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Background: Clinicians could modify dietary interventions during early infancy by monitoring fat and fat-free mass accretion in very preterm infants., Methods: Preterm infants were randomly assigned to either having reports on infant body composition available to the clinicians caring for them (intervention group) or not having reports available (control group). All infants underwent serial assessments of body composition by air-displacement plethysmography before 32 weeks of postmenstrual age (PMA) and at 36 weeks PMA. The primary outcome was percent body fat (%BF) at 3 months of corrected age (CA)., Results: Fifty infants were randomized (median gestational age: 30 weeks; mean ± SD birth weight: 1387 ± 283 g). The mean %BF increased from 7 ± 4 before 32 weeks PMA to 20 ± 5 at 3 months CA. The differences in mean %BF between the intervention group and the control group were not statistically significant at 36 weeks PMA (14.5 vs. 13.6) or 3 months CA (20.8 vs. 19.4). Feeding practices and anthropometric measurements during hospitalization did not differ between groups., Conclusions: Serial assessments of body composition in both intervention and control groups showed consistent increments in %BF. However, providing this information to clinicians did not influence nutritional practices or growth., Impact: Serial assessments of body composition in preterm infants at 32 and 36 weeks postmenstrual age show consistent increments in % body fat up to 3 months of corrected age. However, providing this information to the clinician did not influence nutritional practices or growth.

Objective: To determine whether higher-volume feedings improve postnatal growth among infants born very preterm., Study Design: Randomized clinical trial with 1:1 parallel allocation conducted from January 2015 to June 2018 in a single academic medical center in the US. In total, 224 infants with a birth weight 1001-2500 g born at <32 weeks of gestation were randomized to higher-volume (180-200 mL/kg/d) or usual-volume (140-160 mL/kg/d) feedings after establishing full enteral feedings (≥120 mL/kg/d). The primary outcome was growth velocity (g/kg/d) from randomization to study completion at 36 weeks of postmenstrual age or hospital discharge if earlier., Results: Growth velocity increased among infants in the higher-volume group compared with the usual-volume group (mean [SD], 20.5 [4.5] vs 17.9 [4.5] g/kg/d; P < .001). At study completion, all measurements were higher among infants in the higher-volume group compared with the usual-volume group: weight (2365 [324] g, z score -0.60 [0.73] vs 2200 [308] g, z score -0.94 [0.71]; P < .001); head circumference (31.9 [1.3] cm, z score -0.30 [0.91] vs 31.4 [1.3] cm, z score -0.53 [0.84]; P = .01); length (44.9 [2.1] cm, z score -0.68 [0.88] vs 44.4 [2.0], z score -0.83 [0.84]; P = .04); and mid-arm circumference (8.8 [0.8] cm vs 8.4 [0.8] cm; P = .002). Bronchopulmonary dysplasia, patent ductus arteriosus, necrotizing enterocolitis, or other adverse outcomes did not differ between groups., Conclusions: In infants born very preterm weighing 1001-2500 g at birth, higher-volume feedings increased growth velocity, weight, head circumference, length, and mid-arm circumference compared with usual-volume feedings without adverse effects., Trial Registration: ClinicalTrials.gov; NCT02377050., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Trophic feeding compared to no enteral feeding prevents atrophy of the gastrointestinal tract. However, the practice of extending the duration of trophic feeding often delays initiation of full enteral feeding in extremely preterm infants. We hypothesized that a short duration of trophic feeding (3 days or less) is associated with early initiation of full enteral feeding., Methods: A total of 192 extremely preterm infants (23-28 weeks' gestation) born between 2013 and 2015 were included. Infants were divided into 2 groups according to the duration of trophic feeding (short vs. extended). The primary outcome was time to achieve full enteral feeding and the safety outcome was necrotizing enterocolitis (NEC) and/or death., Results: A short duration of trophic feeding was associated with a reduction in time to achieve full enteral feeding after adjustment for birth weight, gestational age, race, sex, type of enteral nutrition, and day of initiation of trophic feeding (mean difference favoring a short duration of trophic feeding: -4.1 days; 95% CI: -2.3 to -5.8; p < 0.001). A short duration of trophic feeding was not associated with a higher risk of NEC and/or death after achieving full enteral feeding (AOR: 0.91; 95% CI: 0.30-2.77; p = 0.87)., Conclusions: A short duration of trophic feeding is associated with early initiation of full enteral feeding. A short duration of trophic feeding is not associated with a higher risk of NEC, but our study was underpowered for this safety outcome. Randomized trials are needed to test this study hypothesis., (© 2017 S. Karger AG, Basel.)

Background and Objectives: Serum creatinine (SCr)-based AKI definitions have important limitations, particularly in very low-birth-weight (VLBW) neonates. Urine biomarkers may improve our ability to detect kidney damage. We assessed the association between 14 different urine biomarkers and AKI in VLBW infants., Design, Setting, Participants, & Measurements: We performed a prospective cohort study on 113 VLBW infants (weight ≤1200 g or <31 weeks' gestation) admitted to a regional neonatal intensive care unit at the University of Alabama at Birmingham between February 2012 and June 2013. SCr was measured on postnatal days 1, 2, 3, and 4 and was combined with clinically measured SCr to determine AKI according to Kidney Disease Improving Global Outcomes AKI definition (increase in SCr ≥0.3 mg/dl or ≥50% increase from previous lowest value). Urine was collected on the first 4 days (average number of urine collections, 3; range, 1-4). The maximum urine biomarkers and urine biomarker/creatinine levels were calculated for 12 urine biomarkers, and the minimum urine biomarker and biomarker/creatinine levels were assessed for two urine biomarkers. We compared these values between infants with and those without AKI. Ideal cutoffs, area under the receiver-operating characteristic curve , and area under the curve adjusted for gestational age were calculated., Results: Cumulative incidence of AKI during the first 2 postnatal weeks was 28 of 113 (25%). Infants with AKI had higher maximum levels of urine cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, clusterin, and α glutathione S-transferase (2.0, 1.8, 1.7, 1.7, and 3.7 times higher, respectively) than infants without AKI. In addition, infants with AKI had lower minimum levels of epithelial growth factor and uromodulin than those without AKI (1.4 and 1.6 times lower, respectively). Most but not all participants had their maximum (or minimum) biomarker values preceding AKI. These associations remained after adjustment for gestational age., Conclusions: Urine biomarkers measured in the first 4 days of life are associated with AKI during the first postnatal weeks. Further evaluations are necessary to determine whether these biomarkers can predict important clinical outcomes. In addition, intervention studies that use biomarkers to stratify enrollment groups are needed before bedside evaluations can be incorporated into care., (Copyright © 2016 by the American Society of Nephrology.)

Background: Urine proteins may help in understanding physiology and diagnosing disease in premature infants. Determining how urine proteins vary by degree of prematurity, sex, and postnatal day is warranted., Methods: We performed a prospective cohort study to assess the independent correlation of 14 urine biomarkers (measured on postnatal days 1-4) with gestational age (GA), sex, and postnatal age in 81 premature infants (mean, 1017 g) without acute kidney injury using a random-effects mixed model., Results: Neutrophil gelatinase-associated lipocalin (NGAL) and vascular endothelial growth factor (VEGF) showed significant associations for sex, GA, and postnatal age. Cystatin C, osteopontin (OPN), and trefoil factor 3 (TFF3) were associated with postnatal age and GA, but not sex. Epithelial growth factor (EGF) and uromodulin were associated with GA only. Clusterin was associated with postnatal age and sex. Albumin was associated with sex only. Beta-2-microglbulin (B2M), osteoactivin, kidney injury molecule -1 (KIM-1), and alpha glutathione S-transferase (αGST) were associated with postnatal age only., Conclusions: Postnatal age affects B2M, cystatin C, NGAL, OPN, clusterin, Kim-1, osteoactivin, TFF3, VEGF, αGST. GA affects cystatin C, EGF, NGAL, OPN, UMOD, TFF3, and VEGF. Sex affects albumin, NGAL, and clusterin. Interpretation of urine biomarkers will need to account for these associations.

Objectives: To test the hypothesis that noninvasive urinary biomarkers may improve early identification, differentiate causes, and predict outcomes of acute kidney injury (AKI) in very low birth weight subjects., Study Design: We performed 2 nested case-control studies to compare the ability of 6 urine biomarkers to predict AKI (rise in serum creatinine of at least 0.3 mg/dL) and mortality (death before 36 weeks postmenstrual age)., Results: Compared to subjects without AKI (n = 21), those with AKI (n = 9) had higher maximum neutrophil gelatinase-associated lipocalin (OR = 1.2 [1.0, 1.6]; P < .01; receiver operator characteristics [ROC] area under the curve [AUC] = .80) and higher maximum osteopontin (OR = 3.2 [1.5, 9.9]; P < .01; ROC AUC = 0.83). Compared with survivors (n = 100), nonsurvivors (n = 23) had higher maximum kidney injury molecule 1 (OR = 1.1 [1.0, 1.2]; P < .02; ROC AUC = 0.64) and higher maximum osteopontin (OR = 1.8 (1.2, 2.7); P < .001; AUC of ROC = 0.78). The combination of biomarkers improved predictability for both AKI and mortality. Controlling for gestational age and birth weight did not affect results considerably., Conclusions: Urinary biomarkers can predict AKI and mortality in very low birth weight infants independent of gestational age and birth weight., Competing Interests: statement None of the other authors have any conflicts of interest to declare for this study., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Acute kidney injury (AKI) is common in premature infants and is associated with poor outcomes. Novel biomarkers can detect AKI promptly. Because premature infants are born with underdeveloped kidneys, baseline biomarker values may differ. We describe baseline values of urinary neutrophil gelatinase-associated lipocalin (NGAL), IL-18, kidney injury molecule-1 (KIM-1), osteopontin (OPN), beta-2 microglobulin (B2mG), and Cystatin-C (Cys-C). Next, we test the hypothesis that these biomarkers are inversely related to GA. Candidate markers were compared according to GA categories in 123 infants. Mixed linear regression models were performed to determine the independent association between demographics/interventions and baseline biomarker values. We found that urine NGAL, KIM-1, Cys-C, and B2mG decreased with increasing GA. With correction for urine creatinine (cr), these markers and OPN/cr decreased with increasing GA. IL-18 (with or without correction for urine creatinine) did not differ across GA categories. Controlling for other potential clinical and demographic confounders with regression analysis shows that NGAL/cr, OPN/cr, and B2mG/cr are independently associated with GA. We conclude that urine values of candidate AKI biomarkers are higher in the most premature infants. These findings should be considered when designing and analyzing biomarker studies in newborn with AKI.

Rationale: Benefits of identifying risk factors for bronchopulmonary dysplasia in extremely premature infants include providing prognostic information, identifying infants likely to benefit from preventive strategies, and stratifying infants for clinical trial enrollment., Objectives: To identify risk factors for bronchopulmonary dysplasia, and the competing outcome of death, by postnatal day; to identify which risk factors improve prediction; and to develop a Web-based estimator using readily available clinical information to predict risk of bronchopulmonary dysplasia or death., Methods: We assessed infants of 23-30 weeks' gestation born in 17 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and enrolled in the Neonatal Research Network Benchmarking Trial from 2000-2004., Measurements and Main Results: Bronchopulmonary dysplasia was defined as a categorical variable (none, mild, moderate, or severe). We developed and validated models for bronchopulmonary dysplasia risk at six postnatal ages using gestational age, birth weight, race and ethnicity, sex, respiratory support, and Fi(O(2)), and examined the models using a C statistic (area under the curve). A total of 3,636 infants were eligible for this study. Prediction improved with advancing postnatal age, increasing from a C statistic of 0.793 on Day 1 to a maximum of 0.854 on Day 28. On Postnatal Days 1 and 3, gestational age best improved outcome prediction; on Postnatal Days 7, 14, 21, and 28, type of respiratory support did so. A Web-based model providing predicted estimates for bronchopulmonary dysplasia by postnatal day is available at https://neonatal.rti.org., Conclusions: The probability of bronchopulmonary dysplasia in extremely premature infants can be determined accurately using a limited amount of readily available clinical information.

Acute kidney injury (AKI) independently predicts mortality in children and adults. Our understanding of the epidemiology of AKI in very LBW (VLBW) infants is limited to retrospective studies. After adjustment for demographics, comorbidities, and interventions, infants with AKI have decreased survival compared with those without AKI. The study was conducted in regional quaternary care NICU of the University of Alabama at Birmingham. VLBW infants were followed prospectively and were classified into a serum creatinine (SCr)-based classification for AKI. Forty-one of 229 (18%) VLBW infants developed AKI. Those with AKI were more likely to have umbilical artery catheters, assisted ventilation, blood pressure medications, and lower 1-and 5-min Apgar scores. Of the infants with AKI, 17 of 41 (42%) died compared with 9 of 188 (5%) of those without AKI (p < 0.001). AKI was associated with mortality with a crude hazard ratio (HR) of 9.3 (95% CI, 4.1-21.0). After adjusting for potential confounders, those with AKI had higher chance of death as the adjusted HR was 2.4 (95% CI 0.95-6.04). AKI is associated with mortality in VLBW infants. Efforts to prevent and ameliorate the impact of AKI may improve the outcomes in this vulnerable population.

Objectives: To determine (1) the magnitude of clustering of bronchopulmonary dysplasia (36 weeks) or death (the outcome) across centers of the Eunice Kennedy Shriver National Institute of Child and Human Development National Research Network, (2) the infant-level variables associated with the outcome and estimate their clustering, and (3) the center-specific practices associated with the differences and build predictive models., Methods: Data on neonates with a birth weight of <1250 g from the cluster-randomized benchmarking trial were used to determine the magnitude of clustering of the outcome according to alternating logistic regression by using pairwise odds ratio and predictive modeling. Clinical variables associated with the outcome were identified by using multivariate analysis. The magnitude of clustering was then evaluated after correction for infant-level variables. Predictive models were developed by using center-specific and infant-level variables for data from 2001 2004 and projected to 2006., Results: In 2001-2004, clustering of bronchopulmonary dysplasia/death was significant (pairwise odds ratio: 1.3; P < .001) and increased in 2006 (pairwise odds ratio: 1.6; overall incidence: 52%; range across centers: 32%-74%); center rates were relatively stable over time. Variables that varied according to center and were associated with increased risk of outcome included lower body temperature at NICU admission, use of prophylactic indomethacin, specific drug therapy on day 1, and lack of endotracheal intubation. Center differences remained significant even after correction for clustered variables., Conclusion: Bronchopulmonary dysplasia/death rates demonstrated moderate clustering according to center. Clinical variables associated with the outcome were also clustered. Center differences after correction of clustered variables indicate presence of as-yet unmeasured center variables.

The independent impact of acute kidney injury (AKI) on survival in very low birthweight (VLBW; < or =1,500 g) critically ill infants has not been studied. Cases (non-survivors n = 68) were matched to, at most, two controls (survivors n = 127) by incidence density sampling with replacement, birthweight (+/- 50 g), gestational age (+/- 1 week), and availability of serum creatinine (SCr) levels before the index patient's time of death. Maternal/infant demographic characteristics, co-morbidities, complications and interventions were explored. No difference existed between patients and controls in mean gestational age and birthweight (the matching variables), race, or gender. Compared with the controls, cases had younger mothers, less placental separation, fewer occurrences of hyponatremia, more intra-ventricular hemorrhage, and received chest compressions and cardiac drugs. A 1 mg/dl increase in SCr was associated with almost two-times higher odds of death [odds ratio (OR) = 1.94, 95% confidence interval (95% CI) 1.13-3.32]. OR increased when confounding variables were adjusted (adjusted OR 3.44, 95% CI 1.23-9.61). Similarly, a 100% increase in SCr from trough level was associated with an increased OR = 1.53 (95% CI 1.14-2.04) and became stronger, after adjustment of variables (adjusted OR = 1.90, 95% CI 1.10-3.27). After confounding variables had been controlled for, AKI was independently associated with mortality in VLBW infants. Further prospective multi-center studies are needed to determine whether this association exists.

Objective: To predict death or neurodevelopmental impairment (NDI) in extremely low birth weight infants by classification trees with recursive partitioning and automatic selection of optimal cut points of variables., Study Design: Data from the Trial of Indomethacin Prophylaxis in Preterms were randomly divided into development (n=784) and validation sets (n=262). Three models were developed for the combined outcome of death (8 days to 18 months) or NDI (cerebral palsy, cognitive delay, deafness, or blindness at 18 months corrected age): antenatal: antenatal data; early neonatal: antenatal+first 3 days data; and first week: antenatal, first 3 days, and 4th to 8th days data. Decision trees were tested on the validation set., Results: Variables associated with death/NDI in each model were: Antenatal: Gestation01 mL/kg/d. First week: Birth weight3 mL/kg/d. Birth weight>787 g: cranial echodense intraparenchymal lesion and transfusion>1 mL/kg/d. Correct classification rates were 61% to 62% for all models., Conclusions: The ability to predict long-term morbidity/death in extremely low birth weight infants does not improve significantly over the first week of life. Effects of different variables depend on age.

Objective: To compare multiple logistic regression and neural network models in predicting death for extremely low birth weight neonates at 5 time points with cumulative data sets, as follows: scenario A, limited prenatal data; scenario B, scenario A plus additional prenatal data; scenario C, scenario B plus data from the first 5 minutes after birth; scenario D, scenario C plus data from the first 24 hours after birth; scenario E, scenario D plus data from the first 1 week after birth., Methods: Data for all infants with birth weights of 401 to 1000 g who were born between January 1998 and April 2003 in 19 National Institute of Child Health and Human Development Neonatal Research Network centers were used (n = 8608). Twenty-eight variables were selected for analysis (3 for scenario A, 15 for scenario B, 20 for scenario C, 25 for scenario D, and 28 for scenario E) from those collected routinely. Data sets censored for prior death or missing data were created for each scenario and divided randomly into training (70%) and test (30%) data sets. Logistic regression and neural network models for predicting subsequent death were created with training data sets and evaluated with test data sets. The predictive abilities of the models were evaluated with the area under the curve of the receiver operating characteristic curves., Results: The data sets for scenarios A, B, and C were similar, and prediction was best with scenario C (area under the curve: 0.85 for regression; 0.84 for neural networks), compared with scenarios A and B. The logistic regression and neural network models performed similarly well for scenarios A, B, D, and E, but the regression model was superior for scenario C., Conclusions: Prediction of death is limited even with sophisticated statistical methods such as logistic regression and nonlinear modeling techniques such as neural networks. The difficulty of predicting death should be acknowledged in discussions with families and caregivers about decisions regarding initiation or continuation of care.

Background: A National Institute of Child Health and Human Development Neonatal Research Network randomized trial showed that vitamin A supplementation reduced bronchopulmonary dysplasia (O2 at 36 weeks' postmenstrual age) or death in extremely low birth weight (ELBW) neonates (relative risk [RR]: 0.89). As with postnatal steroids or other interventions, it is important to ensure that there are no longer-term adverse effects that outweigh neonatal benefits., Primary Objective: To determine if vitamin A supplementation in ELBW infants during the first month after birth affects survival without neurodevelopmental impairment at a corrected age of 18 to 22 months., Design/methods: Infants enrolled in the National Institute of Child Health and Human Development vitamin A trial were evaluated at 18 to 22 months by carefully standardized assessments: Bayley Mental Index (MDI) and Psychomotor Index (PDI), visual and hearing screens, and physical examination for cerebral palsy (CP). The medical history was also obtained. Neurodevelopmental impairment (NDI) was predefined as > or =1 of MDI <70, PDI <70, CP, blind in both eyes, or hearing aids in both ears., Results: Of 807 enrolled infants, 133 died before and 16 died after discharge. Five hundred seventy-nine (88%) of the 658 remaining infants were followed up. The primary outcome of NDI or death could be determined for 687 of 807 randomized infants (85%). Baseline characteristics and predischarge and postdischarge mortality were comparable in both study groups. NDI or death by 18 to 22 months occurred in 190 of 345 (55%) infants in the vitamin A group and in 204 of 342 (60%) of the control group (RR: 0.94; 95% confidence interval: 0.80-1.07). RRs for low MDI, low PDI, and CP were also <1.0. We found no evidence that neonatal vitamin A supplementation reduces hospitalizations or pulmonary problems after discharge., Conclusion: Vitamin A supplementation for ELBW infants reduces bronchopulmonary dysplasia without increasing mortality or neurodevelopmental impairment at 18 to 22 months. However, this study was not powered to evaluate small magnitudes of change in long-term outcomes.

Objectives: The purpose of this study was to investigate possible bias in the evaluation of neurodevelopment and somatic growth at 18 to 22 months' postmenstrual age among extremely low birth weight (ELBW) survivors (401-1000 g at birth)., Methods: Data from a cohort of 1483 ELBW infant survivors who were born January 1993 through December 1994 and cared for at centers in the Neonatal Research Network of the National Institute of Child Health and Human Development were examined retrospectively. Children who were compliant with an 18- to 22-month follow-up visit, who visited but were not measured, or who made no visit were compared regarding 4 outcomes: 1) Bayley Scales of Infant Development, 2nd edition, Mental Developmental Index (MDI) <70 and 2) Psychomotor Developmental Index (PDI) <70, 3) presence or absence of cerebral palsy, and 4) weight <10th percentile for age. Logistic regression models were used to predict likelihood of these outcomes for children with no follow-up evaluation, and predicted probability distributions were compared across the groups., Results: Compared with children who were lost to follow-up, those who were compliant with follow-up were more likely to have been 1 of a multiple birth, to have received postnatal glucocorticoids, and to have had chronic lung disease. These factors were significantly associated with MDI and PDI <70 in the compliant group. Chronic lung disease was associated with increased risk of cerebral palsy (CP). MDI and PDI scores <70 were found in 37% and 29% of children who were evaluated at follow-up, respectively. Prediction models revealed that 34% and 26% of infants in the no-visit group would have had MDI and PDI scores <70. Compliant children tended to have greater incidence of MDI <70 compared with those predicted in the no-visit group but not PDI <70. CP was identified in 17% of the compliant group and predicted for 18% of the no-visit group. Predicted probabilities of having CP were marginally higher among the no-visit infants compared with those who were compliant with follow-up. There were no statistically significant somatic growth differences among the compliant, visit but not measured, and no-visit groups., Conclusion: ELBW infant survivors who weighed 401 to 1000 g at birth and who are compliant with follow-up evaluations may have worse Bayley Scales of Infant Development, 2nd edition, MDI scores than infants with no visit. Thus, follow-up studies based on infants who are compliant with follow-up care may lead to an overestimation of adverse outcomes in ELBW survivors.

Since 1959, when it was reported that many preterm infants had surfactant deficiency, there has been a remarkable improvement in the prevention of respiratory distress syndrome (RDS) and in the care of infants who develop RDS. Antenatal corticosteroids and surfactant replacement have improved the care of very low birth weight infants.

Objective: Vitamin A supplementation reduces bronchopulmonary dysplasia (BPD)/death in extremely low birth weight neonates. It was hypothesized that compared with the standard regimen of 5000 IU 3 times per week for 4 weeks, (1) a higher dose (10,000 IU 3 x per week) would increase serum retinol and retinol binding protein (RBP) and lower relative dose responses (RDR), and (2) once-per-week dosing (15,000 IU once per week) would lead to equivalent levels, RBP, and RDR., Study Design: Extremely low birth weight neonates (n = 120) receiving O(2)/mechanical ventilation at 24 hours were randomly assigned to (1) standard, (2) higher dose, or (3) once-per-week regimens. Measures of vitamin A deficiency were serum retinol <20 microg/dL, RBP <2.5 mg/dL, and/or RDR >10% on day 28. BPD was defined as O(2)/mechanical ventilation at 36 weeks' postmenstrual age., Results: Groups were similar at enrollment (median gestational age, 25 weeks; birth weight, 689 g). Possible toxicity was seen in <5%. The higher dose regimen did not increase retinol or RBP, decrease RDR, or improve outcomes. Infants in the once-per-week regimen had lower retinol levels and higher RDR without an effect on outcomes., Conclusions: Compared with the standard regimen, once-per-week dosing worsened, and higher doses did not reduce, vitamin A deficiency. Therefore, the standard regimen is recommended.

Aims: To compare the prediction of mortality in individual extremely low birth weight (ELBW) neonates by regression analysis and by artificial neural networks., Study Design: A database of 23 variables on 810 ELBW neonates admitted to a tertiary care center was divided into training, validation, and test sets. Logistic regression and neural network models were developed on the training set, validated, and outcome (mortality) predicted on the test set. Stepwise regression identified significant variables in the full set. Regression models and neural networks were then tested using data sets with only the identified significant variables, and then with variables excluded one at a time., Results: The area under the curve (AUC) of receiver operating characteristic (ROC) curves for neural networks and regression was similar (AUC 0.87+/-0.03; p=0.31). Birthweight or gestational age and the 5-min Apgar score contributed most to AUC., Conclusions: Both neural networks and regression analysis predicted mortality with reasonable accuracy. For both models, analyzing selected variables was superior to full data set analysis. We speculate neural networks may not be superior to regression when no clear non-linear relationships exist.

Objective: (1) Identify major determinants of adverse neurodevelopmental outcome in extremely low birth weight (ELBW) infants. (2) Compare neural networks and regression analysis in the prediction of major handicaps and Bayley scores (MDI and PDI) in individual ELBW neonates followed to 18 months., Study Design: Retrospective cohort study of regional tertiary care NICU database. A database with 21 selected variables was divided into training (n = 144) and test sets (n = 74). The training set was used to train a neural network and develop regression equations to predict outcomes in the test set., Results: Determinants (descending order of contribution to variance): Major handicap: intraventricular hemorrhage (IVH) grade, necrotizing enterocolitis > or = stage II, black race, and no chorioamnionitis; low MDI: IVH grade, plurality, bronchopulmonary dysplasia (BPD), lower maternal grade, and no chorioamnionitis; low PDI: IVH grade, BPD, periventricular leukomalacia, lower maternal grade, and no chorioamnionitis. Regression techniques and neural networks were comparable and had relatively low sensitivity and correlation with adverse outcomes., Conclusion: Much of the variance in ELBW neurologic outcome cannot be explained by either regression analysis or neural network approaches.

Objective: To determine whether the rate of feed advancement affects the incidence of necrotizing enterocolitis (NEC)., Study Design: Prospective randomized controlled trial involving 185 formula-fed infants with birth weight 501 to 1500 g and gestational age /=II) was similar in both groups (slow 13% and fast 9%, P =.5). The incidence of perforation (Bell stage III) was also similar in both groups (slow 4% and fast 2%, P =.8). Feeds were started at a comparable postnatal age in both groups (median age: slow 5 days and fast 4 days, P =.9). Although the neonates in the fast group attained full enteral intake earlier (median days [25th and 75th percentiles]: slow 15 [12, 21] and fast 11 [8, 15], P <.001) and regained their birth weight earlier (slow 15 [11, 20] and fast 12 [8, 15], P <.05), their ages at discharge were not statistically different (slow 47 [31, 67] and fast 43 [29, 62], P =.3), Conclusions: A greater than twofold difference in the rate of feed advancement from 15 cc/kg/d to 35 cc/kg/d did not affect the incidence of NEC >/= stage II. Factors other than feed advancement appear to be more important in the pathogenesis or progression of NEC.