endocrine criteria. The children's hepatitis B antibody response was mostly <10 mIU/mL before and ≥10 mIU/mL after vaccination. There was a relationship between sex and 25(OH)D status, with median 25(OH)D levels higher in females (18.2 ng/mL) than in males (9.8 ng/mL). However, the relationship between vitamin 25(OH)D status and anti-HBsAg levels pre- and post-vaccination was not significant. Discussion: However, some research found that vitamin D supplementation after immunisation did not impact vaccine response, several studies have reported that vitamin D can decrease HBV replication through various mechanisms, including reducing viral transcription and interfering with viral protein synthesis. Conclusion: There was no relationship between 25(OH)D status and anti-HBsAg levels. Further research is needed to elucidate the underlying mechanisms and establish optimal treatment strategies.

The Association between Vitamin D, Interleukin-4, and Interleukin-10 Levels and CD23+ Expression with Bronchial Asthma in Stunted Children.

Children with stunted growth have an increased risk of wheezing, and studies have shown that low levels of vitamin D and interleukin (IL)-10, along with increased IL-4 levels and CD23+ expression, are present in stunted and asthmatic children. To date, it is not known whether these factors are related to the incidence of asthma in stunted children. This case-control study investigated the association between vitamin D, IL-4, and IL-10 levels and CD23+ expression with bronchial asthma in stunted children. The study included 99 children aged 24-59 months, i.e., 37 stunted-sthmatic children (cases), 38 stunted children without asthma, and 24 non-stunted children with asthma. All children were tested for their 25(OH)D levels using chemiluminescent immunoassay (CLIA), IL-4 and IL-10 levels were measured through enzyme-linked immunosorbent assay (ELISA) testing, and CD23+ expression was measured through flow cytometry bead testing. The data were analyzed using chi-squared, Kruskal-Wallis, and Mann-Whitney tests. The results showed that stunted asthmatic children had a higher incidence of atopic family members than those without asthma. Additionally, stunted asthmatic children had a higher prevalence of vitamin D deficiency (48.6%) than the control group (44.7% and 20.8%). Furthermore, stunted asthmatic children had significantly lower levels of 25(OH)D [20.55 (16.18-25.55), p = 0.042] and higher levels of IL-4 [1.41 (0.95-2.40), p = 0.038], although there were no significant differences in IL-10 levels and CD23+ expression. The study concluded that low vitamin D and high IL-4 levels are associated with bronchial asthma in stunted children, while IL-10 and CD23+ do not show a significant association.

Epigenetic Regulation Interplays with Endometriosis Pathogenesis in Low-Birth-Weight Patients via the Progesterone Receptor B-VEGF-DNMT1 Axis.

BACKGROUND: Low birth weight (LBW) is a risk factor associated with endometriosis. Our study aimed to analyze the risk of endometriosis in women with a LBW history and the relationships of progesterone receptor B (PR-B) gene promoter methylation, DNA methyltransferase-1 (DNMT1) expression, PR-B expression, and vascular endothelial growth factors (VEGF) with endometriosis. METHODS: This study was conducted in two stages, a retrospective case-control design and a cross-sectional design, with 52 cases of endometriosis and 30 controls, which were further subdivided into LBW and non-LBW groups, at Hasan Sadikin General Hospital and its hospital networks from October 2017 to August 2021. Menstrual blood was taken from subjects and analyzed using pyrosequencing techniques to assess DNA methylation, while q-RT PCR was used to assess gene expression. RESULTS: There were significant differences in PR-B methylation, DNMT1 expression, PR-B expression, and VEGF expression (p < 0.001) between the case and control groups. There was a significant negative correlation between PR-B methylation and PR-B expression (r = -0.558; p = 0.047). Based on a multiple logistic analysis, the most dominant factor affecting endometriosis incidence is PR-B (OR 10.40, 95% CI 3.24-33.4, R2 = 45.8). We found that patients with a low birth weight history had a 1.41-times-higher risk of developing endometriosis (95% CI 0.57-3.49, p = 0.113), although the relationship was not statistically significant. CONCLUSION: Endometriosis is associated with PR-B gene promoter hypermethylation, decreased PR-B expression, and increased DNMT1 and VEGF expression. The methylation of PR-B is the most dominant factor affecting endometriosis incidence.

The Chemoprotective Role of Vitamin D in Skin Cancer: A Systematic Review.

Introduction: Research in mice showed that vitamin D receptor deficiency was correlated with an increased rate of non-melanoma skin cancer. Therapeutic supplemental vitamin D has also been reported to reduce cell growth in both melanoma and non-melanoma skin cancer. This paper aims to describe the existing research studies that discuss the potential and role of vitamin D in the management of skin cancer. Methods: Articles were searched from three databases (PubMed, ScienceDirect, Scopus) and manual search. 18 articles were included. These were further divided into in vivo and in vitro studies. The literature search was based on the following Patients, Intervention, Control, and Outcome (PICO) criteria: Patients with any types of skin cancer; Vitamin D and their derivates as the intervention; placebo or standard regimen as control, and survival rate or response rate as primary outcome. Results: From the three databases, we obtained 802 studies. Prior to screening of the literature obtained, several studies were excluded. In the eligibility assessment, seven studies were excluded due to their outcomes being not eligible for analysis, and two studies were excluded due to inaccessible full texts. The remaining 18 studies were included. Five studies had a clinical research design (randomized controlled trial or interventional study), which use vitamin D3 as vitamin D derivatives and the results showed that the administration of vitamin D3 reduces the proliferation of skin cancer cells. Similar results were also reported in studies with pre-clinical research designs, either in vivo or in vitro, where six were in vivo studies and nine studies were in vitro studies. Conclusion: Our literature review revealed that that vitamin D derivatives, such as 1,25(OH)2D3 or 20(OH)D3 can effectively reduce the proliferation of skin cancer cells by contributing in the inhibition of cell growth and development, highlighting vitamin D's role as good prognostic factor.

Correlation between Cord Blood Vitamin D Levels and Problem-Solving Neurodevelopment in Early Childhood: A Cohort Study in Rural Indonesia.

Vitamin D influence on brain development and subsequent postnatal neurodevelopment remains controversial. We explored the correlation between cord blood vitamin D levels and longitudinal neurodevelopment in early childhood. A cohort study was conducted on term infants with no congenital abnormalities, born from pregnant women from a cohort study. Cord blood samples were collected to measure vitamin D. Neurodevelopment was examined three times in infants aged 6, 12 and 24 months using the Ages and Stages Questionnaire-3, which comprises 30 questions of five developmental domains: gross motor, fine motor, communication, problem-solving and social-personal. Statistical analysis was conducted with Spearman's rank correlation and multiple linear regression. Of the 141 babies born from previous cohort studies, only 116 participants were included. The mean level of cord blood vitamin D was 16.2 ng/mL. The percentage participants with vitamin D deficiency and insufficiency were 12.9 and 65.5, respectively. Cord blood vitamin D and the problem-solving domain for infant aged 12 and 24 months were correlated (r = 0.217 and 0.414, respectively). Multiple linear regression showed a decreased problem-solving domain score of 0.641 associated with decreased vitamin D levels. In conclusion, cord blood vitamin D levels correlated with infant neurodevelopmental status.

Stunting as a Risk Factor for Asthma: The Role of Vitamin D, Leptin, IL-4, and CD23.

Stunting, which results from chronic malnutrition, is common in children from low- and middle-income countries. Several studies have reported an association between obesity and asthma. However, only a handful of studies have identified stunting as a significant risk factor for wheezing, a symptom of asthma, although the underlying mechanism remains unclear. This article aimed to review possible mechanisms underlying asthma in stunted children. Overall, changes in diet or nutritional status and deficiencies in certain nutrients, such as vitamin D, can increase the risk of developing asthma. Vitamin D deficiency can cause linear growth disorders such as stunting in children, with lower levels of 25(OH)D found in underweight and stunted children. Stunted children show a decreased lean body mass, which affects lung growth and function. Low leptin levels during undernutrition cause a Th1-Th2 imbalance toward Th2, resulting in increased interleukin (IL)-4 cytokine production and total immunoglobulin E (IgE). Studies in stunted underweight children have also found an increase in the proportion of the total number of B cells with low-affinity IgE receptors (CD23+). CD23+ plays an important role in allergen presentation that is facilitated by IgE to T cells and strongly activates allergen-specific T cells and the secretion of Th2-driving cytokines. Stunted children present with low vitamin D and leptin levels, impaired lung growth, decreased lung function, and increased IL-4 and CD23+ levels. All of these factors may be considered consequential in asthma in stunted children.

Calcitriol potentially alters HeLa cell viability via inhibition of autophagy.

Objective: This study was conducted to evaluate the effect of Calcitriol on cellular death in HeLa cells via autophagy and turn over due to mitochondria homeostasis. Methods: HeLa cell lines were grown in 24-well plates and treated with Calcitriol at varying doses (0.013 µM-0.325 µM) for varying time periods (2, 6, 12, and 18 h). Cell proteins were extracted with scrapers and lysed using RIPA buffer. Western blots were performed for proteins involved with autophagy (Lc3, p62), signaling (mTOR, PI3K, HIF1α), mitochondria (PGC1α, COX4, and Tom 20), and apoptosis (Caspase 3, Caspase 9, and PARP). Protein carbonyl levels were determined by measuring the indirect ROS level. An inhibition study using L-mimosine was performed to analyze the significance of HIF1α. Results: Calcitriol treatment induced cytotoxicity in a dose- and time-dependent manner and caused growth arrest in HeLa cells. The PI3K-AKT-mTOR pathway was activated, leading to inhibition of autophagy and alterations in mitochondria biogenesis homeostasis. Treatment with Calcitriol produced protein carbonyl levels similar to those in the cisplatin-treated and control groups. Increased ROS levels may cause toxicity and induce cell death specifically in cancer cells but not in normal cells. The inhibition of HIF1α partially rescued the HeLa cells from the toxic effects of Calcitriol treatment. Conclusion: We suggest that Calcitriol may shut down mitochondrial homeostasis in HeLa cells by inducing the PI3K-AKT-mTOR pathway and inhibiting autophagy, which leads to cell death.

Exploring alternative cytokines as potential biomarkers for latent tuberculosis infection in pregnant women.

BACKGROUND: Interferon gamma release assays (IGRAs) are widely used to determine latent tuberculosis infection status. However, its pregnancy-affected performance and cost-expensive nature warrants for different alternatives for pregnant women. This study aims to evaluate the diagnostic performance of several alternative cytokines, including interleukin 2 (IL-2), interleukin 10 (IL-10), and interferon gamma-induced protein 10 (IP-10) to identify latent tuberculosis status in pregnant women. MATERIALS AND METHODS: 123 pregnant womens were recruited for this study. The IGRA status was determined by using QuantiFERON Gold In-Tube. Meanwhile, we measured the level IL-2, IL-10, and IP-10 by using sandwich-microELISA method. We performed normality and comparison test by SPSS. In addition, receiver-operator characteristic (ROC) analyses and the optimal cutoff scores were identified using the EasyROC webtool. RESULTS: We showed that IL-2, IL-10, and IP-10 were able to discriminate between IGRA-negative and IGRA-positive pregnant women. Moreover, IP-10 showed the highest discriminatory and diagnostic performance when compared to IL-2 and IL-10 with area under the curve (AUC) of 0.96 and cutoff point of 649.65 pg/mL. CONCLUSIONS: Our study showed that IP-10 can be considered as a promising alternative biomarker for IGRAs to diagnose LTBI in pregnant women.

Calcitriol Inhibits Proliferation and Potentially Induces Apoptosis in B16-F10 Cells.

BACKGROUND Melanoma is one of the most aggressive types of cancer and it has shown a remarkable surge in incidence during the last 50 years. Melanoma has been projected to be continuously rising in the future. Therapy for advanced-type melanoma is still a challenge due to the low response rate and poor 10-year survival. Interestingly, several epidemiological and preclinical studies had reported that vitamin D deficiency was associated with disease progression in several cancer types. In vivo and in vitro studies revealed anti-proliferative, anti-angiogenic, apoptosis, and differentiation induction effects of calcitriol in various cancers. However, information on the effects of calcitriol (1,25(OH)2D3) on melanoma is still limited, and its mechanism remains unclear. MATERIAL AND METHODS In the present study, by utilizing B16-F10 cells, which is a melanoma cell line, we explored the anti-proliferative effect of calcitriol using cell viability assay, near-infrared imaging, expression of apoptosis-related genes using real-time polymerase chain reactions (PCR), and the expression of apoptosis proteins levels using western blot. In addition, we also assessed calcitriol uptake by B16-F10 cells using high-performance liquid chromatography (HPLC). RESULTS We found that calcitriol inhibits melanoma cell proliferation with an IC50 of 93.88 ppm (0.24 µM), as shown by cell viability assay. Additionally, we showed that B16-F10 cells are capable of calcitriol uptake, with a peak uptake time at 60 min after administration. Calcitriol was also able to induce apoptosis-related proteins such as caspase-3, caspase 8, and caspase-9. These effects of calcitriol reflect its potential utility as a potent adjuvant therapy for melanoma. CONCLUSIONS Calcitriol inhibits cell proliferation and induces apoptosis in B16-F10 cells.

Comparison of clinical presentation and outcome of childhood-onset and adulthood-onset of systemic lupus erythematosus among Indonesian patients.

INTRODUCTION: The clinical presentation of childhood-onset systemic lupus erythematosus (SLE) is generally perceived to differ from that of adult-onset SLE. OBJECTIVE: We aimed to compare the demographic and clinical manifestation between childhood-onset vs. adult-onset SLE in a cohort of Indonesian patients at tertiary care centers. METHODS: This retrospective study included patients in the Hasan Sadikin Lupus Registry from 2008 until December 2017. The demographics, clinical presentations, and outcomes were compared between childhood-onset SLE (<18 years old) (Group 1) and adult-onset SLE (≥18 years old) (Group 2). RESULTS: Eight hundred seventy patients were involved into this study. The proportion of childhood-onset SLE was 20% (174 patients). The mean age of group 1 versus group 2 was 13.56 ± 3.04 vs 30.41 ± 8.54 years. The following clinical manifestations at SLE diagnosis were significantly more common in childhood-onset than in adult-onset SLE patients: hematological disorder (p = 0.033) and arthritis (p = 0.006). While discoid rash (p = 0.036) and photosensitivity (p < 0.001) were significantly found higher in adult-onset SLE. Cyclophosphamide therapy was significantly more common to be used in childhood-onset (38.5% vs 21.0%, p = <0.001). However, frequency of mortality on follow-up tended to be higher in childhood-onset group (11.5% vs 7.0%, p = 0.208). CONCLUSION: Arthritis and hematologic involvements at SLE diagnosis were more prominent in childhood-onset compared to adult-onset patients, and mortality in childhood-onset SLE during follow-up relatively higher. This data may suggest the need for more aggressive management approach to childhood-onset patients with SLE.

Low serum 25-hydroxyvitamin D (vitamin D) level among children with ventricular septal defect: how big is the risk for pulmonary hypertension?

INTRODUCTION: Ventricular septal defect is the most common CHD, leading to pulmonary hypertension. Significantly lower 25-hydroxyvitamin D level was reported in children with CHD compared with healthy controls. The current study aimed to investigate the correlation between 25-hydroxyvitamin D level and pulmonary hypertension in children with ventricular septal defect. METHODS: A cross-sectional study was conducted on ventricular septal defect paediatric patients from January to June, 2019. Serum 25-hydroxyvitamin D was measured using electrochemiluminescence. Pulmonary hypertension was defined as mean pulmonary artery systolic pressure > 20 mmHg for children >3 months of age at sea level, measured by Doppler echocardiography. RESULTS: From forty-four subjects, the majority of the subjects were female (56.8%) with normal nutritional status and perimembranous ventricular septal defect. Bivariate analysis showed that 25-hydroxyvitamin D level was associated with pulmonary hypertension (p < 0.01), type and size of ventricular septal defect (p = 0.02), and heart failure (p < 0.01). Higher 25-hydroxyvitamin D level was correlated with better nutritional status (p = 0.04, r = 0.26), and lower 25-hydroxyvitamin D level was correlated with the occurence of perimembranous ventricular septal defect (p = 0.01, r = -0.39), larger defect size (p < 0.01, r = -0.70), history of pneumonia (p = 0.02, r = -0.31), and heart failure (p < 0.01, r = -0.64). Subjects with 25-hydroxyvitamin D deficiency had prevalence ratio of 24.0 times for pulmonary hypertension. Higher pulmonary artery pressure was correlated to the occurence perimembranous ventricular septal defect (p = 0.01, r = 0.47), larger defect size (p < 0.01, r = 0.78), history of pneumonia (p = 0.01, r = 0.38), and heart failure (p < 0.01, r = 0.75). CONCLUSION: Children with ventricular septal defect who had low 25-hydroxyvitamin D level posed a higher risk of having pulmonary hypertension.

Corrigendum: Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.3389/fnut.2021.660420.].

Vitamin D Inhibits Lipopolysaccharide (LPS)-Induced Inflammation in A549 Cells by Downregulating Inflammatory Cytokines.

BACKGROUND Studies have shown that lung inflammation affects lung function, with life-threatening results. Vitamin D may play an important role in inhibiting inflammatory cytokines. Vitamin D deficiency is related to several lung problems, including respiratory distress syndrome, alveolar inflammation, epithelial damage, and hypoxia. Few studies have evaluated the benefits of vitamin D in preventing inflammation in alveolar cells. MATERIAL AND METHODS We developed a cell inflammation model induced by lipopolysaccharide (LPS) treatment. The effects of vitamin D on LPS-induced inflammation in A549 cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the anti-inflammatory mechanism of vitamin D was evaluated using western blot analysis. RESULTS Our results indicated that vitamin D promoted A549 cell survival following LPS-induced inflammation by downregulating nuclear factor nuclear factor kappa light chain enhancer of activated B cells, tumor necrosis factor-alpha, interleukin (IL)-1ß, IL-6, and IL-12. CONCLUSIONS Our results indicated that vitamin D has the potential to manage lung inflammation, although further studies are needed.

Strategies and Future Opportunities for the Prevention, Diagnosis, and Management of Cow Milk Allergy.

The prevalence of food allergy has increased over the last 20-30 years, including cow milk allergy (CMA) which is one of the most common causes of infant food allergy. International allergy experts met in 2019 to discuss broad topics in allergy prevention and management of CMA including current challenges and future opportunities. The highlights of the meeting combined with recently published developments are presented here. Primary prevention of CMA should start from pre-pregnancy with a focus on a healthy lifestyle and food diversity to ensure adequate transfer of inhibitory IgG- allergen immune complexes across the placenta especially in mothers with a history of allergic diseases and planned c-section delivery. For non-breastfed infants, there is controversy about the preventive role of partially hydrolyzed formulae (pHF) despite some evidence of health economic benefits among those with a family history of allergy. Clinical management of CMA consists of secondary prevention with a focus on the development of early oral tolerance. The use of extensive Hydrolysate Formulae (eHF) is the nutrition of choice for the majority of non-breastfed infants with CMA; potentially with pre-, probiotics and LCPUFA to support early oral tolerance induction. Future opportunities are, among others, pre- and probiotics supplementation for mothers and high-risk infants for the primary prevention of CMA. A controlled prospective study implementing a step-down milk formulae ladder with various degrees of hydrolysate is proposed for food challenges and early development of oral tolerance. This provides a more precise gradation of milk protein exposure than those currently recommended.

Growth Patterns of Indonesian Infants with Cow's Milk Allergy and Fed with Soy-Based Infant Formula.

PURPOSE: The use of soy-based infant formula has increased widely in infants with cow's milk allergy (CMA). This study aimed to provide evidence on the growth pattern of CMA infants fed with soy-based infant formula in an Indonesian setting. METHODS: A multi-site, intervention study was conducted among full-term and normal birth weight CMA infants. Within six months, the subjects were provided with a soy-based infant formula. Weight, height, and head circumference were measured at baseline, weeks 4, 8, 12, 16, 20, and 24. Adverse events were recorded by scoring atopic dermatitis and symptom-based clinical scores. RESULTS: Based on the World Health Organization growth chart, we found that most of subjects had normal nutritional status for weight-for-age, length-for-age, weight-for-length, and head-circumference-for-age. There were statistically significant differences between baseline and end-line for weight-for-age, length-for-age, weight-for-length, and head circumference-for-age nutritional status. No allergic symptoms or intolerance toward soy formula were observed at the end of the intervention period. CONCLUSION: These results show that infants fed with soy-based infant formula have a normal pattern of growth.

Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis.

Background: This systematic review and meta-analysis aimed to assess whether low serum 25-hydroxyvitamin D (25-OHD) level is associated with susceptibility to COVID-19, severity, and mortality related to COVID-19. Methods: Systematic literature searches of PubMed, Scopus, and Embase database up until 9 December 2020. We include published observational prospective and retrospective studies with information on 25-OHD that reported main/secondary outcome. Low serum 25-OHD refers to participants with serum 25-OHD level below a cut-off point ranging from 20 to 30 ng/mL. Other cut-off values were excluded to reduce heterogeneity. The main outcome was mortality defined as non-survivor/death. The secondary outcome was susceptibility and severe COVID-19. Results: There were 14 studies comprising of 999,179 participants. Low serum 25-OHD was associated with higher rate of COVID-19 infection compared to the control group (OR = 2.71 [1.72, 4.29], p < 0.001; I 2: 92.6%). Higher rate of severe COVID-19 was observed in patients with low serum 25-OHD (OR = 1.90 [1.24, 2.93], p = 0.003; I 2: 55.3%), with a sensitivity of 83%, specificity of 39%, PLR of 1.4, NLR of 0.43, and DOR of 3. Low serum 25-OHD was associated with higher mortality (OR = 3.08 [1.35, 7.00], p = 0.011; I 2: 80.3%), with a sensitivity of 85%, specificity of 35%, PLR of 1.3, NLR of 0.44, and DOR of 3. Meta-regression analysis showed that the association between low serum 25-OHD and mortality was affected by male gender (OR = 1.22 [1.08, 1.39], p = 0.002), diabetes (OR = 0.88 [0.79, 0.98], p = 0.019). Conclusion: Low serum 25-OHD level was associated with COVID-19 infection, severe presentation, and mortality.

First Trimester Ferritin Is Superior over Soluble Transferrin Receptor and Hepcidin in Predicting Anemia in the Third Trimester: Result from a Cohort Study in Indonesia.

INTRODUCTION: Anemia in the third trimester has been identified as a risk factor for maternal and fetal morbidity that might lead to mortality. Due to its high cost, finding the best marker to predict anemia became more important to allow early prevention. Only one of ferritin, hepcidin, or soluble transferrin receptors can be picked for the prediction of anemia in the third trimester especially in low-resource setting. OBJECTIVE: This study aimed at defining the best marker among ferritin, hepcidin, or soluble transferrin receptor (sTfR) in the first trimester for prediction of anemia in the third trimester. Materials, Methods, and Setting. This diagnostic study was nested on the cohort study of vitamin D and its impact during pregnancy in Indonesia. Singleton pregnant mothers with normal fetus were recruited in the first trimester from four cities in West Java, Indonesia. The 304 pregnant women were screened for hepcidin, ferritin, and sTfR level in the sera. All biomarkers were measured by ELISA. Complete blood count (CBC) was done by impedance method measurement (SysmexR). Only subjects with complete data were included in analysis for diagnostic study to compare the three markers by finding the best receiver operating curve (RoC), likelihood ratio (LR), and risk estimate (RR). RESULT: One-hundred and eighty-one pregnant women were eligible for analysis. The result of this study showed that the serum ferritin level in the first trimester was the best marker to predict anemia in the third trimester of pregnancy. Hepcidin and sTfR performed poorly. A new cutoff point of ferritin level ≤27.23 ng/ml yielded the best ROC with 67% area under curve (95% CI 60%-75%, p < 0.0001, Youden index J 0.28), specificity 86.29% (95% CI 79.0%-91.8%), LR (+) 3.07 (95% CI 1.8-5.3), and RR 2.48 (95% CI 1.67-3.68). These last figures were better than the previously used cutoff point of ferritin level below 30 ng/ml. CONCLUSION: This study provided evidence that the serum ferritin level ≤27.23 ng/ml in the first trimester was the best marker to predict anemia in the third trimester. It was valuably useful for secondary screening of anemia in pregnancy, targeting subjects who may need rigorous approach for iron deficiency treatment in the prevention of anemia in pregnancy.