Anthropometric trends from 1997 to 2012 in infants born at ⩽28 weeks' gestation or less.

OBJECTIVE: Postnatal growth failure is common after preterm birth, in particular for infants born at ⩽28 weeks' gestation, but it is unknown if growth-to-term equivalent age has improved over the years as neonatal intensive care in general, and infant nutrition in particular, have improved. The objective of the study was to evaluate anthropometric trends at NICU discharge for infants born at ⩽28 weeks' gestation using a large national database. STUDY DESIGN: Analysis of growth in weight, length, head circumference and body mass index (kg m2) in 23 005 infants born in 1997 to 2012 who survived to neonatal intensive care unit discharge at ⩽41 weeks' postmenstrual age. RESULTS: Discharge weight, length, head circumference and body mass index were converted to Z-scores using a reference database, and growth trends over the 16 years were summarized. Discharge results also were summarized for common neonatal morbidities, including chronic lung disease. Gestational age at birth and postmenstrual age at discharge were similar across the 16 years. Discharge weight, length and head circumference Z-scores were all below the median, but head circumference Z-scores consistently were closer to the median than were weight and length. In 1997 compared with 2012, the weight Z-score improved from -1.5 to -0.6; the length Z-score increased the least, from -1.68 to just -1.16; the head circumference Z-score improved from -0.68 to -0.30; and the body mass index Z-score increased from -0.66 to 0.19. Percent small-for-gestational age at birth was stable across the years at 8.4 to 9.3%, and the frequency of postnatal growth failure at discharge improved from 55.4% in 1997 to 19.6% in 2012. CONCLUSIONS: Growth-to-discharge progressively improved from 1997 to 2012, but Z-scores remained below the reference median for weight, length and head circumference. Length Z-scores were consistently significantly less than for weight, and body mass index Z-scores have been above the reference median since 2002. Prospective studies are needed to quantify anthropometric trends in relation to body composition and to current nutritional strategies.

Impact of l-carnitine supplementation on metabolic profiles in premature infants.

OBJECTIVE: To describe the influence that of l-carnitine supplementation on acylcarnitine (AC) profiles and hospital outcomes in premature infants. STUDY DESIGN: This study is a secondary analysis of previously reported work. Metabolic profiles were obtained using standard newborn techniques on infants born between 23 and 31 completed weeks of gestation. The profiles were drawn within the first 24 h after birth and on approximately days 7, 28 and 42 of life, or at the time of discharge. A single, central, contract laboratory analyzed and managed the samples. RESULTS: We studied 995 patients; none was subsequently diagnosed with an inborn error of metabolism. l-Carnitine was added to parenteral nutrition in 390 (39%) study subjects; 592 (60%) did not receive supplementation. Non-supplemented infants were more likely to develop low levels of free carnitine (FC; <7 µm) on day 28; (41% vs 5%, P<0.01); and FC values were lower on day 7. Despite higher levels of FC and fewer patients with significant carnitine deficiencies, we found no evidence that l-carnitine supplementation was associated with improved short-term hospital outcomes. CONCLUSION: l-Carnitine supplementation is common in prematurely born neonates and is associated with higher carnitine levels, but is not associated with improved short-term hospital outcomes.

Major anomalies and birth-weight influence NICU interventions and mortality in infants with trisomy 13 or 18.

OBJECTIVE: To describe neonatal intensive care unit (NICU) medical interventions and NICU mortality by birth weight and major anomaly types for infants with trisomy 13 (T13) or 18 (T18). STUDY DESIGN: Retrospective cohort analysis of infants with T13 or T18 from 2005 to 2012 in the Pediatrix Medical Group. We classified infants into three groups by associated anomaly type: neonatal surgical, non-neonatal surgical and minor. Outcomes were NICU medical interventions and mortality. RESULTS: 841 infants were included from 186 NICUs. NICU mortality varied widely by anomaly type and birth weight, from 70% of infants <1500 g with neonatal surgical anomalies to 31% of infants ⩾2500 g with minor anomalies. Infants ⩾1500 g without a neonatal surgical anomaly comprised 66% of infants admitted to the NICU; they had the lowest rates of NICU medical interventions and NICU mortality. CONCLUSIONS: Risk stratification by anomaly type and birth weight may help provide more accurate family counseling for infants with T13 and T18.

The epidemiology, prevalence and hospital outcomes of infants with gastroschisis.

OBJECTIVE: The purpose of this study is to evaluate recent trends in prevalence of gastroschisis among infants admitted for neonatal intensive care in the United States. STUDY DESIGN: Retrospective review of a de-identified patient data. The current study extends our observations through the end of 2007 to 2015. RESULTS: During the study period (1 January 1997 to 12 December 2015), there were 1 158 755 total discharges; 6023 (5.2/1000) had gastroschisis and 1885 (1.6/1000) had an omphalocele. Between 1997 and 2008, the reported rate of gastroschisis increased from 2.9 to 6.4/1000 discharges. From 2008 to 2011, the values have slowly decreased from 6.4 to 4.7/1000 discharges and since 2011 have been stable. The largest drop in the prevalence was in mothers who were <20 years old. In contrast, the reported rate of omphalocele was stable at 1 to 2/1000 discharges. CONCLUSION: The prevalence of gastroschisis increased from 1997 to 2008, and then declined thereafter.

The complete blood cell count in a refined cohort of preterm NEC: the importance of gestational age and day of diagnosis when using the CBC to estimate mortality.

OBJECTIVE: The value of the white blood cell count (WBC) in necrotizing enterocolitis (NEC) is controversial. One reason for this confusion may be that the various WBC lineages change substantially with increasing gestational age and thereby age of NEC onset. This study postulated that if a data set was large enough and the diagnosis of NEC clean enough, absolute WBC counts would facilitate prediction of NEC mortality. The objective of this study was to determine whether absolute WBC counts enhance the prediction of NEC mortality. STUDY DESIGN: A de-identified data subset from the Pediatrix national data set specific to the diagnoses of NEC in patients who had a CBC drawn on the day of diagnosis (exclusive of the diagnoses of spontaneous intestinal perforations and congenital anomalies) was the target for analysis. Values of primary interest included: gestation, day of diagnosis, absolute WBC count, platelet count, hematocrit, mortality and the day of diagnosis. Stepwise regression analysis was used to predict mortality. RESULT: A total of 4059 (79%) survivors and 1107 (21%) infants who died with a diagnosis of medical or surgical NEC were included in the data set. Associations with mortality were found with low gestational age, low platelet count, low hematocrit, high band/segmented neutrophil ratio, earlier day of diagnosis, high birth weight z-score, non-white race, no antenatal steroids in gestations above 24 weeks, absolute lymphocyte count adjusted for gestational age, and absolute monocyte count high and low values. A stepwise regression analysis yielded a receiver-operator curve of 0.819 with a sensitivity of 65% and specificity of 84%. CONCLUSION: Absolute WBC values enhance prediction of NEC survival when used in combination with readily available data on the day of NEC diagnosis.

Can a national dataset generate a nomogram for necrotizing enterocolitis onset?

OBJECTIVE: Mother's own milk and donor human milk use is increasing as a means of necrotizing enterocolitis (NEC) prevention. Early onset of enteral feeding has been associated with improvement of many outcomes but has not been shown to reduce the incidence of NEC. Better definition of the window of risk for NEC by gestational strata should improve resource management with respect to donor human milk and enhance our understanding of NEC timing and pathogenesis. Our objective was to establish a NEC dataset of sufficient size and quality, then build a generalizable model of NEC onset from the dataset across gestational strata. STUDY DESIGN: We used de-identified data from the Pediatrix national dataset and filtered out all diagnostic confounders that could be identified by either specific diagnoses or logical exclusions (example dual diagnoses), with a specific focus on NEC and spontaneous intestinal perforation (SIP) as the outcomes of interest. The median day of onset was plotted against the gestational age for each of these diagnoses and analyzed for similarities and differences in the day of diagnosis. RESULT: Onset time of medical NEC was inversely proportional to gestation in a linear relationship across all gestational ages. We found the medical NEC dataset displayed characteristics most consistent with a homogeneous disease entity, whereas there was a skew towards early presentation in the youngest gestation groups of surgical NEC (suggesting probable SIP contamination). CONCLUSION: Our national dataset demonstrates that NEC onset occurs in an inverse stereotypic, linear relationship with gestational age at birth. Medical NEC is the most reliable sub-cohort for the purpose of determining the temporal window of NEC risk.

Reclassification of clinical sleep disorders using traditional models of syndromic, neuroanatomic, pathophysiological and etiological diagnosis.

Existing classifications of central nervous system sleep disorders do not often provide tools to diagnose the majority of patients complaining of sleep-related symptoms, nor always guide effective treatment. I present a novel classification system that completely separates clinical syndromes from anatomical localization, pathophysiology, and etiology. The clinical syndrome I present can describe the majority of patients, but can be fractionated into individual subgroups for further study. By then separating the anatomy and physiology from the symptoms, an avenue of research becomes available to study the different possible structures that regulate sleep, that may be damaged and cause syndromes of sleep dysfunction. Some of these may produce symptoms that overlap with narcolepsy and some may be distinct. Because the clinical syndrome should be distinguished from anatomy or physiology, I have proposed the term narcoleptiform syndrome for the clinical syndrome. The model also clearly separates etiology from anatomy in a classical neurological manner. This allows etiology, localization and symptoms to be studied separately. It is likely that different etiologies may produce damage in areas that produce similar syndromes. For example, in this model, different causes of damage to the orexin nucleus would result in the same clinical syndrome. This reinforces the concept of studying anatomy, symptoms and etiology separately. By studying the relationship of syndromes or symptoms to anatomic localization and pathophysiology, it should be possible to test novel approaches to treatment based on different underlying structure or function. For example, patients with lesions in the ventrolateral preoptic nucleus or the thalamic intralaminar nuclei may both present with insomnia symptoms but need different treatment; or they might present with symptoms overlapping narcolepsy (a narcoleptiform syndrome) yet need different treatment. In some cases, a single treatment may cross over more than one location, and the best predictor might be symptoms. These are issues that need to undergo careful study on a syndromic, anatomic and physiological bases. This novel model opens up new avenues for understanding central nervous system sleep disorders, providing testable hypotheses regarding diagnosis and treatment.

Impact of duration of rupture of membranes on outcomes of premature infants.

OBJECTIVE: The primary aim of the study was to determine how the risk of adverse outcomes was related to the duration of the latency period and gestational age at birth following preterm premature rupture of the fetal membranes (PPROM). STUDY DESIGN: Retrospective review of infants discharged from 330 neonatal intensive care units. We defined four subgroups based on gestational age: 23 to 25, 26 to 28, 29 to 31 and 32 to 34 weeks. Each gestational age group was evaluated by duration of ROM: <24 h, 1 to 7 days, 8 to 14 days, 15 to 21 days, 21 to 28 days and >28 days and compared with a referent group (PPROM of >24 h but <7 days). RESULT: In all, 239 808 non-anomalous infants 23 to 34 weeks' gestational age were identified; 37 233 (15.5%) had rupture of membranes (ROM) >24 h. Compared with a reference group (PPROM of >24 h but <7 days), the risk of mortality for PPROM of 8 to 14, 15 to 21 and 21 to 28 days varied depending on gestational age at birth. Only PPROM >28 days was consistently associated with increased mortality and decreased likelihood of survival without morbidity in all gestational age subgroups. CONCLUSION: PPROM for >28 days is associated with an increased risk of death and morbidity.

Discrimination of GutCheck(NEC): a clinical risk index for necrotizing enterocolitis.

OBJECTIVE: Better measures are needed to identify infants at risk for developing necrotizing enterocolitis (NEC) and facilitate communication about risk across transitions. Although NEC is multi-factorial, quantification of composite risk for NEC in an individual infant is not clearly defined. The objective of this study was to describe the derivation, validation and calibration testing of a novel clinical NEC risk index, GutCheck(NEC). Individual risk factors were weighted to assess composite odds of developing NEC. GutCheck(NEC) is designed to improve communication about NEC risk and coordination of care among clinicians across an infant's clinical course. STUDY DESIGN: On the basis of a synthesis of research evidence about NEC risk and an e-Delphi study including 35 neonatal experts, we identified NEC risk factors believed by the experts to be most relevant for a NEC risk index, then applied a logistic model building process to derive and validate GutCheck(NEC). De-identified data from the Pediatrix BabySteps Clinical Data Warehouse (discharge date 2007 to 2011) were split into three samples for derivation, validation and calibration. By comparing infants with medical NEC, surgical NEC and those who died to infants without NEC, we derived the logistic model using the un-matched derivation set. Discrimination was then tested in a case-control matched validation set and an un-matched calibration set using receiver operating characteristic curves. RESULT: Sampled from a cohort of 58 820 infants, the randomly selected derivation set (n=35 013) revealed nine independent risk factors (gestational age, history of packed red blood cell transfusion, unit NEC rate, late-onset sepsis, multiple infections, hypotension treated with inotropic medications, Black or Hispanic race, outborn status and metabolic acidosis) and two risk reducers (human milk feeding on both days 7 and 14 of life, and probiotics). Unit NEC rate carried the most weight in the summed score. Validation using a 2:1 matched case-control sample (n=360) demonstrated fair to good discrimination. In the calibration set (n=23 447), GutCheck(NEC) scores (range 0 to 58) discriminated those infants who developed surgical NEC (area under the curve (AUC)=0.84, 95% confidence interval (CI) 0.82 to 0.84) and NEC leading to death (AUC=0.83, 95% CI 0.81 to 0.85), more accurately than medical NEC (AUC= 0.72, 95% CI 0.70 to 0.74). CONCLUSION: GutCheck(NEC) represents weighted composite risk for NEC and discriminated infants who developed NEC from those who did not with very good accuracy. We speculate that targeting modifiable NEC risk factors could reduce national NEC prevalence.

Characteristics of patients who die of necrotizing enterocolitis.

OBJECTIVE: Necrotizing enterocolitis (NEC) is associated with high morbidity and mortality among infants admitted for intensive care. The factors associated with mortality and catastrophic presentation remain poorly understood. Our objective was to describe the factors associated with mortality in infants with NEC and to quantify the degree to which catastrophic presentation contributes to mortality in infants with NEC. Catastrophic NEC was defined before data analysis as NEC that led to death within 7 days of diagnosis. STUDY DESIGN: We performed a retrospective review of the Pediatrix's Clinical Data Warehouse (1997 to 2009, n=560,227) to compare the demographic, therapeutic and outcome characteristics of infants who survived NEC vs those who died. Associations were tested by bivariate and multivariate analysis. RESULT: We compared the 5594 infants diagnosed with NEC and who were discharged home with 1505 infants diagnosed with NEC who died. In multivariate analysis, the factors associated with death (P<0.01 in analysis) were lower estimated gestational age, lower birth weight, treatment with assisted ventilation on the day of diagnosis of NEC, treatment with vasopressors at the time of diagnosis, and Black race. Patients who received only ampicillin and gentamicin on the day of diagnosis were less likely to die. Two-thirds of NEC deaths occurred quickly (<7 days from diagnosis), with a median time of death of one day from time of diagnosis. Infants who died within 7 days of diagnosis had a higher birth weight, more often were on vasopressors and high frequency ventilation at the time of diagnosis compared with patients who died at 7 or more days. Although mortality decreased with increasing gestational age, the proportion of deaths that occurred within 7 days was relatively consistent (65 to 75% of the patients who died) across all gestational ages. CONCLUSION: Mortality among infants who have NEC remains high and infants who die of NEC commonly (66%) die quickly. Most of the factors associated with mortality are related to immaturity, low birth weight and severity of illness.

Elevation in plasma creatinine and renal failure in premature neonates without major anomalies: terminology, occurrence and factors associated with increased risk.

OBJECTIVE: The goal of this study was to describe the changes in plasma creatinine levels that occur in prematurely born neonates, to better understand the use of the terms 'renal dysfunction' and 'renal failure' among premature neonates, as well as to evaluate the demographic and outcome characteristics associated with renal problems in preterm neonates who have no major congenital anomalies. STUDY DESIGN: Retrospective review of the Pediatrix neonatal intensive care patient clinical data warehouse. RESULT: The study cohort consisted of neonates born with an estimated gestational age of ≤ 30 completed weeks in whom there was no report of any major anomalies (n=66,526). In this group of 66,526 neonates, there were 64,030 (96.2%) with no report of renal dysfunction or failure, 1239 (1.9%) in whom there was a diagnosis of renal dysfunction and 1257 infants (1.9%) with a diagnosis of renal failure. The clinical circumstances most strongly associated with a diagnosis of renal dysfunction and/or renal failures were low gestational age and birth weight. In addition, multivariate analysis showed that the factors associated with an increased risk of renal problems were vasopressor use during the first 7 days after birth, grade 3 or 4 intraventricular hemorrhage, a patent ductus arteriosus, necrotizing enterocolitis, male gender, the use of indomethacin, a positive blood culture during the first 7 days after birth, the use of high-frequency ventilation in the first 2 days after birth, non-White race and prolonged exposure to antibiotics. Mortality was higher in patients with renal problems than in neonates without renal problems (39.1 vs 10.2%, P<0.01) and higher in neonates with renal failure than in neonates with renal dysfunction (57.6 vs 20.1%, P<0.01). CONCLUSION: Renal dysfunction and/or failure are common diagnoses, especially in extremely premature neonates and there are potentially modifiable factors that increase the risk of renal problems.

Treatment of the narcoleptiform sleep disorder in chronic fatigue syndrome and fibromyalgia with sodium oxybate.

This study investigates the response of the underlying sleep disorder associated with Chronic Fatigue Syndrome (CFS) and fibromyalgia (FM) to treatment. We retrospectively reviewed 118 cases clinically consistent with CFS or FM, treated in a neurology practice. Abnormal findings on sleep studies and associated human leukocyte antigen markers, and a clinical pattern suggestive of narcolepsy, are present in a high proportion of patients. When considered appropriate based on the clinical picture and test results, treatment with sodium oxybate was offered to these patients. Sixty percent of patients treated with oxybate experienced significant relief of pain, while 75% experienced significant relief of fatigue. We postulate that the response to oxybate in CFS and FM suggests a disturbance of sleep similar to narcolepsy. These findings support this novel approach to intervention and further research. The inability to distinguish CFS and FM by testing and response to treatment suggests that they may represent variations of the same disorder or may be closely related disorders.

The changing pattern of inhaled nitric oxide use in the neonatal intensive care unit.

OBJECTIVE: The purpose of this study was to evaluate the demographic characteristics and outcomes of neonates who were admitted to a neonatal intensive care unit and treated with inhaled nitric oxide (iNO) during the years 2000-08. The goal of studying this group of neonates was to evaluate how iNO use has evolved in infants and to estimate the frequency of off-label use of this drug in this population. STUDY DESIGN: Retrospective review of the Pediatrix Clinical Data Warehouse de-identified data set. Pediatrix Medical Group provides intensive care services in 244 hospitals in 32 states and Puerto Rico. Nine (3.7%) centers provide extracorporeal membrane oxygenation. RESULT: There were 494 255 neonates in the data set; 4316 (0.9%) were treated with iNO. The use of iNO increased from 154 of 32 967 patients in 2000 to 921 of 75 911 patients in 2008; a 2.6-fold increase (0.47 to 1.23%). There were 155 872 infants <34 weeks estimated gestational age discharged between 1 January 2000 and 31 December 2008; 1656 (1.1%) were treated with iNO. Since approval in 2000, the reported use of iNO in neonates <34 weeks increased from 0.3 to 1.8% in 2008; a sixfold increase in the reported use of iNO. The biggest increase occurred in infants between 23 and 26 weeks' gestational age (0.8 to 6.6%). In contrast, the increase in iNO use among neonates born ≥34 weeks has only increased from 0.5 to 1%. CONCLUSION: The use of iNO has increased and the greatest increase has been the off-label use among preterm neonates.

A retrospective review of the sleep characteristics in patients with chronic fatigue syndrome and fibromyalgia.

This study characterizes findings on sleep testing and Human Leukocyte Antigen (HLA) markers in a group of patients with fibromyalgia (FM) and chronic fatigue syndrome (CFS). One hundred eighteen patients seen in a general neurology practice over 5 years meeting standard clinical criteria for FM or CFS were analyzed retrospectively. Cases of untreated sleep apnea or restless legs syndrome were excluded prior to inclusion in this study. Ninety-two patients had multiple sleep latency testing (MSLT). Seventy-three (80%) were abnormal by standard criteria. Of 57 females having positive MSLTs, 22 (39%) had one or more periods of sleep onset rapid eye movement (SOREM), and 5 of 16 (31%) males with positive MSLTs had one or more SOREM. Highly fragmented sleep, as previously described in FM, was seen but not analyzed quantitatively. HLA DQB1*0602 was obtained in 74 patients, and positive in 32 (43%), P < 0.0001 compared with published values in 228 populations. In our patients, who presented with neuromuscular fatigue or generalized pain, we found a sleep disorder characterized by objective hypersomnia. Some patients had characteristics of narcolepsy. Objective assessment by sleep studies can assist the diagnostic process, aid future research, and provide rationale for treatment.

Meconium aspiration syndrome remains a significant problem in the NICU: outcomes and treatment patterns in term neonates admitted for intensive care during a ten-year period.

OBJECTIVE: The purpose of this study was to evaluate the demographic and treatment characteristics of neonates (>or=37 weeks' estimated gestational age) who were admitted to a neonatal intensive care unit (NICU) for a diagnosis of meconium aspiration syndrome (MAS) during the years 1997 to 2007. The goals in studying this group of neonates were to better estimate the magnitude of abnormal outcomes and to determine the proportion of these infants exposed to specific therapeutic interventions. STUDY DESIGN: Retrospective review of an administrative de-identified data set. RESULT: A total of 415,772 neonates formed the starting data set and 162,075 (39%) were >or=37 weeks. Of the 162,075 term neonates, 7518 (1.8% of all neonates and 4.6% of term NICU admissions) had an admission diagnosis of MAS. In the 7518 neonates, the following outcomes were observed: 6124 (81.5%) were discharged home; 679 (9%) were acutely transferred to a higher level of intensive care; 416 (5.5%) were transferred to another clinical service within the hospital; 178 (2.4%) were transferred to another NICU for convalescent care and 88 (1.2%) died. There were 33 (0.4%) who did not have data on outcome at discharge. During the period between 2002 and 2005, acute transfer rates decreased (12.4 to 9%) and the reported rate for death remained relatively constant between 0.9 and 1.5%. There were 107 (1.4%) neonates who were treated (n=61) with, or transferred, for extracorporeal membrane oxygenation (ECMO) (n=46). Three of the sixty-one neonates (4.9%) who were treated with ECMO died. CONCLUSION: Term neonates who are admitted with a diagnosis of MAS continue to represent a high-risk population with significant morbidity, and they often require intensive therapies.

The influence of amino-acid supplementation, gestational age and time on thyroxine levels in premature neonates.

OBJECTIVE: Newborn screening laboratories vary in the values that are used to define congenital hypothyroidism. Defining congenital hypothyroidism is particularly complex in premature neonates because prematurely born infants often have a low free thyroxine value and low or normal TSH value, termed as transient hypothyroxinemia of prematurity. In a multicenter (n=11 sites) trial, we randomly allocated premature neonates with a gestational age of 23 to 29 and 6/7 weeks to one of two parenteral nutrition approaches. The primary objective of our trial was to measure the effect of two distinct strategies of parenteral nutrition on neonatal growth and blood amino acids. A protocol defined secondary aim of our clinical trial was the evaluation of the influence of gestational age, time and the degree of amino-acid supplementation on total thyroxine levels. We hypothesized that an increase of amino-acid supplementation would be associated with the normalization of serum amino acids and that this would improve thyroxine synthesis. STUDY DESIGN: Premature neonates (23 to 29 and 6/7 weeks) were randomly allocated to one of two approaches to intravenous amino-acid administration. In one group, amino-acid supplementation started at 1.0 g kg(-1) per day and advanced by 0.5 g kg(-1) per day to a maximum of 2.5 g kg(-1) per day (2.5 group). The other group received amino acids at 1.5 g kg(-1) per day and advanced by 1.0 g kg(-1) per day to a maximum of 3.5 g kg(-1) per day (3.5 group). Filter paper blood spots were obtained on the day of randomization, and on days 7 and 28 of age to monitor laboratory values. RESULT: Enrollment included 122 neonates, 64 in the 3.5 group and 58 in the 2.5 group. There were no differences in demographics or baseline characteristics between the two treatment groups. There were no significant differences in thyroid levels at baseline, on days 7 and 28 between the two treatment groups. Growth was similar in both groups. It was noted that thyroxine levels changed over time and that the changes with time were greatest in the most preterm neonates. CONCLUSION: The degree of amino-acid supplementation does not influence thyroxine levels and both time from birth and gestational age do influence thyroxine levels.

Demographic and nutritional factors associated with prolonged cholestatic jaundice in the premature infant.

OBJECTIVE: The primary aim of this study was to determine if an association exists between amino-acid levels and development of cholestasis. The secondary aim of our amino-acid dose comparison trial was to identify factors associated with the development of prolonged cholestatic jaundice. STUDY DESIGN: We compared demographic characteristics and amino-acid levels in neonates who developed cholestasis with those who did not. Parenteral-associated cholestatic liver disease was defined as a direct serum bilirubin above 5 mg per 100 ml any time during the first 28 days after birth in neonates with no history of biliary atresia or viral hepatitis. We obtained filter paper blood spots for amino acid and acylcarnitine measurements on the day of randomization and days 7 and 28 of age to identify a profile of values that could be used to identify neonates with evidence of abnormal liver function. RESULT: We enrolled 122 neonates in our study; 13 (10.7%) developed cholestasis. Neonates who developed cholestasis were more immature, had lower birth weight, were exposed to parenteral nutrition for a longer period, had a higher cumulative dose of amino acids, were less often on enteral nutrition by day 7 of age, more often had a patent ductus arteriosus and severe intraventricular hemorrhage and were more commonly treated with steroids by 28 days of age. Amino acid and acylcarnitine values were not different for the two groups on the day of randomization. On day 7 (parenteral phase of nutrition), blood urea nitrogen, citrulline, histidine, methionine and succinyl carnitine were higher, and serine, glutamate and thyroxine levels were lower in the neonates who developed cholestasis than in who did not. CONCLUSION: Cholestasis remains an important complication of parenteral nutrition, and several clinical and biochemical factors may be helpful in identifying high-risk patients.

Role of multiple site blood cultures to document the clearance of bacteremia in neonates.

OBJECTIVE: To evaluate the usefulness of two-site blood cultures for the documentation of bacterial clearance during initial treatment of culture proven neonatal sepsis. DESIGN/METHODS: Clinical data were prospectively collected for 216 neonates who had blood cultures drawn for evaluation of possible sepsis. A positive diagnostic blood culture was followed by repeat blood cultures from two different peripheral sites after initiation of antimicrobial therapy. RESULTS: Follow-up two-site cultures were drawn on 25 occasions at a median interval of 3 days after start of antimicrobial therapy for culture-proven sepsis in 15 neonates. On 12 occasions, follow-up blood cultures were both negative. On eight occasions, follow-up blood cultures grew the same organisms from both sites. However, follow-up two-site cultures on five occasions in four of the 15 infants grew organisms from one site but not the second site. CONCLUSIONS: Two-site blood cultures seem necessary to document bacterial clearance in response to antimicrobial therapy for culture-proven sepsis, and may help determine the appropriate duration of antimicrobial therapy by reducing false-negative results.