Comparative Growth Outcomes in Preterm Infants Fed Either Mother's Own Milk or Donor Human Milk.

Objective: To compare growth velocity (GV) in preterm infants fed mother's own milk (MOM) fortified with human milk-based fortifier (HMBF) to those who received donor human milk (DHM) fortified with HMBF. Study Design: A retrospective study of preterm infants with birth weight <1,250 g receiving an exclusive human milk diet. Maternal and infant charts were reviewed for feeding, growth, and short-term neonatal morbidities. Results: On regression analysis, after adjusting (gestational age, multiple births, antenatal steroids, and small for gestational age), no significant difference was observed between the two groups in GV from birth to 32 weeks postmenstrual age (ß-coefficient 0.83, 95% confidence interval [CI]: -0.47 to 2.14, p = 0.21), GV from the day of regaining of birth weight to discharge (ß-coefficient -0.015, 95% CI: -1.08 to 1.05, p = 0.98). The rate of Grade 3 and 4 intraventricular hemorrhage was significantly higher in the DHM group (19.6% compared to 5.5% in MOM, p = 0.03). Conclusion: At our institution, there was no difference in GV of preterm infants fed HMBF-fortified MOM versus HMBF-fortified DBM.

Breast milk vs 24% sucrose for procedural pain relief in preterm neonates: a non-inferiority randomized controlled trial.

OBJECTIVES: To compare the pain scores between the two groups, breast milk (BM) and 24% sucrose, in preterm neonates undergoing automated heel lance for the blood draw. METHODS: The study is designed as a randomized, single-blinded, non-inferiority trial. Infants born between 30 1/7weeks and 36 6/7 weeks of gestation were randomly assigned to receive either 24% sucrose or expressed BM. The Premature Infant Pain Profile-Revised (PIPP-R) was utilized to provide pain scores. RESULTS: No differences were noted in the baseline characteristics between the two groups. The quantile regression estimates for PIPP-R scores during the procedure were statistically non-significant at all percentile levels of distribution (50%ile coefficient 0, 95% CI -0.49 to 0.49). CONCLUSION: We conclude that BM is not inferior to 24% sucrose in providing analgesia during heel lance in moderate and late preterm infants. TRIAL REGISTRATION: This trial was registered at www. CLINICALTRIALS: gov (identifier NCT04898881).

Effect of an exclusive human milk diet on feeding tolerance in preterm infants.

OBJECTIVE: To compare the time to full enteral feeds in preterm infants fed exclusive human milk (EHM) - mother's own milk (MOM) fortified with human milk-based fortifier (HMBF), to those who received partial human milk (PHM) - MOM fortified with bovine milk-based fortifier (BMBF), and exclusive formula. STUDY DESIGN: A single-center retrospective study of infants with birth weight <1250 g from 2013 to 2018. Data on feeding, growth and other short-term neonatal morbidities were collected. RESULTS: On regression analysis, time to full enteral feeds was significantly higher in PHM compared to EHM group (ß-coefficient 4.14, 95% CI 0.00-8.29) and formula-fed group compared to EHM (ß-coefficient 4.3, 95% CI 0.32-8.20). No significant differences in growth velocity, length of stay and other morbidities were found between the groups. CONCLUSION: Infants in EHM had better feeding tolerance and reached their enteral feed goals sooner compared to PHM and formula-fed groups.

Feeding during transfusion and the risk of necrotizing enterocolitis in preterm infants.

OBJECTIVE: To evaluate the effect of withholding feeds during transfusion on transfusion associated acute gut injury (TRAGI). STUDY DESIGN: Data were collected on 125 preterm infants before and after the practice of withholding feeds for 12-24 h during transfusion was instituted. Logistic regression was used to examine effects of withholding feeds on TRAGI rates. RESULTS: A total of 19 (15%) infants developed NEC; 6/19 (32%) had TRAGI. Postnatal hydrocortisone use was associated with TRAGI (OR 8.97; 95% CI 1.17-68.46, p = 0.034). There was no difference in NEC rates (15.8 vs. 14.7%) and the proportions (22.2 vs. 40%) of TRAGI in the two time periods before and after instituting the standardized feeding regimen and practice of holding feeds during transfusion. CONCLUSION: No significant decrease was noted in the rates of TRAGI after feeds were withheld during transfusion. Further studies are warranted to explore the relationship between feeds during transfusion and NEC.

Higher daily doses of caffeine lowered the incidence of moderate to severe neurodevelopmental disabilities in very low birth weight infants.

AIM: We determined the influence of cumulative dosing of caffeine citrate on the neurodevelopmental outcomes of low birth weight (VLBW) infants at 18-22 months of postmenstrual age. METHODS: This retrospective chart analysis was conducted at Detroit Medical Center, Michigan, USA. The 181 infants we included were born between January 2006 and December 2016, were less than 32 weeks of gestational age and weighed less than 1500 grams. Data on their perinatal and postnatal characteristics were retrieved from their medical records and they were assessed using the Bayley Scales of Infant Development - Third Edition. RESULTS: The 64 infants with no neurodevelopmental disability or a mild disability received a significantly higher average daily dose (mg/kg/day) of caffeine citrate with a median of 7.58 (range 2.7-12.2) mg/kg/day, than the 79 infants with a moderate to severe disability, who received a median of 6.47 (range 3.1-12.5, p = 0.01). The total cumulative dose had no effect on bronchopulmonary dysplasia or neurodevelopmental outcomes. CONCLUSION: A higher average daily dose of caffeine citrate was associated with better neurodevelopmental outcomes of VLBW infants. However, the cumulative dose did not have an impact on their short-term or long-term outcomes. Further research is needed to confirm our findings.

Timely empiric antimicrobials are associated with faster microbiologic clearance in preterm neonates with late-onset bloodstream infections.

AIM: The impact of timely empiric antimicrobial therapy on neonates is unclear. Our aim was to examine rates of effective timely empiric antimicrobial therapy on preterm neonates, together with the associated outcomes. METHODS: We performed a single-centre retrospective study of preterm infants (<32 weeks of gestational age) with a late-onset (>72 h of age) bloodstream infection (BSI). Empiric antimicrobial administration took place before the results of blood culture were available and its timing was determined by the electronic medical records. RESULTS: Our cohort (n = 105) was predominantly female (59%) and black (83%) with a mean (SD) gestational age of 27.4 (2.3) weeks and birthweight of 948 (335) g. Effective empiric antimicrobials were initiated in 114 (69%) of 165 BSI episodes, and a third of the BSIs without empiric antimicrobials were found to be fungal. Both antimicrobial timing (r = 0.27, p = 0.002) and fungal organism (r = 0.35, p = 0.0001) showed significant correlations and were independently associated with time to clearance. Neither variable was associated with survival or length of stay. CONCLUSION: Two-thirds of preterm infants with late-onset BSIs received effective empiric antimicrobials. Timely empiric antimicrobials were associated with shorter time to microbiologic clearance. These data suggest the need for standardised guidelines and quality improvement initiatives.

Impact of small-for-gestational age (SGA) status on gentamicin pharmacokinetics in neonates.

We compared gentamicin pharmacokinetics among neonates born small-for-gestational age (SGA) and appropriate for gestational age (AGA). We further compared gentamicin pharmacokinetics in subgroups of AGA and SGA neonates born preterm and term and treated within and after the initial week of age. Steady state peak and trough serum gentamicin concentrations were used to calculate clearance (Cl), elimination constant (Kel), volume of distribution (Vd), and half-life (t1/2 ) in infants (n = 236) who received ≥48 hours therapy. Statistical analyses (SPSS 17.0) included chi-square and the non-parametric Mann-Whitney U-test. SGA infants treated early (≤7days) (n = 29) and at postmenstrual ages ≤32 weeks (n = 23) had significantly lower median Kel (0.069/h vs. 0.081/h and 0.067/h vs. 0.075/h) and clearance (0.58 mL/kg/min vs. 0.68 mL/kg/min and 0.46 mL/kg/min vs. 0.65 mL/kg/min), compared to those born AGA. There were no significant differences in pharmacokinetic profiles with later therapy or at more mature ages. The prolonged half-life of gentamicin may need to be considered in dosing regimens for preterm SGA infants in the initial week of life.

An algorithm to detect adverse drug reactions in the neonatal intensive care unit.

Critically ill newborns in neonatal intensive care units (NICUs) are at greater risk of developing adverse drug reactions (ADRs). Differentiation of ADRs from reactions associated with organ dysfunction/immaturity is difficult. Current ADR algorithm scoring was established arbitrarily without validation in infants. The study objective was to develop a valid and reliable algorithm to identify ADRs in the NICU. Algorithm development began with a 24-item questionnaire for data collection on 100 previously suspected ADRs. Five pediatric pharmacologists independently rated cases as definite, probable, possible, and unlikely ADRs. Consensus "gold standard" was reached via teleconference. Logistic regression and iterative C programs were used to derive the scoring system. For validation, 50 prospectively collected ADR cases were assessed by 3 clinicians using the new algorithm and the Naranjo algorithm. Weighted kappa and intraclass correlation coefficient (ICC) were used to compare validity and reliability of algorithms. The new algorithm consists of 13 items. Kappa and ICC of the new algorithm were 0.76 and 0.62 versus 0.31 and 0.43 for the Naranjo algorithm. The new algorithm developed using actual patient data is more valid and reliable than the Naranjo algorithm for identifying ADRs in the NICU population. Because of the relatively small and nonrandom samples, further refinement and additional testing are needed.

Fluctuations of anti-Xa concentrations during maintenance enoxaparin therapy for neonatal thrombosis.

AIM: To evaluate fluctuations in anti-Xa concentrations in infants treated with enoxaparin for thrombosis and describe clinical outcomes. METHODS: A retrospective chart review was performed on infants treated with enoxaparin in the Neonatal Intensive Care Unit, and data on enoxaparin doses, anti-Xa concentrations, clinical characteristics and outcomes were abstracted. RESULTS: Our cohort (n = 26) had a median gestation of 36 (range, 23-41) weeks, birthweight of 2522 (510-3912) grams and 5-min Apgar score of 8(4-9). Fifteen (57.7%) infants were males. Thromboses was diagnosed at a median age of 22 (range, 1-97) days; enoxaparin was initiated at 27.5 (range, 4-98) days at a mean (SD) dose of 1.4 (0.3) mg/kg every 12 h. Therapeutic anti-Xa concentrations (0.5-1 U/mL) were achieved at a mean (SD) dose of 2.1 (0.6) mg/kg at 12.5 (12.2) days of treatment. Of the 143 anti-Xa concentrations, 39 (27%) were within the therapeutic range. During maintenance therapy following initial therapeutic anti-Xa concentration, 40% concentrations were therapeutic. Minor bleeding was noted in four infants and intracranial bleed in one infant; four infants died. During treatment, thrombocytopenia, renal and hepatic impairment during treatment were noted in 7, 2 and 4 infants, respectively. Clot resolution was observed in 21 (81%) infants. CONCLUSIONS: Anti-Xa concentrations fluctuate during maintenance enoxaparin therapy, with therapeutic levels being achieved only sporadically in young infants. Despite this, enoxaparin appears efficacious in thrombosis resolution. Further studies on the impact of stringent control of concentrations on outcomes in this population are warranted.

The risk of necrotizing enterocolitis after indomethacin tocolysis.

BACKGROUND: Postnatal indomethacin is reportedly associated with an increased incidence of necrotizing enterocolitis (NEC) in preterm infants. Because indomethacin readily crosses the placenta, we hypothesized that antenatal indomethacin (AI) would increase the risk for NEC in preterm infants. OBJECTIVE: The goal of this study was to explore the association between AI and NEC in preterm infants. METHODS: Medical records of preterm infants, 23 to 32 weeks' gestational age, without major congenital anomalies, were reviewed. Maternal and neonatal data were abstracted. Association of AI within 15 days before delivery (predictor variable) and classification of NEC according to modified Bell's stage 2a or higher in the first 15 days after delivery (early NEC [primary outcome variable]) was explored by using bivariate analyses, multivariate logistic regression, and propensity score analysis. RESULTS: Of 628 eligible infants, 63 received AI and 28 developed early NEC. AI exposure was significantly associated with multiple gestation, race, antenatal corticosteroids and magnesium sulfate, lower birth weight and gestational age, umbilical arterial catheter placement, respiratory distress syndrome, postnatal vasopressors and antibiotics, patent ductus arteriosus, sepsis, NEC, intraventricular hemorrhage, and mortality. On multivariate logistic regression controlling for covariates, AI was significantly associated with early NEC (adjusted odds ratio: 7.193 [95% confidence interval: 2.514-20.575]; number needed to harm: 5). The results remained significant when analyses were repeated using AI exposure within 5 days before delivery as a predictor variable; on analyses stratified according to gestational age; and on propensity score analysis. CONCLUSIONS: AI was associated with NEC in preterm infants in the first 15 days of life in this study, as were multiple other clinical factors.

Colistin Therapy in a 23-Week Gestational-Age Neonate with Multidrug-Resistant Acinetobacter baumannii Pneumonia.

Multidrug-resistant pathogens are becoming more difficult to treat with significantly increasing infection rates. The lack of new antibiotics to combat these strains has led to the resurgence of older antibiotics. This case highlights the first reported use of colistimethate sodium treatment in a 23-week gestational-age neonate with multidrug-resistant Acinetobacter baumannii pneumonia who developed acute renal failure and seizures shortly after initiation of treatment.

Experience with caspofungin in the treatment of persistent fungemia in neonates.

OBJECTIVE: To review our experience of caspofungin in the treatment of persistent candidemia in the neonatal intensive care unit. STUDY DESIGN: This was a retrospective chart review on 13 infants in whom caspofungin was added to conventional antifungals (amphotericin B and/or fluconazole or flucytosine) for the treatment of refractory candidemia. RESULTS: A total of 12 infants were preterm (gestational age, 24 to 28 weeks) and one was term; the median birth weight was 800 g (range, 530 to 5600 g). Candidemia (Candida albicans in five, C. parapsilosis in six, C. albicans and C. parapsilosis in one and C. tropicalis in one) persisted despite 6 to 30 days of conventional antifungal therapy. After the addition of caspofungin, sterilization of blood cultures was achieved in 11 infants at the median time of 3 days (range, 1 to 21 days). Adverse events included thrombophlebitis (one patient), hypokalemia (two patients) and elevation of liver enzymes (four patients). Three infants had a second episode of candidemia and seven patients died. CONCLUSION: Caspofungin may be an efficacious addition for treatment of candidemia refractory to conventional antifungal therapy. This drug should be further investigated in neonates.