Antenatal methadone vs buprenorphine exposure and length of hospital stay in infants admitted to the intensive care unit with neonatal abstinence syndrome.

OBJECTIVE: Antenatal exposure to methadone or buprenorphine often causes neonatal abstinence syndrome (NAS) in newborns. However, comparative effects on affected infants' hospital courses are inconclusive. We sought to estimate the relationship of antenatal exposure with methadone or buprenorphine and infants' length of stay among hospitalized infants with NAS. STUDY DESIGN: This was a retrospective cohort study of hospitalized infants with NAS with either maternal exposure. Eligible infants were singleton infants born ⩾36 weeks' gestation and diagnosed with NAS<7 days of age between 2011 and 2014 in the Pediatrix Clinical Data Warehouse. Infant with congenital anomalies and those of multiple gestation were excluded. RESULTS: Of 3364 eligible infants, 2202 (65%) were exposed to methadone and 1162 (34%) to buprenorphine. Infants exposed to buprenorphine had a lower rate of pharmacologic treatment for NAS (88 vs 91%, P<0.001). Median length of hospital stay was shorter among infants exposed to buprenorphine (21 days (inter-quartile range; 13-31) vs methadone (24 days (15-38), P<0.0001)). On multivariable Cox proportional hazard analyses, buprenorphine was associated with a shorter length of stay (hazard ratio (HR)=1.47 (95% confidence interval (CI): 1.32-1.62, P<0.001) after controlling for maternal age, parity, race or ethnicity, prenatal care, smoking status, use of antidepressants, use of benzodiazepines, and infant gestational age, small for gestational age status, cesarean delivery, sex, out born status, type of pharmacotherapy, breast milk use, year and center. We observed similar results in model using infants matched 1:1 with propensity scores for antenatal medication exposure (HR 1.39 for buprenorphine, CI 1.32-1.62, P<0.001). CONCLUSION: Among infants born ⩾36 weeks' gestation with NAS, antenatal buprenorphine exposure was associated with a decreased length of stay relative to antenatal methadone exposure.

Association of in utero magnesium exposure and spontaneous intestinal perforations in extremely low birth weight infants.

OBJECTIVE: The objective of this study is to determine whether antenatal exposure to magnesium is associated with spontaneous intestinal perforation (SIP) in extremely low birth weight (ELBW) infants (⩽1000 g). STUDY DESIGN: We identified all ELBW infants admitted to 1 of 323 neonatal intensive care units from 2007 to 2013. We used multivariable conditional logistic regression to compare outcomes in the first 21 days after birth between infants exposed and unexposed to magnesium in utero. RESULTS: Of the 28 035 infants, 11 789 (42%) were exposed to antenatal magnesium (AM). There was no difference in the risk of SIP, odds ratio=1.08 (95% confidence interval; 0.91 to 1.29), between infants exposed and unexposed to AM. Mortality in the first 21 days after birth was lower in the magnesium-exposed infants, odds ratio=0.76 (0.70 to 0.83). CONCLUSION: AM exposure in ELBW infants was not associated with increased risk of SIP.

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.

Risk factors for group B streptococcal disease in neonates of mothers with negative antenatal testing.

OBJECTIVE: The aim of this study was to identify risk factors for early-onset group B Streptococcus (EOGBS) disease in neonates of mothers with negative antenatal screening. STUDY DESIGN: We performed a retrospective cohort study of neonates born to mothers with negative antenatal GBS screening between 2002 and 2012. Our primary outcome was EOGBS infection. We used multivariable logistic regression to assess factors associated with EOGBS. RESULTS: EOGBS was confirmed in 492 of the 179 818 neonates that met the study inclusion criteria. Risk factors for EOGBS included black race (reference: white, odds ratio (OR) =1.81 (95% confidence interval: 1.43, 2.31)), maternal age <18 years (reference: >35 years, OR=2.63 (1.54, 4.51)) and maternal age 18 to 35 years (reference: >35 years, OR=1.94 (1.30, 2.88)). CONCLUSION: Maternal age <18 years and black race were the strongest predictors of EOGBS. Further research investigating contributors to the discordance between screening results and neonatal outcomes in these populations is needed.

Changing antiepileptic drug use for seizures in US neonatal intensive care units from 2005 to 2014.

OBJECTIVE: Neonatal seizures are a common problem in the neonatal intensive care unit and are frequently treated with antiepileptic drugs. Limited data exist on current or changing antiepileptic drug use for seizures in the neonatal intensive care unit.We sought to describe trends of antiepileptic drug exposure in a large volume of US neonatal intensive care unit from 2005 to 2014 and we hypothesized increasing levetiracetam exposure over the 10-year study period. STUDY DESIGN: Retrospective cohort study of infants from the Pediatrix Medical Group Clinical Data Warehouse, a large, multicenter, deidentified data set. Data were analyzed for trends in 2-year time periods. Our cohort included infants with a diagnosis of seizures who received an antiepileptic drug that were discharged from the neonatal intensive care unit from 1 January 2005 to 31 December 2014. RESULTS: Among 778 395 infants from 341 facilities, we identified 9134 infants with a seizure diagnosis who received an antiepileptic drug. Phenobarbital was used in 98% of the cohort. From 2005-2006 to 2013-2014 phenobarbital exposure declined from 99 to 96% (P<0.001), phenytoin exposure decreased from 15 to 11% (P<0.001) and levetiracetam exposure increased 10-fold from 1.4 to 14% (P<0.001). Overall, <1% of infants were exposed to carbamazepine, lidocaine or topiramate. CONCLUSIONS: Infants with seizures were overwhelmingly exposed to phenobarbital, despite a significant increase in levetiracetam exposure. The use of phenytoin declined and has been surpassed by levetiracetam as the second most widely used antiepileptic in the neonatal intensive care unit. These changes in antiepileptic drug usage patterns have occurred in the absence of novel efficacy data in neonates.

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.

Sildenafil and retinopathy of prematurity risk in very low birth weight infants.

OBJECTIVE: To examine the effect of sildenafil therapy on development of severe retinopathy of prematurity (ROP) requiring surgical intervention in premature infants. STUDY DESIGN: We identified premature infants who were discharged from Pediatrix Medical Group neonatal intensive care units from 2003 to 2012 and who received an ophthalmologic exam. We matched each infant exposed to sildenafil before first eye exam to three nonexposed infants using propensity scoring to control for differences in baseline infant characteristics. We evaluated the association between sildenafil exposure and development of severe ROP using conditional logistic regression. RESULT: Of the 57 815 infants meeting inclusion criteria, 88 were exposed to sildenafil. We matched 81/88 (92%) sildenafil-exposed with 243 nonexposed infants. There was no difference in the proportion of infants who developed severe ROP in the sildenafil-exposed vs nonexposed groups (17/81 (21%) vs 38/243 (16%), P=0.27). On adjusted analysis, there was no difference in severe ROP in the sildenafil-exposed vs nonexposed infants (odds ratio=1.46, 95% confidence interval=0.76 to 2.82, P=0.26). CONCLUSION: We did not observe an association between risk of severe ROP and sildenafil exposure before first eye exam in this cohort of premature infants.

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.

Urinary tract infection concordance with positive blood and cerebrospinal fluid cultures in the neonatal intensive care unit.

OBJECTIVE: Urinary tract infections (UTI) are common in the neonatal intensive care unit (NICU). Blood, urine and cerebrospinal fluid (CSF) cultures are frequently obtained to evaluate for infection. We sought to determine the concordance between positive urine cultures and blood or CSF cultures. STUDY DESIGN: Infants <121 days of age with a UTI admitted to 322 NICUs managed by the Pediatrix Medical Group from 1997 to 2010 were identified. UTIs were defined by isolation of a single pathogenic organism in a urine sample obtained by catheterization or suprapubic tap. The UTI was concordant if the same organism was identified in the blood or CSF within 3 days of the urine culture. RESULT: Of 5681 infants with a urine culture, 984 had 1162 UTIs. In total, 976 UTIs (84%) had a blood culture collected within 3 days, and 127 (13%) were concordant. Of the 1162 UTIs, 77 (7%) had a CSF culture collected within 3 days, and 2 (3%) were concordant. CONCLUSION: Collection of a urine culture in infants evaluated for late-onset sepsis is important. Concordance was observed in 13% of blood cultures and 3% of CSF cultures. These findings may be related to the initiation of empirical antimicrobial therapy before evaluation for disseminated infection or poor blood culture sensitivity.

Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units.

BACKGROUND: Very-low-birth-weight (VLBW, <1500 g birth weight) infants are at high risk for both early- and late-onset sepsis. Prior studies have observed a predominance of Gram-negative organisms as a cause of early-onset sepsis and Gram-positive organisms as a cause of late-onset sepsis. These reports are limited to large, academic neonatal intensive care units (NICUs) and may not reflect findings in other units. The purpose of this study was to determine the risk factors for sepsis, the causative organisms, and mortality following infection in a large and diverse sample of NICUs. METHODS: We analysed the results of all cultures obtained from VLBW infants admitted to 313 NICUs from 1997 to 2010. RESULTS: Over 108,000 VLBW infants were admitted during the study period. Early-onset sepsis occurred in 1032 infants, and late-onset sepsis occurred in 12,204 infants. Gram-negative organisms were the most commonly isolated pathogens in early-onset sepsis, and Gram-positive organisms were most commonly isolated in late-onset sepsis. Early- and late-onset sepsis were associated with increased risk of death controlling for other confounders (odds ratio 1.45 [95% confidence interval [CI] 1.21,1.73], and OR 1.30 [95%CI 1.21, 1.40], respectively). CONCLUSIONS: This is the largest report of sepsis in VLBW infants to date. Incidence for early-onset sepsis and late-onset sepsis has changed little over this 14-year period, and overall mortality in VLBW infants with early- and late-onset sepsis is higher than in infants with negative cultures.

Sepsis in young infants with congenital heart disease.

BACKGROUND: We sought to describe the incidence, pathogen distribution, and mortality associated with blood culture-proven sepsis in young infants with congenital heart disease (CHD) admitted to a neonatal intensive care unit (NICU). METHODS: Cohort study of all blood cultures obtained from infants with CHD between 4 and 120 days of age cared for in 250 NICUs managed by the Pediatrix Medical Group in the United States between 1996 and 2007. RESULTS: Of 11,638 infants with CHD, 656 (6%) had 821 episodes of sepsis: a cumulative incidence of 71/1000 admissions. Gram-positive organisms were the most common cause (64%), and coagulase-negative Staphylococcus and Staphylococcus aureus were the most frequently isolated species. On multivariable regression, infants with sepsis were more likely to die compared to infants with sterile blood cultures (odds ratio [OR] = 1.53 [95% confidence interval: 1.09, 2.13]). Infants with Gram-negative bacteraemia and candidaemia were more likely to die than infants with sterile blood cultures (OR = 2.01 [1.20, 3.37], and OR = 3.18 [1.60, 6.34], respectively). CONCLUSION: Infants with CHD have a high incidence of culture-proven sepsis, especially with staphylococcal organisms. Gram-negative bacteraemia and candidaemia are strongly associated with increased mortality in this group of young infants.

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.

Factors associated with mortality in neonates with gastroschisis.

PURPOSE: The ongoing epidemic of gastroschisis has created multiple challenges and continues to raise questions concerning the optimal management of these high-risk patients. Although the overall survival rate has increased over the past 3 decades, morbidity and mortality remain significant. The purpose of this study was to analyze the main factors associated with mortality in neonates admitted to an intensive care unit for the management of this abdominal wall defect. METHODS: This study is a retrospective review of a large de-identified neonatal intensive care dataset encompassing 284 institutions in 32 states and Puerto Rico, from 1/1/1997 to 1/1/2010. Of the 629 440 neonates in the dataset, a total of 3 456 newborns were diagnosed with gastroschisis (5.5/1 000 hospital discharges). Of these, 685 were transferred to other centers and data was missing on 22, leaving 2 749 infants available for analysis. RESULTS: Out of these 2 749 infants of whom we knew the outcome, 115 (4.2%) died. Multivariate logistic regression showed that the factors independently associated with an increased risk of death were male gender, immature gestational age, low birth weight, low 5 min Apgar Score, the need for vasopressors during the first week after birth and the need for high levels of oxygen support. The presence of associated anomalies, vaginal delivery, treatment with surfactant and the need for ventilator support on the day of birth were not independent risk factors associated with an increased mortality. CONCLUSION: Premature delivery and low birth weight are the most important factors associated with an increased risk of mortality. Cesarean section does not appear to reduce the risk.

Repeat lumbar punctures in infants with meningitis in the neonatal intensive care unit.

OBJECTIVE: The purpose of this study is to examine the results of repeat lumbar puncture in infants with initial positive cerebrospinal fluid (CSF) cultures in order to determine the clinical characteristics and outcomes of infants with repeat positive cultures. STUDY DESIGN: Cohort study of infants with an initial positive CSF culture undergoing repeat lumbar puncture between 1997 and 2004 at 150 neonatal intensive care units managed by the Pediatrix Medical group. We compared the clinical outcomes of infants with repeat positive cultures and infants with repeat negative cultures. RESULT: We identified 118 infants with repeat CSF cultures. Of these, 26 infants had repeat positive cultures. A higher proportion with repeat positive cultures died compared with those with repeat negative cultures, 6/23 (26%) vs. 6/81 (7%), respectively (P=0.02). CONCLUSION: Among infants with a positive CSF culture, a repeat positive CSF culture is common. The presence of a second positive culture is associated with increased mortality.

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.

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.

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.

Neonatal Candida meningitis: significance of cerebrospinal fluid parameters and blood cultures.

OBJECTIVE: The purpose of this study was to examine the frequency of normal cerebrospinal fluid (CSF) parameters in Candida meningitis and the proportion of candidemia associated with Candida meningitis. STUDY DESIGN: We evaluated the initial lumbar puncture results from infants discharged from 150 Neonatal Intensive Care Units between 1997 and 2004. Candida meningitis was diagnosed by a positive CSF culture or positive Gram stain for yeast. We calculated two-tailed P-values using non-parametric testing, Mann-Whitney, Kruskal-Wallis or Fisher's exact tests where appropriate. RESULTS: Twenty infants had culture-positive Candida meningitis. Normal CSF parameters were found in 43% (3/7) of the infants with Candida meningitis and only 37% (7/19) of them had positive blood cultures for Candida. CONCLUSION: Normal CSF parameters do not exclude the diagnosis of neonatal Candida meningitis. The majority of infants in this cohort with Candida meningitis did not have evidence of candidemia at the time of diagnosis.