Shamik Trivedi

Reducing necrotizing enterocolitis in very low birth weight infants using quality-improvement methods.

Objective:Owing to a rise in necrotizing enterocolitis (NEC, stage ⩾2) among very low birth weight (VLBW, birth weight <1500 g) infants from 4% in 2005 to 2006 to 10% in 2007 to 2008, we developed and implemented quality improvement (QI) initiatives. The objective was to evaluate the impact of QI initiatives on NEC incidence in VLBW infants.Study Design:In September 2009, we developed an NEC QI multidisciplinary team that conducted literature reviews and reviewed practices from other institutions to develop a feeding protocol, which was implemented in December 2009. The team tracked intervention compliance and occurrence of NEC stage ⩾2. In May 2010, we reviewed our nasogastric tube practice and relevant literature to develop a second intervention that reduced nasogastric tube indwelling time. The infants were divided into three groups: baseline (January 2008 to Novovember 2009, n219), QI phase 1 (December 2009 to May 2010, n62) and QI phase 2 (June 2010 to November 2011, n170).Result:The NEC incidence did not decrease after implementation of the feeding protocol in QI phase 1 (19.4%) but did decline significantly after changing nasogastric tube management in QI phase 2 (2.9%). Multivariable logistic regression analysis demonstrated a significant relationship between QI phase and the incidence of NEC.Conclusion:QI initiatives were effective in decreasing NEC incidence in our high human milk-feeding NICU. Nasogastric tube bacterial contamination may have contributed to our peak in NEC incidence.

A novel method for assessing cerebral autoregulation in preterm infants using transfer function analysis.

Background:Autoregulatory dysfunction is an important contributor to brain injury in premature infants, particularly intraventricular hemorrhage (IVH). The autoregulatory system acts as a filter that dampens the systemic blood flow to follow a normal cerebral perfusion profile.Methods:Simultaneous arterial blood pressure and cerebral near-infrared spectroscopy (NIRS) data were collected from infants born before 28 wk estimated gestational age. The resulting data were preprocessed and then divided into nonoverlapping 20-min epochs. The transfer function estimate was calculated to determine dampening ability.Results:Sixty-two infants were prospectively recruited with a mean estimated gestational age of 25.4 ± 1.3 wk and birth weight of 832 ± 199 g. 67% were male, 24/62 had IVH, 17/62 received dopamine, 47/62 had antenatal steroid exposure, and 22/62 received fentanyl.Advancing estimated gestational age and birth weight z-score predicted stronger dampening while African-American race and IVH of any grade predicted weaker dampening.Conclusion:This preliminary report suggests an impairment in dampening ability associated with immaturity, decreased birth weight z-score, and African-American race. Decreased dampening is also associated with IVH, although these results cannot distinguish between decreased dampening as an antecedent or sequela of IVH. These observations should be studied in a larger sample.

Safety and Short-Term Outcomes of Therapeutic Hypothermia in Preterm Neonates 34-35 Weeks Gestational Age with Hypoxic-Ischemic Encephalopathy

Objective To evaluate the safety and short‐term outcomes of preterm neonates born at 34‐35 weeks gestation with hypoxic‐ischemic encephalopathy (HIE) treated with therapeutic hypothermia. Study design Medical records of preterm neonates born at 34‐35 weeks gestational age with HIE treated with therapeutic hypothermia were retrospectively reviewed. Short‐term safety outcomes and the presence, severity (mild, moderate, severe), and patterns of brain injury on magnetic resonance imaging were reviewed using a standard scoring system, and compared with a cohort of term neonates with HIE treated with therapeutic hypothermia. Results Thirty‐one preterm and 32 term neonates were identified. Therapeutic hypothermia‐associated complications were seen in 90% of preterm infants and 81.3% of term infants (P = .30). In the preterm infants, hyperglycemia (58.1% vs31.3%, P = .03) and rewarming before completion of therapeutic hypothermia (19.4% vs 0.0%, P = .009) were more likely compared with term infants. All deaths occurred in the preterm group (12.9% vs 0%, P = .04). Neuroimaging showed the presence of injury in 80.6% of preterm infants and 59.4% of term infants (P = .07), with no differences in injury severity. Injury to the white matter was more prevalent in preterm infants compared with term infants (66.7% vs 25.0%, P = .001). Conclusions Therapeutic hypothermia in infants born at 34‐35 weeks gestational age appears feasible. Risks of mortality and side effects warrant caution with use of therapeutic hypothermia in preterm infants.

Response to dopamine in prematurity: a biomarker for brain injury?

Objective:To identify factors associated with responsiveness to dopamine therapy for hypotension and the relationship to brain injury in a cohort of preterm infants.Study Design:The pharmacy database at St Louis Children’s Hospital was retrospectively queried to identify infants who (a) were born <28 weeks gestation between 2012 and 2014, (b) received dopamine and (c) had blood pressure measurements from an umbilical arterial catheter. A control group was constructed from contemporaneous infants who did not receive dopamine. Mean arterial blood pressure (MABP) at baseline, 1 h and 3 h after initiating dopamine were obtained for each dopamine-exposed infant. MABP measurements at matched time points were obtained in the control group.Result:Sixty-nine dopamine-treated and 45 control infants were included. Mean ΔMABP at 3 h was 4.5±6.3 mm of Hg for treated infants vs 1±2.9 for the control. Median dopamine starting dose was 2.5 μg kg−1 min−1. Dopamine-treated infants were less mature and of lower birth weight while also more likely to be intubated at 72 h, diagnosed with intraventricular hemorrhage (IVH) and to die. Failure to respond to dopamine was associated with greater likelihood of developing IVH (odds ratio (OR) 5.8, 95% confidence interval (CI) 1.1–42.3), while a strong response (ΔMABP>10 mm Hg) was associated with a reduction in risk of IVH (OR 0.1, 95% CI 0.01–0.8).Conclusion:Low–moderate dose dopamine administration results in modest blood pressure improvements. A lack of response to dopamine is associated with a greater risk of IVH, whereas a strong response is associated with a decreased risk. Further research into underlying mechanisms and management strategies is needed.

Early hyperoxia burden detected by cerebral near-infrared spectroscopy is superior to pulse oximetry for prediction of severe retinopathy of prematurity.

Objective:Fractional tissue oxygen extraction (FTOE) is a measure derived from cerebral near-infrared spectroscopy (NIRS) and simultaneous pulse oximetry (SpO2), capturing the proportion of oxygen delivered in arterial blood that is used by the target tissue. FTOE may provide a better proxy measurement of retinal hyperoxia than pulse oximetry alone and could provide insight into the risk for retinopathy of prematurity (ROP). In this study, we directly compared hyperoxia burden calculated from FTOE with hyperoxia burden calculated from SpO2 alone in order to assess the strength of association between hyperoxia and severe ROP.Study Design:Infants born before <30 weeks and weighing <1500 g underwent synchronized SpO2 and FTOE recording over the first 4 days following birth. After error correction of the raw recording, hyperoxia burden was calculated as the percentage of the total SpO2 or FTOE recording with measurements exceeding defined thresholds (90/93/95% and 20/15/10%, respectively) and was compared with the outcome of severe ROP, defined as ROP requiring laser therapy, after controlling for important covariates.Result:A total of 63 infants were included with a mean±s.d. gestational age of 25.8±1.5 weeks and birth weight of 898.5±206.9 g; 13/63 (20%) had severe ROP. SpO2 hyperoxia burden was not associated with severe ROP at any threshold. FTOE hyperoxia burden was associated with severe ROP at the 15% (P=0.04) and 10% (P=0.03) thresholds. Infants with severe ROP spent 20% and 50% more time exceeding the 15% and 10% thresholds, respectively, as compared with those without severe ROP.Conclusion:In the first 96 h of life, FTOE but not SpO2 hyperoxia burden is associated with severe ROP. These preliminary results suggest that NIRS may be a viable alternative technology for targeted oxygen saturation guidelines.

The effect of therapeutic hypothermia on heart rate variability

Objective:Heart rate variability (HRV) reflects integrity of the autonomic nervous system. However, no study has investigated the impact of therapeutic hypothermia (TH) on HRV measures in infants with hypoxic–ischemic encephalopathy (HIE). In this study, we evaluate the influence of temperature on measures of HRV for a group of infants with favorable outcomes, as compared with a control group of infants with unfavorable outcomes.Study Design:Term-born infants with moderate-severe HIE underwent standard TH treatment and prospective electroencephalography (EEG) and electrocardiogram (ECG) recording. Infants with favorable outcome (no seizures, normal/mild EEG scores at 96 h, no magnetic resonance imaging brain injury and normal neurodevelopmental scores at 18 to 24 months) were matched on gestational age, sex and worst encephalopathy score to a group of infants with unfavorable outcomes. Time- and frequency-domain HRV measures were calculated from 60 min of ECG data obtained at three time points: 24 h (hypothermia), 48 h (hypothermia) and 96 h (normothermia). The effect of time and temperature were evaluated using repeated-measures analysis of variance.Results:Sixteen infants were included (8 favorable, 8 unfavorable). For both groups of infants, an increase in the HR, RR and HF power was associated with an increase in temperature, but was not associated with any other HRV measure. In contrast, measures of HRV increased over time, as encephalopathy decreased, for infants with favorable outcomes (reflecting increased cortical-autonomic integration), but not for those with unfavorable outcomes.Conclusions:In general, the effect of hypothermia on measures of HRV is limited to changes in heart rate (bradycardia) and respiratory rate, as opposed to changes in true variability. This supports the hypothesis that persistent changes in HRV are driven by the underlying brain injury and not by the process of TH.

Re-examining the arterial cord blood gas pH screening criteria in neonatal encephalopathy

Objective Screening criteria for neonatal encephalopathy remain a complex combination of subjective and objective criteria. We examine the utility of universal cord blood gas testing and mandatory encephalopathy evaluation for infants with pH ≤7.10 on umbilical cord arterial blood gas (cABG) as a single screening measure for timely identification of moderate/severe encephalopathy. Design, setting, patients Infants born at a single centre between 2008 and 2015, who were ≥36 weeks, had no congenital anomalies and had a cABG pH ≤7.10 were identified for a retrospective cohort study. Maternal/perinatal and patient factors were collected. Results 27 028 infants were born during the study period; 412 met all inclusion criteria. Of those, 35/85 infants with pH <7.00 and 34/327 infants with pH between 7.00 and 7.10 had moderate/severe encephalopathy. Encephalopathy was identified on the basis of pH and examination alone (no other perinatal criteria present) in 5/35 and 13/34 infants in the two pH groups, respectively. A cABG pH threshold of ≤7.10 was associated with a sensitivity of 74.2% and a specificity of 98.7% for detection of moderate/severe encephalopathy. Based on these data, 25 infants with cABG pH between 7.00 and 7.10 will need to be screened to identify one neonate with moderate/severe encephalopathy, who might have otherwise been missed using conventional screening, a 15% increase in appropriate selection and treatment over current methods. Conclusion Universal cord blood gas screening with a pH threshold ≤7.10 and mandatory encephalopathy examination results in greater detection of infants with moderate/severe encephalopathy and timely initiation of therapeutic hypothermia.