Francis J. Bednarek

Variations in blood transfusions among newborn intensive care units

OBJECTIVES Very low birth weight (< 1500 g) infants frequently require packed red blood cell transfusions, and transfusion rates vary among neonatal intensive care units (NICUs). We analyzed transfusions and compared outcomes among NICUs. 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.

Factors associated with treatment for hypotension in extremely low gestational age newborns during the first postnatal week.

OBJECTIVE. The goals were to identify the blood pressures of extremely low gestational age newborns that prompt intervention, to identify other infant characteristics associated with receipt of therapies intended to increase blood pressure, and to assess the interinstitutional variability in the use of these therapies. 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.

Stabilizing immature breathing patterns of preterm infants using stochastic mechanosensory stimulation

Breathing patterns in preterm infants consist of highly variable interbreath intervals (IBIs) that might originate from nonlinear properties of the respiratory oscillator and its input-output responses to peripheral and central signals. Here, we explore a property of nonlinear control, the potential for large improvement in the stability of breathing using low-level exogenous stochastic stimulation. Stimulation was administered to 10 preterm infants (postconceptional age: mean 33.3 wk, SD 1.7) using a mattress with embedded actuators that delivered small stochastic displacements (0.021 mm root mean square, 0.090 mm maximum, 30-60 Hz); this stimulus was subthreshold for causing arousal from sleep to wakefulness or other detectable changes in the behavioral state evaluated with polysomnography. We used a test-retest protocol with multiple 10-min intervals of stimulation, each paired with 10-min intervals of no stimulation. Stimulation induced an approximately 50% reduction (P = 0.003) in the variance of IBIs and an approximately 50% reduction (P = 0.002) in the incidence of IBIs > 5 s. The improved stability of eupneic breathing was associated with an approximately 65% reduction (P = 0.04) in the duration of O(2) desaturation. Our findings suggest that nonlinear properties of the immature respiratory control system can be harnessed using afferent stimuli to stabilize eupneic breathing, thereby potentially reducing the incidence of apnea and hypoxia.

Perinatal risk and severity of illness in newborns at 6 neonatal intensive care units.

OBJECTIVES This multisite study sought to identify (1) any differences in admission risk (defined by gestational age and illness severity) among neonatal intensive care units (NICUs) and (2) obstetric antecedents of newborn illness severity. 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.

The platelet hyporeactivity of extremely low birth weight neonates is age-dependent

INTRODUCTION We have previously demonstrated that, as compared to adults, the platelets of extremely low birth weight (ELBW) neonates are markedly hyporeactive on day 0-1 of life. The purpose of this study was to examine the age dependency of this hyporeactivity. 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.

Blood Gases and Retinopathy of Prematurity: The ELGAN Study

Objective: This study tested the hypothesis that preterm infants who had a blood gas derangement on at least 2 of the first 3 postnatal days are at increased risk for more severe retinopathy of prematurity (ROP). 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 PCO2 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 PaO2 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 PCO2, low pH and high PaO2 appear to be at increased risk of more severe ROP.

SNAP-II and SNAPPE-II and the Risk of Structural and Functional Brain Disorders in Extremely Low Gestational Age Newborns: The ELGAN Study

Background: Illness severity measures predict death and illnesses in the newborn. It is unknown how well they predict brain lesions evident on ultrasound scans or neurodevelopmental dysfunctions in preterm infants. 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 <55 were consistently predicted by both high SNAP-II and 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.

Systemic responses of preterm newborns with presumed or documented bacteraemia.

Aim:  To compare the frequency of elevated concentrations of inflammation‐related proteins in the blood of infants born before the 28th week of gestation who had documented bacteraemia and those who had presumed (antibiotic‐treated but culture‐negative) bacteraemia to those who had neither.

Aggressive respiratory support and unilateral nephrectomy for infants with severe perinatal autosomal recessive polycystic kidney disease.

Newborn infants with severe autosomal recessive polycystic kidney disease often receive minimal intervention because poor respiratory and renal outcomes are anticipated. We describe two patients whose respiratory failure was successfully treated with aggressive intervention. Massive kidneys restricted gastrointestinal capacity and limited feedings. Uninephrectomy allowed adequate enteral feedings and preserved sufficient renal function for homeostasis and growth.

Nephrocalcinosis in premature infants: variability in ultrasound detection

OBJECTIVE:To measure variability among radiologists in the ultrasound diagnosis of nephrocalcinosis in premature infants.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. κ coefficients were calculated to assess variability in identification of nephrocalcinosis among the radiologists.RESULTS:The κ coefficient (± confidence intervals) using a 5.0-MHz transducer was 0.143 (0.108, 0.178); using the 7.5-MHz transducer, the κ 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.