Anthropometric measures as biomarkers of neurodevelopmental outcomes of newborns with moderate to severe hypoxic ischemic encephalopathy.

BACKGROUND: Perinatal asphyxia is a prominent cause of neonatal mortality in the developing world. Growth in head circumference is associated with improved neurodevelopment. Previous studies found a positive correlation between additional dietary supplementation and growth in head circumference among newborns with perinatal brain injury. This study aims to evaluate the association between anthropometric parameters and developmental outcomes in newborns with hypoxic ischemic encephalopathy (HIE). METHODS: Newborns at ≥36 weeks gestation with moderate to severe HIE were included in the study and growth parameters were monitored. Newborns with life-threatening anomalies were excluded. None of the study participants received therapeutic hypothermia (TH). Developmental Assessment Scale for Indian Infants (DASII) was used to evaluate neurodevelopmental outcomes at 1 year of age. RESULTS: Of 76 study participants, 46 were followed for 12 months, 28 died, and 2 were lost to follow-up. HIE stage III, Apgar score <5 at 5 minutes of age, pH ≤ 7.1 on first blood gas and base deficit > - 16 was associated with death or disability at 1 year of age. All anthropometric parameters were significantly lower in presence of death or disability. pH ≤ 7.1 at birth (odds ratio: 11.835, 95% CI 2.273-61.629, p = 0.003) and weight gain at one year (odds ratio 1.001, 95% CI 1.000-1.002, p = 0.03) were significantly associated with death and disability. CONCLUSION: pH > 7.1 at birth, and weight gain were associated with better neurodevelopmental outcomes at 1 year of age. Thus, in addition to TH, nutritional interventions may potentially improve outcomes among newborns with HIE.

Does clinical status 1 week after therapeutic hypothermia predict brain MRI abnormalities?

OBJECTIVE: Hypothermia improves clinical outcomes and brain magnetic resonance imaging (MRI) findings in infants with hypoxic-ischemic encephalopathy. We hypothesized that clinical status following hypothermia predicts brain MRI abnormalities, and helps determine which infants need an early MRI evaluation before discharge. The objective of this study was to determine whether the clinical evaluation 1 week after completion of 72 h of hypothermia treatment predicts the presence of brain MRI abnormalities related to hypoxia-ischemia. STUDY DESIGN: The medical records of 83 consecutively cooled infants who underwent brain MRI were reviewed. Clinical evaluation by day 10 of life consisted of assessment of oral feeding ability, spontaneous activity, need for mechanical ventilation and a history of clinical seizures. Logistic regression analysis was performed using all four covariates, with an abnormal MRI as the primary outcome. Brain MRI with lesions in both the basal nuclei and the cortex was considered to be severely abnormal. RESULT: MRI was abnormal in 46 (55%) infants. Univariate analysis identified all of the criteria as being significantly associated with an abnormal MRI. On multivariate analysis, only feeding difficulty (P<0.001, OR 9.5, 95% confidence interval (CI) 3 to 29.8) and a history of clinical seizures (P<0.001, OR 12, 95% CI 3 to 46.5) were significantly associated with an abnormal MRI. The areas under the receiver operating characteristic curve for feeding ability and seizure activity combined (0.86, 95% CI 0.77 to 0.94) indicated good accuracy with respect to the primary outcome. The negative predictive values of feeding difficulty and seizure activity for a severely abnormal MRI were 91% and 96%, respectively. CONCLUSION: Infants who do not have a history of clinical seizures and who attained full oral feeding by 1 week after hypothermia are unlikely to have an abnormal brain MRI. This simple assessment provides significant prognostic information that can be useful in parental counseling, and may allow selective use of pre-discharge MRI.

Does phenobarbital improve the effectiveness of therapeutic hypothermia in infants with hypoxic-ischemic encephalopathy?

OBJECTIVE: To determine whether phenobarbital (PB) given before therapeutic hypothermia to infants with hypoxic-ischemic encephalopathy (HIE) augments the neuroprotective efficacy of hypothermia. STUDY DESIGN: Records of 68 asphyxiated infants of 36 weeks' gestation, who received hypothermia for moderate or severe HIE were reviewed. Some of these infants received PB prophylactically or for clinical seizures. All surviving infants had later brain magnetic resonance imaging (MRI). The composite primary outcome of neonatal death related to HIE with worsening multiorgan dysfunction despite maximal treatment, and the presence of post-hypothermia brain MRI abnormalities consistent with hypoxic-ischemic brain injury, were compared between the infants who received PB before initiation of hypothermia (PB group, n=36) and the infants who did not receive PB before or during hypothermia (No PB group, n=32). Forward logistic regression analysis determined which of the pre-hypothermia clinical and laboratory variables predict the primary outcome. RESULT: The two groups were similar for severity of asphyxia as assessed by Apgar scores, initial blood pH and base deficit, early neurologic examination, and presence of an intrapartum sentinel event. The composite primary outcome was more frequent in infants from the PB group (PB 78% versus No PB 44%, P=0.006, odds ratio 4.5, 95% confidence interval 1.6 to 12.8). Multivariate analysis identified only the PB receipt before initiation of hypothermia (P=0.002, odds ratio 9.5, 95% confidence interval 2.3 to 39.5), and placental abruption to be independently associated with a worse primary outcome. CONCLUSION: PB treatment before cooling did not improve the composite outcome of neonatal death or the presence of an abnormal post-hypothermia brain MRI, but the long-term outcomes have not yet been evaluated.

Effects of therapeutic hypothermia on multiorgan dysfunction in asphyxiated newborns: whole-body cooling versus selective head cooling.

OBJECTIVE: Multiorgan dysfunction in asphyxiated newborns receiving therapeutic hypothermia achieved by either selective head cooling (SHC) or whole-body cooling (WBC) has not been well characterized. The beneficial effect of SHC in organs other than the brain may potentially be limited because unlike WBC, SHC aims to achieve effective brain cooling with less-systemic hypothermia. However, the relative effects of SHC and WBC with currently available cooling protocols on multiorgan dysfunction are unknown.The aim of this study was to compare the multiorgan dysfunction in infants receiving therapeutic hypothermia induced by either SHC or WBC. STUDY DESIGN: In 59 asphyxiated newborns who received therapeutic hypothermia by either SHC (n=31) or WBC (n=28), the severity of pulmonary, hepatic and renal dysfunction and coagulopathy and electrolyte disturbances were assessed before the start of cooling (baseline), and at specific time intervals (24, 48 and 72 h) throughout cooling. Enrollment criteria, clinical monitoring and treatment during cooling, whether SHC or WBC, were similar, as reported earlier. RESULT: The presence of clinical respiratory distress, along with the need for ventilatory support for varying duration during cooling, was similar in both the WBC and SHC groups (100 vs 94%, P=0.49, OR 1.9, 95% CI 1.5-2.5). The use of fresh frozen plasma and platelet transfusion to treat coagulopathy and thrombocytopenia was similar (WBC 48% vs SHC 58%, P=0.59, OR 0.7, 95% CI 0.2-1.9, and WBC 41% vs SHC 32%, P=0.58, OR 1.4, 95% CI 0.5-4.2, respectively), and equivalent numbers of infants from both groups were treated with vasopressors for >24 h (WBC 59% vs SHC 55%, P=0.79, OR 1.2, 95% CI 0.4-3.4). The incidence of oliguria (urine output <0.5 ml kg(-1) h(-1) for >24 h after birth) and rising serum creatinine (with maximum serum creatinine >0.9 mg dl(-1)) was also similar (WBC 18% vs SHC 39%, P=0.15, OR 0.4, 95% CI 0.1-1.3, and WBC 48% vs SHC 58%, P=0.59, OR 0.7, 95% CI 0.2-1.9, respectively). Laboratory parameters to assess the differential effect of WBC versus SHC on multiorgan dysfunction during 72 h of cooling, which include serum transaminases (serum aspartate aminotransferase and alanine aminotransferase), prothrombin time, partial thromboplastin time, INR, platelet counts, serum creatinine, serum sodium, serum potassium and serum calcium, were similar between the groups at the initiation of cooling and did not differ with the method of cooling. CONCLUSION: Multiorgan system dysfunction in asphyxiated newborns during cooling remains similar for both cooling methods. Concerns regarding a differential effect of WBC versus SHC on multiorgan dysfunction, other than of the brain, should not be a consideration in selecting a method to produce therapeutic hypothermia.

Role of multiple site blood cultures to document the clearance of bacteremia in neonates.

OBJECTIVE: To evaluate the usefulness of two-site blood cultures for the documentation of bacterial clearance during initial treatment of culture proven neonatal sepsis. DESIGN/METHODS: Clinical data were prospectively collected for 216 neonates who had blood cultures drawn for evaluation of possible sepsis. A positive diagnostic blood culture was followed by repeat blood cultures from two different peripheral sites after initiation of antimicrobial therapy. RESULTS: Follow-up two-site cultures were drawn on 25 occasions at a median interval of 3 days after start of antimicrobial therapy for culture-proven sepsis in 15 neonates. On 12 occasions, follow-up blood cultures were both negative. On eight occasions, follow-up blood cultures grew the same organisms from both sites. However, follow-up two-site cultures on five occasions in four of the 15 infants grew organisms from one site but not the second site. CONCLUSIONS: Two-site blood cultures seem necessary to document bacterial clearance in response to antimicrobial therapy for culture-proven sepsis, and may help determine the appropriate duration of antimicrobial therapy by reducing false-negative results.

Can neutrophil responses in very low birth weight infants predict the organisms responsible for late-onset bacterial or fungal sepsis?

OBJECTIVE: To examine neutrophil counts and various neutrophil indices in preterm very low birth weight (VLBW) newborn infants (birth weight <1500 g) with culture-proven late-onset sepsis to determine whether the neutrophil responses could predict the responsible infectious agent. STUDY DESIGN: Neutrophil parameters were examined during episodes of culture-proven sepsis in a cohort of 1026 VLBW infants, born over a 6-year period and admitted to two different neonatal intensive care units. Revised reference ranges of Mouzinho et al. for circulating neutrophil counts in VLBW infants were used to define the abnormal neutrophil indices. RESULTS: One hundred sixty-two of 1026 (15.8%) VLBW infants had blood culture-proven late-onset infection. Infections included Gram-positive bacteria (113/162, 70%), Gram-negative bacteria (30/162, 18%) and fungi (19/162, 12%). Of the 162 sepsis episodes, only nine (5.5%) were associated with neutropenia (absolute total neutrophil (ATN) <1100/mm3). Six of the 30 (20%) infants with Gram-negative bacterial sepsis were neutropenic compared to 2.6% infants with Gram-positive bacterial sepsis and none with fungal sepsis (odds ratio: 11; 95% confidence interval: 2.6, 47.3). Neutrophil counts and various neutrophil indices were similar in infants with late-onset Gram-positive bacterial and fungal sepsis; but total white blood cells, and ATN count were significantly lower (P = 0.004 and 0.001, respectively) in infants with late-onset Gram-negative bacterial sepsis. CONCLUSIONS: In VLBW infants, common organisms causing infection have different effects on neutrophil responses. Occurrence of neutropenia during evaluation of sepsis in sick VLBW infants is more common with Gram-negative bacterial infection.

A study of the role of multiple site blood cultures in the evaluation of neonatal sepsis.

BACKGROUND: The optimal number of blood cultures needed to document sepsis in an ill neonate has undergone little critical evaluation. Multiple site cultures may improve pathogen detection if intermittent bacteremia occurs, or if a low density of bacteria is present in the blood. We hypothesized, however, that bacterial clearance is slower and bacteremia more continuous in septic neonates, so that a single site blood culture should be sufficient to accurately document true septicemia. OBJECTIVE: To determine the need for multiple site blood cultures in the evaluation of neonates for sepsis. DESIGN/METHODS: Clinical data were prospectively collected for 216 neonates who had 269 pairs of blood cultures taken from two different peripheral sites for the evaluation of possible sepsis. A minimum of 1 ml of blood was obtained from the two peripheral sites within 15-30 min of each other. Based on prior retrospective data, we determined that 203 infants would need to have two site blood cultures to demonstrate a significant improvement in pathogen detection at an alpha of 0.05 and a beta of 0.20 (80%) power. RESULTS: A total of 186 culture pairs were taken for evaluation of early-onset sepsis in 186 neonates, while 83 pairs were drawn for evaluation of late-onset sepsis in 43 neonates. In all, 21 neonates from the late-onset group were evaluated more than once, and 12 neonates were evaluated for both early- and late-onset sepsis. In all, 20 (9.2%) of 216 neonates had 22 episodes of culture-proven sepsis at a median age of 18 days. All neonates with positive cultures had the same organism with a similar sensitivity pattern obtained from the two different peripheral sites. The other 196 study neonates had negative blood cultures from both sites. The single episode of early-onset sepsis was caused by Listeria monocytogenes, while all remaining episodes were late-onset with the following organisms: Staphylococcus epidermidis (7), methicillin-resistant Staphylococcus aureus (MRSA) (3), combined MRSA and Candida albicans (2), Candida albicans alone (2), late-onset Group B beta-hemolytic Streptococcus (GBS) (2), Klebsiella pneumoniae (2), Enterococcus fecalis (1), Escherichia coli (1), and Serratia marcescens (1). Since no infant grew organisms from only one of the two sites, the data indicate that the diagnosis of sepsis would have been made correctly in all infants with a single site culture. CONCLUSIONS: Two site blood cultures for the initial evaluation of neonatal sepsis do not have a better yield in pathogen detection. Sepsis in neonates can be detected with no loss of accuracy with a single site blood culture with blood volume of>or=1 ml.