Very Low Birth Weight Infants Research Articles

Implementing an exclusive human milk diet for preterm infants: real-world experience in diverse NICUs

BackgroundHuman milk–based human milk fortifier (HMB-HMF) makes it possible to provide an exclusive human milk diet (EHMD) to very low birth weight (VLBW) infants in neonatal intensive care units (NICUs). Before the introduction of HMB-HMF in 2006, NICUs relied on bovine milk–based human milk fortifiers (BMB-HMFs) when mother's own milk (MOM) or pasteurized donor human milk (PDHM) could not provide adequate nutrition. Despite evidence supporting the clinical benefits of an EHMD (such as reducing the frequency of morbidities), barriers prevent its widespread adoption, including limited health economics and outcomes data, cost concerns, and lack of standardized feeding guidelines.MethodsNine experts from seven institutions gathered for a virtual roundtable discussion in October 2020 to discuss the benefits and challenges to implementing an EHMD program in the NICU environment. Each center provided a review of the process of starting their program and also presented data on various neonatal and financial metrics associated with the program. Data gathered were either from their own Vermont Oxford Network outcomes or an institutional clinical database. As each center utilizes their EHMD program in slightly different populations and over different time periods, data presented was center-specific. After all presentations, the experts discussed issues within the field of neonatology that need to be addressed with regards to the utilization of an EHMD in the NICU population.ResultsImplementation of an EHMD program faces many barriers, no matter the NICU size, patient population or geographic location. Successful implementation requires a team approach (including finance and IT support) with a NICU champion. Having pre-specified target populations as well as data tracking is also helpful. Real-world experiences of NICUs with established EHMD programs show reductions in comorbidities, regardless of the institution’s size or level of care. EHMD programs also proved to be cost effective. For the NICUs that had necrotizing enterocolitis (NEC) data available, EHMD programs resulted in either a decrease or change in total (medical + surgical) NEC rate and reductions in surgical NEC. Institutions that provided cost and complications data all reported a substantial cost avoidance after EHMD implementation, ranging between $515,113 and $3,369,515 annually per institution.ConclusionsThe data provided support the initiation of EHMD programs in NICUs for very preterm infants, but there are still methodologic issues to be addressed so that guidelines can be created and all NICUs, regardless of size, can provide standardized care that benefits VLBW infants.

Association of Hospital Adoption of Probiotics With Outcomes Among Neonates With Very Low Birth Weight

For neonates with very low birth weight (VLBW), randomized clinical trials (RCTs) indicate that probiotic treatment decreases the risk of necrotizing enterocolitis (NEC), with smaller decreases in the risk of sepsis and death. There is little evidence on the rate of probiotic adoption in US neonatal intensive care units (NICUs) and whether the benefits seen in trials have materialized in practice. To estimate changes in probiotic use among neonates with VLBW and to test whether neonates with VLBW treated at NICUs adopting routine probiotic use experience better outcomes compared with neonates treated at nonadopting NICUs. This cohort study used Vermont Oxford Network data on neonates with VLBW in US NICUs from January 1, 2012, to December 31, 2019. Data were analyzed from January 2022 through February 2023. Probiotics adoption vs nonadoption. Adopting NICUs were defined as those that currently or previously treated at least 20% of neonates with VLBW with probiotics. The primary outcomes were rates of NEC, in-hospital mortality, and sepsis, defined as bacterial or fungal infection occurring after day 3 from birth. A difference-in-differences analysis compared changes in VLBW infant outcomes between adopting and nonadopting NICUs before and after hospital-level adoption of probiotics. Additional analyses used the proportion of neonates treated with probiotics in each neonate's birth NICU and year. The analysis included 307 905 neonates with VLBW (mean [SD] gestational age, 28.4 [2.9] weeks; 50.0% male) at 807 US hospitals. The rate of probiotic treatment of neonates with VLBW rose from 1572 of 38 296 neonates (4.1%) in 2012 to 4788 of 37 910 (12.6%) in 2019. Only 123 of 745 NICUs (16.5%) adopted probiotics by 2019, with 4591 of 6017 neonates with VLBW (76.3%) receiving probiotics in 2019 at adopting NICUs. Incidence of NEC declined by 18% at adopting NICUs (odds ratio [OR], 0.82; 95% CI, 0.70-0.95; P = .10) compared with nonadopting NICUs. Probiotic adoption was not associated with a significant reduction in sepsis (OR, 1.11; 95% CI, 0.98-1.25; P = .09) or mortality (OR, 0.93; 95% CI, 0.80-1.08; P = .33). In this cohort study, adoption of routine use of probiotics increased slowly in US NICUs and was associated with lower NEC risk but not with sepsis or mortality among neonates with VLBW. The findings for probiotic adoption and NEC, sepsis, and mortality were smaller than would have been predicted by the totality of RCT evidence but are consistent with a meta-analysis restricted to studies at low risk of bias.

Late-Onset Sepsis in Very Low Birth Weight Premature Infants: A 10-Year Review of a Brazilian Tertiary University Hospital-the Challenge Remains.

This study aimed to assess the incidence of late-onset sepsis (LOS), associated risk factors, and short-term prognosis in very low birth weight (VLBW) infants in a 10-year period. A cohort study was conducted with 752 VLBW preterm infants-23 to 33 gestational weeks and 400 to 1,500 g birth weight-admitted to a neonatal intensive care unit from 2008 to 2017 and who survived over 72 hours. LOS was defined as clinical and laboratory signs of infection, whether or not confirmed by blood culture. VLBW infants were divided into groups and compared: no LOS versus proven LOS versus clinical LOS. Study variables included maternal, birth, and neonatal data, morbidities, procedures, etiological agents, and outcome-death, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage, and retinopathy of prematurity (ROP). Analysis of variance with multiple Tukey's or Wald's comparison with gamma distribution, and stepwise multiple logistic regression model, adjusted for year, and gestational age, were used for statistical analysis. LOS incidence was 39% (proven LOS: 29%; clinical LOS: 10%). Septic VLBW infants showed higher mortality (proven LOS: 23.2%; clinical LOS: 41.9%) compared with no LOS (8.9%). Coagulase-negative staphylococci (56%), Gram-negative (26%), and fungi (8%) were the most frequent etiological agents. In comparing the groups, septic VLBW infants had lower gestational age and birth weight, presented more morbidities, and underwent more invasive procedures. The risk factors for proven and clinical LOS were days of mechanical ventilation and parenteral nutrition. LOS was associated with increased risk of death, BPD, and ROP. LOS showed high incidence and mortality, often caused by Gram-positive bacteria. Care interventions were the main risk factors associated. LOS had a major negative impact on short-term prognosis in VLBW infants. LOS reduction strategies are necessary and urgent. · LOS is associated with clinically significant neonatal morbidities and death in VLBW premature infants.. · There is association between LOS and duration of intensive care interventions.. · Quality improvement initiatives can be a pathway for LOS reduction..

Dilemmas in establishing preterm enteral feeding: where do we start and how fast do we go?

Beginning and achieving full enteral nutrition is a key step in the care of preterm infants, particularly very low birth weight (VLBW) infants. As is true for many organ system-specific complications of prematurity, the gastrointestinal tract must complete in utero development ex utero while concurrently serving a physiologic role reserved for after completion of full term development. The preterm gut must assume the placental function of the interface between a source of energy, precursors for anabolism, and micronutrients, and the developing infant-through digestion and absorption of milk, instead of directly from the mother via the uteroplacental interface. The benefits of enteral nourishment in preterm infants are counterbalanced by gastrointestinal complications of prematurity: dysmotility leading to difficulty establishing and advancing feeds, and the risk of necrotizing enterocolitis (NEC). Concern for these complications can prolong the need for parenteral nutrition with an associated increase in risk for central line-associated bloodstream infection (CLABSI) and parenteral nutrition (PN)-associated cholestasis or liver disease (PNALD). Thus, a daily issue facing neonatologists caring for preterm infants is how to optimally begin, advance, and reach full enteral nutrition sufficient to satisfy the nutrient, energy, and fluid requirements of VLBW infants while minimizing risk. In this perspective, we provide an overview of the approaches and supporting data for starting and advancing enteral feeds in preterm infants, particularly very low birth weight infants, and we discuss the significant gaps in knowledge that accompany current approaches. This framework recognizes the dilemmas of preterm feeding initiation andadvancement and identifies areas of opportunity for further investigation.

Expanding Medicaid Payment for Pasteurized Donor Human Milk in High-Risk Neonates.

Pasteurized donor human milk (PDHM) is associated with a reduced incidence of necrotizing enterocolitis in very low birth weight (VLBW) infants. Absence of Medicaid and private insurance payment for PDHM use in neonatal intensive care units contributes to disparities based on state of birth and socioeconomic level. Before 2017, 5 states had policies for PDHM coverage, incorporating less than 30% of VLBW infants born nationally. In this case study, we outline the partnership of local American Academy of Pediatrics (AAP) chapters with the national AAP Section on Neonatal-Perinatal Medicine to create a PDHM Advocacy Toolkit to facilitate Medicaid PDHM coverage. Over 5 years, neonatologist-led advocacy, incentivized via AAP funds, contributed to 5 additional states providing Medicaid payment for PDHM, resulting in over 55% of VLBW infants born nationally in states with funded coverage. Partnerships with state AAP chapters, pilot grant funding with deliverables, emphasis on advocacy coaching, and modification of the generalized toolkit to suit local needs were essential in engineering Medicaid PDHM payment. Together these actions provide a template for other pediatric subspecialists to help advance niche-focused advocacy issues at the state level.

Identification of new biomarkers and immune infiltration characteristics of sepsis in very low birth weight infants.

Sepsis is a life-threatening condition, especially in very low birth weight (VLBW) infants, and its pathogenesis remains unclear. Effective biomarkers need to be found to diagnose and treat the disease at an early stage. The Gene Expression Omnibus (GEO) database was screened and analyzed for differentially expressed genes (DEGs) in VLBW infants with sepsis. DEGs were then analyzed for functional enrichment. A weighted gene co-expression network analysis (WCGNA) was performed to identify the key modules and genes. The optimal feature genes (OFGs) were created using three machine learning algorithms. The single-sample Gene Set Enrichment Analysis (ssGSEA) scored the degree of immune cell enrichment between septic and control patients, and the correlation between OFGs and immune cells was evaluated. A total of 101 DEGs were identified between the sepsis and control samples. DEGs were mainly associated with immune responses and inflammatory signaling pathways in the enrichment analysis. In the WGCNA analysis, the MEturquoise module was significantly correlated with sepsis in VLBW infants (cor = 0.57, P < 0.001). By intersecting OFGs derived from three machine learning algorithms, two biomarkers were identified: glycogenin 1 (GYG1) and resistin (RETN). The area under the curves of GYG1 and RETN was greater than 0.97 in the testing set. The ssGSEA indicated immune cells infiltration in septic VLBW infants, and GYG1 and RETN revealed close correlations with immune cells. New biomarkers offer promising insights into the diagnosis and treatment of sepsis in VLBW infants.

Analysis of predictive parameters for extubation in very low birth weight preterm infants.

Mechanical ventilation is the primary treatment for preterm infants with respiratory failure. Prolonged intubation may lead to complications; thus, early extubation is desirable. No standard criteria exist for determining the appropriateness of extubating very-low-birth-weight (VLBW) infants. This study explored the predictors of successful extubation in preterm VLBW infants. This retrospective cohort study included 60 preterm VLBW infants who underwent their first extubation in the neonatal intensive care unit in a regional hospital in Hsinchu, Taiwan, between January 2017 and November 2020. Successful extubation was defined as having no requirement of reintubation within 3 days of extubation. Potentially predictive variables, including demographics, prenatal characteristics, and ventilator parameters were compared between a successful extubation group and failed extubation group. Of the 60 infants, 47 (78.33%) underwent successful extubation. The successful extubation group had higher Apgar scores at 1 (7 vs. 6, P=0.02) and 5min (9 vs. 7, P=0.007) than those of the failed extubation group. Ventilator inspiratory pressure and mean airway pressure were significantly lower at 24, 16, 8, and 1h before extubation and upon its completion in the successful extubation group. The areas under a number of the receiver operating characteristic curve curves in this study were moderate, specifically, 0.72, 0.74, and 0.69. Statistical analysis revealed an association between ventilator parameters before 1h extubation (IP>17.5cmH2O, MAP >7.5 cmH2O, RSS >1.82) and extubation failure (odds ratio 1.73, 2.27, 2.46 and 95% confidence interval:1.16-2.6, 1.26-4.08, 1.06-5.68, respectively). Higher Apgar scores at birth, lower ventilator inspiratory pressure, and mean airway pressure 24, 16, 8, and 1h and 1h RSS prior to extubation are associated with successful extubation in VLBW preterm infants.

Dose pulmonary hemorrhage increase the risk of bronchopulmonary dysplasia in very low birth weight infants?

Objective To evaluate the association between pulmonary hemorrhage and bronchopulmonary dysplasia (BPD) in very low birth weight infants (VLBWIs). Methods The study participants were all VLBW newborns admitted from January 1, 2019 to December 31, 2021. The BPD subjects finally included were VLBWIs who survived until the diagnosis was established. This study was divided into pulmonary hemorrhage group (PH group, n = 35) and non-pulmonary hemorrhage group (Non-PH group, n = 190). Results By univariate analysis it was found that premature rupture of membranes, tracheal intubation in the delivery room, duration of mechanical ventilation, course of invasive ventilation (≥3 courses), pulmonary surfactant (>1 dose), medically and surgically treated patent ductus arteriosus, grade III-IV RDS, early onset sepsis, BPD and moderate to severe BPD showed significant differences between groups (p < .05). By Multivariate analysis, pulmonary hemorrhage did not increase the risks of BPD and moderate to severe BPD (adjusted OR for BPD = 1.710, 95% CI 0.581–5.039; adjusted OR for moderate to severe BPD = 2.401, 95% CI 0.736–7.834). Conclusion It suggests that pulmonary hemorrhage is not associated with the development of BPD and moderate to severe BPD in VLBWIs.

Cesarean delivery was associated with low morbidity in very low birth weight infants: A retrospective cohort study.

To estimate the relationship among the cesarean delivery (CD), mortality and morbidity in very low birth weight (VLBW) infants weighing less than 1500 g. This retrospective cohort study enrolled 242 VLBW infants delivered between the 24 to 31week of gestation from 2015 to 2021. We compared CD with vaginal delivery (VD). The primary outcome was a composite neonatal morbidity including bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, late-onset sepsis and retinopathy of prematurity. The secondary outcome included mortality within 28 days. A multivariate logistic regression was used and adjusted for birthweight, twin pregnancy and antenatal steroids intake. The overall CD rate was 80.6%. Compared with VD, a significantly lower composite neonatal morbidity was associated with CD (adjusted odds ratio, 0.33, 95% confidence interval, 0.12-0.90, P = .031). The relationship between CD and neonatal morbidity disappeared when the VLBW infants were stratified according to the gestational age. No significant difference was observed between the VD and CD cohorts regarding mortality. Compared with VD, CD was associated with a lower morbidity in VLBW infants. Further studies are required to clarify how this association is influenced by gestational age.

Improving Early Colostrum Administration to Very Low Birth Weight Infants in a Level 3 Neonatal Intensive Care Unit: A Quality Improvement Initiative

To increase early oral immune therapy (OIT) with colostrum administered to the buccal mucosa in order to improve our human milk practices for very low birth weight (VLBW) infants admitted to a level 3 NICU. Using the Institute for Healthcare Improvement's (IHI) Model for Improvement, several interventions aimed at increasing early OIT administration were implemented. Four key drivers included: optimizing evidence based OIT guidelines, personnel alignment and engagement, optimal electronic health record (EHR) use for ordering practices, and timely lactation consultant involvement. The primary outcome measure was early OIT administration, while secondary outcome measures examined all OIT administration and human milk at discharge. Process measures included the percentage of staff members who were compliant with OIT protocol. Early OIT administration increased from a baseline mean of 6% to 55% in the 12-month study period. Percentage of total (early and late) OIT administration to VLBW infants increased from a baseline of 21% to 85%. Average human milk at discharge for VLBW infants remained at 44%, without significant improvement. A multidisciplinary quality improvement initiative led to significant improvement in OIT administration to infants at a level 3 NICU.

Restrictive Use of Empirical Antibiotics Is Associated with Improved Short Term Outcomes in Very Low Birth Weight Infants: A Single Center, Retrospective Cohort Study from China.

Antibiotics are essential for treating neonatal sepsis, but abuse or inappropriate use of antibiotics have harmful adverse effects. The inappropriate use of antibiotics has led to the significant increase in bacterial antimicrobial resistance in the neonatal intensive care unit (NICU). The aim of this study was to retrospectively analyze the changes in antibiotic usages in a NICU after the implementation of an antibiotic stewardship program and to determine the impact of this implementation on the short-term clinical outcomes of very low birth weight (VLBW) infants. The antibiotic stewardship program was initiated in the NICU in early 2015. For analysis, all eligible VLBW infants born from 1 January 2014 to 31 December 2016 were enrolled, and we classified the year 2014 as pre-stewardship, 2015 as during stewardship, and 2016 as post-stewardship. A total of 249 VLBW infants, including 96 cases in the 2014 group, 77 cases in the 2015 group, and 76 cases in the 2016 group, were included for final analysis. Empirical antibiotics were used in over 90% of VLBW infants in all three groups during their NICU stay. Over the 3-year period, the duration of an initial antibiotic course was significantly reduced. The proportion of patients receiving an initial antibiotic course for ≤3 days gradually increased (2.1% vs. 9.1% vs. 38.2%, p < 0.001), while the proportion of babies treated with an initial antibiotic course >7 days significantly decreased (95.8% vs. 79.2% vs. 39.5%, p < 0.001). The total days of antibiotic usage during the entire NICU stay also showed a significant reduction (27.0 vs. 21.0 vs. 10.0, p < 0.001). After adjusting for confounders, the reduction in antibiotic usage was associated with decreased odds of having an adverse composite short-term outcome (aOR = 5.148, 95% CI: 1.598 to 16.583, p = 0.006). To assess the continuity of antibiotic stewardship in the NICU, data from 2021 were also analyzed and compared to 2016. The median duration of an initial antibiotic course further decreased from 5.0 days in 2016 to 4.0 days in 2021 (p < 0.001). The proportion of an initial antibiotic course in which antibiotics were used for ≤3 days increased (38.2% vs. 56.7%, p = 0.022). Total antibiotic usage days during the entire NICU stay also decreased from 10.0 days in 2016 to 7.0 days in 2021 (p = 0.010). The finding of this study strongly suggests that restricting antibiotic use in VLBW infants is beneficial and can be achieved safely and effectively in China.

IMPACT OF DONOR MILK ON CLINICAL PARAMETRES STUDIED AMONG VERY LOW BIRTH INFANTS OF AN NICU OF A TERTIARY TEACHING HOSPITAL

Background: Low birth infants account for 27% of total live births in India. India has a large burden of very low birth weight (VLBW) babies, i.e. those who are &lt;1500 g, account for about 5% of all live births(1) and their nutritional rehabilitation is major concern.But every infant is unable to benefit from mothers milk because of maternal illness, death or lactation failure. This is when donors milk help for these VLBW infants who are unable to get their own mothers milk. Hence, understanding the impact of donor milk on various clinical parameters affecting a VLBWinfant is important. Aim: To study impact of donor milk on various parameters studied among VLBWinfants of an NICU of a tertiary teaching hospital. Methods: Ours is a retrospective comparative study over a period of 10 months in an NICU of a tertiary teaching hospital. 119 infants were enrolled. The data was collected from case records of these infants. Appropriate test of significance was applied to get the results. Results: In our study, the average length of NICU stay was 5.1 days lesser and overall weight centiles on dischargefor donor milk given babies was higherthan those who were not given donor milk. There was a significant association between administration of donor milk lack of caffeine administration(p=0.042).There was no significant association of donors milk with RDS(p=0.08), duration of mechanical ventilation for &gt;96 hours(p=0.58), bronchopulmonary dysplasia(p=0.55), inotropes administration(p=0.11),IVH(p=0.5029) and sepsis(p=0.68). Conclusion: By seeing the beneficial effects of donor milk on weight and overall hospitalization duration, promoting milk donation in postnatal wards and establishment of community human milk banks we can improve quality of health care and nutrition to VLBW babies and thus decrease infant mortality rate.

Effects of prophylactic probiotics supplementation on infants born very preterm or very low birth weight.

To evaluate the effects of guideline-driven prophylactic supplementation of a multi-strain neonatal intensive care unit-specific probiotic product on infants born very preterm (VP) or very low birth weight (VLBW). A prospective cohort of 125 infants born in one year after implementation who received probiotics were compared to a retrospective cohort of eligible 126 VP or VLBW infants who did not receive probiotics. The primary outcome of interest was necrotizing enterocolitis (NEC). The incidence of NEC decreased from 6.3 to 1.6%. After adjusting for multiple variables, there were no significant differences in primary or other outcomes of interest; odds ratio (95% confidence interval) NEC 0.27 (0.05-1.33), death 0.76 (0.26-2.21) and late-onset sepsis 0.54 (0.18-1.63). No adverse effects related to probiotics supplementation were observed. Although nonsignificant, prophylactic probiotics supplementation in infants born VP or VLBW was associated with reduction of NEC.

Impact of preterm premature rupture of membranes and oligohydramnios on in-hospital outcomes of very-low-birthweight infants

Objective To analyze neonatal outcomes in very-low-birthweight (VLBW) infants depending on the presence of preterm premature rupture of membranes (PPROM), oligohydramnios, or both. Methods The electronic medical records of VLBW infants admitted during the study period, January 2013 to September 2018, were reviewed. Neonatal outcomes (primary outcome: neonatal death; secondary outcome: neonatal morbidity) were compared depending on whether the infant was affected by PPROM or oligohydramnios. Logistic regression analysis was performed to assess the association of PPROM and oligohydramnios with neonatal outcomes. Results Three hundred and nineteen VLBW infants were included: (1) 141 infants in the PPROM group vs. 178 infants in the non-PPROM group, and (2) 54 infants in the oligohydramnios group vs. 265 infants in the non-oligohydramnios group. The infants affected by PPROM were at significantly younger gestational ages at birth with lower 5-min Apgar scores than those not affected by PPROM. Histologic chorioamnionitis was significantly more frequent in the PPROM group than in the non-PPROM group. The proportions of small-for-gestational-age infants and infants affected by multiple births were significantly higher in the non-PPROM group. The median (interquartile range) PPROM latency and onset were 50.5 (9.0 − 103.0) h and 26.6 (24.1 − 28.5) weeks, respectively. Based on the logistic regression analysis assessing the association of PPROM and oligohydramnios with the significant neonatal outcome, oligohydramnios was significantly associated with neonatal death (odds ratio [OR] = 2.831, 95% confidence interval [CI] 1.447 − 5.539), air leak syndrome (OR = 2.692, 95% CI 1.224 − 5.921), and persistent pulmonary hypertension (PPH) (OR = 2.380, 95% CI 1.244 − 4.555). PPROM per se was not associated with any neonatal outcome. However, early onset PPROM and prolonged PPROM latency were associated with neonatal morbidity and mortality. When PPROM was accompanied by oligohydramnios, it was associated with increased odds for PPH (OR = 2.840, 95% CI 1.335 − 6.044), retinopathy of prematurity (OR = 3.308, 95% CI 1.325 − 8.259), and neonatal death (OR = 2.282, 95% CI 1.021 − 5.103). Conclusion PPROM and oligohydramnios affect neonatal outcomes differently. Oligohydramnios, but not PPROM, is a significant risk factor for adverse neonatal outcomes, which is presumably related to pulmonary hypoplasia. Prenatal inflammation appears to complicate neonatal outcomes in infants affected by early PPROM and prolonged PPROM latency.

Population pharmacokinetics of vancomycin in very low birth weight neonates.

Vancomycin dosing in very low birth weight (VLBW) neonates is challenging. Compared with the general neonatal population, VLBW neonates are less likely to achieve the vancomycin therapeutic targets. Current dosing recommendations are based on studies of the general neonatal population, as only a very limited number of studies have evaluated vancomycin pharmacokinetics in VLBW neonates. The main aim of this study was to develop a vancomycin population pharmacokinetic model to optimize vancomycin dosing in VLBW neonates. This multicenter study was conducted at six major hospitals in Saudi Arabia. The study included VLBW neonates who received vancomycin and had at least one vancomycin serum trough concentration measurement at a steady state. We developed a pharmacokinetic model and performed Monte Carlo simulations to develop an optimized dosing regimen for VLBW infants. We evaluated two different targets: AUC0-24 of 400-600 or 400-800 µg. h/mL. We also estimated the probability of trough concentrations >15 and 20 µg/mL. In total, we included 236 neonates, 162 in the training dataset, and 74 in the validation dataset. A one-compartment model was used, and the distribution volume was significantly associated only with weight, whereas clearance was significantly associated with weight, postmenstrual age (PMA), and serum creatinine (Scr). We developed dosing regimens for VLBW neonates, considering the probability of achieving vancomycin therapeutic targets, as well as different toxicity thresholds. The dosing regimens were classified according to PMA and Scr. These dosing regimens can be used to optimize the initial dose of vancomycin in VLBW neonates.

Factors associated with the development of epilepsy in very low birth weight infants

The survival rate of very low birth weight (VLBW) infants has recently improved. However, the occurrence of and factors associated with epilepsy in VLBW infants remain unknown. This study aimed to clarify the incidence, characteristics, and factors associated with epilepsy development in VLBW infants. All VLBW infants admitted to our hospital between 2012 and 2017 were included in this study. VLBW infants with a follow-up period of <1 year were excluded. Chromosomal abnormalities, brain anomalies, severe intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), and hypoxic ischemic encephalopathy (HIE) were considered to be risk factors. Epilepsy occurred in 21/526 (4.0%) VLBW infants. Chromosomal abnormalities, brain anomalies, severe IVH, cystic PVL, HIE, neonatal seizures, advanced maternal age, maternal diabetes mellitus, no administration of antenatal corticosteroids, and low Apgar scores at 1 and 5min were associated with a risk of epilepsy. The median time to epilepsy onset was 8 months (range: 0-59 months), and the onset occurred within 2 years in 15/21 patients (71.4%) and within 4 years in 18/21 patients (85.7%). VLBW infants with risk factors developed epilepsy earlier and at a significantly higher rate than those without risk factors. Among infants who had risk factors and who developed epilepsy, 86.7% did so within 2 years of age, compared to 33.3% of those who developed epilepsy but did not have risk factors. These findings regarding factors associated with a risk of development of epilepsy and temporal feature of epilepsy may contribute to the development of monitoring and treatment protocols for epilepsy in VLBW infants.

The impact of kangaroo mother care on work of breathing and oxygen saturation in very low birth weight infants with respiratory insufficiency.

Kangaroo mother care (KMC) is defined as prolonged skin to skin care between a mother and infant with the infant lying in prone position on mom's chest. KMC decreases morbidity and mortality and promotes physiologic stability. The aim of this study is to measure work of breathing (WOB) during KMC in very low birth weight (VLBW) infants on non-invasive respiratory support. A prospective observational pilot study was conducted comparing WOB indices during standard care (SC) and KMC. Respiratory inductive plethysmography (RIP) measured WOB indices non-invasively: phase angle and labored breathing index. VLBW infants who were stable on non-invasive respiratory support were randomized to receive RIP measurements during KMC or during SC first. Summary statistics and mixed linear models were used to compare WOB and vital signs. A total of 32 infants were consented for the study, data collection and analysis was completed on 28 infants. There were no significant differences in mean phase angle during KMC or SC (73.5±4.6 SE deg vs 66.8±3.9 SE deg, p = 0.25). No differences in WOB and vital signs were detected. Controlling for respiratory support or randomization/first location did not change the results. In this pilot cohort, infants demonstrated no differences in work of breathing indices or oxygen saturation during KMC or SC while receiving non-invasive respiratory support. KMC appears to be safe and well tolerated with no worsened WOB. Larger studies should be performed to confirm our findings.

Umbilically and Peripherally Inserted Thin Central Venous Catheters Have Similar Risks of Complications in Very Low-Birth-Weight Infants.

Catheter complications can be life-threatening in very low-birth-weight (VLBW) infants. We retrospectively evaluated non-elective removals of the first thin (1-2F) umbilical vein catheters (tUVCs (n = 92)) and peripherally inserted central venous catheters (PICCs (n = 103)) among 195 VLBW infants. Catheters were removed non-electively in 78 infants (40%), typically due to suspected infection (n = 42) or catheter dislocation (n = 30). Infants with complications had lower birth weights and gestational ages than others. The frequencies and causes of catheter removal were similar in the tUVC and PICC groups. Thirty-one infants had true catheter infections. The number of infections/1000 catheter days was higher in the tUVC group than in the PICC group. In a multivariable analysis, gestational age was associated with catheter infection, but catheter type was not. The odds of catheter complications decreased with increasing gestational age, but no clear association with thin catheter type was found.

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.

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. 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. 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). 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.

A multicenter prospective cohort study of late-onset sepsis and its poor prognosis in very low birth weight infants

Objective: To investigate the prevalence and poor prognosis of late-onset sepsis (LOS) in very low birth weight infant (VLBWI). Methods: This prospective, multicenter observational cohort study was conducted based on the data from Sina-Northern Neonatal Network (SNN). The general data, perinatal information and poor prognosis of 6 639 VLBWI, who were admitted to the 35 neonatal intensive care units from 2018 to 2021, were collected and analyzed. According to the occurrence of LOS during hospitalization, the VLBWI were assigned to the LOS group and non-LOS group. The LOS group was further divided into 3 subgroups according to the occurrence of neonatal necrotizing enterocolitis (NEC) and purulent meningitis. The Chi-square test or Fisher exact probability method, independent sample t test, Mann-Whitney U test and multivariate Logistic regression model were used to analyze the relationship between LOS and poor prognosis in VLBWI. Results: A total of 6 639 eligible VLBWI were enrolled, including 3 402 cases (51.2%) of males and 1 511 cases (22.8%) with LOS. The incidences of LOS in extremely low birth weight infants (ELBWI) and extremely preterm infants were 33.3% (392/1 176) and 34.2% (378/1 105), respectively. There were 157 cases (10.4%) who died in the LOS group and 48 cases (24.9%) in the subgroup of LOS complicated with NEC. Multivariate Logistic regression analysis showed that LOS complicated with NEC was associated with increased mortality and incidence of grade Ⅲ-Ⅳ intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL), moderate or severe bronchopulmonary dysplasia (BPD), and extrauterin growth retardation (EUGR) (ORadjust=5.27, 2.59, 3.04, 2.04; 95%CI 3.60-7.73, 1.49-4.50, 2.11-4.37, 1.50-2.79; all P<0.01); LOS complicated with purulent meningitis was also associated with increased mortality and incidence of grade Ⅲ-Ⅳ IVH or PVL, and moderate or severe BPD (ORadjust=2.22, 8.13, 3.69, 95%CI 1.30-3.37, 5.22-12.67, 2.49-5.48; all P<0.01); the infants without NEC or purulent meningitis in the LOS group was only associated with increased incidence of moderate or severe BPD (ORadjust=2.20, 95%CI 1.83-2.65, P<0.001). After ruling out contaminated bacteria, a total of 456 cases showed positive blood culture, including 265 cases (58.1%) of Gram-negative bacteria, 126 cases (27.6%) of Gram-positive bacteria, and 65 cases (14.3%) of fungi. The most common pathogenic bacteria was Klebsiella pneumoniae (n=147, 32.2%), followed by coagulase-negative Staphylococcus (n=72, 15.8%) and subsequently Escherichia coli (n=39, 8.6%). Conclusions: The incidence of LOS is high in VLBWI. Klebsiella pneumoniae is the most common pathogenic bacteria, followed by coagulase-negative Staphylococcus and Escherichia coli. LOS is associated with a poor prognosis for moderate to severe BPD. The prognosis of LOS complicated with NEC is poor with the highest mortality, and the risk of brain damage is significantly increased when LOS complicated with purulent meningitis.