Is low cerebral near infrared spectroscopy oximetry associated with neurodevelopment of preterm infants without brain injury?

OBJECTIVES: To evaluate the association between low regional cerebral oxygen saturation (rScO2) and neurodevelopment in preterm infants classified as no brain injury (NBI). METHODS: We retrospectively reviewed data of rScO2 monitoring during the first 3 days of life of infants with a gestational age (GA)<28 weeks or birth weight (BW)<1,000 g, with and without brain injury (BI). BI was defined as intraventricular haemorrhage, cystic periventricular leukomalacia or cerebellar haemorrhage. Univariate and multivariate analyses were used to study the association of rScO2<55% for more than 10 h in the first 3 days of life (NIRS<55%>10H) and the 24 months neurodevelopment. RESULTS: Of the 185 patients who met the inclusion criteria, 31% were classified as BI infants and 69% NBI. BI compared to NBI infants had a significantly lower GA and a higher incidence of complications of prematurity. Mean rScO2 in the first 72 h of life was significantly lower in BI than NBI. NIRS<55%>10H in NBI patients was negatively associated with neurodevelopmental scores both at the univariate and multivariate analysis (p<0.05). NBI infants with NIRS<55%>10H were found to have lower systemic oxygenation than their counterparts with rScO2<55% for less than 10 h. CONCLUSIONS: NIRS<55%>10H in NBI small preterm infants was found to be an independent predictor of neurodevelopment at 24 months and it was associated with low systemic saturation values.

Esophageal impedance baseline in infants with bronchopulmonary dysplasia: A pilot study.

BACKGROUND: Bronchopulmonary dysplasia (BPD) may induce gastroesophageal reflux (GER). Esophageal impedance baseline values (BI) reflect mucosal inflammation. Our aim was to evaluate BI levels in preterm infants with BPD compared with those without BPD and to identify BI predictors. METHODS: This is a retrospective pilot study including infants born <32 weeks' gestational age (GA) who underwent esophageal multichannel intraluminal impedance (MII)-pH. Univariate/multivariate analysis were performed to compare data between BPD and non-BPD infants and to identify BI predictors. A subgroup analysis was performed in infants born <29 weeks' GA, at highest risk for BPD. RESULTS: Ninety-seven patients (median GA 285/7 weeks, mean postnatal age 49 days, 29 with BPD), were studied. BPD infants had significantly lower birth weight compared with non-BPD infants (750 vs. 1275 g), were more immature (274/7 vs. 290/7 weeks GA), were older at MII-pH (79 vs. 38 days) and received less fluids during MII-pH (147 vs. 161 ml/kg/day). The same findings were found in the group of 53 infants born <29 weeks. BPD versus non-BPD infants had significantly lower BI (2050 vs. 2574 ohm, p = 0.007) (<1000 ohm in five BPD infants vs. one non-BPD) whereas the other MII-pH parameters were not significantly different. Multiple regression analysis found that increasing chronological age was positively associated with BI (B = 9.3, p = 0.013) whereas BPD was associated with lower BI (B = -793.4, p < 0.001). CONCLUSIONS: BPD versus non-BPD infants had significantly lower BI despite similar MII-pH data. BPD and chronological age predicted BI, whereas only BPD predicted BI in the most immature infants.

Early nasal continuous positive airway pressure failure prediction in preterm infants less than 32 weeks gestational age suffering from respiratory distress syndrome.

BACKGROUND: Early continuous positive airway pressure (CPAP) and surfactant replacement are effective treatments for neonatal respiratory distress syndrome (RDS). CPAP is the first line in preterm infants needing respiratory support, with surfactant replacement in case of CPAP failure (CPAP-F). OBJECTIVES: To analyze incidence and factors associated with CPAP-F in preterm infants with RDS. DESIGN, SETTING AND PATIENTS: Single-center retrospective database analysis (2004-2017) of inborn infants, gestational age (GA) 24 + 0/7-31 + 6/7 weeks, not intubated on admission to the neonatal intensive care unit, managed with CPAP. CPAP-F was defined as intubation and surfactant administration in the first 72 h of life; CPAP success (CPAP-S) was CPAP alone without need for additional RDS treatments. Demographic, respiratory, and clinical data associated with CPAP-F were studied using logistic regression analysis. RESULTS: A total of 562 infants met the inclusion criteria: 252 (44.8%) were CPAP-F and 310 (55.2%) were CPAP-S. The CPAP-F, compared to CPAP-S group, had lower GA and birth weight, and were less likely to receive antenatal steroids or to be vaginal births. Logistic regression showed that the fraction of inspired oxygen (FiO2 ) ≥ 0.23 between 180 and 240 min of life (FiO2 180-240 min) was the strongest factor associated with CPAP-F (odds ratio: 16.01 [95% confidence interval: 10.34-24.81]). CONCLUSION: FiO2 180-240 min was highly predictive of CPAP-F in preterm infants. With this model for surfactant administration/CPAP-F, 11.2% of infants would have unnecessarily received treatment, but importantly, 27.7% would have been treated much earlier, with a potential reduction in air leaks and duration of mechanical ventilation.

Blood urea in preterm infants on routine parenteral nutrition: A multiple linear regression analysis.

BACKGROUND: Blood urea is considered a marker of amino acid utilization in preterm infants on routine parenteral nutrition. However, the association between blood urea and intravenous amino acid intake remains debated. AIMS: To evaluate the association between blood urea and both nutrition and clinical data, in a large cohort of preterm infants. METHODS: Consecutively admitted preterm infants with a gestational age of less than 32 weeks and a birth weight lower than 1250 g on routine parenteral nutrition from the first hour of life were studied. Clinical and nutrition data collected hourly during the hospitalization were used in multiple linear regression analysis. RESULTS: We studied 674 patients and 1863 blood urea determinations. Blood urea concentration was positively associated with blood creatinine concentration, intravenous amino acid intake, patent ductus arteriosus and respiratory distress syndrome, and negatively associated with intravenous non-protein energy intakes, daily weight change, gestational age, being small for gestational age, antenatal steroids therapy and reverse flow in the umbilical artery (p < 0.001; R = 0.7). CONCLUSIONS: From a nutrition perspective, in our large cohort of small preterm infants blood urea was positively correlated with intravenous amino acid intake and negatively correlated with intravenous non-protein energy intake. This is in line with current knowledge in human physiology and suggest that a reduction of intravenous amino acid intake based on blood urea concentrations was justified.

Response to therapy among neonates with gastro-esophageal reflux is associated with esophageal clearance.

BACKGROUND: Few studies evaluated the efficacy of pharmacological therapy for gastro-esophageal reflux disease (GERD) in newborns, whose safety has been questioned. Esophageal basal impedance (BI) is a marker of mucosal integrity, and treatment with proton pump inhibitors significantly increases BI in infants; however, no correlation with clinical improvement was reported. AIMS: To evaluate the relationship between BI and other esophageal pH-impedance parameters and clinical response to therapy in newborns with GERD. STUDY DESIGN: Multicenter retrospective study. SUBJECTS: Infants who received omeprazole or ranitidine for GERD. OUTCOME MEASURES: Complete response to therapy was defined as symptom decrease by ≥50% compared to baseline, partial response as symptom decrease <50%, no response as no symptom decrease based on chart analysis. Response to therapy was assessed 2 and 4 weeks after the onset of therapy. Univariate and multivariate statistics were performed to assess associations between response to therapy and clinical/pH-impedance parameters. RESULTS: We studied 60 infants (51 born preterm): 47 received omeprazole, 13 ranitidine. Response to therapy was associated with decreasing esophageal clearance time: odds ratio 0.308, 95%CI 0.126-0.753, p = 0.010 at 2 weeks, odds ratio 0.461, 95%CI 0.223-0.955, p = 0.037 at 4 weeks. CONCLUSIONS: Clinical response to therapy among infants with GERD was associated with esophageal clearance but not with esophageal BI level.

Oxygen saturation to fraction of inspired oxygen ratio in preterm infants on routine parenteral nutrition with conventional or fish oil containing lipid emulsions.

INTRODUCTION: The benefits of intravenous (IV) fish oil (FO), as a source of n-3 long-chain polyunsaturated fatty acids, on lung growth in preterm infants, remain controversial. AIM: To evaluate if IV FO improves lung growth in small preterm infants on routine parenteral nutrition (PN). MATERIALS AND METHODS: We retrospectively reviewed prospectively collected data of preterm infants with a birth weight <1250 g who received routine PN from birth. We compared patients who received FO containing IV lipid emulsions with infants who received conventional emulsions (CNTR). The oxygen saturation (SpO2 ) to a fraction of inspired oxygen (FiO2 ) ratio (SFR) at 36 weeks (W) of gestation was chosen as the primary outcome variable to assess lung growth. RESULTS: Four hundred and seventy-seven infants were studied: 240 received IV FO and 237 CNTR. While exposure to antenatal glucocorticoids was higher in IV FO group than in CNTR (95 vs 90%, P = .04), there were no differences in birth data, enteral and parenteral nutrition intakes, ventilator supports and drug therapies. The incidence of the most common complications of prematurity at 36 W was not different (bronchopulmonary dysplasia was 27 vs 21% in IV FO vs CNTR infants, P = .1). Weight gain from birth to 36 W was marginally, but significantly, higher (+0.5 g/kg/d, P = .03) in IV FO group vs CNTR. SFR increased from 32 W to 36 W in all study patients (P < .001). IV FO infants had significantly lower SpO2 from 33 W to 35 W (P < .001) and lower (worse) SFR at 36 W (432 ± 57 vs 444 ± 51, P = .026) compared to CNTR. CONCLUSION: Contrary to our hypothesis, the use of FO containing IV lipid emulsions for the routine PN of the preterm infant did not improve lung growth compared to the infants who received conventional IV lipid emulsions.

Oxygen saturation/FIO2 ratio at 36 weeks' PMA in 1005 preterm infants: Effect of gestational age and early respiratory disease patterns.

OBJECTIVE: To assess oxygen diffusion at 36 weeks' post-menstrual age in preterm infants by means of the non-invasive oxygen saturation/fraction of inspired oxygen ratio (36w-SFR) and to identify factors associated with 36w-SFR - ie, gestational age (GA) and early respiratory disease patterns (ERP). METHODS: Retrospective analysis of prospectively collected data. SETTING: Neonatal Intensive Care Unit. PATIENTS: 1005 preterm infants born below 32 weeks' GA. INTERVENTIONS: 36w-SFR was the mean of SFR values over 24 h on the day infants reached 36 weeks' PMA. MAIN OUTCOME MEASURES: 36w-SFR. STATISTICS: descriptive statistics, univariate, and multivariate analysis to study associations of 36w-SFR, including GA and ERP. RESULTS: 36w-SFR was significantly different between infants with and without bronchopulmonary dysplasia (BPD) (371 vs 467, P < 0.001), and according to ERP (LowFIO2 466, pulmonary improvement-PI 460, pulmonary deterioration-PD 405, early persistent pulmonary deterioration-EPPD 344, P < 0.001). Significant differences were found either in BPD and in non-BPD patients according to ERP (P < 0.001). Patients without BPD had significant differences in 36w-SFR according to GA (P < 0.001), while infants with BPD and increasing GA at birth had a non-significant trend for increased 36w-SFR (P = 0.621). Factors associated with 36w-SFR were GA, being small for GA, sepsis, human milk feeding, and ERP. CONCLUSIONS: Preterm infants without BPD had a spectrum of oxygen diffusion impairment that was inversely associated with GA at birth. Infants with different patterns of ERP had significant differences in 36w-SFR.

Does intravenous fish oil affect the growth of extremely low birth weight preterm infants on parenteral nutrition?

BACKGROUND & AIMS: Long chain n-3 fatty acids (n-3 LCPUFA) play a pivotal role during central nervous system development and the provision of docosahexaenoic acid (DHA) is recommended for the preterm infant. However, there are concerns that oral fish oil, which is a good source of DHA, may adversely affect growth of preterm infants, as it decreases arachidonic acid (ARA). It has been about ten years since fish oil was added to the fat blend of intravenous (IV) lipid emulsions (LE) but information on growth and other clinical outcomes of preterm infants is still scarce. We studied the effect of fish oil containing IV LE vs standard IV LE on growth in a large cohort of preterm infants who received routine parenteral nutrition (PN). METHODS: We retrospectively reviewed growth data of 546 preterm infants with a birth weight (BW) < 1250 g consecutively admitted to our NICU between Oct-2008 and Jun-2017 who received PN starting from the first day of life. Individual patients received only one of 5 commercially available IV LE. For the purpose of this study we grouped the patients who received the fish oil containing LE (IV-FO) and those who received conventional LE (CNTR). We compared PN and enteral nutrition (EN) intakes, and growth from birth to 36+0 weeks post-menstrual age (W PMA). RESULTS: Demographics, birth data and the incidence of the main complications of prematurity were similar between the two groups (IV-FO: n = 240, Gestational age (GA) 197 ± 16 d, BW 942 ± 181 g; CNTR: n = 237, GA 199 ± 17 d, BW 960 ± 197 g). No difference was found in PN and EN energy and macronutrient intakes from birth to 36+0W PMA, as well as in the proportion of human milk to infant milk formula. Weight gain from the regained BW to 36+0W PMA was slightly but significantly higher in IV-FO group: 17.3 ± 2.8 and 16.8 ± 2.7 g∙kg-1∙d-1, IV-FO and CNTR respectively (p = 0.03). There was no difference in length gain and head growth nor in body size at 36+0W PMA between the two groups. CONCLUSIONS: The use of IV fish oil did not negatively affect weight gain in a cohort of preterm infants. Large randomized controlled trials are needed to assess the effect of IV fish oil on the complication of prematurity and on selected domains of infant development.

Neonatal outcome of small for gestational age preterm infants.

Small for gestational age (SGA) preterm neonates (birth weight < -2 SDS) are considered to have increased risk of bronchopulmonary dysplasia (BPD) compared to appropriate for GA (AGA) neonates. It is unclear if SGA infants have increased risk for respiratory distress syndrome (RDS) and mortality. We analyzed data from 515 neonates born <30 weeks GA, 98(19%) were SGA. SGA were compared to AGA by univariate analysis and logistic regression analysis (LRA). Significant variables at univariate analysis were IUGR (67 vs 7%, p = 0.000), chorioamnionitis (1 vs 13%, p = 0.017), pre-eclampsia (62 vs 18%, p = 0.000), surfactant retreatment (47 vs 25%, p = 0.000), BPD (32 vs 20%, p = 0.015), death (30 vs 12%, p = 0.000), SatO2/FiO2 on day 3 (376 vs 433, p = 0.013), and SatO2/FiO2 ratio on day 28 (400 vs 448, p = 0.000). LRA found the following associations: regarding mortality, a decreased Sat/FiO2 ratio on day 3 (OR 1.99, 95% CI 1.26-3.16, p = 0.003); regarding BPD, surfactant retreatment (3.70, 2.11-6.49, p = 0.000), being SGA (2.69, 1.36-5.36, p = 0.005), decreasing GA (1.05, 1.03-1.08, p = 0.000), decreasing SatO2/FiO2 ratio on day 3 (1.25, 1.11-1.40, p = 0.000); and regarding severe RDS, pre-eclampsia (2.68, 1.58-4.55, p = 0.000) and decreasing GA (1.06, 1.04-1.08, p = 0.000). CONCLUSIONS: In our cohort of preterm infants, being SGA was significantly associated with BPD, but not with increased risk of mortality or RDS due to multiple pathophysiologic mechanisms. What is Known: • Small for gestational age preterm neonates are considered to have increased risk of bronchopulmonary dysplasia (BPD) compared to appropriate for GA neonates. • It is still unclear if SGA infants have increased risk for respiratory distress syndrome (RDS) and mortality. What is New: • In our cohort of 515 preterm infants (19% SGA), being SGA was significantly associated with BPD, but not with increased risk of mortality or RDS. • These results may be explained by the heterogeneity of mechanisms leading to SGA condition and by multiple mechanisms involving lung growth impairment and other factors.

New Insights on Early Patterns of Respiratory Disease among Extremely Low Gestational Age Newborns.

BACKGROUND: The analysis of early patterns of lung disease among preterm infants may help to identify predictors of pulmonary deterioration. OBJECTIVES: To analyze FIO2 requirement in the first 14 days of life among preterm infants and to find predictors of bronchopulmonary dysplasia (BPD). METHODS: Retrospective cohort study. SETTING: 3 Italian level III NICUs. POPULATION: infants born between 240/7 and 276/7 weeks' gestational age (GA) who survived to 14 days. A consecutive sample of 588 infants was analyzed. Daily mode FIO2 in the first 2 weeks of life were analyzed according to the criteria defined by Laughon et al. [Pediatrics 2009;123:1124-1131], who found 3 early respiratory patterns: consistently low FIO2 (LowFIO2), pulmonary deterioration (PD), and early persistent pulmonary deterioration (EPPD). Factors associated with pulmonary deterioration were studied by univariate and multivariate analysis. RESULTS: Forty percent of infants had low FIO2, 18% had pulmonary deterioation, 21% had early persistent pulmonary deterioration, and 21% had a previously unreported pattern (pulmonary improvement, PI). The prevalence of BPD was 7% in the LowFIO2 group, 28% in the PI group, 44% in the PD group, and 62% in the EPPD group (p = 0.000). Infants with lung deterioration were more frequently males (OR = 2.019, CI: 1.319-3.090, p = 0.001), had lower GA (OR = 0.945, CI: 0.915-0.975, p = 0.000), higher incidence of severe respiratory distress syndrome (OR = 2.956, CI: 1.430-6.112, p = 0.003), and lack of postnatal caffeine (OR = 0.167, CI: 0.052-0.541, p = 0.003). CONCLUSIONS: We report 4 distinct patterns of early respiratory disease associated with significantly different prevalence of BPD and discuss risk factors for lung deterioration.

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.