A neonate with congenital amegakaryocytic thrombocytopenia associated with a chromosomal microdeletion at 21q22.11 including the gene RUNX1.

We observed a neonate who had severe thrombocytopenia wherein evaluations for neonatal immune-mediated thrombocytopenia and congenital infections were negative, and the marrow findings were consistent with congenital amegakaryocytic thrombocytopenia (CAMT). A genomic microarray identified a microdeletion at 21q22.11 including the gene RUNX1. Two somewhat similar cases were recently reported, but with multiple congenital anomalies that are not present in our case. We propose that a 21q22 deletion resulting in RUNX1 haploinsufficiency can produce a phenotype similar to CAMT with various associated anomalies depending on which adjacent genes are absent or disrupted.

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.

Thrombocytosis in neonates and young infants: a report of 25 patients with platelet counts of > or = 1000000 microl(-1).

OBJECTIVE: Thrombocytosis has been reported in neonates and young infants, but little is known of its prevalence, timing of onset, associated conditions, sequelae and outcomes. To better understand this condition, we used the data repositories of a multi-hospital health-care system to identify all individuals or=1000000 microl(-1). STUDY DESIGN: We identified all infants with extreme thrombocytosis (using the Sutor definition of a platelet count of >or=1000000 microl(-1)) during the period of January 2003 through December 2008 in any Intermountain Healthcare facility. We obtained the information provided in this report from electronic and paper records. RESULT: Among 40 471 infants who had one or more platelet counts performed in this period, 25 had extreme thrombocytosis. No cases were identified in the first week after birth, 40% were recognized between the second and fourth weeks and 40% between the fifth and eighth week. The prevalence of thrombocytosis had no relationship with birth weight or gestational age but a slight predominance of female patients (15/25) was noted. In all, 26 episodes were found among the 25 infants: 12 episodes involved an antecedent infectious disease, 8 had an antecedent surgical procedure, 4 had the anemia of prematurity and 1 each had congenital adrenal hyperplasia and opiate withdrawal syndrome. No pathological thromboses or hemorrhages or other sequelae were detected and all episodes resolved with no deaths. CONCLUSION: The thrombocytosis cases that we report were all consistent with reactive thrombocytosis (also known as secondary thrombocytosis); none seemed to be essential (primary) thrombocytosis. We speculate that the pathogenesis involves increased platelet production due to megakaryopoietic stimulators induced by an infectious or inflammatory condition. From this series and previous reports, young infants with platelet counts up to 1300000 microl(-1) do not seem to have a significant risk of thrombotic or hemorrhagic problems, and do not generally require anti-platelet or cytoreductive treatment.

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.

Attitudes of NICU professionals regarding feeding blood-tinged colostrum or milk.

OBJECTIVE: Mothers of neonatal intensive care unit (NICU) patients sometimes bring expressed milk that is blood tinged to the NICU. In certain instances, the blood contamination appears minimal, whereas in others, the milk is quite dark pink. We have observed inconsistencies in practice regarding whether or not to feed blood-tinged colostrum or milk to NICU patients. We know of no evidence that establishes best practice in this area, and thus we sought to determine attitudes of NICU professionals on which to base a potentially best practice. STUDY DESIGN: We conducted a web-based anonymous survey of attitudes of NICU professionals at Intermountain Healthcare regarding feeding blood-tinged expressed milk to NICU patients. These professionals included neonatologists, neonatal nurse practitioners, NICU nurses, NICU dieticians and lactation consultants. RESULT: Survey results were returned from 64% (426 of 667) of those to whom it was sent. A total of 75% of respondents reported that their practice was NOT to feed the blood-tinged milk illustrated in the figure as sample 2, and nearly all respondents (98%) reported that they would NOT feed the milk illustrated as sample 3. The majority of the neonatologists (56%) and the lactation consultants (58%) recommended feeding moderately bloody milk (sample 2), whereas only 22% of the neonatal nurse practitioners (NNPs), NICU nurses and NICU dieticians recommended feeding such samples (<0.001). The most frequently selected reason for NOT feeding blood-tinged milk was that it would likely cause gastrointestinal upset and feeding intolerance (selected by 77%). The majority (87%) overestimated the amount of blood contaminating a milk sample (sample 3). CONCLUSION: As colostrum and human milk feedings can be of value to NICU patients, evidence should be assembled to document whether feeding blood-tinged samples indeed have the problems listed by the survey respondents. Such evidence is needed to enable informed decisions involving the benefits vs risks of feeding blood-tinged expressed milk to NICU patients.

Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system.

OBJECTIVE: Identifying a platelet count as abnormal (thrombocytopenia or thrombocytosis) can facilitate recognizing various disease states. However, the published reference ranges for platelet counts in neonates may be imprecise, as they were generated from relatively small sample sizes and compiled before modern platelet enumeration methods. STUDY DESIGN: We derived new neonatal reference ranges for platelet counts and mean platelet volume (MPV) measurements using electronic data accumulated during a recent 6-year period from a multihospital healthcare system. RESULT: Platelet counts were obtained between the first and the 90th day after birth, from 47,291 neonates delivered at 22 to 42 weeks gestation. The first platelet counts obtained in the first 3 days of life, increased over the range of 22 to 42 weeks gestation. In those born < or =32 weeks gestation, the lower reference range (5th percentile) was 104,200 microl(-1), but it was 123,100 microl(-1) in late-preterm and -term neonates. Advancing postnatal age had a significant effect on platelet counts; during the first 9 weeks, the counts fit a sinusoidal pattern with two peaks; one at 2 to 3 weeks and a second at 6 to 7 weeks. The upper limit of expected counts (95th percentile) during these peaks were as high as 750,000 microl(-1). CONCLUSION: The figures herein describe reference ranges for platelet counts and MPV determinations of neonates at various gestational ages during their first 90 days. Expected values differ substantially from the 150,000 microl(-1) to 450,000 microl(-1) range previously used to define neonatal thrombocytopenia and thrombocytosis. The new definitions will render the diagnoses of neonatal thrombocytopenia and thrombocytosis less commonly than when the old definitions were used, because the new ranges are wider than 150,000 microl(-1) to 450,000 microl(-1).

Using umbilical cord tissue to detect fetal exposure to illicit drugs: a multicentered study in Utah and New Jersey.

OBJECTIVE: We assessed umbilical cord tissue as a means of detecting fetal exposure to five classes of drugs of abuse. STUDY DESIGN: In a multicentered study in Utah and New Jersey, we collected umbilical cord tissue when high-risk criteria were met for maternal illicit drug use. The deidentified umbilical cord specimens were analyzed for five drug classes: methamphetamine, opiates, cocaine, cannabinoids and phencyclidine. For each umbilical cord specimen, an enzyme-linked immunosorbent assay (ELISA)-based screening test was compared with a 'gold standard' test, consisting of gas or liquid chromatography tandem mass spectrometry. RESULT: A total of 498 umbilical cord samples were analyzed of which 157 (32%) were positive using mass spectrometric detection. The sensitivity and specificity of the ELISA-based test for each class of drugs tested were as follows: methamphetamine 97 and 97%, opiates 90 and 98%, cocaine 90 and 100%, cannabinoids 96 and 98% and phencyclidine (only 1 of the 498 umbilical cord sample was positive for phencyclidine) 100 and 100%. CONCLUSION: We judge that the performances of the ELISA-based tests are sufficient for clinical testing of fetal exposure to methamphetamine, opiates, cocaine and cannabinoids. Studies obtained on umbilical cord tissue can result in a more rapid return to the clinician than meconium testing, because waiting for meconium to be passed sometimes requires many days. Moreover, in some cases the meconium is passed in utero making collection impossible, whereas umbilical cord tissue should always be available for drug testing.

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.

Hematological abnormalities during the first week of life among neonates with trisomy 18 and trisomy 13: data from a multi-hospital healthcare system.

Limited information is available on the expected hematological values of newborn infants with trisomy 18 or trisomy 13 syndromes. About 50% of patients with these conditions survive beyond the first week of life, and some have complete blood counts (CBCs) obtained to assist in medical management. We tabulated all CBC data that had been obtained on patients with either trisomy, during their first week of life, using data from an 18 hospital healthcare system. We posited that describing the CBC findings would assist clinicians in providing care for these patients who survive beyond the first days. During the period of January 1, 2001 through December 31, 2006, 174,480 live births were recorded at the 18 hospitals. Trisomy 18 was recognized in 28 (prevalence estimate, 1 in 6,231) and trisomy 13 in 22 (prevalence estimate, 1 in 7,931). Twenty-four of these had one or more CBCs obtained before the seventh day. Thrombocytopenia was the most common hematological abnormality detected, occurring in 83% of those with trisomy 18 and 75% of those with trisomy 13. Three patients with trisomy 18, and 1 with trisomy 13, received platelet transfusions. The second most commonly detected abnormality was neutrophilia. Eighty-three percent of neonates with trisomy 13, and 42% with trisomy 18, had neutrophil concentrations above the upper limit of normal for age. Abnormal erythrocyte values were the third most common hematological abnormalities detected. These were much more common among neonates with trisomy 18. Only 43% of patients with trisomy 18 had normal erythrocyte values; anemia was detected in 40% and polycythemia in 17%. Only one neonate with trisomy 13 had abnormal erythrocyte findings (polycythemia). These data should assist clinicians caring for neonates with trisomy 18 or 13, demonstrating how common hematological abnormalities exist among these patients.

The erythrocyte indices of neonates, defined using data from over 12,000 patients in a multihospital health care system.

OBJECTIVE: The erythrocyte indices (mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) and mean corpuscular hemoglobin (MCH)) were originally reported using hand-calculated values, based on a centrifuge-spun hematocrit, a counting-chamber erythrocyte count and a hemoglobin concentration measured by any number of hemoglobinometry methods. Modern blood cell analyzers measure the MCV, and calculate the MCHC and MCH, on the basis of logs higher sample sizes than employed in the original methods. STUDY DESIGN: With a single type of automated blood cell counter (Beckman Coulter LH 750; Fullerton, CA, USA), we determined the ranges of erythrocyte indices among neonates of 22 to 42 weeks gestation. Data were accumulated during a 3-year period from a multihospital health care system, using all indices reported on untransfused neonates during their first day of life. RESULT: Erythrocyte indices were obtained from 17,634 tests performed on 12,016 neonates. The MCV and the MCH decreased with advancing gestational age. For instance, the MCV diminished from 119+/-7 fl (mean+/-s.d.) in neonates < or =25 weeks gestation to 106+/-4 fl at 40 weeks. The MCH diminished from 40+/-2 pg in neonates < or =25 weeks gestation to 36+/-2 pg at 40 weeks. The MCHC did not change appreciably with gestational age (34+/-1 pg dl(-1)). CONCLUSION: The results describe the expected values for erythrocyte indices on the first day of life among untransfused neonates. Additional study is needed to determine the relevance of very high or low erythrocyte indices in this population and to understand any physiological advantage of these very large erythrocytes during fetal development.

ETCare: a randomized, controlled, masked trial comparing two solutions for upper airway care in the NICU.

BACKGROUND: Small quantities of normal saline are sometimes instilled into the endotracheal tube of intubated neonates, to assist with the removal of thick secretions and maintain patency of the endotracheal tube. However, saline is detrimental to the innate immune system of the upper airway mucosa, rapidly unfolding and inactivating antimicrobial peptides such as LL-37. We previously reported the preparation and feasibility testing of 'ETCare', a low-sodium, physiologically based solution for airway care, and we now report results of a randomized, masked, controlled, two-centered study testing ETCare vs sterile saline among 60 intubated NICU patients. STUDY DESIGN: Sixty intubated NICU patients were randomized to having their airway care with ETCare vs saline. Three hypotheses were tested: (1) tolerance - patients will tolerate ETCare for airway care as well as they tolerate saline, (2) nosocomial infections - ETCare will result in fewer tracheal aspirates where organisms grow and fewer cases of nosocomial sepsis, and (3) chronic lung disuse - ETCare will result in fewer patients discharged home on supplemental O2. RESULTS: Thirty NICU patients with an endotracheal tube in place were randomized to receive their airway care with ETCare, and 30 to receive their care with saline. Only the pharmacist was aware of the randomization; the two solutions were visually indistinguishable and were dispensed in identical syringes. Tolerance of the solutions was similar. The ETCare recipients had trends toward fewer positive blood cultures (odds ratios (OR), 0.48; 95% confidence interval (CI), 0.13 to 1.68), and fewer discharges home on supplemental O2 (OR, 0.43; 95% CI, 0.14 to 1.32; P=0.075). CONCLUSIONS: On the basis of this study and our previous 10-patient feasibility trial, we maintain that, for airway care, intubated NICU patients tolerate ETCare as well as saline. Data from this study can be used in estimating the sample sizes needed for a phase III trial. We speculate that such a trial will demonstrate that, compared with saline, ETCare will result in fewer nosocomial infections and less chronic lung disease.

Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease.

BACKGROUND: Prolonged use of parenteral nutrition (PN) in neonates can lead to parenteral nutrition-associated liver disease (PNALD), manifested by elevated direct bilirubin concentrations, and in some cases progressing to hepatic failure. When new potential means of preventing PNALD in the neonatal intensive care unit (NICU), such as Omegaven usage, are tested in clinical trials, the studies should enroll neonates at a very high risk of developing PNALD. However, it is not always clear, in the first days of life, which neonates are most likely to develop PNALD. Therefore, preparatory to devising studies of prophylaxis against PNALD, we conducted an evaluation of all NICU patients who received PN for >or=14 day, assessing their likelihood of developing PNALD. METHODS: We performed an historic cohort analysis of all neonates in the Intermountain Healthcare system, receiving PN for 14 days or more during their stay, with dates of birth between 1 January, 2002 and 30 June, 2006. RESULTS: During the 4(1/2)-year period, 9861 neonates were cared for in the Intermountain Healthcare NICUs. Of these, 9547 (96.8%) survived for at least 28 days, and of these 6543 (68.5%) received PN. Twenty-one percent (1366 patients) of those receiving PN, received it for >or=14 days. PNALD was ascertained in this group by a direct bilirubin >or=2.0 mg/dl. Neonates receiving PN for 14-28 days had a 14% incidence of PNALD, those receiving PN for 29-56 days had a 43% incidence, those receiving PN for 57-100 days had a 72% incidence and those receiving PN for >100 days had a 85% incidence. Groups of patients identifiable on the first day of life as having the highest risk of developing PNALD were birth weight <500 g (odds ratio (OR), 30.7), birth weight 500-749 g (OR, 13.1), gastrochisis (OR, 20.3) and jejunal atresia (OR, 24.0). Among 357 patients who developed PNALD, the highest direct bilirubin concentrations correlated with the highest serum alkaline phosphatase and transaminase concentrations. Deaths after 28 days were much more common in those with the highest direct bilirubin and transaminase concentrations (P<0.0001). CONCLUSIONS: In the first days of life, certain NICU patients can be identified as being at very high risk for developing PNALD. These are patients <750 g birth weight, those with gastrochisis and those with jejunal atresia. We speculate that these groups would be reasonable subjects for including in a PNALD prophylaxis trial, testing new preventative strategies such as Omegaven usage.

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.

D-Penicillamine administration and the incidence of retinopathy of prematurity.

OBJECTIVE: We compared the development of retinopathy of prematurity (ROP) among 49 preterm neonates:; 15 who were treated during the first 2 weeks of life with D-penicillamine and 34 who were not. METHODS: During a 15-month period beginning 1 March, 2005, 15 preterm neonates <1000 g birth weight or < or =29 weeks gestation enterally received a 14-day course of D-penicillamine, and 34 did not, in an open-label non-randomized trial. We compared the outcomes of developing 'ROP any stage' and 'ROP requiring surgery' in the recipients vs the non-recipients. Potential toxicities of the D-penicillamine were examined by comparing specific laboratory tests, growth velocities, transfusion requirements, discharge hemoglobin concentrations and supplemental O(2) at discharge. RESULTS: The 34 non-treated and the 15 D-penicillamine treated patients were of similar gestational age (26.5+/-1.8 vs 26.6+/-2.2 weeks, mean+/-s.d.) and birth weight (887+/-222 vs 849+/-187 g). Four of the 34 non-recipients died. Eighteen of the 30 survivors (60%) developed ROP and seven of the 30 (23%) had ROP surgery. One of the 15 D-penicillamine recipients died. Three of the 14 survivors (21%) developed ROP (P=0.01 vs non-recipients) and all three had ROP laser surgery. No increase in elevated creatinine, direct or indirect bilirubin, thrombocytopenia or neutropenia was apparent in those treated with D-penicillamine. The D-penicillamine recipients did not receive more transfusions and did not have lower hemoglobin concentrations at discharge. They did not have lower velocities of weight gain at 14, 28 and 56 days, and were not discharged on supplemental O(2) at a rate exceeding that of the non-recipients. CONCLUSIONS: In this non-randomized, single-centered comparison analysis, a 14-day course of D-penicillamine resulted in no apparent short-term toxicity. The treatment was associated with elimination of Stage I and Stage II ROP, decreasing the overall odds of developing ROP from 60 to 21%. However, this approach did not reduce the odds of ROP surgery. Perhaps higher doses of D-penicillamine or longer treatment periods or other prophylactic approaches will be required to reduce ROP surgery among the most immature neonates.

Hematological abnormalities during the first week of life among neonates with Down syndrome: data from a multihospital healthcare system.

Various hematological abnormalities have been reported among neonates with Down syndrome. Thrombocytosis, thrombocytopenia, polycythemia, neutrophilia, transient myeloproliferative disorder (TMD), and congenital leukemia have all been reported. The two largest case series previously reported involved 63 and 31 cases. To acquire hematological data from a larger case series, we obtained all CBCs done during the first week after birth on all neonates with Down syndrome cared for in an Intermountain Healthcare (IHC) hospital with a date of birth between January 1, 2001 and December 31, 2005. During this period, 145,522 live births were recorded at 18 hospitals. Down syndrome was recognized in 226 (1 in 644). One hundred fifty-eight (70%) of these had one or more CBCs obtained before the seventh day (144 hr). Neonates who did versus did not have a CBC in the first week had a similar gestational age, birth weight, percentage who were LGA and SGA, and length of stay. Neutrophilia was the most common hematological abnormality detected, with 80% of absolute neutrophil counts above the upper limit of normal for age. Six percent (9/158) had blasts identified on the blood film and three, where this was persistent, were referred to the pediatric hematology service for further evaluation. The next most commonly detected abnormality was thrombocytopenia, with 66% of platelet counts <150,000/microl, and with 6% of counts <50,000/microl. The mean platelet volume did not correlate with the platelet count, but tended to run slightly large (9.2 +/- 1.3 fl), with 24% of values above 10 fl. Only one had a platelet transfusion. Polycythemia was the next most common hematological abnormality detected, with 33% of hematocrit values above 65% or hemoglobin concentrations above 22 g/dl. Six had a reduction transfusion. One patient had significant anemia (hematocrit <15%) and received an erythrocyte transfusion. One had neutropenia associated with an infection after bowel surgery. Neutrophilia, thrombocytopenia, and polycythemia were the most common hematological abnormalities observed among neonates with Down syndrome. Anemia, thrombocytosis, and neutropenia were not more common than among neonates who do not have Down syndrome. Hematological abnormalities were so common in this group that it seems reasonable to recommend that one or more CBCs be obtained on all neonates with Down syndrome.

Low blood neutrophil concentrations among extremely low birth weight neonates: data from a multihospital health-care system.

OBJECTIVE: A blood neutrophil concentration < 1000/microl has been reported to occur in about 8% of neonatal intensive care unit (NICU) patients, at some time during their hospital stay. However, the incidence of this finding among extremely low birth weight (ELBW) neonates (< 1000 g birth weight) is not known. Using data from four NICU's in one health-care system, we sought to estimate the incidence, timing, causes, severity and duration of neutrophil counts < 1000/microl among ELBW neonates. We also tabulated the treatments used for this condition and associations with mortality. METHODS: We performed an historic cohort analysis of all ELBW neonates born during the 36-month period, 1 July 2002 to 30 June 2005, cared for in the four Intermountain Healthcare level III NICU's. RESULTS: Three hundred and thirty-eight ELBW neonates were the subjects of the analysis. Complete blood cell counts (CBCs) were obtained in all (range, 1 to 123 CBCs/patient). Thirty-eight percent (128/338) had one or more neutrophil counts < 1000/microl. In 57% the low neutrophil count persisted for < 24 h; in 43% it persisted for 1 to 7.5 days. Most of the cases (74%) were detected during the first 3 days of life. Twenty-two percent of cases were not detected until after the first week. Low neutrophil counts were more common among the smallest patients, with a 63% incidence in those < or = 500 g, 44% in those 501 to 600 g and 34% in those 801 to 999 g. When low neutrophil counts were recognized during the first 3 days of life, the patients were typically either small for gestational age (SGA; weight < 10th percentile for gestational age) or born after pregnancy-induced hypertension (PIH) (68%), or had early-onset bacterial infection (6%). When recognized after the first 3 days, the patients typically had necrotizing enterocolitis (31%) or a nosocomial bacterial infection (19%). Alloimmune mechanisms were not tested for in any of the cases. No cause for the low counts was identified among 35% of the neutropenic patients. Intravenous immunoglobulins was administered to 28% of cases, and 100% of these were given according to our written guidelines. Recombinant granulocyte-colony stimulating factor was administered to 13% of cases, and 69% of these were given according to guidelines. Neither the presence of low neutrophil counts nor the severity (lowest recorded count) correlated with mortality rate, except in proven early-onset sepsis. CONCLUSIONS: We observed low neutrophil counts among ELBW neonates at a rate five times that reported in the general NICU population. Most cases were present in the first days of life and occurred in SGA neonates or those with PIH. In over 1/3, no cause was discovered. We maintain that more consistency is needed in evaluating and treating neutropenia among ELBW neonates.

Thrombocytopenia among extremely low birth weight neonates: data from a multihospital healthcare system.

OBJECTIVES: Thrombocytopenia is common in neonatal intensive care units (NICU), with 18 to 35% of patients developing this problem before hospital discharge. It might be even more common among extremely low birth weight neonates (ELBW, < or = 1000 g birth weight). However, little is known about thrombocytopenia in the ELBW population. We sought to determine the incidence, timing, causes, platelet transfusions given, and outcomes of thrombocytopenia among ELBW neonates. STUDY DESIGN: We performed a cohort analysis of all 284 ELBW neonates born during 2003 and 2004 cared for in any of the Intermountain Healthcare level III NICUs. RESULTS: Multiple platelet counts were obtained in all 284 (range, 4 to 441 platelet counts/patient). Of the 284, 208 (73%) had one or more platelet counts < or =150 000/microl. Most were detected during the first days of life; 80% were detected during the first week and only 20% were detected thereafter. Thrombcytopenia was more common among the smallest patients; 85% incidence among those < or =800 g, 60% among those 801 to 900 g, and 53% among those 901 to 1000 g. Platelet transfusions were given to 129 of the 208 thrombocytopenic neonates. More than 90% were given prophylactically (the patient was not bleeding). The mortality rate among those that received platelet transfusions was twice that of those that received no platelet transfusions (P < 0.01). In 48% of cases, the cause of the thrombocytopenia went undiagnosed. The most common explanations were being small for gestational age or delivered to a hypertensive mother, DIC, bacterial infection, fungal infection, and necrotizing enterocolitis, respectively. CONCLUSIONS: We observed thrombocytopenia among ELBW neonates at a rate more than twice that reported among the general NICU population. Much remains to be discovered about the etiology and best treatments of thrombocytopenia among ELBW neonates.

Age- and microenvironment-associated influences by platelet-derived growth factor on T cell function.

Platelet-derived growth factor (PDGF) is produced by numerous cell types in response to a variety of activation signals. Although the role of PDGF in cellular proliferation is well established, the immunomodulatory effects of this peptide growth factor are only now being delineated. We previously established that PDGF alters the profile of lymphokines produced by activated T cells obtained from the peripheral lymph nodes of adult mice. We now report that T cells residing in lymphoid organs that receive their major afferent lymphatic drainage from gut mucosa are relatively resistant to the effects of this growth factor. As the vast majority of peripheral T cells are in the recirculating T cell pool, these findings suggest that tissue-specific microenvironmental factors function to regulate the sensitivity of T cells to PDGF-mediated influences. Additional studies have determined that the normal process of aging is accompanied by a systemic loss in T cell responsiveness to PDGF. Although the T cells of immature (2-wk-old) and young adult mice are responsive to the immunomodulatory influences of PDGF, T cells of aged animals (> 100 wk) are relatively resistant to its effects. Some of the immune abnormalities noted to occur during the aging process appear to represent a consequence of the dysregulated production of IL-6. We therefore evaluated whether IL-6 was responsible for modifying the sensitivity of T cells to PDGF. Data presented herein demonstrate that IL-6 abrogates the ability of PDGF to modify lymphokine production by T cells after activation. Therapeutic measures capable of reducing spontaneous IL-6 production in aged mice restored the ability of their T cells to respond to PDGF, suggesting that the dysregulated production of IL-6 within the aged host interferes with the ability of PDGF to convey important microenvironmental information to T cells residing in peripheral lymphoid organs.