Real-life effects, complications, and outcomes in 39 critically ill neonates receiving continuous kidney replacement therapy.

BACKGROUND: Continuous kidney replacement therapy (CKRT) has been expanded from simple kidney replacement therapy to the field of critical illness in children. However, CKRT is rarely used in critically ill neonates in the neonatal intensive care unit (NICU). This study aimed to describe patients' clinical characteristics at admission and CKRT initiation, CKRT effects, short-term outcomes, and predictors of death in critically ill neonates. METHODS: A 7-year single-center retrospective study in a tertiary NICU. RESULTS: Thirty-nine critically ill neonates received CKRT between May 2015 and April 2022 with a mortality rate of 35.9%. The most common primary diagnosis was neonatal sepsis in 15 cases (38.5%). Continuous veno-venous hemodiafiltration and continuous veno-venous hemofiltration were applied in 43.6% and 56.4% of neonates, respectively. The duration of CKRT was 44 (18, 72) h. Thirty-one patients (79.5%) had complications due to CKRT-related adverse events, and the most common complication was thrombocytopenia. Approximately 12 h after the CKRT initiation, urine volume, mean arterial pressure, and pH were increased, and serum creatinine, blood urea nitrogen, and blood lactate were decreased. In the multivariate logistic regression analysis, neonatal critical illness score [odds ratio 0.886 (0.786 ~ 0.998), P = 0.046] was an independent risk factor for death in critically ill neonates who received CKRT. CONCLUSIONS: CKRT can be an effective and feasible technique in critically ill neonates, but the overall mortality and CKRT-related complications are relatively high. Furthermore, the probability of death is greater among neonates with greater severity of illness at CKRT initiation. A higher resolution version of the Graphical abstract is available as Supplementary information.

[Diagnosis and treatment of a child with alveolar capillary dysplasia with misalignment of pulmonary veins due to variant of FOXF1 gene].

OBJECTIVE: To explore the diagnosis, treatment and genetic characteristics of a neonate with severe pulmonary hypertension and respiratory failure. METHODS: Perinatal history, clinical manifestations, laboratory finding and diagnosis and treatment data of the child were collected. Whole exome sequencing was carried out for the child, and Sanger sequencing was used to verify the candidate variants. RESULTS: The female neonate has developed progressive respiratory failure and refractory pulmonary hypertension shortly after birth. Conventional treatment such as mechanical ventilation, vasoactive drugs, and inhaled nitric oxide were ineffective. She has developed sustained pulmonary hypertension after weaning from extracorporeal membrane oxygenation therapy, and had died after the treatment had ceased. Whole exome sequencing revealed that she has harbored a heterozygous de novo variant of c.682_683insGCGGCGGC (p.G234Rfs*148) of the FOXF1 gene, which was predicted as pathogenic based on guidelines from the American College of Medical Genetics and Genomics (ACMG), with evidence items of PVS1_Strong+PM2_Supporting+PS2. Based on her clinical manifestations and result of genetic testing, the child was diagnosed with alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV). CONCLUSION: Discovery of the c.682_683insGCGGCGGC (p.G234 Rfs*148) variant of the FOXF1 gene has expanded the mutational spectrum of the FOXF1 gene, which has facilitated implementation of specific treatment and provided a basis for clinical diagnosis and genetic counseling.

[Clinical effect of continuous blood purification in treatment of multiple organ dysfunction syndrome in neonates].

OBJECTIVE: To study the clinical effect and complications of continuous blood purification (CBP) in the treatment of multiple organ dysfunction syndrome (MODS) in neonates. METHODS: A retrospective analysis was performed for the clinical data of 21 neonates with MODS who were admitted to the neonatal intensive care unit from November 2015 to April 2019 and were treated with CBP. Clinical indices were observed before treatment, at 6, 12, 24, and 36 hours of CBP treatment, and at the end of treatment to evaluate the clinical effect and safety of CBP treatment. RESULTS: Among the 21 neonates with MODS undergoing CBP, 17 (81%) had response to treatment. The neonates with response to CBP treatment had a significant improvement in oxygenation index at 6 hours of treatment, a significant increase in urine volume at 24 hours of treatment, a stable blood pressure within the normal range at 24 hours of treatment, and significant reductions in the doses of the vasoactive agents epinephrine and dopamine at 6 hours of treatment (P<0.05), as well as a significant reduction in serum K+ level at 6 hours of treatment, a significant improvement in blood pH at 12 hours of treatment, and significant reductions in blood lactic acid, blood creatinine, and blood urea nitrogen at 12 hours of treatment (P<0.05). Among the 21 neonates during CBP treatment, 6 experienced thrombocytopenia, 1 had membrane occlusion, and 1 experienced bleeding, and no hypothermia, hypotension, or infection was observed. CONCLUSIONS: CBP is a safe, feasible, and effective method for the treatment of MODS in neonates, with few complications.

Quality Improvement to Increase Breastfeeding in Preterm Infants: Systematic Review and Meta-Analysis.

Background and Objective: Due to its numerous health benefits, breast milk (BM) is recommended for preterm infants. Despite such recommendations, the rates of breastfeeding in preterm infants are lower than that in term infants. Quality improvement (QI) bundles increase breastfeeding in preterm infants, but their replication in neonatal intensive care units has had inconsistent outcomes. Methods: We used the Population or Problem, Intervention, Comparison, and Outcomes (PICO) framework to develop our search strategy, and searched MEDLINE, Embase, and the Cochrane Library from inception through January 15, 2021. Studies describing any active QI intervention to increase BM use in preterm infants were included. The primary outcome measure was the rate of any breastfeeding or exclusive mother's own milk (MOM) at discharge or during hospitalization. Results: Sixteen studies were eligible for inclusion and showed an acceptable risk of bias, and included 1 interrupted time series, study 3 controlled before-and-after studies, and 12 uncontrolled before-and-after studies; of these, 3 studies were excluded due to insufficient dichotomous data, 13 were included in the meta-analysis. In the meta-analysis, the rate of any breastfeeding was significantly improved at discharge and during hospitalization after QI [risk ratio (RR) = 1.23, 95% confidence interval (CI): 1.14-1.32, P < 0.00001 and RR = 1.89, 95% CI: 1.09-3.29, P = 0.02, respectively]. The rate of exclusive MOM after QI was also significantly increased at discharge (RR = 1.51, 95% CI: 1.04-2.18, P = 0.03), but not during hospitalization (RR = 1.53, 95% CI: 0.78-2.98, P = 0.22). However, after sensitivity analysis, the comprehensive results still suggested that QI could significantly improve the rate of exclusive MOM during hospitalization (RR = 1.21, 95% CI: 1.08-1.35, P = 0.001). Funnel plots and Egger's test indicated publication bias in the rate of any BF at discharge. We corrected publication bias by trim and fill analysis, and corrected RR to 1.272, 95% CI: (1.175, 1.369), which was consistent with the results of the initial model. Conclusions: A QI bundle appears to be effective for promoting BM use in preterm infants at discharge or during hospitalization.

Is preterm donor milk better than preterm formula for very-low-birth-weight infants?

BACKGROUND: Preterm human milk has advantages over preterm formula (PF), but it may compromise some functions after pasteurization. OBJECTIVE: To explore the effects of preterm donor milk (DM) on growth, feeding tolerance, and severe morbidity in very-low-birth-weight infants. METHOD: This was a single-center, prospective cohort study that included 304 preterm infants weighing <1,500 g or of gestational age <32 weeks. If the mother's own milk was insufficient, the parents decided to use PF (n = 155) or DM (n = 149). The two groups were uniformly managed according to the standard NICU protocol. Growth parameters, feeding tolerance, and severe morbidity such as necrotizing enterocolitis, were compared between the two groups. RESULTS: The daily weight gain and weekly head growth in the DM group were not different from those in the PF group (P > 0.05). Feeding intolerance in the DM group was significantly lower than that in PF group (P < 0.05), and parenteral nutrition time and hospitalization time were also shorter than that in the PF group (P < 0.05). Moreover, the incidence of necrotizing enterocolitis and sepsis was also significantly lower in the DM group (P < 0.05). CONCLUSION: The study indicated that preterm DM does not affect the growth of very-low-birth-weight infants. Further, it significantly reduces feeding intolerance, helps achieve full enteral feeding early, and has protective effects against necrotizing enterocolitis and sepsis. Thus, compared with formula, preterm DM can lower the rate of infection in preterm infants and is worthy of promotion.

A novel synonymous ABCA3 variant identified in a Chinese family with lethal neonatal respiratory failure.

BACKGROUND: Lethal respiratory failure is primarily caused by a deficiency of pulmonary surfactant, and is the main cause of neonatal death among preterm infants. Pulmonary surfactant metabolism dysfunction caused by variants in the ABCA3 gene is a rare disease with very poor prognosis. Currently, the mechanisms associated with some ABCA3 variants have been determined, including protein mistrafficking and impaired phospholipid transport. However, some novel variants and their underlying pathogenesis has not been fully elucidated yet. In this study we aimed to identify the genetic features in a family with lethal respiratory failure. METHODS: We studied members of two generations of a Chinese family, including a female proband, her parents, her monozygotic twin sister, and her older sister. Trio whole exome sequencing (WES) were used on the proband and her parents to identify the ABCA3 variants. Sanger sequencing and real-time quantitative polymerase chain reaction (PCR) were used on the monozygotic twin sister of proband to validate the ABCA3 synonymous variant and exon deletion, respectively. The potential pathogenicity of the identified synonymous variant was predicted using the splice site algorithms dbscSNV11_AdaBoost, dbscSNV11_RandomForest, and Human Splicing Finder (HSF). RESULTS: All patients showed severe respiratory distress, which could not be relieved by mechanical ventilation, supplementation of surfactant, or steroid therapy, and died at an early age. WES analysis revealed that the proband had compound heterozygous ABCA3 variants, including a novel synonymous variant c.G873A (p.Lys291Lys) in exon 8 inherited from the mother, and a heterozygous deletion of exons 4-7 inherited from the father. The synonymous variant was consistently predicted to be a cryptic splice donor site that may lead to aberrant splicing of the pre-mRNA by three different splice site algorithms. The deletion of exons 4-7 of the ABCA3 gene was determined to be a likely pathogenic variant. The variants were confirmed in the monozygotic twin sister of proband by Sanger sequencing and qPCR respectively. The older sister of proband was not available to determine if she also carried both ABCA3 variants, but it is highly likely based on her clinical course. CONCLUSIONS: We identified a novel synonymous variant and a deletion in the ABCA3 gene that may be responsible for the pathogenesis in patients in this family. These results add to the known mutational spectrum of the ABCA3 gene. The study of ABCA3 variants may be helpful for the implementation of patient-specific therapies.

Efficiency of high-frequency oscillatory ventilation combined with pulmonary surfactant in the treatment of neonatal meconium aspiration syndrome.

The aim of this study was to investigate the clinical efficiency of the use high-frequency oscillatory ventilation (HFOV) combined with pulmonary surfactant (PS) for the treatment of neonatal meconium aspiration syndrome (MAS). Clinical data of 53 MAS patients admitted to neonatal intensive care unit (NICU) was collected and the patients were divided into 3 groups according to the different treatment approach: group 1 conventional mechanical ventilation (CMV); group 2 HFOV; group 3 HFOV + PS. By monitoring the changes in oxygenation function indicators such as inhaled oxygen concentration (FiO2), oxygenation index (OI) and arterial oxygen tension/alveolar arterial oxygen tension (a/ApO2) of three groups after 2, 12, 24, 48 h of treatment, the usage of the ventilator, duration of hospitalization, changes in clinical manifestations and outcomes of three groups were analyzed. As compared to group 1, the difference in all the oxygenation function indicators after treatment in group 2 and group 3 was statistically significant at different points in time (P < 0.05). However, the timing and extent of the change in the indicators in group 3 were more significant than in group 2; as compared to group 1, the ventilation time, duration of the oxygen therapy and hospitalization time of group 2 and group 3 were significantly shorter and the difference was statistically significant (P < 0.05). Early use of HFOV combined with PS to treat MAS has significant therapeutic effect, especially for the treatment of severe MAS where it can be used as a safer and more effective rescue measure.