Clinical Risk Factors for Retinopathy of Prematurity Reactivation after Intravitreal Antivascular Endothelial Growth Factor Injection.

OBJECTIVE: To assess the rate and risk factors for reactivation of retinopathy of prematurity (ROP) after intravitreal injection (IVI) of antivascular endothelial growth factor (VEGF) agents. STUDY DESIGN: Infants who received IVI therapy between 2017 and 2022 were enrolled and divided into 2 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 = .008) for reactivation. Other risk factors included infants with periventricular leukomalacia (OR 13.8, P = .003), patent ductus arteriosus ligation (OR 10.7, P = .032), and infants who still required invasive mechanical ventilation on the day of IVI therapy (OR 7.0, P = .018). CONCLUSIONS: All anti-VEGF agents carry a risk of ROP reactivation, with the risk being greater 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.

TEN-YEAR EPIDEMIOLOGY OF RETINOPATHY OF PREMATURITY TREATMENT IN TAIWAN.

PURPOSE: To understand the epidemiology of retinopathy of prematurity (ROP) requiring treatment in Taiwan from 2002 to 2011. METHODS: This retrospective cross-sectional study enrolled 11,180 premature patients with a length of stay >28 days who survived during hospitalization. The incidence of the first ROP treatment was analyzed. RESULTS: Among ROP patients (n = 4,096), 6.5% (n = 265) received treatment. The most frequently performed treatment was laser administration (n = 199), followed by intravitreal anti-vascular endothelial growth factor (VEGF) injection (n = 38), scleral buckle or pars plana vitrectomy (n = 14), and cryotherapy (n = 14). The incidence of ROP requiring treatment increased during the study period, as did the use of intravitreal anti-VEGF injection. Shifts in the treatment modality from cryotherapy and scleral buckle/pars plana vitrectomy to laser treatment after 2003 and from laser treatment to intravitreal anti-VEGF injection after 2010 were observed. CONCLUSION: In Taiwan, the incidence of the use of intravitreal anti-VEGF injection for treating ROP increased between 2002 and 2011. Laser treatment was less frequently used than intravitreal anti-VEGF injection in 2011.

Baseline cardiac output and its alterations during ibuprofen treatment for patent ductus arteriosus in preterm infants.

BACKGROUND: Infants with hemodynamically significant patent ductus arteriosus (PDA) may physiologically compensate with a supranormal cardiac output (CO). As such, a supranormal CO may be a surrogate marker for a significant PDA or indicate a failed response to PDA closure by ibuprofen. Electrical cardiometry (EC) is an impedance-based monitor that can continuously and non-invasively assess CO (COEC). We aimed to trend COEC through ibuprofen treatment for PDA in preterm infants. METHODS: We reviewed our database of preterm infants receiving ibuprofen for PDA closure. Response to ibuprofen was defined as no ductal flow in echocardiography ≤24 h after treatment. Responders were compared with gestational age (GA) and postnatal age matched non-responders and their trends of COEC were compared. Both groups' baseline COEC were further compared to the reference infants without PDA. RESULTS: Eighteen infants (9 responders and 9 non-responders) with median (interquatile range) GA 27.5 (26.6-28.6) weeks, birthweight 1038 (854-1218) g and age 3.5 (3.0-4.0) days were studied. There were positive correlations between COEC and ductal diameter and left atrium/ aortic root ratio (r = 0.521 and 0.374, p < 0.001, respectively). Both responders and non-responders had significantly higher baseline COEC than the reference. Although there was no significant within-subject alteration of COEC during ibuprofen treatment, there was a between-subject difference indicating non-responders had generally higher COEC. CONCLUSIONS: The changes of COEC during pharmacological closure of PDA is less drastic compared to surgical closure. Infants with PDA had higher baseline COEC compared to those without PDA, and non-responders had higher COEC especially at baseline compared to responders.

Changes in systemic vascular endothelial growth factor levels after intravitreal injection of aflibercept in infants with retinopathy of prematurity.

BACKGROUND: To investigate the levels of VEGF in the systemic circulation of patients with type 1 ROP who received intravitreal injections of 1 mg (0.025 mL) aflibercept (IVA) or 0.625 mg (0.025 mL) bevacizumab (IVB). METHODS: Patients who had type 1 ROP and received either IVA or IVB were enrolled in this prospective study. Serum and plasma samples were collected prior to and up to 12 weeks after IVB or IVA treatment. The serum and plasma VEGF levels were measured using enzyme-linked immunosorbent assays (ELISAs), and the platelet levels in the blood were also quantified. The serum and plasma levels of VEGF, as well as the ratio of VEGF to platelet count (VEGF/PLT) were measured prior to and up to 12 weeks after anti-VEGF treatment. RESULTS: In total, 14 patients with type 1 ROP were enrolled in this study; five patients received IVA, and nine patients received IVB. Following either IVA or IVB treatment, all the eyes (100%) showed complete resolution of ROP-induced abnormal neovascularization and presented continued vascularization toward the peripheral retina. Compared to baseline, the serum VEGF levels were significantly reduced in the ROP patients up to 12 weeks after either IVA or IVB treatments (all P < 0.05). At 2, 4, and 8 weeks after intravitreal injection, the serum VEGF levels were more suppressed in the IVB group than in the IVA group (P = 0.039, P = 0.004, and P = 0.003, respectively). The serum VEGF/PLT ratio after IVA or IVB showed similar reductions and trends as the serum VEGF data. Changes in the plasma VEGF levels could not be properly assessed because some of the samples had VEGF levels below the detection limit of the ELISA. CONCLUSIONS: Serum VEGF levels and the VEGF/PLT ratio in patients with type 1 ROP were suppressed for 3 months after treatment with either IVA or IVB, but the suppression of systemic VEGF was more pronounced in patients treated with IVB than those treated with IVA.

Incidence, clinical features, and implications on outcomes of neonatal late-onset sepsis with concurrent infectious focus.

BACKGROUND: Neonatal bloodstream infection (BSI) is the most important cause of morbidity and mortality in the neonatal intensive care unit (NICU). Although most neonatal BSIs are primary bacteremia, some are associated with a focus of infection. This distinction is not well characterized. METHODS: All patients with neonatal late-onset sepsis (LOS) between January 2006 and December 2013 were enrolled. LOS was categorized as a BSI with a concurrent focus of infection if LOS occurred before or within 24 h after the diagnosis of a specific infectious entity, and as "primary bacteremia" if no concurrent focus of infection was identified. Data concerning demographics, hospital course, microbiology, and outcomes were compared via univariate and multivariate analyses. RESULTS: Of 948 episodes of neonatal LOS, 781 (82.4%) were primary bacteremia, whereas 167 (17.6%) were associated with a known focus of infection, including meningitis (n = 51, 5.4%), ventilator-associated pneumonia (VAP) (n = 36, 3.8%), catheter-related bloodstream infections (n = 57, 6.0%), and necrotizing enterocolitis (NEC) (n = 21, 2.2%). The majority of NEC-associated BSIs were caused by gram-negative bacilli (85.7%). Group B streptococcus accounted for nearly one-third of all meningitis cases (29.4%). Although sepsis-attributable mortality was comparable between primary bacteremia and neonatal BSIs with a focus of infection, neonatal BSIs with meningitis, VAP, and NEC had significantly higher rates of infectious complications. The independent risk factors of sepsis-attributable mortality were infectious complications (Odds ratio [OR] 6.98; 95% confidence interval [CI] 3.64-13.39, P < 0.001); history of one or more than one previous episode(s) of BSI (OR 2.40 and 7.40; 95% CI 1.21-4.74 and 3.70-14.78, P = 0.012 and <0.001, respectively); and underlying secondary pulmonary hypertension in neonates (OR 4.77; 95% CI 1.91-11.96, P = 0.001). CONCLUSIONS: A considerable proportion of neonatal LOS can be associated with known infectious foci in the NICU. The microbiologic etiology of neonatal LOS with a concurrent focus of infection is significantly different from that of primary bacteremia. Neonatal BSIs with concurrent meningitis, VAP, or NEC are significantly more likely to have infectious complications. This association independently leads to sepsis-attributable mortality.

SERUM VASCULAR ENDOTHELIAL GROWTH FACTOR AFTER BEVACIZUMAB OR RANIBIZUMAB TREATMENT FOR RETINOPATHY OF PREMATURITY.

PURPOSE: To investigate vascular endothelial growth factor (VEGF) levels in the systemic circulation after intravitreal injections of bevacizumab (IVB) or ranibizumab (IVR) in patients with Type 1 retinopathy of prematurity (ROP). METHODS: Patients who had Type 1 ROP and received IVB or IVR were enrolled. Serum samples were collected before and up to 12 weeks after IVB or IVR treatment. The main outcome measurements were serum levels of VEGF up to 12 weeks after anti-VEGF treatment. RESULTS: In total, 10 patients with Type 1 ROP were enrolled in this study. All the eyes had complete resolution of abnormal neovascularization of ROP after IVB or IVR. In the direct comparison of IVB with IVR, serum VEGF was found to be suppressed more in patients with Type 1 ROP who received IVB treatment, compared with those who received IVR treatment (P = 0.01, P = 0.03, and P = 0.03, respectively, 2, 4, and 8 weeks after intravitreal injection). CONCLUSION: Serum VEGF levels in patients with Type 1 ROP were suppressed for 2 months after treatment with IVB, and VEGF levels were less affected after IVR treatment. Further studies are warranted to investigate the long-term effects of VEGF changes in ROP patients.

Intra-observer reliability of Prechtl's method for the qualitative assessment of general movements in Taiwanese infants.

[Purpose] The aim of this study was to examine the intra-observer reliability for Prechtl's General Movements Assessment in Taiwanese infants. This includes the global General Movements Assessment, the Optimality List for Preterm General Movements and Writhing Movements, and the Assessment of Motor Repertoire-3 to 5 Months. [Subjects and Methods] Fifty-nine videos of 37 infants were observed and rated by one physical therapist twice. [Results] The intra-observer reliability ranged from good to very good for the global General Movements Assessment. The overall intra-observer reliabilities for the total score of the Optimality List from preterm up to postmenstrual age 46 weeks and the total score of the Assessment of Motor Repertoire for postmenstrual age 49 to 60 weeks were both good. [Conclusion] The results suggest that the intra-observer reliability of a certified physical therapist was satisfactory for Prechtl's method in Taiwanese infants.

Characteristics of neonates with culture-proven bloodstream infection who have low levels of C-reactive protein (≦10 mg/L).

BACKGROUND: Elevated C-reactive protein (CRP) level is widely used in clinical practice as a marker to distinguish between neonates with or without sepsis. However, some neonates with bacteremia have a CRP level within the normal range and they are not well characterized. METHODS: All episodes of neonatal culture-proven bloodstream infections (BSIs) between July 2004 and June 2012 were enrolled. Patients characteristics were compared for three CRP groups (low, ≤ 10 mg/L; intermediate, 11-100 mg/L; and high, > 100 mg/L) using the Chi-square test and one-way ANOVA. The sepsis-attributable mortality rates were compared using logistic regression analyses. RESULTS: Of 986 episodes of neonatal BSI, 247 (25.1 %) had CRP ≤10 mg/L at the onset of clinical sepsis. In the low CRP group, patients had lower gestational age and birth weight, and an earlier occurrence of BSI. Patients with underlying gastrointestinal pathology, renal disorders, cholestasis, and pulmonary hypertension had a non-significant elevated CRP level at the onset of sepsis. In the blood culture of the low CRP group, coagulase-negative staphylococci (CoNS) were relatively more common (55.9 %, p < 0.001) than the other two groups, although one-fourth were infected with gram-negative bacilli (19.0 %), fungi (2.8 %), or polymicrobial pathogens (3.6 %). Of the BSIs with initial low CRP, 29.1 % were treated with inadequate antibiotics, 13.0 % progressed to septic shock, and 5.3 % had infectious complications. The sepsis-attributable mortality rate was lower in the low CRP group (4.9 %) than in the high CRP group (13.6 %). CONCLUSIONS: A considerable proportion of neonatal BSIs had a normal or low initial CRP level (≤10 mg/L), which was more likely to occur in low birth weight or extremely preterm infants, those with earlier onset of sepsis, and those infected with CoNS. Plasma CRP level should not be used to rule out severe culture-proven sepsis or guide the empirical choice of antibiotics.

Hemodynamic alterations recorded by electrical cardiometry during ligation of ductus arteriosus in preterm infants.

UNLABELLED: This is a prospective study using non-invasive electrical cardiometry to measure hemodynamic changes during surgical ligation of patent ductus arteriosus (PDA) in very low birth weight (VLBW, ≤1500 g) infants. The aims of this study were to examine hemodynamic aberration caused by abrupt closure of a ductal shunting and to define factors that affect hemodynamic changes. Simultaneous measurements of heart rate (HR), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR) were collected at ten time points: 1 h prior to anesthesia, at the beginning of anesthesia, starting of surgery, immediately after PDA being ligated, and 1 h followed by 6, 12, 18, 24, and 48 h after the surgery. Thirty infants with gestational age of 27.7 ± 2.0 weeks and birth weight of 929 ± 280 g were studied. Upon sudden termination of ductal shunting, there was a significant decline in CO to 73 % of presurgery baseline. The deterioration in CO was associated with a decreased SV rather than HR. At the same time, there was an increase of SVR following ductal ligation. Magnitude of CO and SV reduction were higher in smaller infants (≤1 kg), and recovery was to a lesser degree in infants with more severe PDA. CONCLUSION: Reduced stroke volume and elevated vascular resistance contribute to the major hemodynamic aberrations in VLBW infants receiving PDA ligation surgery.

Thermal Blanket to Improve Thermoregulation in Preterm Infants: A Randomized Controlled Trial.

OBJECTIVE: To determine the effectiveness of temperature-controlled thermal blanket as additional thermoprotection. DESIGN: Randomized controlled prospective study. SETTING: Single-center tertiary neonatal unit. PATIENTS: Inborn very low-birth-weight (< 1,500 g) infants. INTERVENTIONS: Infants were prospectively assigned to thermal blanket group or control at 1:1 ratio. Additional to radiant warmers, a prewarmed blanket of Blanketrol II (Cincinnati Sub-Zero Products, Cincinnati, OH) was applied as mattress for thermal blanket group. The outcomes included temperature and blood pressure changes. We defined hypothermia as temperature less than 36°C and hypotension as mean arterial pressure less than index infant's gestational age in weeks. MEASUREMENTS AND MAIN RESULT: Total 80 very low-birth-weight infants were allocated, and there was no between-group demographic dissimilarity. At 30th minute, fewer infants in thermal blanket group were hypothermic (43% vs 68%; p = 0.025). These infants had significantly lower prevalence of hypotension, which associated with less dopamine use in the first 6 hours of life (25% vs 50%; p = 0.016). There was no hyperthermia more than 37.5°C episode. CONCLUSIONS: By using thermal blanket to provide additional thermal protection for very low-birth-weight infants, the degree of hypothermia was improved, which related to fewer hypotensive cases and less dopamine usage.

Natural history of retinopathy of prematurity: two-year outcomes of a prospective study.

PURPOSE: To investigate the 2-year outcomes of the natural history of retinopathy of prematurity (ROP) in Taiwan. METHODS: A prospective study was conducted at two tertiary medical centers. Premature infants were screened and examined for ROP. The postmenstrual ages of developing each stage of ROP and the associated risk factors were recorded. RESULTS: A total of 698 infants were included. The incidences of ROP and treatment-requiring ROP in all patients with ROP were 29.7% and 37.2%. When only including patients with birth weight of 1,250 g or less, the incidences were 62.2% and 39.1%, respectively. In patients with ROP with birth weight over 1,250 g, 25% of them developed treatment-requiring ROP. The median postmenstrual ages for the development of Stage 1, Stage 2, and Type 1 ROP were 33.0, 34.0, and 34.7 weeks, respectively. Gestational age at birth and birth weight were the most important factors associated with treatment-requiring ROP (hazard ratios of 0.3 and 0.6). CONCLUSION: Our hospital-based study reveals an earlier postmenstrual age of developing ROP in this Asian population than in the Early Treatment for ROP study. Infants with birth weight over 1,250 g could still develop treatment-requiring ROP. Suboptimal oxygen control, different genetic dispositions among different races, inconsistencies in ROP diagnosis, and earlier screening might account for such a phenomenon.

Stool fatty acid soaps, stool consistency and gastrointestinal tolerance in term infants fed infant formulas containing high sn-2 palmitate with or without oligofructose: a double-blind, randomized clinical trial.

BACKGROUND: Formula-fed (FF) infants often have harder stools and higher stool concentrations of fatty acid soaps compared to breastfed infants. Feeding high sn-2 palmitate or the prebiotic oligofructose (OF) may soften stools, reduce stool soaps, and decrease fecal calcium loss. METHODS: We investigated the effect of high sn-2 palmitate alone and in combination with OF on stool palmitate soap, total soap and calcium concentrations, stool consistency, gastrointestinal (GI) tolerance, anthropometrics, and hydration in FF infants. This double-blind trial randomized 165 healthy term infants 25-45 days old to receive Control formula (n = 54), formula containing high sn-2 palmitate (sn-2; n = 56), or formula containing high sn-2 palmitate plus 3 g/L OF (sn-2+OF; n = 55). A non-randomized human milk (HM)-fed group was also included (n = 55). The primary endpoint, stool composition, was determined after 28 days of feeding, and was assessed using ANOVA accompanied by pairwise comparisons. Stool consistency, GI tolerance and hydration were assessed at baseline, day 14 (GI tolerance only) and day 28. RESULTS: Infants fed sn-2 had lower stool palmitate soaps compared to Control (P = 0.0028); while those fed sn-2+OF had reduced stool palmitate soaps compared to both Control and sn-2 (both P < 0.0001). Stool total soaps and calcium were lower in the sn-2+OF group than either Control (P < 0.0001) or sn-2 (P < 0.0001). The HM-fed group had lower stool palmitate soaps, total soaps and calcium (P < 0.0001 for each comparison) than all FF groups. The stool consistency score of the sn-2+OF group was lower than Control and sn-2 (P < 0.0001), but higher than the HM-fed group (P < 0.0001). GI tolerance was similar and anthropometric z-scores were <0.2 SD from the WHO growth standards in all groups, while urinary hydration markers were within normal range for all FF infants. CONCLUSIONS: Increasing sn-2 palmitate in infant formula reduces stool palmitate soaps. A combination of high sn-2 palmitate and OF reduces stool palmitate soaps, total soaps and calcium, while promoting softer stools. TRIAL REGISTRATION: This study was registered on http://www.clinicaltrials.gov: number NCT02031003.

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.

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.

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.

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.

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.

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.

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.

Diaphragmatic paralysis among very low birth weight infants following ligation for patent ductus arteriosus.

Management of diaphragmatic paralysis (DP) among newborn infants remains controversial, especially for very low birth weight (VLBW) infants following ligation for patent ductus arteriosus (PDA). This study aimed to characterize the impact of DP after PDA ligation among VLBW infants. Clinical characteristics of DP cases treated with either diaphragmatic plication or conservative methods were described as well. The medical records of VLBW infants who underwent PDA ligation in Chang Gung Memorial Hospital between January 2000 and December 2011 were retrospectively reviewed, and DP was suspected if postligation chest X-rays showed an elevation of the left diaphragm as confirmed by a chest ultrasonograph. For each DP case, three other infants that received PDA ligation with proximate birth dates and who were closely matched in terms of gestational age (±1 week) and birth weight (±10 %) were selected as the control group. A total of eight preterm infants were diagnosed as having DP and 24 infants were selected as the control group. The affected infants usually presented with respiratory distress and extubation failure. The study demonstrated that, among our patient population, DP was associated with a significantly longer duration of ventilator dependency (56.1 ± 16.0 vs. 29.8 ± 17.7 days, p = 0.001) and a higher incidence of severe bronchopulmonary dysplasia (87.5 vs. 23 %, p = 0.002). For selective infants with DP-related ventilatory failure after PDA ligation, surgical plication may facilitate extubation. Diaphragmatic paralysis should be evaluated carefully among VLBW infants receiving PDA ligation because of its adverse impact on ventilator dependency and correlation to a higher incidence of severe bronchopulmonary dysplasia.