Ruth Shainkin-Kestenbaum

Serum amyloid A: an early and accurate marker of neonatal early-onset sepsis

Objectives:To evaluate the accuracy of serum amyloid A (SAA), an acute phase protein in the detection of neonatal early-onset sepsis, by means of a fast automated SAA kit.Study Design:Full-term infants <72 h of age, who had risk factors and/or were suspected of having sepsis, were eligible for study. The levels of SAA were taken at 0, 24 and 48 h post sepsis evaluation. Thirty matched infants served as a control group for comparing SAA concentrations.Results:Of 104 infants eligible for entry to the study, 23 had sepsis and 81 had not sepsis. The SAA levels of the septic group were significantly higher than those of the nonseptic group at 0, 24 and 48 h (P<0.01 for all time points). In comparison with C-reactive protein (CRP), SAA levels rose earlier and in a sharper manner, had higher levels and returned faster to normal values in infants with early onset sepsis. At 0 h post-sepsis evaluation, serum SAA had an overall better diagnostic accuracy for predicting early onset sepsis than CRP (sensitivity (96 vs 30%), specificity (95 vs 98%), positive predictive value (85 vs 78%), negative predictive value (99 vs 83%), positive likelihood ratio (19 vs 12), and negative likelihood ratio (0.05 vs 0.71).Conclusions:SSA is advocated as an inflammatory marker of neonatal early-onset sepsis.

Bone turnover markers and bone strength during the first weeks of life in very low birth weight premature infants.

Abstract Objective: To determine the association between changes in bone turnover markers and bone strength of very low birth weight infants during the first eight postnatal weeks. Study design: Twelve very low birth weight premature infants [mean gestational age: 28.4+-0.6 weeks, mean birth weight: 1131+-62 grams] participated in the study. Bone strength was evaluated weekly by quantitative ultrasound measurements of tibial bone speed of sound (SOS, Sunlight Omnisense™). Bone specific alkaline phosphatase (BSAP), a marker of bone formation, and carboxy terminal cross-links telopeptide of type-I collagen (ICTP), a marker of bone resorption, were collected at the ages of one, four and eight weeks. Results: BSAP increased significantly (from 119.9+-16.2 U/L to 132.1+-11.9 U/L and 152.1+-15.7 U/L at one, four and eight weeks of life, respectively, p<0.05). ICTP decreased significantly during the study period (from 122.3+-8.7 ng/ml to 96.0+-4.8 ng/ml and 92.3+-5.4 ng/ml at one, four and eight weeks of life, respectively; p<0.05). There was a significant decrease in bone SOS (from 2886+-29 m/sec to 2792+-30 m/sec and 2753+-30 m/sec at birth, four weeks and eight weeks of life, respectively; p<0.02). There was no correlation between the levels of bone markers and bone SOS. Conclusion: In VLBW premature infants, there is a significant decrease in bone strength concomitant with biochemical evidence for new bone formation (increase in BSAP and a decrease in ICTP) during the first eight postnatal weeks. Changes in the biochemical markers could not predict the changes in bone strength.

Serum Amyloid A Protein Is a Useful Inflammatory Marker during Late-Onset Sepsis in Preterm Infants

Background: Few studies demonstrated that serum amyloid A (SAA), a non-specific acute-phase reactant, could be used as a reliable early marker for the diagnosis of late-onset sepsis (LOS). Objectives: To evaluate the diagnostic value and the dynamics of SAA levels during the course of LOS and to compare it to those of other inflammatory markers. Methods: Levels of SAA, C-reactive protein (CRP) and IL-6 together with clinical variables, biochemical parameters and cultures retrieved from all preterm infants suspected of LOS were checked at the first suspicion of sepsis and after 8, 24, 48 and 72 h. Results were compared to healthy, matched infants. Results: One hundred and sixteen infants were included in the study, 38 in the sepsis and 78 in the non-sepsis group. High levels of SAA were observed at sepsis onset, with a gradual decline thereafter, while CRP levels increased only at 24 h after sepsis onset. In the sepsis group, levels of SAA returned faster to baseline than CRP levels. Receiver-operating characteristic analysis values revealed that SAA at 10 µg/ml had the highest sensitivity at 0, 8 and 24 h after sepsis onset (95, 100 and 97%, respectively) and a negative predictive value (97, 100 and 98%, respectively). Conclusions: SAA is an accurate acute-phase protein during LOS in preterm infants. Quick and reliable SAA kits can make this marker a useful tool in LOS in preterm infants.

The prognostic virtue of inflammatory markers during late-onset sepsis in preterm infants.

AIM Late-onset sepsis (occurring after the first three days of life) is a serious complication in preterm infants. In order to assess the possible prognostic virtues of the acute phase inflammatory response in the disease, we compared the inflammatory response of preterm infants who died within 72 hours (h) (fulminant sepsis) to infants who recovered from the disease (non-fulminant sepsis). METHODS Of 42 preterm infants that were evaluated: 10 had fulminant sepsis and 32 non-fulminant sepsis. Acute phase inflammatory response markers-C-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-6 levels and white blood cell (WBC) counts were measured at the first suspicion of LOS and after 8, 24 and 48 h. RESULTS Small for gestational age (SGA) infants who were treated with fewer days of antibiotics characterized the fulminant sepsis group. The initial high levels of inflammatory markers were similar in both groups, but as early as 8 h after onset significantly lower levels of SAA, CRP and WBC counts were documented in the fulminant sepsis group. The inflammatory response remained low at 24 and 48 h in the fulminant sepsis group, while in the survivors, significantly increased inflammatory markers were measured. Decreases in the levels of the inflammatory markers preceded episodes of metabolic acidosis and arterial hypotension that were more common in the fulminant sepsis group. Infant mortality correlated inversely with SAA levels at 8 h and with CRP and WBC counts at 24 h after onset. CONCLUSION SAA, CRP and WBC counts can be used as prognostic markers in LOS in preterm infants, with SAA being the earliest prognostic marker.

Serum amyloid A protein in the early detection of late-onset bacterial sepsis in preterm infants.

Abstract In order to evaluate serum amyloid A as an early diagnostic marker of late-onset sepsis, seventy-nine preterm infants with clinically suspected sepsis and 40 healthy matched controls were assayed for serum amyloid A. In parallel, clinical and biochemical variables that are used to evaluate neonatal sepsis were compared. Forty-two episodes were diagnosed as sepsis. Serum amyloid A levels were elevated in the sepsis group (187.6 ± 78.3 μg/ml), compared with infants who had no sepsis (10.2±8.3 μg/ml) and the control group (6.9 ± 3.3 μg/ml), and were significantly higher in gram-negative compared to gram-positive sepsis (221.8 ± 84.4 μg/ml vs.48.5 ± 22.2 μg/ml). Analysis of the data suggests serum amyloid A has the highest sensitivity (100%), specificity (93%) and positive predictive value (96%) for sepsis among the clinical and biochemical parameters that were tested. In conclusion, serum amyloid A seems to be a reliable early marker for the diagnosis of late-onset sepsis in preterm infants.

The Effects of Exercise on Body Weight and Circulating Leptin in Premature Infants

OBJECTIVE: To assess the effect of daily movements on weight gain, serum leptin, and insulin-like growth factor I (IGF-I) in premature infants.STUDY DESIGN: Twenty very-low-birth-weight premature infants were matched and randomized to a daily movement (n=10) and control groups (n=10). Daily movement consisted of passive range of motion with gentle compression of both the upper and lower extremities 5 days per week for 4 weeks.RESULTS: Daily movements led to a significant increase in weight gain (784±51 vs 608±26 g in movements and controls, respectively, p<0.02), and to a significant increase in leptin (0.60±0.19 vs 0.13±0.06 ng/ml in movements and controls, respectively, p<0.05). Changes in body weight correlated with changes in serum leptin (r=0.48, p<0.03). IGF-I also increased following daily movements (18.8±4.1 vs 9.2±4.1 ng/ml in movements and controls, respectively); however, this increase was not statistically significant.CONCLUSION: A relatively brief range of motion daily movement intervention was associated with greater weight gain and increased leptin levels in very-low-birth-weight premature infants. This may suggest that at least part of the daily movements associated with increase in body weight resulted from an increase in adipose tissue.

Vitamin E levels during early iron supplementation in preterm infants.

On the basis of preliminary data, this larger bi-institutional continuation trial evaluating the efficacy and safety of early iron supplementation in preterm infants calls attention to the levels of vitamin E, a marker of antioxidant activity, during iron treatment. A total of 116 preterm infants were randomly assigned to receive at 2 or 4 weeks of age ( N = 62, N = 54, respectively) 5 mg/kg/d of nonionic iron polymaltose complex concomitantly with a daily dose of 25 IU vitamin E (as dl-alpha-tocopherol acetate) from 2 weeks of age. Vitamin E (alpha-tocopherol) levels, iron, ferritin, hemoglobin concentration, and reticulocyte count were recorded from 2 to 8 weeks of age. The morbidities of prematurity associated with free radicals formation were also documented. A gradual increase of alpha-tocopherol levels within physiological range (0.8 to 3.5 mg/dL) was found in the 2-week and 4-week groups during the study period with no difference among the groups ( P > 0.05 for all comparisons). At 8 weeks of age, iron and ferritin levels, hemoglobin concentration, and reticulocyte count were higher in the 2-week group. No correlation was observed between timing of both iron and vitamin E supplement and hemolysis or morbidities associated with prematurity. Thus, treatment of iron with vitamin E supplement at 2 weeks of age is, in our experience, an efficacious and safe treatment for improving anemia in preterm infants.

Enriched post-discharge formula versus term formula for bone strength in very low birth weight infants: a longitudinal pilot study

Abstract Aim: To initiate a longitudinal pilot study comparing the effect of nutrient-enriched post-discharge formula (PDF) with standard term formula (TF) on bone strength of very low birth weight (VLBW) infants in the first six months post-term. Methods: Two matched groups of VLBW infants were randomly assigned to enriched PDF (n=10) or TF (n=10) at corrected age of 40 weeks. Anthropometric measurements of growth and measurements of bone speed of sound (SOS) indicating bone strength and bone turnover markers (bone-specific alkaline phosphatase and cross-linked carboxy terminal telopeptide of type I collagen) were taken at term and at three and six months corrected age. Results: The anthropometric measurements of infants fed PDF and TF were comparable at three and six months corrected age. Bone SOS of the PDF group increased from 2760±113 m/s at term to 2877±90 m/s and 3032±60 m/s at three and six months corrected age, respectively (P<0.001). Likewise, bone SOS of the TF group increased from 2695±116 m/s at term to 2846±72 and 2978±83 m/s at three and six months, respectively (P<0.001). No statistically significant difference was found between the groups in terms of growth and bone SOS measurements. The levels of both bone turnover markers decreased significantly during the study period (P<0.001 for both groups). Conclusion: Feeding with PDF after term had no short-term beneficial effect on bone strength and bone turn-over of VLBW infants.