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Abstract Background The gut microbiota is believed to influence neurodevelopment through the gut–brain axis, but prior studies have shown inconsistent results regarding early childhood antibiotic exposure and subsequent risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). The purpose of this study was to evaluate the hypothesis that exposure to antibacterial agents in the first 2 years of life increases the risk of ASD and/or ADHD. Methods This was a retrospective cohort study using 2003–2019 data from the National Health Insurance Research Database in Taiwan. Livebirths born between 2004 and 2016 were identified and separated into singleton, full sibling, and exposure-discordant sibling pair cohorts. The exposure group included children who filled at least one prescription for antibacterial agents between 0 and 2 years old in outpatient settings. The outcome, ASD and/or ADHD, was defined by at least one inpatient or outpatient diagnosis. The maximum follow-up age was 15 years in this study. Potential neonatal, maternal and paternal confounders were adjusted for. Cox proportional hazards models were used to estimate the relative event risk. Results The final sample contained 946,581 children in the singleton cohort, 1,142,693 children in the full sibling cohort, and 352,612 children in the exposure-discordant sibling pair cohort. Antibiotic exposure marginally increased the risk of ASD and/or ADHD in the singleton cohort (adjusted hazard ratio [aHR]: 1.06, 95% confidence interval [CI]: 1.04–1.07) and in the full sibling cohort (aHR: 1.03, 95% CI: 1.01–1.04). A slight decrease in the risk of ASD and/or ADHD was observed in the exposure-discordant sibling pair cohort (aHR: 0.92, 95% CI: 0.90–0.94). Conclusions The results suggest that early life antibiotic exposure has minimal impact on the risk of ASD and/or ADHD. Given that the estimated effects are marginal and close to null, concerns about ASD and/or ADHD risk increase should not postpone or deter timely and reasonable antibiotic use.

Objective: Treatment of severe asthma exacerbation could be challenging, especially in the initial hours of acute attack when systemic corticosteroid is yet to take effect. In spite of using inhaled agents, the role of non-invasive ventilation (NIV), including Bilevel Positive Airway Pressure (BiPAP), had been addressed recently. Methods: We reviewed 5-year experience in our hospital for records of patients who were admitted to pediatric intensive care unit because of severe asthma attack. The included admission records from 2012 to 2017 were grouped according to BiPAP use (Yes/No). Clinical parameters (heart rate (HR), respiratory rate (RR), SpO2 and serum pCO2) at selected time intervals of treatment were collected for both groups and analyzed. Results: We included data of 46 admissions from 33 different patients (24 with BiPAP and 21 without BiPAP.) The BiPAP group had significantly higher initial RR as well as higher severity scores compared with the other group (p < 0.001). The RR improved significantly in the following time intervals in BiPAP group. There was no significant difference in HR between groups in any of the time intervals. The serum pCO2 levels decreased significantly after initiation of ventilation support in the BiPAP group, and SpO2 levels improved significantly for both groups. Conclusion: BiPAP seemed efficient in improving respiratory rate and oxygenation in our study. It does not seem to cause additional irritation regarding that HR was not increased in BiPAP group compared with non-BiPAP group. Overall, BiPAP ventilation is safe and efficient in treating children with severe asthma attack.

Background: Preterm infants require higher calcium and phosphate intake than term infants to facilitate adequate bone growth, but this is rarely met in parenteral nutrition (PN) solution because of the limited solubility of calcium and phosphate. This study aimed to evaluate the solubility of organic phosphate with calcium gluconate in neonatal PN solutions, simulating its clinical use. Methods: PN solutions were composed of calcium gluconate at 50 mEq/L and sodium glycerophosphate (NaGP) at 25 mmol/L. Another component included 1% or 4% amino acid and 10% or 20% dextrose. For comparison, PN solution composed of potassium phosphate was also evaluated. Each solution was evaluated using the following methods: visual inspection, light obscuration particle count test, and pH measurement. To simulate the clinical condition, the solution was tested after compounding, after being stored at 25 °C for 24 h, and after being stored at 2°C-8°C for 2 or 9 days and subsequently at 25 °C for 24 h. Results: There was no visual deposition in PN solution using NaGP in any of the concentrations and under any stored condition. The solution fulfilled the criteria of physical compatibility as < 25 particles/mL measuring ≥10 μm in diameter and

BackgroundMethylxanthines (caffeine; aminophylline/theophylline) are commonly used for apnea of prematurity (AOP) treatment. We aimed to compare the efficacy and adverse effects of caffeine and aminophylline/theophylline.MethodsA retrospective case–control gestational age-matched study investigates patients born between January 2017 and December 2018, 23–35 weeks gestation with birth weights >500 g treating AOP with caffeine or aminophylline/theophylline.ResultsThere were 144 cases (48 in caffeine group and 96 in aminophylline/theophylline group). The median treatment durations were 11 and 17 days in caffeine and aminophylline/theophyllinegroup (p = 0.002). When tachycardia is defined as heart rate ≥160 bpm, the rates were 8.3 and 34.4% in caffeine and control group (p = 0.001). When tachycardia is defined as 10 bpm over baseline heart rate, the rates were 41.7 and 63.5% in caffeine and aminophylline/theophylline group (p = 0.01). Stratified by gestational age and sex, significant reductions in tachycardia rates with caffeine than with theophylline were limited to male infants and infants born at

IntroductionIn very low birth weight (VLBW) infants, hypothermia immediately following birth is common even in countries rich in medical resources. The purpose of this study is to design a standard prevention bundle that decreases the rate of hypothermia among infants after birth and to investigate efficacy of the bundle and short-term outcomes for VLBW infants.MethodsThis quality improvement project was conducted from February 2017 to July 2018 on all VLBW preterm infants admitted at a single referral level III neonatal intensive care unit. The infants were classified into the pre-intervention (February to September 2017) and post-intervention (October 2017 to July 2018) groups according to the time periods when they were recruited. During the pre-intervention period, we analyzed the primary causes of hypothermia, developed solutions corresponding to each cause, integrated all solutions into a prevention bundle, and applied the bundle during the post-intervention period. Afterwards, the incidence of neonatal hypothermia and short-term outcomes, such as intraventricular hemorrhage (IVH), acidosis, and shock requiring inotropic agents, in each group were compared.ResultsA total of 95 VLBW infants were enrolled in the study, including 37 pre-intervention, and 58 post-intervention cases. The incidence of hypothermia in preterm infants decreased significantly upon the implementation of our prevention bundle, both in the delivery room (from 45.9% to 8.6%) and on admission (59.5% to 15.5%). In addition, the short-term outcomes of VLBW infants improved significantly, especially with the decreased incidence of IVH (from 21.6% to 5.2%, P = 0.015).ConclusionsOur standardized prevention bundle for preventing hypothermia in VLBW infants is effective and decreased the IVH rate in VLBW infants. We strongly believe that this prevention bundle is a simple, low-cost, replicable, and effective tool that hospitals can adopt to improve VLBW infant outcomes.

Oligohydramnios is not a rare prenatal finding. However, recurrent oligohydramnios is uncommon, and genetic etiology should be taken into consideration. We present two families with recurrent fetal oligohydramnios that did not respond to amnioinfusion. Rapid trio-whole-exome sequencing (WES) revealed mutations in the AGT gene in both families within 1 week. The first family had a compound heterozygous mutation with c.856 + 1G > T and c.857-619_1269 + 243delinsTTGCCTTGC changes. The second family had homozygous c.857-619_1269 + 243delinsTTGCCTTGC mutations. AGT gene mutation may lead to autosomal recessive renal tubular dysgenesis, a rare and lethal disorder that can result in early neonatal death. Both the alleles identified are known alleles associated with pathogenicity. Our findings suggest that trio-WES analysis may help rapidly identify causative etiologies that can inform prompt counseling and decision-making prenatally.

Severe pulmonary hemorrhage is a serious complication with a high mortality rate in preterm infants with respiratory distress syndrome (RDS) after surfactant therapy. The aim of this study is to evaluate the efficacy of our current management strategy for neonates with severe pulmonary hemorrhage. Materials and methods: Very-low-birth-weight (VLBW) infants who developed severe pulmonary hemorrhage were studied from January 2006 to August 2011. Treatment for severe pulmonary hemorrhage in our neonatal intensive care unit (NICU) included intratracheal epinephrine spraying/irrigation, blood component therapy, and as necessary, surfactant supplement therapy was administered in cases that secondary RDS was diagnosed. High frequency oscillatory ventilation (HFOV) was utilized when hypoxia or respiratory acidosis persisted under conventional mechanical ventilation (CMV). We then described the clinical courses of severe pulmonary hemorrhage following our management. Results: A total of 18 (3.2%) out of 469 VLBW infants developed severe pulmonary hemorrhage. The mean gestational age was 27 weeks, the mean birth weight was 822 g, and the onset age was 2.5 days after birth. There was no severe pulmonary hemorrhage-associated mortality during this period with the exception of one case, in which an infant died after the parents refused to do further therapy. Sixteen (88.8%) neonates had RDS and 13 received surfactant therapy. Twelve (66.6%) cases developed secondary RDS following the onset of severe pulmonary hemorrhage, and four cases received surfactant supplement therapy. In the surfactant supplement group, alveolar-arterial oxygen difference (AaDO2) and oxygenation index (OI) during the 2–4 hours postpulmonary hemorrhage period showed statistically significant improvement, whereas the other group only showed a tendency toward improvement without reaching statistical significance when compared to the baseline data. Duration of high oxygen requirement [defined as fraction of inspired oxygen (FiO2) > 40%] was also less in the surfactant supplement group. Conclusion: This data suggests that our current strategy is effective for treating severe pulmonary hemorrhage in VLBW infants. Surfactant therapy for severe pulmonary hemorrhage may also be beneficial for improving lung function and may shorten the duration of high oxygen requirement.

BackgroundPreeclampsia remains a leading cause of maternal mortality and preterm delivery. Both preeclampsia and bronchopulmonary dysplasia (BPD) of prematurity are associated with impaired angiogenesis. However, the relationship between maternal preeclampsia and BPD remains controversial. This study aims to test whether or not preeclampsia is associated with development of BPD in a cohort of premature infants.Materials and methodsWe conducted a retrospective cohort study assessing the association between preeclampsia and the risk of developing BPD in very-low-birth-weight (VLBW) infants registered in the Premature Baby Foundation of Taiwan from 1997 through 2006. All 21 neonatal departments in Taiwan participated in the data collection. A total of 8,653 VLBW infants were registered in the database. The exclusion criteria included congenital anomalies, chromosome anomalies, infants that died before 36 weeks post-conceptual (PCA), and those whose BPD status were unavailable. BPD was defined as oxygen dependence at 36 weeks postmenstrual age. The association between maternal preeclampsia and BPD was assessed using a multivariate-adjusted logistic regression model.ResultsIn the end, a total of 5,753 cases were enrolled in this study. The incidence of preeclampsia was 14.7% (n=847) and the overall incidence of BPD was 34.9%. Infants with maternal preeclampsia had a higher gestational age, higher incidence of cesarean section and being small for their gestational age, lower incidence of respiratory distress syndrome, patent ductus arteriosus, and sepsis. BPD occurred significantly less frequently in the maternal preeclampsia group (24.1% vs. 36.7%; adjusted odds ratio: 0.78; 95% confidence interval, 0.62-0.98). Subgroup analysis showed that the association between preeclampsia and BPD was significant only in those VLBW infants with a gestational age between 31-34 weeks.ConclusionThis data supports the association between fetal exposure to maternal preeclampsia and a reduced risk of BPD in relatively mature VLBW infants.

Background: Macrophage migration plays a critical role in inflammation and the development of pathological processes. Thus, inhibiting macrophage migration is a potential approach for reducing inflammation. Besides, mitigation of inflammatory mediators also inhibits macrophage migration. Morin hydrate (MH), a bioflavonoid found in fruits, vegetables, and herbs, has demonstrated various pharmacological effects, including anti-inflammatory and immunosuppressive properties. However, the specific molecular mechanisms underlying MH's anti-inflammatory effects and its impact on macrophage migration remain unclear. This study focused on MH's anti-inflammatory molecular mechanism and also elucidated how it is associated with inhibiting macrophage migration. Methods: The anti-inflammatory and antimigration effects of MH were investigated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, a murine macrophage cell line. The production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) were assessed by various assays. Additionally, the expression of key signaling molecules, such as extracellular signal-regulated kinase (ERK), JNK, p65, pSrc, focal adhesion kinase (FAK), β-catenin, COX-2, p-p38, and p-Akt, was analyzed in response to MH treatment. Results: MH treatment reduced LPS-induced NO production and downregulated the mRNA and protein expression of iNOS in RAW264.7 cells. It concentration dependently inhibited the expression of ERK and JNK. At a high concentration of 20 µM, MH also suppressed the expression of p65, pSrc, and pFAK. Moreover, MH effectively attenuated LPS-induced β-catenin expression, while it did not exhibit a significant effect on COX-2, p-p38, and p-Akt expressions in LPS-stimulated RAW264.7 cells. Furthermore, MH pretreatment inhibited the migration of LPS-induced macrophages. Conclusion: This study reveals that MH exerts its anti-inflammatory effects by inhibiting NO production, downregulating iNOS expression, and modulating ERK/JNK and p65 phosphorylation. Additionally, MH suppresses Src/FAK phosphorylation and downregulates β-catenin expression induced by LPS. The findings demonstrate a complex interplay between the inflammatory response and MH's impact on macrophage migration being intertwined with its anti-inflammatory properties. [ABSTRACT FROM AUTHOR]