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- The C in TORCH: A Cost-Effective Alternative to Screening Small-for-Gestational-Age Infants. [JOURNAL ARTICLE]
- Neonatology 2014 Apr 8; 106(1):24-29.
Background: Infants born with birth weights under the 10th percentile for their gestational age are classified as small for gestational age (SGA). TORCH infections are reported to be associated with SGA infants. With the low incidence of infections, screening is likely to be expensive and of low utility. Objective: The objective of this study was to determine the utility and cost-effectiveness of screening SGA infants with TORCH serology titers, urine cytomegalovirus (CMV) cultures and cranial ultrasounds. Methods: A retrospective review was conducted on all infants admitted to the neonatal intensive care unit (NICU) at Los Angeles County and University of Southern California (LAC+USC) Medical Center from January 2003 to December 2011 with a diagnosis of SGA or intrauterine growth restriction. Birth characteristics such as birth weight, length, head circumference and gestational age were recorded. TORCH titer results, urine CMV results and cranial ultrasound findings were collected. Results: Between 2003 and 2011, 232 SGA infants were admitted to the NICU at LAC+USC Medical Center. Of these, 117 infants (50%) had TORCH titer testing performed; there was only 1 positive CMV IgM and 1 positive HSV IgM result. Repeat urine CMV testing was performed on 109 infants (47%), with a total of 296 urine CMV samples collected from these infants; 6 infants had positive results, of whom 3 had repeat positive urine CMV samples. Overall, 149 of the infants had a cranial ultrasound done, none of which were positive for calcifications. Conclusions: TORCH titer testing, urine CMV screening and cranial ultrasound screening are of low yield in screening clinically asymptomatic SGA infants for TORCH infections. Given the low number of positive results, a cost-effective alternative of selective TORCH testing may be limited to infants with additional clinical findings. This study serves as a reminder to periodically examine testing practices and patient population to maximize cost-effectiveness. © 2014 S. Karger AG, Basel.
- Hypothermia Makes Cerebral Resistance Index a Poor Prognostic Tool in Encephalopathic Newborns. [JOURNAL ARTICLE]
- Neonatology 2014 Mar 25; 106(1):17-23.
Background: Severe neonatal encephalopathy (NE) of hypoxic-ischaemic origin may cause death or life-long disability. Acute encephalopathy may also affect cerebrovascular control. Pourcelot's cerebrovascular resistance index (RI) ≤0.55 was predictive of poor outcome in normothermic NE infants. Recent studies have questioned its predictive power during therapeutic hypothermia (HT). Objective: To assess the predictive power of RI during HT and after rewarming. Methods: 45 infants with NE treated with HT for 72 h had their RI calculated during early (median 11 h) and late (median 62 h) cooling and after rewarming (median 89 h). Poor outcome was defined as death or abnormalities on day 10 magnetic resonance imaging shown to predict severe neuromotor disability. Results: RI ≤0.55 during cooling did not differentiate between good and poor outcome (late cooling, p = 0.08), but was powerful after rewarming (p = 0.004). RI ≤0.55 predicted true poor outcome in 43% (95% confidence interval (CI): 12, 80) during late cooling and in 100% (95% CI: 31, 100) after rewarming. RI >0.55 predicted good outcome in 86% (95% CI: 69, 95) during late cooling and in 89% (95% CI: 74, 96) after rewarming. Conclusions: Low RI is not predictive of poor outcome during HT in NE infants, but regains the predictive power seen in normothermic infants after rewarming. © 2014 S. Karger AG, Basel.
- The Effect of Blood Glucose and pCO2 on Spectral EEG of Premature Infants during the First Three Days of Life. [JOURNAL ARTICLE]
- Neonatology 2014 Mar 7; 105(4):297-305.
Background: Spectral EEG analysis using automated quantification of total absolute band power (tABP) expresses brain function. We hypothesized that pCO2 or blood glucose affects tABP during the critical first days of life in premature infants. Objective: To use automated tABP quantification to determine whether EEG background activity in premature infants during the first 3 days of life is influenced by pCO2 or blood glucose levels. Methods: Preterm infants, group 1 [gestational age (GA) = 24-27 weeks] and group 2 (GA = 28-30 weeks), underwent continuous EEG monitoring for 3 days after birth. Biochemical data were extracted from the observational datasheet used during monitoring. Blood samples were taken at the request of the attending physician. Statistical analyses were performed as repeated measurements using linear mixed models with a random intercept. The effect of time was treated as a fixed covariate and the GA groups as a fixed factor in all models. Continuous data were described using the mean ± SD or median and range, and categorical data were described using the number of patients and percentages unless otherwise indicated. Results: There was an association between increased pCO2 and tABP and between increased blood glucose and tABP. Further, there were no differences in the responses between groups 1 and 2. Conclusion: Both hyperglycemia and hypercapnia showed a negative effect on brain activity decreasing tABP during the first 3 days of life in premature infants. © 2014 S. Karger AG, Basel.
- Early Enteral Fat Supplementation Improves Protein Absorption in Premature Infants with an Enterostomy. [JOURNAL ARTICLE]
- Neonatology 2014 Mar 6; 106(1):10-16.
Background: Early enteral fat supplementation and fish oil (FO) stimulates post-resection intestinal adaptation in rats and increases fat absorption in premature infants with bowel resection and an enterostomy. Objective: To test the hypothesis that early fat supplement and FO increases post-resection protein absorption, intestinal RNA, protein without decreasing intestinal arachidonic acid (AA) in premature infants with an enterostomy. Methods: 36 premature infants (<2 months old) with an enterostomy after surgical treatment for necrotizing enterocolitis or spontaneous intestinal perforation who tolerated enteral feeding at 20 ml/kg/day were randomized to usual care (control, n = 18) or early supplementing enteral Microlipid (ML) and FO (treatment, n = 18). Intralipid was decreased as the dose of enteral fat was increased. Daily weight, ostomy output and nutritional intake were recorded. Weekly 24-hour ostomy effluent was collected to measure fecal protein. Protein absorption was calculated by subtracting fecal protein from dietary protein. Tissue samples from the functional stoma and the nonfunctional distal diverted end were collected during bowel reanastomosis to measure RNA, protein, and fatty acid (FA) profile. Results: Compared to controls, the treatment group had higher protein absorption (g/kg/day) and intestinal RNA and protein (μg/mg tissue) proximal to the ostomy. The two groups had similar FA profiles except that the treatment group had higher n-3 eicosapentaenoic acid (EPA, μg/mg tissue) proximal to the ostomy. Conclusion: Early supplementation of enteral ML and FO to premature infants with an enterostomy increased dietary protein absorption, intestinal RNA, protein and n-3 EPA content without altering other FA content. © 2014 S. Karger AG, Basel.
- Hierarchical Maturation of Innate Immune Defences in Very Preterm Neonates. [JOURNAL ARTICLE]
- Neonatology 2014 Mar 6; 106(1):1-9.
Background: Preterm neonates are highly vulnerable to infection. Objectives: To investigate the developmental contribution of prematurity, chorioamnionitis and antenatal corticosteroids (ANS) on the maturation of neonatal microbial pathogen recognition responses. Methods: Using standardized protocols, we assayed multiple inflammatory cytokine responses (IL-1β, IL-6, TNF-α and IL-12/23p40) to three prototypic Toll-like receptor (TLR) agonists, i.e. TLR4 (lipopolysaccharide), TLR5 (flagellin) and TLR7/8 (R848), and to the non-TLR retinoic acid-inducible gene I (RIG-I)-like receptor agonist, in cord blood mononuclear cells from neonates born before 33 weeks of gestation and at term. Results: TLR responses develop asynchronously in preterm neonates, whereby responses to TLR7/8 were more mature and were followed by the development of TLR4 responses, which were also heterogeneous. Responses to TLR5 were weakest and most immature. Maturity in TLR responses was not influenced by sex. Overall, we detected no significant contribution of ANS and chorioamnionitis to the developmental attenuation of either TLR or RIG-I responses. Conclusions: The maturation of anti-microbial responses in neonates born early in gestation follows an asynchronous developmental hierarchy independently of an exposure to chorioamnionitis and ANS. Our data provide an immunological basis for the predominance of specific microbial infections in this age group. © 2014 S. Karger AG, Basel.
- Relationship of Salivary and Plasma Cortisol Levels in Preterm Infants: Results of a Prospective Observational Study and Systematic Review of the Literature. [JOURNAL ARTICLE]
- Neonatology 2014 Mar 5; 105(4):312-318.
Background and Objectives: (1) To investigate the relationship of salivary and plasma cortisol levels in preterm infants with a focus on the usability of salivary cortisol in diagnostic work-up of infants at risk of adrenal insufficiency. (2) To perform a systematic review addressing this question. Methods: Clinical study: We conducted a prospective observational single-center study in preterm infants. We analyzed plasma and saliva cortisol concentrations by enzyme immunoassay. Correlation analysis was used to determine the relation between salivary and plasma cortisol levels and the agreement of the measurement methods was analyzed according to Bland-Altman. Systematic review: A systematic literature search (PubMed and Embase) on the relationship of salivary and plasma cortisol levels in neonates was performed in November 2012. Results: Clinical study: We enrolled 58 preterm infants (median (interquartile range) gestational age at birth was 31.4 (28.1-32.7) weeks, birth weight 1,340 (974-1,745) g, respectively). Correlation analyses revealed a relationship of plasma cortisol and salivary cortisol levels. Rank correlation coefficient was 0.6. Estimating plasma cortisol levels based on measured salivary cortisol levels showed poor agreement of the two methods for determining plasma cortisol levels (direct and via salivary cortisol). Sensitivity and specificity of salivary cortisol for the detection of adrenal insufficiency were 0.66 and 0.62, respectively. Systematic review: Six studies in preterm infants and term neonates depicting the correlation of salivary and plasma cortisol were identified with a range of saliva-plasma correlation coefficients from 0.44 to 0.83. Conclusions: Substitution of plasma cortisol by salivary cortisol determination cannot be recommended in preterm infants because of unsatisfactory agreement between methods. © 2014 S. Karger AG, Basel.
- Plotting Transcutaneous Bilirubin Measurements on Specific Transcutaneous Nomogram Results in Better Prediction of Significant Hyperbilirubinemia in Healthy Term and Near-Term Newborns: A Pilot Study. [JOURNAL ARTICLE]
- Neonatology 2014 Mar 1; 105(4):306-311.
Background: The American Academy of Pediatrics has recommended a systematic assessment before discharge for the risk of severe hyperbilirubinemia. Plotting total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) on a TSB hour-specific nomogram is proposed as a tool for laboratory evaluation. Objectives: The aim of this study was to compare the predictive characteristics, particularly the incidence of false negative rate (FNR), of the practice of plotting TcB values on the TSB hour-specific risk nomogram versus on transcutaneous nomogram. Methods: Paired TSB and TcB measurements were conducted on 141 newborns. Risk of developing significant hyperbilirubinemia was defined as infants with bilirubin level ≥75% on TSB or ≥95% on TcB nomogram. TSB values, plotted on the TSB nomogram of Bhutani et al. [Pediatrics 1999;103:6-14], were used as reference. TcB values were plotted on the TSB nomogram and on the transcutaneous nomograms of Maisels and Kring [Pediatrics 2006;117:1169-1173] and Fouzas et al. [Pediatrics 2010;125:e52-e57]. Results: Plotting TcB measurements on a TSB nomogram resulted in a trend towards a higher FNR when compared to Maisels' and Fouzas' nomograms (18.0/1,000 compared to 10.2/1,000 and 8.6/1,000 respectively). Although not statistically significant, plotting TcB on transcutaneous nomogram resulted in better predictive values with the Fouzas' nomogram, having the best sensitivity (90.0%) and specificity (87.79%) as well as the highest positive (35.97%) and negative (99.14%) predictive value. Conclusion: Plotting TcB on a TSB nomogram may result in increased rate of FNR and decreased predictive characteristics. The practice of plotting TcB on a TSB nomogram needs further evaluation. © 2014 S. Karger AG, Basel.
- Pap, Gruel, and Panada: Early Approaches to Artificial Infant Feeding. [JOURNAL ARTICLE]
- Neonatology 2014 Feb 26; 105(4):267-274.
This paper collects information on artificial infant feeding published before 1860, the year when commercial formula became available. We have extensive artifactual evidence of thousands of feeding vessels since the Bronze Age. Special museum collections can be found in London, Paris, Cologne, Fécamp, Toronto, New Mexico, and elsewhere. The literature on the use of animal milk for infant feeding begins with Soranus in the 2nd century CE. Literature evidence from the very first printed books in the 15th century proves that physicians, surgeons, midwives, and the laity were aware of the opportunities and risks of artificial infant feeding. Most 17th to 19th century books on infant care contained detailed recipes for one or several of the following infant foods: pap, a semisolid food made of flour or bread crumbs cooked in water with or without milk; gruel, a thin porridge resulting from boiling cereal in water or milk, and panada, a preparation of various cereals or bread cooked in broth. During the 18th century, the published opinion on artificial feeding evolved from health concerns to a moral ideology. This view ignored the social and economic pressures which forced many mothers to forego or shorten breast-feeding. Bottle-feeding has been common practice throughout history. © 2014 S. Karger AG, Basel.
- A Double-Blind Randomised Controlled Trial of Fish Oil-Based versus Soy-Based Lipid Preparations in the Treatment of Infants with Parenteral Nutrition-Associated Cholestasis. [JOURNAL ARTICLE]
- Neonatology 2014 Feb 26; 105(4):290-296.
Background: Infants receiving prolonged parenteral nutrition (PN) are at risk of PN-associated cholestasis (PNAC). This can progress to hepatic failure and death if PN cannot be discontinued. Fish oil-based parenteral lipid preparation (FOLP) has been shown to be beneficial in case studies. Objectives: (1) To evaluate whether FOLP could halt or reverse the progression of PNAC compared with soy-based parenteral lipid preparation (SLP) and (2) to assess the effects of FOLP on liver function and physical growth. Methods: Design: double-blind randomised controlled trial. Setting: level III neonatal intensive care unit. Participants: infants with PNAC (plasma-conjugated bilirubin concentration ≥34 µmol/l or 2 mg/dl) expected to be PN-dependent for >2 weeks. Intervention: to receive either FOLP or SLP at 1.5 g/kg/day. Primary outcome measure: reversal of PNAC within 4 months after commencement of lipid treatment; secondary outcomes: rate of change of weekly liver function tests, infant growth parameters, blood lipid profile and episodes of late-onset sepsis. Results: A total of 9 infants were randomised to the FOLP group and 7 to the SLP group. There was no significant difference in reversal of PNAC at 4 months between groups. Rates of increase of plasma-conjugated bilirubin and alanine aminotransferase in the SLP group were significantly greater than the FOLP group (13.5 vs. 0.6 µmol/l per week and 9.1 vs. 1.1 IU/l per week, respectively, p = 0.03). Increased enteral nutrition was associated with significant improvement of PNAC in infants receiving FOLP compared with SLP (-8.5 vs. -1.6 µmol/l per 10% increase in enteral nutrition, respectively). The study was terminated prematurely. Conclusions: progression of PNAC in PN-dependent infants can be halted by replacing SLP with FOLP and reversed by increasing the proportion of enteral nutrition in infants receiving FOLP. Replacement of SLP with FOLP in PN-dependent infants who develop PNAC may be considered. © 2014 S. Karger AG, Basel.
- A Summary of the Iodine Supplementation Study Protocol (I2S2): A UK Multicentre Randomised Controlled Trial in Preterm Infants. [JOURNAL ARTICLE]
- Neonatology 2014 Feb 27; 105(4):282-289.
This paper summarises the study protocol for the randomised controlled trial of iodine supplementation in preterm infants. Iodine is essential for the synthesis of thyroxine, and thyroxine is essential for normal brain development in utero and for the first 2-3 years of life. The recommended iodine intake in parenteral nutrition regimens is 1 μg/kg/day and commercially available parenteral solutions for infants reflect these recommendations. In the absence of other iodine sources, infants are vulnerable to negative iodine balance and insufficiency. As many preterm infants are fed parenterally for prolonged periods with solutions which have been shown to be iodine-deficient, the I2S2 Trial was designed to establish whether iodine supplementation of preterm infants benefits neurodevelopment. © 2014 S. Karger AG, Basel.