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.

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.

Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition.

The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

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.

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.

Kinetic and immunologic evidence for the absence of glucose-6-phosphatase in early human chorionic villi and term placenta.

The existence of the enzyme glucose-6-phosphatase (G6Pase) in early and term human placenta was investigated by comparing the characteristics of placental microsomal glucose 6-phosphate (G6P) hydrolytic activity and liver G6Pase. Placental microsomes exhibited similar apparent Km values for G6P and beta-glycerophosphate in intact and deoxycholate-treated microsomes, heat stability at acidic pH, low latency of mannose 6-phosphate hydrolysis, very low activity of pyrophosphate: glucose phosphotransferase, and undetectable [U-14C]G6P transport into the placental microsomes, all of which indicated that specific G6Pase activity does not exist in placenta. Immunological evidence of the absence of both 36.5 kDa and T2 proteins, which represent the G6Pase catalytic protein and the phosphate/pyrophosphate transporter protein, respectively, confirmed that early and term human placenta are devoid of the multicomponent G6Pase enzyme.

Alpha-fetoprotein in the early neonatal period--a large study and review of the literature.

BACKGROUND: Alpha-fetoprotein (AFP) is a glycoprotein molecule, which has similarity to albumin and is produced by the fetal liver. Its biological role is unclear and factors that may influence its concentrations in neonates are only partially identified. However, it has an important role as a diagnostic marker, especially in certain tumors and liver diseases of childhood. Its normal reference values in newborns have not been well defined. METHODS: Serum AFP concentrations were measured and characterized in 260 term and near-term newborns [gestational age (GA)> or =34 weeks, birthweight (BW)> or =1700 g] at birth [umbilical cord (UC) blood] and upon discharge from the nursery at 60+/-24 h of life (venous sample). RESULTS: Due to the nonnormal distribution of AFP levels, it is useful to relate to reference interval for AFP concentrations at birth that was 15.7-146.5 microg/ml, based on 95% confidence interval (CI). The median value of 48.3 microg/ml is also a useful reference. However, mean AFP concentrations at birth that were 61.6+/-44.8 microg/ml are less informative due to the large standard deviation (S.D.). Upon discharge, AFP concentrations dropped to 9.7-111.9 microg/ml (95% CI) with a median of 34.2 microg/ml. A significant negative correlation was found between AFP serum levels and gestational age and to a lesser extent with birthweight. No significant differences were found between males and females. CONCLUSIONS: Normal reference intervals for AFP in term and near-term newborns have been defined, but need to be addressed with caution due to the wide range of normal values. AFP levels at birth decrease as gestation advances and the newborn weighs more.

Possible importance of increased intra-abdominal pressure for the development of necrotizing enterocolitis.

BACKGROUND/PURPOSE: Despite extensive clinical and laboratory investigations, many aspects of the pathogenesis of necrotizing enterocolitis (NEC) remain unclear. In the present work we describe 5 neonates with NEC in whom intra-abdominal pressure (IAP) was measured to investigate the potential role of abdominal compartment syndrome (ACS) in the development of NEC and to correlate the severity of NEC with the value of IAP. METHODS: IAP pressure was determined in two groups - Group A consisting of five patients without NEC (Control) and Group B consisting of five patients who developed NEC - by measuring the urinary bladder pressure (UBP). The correlation between increased IAP and severity of NEC, complications of NEC and indications for surgery was investigated. RESULTS: In four patients from Group B, the general condition deteriorated despite aggressive supportive treatment, and a laparotomy was performed. These neonates demonstrated a significant increase (compared to Control patients) in UBP (9.0+/-2.5 vs. 4.8+/-1.4 mmHg, p=0.001), which increased progressively with exacerbation of NEC and reached a peak value of 13.3+/-2.4 mmHg before operation. The elevated IAP was accompanied by hemodynamic instability in all patients, respiratory instability in 3 patients and decreased urinary output in one patient. One patient remained unstable and died 6 h after operation. In the fifth patient from Group B, intestinal obstruction developed two weeks after NEC and did not result in increased IAP. CONCLUSIONS: Our results suggest that IAP is associated with an exacerbation of NEC. Thus, this study provides further information which may improve our understanding of the pathogenic process of NEC.

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.

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.

The role of umbilical cord alpha fetoprotein as a screening tool for neonatal hyperbilirubinemia.

Our aim was to test whether alpha fetoprotein (AFP) might serve as a marker of hepatic immaturity sufficient to predict an increased risk for neonatal hyperbilirubinemia (NHB) in term babies. We checked umbilical cord AFP (UC AFP) levels in 174 healthy full-term infants (male/female ratio 1.26:1) at birth. Bilirubin levels were measured upon discharge from the nursery on day 3 of life (mean, 57 +/- 10 hours of life). Mean UC AFP was 60.2 +/- 45.9 mg/L. UC AFP levels were linearly correlated with subsequent bilirubin levels, and significantly higher bilirubin levels were found in neonates whose UC AFP levels were 100 mg/L or more. Although statistically significant correlation between UC AFP and subsequent NHB exists, UC AFP cannot currently be recommended for use in clinical practice because of its inability to serve as a screening tool for significant NHB in the individual newborn.