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To predict mortality or length of stay (LOS)109 days (90th percentile) among infants with congenital diaphragmatic hernia (CDH).We conducted a retrospective analysis using the Children's Hospital Neonatal Database during 2010 to 2014. Infants born34 weeks gestation with CDH admitted at 22 participating regional neonatal intensive care units were included; patients who were repaired or were at home before admission were excluded. The primary outcome was death before discharge or LOS109 days. Factors associated with this outcome were used to develop a multivariable equation using 80% of the cohort. Validation was performed in the remaining 20% of infants.The median gestation and age at referral in this cohort (n=677) were 38 weeks and 6 h, respectively. The primary outcome occurred in 242 (35.7%) infants, and was distributed between mortality (n=180, 27%) and LOS109 days (n=66, 10%). Regression analyses showed that small for gestational age (odds ratio (OR) 2.5, P=0.008), presence of major birth anomalies (OR 5.9, P0.0001), 5- min Apgar score ⩽3 (OR 7.0, P=0.0002), gradient of acidosis at the time of referral (P0.001), the receipt of extracorporeal support (OR 8.4, P0.0001) and bloodstream infections (OR 2.2, P=0.004) were independently associated with death or LOS109 days. This model performed well in the validation cohort (area under curve (AUC)=0.856, goodness-of-fit (GF) χ(2), P=0.16) and acted similarly even after omitting extracorporeal support (AUC=0.82, GF χ(2), P=0.05).Six variables predicted death or LOS ⩾109 days in this large, contemporary cohort with CDH. These results can assist in risk adjustment for comparative benchmarking and for counseling affected families.

To assess the impact of intercenter variation and patient factors on end-of-life care practices for infants who die in regional neonatal intensive care units (NICUs).We conducted a retrospective cohort analysis using the Children's Hospital Neonatal Database during 2010-2016. A total of 6299 nonsurviving infants cared for in 32 participating regional NICUs were included to examine intercenter variation and the effects of gestational age, race, and cause of death on 3 end-of-life care practices: do not attempt resuscitation orders (DNR), cardiopulmonary resuscitation within 6 hours of death (CPR), and withdrawal of life-sustaining therapies (WLST). Factors associated with these practices were used to develop a multivariable equation.Dying infants in the cohort underwent DNR (55%), CPR (21%), and WLST (73%). Gestational age, cause of death, and race were significantly and differently associated with each practice: younger gestational age (28 weeks) was associated with CPR (OR 1.7, 95% CI 1.5-2.1) but not with DNR or WLST, and central nervous system injury was associated with DNR (1.6, 1.3-1.9) and WLST (4.8, 3.7-6.2). Black race was associated with decreased odds of WLST (0.7, 0.6-0.8). Between centers, practices varied widely at different gestational ages, race, and causes of death.From the available data on end-of-life care practices for regional NICU patients, variability appears to be either individualized or without consistency.

Background/purpose Infants with severe chronic lung disease (sCLD) may require surgical procedures to manage their medical problems; however, the scope of these interventions is undefined. The purpose of this study was to characterize the frequency, type, and timing of operative interventions performed in hospitalized infants with sCLD. Methods The Children's Hospital Neonatal Database was used to identify infants with sCLD from 24 children's hospital's NICUs hospitalized over a recent 16-month period. Results 556 infants were diagnosed with sCLD; less than 3% of infants had operations prior to referral and 30% were referred for surgical evaluation. In contrast, 71% of all sCLD infants received ≥1 surgical procedure during the CHND NICU hospitalization, with a mean of 3 operations performed per infant. Gastrostomy insertion (24%), fundoplication (11%), herniorrhaphy (13%), and tracheostomy placement (12%) were the most commonly performed operations. The timing of gastrostomy (PMA 48±10 wk) and tracheostomy (PMA 47±7 wk) insertions varied, and for infants who received both devices, only 33% were inserted concurrently (13/40 infants). Conclusions A striking majority of infants with sCLD received multiple surgical procedures during hospitalizations at participating NICUs. Further work regarding the timing, coordination, perioperative complications, and clinical outcomes for these infants is warranted.

To estimate the risk of death or tracheostomy placement (D/T) in infants with severe bronchopulmonary dysplasia (sBPD) born32 weeks' gestation referred to regional neonatal intensive care units.We conducted a retrospective cohort study in infants born32 weeks' gestation with sBPD in 2010-2011, using the Children's Hospital Neonatal Database. sBPD was defined as the need for FiO2 ⩾ 0.3, nasal cannula support2 l min(-1) or positive pressure at 36 weeks' post menstrual age. The primary outcome was D/T before discharge. Predictors associated with D/T in bivariable analyses (P0.2) were used to develop a multivariable logistic regression equation using 80% of the cohort. This equation was validated in the remaining 20% of infants.Of 793 eligible patients, the mean gestational age was 26 weeks' and the median age at referral was 6.4 weeks. D/T occurred in 20% of infants. Multivariable analysis showed that later gestational age at birth, later age at referral along with pulmonary management as the primary reason for referral, mechanical ventilation at the time of referral, clinically diagnosed pulmonary hypertension, systemic corticosteroids after referral and occurrence of a bloodstream infection after referral were each associated with D/T. The model performed well with validation (area under curve 0.86, goodness-of-fit χ(2), P = 0.66).Seven clinical variables predicted D/T in this large, contemporary cohort with sBPD. These results can be used to inform clinicians who counsel families of affected infants and to assist in the design of future prospective trials.

The Children's Hospitals Neonatal Consortium is a multicenter collaboration of leaders from 27 regional neonatal intensive care units (NICUs) who partnered with the Children's Hospital Association to develop the Children's 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.

Adoption of electronic health records continues to proceed rapidly. Neonatology offers unique barriers that must be addressed within the continued development of the electronic health record. Reducing these barriers can lead to improvements in the quality and safety of health-care delivery for the neonatal patient.

To characterize the population and short-term outcomes in preterm infants with surgical necrotizing enterocolitis (NEC).Preterm infants with surgical NEC were identified from 27 hospitals over 3 years using the Children's Hospitals Neonatal Database; infants with gastroschisis, volvulus, major congenital heart disease or surgical NEC that resolved prior to referral were excluded. Patient characteristics and pre-discharge morbidities were stratified by gestational age (28 vs 28(0/7) to 36(6/7) weeks' gestation).Of the 753 eligible infants, 60% were born at28 weeks' gestation. The median age at referral was 14 days; only 2 infants were inborn. Male gender (61%) was overrepresented, whereas antenatal steroid exposure was low (46%). Although only 11% had NEC totalis, hospital mortality (28 weeks' gestation: 41%; 28(0/7) to 36(6/7) weeks' gestation: 32%, P=0.02), short bowel syndrome (SBS)/intestinal failure (IF) (20% vs 26%, P=0.06) and the composite of mortality or SBS/IF (50% vs 49%, P=0.7) were prevalent. Also, white matter injury (11.7% vs 6.6%, P=0.02) and grade 3 to 4 intraventricular hemorrhages (23% vs 2.7%, P0.01) were commonly diagnosed. After referral, the median length of hospitalization was longer for survivors (106 days; interquartile range (IQR) 79, 152) relative to non-survivors (2 days; IQR 1,17; P0.001). These survivors were prescribed parenteral nutrition infrequently after hospital discharge (28 weeks': 5.2%; 28(0/7) to 36(6/7) weeks': 9.9%, P=0.048).After referral for surgical NEC, the short-term outcomes are grave, particularly for infants born28 weeks' gestation. Although analyses to predict outcomes are urgently needed, these data suggest that affected infants are at a high risk for lengthy hospitalizations and adverse medical and neuro-developmental abnormalities.

The optimal surgical approach in infants with gastroschisis (GS) is unknown. The purpose of this study was to estimate the association between staged closure and length of stay (LOS) in infants with GS.We used the Children's Hospital Neonatal Database to identify surviving infants with GS born ≥34 weeks' gestation referred to participating NICUs. Infants with complex GS, bowel atresia, or referred after 2 days of age were excluded. The primary outcome was LOS; multivariable linear regression was used to quantify the relationship between staged closure and LOS.Among 442 eligible infants, staged closure occurred in 68.1% and was associated with an increased median LOS relative to odds ration (OR):primary closure (37 vs. 28 days, p0.001). This association persisted in the multivariable equation (β=1.35, 95% CI: 1.21, 1.52, p0.001) after adjusting for the presence of necrotizing enterocolitis, short bowel syndrome, and central-line associated bloodstream infections.In this large, multicenter cohort of infants with GS, staged closure was independently associated with increased LOS. These data can be used to enhance antenatal and pre-operative counseling and also suggest that some infants who receive staged closure may benefit from primary repair.

To characterize postnatal growth failure (PGF), defined as weight10th percentile for postmenstrual age (PMA) in preterm (≤ 27 weeks' gestation) infants with severe bronchopulmonary dysplasia (sBPD) at specified time points during hospitalization, and to compare these in subgroups of infants who died/underwent tracheostomy and others.Retrospective review of data from the multicenter Children's Hospital Neonatal Database (CHND).Our cohort (n = 375) had a mean ± standard deviation gestation of 25 ± 1.2 weeks and birth weight of 744 ± 196 g. At birth, 20% of infants were small for gestational age (SGA); age at referral to the CHND neonatal intensive care unit (NICU) was 46 ± 50 days. PGF rates at admission and at 36, 40, 44, and 48 weeks' PMA were 33, 53, 67, 66, and 79% of infants, respectively. Tube feedings were administered to70% and parenteral nutrition to a third of infants between 36 and 44 weeks' PMA. At discharge, 34% of infants required tube feedings and 50% had PGF. A significantly greater (38 versus 17%) proportion of infants who died/underwent tracheostomy (n = 69) were SGA, compared with those who did not (n = 306; p0.01).Infants with sBPD commonly had progressive PGF during their NICU hospitalization. Fetal growth restriction may be a marker of adverse outcomes in this population.

To characterize the treatments and short-term outcomes in infants with severe bronchopulmonary dysplasia (sBPD) referred to regional neonatal intensive care units.Infants born32 weeks' gestation with sBPD were identified using the Children's Hospital Neonatal Database. Descriptive outcomes are reported.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.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.

Objective. The association between high-frequency ventilation (HFV) and intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) has been debated. Purpose. To determine if premature neonates treated with HFV are at greater risk for developing IVH and/or PVL than neonates treated with conventional ventilation, we completed a meta-analysis of all prospective randomized control trials comparing HFV and conventional ventilation in the management of respiratory distress syndrome. Methods. The meta-analysis included nine studies comparing HFV and conventional ventilation in the management of preterm neonates. To summarize the data, we calculated the difference in absolute risk for IVH and PVL between neonates treated with HFV and those treated with standard ventilation. These differences were combined to determine an overall difference in the absolute risk and its confidence interval. We examined the effect of estimated gestational age, birth weight, surfactant, and age at study entry on the results. Because one trial (HIFI study) was much larger than the other studies, it dominated the analysis, so we evaluated the data with and without including data from the HIFI trial. Results. The occurrences of IVH and PVL ranged from 14% to 47% and 5% to 16%, respectively. This variation may be explained by the difference in the populations of neonates treated. The meta-analysis showed that use of HFV was associated with an increased risk of PVL (odds ratio = 1.7 with a confidence interval of 1.06 to 2.74), but not IVH or severe (≥grade 3) IVH. When the results of the HIFI study were excluded, there were no differences between HFV and conventional ventilation in the occurrence of IVH or PVL. Conclusions. The association between HFV and adverse neurologic outcomes is primarily influenced by the results of the HIFI trial. Meta-analysis of more recent studies does not confirm the findings of the HIFI trial and suggests that HFV is not associated with increased occurrence of NH or PVL.

Neuroblastoma, Hirschsprung's disease, and central hypoventilation (Ondine's 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 child's 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)

Congenital diaphragmatic hernia (CDH) is a defect seen in approximately 1 in 3500 live births. A complication of CDH is the herniation of abdominal contents into the chest cavity through the defect, which may prevent normal intrauterine development of the lungs. The resultant pulmonary hypoplasia and pulmonary hypertension causes respiratory distress in the newborn, usually requiring some form of intervention before the defect is surgically corrected (Embryology for Surgeons. Baltimore, MD: Williams & Wilkins; 1994:491-539). Extracorporeal membrane oxygenation, which involves cannulation of the superior vena cava (SVC), is often used to manage these infants. However, the mediastinal shift that often occurs with CDH can cause an abnormal acute angulation of the SVC, which during cannulation can result in trauma and possible perforation of the SVC. We present 2 autopsy cases where the infants accidentally died as a result of extracorporeal membrane oxygenation cannulation.

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 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.

Publisher Summary This chapter discusses the neonatal intracranial hemorrhage and hypoxia. The primary location of these hemorrhages is the subependymal and periventricular region, in the germinal matrix tissue over the head of the caudate nucleus at the level of the foramen of Monro. It is found that before 26 to 28 weeks of gestation, the germinal matrix is a highly vascularized zone of the developing brain, a site of proliferating neuron and glial precursors. Most of these risk factors presumably influence the development of periventricular-intraventricular hemorrhage (PVH-IVH) through their varied effects on cerebral blood flow, especially to the germinal matrix vessels. A number of clinical studies suggest that the fundamental or common thread for many of these risk factors associated with the development of PVH-IVH was a loss of cerebral autoregulation. PVH-IVH may not be the final determinant of the cerebral injury but rather the hemorrhage is followed by significant decreases in cerebral blood flow in the affected hemisphere.

Background Mortality in severe congenital diaphragmatic hernia (CDH), defined as requirement for extracorporeal membrane oxygenation (ECMO), remains variable. Predictors of mortality and poor long-term neurodevelopmental outcome have not been well described. Objective To describe mortality and poor neurodevelopmental outcome in CDH-ECMO infants and identify associated risk factors pre-ECMO. Methods We retrieved data for CDH-ECMO infants at CHOA (1991-2004). Predictive risk factors included pre-ECMO birth weight (BW), gestational age (GA), pH, PaO2, PaCO2, oxygenation index (OI), mean airway pressure (MAP), prothrombin time (PT), and others. Chi square, Student t-test, and logistic regression were used when appropriate (significance: p Results Of 70 infants with CDH-ECMO, 12 (17.14%) were placed on venoarterial ECMO, 58 (82.85%) on venovenous ECMO (3 converted to arterial). GA was 38.2 ± 1.9 w; BW was 3160 ± 480 g. A total of 47 (67%) infants survived. There was no difference in pre-ECMO MAP (18.3 ± 3.9 CM H2O vs. 18.8 ± 4.7 CM H2O) or OI (54.6 ± 23.4 vs. 66.3 ± 32.9) between survivors and nonsurvivors. Before ECMO, nonsurvivors had a significantly higher PaCO2 (70 ≤ 24.2 vs. 57.9 ± 19.8 torr; p = .034), lower pH (7.17 ± 0.14 vs. 7.24 ± 0.14; p = .038) and higher PT (44.6 ± 6.2 vs. 18.7 ± 4.9; p = .042). A total of 23 (49%) survivors had neurodevelopmental evaluation (Bayley Scales of Infant Development) at 12 months and 18 (38%) at 24 months of age. At 12 months, mean Mental Developmental Index (MDI) was 84.77 ± 17.59 (50 to 107) and the Psychomotor Developmental Index (PDI) was 75.16 ± 21.29 (50 to 108). At 24 months, MDI was 84.23 ± 18.34 (50 to 115) and PDI was 71.58 ± 19.61 (50 to 103). At 12 and 24 months 13% of the infants had an MDI ≤ 70 and 38% had a PDI ≤ 70. A significantly higher OI pre-ECMO was predictive of MDI/PDI > 70 (59.1 ± 11.1 vs. 42.4 ± 15.6; p = .017). Conclusion In this population, 67% of infants CDH-ECMO survive to discharge. Higher PaCO2, lower pH, and higher PT pre-ECMO were significant predictors for mortality. CDH-ECMO survivors are at risk for cognitive delay and more severe neuromotor delay at 12 and 24 months of age. Higher OI pre-ECMO was a significant predictor for worse long-term outcome. Risk/benefit of using ECMO before prolonged hypercarbia, acidemia, coagulopathy, and high OI needs to be evaluated.

In an effort to clarify the pathogenesis of one type of perinatal brain damage, this article deals specifically with the effects of intrauterine asphyxia on the central nervous system of the full-term infant.

To determine the incidence of subependymal (SEH) or intraventricular hemorrhage (IVH) and its short-term outcome, infants of less than 35 weeks' gestation who required intensive care were evaluated and computerized tomographic scans obtained. If the scans showed blood, serial scans were followed until the hemorrhage had resolved and ventricle size was stable. Hemorrhage was quantitated; Seventy-seven of 191 (40.3%) infants were shown to have SEH, IVH, or both; 22 of them (28%) died, and hemorrhage was thought to be the primary cause of death in 17. Fifty-five survivors (71%) with SEH, IVH, or a combination of the two had serial follow-up scans. Six had SEH alone; 49 had IVH. Severe progressive hydrocephalus developed in 12 (22%) infants. Thirty-seven (75.5%) die not show progressive hydrocephalus. The degree of hemorrhage in these 37 was mild in 14, moderate in 13, and marked in 10. Of those with progressive hydrocephalus, hemorrhage was marked in 8 and moderate in 4. Hydrocephalus resolved spontaneously in 4 of the 12. Medical treatment (repeated lumbar punctures) was successful in 3, but failed in 4. Hydrocephalus was managed by shunt surgery in 5. This study revealed that the quantity of blood is prognostically important with regard to both survival (p less than 0.001) and development of progressive hydrocephalus (p less than 0.05). Furthermore, hydrocephalus, even if progressive, may not necessitate surgical management

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.

A prospective study was undertaken using a range-gated, pulsed Doppler velocimeter to study flowpressure relationships in the anterior cerebral artery. Serial velocity and pressure studies were performed with each infant serving as his or her own control. The hypothesis tested was that ill preterm infants sustaining subependymal/intraventricular hemorrhage would have absent autoregulation. The hypothesis has been tested in 88 studies on 32 infants. Of 32 infants studied, 15 were judged to be pressure passive; nine of these children bled. The other 17 infants were not pressure passive; eight of these children bled (P > .05). From these studies, it may be concluded that the pressure passive state is not the final common link in the genesis of subependymal/intravertricular hemorrhage. Pulsed Doppler ultrasound may provide an extremely useful noninvasive technique for studing both the arterial and venous sides of the cerebral circulation.

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.

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 less than 4. The other group of neonates (nine subjects) had relatively higher breathing rates, RSA power less than 20% of total power, and low frequency to RSA power ratio greater than 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.

To the Editor.— Doppler ultrasound assessment of flow velocity in cerebral vessels in neonates has generated intense interest since the technique was originally applied to the preterm infant by Bada et al.1 The value and indication both as a research tool and useful clinical tool have yet to be defined. We have been using a range-gated, pulsed Doppler instrument with a specially designed transducer for the past 18 months and would like to add some comments to those of Bejar et al2 and Volpe et al3 concerning Doppler ultrasound, pulsatility index, patent ductus arteriosus effects on cerebral flow, and autoregulation.

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.

We appreciate the comments of Drs McDonald and Hathaway. None of the infants studied demonstrated any clinical evidence of coagulopathy. Assessment of coagulation is not performed in infants in our nurseries unless there are signs of a bleeding diathesis.

Since 1977, an ongoing study has assessed neurodevelopmental outcome of CT-documented SEH/IVH in infants 90. Intermediate-no or minor neurologic deficit and D.I. = 70-90: Poor-significant neurologic deficit or D.I.

Eighteen preterm infants with severe progressive post-hemorrhagic hydrocephalus (PPH) following IVH were managed with serial lumbar punctures (LP) according to the following protocol. Daily serial LP with measurement of opening and closing pressure (OP,CP) were performed for no more than four weeks. Sufficient CSF was removed with each LP to lower OP by half. If OP became normal (≤ 80 mm H2O) and remained so for two successive days, LP was deferred for 48 hours and then repeated. If OP remained ≤ 80 mm H2O LP management was discontinued and the patient observed. If hydrocephalus progressed after discontinuation of LP or symptoms of increased intracranial pressure developed during LP management, shunt was effected. Of the 18 infants thus far studied, 11 responded to LP management. OP in 10 of the 11 was ≤ 80 mm H2O by three weeks; none of the non-responders demonstrated OP ≤ 80 mm H2O prior to three weeks of therapy (p=0.0002). Initial CSF protein and sugar and response of CSF protein and sugar to LP were not predictive of response. In conclusion, attainment of OP of ≤ 80 mm H2O for 3 successive days within a 21 day period of serial LP management is highly predictive of PPH response to LP management.

Subependymal (SEH) and intraventricular hemorrhage (IVH) in infants less than 35 weeks gestation, requiring intensive care for 24 hours or longer, were studied prospectively. Initial computerized tomographicscan (CT scan) was obtained, and, if positive for blood, head circumference, clinical course, and serial scans were followed until ventricular size was normal. 29/58 infants were shown to have SEH and/or IVH, 26 by CT scan, I by ventricular tap, 2 on autopsy. 8 infants died. 6 of these had marked IVH, 3 shown by CT scan, I by ventricular tap, 2 by autopsy. Acute hydrocephalus of only mild to moderate degree occurred in the 3 fatalities with positive scans. The 23 survivors with positive scans had follow-up scans. 18/23 did not show progressive hydrocephalus, and of these 4 had only SEH. Of the others, 10 had mild, 3 moderate, and I marked IVH. 5 survivors with IVH developed severe progressive hydrocephalus. 2/5 had only mild IVH, which resolved spontaneously. 3/5 required treatment. IVH was moderate in 1, marked in 2. Serial head circumference was not predictive of need for treatment. The incidence of SEH and IVH was 50% in study infants and was not related to gestational age. The quantity of blood may be prognostically significant. No infant with SEH or mild IVH required treatment. Progressive hydrocephalus developed in 2 and resolved spontaneously. 7/10 infants with moderate to marked IVH survived. 3 required treatment.

151 consecutive newborn infants 50, peak inflation pressure >25 cm H2O and 1:E ratio > 1:1. The only factor significantly related to SEH/IVH in SGA infants was the occurrence of alveolar rupture. 14/20 AGA infants and 16/20 SGA infants with alveolar rupture had SEH/IVH. SGA infants appear to be at higher risk of SEH/IVH than AGA infants. The occurrence of SEH/IVH in the preterm SGA infant may be on a different basis than in the AGA infant and related to prenatal nutritional status rather than postnatal iatrogenic events. Prenatal or intrapartum events superimposed upon decreased supportive tissue in the germinal matrix of the SGA infant may play an important role in the evolution of SEH/IVH in the preterm SGA infant.