Reference intervals for stool calprotectin in preterm neonates and their utility for the diagnosis of necrotizing enterocolitis.

OBJECTIVE: Calprotectin is an antimicrobial protein found in stool when released by granulocytes. We sought to create stool calprotectin reference ranges in preterm neonates and to evaluate whether levels exceeding the upper reference interval are diagnostic for necrotizing enterocolitis (NEC). STUDY DESIGN: Stool calprotectin was measured in premature neonates without gastrointestinal pathology to create reference intervals. For comparison, levels from infants undergoing "rule out NEC" evaluations were plotted on these reference intervals. RESULTS: Stool calprotectin reference intervals were created according to gestational age at birth and corrected gestational age. Levels during "rule out NEC" evaluations were more often above the upper reference interval with NEC vs. those without NEC. CONCLUSIONS: Stools from preterm neonates have a higher range of calprotectin than stools from healthy term neonates. In evaluating preterm neonates for NEC with stool calprotectin, a calprotectin upper reference interval that incorporates corrected gestational age best predicts the diagnosis of NEC.

ABO hemolytic disease of the fetus and newborn: thirteen years of data after implementing a universal bilirubin screening and management program.

OBJECTIVE: ABO hemolytic disease occurs among neonates with blood groups A or B delivered to group O women. Extreme neonatal hyperbilirubinemia due to ABO disease has been reported, but its frequency is not well known. We sought to determine the odds of developing severe ABO hemolytic disease in the 13 years since adopting universal bilirubin screening/management in the Intermountain Healthcare system. STUDY DESIGN: We conducted a retrospective analysis of neonates born between 2004 and 2016, defining "severe hemolytic disease" as; (1) total serum bilirubin (TSB) >25 mg/dL, or (2) hospital readmission for jaundice, or (3) bilirubin encephalopathy. Neonates born to group O (+) mothers were included and considered either; (1) Controls (not at risk for ABO disease because they were group O), (2) Study subjects (at risk for ABO disease because they were group A or B). RESULTS: Of 400,531 live births, 47% were to group O women; 86% of whom were group O (+). Overall, 42,529 (27%) neonates born to group O (+) women had their blood group determined; 29,729 (68%) were O, 10,682 (25%) A, and 3109 (7%) B. Peak TSBs during the first 10 days were higher in group A (11.0 ± 4.2 mg/dL) and B (11.5 ± 4.3) than group O neonates (10.3 ± 4.1). However the relative risks of a TSB ≥25 mg/dL, readmission for jaundice, or kernicterus, were the same in the control vs. study groups. CONCLUSIONS: In our health system, severe hemolytic disease in neonates born to group O (+) woman is not more likely in group A or B neonates than in controls (group O). We recognize that in other practices, particularly those who do not have a universal bilirubin screening/management program, ABO hemolytic disease severity might be different than in our system.

The iron status at birth of neonates with risk factors for developing iron deficiency: a pilot study.

OBJECTIVE: Small-for-gestational-age (SGA) neonates, infants of diabetic mothers (IDM) and very-low-birth weight premature neonates (VLBW) are reported to have increased risk for developing iron deficiency and possibly associated neurocognitive delays. STUDY DESIGN: We conducted a pilot study to assess iron status at birth in at-risk neonates by measuring iron parameters in umbilical cord blood from SGA, IDM, VLBW and comparison neonates. RESULTS: Six of the 50 infants studied had biochemical evidence of iron deficiency at birth. Laboratory findings consistent with iron deficiency were found in one SGA, one IDM, three VLBW, and one comparison infant. None of the infants had evidence of iron deficiency anemia. CONCLUSIONS: Evidence of biochemical iron deficiency at birth was found in 17% of screened neonates. Studies are needed to determine whether these infants are at risk for developing iron-limited erythropoiesis, iron deficiency anemia or iron-deficient neurocognitive delay.

Recombinant tissue plasminogen activator to restore catheter patency: efficacy and safety analysis from a multihospital NICU system.

OBJECTIVE: In 2001, the US Food and Drug Administration approved recombinant tissue plasminogen activator (alteplase, Cathflo Activase) to reestablish patency of central catheters occluded, presumably, by a fibrin clot. We conducted a multicenter quality improvement study to determine the value of this procedure in our Neonatal Intensive Care Unit (NICUs), including analyses of efficacy, safety and costs. STUDY DESIGN: We conducted a retrospective quality analysis of neonates in level III NICUs, who received alteplase for the purpose of reestablishing patency of occluded central catheters. RESULTS: Alteplase was administered to 169 neonates, each given one to four doses, totaling 205 episodes of administration. The most common type of catheter where alteplase was used was percutaneously inserted central catheter (PICC) lines (78% of uses), 8% were umbilical venous catheters (UVCs), 6% arterial lines, 5% chest tubes and 3% other catheters. Postnatal age at first dose ranged from 0 to 132 days (median, 12); dosed patients were 22 to 41 weeks gestation at birth (median, 31). Fifty-eight percentage of administrations restored catheter function. Success was more likely at younger postnatal age (10±2 days old in successful vs 14±1 days in unsuccessful treatments; P=0.023). Seventy-two percentage of the re-canalized catheters remained functional until they were no longer needed (2 to 30 days later). Nine percentage of episodes were treated with a second dose 1 to 17 days later for re-occlusion and 50% of those were successful. Bleeding consequences were identified in only one case, where three separate lines were treated (chest tube, PICC and UVC) within a 6-h period. Costs to the health system of doses, minus savings to the system by not needing to replace lines, averaged a net of $34 per dose. CONCLUSIONS: The apparent safety and favorable value analysis prompted us to develop a consistent approach to alteplase usage in the Intermountain Healthcare NICUs, using the data in this report to standardize the guidelines across our health system.

Elevated fecal calprotectin levels during necrotizing enterocolitis are associated with activated neutrophils extruding neutrophil extracellular traps.

OBJECTIVE: Neonates with necrotizing enterocolitis (NEC) have higher calprotectin levels in stool than do healthy neonates. However, it is not known whether high stool calprotectin at the onset of bowel symptoms identifies neonates who truly have NEC vs other bowel disorders. STUDY DESIGN: Neonates were eligible for this study when an x-ray was ordered to 'rule-out NEC'. Stool calprotectin was quantified at that time and in a follow-up stool. Each episode was later categorized as NEC or not NEC. The location of calprotectin in the bowel was determined by immunohistochemistry. RESULTS: Neonates with NEC had higher initial and follow-up stool calprotectin levels than did neonates without NEC. Calprotectin in bowel from neonates with NEC was within neutrophil extracellular traps (NETs). CONCLUSION: At the onset of signs concerning for NEC, fecal calprotectin is likely to be higher in neonates with NEC. Calprotectin in their stools is exported from neutrophils via NETs.

Comparing automated vs manual leukocyte differential counts for quantifying the 'left shift' in the blood of neonates.

OBJECTIVE: The neutrophil 'left shift' can be measured via the immature to total (I/T) neutrophil ratio or the absolute bands per µl using a manual differential count. It can also be measured from an automated differential count by the immature granulocyte percentage (IG%) or the absolute IG per µl. In neonates, it is unknown if the manual or automated differential count is superior. STUDY DESIGN: We directly compared complete blood counts (CBCs) with manual and automated differential counts from infants <90 days old, and documented whether or not each neonate was infected. We developed reference intervals for I/T ratio, bands per µl, IG% and IG per µl using values from non-infected neonates. RESULTS: The database had 10 714 CBCs. The upper reference interval for I/T ratio was 0.29 in the first 48 h and 0.31 thereafter; bands per µl was 3710 µl(-1) in the first 48 h and 1785 µl(-1) thereafter. IG% was 6.2% then 4.2%; IG per µl was 1460 µl(-1) then 613 µl(-1). Statistical performances of the four methods were equivalent for identifying infection. CONCLUSIONS: We developed reference intervals for four methods of quantifying a neonate's 'left shift'. The information from automated differentials is not inferior to that from manual differentials in identifying infections, but automated differentials have the advantages of a larger sample size, being less expensive, and faster performance times.

Whole-blood viscosity in the neonate: effects of gestational age, hematocrit, mean corpuscular volume and umbilical cord milking.

OBJECTIVE: The American College of Obstetrics and Gynecology Committee on Obstetric Practice recently endorsed delayed cord clamping at preterm delivery. However, the committee report expressed the concern by some practitioners that delayed clamping or cord milking might induce hyperviscosity in preterm neonates. To address this issue we: (1) established reference ranges for whole-blood viscosity among preterm neonates (viscosity reference ranges had previously been reported only in term neonates) and (2) determined the effect of umbilical cord milking at deliveries <32 weeks gestation on subsequent blood viscosity measurements. STUDY DESIGN: This was a prospective study in two Neonatal Intensive Care Units. Blood viscosity was measured using a cone and plate viscometer. Associations were sought with gestation, hematocrit/hemoglobin and mean corpuscular volume. Reference ranges were determined for preterm infants <32 weeks gestation. Then, after umbilical cord milking at deliveries <32 weeks, viscosity was measured at birth and again during the 12 h after birth. In neonates with viscosities >95th % range, we sought signs of hyperviscosity (plethora, hypotonia, hypoglycemia, hyperbilirubinemia, thrombocytopenia). RESULT: Viscosity at higher and lower sheer rates were linearly related (n=32, r=0.971). Within the range of hematocrits measured (29-63%) viscosity correlated with hematocrit (r=0.877) and hemoglobin (r=0.853) but not with erythrocyte size (r=0.179). Viscosity was related to gestational age (n=58), primarily due to the lower hematocrits at lower gestational ages. In the 12 h after cord milking viscosity ranged from 3.1 to 9.5 centipoise. Three of twenty preterm, neonates had viscosities >95th % reference range. However, all values were well below those where hyperviscosity is defined in term neonates and all lacked features of hyperviscosity. CONCLUSION: Cord blood viscosity is directly proportional to hematocrit/hemoglobin, lower at early gestation and not associated with erythrocyte size. Cord milking at preterm delivery is associated with a low risk of clinical hyperviscosity. Practioners should not refrain from cord milking at preterm delivery because of a concern that it will commonly cause neonatal hyperviscosity.

Using umbilical cord blood for the initial blood tests of VLBW neonates results in higher hemoglobin and fewer RBC transfusions.

OBJECTIVE: We previously described a method for reducing early phlebotomy losses from very low birth weight (VLBW) neonates by obtaining the initial blood tests from otherwise discarded fetal blood from the placenta. In the present study we sought to; (1) measure the feasibility of performing this method in actual practice, (2) test the hypothesis that this method would result in higher hemoglobin concentrations and lower erythrocyte transfusion rates in the first week after birth. METHODS: We conducted two studies in three Intermountain Healthcare NICUs. The first was a feasibility analysis involving 96 VLBW neonates, measuring the success of obtaining the NICU admission laboratory blood tests this way. The second study used case-control methodology to test the hypothesis that this method would result in a higher blood hemoglobin 12 to 24 h after birth, and a lower proportion receiving an erythrocyte transfusion in the first week. RESULT: In 91 of 96 VLBW neonates (95%) the initial blood tests were successfully obtained with this method. The success rate was not diminished by delayed cord clamping or cord milking, as it was successful in 35 of 36 (97%) such instances. Cases and controls were well matched on demographic and level of illness comparisons. Among cases the hemoglobin generally increased between birth and 12 to 24 h later, but among controls the hemoglobin generally decreased (P<0.05). In the week following birth fewer cases received vasopressors (P<0.01) and erythrocyte transfusions (P<0.001). CONCLUSION: We judge that it is feasible to collect the initial blood tests of VLBW neonates using otherwise discarded umbilical cord/placental blood, in that this can be accomplished in about 95% of VLBW deliveries. This method, which can be used in addition to either delayed clamping of the umbilical cord or cord milking, results in higher hemoglobin concentrations, less vasopressor use and fewer transfusions in the first week.

Severe neonatal anemia from fetomaternal hemorrhage: report from a multihospital health-care system.

OBJECTIVE: The incidence of fetomaternal hemorrhage that is severe enough to cause neonatal anemia is not known. Owing to its relative rarity, much of the literature describing this condition is in the form of case reports and small case series. We performed a large, muiticentered, sequential, case series to determine the incidence, antecedents and outcomes. STUDY DESIGN: From the multicentered databases of Intermountain Healthcare, we obtained records of all neonates with hematocrit (Hct) <30% or hemoglobin (Hgb) <10 g dl(-1) on the day of birth, who had Kleihauer-Betke staining or flow cytometric evidence of fetomaternal hemorrhage. RESULT: Among 219,853 live births, 24 had anemia with evidence of fetomaternal hemorrhage (incidence estimate, 1 per 9160 live births). The initial Hgb ranged from 1.4 to 10.2 g dl(-1) (Hct 29.8%). The initial Hgb was <7 g dl(-1) in 18 (67%), <5 g dl(-1) in 12 (50%) and was <3 g dl(-1) in 7 (29%). All 7 mothers in whom neonatal Hgb was <3 g dl(-1) had reported absent fetal movement, as did 13 of 18 mothers when the initial Hgb was <7 g dl(-1). Outcomes were poorer in those with the lowest initial Hgb; in the two lowest, one died on day 1, and the other developed a grade 4 intraventricular hemorrhage (IVH). The adverse outcomes of death, IVH, periventricular leukomalacia, bronchopulmonary dysplasia or hypoxic-ischemic encephalopathy were common; occurring in 71% (17 of the 24), including all with an initial Hgb <5 g dl(-1) and all born at ≤35 weeks of gestation. CONCLUSION: Fetomaternal hemorrhage is a rare but sometimes devastating condition. Those with fetomaternal hemorrhage and an initial Hgb of <5 g dl(-1) are expected to need resuscitation at birth, to receive emergent transfusion support and to be at risk for death and major morbidities. Antenatal suspicion of this diagnosis should occur when absent fetal movement is reported. Improvements in rapid diagnosis are needed to prepare first responders and transfusion services.

Fulminant necrotizing enterocolitis in a multihospital healthcare system.

OBJECTIVE: A subset of necrotizing enterocolitis (NEC) cases is fulminant, characterized by rapid progression to death with massive bowel necrosis found at laparotomy or autopsy. We sought to identify and report all such cases in a multihospital healthcare system during the past 9 years and to characterize this entity using case-control methodologies. STUDY DESIGN: This was a multicentered, cross-sectional, historic cohort study conducted using Intermountain Healthcare hospital patient data. All neonates who died of NEC within 48 h of onset, during 2001 to 2009, were compared with two matched control groups: (1) demographically matched controls who developed non-fulminant NEC, (2) demographically matched controls that did not develop NEC. RESULT: During this period, 2 71 327 live births occurred in the Intermountain Healthcare hospitals. Of these, 318 had a diagnosis of NEC (Bell stage ≥II). Also during this period, 205 other neonates were transferred into an Intermountain hospital for treatment of NEC. Of these 523 NEC cases, 35 (6.7%) had a fulminant course. Compared with the non-fulminant cases, the fulminant group were born at lower weight (1088±545 vs 1652±817 g, P=0.000) and earlier gestational age (27.5±3.3 vs 31.1±4.4 weeks, P=0.000), and were more likely to have: (1) radiographic evidence of portal venous air (P=0.000), (2) hematocrit <22% (P=0.000), (3) increase in feeding volume >20 ml/kg/day (P=0.003), (4) immature to total (I/T) neutrophil ratio >0.5 (P=0.005), (5) blood lymphocyte count <4000/µl (P=0.018), (6) an increase in concentration of human milk fortifier within 48 h before developing NEC (P=0.020). CONCLUSION: Portal venous air, anemia, rapid feeding escalation, a high I/T neutrophil ratio, a low lymphocyte count and recent increases in fortifier may all be associated with fulminant NEC.

Neonates presenting with bloody stools and eosinophilia can progress to two different types of necrotizing enterocolitis.

OBJECTIVE: We hypothesized that neonates with bloody stools and concomitant eosinophilia are likely to have atopic enteropathy rather than necrotizing enterocolitis (NEC). STUDY DESIGN: This was a retrospective cross-sectional study using electronic medical records and paper charts. Records of neonates admitted to any Intermountain Healthcare NICU between 1 January 2005 and 30 June 2010 were eligible if 'bloody stools' were listed in any archive. Qualifying records were divided into two groups depending on whether or not within 72 h of passing bloody stool eosinophil counts were above the 95th percentile reference range limit for age. RESULT: Bloody stools were identified in 275 predominantly Caucasian neonates. Fifty-four of these had eosinophilia and 221 had normal eosinophil counts. Those with eosinophilia were born at a slightly younger gestational age (31.3 ± 4.6 vs 32.6 ± 4.0 weeks, mean ± s.d., P=0.032). Contrary to our hypothesis, those with eosinophilia did not have a lower rate of pneumatosis or bowel resection, or death ascribed to NEC. Eosinophilia was more common among those who had a red blood cell (RBC) transfusion within 48 h before passing bloody stools (P<0.001). Those with a recent RBC transfusion were the only neonates to have NEC surgery or to die from NEC. Preceding the bloody stools, those with no antecedent transfusion had been fed a larger volume (P=0.014), and had trends toward receiving calorically enriched feedings (P=0.055) and recent addition of human milk fortifier (P=0.060). Eosinophil counts following RBC transfusion tended to increase for 3-6 days, but when bloody stools were not preceded by transfusion the eosinophil counts were more static over that period. CONCLUSION: In this predominantly Caucasian group of neonates with bloody stools, the presence of eosinophilia did not identify a benign condition distinct from NEC. A total of 44% of these neonates had transfusion-associated NEC. Eosinophils could have a previously unrecognized role in the pathogenesis of this NEC subtype.

Effect of ampicillin on bleeding time in very low birth-weight neonates during the first week after birth.

OBJECTIVE: On the day of birth, the bleeding time of very low birth-weight (VLBW, <1500 g) neonates is generally prolonged, compared with term neonates. However, their bleeding time generally improves (shortens) over the next 7 to 10 days. Ampicillin can prolong the bleeding times of term and late preterm neonates, but its effect on VLBW neonates, who already have a somewhat prolonged bleeding time initially, is not known. STUDY DESIGN: This was a prospective, single-centered, paired, before vs after test of the effect of ampicillin on template bleeding time and PFA-100 time (platelet function analyzer). Ampicillin was dosed at every 12 h intravenously, but decisions about discontinuation were made by the responsible clinician, independent of this study. RESULT: A total of 20 VLBW neonates were studied. They ranged from 23- to 30-weeks gestation at birth and weighed 500 t 1410 g. Initial bleeding times averaged 166 s (95% CI, 138 to 194) and initial PFA-100 times averaged 119 s (95% CI, 90 to 148). In all, 10 had ampicillin dosing stopped after a shorter course (4 to 7 doses) and 10 had it continued for a longer course (10 to 15 doses). Blood cultures were sterile in all 20, and no differences in laboratory or clinical features were found between those treated with a shorter vs longer course. After stopping the ampicillin following a short course the bleeding times and PFA-100 times were similar to the initial values. However, after a longer course the bleeding times were prolonged by an average of 2 min, to 284 s (95% CI, 242 to 326; P=0.001 vs initial). The PFA-100 times also trended longer by an average of 44 s (P=0.07). The number of doses of ampicillin received in the first week correlated with the degree of prolongation in bleeding time (r=0.68). CONCLUSION: Over the first week of life, a period when the bleeding time of VLBW neonates normally shortens, the opposite occurred (the bleeding time lengthened) if ≥ 10 doses of ampicillin were administered.

Pyruvate kinase deficiency as a cause of extreme hyperbilirubinemia in neonates from a polygamist community.

Neonatal hemolytic jaundice is a risk factor for kernicterus. Pyruvate kinase (PK) deficiency is a rare cause of neonatal hemolytic jaundice, with a prevalence estimated at 1 case per 20,000 births in the United States, but with a higher prevalence among the Amish communities in Pennsylvania and Ohio. We discovered four neonates with PK deficiency born in a small community of polygamists. All four had early, severe, hemolytic jaundice. PK deficiency should be considered in neonates with early hemolytic, Coombs-negative, non-spherocytic jaundice, particularly in communities with considerable consanguinity. Such cases should be recognized early and managed aggressively to prevent kernicterus.

Antecedents of Bell stage III necrotizing enterocolitis.

OBJECTIVE: New biopharmaceuticals hold promise for preventing or treating necrotizing enterocolitis. However, it is unclear whether any such biopharmaceutical that requires enteral administration could be administered using an 'early-treatment' paradigm. This study was undertaken to assess this issue based on data from every case of Bell stage III NEC cared for during the past 7 years at Intermountain Healthcare. STUDY DESIGN: Patients with Bell stage III NEC were identified from electronic medical record repositories and the diagnosis was validated using operative reports. Electronic and paper records of each patient were then used to identify potential clinical and laboratory antecedents occurring within the 48 h period preceding the diagnosis of NEC. RESULT: One hundred eighteen patients had Stage III NEC. The earliest recognized antecedents were nonspecific for NEC (apnea/bradycardia, skin mottling and irritability). These were recorded at 2.8+/-2.1, 4.5+/-3.1 and 5.4+/-3.7 (mean+/-s.d.) hours, respectively, before NEC was diagnosed. The most commonly identified gastrointestinal antecedents were blood in the stools, increased abdominal girth and elevated pre-feeding gastric residuals or emesis. These were identified 2.0+/-1.9, 2.8+/-3.1 and 4.9+/-4.0 h before NEC was recognized. Thirty-eight percent had a blood transfusion (18+/-12 h) preceding the NEC. Tachycardia, tachypnea, hypotension and diarrhea were rarely identified as antecedents and no consistent laboratory antecedents were discovered. CONCLUSION: We judge that an 'early treatment of NEC' paradigm testing any pharmacological agent that must be administered enterally is not feasible. The first recognized antecedents of Bell stage III NEC are nonspecific for gastrointestinal pathology and insufficient time exists for dosing between the first gastrointestinal signs and placement of the gastric decompression tube.

Isolated elevated blood neutrophil concentration at altitude does not require NICU admission if appropriate reference ranges are used.

OBJECTIVE: The Intermountain Healthcare hospitals use a clinical pathway algorithm for early-onset infection, which is based on the 2002 Centers for Disease Control and Prevention (CDC) guidelines for perinatal group B streptococcal disease. As part of this pathway, neonates in the well baby nursery, who seem to be well but have risk factors for infection, receive a 'limited laboratory evaluation including a CBC', and if the complete blood cell count (CBC) is abnormal, antibiotic treatment and neonatal intensive care unit (NICU) monitoring are initiated. We recently found that reference ranges for absolute neutrophil counts (ANCs) are much wider at our altitude (4800 to 5000 ft) than at sea level. On this basis, we speculated that some well babies with risk factors for infection are mistakenly judged as having an abnormal CBC, and are unnecessarily admitted to the NICU. STUDY DESIGN: This was a retrospective observational cohort study of neonates of >37 weeks gestation admitted to either of two Intermountain Healthcare NICUs for intravenous antibiotic treatment during a recent 36-month period. RESULTS: During the study period 3217 patients were admitted to the two NICUs, 1049 (32.6%) of which were born at>37 weeks gestation. Of these, 14 (1.3%) were found to have been admitted to the NICU on the basis of an abnormal CBC (elevated ANC), when in retrospect, using the appropriate ANC chart, their CBCs were completely normal. None of the 14 neonates had a leukocyte left shift (immature to total neutrophil ratio >0.3) or thrombocytopenia. None were treated with supplemental oxygen or mechanical ventilation in the NICU. All 14 had sterile blood cultures. All had antibiotics stopped in 48 to 72 h, and all were discharged home as well babies. CONCLUSION: We identified 14 neonates who, while in the well baby nursery, were found to have risk factors for early-onset infection, but did not seem to be infected, and were subsequently admitted to a NICU for intravenous antibiotic treatment and monitoring under the mistaken impression that they had an abnormal CBC. We maintain that use of an appropriate neutrophil reference range chart can reduce NICU admissions and can limit unnecessary antibiotic exposure.

Adherence to NICU transfusion guidelines: data from a multihospital healthcare system.

OBJECTIVE: We critically reviewed every NICU blood component transfusion (packed erythrocytes, platelets, frozen plasma (FP) and cryoprecipitate) administered during a one-year period. This was done to determine the proportion of transfusions given out of compliance with the Intermountain Healthcare transfusion guidelines, and to look for patterns of non-compliance that could be addressed by quality improvement measures. STUDY DESIGN: A detailed review was made of every transfusion administered to patients with a date of birth of 1 January 2006 through 31 December 2006, in any of three level III, perinatal-center-associated NICUs within Intermountain Healthcare. RESULT: During 2006 the three NICUs cared for 1759 neonates. Seventeen percent of these received one or more (median 3) erythrocyte transfusions, 4% received one or more (median 3) platelet transfusions, 6% received one or more (median 1) FP infusions and 2% received cryoprecipitate (median 1 dose). Seventy percent of the erythrocyte transfusions were given in compliance with the guidelines, as were 69% of the platelet transfusions, 65% of the FP transfusions and 94% of the cryoprecipitate administrations. Patients who received large numbers of transfusions were more likely to receive transfusion that violated the guidelines. Forty-five percent of patients who received 1 to 3 transfusions received all transfusions within guidelines. However, only 18% of patients who received 4 to 10 transfusions received all within guidelines. No patient who received >10 transfusions received all within the guidelines. Erythrocyte transfusions given early in the hospital course were likely to be within guidelines; 72% (588/818) in the first 29 days were compliant with guidelines, but compliance fell to 61% (144/237) for transfusions administered after 29 days (P=0.002). About half of the platelet transfusions given early in the hospital course were in violation of guidelines, but after day 9, 83% of platelet transfusions were compliant with guidelines (P=0.000). CONCLUSION: Opportunities exist in our healthcare system to improve compliance with our transfusion guidelines. Such opportunities are greatest among neonates receiving multiple transfusions, among those receiving erythrocyte transfusions late in their NICU course and among those receiving platelet transfusions early in their NICU course.

Necrotizing enterocolitis during the first week of life: a multicentered case-control and cohort comparison study.

OBJECTIVE: Necrotizing enterocolitis (NEC) is rare during the first week of life; most cases occur after 2 to 4 weeks. We hypothesized that when NEC develops in the first week, certain predisposing factors and feeding practices are identifiable. To test this, we sought to identify every case of NEC diagnosed during the first week within the Intermountain Healthcare system during the most recent 6-year period. STUDY DESIGN: Data were collected from neonates admitted to any Intermountain Healthcare neonatal intensive care unit (NICU) with a date of birth from 1 January 2001 through 31 December 2006. Electronic and paper records were obtained for all with a diagnosis of NEC (Bell stage >or=II) within the first 168 h. X-rays, physician notes, nursing records, laboratory reports and operative reports were subjected to critical review to reexamine the diagnosis of NEC. Among those with confirmed NEC, we recorded underlying conditions and every feeding given prior to the diagnosis of NEC. Comparisons were made with patients that did not develop NEC, yet were cared for in the same NICUs, during the same period of time, and of the same gestational ages. RESULT: A total of 28 neonates were identified electronically as having NEC during the first week. Critical review confirmed this in 21, but 5 were determined at laparotomy to have had spontaneous intestinal perforation, and 2 others were found on surgical reports to have had a congenital infarction of the colon. Total 20 of the 21 confirmed cases developed NEC while in a NICU being treated for another condition. The exception was a small-for-gestational-age neonate in a well baby nursery. Compared to 6100 controls, the 21 with early NEC were more likely to have had a meconium-positive test for illicit drug exposure (P<0.005), early onset sepsis (P<0.034) and respiratory distress (P<0.039). They were less likely than case-controls to have been fed human milk (P=0.003) and were more likely to have been fed formula exclusively (P=0.019). None who were fed human milk exclusively developed early NEC. Twelve of the twenty-one were fed (by gavage or bottle) amounts exceeding the upper limit of volumes taken by breastfed neonates. CONCLUSION: We speculate that the prevalence of NEC during the first week could be reduced by identifying at-risk patients, feeding them human milk exclusively for the first week and using feeding volumes that do not exceed that taken by healthy breastfed neonates.

Do platelet transfusions in the NICU adversely affect survival? Analysis of 1600 thrombocytopenic neonates in a multihospital healthcare system.

OBJECTIVE: Several studies have indicated a correlation between the number of platelet transfusions received by newborn intensive care unit (NICU) patients and the mortality rate. The number of platelet transfusions might be a marker for level of illness, and thus predictive of mortality. However, an alternative hypothesis is that multiple platelet transfusions themselves are harmful in this population. STUDY DESIGN: We evaluated data from all thrombocytopenic neonates cared for in the Intermountain Healthcare NICUs in the past 4 years, seeking associations between the lowest platelet count recorded, number of platelet transfusions received and mortality rate. We also conducted a sensitivity analysis to examine the hypothesis that platelet transfusions were responsible for some fraction of the mortality rate. RESULT: Transfusion and outcome data were examined from 1600 thrombocytopenic NICU patients. At any level of platelet count, some patients received platelet transfusions but others did not. However, at all levels of platelet count, those that received platelet transfusions had a higher mortality rate. Neonates not given any platelet transfusions had a mortality rate of 2%, those with 1 or 2 transfusions had a mortality rate of 11% (P<0.001); those with >10 had a mortality rate of 35% (P<0.001); and those with > or = 20 had a mortality rate of 50% (P<0.001). A sensitivity analysis suggested that the platelet transfusions themselves were very likely responsible for some fraction of the increasing mortality rate. CONCLUSION: The number of platelet transfusions administered in the NICU predicts the mortality rate. Some of this correlation is ascribable to unknown and unmeasured factors such as level of illness. However, the present data and the sensitivity analysis both suggest that some of this correlation is due to harmful effects of multiple platelet transfusions in this group of patients.

Necrotizing enterocolitis in term neonates: data from a multihospital health-care system.

OBJECTIVE: In the past 5(1/2) years, 30 term or near-term neonates in the Intermountain Healthcare system developed necrotizing enterocolitis (NEC) Bell's stage > or =II. We sought to identify possible explanations for why these patients developed NEC, by comparing them with 5847 others that did not develop NEC, from the same hospitals and of the same gestational ages, cared for during the same 5 1/2-year period. STUDY DESIGN: Data were collected from neonates admitted to any of the Intermountain Healthcare NICUs with a birth date from 1 January 2001 to 30 June 2006, and a gestational age >36 weeks. A variety of patient features and feeding practices were compared between those that did vs did not develop NEC. RESULT: Forty-one neonates >36 weeks gestation were listed in the discharge records as having NEC of Bell's stage II or higher. However, on review of these 41 medical records, 11 were seen to have had NEC of Bell's stage I, whereas the remaining 30 had radiographs and clinical courses indicative of Bell's stage > or =II. Those 30 formed the basis of this study. Twenty-eight of the 30 developed NEC after having been admitted to an NICU for some other reason; the other two developed NEC at home, within 2 days of being discharged from an NICU. The 30 that developed NEC were more likely than the 5847 that did not develop NEC, to have congenital heart disease (P=0.000), polycythemia (P=0.002), early-onset bacterial sepsis (P=0.004) or hypotension (P=0.017). All 30 received enteral feedings before NEC developed; 29 were fed either artificial formula or a mixture of formula and breast milk. The one that was exclusively fed human milk was fed human milk with added fortifier (24 cal/oz). The 30 that developed NEC were more likely to be fed formula exclusively (P=0.000). Seven of the 30 had a laparotomy for NEC; two of the seven had total bowel necrosis and support was withdrawn. The other five had perforations and bowel resections. The mortality rate was 13% (4/30). CONCLUSION: In our series, NEC among term or near-term neonates was exclusively a complication developing among patients already admitted to a NICU for some other reason. We speculate that the combination of reduced mesenteric perfusion and feeding with artificial formula were factors predisposing them to develop NEC.