D K Lambert

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 ⩾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 4½-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 ⩾14 days. PNALD was ascertained in this group by a direct bilirubin ⩾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.

Comparing two methods of delivering high-flow gas therapy by nasal cannula following endotracheal extubation: a prospective, randomized, masked, crossover trial

Objective:We compared two methods of delivering high-flow gas therapy by nasal cannula, applied immediately after planned endotracheal extubations of NICU patients.Study design and methods:Thirty NICU patients who were about to be extubated from mechanical ventilation were randomized into two groups; Group 1 received Vapotherm® for the first 24 h after extubation, then standard high-flow nasal cannula for the next 24 h, and Group 2 received standard high-flow therapy for the first 24 h, then Vapotherm® for the next 24 h. At 24 h after extubation and again 48 h after extubation, a neonatologist who was not aware which modality the patient had been receiving examined the nasal mucosa and applied a scoring system. A research nurse who was unaware of the modality abstracted respiratory rates and respiratory effort scores from a specific study-bedside record. The experimental design was such that a patient could ‘fail’ extubation either by reintubation for mechanical ventilation, or by rescue to the opposite modality before completing the 24-h test period.Results:Fifteen patients were randomized to Group 1 and 15 to Group 2. No differences were apparent between the groups in birth weight, gestational age, age at study entry, gender or underlying pulmonary disorder. Respiratory rates were similar while on Vapotherm® (52±13 breaths/min, mean±s.d.) and high-flow (54±14/min). At 24 h after starting the modality, those on Vapotherm® had more normal examinations of the nasal mucosa (2.7±1.2 vs 7.8±1.7, P<0.0005) and lower respiratory effort scores (1.2±0.6 vs 2.0±0.9, P<0.05) than did those on high-flow. No patients failed while on Vapotherm®, but seven failed while on high-flow (two reintubations and five rescue switches to Vapotherm®, P<0.005).Conclusions:Among NICU patients immediately following extubation, Vapotherm® performed better than a standard high-flow nasal cannula in maintaining a normal appearing nasal mucosa, a lower respiratory effort score, and averting reintubation.

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

Objective:In the past 5½ years, 30 term or near-term neonates in the Intermountain Healthcare system developed necrotizing enterocolitis (NEC) Bells stage ⩾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 5½-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 Bells stage II or higher. However, on review of these 41 medical records, 11 were seen to have had NEC of Bells stage I, whereas the remaining 30 had radiographs and clinical courses indicative of Bells stage ⩾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.

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 ⩾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.

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

Objective:A blood neutrophil concentration <1000/μl 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 NICUs in one health-care system, we sought to estimate the incidence, timing, causes, severity and duration of neutrophil counts <1000/μl 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 NICUs.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/μl. 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 ⩽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.

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.

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.

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 ⩾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.

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.

Effects of Instituting the “BEST Program” (Breast Milk Early Saves Trouble) in a Level III NICU:

A program is developed to increase the use of breast milk during the first week, for patients < 2 kg birth weight. This is termed the “BEST program,” using the acronym “Breast milk Early Saves Trouble.” An analysis of feeding practices and outcomes during the 12 months before versus the 12 months after implementing this program was conducted. Demographic features of the patients in the 2 periods were similar. In the “Before Intervention” period, 33% received human milk exclusively in the first 7 feeding days; 50% in the “Intervention” period (P = .009). In the Before Intervention period, 74% received some breast milk; 82% in the Intervention group (P = .046). Banked human milk increased from 2% to 33% of patients (P ≥ .001), and a trend was seen in more mothers who initially wanted to bottle-feed but subsequently changed to breastfeeding (P = .08). A trend was also seen in more infants discharged home breastfeeding (P = .09). J Hum Lact. 24(3):248-251. Desarrollamos un programa para aumentar el uso de leche materna durante la primera semana en pacientes con < 2 kg de peso al nacer. Determinamos este el “B.E.S.T. Program”, usando el acrónimo “Leche materna temprana para evitar problemas”. Hicimos un análisis de las prácticas de lactancia y los resultados durante 12 meses antes vs 12 meses después de la implementación del programa. Las características demográficas de los pacientes en los dos periodos fueron similares. En la intervención antes del periodo, 33% recibieron leche materna exclusiva en los primeros siete días; 50% en el periodo de intervención (P = 0.009). En el período antes de la intervención, 74% recibieron leche materna; 82% en el grupo de intervención (P = 0.046). La solicitud de leche de banco aumentó de 2% a 33% de los pacientes (P ≥ 0.001), y se vio una tendencia de que mas madres que inicialmente deseaban alimentar con biberón pero subsecuentemente cambiaron a lactancia materna (P = 0.08). Una tendencia que también se observó fue que mas bebes salieron del hospital con lactancia materna (P = 0.09).