Case Report: Neurally adjusted ventilatory assist as an effective rescue treatment for pulmonary interstitial emphysema in extremely low birth weight infants.

Pulmonary interstitial emphysema (PIE) is a complication observed in extremely low birth weight (ELBW) infants on mechanical ventilation. Despite various proposed therapeutic interventions, the success rates have shown inconsistency. Neurally adjusted ventilatory assist (NAVA) stands out as a novel respiratory support mode, offering lower pressure and tidal volume in comparison to conventional ventilation methods. In this case report, we present five ELBW infants with refractory PIE who were transitioned to NAVA ventilation. Following the switch to NAVA, all cases of PIE gradually resolved. In contrast to traditional modes, NAVA provided respiratory support with significantly lower fraction of inspired oxygen, reduced peak inspiratory pressure, diminished mean airway pressure, and decreased tidal volume within 7 days of NAVA utilization (p = 0.042, 0.043, 0.043, and 0.042, respectively). Consequently, we propose that NAVA could serve as a valuable rescue treatment for ELBW infants with PIE.

Analgesic Effect of Low-Level Laser Therapy before Heel Lance for Pain Management in Healthy Term Neonates: A Randomized Controlled Trial.

Currently, the prevention, assessment, and management of procedural pain in neonates continues to challenge clinicians and researchers. Objective. To investigate the analgesic effect of low-level laser therapy (LLLT) during heel lance compared to breast milk (BM) feeding in healthy term neonates. In this randomized controlled trial, healthy term neonates who underwent heel lance were randomly assigned to an LLLT or a BM group. The LLLT group received laser therapy to the heel lance site for 20 s before heel lance. The BM group received 5 mL expressed BM via a syringe before heel lance. The primary outcomes were behavioral responses. The secondary outcomes were physiological responses and levels of salivary cortisol and α-amylase. A total of 125 neonates were included, of whom 55 in the LLLT group and 59 in the BM group completed the study. There were no significant differences in latency to first cry and cry duration between the two groups. The squeeze time was significantly shorter in the LLLT group than in the BM group (p = 0.047). There were no significant differences in pain scores, heart rate, respiratory rate, oxygen saturation, and blood pressure before and after heel lance between the two groups. There were no significant differences in salivary cortisol and α-amylase levels in the LLLT group before and after heel lance; however, the differences were significant in the BM group. These findings suggest that the analgesic effect of LLLT is similar to that of BM during heel lance in healthy term neonates. LLLT has potential as an analgesic treatment.

Neurally adjusted ventilatory assist for rapid weaning in preterm infants.

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a new mode of subject-triggered ventilation. Experience with the use of NAVA in preterm infants is limited. This study compared the effects of invasive mechanical ventilation with NAVA to conventional intermittent mandatory ventilation (CIMV) in terms of reducing the duration of oxygen requirement and invasive ventilator support in preterm infants. METHODS: This was a prospective study. We enrolled infants of less than 32 weeks' gestation who were then randomized to receive either NAVA or CIMV support during hospitalization. We recorded and analyzed data on the maternal history during pregnancy, use of medications, neonatal data at admission, neonatal diseases, and respiratory support in the neonatal intensive care unit. RESULTS: There were 26 preterm infants in the NAVA group and 27 preterm infants in the CIMV group. Significantly fewer infants in the NAVA group received supplemental oxygen at 28 days of age (12 [46%] vs. 21 [78%], p = 0.0365), and they required significantly fewer days of invasive ventilator support: 7.73 (± 2.39) vs. 17.26 (± 3.65), p = 0.0343. CONCLUSIONS: Compared with CIMV, NAVA appears to allow for more rapid weaning from invasive ventilation and decreases the incidence of bronchopulmonary dysplasia, especially in preterm infants with severe respiratory distress syndrome treated with surfactants.

Neurally adjusted ventilatory assist in infants: A review article.

Neurally adjusted ventilatory assist (NAVA) and non-invasive (NIV)-NAVA are innovative modes of synchronized and proportional respiratory support. They can synchronize with the patients' breathing and promote patient comfort. Both techniques are increasingly being used these years, however experience with their use in newborns and premature infants in Taiwan is relatively few. Because increasing evidence supports the use of NAVA and NIV-NAVA in newborns and premature infants requiring respiratory assist to achieve better synchrony, the aim of this article is to discuss whether NAVA can provide better synchronization and comfort for ventilated newborns and premature babies. In a review of recent literature, we found that NAVA and NIV-NAVA appear to be superior to conventional invasive and non-invasive ventilation. Nevertheless, some of the benefits are controversial. For example, treatment failure in premature infants is common due to insufficient triggering of electrical activity of the diaphragm (EAdi) and frequent apnea, highlighting the differences between premature infants and adults in settings and titration. Further, we suggest how to adjust the settings of NAVA and NIV-NAVA in premature infants to reduce clinical adverse events and extubation failure. In addition to assist in the use of NAVA, EAdi can also serve as a continuous and real-time monitor of vital signs, assisting physicians in the administration of sedatives, evaluation of successful extubation, and as a reference for the patient's respiratory condition during special procedures.

The appropriate frequency of dressing for percutaneous central venous catheters in preventing catheter-related blood stream infection in NICU - A randomized controlled trial.

BACKGROUND: Complications of percutaneous central venous catheters (PCVCs) include catheter-related blood stream infection (CRBSI), occlusion, leakage, and phlebitis, which may lead to sepsis or prolonged hospitalization. The primary objective of this randomized controlled trial was to determine the appropriate frequency of dressing for percutaneous central venous catheters in preventing CRBSI, every week regularly vs. non-regularly, in premature neonates in NICU. METHODS: Patients in NICU requiring PCVCs from March 2019-May 2020 were enrolled. Enrolled patients were randomly assigned into 2 groups: regular dressing group (RD), for which dressings were changed every week regularly, or additionally when oozing was noticed; and non-regular dressing group (ND), for which dressings were changed only when oozing was visible. The incidence of CRBSI, occlusion, leakage, and phlebitis were compared between the two groups using the Chi-squared test. The incidence of catheter-related complications was defined as numbers of episodes per 1000 catheter-days. RESULTS: A total of 197 PCVCs were enrolled. The ND and RD groups had 99 and 98 PCVCs, respectively. The average CD interval was 9.3 days in ND group and 5.8 days in RD group. The incidence of CRBSI in RD group was 0‰, which was significantly lower than that of ND group, which was 2.0‰ (p = 0.048), but no significant differences were found between groups in the incidence of occlusion, leakage, and phlebitis of PCVCs. CONCLUSION: Regular dressing changes every week and when oozing occurs while maintaining the protocol of maximum sterile barrier precautions is the best method and frequency of dressings of PCVCs.

The role of ultrasonography for detecting tip location of percutaneous central venous catheters in neonates-a single-center, prospective cohort study.

BACKGROUND: Percutaneous central venous catheters (PCVCs) are used commonly and widely in the neonatal intensive care unit (NICU). Malposition of PCVCs may cause life-threatening complications and prolong hospitalization. In Taiwan, conventional chest-abdomen radiography (CXR) has been used widely and routinely for assessing tip location of PCVCs. Compared to ultrasonography (US), CXR cannot provide real-time assessment, and patients are exposed to radiation. Therefore, this study aimed to analyze the role of US in detecting PCVC tip location in the lower extremities. METHODS: Neonates who received PCVC insertion in the lower extremities in NICU from March 2019 to April 2020 were enrolled in this prospective cohort study. PCVC tip location was confirmed finally by conventional CXR after US examination and patients were included in the sono group; those not assessed by US formed the non-sono group. In addition, PCVCs inserted in 2018 for which tip location was evaluated only by CXR, were reviewed retrospectively and these cases were included in the non-sono group. Withdrawal rates between the two groups were analyzed using Chi-square test. RESULTS: The sono group included 166 neonates with PCVCs and 141 were in the non-sono group. Median gestational age at date of PCVC insertion was 33.21 and 32.71 weeks in sono and non-sono groups, respectively (p = 0.37). Withdrawal rates were 10.84% and 65.95% (p < 0.001) and duration for catheter location confirmation were 2-4.75 min and 75-247.25 min (p < 0.001), respectively. CONCLUSION: US provides more reliable images than conventional radiography alone for identifying PCVC tip locations in the lower extremities. It can effectively reduce catheter insertion duration, and was associated with fewer manipulations.

A novel method to detect bacterial infection in premature infants: Using a combination of inflammatory markers in blood and saliva.

BACKGROUND: Opportunistic infection leads to high morbidity and mortality in premature babies due to their immature immune system. Biomarkers in blood have been reported to detect bacterial infection in neonates. However, serial blood exams pose iatrogenic anemia in premature babies. Thus, this study aimed to identify cytokines in saliva, which can help to diagnose bacterial infection in premature babies via a non-invasive method. METHODS: Premature neonates were enrolled from Aug. 2012 to Feb. 2015 after completing informed consent. Babies with congenital anomalies, bronchopulmonary dysplasia, necrotizing enterocolitis and any surgical indicated diseases were excluded. Salivary samples collection and septic work-up were performed when bacterial infection was clinically suspected, as well as one week after antimicrobial treatment. The level of salivary cytokines was detected by MILLPLEX® MAP and analyzed by Mann-Whitney U test. RESULTS: There were 16 episodes of bacterial infection in 10 cases. Culture-positive group had significantly higher levels of salivary Interleukin (IL) 6, IL-8, macrophage inflammatory protein (MIP)1α, MIP-1ß and tumor necrosis factor (TNF)-α than that in the culture-negative group (p = 0.002, 0.006, 0.001, <0.001, 0.009), and blood C-reactive protein and sugar as well (p < 0.001, 0.026). After adjusting postmenstrual age by logistic regression, blood sugar level was the most significant biomarker (p = 0.019). In combination of blood and salivary biomarkers, blood sugar higher than 67 mg/dL and salivary IL-6 higher than 367.25 pg/mL concurrently, would accurately detect bacterial infection in premature babies. CONCLUSION: This non-invasive method might help us to accurately diagnose bacterial infection in premature babies.

The equations of the inserted length of percutaneous central venous catheters on neonates in NICU.

BACKGROUND: In neonatal intensive care units, a percutaneous central venous catheter (PCVC) is inserted peripherally and threaded into a central venous location, when intravenous access is anticipated for an extended period of time. The tip location of PCVCs should be checked by an X-ray after the procedure. The present study aimed to determine an equation to estimate the optimal insertion length of PCVCs in neonates prior to the procedure. METHODS: The data of all neonates who had PCVC insertion between May 1st 2015 and April 30th 2016 was reviewed. Their gender, body weight and body length at the insertion date, any complications and the tip culture of their PCVCs were recorded. The tip location of the PCVC, which was confirmed by X-ray, was either in the inferior vena cava near to the diaphragm or in the superior vena cava before the right atrial junction, depending on the insertion site. We analyzed the correlation among inserted length of PCVCs, body weight and body length by linear regression to determine an equation for estimating the optimal insertion length of PCVCs. The accuracy of the equations was evaluated prospectively by Pearson's correlation analysis, and the adjusting rate of PCVCs after the initial insertion was compared between the traditional method and using the equation. RESULTS: The equation of PCVCs inserted in the foot was "insertion length (cm) = 16 + 4.27 × body weight (kg)", in the femoral vein was "inserted length (cm) = 9.8 + 1.7 × body weight (kg)", in the popliteal vein was "inserted length (cm) = -0.3 + 0.45 × body length (cm)", in the hand was "inserted length (cm) = 4.46 + 0.32 × body length (cm)", and in the axillary vein was inserted length (cm) = 1 + 0.18 × body length (cm). The adjusting rate of PCVCs after initial insertion was decreased from 73.5% to 53% following use of the equation. CONCLUSIONS: Equations provided a convenient and accurate method to estimate the optimal insertion length of PCVCs before their placement.

Gestational age, not transient hyperthyrotropinemia impacts brain white matter diffusion tensor imaging in premature infants.

Transient hypothyroidism is common in premature infants and increases the risk of adverse neurodevelopmental outcomes. Thyroid hormone (TH) is involved in oligodendrocyte development and myelination, however, whether transient hypothyroidism is associated with oligodendrocyte dysplasia and abnormal myelination is unclear. The aim of the present study was to investigate correlations among TH levels, neurodevelopmental outcomes and white matter (WM) microstructure in premature infants. The authors designed a cohort study recruiting 81 premature infants (age, 23-35 weeks). A total of 17 were born with a gestational age (GA) <30 weeks (early preterm group) and 64 of them were born with a GA ≥30 weeks (late preterm group). For outcome measurement, thyroid stimulating hormone (TSH) levels at 0, 18, and 24 h of admission were measured. Neurodevelopmental outcomes were assessed using Bayley III test. Diffusion tensor imaging was used to explore the characterization of WM microstructure. The data demonstrated that GA, however not TSH level was associated with neurodevelopmental outcomes in the following 2 years. Fractional anisotrophy (FA) increased with TSH0 levels over anterior limb of internal capsule, while axial diffusivity decreased with TSH0 levels over splenium of corpus callosum (CC). The late preterm group had more intact WM integrity over the internal and external capsule (EC) in FA compared with the early preterm group. Infants with motor dysfunction had significantly increased mean diffusivity (MD) values at regions of interest in the genu and splenium of CC. The results of the present study demonstrated that GA, however not transient hypothyroidism influenced neurodevelopmental outcomes in the premature infants. FA increased with age in a regionally-specific manner over regions of the internal capsule and EC. MD may act as a potential predictor for motor function in premature babies.

Analysis of early-onset bloodstream infection due to Escherichia coli infection in premature babies.

In early-onset bacteremia among preterm neonates, Escherichia coli (E. coli) is the main pathogen and can cause a high mortality rate. Thus, the predictive factors of mortality and extended-spectrum ß-lactamase (ESBL)-producing E. coli in preterm babies with E. coli early-onset bacteremia were reported.We retrospectively reviewed preterm neonates who had E. coli bacteremia occurring within 3 days after birth between 2004 and 2015. Maternal and perinatal information were collected from their medical records and analyzed by comparing the survival and nonsurvival groups, and also the ESBL-producing and non-ESBL-producing E. coli bacteremia groups. Mann-Whitney U test, Fisher exact test, and multivariate Cox proportional-hazard model were used for statistical analysis.A total of 27 preterm babies had E. coli bacteremia. The overall mortality rate was 55.56% (15 deaths). Five babies had ESBL-producing E. coli. The low systolic blood pressure of <48 mm Hg and low absolute neutrophil count of <2318 cells/mm were the most significant factors in predicting mortality. Moreover, the level of serum alanine aminotransferase was significantly lower in the ESBL-producing E. coli group than that in the non-ESBL-producing E. coli group.Therefore, the lower systolic blood pressure and absolute neutrophil count were the risk factors of mortality in preterm babies with early-onset E. coli bacteremia, and alanine aminotransferase could be a significant factor in predicting ESBL-producing E. coli.

Early Erythropoietin Administration does not Increase the Risk of Retinopathy in Preterm Infants.

BACKGROUND: Erythropoietin (EPO) administration prevents anemia of prematurity and may be associated with a significant increase in the risk of retinopathy of prematurity (ROP) in preterm infants. Nonetheless, early EPO treatment may prevent damage following retinal neovascularization. The aim of this meta-analysis was to elucidate whether EPO administration increases the risk of ROP. METHODS: We searched MEDLINE, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the Cochrane Central Register of Controlled Trials with no language restrictions. Randomized controlled trials that reported the association between EPO treatment in preterm infants and ROP were eligible. All of the included studies were stratified into two groups according to the age of initiation of EPO treatment: before 8 days of age (early EPO), and 8-28 days of age (late EPO). RESULTS: Thirteen studies were identified that included a total of 1999 preterm infants. EPO administration did not increase the risk of ROP of any stage or Stage ≥3 (any relative risk: 0.99, 95% confidence interval: 0.84-1.16, p = 0.89; Stage ≥3 relative risk: 1.34, 95% confidence interval: 0.90-1.99, p = 0.15). This trend remained unchanged in both the early and late EPO groups. There did not seem to be any evidence of publication bias for outcomes as the funnel plots were symmetrical. CONCLUSION: EPO administration did not significantly increase the risk of ROP of any stage reported or Stage ≥3. Further clinical trials investigating the impact of EPO on ROP in premature infants should include all confounding factors to clarify this important issue.

Nasogastric Tube Placement and Esophageal Perforation in Extremely Low Birth Weight Infants.

Perforation of the esophagus associated with placement of nasogastric tubes is not uncommon in preterm infants. Herein we report three cases of iatrogenic esophageal perforation associated with nasogastric tube placement. With nonsurgical management of parenteral nutrition and broad-spectrum antimicrobial therapy, all three neonates survived without sequelae. Effective strategies to prevent such complications are discussed.

Refractive Error in Patients with Retinopathy of Prematurity after Laser Photocoagulation or Bevacizumab Monotherapy.

PURPOSE: To evaluate the refractive development of premature infants with retinopathy of prematurity (ROP) after treatment with laser photocoagulation or intravitreal injection of bevacizumab (IVB). METHODS: The medical records of patients with ROP treated between 2003 and 2012 who underwent yearly follow-ups were retrospectively reviewed. Patients with residual ROP abnormalities were excluded. The cycloplegic refraction at 3 years of age, assessed using an autorefractometer, was recorded. RESULTS: In total, 54 eyes from 54 patients were enrolled. Patients were divided into 4 groups: group 1, including 14 eyes of 14 patients treated with laser therapy; group 2, 15 eyes of 15 patients treated with IVB; group 3, 13 eyes of 13 patients with non-type 1 ROP under conservative follow-up, and group 4, 12 eyes of 12 premature patients without ROP. The mean spherical equivalent at 3 years of age was -1.71 ± 1.27 dpt in group 1, -1.53 ± 2.20 dpt in group 2, 0.63 ± 1.37 dpt in group 3, and 0.41 ± 1.95 dpt in group 4. The mean refractive error differed significantly among the 4 groups (p < 0.001). Patients in groups 1 and 2 were more prone to myopia compared with those in groups 3 and 4. Furthermore, patients with type 1 ROP treated by laser photocoagulation (group 1) and those treated by IVB (group 2) had similar refraction (p = 1). CONCLUSIONS: The results of this study suggest that treatment-demanding ROP eyes are susceptible to more severe myopia with age compared with eyes without ROP or those with spontaneously regressed ROP. In addition, the myopic status between laser and IVB treatment did not differ statistically.

Severe bronchopulmonary dysplasia is associated with higher fluid intake in very low-birth-weight infants: a retrospective study.

OBJECTIVE: This study aims to investigate the association between fluid intake in the first 4 days of life and the subsequent severity of bronchopulmonary dysplasia (BPD) in very low-birth-weight infants (VLBWI). STUDY DESIGN: A retrospective chart review of 75 infants with a gestational age of less than 32 weeks and a birth weight of < 1,500 g was performed. Demographic, clinical data, associated maternal risk factors, and amount of fluid received in the first 4 days of life were analyzed. RESULTS: Severe BPD was associated with a lower gestational age (27.04 ± 2.073 wks vs. 28.70 ± 1.706 wks, p=0.001), lower birth weight (981.44 ± 244.54 vs. 1,199.63 ± 165.39 g, p < 0.001), use of surfactant (91.7 vs. 63%, p=0.002), patent ductus arteriousus (PDA) (70.8 vs. 37%, p=0.004), pulmonary hemorrhage (14.6 vs. 0%, p=0.045), and more fluids received from the 2nd to 4th days of life (346.44 ± 42.38 mL/kg vs. 323.91 ± 27.62 mL/kg, p=0.007). A cut off point of 345 mL/kg of fluids from the 2nd to 4th days of life was selected using receiver operating characteristic curve analysis, and remained a significant risk factor even after multiple logistic regression analysis. CONCLUSION: Our findings demonstrate that VLBWI who received higher fluid intake from the 2nd to 4th days of life are at an increased risk of developing severe BPD.

Using WINROP as an adjuvant screening tool for retinopathy of prematurity in southern Taiwan.

OBJECTIVE: To study the efficacy of the WINROP (https://winrop.com) algorithm in Taiwan, a middle income, moderately developed country in Asia. STUDY DESIGN: We enrolled all preterm infants born with a gestational age less than 32(+0) weeks from September 2008 to August 2010. The results of serial retinopathy of prematurity examinations according to the screening guidelines in our hospital were recorded. Weekly body weight was also recorded for the WINROP algorithm. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Overall, 148 infants were included. Seventeen infants (11.5%) received treatment for retinopathy of prematurity. But, six infants (35.3%) were missed when severe retinopathy of prematurity was predicted with WINROP algorithm. The sensitivity is only 64.7%. However, when focusing on the preterm infants with a birth weight < 1,000 g or gestational age < 28 weeks, it could predict the need for treatment up to 13 weeks in advance. CONCLUSION: The WINROP algorithm is a very effective noninvasive screening tool for retinopathy of prematurity, especially in preterm infants with a birth weight < 1,000 g or a gestational age < 28 weeks. However, the overall sensitivity in this report from Taiwan was not as high as that reported in highly developed countries.

Pathogenesis implication for necrotizing enterocolitis prevention in preterm very-low-birth-weight infants.

Recent reports show that the incidence of and deaths caused by necrotizing enterocolitis (NEC) in preterm very-low-birth-weight (PVLBW) infants are on the rise. Unfortunately, NEC often rapidly progresses from early signs of intestinal inflammation to extensive necrosis within a matter of hours, making treatment and secondary prevention extremely difficult to achieve. Primary prevention should thus be the priority. Recent studies provide information that enhances our understanding of the pathophysiology and provides more practical options for the prevention of NEC. The most accepted hypothesis at present is that enteral feeding (providing substrate) in the presence of abnormal intestinal colonization by pathogens provokes an inappropriately heightened inflammatory response in immature intestinal epithelial cells of PVLBW infants. Seventy-four relevant articles were reviewed. Our focus was on the present understanding of the pathophysiology of NEC in the context of developing optimal strategies to prevent NEC in PVLBW infants. Strategies such as antenatal glucocorticoids, postnatal breast milk feeding, and cautious approach to enteral feeding failed to eliminate NEC in PVLBW infants because these strategies did not address the complexity of the pathogenesis. Probiotics seem to be the most significant advance in NEC prevention at present because of the significant range of beneficial effects at various levels of gut function and defense mechanism and the present evidence based on 19 randomized controlled trials.

High aspartate aminotransferase level predicts poor neurodevelopmental outcome in infants with meconium aspiration syndrome.

OBJECTIVE: The aim of our study is to clarify the perinatal predictive factors of meconium aspiration syndrome (MAS) with neurodevelopmental delay (ND) in infants. MATERIALS AND METHODS: In this retrospective study, data were collected from the infants born between 1990 and 2008. They all had primary diagnosis of MAS. Multivariable analyzed perinatal predictive factors of MAS with ND. The developmental status of these infants was followed at least 2 years with the Wechsler Intelligence Scale for Children. RESULTS: A total of 114 surviving babies met the criteria of MAS. Six babies were defined as ND group. Lower 5-minute Apgar score and diastolic blood pressure were significantly related to the ND group. Elevated asparatate aminotransferase (AST), nucleated red blood cells, and white blood cells at the time of admission were significantly high in ND group. Furthermore, AST had area under the receiver operating characteristic curve of 0.879, (95% confidence interval: 0.801, 0.934), p < 0.0001. At 96 mg/dL, it had 83.33% sensitivity, 80.81% specificity, and negative predictive value of 98.8. Multivariable logistic regression analysis revealed AST was the only significant predictive factor for MAS with ND. CONCLUSION: Early intervention should be recommended in infants having MAS with high AST level at birth for improving their neurodevelopmental outcomes.