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New noninvasive methods for monitoring cerebrovascular pressure reactivity coupled with a blood-based assay for brain-specific injury in preterm infants could allow early diagnosis of brain injury and set the stage for improved timing and effectiveness of interventions. Using an adaptation of near-infrared spectroscopy, we report a case of a very low birth weight infant undergoing hemoglobin volume index monitoring as a measure of cerebrovascular pressure reactivity. During the monitoring period, this infant demonstrated significant disturbances in cerebrovascular pressure reactivity that coincided with elevation of serum glial fibrillary acidic protein and new findings of brain injury on head ultrasound. This case report demonstrates the potential of emerging noninvasive monitoring methods to assist in both detection and therapeutic management to improve neurologic outcomes of the very low birth weight neonate.

Background: Pagibaximab, a human chimeric monoclonal antibody developed against lipoteichoic acid, was effective against staphylococci preclinically and seemed safe and well tolerated in phase 1 studies., Objective: To evaluate the clinical activity, pharmacokinetics, safety, and tolerability of weekly pagibaximab versus placebo infusions in very low birth weight neonates., Patients and Methods: A phase 2, randomized, double-blind, placebo-controlled study was conducted at 10 NICUs. Patients with a birth weight of 700 to 1300 g and 2 to 5 days old were randomly assigned to receive 3 once-a-week pagibaximab (90 or 60 mg/kg) or placebo infusions. Blood was collected for pharmacokinetics, bacterial killing, and safety analyses. Adverse event and clinical outcome data were collected., Results: Eighty-eight patients received pagibaximab at 90 (n = 22) or 60 (n = 20) mg/kg or placebo (n = 46). Groups were not different in demography, mortality, or morbidity. Pagibaximab demonstrated linear pharmacokinetics, a 14.5-day half-life, and nonimmunogenicity. Definite staphylococcal sepsis occurred in 0%, 20%, and 13% (P < .11) and nonstaphylococcal sepsis occurred in 0%, 10%, and 15% (P < .15) of patients in the 90 mg/kg, 60 mg/kg, and placebo groups, respectively. In all patients with staphylococcal sepsis, estimated or observed pagibaximab levels were <500 μg/mL (target level) at infection., Conclusions: Three once-a-week 90 or 60 mg/kg pagibaximab infusions, in high-risk neonates, seemed safe and well tolerated. No staphylococcal sepsis occurred in infants who received 90 mg/kg. Target levels were only consistently achieved after 2 to 3 doses. Dose optimization should enhance protection.

Objective: Newborn-screening false-positive rates (FPRs) are disproportionately increased in preterm infants. The objective of this study was to determine variation in newborn screening FPRs according to birth weight and gestational age. Our secondary objective was to examine the effect of postnatal age on FPRs in preterm infants., Methods: The Ohio State Newborn Screening Program Database was analyzed to determine the overall and birth weight-specific FPRs for 18 analytes. Data were stratified into birth weight categories (<1000 g, 1000-1499 g, 1500-2499 g, 2500-3999 g, and >4000 g). In addition, to examine the effect of postnatal age on FPRs, we examined the 2 analytes with the highest FPRs, thyrotropin with back-up thyroxine and 17-hydroxyprogesterone, in infants whose gestational age was <32 weeks, determined on the basis of postnatal age at screening., Results: Data from 448 766 neonates were reviewed. Infants with very low birth weight (VLBW) comprised 1.9% of the study cohort, but accounted for 18% of false-positive results. For 14 of 18 analytes studied, FPRs increased with decreasing birth weight/gestational age and were significantly increased in infants with VLBW compared with infants who weighed 2500 to 3999 g (P < .001). Thyrotropin/back-up thyroxine and 17-hydroxyprogesterone accounted for 62% of total false-positive results in VLBW infants. When blood specimens were collected at a postnatal age of ≥ 48 hours in infants born at <32 weeks, a 44% relative reduction in 17-hydroxyprogesterone false-positive results was detected., Conclusions: False-positive newborn-screening rates are disproportionately increased in VLBW infants. FPRs may be reduced by delaying screening of <32 weeks' gestation, preterm infants until 24 to 48 hours' postnatal age.

Objective: The goal was to analyze the relationship between changes in serum sodium levels during the first month of life and impaired functional outcomes at 2 years of age for very preterm infants., Methods: All very preterm infants who were born at <33 weeks of gestation between January 1, 2003, and July 31, 2004, were hospitalized in the NICU, and survived to discharge were included in this study. Changes in serum sodium levels were measured, and infants were evaluated at corrected age of 2 years., Results: The analysis involved 237 patients, for whom 3927 serum sodium determinations were performed during the first month of life. We defined 3 tertiles of changes in serum sodium levels. A total of 84 infants demonstrated small changes in serum sodium levels (<8 mEq/ L), 86 demonstrated large changes (8 -13 mEq/L), and 67 demonstrated very large changes (13 mEq/L). The reference group was represented by the first tertile. At 2 years of age, large and very large changes in serum sodium levels were significantly associated with risk of impaired functional outcomes, after adjustment for gestational age and perinatal and neonatal hospitalization characteristics (large changes: odds ratio: 3.5 [95% confidence interval: 1.1-11.8]; P = .04; very large changes: odds ratio: 5.1 [95% confidence interval: 1.3-13.6]; P = .02)., Conclusions: Although large and very large changes in serum sodium levels may simply reflect the severity of illness and/or the quality of care, a causal relationship with outcomes cannot be excluded. Cautious fluid and electrolyte management is recommended for very premature infants.

Background: Bilirubin is toxic to the brain and enters the brain in unbound form. Serum unconjugated, unbound bilirubin may be a good predictor of bilirubin encephalopathy. Unbound bilirubin levels may depend on the bilirubin-binding capacity of albumin, which has not been described for neonates of <28 weeks' gestation., Objective: The purpose of this work was to determine the ontogeny of bilirubin-binding capacity and the effect of clinical status in very preterm neonates., Methods: A total of 152 neonates (23-31 weeks' gestational age; 440-1300 g) were enrolled prospectively. At 5 days of age, total serum bilirubin and unbound bilirubin were measured with the unbound bilirubin-A1 analyzer (Arrows Co, Osaka, Japan) and albumin with the Bromocresol-purple method. Scatchard plots were used to estimate bilirubin-binding affinity and capacity. Clinical status for each infant was rated as high, moderate, or low risk by using a modified Score for Neonatal Acute Physiology model. Low risk was considered clinically stable., Results: Unbound bilirubin has a significant, direct correlation to total bilirubin and is greater in unstable than in stable neonates. For the entire cohort, bilirubin-binding capacity had a direct relationship to gestational age. The bilirubin-binding capacities of infants in the low- and high-risk groups also had a direct relationship to gestational age. Bilirubin-binding capacity was greater in the low-risk group (20.8 +/- 4.6 mg/dL; 356 +/- 79 micromol/L) than in the moderate- (17.8 +/- 3.5 mg/dL; 304 +/- 60 micromol/L) or high- (17.3 +/- 3.4 mg/dL; 296 +/- 58 micromol/L) risk groups. Bilirubin-binding affinity did not differ by clinical risk status or gestational age., Conclusions: In very preterm, very low birth weight infants, bilirubin-binding capacity is directly proportional to gestational age. Bilirubin-binding capacity is lower and unbound bilirubin higher in unstable than in stable neonates. These data may be useful in guiding the management of hyperbilirubinemia in very low birth weight infants.

Background: Iron deficiency in early childhood may impair neurodevelopment. In a masked, randomized, controlled trial of early versus late enteral iron supplementation in preterm infants with birth weights of <1301 g, early iron supplementation reduced the incidence of iron deficiency and the number of blood transfusions., Objective: We sought to examine whether early enteral iron supplementation improves neurocognitive and motor development in these infants., Methods: Children who participated in the above mentioned trial were evaluated by applying the Kaufmann Assessment Battery for Children and the Gross Motor Function Classification Scale at the age of school entry., Results: Of the 204 infants initially randomized, 10 died and 30 were lost to follow-up. A total of 164 (85% of the survivors) were evaluated at a median corrected age of 5.3 years. In this population (n = 164), the mean (+/-SD) mental processing composite in the early iron group was 92 (+/-17) versus 89 (+/-16) in the late iron group. An abnormal neurologic examination was found in 17 of 90 versus 26 of 74, and a Gross Motor Function Classification Scale score of >1 was found in 2 of 90 versus 5 of 74, respectively. Fifty-nine of 90 children in the early iron group were without disability, compared with 40 of 74 in the late iron group. Severe disability was found in 5 of 90 versus 6 of 74 children and 67 of 90 versus 49 of 74 qualified for regular schooling, respectively., Conclusions: Early enteral iron supplementation showed a trend toward a beneficial effect on long-term neurocognitive and psychomotor development and showed no evidence for any adverse effect. Because the initial study was not designed to evaluate effects on neurocognitive development, the power was insufficient to detect small but potentially clinically relevant improvements. Additional studies are required to confirm the trend towards a better outcome observed in the early iron group.

Objective: To reduce hyperoxia in very low birth weight infants who receive supplemental oxygen, the Children's Mercy Hospital neonatal respiratory quality improvement committee introduced the potentially better practice of oxygen saturation targeting and identified strategies to overcome barriers to implementation of this practice., Methods: Using rapid-cycle quality improvement projects, this center adapted an oxygen saturation targeting protocol and tracked hourly oxygen saturation as measured by pulse oximetry in very low birth weight infants who received supplemental oxygen., Results: The percentage of time in the range of 90% to 94% of oxygen saturation as measured by pulse oximetry increased from 20% to an average of 35% after implementation of the protocol. The percentage of time with oxygen saturation as measured by pulse oximetry >98% dropped from 30% to an average of 5% to 10%., Conclusions: A well-planned strategy for implementing oxygen saturation targeting can result in a sustained change in clinical practice as well as change in the culture of the NICU regarding the use of oxygen.

Objective: Survival rates for preterm infants who weigh between 501 and 1500 g at birth have continued to improve over time. In response to this continuing decrease in birth weight of surviving preterm infants, Enfamil Human Milk Fortifier has recently been reformulated to meet the nutritional requirements of these smaller, more rapidly growing infants. It now provides an increased protein level of 1.1 g/58 kJ, a decreased carbohydrate level of 0.2 g/58 kJ, and a combined linoleic and alpha-linolenic fatty acid content of 157 mg/58 kJ. As these very small preterm infants have an increased requirement for dietary iron, the fortifier has been supplemented with 1.44 mg/58 kJ of iron, an amount of iron similar to that provided in a typical iron-fortified term infant formula. An iron-fortified product obviates the need for administration of an iron supplement, a hyperosmolar-inducing intervention. The purpose of this prospective, double-blind, randomized, controlled study was to evaluate growth, safety, and efficacy in a population of very low birth weight (VLBW) preterm infants who received human milk fortified with either the reformulated iron-fortified powdered human milk fortifier test product (HMF-T) or a powdered commercially available human milk fortifier control product (HMF-C)., Methods: Infants who weighed < or =1500 g, had a gestational age < or =33 weeks postmenstrual age, and had an enteral intake of at least 100 mL/kg per day of unfortified human milk were stratified by gender and birth weight and randomized to receive HMF-T or HMF-C product from study day 1 to study day 28, hospital discharge, or the termination of human milk feedings, whichever came first. Unless medically indicated, investigators were not to administer iron supplements from study days 1 to 14. Infants were assessed serially for growth; enteral and parenteral intake; serum chemistry and hematologic values; clinical histories, including the administration of blood transfusions; feeding tolerance; respiratory outcomes; and morbidities, including adverse events., Results: Of the 181 participating infants in this study, 96 received HMF-T and 85 received HMF-C. At randomization, there were no significant differences in infant characteristics between the fortifier groups. The percentage of participants who remained in the study for 28 days was similar between fortifier groups (57% HMF-T, 46% HMF-C). For both fortifier groups, the most frequent reasons for discontinuing the study before study day 28 were unavailability of human milk and hospital discharge. Rate of weight gain was similar between the fortifier groups (17.5 +/- 0.53 g/kg per day for HMF-T and 17.3 +/- 0.59 g/kg per day for HMF-C). Mean achieved weight, length, and head circumference were comparable between groups across the 28-day study period. Total protein intake from enteral and parenteral nutrition was significantly greater for the HMF-T fortifier group; however, this difference did not result in any difference in growth between the 2 fortifier groups. An analysis of the growth and energy intake data of a subset of the intent-to-treat population who adhered more strictly to the study feeding protocol yielded results similar to those seen for the intent-to-treat population. There were no clinically significant differences in the results of laboratory studies between the groups at study days 0, 14, and 28. Anemia of prematurity was prevalent in both study groups; by study day 28, median hematocrit levels were 27.0% (interquartile range [IQR]: 24.0%-29.6%) for the HMF-T group and 26.0% (IQR: 24.0%-31.0%) for the HMF-C group. Median ferritin levels were 77.0 ng/mL (IQR: 37-155 ng/ml) for HMF-T and 92.0 ng/mL (IQR: 33-110 ng/mL) for HMF-C. There were no significant differences between the study fortifier groups in regard to the receipt of medically indicated iron supplements on or before study day 14 or in the administration of blood transfusions before study day 0 or from study days 0 through 14. However, from study day 15 to study day 28, fewer HMF-T infants (n = 12) required a blood transfusion than did HMF-C infants (n = 20). Although the higher levels of iron in the HMF-T fortifier (1.44 mg vs 0.35 mg for HMF-C per 4 packets of powdered fortifier) did not prevent anemia per se, it did reduce the frequency of one of the most serious outcomes of anemia: the need for a blood transfusion. There was no statistically significant difference between fortifier groups in regard to feeding tolerance. Rates of suspected sepsis (26% HMF-T vs 31% HMF-C) and confirmed sepsis (5% HMF-T, 7% HMF-C) were low as were the rates of suspected necrotizing enterocolitis (NEC; 6% HMF-T and 5% HMF-C) and confirmed Bell's stage 2 or more NEC (1% HMF-T and 1% HMF-C). There were no statistically significant differences between the study fortifier groups in regard to the incidence of confirmed and suspected sepsis and NEC., Conclusion: Both human milk fortifiers studied are safe, are well tolerated, and facilitate comparable good growth; however, using the iron-fortified product may reduce the need for blood transfusions in VLBW infants. The similar low rates of suspected and confirmed NEC and sepsis seen in both fortifier groups in this study refutes the premise that the inclusion of iron in fortifiers will increase the incidence of sepsis and NEC. Indeed, the incidence for NEC and sepsis for both groups in this study was lower than is reported for VLBW infants and similar to that seen for infants who are fed human milk.

Objective: Neonatal candidemia is often fatal. Empirical antifungal therapy is associated with improved survival in neonates and patients with fever and neutropenia. Although guidelines for empirical therapy exist for patients with fever and neutropenia, these do not exist for neonates., Methods: A multicenter, retrospective, cohort study was conducted of neonatal intensive care unit patients (N = 6172) who had a blood culture (N = 21,233) after day of life 3 and whose birth weight was or=28 weeks. We developed a candidemia score on the basis of the ORs from the multivariable model. Children with a candidemia score >or=2 points were classified as having a "positive" score, and a score of >or=2 points had a sensitivity of 85% and a specificity of 47%., Conclusions: We developed a clinical predictive model for neonatal candidemia with high sensitivity and moderate specificity for candidemia. On the basis of our model, when a physician obtains a blood culture, the physician should consider providing antifungal therapy to neonates who are <25 weeks' estimated gestational age and to neonates who have thrombocytopenia at the time of blood culture. In addition, if a physician obtains a blood culture from a child who is 25 to 27 weeks' estimated gestational age and is not thrombocytopenic but has a history of third-generation cephalosporin or carbapenem exposure in the 7 days before the blood culture, then the physician should consider administration of empirical antifungal therapy.

Objective: Thrombocytopenia is commonly observed in very low birth weight (VLBW) neonates with sepsis. Specific platelet responses to different infectious agents have not been extensively characterized. The objectives of this study were to examine platelet counts and platelet indices in preterm neonates with culture-proven sepsis to determine if there are organism-specific platelet responses., Study Design: We analyzed a cohort of all VLBW neonates (birthweight <1500 g) born over a 4-year period and admitted to a single level III neonatal intensive care unit (N = 943). Thrombocytopenia was defined as a platelet count <100,000/mm(3). Platelet count, nadir, duration of thrombocytopenia, and mean platelet volume (MPV) were examined during episodes of culture-proven sepsis. Analysis of variance, Kruskal-Wallis, Mann-Whitney U, and chi(2) tests were used to compare groups, and data are expressed as mean +/- standard deviation., Results: Sepsis was diagnosed in 154 (16%) of 943 patients in the study population. Of the sepsis episodes, 54% were associated with thrombocytopenia and 61% with an elevation in MPV. Infections were grouped by organism type: Gram-positive bacteria (117/154, 76%), Gram-negative bacteria (24/154, 16%), and fungi (13/154, 8%). When compared with patients with Gram-positive sepsis, those with Gram-negative or fungal sepsis had a significantly lower initial platelet count, a lower platelet nadir, a higher incidence of thrombocytopenia, and a greater duration of thrombocytopenia. The decrease in platelet count from baseline was also significantly less in the Gram-positive infections than in the fungal infections. Although there was an overall increase in MPV from baseline, there were no differences between groups., Conclusions: In our population of VLBW infants, sepsis is frequently associated with thrombocytopenia and an elevation in MPV. However, fungal and Gram-negative pathogens are associated with a lower platelet count and more prolonged thrombocytopenia compared with Gram-positive pathogens. We conclude that common pathogens causing sepsis have different effects on platelet kinetics.

Objective: To evaluate longitudinal change in arterial blood plasma levels of soluble adhesion molecules in infants of <30 weeks' gestation with respiratory distress syndrome (RDS) and to look for differences in these levels in neonates who subsequently developed bronchopulmonary dysplasia (BPD) compared with those neonates who did not, and also to investigate the effect of dexamethasone treatment on levels of soluble adhesion molecules in plasma., Methods: We measured plasma concentrations of soluble L-selectin (sL-selectin), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 on days 1, 3, 7, 14, 21, and 28 of life and before and 2 to 3 days after initiating a 6-day course of dexamethasone treatment. Infants with RDS were followed until discharge and were classified as non-BPD and either 1) BPD day 28 reflecting oxygen requirement on day 28 but not at 36 corrected weeks or 2) BPD 36 weeks reflecting oxygen requirement at 36 (corrected) weeks' gestation. The classification of presence or absence of BPD by oxygen requirement was supported by and was consistent with radiologic findings of BPD for all infants. The difference between BPD day 28 and BPD 36 weeks was supported by more extensive radiologic effects in the latter., Results: The arterial plasma level of sL-selectin in infants who had RDS and did not develop BPD was significantly decreased compared with term healthy infants, as was the level of sE-selectin. Compared with infants who had RDS and did not develop BPD, sL-selectin levels were even further decreased in infants who had RDS and did develop BPD both at birth and throughout the first 4 weeks of life (day 1 through day 28). Infants with BPD also showed increasing levels of sE-selectin during this period of time, whereas infants without BPD did not. Levels of soluble intercellular adhesion molecule-1 in infants without BPD were not different from infants with BPD initially but increased in infants with BPD compared with infants without BPD, significant on day 28 in both groups. Dexamethasone treatment increased concentration of sL-selectin and decreased concentration of sE-selectin., Conclusions: Low sL-selectin may be an early indicator of enhanced risk for BPD. Low levels of sL-selectin and increasing levels of sE-selectin may be risk factors for BPD. The effects of dexamethasone treatment include significant modulation of adhesion molecules.

Objective: Systemic carnitine deficiency may present with apnea, hypotonia, and poor growth. Premature infants often manifest these symptoms and are at risk of developing carnitine deficiency because of immaturity of the biosynthetic pathway, lack of sufficient predelivery transplacental transport, and lack of sufficient exogenous supplementation. This study was undertaken to examine the effect of carnitine supplementation in premature infants., Methods: Eighty preterm infants <1500 g were enrolled in a prospective, double-blind, placebo-controlled study of carnitine supplementation within 96 hours of delivery. Growth, length of hospital stay, and frequency and severity of apnea were the primary outcome measures., Results: Weight gain and change in length, fronto-occipital head circumference, mid arm circumference, and triceps skinfold thickness were similar between the carnitine-supplemented and placebo groups. The amount and severity of apnea and the overall length of hospitalization were also similar between the 2 groups. The carnitine levels in the supplemented group were significantly higher than in the placebo group at 4 and 8 weeks after study entry., Conclusion: Although preterm infants <1500 g have low carnitine levels, routine supplementation with carnitine has no demonstrable effect on growth, apnea, or length of hospitalization and thus seems to be unnecessary.

Transient hypothyroxinemia in infants born to mothers with poorly controlled Graves' disease was first reported in 1988. We report that short-term hyperthyroidism followed by hypothyroidism with low basal thyroid-stimulating hormone (TSH) levels developed in a very low birth weight infant born at 27 weeks of gestation to a noncompliant mother with thyrotoxicosis attributable to Graves' disease. We performed serial thyrotropin-releasing hormone (TRH) tests in this infant and demonstrated that TSH unresponsiveness to TRH disappeared at 6.5 months of age. The maternal thyroid function was free triiodothyronine (FT(3)), 21.1 pg/mL; free thyroxine (FT(4)), 8.1 ng/dL; TSH, <0.03 microU/mL; thyroid-stimulating hormone receptor antibody, 52% (normal: <15%); thyroid-stimulating antibody, 294% (normal: <180%); and thyroid-stimulation blocking antibody, 9% (normal: <25%) on the day of delivery. A nonstress test revealed fetal tachycardia >200 beats per minute, and a male infant weighing 1152 g was born by emergency cesarean section. Thyroid-stimulating hormone receptor antibody was 16% and thyroid-stimulating antibody was 370% in the cord blood. We administered 10 mg/kg per day of oral propylthiouracil from day 1. Tachycardia along with elevated FT(4) and FT(3) levels in the infant decreased from 200/minute to 170/minute, 4.7 ng/dL to 2.9 ng/dL, 7.0 pg/mL to 4.8 pg/mL, respectively, in the first 33 hours. At 5 days, FT(4) and FT(3) were 1.1 ng/dL and 2.9 pg/mL, respectively, and we stopped propylthiouracil administration. Although FT(4) decreased to 0.4 ng/dL, TSH was quite low and did not respond to intravenous TRH by 14 days of age. We began daily levothyroxine 5-micro/kg supplementation. The responsiveness of TSH to TRH did not become significant until 4 months old and normalized at 6.5 months old. At this time, levothyroxine was stopped. We conclude that placental transfer of thyroid hormones may cause hyperthyroidism in the fetal and early neonatal periods and lead to transient pituitary hypothyroidism in an infant born to a mother with uncontrolled Graves' disease.

Background: Neutropenia, defined as absolute neutrophil count (ANC) <1500/mm(3), affects 6% to 58% of premature infants in the first week of life. This early-onset neutropenia in premature infants has previously been correlated with sepsis, maternal hypertension, severe asphyxia, and periventricular hemorrhage. Late-onset neutropenia, defined as ANC <1500/mm(3) at a postnatal age of >/=3 weeks, has not been previously reported., Objectives: The purposes of this study were to determine the prevalence of late-onset neutropenia in very low birth weight (VLBW) infants and to examine the factors that may be associated with this phenomenon., Methods: A weekly complete blood cell count (CBC) was performed routinely in all premature infants with birth weight

Objective: In very low birth weight (VLBW) infants, diagnostic and therapeutic decisions depend on hematologic values. As few data are available, we studied the course during the first 6 weeks of life., Design: Four prospective longitudinal cohort studies were retrospectively combined assessing hematologic profiles of 562 VLBW infants. For characterization of red blood cells and iron, infants receiving erythropoietin were excluded. For characterization of white blood cells and platelets, infants receiving antibiotics were excluded., Results: The third (3rd)/median/97th percentiles on day 3 were as follows: hemoglobin: 11.0/15.6/19.8 g/dL; hematocrit: 35/47/60%; red blood cells: 3.2/4.2/5.3 x 10(12)/L; reticulocytes:. 6/7.1/27.8%; platelets: 58/203/430 x 10(9)/L; white blood cells: 3. 6/9.5/38.3 x 10(9)/L; neutrophils:.7/4.7/25.3 x 10(9)/L; ferritin: 27/140/504 ng/mL; iron:.8/7.5/26.7 micromol/L; transferrin saturation: 2.6/22.7/79.8%. Transferrin saturation was <24% in 51%, ferritin concentration <100 ng/mL in 32%, and platelets <150 x 10(9)/L in 29% of this population. The steady decrease of red cell parameters was mitigated by transfusions. Neutrophils decreased steadily, and were <1.75 x 10(9)/L in 35% at 6 weeks., Conclusions: Iron indices and platelet counts on day 3 and neutrophil counts at 2 to 6 weeks of age are lower than previously assumed in VLBW infants and lower than in larger prematures.

Objectives: Premature infants experience brain injury, ie, germinal matrix-intraventricular hemorrhage (GMH-IVH) and periventricular leukomalacia (PVL), in considerable part because of disturbances in cerebral blood flow (CBF). Because such infants are susceptible to major fluctuations in mean arterial blood pressure (MAP), impaired cerebrovascular autoregulation would increase the likelihood for the changes in CBF that could result in GMH-IVH and PVL. The objectives of this study were to determine whether a state of impaired cerebrovascular autoregulation could be identified reliably and conveniently at the bedside, the frequency of any such impairment, and the relation of the impairment to the subsequent occurrence of severe GMH-IVH and PVL., Patients and Methods: To monitor the cerebral circulation continuously and noninvasively, we used near-infrared spectroscopy (NIRS) to determine quantitative changes in cerebral concentrations of oxygenated hemoglobin (HbO(2)) and deoxygenated hemoglobin (Hb) from the first hours of life. Our previous experimental study showed a strong correlation between a measure of cerebral intravascular oxygenation (HbD), ie, HbD = HbO(2) - Hb, determined by NIRS, and volemic CBF, determined by radioactive microspheres. We studied 32 very low birth weight premature infants (gestational age: 23-31 weeks; birth weight: 605-1870 g) requiring mechanical ventilation, supplemental oxygen, and invasive blood pressure monitoring by NIRS from 1 to 3 days of age. MAP measured by arterial catheter pressure transducer and arterial oxygen saturation measured by pulse oximetry were recorded simultaneously. The relationship of MAP to HbD was quantitated by coherence analysis., Results: Concordant changes (coherence scores >. 5) in HbD and MAP, consistent with impaired cerebrovascular autoregulation, were observed in 17 of the 32 infants (53%). Eight of the 17 infants (47%) developed severe GMH-IVH or PVL or both. Of the 15 infants with apparently intact autoregulation, ie, coherence scores <.5, only 2 (13%) developed severe ultrasonographic lesions. Thus, for the entire study population of 32 infants, 8 of the 10 with severe lesions exhibited coherence scores >.5., Conclusions: We conclude that NIRS can be used in a noninvasive manner at the bedside to identify premature infants with impaired cerebrovascular autoregulation, that this impairment is relatively common in such infants, and that the presence of this impairment is associated with a high likelihood of occurrence of severe GMH-IVH/PVL.

Background: Normative data for hematologic values in the very low birth weight infants are limited and inconsistent, with the reported mean hematocrit (HCT) in these infants ranging from 43.5% to 60%. No data are available on the effect of race., Objectives: To establish normative data for hemoglobin (Hb) and HCT by arterial sampling obtained during the first 3 hours after birth in black and white premature infants

Unlabelled: Transient hypothyroxinemia (TH) of prematurity has been correlated with poor neurodevelopmental outcome. However, the relationship between thyroid function and neonatal mortality and brain injury has not been described., Objective: To investigate the relationship between thyroid function and neonatal outcome., Methods: Review of infants weighing <1500 grams admitted to a single level III newborn intensive care unit (n = 342). Serum total T4 values of initial newborn screening of infants dying before hospital discharge were compared with those of surviving infants. Total T4 values from infants with and without intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) also were compared., Results: T4 values strongly correlated with gestational age (r = .56). Overall, 289 (85%) of 342 infants had TH. None of the infants had true congenital hypothyroidism. T4 values of infants with cystic PVL (n = 15) were not statistically different from those for infants who did not develop cystic PVL. Infants with IVH (n = 58) had a lower T4 value than did infants who did not develop IVH (5.4 +/- 3.4 microg/dL vs 7.8 +/- 3.6 microg/dL). Infants who died before hospital discharge (n = 24) had a lower T4 value than did infants discharged to home (3.4 +/- 2.2 vs 7.9 +/- 3.7 microg/dL). After controlling for potential confounding variables, T4 value remained associated with an increased odds of IVH (odds ratio: 1.2; 95% confidence interval: 1.05 to 1.4) and mortality (odds ratio: 2.3; 95% confidence interval 1.6 to 3.4)., Conclusions: In our population of very low birth weight infants, TH has an incidence of 85%. Very low T4 values on initial newborn screening are associated with increased odds of death and IVH. Additional investigation is needed to determine whether low serum thyroxine level contributes to IVH and neonatal death or whether it is simply an associated factor.

Background: Continuous noninvasive monitoring of arterial carbon dioxide (CO2) in neonatal intensive care unit (NICU) patients would help clinicians avoid complications of hypocarbia and hypercarbia. End-tidal CO2 monitoring has not been used in this population to date, but recent technical advances and the introduction of surfactant therapy, which improves ventilation-perfusion matching, might improve the clinical utility of end-tidal monitoring., Objective: To determine the accuracy and precision of end-tidal CO2 monitoring in NICU patients., Design: Nonrandomized recording of simultaneous end-tidal and arterial CO2 pairs., Setting: Two university NICUs., Patients: Forty-five newborn infants receiving mechanical ventilation who had indwelling arterial access, and a predefined subsample of infants who were <1000 g birth weight, <8 days of age, and who received surfactant therapy (extremely low birth weight -ELBW- <8)., Outcome Measures: The correlation coefficient, degree of bias, and 95% confidence interval were determined for both the overall population and the ELBW <8 subgroup. Those factors which significantly influenced the bias were identified. The ability of the end-tidal monitor to alert the clinician to instances of hypocarbia or hypercarbia was determined., Results: There were 411 end-tidal/arterial pairs analyzed from 45 patients. The correlation coefficient was 0.833 and the bias was -6. 9 mm Hg (95% confidence interval, +/-11.5 mm Hg). The results did not differ markedly in the ELBW <8 infants. Measures of the degree of lung disease, the ventilation index and the oxygenation index, had small influences on the degree of bias. This type of capnometry identified 91% of the instances when the arterial CO2 pressure was between 34 and 54 mm Hg using an end-tidal range of 29 to 45 mm Hg. End-tidal values outside this range had a 63% accuracy in predicting hypocarbia or hypercarbia., Conclusion: End-tidal CO2 monitoring in NICU patients is as accurate as capillary or transcutaneous monitoring but less precise than the latter. It may be useful for trending or for screening patients for abnormal arterial CO2 values.

Objective: To study the effect of sepsis on circulating neutrophils in very low birth weight neonates and to assess the usefulness of recently revised reference ranges for circulating neutrophils in the diagnosis of sepsis in this population by comparison with previously reported reference ranges., Methods: Neutrophil parameters (absolute total neutrophils, absolute total immature neutrophils, and the immature:total neutrophil proportion) were analyzed retrospectively in 202 sepsis episodes in 192 neonates (birth weight = 1055 +/- 246 g, X +/- SD; estimated gestational age = 29 +/- 2 weeks) between birth and 30 days of age. The percentage of values lying outside the reference ranges reported recently by Mouzinho et al and previously by Manroe et al were compared. To more accurately assess possible differences in specificity between the two reference ranges, neonates with early-onset group B streptococcal infection (n = 19) were compared with a matched control group (n = 51) using conditional logistic regression., Results: Greater sensitivity was observed using the previous reference ranges of Manroe et al over the entire study period (0 to 720 hours) both for the initial and the second complete blood count (CBC). The previous reference ranges also were more sensitive than the revised ranges for the initial CBC at 0 to 72 and at 73 to 720 hours and for infections attributable to coagulase-negative staphylococci. However, specificity in neonates without group B streptococcal infection was significantly greater with the revised reference ranges compared with those of Manroe et al (initial CBC, 73% vs 45%; serial CBCs, 59% vs 10%)., Conclusion: The observed differences in sensitivities may be of limited clinical significance because very low birth weight infants often are begun on antibiotic therapy regardless of laboratory values. However, the striking differences in specificity using the revised reference ranges suggest that these ranges may be clinically useful in determining length of antimicrobial therapy in infants in whom cultures remain sterile.

Objective: To explore the relationship between chorioamnionitis, postnatal cortisol concentrations, and acute respiratory distress in very low birth weight infants., Methods: Appropriate for gestational age infants weighing between 501 to 1500 g at birth were enrolled into this prospective, observational study, and data regarding respiratory distress on the first day of life were recorded. Serum cortisol concentrations were measured on (a) day 2, (b) day 3 or 4, and (c) day 5, 6, or 7 of life. On day (b) or (c), 3.5 microg/kg of cosyntropin (an adrenocorticotrophic hormone analog) was given, and a repeat specimen was drawn 30 minutes later. Chorioamnionitis was diagnosed by placental examination by one author (R.L.N.)., Results: Forty-two infants exposed to chorioamnionitis and 37 infants not exposed were enrolled. Chorioamnionitis correlated inversely with gestational age, and was associated with decreased measures of acute respiratory support (exogenous surfactant, fraction of inspired oxygen, and ventilator support at 12 and 24 hours). Infants with chorioamnionitis had higher cortisol concentrations, both basal and stimulated. Gestational age was not significantly related to basal cortisol, but did correlate positively with stimulated values. Cortisol values from the 16 infants exposed to prenatal glucocorticoid therapy were excluded from these analyses., Conclusions: These results provide evidence that prenatal inflammation leads to adrenal stimulation, resulting in increased cortisol secretion and accelerated lung maturation. The enhanced response to cosyntropin stimulation seen in these infants may reflect an increased adrenal capacity to respond to postnatal stressors. Because of the apparent magnitude of the effect of chorioamnionitis on cortisol measures, this factor should be included in future investigations of adrenal function in very low birth weight newborns.