Susceptible Infants Research Articles

Acoustofluidic-based therapeutic apheresis system

Therapeutic apheresis aims to selectively remove pathogenic substances, such as antibodies that trigger various symptoms and diseases. Unfortunately, current apheresis devices cannot handle small blood volumes in infants or small animals, hindering the testing of animal model advancements. This limitation restricts our ability to provide treatment options for particularly susceptible infants and children with limited therapeutic alternatives. Here, we report our solution to these challenges through an acoustofluidic-based therapeutic apheresis system designed for processing small blood volumes. Our design integrates an acoustofluidic device with a fluidic stabilizer array on a chip, separating blood components from minimal extracorporeal volumes. We carried out plasma apheresis in mouse models, each with a blood volume of just 280 μL. Additionally, we achieved successful plasmapheresis in a sensitized mouse, significantly lowering preformed donor-specific antibodies and enabling desensitization in a transplantation model. Our system offers a new solution for small-sized subjects, filling a critical gap in existing technologies and providing potential benefits for a wide range of patients.

Correlation of vitamin A levels in umbilical cord blood with neonatal pulmonary diseases

ObjectiveTo study the relationship between umbilical cord blood vitamin A (VA) and neonatal lung diseases and explore the impact of umbilical cord blood VA on neonatal lung diseases. MethodUmbilical vein blood was collected at birth, and its VA content was measured. According to the VA levels in umbilical cord blood, a VA deficiency (VAD) group, a marginal deficiency group and a normal group were created and followed up until 28 days after birth. ResultsThe umbilical cord blood VA level in the neonatal group with lung disease was 0.13 ± 0.05 mg/L, while the result for the VA level in the non-lung disease group was 0.15 ± 0.05 mg/L. The umbilical cord blood VA levels in the neonatal lung disease group were significantly lower than those in the non-lung disease group. The incidence of neonatal pulmonary diseases was highest in the VAD group, and the incidence decreased as the level of VA in umbilical cord blood increased. Umbilical cord blood VAD and premature birth were found to be independent risk factors for neonatal respiratory disease. ConclusionUmbilical cord blood VAD and premature birth are independent risk factors for neonatal pulmonary diseases. The lower the level of VA in umbilical cord blood, the more susceptible infants will be to neonatal respiratory infections in the neonatal period.

Age Structured Deterministic Model of Diphtheria Infection

Age-structured mathematical model of diphtheria infection has been formulated with specific epidemiological classes such as S1, susceptible infant at time t (0-1years), S2, susceptible school children population at time t, V, vaccination population at time t, E, exposed population at time t, I1, asymptomatic infection population at time t, I2, symptomatic infection population at time t, ID, detected infectious humans at time t (asymptomatic and symptomatic) population through testing, R, recovered population at time t. It was established through theorems and proofs that the model is epidemiologically meaningful, and that all its state variables are positive (non-negative) at time t>0 in the domain ℘, and that the domain ℘ is indeed bounded. Using the next generation matrix, the reproduction ratio Rb of the system was determined. Using dynamical system theory, it was established that the system is locally stable. A matrix-theoretic method was used in the construction of an appropriate Lyapunov function for the global stability analysis of the formulated model, and also established that the system is globally asymptotically stable if Rb≤1 and unstable otherwise.

Disparities in the impact of heat wave definitions on emergency department visits during the first year of life among preterm and full-term infants in California

IntroductionHeat waves will be aggravated due to climate change, making this a critical public health threat. However, heat wave definitions to activate alert systems can be ambiguous, highlighting the need to assess a range of definitions to identify those that contribute to the most adverse health outcomes. Additionally, children are highly susceptible to the impacts of heat waves, especially infants, despite the lack of focus on this subpopulation. We aimed to assess the relationship between 30 heat wave definitions and the first all-cause emergency department (ED) visits for California infants. We also examined modification of this relationship by preterm birth status and demographic characteristics to identify possible health disparities. MethodsLive-born, singleton deliveries from the Study of Outcomes in Mothers and Infants born in 2014–2018 were included. Thirty heat wave definitions were assessed based on temperature metrics (minimum/maximum temperatures), thresholds (90th; 92.5th; 95th; 97.5th; 99th percentiles), and duration (1-; 2-; 3-days). A time-stratified case-crossover design assessed heat wave impacts on ED visits using infants with a warm season ED visit (May–October) within the first year of life (n = 228,250). Effect modification by preterm birth status, age, sex, race/ethnicity, education, and delivery payment type was also investigated. ResultsInfants demonstrated increased risk of an ED visit with exposure to all heat definitions. The 3-day minimum temperature 99th percentile definition had the highest adjusted odds ratio (AOR: 1.14; 95% CI: 1.05–1.23) for the total population. Term infants were more affected by some heat waves than preterm infants. Effect modification was additionally identified, such as by maternal education. DiscussionThis study provides insight on the heat wave definitions that lead to adverse health outcomes and the identification of the most susceptible infants to these impacts, which has implications on heat-related interventions.

A highly sensitive nanobody-based ELISA for bovine β-lactoglobulin to classified donated human milk destined to susceptible newborns

The β-lactoglobulin protein from cow's milk is a common allergen present in human milk that leads to serious allergic reactions in susceptible infants. This creates a serious safety issue in Human Milk Banks, and the best practice to assure the safety of susceptible newborns would be to classify the donated human milk according to its content of β-lactoglobulin. To provide a simple and fast assay to detect this molecule in human milk we developed a nanobody-based sandwich ELISA. The capture and detection nanobodies were isolated by phage display from a llama immunized with the antigen using a sequential selection strategy for antibody pair identification. This allowed to attain a highly sensitive test with a limit of quantitation of 40 pg/mL and extended lineal range of up to 3000 pg/mL, showing an excellent performance with human milk. For these characteristics, the ELISA developed might be useful for the classification of donated human milk according to their β-lactoglobulin content, improving the quality of milk destined to susceptible newborns.

Whole-exome sequencing analysis identifies novel variants associated with Kawasaki disease susceptibility

BackgroundKawasaki disease (KD) is an acute pediatric vasculitis affecting genetically susceptible infants and children. Although the pathogenesis of KD remains unclear, growing evidence links genetic susceptibility to the disease.MethodsTo explore the genes associated with susceptibility in KD, we applied whole-exome sequencing to KD and control subjects from Yunnan province, China. We conducted association study analysis on the two groups.ResultsIn this study, we successfully identified 11 significant rare variants in two genes (MYH14 and RBP3) through the genotype/allele frequency analysis. A heterozygous variant (c.2650G > A, p.V884M) of the RBP3 gene was identified in 12 KD cases, while eight heterozygous variants (c.566G > A, p.R189H; c.1109 C > T, p.S370L; c.3917T > G, p.L1306R; c.4301G > A, p.R1434Q; c.5026 C > T, p.R1676W; c.5329 C > T, p.R1777C; c.5393 C > A, p.A1798D and c.5476 C > T, p.R1826C) of the MYH14 gene were identified in 8 KD cases respectively.ConclusionThis study suggested that nine variants in MYH14 and RBP3 gene may be associated with KD susceptibility in the population from Yunnan province.

Impact of Protein Binding Capacity and Daily Dosage of a Drug on Total Serum Bilirubin Levels in Susceptible Infants.

Hyperbilirubinemia is a common pathological condition in neonates. Free bilirubin can penetrate the blood-brain barrier (BBB), which can lead to bilirubin neurotoxicity. In the context of predicting the risk of bilirubin neurotoxicity, although the specificity and sensitivity of free bilirubin levels are higher than those of total serum bilirubin (TSB), free bilirubin is not widely monitored in clinical practice. The threshold TSB levels at which phototherapy must be administered have been established previously. However, TSB levels are not well correlated with neurodevelopmental outcomes. Currently, TSB levels are commonly used to guide phototherapy for neonatal hyperbilirubinemia. Some clinical drugs can displace bilirubin from its albumin-binding sites, and consequently upregulate plasma bilirubin. Daily dosages play a vital role in regulating bilirubin levels. A drug with both a high protein binding capacity and high daily dosage significantly increases bilirubin levels in infants. Premature or very low birth weight (VLBW) infants are vulnerable to the upregulation of bilirubin levels as they exhibit the lowest reserve albumin levels and consequently the highest bilirubin toxicity index. Because bilirubin is involved in maintaining the balance between pro-oxidant and antioxidant agents, the downregulation of bilirubin levels is not always desirable. This review provides insights into the impact of protein binding capacity and daily dosage of drugs on the bilirubin levels in susceptible infants.

Cronobacter Species in the Built Food Production Environment: A Review on Persistence, Pathogenicity, Regulation and Detection Methods.

The powdered formula market is large and growing, with sales and manufacturing increasing by 120% between 2012 and 2021. With this growing market, there must come an increasing emphasis on maintaining a high standard of hygiene to ensure a safe product. In particular, Cronobacter species pose a risk to public health through their potential to cause severe illness in susceptible infants who consume contaminated powdered infant formula (PIF). Assessment of this risk is dependent on determining prevalence in PIF-producing factories, which can be challenging to measure with the heterogeneity observed in the design of built process facilities. There is also a potential risk of bacterial growth occurring during rehydration, given the observed persistence of Cronobacter in desiccated conditions. In addition, novel detection methods are emerging to effectively track and monitor Cronobacter species across the food chain. This review will explore the different vehicles that lead to Cronobacter species' environmental persistence in the food production environment, as well as their pathogenicity, detection methods and the regulatory framework surrounding PIF manufacturing that ensures a safe product for the global consumer.

Hemangioma-related gene polymorphisms in the pathogenesis of intraventricular hemorrhage in preterm infants

PurposeThe aim of this study was to evaluate the possible relationship between four single nucleotide polymorphisms of hemangioma-linked genes encoding for anthrax toxin receptor 1 (ANTXR1 G976A), R kinase insert domain receptor (KDR T1444C), adrenoceptor beta 2 (ADRB C79CG), and insulin-like growth factor 1 receptor (IGF-1R G3174A) and the occurrence of IVH in a population of preterm infants.MethodsThe study includes a population of 105 infants born from 24 + 0 to 32 + 0 weeks of gestation and hospitalized at the Department of Neonatology (III level hospital) of Poznan University of Medical Science. Intraventricular hemorrhage was diagnosed with the use of cranial ultrasound. The classification of intraventricular bleeding was based on the Papile IVH classification.ResultsThe incidence of IVH was higher in infants with lower birth weight, lower APGAR scores, and low birth weight. The study revealed that IVH was approximately two times less likely to occur in infants with the allele G of IGF-1R 3174G > A.ConclusionIdentifying susceptible premature infants through genetic analysis could be a potential way to alleviate severe IVH and its subsequent consequences. Further research examining a wider range of relevant gene polymorphisms could help highlight any genetic patterns in this deleterious bleeding complication.

MANIFESTATION OF MATERNAL VAGINAL COLONIZATION OF GROUP B STREPTOCOCCUS IN PRETERM PREMATURE RUPTURE OF MEMBRANES

Objectives: To look at the manifestation of maternal vaginal colonization of Group B Streptococcus in pre-term premature rupture of membranes.Methods and materials: This cross sectional study was conducted at Department of Obstetrics and Gynecology, Lady Reading Hospital, Peshawar from November 02 ,2020 to May 02, 2021. By using chi square test, Group B streptococcus (GBS ) was stratifi ed among age, gravidy, parity, BMI and booking status to see the eff ect modifi cation value ≤ 0.05 was taken as significant. Those co comorbidities that aff ect the results were excluded. All data was entered, processed, and analyzed on SPSS version 21.0.Results: Out of total 126 patients, mostly in 15-25 Years of age [04(3.17%),P value,0.889] were reported as compare to 26-35 Years of age 03(2.38%) and 0.79% years among 36-45 Years. Simailrly the frequency of Group B streptococcus (GBS) was prevalent among 15-20 kg/m2 category [04(3.17%),P value,0.083] as compare to 21-25 kg/m2 02(01.58%) and 26-30 kg/m2 having 02(01.58%)Conclusion: The gastrointentinal and vaginal epithelium of healthy women colonized by Group B Streptococcus(GBS) pose a greater risk of serious pathologies in the susceptible infant by a transmission during parturition or ascending intrauterine infection. The incidence of early-onset GBS sepsis has decreased as a result of universal screening and intra partum antibiotic prophylaxis.

"Impact of a Drug on Total Serum Bilirubin Levels in Susceptible Infants"

Zon-Min Lee1, Ling-Sai Chang2* and Hong-Ren Yu3 Author Affiliations 1Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Taiwan 2Kawasaki Disease Center and Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Taiwan 3Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Taiwan Received: June 11, 2022 | Published: June 21, 2022 Corresponding author: Ling-Sai Chang, Kawasaki Disease Center and Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Taiwan DOI: 10.26717/BJSTR.2022.44.007086

Measles susceptibility in maternal-infant dyads—Bamako, Mali

Measles is endemic in Africa; measles mortality is highest among infants. Infant measles antibody titer at birth is related to maternal immune status. Older mothers are likelier to have had measles infection, which provides higher antibody titers than vaccine-induced immunity. We investigated the relationship between maternal age and measles susceptibility in mother-infant pairs in Mali through six months of infancy.We measured serum measles antibodies in 340 mother-infant pairs by plaque reduction neutralization test (PRNT) and calculated the proportion of mothers with protective titers (>120 mIU/mL) at delivery and the proportion of infants with protective titers at birth, and at three and six months of age. We explored associations between maternal age and measles antibodies in mothers and infants at the timepoints noted.Ten percent of Malian newborns were susceptible to measles; by six months nearly all were. Maternal and infant antibody titers were highly correlated. At delivery, 11% of mothers and 10% of newborns were susceptible to measles. By three and six months, infant susceptibility increased to 72% and 98%, respectively. Infants born to younger mothers were most susceptible at birth and three months. Time to susceptibility was 6.6 weeks in infants born to mothers with measles titer >120–<430 mIU/mL versus 15.4 weeks when mothers had titers ≥430 mIU/mL.Maternal and newborn seroprotective status were positively correlated. Improved strategies are needed to protect susceptible infants from measles infection and death. Increasing measles immunization coverage in vaccine eligible populations, including nonimmune reproductive-aged women and older children should be considered.

Identification of rare coding variants associated with Kawasaki disease by whole exome sequencing.

Kawasaki disease (KD) is an acute pediatric vasculitis that affects genetically susceptible infants and children. To identify coding variants that influence susceptibility to KD, we conducted whole exome sequencing of 159 patients with KD and 902 controls, and performed a replication study in an independent 586 cases and 732 controls. We identified five rare coding variants in five genes (FCRLA, PTGER4, IL17F, CARD11, and SIGLEC10) associated with KD (odds ratio [OR], 1.18 to 4.41; p = 0.0027–0.031). We also performed association analysis in 26 KD patients with coronary artery aneurysms (CAAs; diameter > 5 mm) and 124 patients without CAAs (diameter < 3 mm), and identified another five rare coding variants in five genes (FGFR4, IL31RA, FNDC1, MMP8, and FOXN1), which may be associated with CAA (OR, 3.89 to 37.3; p = 0.0058–0.0261). These results provide insights into new candidate genes and genetic variants potentially involved in the development of KD and CAA.

The Brainstem-Informed Autism Framework: Early Life Neurobehavioral Markers.

Autism spectrum disorders (ASD) have long-term implications on functioning at multiple levels. In this perspective, we offer a brainstem-informed autism framework (BIAF) that traces the protracted neurobehavioral manifestations of ASD to early life brainstem dysfunctions. Early life brainstem-mediated markers involving functions of autonomic/arousal regulation, sleep-wake homeostasis, and sensorimotor integration are delineated. Their possible contributions to the early identification of susceptible infants are discussed. We suggest that the BIAF expands our multidimensional understanding of ASD by focusing on the early involvement of brainstem systems. Importantly, we propose an integrated BIAF screener that brings about the prospect of a sensitive and reliable early life diagnostic scheme for weighing the risk for ASD. The BIAF screener could provide clinicians substantial gains in the future and may carve customized interventions long before the current DSM ASD phenotype is manifested using dyadic co-regulation of brainstem-informed autism markers.

Influencing factors and necessity of post-vaccination serologic testing follow-up for HBsAg-positive mothers and their infants: A 5-year prospective study in Zhejiang Province, China (2016-2020).

In 2016, China officially proposed for the first time that infants born to HBsAg-positive mothers should be tested for HBsAg and anti-HBs 1-2months after their third dose of HepB, also known as the post-vaccination serological testing programme. This study aimed to systematically evaluate the implementation and influencing factors of PVST to further reduce HBV infection risk in infants and improve the protective effect of HepB to the greatest extent. A prospective observational study was conducted to investigate the interruption of MTCT of hepatitis B. Univariate and multivariate analyses were applied to explore factors associated with the PVST follow-up rate among HBsAg-positive mothers and their infants. Additionally, bivariate analysis was performed on HBsAg and anti-HBs results in infants born to HBsAg-positive mothers. Here, the participation rate of PVST was 67.08% among 2120 pairs of positive mothers and infants. The HBsAg-positive rate among participants was 0.77%, whereas the anti-HBs positive rate was 96.84%, and both negative rates were 2.39%. Among infants with double negative results (34), only 15 completed three doses of HepB and PVST again, and 14 (93.33%) of which the antibody test results turned positive. Older mothers with high educational levels who reside in the local area were the most likely to PVST follow-up. The PVST programme is necessary to evaluate the HepB response status of newborns after vaccination. Moreover, revaccination for susceptible infants can effectively improve the MTCT-blocking rate of hepatitis B. Therefore, the scope of PVST projects in Zhejiang and China should be expanded.

Lipid peroxidation products as predictors of oxidant-mediated disease in preterm infants

Background Preterm infants are susceptible to “oxygen radical diseases” (ORD). 8-isoprostane (8-IP) is a bioactive eicosanoid generated by reactive oxygen species-catalyzed peroxidation of arachidonic acid. Malondialdehyde (MDA) is generated by the decomposition of oxidant-induced lipid hydroperoxides. We hypothesize that the development of ORD is associated with elevated plasma 8-IP on day 0–1, and increasing urine levels of MDA in the first month. Methods Preterm (<32 weeks, n = 39) and term (n = 39) infants were recruited at birth. Plasma 8-IP was quantified by ELISA on day 0–1, and urine MDA by colorimetric assay of thiobarbituric acid reactive substances (TBARS) on days 0–1, 7, 14, 21, and 28. ORD was defined as retinopathy of prematurity ≥ stage 1, pneumatosis, or oxygen requirement at 36 weeks corrected gestational age. Results Plasma 8-IP was higher on day 0–1 in preterm infants who developed ORD compared to term infants. Urine TBARS levels increased in preterm infants from day 0–1 to day 28 but were not different in infants with or without ORD. Preterm infants who developed ORD demonstrated a significant rise in urine TBARS levels from day 1 to 14. Conclusions Elevated plasma 8-IP on day 1 is associated with ORD in preterm infants. If validated as a biomarker for ORD, it may be useful in directing antioxidant therapies to the most susceptible infants. Urine TBARS during the first month are not significantly different in term infants, preterm infants with ORD, and preterm infants without ORD, but rapid rise of TBARS in the first 2 weeks may be associated with ORD.

Examining the role of socioeconomic status and temperament in the hair cortisol levels of infants.

Socioeconomic status (SES) appears to be an important contextual factor in children's developmental outcomes, including their responses to stress. However, some children are more susceptible to its effects than others. Hair cortisol is a newer method of assessing the activity of the HPA axis, providing cumulative cortisol levels. The present article examined whether temperament (negative emotionality) moderates the association between an SES index and the hair cortisol concentration (HCC) of infants. Sixty infants from 6 to 15months of age were recruited, of which 49 had sufficient hair for cortisol analysis. The SES index was calculated from the education levels of the mothers, family income, and a scale measuring the quality of the home environment. Negative emotionality was measured with the three sub-scales of the Infant Behavior Questionnaire (falling reactivity, distress to limitations, and fear). Among infants low in negative emotionality, there was no association between SES and cortisol. In contrast, among those high in negative emotionality, a significant association was obtained. These infants showed lower levels of HCC in lower-SES environments. The findings suggest that there are individual differences in reacting to the environment, and low levels of cortisol (not high) were found in susceptible infants in lower-SES families.

Ambient Air Pollution and Sudden Infant Death Syndrome in Korea: A Time-Stratified Case-Crossover Study.

Sudden infant death syndrome (SIDS) is an occasional cause of unexpected mortality in infancy. While various etiological factors have been hypothesized, air pollution has been consistently presented as an environmental factor. In this study, we aimed to estimate the risk of SIDS in relation to exposure to air pollution and the effects of its modifying factors. A mortality dataset with supplementary infant mortality survey data from Statistics Korea was used and combined the concentration of ambient air pollution data from AirKorea based on the date of death and residential addresses of the SIDS cases. Odds ratios (ORs) were estimated according to birthweight, gestational age, maternal age, and infant age using a time-stratified case-crossover study design. The risk of exposure to particulate matter of less than 10 μm in diameter (PM10), nitrogen dioxide (NO2), carbon monoxide (CO), and sulfur dioxide was estimated. The number of deaths due to SIDS was 454 (253 males and 201 females). The OR per 27.8 µg/m3 increment of PM10 was 1.14 (95% confidence interval [CI]: 1.03–1.25) and that per 215.8 ppb of CO was 1.20 (95% CI: 1.03–1.40) in all infants. In females, an increase in NO2 and CO levels was associated with a higher risk of SIDS in low-birthweight and preterm infants. The OR per 15.7 ppb increment in NO2 was highest among preterm infants, with a value of 5.12 (95% CI: 1.27–20.63), and low-birthweight individuals, with a value of 4.11 (95% CI: 1.74–9.72), at a moving average of 0 to 3 days. In males, however, no significant association was found. In the present study, exposure to air pollution was associated with an increased risk of SIDS. This association was more evident in susceptible infants with a low-birthweight or in cases of preterm birth.

Solid foods should be introduced into susceptible infants’ diets early in life-CON

Solid foods should be introduced into susceptible infants’ diets early in life-CON

Genetic Approaches to Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) remains a common and challenging complication of prematurity, with limited effective strategies at the neonatologist's disposal. Throughout the years, our understanding of this complex syndrome has broadened. Instead of solely attributing this disease to the effects of prematurity and injuries to the lung from mechanical ventilation, it is now accepted to be a multifactorial disease. Recent research efforts have focused on investigating the gene-environment interactions that may influence an infant's susceptibility toward the development of BPD. So far, success has been limited but promising, offering hope that in the future, novel therapies will be available to ameliorate the risk for BPD.