Effects of neurodevelopmental risk factors on brainstem maturation in premature infants.

BACKGROUND: Interpeak latencies (IPL), as measured by the auditory brainstem-evoked responses (ABR) test, represent the conduction time, and therefore the maturation of the brainstem auditory pathway. We aimed to study the effect of various risk factors for the neurodevelopmental delay on the conduction time in the auditory pathway among normal hearing premature infants, at term postmenstrual age (PMA). METHODS: Retrospective analysis of 239 premature infants (gestational age 32.5 ± 2.1 weeks, birth weight 1827 ± 483 g). Interpeak latencies, demographic data, and risk factors were recorded. RESULTS: Sex, PMA at ABR test, being small for gestational age (SGA), intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL), and days of invasive ventilation were found to significantly affect the IPL's in the auditory pathway in a univariate analysis. Multivariable regression analysis revealed that male sex and less advanced PMA at the examination were independent factors associated with prolonged IPL's, while bronchopulmonary dysplasia, IVH or PVL and being SGA shortened the IPL's. Non-invasive mechanical ventilation, did not affect the caudal part of the auditory pathway, despite its high noise level. CONCLUSIONS: Among various risk factors for the neurodevelopmental delay, male sex was associated with delayed, while IVH or PVL, BPD and SGA could be associated with accelerated auditory brainstem maturation. IMPACT: Auditory brainstem-evoked response (ABR) test, among normal hearing infants, can serve as a clinical tool to assess brainstem auditory maturation. Different neurodevelopmental risk factors could have different effects on the maturity of the auditory pathway. Male sex is significantly associated with prolonged interpeak latencies (IPL) among preterm and term infants, while intraventricular hemorrhage or periventricular leukomalacia, bronchopulmonary dysplasia, and being small for gestation age may be associated with shortened IPL The corrected age at ABR testing is of significance, among preterm and term infants.

Consensus approach to nasal high-flow therapy in neonates.

OBJECTIVE: Nasal high-flow therapy (nHFT) is commonly used for noninvasive respiratory support in the neonatal intensive care unit. Our objective was to determine which aspects of neonatal nHFT have achieved adequate evidence base to support consensus among experienced clinical investigators, and to document areas lacking consensus to promote future investigations. STUDY DESIGN: Prospective, modified Delphi collation of tabular queries related to specific aspects of neonatal nHFT. Seven international nHFT clinical researchers were queried regarding approaches to initiation, escalation, weaning and discontinuing nHFT. Completed tables were reviewed independently by each investigator, results clarified and discussed and areas of consensus determined. RESULTS: Consensus agreement was reached for many aspects of nHFT including: need for adequate heating and humidification, need to prevent nares occlusion, maximum flow rate of 8 l min-1, assessment of fraction of inspired oxygen (FiO2) and work of breathing for either flow escalation or weaning, equivalence of nHFT to nasal continuous positive airway pressure (nCPAP) for noninvasive support of infants of ⩾28 weeks with resolving respiratory distress and use of nHFT for noninvasive support of stable infants on nCPAP. There was general agreement for initial gas flow rates in the range of 4 to 6 l min-1 and for nHFT as primary therapy for mild respiratory distress. There was no consensus on the approach to discontinuing nHFT. CONCLUSIONS: Among an experienced group of nHFT clinical researchers, there was general consensus in the approach to neonatal nHFT. Additional randomized studies are indicated to provide better evidence related to several aspects of nHFT, as well as to identify other clinical conditions where nHFT may provide safe, effective noninvasive support.

Inhaled hydrofluoalkane-beclomethasone dipropionate in bronchopulmonary dysplasia. A double-blind, randomized, controlled pilot study.

OBJECTIVE: The efficacy of inhaled steroids in spontaneously breathing infants with established bronchopulmonary dysplasia (BPD) is debatable. The inhaled steroid hydrofluoalkane-beclomethasone dipropionate (QVAR) is unique in its small particle size that results in higher lung deposition. Our objective was to determine if inhaled QVAR could decrease respiratory rehospitalizations of infants with established BPD. STUDY DESIGN: Double-blind, randomized placebo-controlled, multicenter pilot study. Preterm infants with moderate-to-severe BPD were randomized to inhaled QVAR 100 µg per dose or placebo twice daily via Aerochamber with face mask. Treatment was administered daily from recruitment at 36 weeks post menstrual age until 3 months post discharge. Analysis was carried out by intention to treat. RESULTS: The QVAR (n=18) and placebo (n=20) groups were comparable in birth and recruitment characteristics. Length of stay (108.5±26.3 vs 108.7±36.0 days) and infants requiring oxygen at discharge (5/17 vs 6/19) or at study end (0/17 vs 2/19) were comparable. Respiratory rehospitalizations/infant (0.1±0.5 vs 0.4±0.6), rehospitalization days (0.5±1.5 vs 4.1±10.3), and post-discharge additive inhaled (0.3±0.9 vs 6.4±21.5 days), systemic (0.7±2.8 vs 1.0±1.4 days) and combined (inhaled/systemic) steroids (1.0±2.9 vs 7.8±25.8 days) tended to be lower in the QVAR compared with the placebo group. Blood pressure, height and weight gain, and urine cortisol/creatinine ratio at study end were comparable between groups. CONCLUSIONS: Our study was unable to detect a significant effect of inhaled QVAR on the respiratory course of established BPD. The study was underpowered. Possible benefits of QVAR could be masked by a tendency toward higher use of additional steroids in the placebo group.

Antenatal corticosteroid treatment in singleton, small-for-gestational-age infants born at 24-31 weeks' gestation: a population-based study.

OBJECTIVE: To assess the impact of antenatal corticosteroid therapy on mortality and severe morbidities in preterm, small-for-gestational-age (SGA) neonates compared with preterm non-SGA neonates. DESIGN: Population-based study. SETTING/POPULATION: Israel National Very Low Birth Weight infant database from 1995-2012. METHODS: Singleton infants of 24-31 weeks' gestation, without major malformations. Antenatal corticosteroids were considered either any treatment or no treatment. MAIN OUTCOME MEASURES: Univariate and multivariable logistic regression analyses were performed to assess the effect of antenatal corticosteroids on neonatal mortality and a composite adverse outcome of mortality or severe neonatal morbidity. RESULTS: Among the 10 887 study infants, 1771 were SGA. Of these, 70.4% of SGA and 66.7% of non-SGA neonates were exposed to antenatal corticosteroids. Among SGA neonates, antenatal corticosteroids were associated with decreased mortality (32.2 versus 19.3%, P < 0.0001) and composite adverse outcome (54.1 versus 43.4%, P < 0.0001), similar to the effect in non-SGA neonates (mortality 26.7 versus 12.2%, P < 0.0001; composite outcome 50.5 versus 34.6%, P < 0.0001). Multivariable logistic regression analyses demonstrated a 50% reduction in mortality risk among SGA and 57% reduction in non-SGA neonates exposed to corticosteroids [OR = 0.50, 95% confidence interval (95% CI) 0.39-0.64 and OR = 0.43, 95% CI 0.38-0.47, respectively], P-value for interaction = 0.08. Composite adverse outcome risk was significantly reduced in SGA (OR = 0.67, 95% CI 0.54-0.83) and non-SGA infants (OR = 0.57, 95% CI 0.52-0.63), P-value for interaction = 0.04. CONCLUSIONS: Antenatal corticosteroids significantly reduced mortality and severe morbidities among preterm SGA neonates, with slightly a less pronounced effect compared with non-SGA preterm infants. Antenatal corticosteroids should be given to fetuses suspected of intrauterine growth retardation, at risk for preterm delivery, in order to improve perinatal outcome. TWEETABLE ABSTRACT: Antenatal steroids reduced mortality and severe morbidities among singleton, preterm SGA neonates.

Transcutaneous PCO2 monitoring in infants hospitalized with viral bronchiolitis.

UNLABELLED: Our objective was to assess within a feasibility study the correlation and agreement of transcutaneous carbon dioxide (PtcCO2) monitoring with venous carbon dioxide (PvCO2) in infants with bronchiolitis in the emergency room (ER) and pediatric department. Sixty infants (aged 3.6 ± 3.3 months) admitted to our ER with bronchiolitis were included. PtcCO2 measurements (SenTec Digital Monitoring System) collected prospectively were compared with simultaneous PvCO2 drawn for patient care. Analysis included 100 measurements. The correlation of PtcCO2 and PvCO2 (r = 0.71, p < 0.001) was good, and the agreement (mean difference ± standard deviation of the differences 1.9 ± 7.0 mmHg) was adequate; average PtcCO2 was slightly lower than PvCO2. Changes in PtcCO2 and PvCO2 for consecutive measurements within each patient correlated (r = 0.41, p < 0.01). The level of PtcCO2 correlated with disease severity clinical score (p < 0.001). CONCLUSIONS: PtcCO2 monitoring was feasible in the ER and pediatric department and was found to have a good correlation and adequate agreement with PvCO2 in infants with bronchiolitis. Because the standard deviation of the differences was relatively high, though comparable to the literature, we suggest that PtcCO2 should not replace blood gas but rather serve as a complementary tool for trending and for real-time continuous assessment of the CO2 levels.

What is the clinical relevance of respiratory syncytial virus bronchiolitis?: findings from a multi-center, prospective study.

Acute bronchiolitis (AB) is caused primarily by respiratory syncytial virus (RSV). Recent laboratory tools have implicated a variety of other pathogens; however, their clinical relevance has not been clearly defined. The purpose of this study was to determine whether the etiological agents of AB affect its course. A multicenter prospective study was performed in previously healthy children <24 months of age who presented with <4 days duration of AB. Subjects were divided into the following groups: "only RSV," "also RSV," "no RSV," and "no pathogen." The clinical severity score on admission as well as the overall severity of disease was assessed. RSV was the most common cause of AB (77.5 %). "Only RSV" or "also RSV" patients had a higher clinical score on admission compared to those with "no RSV," p < 0.001 and p < 0.02, respectively. "Only RSV" and "also RSV" patients had a higher disease severity score when compared to patients with "no RSV," 5.9 ± 1.4 vs. 5.1 ± 1.5, p < 0.001, and 5.6 ± 1.4 vs. 5.1 ± 1.5, p < 0.02, respectively. Disease severity did not vary as a function of transfer to the pediatric intensive care unit (PICU) or duration of supplemental oxygen, yet, "only RSV" was associated with a longer length of stay (LOS) than "no RSV," p < 0.02. "Only RSV"-related AB was associated with a more severe initial clinical presentation and a longer LOS. There appears to be little immediate clinical benefit to diagnosing RSV AB to the individual patient, but the application of these diagnostic methods may have significant cost-saving implications and, thus, deserves consideration by medical professionals and health policy analysts.

Nasal respiratory support in premature infants: short-term physiological effects and comfort assessment.

AIM: To evaluate the effects of nasal respiratory support on physiologic parameters and comfort of premature infants, when compared to spontaneous breathing without nasal respiratory support. METHODS: This was a prospective, randomized, controlled, cross-over clinical study. Infants were enrolled into the study when in 'stable' condition (when discontinuation of nasal respiratory support was considered appropriate). Infants were randomized to receive first 3 h of nasal respiratory support (nasal continuous positive airway pressure or nasal intermittent mandatory ventilation) or to spontaneous breathing, and then were crossed-over to the other assignment. Each infant served as his own control. RESULTS: Fifty-four infants were included in the study (birth-weight: 1528 +/- 545 g; gestational age: 30.5 +/- 2.7 weeks). Average values of systolic, diastolic and mean blood pressure and discomfort score were significantly higher while respiratory rate was significantly slower on nasal respiratory support compared to spontaneous breathing. Heart rate was comparable on both modes. CONCLUSIONS: Nasal respiratory support in 'stable' premature infants is associated with increased blood pressure and increased discomfort, despite a decreased respiratory rate. The clinical importance of these effects is modest. Medical teams should consider these effects and balance its need with its adverse effects according to the clinical condition.

Unintentional exposure of neonates to conventional radiography in the Neonatal Intensive Care Units.

OBJECTIVE: To evaluate the extent of unintentional exposure to X-rays performed during routine diagnostic procedures in the Neonatal Intensive Care Units (NICUs). STUDY DESIGN: During a 1-month period, 157 consecutive neonates from five level-III NICUs were recruited for this study. The mean birth weight was 1747+/-911 g (range: 564-4080 g), and gestational age was 31.6+/-3.6 weeks (range: 24-41 weeks). A total of 500 radiographs were performed including chest (68%), abdomen (17%) and combined chest and abdomen (15%). The average number of radiographs taken per infant was 4.2+/-3.6 (range: 1-21). Unintentional inclusion of body regions other than those ordered was determined by comparing the areas that should be included in the radiation field according to International recommendations, to those that appeared in the actual radiograph. RESULT: A comparison of the recommended borders to the actual boundaries of the radiographs taken show an additional exposure to radiation in all three procedures: 85% of chest radiographs also included the whole abdomen, 64% of abdomen radiographs included both thigh and upper chest and 62% of chest and abdomen radiograph included the thigh. (The range in all procedures was from ankle to upper head.) Between 2 and 20% of the relevant targeted body tissues were not included in the exposed fields resulting in missing data. The gonads of both sexes were exposed in 7% in all chest X-rays. Among male infants, the testes were exposed in 31% of plain abdomen radiographs and 34% of chest and abdomen radiographs. CONCLUSION: In the NICUs participating in the study, neonates are currently being exposed to X-ray radiation in nonrelevant body regions. Higher awareness and training of the medical teams and radiographers are required to minimize unnecessary exposure of newborns to ionizing radiation.

Cardiac troponin I serum concentrations in newborns: a study and review of the literature.

BACKGROUND: Serum cardiac troponin I (cTnI) is a specific marker of cardiac injury. The use of cTnI in neonates, especially in relation to perinatal asphyxia has not been extensively examined. We defined the range of normal values of cTnI in newborns, and study factors that may influence these concentrations. METHODS: Serum cTnI concentrations were measured on the third day of life in 179 normal newborns: 157 were term (after 37 weeks, mean: 39.7+/-1.1, range: 37-42) and 22 were premature infants (mean: 32.6+/-2.9, range: 27-36 weeks). RESULTS: Mean cTnI for the term infants was 0.63+/-0.58 ng/ml (median: 0.50, range: 0.00-4.30). The concentration of 1.80 ng/ml, can serve as the upper limit of normal values. There was a borderline significant trend for higher cTnI in preterm infants. The number of newborns with cTnI>1.80 ng/ml was significantly higher after delivery by caesarean section, compared to vaginal delivery (14.6% vs. 2.9%, p<0.02). No other significant associations were found between cTnI and perinatal or neonatal parameters. CONCLUSIONS: Normal reference values for cTnI in healthy term newborns were defined, but need to be addressed with caution due to the wide range of normal values.

Hood versus mask nebulization in infants with evolving bronchopulmonary dysplasia in the neonatal intensive care unit.

OBJECTIVE: To compare infants' discomfort, nursing-time and caregiver preference, and assess the clinical efficiency (as a secondary outcome) of hood versus facemask nebulization in infants with evolving bronchopulmonary dysplasia (BPD) in the neonatal intensive care unit. STUDY DESIGN: A prospective, open, randomized, controlled crossover clinical trial. In total, 10 infants with BPD who were on inhaled beta-agonist bronchodilators and corticosteroids were randomly assigned to receive their nebulized treatments either by a facemask, or by a hood for 2-3 days, and then crossover to receive the same treatments with the other technique for another 2-3 days. Infants' discomfort, nursing-time, caregiver preference and clinical efficiency were compared. RESULTS: At baseline there was no significant clinical difference between the groups. Nurse-time required for administering the hood nebulization (mean+/-s.e.m.: 1.9+/-0.1 min) was significantly shorter than the time for mask nebulization (12.0+/-0.6 min, P<0.0001). Infants' discomfort score was significantly lower (0.1+/-0.04) for hood versus mask nebulization (2.5+/-0.2, P<0.0001). Nurses and parents unequivocally preferred the hood treatment. During both mask and hood nebulization therapies (2-3 days) clinical efficiency was comparable. While both methods caused an immediate (20 min post) clinical improvement, the immediate respiratory assessment change score was significantly greater for the hood versus the mask nebulization (0.62+/-0.27 versus 0.13+/-0.14, P<0.05). CONCLUSIONS: Nebulization of aerosolized medications in infants with evolving BPD by hood was less time-consuming for caregivers and was much better tolerated by the infants while being at least as effective as the conventional facemask nebulization.

Breathing patterns in term infants delivered by caesarean section.

AIM: To compare the breathing patterns of infants born by elective caesarean section to those infants delivered by caesarean section after a failed trial of labour. METHODS: Healthy term infants born by caesarean section were studied. The study group (n = 13) had no trial of labour, whereas infants in the control group (n = 13) failed a trial of labour. Polysomnographic study was performed at 36 h of age. Heart and respiratory rate, type and duration of apnoeas, arterial oxygen saturation and lower limb movements were analysed. RESULTS: Term infants born by elective caesarean section had a shorter duration of pregnancy and weighed less. Their heart rate was faster, they had more mixed apnoeas, and during quiet sleep they had more central apnoeas of longer duration. CONCLUSION: Cardiorespiratory patterns in infants delivered by elective caesarean section are different from those delivered by caesarean section after a failed trial of labour.

In the eye of the beholder: how accurate is clinical estimation of jaundice in newborns?

AIM: Hour-specific serum total bilirubin (STB) percentiles have proved useful in predicting which babies will develop significant neonatal hyperbilirubinemia (NHB) requiring intervention. This study investigated whether this assessment could be performed visually instead of by blood test. The aim was to evaluate the ability of experienced clinicians to determine accurately the level of clinical jaundice in neonates by visual means. METHODS: Four neonatologists were asked to estimate the level of bilirubin in a group of 283 term clinically jaundiced infants before discharge from the nursery on day 3 of life. Their clinical estimation was compared with actual measurement of STB from samples drawn simultaneously. RESULTS: Clinical estimation of STB had a high correlation to actual serum bilirubin levels (Pearson's correlation coefficient = 0.682, p < 0.001). CONCLUSION: Clinical impression of jaundice by the eye of an experienced clinician is a reliable method to assess newborns for significant NHB and may diminish the need for universal serum sampling.

Sidestream end-tidal capnometry as related to infant's position and maturation.

UNLABELLED: The objective of this study was to investigate the effect of body position on sidestream, end-tidal carbon dioxide (EtCO2) wave measurements in maturing infants. Sidestream EtCO2 wave patterns were analysed longitudinally in 20 preterm infants (born at > or = 32 wk) at 32-37 wk gestation, and in 39 full-term controls. Capnography measurements included maximal EtCO2, inspired CO2 and frequency of apnoea events (>3 s) in the supine, supine with inclination, side and prone positions. Apnoea frequency decreased during maturation, and was less prevalent in the prone than in the supine and side positions in preterm as well as in term infants (p < 0.05). No clinically significant apnoea episodes were found in our cohort. EtCO2 in term infants was lower than that in preterm infants (p < 0.05) and was not affected by sleep position in the most premature (<33 wk) and in term infants (>36 wk). EtCO2 was higher in the prone position than in supine or side positions in infants between 33 and 35 wk gestation (p < 0.01). CONCLUSION: Short apnoeic episodes decrease during maturation, and are less prevalent in the prone position in maturing infants (32-37 wk). Only modest changes in EtCO2 were recorded in the different positions during maturation.

The role of high-dose oral iron supplementation during erythropoietin therapy for anemia of prematurity.

OBJECTIVE: To assess whether a high intake of oral iron would increase the effect of recombinant human erythropoietin (rHuEPO) on hemoglobin synthesis. METHODS: We studied 30 preterm infants (gestational age 29+/-1.8 weeks, birth weight 1161+/-200 g, at age of 28+/-10 days) who were randomly assigned to receive either 8 mg/kg per day (n=15) or 16 mg/kg per day of oral iron during a course of rHuEPO therapy (900 microg/kg per week) for a duration of 4 weeks. Both groups were comparable in regard to clinical and laboratory data at the time of enrollment. RESULTS: rHuEPO caused a significant increase in reticulocyte count in the low- and high-dose iron groups, 17.1+/-5.3 to 34.7+/-9.2 and 16.3+/-3.3 to 42.5+/-5.6 (10(9)/l), respectively (p<0.05). However, in both groups, hematocrit values remained stable at the end of the study as compared to baseline (0.35+/-0.03% vs. 0.30+/-0.03%, 0.35+/-0.05% vs. 0.30+/-0.03%, NS) and in both groups there was a comparable and significant decrease in ferritin level (259+/-109 to 101+/-40 and 168+/-54 to 69+/-38 microg/l, respectively; p<0.01). The rates of bloody stools without any evidence of necrotizing enterocolitis were not significantly different between the two treatment groups (1/15 vs. 4/15, NS). CONCLUSION: We conclude that a higher dose (16 mg/kg per day) of oral iron is not more beneficial when compared to a lower dose (8 mg/kg per day) during rHuEPO therapy for anemia of prematurity. Further studies will define the optimal dosage and route of administration of iron supplementation during rHuEPO therapy.

Potential role of high-frequency ventilation in the treatment of severe congenital pleural effusion.

Newborns with severe congenital pleural effusions often present with respiratory failure at birth. We describe two premature infants born at 31 and 33 weeks of gestation with bilateral pleural effusions. Both were drained prior to delivery under ultrasound guidance. The first infant had severe bilateral congenital chylothorax with pulmonary hypertension; the second infant had severe nonimmune hydrops fetalis. Both could be adequately oxygenated but failed to respond to conventional mechanical ventilation (CMV) and chest tube drainage, so that CO(2) elimination could not be accomplished. Both infants were successfully treated with high-frequency ventilation (HFV). We suggest that HFV may be of significant value in establishing adequate ventilation in cases of severe congenital pleural effusions.

Intrapartum drainage of fetal pleural effusion.

Our objective was to describe our experience with intrapartum thoracocentesis in fetuses with severe bilateral pleural effusion. We describe the outcome of four consecutive cases of fetal pleural effusion due to chylothorax that were managed by intrapartum thoracocentesis. These fetuses were not candidates for pleuro-amniotic shunting either because of the need for prompt delivery (three fetuses) or because of advanced gestational age (one fetus). Thoracocentesis was performed in the operating theatre under ultrasound guidance prior to Caesarean delivery. Gestational age at the time of diagnosis and thoracocentesis ranged between 26-34 weeks and 31-34 weeks respectively. Bilateral thoracocentesis was performed in two fetuses and unilateral in the remaining two fetuses. All four infants were born in a relatively good condition; however, all eventually required intubation, ventilation and chest tubes. Chest tubes were introduced between 2 h and 5 days after delivery in three infants, and immediately after birth in one infant who was hydropic. Two infants survived and are developing normally. One infant died from sepsis following successful pleurodesis and one from aspiration on day 51. Our conclusions are that intrapartum thoracocentesis seems to be a relatively simple procedure, that allows newborns with pleural effusion, to breathe spontaneously or be more easily ventilated. This in turn, reduces the need to introduce chest tubes in an emergency situation.

Pulmonary cyst caused by septic emboli in the preterm infant.

A pulmonary cyst appeared in a growing preterm infant. The presumptive diagnosis was septic pulmonary embolism associated with the central venous catheter. The infant was successfully treated with antibiotic therapy and removal of the central venous catheter.