The concomitant use of vancomycin and piperacillin-tazobactam is associated with acute kidney injury (AKI) in extremely low birth weight infants (ELBW).

BACKGROUND: Late-onset sepsis is common in extremely low birth weight (ELBW) infants, and it leads to the use of antibiotics to cover resistant organisms, which can be nephrotoxic. Here we have investigated the role of vancomycin plus piperacillin-tazobactam on the rate of acute kidney injury (AKI). METHODS: In a retrospective case-control study, medical records of all ELBW infants who were admitted to our Neonatal Intensive Care Unit (NICU) with late onset sepsis who were prescribed vancomycin plus piperacillin-tazobactam were reviewed for demographics, clinical characteristics, use of potential nephrotoxic medications and outcomes. RESULTS: During the study period, 264 patients were admitted, of whom 28.4%(75/264) received vancomycin plus piperacillin-tazobactam and were matched with 64 controls. There were no differences in gestational age or birth weight between cases and controls [688±160 vs. 689±162 grams (p = 0.99), and 24.7±1.8 vs. 24.7±1.6 weeks (p = 0.99) respectively]. There was no difference in the rate of sepsis between cases and controls [76%(55/72) vs. 64%(41/64) respectively, p = 0.11]. Infants exposed to vancomycin plus piperacillin-tazobactam had a higher percentage of concomitant use of vasopressors and amphotericin. To adjust for confounders, a logistic regression analysis was conducted with AKI as the dependent variable. Use of vasopressors and vancomycin plus piperacillin-tazobactam were the only risk factors associated with AKI with an adjusted OR (95%CI) of 4.08 (1.90-8.74), p < 0.001; and 2.87 (1.26-6.53), p = 0.01 respectively. CONCLUSION: The use of vancomycin plus piperacillin-tazobactam in ELBW infants is associated with an increased risk for AKI.

Low caloric intake and high fluid intake during the first week of life are associated with the severity of bronchopulmonary dysplasia in extremely low birth weight infants.

OBJECTIVE: To study whether there is an association between nutritional intake during the first week of life and severity of bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants. METHODS: In a retrospective cohort study, medical records of all ELBW infants admitted to our Neonatal Intensive Care Unit (2010-2017) were reviewed for infants' demographics, clinical characteristics, nutritional intake during their first week of life, and BPD risk factors. RESULTS: During the study period 226 infants were identified of whom 67% (151/226) had moderate-severe BPD and the rest served as controls. Overall infants with moderate-severe BPD were younger, smaller, and spent more time on mechanical ventilation than their controls [(mean±standard deviation) 24.7±1.7 vs. 26.8±2.0 weeks gestational age (p < 0.001); 678±154 vs. 837±129 grams (p < 0.001); and 37.9±23.6 vs. 13.7±15.3 days (p < 0.001) respectively]. During the first week of life, the average caloric, carbohydrate, protein and lipid intakes were significantly lower, and the average fluid intake was significantly higher in the moderate-severe BPD than the control group. After adjustment for confounders, fluid intake, and days on mechanical ventilation were significantly associated with moderate-severe BPD with an odds ratio [OR (95% confidence interval)] of 1.03 (1.01-1.04), and 1.05 (1.03-1.07) respectively. Daily caloric intake was associated with an increased risk for moderate-severe BPD [OR: 0.94 (0.91-0.97)]. CONCLUSION: Low caloric intake, and high fluid intake during the first week of life are associated with the severity of BPD in ELBW infants.

Enteral fish oil supplementation in the resolution of parenteral nutrition associated cholestasis.

OBJECTIVE: To analyze safety, tolerance and efficacy of enteral omega-3 fatty acids (FAs) in the resolution of Parenteral Nutrition Associated Cholestasis (PNAC) and postnatal growth among preterm neonates. STUDY DESIGN: This is a single center retrospective case-control study of all neonates born less than 32 weeks of gestation and developed PNAC (Direct bilirubin >2 mg/dl). Infants who received enteral omega-3 FAs supplementation (1 g/Kg/d) served as cases and were compared with gestational age, gender and direct bilirubin level matched controls who did not receive enteral omega-3 FAs supplementation. RESULTS: A total of 48 infants were analyzed, 24 who received enteral omega-3 fatty acids were matched with 24 controls. The omega-3 FAs and control groups were similar in gestational age (weeks) and birth weight (gram). Overall there were no differences between the two groups in infants' demographics or clinical characteristics including risk factors for the development of PNAC. Infants who received enteral omega-3 FAs had significantly fewer days of cholestasis (p = 0.025) and a higher average daily weight gain (grams/day) (p = 0.011) than their controls. In a linear regression analysis with days of cholestasis as the dependent variable and Ursodeoxycholic acid (UDCA) and Omega-3 FAs as independent variables, enteral omega-3 FAs remained associated with a shorter duration of cholestasis, p < 0.001. CONCLUSION: Enteral fish oil is inexpensive, safe & well tolerated in preterm neonates with no contraindications to enteral feeding. Enteral omega-3 FAs are easy to administer and help in rapid resolution of PNAC while promoting postnatal weight gain in preterm infants.

Slow enteral feeding decreases risk of transfusion associated necrotizing enterocolitis.

BACKGROUND: Necrotizing Enterocolitis (NEC) is a multifactorial condition where PRBC transfusion is associated with necrotizing enterocolitis (TANEC) in about a third of all cases of NEC. We have investigated the role of feeding practices in incidence of TANEC. We sought to compare infants diagnosed with TANEC versus infants diagnosed with classic NEC and investigated the effects of a standardized slow enteral feeding (SSEF) protocol on TANEC incidence as well as the effects of SSEF on growth of infants with NEC. METHODS: We conducted a retrospective cohort study, where medical records of infants born in a tertiary care neonatal intensive care unit (level IIIb) from January 1997 to May 2014 with birth weight < 1500 grams and gestational age≤34 weeks with NEC stage IIa or greater according to the modified Bell's staging were reviewed. RESULTS: During the study period, 111 infants developed NEC, and 41/111 (37%) were diagnosed with TANEC. Infants with TANEC were smaller, more premature, had higher SNAPPE scores and were more anemic prior to transfusion compared with infants with 'classic NEC'. The severity of NEC did not differ between the two groups, however, infants with TANEC had worse outcomes and longer NICU stays. Introduction of SSEF protocol, led to a significant decrease in TANEC. There was no difference in weight and head circumference of infants in the two groups at 2 years corrected age. CONCLUSION: SSEF led to a significant reduction in the incidence of TANEC without impairing growth at 2 years corrected age.

Antenatal dexamethasone treatment leads to changes in gene expression in a murine late placenta.

Antenatal steroids like dexamethasone (DEX) are used to augment fetal lung maturity and there is a major concern that they impair fetal growth. If delivery is delayed after using antenatal DEX, placental function and hence fetal growth may be compromised even further. To investigate the effects of DEX on placental function, we treated 9 pregnant C57/BL6 mice with DEX and 9 pregnant mice were injected with saline to serve as controls. Placental gene expression was studied using microarrays in 3 pairs and other 6 pairs were used to confirm microarray results by semi-quantitative RT-PCR, real-time PCR, in situ hybridization, western blot analysis and Oligo ApopTaq assay. DEX-treated placentas were hydropic, friable, pale, and weighed less (80.0+/-15.1mg compared to 85.6.8+/-7.6mg, p=0.05) (n=62 placentas). Fetal weight was significantly reduced after DEX use (940+/-32mg compared to 1162+/-79mg, p=0.001) (n=62 fetuses). There was >99% similarity within and between the three gene chip data sets. DEX led to down-regulation of 1212 genes and up-regulation of 1382 genes. RT-PCR studies showed that DEX caused a decrease in expression of genes involved in cell division such as cyclins A2, B1, D2, cdk 2, cdk 4 and M-phase protein kinase along with growth-promoting genes such as EGF-R, BMP4 and IGFBP3. Oligo ApopTaq assay and western blot studies showed that DEX-treatment increased apoptosis of trophoblast cells. DEX-treatment led to up-regulation of aquaporin 5 and tryptophan hydroxylase genes as confirmed by real-time PCR, and in situ hybridization studies. Thus antenatal DEX treatment led to a reduction in placental and fetal weight, and this effect was associated with a decreased expression of several growth-promoting genes and increased apoptosis of trophoblast cells.

Myocardial performance and baroreceptor reflexes in preterm neonates: an echocardiographic evaluation using the tilt-table test.

The hemodynamic consequence of head-up position in preterm infants is not known, so we used the tilt-table test to assess changes in myocardial performance and baroreceptor reflexes. Twenty-five preterm infants with gestational age (GA) (mean +/- SD) 31 +/- 2.9 weeks (range 25-35.5 weeks), birth weight of 1612 +/- 642 g (range 520-3260 g) were studied in supine, 30 degrees, and 60 degrees head-up positions. GA had a significant effect on heart rate (HR) (p = 0.007), systolic blood pressure (SBP) (p = 0.03), left ventricular (LV) cavity dimensions (p = 0.001), cardiac output (CO) (p = 0.001), LV ejection time (LVETc) (p = 0.05), and end systolic wall stress (ESWS) (p = 0.003). An inverse relationship was seen between velocity of circumferential fiber shortening (VcFs) and ESWS (slope b = -0.019 +/- 0.008, p = 0.003). Results of tilt tests showed that at supine, 30 degrees, and 60 degrees, respectively, HR was 162 +/- 10.5, 162 +/- 9, and 164 +/-12 (p = NS); SBP (mmHg) was 73 +/- 11, 72.5 +/- 9.5, and 78 +/- 10 (p = NS); CO (L/kg/min) was 0.4 +/- 0.16, 0.4 +/- 0.15, and 0.43 +/- 0.16 (p = NS); ESWS (g/cm2) was 38.7 +/- 8.3, 40.9 +/- 9.9, and 43.4 +/- 10.7 (p = NS); and VcFs (circ/sec) was 1.35 +/- 0.3, 1.28 +/- 0.4, and 1.26 +/- 0.2 (p = NS). LV filling pattern as seen by early/late atrial Doppler flow velocity ratio did not change with tilt (p = NS). Myocardial performance improved with increasing GA. No significant differences in myocardial performance were found between baseline and head-up tilt positions.

Cord blood and postnatal serum leptin and its relationship to steroid use and growth in sick preterm infants.

OBJECTIVE: To study the effect of prenatal and postnatal glucocorticoids use on serum leptin and weight gain in sick preterm infants and its correlation with caloric intake. METHODS: Serum leptin was measured in 24 neonates at day 1 (cord), 14 and 28 by radioimmunoassay. Total caloric intake (enteral and parenteral) and weight were measured on days 14 and 28 of life. RESULTS: Mean birth weight and gestational age of study infants were 864 +/- 273 g (mean +/- SD) (range 520-1755 g), and 26.6 +/- 2.4 weeks (23-32 weeks) respectively. Cord blood leptin was greater in infants whose mothers received antenatal steroids (1.98 +/- 1.05 ng/ml vs 0.94 +/- 0.39 ng/ml, p=0.004). Serum leptin increased postnatally from 1.52 +/- 1.0 ng/ml at birth to 2.2 +/- 1.3 ng/ml on day 28 of life (p=0.03). Mean serum leptin had an inverse exponential relationship with postnatal weight gain by day 28 of life (R2=0.56). Total caloric intake on days 14 and 28 of life did not correlate with postnatal weight gain. CONCLUSIONS: Increased serum concentration of leptin following glucocorticoids may be associated with poor weight gain in sick preterm infants.

Early detection of bacteremia in the neonatal intensive care unit using the new BACTEC system.

OBJECTIVE: With the newer techniques of culture analysis such as the BACTEC 9240 fluorometric detection system, detecting bacteremia in the neonate may be possible in a significantly shorter time. We hypothesized that neonatal bacteremia can be detected in less than 48 hours by this method. STUDY DESIGN: Our study included a retrospective review of 613 blood cultures obtained during the period August 1, 1995 to March 18, 1996 taken from 325 infants who had cultures drawn with a sepsis work-up and/or repeat cultures who had initial positive cultures in our Neonatal Intensive Care Unit. Results of blood cultures were studied in conjunction with the variables of body weight, gestational age, organism grown, complete blood count (CBC), and timing of positive cultures. Statistical analyses were performed using Fisher's and two-tailed Student's t tests. RESULTS: The results showed that of 325 infant blood cultures 49 (15%) were positive. Of these, 64% were coagulase-negative staphylococci, 14% viridans streptococci, 8% Escherichia coli, 4% Enterococcus sp., 4% Pseudomonas sp., 2% Enterobacter sp., 2% Klebsiella sp., and 2% Candida albicans. Of the positive blood cultures taken from infants not on antibiotics at the time of culture, 54% were detected positive at 18 hours, 71% at 24 hours, and 100% by 30 hours. Detection time by organism type was as follows: coagulase-negative staphylococci, 21.7 hours; viridans streptococci, 15.6 hours; E. coli, 7.5 hours; Enterococcus sp., 12 hours; Enterobacter sp., 5 hours; Klebsiella sp., 10 hours; and Pseudomonas sp., 12 hours. CONCLUSION: Our results indicate that the BACTEC 9240 fluorometric detection system helps in early identification of neonatal bacteremia (in 24 to 30 hours), with Gram-negative organisms being detected earlier than Gram-positive organisms (p < 0.05) and having significantly higher immature neutrophils in a CBC (I:T ratio of > or = 0.2 (p < 0.001). Early detection of neonatal bacteremia using this method will allow earlier diagnosis and appropriate treatment of the potentially bacteremic and bacteremic infant.

Hospital readmission and morbidity following early newborn discharge.

To examine causes of newborn hospital readmission and morbidity related to early nursery discharge, we reviewed the charts of 664 newborns readmitted from home under the age of 15 days, between 1993 and 1995. Early discharge (ED) was defined as nursery length of stay of < or = 2 days. Morbidity related to ED: onset of symptoms within 1 day of ED; and in diseases with insidious onset: serum bilirubin level > 20 mg/dL (340 mumol/L), or dehydration following poor breastfeeding since birth. Seventeen percent of all readmitted infants had ED-related morbidity; 9% had major morbidity. Onset of symptoms prior to the age of 3 days occurred in 43% of ductal-dependent cardiac lesions, intestinal obstruction, seizures, and major infections. Morbidity was less pronounced in infants who were followed up within 2 days following ED. Specific findings related to subsequent morbidity were identified in the perinatal history of infants who were readmitted with major infections and with hyperbilirubinemia. Our findings suggest that: (1) close to half of the cases with acute-onset major morbidity can be identified within 3 days of birth, and (2) attention to the perinatal history and timely follow-up will contribute to a reduction in both morbidity and complications.

Neonatal cord blood leptin: its relationship to birth weight, body mass index, maternal diabetes, and steroids.

Leptin is a 16-kD protein encoded by the ob/ob (obesity) gene. In rodents it plays a role in obesity, diabetes, fertility, and neuroendocrine function. In humans serum concentrations of leptin correlate with total body fat in both adults and children. We measured cord blood leptin in 186 neonates that included 82 appropriate for gestational age (AGA), 47 large for gestational age (LGA), 20 infants of diabetic mothers, 52 preterm infants, and 15 intrauterine growth-retarded (IUGR) infants. There were 16 pairs of twins. The mothers of 17 preterm infants were treated with steroids before delivery. Leptin (mean +/- SD) concentration in term, AGA infants (39.4 +/- 1.1 wk) with birth weight (BW) of 3.2 +/- 0.3 kg, body mass index (BMI) of 12.6 +/- 1.1 was 4.01 +/- 3.5 ng/mL. BW correlated with cord leptin (p = 0.002) in a multivariate analysis controlling for potential confounders. Both LGA infants and infants of diabetic mothers had higher cord leptin concentration 7.3 +/- 3.8 and 6.1 +/- 4.8 ng/mL, respectively, compared with AGA infants (p < 0.05). Preterm infants had a mean leptin level of 1.8 +/- 0.97 ng/mL and a 3-fold elevation was seen if mothers received steroids antenatally (p = 0.006). IUGR infants had increased leptin (6.5 +/- 3.9 ng/mL, p = 0.03). Concerning the twin pairs, the smaller had a higher leptin level compared with larger twin (4.1 +/- 9.51 versus 2.8 +/- 5.14, p = NS). Neonatal cord leptin concentrations correlate well with BW and BMI. No gender differences were found in cord blood leptin. Maternal obesity had no effect on cord leptin, whereas exogenous maternal steroids increased neonatal leptin concentrations.

Spectrum of clinical and cardiac dysfunction in bronchopulmonary dysplasia: early prediction of long-term morbidity.

OBJECTIVES: The objective of this study was to correlate the severity of bronchopulmonary dysplasia (BPD) in infants < or = 28 weeks' gestation with clinical and radiologic scoring and cardiac function as measured by echocardiography. STUDY DESIGN: Twenty-five infants with a mean birth weight of 909 gm and gestational age 26 weeks were studied. All infants were categorized with a clinical and radiologic scoring system at 1 and 3 months. All infants were studied with two-dimensional, M-mode, and Doppler echocardiography. RESULTS: A significant correlation was found between clinical and radiologic scores at 1 month (r = 0.42) and between radiologic scorings at 1 and 3 months (r = 0.67). Severe BPD is directly related with mean airway pressure on day 7 of life (p < 0.05), use of intralipids (p < 0.05), and average oxygen exposure (p < 0.05). Left ventricular posterior wall thickness is directly correlated to severity of BPD (p < 0.05), and transmitral flow velocities and early diastolic/atrial contraction flow velocity ratio are inversely related to severity of BPD (p < 0.05). CONCLUSIONS: Severe BPD can be predicted at an early age, and certain subtle cardiac dysfunctions can be used as early markers of BPD.

A bacteriological study of the environment of pediatric ward and neonatal nursery.

The hospital environment is full of pathogens which may cause nosocomial infections. A bacteriological survey of hospital air, floor, water, milk and fomites was done. The air survey showed large number of bacteria carrying particles in air. A direct relation between floor area per person and bacterial contamination of air was established. The floor survey showed that there is abundance of bacteria on the hospital floors, much more than the accepted fair standards of house keeping. The hospital water had a high coliform and total bacterial count and stored tank water was more dirty. Neonatal nursery milk also had high total bacterial and coliform counts. Regular surveillance of hospital environment may help to reduce the incidence of cross infection.