Aloka L. Patel

Accuracy of methods for calculating postnatal growth velocity for extremely low birth weight infants.

Objective. No uniform method for calculating growth velocity (GV) (grams per kilogram per day) among extremely low birth weight (ELBW) infants has been reported. Because the calculation of actual GV is so labor intensive, investigators have estimated GV with varying approaches, making comparisons across studies difficult. This study compares the accuracy of 3 mathematical methods used for estimating average GV, namely, 2-point models using the difference between weights at 2 time points divided by time and weight (either birth weight [BW] or average weight), linear regression models that are normalized for either BW or average weight, and an exponential model. The accuracy of all models was compared with actual GVs calculated from daily weight measures for a group of ELBW infants. Methods. Actual GVs were calculated from daily weights for 83 ELBW infants admitted to the special care nursery and were compared with estimated GVs from each of the 5 models for the same infants. Results. The exponential model, using weights from 2 time points, ie, GV = [1000 × ln(Wn/W1)]/(Dn − D1), was extremely accurate, with mean absolute errors of 0.02% to 0.10%. The 2-point and linear models were highly inaccurate when BW was used in the denominator, with mean absolute errors of 50.3% to 96.4%. The 2-point and linear models were fairly accurate when average weight was used in the denominator, with mean absolute errors of 0.1% to 8.97%. Additional analyses showed that the accuracy of the 2-point and linear model estimates was affected significantly by the combination of BW, length of stay, and chronic lung disease, whereas the exponential model was not affected by these combined factors. Conclusions. GV estimates calculated with 3 commonly used models varied widely, compared with actual GVs; however, the exponential model estimates were extremely accurate. The exponential model provides the accuracy and ease of use that are lacking in current methods applied to infant growth research.

Impact of early human milk on sepsis and health-care costs in very low birth weight infants

Objective:To study the incidence of sepsis and neonatal intensive care unit (NICU) costs as a function of the human milk (HM) dose received during the first 28 days post birth for very low birth weight (VLBW) infants.Study design:Prospective cohort study of 175 VLBW infants. The average daily dose of HM (ADDHM) was calculated from daily nutritional data for the first 28 days post birth (ADDHM-Days 1–28). Other covariates associated with sepsis were used to create a propensity score, combining multiple risk factors into a single metric.Result:The mean gestational age and birth weight were 28.1±2.4 weeks and 1087±252 g, respectively. The mean ADDHM-Days 1–28 was 54±39 ml kg−1 day−1 (range 0–135). Binary logistic regression analysis controlling for propensity score revealed that increasing ADDHM-Days 1–28 was associated with lower odds of sepsis (odds ratio 0.981, 95% confidence interval 0.967–0.995, P=0.008). Increasing ADDHM-Days 1–28 was associated with significantly lower NICU costs.Conclusion:A dose–response relationship was demonstrated between ADDHM-Days 1–28 and a reduction in the odds of sepsis and associated NICU costs after controlling for propensity score. For every HM dose increase of 10 ml kg−1 day−1, the odds of sepsis decreased by 19%. NICU costs were lowest in the VLBW infants who received the highest ADDHM-Days 1–28.

Posttransplant Lymphoproliferative Disease in Children: Correlation of Histology to Clinical Behavior

Purpose To determine whether the morphologic features of posttransplant lymphoproliferative disease (PTLD) correlated to a response to therapy. Patients and Methods We reviewed our experience with PTLD in the pediatric population. We identified 32 patients with a total of 36 episodes of PTLD. The diagnosis was confirmed by tissue examination and classified according to the degree of monomorphic features of the lesion. Thirty-four of 36 episodes were managed with immunosuppression reduction, and the patients were assessed for their response to this strategy. Chemotherapy was used to treat 10 of 15 patients who had progressive disease, and their subsequent course was also analyzed. Results Sixteen of 17 (94%) patients with polymorphic morphology responded to immunosuppression reduction compared with only 5 of 17 (29%) patients with monomorphic features (P < 0.001). All of the patients with progressive disease who did not receive additional therapy died. Standard chemotherapy regimens for lymphoma were administered to 10 patients with progressive disease, with a high response rate (90%), durable remissions, and acceptable toxicity. Conclusions We conclude that the morphologic characteristics of PTLD provide information to potentially help guide treatment strategies in the management of this disease. Standard chemotherapy regimens for malignant lymphoma appear to be a viable treatment option for patients with progressive disease, although further investigation is needed.

Calculating postnatal growth velocity in very low birth weight (VLBW) premature infants

Objective:Currently, there is no standardized approach to the calculation of growth velocity (GV; g kg –1 day–1) in hospitalized very low birth weight (VLBW) infants. Thus, differing methods are used to estimate GV, resulting in different medical centers and studies reporting growth results that are difficult to compare. The objective of this study was to compare actual GV calculated from infant daily weights during hospitalization in a Neonatal Intensive Care Unit (NICU) with estimated GV using two mathematical models that have been shown earlier to provide good estimated GVs in extremely low birth weight (ELBW) infants: an exponential model (EM) and a 2-Point model (2-PM).Study Design:Daily weights from 81 infants with birth weights (BWs) of 1000 to 1499 g were used to calculate actual GV in daily increments from two starting points: (1) birth and (2) day of life (DOL) of regaining BW. These daily GV values were then averaged over the NICU stay to yield overall NICU GV from the two starting points. We compared these actual GV with estimated GV calculated using the EM and 2-PM methods.Results:The mean absolute difference between actual and EM estimates of GV showed <1% error for 100% of infants from both starting points. The mean absolute difference between actual and 2-PM estimates showed <1% error for only 38 and 44% of infants from birth and regaining BW, respectively. The EM was unaffected by decreasing BW and increasing length of NICU stay, whereas the accuracy of the 2-PM was diminished significantly (P<0.001) by both factors.Conclusion:In contrast to the 2-PM, the EM provides an extremely accurate estimate of GV in larger VLBW infants, and its accuracy is unaffected by common infant factors. The EM has now been validated for use in all VLBW infants to assess growth and provides a simple-to-use and consistent approach.

Supporting Breastfeeding in the Neonatal Intensive Care Unit : Rush Mother’s Milk Club as a Case Study of Evidence-Based Care

The translation of the evidence for the use of human milk (HM) in the neonatal intensive care unit (NICU) into best practices, toolkits, policies and procedures, talking points, and parent information packets is limited, and requires use of evidence-based quality indicators to benchmark the use of HM, consistent messaging by the entire NICU team about the importance of HM for infants in the NICU, establishing procedures that protect maternal milk supply, and incorporating lactation technologies that take the guesswork out of HM feedings and facilitate milk transfer during breastfeeding.

The NFKB1 (g.-24519delATTG) variant is associated with necrotizing enterocolitis (NEC) in premature infants.

OBJECTIVE While it is known that gene-environment interactions contribute to necrotizing enterocolitis (NEC) pathogenesis, characterization of genetic risk-factors that can predict NEC in preterm infants remains nascent. We hypothesized that altered intestinal immune responses arising from sequence variation in the toll-like receptor (TLR) pathway genes contribute to NEC susceptibility. MATERIALS AND METHODS Very low birth weight (VLBW) infants were recruited prospectively in a multi-center, cohort study involving collection of blood samples along with collation of clinical information. DNA obtained from blood samples was used to genotype nine single nucleotide polymorphisms (SNPs) in eight TLR pathway genes by single-base extension. Prevalence of the variant allele was compared between cases and controls using Fishers exact test. RESULTS In our cohort of 271 infants, 15 infants (5.6%) developed NEC, and five died from it. Infants with NEC were less mature (P < 0.001), and were more likely to be African-American (P = 0.007). SNPs in the TLR2, TLR4, TLR5, TLR9, IRAK1, and TIRAP genes were not associated with NEC. The NFKB1 (g.-24519delATTG) variant was present in all infants with NEC but only in 65% of infants without NEC (P = 0.003), while the NFKBIA (g.-1004A>G) variant was present in 13.3% of infants with NEC but in 49% of infants without NEC (P = 0.007). After correcting for multiple comparisons, the NFKB1 and NFKBIA variants remained associated with NEC (P < 0.05). CONCLUSIONS These data suggest that TLR genetic variants can alter susceptibility to NEC in VLBW infants and support the hypothesis that genetically programmed differences in the innate immune response contribute to NEC pathogenesis.

Cost Savings of Human Milk as a Strategy to Reduce the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants

Background: Necrotizing enterocolitis (NEC) is a costly morbidity in very low birth weight (VLBW; <1,500 g birth weight) infants that increases hospital length of stay and requires expensive treatments. Objectives: To evaluate the cost of NEC as a function of dose and exposure period of human milk (HM) feedings received by VLBW infants during the neonatal intensive care unit (NICU) hospitalization and determine the drivers of differences in NICU hospitalization costs for infants with and without NEC. Methods: This study included 291 VLBW infants enrolled in an NIH-funded prospective observational cohort study between February 2008 and July 2012. We examined the incidence of NEC, NICU hospitalization cost, and cost of individual resources used during the NICU hospitalization. Results: Twenty-nine (10.0%) infants developed NEC. The average total NICU hospitalization cost (in 2012 USD) was USD 180,163 for infants with NEC and USD 134,494 for infants without NEC (p = 0.024). NEC was associated with a marginal increase in costs of USD 43,818, after controlling for demographic characteristics, risk of NEC, and average daily dose of HM during days 1-14 (p < 0.001). Each additional ml/kg/day of HM during days 1-14 decreased non-NEC-related NICU costs by USD 534 (p < 0.001). Conclusions: Avoidance of formula and use of exclusive HM feedings during the first 14 days of life is an effective strategy to reduce the risk of NEC and resulting NICU costs in VLBW infants. Hospitals investing in initiatives to feed exclusive HM during the first 14 days of life could substantially reduce NEC-related NICU hospitalization costs.

Efficacy of Fluconazole Prophylaxis for Prevention of Invasive Fungal Infection in Extremely Low Birth Weight Infants

Background: Invasive fungal infections (IFI) are an important cause of late-onset disease in extremely low birth weight (ELBW) infants. Despite prior trials of fluconazole prophylaxis in neonates, application of this regimen remains controversial. Review of our neonatal intensive care unit aggregate annual number of fungal isolates from sterile sites in ELBW infants from 1997 to 2006 suggested a significant decrease following the institution of routine prophylactic fluconazole in February 2002. We undertook a retrospective study to document the efficacy and adverse effects of routine fluconazole prophylaxis. Methods: ELBW infants admitted during 2000 to 2006 were divided into 2 groups: Control group—admitted before the institution of fluconazole prophylaxis, and Fluconazole group—admitted after institution of fluconazole prophylaxis. Primary outcome was the frequency of IFI. Secondary outcome was the frequency of cholestasis, which has been rarely reported with fluconazole use. Results: Data were extracted from 262 infant records: control 99, fluconazole 163. Baseline demographics and potentially confounding variables differed between the 2 groups with greater birth weight, greater gestational age, shorter durations of ventilation and central catheter use, and earlier start of feeding in the control group, reflecting healthier control infants. Frequency of IFI was 7.1% in the control group versus 1.8% in the fluconazole group, P = 0.045. Logistic regression revealed that fluconazole prophylaxis was independently associated with a lower risk of IFI. There was no difference in the frequency of cholestasis between the control and fluconazole groups. Conclusions: Prophylactic administration of fluconazole to all ELBW infants was associated with significantly decreased rates of IFI without associated adverse effects.

Management of Breastfeeding During and After the Maternity Hospitalization for Late Preterm Infants

Among infants born moderately and late preterm or early term, the greatest challenge for breastfeeding management is the late preterm infant (LPI) who is cared for with the mother in the maternity setting. Breastfeeding failure among LPIs and their mothers is high. Evidence-based strategies are needed to protect infant hydration and growth, and the maternal milk supply, until complete feeding at breast can be established. This article reviews the evidence for lactation and breastfeeding risks in LPIs and their mothers, and describes strategies for managing these immaturity-related feeding problems. Application to moderately and early preterm infants is made throughout.

Economic Benefits and Costs of Human Milk Feedings: A Strategy to Reduce the Risk of Prematurity-Related Morbidities in Very-Low-Birth-Weight Infants

Infants born at very low birth weight (VLBW; birth weight <1500 g) are at high risk of mortality and are some of the most expensive patients in the hospital. Additionally, VLBW infants are susceptible to prematurity-related morbidities, including late-onset sepsis, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, and retinopathy of prematurity, which have short- and long-term economic consequences. The incremental cost of these morbidities during the neonatal intensive care unit (NICU) hospitalization is high, ranging from