Hemodynamic assessment by neonatologist using echocardiography: Primary provider versus consultation model.

Hemodynamic instability is very common in sick neonates and the currently used traditional hemodynamic monitoring tools lack sensitivity and specificity. Hemodynamic evaluation on echocardiography can provide direct information regarding the pathophysiology causing the hemodynamic instability and help the bedside clinician in making a personalized treatment approach based upon the deranged pathophysiology. Assessment of cardiac function and hemodynamics is essential in the management of neonates with cardiorespiratory failure, and hence neonatologist-performed echocardiography is becoming an essential tool in modern neonatal care. Depending on the level and size of the NICU, there is a daily need for echocardiography, and for a subset of sick infants, serial echocardiographic assessments are warranted. Comprehensive guidelines for neonatologists performing echocardiography and targeted neonatal echocardiography have been published providing a framework for training and quality assurance. There has been a significant interest among the providers to learn echocardiography skills. This manuscript explores the various needs of neonatal care providers around echocardiography, the current challenges neonatologists face in learning echocardiography, and how they, especially neonatal fellows, can learn these important skills during their training.

Milrinone in persistent pulmonary hypertension of newborn: a scoping review.

Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition in newborns admitted to the neonatal intensive care units (NICUs). PPHN has still a high mortality and morbidity. Inhaled nitric oxide (iNO) is the first line vasodilator therapy for PPHN in high income countries. In low-to-middle income countries (LMICs), availability of iNO remains scarce and expensive. The purpose of this scoping review was to evaluate the current existing literature for milrinone therapy in PPHN and to identify the knowledge gaps in milrinone use in infants with PPHN. The available evidence for milrinone remains limited both as monotherapy and as an adjuvant to iNO. The studies were heterogeneous, conducted in different settings, with different populations and more importantly the endpoints of these trials were short-term outcomes such as changes in oxygenation and blood pressure. Large prospective studies investigating long-term outcomes, mortality, and the need for Extracorporeal membrane oxygenation (ECMO) are warranted. Randomized controlled trials with milrinone as monotherapy are needed in LMICs where iNO availability remains limited. IMPACT: Milrinone has a potential role in the management of PPHN both as an adjuvant to iNO as well as a monotherapy. This scoping review identified the problems existing in the published literature on milrinone and the barriers to generalization of these results. Multi-centre randomized controlled trials on milrinone, especially involving centers from low- and middle-income countries are needed, where it can be evaluated as first-line pulmonary vasodilator therapy.

Effect of Maternal Preeclampsia on Cardiac Structure and Function in Very Low Birth Weight Infants.

OBJECTIVE: We aimed to determine whether exposure to severe maternal preeclampsia (PE) in very low birth weight (VLBW) infants is associated with hypertrophic cardiac changes and altered hemodynamics. STUDY DESIGN: Case-control study of VLBW infants born at Los Angeles General Medical Center from May 2015 to August 2023, who had an echocardiogram within the first 7 days of life. Cases were infants exposed to maternal PE and controls were infants not exposed to maternal PE matched by birth weight (BW) 1:1. Laboratory, placental pathology results, hemodynamic data and clinical outcomes were collected and compared between cases and control infants. RESULTS: A total of 43 cases matched by BW with control infants were studied. There were no significant anatomical cardiac changes by echocardiography between cases and control infants. Cases had significantly higher blood pressure within the first 72 hours of life and lower ejection fraction (EF), fractional shortening, and peak systolic flow velocity through their patent ductus arteriosus (PDA) within the first week of life. Cases were more likely to be smaller despite being born at a later gestational age (GA), as well as small for GA with placental weight less than 10th percentile compared to control infants. CONCLUSION: Our findings indicate that infants born to mothers with PE have higher systemic vascular resistance as evidenced by elevated blood pressure, and lower EF and shortening fraction and higher pulmonary vascular resistance as evidenced by lower peak flow velocity through the PDA. We did not observe hypertrophic cardiac changes in exposed infants. These findings should be considered in clinical decision-making during management of these infants. KEY POINTS: · VLBW infants exposed to severe PE have higher rate of Small for gestational age and smaller placentas.. · VLBW infants exposed to severe PE have higher systemic vascular resistance during transitional period and lower EF and fractional shortening.. · VLBW infants exposed to severe PE have higher pulmonary vascular resistance..

Effect of assessing velocity time integral at different locations across ventricular outflow tracts when calculating cardiac output in neonates.

This study aims to evaluate the effect of assessing velocity time integral at different locations across ventricular outflow tracts for calculating cardiac output (CO) in neonates. Velocity time integral (VTI) and CO were measured at 3 different locations across right and left ventricular outflow tracts using transthoracic echocardiography in healthy term neonates without any major congenital heart disease. ANOVA with Bonferroni correction was used to determine the differences between the VTI and CO sampled at these three locations. Forty-one neonates met inclusion criteria with mean gestational age of 38.6 ± 1 weeks and mean birth weight of 3155 ± 463 g. The median hours after birth when echocardiography was obtained was 23 h (range 11-68 h after birth). Left CO were 121 ± 30 mL/kg/min, 155 ± 38 mL/kg/min, and 176 ± 36 mL/kg/min measured below the valve, hinges of the valve, and tip of the valve, respectively. Right CO were 197 ± 73 mL/kg/min, 270 ± 83 mL/kg/min, and 329 ± 104 mL/kg/min measured below the valve, hinges of the valve, and tip of the valve, respectively. A statistically significant difference (P < 0.001) was found in the VTI and CO measured at the 3 different locations across both left and right ventricular outflow tracts.     Conclusions: There is a significant difference in measurements of VTI and CO depending on the location of Doppler gate sampling across the ventricular outflow tracts. Consistency and precision in Doppler gate location are essential for measuring VTI and calculating CO while assessing changes in hemodynamic status in critically ill infants. What is Known: • Targeted Neonatal Echocardiography is increasingly applied to measure cardiac output in critically ill neonates and serial assessments are performed to assess the trend in changes in cardiac output. • Noninvasive measurement using velocity time integral to calculate cardiac output is commonly performed. However, location of Doppler sample gate to measure ventricular outflow tract velocity time integral is not consistent. What is New: • Statistically significant changes in measured velocity time integral and cardiac output are noted based on the location of Doppler gate sampling. • To monitor the cardiac output for trending, it is important to be consistent with regards to the location of the Doppler sample gate to assess changes in cardiac output in critically ill newborns.

Outcomes of patent foramen ovale greater than 3 mm at birth in extremely low birthweight infants.

BACKGROUND: Foramen ovale (FO) is an obligate fetal shunt that typically resolves after birth, although patency throughout life is not uncommon. The natural history of patent FO (PFO) is known in term infants, but less is known about its course in extremely preterm infants. We describe the echocardiographic changes in FO size from birth to discharge in extremely low birth weight (ELBW) infants in this retrospective study. METHODS: Cohort was divided based on size of FO at birth. Size of FO at discharge was measured and evaluated relative to postnatal weight gain. Demographics and clinical outcomes were compared between the two groups. RESULTS: Of the 54 ELBW infants, 50 were born with FO less than 3 mm in diameter (small), and 4 were born with FO greater than 3 mm (large). Of small defects, the majority (44/50, 88%) did not increase in size with weight gain, and minority (6/50, 12%) increased in size, and three of these 6 patients, FO grew to be slightly larger than 3 mm. In contrast, all large defects (4 of 4, 100%) nearly doubled in size with postnatal growth. These 4 ELBW infants with enlargement of FO had a flap valve evident on echocardiogram obtained prior to discharge, and subsequently closed on outpatient follow-up echocardiograms, although time to resolution was variable (6 months - 3 years). One infant had presumptive resolution because of the presence of flap valve. CONCLUSION: No maternal or neonatal demographic characteristics were predictive of FO enlargement, although, demonstrable flap valve on discharge echocardiogram correlated with resolution of FO on outpatient follow-up echocardiogram. Therefore, based on our data, we recommend that ELBW infants born with large FO should have echocardiographic re-evaluation of the atrial septal opening prior to discharge, to specify the presence of a flap valve or lack thereof, which is an important detail that can help a neonatologist determine the need for outpatient cardiac follow-up.

Transient Hypoglycemia and Biochemical Differences in Infants Less Than 1,250 G at Birth Fed Human Milk with Human Milk-Derived Fortifier versus Cow Milk-Derived Fortifier.

OBJECTIVE: Fortification of human milk (HM) with either human milk-derived fortifier (HMDF) or cow milk-derived fortifier (CMDF) is important in preterm infants. The objective is to compare the incidence of hypoglycemia, and biochemical values in infants less than 1,250 g at birth fed HMDF versus CMDF. STUDY DESIGN: It is a retrospective cohort study on infants less than 1,250 g at birth who were fed with HMDF or CMDF. Hypoglycemia was defined as blood glucose (BG) level equal to or less than 60 mg/dL within 72 hours of full enteral feeds when off total parenteral nutrition and intravenous fluids. RESULTS: Ninety infants were enrolled (HMDF = 61, CMDF = 29). HMDF group had a higher rate of hypoglycemia (46 vs. 24%; p = 0.048) after achievement of full enteral feeding. The median minimum BG was lower (61 vs. 71; p ≤ 0.01), while blood urea nitrogen (12 vs. 6; p ≤ 0.01) and albumin (3.1 vs. 2.7; p ≤ 0.01) were higher in HMDF group compared with CMDF. CONCLUSION: At full enteral feedings in infants less than 1,250 g at birth, an HMDF diet may predispose to hypoglycemia needing intervention. Close monitoring of BG levels once off parenteral nutrition is recommended. KEY POINTS: · Exclusive human milk (EHM) feeding results in better nutritional indices.. · EHM feeding at higher calorie/ounce improves growth.. · Blood glucose needs to be monitored when off TPN during EHM feeding..

Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial.

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Effectiveness of Simulation Training in Acquiring Echocardiography Skills among Neonatology Care Providers.

OBJECTIVE: The objective of this study was to test the hypothesis that simulation training improves echocardiography skills. STUDY DESIGN: In this prospective study, 43 participants (16 neonatologists, 26 neonatology fellows, and 1 nurse practitioner) were tested on the simulator after 4 hours of didactic sessions on topographical cardiac anatomy and standard echocardiographic views. Participants were given 20 minutes to obtain and save the standard views. After the simulation hands-on training for 8 hours over 3 days, they were tested again. Each image was scored from 0 to 3 based on the image quality. Pre- and postsimulator training data were compared using both automated and visual scoring methods. RESULTS: After the hands-on simulator training, the automated median (interquartile) score for the quality of acquired images increased from 36 (22, 43) to 55 (48, 58), p < 0.0001. The increase was similar using visual scoring. The number of views with acceptable or good image quality (scores of 2 or 3) increased from 11 (6, 16) to 20 (17, 21), p < 0.0001. The neonatology fellows and faculty, as well as those with or without prior echocardiography experience, demonstrated significant improvement. CONCLUSIONS: Echocardiography simulation is an effective tool in improving echocardiography skills among neonatology care providers. KEY POINTS: · Simulation is effective in acquiring echocardiography skills among neonatology care providers.. · Simulation improves image acquisition in those with and without prior echocardiography experience.. · Effectiveness of simulation in retaining the acquired echocardiography skill should be investigated..

Bronchopulmonary dysplasia predicted at birth by artificial intelligence.

AIM: To develop a fast bedside test for prediction and early targeted intervention of bronchopulmonary dysplasia (BPD) to improve the outcome. METHODS: In a multicentre study of preterm infants with gestational age 24-31 weeks, clinical data present at birth were combined with spectral data of gastric aspirate samples taken at birth and analysed using artificial intelligence. The study was designed to develop an algorithm to predict development of BPD. The BPD definition used was the consensus definition of the US National Institutes of Health: Requirement of supplemental oxygen for at least 28 days with subsequent assessment at 36 weeks postmenstrual age. RESULTS: Twenty-six (43%) of the 61 included infants developed BPD. Spectral data analysis of the gastric aspirates identified the most important wave numbers for classification and surfactant treatment, and birth weight and gestational age were the most important predictive clinical data. By combining these data, the resulting algorithm for early diagnosis of BPD had a sensitivity of 88% and a specificity of 91%. CONCLUSION: A point-of-care test to predict subsequent development of BPD at birth has been developed using a new software algorithm allowing early targeted intervention of BPD which could improve the outcome.

Proportion of Retinopathy of Prematurity That Was Treated across Regions in the United States.

OBJECTIVES: Retinopathy of prematurity (ROP) is the leading preventable cause of blindness in children worldwide. Major eye and visual problems are strongly linked to ROP requiring treatment. Objectives of the study are to: (1) evaluate the trends and regional differences in the proportion of treated ROP, (2) describe risk factors, and (3) examine if treated ROP predicts mortality. STUDY DESIGN: Retrospective data analysis was conducted using the Kids' Inpatient Database from 1997 to 2012. ROP was categorized into treated ROP (requiring laser photocoagulation or surgical intervention) and nontreated ROP. Bivariate and multivariate logistic regression analyses were performed. RESULTS: Out of 21,955,949 infants ≤ 12 months old, we identified 70,541 cases of ROP and 7,167 (10.2%) were treated. Over time, the proportion of treated ROP decreased (p = < 0.001). While extremely low birth weight infants cared for in the Midwest was associated with treated ROP (adjusted odds ratio [aOR] = 29.05; 95% confidence interval [CI]: 10.64-79.34), black race (aOR = 0.57; 95% CI: 0.51-0.64) care for in the birth hospital (aOR = 0.44; 95% CI: 0.41-0.48) was protective. Treated ROP was not associated with mortality. CONCLUSION: The proportion of ROP that is surgically treated has decreased in the United States; however, there is variability among the different regions. Demographics and clinical practice may have contributed for this variability.

Systemic to Pulmonary Collaterals in Extremely Low Birth Weight Infants: Incidence, Clinical Significance, and Hemodynamic Features.

OBJECTIVE: This study aimed to determine the incidence of systemic to pulmonary collaterals (SPCs) in extremely low birth weight infants and to assess its clinical and hemodynamic significance beyond the neonatal period. STUDY DESIGN: Retrospective cohort study was conducted on 61 infants with echocardiogram performed at the time of discharge to determine the presence of SPC and to measure the right and left ventricular outputs and left atrium to aortic ratio. We compared two groups: small or no SPC (Group 1) to moderate or large SPC (Group 2) on demographics, clinical outcomes, and echocardiographic parameters. RESULTS: Sixty-one infants were included. The incidence of SPC was 57%; 21% of infants had moderate or large shunts and 31% had small SPC. Demographics, clinical outcomes, and echocardiographic parameters were not significantly different between small or no SPC and moderate to large SPC. CONCLUSION: More than half of the infants had SPC. The size of the shunt did not affect the clinical outcomes nor the echocardiographic parameters measured. All infants had cardiac output above the normative mean.

Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial.

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group. Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Effects of Patent Ductus Arteriosus on Organ Blood Flow in Infants Born Very Preterm: A Prospective Study with Serial Echocardiography.

OBJECTIVE: To characterize the effects of a patent ductus arteriosus (PDA) on different organ blood flows in infants born preterm. STUDY DESIGN: Infants born preterm at ≤30 weeks of gestational age had daily echocardiography and Doppler assessments of middle cerebral artery, celiac artery, superior mesenteric (SMA), and renal arteries (RA) during the first postnatal week. Abnormal organ blood flow was defined as either reverse or absent diastolic flow, abnormally low mean or systolic velocities, or abnormally high pulsatility or resistance index. RESULTS: Twenty-five infants born very preterm (gestational age 27.0 ± 2.1 weeks) were enrolled. PDA presence at time of measurement increased the risk of abnormal organ blood flows (39% vs 8%, P < .001). Ductal diameter and left atrium-to-aortic root (LA/Ao) ratio correlated positively with resistance index (celiac artery, SMA, RA), and negatively with mean velocity (ductal diameter: SMA, RA; LA/Ao ratio: RA). A PDA >2.0 mm, LA/Ao ratio >1.4, and their combination were associated with 8.0 (95% CI 1.6-39.4)-, 6.7 (1.3-34.7)-, and 38.2 (3.2-455.5)-fold increase in risk of abnormal organ blood flow index, respectively. Abnormal descending aorta flow was detected in only 2% of measurements. CONCLUSIONS: Ductal size >2.0 mm and LA/Ao >1.4, especially in combination, are associated with a greater risk of abnormal organ blood flows. We suggest that Doppler assessment of the renal and superior mesenteric arteries are more likely to detect systemic hypoperfusion than the descending aorta.

Synthetic Surfactant CHF5633 Compared with Poractant Alfa in the Treatment of Neonatal Respiratory Distress Syndrome: A Multicenter, Double-Blind, Randomized, Controlled Clinical Trial.

OBJECTIVE: To compare efficacy and safety of a new synthetic surfactant, CHF5633, enriched with surfactant proteins, SP-B and SP-C peptide analogues, with porcine surfactant, poractant alfa, for the treatment of respiratory distress syndrome in infants born preterm. STUDY DESIGN: Neonates born preterm on respiratory support requiring fraction of inspired oxygen (FiO2) ≥0.30 from 240/7 to 266/7 weeks and FiO2 ≥0.35 from 270/7 to 296/7 weeks of gestation to maintain 88%-95% oxygen saturation were randomized to receive 200 mg/kg of CHF5633 or poractant alfa. If necessary, redosing was given at 100 mg/kg. Efficacy end points were oxygen requirement (FiO2, respiratory severity score [FiO2 × mean airway pressure]) in the first 24 hours, 7 and 28 days, discharge home, and/or 36 weeks of postmenstrual age; mortality and bronchopulmonary dysplasia at 28 days and 36 weeks of PMA. Adverse events and immunogenicity were monitored for safety. RESULTS: Of the 123 randomized neonates, 113 were treated (56 and 57 in CHF5633 and poractant alfa groups, respectively). In both arms, FiO2 and respiratory severity score decreased from baseline at all time points (P < .001) with no statistically significant differences between groups. Rescue surfactant use (19 [33.9%] vs 17 [29.8%]), bronchopulmonary dysplasia (31 [55.4%] and 32 [56.1%]), and mortality at day 28 (4 [7.1%] and 3 [5.3%]) were similar in the CHF5633 and poractant alfa groups, respectively. In 2 (3.4%) and 1 (1.7%) neonates, adverse drug reactions were reported in CHF5633 and poractant alfa groups, respectively. No immunogenicity was detected. CONCLUSIONS: Treatment with CHF5633 showed similar efficacy and safety as poractant alfa in neonates born preterm with moderate-to-severe respiratory distress syndrome. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02452476.

High unbound bilirubin for age: a neurotoxin with major effects on the developing brain.

Neonatal hyperbilirubinemia is one of the most frequent diagnoses made in neonates. A high level of unconjugated bilirubin that is unbound to albumin is neurotoxic when the level exceeds age-specific thresholds or at lower levels in neonates with neurotoxic risk factors. Lower range of unbound bilirubin results in apoptosis, while moderate-to-high levels result in neuronal necrosis. Basal ganglia and various brain stem nuclei are more susceptible to bilirubin toxicity. Proposed mechanisms of bilirubin-induced neurotoxicity include excessive release of glutamate, mitochondrial energy failure, release of proinflammatory cytokines, and increased intracellular calcium concentration. These mechanisms are similar to the events that occur following hypoxic-ischemic insult in neonates. Severe hyperbilirubinemia in term neonates has been shown to be associated with increased risk for autism spectrum disorders. The neuropathological finding of bilirubin-induced neurotoxicity also includes cerebellar injury with a decreased number of Purkinje cells, and disruption of multisensory feedback loop between cerebellum and cortical neurons which may explain the clinical characteristics of autism spectrum disorders. Severe hyperbilirubinemia occurs more frequently in infants from low- and middle-income countries (LMIC). Simple devices to measure bilirubin, and timely treatment are essential to reduce neurotoxicity, and improve outcomes for thousands of neonates around the world.

Evolution of surfactant therapy for respiratory distress syndrome: past, present, and future.

Respiratory distress syndrome (RDS) due to surfactant deficiency is the most common cause of respiratory failure in preterm infants. Tremendous progress has been made since the original description that surfactant deficiency is the major cause of RDS. Surfactant therapy has been extensively studied in preterm infants and has been shown to significantly decrease air leaks and neonatal and infant mortality. Synthetic and animal-derived surfactants from bovine as well as porcine origin have been evaluated in randomized controlled trials. Animal-derived surfactants generally result in faster weaning of respiratory support, shorter duration of invasive ventilation, and decreased mortality when compared to first- or second-generation of synthetic surfactants, but some of the second-generation synthetic surfactants are at least not inferior to the animal-derived surfactants. Using a higher initial dose of porcine derived surfactant may provide better outcomes when compared with using lower doses of bovine surfactants, likely, due to compositional difference and/or the dose. Third-generation synthetic surfactant containing peptide analogs of surfactant protein B and C are currently being studied. Less invasive intra-tracheal surfactant administration techniques in spontaneously breathing neonate receiving noninvasive ventilator support are also being evaluated. In the present era, prophylactic surfactant is not recommended as it may increase the risk of lung injury or death. In the future, surfactants may be used as vector to deliver steroids, or used in combination with molecules, such as, recombinant Club Cell Protein-10 (rhCC-10) to improve pulmonary outcomes. Also, noninvasive surfactant administration techniques, such as aerosolization or atomization of surfactant may play a greater role in the future.

Graded oxygen saturation targets and retinopathy of prematurity in extremely preterm infants.

BACKGROUND: We compared the incidence of severe retinopathy of prematurity (ROP) and need for laser treatment before and after implementing graded pulse oximeter oxygen saturation (SpO2) targets in extremely preterm infants. Mortality and other secondary outcomes were compared. METHODS: Before 2002, we used 90-94% as the SpO2 target in infants 24(0/7)-27(6/7)wk gestation and birth weight <1,000 g until 35(6/7) wk postmenstrual age (PMA). We implemented graded SpO2 targets based on vaso-obliterative and vaso-proliferative phases of ROP in 2002. Group 1 (1995-2001) before, and Group 2 (2003-2010) after implementation of graded SpO2 targets based on PMA (83-89% until 32(6/7) wk, 90-94% until 35(6/7) wk and >94% at ≥ 36 wk PMA). RESULTS: There were 267 patients in Group 1 and 220 in Group 2. There was no significant difference in birth weight or gestational age. Severe ROP (adjusted OR: 0.18, 95% CI: 0.11, 0.30; P < 0.001) and laser surgery rates (adjusted OR: 0.31, 95% CI: 0.18, 0.52; P < 0.001) decreased significantly in Group 2. There was no difference in mortality (adjusted OR: 0.74, 95% CI: 0.37, 1.49; P = 0.40). CONCLUSION: In this retrospective cohort study, implementation of graded SpO2 targets decreased severe ROP and need for laser therapy, without increasing mortality.