Correlation between Invasive and Noninvasive Blood Pressure Measurements in Extremely Low Gestational Age Newborns.

OBJECTIVE: This work aimed to study the correlation between invasive blood pressure (IBP) and non-IBP (NIBP) in extremely low gestational age newborns (ELGANs) during their first 72 hours of life. STUDY DESIGN: In a retrospective cohort study, IBP and simultaneous NIBP measurements during the first 72 hours of life were recorded in ELGANs. Medical records were reviewed for potential risk factors that affect BP. The % difference in mean arterial BP (% Diff-BP) measurements was calculated as (IBP-NIBP)/IBP. Hypotension was defined as mean arterial Bp < gestational age (GA). RESULTS: In total, 236 infants and 1,340 paired IBP-NIBP measurements were studied. Infants had a (mean ± standard deviation) GA of 25.4 ± 21.6 weeks and a birth weight of 810 ± 249 g. Overall, there was a significant correlation between IBP and NIBP of 0.887 (Spearman Rho; p < 0.001). However, the agreement between IBP and NIBP was poor, with a mean difference (95% limits of agreement) of 0.20 (-5.48; 5.89). The mean % Diff-BP (±standard deviation) was 0.39 ± 8.25%. In hypotensive infants, NIBP overestimated IBP measurements, with an agreement of -0.67 (-4.17; 2.83). CONCLUSION: Mean arterial NIBP correlates with IBP in ELGANs. However, there is a poor agreement between methods. In hypotensive infants, NIBP overestimates IBP measurements.

Comparison of different definitions of acute kidney injury in extremely low birth weight infants.

BACKGROUND: The definition of acute kidney injury (AKI) has evolved over the years, and three definitions have been adapted including pediatric risk injury failure, loss of kidney function (pRIFLE), Acute Kidney Injury Network (AKIN), and Neonatal Modified Kidney Disease Improving Global Outcomes (KDIGO). We sought to report the prevalence and outcome of (AKI) according to the three existing definitions in extremely low birth weight (ELBW) infants. METHODS: In a retrospective cohort study, medical records of all ELBW infants (<1000 g) admitted to our neonatal intensive care unit (NICU) between Jan 2002 and Dec 2011 were reviewed. Infants' demographics, anthropometric measurements, and clinical characteristics were collected at the time of birth and at discharge from the NICU. Infants were staged according to the three different definitions. RESULTS: During the study period, 483 ELBW infants met our inclusion criteria. The incidence of AKI was 56, 59, and 60% according to pRIFLE, AKIN, and KDIGO, respectively. Mortality, NICU length of stay, and serum creatinine (SCr) at NICU discharge were higher in infants with advanced AKI stages regardless of the definition. In addition, discharge NICU weight and length z scores were lower in infants with advanced AKI stages. SCr at 72 h of life and SCr peak were predictable of NICU mortality [AUC 0.667 (95% CI 0.604-0.731), p < 0.001 and AUC 0.747 (95% CI 0.693-0.801), p < 0.001, respectively]. CONCLUSION: Regardless of the definition, advanced AKI is associated with increased mortality, prolonged NICU length of stay, and poor growth in ELBW infants. SCr at 72 h of life and SCr peak may be predictable of NICU mortality.

Outcome of extremely low birth weight infants with a history of neonatal acute kidney injury.

OBJECTIVE: To study the outcome of extremely low birth weight (ELBW) infants with a history of acute kidney injury (AKI). METHOD: In a retrospective, case control study, medical records of all ELBW infants admitted to the neonatal intensive care unit (NICU) between Jan 2002 and Dec 2011 were reviewed. Medical records were reviewed for infants' demographics, blood pressure (BP) at NICU discharge and at ≥3 years, and estimated glomerular filtration rate (eGFR) at ≥2 years. RESULTS: During the study period, 222 patients met the inclusion criteria, of whom 10% (23 out of 222) had AKI stage 2 and 3, 39% (87 out of 222) had AKI stage 1, and the rest did not have AKI. At NICU discharge, there was a difference in diastolic BP (DBP) among infants who had AKI stages 2 and 3, those who had stage 1, and those who did not have AKI (53 ± 12 vs 46 ± 9 vs 46 ± 11 mmHg respectively; p = 0.007), and 11% (23 out of 209) had hypertension (HTN). Although there was a significant correlation between the rise in SCr and DBP at NICU discharge in infants with AKI (R = 0.304; p = 0.004), there was no difference in HTN between infants with and those without AKI. At ≥2 years of age, 4% (5 out of 120) across all groups had an eGFR < 90 ml/min/1.73m2 or chronic kidney disease (CKD). At ≥3 years of age, 5% (11 out of 222) had HTN. CONCLUSION: At NICU discharge, infants with AKI stages 2 and 3 have a higher DBP than infants with stage 1 AKI and those who did not have AKI. However, there is no difference in the rate of HTN between the two groups. At ≥2 years ELBW infants are at risk for CKD independently of whether or not they develop neonatal AKI.

Missed Opportunities in Guideline-Based Fatty Liver Screening Among 3.5 Million Children.

OBJECTIVE: Determine screening rates and examine socio-demographic characteristics of metabolic dysfunction-associated steatotic liver disease (MAFLD) screening in a large population of obese children. METHODS: We used Explorys (IBM) which contains aggregated population-level electronic health record data from approximately 360 hospitals and 317,000 providers across the United States to determine MAFLD screening rates. In children 10 to 14 years, obesity was determined based on body mass index ≥ 95%, or encounter with an international classification of disease obesity code. We determined screening rates by calculating the percentage of children with obesity who had an alanine aminotransferase tested, further analyzed by gender, race, and insurance. RESULTS: Of 3,558,420 children, 513,170 (14.4%) were obese. Of obese children, only 9.3% were screened for MAFLD. Females were more likely screened than males (odds ratio (OR) 1.09 (95% confidence intervals (CI): 1.07-1.12)); White children were more likely screened than non-White children (OR 1.21 (95% CI: 1.18-1.23)), and children with Medicaid more likely screened than children with non-Medicaid insurance (OR 1.34 (95% CI: 1.32-1.37)). CONCLUSIONS: The percentage of obese children receiving screening for MAFLD was low. Female gender, White race, and Medicaid insurance were associated with increased screening rates. These findings highlight the need to increase adherence to MAFLD screening. Reporting screening as a health quality measure may reduce implementation gaps in MAFLD screening.

Risk factors associated with acute kidney injury in extremely low birth weight (ELBW) infants.

The aim of this study was to determine the incidence, risk factors, and outcome of acute kidney injury (AKI) in extremely low birth weight (ELBW) infants. In a case-control study, medical records of all ELBW infants who were admitted to our Neonatal Intensive Care Unit (NICU) between 1 January 2000 and 31 January 2008 were reviewed. During the study period, 12.5% (59/472) of all ELBW infants developed AKI. Forty-six infants with available medical records were matched to 46 controls. The mean gestational age and birth weight of infants with AKI and their controls were 24.7 ± 1.8 vs. 24.9 ± 1.9 weeks (p = 0.61) and 614 ± 128 vs. 616 ± 127 g (p = 0.93), respectively. Infants with AKI had a higher mean airway pressure, a lower mean arterial blood pressure, and higher exposure to cefotaxime than their controls. Infants with AKI also had an increased mortality in comparison to their controls [33/46 (70%) vs. 10/46 (22%), respectively; p < 0.0001), and oliguric patients had a higher mortality than nonoliguric patients [31/38 (81%) vs. 2/8 (25%), respectively, p = 0.003]. Based on our results, we conclude that a high mean airway pressure, low blood pressure, and the use of cefotaxime are associated with renal failure in ELBW infants. AKI in ELBW infants is also associated with an increased mortality, especially in the presence of oliguria.

Advances in Neonatal Acute Kidney Injury.

In this state-of-the-art review, we highlight the major advances over the last 5 years in neonatal acute kidney injury (AKI). Large multicenter studies reveal that neonatal AKI is common and independently associated with increased morbidity and mortality. The natural course of neonatal AKI, along with the risk factors, mitigation strategies, and the role of AKI on short- and long-term outcomes, is becoming clearer. Specific progress has been made in identifying potential preventive strategies for AKI, such as the use of caffeine in premature neonates, theophylline in neonates with hypoxic-ischemic encephalopathy, and nephrotoxic medication monitoring programs. New evidence highlights the importance of the kidney in "crosstalk" between other organs and how AKI likely plays a critical role in other organ development and injury, such as intraventricular hemorrhage and lung disease. New technology has resulted in advancement in prevention and improvements in the current management in neonates with severe AKI. With specific continuous renal replacement therapy machines designed for neonates, this therapy is now available and is being used with increasing frequency in NICUs. Moving forward, biomarkers, such as urinary neutrophil gelatinase-associated lipocalin, and other new technologies, such as monitoring of renal tissue oxygenation and nephron counting, will likely play an increased role in identification of AKI and those most vulnerable for chronic kidney disease. Future research needs to be focused on determining the optimal follow-up strategy for neonates with a history of AKI to detect chronic kidney disease.

Assessment of neonatal adrenal size using high resolution 2D ultrasound and its correlation with birth demographics and clinical outcomes.

OBJECTIVE: Assessment of adrenal function in a sick neonate remains a challenge in spite of major advances in neonatal care. We used 2D ultrasound of adrenal glands to assess maturity of adrenal glands in extremely preterm infants and sick term and near term infants. STUDY DESIGN: We collected demographics details of 99 mother-infants pairs (24-41 weeks) and obtained 2D ultrasound scans of adrenal glands in first week of life to measure adrenal volume, fetal zone size, and adrenal to kidney ratios. Relationship between adrenal measurements, antenatal factors, and postnatal outcomes were studied. RESULTS: We reported normative adrenal gland volume data during gestation from 80 appropriate for gestational age (AGA) infants. In a binary analysis, adrenal size was significantly related to gender, race, intrauterine growth restriction (IUGR), maternal chorioamnionitis, and maternal hypertension. Linear regression analysis showed that fetal zone is significantly related to not only gestational age but also chorioamnionitis and later development of intraventricular hemorrhage (IVH). Adrenal volume likewise is also related to gestational age, preeclampsia, and IVH. CONCLUSIONS: Antenatal maternal factors and uterine environment affects adrenal growth and development thus postnatal high resolution 2D US scan of adrenal glands can provide useful information to predict outcomes. This information can complement hormone and adrenocorticotrophic hormone (ACTH) stimulation assays.

Serum neurotrophins at birth correlate with respiratory and neurodevelopmental outcomes of premature infants.

OBJECTIVE: Preterm birth is a significant cause of infant morbidity and mortality, which are primarily the result of respiratory and neurodevelopmental complications. However, no objective biomarker is currently available to predict at birth the risk and severity of such complications. Thus, we sought to determine whether serum neurotrophins concentrations measured at birth correlate with risk for later development of bronchopulmonary dysplasia (BPD) and long-term neurodevelopmental outcomes. METHODS: This study prospectively included 223 newborns admitted to neonatal intensive care units (NICU) and divided into three groups: (i) preterm infants who developed BPD; (ii) preterm infants who did not develop BPD; (iii) term infants. An exploratory cohort was enrolled in West Virginia, followed by a validation cohort recruited in four NICUs in Ohio. Specimens for serum and tracheal neurotrophins concentrations were collected within 48 h of admission. Infants requiring a fraction of inspired oxygen >0.21 for at least 28 days were diagnosed with BPD. Neurodevelopmental outcomes were extrapolated from Bayley Scales of Infant Development-Third Edition (BSID-III) administered at the 24-month follow-up visit. RESULTS: Serum brain-derived neurotrophic factor (BDNF) concentration at birth had significant negative correlation with later diagnosis of BPD (P = 0.011) and with duration of invasive ventilation and oxygen supplementation (P = 0.009 and 0.015, respectively). Serum nerve growth factor (NGF) concentration at birth had significant positive correlation with BSID-III cognitive and language composite scores at 24 months (P < 0.001 and 0.010, respectively). CONCLUSIONS: These data suggest that serum neurotrophins concentrations measured at birth provide prognostic information on subsequent respiratory and neurodevelopmental outcomes.

Cerebrospinal fluid values in very low birth weight infants with suspected sepsis at different ages.

OBJECTIVES: Lumbar puncture can be an essential part of the septic work-up in premature infants who are at risk for sepsis and meningitis. Cerebrospinal fluid (CSF) values for cell counts, protein concentrations, and glucose concentrations in children and full-term infants are well established. CSF values in premature infants, however, have not been well studied. We sought to determine CSF values in very low birth weight premature infants at different ages (birth, postmenstrual age, and postnatal age). DESIGN: Medical records of all very low birth weight premature infants with suspected sepsis who were admitted to our neonatal intensive care unit between 1991 and 2005 were reviewed. Infants were excluded if they had evidence of intraventricular hemorrhage, sepsis/meningitis, or major congenital abnormalities or had a traumatic lumbar puncture. SETTING: Neonatal intensive care unit. PATIENTS: Patients were 455 infants who underwent lumbar puncture. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records of 455 infants who underwent 648 lumbar punctures were reviewed. Of these, 243 infants met our inclusion criteria, and 88 patients underwent lumbar puncture only at birth. Patients' mean gestational age and birth weight were 28.8 +/- 2.6 wks and 1080 +/- 279 g, respectively. There were no correlations between gestational age and CSF white blood cell (WBC) count or between gestational age and CSF protein concentrations at birth. CSF WBC count remained unchanged at different postmenstrual ages. However, CSF protein concentration decreased with advancing postmenstrual age (Spearman's rho correlation coefficient, r = -.29; p < .01), and both CSF WBC count and CSF protein concentration decreased with advancing postnatal age (Spearman's rho correlation coefficient, r = -.319 and r = -.376, respectively; p < .01). A subgroup analysis revealed differences in CSF WBC count and CSF protein concentrations between infants who had a lumbar puncture at birth, at 2 wks, and at 3 wks of life at the same postmenstrual age. CONCLUSIONS: In very low birth weight premature infants, CSF WBC count and CSF protein concentrations vary with advancing postnatal and postmenstrual ages.

Usefulness of Assessment of Stool Form by the Modified Bristol Stool Form Scale in Primary Care Pediatrics.

PURPOSE: Rome criteria are considered the gold standard for diagnosing functional constipation. The modified Bristol stool form scale (m-BSFS) was validated to measure stool form in children. However, neither the potential use of the m-BSFS as a tool to facilitate the diagnosis of potential constipation, nor the agreement between m-BSFS and stool consistency by Rome has been studied. Our objective is to determine if m-BSFS is a reliable tool to facilitat detection of constipation; and the agreement between stool form by m-BSFS and hard stool criteria in Rome. METHODS: A survey tool with the Rome III criteria and the m-BSFS was developed. A Likert-scale addressed frequency of each stool form on the m-BSFS. Responses to Rome III and m-BSFS were compared. RESULTS: The sensitivity and specificity of the m-BSFS was 79.2% and 66.0% respectively; and in children <4 years. improved to 81.2% and 75.0% respectively. There was poor agreement between hard stools by m-BSFS and the painful or hard bowel movement question of Rome Criteria. CONCLUSION: The potential utility of m-BSFS as a reasonably good tool to facilitate the diagnosis of potential constipation in children is shown. The poor agreement between painful or hard stool question in Rome III, and ratings for hard stool on the m-BSFS illustrates that one's perception may differ between a question and a picture. A useful pictorial tool to appraise stool form may, thus, be a favorable complement in the process of enquiry about bowel habits in well-child care.

Fluid Overload and Renal Angina Index at Admission Are Associated With Worse Outcomes in Critically Ill Children.

Objectives: We investigated the association of fluid overload and oxygenation in critically sick children, and their correlation with various outcomes (duration of ventilation, ICU stay, and mortality). We also assessed whether renal angina index (RAI) at admission can predict mortality or acute kidney injury (AKI) on day 3 after admission. Design and setting: Prospective study, pediatric intensive care in a tertiary hospital. Duration: June 2013-June 2014. Patients: Patients were included if they needed invasive mechanical ventilation for >24 h and had an indwelling arterial catheter. Patients with congenital heart disease or those who received renal replacement therapy (RRT) were excluded. Methods: Oxygenation index, fluid overload percent (daily, cumulative), RAI at admission and pediatric logistic organ dysfunction (PELOD) score were obtained in all critically ill children. KDIGO classification was used to define AKI, using both creatinine and urine output criteria. Admission data for determination of RAI included the use of vasopressors, invasive mechanical ventilation, percent fluid overload, and change in kidney function (estimated creatinine clearance). Univariable and multivariable approaches were used to assess the relations between fluid overload, oxygenation index and clinical outcomes. An RAI cutoff >8 was used to predict AKI on day 3 of admission and mortality. Results: One hundred and two patients were recruited. Fluid overload predicted oxygenation index in all patients, independent of age, gender and PELOD score (p < 0.05). Fluid overload was associated with longer duration of ventilation (p < 0.05), controlled for age, gender, and PELOD score. Day-3 AKI rates were higher in patients with a RAI of 8 or more, and higher areas under the RAI curve had better prediction rates for Day-3 AKI. An RAI <8 had high negative predictive values (80-95%) for Day-3 AKI. RAI was better than traditional markers of pediatric severity of illness (PELOD) score for prediction of AKI on day 3. Conclusions: This study emphasizes that positive fluid balance adversely affects intensive care in critically ill children. Further, the RAI prediction model may help optimize treatment and improve clinical prediction of AKI.

Effects of (r,r)- and (r,r/s,s)-formoterol on airway relaxation and contraction in an experimental rat model.

BACKGROUND: Racemic (R,R/S,S)-formoterol is a long-acting ß-agonist composed of a 50:50 mixture of (R,R)- and (S,S)-enantiomers. OBJECTIVE: The aim of this study was to determine whether (R,R)-formoterol and (R,R/S,S)-formoterol have differing effects on airway contraction and relaxation in vitro. METHODS: Cylindrical airway segments 3-mm long were isolated from the mid-trachea of healthy Sprague-Dawley rats and placed in a modified Krebs-Henseleit solution. Dose-response curves of bethanechol-induced contraction (measured as milligrams of tension) and the concentration of bethanechol that elicited 50% to 75% of maximal contraction (EC50-75) were determined. The air-way cylinders were then precontracted with bethanechol at the EC50-75 and exposed to different concentrations of (R,R)-formoterol (0.0001-1.0 µM) or (R,R/S,S)-formoterol (0.0002-2.0 µM). Each concentration of the 2 formoterol formulations contained the same amount of (R,R)-enantiomer (eg, [R,R]-formoterol 0.0001 µM and [R,R/S,S]-formoterol 0.0002 1JM contained the same amount of [R,R]-enantiomer). The relaxation percentage in response to formoterol was calculated as a reduction in tension (in milligrams) in relation to baseline tension in the precontracted state, with each tracheal cylinder serving as its own control. To determine the effect of (R,R)-formoterol on airway contraction, tracheal cylinders were incubated with (R,R)- or (R,R/S,S)-formoterol before electrical field stimulation (EFS). RESULTS: Tracheae from 56 three-week-old Sprague-Dawley rats were used in the study. The relaxation percentage of precontracted trachea was significantly greater after exposure to (R,R)-formoterol than to (R,R/S,S)-formoterol at a 2-fold higher concentration (P = 0.03; general linear model with repeated measures analysis comparing the 2 groups of animals). However, in a post hoc analysis, the mean (SE) relaxation percentage of precontracted trachea was significantly greater only after exposure to (R,R)-formoterol 0.01 µM than to (R,R/S,S)-formoterol 0.02 µM (15.6% [5.8%] vs 39.0% [5.6%]; P < 0.05, unpaired t test). EFS-induced airway contraction was significantly less in tracheal cylinders incubated in (R,R)-formoterol compared with those incubated in (R,R/S,S)-formoterol at a 2-fold higher concentration (P = 0.05; general linear model with repeated measures analysis comparing the 2 groups of animals). However, in the post hoc analysis, mean (SE) EFS-induced tracheal contraction was significantly less only in (R,R)-formoterol 0.01 µM compared with (R,R/S,S)-formoterol 0.02 µM at 10 V (1070 [55] mgvs 1225 [28] mg; P < 0.05, unpaired t test). CONCLUSION: We found that (R,R)-formoterol may induce greater relaxation of precontracted airway smooth muscle cells than (R,R/S,S)-formoterol and that (R,R)-formoterol may have a greater inhibitory effect on the endogenous cholinergic and excitatory nonadrenergic, noncholinergic contractile airway responses than (R,R/S,S)-formoterol. We speculate that the presence of the (S,S)-enantiomer in (R,R/S,S)-formoterol may impair airway relaxation of pre-contracted trachea in rats.

Prevalence of diabetes and obesity in association with prematurity and growth restriction.

Intrauterine growth restriction (IUGR) is when fetuses and newborn infants have not reached their true growth potential as genetically defined. Fetuses with IUGR develop in a less than ideal environment that leads to epigenetic changes and marks infants' metabolism for the rest of their lives. Epigenetic changes affect insulin-like growth factor-1 (IGF-1) levels and lead to insulin resistance and ultimately to a metabolic syndrome. The metabolic syndrome is a constellation of illnesses that raise one's risk for type 2 diabetes mellitus, coronary artery disease, and ischemic heart disease, including hypertension, dyslipidemia, central obesity, insulin resistance, and inflammation. The association between IUGR or prematurity and long-term insulin resistance, obesity, hypertension, and metabolic syndrome remains unclear. While studies have shown an association, others have not supported such association. If alteration of intrauterine growth can ultimately lead to the development of metabolic derangements in childhood and adulthood, and if such association is true, then early interventions targeting the health of pregnant women will ensure the health of the population to follow.

Respiratory severity score and extubation readiness in very low birth weight infants.

BACKGROUND: The respiratory severity score (RSS) is a byproduct of mean airway pressure (MAP) and fraction of inspired oxygen (FiO2). We sought to determine whether RSS could be used as a screening tool to predict extubation readiness in very low birth weight (VLBW) infants. METHODS: In a retrospective cohort study, medical records of all VLBW infants admitted to our unit (6/1/09-2/28/12) were reviewed for infants' demographics, prenatal characteristics, and medication use. Also, records were reviewed for unplanned vs. planned extubation, blood gas, ventilator parameters and signs of severe respiratory failure [RF, defined as partial pressure of carbon dioxide (pCO2) > 65, pH < 7.20, FiO2 > 50%, and MAP > 10 cm] on the day of extubation. RESULTS: During the study period 31% (45/147) failed extubation. Overall, infants who failed extubation had a lower birth weight (BW) and gestational age (GA), and on the day of extubation had a higher RSS and percentage of having one or more signs of severe RF. In a logistic regression model, adjusting for BW, GA, RSS and RF, RSS remained the only risk factor associated with extubation failure [adjusted OR 1.63 (95% CI: 1.10-2.40); p = 0.01]. RSS had a sensitivity of 0.86 (95% CI: 0.72-0.94) at a cutoff of 1.26 and a specificity of 0.88 (95% CI: 0.80-0.94) at a cutoff of 2.5. There was no difference in extubation failure between unplanned vs. planned extubation [41% (9/22) vs. 29% (36/125); p = 0.25]. CONCLUSION: An elevated RSS is associated with extubation failure. Successful unplanned extubation is common in VLBW infants.