Comparison of Cardiac Output Measurement by Electrical Velocimetry with Echocardiography in Extremely Low Birth Weight Neonates

<b><i>Introduction:</i></b> Electrical velocimetry (EV) offers a noninvasive tool for continuous cardiac output (CO) measurements which might facilitate hemodynamic monitoring and targeted therapy in low birth neonates, in whom other methods of CO measurement are not practicably feasible. <b><i>Methods:</i></b> This prospective observational study compared simultaneous cardiac output measurements by electrical velocimetry (CO_EV) with transthoracic echocardiography (CO_TTE) in extremely low birth weight (ELBW) neonates in the neonatal intensive care unit (NICU). Echocardiography was performed by 1 single examiner. Data were analyzed by Bland-Altman analysis and independent-samples analysis of variance. A mean percentage error (MPE) of &#x3c;30% and limits of agreement (LOA) up to ±30% were considered clinically acceptable. <b><i>Results:</i></b> Thirty-eight ELBW neonates were studied and yielded 85 pairs of CO_EV and CO_TTE measurements. Bland-Altman analysis showed an overall bias (the mean difference) and LOA of −126 and −305 to +52 mL min⁻¹, respectively, and an MPE of 66%. Patients with patent ductus arteriosus had a higher bias with LOA and MPE of −166.8, −370.7 to +37 mL min⁻¹, and 69%, respectively. The overall true precision was 58%. <b><i>Conclusion:</i></b> This study showed high bias and lack of agreement between EV and TTE for measurement of CO in ELBW infants in NICU, limiting applicability of EV to monitor absolute values.

ELBW and ELGAN outcomes in developing nations–Systematic review and meta-analysis

Context Morbidity and mortality amongst extremely low birth weight (ELBW) and extremely low gestational age neonates (ELGANs) in developing nations has not been well studied. Objectives Evaluate survival until discharge, short- and long-term morbidities of ELBW and ELGANs in LMICs. Data sources CENTRAL, EMBASE, MEDLINE and Web of Science. Study selection Prospective and retrospective observational studies were included. Data extraction and synthesis Four authors extracted data independently. Random-effects meta-analysis of proportions was used to synthesize data, modified QUIPS scale to evaluate quality of studies and GRADE approach to ascertain the certainty of evidence (CoE). Results 192 studies enrolling 22,278 ELBW and 18,338 ELGANs were included. Survival was 34% (95% CI: 31% - 37%) (CoE–low) for ELBW and 39% (34% - 44%) (CoE—moderate) for ELGANs. For ELBW neonates, the survival for low-income (LI), lower middle-income (LMI) and upper middle income (UMI) countries was 18% (11% - 28%), 28% (21% - 35%) and 39% (36% - 42%), respectively. For ELGANs, it was 13% (8% - 20%) for LI, 28% (21% - 36%) for LMI and 48% (42% - 53%) for UMI countries. There was no difference in survival between two epochs: 2000–2009 and 2010–2020. Except for necrotising enterocolitis [ELBW and ELGANs—8% (7% - 10%)] and periventricular leukomalacia [ELBW—7% (4% - 11%); ELGANs—6% (5%-7%)], rates of all other morbidities were higher compared to developed nations. Rates of neurodevelopmental impairment was 17% (7% - 34%) in ELBW neonates and 29% (23% - 37%) in ELGANs. Limitations CoE was very low to low for all secondary outcomes. Conclusions Mortality and morbidity amongst ELBW and ELGANs is still a significant burden in LMICs. CoE was very low to low for all the secondary outcomes, emphasizing the need for high quality prospective cohort studies. Trial registration PROSPERO (CRD42020222873).

Developing a Small Baby Program for the Extremely Low Birth Weight: The Wee CARE Team

The Children's Hospital at Providence (TCHaP) is a hospital within a hospital, in the heart of Alaska's biggest city, Anchorage. TCHaP admits up to 60 extremely low birth weight (ELBW) neonates per year. The ELBW population, although small in number, contributes disproportionately to rates of death or serious morbidities. Nationally, ELBW is defined as a neonate born at a gestational age between 22 and 29 weeks. In 2014, only 38 percent of neonates born in Alaska <28 weeks survived without experiencing major morbidities. For those born <26 weeks, morbidity-free survival dropped to 25 percent. Discussions were held among NICU nursing leaders, clinical nurses, and physicians about current co-morbidities and potentially best practices to improve outcomes. Subsequently, the group decided to develop best practices for managing the care of the ELBW, which started by organizing a group of specialists. This group at TCHaP is called the Wee CARE team.

Invasive candidiasis in a Brazilian neonatal intensive care unit

Objectives: to describe the epidemiology of invasive candidiasis in a neonatal intensive care unit. Methods: cross-sectional study that included all neonates with invasive candidiasis confirmed by blood culture from April 2015 to June 2018. Demographic, clinical and microbiological data were analyzed, comparing neonates with extreme low birth weight (ELBW) with neonates ≥ 1000g birth weight, considering a p <0.05 as statistically significant. Results: there were 38 cases of invasive candidiasis, resulting in an overall incidence of 2.5%. Twelve (32%) were ELBW neonates and 26 (68%) neonates ≥ 1000g birth weight, an incidence of 4.4% and 2.0%, respectively. Abdominal surgery was more frequent among neonates with birth weight ≥ 1000g compared to ELBW neonates (85% vs. 17%; p <0.01), as well as the median in days of antibiotics use (18 vs. 10.5; p = 0.04). The median in days of mechanical ventilation was more frequent among ELBW neonates (10 vs. 5.5; p = 0.04). The majority of Candida species were non-albicans (64%). Fatality rate was 32%. Conclusions: the incidence of invasive candidiasis among neonates with birth weight ≥ 1000g was higher than that found in the literature. This group has a higher proportion of gastrointestinal malformations that require surgery. Thus, fluconazole prophylaxis may be necessary for a broader group of neonates.

OUTCOME OF LOW BIRTH WEIGHT NEONATES WITH RELATION TO EARLY ANEMIA.

Background: Weight of newborn is a universal predictor of health during childhood. Haematological prole varies with period of gestation in low birth weight neonates i.e., <2500 grams. They have different haematological prole as compared to normal birth weight neonates. Aim of this study is to relate early morbidity and mortality of low birth weight neonates and their haemoglobin at days 1, 4 and 7. Materials and methods: A prospective cross-sectional study was conducted from January 2019 to June 2020 on children weighing below 2500 grams admitted within 24 hours of birth in Department of Paediatrics, SGRDIMSR, Amritsar. A total of 110 neonates were enrolled in this study following the inclusion and exclusion criteria. Haemoglobin levels of these were measured on days 1, 4 and 7. The data obtained was compiled and analysed to reach valid conclusions in relation to outcome in form of morbidity and mortality of the subjects. Results: Among 110 neonates majority belong to category of birth weight between 1500-2500 grams (70%). Lowest mean haemoglobin levels were seen in ELBW (<1000 grams) neonates. Fall in haemoglobin from day 1 to 7 in all the neonates was seen and was statistically signicant. Anaemia was signicantly related to PNA and mortality. Lowest mean haemoglobin values were seen in neonates with PNA as a morbidity on day 7 (13.04±2.32). Neonates who died had even lower haemoglobin level on day 7 (12.17±2.03). Conclusion: It was concluded that ELBW neonates had higher risk of early anaemia as compared to LBW and VLBW neonates. Anaemia was also signicantly present in neonates who died and those who had PNA. Thus early anaemia is associated with PNA, ELBW and Mortality.

Creatinine Trends to Detect Ibuprofen-Related Maturational Adverse Drug Events in Neonatal Life: A Simulation Study for the ELBW Newborn

Background: Recognizing a change in serum creatinine concentrations is useful to detect a renal adverse drug reaction signal. Assessing and characterizing the nephrotoxic side-effects of drugs in extremely low birth weight (ELBW, ≤1000 g) neonates remain challenging due to the high variability in creatinine in this population. This study aims to investigate and quantify the impact of ibuprofen treatment on kidney function, reflected by serum creatinine.Method: A recently developed dynamical model for serum creatinine was used to simulate creatinine profiles for typical, reference ELBW neonates with varying gestational and postnatal ages whilst being exposed to ibuprofen treatment.Results: The increase of serum creatinine concentrations due to ibuprofen treatment is most apparent during the first week of life. The difference in serum creatinine values between ibuprofen-exposed vs. non-exposed neonates decreases with increasing postnatal age, independent of gestational age.Conclusion: The difference in serum creatinine concentrations between ibuprofen-exposed vs. non-exposed neonates decreases with postnatal age, indicating an increased clearing capacity and resulting in a weak ibuprofen-related adverse drug reaction signal beyond early neonatal life.

Amikacin or Vancomycin Exposure Alters the Postnatal Serum Creatinine Dynamics in Extreme Low Birth Weight Neonates

Background: Disentangling renal adverse drug reactions from confounders remains a major challenge to assess causality and severity in neonates, with additional limitations related to the available tools (modified Kidney Disease Improving Global Outcome, or Division of Microbiology and Infectious Diseases pediatric toxicity table). Vancomycin and amikacin are nephrotoxic while still often prescribed in neonates. We selected these compounds to assess their impact on creatinine dynamics as a sensitive tool to detect a renal impairment signal. Methods: A recently developed dynamical model that characterized serum creatinine concentrations of 217 extremely low birth weight (<1000 g, ELBW) neonates (4036 observations) was enhanced with data on vancomycin and/or amikacin exposure to identify a potential effect of antibiotic exposure by nonlinear mixed-effects modelling. Results: Seventy-seven percent of ELBW patients were exposed to either vancomycin or amikacin. Antibiotic exposure resulted in a modest increase in serum creatinine and a transient decrease in creatinine clearance. The serum creatinine increase was dependent on gestational age, illustrated by a decrease with 56% in difference in serum creatinine between a 24 or 32-week old neonate, when exposed in the 3rd week after birth. Conclusions: A previously described model was used to explore and quantify the impact of amikacin or vancomycin exposure on creatinine dynamics. Such tools serve to explore minor changes, or compare minor differences between treatment modalities.

Amikacin or Vancomycin Exposure Alters the Postnatal Serum Creatinine Dynamics in ELBW Neonates

Background: Disentangling adverse drug reactions from confounders remains a major challenge to assess causality and severity in neonates. Vancomycin and amikacin are perceived as nephrotoxic and often prescribed in neonates. We selected these compounds to assess their impact on creatinine dynamics as sensitive tool to detect a renal impairment signal. Methods: A recently developed dynamical model that characterized serum creatinine concentrations of 217 ELBW neonates (4036 serum creatinine observations) was enhanced with data on individual administration of vancomycin and/or amikacin to identify a potential effect of antibiotic exposure by nonlinear mixed-effects modelling analysis. Results: Of our ELBW patients, 77% were exposed to either vancomycin or amikacin. Antibiotic exposure resulted in transient lower overall creatinine clearance and a modest increase in serum creatinine. Dependency on gestational age was observed in the difference in serum creatinine when exposed to antibiotics during the third week after birth (difference in creatinine for a neonate at 24 weeks gestation decreased with 56% for a 32-week-old neonate). Conclusions: A previously described model on creatinine dynamics was used to explore and quantify the impact amikacin or vancomycin exposure on creatinine dynamics. Such tools can be used to explore minor changes, or compare minor differences between treatment modalities.

Characterizing dynamics of serum creatinine and creatinine clearance in extremely low birth weight neonates during the first 6 weeks of life

Background Characterizing the dynamics of serum creatinine concentrations (Scr) and associated creatinine clearance (CLcr) as a measure of kidney function in extremely low birth weight (≤ 1000 g; ELBW) neonates remains challenging. Methods We performed a retrospective study that included longitudinal Scr (enzymatic assay) data from 148 ELBW neonates up to 6 weeks after birth. Change of Scr and inter-individual variability was characterized with nonlinear mixed-effect modeling. Key covariates such as gestational age (GA), mode of delivery (MOD), and treatment with ibuprofen or inotropic agents were investigated. Results A total of 2814 Scr concentrations were analyzed. GA was associated with Scr at birth (higher with advancing GA), and GA and MOD showed an association with postnatal maturation of CLcr (faster clearance increase with advancing GA and after C-section). Small CLcr decrease (≤ 5%) was quantified during ibuprofen treatment. For a GA of 27 weeks, mean Scr (estimated CLcr) at birth was 0.61 mg/dl (0.23 ml/min), increasing to 0.87 mg/dl (0.27 ml/min) at day three, and decreasing to 0.36 mg/dl (0.67 ml/min) at day 42 after birth. Conclusions We report the first mathematical model able to characterize Scr and CLcr in ELBW neonates during the first 6 weeks of life in a quantitative manner as a function of GA, MOD, and ibuprofen treatment. This model allows the derivation of GA-adjusted reference ranges for ELBW neonates and provides a rationale for normative Scr concentrations, and as such will help clinicians to further optimize monitoring and treatment decisions in this vulnerable patient population.