Francine D. Dykes

Breath Amplitude Modulation of Heart Rate Variability in Normal Full Term Neonates

ABSTRACT. The relationship between heart rate variability and respiration patterns was investigated using spectral analysis techniques in nine full-term infants whose ages ranged from 39-75 h. All the infants were studied during sleep, although no attempt was made to classify rapid eye movement or nonrapid eye movement states prospectively. The data obtained were examined to determine which aspects of neonatal breathing patterns are correlated with heart rate variability. Three spectral regions of heart rate variability could be identified: a very low frequency region below 0.02 Hz; a low frequency region from 0.02-0.20 Hz; and a high frequency region above 0.20 Hz. The dominant heart rate variability activity in these neonates was seen in the very low and low frequency regions, with little activity in the high frequency regions. In contrast to older infants and adults, respiration and heart rate variability were not strongly related through a high frequency region respiratory sinus arrhythmia but rather through a breath amplitude sinus arrhythmia which occurs in the low frequency region of the spectrum. The prominent very low frequency activity and the low frequency activity ascribed to breath amplitude modulation may result from autonomic nervous system mediation of chemoregulation.

Posthemorrhagic hydrocephalus in high-risk preterm infants: Natural history, management, and long-term outcome*

The natural history, medical management, and outcome in infants with progressive posthemorrhagic hydrocephalus after intraventricular hemorrhage were studied prospectively. Infants with asymptomatic severe posthemorrhagic hydrocephalus were managed with a predetermined protocol. Outcome between groups at 1 to 2 years and at more than 3 years was compared. The natural history study, restricted to the inborn population, revealed that posthemorrhagic hydrocephalus developed in 53 of 409 infants with intraventricular hemorrhage. The progression of hydrocephalus either was arrested or regressed in 35 of 53 infants; progression to severe hydrocephalus occurred in 18 of 53 infants. The severe posthemorrhagic hydrocephalus was asymptomatic in 16 of 18 infants. The management and outcome study included both inborn and outborn infants. Of 50 infants, 12 had symptomatic severe hydrocephalus and 38 had asymptomatic severe hydrocephalus. The 16 infants managed with close observation were as likely to remain shunt free as the 22 infants managed with serial lumbar punctures. Of 38 infants, 20 were managed without shunts. At 3 to 6 years, the outcome of infants in the close observation group did not differ from that in the lumbar puncture group. Long-term outcome of infants with progression to asymptomatic severe hydrocephalus did not differ from that of infants in whom disease progression was arrested. Poor outcome in infants with intraventricular hemorrhage and subsequent posthemorrhagic hydrocephalus was related to severity of hemorrhage and gestational age at birth less than 30 weeks. Because long-term outcome of infants with severe hydrocephalus did not differ from that of infants in whom the progression of hydrocephalus was arrested or whose condition improved before hydrocephalus became severe, we currently attempt medical management of these infants.

Heart rate variability analysis in full-term-infants : Spectral indices for study of neonatal cardiorespiratory control

ABSTRACT: The heart rate and respirations of twenty healthy full-term infants between 30 and 60 h postnatal age were studied during quiet sleep with the objective of defining spectral indices which represent normal neonatal heart rate variability (HRV) characteristics. Total HRV power and the distribution of power across different frequency bands varied considerably among infants. Cluster analysis on the measured variables indicated that the population divided into two groups that represented significantly different patterns of HRV behavior. In one group (11 subjects), infants had lower breathing rates and HRV power in a band about the respiration frequency [respiratory sinus arrhythmia (RSA) band] was more than 20% of the total power (TP). Additionally, the ratio of low frequency band power to RSA band power was <4. The other group of neonates (nine subjects) had relatively higher breathing rates, RSA power <20% of total power, and low frequency to RSA power ratio >4. Regression analysis of low frequency versus TP and RSA versus TP graphs gave strong support to the hypothesis that there were indeed two distinct patterns of HRV behavior. Separation of apparently normal neonates into two groups may be attributed partially to differences in respiratory rates and breathing patterns. However, it is possible that differences in the balance between sympathetic and parasympathetic nervous system control, perhaps related to autonomic maturation, also contribute to group separation. The indices developed from HRV spectral analysis in this investigation may be of value in the study of cardiorespiratory control in neonates.

Validation of the cas neonatal NIRS system by monitoring VV-ecmo patients : Preliminary results

The CAS neonatal NIRS system determines absolute regional brain tissue oxygen saturation (SnO2) and brain true venous oxygen saturation (SnvO2) non-invasively. Since NIRS-interrogated tissue contains both arterial and venous blood from arterioles, venules, and capillaries, SnO2 is a mixed oxygen saturation parameter, having values between arterial oxygen saturation (SaO2) and cerebral venous oxygen saturation (SvO2). To determine a reference for SnO2, the relative contribution of SvO2 to SaO2 drawn from a brain venous site vs. systemic SaO2 is approximately 70:30 (SvO2:SaO2). If the relationship of the relative average contribution of SvO2 and SaO2 is known and does not change to a large degree, then NIRS true venous oxygen saturation, SnvO2, can be determined non-invasively using SnO2 along with SaO2 from a pulse oximeter.

The complete spectrum of neurocristopathy in an infant with congenital hypoventilation, Hirschsprung's disease, and neuroblastoma

Neuroblastoma, Hirschsprungs disease, and central hypoventilation (Ondines curse) are considered aberrations of neural crest cell growth, migration, or differentiation, and as such are considered to be under the general heading of neurocristopathy. Their combined occurrence in a newborn infant presenting with total colonic aganglionosis, central hypoventilation, and multifocal neuroblastoma had not been reported previously. A 2.3-kg white full-term girl required endotracheal intubation because of persistent apnea in the first hours of life. She had progressive abdominal distension and failure to pass meconium; a barium enema was performed, which showed microcolon with meconium pellets at the distal ileum. During laparotomy the distal ileum was found to be obstructed with inspissated meconium; an ileostomy and appendectomy were performed. The resected specimens were aganglionic. An additional 20 cm of aganglionic ileum was removed, and a normally innervated ileostomy was constructed. Numerous attempts at extubation failed because of apnea. The results of an extensive apnea workup, including electroencephalogram, magnetic resonance imaging (MRI), bronchoscopy, and pH probe study, were normal. Sleep studies showed congenital central hypoventilation syndrome, and the patient underwent a tracheostomy. At 3 months, an abdominal ultrasound examination performed within a septic workup showed a right suprarenal mass extending across the midline. Thoracic and abdominal MRI scans showed large bilateral adrenal and posterior mediastinal masses. The serum catecholamines and ferritin level were markedly elevated, suggestive of neuroblastoma. In light of the childs multiple problems, the family chose to forgo further workup (including a tissue biopsy) and therapy. In the following 2 months her tumor load rapidly progressed, and she died of respiratory insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

The Children’s Hospitals Neonatal Database: an overview of patient complexity, outcomes and variation in care

The Childrens Hospitals Neonatal Consortium is a multicenter collaboration of leaders from 27 regional neonatal intensive care units (NICUs) who partnered with the Childrens Hospital Association to develop the Childrens Hospitals Neonatal Database (CHND), launched in 2010. The purpose of this report is to provide a first summary of the population of infants cared for in these NICUs, including representative diagnoses and short-term outcomes, as well as to characterize the participating NICUs and institutions. During the first 2 1/2 years of data collection, 40910 infants were eligible. Few were born inside these hospitals (2.8%) and the median gestational age at birth was 36 weeks. Surgical intervention (32%) was common; however, mortality (5.6%) was infrequent. Initial queries into diagnosis-specific inter-center variation in care practices and short-term outcomes, including length of stay, showed striking differences. The CHND provides a contemporary, national benchmark of short-term outcomes for infants with uncommon neonatal illnesses. These data will be valuable in counseling families and for conducting observational studies, clinical trials and collaborative quality improvement initiatives.

Range-gated pulsed Doppler ultrasonographic evaluation of carotid arterial blood flow in small preterm infants with patent ductus arteriosus

Range-gated pulsed Doppler (RGPD) ultrasonography was utilized to study the effect of a patent ductus arteriosus (PDA) on carotid arterial blood flow in small preterm infants. Carotid arterial flow velocity studies were performed on 23 preterm infants, sampling right and left carotid arteries. Studies on seven infants after PDA ligation and on seven who developed no evidence of PDA were used as controls. A strong relationship was demonstrated between diastolic reversal in the carotid arteries and PDA. The results of this study indicate that the RGPD flow velocity curve from the carotid artery is more sensitive than M-mode echocardiography or clinical examination in detecting PDA, and that PDA in small preterm infants is associated with a distinct abnormality in the carotid arterial flow pattern.

Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report from the Children’s Hospitals Neonatal Consortium HIE focus group

Objective:To characterize infants affected with perinatal hypoxic ischemic encephalopathy (HIE) who were referred to regional neonatal intensive care units (NICUs) and their related short-term outcomes.Study Design:This is a descriptive study evaluating the data collected prospectively in the Children’s Hospital Neonatal Database, comprised of 27 regional NICUs within their associated children’s hospitals. A consecutive sample of 945 referred infants born ⩾36 weeks’ gestation with perinatal HIE in the first 3 days of life over approximately 3 years (2010–July 2013) were included. Maternal and infant characteristics are described. Short-term outcomes were evaluated including medical comorbidities, mortality and status of survivors at discharge.Result:High relative frequencies of maternal predisposing conditions, cesarean and operative vaginal deliveries were observed. Low Apgar scores, profound metabolic acidosis, extensive resuscitation in the delivery room, clinical and electroencephalographic (EEG) seizures, abnormal EEG background and brain imaging directly correlated with the severity of HIE. Therapeutic hypothermia was provided to 85% of infants, 15% of whom were classified as having mild HIE. Electrographic seizures were observed in 26% of the infants. Rates of complications and morbidities were similar to those reported in prior clinical trials and overall mortality was 15%.Conclusion:Within this large contemporary cohort of newborns with perinatal HIE, the application of therapeutic hypothermia and associated neurodiagnostic studies appear to have expanded relative to reported clinical trials. Although seizure incidence and mortality were lower compared with those reported in the trials, it is unclear whether this represented improved outcomes or therapeutic drift with the treatment of milder disease.

Therapeutic interventions and short-term outcomes for infants with severe bronchopulmonary dysplasia born at <32 weeks' gestation.

Objective:To characterize the treatments and short-term outcomes in infants with severe bronchopulmonary dysplasia (sBPD) referred to regional neonatal intensive care units.Study Design:Infants born <32 weeks’ gestation with sBPD were identified using the Children’s Hospital Neonatal Database. Descriptive outcomes are reported.Result:A total of 867 patients were eligible. On average, infants were born at 26 weeks’ gestation and referred 43 days after birth. Infants frequently experienced lung injury (pneumonia: 24.1%; air leak: 9%) and received systemic corticosteroids (61%) and mechanical ventilation (median duration 37 days). Although 91% survived to discharge, the mean post-menstrual age was 47 weeks. Ongoing care such as supplemental oxygen (66%) and tracheostomy (5%) were frequently needed.Conclusion:Referred infants with sBPD sustain multiple insults to lung function and development. Because affected infants have no proven, safe or efficacious therapy and endure an exceptional burden of care even after referral, urgent work is required to observe and improve their outcomes.

1607 PROSPECTIVE LONG-TERM FOLLOW-UP OF PREMATURES WITH SUBEPENDYMAL/INTRAVENTRICULAR HEMORRHAGE (SEH/IVH)

Since 1977, an ongoing study has assessed neurodevelopmental outcome of CT-documented SEH/IVH in infants <35 weeks gestation requiring intensive care. Scans were graded: normal, SEH, mild, moderate, or marked IVH. Follow-up status, at mean corrected age of 34 months, was assessed by neurologic exams, Bayley and Stanford-Binet tests. Outcome was designated: Good-no neurologic deficit and Developmental Index (D.I.) > 90. Intermediate-no or minor neurologic deficit and D.I. = 70-90: Poor-significant neurologic deficit or D.I.<70. The following groups were compared: a) 33/41 surviving SEH/IVH infants with 30/49 non-IVH; b)22 SEH/IVH infants paired with controls, matched for Apgar, gestation and birth weight c) intragroup, according to degree of hemorrhage. Of the 33 SEH/IVH infants, 21 had good outcomes, 8 intermediate, 4 poor. Of controls, outcome was good in 19, intermediate in 8, poor in 3. Among match-control pairs, there was a balanced distribution in outcome. Intragroup comparison showed: 13 had marked IVH with 8 good outcomes, 3 intermediate, 2 poor; 10 had moderate IVH with 5 good, 3 intermediate, 2 poor, 10 had mild IVH or SEH with 8 good, 2 intermediate, 0 poor. By all methods of comparison, outcome in SEH/IVH infants was not significantly different from controls. Marked IVH did not preclude good outcome (60% good). Other neonatal disease may affect outcome more than hemorrhage.