Pediatrics and Neonatology最新文献

Background: Tacrolimus is an essential immunosuppressive medication in paediatric patients' post-liver transplantation. Achieving tacrolimus target concentration in early post-transplantation is crucial to minimise the risk of acute rejection; however, this is challenging due to inter- and intra-patient variability in tacrolimus metabolism and clearance. Therefore, our study aims to describe tacrolimus trough concentration variability and pharmacokinetics in paediatric post-liver transplantation during the first two weeks post-transplantation.

Method: This retrospective multicentre observational study included paediatric patients post-liver transplantation. Post-operative data was collected within the initial 14 days using electronic health records, including daily tacrolimus doses, measured trough concentrations, graft data, surgical data, and documented acute rejection. Pharmacokinetic analysis was completed using the Monolix software. We used the empirical Bayesian estimates of clearance and volume of distribution for covariate testing to assess possible correlations. We performed a stepwise regression analysis (alpha = 0.05).

Results: Ninety-one paediatric patients were included in the study, with a mean age of 4.1 years (SD = 4.6). The mean graft-to-recipient weight ratio (GRWR) was 3% (SD = 6). The vast majority of the patients received the liver from living donors (n = 84, 92.3%). The average time needed to reach therapeutic concentration was 4.6 (SD = 2.8) days. The initial clearance (Clini) was very low at baseline (0.012 L/h), then increased dramatically to 9.84 L/h at 14 days post-transplantation. The clearance appeared to be time-dependent, and the time needed to reach 50% of maximum clearance was five days post-transplantation. The covariates that significantly affected clearance included bodyweight and aspartate transaminase, while the only significant covariate for volume of distribution was bodyweight.

Conclusion: Tacrolimus is a drug with high intra- and interindividual variability, making dosing challenging in the paediatric liver transplantation population. Prospective studies with more intensive sampling are needed to address the time-dependent changes in clearance, which will aid in establishing the optimal dosing regimens in this population.

Background: Magnesium sulfate (MgSO₄) is a tocolytic agent used to treat gestational hypertension and to prevent preterm labor. Neonatal hypocalcemia is a well-known side effect of maternal MgSO₄ use. Cases of neonatal hypercalcemia after maternal MgSO₄ have been reported. Little is known about neonatal hypercalcemia following maternal MgSO₄ therapy. We investigated the frequency and risk factors of neonatal hypercalcemia in this setting.

Methods: This case-control study investigated serum calcium in neonates born within 24 h after maternal MgSO₄ administration. We reviewed the electronic medical records of Saitama City Hospital for pregnant women who were treated with MgSO₄ between January 2016 and December 2021. There were 504 pregnant women that were treated with MgSO₄. We enrolled 257 neonates. Hypercalcemia was defined as serum albumin-corrected calcium greater than 2.74 mmol/L (11 mg/dL). We collected the perinatal information from the mothers and neonates.

Results: Twenty-one neonates (8%) had hypercalcemia at birth (H group). Umbilical arterial ionized calcium, neonatal plasma ionized calcium, and total serum calcium were significantly higher in H group than in N group. Neonatal serum albumin, on the other hand, was lower in H group than in N group. Neonates in H group were born earlier (28.4 ± 3.1 vs. 32.4 ± 3.1 wk, p < 0.001) and more likely to be born to mothers with pathological chorioamnionitis (91.0% vs. 12.7%, p < 0.001) than neonates who were normocalcemic (N group). Serum alkaline phosphatase was lower in H group (661 ± 276 vs. 816 ± 265 U/L, p = 0.01). Multivariate analysis showed that earlier gestational age and chorioamnionitis were significant risk factors.

Conclusion: Hypercalcemia after maternal MgSO₄ was seen in 8% of neonates. Maternal chorioamnionitis and earlier gestational age were associated with this condition.

Background: Pulmonary air leak may cause serious complications and mortality in neonates, especially preterm infants. Its incidence and perinatal risk factors in preterm infants might differ from those in term infants. We investigated the incidence, perinatal risk factors and morbidities associated with pulmonary air leak in very-low-birth-weight (VLBW) preterm infants in Taiwan.

Methods: Data from 2011 to 2015 from the nationwide multihospital registry of the Taiwan Premature Infant Follow-up Network were analyzed. Preterm infants with pulmonary air leak, including pneumothorax and pneumomediastinum, were enrolled. Data on perinatal characteristics, the course of resuscitation in the delivery room, the management of respiratory distress syndrome (RDS), and the clinical outcomes of pulmonary air leak were collected and compared between VLBW preterm infants with and without pulmonary air leak.

Results: We included 5906 VLBW preterm infants with a mean gestational age of 28.6 ± 3 weeks and mean birth weight of 1078 ± 284 g. Of them, 379 neonates (6.4%) had pulmonary air leak, with 5.4% and 1% having isolated pneumothorax and isolated pneumomediastinum, respectively. Independent risk factors for pulmonary air leak in VLBW preterm infants were male sex, a 5-min Apgar score <7, and RDS treated with surfactant. VLBW preterm infants who had higher gestational age or received nasal continuous positive airway pressure (NCPAP) had a lower risk of pulmonary air leak. However, pulmonary air leak was associated with higher rates of severe retinopathy of prematurity, severe intraventricular hemorrhage, chronic lung disease, and mortality.

Conclusions: NCPAP appeared to protect against pulmonary air leak in VLBW preterm infants. Clinicians should be aware of the risk factors for pulmonary air leak in such infants and promptly initiate meticulous ventilation strategies as needed.

Background: Extremely low birthweight (ELBW) infants invariably receive multiple antibiotic therapies during hospitalization. However, the causes of high cumulative antibiotic exposure, as well as the impact of such exposure on the outcomes of preterm infants, particularly long-term neurodevelopmental outcomes, remain to be elucidated. Furthermore, the cumulative effects of simultaneous use of multiple antibiotics are often overlooked.

Methods: We included ELBW infants born between January 1, 2016, and December 31, 2020. The duration of antibiotic therapy was calculated as Days of Therapy (DOT), with each antibiotic administered during the first month of life added cumulatively. The infants were divided into two groups: the low cumulative antibiotic exposure group and the high cumulative antibiotic exposure group.

Results: Of 453 eligible ELBW infants, 358 met the inclusion criteria. Multivariable logistic regression indicated a low birthweight [adjusted odds ratio (aOR) 0.996, 95% confidence interval (CI) 0.994, 0.998], chorioamnionitis (aOR 2.195, 95% CI 1.145, 4.210), sepsis (aOR 2.538, 95% CI 1.417, 4.544), and necrotizing enterocolitis (aOR 11.798, 95% CI 2.637, 52.784) as independent factors associated with high cumulative antibiotic exposure. These infants were associated with poor short-term outcomes, including mortality (aOR 9.031, 95% CI 2.433, 33.448), moderate to severe bronchopulmonary dysplasia (aOR 2.895, 95% CI 1.471, 5.699), and retinopathy of prematurity necessitating therapy (aOR 2.503, 95% CI 1.363, 4.597). Although infants in the low cumulative antibiotic exposure group had higher neurodevelopmental scores across all three BSID-III domains at each corrected age compared to those in the high cumulative antibiotic exposure group, the cumulative antibiotic exposure did not significantly influence the score changes in the linear mixed-effects models.

Conclusions: High cumulative antibiotic exposure in early life is associated with adverse short-term outcomes in ELBW infants. The impacts on long-term neurodevelopmental require further investigation. When prescribing antibiotics to infants, caution should be exercised to avoid unnecessary exposure.

Background: Hepatopulmonary syndrome (HPS) is a complication in biliary atresia (BA) children following hepatoportoenterostomy. Liver transplantation (LT) was the definitive treatment of HPS. However, little was known about the risk factors between HPS and mortalities. We aimed to evaluate the role of HPS and the predictors of complications after LT in BA children.

Methods: One hundred and twenty (54 males and 66 females) children with BA receiving LT were retrospectively enrolled. The primary outcome was postoperative biliary/vascular complication rates and the secondary outcome was post-LT mortality rates.

Results: Among 120 BA children receiving LT, six (5%) children were diagnosed with HPS before LT. The overall survival rate of LT in BA children was 80% and the overall survival rate of LT in BA children with and without HPS was 17% and 83%, respectively. Vascular complications and HPS were predictors for poor overall survival rates both in univariate logistic regression analyses (hazard ratio [HR], 11.63 and 5.96; P < 0.0001 and P = 0.001, respectively) and multivariate logistic regression analyses (HR, 10.02 and 4.16; P < 0.0001 and P = 0.007, respectively). Kaplan-Meier analysis indicated the predictive role of HPS on poor overall survival rates (P < 0.0001), higher risks of biliary complications (P < 0.0001), and higher risks of jaundice (P < 0.01) post-LT.

Conclusion: The present study comprising children over long-term follow-up revealed that the development of pre-LT HPS had a poor impact on overall survival rates and higher risks of biliary complications in BA children receiving LT.

Background: The prevention and treatment of pneumonia and lung injury in preterm infants are major challenges for pediatricians worldwide. Few studies have analyzed the composition of bacterial colonies in the airway and intestine and their relationship with toll-like receptors (TLRs) as it relates to pneumonia in preterm infants.

Methods: This study included 70 infants born at 32-35 weeks gestation. Oral-tracheal aspirates at the time of birth, first-pass meconium, and serum specimens were collected. Bacterial deoxyribonucleic acid (DNA) was extracted from the Oral-tracheal aspirates and meconium, and 16S ribosomal ribonucleic acid (rRNA) genes were amplified and sequenced. The levels of TLR2 and TLR4 were analyzed using an enzyme-linked immunosorbent assay. Preterm infants were classified into non-pneumonia (A) and pneumonia (B) groups according to their clinical manifestations.

Results: Significant differences in the alpha and beta diversities were observed between the two groups. Infants with pneumonia had less bacterial diversity in the airways and intestinal flora at birth than those without pneumonia. The three most predominant phyla in the airways at birth were Proteobacteria, Firmicutes, and Actinobacteria. The levels of TLR2 and TLR4 in oral-tracheal aspirates were higher in infants with pneumonia than in those without pneumonia, although serum TLR2 and TLR4 levels did not differ between the groups. Streptococcus in the oral tracheal aspirate was negatively correlated with TLR2 and TLR4 levels, and Ureaplasma in the oral-tracheal aspirate was negatively correlated with TLR4 levels in the airway.

Conclusion: Reduced perinatal microbiota diversity is associated with the levels of TLR2 and TLR4, and may also have a significant impact on the development of pneumonia.