Secondary hyperparathyroidism is associated with postpartum blood pressure in preeclamptic women and normal pregnancies.

BACKGROUND: Preeclampsia has been associated with features of secondary hyperparathyroidism. In this study, we examine the relationships of calcium metabolism with blood pressure (BP) in preeclamptic women and in a control group of normal (NORM) pregnancies in the postpartum. METHODS: Sixty-three consecutive preeclamptic women (age 35 ±â€Š6 years) were studied 4 weeks after delivery. We collected clinical and lab information on pregnancy and neonates and measured plasma and urinary calcium and phosphate, plasma parathyroid hormone (PTH) and 25-hydroxy vitamin D [25(OH)D], and performed 24-h ambulatory BP monitoring. BP and calcium metabolism of 51 preeclamptic were compared with 17 NORM pregnant women that matched for age, race, and postpartum BMI. RESULTS: 25(OH)D deficiency (<10 ng/ml) was found in 3% of preeclamptic women, insufficiency (10-30 ng/ml) in 67%, and NORM values (31-100 ng/ml) in the remaining 30%. Elevated plasma PTH (≥79 pg/ml) was found in 24% of preeclamptic women who had 25(OH)D plasma levels of 21.4 ±â€Š8.3 ng/ml. In these women, PTH levels was independently associated with 24-h SBP and DBP and daytime and night-time DBP. Prevalence of nondippers and reverse dippers was elevated (75% and 33%, respectively). No associations between calcium metabolism and neonates' characteristics of preeclamptic women were observed. Prevalence of vitamin D deficiency and insufficiency and of elevated plasma PTH levels were comparable in matched groups. Considering preeclamptic women and matched controls as a whole group, office SBP and DBP levels were associated with PTH independently of preeclampsia and other confounders. CONCLUSION: Features of secondary hyperparathyroidism are common in the postpartum. Preeclampsia and increased PTH levels were both independent factors associated with increased BP after delivery, and both might affect the future cardiovascular risk of these women.

Surfactant-secreted phospholipase A2 interplay and respiratory outcome in preterm neonates.

Secreted phospholipase A2 hydrolyzes surfactant phospholipids and is crucial for the inflammatory cascade; preterm neonates are treated with exogenous surfactant, but the interaction between surfactant and phospholipase is unknown. We hypothesize that this interplay is complex and the enzyme plays a relevant role in neonates needing surfactant replacement. We aimed to: 1) identify phospholipases A2 isoforms expressed in preterm lung; 2) study the enzyme role on surfactant retreatment and function and the effect of exogenous surfactant on the enzyme system; and 3) verify whether phospholipase A2 is linked to respiratory outcomes. In bronchoalveolar lavages of preterm neonates, we measured enzyme activity (alone or with inhibitors), enzyme subtypes, surfactant protein-A, and inflammatory mediators. Surfactant function and phospholipid profile were also tested. Urea ratio was used to obtain epithelial lining fluid concentrations. Follow-up data were prospectively collected. Subtype-IIA is the main phospholipase isoform in preterm lung, although subtype-IB may be significantly expressed. Neonates needing surfactant retreatment have higher enzyme activity (P = 0.021) and inflammatory mediators (P always ≤ 0.001) and lower amounts of phospholipids (P always < 0.05). Enzyme activity was inversely correlated to surfactant adsorption (ρ = -0.6; P = 0.008; adjusted P = 0.009), total phospholipids (ρ = -0.475; P = 0.05), and phosphatidylcholine (ρ = -0.622; P = 0.017). Exogenous surfactant significantly reduced global phospholipase activity (P < 0.001) and subtype-IIA (P = 0.005) and increased dioleoylphosphatidylglycerol (P < 0.001) and surfactant adsorption (P < 0.001). Enzyme activity correlated with duration of ventilation (ρ = 0.679, P = 0.005; adjusted P = 0.04) and respiratory morbidity score at 12 mo postnatal age (τ-b = 0.349, P = 0.037; adjusted P = 0.043) but was not associated with mortality, bronchopulmonary dysplasia, or other long-term respiratory outcomes.

Patent ductus arteriosus in preterm infants born before 30 weeks' gestation: high rate of spontaneous closure after hospital discharge.

AimThe aim of this study was to determine the spontaneous closure rate of patent ductus arteriosus at a 2-year follow-up, following failed medical therapy and beyond initial hospital discharge, and to evaluate in-hospital spontaneous or pharmacological closure rates.Materials and methodsA retrospective evaluation was conducted in a cohort of preterm infants admitted to the Neonatal ICU of Ancona between January, 2004 and June, 2013. Inclusion criteria were gestational age between 24+0 and 29+6 weeks or birth weight 1.5 mm, a left atrium-to-aorta ratio >1.4, and/or reversal of end-diastolic flow in the aorta >30% of the anterograde. First-line treatment was intravenous ibuprofen. Intravenous indomethacin was used if ibuprofen failed. Surgical ligation was considered in haemodynamically significant patent ductus arteriosus after medical treatment. RESULTS: A total of 593 infants met the inclusion criteria, and patent ductus arteriosus was diagnosed in 317 (53.4%). Among them, 283 (89.3%) infants had haemodynamically significant patent ductus arteriosus, with pharmacological closure achieved in 228 (80.6%) infants and surgical ligation performed in 20 (7.1%). Follow-up at 24 months was available for 39 (81.3%) of 48 infants with patent ductus arteriosus at the hospital discharge: 36 (92.3%) underwent spontaneous closure, two (5.1%) underwent surgical ligation, and one (2.6%) had a patent ductus arteriosus.DiscussionA significant number of patent ductus arteriosus that fail pharmacological closure undergo spontaneous closure by the age of 2 years. This information should be taken into account when considering surgery or additional attempts of pharmacological closure.

Modes of Death in a Pediatric Cardiac ICU.

OBJECTIVE: To determine epidemiology and proximate causes of death in a pediatric cardiac ICU in Southern Europe. DESIGN: Retrospective chart review. SETTING: Single-center institution. PATIENTS: We concurrently identified 57 consecutive patients who died prior to discharge from the cardiac ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over the study period, there were 57 deaths for a combined mortality rate of 2.4%. Four patients (7%) were declared brain dead, 25 patients (43.8%) died after a failed resuscitation attempt, and 28 patients (49.1%) died after withholding or withdrawal of life-sustaining treatment. Cardiorespiratory failure was the most frequent proximate cause of death (39, 68.4%) followed by brain injury (14, 24.6%) and septic shock (4, 7%). Older age at admission, presence of mechanical ventilation and/or device-dependent nutrition support, patients on a left-ventricular assist device and longer cardiac ICU stay were more likely to have life support withheld or withdrawn. CONCLUSIONS: Almost half of the deaths in the cardiac ICU are predictable, and they are anticipated by the decision to limit life-sustaining treatments. Brain injuries play a direct role in the death of 25% of patients who die in the cardiac ICU. Patients with left-ventricular assist device are associated with withdrawal of treatment.

The Role of Regional Oxygen Saturation Using Near-Infrared Spectroscopy and Blood Lactate Levels as Early Predictors of Outcome After Pediatric Cardiac Surgery.

BACKGROUND: The purpose of the study was to evaluate the association between regional oxygen saturation (rSO2) desaturation score (calculated by multiplying the rSO2 < 50% by time in seconds the preoperative baseline value) measured with near-infrared spectroscopy and the peak of lactate with postoperative major morbidities in pediatric patients who undergo cardiac surgery. METHODS: We retrospectively analyzed the postoperative course of 152 patients between January 2012 and December 2013, for whom we continuously monitored cerebral rSO2 using near-infrared spectroscopy and serial arterial blood lactate levels for at least 48 hours. RESULTS: The median age at surgery was 128 days (interquartile range [IQR], 17-537 days). Thirty-nine patients had a single ventricle physiology (26%) and 135 patients (89%) required the use of cardiopulmonary bypass (median time of 130 minutes; IQR, 93-172 minutes). Median postoperative peak lactate level was 3 mmol/L (IQR, 2-5.3 mmol/L); 52 patients (34%) had a postoperative lactate level > 4.6 mmol/L. The median postoperative rSO2 desaturation score was 157 (IQR, 0-2050); 62 patients (41%) had an rSO2 desaturation score > 345. Fifty-seven patients (37%) had postoperative major morbidities. Using a multivariable regression model only rSO2 desaturation score > 345 was independently associated with major morbidities after surgery (odds ratio, 27.26; 95% confidence interval, 10.18-73.00). The proportion of patients with an rSO2 desaturation score > 345 within 240 minutes after surgery was higher than the rate of those who showed a peak of lactate > 4.6 mmol/L (84% vs 59%; P = 0.05). CONCLUSIONS: The postoperative rSO2 desaturation score has a stronger association with major postoperative morbidities than lactate and it also provides an earlier warning sign of hemodynamic or metabolic compromise.

Short-Term Stability of Whole Blood Polyunsaturated Fatty Acid Content on Filter Paper During Storage at -28 °C.

Finger or heel-pricked blood sampling for fatty acid analysis is suitable especially in newborn infants where blood sampling is difficult and phlebotomy for research can be unethical. The aim of this study was to evaluate dried blood long chain polyunsaturated fatty acids (LC-PUFA) stability during storage at -28 °C. We collected 12 blood cord samples that were analyzed immediately after blood drawing, with and without drying the blood on filter paper. Dried samples were then analyzed 7 days and 1, 3, and 6 months after collection. Butylated hydroxytoluene was added to all samples. Fatty acid composition and (13)C enrichment were measured by gas chromatography and by gas chromatography-isotope ratio mass spectrometry, respectively. The fatty acid composition, expressed in mol%, of the major LC-PUFA at day 7 was not statistically different from time 0, however lower values were found by the first month of storage. The (13)C enrichment of 20:4n-6 and 22:6n-3 did not differ during the whole study period. LC-PUFA analysis from dried umbilical cord blood in neonates should be performed within a week, major losses of LC-PUFA occur afterwards. However, fatty acids obtained from dried blood maintain their (13)C enrichment value for up to 6 months and thus these samples are suitable for natural abundance isotopic studies.

Cardiopulmonary Bypass Increases Plasma Glial Fibrillary Acidic Protein Only in First Stage Palliation of Hypoplastic Left Heart Syndrome.

BACKGROUND: Univentricular congenital heart defects require open-heart surgery soon after birth, and are associated with risk of brain injury and poor neurologic outcome. METHODS: This is a prospective, observational study on children undergoing cardiac surgery. Plasma glial fibrillary acidic protein (GFAP), as an early marker of brain injury, was measured by ELISA at the end of anaesthesia induction, initiation of cardiopulmonary bypass (CPB), the end of cooling, the end of rewarming, the end of CPB, and after protamine administration. We recorded clinical and surgical parameters to assess which CPB phase and clinical parameters were associated with a GFAP increase. RESULTS: We studied 13 children less than 50 months of age: 8 underwent Norwood or Damus-Kaye-Stansel palliation (group 1) and 5 underwent Fontan procedure (group 2). A GFAP increase was only observed in group 1, with the highest median value at the end of rewarming. No quantifiable levels of GFAP were measured at pre-bypass and the start of CPB stages in all patients. End of cooling and CPB-end GFAP, GFAP maximum value, and GFAP area under the curve all correlated with the CPB time spent at a cerebral regional saturation < 45% (P = 0.021, 0.028, 0.007, 0.021, respectively). CONCLUSIONS: Children with univentricular heart defects exhibit a CPB plasma-GFAP increase only after stage 1 palliation. The maximum GFAP increase occurred at the end of rewarming. Further studies are needed to identify which clinical or surgical parameter(s) could reflect a GFAP increase during surgery for congenital heart defects, and whether GFAP levels correlate with the neurologic outcome.

Double blind exploratory study on de novo lipogenesis in preterm infants on parenteral nutrition with a lipid emulsion containing 10% fish oil.

BACKGROUND & AIMS: Provision of long chain polyunsaturated fatty acids (LCP) both of the omega-3 and omega-6 families is recommended for preterm infants (PI). Fish oil (FO) contains omega-3 and omega-6 LCP and it is incorporated in the fat blend of the new generation lipid emulsions (LE). Omega-3 LCP have been shown to reduce the expression of genes involved in lipogenesis, which could be important for several organs development. The aim of this study was to ascertain if the use of intravenous FO has an effect on lipogenesis in PI. METHODS: Forty PI were randomized to receive two LE: MSF (50:40:10 Medium Chain Triglycerides (MCT): Soybean oil (SO): FO) or MS (50:50 MCT:SO). We measured plasma lipids on day 7 and the fractional and absolute synthesis rates (FSR and ASR) of cholesterol and of selected fatty acids (FA) after (2)H2O body water labeling. RESULTS: Plasma phospholipids (PL), free cholesterol (FC), and cholesterol esters (CE) concentrations were all lower in MSF than in MS. In spite of lower plasma FC and CE concentrations, cholesterol biosynthesis was similar between the two study groups (FC: FSR 16.0 ± 1.4 vs 14.1  ± 1.1%/d, p = 0.74; ASR 6.8 ± 0.6 vs 7.1 ± 0.6 mg kg(-1) d(-1), p = 0.93; CE: FSR 3.6 ± 0.5 vs 4.2 ± 0.4%/d, p = 0.38; ASR: 3.3 ± 0.4 vs 4.4 ± 0.5 mg kg(-1) d(-1), p = 0.13, in MSF and MS respectively). FSR and ASR of selected FA were, or tended to be, lower in MSF than in MS. ASR of PL palmitate (4.0 ± 0.3 vs 4.8 ± 0.4 mg kg(-1) d(-1), p = 0.045), PL oleate (0.2 ± 0.04 vs 0.4 ± 0.05 mg kg(-1) d(-1), p = 0.02) and CE oleate (0.5 ± 0.1 vs 0.9 ± 0.1 mg kg(-1) d(-1), p = 0.03) were significantly lower in MSF than in MS. There were no differences in plasma TG FA biosynthesis. CONCLUSIONS: Cholesterol biosynthesis was not affected by 10% FO during neonatal parenteral nutrition. Ten percent FO caused a statistically significant reduction in the lipogenesis of selected FA and an overall tendency towards a reduced lipogenesis. The magnitude seems to be limited and the biological significance is unknown. Our data warrant follow-up studies in PI who receive intravenous FO, especially in those infants who receive larger doses than in the present study. Since this trial started in 2007, trial registration was not required.

Surfactant protein B and A concentrations are increased in neonatal pneumonia.

BACKGROUND: Term newborns with pneumonia show a reduced pulmonary compliance due to multiple and ill-defined factors. Surfactant proteins' (SPs) changes could have a role in the reduced compliance but the matter is still unsettled. The aim of this study was to clarify the meaning of SPs changes during pneumonia in term newborns. METHODS: In 28 term ventilated newborns, 13 with pneumonia and 15 with no lung disease, we measured SP-B, SP-A, disaturated-phosphatidylcholine (DSPC), and total phospholipids (PL) concentrations in tracheal aspirates at intubation and close to extubation. We also measured DSPC kinetics using (U-(13)C-PA)dipalmitoyl-phosphatidylcholine. RESULTS: At baseline, SP-B, expressed as % of PL, was significantly different between the groups, being 3.5-fold higher in pneumonia than controls. Conversely, SP-A did not vary between the groups. At extubation, SP-B and SP-A concentrations had decreased significantly in newborns with pneumonia, while there was no significant change in controls. DSPC t1/2 was significantly shorter in the pneumonia group (11.8 (5.5-19.8) h vs. 26.6 (19.3-63.6) h, P = 0.011). CONCLUSION: In term newborns with pneumonia, SP-B increases with respect to PL, and DSPC is turned over at a faster rate. Disease's resolution is associated with the restoration of the normal ratio between SP-B and PL.

Airway metabolic anomalies in adolescents with bronchopulmonary dysplasia: new insights from the metabolomic approach.

OBJECTIVES: To assess a group of adolescents with bronchopulmonary dysplasia (BPD) from a biochemical-metabolic standpoint, applying the metabolomic approach to studying their exhaled breath condensate (EBC). STUDY DESIGN: Twenty adolescents with BPD (mean age 14.8 years) and 15 healthy controls (mean age 15.2 years) were recruited for EBC collection, exhaled nitric oxide measurement, and spirometry. The EBC samples were analyzed using a metabolomic approach based on mass spectrometry. The obtained spectra were analyzed using multivariate statistical analysis tools. RESULTS: A reliable Orthogonal Projections to Latent Structures-Discriminant Analysis model showed a clear discrimination between cases of BPD and healthy controls (R(2) = 0.95 and Q(2) = 0.92). The search for putative biomarkers identified an altered complex lipid profile in the adolescents with BPD. CONCLUSIONS: The metabolomic analysis of EBC distinguishes cases of BPD from healthy individuals, suggesting that the lung of survivors of BPD is characterized by long-term metabolic abnormalities. The search for putative biomarkers indicated a possible role of an altered surfactant composition, which may persist far beyond infancy.

Neurologic injury in neonates with congenital heart disease during extracorporeal membrane oxygenation: an analysis of extracorporeal life support organization registry data.

The aim of this article is to describe the epidemiology and factors associated with acute neurologic injury in neonates with congenital heart disease (CHD) undergoing extracorporeal membrane oxygenation (ECMO). It is a retrospective cohort study. Multi-institutional data for purposes of this study were obtained from the extracorporeal life support organization registry Neonates with CHD supported with ECMO during 2005-2010. Of 1,898 neonates with CHD supported with ECMO, 273 (14%) had neurologic injury. Birth weight less than 3 kg (odds ratio [OR]: 1.5; 95% confidence intervals [CI]: 1.1-1.9), pre-ECMO blood pH ≤ 7.15 (OR: 1.5, 95% CI: 1.1-2.1) need for cardiopulmonary resuscitation before ECMO (OR: 1.7, 95% CI: 1.5-2.0) increased neurologic injury. In-hospital mortality was higher in patients with neurologic injury compared with those without (73% vs. 53%; p < 0.001). Neonates with CHD undergoing ECMO are highly vulnerable to acute neurologic injury regardless of cardiac lesion-specific physiology or the occurrence of cardiac surgery. The incidence of neurologic injuries in this population is higher in sicker patients. Severity of illness should therefore become the main target for improvement. Timely deployment of ECMO may therefore influence the development of ECMO complications.

Surface film formation in vitro by infant and therapeutic surfactants: role of surfactant protein B.

BACKGROUND: Pulmonary surfactant provides an alveolar surface-active film that is critical for normal lung function. Our objective was to determine in vitro film formation properties of therapeutic and infant surfactants and the influence of surfactant protein (SP)-B content. METHODS: We used a multiwell fluorescent assay measuring maximum phospholipid surface accumulation (Max), phospholipid concentration required for half-maximal film formation (½Max), and time for maximal accumulation (tMax). RESULTS: Among five therapeutic surfactants, calfactant (highest SP-B content) had film formation values similar to natural surfactant, and addition of SP-B to beractant (lowest SP-B) normalized its Max value. Addition of budesonide to calfactant did not adversely affect film formation. In tracheal aspirates of preterm infants with evolving chronic lung disease, SP-B content correlated with ½Max and tMax values, and SP-B supplementation of SP-B-deficient infant surfactant restored normal film formation. Reconstitution of normal surfactant indicated a role for both SP-B and SP-C in film formation. CONCLUSION: Film formation in vitro differs among therapeutic surfactants and is highly dependent on SP-B content in infant surfactant. The results support a critical role of SP-B for promoting surface film formation.

Surfactant protein C metabolism in human infants and adult patients by stable isotope tracer and mass spectrometry.

Surfactant protein C (SP-C) is deemed as the surfactant protein most specifically expressed in type II alveolar epithelial cells and plays an important role in surfactant function. SP-C turnover in humans and its meaning in the clinical context have never been approached. In this study, we used mass spectrometry to investigate SP-C turnover in humans. We studied four infants and eight adults requiring mechanical ventilation. All patients had no lung disease. Patients received a 24-h continuous infusion of (13)C-leucine as precursor of SP-C, and serial tracheal aspirates and plasma samples were obtained every 6 h till 48 h. SP-C was isolated from tracheal aspirates by sorbent-phase chromatography. (13)C-leucine SP-C enrichment could be successfully measured in three infant and in four adult samples by using mass spectrometry coupled with a gas chromatographer. Median SP-C fractional synthesis rate, secretion time, and peak time were 15.7 (14.1-27.5)%/day, 6.0 (4.7-11.5) h, and 24 (20-27) h. In conclusion, this study shows that it is feasible to accurately determine SP-C turnover in humans by stable isotopes.

Higher docosahexaenoic acid, lower arachidonic acid and reduced lipid tolerance with high doses of a lipid emulsion containing 15% fish oil: a randomized clinical trial.

BACKGROUND & AIMS: Lipid emulsions containing fish oil, as source of long chain omega 3 fatty acids, have recently became available for parenteral nutrition in infants, but scanty data exist in extremely low birth weight preterms. The objective of this study was to compare plasma fatty acids and lipid tolerance in preterm infants receiving different doses of a 15% fish oil vs. a soybean oil based lipid emulsion. METHODS: Preterm infants (birth weight 500-1249 g) were randomized to receive parenteral nutrition with MOSF (30% Medium-chain triglycerides, 25% Olive oil, 30% Soybean oil, 15% Fish oil) or S (S, 100% Soybean oil) both at two levels of fat intake: 2.5 or 3.5 g kg(-1) d(-1), named 2.5Fat and 3.5Fat respectively. Plasma lipid classes and their fatty acid composition were determined on postnatal day 7 and 14 by gas chromatography together with routine biochemistry. RESULTS: We studied 80 infants. MOSF infants had significantly higher plasma phospholipid Docosahexaenoic acid and Eicosapentaenoic and lower Arachidonic acid. Plasma phospholipids, triglycerides and free cholesterol were all significantly higher in the MOSF-3.5Fat group, while cholesterol esters were lower with MOSF than with S. The area under the curve of total bilirubin was significantly lower with MOSF than with S. CONCLUSIONS: The use of a lipid emulsion with 15% FO resulted in marked changes of plasma long-chain fatty acids. Whether the benefits of increasing Docosahexaenoic acid outweigh the potential negative effect of reduced Arachidonic acid should be further studied. MOSF patients exhibited reduced lipid tolerance at 3.5 g kg(-1) d(-1) fat intake. The trial was conducted between January 2008 and December 2012 so we had not registered it in a public trials registry as it is now required for trials that started after July 2008.

Null ABCA3 in humans: large homozygous ABCA3 deletion, correlation to clinical-pathological findings.

A study was undertaken to analyze the clinical presentation, pulmonary function, and pathological features in two female siblings with neonatal pulmonary surfactant metabolism dysfunction, type 3 (MIM 610921). The clinical records of the siblings were examined; the genes encoding surfactant protein B (SFTPB), surfactant protein C (SFTPC), and ATP-binding cassette transporter 3 protein (ABCA3) were analyzed with direct sequencing and Southern blotting. The infants were homozygous for a 5,983 bp deletion in ABCA3 including exons 2-5 as well as the start AUG codon and a putative Golgi exit signal motif. Dense abnormalities of lamellar bodies at electron microscopy and absence of ABCA3 at immunohistochemical staining were in agreement with the presence of two null alleles. In addition, an increased lipid synthesis suggested a compensatory mechanism. The clinical course in the two sisters was influenced by different environmental factors like the time needed for molecular confirmation, the ventilatory assistance adopted, the occurrence of infections. A less aggressive clinical approach did not improve the course of the disease; the prognosis was always poor. Development of a fast molecular test, able to detect also structural variants, is needed.

Pulmonary surfactant synthesis after unilateral lung injury in mice.

Aspiration pneumonitis can lead to alveolar surfactant dysfunction. We employed a murine model of unilateral aspiration to compare surfactant synthesis in the injured (I) and noninjured (NI) contralateral lung. Mice were instilled with hydrochloric acid in the right bronchus and, after 18 h, an intraperitoneal dose of deuterated water was administered as precursor of disaturated phosphatidylcholine (DSPC)-palmitate. Selected bronchoalveolar lavage fluid (BALF) was collected at scheduled time points and lungs were removed. We measured DSPC-palmitate synthesis in lung tissue and secretion in BALF by gas chromatography-isotope ratio mass spectrometry, together with total proteins and myeloperoxidase activity (MPO) by spectrophotometry. BALF total proteins and MPO were significantly increased in the I lungs compared with NI and naïve control lungs. The DSPC pool size was significantly lower in the BALF of the I lungs compared with naïve controls. DSPC synthesis was accelerated in the I and NI lungs. DSPC secretion of the I lungs was similar to their respective naïve controls, and it was markedly lower compared with their respective NI contralateral lungs. DSPC synthesis and secretion were faster, especially in the NI lungs, compared with naïve control lungs, as a possible compensatory mechanism due to a cross-talk between the lungs triggered by inflammation, hyperventilation, and/or undetermined type II cell reaction to the injury.

In vivo effect of pneumonia on surfactant disaturated-phosphatidylcholine kinetics in newborn infants.

BACKGROUND: Bacterial pneumonia in newborns often leads to surfactant deficiency or dysfunction, as surfactant is inactivated or its production/turnover impaired. No data are available in vivo in humans on the mechanism of surfactant depletion in neonatal pneumonia. We studied the kinetics of surfactant's major component, disaturated-phosphatidylcholine (DSPC), in neonatal pneumonia, and we compared our findings with those obtained from control newborn lungs. METHODS: We studied thirty-one term or near-term newborns (gestational age 39.7±1.7 weeks, birth weight 3185±529 g) requiring mechanical ventilation. Fifteen newborns had pneumonia, while 16 newborns were on mechanical ventilation but had no lung disease. Infants received an intratracheal dose of 13C labeled dipalmitoyl-phosphatidylcholine at the study start. We measured the amount and the isotopic enrichment of DSPC-palmitate from serial tracheal aspirates by gas chromatography and gas chromatography-mass spectrometry, respectively, and we calculated the DSPC half-life (HL) and pool size (PS) from the isotopic enrichment curves of surfactant DSPC-palmitate. RESULTS: The mean DSPC amount obtained from all tracheal aspirates did not differ between the two groups. DSPC HL was 12.7 (6.5-20.2) h and 25.6 (17.9-60.6) h in infants with pneumonia compared with control infants (p = 0.003). DSPC PS was 14.1 (6.6-30.9) mg/kg in infants with pneumonia and 34.1 (25.6-65.0) mg/kg in controls, p = 0.042. Myeloperoxidase (MPO) activity, as a marker of lung inflammation, was 1322 (531-2821) mU/ml of Epithelial Lining Fluid (ELF) and 371(174-1080) mU/ml ELF in infants with pneumonia and in controls, p = 0.047. In infants with pneumonia, DSPC PS and HL significantly and inversely correlated with mean Oxygenation Index (OI) during the study (DSPC PS vs. OI R = -0.710, p = 0.004 and HL vs. OI R = -0.525, p = 0.044, respectively). CONCLUSIONS: We demonstrated for the first time in vivo in humans that DSPC HL and PS were markedly impaired in neonatal pneumonia and that they inversely correlated with the degree of respiratory failure.

Targeting 2.5 versus 4 g/kg/day of amino acids for extremely low birth weight infants: a randomized clinical trial.

OBJECTIVE: To compare the effect of 2.5 vs 4 g/kg/d of amino acid (AA) in parenteral nutrition of extremely low birth weight infants on metabolic tolerance, short-term growth, and neurodevelopment. STUDY DESIGN: One hundred thirty-one infants with birth weight between 500 and 1249 g were randomized to 2.5 (standard AA [SAA] group) or 4 (high AA [HAA] group) g/kg/d AA intake, with equal nonprotein energy. The primary outcome was body size at 36 weeks. RESULTS: One hundred thirty-one patients were randomized and 114 analyzed (58 SAA group and 56 HAA group). Study groups had similar demographics and clinical characteristics. Elevated blood urea (BU >70 mg/dL = BU nitrogen >32.6 mg/dL) occurred in 24% vs 59% (P = .000) and hyperglycemia (>175 mg/dL) in 34% vs 11% (P = .003) of the SAA and HAA patients, respectively. Body weight, length, and head circumference at 36 weeks and 2 years were similar between groups. Bayley Scales of Infant and Toddler Development, Third Edition score was 94 ± 13 in the SAA group and 97 ± 15 in the HAA group (P = .35). CONCLUSIONS: The HAA group had higher BU levels and better glucose control. An extra 8 g/kg of AA over the first 10 days of life did not improve growth and neurodevelopment.

The effect of 5 intravenous lipid emulsions on plasma phytosterols in preterm infants receiving parenteral nutrition: a randomized clinical trial.

BACKGROUND: Elevated plasma phytosterol concentrations are an untoward effect of parenteral nutrition (PN) with vegetable oil-based lipid emulsions (LEs). Phytosterols are elevated in neonatal cholestasis, but the relation remains controversial. OBJECTIVE: The objective was to study the effect of 5 LEs on plasma phytosterols in preterm infants. DESIGN: One hundred forty-four consecutive admitted preterm infants (birth weight: 500-1249 g) were studied. Patients were randomly assigned to receive 1 of 5 different LEs: S [100% soybean oil (SO)], MS [50% medium-chain triglycerides (MCTs) and 50% SO], MSF (50% MCTs, 40% SO, and 10% fish oil (FO)], OS (80% olive oil and 20% SO), or MOSF (30% MCTs, 25% olive oil, 30% SO, and 15% FO). Phytosterols in the LEs and in plasma (on postnatal day 7 and day 14) were measured by gas chromatography-mass spectrometry. RESULTS: Patients in the S group had significantly higher total phytosterol intakes than did the other study groups. On PN days 7 and 14, plasma phytosterol concentrations were highest in the S group and lowest in the MOSF group. Despite similar ß-sitosterol intakes between the MS and MSF groups, plasma concentrations were significantly lower in the MSF than in the MS group. Only 3 patients (2.1%) developed cholestasis: 1 in the MS, 1 in the MSF, and 1 in the MOSF group. No cases of cholestasis were observed in the S and OS groups. CONCLUSIONS: In uncomplicated preterm infants receiving routine PN, we found a correlation between phytosterol intake and plasma phytosterol concentrations; however, cholestasis was rare and no difference in liver function at 6 wk was observed.

Neurologic complications in neonates supported with extracorporeal membrane oxygenation. An analysis of ELSO registry data.

BACKGROUND: Neurologic complications in neonates supported with extracorporeal membrane oxygenation (ECMO) are common and diminish their quality of life and survival. An understanding of factors associated with neurologic complications in neonatal ECMO is lacking. The goals of this study were to describe the epidemiology and factors associated with neurologic complications in neonatal ECMO. PATIENTS AND METHODS: Retrospective cohort study of neonates (age ≤30 days) supported with ECMO using data reported to the Extracorporeal Life Support Organization during 2005-2010. RESULTS: Of 7,190 neonates supported with ECMO, 1,412 (20 %) had neurologic complications. Birth weight <3 kg [odds ratio (OR): 1.3; 95 % confidence intervals (CI): 1.1-1.5], gestational age (<34 weeks; OR 1.5, 95 % CI 1.1-2.0 and 34-36 weeks: OR 1.4, 95 % CI 1.1-1.7), need for cardiopulmonary resuscitation prior to ECMO (OR 1.7, 95 % CI 1.5-2.0), pre-ECMO blood pH ≤ 7.11 (OR 1.7, 95 % CI 1.4-2.1), pre-ECMO bicarbonate use (OR 1.3, 95 % CI 1.2-1.5), prior ECMO exposure (OR 2.4, 95 % CI 1.6-2.6), and use of veno-arterial ECMO (OR 1.7, 95 % CI 1.4-2.0) increased neurologic complications. Mortality was higher in patients with neurologic complications compared to those without (62 % vs. 36 %; p < 0.001). CONCLUSIONS: Neurologic complications are common in neonatal ECMO and are associated with increased mortality. Patient factors, pre-ECMO severity of illness, and use of veno-arterial ECMO are associated with increased neurologic complications. Patient selection, early ECMO deployment, and refining ECMO management strategies for vulnerable populations could be targeted as areas for improvement in neonatal ECMO.