Emidio M. Sivieri

Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns

Objective. To assess the predictive ability of a universal predischarge serum bilirubin measurement to screen for risk of subsequent significant hyperbilirubinemia in the direct Coombs negative healthy term and near-term newborn during the first postnatal week. Methods. Total serum bilirubin (TSB) levels were obtained at the time of the routine metabolic screen in all term and near-term newborns cared for in the Pennsylvania Hospital Well Baby Nursery (n = 13 003). Postnatal age (in hours) at the time of TSB measurement was recorded. A percentile-based bilirubin nomogram for the first week was constructed from hour-specific predischarge and postdischarge TSB values of newborns (n = 2840; median BW = 3230 g and median gestational age = 39 weeks) who met classification criteria for healthy newborns (excluding those with a positive direct Coombs test or those requiring phototherapy before age 60 hours) and who were enrolled in a hospital supervised home or outpatient follow-up program. The accuracy of the predischarge TSB as a predictor of subsequent degree of hyperbilirubinemia was determined. Results. The study patients in the nomogram were racially diverse. Nearly 60% were breastfed. Predischarge, 6.1% of the study population (172/2840) had TSB values in the high-risk zone (≥95th percentile) at 18 to 72 hours; of these, 39.5% (68/172) remained in that zone (likelihood ratio [LR] = 14.08, sensitivity = 54%; specificity = 96.2%, probability = 39.5%). Predischarge, 32.1% of the population (912/2840) had TSB values in the intermediate-risk zone. In a clinically significant minority of these newborns (58/912 or 6.4%), the postdischarge TSB moved into the high-risk zone (LR of this move: 3.2 from the upper-intermediate zone and .48 from the lower-intermediate risk zone). The predischarge TSB in 61.8% of the newborns (1756/2840) was in the low-risk zone (<40th percentile) and there was no measurable risk for significant hyperbilirubinemia (LR = 0, sensitivity = 100%; specificity = 64.7%; probability = 0%). Conclusions. An hour-specific TSB before hospital discharge can predict which newborn is at high, intermediate or low risk for developing clinically significant hyperbilirubinemia (specifically defined as TSB levels ≥95th percentile for age in hours). Risk designation and subsequent increases or decreases of in TSB can be easily monitored on an hour-specific percentile based predictive bilirubin nomogram. A predischarge TSB measured as a universal policy would facilitate targeted intervention and follow-up in a safe, cost-effective manner. In conjunction with bilirubin practice parameter of the American Academy of Pediatrics, it could reduce the potential risk for bilirubin-induced neurologic dysfunction.

Clinical report from the pilot USA Kernicterus Registry (1992 to 2004)

To identify antecedent clinical and health services events in infants (⩾35 weeks gestational age (GA)) who were discharged as healthy from their place of birth and subsequently sustained kernicterus. We conducted a root-cause analysis of a convenience sample of 125 infants ⩾35 weeks GA cared for in US healthcare facilities (including off-shore US military bases). These cases were voluntarily reported to the Pilot USA Kernicterus Registry (1992 to 2004) and met the eligibility criteria of acute bilirubin encephalopathy (ABE) and/or post-icteric sequelae. Multiple providers at multiple sites managed this cohort of infants for their newborn jaundice and progressive hyperbilirubinemia. Clinical signs of ABE, verbalized by parents, were often inadequately elicited or recorded and often not recognized as an emergency. Clinical signs of ABE were reported in 7 of 125 infants with a subsequent diagnosis of kernicterus who were not re-evaluated or treated for hyperbilirubinemia, although jaundice was noted at outpatient visits. The remaining infants (n=118) had total serum bilirubin (TSB) levels >20 mg per 100 ml (342 μmol l−1; range: 20.7 to 59.9 mg per 100 ml). No specific TSB threshold coincided with onset of ABE. Of infants <37 weeks GA with kernicterus, 34.9% were LGA (large for gestational age) as compared with 24.7% of term infants (>37 weeks GA). Although >90% mothers initiated breast-feeding, assessment of milk transfer and lactation support was suboptimal in most. Mortality was 4% (5 of 125) in infants readmitted at age ⩽1 week. Along with a rapid rise of TSB (>0.2 mg per 100 ml per hour), contributing factors, alone or in combination, included undiagnosed hemolytic disease, excessive bilirubin production related to extra-vascular hemolysis and delayed bilirubin elimination (including increased enterohepatic circulation, diagnosed and undiagnosed genetic disorders) in the context of known late prematurity (<37 weeks), glucose 6-phosphate-dehydrogenase deficiency, infection and dehydration. Readmission was at age ⩽5 days in 81 of 118 (69%) infants and <10 days in 101 of 118 (86%) infants. TSB levels were ⩽35 mg per 100 ml (598 μmol l−1) in 46 (39%) infants, of whom one died before exchange transfusion, one was untreated and one was lost to follow-up. Timely and efficacious bilirubin reduction interventions defined by ‘crash-cart’ initiation of immediate intensive phototherapy and urgent exchange transfusion were accomplished in 11 of 43 infants, which were compared with 12 of 43 infants in whom a timely exchange sometimes could not be accomplished. No overt sequelae were found in 8 of 11 infants (73%) treated with a ‘crash-cart’ approach compared with none without sequelae when exchange was delayed by pre-admission delays, technical factors or need to transfer to a tertiary facility. None of the remaining 20 of 43 infants treated only with phototherapy escaped sequelae. Regardless of age at readmission and intervention, infants with peak measured TSB >35 mg per 100 ml had post-icteric sequelae (n=73). There was a narrow margin of safety between birthing hospital discharge or home birth and readmission to a tertiary neonatal/pediatric facility. Progression of hyperbilirubinemia to hazardous levels and onset of neurological signs were often not identified as infants care and medical supervision transitioned during the first week after birth. The major underlying root cause for kernicterus was systems failure of services by multiple providers at multiple sites and inability to identify the at-risk infant and manage severe hyperbilirubinemia in a timely manner.

Cardiopulmonary Function in Very Preterm Lambs during Liquid Ventilation

Summary: Cardiopulmonary function was evaluated in very preterm lambs (106 ± 0.7 S.E. days gestation, 1.66 ± 0.12 S.E. kg birth weight) during fluorocarbon ventilation. Lambs were delivered by cesarean section after epidural anesthesia. Indwelling arterial, venous, and tracheal cannulae were placed before clamping the cord. Lambs were then mechanically ventilated with oxygenated fluorocarbon for approximately 2 h. During this period it was possible to maintain adequate gas exchange and stable cardiac function. Transpulmonary pressure, liquid flow, and tidal volume tracings enabled determination of lung compliance, CL = 0.58 ± 0.12 S.E. ml · cmH2O · kg-1, inspiratory resistance, R1 = 3600 ± 604 S.E. cmH2O · liter−1 · sec−1, and expiratory resistance, RE = 4034 ± 2183 S.E. cmH2O/liter/sec. Lung compliance of the 106-day-old fluorocarbon-filled lung is similar to the more mature 138-143-day-old air-filled lung in preterm lambs. Based on the data presented herein we have extended the viability of the preterm lamb to the limit of pulmonary capillary development rather than that of the pulmonary surfactant system.

Sequential Effects of Acute Meconium Obstruction on Pulmonary Function

Summary: The relationship between pulmonary function and the migration of meconium to distal airways was determined in 10 rabbits (mean weight 2.6 kg) after insufflation of a meconium-saline mixture (1-2 ml/kg). Animals were anesthetized, cannulated, intubated, and mechanically ventilated with 100% oxygen. Lung mechanical dysfunction was most severe during the early phase of meconium migration, 15 min postinsufflation. Substantial increases in inspiratory lung resistance (RI) and expiratory lung resistance (RE) suggest that the site of obstruction at 15 min was the large airways. A decrease in dynamic lung compliance with unchanged static compliance characterizes the obstruction as partial. At 15 min and throughout the migration process, RE was greater than RI, demonstrating a check-valve effect. This phenomenon was substantiated by an increased functional residual capacity (FRC) in all rabbits, presumably due to gas trapping. Secondary to these changes, marked hypoxemia, hypercapnea, and acidosis developed in spite of assisted ventilation with 100% oxygen. At 60 and 120 min postinsufflation, both RI and RE decreased as compared to 15 min. This suggests that the predominant site of obstruction shifted to medium and small airways concomitant with the migration of meconium. Widespread and uneven distribution of meconium still produced significant frequency dependence of lung compliance. Static compliance remained unchanged, indicating that meconium does not affect surface-active or tissue properties of the lung within 120 min postinsufflation. These data suggest that effective respiratory management after meconium aspiration is dependent on the degree of meconium migration, as reflected by pulmonary mechanics.Speculation: Significant effects of meconium aspiration on lung function are attributable to migrating obstructive phenomena, which result in a more severe lung dysfunction in earlier stages postinsufflation of meconium than in progressively later stages. It is appealing to speculate that noninvasive pulmonary function measurements made in newborn infants may quantitate the degree of mechanical obstruction and meconium migration in the airways. This information would provide guidelines for effective respiratory management of infants with meconium aspiration syndrome (MAS). Based on the present animal model, elevated oxygen therapy should be employed early to offset the severe hypoxemia. In addition, the check-valve effect (RE > RI) indicates the use of a low I/E ratio in assisted ventilation. It has been shown that continuous positive airway pressure improves arterial oxygen tension in some newborns with MAS. However, in light of the mechanical dysfunction resulting in an increased FRC, caution is recommended in the use of end distending pressure within 2 hr after meconium aspiration.

Energetics and mechanics of nutritivesucking in the preterm and term neonate

Energetics and mechanics of sucking in preterm and term neonates were determined by simultaneous records of intraoral pressure, flow, volume, and work of individual sucks. Nine term infants (mean postconceptional age: 38.6 +/- 0.7 SD weeks; mean postnatal age: 18.4 +/- 6.1 SD days) and nine preterm infants (mean postconceptional age: 35.2 +/- 0.7 SD weeks; mean postnatal age: 21.9 +/- 5.4 SD days) were studied under identical feeding conditions. Preterm infants generated significantly lower peak pressure (mean values of 48.5 cm H2O compared with 65.5 cm H2O in term infants; P less than 0.01), and the volume ingested per such was generally less than or equal to 0.5 mL. Term infants demonstrated a higher frequency of sucking, a well-defined suck-pause pattern, and a higher minute consumption of formula. Energy and caloric expenditure estimations revealed significantly lower work performed by preterm infants for isovolumic feeds (1190 g/cm/dL in preterm infants compared with 2030 g.cm/dL formula ingested in term infants; P less than 0.01). Furthermore, work performed by term infants was disproportionately higher for volumes greater than or equal to 0.5 mL ingested. This study indicates that preterm infants expend less energy than term infants to suck the same volume of feed and also describes an objective technique to evaluate nutritive sucking during growth and development.

Effect of HFNC flow rate, cannula size, and nares diameter on generated airway pressures: An in vitro study

Increased use of non‐invasive forms of respiratory support such as CPAP and HFNC in premature infants has generated a need for further investigation of the pulmonary effects of such therapies. In a series of in vitro tests, we measured delivered proximal airway pressures from a HFNC system while varying both the cannula flow and the ratio of nasal prong to simulated nares diameters. Neonatal and infant sized nasal prongs (3.0 and 3.7 mm O.D.) were inserted into seven sizes of simulated nares (range: 3–7 mm I.D. from anatomical measurements in 1–3 kg infants) for nasal prong‐to‐nares ratios ranging from 0.43 to 1.06. The nares were connected to an active test lung set at: TV 10 ml, 60 breaths/min, Ti 0.35 sec, compliance 1.6 ml/cm H2O and airway resistance 70 cm H2O/(L/sec), simulating a 1–3 kg infant with moderately affected lungs. A Fisher & Paykel Healthcare HFNC system with integrated pressure relief valve was set to flow rates of 1–6 L/min while cannula and airway pressures and cannula and mouth leak flows were measured during simulated mouth open, partially closed and fully closed conditions.

Language Development Survey Provides a Useful Screening Tool for Language Delay in Preterm Infants

Developmental language disorder has been reported in 3% to 10% of term infants and 30% of preterm infants (<34 weeks gestation). Screening for language delay in preterm infants can be costly and time-consuming. The objective of this study was to assess the expressive language development of preterm infants using the Language Development Survey (LDS). A total of 178 preterm infants born at 23 to 34 weeks between 2006 and 2008 were enrolled. The LDS was completed by parents between 22 and 26 months at or shortly before 2-year neurodevelopmental assessment using the Bayley III Scale. A total of 26% of former preterm patients had language delay, using LDS. Significant correlations were observed between LDS results and Bayley III scores. Male gender and public health insurance were the most important risk factors for language delay in this cohort. Expressive language delay was present in 26% of preterm infants. LDS is a suitable and inexpensive screening tool for assessing language delay in preterm infants.

Innovative neonatal ventilation and meconium aspiration syndrome.

Respiratory failure remains a major cause of morbidity and mortality in the neonatal population. Infants with hypoxemic respiratory failure because of meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the newborn (PPHN), and pneumonia/sepsis have a potential for increased survival with extracorporeal membrane oxygenation (ECMO). Other treatment options previously limited to inotropic support, conventional ventilatory management, respiratory alkalosis, paralysis and intravenous vasodilators have been replaced by high-frequency oscillatory ventilation (HFOV), surfactant, and inhaled nitric oxide (iNO). HFOV has been advocated for use to improve lung inflation while potentially decreasing lung injury through volutrauma. Other reports describe enhanced efficacy of HFOV when combined with iNO. Subsequent to studies reporting surfactant deficiency or inactivation may contribute to neonatal respiratory failure exogenous surfactant therapy has been implemented with apparent success. Recent studies have shown that iNO therapy in the neonate with hypoxemic respiratory failure can result in improved oxygenation and decreased need for ECMO. In this article, the authors place in context of a system-based strategy the prenatal, natal and postnatal management of babies delivered through meconium stained amniotic fluid (MSAF) so that adverse outcomes are minimized, and the least number of babies require innovative ventilatory support. At Pennsylvania Hospital, over a six-year period (1995 to 2000), 14.5% (3370/23,175 of live births babies were delivered with MSAF. These data show that 4.6% (155/3370) of babies with MSAF sustained MAS. Overall, 26% (40/155) of babies with MAS needed ventilatory support or 0.17% of all live-births); of these only 20% (8/40 or 0.035% of live births) needed innovative ventilatory support. None died or needed ECMO. These data describe the impact of a system-based approach to prevent and manage adverse outcomes related to MSAF at regional Level III perinatal center.

CLINICAL USE OF PULMONARY MECHANICS AND WAVEFORM GRAPHICS

Decades of research have led to the understanding of neonatal pulmonary physiology and have influenced the clinical care that neonatologists provide to the sick newborn. Advances in microprocessor technology have allowed for clinical access of the research-based measurements of neonatal pulmonary functions. These evaluations are not only the integrated evaluation of the three primary vectors of respiration (driving pressure, air flow, and volume measured over time) but also values calculated by known physiologic equations. Clinical use of these data may not only be relevant and helpful in the bedside management, but also provides a uniquely objective and research-oriented data collection for individual newborns.

Factors influencing delivered mean airway pressure during nasal CPAP with the RAM cannula

To measure mean airway pressure (MAP) delivered through the RAM Cannula® when used with a ventilator in CPAP mode as a function of percent nares occlusion in a simulated nasal interface/test lung model and to compare the results to MAPs using a nasal continuous positive airway pressure (NCPAP) interface with nares fully occluded.