Donna A. Goff

Noninvasive Cerebral Perfusion Imaging in High-Risk Neonates

Advances in medical and surgical care of the high-risk neonate have led to increased survival. A significant number of these neonates suffer from neurodevelopmental delays and failure in school. The focus of clinical research has shifted to understanding events contributing to neurological morbidity in these patients. Assessing changes in cerebral oxygenation and regulation of cerebral blood flow (CBF) is important in evaluating the status of the central nervous system. Traditional CBF imaging methods fail for both ethical and logistical reasons. Optical near infrared spectroscopy (NIRS) is increasingly being used for bedside monitoring of cerebral oxygenation and blood volume in both very low birth weight infants and neonates with congenital heart disease. Although trends in CBF may be inferred from changes in cerebral oxygenation and/or blood volume, NIRS does not allow a direct measure of CBF in these populations. Two relatively new modalities, arterial spin-labeled perfusion magnetic resonance imaging and optical diffuse correlation spectroscopy, provide direct, noninvasive measures of cerebral perfusion suitable for the high-risk neonates. Herein we discuss the instrumentation, applications, and limitations of these noninvasive imaging techniques for measuring and/or monitoring CBF.

Time to surgery and preoperative cerebral hemodynamics predict postoperative white matter injury in neonates with hypoplastic left heart syndrome

OBJECTIVE Hypoxic-ischemic white mater brain injury commonly occurs in neonates with hypoplastic left heart syndrome (HLHS). Approximately one half of HLHS survivors will exhibit neurobehavioral symptoms believed to be associated with this injury, although the exact timing of the injury is unknown. METHODS Neonates with HLHS were recruited for pre- and postoperative monitoring of cerebral oxygen saturation, cerebral oxygen extraction fraction, and cerebral blood flow using 2 noninvasive optical-based techniques: diffuse optical spectroscopy and diffuse correlation spectroscopy. Anatomic magnetic resonance imaging was performed before and approximately 1 week after surgery to quantify the extent and timing of the acquired white matter injury. The risk factors for developing new or worsened white matter injury were assessed using uni- and multivariate logistic regression. RESULTS A total of 37 neonates with HLHS were studied. On univariate analysis, neonates who developed a large volume of new, or worsened, postoperative white matter injury had a significantly longer time to surgery (P=.0003). In a multivariate model, a longer time between birth and surgery, delayed sternal closure, and greater preoperative cerebral blood flow were predictors of postoperative white matter injury. Additionally, a longer time to surgery and greater preoperative cerebral blood flow on the morning of surgery correlated with lower cerebral oxygen saturation (P=.03 and P=.05, respectively) and greater oxygen extraction fraction (P=.05 for both). CONCLUSIONS A longer time to surgery was associated with new postoperative white matter injury in otherwise healthy neonates with HLHS. The results suggest that earlier Norwood palliation might decrease the likelihood of acquiring postoperative white matter injury.

Sodium bicarbonate causes dose-dependent increases in cerebral blood flow in infants and children with single-ventricle physiology.

Background:Sodium bicarbonate (NaHCO3) is a common treatment for metabolic acidemia; however, little definitive information exists regarding its treatment efficacy and cerebral hemodynamic effects. This pilot observational study quantifies relative changes in cerebral blood flow (ΔrCBF) and oxy- and deoxyhemoglobin concentrations (ΔHbO2 and ΔHb) due to bolus administration of NaHCO3 in patients with mild base deficits.Methods:Infants and children with hypoplastic left heart syndrome (HLHS) were enrolled before cardiac surgery. NaHCO3 was given as needed for treatment of base deficit. Diffuse optical spectroscopies were used for 15 min postinjection to noninvasively monitor ΔHb, ΔHbO2, and ΔrCBF relative to baseline before NaHCO3 administration.Results:Twenty-two anesthetized and mechanically ventilated patients with HLHS (aged 1 d to 4 y) received a median (interquartile range) dose of 1.1 (0.8, 1.8) mEq/kg NaHCO3 administered intravenously over 10–20 s to treat a median (interquartile range) base deficit of −4 (−6, −3) mEq/l. NaHCO3 caused significant dose-dependent increases in ΔrCBF; however, population-averaged ΔHb and ΔHbO2 as compared with those of controls were not significant.Conclusions:Dose-dependent increases in cerebral blood flow (CBF) caused by bolus administration of NaHCO3 are an important consideration in vulnerable populations wherein risk of rapid CBF fluctuations does not outweigh the benefit of treating a base deficit.

Pulmonary hypertension predicts mortality in infants with omphalocele

OBJECTIVE The objective of this study was to identify predictors of mortality in infants with omphalocele. METHODS Medical records of infants with omphalocele born between January 1992 and June 2012, with follow-up toDecember 2012, were retrospectively reviewed. Survivors and non-survivors were compared. Evidence for pulmonary hypertension was sought between the second and seventh day after birth. All included infants had increased right ventricular pressures (RVP >40 mmhg) on echocardiogram on the second day of life with increased oxygen requirements, therefore, the finding of increased pressure was not considered a result of the transitional circulation. Logistic regression was used to evaluate the importance and independence of various factors. RESULTS Of 51 infants whose records were reviewed, 13 died (25%) and 38 survived (75%). The median time to death was 34 days (range: 4 -408 days). The median follow-up time for those who died was 1.5 years (range: 0.01-15 years) and for survivors was 2.6 years (range: 0.08-15 years). Logistic regression revealed that respiratory insufficiency at birth (OR: 14.8; 95% CI: 2.5-85.0) and pulmonary hypertension (OR: 6.4; 95% CI: 1.1-39.0) were independently associated with mortality. CONCLUSION Respiratory insufficiency after birth and pulmonary hypertension are independent predictors of mortality in infants with omphalocele.

Twin Reversed Arterial Perfusion Sequence A New Method of Parabiotic Twin Mass Estimation Correlated With Pump Twin Compromise

The purpose of this study was to test the hypothesis that using the formula of a prolate ellipsoid to estimate parabiotic twin mass correlates better with findings of pump twin compromise than using the sonographic method of Moore et al (Am J Obstet Gynecol 1990; 163:907–912).

The Impact of Breast Milk, Respiratory Insufficiency and GERD on Enteral Feeding in Infants with Omphalocele.

OBJECTIVES The aim of this study was to document the process of achieving full enteral feeding in infants with omphalocele and to identify factors that affect feeding success. METHODS After institutional review board approval (study no. 5100169), 123 infants with omphalocele, born between 1993 and 2011 were reviewed. Mortalities were excluded. All survivors had complete follow-up. Variables suspected to impact enteral feeding in infants with non-giant versus giant omphalocele were compared. Independent t test, Mann-Whitney, and χ test were used. Regression evaluated for variable independence. RESULTS Of 123 infants with omphalocele, 97 (79%) survived, 62/97 (64%) had non-giant, and 35/97 (36%) giant omphalocele. For survivors, the mean gestational age was 37 ± 4 weeks with median follow-up of 4.4 years (range: 1.4-7.4 years). The median time to full feeds was 4 days (range: 0-85 days) for non-giant versus 8 days (range: 1-96 days) for giant, a significant difference (P < 0.01). Breast milk significantly decreased time to full feeds independent of omphalocele size. Giant omphalocele infants had a significantly higher incidence of respiratory insufficiency at birth (P < 0.01) and sac rupture (P = 0.02), but fewer chromosomal anomalies (P = 0.04). Respiratory insufficiency at birth (P < 0.01) and gastroesophageal reflux disease (P < 0.01) independently delayed feeding in omphalocele infants. CONCLUSIONS Infants with non-giant omphalocele can achieve full enteral feeds within the first week of life, but giant omphalocele infants require significantly more time. Breast milk independently promotes feeding success whereas gastroesophageal reflux disease and respiratory insufficiency at birth independently delay feeding in infants with omphalocele.Objectives: The aim of this study was to document the process of achieving full enteral feeding in infants with omphalocele and to identify factors that affect feeding success. Methods: After institutional review board approval (study no. 5100169), 123 infants with omphalocele, born between 1993 and 2011 were reviewed. Mortalities were excluded. All survivors had complete follow-up. Variables suspected to impact enteral feeding in infants with non-giant versus giant omphalocele were compared. Independent t test, Mann-Whitney, and &khgr;2 test were used. Regression evaluated for variable independence. Results: Of 123 infants with omphalocele, 97 (79%) survived, 62/97 (64%) had non-giant, and 35/97 (36%) giant omphalocele. For survivors, the mean gestational age was 37 ± 4 weeks with median follow-up of 4.4 years (range: 1.4–7.4 years). The median time to full feeds was 4 days (range: 0–85 days) for non-giant versus 8 days (range: 1–96 days) for giant, a significant difference (P < 0.01). Breast milk significantly decreased time to full feeds independent of omphalocele size. Giant omphalocele infants had a significantly higher incidence of respiratory insufficiency at birth (P < 0.01) and sac rupture (P = 0.02), but fewer chromosomal anomalies (P = 0.04). Respiratory insufficiency at birth (P < 0.01) and gastroesophageal reflux disease (P < 0.01) independently delayed feeding in omphalocele infants. Conclusions: Infants with non-giant omphalocele can achieve full enteral feeds within the first week of life, but giant omphalocele infants require significantly more time. Breast milk independently promotes feeding success whereas gastroesophageal reflux disease and respiratory insufficiency at birth independently delay feeding in infants with omphalocele.

High Prevalence of Pulmonary Hypertension Complicates the Care of Infants with Omphalocele

Background: Omphalocele is one of the most common abdominal wall defects. Many newborn infants born with omphalocele present with significant respiratory distress at birth, requiring mechanical ventilatory support, and have clinical evidence of pulmonary hypertension. Little information exists on the prevalence of and risk factors associated with pulmonary hypertension in this cohort of infants. Objectives: To describe the prevalence of and risk factors associated with pulmonary hypertension among infants with omphalocele. Methods: This is a multicenter retrospective chart review of demographic data and clinical characteristics of infants with omphalocele admitted to the neonatal intensive care units of Loma Linda University Childrens Hospital and Childrens Mercy Hospital between 1994 and 2011. Echocardiogram images were reviewed for pulmonary hypertension, and statistical analyses were performed to identify risk factors associated with the presence of pulmonary hypertension. Results: Pulmonary hypertension was diagnosed in 32/56 (57%) infants with omphalocele. Compared to infants without pulmonary hypertension, infants with pulmonary hypertension were more likely to have a liver-containing defect (16/32 [50%] vs. 5/24 [21%], p = 0.03), require intubation at birth (18/32 [56%] vs. 6/24 [17%], p = 0.03), and die during initial hospitalization (12/32 [38%] vs. 2/24 [8%], p = 0.01). Conclusion: The majority of infants with omphalocele have evidence of pulmonary hypertension which is associated with increased mortality. Echocardiograms to screen for pulmonary hypertension should be obtained at ≥2 days of life in infants with omphalocele, especially in those with liver within the omphalocele sac and/or in those infants who require intubation at birth to screen for pulmonary hypertension.

Pre-Operative Cerebral Hemodynamics in Infants with Critical Congenital Heart Disease

We quantified pre-operative cerebral hemodynamics with non-invasive optical spectroscopies in infants with congenital heart disease. We find that cerebral hemodynamics change from birth until surgery and depend on the type of heart defect.

Optically-Measured Dose-Dependent Increase in Cerebral Blood Flow Caused by Sodium Bicarbonate Therapy

Sodium bicarbonate (NaHCO3) is used to treat metabolic acidemia, despite a link between treatment and brain injury. We observe a dose-dependent increase in cerebral blood flow after NaHCO3, possibly explaining the cause of this injury.

Cerebral Oxygen Extraction Decreases with Age in Preoperative Neonates With Congenital Heart Defects

Diffuse optical spectroscopy is used to quantify cerebral oxygen saturation, total hemoglobin concentration, & oxygen extraction fraction in neonates with congenital heart defects. Preoperative cerebral oxygen extraction increased with day of life.