METHODS: The subjects of this study are the 868 infants born at 14 institutions for whom information about protein measurements on at least two of the three protocol days (days 1, 7, and 14) was available and who did not have Bell stage 3 necrotizing enterocolitis or isolated bowel perforation, which were strongly associated with bacteraemia in this sample.

RESULTS: Newborns with presumed early (week 1) bacteraemia had elevated concentrations of only a few inflammation-related proteins, while those who had presumed late (weeks 2-4) bacteraemia did not have any elevations. In contrast, newborns who had documented early bacteraemia had a moderately strong signal, while those who had documented late bacteraemia had a stronger signal with more protein concentrations elevated on two separate occasions a week apart.

CONCLUSIONS: Culture-confirmed early and late bacteraemia are accompanied/followed by systemic inflammatory responses not seen with presumed early and late bacteraemia.

OBJECTIVE: To measure the sensitivity and negative predictive value of 2 serial white blood cell counts and a negative blood culture at 24 hours in predicting a noninfected neonate in the evaluation of early-onset sepsis.

METHODS: We performed a historical cohort study of neonates in the University of Massachusetts Newborn Nursery and neonatal intensive care unit born between 1999 and 2008 who had sepsis evaluations within the first 24 hours of life.

RESULTS: Three thousand two hundred thirteen patients were identified; 59 were excluded due to missing data. Of the 3154 included neonates, 1539 (49%) had 2 normal immature to total neutrophil (I:T) ratios and a negative blood culture at 24 hours. Two of these blood cultures showed growth of bacteria after 24 hours but were considered contaminants, and antibiotics were stopped at 48 hours. None of the 1539 neonates with normal I:T ratios was subsequently diagnosed with sepsis (negative predictive value 100%; [95% confidence interval: 99.905%-100%]).

CONCLUSIONS: In this study, the combination of 2 serial normal I:T ratios and a negative blood culture at 24 hours in the evaluation of early-onset sepsis shortly after birth is indicative of a noninfected neonate. This suggests that antibiotics can safely be stopped at 24 hours in these neonates, which comprises approximately 50% of our study population.

METHOD: 1,042 infants born before 28 weeks' gestational age (GA) were included. An infant was considered to be exposed if his/her blood gas measure was in the highest or lowest quartile for GA on at least 2 of the first 3 postnatal days.

RESULTS: Multivariable models adjusting for confounders indicate that exposure to a PCO(2) in the highest quartile predicts ROP (stage 3, 4 or 5: OR = 1.6, 95% CI = 1.1-2.3); zone 1: 2.0, 1.1-3.6; prethreshold/threshold: 1.9, 1.2-3.0; plus disease: 1.8, 1.1-2.9). Estimates are similar for a low pH for zone 1 (2.1, 1.2-3.8), prethreshold/threshold (1.8, 1.1-2.8), but did not quite achieve statistical significance for ROP stage 3, 4, or 5 (1.4, 0.9-2.0) and plus disease (1.5, 0.9-2.4). A PaO(2) in the highest quartile for GA on at least 2 of the first 3 postnatal days was associated with a doubling of the risk of ROP in zone 1 (2.5, 1.4-4.4) and of prethreshold/threshold disease (2.1, 1.4-3.3), a 70% risk increase for plus disease (1.7, 1.04-2.8), while a 40% risk increase for ROP stage 3 or higher did not achieve statistical significance (1.4, 0.96-2.0).

CONCLUSION: Infants exposed to high PCO(2), low pH and high PaO(2) appear to be at increased risk of more severe ROP.

OBJECTIVES: The primary goal of this study was to estimate the genetic susceptibility to AOP in a cohort of preterm twins. A secondary aim was to identify risk factors associated with AOP in this cohort.

METHODS: A single-center, retrospective study (2000-2008) was performed by using data from 317 premature twin pairs (weeks' gestational age). Heritability estimates were determined by comparing intrapair AOP concordance between 56 monozygotic and 161 dizygotic twin pairs by using structural equation modeling. Risk factors of AOP among a cohort of 543 premature twins were assessed by using mixed-effects logistic regression.

RESULTS: The heritability of AOP was 87% (95% confidence interval [CI]: 0.64-0.97) among same-gender twins. A gender-dependent model revealed that genetic factors accounted for 99% of the variance in male twins (95% CI: 0.89-1.00) and 78% of the variance in female twins (95% CI: 0.49-0.94). Significant risk factors for AOP were low gestational age (P

CONCLUSIONS: These findings suggest that AOP has an important genetic basis underlying this developmental-related disorder of respiratory control. Future genomic studies may provide information on pathophysiological mechanisms that underlie AOP.

METHODS: A total of 1,399 inborn infants born before the 28th week of gestation were given Scores for Neonatal Acute Physiology (SNAP-II and SNAPPE-II) based on data collected within the first 12 h of admission to the intensive care unit and had a protocol brain ultrasound scan read independently by 2 sonologists. Of the surviving 1,149 infants, 1,014 (88%) had a neurologic examination at approximately 24 months post-term equivalent, and 975 (85%) had a Bayley Scales of Infant Development assessment. SNAP-II and SNAPPE-II were dichotomized at arbitrary cut-offs (30 for SNAP-II and 45 for SNAPPE-II), using the highest quartile and decile of the week of gestation as a cut-off, and at a Z score of >1 standard deviation from an external mean.

RESULTS: After adjustment for gestational age, high SNAP-II and SNAPPE-II scores predicted intraventricular hemorrhage, moderate/severe ventriculomegaly and echodense lesions in cerebral white matter. Only 2 SNAP-II extremes, the highest decile for gestational age and a Z score >1, also predicted echolucent lesions in the white matter. Neither SNAP-II nor SNAPPE-II predicted any statistically significant diagnosis of cerebral palsy. MDI and PDI scores SNAPPE-II, whereas scores in the 55-69 range were inconsistently predicted. High SNAP-II and SNAPPE-II inconsistently predicted a positive screen for autism spectrum disorder and small head circumference at 24 months.

CONCLUSION: The physiologic instability in the first 12 post-natal hours identified by illness severity scores conveys information about the risks of brain damage and neurodevelopmental dysfunctions. This risk information might reflect postnatal characteristics in the causal chain. On the other hand, high SNAP scores might be indicators of immaturity and vulnerability.

MATERIALS AND METHODS: On days 0-1, 3-4, and 10-14, peripheral blood was collected from 14 stable ELBW neonates and compared to peripheral blood from normal adults run in parallel. Whole blood flow cytometry was used to examine the activation-dependent increase in platelet surface P-selectin (reflecting degranulation) and platelet surface binding of factor V/Va (reflecting platelet surface procoagulant activity) and decrease in platelet surface glycoprotein (GP) Ib (the von Willebrand factor receptor).

RESULTS: In the physiologic milieu of whole blood, ELBW neonatal platelets on days 0-1 and 3-4 were markedly less reactive than adult platelets. However, by day 10-14, the platelet function of ELBW neonates improved significantly, although not completely to adult levels.

CONCLUSIONS: The age-dependent platelet hyporeactivity of ELBW neonates demonstrated in this study may be a contributing factor to the similar age-dependent propensity of ELBW neonates to intraventricular hemorrhage.

STUDY DESIGN: The investigation used a prospective, pre- and postintervention study design with a double pretest. The 10 birthing centers in Panama that routinely transport the greatest number of newborns received the education program intervention. Primary outcomes were body temperature and serum glucose level on arrival at the referral facility. Length of stay and mortality were evaluated as secondary outcomes. Variation in outcome indicators was compared for 7 months before and after the intervention. Data from all live newborns transported from outlying birthing center study sites during the study dates were included in the investigation. RESULT: A total of 136 and 146 newborns were transported during the observation and postintervention periods, respectively. Significantly more patients in the postintervention group had temperatures within the normal range (56% in postintervention group vs 34% in observation group; P

CONCLUSION: Distribution of a neonatal provider educational program was associated with improved thermal management of transported newborns in Panama. Further study will help to confirm this association and determine the extent to which these findings are generalizable to other resource-constrained settings.

METHODS: The cohort included 1507 extremely low gestational age newborns born at 23 weeks to 27 weeks of gestation, at 14 institutions, between March 2002 and August 2004; 1387 survived the first postnatal week. Blood pressures were measured as clinically indicated. Interventions were grouped as any treatment (ie, vasopressor and/or fluid boluses of >10 mL/kg) and vasopressor treatment, and logistic regression analyses were performed.

RESULTS: At each gestational age, the lowest mean arterial pressures in treated and untreated infants tended to increase with advancing postnatal age. Infants who received any therapy tended to have lower mean arterial pressures than infants who did not, but uniform thresholds for treatment were not apparent. The proportion of infants receiving any treatment decreased with increasing gestational age from 93% at 23 weeks to 73% at 27 weeks. Treatment nearly always began during the first 24 hours of life. Lower gestational age, lower birth weight, male gender, and higher Score for Neonatal Acute Physiology-II values were associated with any treatment and vasopressor treatment. Institutions varied greatly in their tendency to offer any treatment and vasopressor treatment. Neither the lowest mean arterial pressure on the day of treatment nor other characteristics of the infants accounted for center differences in treatment.

CONCLUSIONS: Blood pressure in extremely premature infants not treated for hypotension increased directly with both increasing gestational age and postnatal age. The decision to provide treatment was associated more strongly with the center where care was provided than with infant attributes.

RESULTS: There was variability in rates of thrombocytopenia among NICUs, even after controlling for risk factors (e.g., SNAP, small for gestational (SGA) age and maternal hypertension). One site had a high prevalence of thrombocytopenia, but the lowest percentage of infants with thrombocytopenia who received platelet transfusions. After controlling for SNAP, GA, SGA, Apgar score and incidence of thrombocytopenia, the odds of receiving platelets at this site, relative to the site with the highest transfusion rate, was 0.10 (95% CI 0.02 to 0.43).

CONCLUSIONS: This multicenter study finds a 10-fold variation among NICU in the administration of platelets to their thrombocytopenic infants that cannot be explained by presence of thrombocytopenia or illness severity.

PURPOSE: A multicenter randomized clinical trial was undertaken to ascertain the efficacy of a novel chlorhexidine-impregnated dressing (Biopatch Antimicrobial Dressing) on the CVC sites of neonates for the prevention of catheter tip colonization, CRBSI, and bloodstream infection (BSI) without a source. Setting. Six level III neonatal intensive care units. Patients Studied. Neonates admitted to study units who would require a CVC for at least 48 hours.

METHODS: Eligible infants were randomized before catheter placement to 1 of the 2 catheter site antisepsis regimens: 1) 10% povidone-iodine (PI) skin scrub, or 2) a 70% alcohol scrub followed by placement of a chlorhexidine-impregnated disk over the catheter insertion site. A transparent polyurethane dressing (Bioclusive Transparent Dressing) was used to cover the insertion site in both study groups. Primary study outcomes evaluated were catheter tip colonization, CRBSI, and BSI without an identified source.

RESULTS: Seven hundred five neonates were enrolled in the trial, 335 randomized to receive the chlorhexidine dressing and 370 to skin disinfection with PI (controls). Neonates randomized to the antimicrobial dressing group were less likely to have colonized CVC tips than control neonates (15.0% vs 24.0%, relative risk [RR]: 0.6 95% confidence interval [CI]: 0.5-0.9). Rates of CRBSI (3.8% vs 3.2%, RR: 1.2, CI: 0.5-2.7) and BSI without a source (15.2% vs 14.3%, RR: 1.1, CI: 0.8-1.5) did not differ between the 2 groups. Localized contact dermatitis from the antimicrobial dressing, requiring crossover into the PI treatment group, occurred in 15 (15.3%) of 98 exposed neonates weighing

METHODS: Data on 1476 babies born at a gestational age of less than 32 weeks in 6 perinatal centers were abstracted prospectively. Newborn illness severity was measured with the Score for Neonatal Acute Physiology. Regression models were constructed to predict scores as a function of perinatal risk factors.

RESULTS: The sites differed by several obstetric case-mix characteristics. Of these, only gestational age, small for gestational age. White race, and severe congenital anomalies were associated with higher scores. Antenatal corticosteroids, low Apgar scores, and neonatal hypothermia also affected illness severity. At 2 sites, higher mean severity could not be explained by case mix.

CONCLUSIONS: Obstetric events and perinatal practices affect newborn illness severity. These risk factors differ among perinatal centers and are associated with elevated illness severity at some sites. Outcomes of NICU care may be affected by antecedent events and perinatal practices.

METHODOLOGY: In this prospective multicenter study, renal ultrasounds were performed on 54 very low birth weight infants using a 5.0- and 7.5-MHz transducer, and these ultrasounds were read independently by three radiologists. kappa coefficients were calculated to assess variability in identification of nephrocalcinosis among the radiologists.

RESULTS: The kappa coefficient (+/- confidence intervals) using a 5.0-MHz transducer was 0.143 (0.108, 0.178); using the 7.5-MHz transducer, the kappa coefficient was 0.268 (0.243, 0.293). All three radiologists agreed in their identification of nephrocalcinosis on 3 of 54 ultrasounds using a 5.0-MHz transducer; a total of 6 of 54 ultrasounds obtained using a 7.5-MHz transducer were read as positive by all three radiologists.

CONCLUSION: There is significant variability among radiologists in the ultrasound identification of nephrocalcinosis in premature infants; a 7.5-MHz ultrasound transducer is associated with less variability in recognizing this lesion.

STUDY DESIGN: In a 6-site prospective study, we abstracted all newborns weighing < 1500 g (total = 825) born between October 1994 and September 1995. Transfusion frequency and volume and phlebotomy number were analyzed by site and adjusted for birth weight and illness severity. We compared rates of intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, growth, and length of stay between the high and low transfuser NICUs.

RESULTS: Sites differed significantly in mean birth weight, illness severity, number of transfusions, pretransfusion hematocrit, blood draws, and donor number. Multivariate adjustment for these risks showed that the highest transfusing NICU transfused an additional 24 cc/kg per baby during the first 14 days and 47 cc/kg per baby after 15 days, relative to the lowest transfusing NICU. The presence of arterial catheters increased the frequency of blood transfusions. The rates of intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia were not higher in the 2 lowest transfusing NICUs, nor were there differences in 28-day weight gain or length of stay.

CONCLUSIONS: Major differences in transfusion practices for very low birth weight infants exist among NICUs. Because clinical outcomes were no different in lower transfuser NICUs, it is likely that transfusion and phlebotomy guidelines could result in fewer transfusions, fewer complications, and reduced cost.

STUDY DESIGN: The medical charts of neonates weighing less than 1500 g, admitted to 6 NICUs (A-F), were abstracted. Neonates who had a chest tube or who had undergone surgery were excluded from the study, leaving the records of 1171 neonates. We modeled outcomes by linear or logistic regression, controlling for birth weight ( or =20) using the Score for Neonatal Acute Physiology (SNAP), and adjusted for NICU.

RESULTS: Narcotic use varied by birth weight (g, 21%; 750-999 g, 13%; and 1000-1499 g, 8%), illness severity (low, 9%; medium, 19%; and high, 37%), day (1, 11%; 3, 6%; and 14, 2%), and NICU. We restricted analyses to the 1018 neonates who received mechanical ventilation on day 1. Logistic regression, adjusting for birth weight and SNAP, confirmed a 28.6-fold variation in narcotic administration (odds ratios, 4.1-28.6 vs NICU A). Several short-term outcomes also were associated with narcotic use, including more than 33 g of fluid retention on day 3 and a higher direct bilirubin level (6.8 micromol/L higher [0.4 mg/dL higher], P = .03). There were no differences in weight gain at 14 and 28 days or mechanical ventilatory support on days 14 and 28. Narcotic use was not associated with differences in worst blood pressure or heart rate or with increased length of hospital stay.

CONCLUSIONS: Our study found a 28.6-fold variation among NICUs in narcotic administration in very low-birth-weight neonates. We were unable to detect any major advantages or disadvantages of narcotic use. We did not assess iatrogenic abstinence syndrome or long-term outcomes. These results indicate the need for randomized trials to rationalize these widely differing practices.