Postoperative Outcomes, and Growth and Brain Injury Outcomes in Spontaneous Intestinal Perforation vs Surgical Necrotizing Enterocolitis in Preterm Infants.

OBJECTIVE: To compare the clinical outcomes in preterm infants following surgical necrotizing enterocolitis (sNEC) and spontaneous intestinal perforation (SIP). METHODS: Retro-spective comparison of clinical information in preterm infants with sNEC and SIP admitted between January, 2013 and December 31, 2018. The clinical outcomes were compared in two groups, including postoperative and brain injury detected on brain magnetic resonance imaging (MRI) after clinical and histopathological confirmation of the SIP and the NEC diagnosis. RESULTS: 114 infants had sNEC, and 37 had SIP. Infants with SIP had lower median gestational age [25.1 weeks (23.5, 27.1) vs 26.6 (24.4, 31.0), P=0.03], an earlier mean (SD) age of disease onset [10.1 (11.3) days vs 19.6 (17.9); P<0.001] and lower maternal chorioamnionitis on placental pathology [4 (23.5%) vs 22 (68.8%); P=0.007), received more often Penrose drain therapy (54% vs 33%; P=0.03), had less median (IQR) bowel length loss [3.3 cm (1.72, 4.38) vs 21.4 (9.55, 35.3); P=<0.001] and had more often intact ileocecal valve (91.4% vs 65.7%; P=0.006] compared to those with sNEC. In addition, those with sNEC had lower median (IQR) weight z scores at the time of discharge [-1.88 (-2.80, -1.09) vs -1.14 (-2.22, -0.44); P=0.036] than SIP. There were no significant differences in postoperative ileus, duration of parenteral nutrition, surgical morbidity, length of stay, mortality, white matter, and grey matter injury on brain MRI at term equivalent age in preterm infants with SIP and sNEC. CONCLUSION: In our cohort, preterm infants with SIP and sNEC did not show significant differences in postoperative morbidity and brain MRI abnormalities at term equivalent age. sNEC had lower discharge weight z scores. Larger prospective studies are needed for confirmation of these findings.

Progression of Enteral Feeding Volumes in Extremely Low Birth Weight Infants in the "Connection Trial".

OBJECTIVE: Investigate daily feeding volumes and their association with clinical variables in the early postnatal care of premature infants of the "Connection Trial." STUDY DESIGN: A total of 641 infants of 510 to 1,000-g birth weight (BW, mean: 847 g) and mean 27 weeks' gestational age at birth (GA) were analyzed for total daily enteral (TDE) feeding volumes of 10, 20, 40, 80, and 120 mL/kg/d and their association with 24 clinical variables. Uni- and multivariable Cox regression models were used to calculate hazard ratios (HR) with 95% confidence intervals as a measure of the chance of reaching each of the TDE volumes. RESULTS: Daily feeding volumes were highly variable and the median advancement from 10 to 120 mL/kg/d was 11 mL/kg/d. Univariable analyses showed the lowest chance (HR, 0.22-0.81) of reaching the TDE volumes for gastrointestinal (GI) serious adverse events (SAEs), GI perforation, GI obstruction, and necrotizing enterocolitis, as well as respiratory SAEs, persistent ductus arteriosus, and hypotension. Each GA week, 100-g BW, and point in 5-minute Apgar score at birth associated with 8 to 20% increased chance of reaching the TDE volumes. Multivariable analyses showed independent effects for BW, GA, Apgar score, GI SAEs, abdominal symptoms/signs, respiratory SAEs, days on antibiotics, and hypotension. CONCLUSION: This observational analysis demonstrates the variable and cautious progression of enteral feedings in contemporary extremely low BW infants and the extent to which clinical variables associate with this progression. KEY POINTS: · Total feedings of 10 and 120 mL/kg/d were reached at median 4 and 14 day of age, respectively, and at a daily increase of 11 mL/kg.. · Each incremental GA week, 100-g BW, and point in 5-minute Apgar score associated with 8 to 20% increased chance of reaching enteral feedings of 10 to 120 mL/kg/d.. · Progression of enteral feeding associated with several clinical events and was slower than advocated in common feeding protocols..

Meningitis, urinary tract, and bloodstream infections in very low birth weight infants enrolled in a heart rate characteristics monitoring trial.

BACKGROUND: Displaying heart rate characteristic (HRC) scores was associated with lower sepsis-associated mortality in very low birth weight (VLBW) infants in a multicenter randomized controlled trial (HeRO trial). The aim of this study was to test whether HRC indices rise before diagnosis of urinary tract infection (UTI) or meningitis, with and without concomitant BSI. METHODS: Blood, urine, and cerebrospinal fluid (CSF) culture data after 3 days of age and within 120 days of study enrollment were analyzed from 2989 VLBW infants. The HRC index was analyzed 12 h prior to positive cultures compared to 36 h prior, using paired signed-rank tests. RESULTS: UTI, meningitis, and BSI were diagnosed in 10%, 2%, and 24% of infants, respectively. The mean hourly HRC index was significantly higher 12 h prior to diagnosis of UTI and BSI compared to 36 h prior (UTI 2.07 versus 1.81; BSI 2.62 versus 2.25, both p < 0.0001). The baseline HRC index was higher for meningitis, compared to UTI or BSI, but without a statistically significant rise in the day prior to meningitis diagnosis. CONCLUSIONS: In a large cohort of VLBW infants enrolled in the HeRO trial, the HRC index increased in the 24-h period prior to diagnosis of UTI and BSI but not meningitis.

Neonatal Intensive Care Unit Length of Stay Reduction by Heart Rate Characteristics Monitoring.

OBJECTIVE: To examine the effect of heart rate characteristics (HRC) monitoring on length of stay among very low birth weight (VLBW; <1500 g birth weight) neonates in the HeRO randomized controlled trial (RCT). STUDY DESIGN: We performed a retrospective analysis of length of stay metrics among 3 subpopulations (all patients, all survivors, and survivors with positive blood or urine cultures) enrolled in a multicenter, RCT of HRC monitoring. RESULTS: Among all patients in the RCT, infants randomized to receive HRC monitoring were more likely than controls to be discharged alive and prior to day 120 (83.6% vs 80.1%, P = .014). The postmenstrual age at discharge for survivors with positive blood or urine cultures was 3.2 days lower among infants randomized to receive HRC monitoring when compared with controls (P = .026). Although there were trends in other metrics toward reduced length of stay in HRC-monitored patients, none reached statistical significance. CONCLUSIONS: HRC monitoring is associated with reduced mortality in VLBW patients and a reduction in length of stay among infected surviving VLBW infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00307333.

Comparison of new modeling methods for postnatal weight in ELBW infants using prenatal and postnatal data.

OBJECTIVES: Postnatal infant weight curves are used to assess fluid management and evaluate postnatal nutrition and growth. Traditionally, postnatal weight curves are based on birth weight and do not incorporate postnatal clinical information. The aim of the present study was to compare the accuracy of birth weight-based weight curves with weight curves created from individual patient records, including electronic records, using 2 predictive modeling methods, linear regression (LR) and an artificial neural network (NN), which apply mathematical relations between predictor and outcome variables. METHODS: Perinatal demographic and postnatal nutrition data were collected for extremely-low-birth-weight (ELBW; birth weight <1000 g) infants. Static weight curves were generated using published algorithms. The postnatal predictive models were created using the demographic and nutrition dataset. RESULTS: Birth weight (861 ± 83 g, mean ± 1 standard deviation [SD]), gestational age (26.2 ± 1.4 weeks), and the first month of nutrition data were collected from individual health records for 92 ELBW infants. The absolute residual (|measured-predicted|) for weight was 84.8 ± 74.4 g for the static weight curves, 60.9 ± 49.1 g for the LR model, and 12.9 ± 9.2 g for the NN model, analysis of variance: both LR and NN P<0.01 versus static curve. NPO (nothing by mouth) infants had greater weight curve discrepancies. CONCLUSIONS: Compared with birth weight-based and logistic regression-generated weight curves, NN-generated weight curves more closely approximated ELBW infant weight curves, and, using the present electronic health record systems, may produce weight curves better reflective of the patient's status.

Septicemia mortality reduction in neonates in a heart rate characteristics monitoring trial.

BACKGROUND: Abnormal heart rate characteristics (HRC) wax and wane in early stages of culture-positive, late-onset septicemia (LOS) in patients in the neonatal intensive care unit (NICU). Continuously monitoring an HRC index leads to a reduction in mortality among very low birth weight (VLBW) infants. We hypothesized that the reduction in mortality was due to a decrease in septicemia-associated mortality. METHODS: This is a secondary analysis of clinical and HRC data from 2,989 VLBW infants enrolled in a randomized clinical trial of HRC monitoring in nine NICUs from 2004 to 2010. RESULTS: LOS was diagnosed 974 times in 700 patients, and the incidence and distribution of organisms were similar in HRC display and nondisplay groups. Mortality within 30 d of LOS was lower in the HRC display as compared with the nondisplay group (11.8 vs. 19.6%; relative risk: 0.61; 95% confidence interval: 0.43, 0.87; P < 0.01), but mortality reduction was not statistically significant for patients without LOS. There were fewer large, abrupt increases in the HRC index in the days leading up to LOS diagnosis in infants whose HRC index was displayed. CONCLUSION: Continuous HRC monitoring is associated with a lower septicemia-associated mortality in VLBW infants, possibly due to diagnosis earlier in the course of illness.

Mortality reduction by heart rate characteristic monitoring in very low birth weight neonates: a randomized trial.

OBJECTIVE: To test the hypothesis that heart rate characteristics (HRC) monitoring improves neonatal outcomes. STUDY DESIGN: We conducted a two-group, parallel, individually randomized controlled clinical trial of 3003 very low birth weight infants in 9 neonatal intensive care units. In one group, HRC monitoring was displayed; in the other, it was masked. The primary outcome was number of days alive and ventilator-free in the 120 days after randomization. Secondary outcomes were mortality, number of ventilator days, neonatal intensive care unit stay, and antibiotic use. RESULTS: The mortality rate was reduced in infants whose HRC monitoring was displayed, from 10.2% to 8.1% (hazard ratio, 0.78; 95% CI, 0.61-0.99; P = .04; number needed to monitor = 48), and there was a trend toward increased days alive and ventilator-free (95.9 of 120 days compared with 93.6 in control subjects, P = .08). The mortality benefit was concentrated in infants with a birth weight <1000 g (hazard ratio, 0.74; 95% CI, 0.57-0.95; P = .02; number needed to monitor = 23). There were no significant differences in the other outcomes. CONCLUSION: HRC monitoring can reduce the mortality rate in very low birth weight infants.

The influence of early postnatal nutrition on retinopathy of prematurity in extremely low birth weight infants.

BACKGROUND: Retinopathy of prematurity(ROP) is the most common serious ophthalmic disease in preterm infants. Human milk may provide a protective effect for ROP; however, beneficial effects of human milk preclude randomized trials. Therefore, we conducted a retrospective analysis comparing early postnatal nutrition with ROP development. OBJECTIVE: Evaluate relationship between early postnatal nutriture and ROP surgery. DESIGN/METHODS: Nutrition data was collected for inborn AGA infants, BW 700-1000 g. ROP surgery was the primary outcome variable. A single pediatric ophthalmologist supervised examinations. All infants received triweekly IM vitamin A as chronic lung disease prophylaxis (Tyson: NEJM, 1999). RESULTS: BW and gestational age were 867+/-85 g and 26.3+/-1.2 weeks (n=77, mean+/-1SD). ROP surgery infants(n=11) received more parenteral nutrition, 1648 mL, and less human milk, 13.8 mL/kg-day, and vitamin E, 1.4 mg/kg-day, during the second postnatal week. Human milk was a negative predictor for ROP surgery, odds ratio=0.94. Both groups met vitamin A recommendations; however, 74% was administered via IM injections. Neither group met vitamin E recommendations. CONCLUSIONS: Human milk feeding, parenteral nutrition volume and vitamin E intake were predictors for ROP surgery. IM vitamin A injections provided the majority of vitamin A; vitamin E administration was insufficient. Improving human milk feeding rates and vitamin dosing options may affect ROP surgery rates.

A modified vitamin regimen for vitamin B2, A, and E administration in very-low-birth-weight infants.

INTRODUCTION: Very-low-birth-weight (VLBW; birth weight, <1,500 g) infants receive preterm infant formulas and parenteral multivitamin preparations that provide more riboflavin (vitamin B2) than does human milk and more than that recommended by the American Society of Clinical Nutrition. VLBW infants who are not breast-fed may have plasma riboflavin concentrations up to 50 times higher than those in cord blood. The authors examined a vitamin regimen designed to reduce daily riboflavin intake, with the hypothesis that this new regimen would result in lower plasma riboflavin concentrations while maintaining lipid-soluble vitamin levels. METHODS: Preterm infants with birth weight < or =1,000 g received either standard preterm infant nutrition providing 0.42 to 0.75 mg riboflavin/kg/day (standard group), or a modified regimen providing 0.19 to 0.35 mg/kg/day (modified group). The modified group parenteral vitamin infusion was premixed in Intralipid. Enteral feedings were selected to meet daily riboflavin administration guidelines. Plasma riboflavin, vitamin A, and vitamin E concentrations were measured weekly by high-performance liquid chromatography. Data were analyzed with the independent t test, chi, and analysis of variance. RESULTS: The 36 infants (17 standard group, 19 modified group) had birth weight and gestational age of 779 +/- 29 g and 25.5 +/- 0.3 weeks (mean +/- SEM) with no differences between groups. Modified group infants received 38% less riboflavin (0.281 +/- 0.009 mg/kg/day), 35% more vitamin A (318.3 +/- 11.4 microg/kg/day), and 14% more vitamin E (3.17 +/- 0.14 mg/kg/day) than standard group infants. Plasma riboflavin rose from baseline in both groups but was 37% lower in the modified group during the first postnatal month (133.3 +/- 9.9 ng/mL). Riboflavin intake and plasma riboflavin concentrations were directly correlated. Plasma vitamin A (0.222 +/- 0.022 microg/mL) and vitamin E (22.26 +/- 1.61 /mL) concentrations were greater in the modified group. CONCLUSIONS: The modified vitamin regimen resulted in reduced riboflavin intake and plasma riboflavin concentration, suggesting plasma riboflavin concentration is partially dose dependent during the first postnatal month in VLBW infants. Modified group plasma vitamin A and vitamin E concentrations were greater during the first month, possibly because the vitamins were premixed with parenteral lipid emulsion. Because of the complexity of this protocol, the authors suggest that a parenteral multivitamin product designed for VLBW infants which uses weight-based dosing should be developed.

A survey of neonatal parenteral nutrition design practices in North Carolina.

BACKGROUND: Parenteral nutrition is an important component of postnatal hospital care for very-low-birth-weight infants (VLBW; birth weight < or =1500 g). Designing and preparing parenteral nutrition for VLBW infants is a complicated process requiring many nutrition decisions and mathematical computations, a process most medical centers have developed independently. The goal of this project was to examine the nutrition design practices and resources of regional neonatal intensive care units (NICUs). METHODS: In depth interviews were conducted with neonatal nutrition health-care providers at eight medium to large NICUs in North Carolina to describe the patient population, the nutrition support staff, nutrition decision-making procedures and resources, the design of parenteral nutrition, and problems with parenteral nutrition design and preparation. RESULTS: The eight centers reported an average of 182 VLBW infant admissions and prepared 4810 parenteral nutrition orders per year. Five centers employed experienced neonatal nutrition staff to offer decision support. Six centers used paper parenteral nutrition order forms, all of which provided some decision guidance such as a recommended ordering dose range. Self-reported medical mistakes included incorrect parenteral nutrition additive dilutions and incorrect supplementation of parenteral nutrition additives. CONCLUSIONS: Most NICUs offered nutrition resource personnel and used paper parenteral nutrition order forms, which offered a wide range of decision guidance. About half the reported medical errors could be addressed using electronic parenteral nutrition design; however, a broader, more general approach to the entire design and administration system would reduce more errors. Last, as development of electronic neonatal nutrition resources in the clinical arena progresses, standards for recording neonatal nutrition content, and evaluating the effect of decision support need to be identified.

Increased parenteral amino acid administration to extremely low-birth-weight infants during early postnatal life.

BACKGROUND: Early administration of parenteral amino acids to infants with extremely low birth weight (birth weight < or = 1,000 g) has been encouraged to foster growth. However, excessive intravenous intake of amino acids may cause metabolic acidosis and uremia in extremely low birth weight infants. The hypothesis for this study was that extremely low birth weight infants would tolerate slightly increased early postnatal parenteral amino acid administration and benefit. METHODS: The peak daily parenteral amino acid dosage was increased from 3 g/kg (standard group) to 4 g/kg (modified group). The corrected parenteral amino acid dosage was computed to account for enteral protein intake and keep the combined daily intravenous amino acid and enteral protein intake at or below 3 g . kg -1 . d -1 in the standard group and 4 g . kg -1 . d -1 in the modified group. The primary outcome measure was plasma bicarbonate concentration as an indicator of acid-base status. Data were collected for patient demographics, nutritional intake, serum bicarbonate and serum urea nitrogen concentrations, and outcome. RESULTS: The corrected parenteral amino acid intake of the modified group was 16% greater at postnatal week 1 (3.30 +/- 0.83 g . kg -1 . d -1; mean, +/-1 SD) and 18% greater (3.86 +/- 0.94 g . kg -1 . d -1 ) at postnatal week 2 than the parenteral amino acid intake of the standard group. In the modified group, the mean serum bicarbonate concentration was 19.1 +/- 1.8 mEq/dL at week 1 and 23.9 +/- 2.9 mEq/dL at week 2, with no difference between the groups. At week 1, serum urea nitrogen concentrations were the same in both groups. The mean serum urea nitrogen concentration of the modified group at postnatal week 2 (18.2 +/- 8.8 mg/dL) was unchanged from postnatal week 1, but was greater than that of the standard group at postnatal week 2. Weight gain was the same in both groups. Corrected parenteral amino acid intake at postnatal week 1 correlated directly with weight gain from birth to postnatal week 2 ( P < 0.03) in both groups. CONCLUSIONS: Infants with extremely low birth weight tolerated parenteral amino acid intake of approximately 4 g . kg -1 . d -1. Mild increases of mean serum urea nitrogen concentration and mean weight gain were associated with increased parenteral amino acid administration without significant acidosis.