Sustained acute kidney injury as an independent risk factor for neurodevelopmental and growth outcomes in a single NICU center.

PURPOSE: Acute kidney injury (AKI) is commonly seen in neonatal intensive care units (NICUs) and is potentially associated with adverse prognoses in later stages of life. Our study evaluated the impact of sustained AKI (SAKI) on both neurodevelopmental impairment (NDI) and early growth restriction (EGR) in neonates. METHODS: This case-control study retrospectively analyzed the medical records of neonates diagnosed with SAKI in the NICU of a tertiary medical center during the period from January 2007 to December 2020. Cases without subsequent follow-up and those resulting in death were excluded. We analyzed demographic, biochemical, and clinical outcome data. RESULTS: Of the 93 neonates with SAKI, 51 cases (54.8%) were included in this study, while 42 cases (45.2%) were excluded due to a lack of follow-up or death. An age-matched control group comprised 103 neonates, who had never experienced AKI or SAKI, were selected at random. In total, 59 (38.3%) cases were identified as NDI and 43 (27.9%) as EGR. Multivariate analysis revealed that patients with SAKI had significantly higher risks of developing NDI (odds ratio, [OR] = 4.013, p = 0.001) and EGR (OR = 4.894, p < 0.001). The AKI interval had an area under the receiver operating characteristic curve of 0.754 for NDI at 9.5 days and 0.772 for EGR at 12.5 days. CONCLUSIONS: SAKI is an independent risk factor for both NDI and EGR in neonates. Consequently, regular monitoring, neurological development assessments, and appropriate nutritional advice are crucial to these infants who have experienced renal injury.

Metabolomic Analysis Reveals the Association of Severe Bronchopulmonary Dysplasia with Gut Microbiota and Oxidative Response in Extremely Preterm Infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease mainly affecting premature infants needing ventilation or oxygen for respiratory distress. This study aimed to evaluate the molecular linkages for BPD in very and extremely preterm infants using a metabolomics-based approach. A case-control study of enrolling preterm infants born before 32 weeks gestational age (GA) was prospectively performed. These preterm infants were subsequently stratified into the following two groups for further analysis: no or mild BPD, and moderate or severe BPD based on the 2019 NICHD criteria. Urinary metabolomic profiling was performed using 1H-Nuclear magnetic resonance (NMR) spectroscopy coupled with partial least squares discriminant analysis (PLS-DA) at a corrected age of 6 months. Metabolites significantly differentially related to GA and BPD severity were performed between groups, and their roles in functional metabolic pathways were also assessed. A total of 89 preterm infants born before 32 weeks gestation and 50 infants born at term age (above 37 completed weeks' gestation) served as controls and were enrolled into the study. There were 21 and 24 urinary metabolites identified to be significantly associated with GA and BPD severity, respectively (p < 0.05). Among them, N-phenylacetylglycine, hippurate, acetylsalicylate, gluconate, and indoxyl sulfate were five metabolites that were significantly higher, with the highest importance in both infants with GA < 28 weeks and those with moderate to severe BPD, whereas betaine and N,N-dimethylglycine were significantly lower (p < 0.05). Furthermore, ribose and a gluconate related pentose phosphate pathway were strongly associated with these infants (p < 0.01). In conclusion, urinary metabolomic analysis highlights the crucial role of gut microbiota dysbiosis in the pathogenesis of BPD in preterm infants, accompanied by metabolites related to diminished antioxidative capacity, prompting an aggressive antioxidation response in extremely preterm infants with severe BPD.

Clinical Risk Factors for Retinopathy of Prematurity Reactivation after Intravitreal Anti-Vascular Endothelial Growth Factor Injection.

OBJECTIVE: To assess the rate and risk factors for reactivation of retinopathy of prematurity (ROP) after intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) agents. STUDY DESIGN: Infants who received IVI therapy between 2017 and 2022 were enrolled and divided into two groups: those with and without ROP reactivation. Information on ROP variables and patient variables were analyzed using multivariable logistic regression. RESULTS: A total of 114 infants with 223 eyes were enrolled in the study. The ROP reactivation rate was 11.4% of infants (9.9% of eyes). The mean duration of reactivation was 84 ± 45 days. Among the 223 eyes treated with IVI, reactivation rates were 6% for bevacizumab, 13.9% for aflibercept, and 22.2% for ranibizumab. A multivariable regression model showed that ranibizumab was an independent risk factor (OR: 11.4, p=0.008) for reactivation. Other risk factors included infants with periventricular leukomalacia (OR: 13.8, p=0.003), patent ductus arteriosus ligation (OR: 10.7, p=0.032), and infants who still required invasive mechanical ventilation on the day of IVI therapy (OR: 7.0, p=0.018). CONCLUSIONS: All anti-VEGF agents carry a risk of ROP reactivation, with the risk being higher with ranibizumab 0.25 mg than with bevacizumab 0.625 mg. Reactivation of ROP should be assessed vigilantly, especially in those infants with increased risks. Future research to determine the optimal anti-VEGF selection and dosage in high-risk infants is warranted.

Invasive lactobacillus infection in pediatric patients in a tertiary center in Taiwan - 16 years' experience and literature review.

BACKGROUND: Lactobacilli are common microorganisms in the human body. Some species were used as probiotics supplement for many purposes such as preventing necrotizing enterocolitis, or improving allergic diseases or diarrhea. Previously, Lactobacillus infection was thought of as contamination due to its low pathogenicity. However, there have been reports of invasive Lactobacillus infection in immunocompromised patients or patients with comorbidities. The purpose of this study was to analyze the clinical characteristics, antibiotic treatment and outcomes of pediatric patients with invasive Lactobacillus infection. METHODS: We retrospectively reviewed pediatric patients diagnosed with invasive Lactobacillus infection between 2004 and 2020. Invasive Lactobacillus infection was diagnosed if sterile sites yielded Lactobacillus spp. Clinical manifestations, chronic diseases, potential predisposing factors, medical treatments, antimicrobial susceptibility tests and outcomes were recorded. RESULTS: Fifteen pediatric patients were diagnosed with invasive Lactobacillus infection, accounting for 2.4% of total invasive Lactobacillus infections during the 16-year period. Eleven infections were bacteremia, two were intra-abdominal infections, and two were biliary tract infections. Fever was the most common symptom. Potential predisposing factors were immunocompromised status, central venous device, prolonged antibiotics use and receiving supplemented probiotics for at least one week. All patients survived with favorable outcomes. Most pathogens were identified as Lactobacillus spp, and two were Lactobacillus rhamnosus, which were related to supplemented probiotics. The antimicrobial susceptibility tests showed that Lactobacilli were all sensitive to ampicillin but resistant to glycopeptides. CONCLUSION: Invasive Lactobacillus infections in pediatric patients were rare. Despite its low pathogenicity, Lactobacillus could cause invasive infection in those immunocompromised patients.

The Clinical and Genetic Characteristics of Streptococcus agalactiae Meningitis in Neonates.

Streptococcus agalactiae (Group B Streptococcus, GBS) is an important pathogen of bacterial meningitis in neonates. We aimed to investigate the clinical and genetic characteristics of neonatal GBS meningitis. All neonates with GBS meningitis at a tertiary level medical center in Taiwan between 2003 and 2020 were analyzed. Capsule serotyping, multilocus sequence typing, antimicrobial resistance, and whole-genome sequencing (WGS) were performed on the GBS isolates. We identified 48 neonates with GBS meningitis and 140 neonates with GBS sepsis. Neonates with GBS meningitis had significantly more severe clinical symptoms; thirty-seven neonates (77.8%) had neurological complications; seven (14.6%) neonates died; and 17 (41.5%) survivors had neurological sequelae at discharge. The most common serotypes that caused meningitis in neonates were type III (68.8%), Ia (20.8%), and Ib (8.3%). Sequence type (ST) is highly correlated with serotypes, and ST17/III GBS accounted for more than half of GBS meningitis cases (56.3%, n = 27), followed by ST19/Ia, ST23/Ia, and ST12/Ib. All GBS isolates were sensitive to ampicillin, but a high resistance rates of 72.3% and 70.7% to erythromycin and clindamycin, respectively, were noted in the cohort. The virulence and pilus genes varied greatly between different GBS serotypes. WGS analyses showed that the presence of PezT; BspC; and ICESag37 was likely associated with the occurrence of meningitis and was documented in 60.4%, 77.1%, and 52.1% of the GBS isolates that caused neonatal meningitis. We concluded that GBS meningitis can cause serious morbidity in neonates. Further experimental models are warranted to investigate the clinical and genetic relevance of GBS meningitis. Specific GBS strains that likely cause meningitis requires further investigation and clinical attention.

Molecular characteristics and clinical features of Staphylococcus epidermidis healthcare-associated late-onset bacteremia among infants hospitalized in neonatal intensive care units.

BACKGROUND: Though Staphylococcus epidermidis was the most common pathogen of late-onset sepsis (LOS) in neonatal intensive care units (NICUs), there haves been scanty reports on molecular epidemiology of S. epidermidis isolates from infants stayed in NICU and on correlation of molecular characteristics with clinical features in these infants. METHODS: We collected and characterized S. epidermidis bloodstream isolates from infants hospitalized in NICU of a medical center in Taiwan between 2018 and 2020. Medical records of these infants were retrospectively reviewed. RESULTS: A total of 107 isolates identified from 78 episodes of bacteremia in 75 infants were included for analysis. Of the 78 isolates (episodes), 24 pulsotypes, 11 sequence types (STs), and 5 types of staphylococcal chromosomal cassette (type I-V) were identified. ST59 and its single locus variant ST1124 (37.2%) comprised the most common strain, followed by ST35 (14.1%), ST2 (11.5%), and ST89 (10.3%). All but 5 isolates (73/78, 93.6%) belonged to clonal complex (CC) 2. Comparing infants infected with genetically different strains, the patients with underlying immune disease were significantly associated with ST2 infection (P = 0.021), while no statistically significant differences were found in terms of clinical and laboratory characteristics. Only 3.8% of the isolates were susceptible to oxacillin. CONCLUSIONS: More than 90% of S. epidermidis bloodstream isolates from infants in NICU in Taiwan were resistant to oxacillin. Though diverse, more than 90% of the isolates (episodes) belonged to CC2. No statistically significant differences were found in terms of clinical characteristics among the infants infected with genetically different strains.

Respiratory outcomes in preterm infants following intravitreal bevacizumab for retinopathy of prematurity-a 10-year matched case study.

OBJECTIVES: To evaluate respiratory outcomes in preterm infants with retinopathy of prematurity (ROP) following intravitreal bevacizumab injection (IVB). METHODS: This single-centre study enroled preterm infants with a gestational age (GA) < 34 weeks or a birth weight (BW) < 1500 g with bilateral type 1 ROP who received a single IVB, and a treatment-free control group matched by GA, postmenstrual age, and respiratory status at the time of the IVB. The primary outcome was serial respiratory changes in mean airway pressure (MAP), fraction of inspired oxygen (FiO2), and respiratory severity score (RSS, MAP x FiO2) during the 28-day post-IVB/matching period and overall respiratory improvement at day 28 and at discharge. The duration of supplemental oxygen therapy following IVB/matching was documented. RESULTS: A total of 5578 infants were included. Seventy-eight infants were enroled in the IVB group, and another 78 infants were matched as the control group. Both groups had downward trends in the MAP, FiO2, and RSS over the study period (all P < 0.001), but there were no between-group differences in these measures. The percentage of overall respiratory improvement was similar between the IVB and control groups, so was the duration of invasive and in-hospital oxygen ventilation. A lower percentage of oxygen dependence at discharge in the IVB group (P = 0.03) remained significant after adjusting for GA and BW. CONCLUSIONS: This is a matched case study to evaluate respiratory outcomes in preterm infants following IVB for ROP. We found that the IVBs did not compromise respiratory outcomes in preterm infants during the 28-day post-IVB period and at discharge.

Outcomes of and factors associated with the development of bronchopulmonary dysplasia with pulmonary hypertension in very low birth weight infants: A retrospective study in a medical center.

Introduction: Bronchopulmonary dysplasia (BPD) with pulmonary hypertension (PH) leads to increased morbidity and mortality in extremely preterm infants. Recent studies have analyzed factors associated with development of PH in BPD; however, this research remains inconclusive, and controversy exists regarding the correlation between BPD and PH. This study aimed to investigate potential associated factors, clinical characteristics, and outcomes of BPD with pulmonary hypertension in very low birth weight (VLBW) preterm infants. Methods: We conducted a retrospective study, reviewing the records of infants with gestational age (GA) <32 weeks and birth weight <1,500 g admitted to a tertiary neonatal intensive care unit between January 2020 and October 2021 who were diagnosed with moderate to severe BPD. Echocardiogram was performed at the postmenstrual age of 36 weeks or before discharge. The diagnosis of PH was based on the findings of echocardiogram. Prenatal and postnatal characteristics, demographic data, treatment details, and outcomes were collected and analyzed. Results: A total of 139 VLBW infants with BPD were enrolled and divided into a PH group (n = 25) and a non-PH group (n = 114). The mean GA was 27.3 ± 2.3 weeks and the mean birth weight of infants with BPD was 927.3 ± 293.3 g. A multivariate logistic regression model revealed that a high positive end-expiratory pressure (PEEP) setting (OR: 2.105; 95% CI: 1.472-3.011; p < 0.001) in established BPD and surgical closure of patent ductus arteriosus (PDA; OR: 6.273; 95% CI: 1.574-24.977; p = 0.009) were associated with BPD-PH. Neonates with BPD who developed pulmonary hypertension remained hospitalized for longer (p < 0.001), received invasive mechanical ventilation support for longer (p < 0.001), had a higher incidence of retinopathy of prematurity (ROP; OR: 4.201; 95% CI: 1.561-11.304; p = 0.003), were more likely to require oxygen support at discharge (OR: 5.600; 95% CI: 2.175-14.416; p < 0.001), and were more likely to undergo tracheostomy (OR: 35.368; 95% CI: 4.03-310.43; p < 0.001). Conclusion: PDA ligation and a higher PEEP setting were associated with BPD-PH in our cohort study. Compared with VLBW infants with BPD but without PH, infants with BPD and PH were hospitalized for longer, and also had a higher incidence of oxygen support after discharge, ROP, and tracheostomy.

Systemic Cytokines in Retinopathy of Prematurity.

Retinopathy of prematurity (ROP), a vasoproliferative vitreoretinal disorder, is the leading cause of childhood blindness worldwide. Although angiogenic pathways have been the main focus, cytokine-mediated inflammation is also involved in ROP etiology. Herein, we illustrate the characteristics and actions of all cytokines involved in ROP pathogenesis. The two-phase (vaso-obliteration followed by vasoproliferation) theory outlines the evaluation of cytokines in a time-dependent manner. Levels of cytokines may even differ between the blood and the vitreous. Data from animal models of oxygen-induced retinopathy are also valuable. Although conventional cryotherapy and laser photocoagulation are well established and anti-vascular endothelial growth factor agents are available, less destructive novel therapeutics that can precisely target the signaling pathways are required. Linking the cytokines involved in ROP to other maternal and neonatal diseases and conditions provides insights into the management of ROP. Suppressing disordered retinal angiogenesis via the modulation of hypoxia-inducible factor, supplementation of insulin-like growth factor (IGF)-1/IGF-binding protein 3 complex, erythropoietin, and its derivatives, polyunsaturated fatty acids, and inhibition of secretogranin III have attracted the attention of researchers. Recently, gut microbiota modulation, non-coding RNAs, and gene therapies have shown promise in regulating ROP. These emerging therapeutics can be used to treat preterm infants with ROP.

Neurodevelopmental Outcomes for Retinopathy of Prematurity: A Taiwan Premature Infant Follow-up Network Database Study.

PURPOSE: To evaluate the neurodevelopmental outcomes in premature infants who received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections to treat retinopathy of prematurity (ROP). DESIGN: Retrospective cohort study. METHODS: This study was conducted using the database from the Taiwan Premature Infant Follow-up Network. Demographic data, systemic risk factors, ROP status, and neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) were collected. Patients were divided into 4 groups: prematurity without ROP, ROP without treatment, ROP with laser treatment, and ROP with intravitreal anti-VEGF treatment. A generalized estimating equation was used for analyzing repeated measurements of Bayley-III at the corrected ages of 6, 12, and 24 months. RESULTS: A total of 2090 patients with a mean gestational age of 31.2 weeks were included. The Bayley-III composite scores of patients with ROP treated with anti-VEGF were comparable to those of patients with ROP without treatment (cognitive: P = .491; language: P = .201; motor: P = .151) and premature patients without ROP (cognitive: P = .985; language: P = .452; motor: P = .169) after adjusting for confounders. Patients with ROP treated with laser photocoagulation exhibited poorer cognitive composite scores than did those without treatment (P < .001), premature patients without ROP (P < .001), and those treated with anti-VEGF (P < .001), but they had similar language and motor composite scores. CONCLUSIONS: Intravitreal anti-VEGF treatment for ROP was not associated with adverse neurodevelopment in premature infants. Further studies are needed to determine whether general anesthesia or sedation used in laser treatment for ROP has significant impacts on neurodevelopmental outcomes.

Clonal Complex 12 Serotype Ib Streptococcus agalactiae Strain Causing Complicated Sepsis in Neonates: Clinical Features and Genetic Characteristics.

Streptococcus agalactiae (group B Streptococcus [GBS]) is well known to cause serious diseases in infants. A serotype Ib GBS strain has recently emerged and become prevalent in Southeast Asia. We aimed to investigate the clinical and genetic characteristics of this strain. All neonates with invasive GBS diseases from a tertiary-level medical center in Taiwan between 2003 and 2020 were analyzed. The capsule serotyping, multilocus sequence typing, and antimicrobial resistance analyses were performed on all the invasive GBS isolates, and whole-genome sequencing (WGS) was performed specifically on the type Ib GBS strain. A total of 188 neonates with invasive GBS disease during the study period were identified. The type Ib GBS strain accounted for 7.4% (n = 14) of neonatal GBS invasive diseases. Almost all type Ib GBS isolates belonged to sequence type 12 (13/14, 92.9%) and clonal complex 12. Neonates with type Ib GBS disease had a significantly higher rate of complicated sepsis (10/14, 71.4%; P < 0.05) and sepsis-attributable mortality (6/14, 42.9%; P < 0.05). Additionally, type Ib GBS isolates had significantly higher rates of resistance to erythromycin and clindamycin (both 100%; P < 0.05) than other GBS serotypes. WGS revealed the presence of an ~75-kb integrative and conjugative element, ICESag37, comprising multiple antibiotic resistance and virulence genes, and PI-1 plus PI-2a were noted in all type Ib serotype 12 (ST12) GBS isolates; these isolates may be responsible for its high invasiveness and antimicrobial resistance rates. The genomic characteristics of the type Ib clonal complex 12 (CC12) GBS strain may account for the high illness severity associated with this strain and its antibiotic resistance. Continuous monitoring and advanced strategies to control the spread of type Ib CC12 GBS should be considered. IMPORTANCE A type Ib ST12 GBS strain is not a common isolate in neonatal invasive diseases and has been ignored for a long time. However, the recent literature and our data showed that such a GBS strain is associated with a significantly higher risk of severe sepsis, higher illness severity, and a significantly higher rate of sepsis-attributable mortality. This study found a novel gene cluster, including the presence of ICESag37 and specific pilus genes, carrying multiple antimicrobial resistance and virulence genes, which may be responsible for the clinical characteristics. Because of the higher mortality and severity of illness, we concluded that continuous monitoring of the type Ib ST12 GBS strain is warranted in the future.

Platelet parameters and the association with morbidity and mortality in Preterm Infants.

BACKGROUND: There is growing recognition of the role of platelets in inflammation and immune responses, and platelets have been associated with various cardiovascular diseases. It is also known that neonatal morbidities are related to overall platelet activity, and platelet parameters may have the potential to predict morbidities and mortality in preterm infants. This study aimed to assess the initial platelet parameters and the association with major morbidities and mortality in preterm neonates. METHODS: We retrospectively reviewed data from very preterm neonates with a gestational age (GA) <32 weeks who were admitted between June 2020 and May 2021 for platelet parameters (counts, mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (platelet counts x MPV/10000(%)) at birth. Major morbidities included early- onset sepsis (EOS) ≤3 days after birth, severe intraventricular hemorrhage (IVH) grade ≥3, and early or overall mortality. RESULTS: A total of 197 very preterm neonates were studied. Their mean (±SD) GA was 28.0 ± 2.4 weeks, birth weight was 990 ± 293 g, platelet counts were 245 ± 81 x1000/µL, MPV was 10.0 ± 0.7 fl, PDW was 11.0 ± 1.6 fl, and plateletcrit was 0.24 ± 0.08%. MPV had a weak negative correlation with both GA (r = -0.234, p = 0.001) and BW (r = -0.343, p <0.001). A lower plateletcrit was associated with EOS (0.14 (0.04-0.22) % vs. 0.23 (0.19-0.30) %, p = 0.027), severe IVH ≤7 days after birth (0.18 (0.14-0.27) % vs. 0.23 (0.20-0.30) %, p = 0.022), and early and overall mortality (0.15 (0.20-0.30) % vs. 0.23 (0.20-0.30) %, p = 0.049; 0.20 ± 0.09 % vs. 0.25 ± 0.07 %, p = 0.008). CONCLUSION: A lower plateletcrit within 24 hours of birth was associated with EOS, severe IVH ≤7 days after birth, and first-week and overall mortality in very preterm neonates.

Clinical Characteristics of Infants with Symptomatic Congenital and Postnatal Cytomegalovirus Infection-An 11-Year Multicenter Cohort Study in Taiwan.

(1) Background: Cytomegalovirus (CMV) infection is a prevalent viral disease among infants. The prevalence typically ranges from 0.2% to 2.4% among all newborns. There are limited data regarding the demographic characteristics of infants with symptomatic CMV infections. (2) Methods: In this retrospective cohort study using the Chang Gung Memorial Hospital multicenter database, infants with CMV infection determined by a positive urine culture, positive blood polymerase chain reaction assay or positive immunoglobulin M result for CMV from 2011 through 2021 were included. Clinical characteristics at initial diagnosis, management and outcomes were investigated. Congenital CMV (cCMV) infection is diagnosed within three weeks after birth; postnatal CMV (pCMV) is diagnosed when CMV is detected after the first 3 weeks of life. (3) Results: Among the 505 CMV-infected infants identified, 272 were included in the analysis. According to the age at initial presentation, 21 infants had cCMV infection and 251 had pCMV infection. Higher incidences of prematurity and being small for gestational age and a lower Z score for weight at diagnosis were observed in the cCMV group. While thrombocytopenia (61.9%) was the leading presentation in the cCMV group, hepatitis (59.8%) and prolonged jaundice (21.9%) were more common in the pCMV group. (4) Conclusions: Utilizing an 11-year multicenter database, we demonstrated the characteristics of infants with CMV infection in Taiwan and highlighted the demographic disparities and differing symptoms between the cCMV and pCMV groups. These findings emphasize the necessity for future research to refine screening policies, explore treatment options, and establish follow-up protocols for affected infants.

Association of serum levels of inflammatory cytokines with retinopathy of prematurity in preterm infants.

Introduction: Retinopathy of prematurity (ROP) is a retinal vascular developmental disease associated with risks factors such as supplementary oxygen use or low birth weight/early gestational age. Multiple studies have reported associations between ROP and systemic inflammation. In this study, we investigated serum cytokines associated with ROP development and severity and assessed their applicability as potential biomarkers of ROP. Methods: This prospective study was conducted at an institutional referral center between 2019 and 2021. To measure the serum levels of 40 inflammatory cytokines in eligible premature patients, we collected their serum samples during the enrollment of patients or the intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents and after 2 and 4 weeks. Results: Fifty patients were enrolled. In patients with type 1 ROP who received anti-VEGF agents (n = 22), the levels of serum intercellular adhesion molecule-1 decreased significantly (p < 0.05) at 4 weeks compared with the baseline level, whereas those of serum granulocyte-macrophage colony-stimulating factor increased significantly (p < 0.05). In patients with ROP who did not require any treatment (n = 14), no significant change was noted in the level of any of the 40 inflammatory cytokines. In control infants without ROP (n = 14), the serum levels of tumor necrosis factor-α, interleukin (IL)-15, and IL-12p40 increased significantly (p < 0.05) at 4 weeks. The changes in the levels of serum inflammatory cytokines did not vary significantly among the aforementioned three groups. A generalized estimating equation indicated that zone 1 ROP, stage 3 ROP, older postmenstrual age, respiratory distress syndrome, necrotizing enterocolitis, and sepsis were associated with the changes in serum cytokine levels. Conclusions: Although significant changes (compared with baseline) were observed in the serum levels of certain inflammatory cytokines in patients with type 1 ROP and infants without ROP, no significant difference in cytokine level fluctuations were noted among the three groups. Changes in serum inflammatory cytokine levels may not predict ROP development or severity. Additional comprehensive studies are warranted to establish their definitive role and significance in ROP, emphasizing the need for continued research in this area.

Effects of Probiotics on Gut Microbiomes of Extremely Preterm Infants in the Neonatal Intensive Care Unit: A Prospective Cohort Study.

Background: Probiotics have been previously reported to reduce the incidence of necrotizing enterocolitis (NEC) in extremely preterm infants, but the mechanisms by which the probiotics work remain unknown. We aimed to investigate the effects of probiotics on the gut microbiota of extremely preterm infants. Methods: A prospective cohort study was conducted on 120 extremely preterm neonates (gestational age ≤ 28 weeks) between August 2019 and December 2021. All neonates were divided into the study (receiving probiotics) and the control (no probiotics) groups. Multivariate logistic regression analysis was performed to investigate the significantly different compositions of gut microbiota between these two groups. The effects of probiotics on the occurrence of NEC and late-onset sepsis were also investigated. Results: An increased abundance of Lactobacillus was noted in neonates who received the probiotics (AOR 4.33; 95% CI, 1.89-9.96, p = 0.009) when compared with the control group. Subjects in the probiotic group had significantly fewer days of total parenteral nutrition (median [interquartile range, IQR]) 29.0 (26.8-35.0) versus 35.5 (27.8-45.0), p = 0.004) than those in the control group. The probiotic group had a significantly lower rate of late-onset sepsis than the control group (47.1% versus 70.0%, p = 0.015), but the rate of NEC, duration of hospitalization and the final in-hospital mortality rates were comparable between these two groups. Conclusions: Probiotic supplementation of extremely preterm infants soon after the initiation of feeding increased the abundance of Lactobacillus. Probiotics may reduce the risk of late-onset sepsis, but further randomized controlled trials are warranted in the future.