Joaquim M.B. Pinheiro

The New York State universal newborn hearing screening demonstration project: Ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention

Objective: To determine the ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention through a multi‐center, state‐wide universal newborn hearing screening project. Design: Universal newborn hearing screening was conducted at eight hospitals across New York State. All infants who did not bilaterally pass hearing screening before discharge were recalled for outpatient retesting. Inpatient screening and outpatient rescreening were done with transient evoked otoacoustic emissions and/or auditory brain stem response testing. Diagnostic testing was performed with age appropriate tests, auditory brain stem response and/or visual reinforcement audiometry. Infants diagnosed with permanent hearing loss were considered for hearing aids and early intervention. Ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention were investigated regarding nursery type, risk status, unilateral versus bilateral hearing loss, loss type, loss severity, and state regions. Results: The prevalence of infants diagnosed with permanent hearing loss was 2.0/1000 (85 of 43,311). Of the 85 infants with hearing loss, 61% were from neonatal intensive care units (NICUs) and 67% were at risk for hearing loss. Of the 36 infants fitted with hearing aids, 58% were from NICUs and 78% were at risk for hearing loss. The median age at identification and enrollment in early intervention was 3 mo. Median age at hearing aid fitting was 7.5 mo. Median ages at identification were less for infants from the well‐baby nurseries (WBNs) than for the NICU infants and for infants with severe/profound than for infants with mild/moderate hearing loss, but were similar for not‐at‐risk and at‐risk infants. Median ages at hearing aid fitting were less for well babies than for NICU infants, for not‐at‐risk infants than for at‐risk infants, and for infants with severe/profound hearing loss than for infants with mild/moderate hearing loss. However, median ages at early intervention enrollment were similar for nursery types, risk status, and severity of hearing loss. Conclusions: Early ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention can be achieved for infants from NICUs and WBNs and for infants at risk and not at risk for hearing loss in a large multi‐center universal newborn hearing screening program.

The New York State universal newborn hearing screening demonstration project: outpatient outcome measures.

Objective: To investigate outpatient outcome measures of a multi‐center, state‐wide, universal newborn hearing screening project. Design: Eight hospitals participated in a 3‐yr, funded project. Each hospital designed its own protocol using common criteria for judging whether an infant passed a hearing screening. Infants were tested in the hospital, and those either failing the in‐hospital screening or who were not tested in the hospital (missed) were asked to return 4 to 6 wk after hospital discharge for outpatient rescreening. Those infants failing the outpatient rescreening were referred for diagnostic auditory brain stem response testing. Each hospital used its own audiological equipment and criteria to determine whether a particular infant had a hearing loss. All data were collected and analyzed for individual hospitals, as well as totaled across all hospitals. Data were analyzed in terms of year of program operation, nursery type, and geographic region. Results: Seventy‐two percent of infants who failed the in‐hospital screening returned for outpatient testing. The percentage of in‐hospital fails returning for retesting was significantly higher than the percentage of in‐hospital misses returning for retesting. The percentage of infants returning for retesting increased with successive years of program operation. Some differences were noted in the percentage of infants returning for retesting among hospitals and geographic regions of the state. Some differences in outpatient outcome measures also were noted between infants originally born into the neonatal intensive care unit (NICU) and the well‐baby nursery (WBN). The percentage of infants from the NICU who returned for retesting was slightly higher than that for infants from the WBN. The percentage of infants from the WBN passing the outpatient rescreening was higher than that for the NICU infants. The overall prevalence of hearing loss was 1.96/1000, with that in the NICU being 8/1000 and that in the WBN being 0.9/1000. Positive predictive value for permanent hearing loss based on inpatient screening was approximately 4% and based on outpatient rescreening was approximately 22%. Conclusions: Several outpatient outcome measures changed with successive years of program operation, suggesting that programs improve over time. Also, some outpatient outcome measures differ between NICU and WBN populations. The differences noted across regions of the state in the percentage of infants returning for outpatient retesting require further research to determine whether differences are due to demographic and/or procedural differences.

Mechanism of endothelin-1-induced pulmonary vasoconstriction.

Endothelins are endothelial cell-derived peptides with potent vasoconstrictor properties. We investigated the actions of porcine/human endothelin-1 (ET-1) on the microvasculature of the guinea pig lung perfused at constant flow with Ringers-albumin. We measured the perfusion pressure, distribution of pulmonary vascular resistance (using the double occlusion method), lung weight change, and the pulmonary capillary filtration coefficient. At concentrations of greater than or equal to 10(-10) M, ET-1 produced dose-dependent increases in mean pulmonary artery pressure (EC50, approximately 10(-9.5) M), which were rapid in onset and biphasic (first phase peaking at 1-2 minutes; second phase peaking at 10-15 minutes) up to 60 minutes of the perfusion period. The vasoconstrictor response was sustained for the 60-minute perfusion period. The pulmonary vasoconstriction was inhibited by pretreatment with indomethacin (10(-5) M), the thromboxane A2 receptor antagonist SQ-29,548 (4 x 10(-6) M), or papaverine (10(-5) M). Nifedipine (10(-5) or 10(-7) M) had no effect on the first phase but prevented the second phase of the vasoconstriction. The vasoconstriction was primarily the result of a 10-fold increase in pulmonary venous resistance. Pulmonary edema developed after ET-1 challenge because of the venoconstriction and the resultant pulmonary capillary hypertension. However, the pulmonary capillary filtration coefficient was unchanged, indicating that pulmonary vascular permeability did not increase. ET-1 also had no effect on transendothelial 125I-albumin flux. The results indicate that ET-1 is a potent thromboxane-dependent venoconstrictor in the guinea pig lung.(ABSTRACT TRUNCATED AT 250 WORDS)

New York State universal newborn hearing screening demonstration project: effects of screening protocol on inpatient outcome measures.

Objective: To examine differences among various test protocols on the fail rate at hospital discharge for infants in the well‐baby nursery (WBN) and neonatal intensive care unit (NICU) who received hearing screening through a universal newborn hearing screening demonstration project. Design: The outcomes of several screening protocols were examined. Two technologies were used: transient evoked otoacoustic emissions (TEOAEs) alone or in combination with the auditory brain stem response (ABR). The performance of test protocols in both nurseries within eight hospitals was examined over a 2‐ to 3‐yr period. In the WBN, six hospitals used a screening protocol of TEOAE technology first followed by an ABR (automated or conventional) technology screening for newborns who referred on TEOAE screening. Two hospitals used TEOAE only in the WBN. Seven hospitals used screening protocols in the NICU that used a combination of TEOAE and ABR technologies (TEOAE technology administered first or second, before or after TEOAE, or TEOAE and ABR tests on all infants). Only one hospital used TEOAE technology exclusively for hearing screening. Results: Significant differences among screening protocols were found across hospitals in the first, second, and third years of the program. The combination of TEOAE technology and ABR technology (a two‐technology screening protocol) resulted in a significantly lower fail rate at hospital discharge than the use of a single‐technology (TEOAE). Fail rates at discharge were twice as high using the one‐technology protocol versus two‐technology protocol, even when the best outcomes from program year 3 were considered exclusively. Results of two‐technology versus one‐technology protocols were similar in the NICU. Use of a second technology for screening TEOAE fails significantly reduced every hospital that used the protocols fail rate at discharge. Conclusions: A two‐technology screening protocol resulted in significantly lower fail rates at hospital discharge in both the WBN and NICU nurseries than use of a single‐technology (TEOAE) hearing screening protocol.

Decreasing hypothermia during delivery room stabilization of preterm neonates.

BACKGROUND AND OBJECTIVE: Hypothermia during delivery room stabilization of very low birth weight (VLBW) newborns is independently associated with mortality, yet it occurred frequently both in collaborative networks and at our institution. We aimed to attain admission temperatures in the target range of 36°C to 38°C in ≥90% of inborn VLBW neonates through implementation of a thermoregulation bundle. METHODS: This quality improvement project extended over 60 consecutive months, using sequential plan–do–check–act cycles. During the 14 baseline months, we standardized temperature measurements and developed the Operation Toasty Tot thermoregulation bundle (including consistent head and torso wrapping with plastic, warmed blankets, and a closed stabilization room). We introduced this bundle in month 15 and added servo-controlled, battery-powered radiant warmers for stabilization and transfer in month 21. We provided results and feedback to staff throughout, using simple graphics and control charts. RESULTS: There were 164 inborn VLBW babies before and 477 after bundle implementation. Introduction and optimization of the bundle decreased the incidence of hypothermia, with rates remaining in the target range for the last 13 study months. The incidence of temperatures >38°C was ∼2% both before and after bundle implementation. CONCLUSIONS: This thermoregulation bundle resulted in sustained improvement in normothermia rates during delivery room stabilization of VLBW newborns. Our benchmark goal of ≥90% admission temperatures above 36°C was met without increasing hyperthermia rates. Because these results compare favorably with those of recently published research or improvement collaboratives, we aim to maintain our performance through routine surveillance of admission temperatures.

The Apgar Cycle: A New View of a Familiar Scoring System

Apgar scores are universally recorded, but they should no longer be used to guide resuscitation; thus, some authorities have suggested that the scores should be abandoned. However, the physiological relationships underlying the elements of the Apgar scoring system can be conceptualised as a cycle, wherein the five functions are linked by cardiorespiratory reflexes and metabolically supported by the oxygen pathway. Respiratory effort represents both the main input into the system and its functional output (sustained respirations). The progressive deterioration of functions during asphyxia, and their recovery during resuscitation, are readily understood within the sequence. This depiction helps in learning concepts such as primary and secondary apnoea and bradycardia. The visual model harmonises the pedagogical and practical values of the Apgar scoring system, by placing the rapid assessment of respirations, heart rate and colour during neonatal resuscitation (as taught in the Neonatal Resuscitation Program) in its broader physiological context. The understanding imparted by the Apgar cycle may directly enhance patient care during resuscitation, apart from the attribution of numerical scores.

The Mitochondrial Connection in Auditory Neuropathy

‘Auditory neuropathy’ (AN), the term used to codify a primary degeneration of the auditory nerve, can be linked directly or indirectly to mitochondrial dysfunction. These observations are based on the expression of AN in known mitochondrial-based neurological diseases (Friedreich’s ataxia, Mohr-Tranebjærg syndrome), in conditions where defects in axonal transport, protein trafficking, and fusion processes perturb and/or disrupt mitochondrial dynamics (Charcot-Marie-Tooth disease, autosomal dominant optic atrophy), in a common neonatal condition known to be toxic to mitochondria (hyperbilirubinemia), and where respiratory chain deficiencies produce reductions in oxidative phosphorylation that adversely affect peripheral auditory mechanisms. This body of evidence is solidified by data derived from temporal bone and genetic studies, biochemical, molecular biologic, behavioral, electroacoustic, and electrophysiological investigations.

Mechanisms of endothelin-1-induced pulmonary vasodilatation in neonatal pigs.

1. We determined the contributions of three independent vasodilator mechanisms (cyclo‐oxygenase metabolites, nitric oxide and ATP‐sensitive potassium channels) in the mediation of pulmonary vasomotor effects of endothelin‐1 (ET‐1) in neonatal pigs. 2. Lungs of piglets (2.7 +/‐ 0.3 days old) were perfused at constant flow (60 ml min‐1) with recirculating Ringer‐albumin solution. We measured pulmonary artery pressure (Ppa) and the distribution of pulmonary vascular resistance using the double‐occlusion method. 3. ET‐1 (10(‐12)‐10(‐9) M) produced concentration‐dependent pulmonary vasodilatation. ET‐1 (10(‐9) M) decreased Ppa from 24.5 +/‐ 3.1 to 17.0 +/‐ 3.0 cmH2O with a nadir occurring at 1 min, followed by a slow return to baseline over 60 min (time for half‐recovery (t1/2R) of 17.2 min). The decrease in Ppa was the result of pulmonary precapillary vasodilatation. Endothelin‐3 (ET‐3) (10(‐12) and 10(‐11) M) also induced vasodilatation comparable to equimolar concentrations of ET‐1, whereas the selective ETB receptor agonist IRL 1620 at equimolar concentrations caused a more protracted vasodilatation response. 4. Neither the cyclo‐oxygenase inhibitor indomethacin (10(‐5) M) nor the KATP+ (ATP‐sensitive) potassium channel blocker glibenclamide (10(‐5) M) significantly altered the baseline Ppa; moreover, neither inhibitor affected the ET‐1‐induced vasodilatation, indicating the lack of involvement of cyclo‐oxygenase metabolites and KATP+ channel activity in the mediation of the pulmonary vasodilator response to ET‐1. 5. Addition of 10(‐5) M reduced haemoglobin, which antagonizes the action of nitric oxide (NO), increased Ppa over prehaemoglobin levels. Haemoglobin significantly decreased the duration (t1/2R, 3.8 +/‐ 0.7 min) of pulmonary vasodilatation to ET‐1, but did not abolish the initial phase of the response. L‐N‐Monomethylarginine, an inhibitor of NO synthesis, either alone or in combination with haemoglobin, similarly reduced the duration of ET‐1‐induced pulmonary vasodilatation. 6. The ETA receptor antagonist [Dpr1‐Asp15]‐ET‐1 (Dpr, diaminoproprionic acid) had no effect on pulmonary vasodilatation induced by ET‐1, ET‐3 or IRL 1620 (suc‐(Glu9,Ala11,15)‐ET‐1(8‐21)). This finding combined with the observed relative potencies of the peptides (IRL 1620 > ET‐1 = ET‐3) suggests that pulmonary vasodilatation was mediated by activation of the non‐selective ETB receptor. 7. The results indicate that the sustained ET‐1‐induced pulmonary vasodilatation in neonates is probably mediated via ETB receptor activation and that it is critically dependent on NO.

Detection of endothelin-like immunoreactivity in epithelium and fibroblasts of the human umbilical cord

We studied tissue sections of freshly obtained full-term and premature human umbilical cords using polyclonal antibody to endothelin and immunocytochemistry. Endothelin immunoreactivity was detected in the cytoplasm of epithelial cells and primitive fibroblasts, but not in the endothelial cells of both full-term and premature umbilical cords. Immunoelectron microscopy using indirect immunogold staining technique localized endothelin immunoreactivity to the cytoplasm of the epithelial cells and fibroblasts but not confined to any particular structures. No endothelin immunoreactivity was detected in the nucleus or on the cell membrane. Pre-absorption tests with synthetic endothelin-1, -2, and -3 independently established that the immunoreactivity represented endothelin-1 and -2, but not -3. The presence of endothelin-1 and -2-like immunoreactive materials in epithelial cells and fibroblasts of human umbilical cord suggests a role of endothelin in parturition.

Comparison of renal effects of ibuprofen versus indomethacin during treatment of patent ductus arteriosus in contiguous historical cohorts

BackgroundIbuprofen treatment of patent ductus arteriosus (PDA) has been shown to be as effective as indomethacin in small randomized controlled trials, with possibly fewer adverse effects. However, adverse renal effects of ibuprofen have been noted in some trials and suspected in our practice.The purpose of this study was to examine whether ibuprofen and indomethacin treatment of PDA have comparable effects on renal function as evidenced by urine output and serum creatinine.MethodsRetrospective chart review of 350 patients. Serum creatinine and urine output were recorded prior to start of treatment, during each course and after the last course of treatment. Pre-treatment mean creatinine and urine output values were compared to treatment and post treatment means using 2-factor repeated measures ANOVA.Results165 patients were treated with indomethacin (2005-2006) and 185 received ibuprofen (2007-2008). There was no difference between treatment groups in demographics or baseline renal function. For both groups, the number of treatment courses was inversely correlated with birth weight and gestational age. Analysis of the first course including all patients, revealed significant increase in creatinine and decrease in urine output with both drugs, with a more pronounced effect of indomethacin on creatinine. In the subgroup of 219 patients who received only one treatment course, there was a significant increase in creatinine after indomethacin, but not after ibuprofen. In the 131 who received 2 or more courses, the decrease in urine output and increase in creatinine were not different between drugs. There were significant decreases in urine output observed in the second and third courses of ibuprofen treatment (both by 0.9 mL/kg/hr).ConclusionBoth drugs have a similar short-term effect on renal function. Indomethacin had a more prominent initial effect, while ibuprofen decreased renal function during the second and third courses similarly to indomethacin. The changes in renal function seen with ibuprofen treatment should be considered in fluid and electrolyte management, especially if treatment beyond one course is required.