Articles Translational Investigation nature publishing group Background: To assess the ability of... more Articles Translational Investigation nature publishing group Background: To assess the ability of urinary neutrophil gelatinase-associated lipocalin (UNGAL) to discriminate between culture-positive vs. culture-negative late-onset sepsis evaluations. Methods: This is a prospective observational study of 136 neonates who underwent ≥1 sepsis evaluation at >72 h of age. Urine was obtained at the time of sepsis evaluation to measure UNGAL concentration. Using generalized estimating equations controlling for gender, gestational and postnatal age, acute kidney injury, and within-patient correlations, pair-wise contrasts between mean log UNGAL concentrations of infants with negative sepsis evaluations vs. culture-positive sepsis and presumed sepsis were assessed. Discrimination characteristics at several UNGAL cutoff concentrations were assessed using receiver-operating characteristic curves. results: The predicted mean log UNGAL values of culture-positive sepsis and presumed sepsis vs. negative sepsis evaluations differed significantly (P < 0.001 and P = 0.02, respectively). At a cutoff ≥ 50 ng/ml, UNGAL discriminated between culture-positive sepsis and culture-negative sepsis evaluations with sensitivity = 86%, specificity = 56%, positive predictive value = 41%, negative predictive value = 92%, and number needed to treat = 3. conclusion: UNGAL is a noninvasive biomarker with high negative predictive value at the time of late-onset sepsis evaluation in neonates and could be a useful adjunct to traditional components of sepsis evaluations.
Need for the early identification of sepsis in very low birth weight (VLBW) infants has led to th... more Need for the early identification of sepsis in very low birth weight (VLBW) infants has led to the search for reliable biomarkers. This study aims to determine whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) rises in culture-positive sepsis and, if so, is elevated at the time sepsis is suspected. This is a prospective study of 91 VLBW infants whose urine was collected daily for uNGAL analysis. In 65 episodes of suspected sepsis, four groups were identified: a) culture-positive sepsis; b) single culture positive for Staphylococcus epidermidis; c) and d) negative culture with antibiotic treatment for Ն7 d and Ͻ7 d, respectively. Daily means of uNGAL of each group were estimated for comparison. Mean uNGAL in group A (179 ng/mL) was significantly elevated on the day blood culture was drawn (day 0) compared with the mean of healthy VLBW infants (6.5 ng/mL), and to the means in groups B, C, and D (p Ͻ 0.05). In group A, mean uNGAL was significantly elevated on day 0 and daily for 5 days when compared with that of the day before culture (p Ͻ 0.05 to Ͻ0.005). uNGAL shows promise as an early marker for culture-positive sepsis in VLBW infants.
Elevated urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts acute kidney injury ... more Elevated urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts acute kidney injury (AKI) in children following cardiopulmonary bypass (CPB) during cardiac surgery, but little is known about uNGAL’s predictive ability in neonates in this setting. We sought to determine the relationship between AKI and post-CPB uNGAL in neonates in the first 72 post-operative hours. Methods: Urine samples for uNGAL analysis were collected at preoperative baseline and serially post-operatively from 76 neonates undergoing CPB. Mixed-effects regression models and logistic models assessed associations between uNGAL and AKI (controlling for sex, gestational age, CPB time, surgical complexity, and age at surgery). Receiver-operator curves were applied to define optimal uNGAL cut-off values for AKI diagnosis. Results: Between 0 and 4 h post-operatively, uNGAL values did not differ between neonates with and without AKI. After 4 h until 16 h post-operatively, significant time-wise separation occu...
BACKGROUND: Prolonged storage of transfused red blood cells (RBCs) is associated with hemolysis i... more BACKGROUND: Prolonged storage of transfused red blood cells (RBCs) is associated with hemolysis in healthy adults and inflammation in animal models. We aimed to determine whether storage duration affects markers of hemolysis (e.g., serum bilirubin, iron, and non-transferrin-bound iron (NTBI)) and inflammation (e.g., interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1) in transfused very low birth weight (VLBW) infants. METHODS: Blood samples from 23 independent transfusion events were collected by heel stick before and 2-6 h after transfusion. RESULTS: Serum iron, total bilirubin, NTBI, and MCP-1 levels were significantly increased after transfusion of RBCs (Po0.05 for each comparison). The storage age of transfused RBCs positively correlated with increases in NTBI following transfusion (Po0.001; R 2 = 0.44). No associations between storage duration and changes in the other analytes were observed. CONCLUSION: Transfusion of RBCs into VLBW infants is associated with increased markers of hemolysis and the inflammatory chemokine MCP-1. RBC-storage duration only correlated with increases in NTBI levels following transfusion. NTBI was only observed in healthy adults following 35 days of storage; however, this study suggests that VLBW infants are potentially more susceptible to produce this pathological form of iron, with increased levels observed after transfusion of only 20-day-old RBCs.
Subtle changes in vital signs and their interactions occur in preterm infants prior to overt dete... more Subtle changes in vital signs and their interactions occur in preterm infants prior to overt deterioration from late-onset septicemia (LOS) or necrotizing enterocolitis (NEC). Optimizing predictive algorithms may lead to earlier treatment. For 1,065 very-low-birth-weight (VLBW) infants in two neonatal intensive care units (NICUs), mean, SD, and cross-correlation of respiratory rate, heart rate (HR), and oxygen saturation (SpO2) were analyzed hourly (131 infant-years' data). Cross-correlation (cotrending) between two vital signs was measured allowing a lag of ± 30 s. Cases of LOS and NEC were identified retrospectively (n = 186) and vital sign models were evaluated for ability to predict illness diagnosed in the ensuing 24 h. The best single illness predictor within and between institutions was cross-correlation of HR-SpO2. The best combined model (mean SpO2, SDHR, and cross-correlation of HR-SpO2,) trained at one site with ROC area 0.695 had external ROC area of 0.754 at the oth...
Articles Clinical Investigation nature publishing group Background: We evaluated the potential ut... more Articles Clinical Investigation nature publishing group Background: We evaluated the potential utility of elevated urinary neutrophil gelatinase-associated lipocalin (UNGAL) concentration as a screening test for early identification of acute kidney injury (AKI) in very low birth weight (VLBW) newborns. Methods: Urine for UNGAL analysis was collected prospectively daily until 32 wk postmenstrual age in 91 VLBW newborns, yielding 2,899 specimens. UNGAL values > 50 ng/ml were considered elevated. AKI was defined as two or more consecutive elevations in s[Cr] above the 95 th percentile adjusted for gestational age and chronological age within a 48 h period. We compared UNGAL values taken during the 5 d prior to AKI onset (pre-AKI) to values taken during non-AKI days. results: Overall, 15 episodes of AKI were identified in 13 infants. UNGAL was available in 44 pre-AKI days and 969 non-AKI days. UNGAL > 50 ng/ml occurred more often in pre-AKI days than in non-AKI days (risk ratio 3.48 (1.89, 6.40)). Positive and negative likelihood ratios were 1.92 (1.52, 2.41) and 0.52 (0.34, 0.78), respectively. conclusion: Although UNGAL elevation > 50 ng/ml discriminates between pre-AKI and non-AKI days, high false positive and false negative rates limit utility as a screening test in VLBW newborns.
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung devel... more Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMP...
Background. Ureaplasma urealyticum and its association with chronic lung disease (CLD) of prematu... more Background. Ureaplasma urealyticum and its association with chronic lung disease (CLD) of prematurity has remained a controversial topic. To readdress this question, we performed a longitudinal study using culture and polymerase chain reaction to detect U urealyticum in the respiratory tract of very low birthweight infants throughout their neonatal intensive care unit hospitalizations.Methods. We screened 125 infants weighing <1500 g and/or <32 weeks’ gestational age over a 12-month period, collecting endotracheal, nasopharyngeal, and throat specimens on days of age 1, 3, 7, and weekly thereafter. CLD was defined as dependency on supplemental oxygen at 28 days and at 36 weeks’ postconceptional age.Results. Forty infants (32%) had 1 or more positive specimens by culture or polymerase chain reaction. We identified 3 patterns of U urealyticum colonization: persistently positive (n = 18), early transient (n = 14), and late acquisition (n = 8). We compared the rates of CLD in each ...
JAMA: The Journal of the American Medical Association, 1991
--To examine the added neonatal cost and length of hospital stay associated with fetal cocaine ex... more --To examine the added neonatal cost and length of hospital stay associated with fetal cocaine exposure. --All cocaine-exposed infants in the study population (n = 355) were compared with a random sample of unexposed infants (n = 199). Regression analysis was used to control for the independent effects of maternal age, smoking, alcohol consumption, prenatal care, race, gravidity, and sex of the infant. --A large, public, inner-city hospital studied from 1985 to 1986. --All infants were routinely tested for illicit substances, records were reviewed for maternal histories of substance abuse, and all known cocaine-exposed singleton infants were included. --Cost and length of stay until each infant was medically cleared for hospital discharge and cost and length of stay until each infant was actually discharged from the hospital. --Neonatal hospital costs until medically cleared for discharge were $5200 more for cocaine-exposed infants than for unexposed infants (a difference of $7957 vs $2757 [P = .003]). The costs of infants remaining in the nursery while awaiting home and social evaluation or foster care placement increased this difference by more than $3500 (P less than .0001). Compared with other forms of cocaine, fetal exposure to crack was associated with much larger cost increases ($6735 vs $1226). Exposure to other illicit substances in addition to cocaine was also associated with much larger cost increases ($8450 vs $1283). --At the national level, we estimate that these individual medical costs add up to about $500 million. The large magnitude of these costs indicates that effective treatment programs for maternal cocaine abusers could yield savings within their first year of operation.
use was more common with continuation of antibiotics (39%) than with initiation (4%) of therapy. ... more use was more common with continuation of antibiotics (39%) than with initiation (4%) of therapy. Vancomycin was the most commonly used drug (n ¼ 895 antibiotic-days) of which 284 (32%) days were considered inappropriate. Carbapenems were used less frequently (n ¼ 310 antibioticdays), and 132 (43%) of these days were inappropriate. Common reasons for nonadherence at the time of continuation included failure to narrow antibiotic coverage after microbiologic Results were known and prolonged antibiotic prophylaxis after surgery with chest tube placement. Conclusions.-The CDC 12-Step Campaign can be modified for neonatal populations. Inappropriate antibiotic prescribing was common in the study NICUs. Improvement efforts should target antibiotic use 72 hours after initiation, particularly focusing on narrowing therapy and instituting protocols to limit prophylaxis.
Continuous measurements of minute ventilation (91). oxygen consumption (Vo,), heart rate (HR), ac... more Continuous measurements of minute ventilation (91). oxygen consumption (Vo,), heart rate (HR), activity, and temperature were made in eleven low birth weight infants during the interval between feedings. Significant increases. in Vr, VO,? and HR were noted between quiet and active sleep: (VI ~~~i~~-VI QuieJV~ Quiet) x 100 = 18.4%
This study estimated the strength of association between maternal cocaine use and congenital syph... more This study estimated the strength of association between maternal cocaine use and congenital syphilis after adjustment for other factors, especially the use of prenatal care. The authors reviewed medical chart and laboratory data for 75 liveborn infants treated for congenital syphilis at Harlem Hospital Center (New York City) in 1987, 150 matched control infants, and their mothers. Cocaine use was determined from universal maternal medical histories and infant toxicology screenings, and the sensitivity of each method of ascertainment was evaluated. With the use of either maternal history or positive infant urine toxicology as evidence of cocaine use, 66.2% (49/74) of case infants versus 16.1% (24/149) of control infants were judged to have been exposed to cocaine in utero (odds ratio (OR) = 9.1, 95% confidence interval (Cl) 4.7-29.2). However, in multiple logistic regression, lack of prenatal care was the single variable with the highest adjusted odds ratio (adjusted OR = 11.0, 95% Cl 1.3-93.1); maternal cocaine use had the second-highest adjusted odds ratio (adjusted OR = 4.9, 95% Cl 1.8-13.0). Thus, despite the emergence of maternal cocaine use as a new risk factor, underutilization of prenatal care remains the strongest predictor of congenital syphilis.
Need for the early identification of sepsis in very low birth weight (VLBW) infants has led to th... more Need for the early identification of sepsis in very low birth weight (VLBW) infants has led to the search for reliable biomarkers. This study aims to determine whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) rises in culture-positive sepsis and, if so, is elevated at the time sepsis is suspected. This is a prospective study of 91 VLBW infants whose urine was collected daily for uNGAL analysis. In 65 episodes of suspected sepsis, four groups were identified: a) culture-positive sepsis; b) single culture positive for Staphylococcus epidermidis; c) and d) negative culture with antibiotic treatment for >or=7 d and <7 d, respectively. Daily means of uNGAL of each group were estimated for comparison. Mean uNGAL in group A (179 ng/mL) was significantly elevated on the day blood culture was drawn (day 0) compared with the mean of healthy VLBW infants (6.5 ng/mL), and to the means in groups B, C, and D (p<0.05). In group A, mean uNGAL was significantly elevated on...
Purpose: Increased apnea is a common presenting sign in preterm infants with late onset sepsis (L... more Purpose: Increased apnea is a common presenting sign in preterm infants with late onset sepsis (LOS) and necrotizing enterocolitis (NEC). Respiratory pauses may entrain decreases in heart rate and oxygen saturation, and we hypothesized that an increase in their cross-correlation (CC-HR-SpO2) would occur prior to clinical diagnosis of LOS and NEC. Methods All continuous vital sign data from bedside monitors are stored on all infants in the University of Virginia and Columbia University neonatal intensive care units, including every 2-second recordings of HR and SpO2. CC-HR-SpO2 was calculated in 365 preterm very low birth weight infants for every 10-minute period for their entire NICU stay, resulting in greater than 4 million measurements or 40 infant-years of data. Maximum CC-HR-SpO2 value was identified within each 10-minute window. We then identified cases of blood culture-positive LOS or Bells stage II-III NEC. The relative risk was calculated as the fraction of infants with LOS ...
To assess the ability of urinary neutrophil gelatinase-associated lipocalin (UNGAL) to discrimina... more To assess the ability of urinary neutrophil gelatinase-associated lipocalin (UNGAL) to discriminate between culture-positive versus culture-negative late onset sepsis evaluations. Prospective observational study of 136 neonates who underwent ≥1 sepsis evaluation at >72 hours of age. Urine was obtained at the time of sepsis evaluation to measure UNGAL concentration. Using generalized estimating equations controlling for gender, gestational and postnatal age, acute kidney injury, and within-patient correlations, pair-wise contrasts between mean log UNGAL concentrations of infants with negative sepsis evaluations vs. culture-positive sepsis and presumed sepsis were assessed. Discrimination characteristics at several UNGAL cut-off concentrations were assessed using receiver operator curves. The predicted mean log UNGAL values of culture-positive sepsis and presumed sepsis vs. negative sepsis evaluations differed significantly (p < 0.001 and p = 0.02, respectively). At a cutoff ≥ 5...
BackgroundTo develop serum creatinine (s[Cr]) reference ranges for VLBW infants from birth to 34-... more BackgroundTo develop serum creatinine (s[Cr]) reference ranges for VLBW infants from birth to 34-36 wk post menstrual age (PMA).MethodsRetrospectively identified sample of 218 appropriate-for-GA VLBW infants without risk factors for renal impairment, classified into one of three GA groups: 25-27 wk, 28-29 wk, 30-33 wk. We observed three phases s[Cr] change (initial, decline, and equilibrium), whose characteristics varied by GA group. We used mixed-effects regression models to estimate mean and upper 95(th) prediction interval of s[Cr] for each GA group from birth to 34-36 wk PMA.ResultsIn phase 1, s [Cr] increased after birth, then returned slowly to baseline. The duration of phase 1 and the magnitude of s[Cr] rise decreased with increasing GA. In phase 2, s [Cr] declined abruptly at a rate that increased with GA. A gradual transition to Phase 3, steady state equilibrium with similar s[Cr] among GA groups, began at approximately 34-36 wk PMA. We constructed GA group-specific nomogra...
Articles Translational Investigation nature publishing group Background: To assess the ability of... more Articles Translational Investigation nature publishing group Background: To assess the ability of urinary neutrophil gelatinase-associated lipocalin (UNGAL) to discriminate between culture-positive vs. culture-negative late-onset sepsis evaluations. Methods: This is a prospective observational study of 136 neonates who underwent ≥1 sepsis evaluation at >72 h of age. Urine was obtained at the time of sepsis evaluation to measure UNGAL concentration. Using generalized estimating equations controlling for gender, gestational and postnatal age, acute kidney injury, and within-patient correlations, pair-wise contrasts between mean log UNGAL concentrations of infants with negative sepsis evaluations vs. culture-positive sepsis and presumed sepsis were assessed. Discrimination characteristics at several UNGAL cutoff concentrations were assessed using receiver-operating characteristic curves. results: The predicted mean log UNGAL values of culture-positive sepsis and presumed sepsis vs. negative sepsis evaluations differed significantly (P < 0.001 and P = 0.02, respectively). At a cutoff ≥ 50 ng/ml, UNGAL discriminated between culture-positive sepsis and culture-negative sepsis evaluations with sensitivity = 86%, specificity = 56%, positive predictive value = 41%, negative predictive value = 92%, and number needed to treat = 3. conclusion: UNGAL is a noninvasive biomarker with high negative predictive value at the time of late-onset sepsis evaluation in neonates and could be a useful adjunct to traditional components of sepsis evaluations.
Need for the early identification of sepsis in very low birth weight (VLBW) infants has led to th... more Need for the early identification of sepsis in very low birth weight (VLBW) infants has led to the search for reliable biomarkers. This study aims to determine whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) rises in culture-positive sepsis and, if so, is elevated at the time sepsis is suspected. This is a prospective study of 91 VLBW infants whose urine was collected daily for uNGAL analysis. In 65 episodes of suspected sepsis, four groups were identified: a) culture-positive sepsis; b) single culture positive for Staphylococcus epidermidis; c) and d) negative culture with antibiotic treatment for Ն7 d and Ͻ7 d, respectively. Daily means of uNGAL of each group were estimated for comparison. Mean uNGAL in group A (179 ng/mL) was significantly elevated on the day blood culture was drawn (day 0) compared with the mean of healthy VLBW infants (6.5 ng/mL), and to the means in groups B, C, and D (p Ͻ 0.05). In group A, mean uNGAL was significantly elevated on day 0 and daily for 5 days when compared with that of the day before culture (p Ͻ 0.05 to Ͻ0.005). uNGAL shows promise as an early marker for culture-positive sepsis in VLBW infants.
Elevated urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts acute kidney injury ... more Elevated urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts acute kidney injury (AKI) in children following cardiopulmonary bypass (CPB) during cardiac surgery, but little is known about uNGAL’s predictive ability in neonates in this setting. We sought to determine the relationship between AKI and post-CPB uNGAL in neonates in the first 72 post-operative hours. Methods: Urine samples for uNGAL analysis were collected at preoperative baseline and serially post-operatively from 76 neonates undergoing CPB. Mixed-effects regression models and logistic models assessed associations between uNGAL and AKI (controlling for sex, gestational age, CPB time, surgical complexity, and age at surgery). Receiver-operator curves were applied to define optimal uNGAL cut-off values for AKI diagnosis. Results: Between 0 and 4 h post-operatively, uNGAL values did not differ between neonates with and without AKI. After 4 h until 16 h post-operatively, significant time-wise separation occu...
BACKGROUND: Prolonged storage of transfused red blood cells (RBCs) is associated with hemolysis i... more BACKGROUND: Prolonged storage of transfused red blood cells (RBCs) is associated with hemolysis in healthy adults and inflammation in animal models. We aimed to determine whether storage duration affects markers of hemolysis (e.g., serum bilirubin, iron, and non-transferrin-bound iron (NTBI)) and inflammation (e.g., interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1) in transfused very low birth weight (VLBW) infants. METHODS: Blood samples from 23 independent transfusion events were collected by heel stick before and 2-6 h after transfusion. RESULTS: Serum iron, total bilirubin, NTBI, and MCP-1 levels were significantly increased after transfusion of RBCs (Po0.05 for each comparison). The storage age of transfused RBCs positively correlated with increases in NTBI following transfusion (Po0.001; R 2 = 0.44). No associations between storage duration and changes in the other analytes were observed. CONCLUSION: Transfusion of RBCs into VLBW infants is associated with increased markers of hemolysis and the inflammatory chemokine MCP-1. RBC-storage duration only correlated with increases in NTBI levels following transfusion. NTBI was only observed in healthy adults following 35 days of storage; however, this study suggests that VLBW infants are potentially more susceptible to produce this pathological form of iron, with increased levels observed after transfusion of only 20-day-old RBCs.
Subtle changes in vital signs and their interactions occur in preterm infants prior to overt dete... more Subtle changes in vital signs and their interactions occur in preterm infants prior to overt deterioration from late-onset septicemia (LOS) or necrotizing enterocolitis (NEC). Optimizing predictive algorithms may lead to earlier treatment. For 1,065 very-low-birth-weight (VLBW) infants in two neonatal intensive care units (NICUs), mean, SD, and cross-correlation of respiratory rate, heart rate (HR), and oxygen saturation (SpO2) were analyzed hourly (131 infant-years' data). Cross-correlation (cotrending) between two vital signs was measured allowing a lag of ± 30 s. Cases of LOS and NEC were identified retrospectively (n = 186) and vital sign models were evaluated for ability to predict illness diagnosed in the ensuing 24 h. The best single illness predictor within and between institutions was cross-correlation of HR-SpO2. The best combined model (mean SpO2, SDHR, and cross-correlation of HR-SpO2,) trained at one site with ROC area 0.695 had external ROC area of 0.754 at the oth...
Articles Clinical Investigation nature publishing group Background: We evaluated the potential ut... more Articles Clinical Investigation nature publishing group Background: We evaluated the potential utility of elevated urinary neutrophil gelatinase-associated lipocalin (UNGAL) concentration as a screening test for early identification of acute kidney injury (AKI) in very low birth weight (VLBW) newborns. Methods: Urine for UNGAL analysis was collected prospectively daily until 32 wk postmenstrual age in 91 VLBW newborns, yielding 2,899 specimens. UNGAL values > 50 ng/ml were considered elevated. AKI was defined as two or more consecutive elevations in s[Cr] above the 95 th percentile adjusted for gestational age and chronological age within a 48 h period. We compared UNGAL values taken during the 5 d prior to AKI onset (pre-AKI) to values taken during non-AKI days. results: Overall, 15 episodes of AKI were identified in 13 infants. UNGAL was available in 44 pre-AKI days and 969 non-AKI days. UNGAL > 50 ng/ml occurred more often in pre-AKI days than in non-AKI days (risk ratio 3.48 (1.89, 6.40)). Positive and negative likelihood ratios were 1.92 (1.52, 2.41) and 0.52 (0.34, 0.78), respectively. conclusion: Although UNGAL elevation > 50 ng/ml discriminates between pre-AKI and non-AKI days, high false positive and false negative rates limit utility as a screening test in VLBW newborns.
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung devel... more Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMP...
Background. Ureaplasma urealyticum and its association with chronic lung disease (CLD) of prematu... more Background. Ureaplasma urealyticum and its association with chronic lung disease (CLD) of prematurity has remained a controversial topic. To readdress this question, we performed a longitudinal study using culture and polymerase chain reaction to detect U urealyticum in the respiratory tract of very low birthweight infants throughout their neonatal intensive care unit hospitalizations.Methods. We screened 125 infants weighing <1500 g and/or <32 weeks’ gestational age over a 12-month period, collecting endotracheal, nasopharyngeal, and throat specimens on days of age 1, 3, 7, and weekly thereafter. CLD was defined as dependency on supplemental oxygen at 28 days and at 36 weeks’ postconceptional age.Results. Forty infants (32%) had 1 or more positive specimens by culture or polymerase chain reaction. We identified 3 patterns of U urealyticum colonization: persistently positive (n = 18), early transient (n = 14), and late acquisition (n = 8). We compared the rates of CLD in each ...
JAMA: The Journal of the American Medical Association, 1991
--To examine the added neonatal cost and length of hospital stay associated with fetal cocaine ex... more --To examine the added neonatal cost and length of hospital stay associated with fetal cocaine exposure. --All cocaine-exposed infants in the study population (n = 355) were compared with a random sample of unexposed infants (n = 199). Regression analysis was used to control for the independent effects of maternal age, smoking, alcohol consumption, prenatal care, race, gravidity, and sex of the infant. --A large, public, inner-city hospital studied from 1985 to 1986. --All infants were routinely tested for illicit substances, records were reviewed for maternal histories of substance abuse, and all known cocaine-exposed singleton infants were included. --Cost and length of stay until each infant was medically cleared for hospital discharge and cost and length of stay until each infant was actually discharged from the hospital. --Neonatal hospital costs until medically cleared for discharge were $5200 more for cocaine-exposed infants than for unexposed infants (a difference of $7957 vs $2757 [P = .003]). The costs of infants remaining in the nursery while awaiting home and social evaluation or foster care placement increased this difference by more than $3500 (P less than .0001). Compared with other forms of cocaine, fetal exposure to crack was associated with much larger cost increases ($6735 vs $1226). Exposure to other illicit substances in addition to cocaine was also associated with much larger cost increases ($8450 vs $1283). --At the national level, we estimate that these individual medical costs add up to about $500 million. The large magnitude of these costs indicates that effective treatment programs for maternal cocaine abusers could yield savings within their first year of operation.
use was more common with continuation of antibiotics (39%) than with initiation (4%) of therapy. ... more use was more common with continuation of antibiotics (39%) than with initiation (4%) of therapy. Vancomycin was the most commonly used drug (n ¼ 895 antibiotic-days) of which 284 (32%) days were considered inappropriate. Carbapenems were used less frequently (n ¼ 310 antibioticdays), and 132 (43%) of these days were inappropriate. Common reasons for nonadherence at the time of continuation included failure to narrow antibiotic coverage after microbiologic Results were known and prolonged antibiotic prophylaxis after surgery with chest tube placement. Conclusions.-The CDC 12-Step Campaign can be modified for neonatal populations. Inappropriate antibiotic prescribing was common in the study NICUs. Improvement efforts should target antibiotic use 72 hours after initiation, particularly focusing on narrowing therapy and instituting protocols to limit prophylaxis.
Continuous measurements of minute ventilation (91). oxygen consumption (Vo,), heart rate (HR), ac... more Continuous measurements of minute ventilation (91). oxygen consumption (Vo,), heart rate (HR), activity, and temperature were made in eleven low birth weight infants during the interval between feedings. Significant increases. in Vr, VO,? and HR were noted between quiet and active sleep: (VI ~~~i~~-VI QuieJV~ Quiet) x 100 = 18.4%
This study estimated the strength of association between maternal cocaine use and congenital syph... more This study estimated the strength of association between maternal cocaine use and congenital syphilis after adjustment for other factors, especially the use of prenatal care. The authors reviewed medical chart and laboratory data for 75 liveborn infants treated for congenital syphilis at Harlem Hospital Center (New York City) in 1987, 150 matched control infants, and their mothers. Cocaine use was determined from universal maternal medical histories and infant toxicology screenings, and the sensitivity of each method of ascertainment was evaluated. With the use of either maternal history or positive infant urine toxicology as evidence of cocaine use, 66.2% (49/74) of case infants versus 16.1% (24/149) of control infants were judged to have been exposed to cocaine in utero (odds ratio (OR) = 9.1, 95% confidence interval (Cl) 4.7-29.2). However, in multiple logistic regression, lack of prenatal care was the single variable with the highest adjusted odds ratio (adjusted OR = 11.0, 95% Cl 1.3-93.1); maternal cocaine use had the second-highest adjusted odds ratio (adjusted OR = 4.9, 95% Cl 1.8-13.0). Thus, despite the emergence of maternal cocaine use as a new risk factor, underutilization of prenatal care remains the strongest predictor of congenital syphilis.
Need for the early identification of sepsis in very low birth weight (VLBW) infants has led to th... more Need for the early identification of sepsis in very low birth weight (VLBW) infants has led to the search for reliable biomarkers. This study aims to determine whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) rises in culture-positive sepsis and, if so, is elevated at the time sepsis is suspected. This is a prospective study of 91 VLBW infants whose urine was collected daily for uNGAL analysis. In 65 episodes of suspected sepsis, four groups were identified: a) culture-positive sepsis; b) single culture positive for Staphylococcus epidermidis; c) and d) negative culture with antibiotic treatment for >or=7 d and <7 d, respectively. Daily means of uNGAL of each group were estimated for comparison. Mean uNGAL in group A (179 ng/mL) was significantly elevated on the day blood culture was drawn (day 0) compared with the mean of healthy VLBW infants (6.5 ng/mL), and to the means in groups B, C, and D (p<0.05). In group A, mean uNGAL was significantly elevated on...
Purpose: Increased apnea is a common presenting sign in preterm infants with late onset sepsis (L... more Purpose: Increased apnea is a common presenting sign in preterm infants with late onset sepsis (LOS) and necrotizing enterocolitis (NEC). Respiratory pauses may entrain decreases in heart rate and oxygen saturation, and we hypothesized that an increase in their cross-correlation (CC-HR-SpO2) would occur prior to clinical diagnosis of LOS and NEC. Methods All continuous vital sign data from bedside monitors are stored on all infants in the University of Virginia and Columbia University neonatal intensive care units, including every 2-second recordings of HR and SpO2. CC-HR-SpO2 was calculated in 365 preterm very low birth weight infants for every 10-minute period for their entire NICU stay, resulting in greater than 4 million measurements or 40 infant-years of data. Maximum CC-HR-SpO2 value was identified within each 10-minute window. We then identified cases of blood culture-positive LOS or Bells stage II-III NEC. The relative risk was calculated as the fraction of infants with LOS ...
To assess the ability of urinary neutrophil gelatinase-associated lipocalin (UNGAL) to discrimina... more To assess the ability of urinary neutrophil gelatinase-associated lipocalin (UNGAL) to discriminate between culture-positive versus culture-negative late onset sepsis evaluations. Prospective observational study of 136 neonates who underwent ≥1 sepsis evaluation at >72 hours of age. Urine was obtained at the time of sepsis evaluation to measure UNGAL concentration. Using generalized estimating equations controlling for gender, gestational and postnatal age, acute kidney injury, and within-patient correlations, pair-wise contrasts between mean log UNGAL concentrations of infants with negative sepsis evaluations vs. culture-positive sepsis and presumed sepsis were assessed. Discrimination characteristics at several UNGAL cut-off concentrations were assessed using receiver operator curves. The predicted mean log UNGAL values of culture-positive sepsis and presumed sepsis vs. negative sepsis evaluations differed significantly (p < 0.001 and p = 0.02, respectively). At a cutoff ≥ 5...
BackgroundTo develop serum creatinine (s[Cr]) reference ranges for VLBW infants from birth to 34-... more BackgroundTo develop serum creatinine (s[Cr]) reference ranges for VLBW infants from birth to 34-36 wk post menstrual age (PMA).MethodsRetrospectively identified sample of 218 appropriate-for-GA VLBW infants without risk factors for renal impairment, classified into one of three GA groups: 25-27 wk, 28-29 wk, 30-33 wk. We observed three phases s[Cr] change (initial, decline, and equilibrium), whose characteristics varied by GA group. We used mixed-effects regression models to estimate mean and upper 95(th) prediction interval of s[Cr] for each GA group from birth to 34-36 wk PMA.ResultsIn phase 1, s [Cr] increased after birth, then returned slowly to baseline. The duration of phase 1 and the magnitude of s[Cr] rise decreased with increasing GA. In phase 2, s [Cr] declined abruptly at a rate that increased with GA. A gradual transition to Phase 3, steady state equilibrium with similar s[Cr] among GA groups, began at approximately 34-36 wk PMA. We constructed GA group-specific nomogra...
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Papers by David Bateman