A novel in-line high frequency interrupter for use with bubble CPAP: A feasibility study in a premature lamb model.

BACKGROUND: Recent in vitro testing of high frequency (HF) oscillation applied to bubble continuous positive airway pressure (BCPAP) using a novel flow interrupter device (HFI) demonstrated significantly improved CO2 washout while not altering delivered mean airway pressure (MAP) in a premature infant lung model. This study's aim was to evaluate the safety and efficacy of the HFI paired with BCPAP in an animal model of prematurity prior to clinical testing. DESIGN/METHODS: Twelve fetal lambs, 131-135 days gestation, weight 3.51±0.42 kg, were delivered by Cesarean section. The lambs were supported by mechanical ventilation and weaned to spontaneous breathing with BCPAP at 6 cmH2O. A combined CO2/airflow sensor measured end-tidal (EtCO2) and tidal volume (VT). Blood gases, heart rate (HR), arterial pressure (Part), minute ventilation (MV), MAP, ventilatory efficiency index (VEI), thoracoabdominal phase angle and labored breathing index (LBI) were recorded over a 10-minute baseline period followed by four randomized 10-minute intervals with HFI set to either 8, 10, 12 or 15 Hz. RESULTS: EtCO2 decreased from baseline by 11.1±2.2SE%, 16.6±4.3SE%, 13.5±4.9SE%, and 19.5±4.5SE% at 8, 10, 12, and 15 Hz respectively (p < 0.001). Blood gases, SpO2, HR, Part, MAP, VT, MV, esophageal pressure, phase angle, and LBI underwent no significant change with HF. Respiratory rate decreased, and VEI increased, by 14.9±4.5SD% (p = 0.037) and 83±22SD% (p < 0.011) respectively, averaged over all frequencies. CONCLUSIONS: We demonstrated the safety and efficacy of a novel BCPAP flow interrupter device. HF applied to the respiratory system resulted in significantly improved CO2 clearance and ventilation efficiency with no deleterious physiological effects in a pre-term lamb model.

Neonatal early-onset sepsis evaluations among well-appearing infants: projected impact of changes in CDC GBS guidelines.

OBJECTIVE: To determine (a) the proportion of asymptomatic infants born at ≥35 weeks gestation evaluated for early-onset sepsis (EOS) and exposed to postnatal antibiotics; (b) reasons for and outcomes of the evaluations, and (c) anticipated changes when applying the Centers for Disease Control and Prevention (CDC) 2010 guidelines to this study population. STUDY DESIGN: Retrospective cohort study of infants born at ≥35 weeks gestation in 2008-2009 in a large maternity center. RESULT: Out of the 7226 infants that met the study criteria: 1062 (14.7%) were evaluated for EOS and half of those evaluated, received empiric antibiotics. 70.4% of evaluations were performed owing to maternal intrapartum fever, but 23% were prompted by inadequate Group B Streptococcus (GBS) prophylaxis alone. Three cases of blood culture-proven infection were identified. CONCLUSION: Improved approaches are needed to identify asymptomatic infants who are at risk for EOS to decrease unnecessary evaluations and antibiotic exposure. Transition to the 2010 CDC GBS guidelines may eliminate a quarter of EOS evaluations among these infants.

Pilot trial of late booster doses of surfactant for ventilated premature infants.

OBJECTIVE: Many premature infants at risk for bronchopulmonary dysplasia experience episodes of surfactant dysfunction with reduced surfactant protein B (SP-B). In this study, we investigated the safety and responses to booster doses of surfactant. STUDY DESIGN: A total of 87 infants, 500 to 1250 g birth weight, who were ventilated at 7 to 10 days received 2 or 3 doses of Infasurf (Calfactant, Forest Pharmaceuticals, St Louis, MO, USA) within a 1-week period. RESULT: For 184 doses, occurrence rates of transient bradycardia (13) and plugged endotracheal tube (5) were low, and no other adverse effects were noted. Treatment transiently improved the respiratory severity score (FiO(2) × mean airway pressure), SP-B content (+75%) and surface properties of isolated surfactant. Levels of eight proinflammatory cytokines in tracheal aspirate were interrelated and unchanged from baseline after surfactant treatment. CONCLUSION: Booster doses of surfactant for premature infants with lung disease are safe and transiently improve respiratory status as well as composition and function of endogenous surfactant.

The effect of inhaled nitric oxide on pulmonary function in preterm infants.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) in preterm infants is associated with impaired alveolar growth, inflammation and airway hyperreactivity. In animal models of BPD, inhaled nitric oxide (NO) improves alveolar growth and inhibits airway smooth muscle proliferation. This study was designed to assess the effect of inhaled NO on resistance and compliance in ventilated preterm infants with evolving BPD. STUDY DESIGN: Expiratory resistance and compliance of the respiratory system were measured in 71 ventilated preterm infants, < or = 32 weeks gestation, randomized to NO (n=34) versus placebo (n=37) for > or = 24 days at 7 to 21 days of life. RESULT: At baseline expiratory resistance (231+/-71 versus 215+/-76 cm H(2)O l(-1) s(-1)) and compliance (0.49+/-0.14 versus 0.53+/-0.13 ml cm H(2)O(-1) kg(-1)) were comparable between placebo and NO groups, respectively. There was no effect of NO on expiratory resistance or compliance at 1 h, 1 week or 2 weeks of study gas administration. CONCLUSION: NO had no short- or medium-term effect on expiratory resistance or compliance in ventilated preterm infants.

Unstudied infants: outcomes of moderately premature infants in the neonatal intensive care unit.

BACKGROUND: Newborns of 30-34 weeks gestation comprise 3.9% of all live births in the United States and 32% of all premature infants. They have been studied much less than very low birthweight infants. OBJECTIVE: To measure in-hospital outcomes and readmission within three months of discharge of moderately premature infants. DESIGN: Prospective cohort study including retrospective chart review and telephone interviews after discharge. SETTING: Ten birth hospitals in California and Massachusetts. PATIENTS: Surviving moderately premature infants born between October 2001 and February 2003. MAIN OUTCOME MEASURES: (a) Occurrence of assisted ventilation during the hospital stay after birth; (b) adverse in-hospital outcomes-for example, necrotising enterocolitis; (c) readmission within three months of discharge. RESULTS: With the use of prospective cluster sampling, 850 eligible infants and their families were identified, randomly selected, and enrolled. A total of 677 families completed a telephone interview three months after hospital discharge. During the birth stay, these babies experienced substantial morbidity: 45.7% experienced assisted ventilation, and 3.2% still required supplemental oxygen at 36 weeks. Readmission within three months occurred in 11.2% of the cohort and was higher among male infants and those with chronic lung disease. CONCLUSIONS: Moderately premature infants experience significant morbidity, as evidenced by high rates of assisted ventilation, use of oxygen at 36 weeks, and readmission. Such morbidity deserves more research.

Inter-neonatal intensive care unit variation in discharge timing: influence of apnea and feeding management.

BACKGROUND: Premature infants need to attain both medical stability and maturational milestones (specifically, independent thermoregulation, resolution of apnea of prematurity, and the ability to feed by mouth) before safe discharge to home. Current practice also requires premature infants to be observed in hospital before discharge for several days (margin of safety) after physiologic maturity is recognized. OBJECTIVE: To compare postmenstrual age (PMA) at discharge in a homogeneous population of premature infants cared for in different neonatal intensive care units (NICUs) and to assess the impact on hospital stay of the recognition and recording of physiologic maturity and the required margin of safety. METHODS: We studied premature infants delivered at 30 to 34 6/7 weeks gestational age (GA), free of significant medical or surgical complications. Medical records of 30 eligible infants consecutively discharged from the hospital before July 1997 from each of 15 NICUs in Massachusetts (9 level 2 and 6 level 3) were reviewed. RESULTS: A total of 435 infants were included in the study sample. Mean (+/- standard deviation) GA and birth weight of the study population were 33.2 +/- 1.2 weeks and 2024 +/- 389 g, respectively. Infants were discharged at a similar PMA regardless of GA at birth. Considerable variation in the PMA at discharge between hospital sites was observed (range, 35.2 +/- 0.5 weeks to 36.5 +/- 1.2 weeks). Despite the homogeneous study population, hospitals in which infants had the latest PMA at discharge also recorded mature cardiorespiratory and feeding behavior at an older age. Longer duration of pulse oximetry use was associated with later resolution of apnea. Differences in the duration of the margin of safety between sites did not contribute to variation in hospital stay. CONCLUSION: NICUs vary widely in length of hospital stay for healthy premature infants. We speculate that this variation results in part from differences in monitoring for and documentation of apnea of prematurity and feeding behavior.

No increase in rates of early-onset neonatal sepsis by non-group B Streptococcus or ampicillin-resistant organisms.

OBJECTIVE: We assessed the impact of a risk-based approach to group B Streptococcus (GBS) prophylaxis on the rates of early-onset neonatal sepsis (EONS). STUDY DESIGN: A retrospective cohort study of neonates born at a tertiary-care hospital from 1990 to 1996 was performed. Cases of EONS were identified among neonates born in a period without GBS prophylaxis (1990-1992) and compared with those born in a period with GBS prophylaxis (1993-1996). The antibiotic susceptibility data on each organism isolated in the blood culture were obtained. RESULTS: In the period without prophylaxis, 99 cases of EONS were identified among 25,934 neonates for a rate of 3.8 per 1000 births. In the period with prophylaxis, 90 cases of EONS occurred among 34,262 neonates for a rate of 2.6 per 1000. The rate of GBS-EONS significantly decreased between the 2 periods (from 1.9 to 1.1, P =.01). There was a trend toward a decrease in the rate of EONS caused by non-GBS gram-positive organisms (from 1.2 to 0.7, P =.06). There was no significant increase in the rate of EONS caused by gram-negative or ampicillin-resistant organisms. CONCLUSIONS: A risk-based approach to GBS prophylaxis reduced the incidence of GBS-EONS at a tertiary-care hospital. This decrease was not accompanied by an increase in the incidence of EONS by non-GBS or ampicillin-resistant organisms.

Apnea frequently persists beyond term gestation in infants delivered at 24 to 28 weeks.

BACKGROUND: Apnea of prematurity remains among the most commonly diagnosed conditions in the Newborn Intensive Care Unit and may prolong hospital stays in some infants. Because survival of extremely premature infants has improved markedly, the natural history of apnea in this population needs to be reassessed. OBJECTIVE: To document the natural history of recurrent apnea and/or bradycardia events in infants delivered at 24 to 28 weeks' gestation. METHODS: Medical records of all infants delivered at 24 to 28 weeks' gestation admitted to the Brigham and Women's Hospital Newborn Intensive Care Unit between January 1989 and March 1994 were reviewed to document the clinical course of apnea of prematurity. Subjects were included in the study sample if they were discharged home from the Brigham and Women's Hospital or after transfer to an affiliated hospital. Recordings of apnea and/or bradycardia events were based on nursing observations of monitor alarms and assessment of the infant's condition. RESULTS: Of 457 eligible infants, 226 were included in the study sample and stratified by gestational age at birth assigned by the attending neonatologist. The time to resolution of recurrent apnea/bradycardia events was longer with lower gestational age at birth. Apnea/bradycardia events were frequently observed beyond 36 weeks' postconceptional age in all gestational age groups. The incidence of apnea persisting beyond 38 weeks postconceptional age was significantly higher in the 24- to 27-week infants combined compared with the 28-week infants. CONCLUSIONS: Apnea of prematurity frequently persists beyond term gestation in infants delivered at 24 to 28 weeks' gestational age. These persistent apnea and/or bradycardia events may contribute to prolonged hospitalization. Programs to promote earlier discharge of premature infants should take into account the variability in resolution of apnea and specifically address management of persistent apnea.

Perinatally transmitted neonatal bacterial infections.

Perinatally acquired bacterial infections remain a major contributor to morbidity and mortality in newborn infants, especially those delivered prematurely. Our understanding of the epidemiology, bacteriology, and pathogenesis of these infections has allowed development of better treatment and prevention strategies. Just as the bacteriology of perinatally acquired bacterial infections has changed over the past few decades, however, it is likely to continue to evolve. Whether widespread use of intrapartum antibiotics will alter the bacteriology and antibiotic resistance patterns seen in early-onset neonatal bacterial infections requires ongoing surveillance.

Hypercapnia increases expiratory braking in preterm infants.

In contrast to adults, newborn infants breathe from an elevated end-expiratory lung volume, determined by the interaction of airflow retardation (braking) by the diaphragm and larynx, and expiratory duration. To determine the effect of hypercapnia on this strategy, we examined changes in respiratory muscle activity and the ventilatory response to CO2 breathing in eight premature infants 33-34 wk gestational age in the first 3 postnatal days. We recorded tidal volume, airflow, and electromyograms (EMG) of the laryngeal abductor [posterior cricoarytenoid (PCA)], which abducts the vocal cords, and diaphragm during behaviorally determined quiet sleep in room air and during steady-state inhalation of 2% CO2 in air. As expected, tidal volume increased (P < 0.0005) without a change in inspiratory duration with hypercapnia. Unexpectedly, in all subjects, expiratory duration was longer during CO2 inhalation (P < 0.001), accompanied by marked changes in expiratory flow patterns consistent with increased expiratory braking. Diaphragm post-inspiratory EMG activity increased with hypercapnia (P < 0.005) with no change in baseline diaphragm or PCA EMG activity. Peak inspiratory EMG activity of the diaphragm and PCA increased with CO2 (10 and 37%, respectively; P < 0.05). We conclude that the mechanisms used to elevate end-expiratory lung volume are enhanced during hypercapnia in premature infants. This breathing strategy may be important in maintaining gas exchange in infants with lung disease.

Developmental changes in sequential activation of laryngeal abductor muscle and diaphragm in infants.

In animals and human adults, upper airway muscle activity usually precedes inspiratory diaphragm activity. We examined the interaction of the posterior cricoarytenoid muscle (PCA), which abducts the larynx, and the diaphragm (DIA) in the control of airflow in newborn infants to assess the effect of maturation on respiratory muscle sequence. We recorded tidal volume, airflow, and DIA and PCA electromyograms (EMG) in 12 full-term, 14 premature, and 10 premature infants with apnea treated with aminophylline. In most breaths, onset of PCA EMG activity preceded onset of DIA EMG activity (lead breaths). In all subjects, we also observed breaths (range 6-61%) in which PCA EMG onset followed DIA EMG onset (lag breaths). DIA neural inspiratory duration and the neuromechanical delay between DIA EMG onset and inspiratory flow were longer in lag than in lead breaths (P < 0.05 and P < 0.01, respectively). The frequency of lag breaths was greater in the premature infants [33 +/- 4% (SE)] than in either the full-term infants (21 +/- 3%, P < 0.03) or the premature infants with apnea treated with aminophylline (16 +/- 2%, P < 0.01). We conclude that the expected sequence of onset of PCA and DIA EMG activity is frequently disrupted in newborn infants. Both maturation and respiratory stimulation with aminophylline improve the coordination of the PCA and DIA.