Bio

Bio


Dr. Ariagno is Professor Emeritus of Pediatrics at Stanford University School of Medicine in the Division of Neonatal and Developmental Medicine M. He has been on the faculty at Stanford University since 1975. He received his medical degree from University of Illinois College of Medicine in Chicago and pediatric training at Rush Presbyterian St. Luke?s Hospital in Chicago. His neonatology fellowship was at the University of California San Francisco and Children?s Hospital of San Francisco under Dr. June Brady.
He has been on the Executive Committee of the Section on Perinatal Pediatrics (SoPPe) since 1996. He was appointed Chair of the Research Committee and oversees the Marshall Klaus Perinatal Research Award for Fellows in Neonatal?Perinatal Medicine. He was the organizing Chair and first president of the California Association of Neonatologists (CAN) in 1995 and the first American Academy of Pediatrics (AAP) SoPPe District IX Chair of the combined CAN/AAP organization. At Stanford University he chairs one of the Human Subjects in Medical Research Review Committees (2004-). He is a Certified Simulation Instructor in ?Center for Advanced Pediatric Education? (CAPE) directed by L. Halamek, for simulation and neonatal resuscitation and Co-Director of the CAPE Neonatal Resuscitation SimulationTraining Program. In 2013 he accepted a position as the Senior Oak Ridge Institute for Science and Education (ORISE) Faculty Fellow in Neonatology in the Office of Pediatric Therapeutics and in the Maternal and Pediatric Section, Center forDrug Evaluation and Research at the FDA to represent neonatology and to help strategize how to facilitate the basic neonatal science research needed and to promote the development of drug and new devices for infants.

Administrative Appointments


  • Institution Review Board Chair of Panel 4 for the Protection of Human Subjects, Stanford University School of Medicine (2004 - Present)

Honors & Awards


  • Honored for enduring contributions to clinical excellence and compassionate care, Stanford Hospital and Clinics (2011)
  • Neonatal Education Award, The American Academy of Pediatrics, Section on Perinatal Pediatrics (2009)

Professional Education


  • BS, Lewis University, Biology Chemistry (1964)
  • MD, U. of Illinois College of Med., Medicine (1968)

Community and International Work


  • Visiting Professor King Edward Memorial Hospital, Pune primarily

    Topic

    Study the relationship between Academic Centers and Community Care of mothers and infants

    Populations Served

    India

    Location

    International

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Visiting Professor U. of Nairobi, Kenya, Nairobi and Naivasha

    Topic

    Study the relationship between Academic Center and community health care for mothers and infants

    Populations Served

    East Africa

    Location

    International

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

Research & Scholarship

Current Research and Scholarly Interests


Dr. Ariagno is Professor Emeritus of Pediatrics at Stanford University School of Medicine in the Division of Neonatal and Developmental Medicine.
He has been on the Executive Committee of the Section on Perinatal Pediatrics (SoPPe) since 1996. He was appointed Chair of the Research Committee and oversees the Marshall Klaus Perinatal Research Award for Fellows in Neonatal?Perinatal Medicine. He was the organizing Chair and first president of the California Association of Neonatologists (CAN) in 1995 and the first American Academy of Pediatrics (AAP) SoPPe District IX Chair of the combined CAN/AAP organization. At Stanford University he chairs one of the Human Subjects in Medical Research Review Committees (2004-). He is a Certified Simulation Instructor in ?Center for Advanced Pediatric Education? (CAPE) directed by L. Halamek, for simulation and neonatal resuscitation and Co-Director of the CAPE Neonatal Resuscitation SimulationTraining Program. In 2013 he accepted a position as the Senior Oak Ridge Institute for Science and Education (ORISE) Faculty Fellow in Neonatology in the Office of Pediatric Therapeutics and in the Maternal and Pediatric Section, Center forDrug Evaluation and Research at the FDA to represent neonatology and to help strategize how to facilitate the basic neonatal science research needed and to promote the development of drug and new devices for infants.

Teaching

2013-14 Courses


Publications

Journal Articles


  • Philip Sunshine Festschrift: a quintessential neonatologist with wit and humor. Journal of perinatology Ariagno, R. L. 2011; 31: S9-S10

    View details for DOI 10.1038/jp.2010.181

    View details for PubMedID 21448215

  • Resting heart rate does not predict growth in preterm infants EARLY HUMAN DEVELOPMENT Ruth, V., Kennedy, C., Rehm, R., Ariagno, R., Lee, K. A. 2010; 86 (1): 23-27

    Abstract

    Previous reports indicate that preterm infants with higher baseline heart rate (HR) have greater weight gain than preterm infants with lower baseline HR. To verify this correlation and the potential utility of resting HR as a bench mark for risk of extrauterine growth restriction (EUGR), we studied preterm infants born between 32 and 36weeks gestation. Earlier gestation infants (27 to 31weeks) were included.In retrospective chart review we collected heart rate (HR) and growth data on 156 infants between 27.0 and 34.0weeks gestation from birth to hospital discharge.There was a significant increase in weight gain from day 10 of life in infants with higher resting HR compared to infants with lower resting HR. However, upon controlling for birth weight and gestational age, there was no significant relationship between HR and weight gain for any gestational age group of premature infants.Contrary to previous reports, there was no significant relationship between HR and growth at any gestational age after controlling for birth weight and gestational age. It is important to continue to search for a clinical marker of risk for poor growth in preterm infants and to give an opportunity for nutritional interventions which may support better growth and developmental outcomes.

    View details for DOI 10.1016/j.earlhumdev.2009.12.005

    View details for Web of Science ID 000275597100005

    View details for PubMedID 20089373

  • Can magnetic resonance spectroscopy predict neurodevelopmental outcome in very low birth weight preterm infants? JOURNAL OF PERINATOLOGY Augustine, E. M., Spielman, D. M., Barnes, P. D., Sutcliffe, T. L., Dermon, J. D., Mirmiran, M., Clayton, D. B., Ariagno, R. L. 2008; 28 (9): 611-618

    Abstract

    To determine if metabolite ratios at near-term age predict outcome in very low birth weight preterm infants at 18 to 24 months adjusted age.Thirty-six infants (birth weight

    View details for DOI 10.1038/jp.2008.66

    View details for Web of Science ID 000258990600005

    View details for PubMedID 18615089

  • Survey of neonatology training programs: 2002 to 2003 JOURNAL OF PERINATOLOGY Ariagno, R. L. 2006; 26: S38-S45

    Abstract

    The Committee on Research in Neonatology from the Section on Perinatal Pediatrics, American Academy of Pediatrics presents an overview of the update of the Neonatal-Perinatal Training Program Survey obtained in 2002 to 2003. Our goal was to update the last survey in 1996 and to begin to assess research resources and the potential for training life-career physician scientists (basic and clinical investigators).

    View details for DOI 10.1038/sj.jp.7211521

    View details for Web of Science ID 000241844600010

    View details for PubMedID 16801968

  • National Institute of Child Health and Human Development (NICHD) and American Academy of Pediatrics (AAP) workshop on research in neonatal and perinatal medicine JOURNAL OF PERINATOLOGY Ariagno, R. L. 2006; 26: S3-S4

    View details for DOI 10.1038/sj.jp.7211425

    View details for Web of Science ID 000241844600002

    View details for PubMedID 16801965

  • Fewer spontaneous arousals during prone sleep in preterm infants at 1 and 3 months corrected age JOURNAL OF PERINATOLOGY Ariagno, R. L., van Liempt, S., Mirmiran, M. 2006; 26 (5): 306-312

    Abstract

    This study was performed to determine if there were fewer spontaneous arousals in prone sleep than in supine sleep.Home polysomnography/video recordings were done during daytime naps in 14 preterm infants: four at corrected age of 1 month, nine at both 1 and 3 months, and one only at 3 month. A body movement lasting 3 to 60 s during sleep was used as an indicator of spontaneous arousals.Most arousals had a heart rate increase and change in respiration pattern. The mean duration of the intervals between successive arousals in active and quiet sleep was significantly longer in prone at 1 and 3 months of age. The duration of arousals was significantly shorter at 3 months corrected age compared with one month corrected age during active sleep. The duration of arousals was shorter during quiet sleep at one month compared with active sleep.There were fewer spontaneous arousals that is, longer interval between successive arousals in prone, which may, in part, explain the increase in risk of Sudden Infant Death Syndrome.

    View details for DOI 10.1038/sj.jp.7211490

    View details for Web of Science ID 000241843700010

    View details for PubMedID 16572196

  • Neonatology Research for the 21st Century: Executive summary of the National Institute of Child Health and Human Development-American Academy of Pediatrics Workshop. Part II: Training issues PEDIATRICS Ariagno, R. L., van Marter, L. J., Higgins, R., Raju, T. N. 2005; 115 (2): 475-479

    Abstract

    This is the second part of the executive summary based on the presentations and discussions at a workshop on research in neonatology sponsored by the National Institute of Child Health and Human Development and the American Academy of Pediatrics held in January 2004. In this article, neonatology fellowship training requirements and workforce issues are addressed, and the reasons for the shortage of physician-scientists, particularly of the underrepresented minority ethnic groups, are highlighted. Full-length articles from the presented topics are yet to be published.

    View details for DOI 10.1542/peds.2004-2559

    View details for Web of Science ID 000226725000048

    View details for PubMedID 15687458

  • Research in Neonatology for the 21st Century: Executive summary of the National Institute of Child Health and Human Development-American Academy of Pediatrics Workshop. Part I: Academic issues PEDIATRICS Raju, T. N., Ariagno, R. L., Higgins, R., van Marter, L. J. 2005; 115 (2): 468-474

    Abstract

    This article presents the executive summary of the presentations and discussions at the Workshop on Research in Neonatology sponsored by the National Institute of Child Health and Human Development and the American Academy of Pediatrics Section on Perinatal Pediatrics convened in January 2004. In this article, the scientific aspects are summarized, highlighting the current knowledge gaps and identifying research priorities with a focus on emerging technologies. In a separate article, issues concerning workforce needs and shortages and board-certification requirements are presented. Full-length articles on the presented topics will be published in the Journal of Perinatology.

    View details for DOI 10.1542/peds.2004-2556

    View details for Web of Science ID 000226725000047

    View details for PubMedID 15687457

  • Neonatal brain magnetic resonance imaging before discharge is better than serial cranial ultrasound in predicting cerebral palsy in very low birth weight preterm infants PEDIATRICS Mirmiran, M., Barnes, P. D., Keller, K., Constantinou, J. C., Fleisher, B. E., Hintz, S. R., Ariagno, R. L. 2004; 114 (4): 992-998

    Abstract

    To compare the value of serial cranial ultrasound (US) with a single magnetic resonance imaging (MRI) before discharge in very low birth weight preterm infants to predict cerebral palsy (CP).Infants who weighed <1250 g at birth and were <30 weeks' gestational age underwent conventional brain MRI at near term (36-40 weeks' postmenstrual age) using 1.5 Tesla MRI scanner. Sagittal and axial T1 and T2 fluid attenuated inversion recovery and gradient recalled echo images were obtained. Cranial US was also obtained at least twice during the first 2 weeks of life. MRI and US images were interpreted by 2 independent radiologists, who were masked to clinical outcome, and scored as follows: category 1, no abnormality; category 2, subependymal hemorrhage or mineralization; category 3, moderate to severe ventriculomegaly; category 4, focal parenchymal abnormality with or without ventriculomegaly. For the purpose of this study, 1 and 2 were categorized as "normal," and 3 and 4 were categorized as "abnormal." The infants were assessed at a mean age of 20 and 31 months using the Amiel-Tison standardized neurodevelopmental examination.The sensitivity and specificity of MRI for predicting CP were 71% and 91% at 20 month and 86% and 89% at 31 months, respectively. The sensitivity and specificity of US for predicting CP were 29% and 86% at 20 months and 43% and 82% at 31 months.As a predictor of outcome for CP, MRI at near-term in very low birth weight preterm neonates is superior to US. However, both US and MRI demonstrate high specificity.

    View details for DOI 10.1542/peds.2003-0772-L

    View details for Web of Science ID 000224242200034

    View details for PubMedID 15466096

  • Diffusion tensor brain imaging findings at term-equivalent age may predict neurologic abnormalities in low birth weight preterm infants AMERICAN JOURNAL OF NEURORADIOLOGY Arzoumanian, Y., Mirmiran, M., Barnes, P. D., Woolley, K., Ariagno, R. L., Moseley, M. E., Fleisher, B. E., Atlas, S. W. 2003; 24 (8): 1646-1653

    Abstract

    Low birth weight preterm infants are at high risk of brain injury, particularly injury to the white matter. Diffusion tensor imaging is thought to be more sensitive than conventional MR imaging for detecting subtle white matter abnormalities. The objective of this study was to examine whether diffusion tensor imaging could detect abnormalities that may be associated with later neurologic abnormalities in infants with otherwise normal or minimally abnormal conventional MR imaging findings.We prospectively studied 137 low birth weight (<1800 g) preterm infants. Neonatal conventional MR imaging and diffusion tensor imaging were performed near term-equivalent age before discharge, and neurologic development of the infants was later followed up at 18 to 24 months of age.Among the preterm infants who were fully studied, 63 underwent normal conventional MR imaging. Three of these infants developed cerebral palsy, and 10 others showed abnormal neurologic outcome. Diffusion tensor imaging results for these infants showed a significant reduction of fractional anisotropy in the posterior limb of the internal capsule in neurologically abnormal infants (including those with cerebral palsy) compared with control preterm infants with normal neurologic outcomes.These results suggest that neonatal diffusion tensor imaging may allow earlier detection of specific anatomic findings of microstructural abnormalities in infants at risk for neurologic abnormalities and disability. The combination of conventional MR imaging and diffusion tensor imaging may increase the predictive value of neonatal MR imaging for later neurologic outcome abnormalities and may become the basis for future interventional clinical studies to improve outcomes.

    View details for Web of Science ID 000185400100031

    View details for PubMedID 13679287

  • Development of fetal and neonatal sleep and circadian rhythms SLEEP MEDICINE REVIEWS Mirmiran, M., Maas, Y. G., Ariagno, R. L. 2003; 7 (4): 321-334

    Abstract

    The origin of sleep and circadian rhythms development is found during the fetal period. Both quiet (NREM) and active (REM) sleep are distinguishable during the last 10 weeks of gestation. Comparable to fetuses, low risk preterm infants recorded at 30-40 weeks postconceptional age, had a similar development of sleep i.e. an increase in quiet sleep and a decrease in indeterminate sleep. A further development in sleep organization characterized by increased slow wave and spindle activity during quiet sleep and coupling with circadian rhythm takes place during the first 6 months of life in both term and preterm infants.Circadian rhythm of fetal heart rate synchronized with maternal rest-activity, heart rate, cortisol, melatonin, and body temperature rhythms is present during the last 10 weeks of gestation. Although maternally influenced, circadian rhythm antenatally becomes ultradian at birth. Both preterm and term infants show a significant increase in circadian body temperature rhythm amplitude during the first 3 months of life.

    View details for DOI 10.1053/smrv.2002.0243

    View details for Web of Science ID 000184673200006

    View details for PubMedID 14505599

  • Circadian and sleep development in preterm infants occurs independently from the influences of environmental lighting PEDIATRIC RESEARCH Mirmiran, M., Baldwin, R. B., Ariagno, R. L. 2003; 53 (6): 933-938

    Abstract

    This study investigated the effect of intermediate nursery illumination on circadian rhythm and sleep development of preterm infants. Preterm infants were randomly assigned to one of two intermediate nursery rooms: a dimly lighted room, the dim (control) group, or a day-night lighted room, the cycled (intervention) group. Continuous rectal temperature and sleep were recorded at 36 wk postconceptional age (before discharge) and at 1 and 3 mo corrected age at home. Forty infants, 21 in the dim group and 19 in the cycled group, were recorded. The clinical demographic data and neonatal scores were similar between groups before the intervention. Circadian rhythms and sleep showed significant development with age, but there was no environmental lighting effect. Circadian and sleep organization seems to develop endogenously in preterm infants.

    View details for DOI 10.1203/01.PDR.0000061541.94620.12

    View details for Web of Science ID 000183288600012

    View details for PubMedID 12621096

  • Effect of position on sleep, heart rate variability, and QT interval in preterm infants at 1 and 3 months' corrected age PEDIATRICS Ariagno, R. L., Mirmiran, M., Adams, M. M., Saporito, A. G., Dubin, A. M., Baldwin, R. B. 2003; 111 (3): 622-625

    Abstract

    Prone sleeping position has a strong link to sudden infant death syndrome (SIDS), and the "Back to Sleep" campaign has played an important role in reducing SIDS. We tested the hypothesis that the mechanism of the sleep position effect is based on changes in sleep, arousal, heart rate variability (HRV), and the QT interval of the electrocardiogram.We studied 16 premature infants longitudinally, at 1 and 3 months' corrected age. Videosomnography recordings were made during the infants' normal daytime naps. Each infant was recorded in both supine and prone positions. The recordings were analyzed in 30-second epochs, which were classified as awake, active sleep (AS), quiet sleep (QS), or indeterminate sleep. Electrocardiogram data were sampled with an accuracy of 1 millisecond. Time domain analysis of HRV was measured by standard deviation of all R-R intervals and by the square root of the mean of the sum of the squares of the differences between adjacent R-R intervals. Frequency domain analysis was done for low frequency (0.04-0.14 Hz) and high frequency (0.15-0.5 Hz) HRV. We measured QT, JT, and R-R intervals during AS and QS for each position.We found no significant differences between supine and prone position, either in total sleep time or in percentage of QS. Percentage of AS was significantly lower in the supine position, but only at 1 month corrected age. The incidence of short, spontaneous, sleep transitions was significantly higher in supine, also only at 1 month corrected age. Time domain analysis of HRV showed a significantly lower variability in prone, but only during QS. Frequency domain analysis of HRV showed no differences between the 2 sleeping positions. Both QT and JT intervals were significantly longer in prone during QS, but only at 1 month corrected age.Despite the commonly held belief, prone position did not substantially increase total sleep at these ages. On the other hand, prone sleeping decreased the number of sleep transitions at 1 month corrected age, increased QT and JT intervals, and reduced HRV, thereby potentially increasing the vulnerability for SIDS. This study supports "Back to Sleep" as the position of choice not only for term but also for preterm infants after discharge home.

    View details for Web of Science ID 000181294000044

    View details for PubMedID 12612246

  • Candida (amphotericin-sensitive) lens abscess associated with decreasing arterial blood flow in a very low birth weight preterm infant PEDIATRICS Drohan, L., Colby, C. E., Brindle, M. E., Sanislo, S., Ariagno, R. L. 2002; 110 (5)

    Abstract

    In this report, we review the case of a candidal lens abscess in a premature infant girl who was 28 weeks' gestational age at birth. The culture obtained from the lens abscess grew Candida albicans sensitive to amphotericin B but resistant to flucytosine. This case is unique in that the infant developed a fungal lens cataract at 34 weeks' postconceptional age during the last week of a 30-day course of amphotericin B. The embryonic hyaloid artery system, which perfuses the developing lens, regresses between 29 and 32 weeks of gestation; thus, the mechanism for an infection of the lens may be inoculation of the lens by Candida before hyaloid artery system regression, followed by developmental loss of this blood supply, which makes the lens inaccessible to antimicrobial penetration. Candidal endophthalmitis with lens abscess is an uncommon morbidity that requires prompt recognition and surgical intervention for effective management.

    View details for Web of Science ID 000178971800015

    View details for PubMedID 12415071

  • Cisapride associated with QTc prolongation in very low birth weight preterm infants PEDIATRICS Dubin, A., Kikkert, M., Mirmiran, M., Ariagno, R. 2001; 107 (6): 1313-1316

    Abstract

    No systematic study has been performed to evaluate the effect of cisapride on the QT interval in premature infants. Cisapride, which has recently been withdrawn by the Food and Drug Administration and is no longer an approved therapy, was commonly used for preterm infant care to improve the advance of enteral feedings and to reduce reflux and associated apnea. Our aim was to evaluate the effect of recommended doses of cisapride on the QT interval in this population.Prospective blinded evaluation of electrocardiogram for QT, JT, QTc, and JTc measurements in 25 preterm infants before and after cisapride administration.Twelve of 25 infants (48%) developed repolarization abnormalities with cisapride administration: 32% of the infants (8/25) studied had QTc prolongation (>/=0.450 seconds), whereas 10/25 had JTc prolongation (>/=0.360 seconds). Preterm infants <32 weeks significantly prolonged their QTc interval from 0.41 +/- 0.02 to 0.44 +/- 0.02. The QTc and/or JTc was prolonged in 54% of infants receiving 0.1 mg/kg/dose and 42% receiving 0.2 mg/kg/dose.The QTc and JTc interval significantly prolonged in preterm infants <32 weeks on the recommended dose of cisapride therapy. A QTc >/=0.450 seconds developed in 32% of infants treated with cisapride, whereas the JTc prolonged in 40%. A significant percentage of infants (54%) developed prolonged QTc intervals at a dose of 0.1 mg/kg/dose. From these data we conclude that there is a higher risk of prolongation of the QTc interval and risk of arrhythmias with greater prematurity.

    View details for Web of Science ID 000169105500034

    View details for PubMedID 11389249

  • Cisapride decreases gastroesophageal reflux in preterm infants PEDIATRICS Ariagno, R. L., Kikkert, M. A., Mirmiran, M., Conrad, C., Baldwin, R. B. 2001; 107 (4)

    Abstract

    Gastrointestinal prokinetic agents, such as cisapride, are commonly used in pediatric practice to improve gastric emptying, to decrease emesis, to improve lower esophageal sphincter tone, and to improve irritability and feeding aversion associated with gastroesophageal reflux (GER). Although cisapride seems to be effective in infants from 2 months to 14 years old, data for younger and preterm infants are not available. Whether reflux is a significant cause of reflex apnea or feeding intolerance in the preterm infant is controversial. The objective of this 1-year prospective study, started in 1998, was to determine the efficacy of cisapride for treatment of reflux and reflux-associated apnea (RAAP) in preterm infants. Before this study, the diagnosis of reflux was often made clinically and the effect of therapy on reflux or the decision to increase the dose of cisapride was made empirically. The clinical bias was that persistent apnea, not responding to caffeine, was caused by GER. We reasoned that a systematic approach to the diagnosis and treatment of reflux would improve the care of preterm infants and reduce the risk of toxicity, especially if an increased dose of cisapride showed no improvement in reflux or apnea.Twenty-four preterm infants (24-36 weeks' gestational age) had clinical apnea/pH studies when they were referred by the attending neonatologist for suspected GER. These infants were born at 28.8 +/- 3.1 weeks with birth weight of 1169 +/- 387 g (range: 631-2263 g). Each infant was studied before and 8 days after starting cisapride treatment. Cisapride dose was 0.09 to 0.25 mg/kg every 6 hours enterally. Treatment decisions regarding dose of cisapride were the responsibility of the attending neonatologist. The pH was recorded continuously for 24 hours at 0.25 Hz and was analyzed using EsopHogram software. A single sensor pH catheter was inserted to ~2 cm above the esophageal gastric junction. GER was defined as a drop in esophageal pH below 4.0 for a least 5 seconds, or pathologic GER was defined as a reflux index (RI) >2 standard deviation (SD) from the mean based on published norms for term infants. The following parameters were calculated from the pH recording: number of reflux events per 24 hours, duration of the longest episode, number of episodes >5 minutes per 24 hours, and RI, ie, percentage of time with pH <4.0. Each study had a combined time-lapse video recording and multichannel digital recording. Recorded parameters were: continuous pulse oximetry, electrocardiogram, respiratory effort (piezo sensor), and airflow (temperature sensor at nostrils and mouth). The recording was scored for central apneas of 10 to 14 seconds and >/=15 seconds (prolonged) and >/=10 seconds for obstructive and mixed apneas. RAAP was scored when an apnea (irrespective of the type) occurred within 1 minute of a GER event. Baseline, after cisapride, and follow-up electrocardiograms were performed because of concern about prolonged QTc and cardiac arrhythmias. The infants were 35.6 +/- 4.5 weeks postconceptional age when first studied. Twelve infants (mean birth weight: 1821 +/- 749 g; gestational age: 32 +/- 2 weeks; postconceptional age: 35.6 +/- 2.6 weeks) were identified retrospectively as controls because their baseline GER parameters were within the normal range using Vandenplas' criteria.Overall, cisapride treatment significantly improved the RI from 16.6 +/- 15.2 to 9.1 +/- 8.4 SD. The number of reflux episodes >/=5 minutes was reduced from 7.1 +/- 5.8 to 4.3 +/- 4.4 SD. No significant effect was seen on the total number of refluxes (/24 hours). Eight infants (33%) had no decrease in the RI after a week of treatment. Three of these infants improved after cisapride dose was increased from 0.09 to 0.25 mg/kg/dose every 6 hours. Although 0.09 mg/kg/day is the minimum effective dose, 67% of our infants did respond to this low dose. Cisapride was discontinued in 3 infants because of prolonged QTc >/=0.450 seconds (0.473 in 1 and 0.470 in 2). More data about the effect of cisapride on QTc interval are reported in Pediatrics in a separate article. Only 1 infant showed no improvement with increased dose. Caffeine treatment had no effect on the baseline or follow-up GER values. Although apnea indexes for central and obstructive apnea were similar before and after cisapride, mixed apnea was less during treatment. There was a significant decrease (0.32 +/- 0.40 to 0.12 +/- 0.17/hour) in RAAP when the one infant who had increased reflux on increased dose of cisapride was excluded as an outlier. The statistical difference, before and after cisapride, for the group is significant with the outlier omitted. The clinical significance is unclear because ~50% of the infants had minimal changes in their apnea indexes. Furthermore, ~40% of infants did not have RAAP. (ABSTRACT TRUNCATED)

    View details for Web of Science ID 000168116200015

    View details for PubMedID 11335779

  • Influence of light in the NICU on the development of circadian rhythms in preterm infants SEMINARS IN PERINATOLOGY Mirmiran, M., Ariagno, R. L. 2000; 24 (4): 247-257

    Abstract

    The fetal biological clock is an endogenous clock capable of generating circadian rhythms and responding to maternal entraining signals. By at least the third trimester of pregnancy fetal diurnal rhythms are entrainable by maternal day-night rhythms. Maternal illness during pregnancy and premature birth are obvious clinical factors that may adversely affect circadian rhythm development. Premature birth of the fetus has a most dramatic impact on maternal fetal interactions. The effect on biorhythms appears to be temporary and is greatest on the most immature infants. The results to date support the importance of fetal circadian rhythms and the relative lack of these rhythms in the preterm infant. It is well known that growth and development in the prematurely born infant are influenced by a multitude of factors; clearly, the neonatal intensive care unit is not a surrogate for the maternal placental unit. This article reviews what is known about circadian development in the human infant with an emphasis on the unique circumstances of the preterm infant. The research on the short- and long-term effects of environmental interventions on circadian, sleep, and neurologic development is discussed. Although an earlier onset of circadian development did not result with cycled lighting in the neonatal nursery, there may still be important biological effects that have not been studied. There are sufficient data to state that there is no reason for continuing a chaotic, noncircadian environmental approach for the care of the prematurely born infant.

    View details for Web of Science ID 000089255700004

    View details for PubMedID 10975431

  • Predictive value of neonatal neurological tests for developmental outcome of preterm infants JOURNAL OF PEDIATRICS Maas, Y. G., Mirmiran, M., Hart, A. A., Koppe, J. G., Ariagno, R. L., Spekreijse, H. 2000; 137 (1): 100-106

    Abstract

    There is a need to identify, as early as possible, infants who are at risk for long-term neurological morbidity.To predict neurodevelopment outcome of preterm infants <30 weeks' gestation in a population of 100 infants, we used several neonatal and neurobehavioral tests, including cranial ultrasonography, the Prechtl neurological test, quality of spontaneous general movements, and quality of sleep-wake organization.The Prechtl test at corrected term age and findings on cranial sonograms both had high specificity, but the Prechtl test had better overall positive predictive power for normal neurological and developmental outcomes at 2 years' corrected age. Developmental changes in sleep and the amount of indeterminate sleep did not correlate with outcome. Scoring general movement quality did not predict outcome and did not augment the positive predictive power of the Prechtl test.The Prechtl test at corrected term age (independent of the other tests) is the best positive predictor of normal neurological outcome and Bayley test results at 2 years' corrected age.

    View details for DOI 10.1067/mpd.2000.106901

    View details for Web of Science ID 000088204000021

    View details for PubMedID 10891830

  • Effects of prone and supine position on sleep characteristics in preterm infants PSYCHIATRY AND CLINICAL NEUROSCIENCES Goto, K., Maeda, T., Mirmiran, M., Ariagno, R. 1999; 53 (2): 315-317

    Abstract

    The purpose of this study was to address the influence of sleep position on sleep characteristics in preterm infants. We studied 16 infants at a mean post-conceptional age of 36.5 weeks. Infants were successfully recorded with videopolysomnograph in the supine and prone position. Between the two positions, there were no significant differences in percentage of active sleep and quiet sleep (QS), the occurrence of arousal, and the incidence of apnea. The first QS after the feeding was longer in the prone position. The sleep position could affect sleep characteristics but not respiratory characteristics in preterm infants.

    View details for Web of Science ID 000081146200062

    View details for PubMedID 10459722

  • More awakenings and heart rate variability during supine sleep in preterm infants PEDIATRICS Goto, K., Mirmiran, M., Adams, M. M., Longford, R. V., Baldwin, R. B., Boeddiker, M. A., Ariagno, R. L. 1999; 103 (3): 603-609

    Abstract

    The Task Force of The American Academy of Pediatrics (1996) recommends the nonprone sleeping position for asymptomatic preterm infants to prevent sudden infant death syndrome. The mechanism by which the nonprone sleeping position reduces the rate of sudden infant death syndrome is unclear for full-term infants and the precise effect of sleeping position on sleep and cardiorespiratory characteristics has never been addressed in preterm infants. The purpose of the present study was to clarify the effect of sleeping position on sleep and cardiorespiratory characteristics in preterm infants at an age when they are ready for discharge.Sixteen asymptomatic preterm infants were studied in both supine and prone sleeping positions at 36.5 +/- 0.6 weeks' postconceptional age using videosomnography. Sleep, respiratory, and heart rate characteristics were compared between the two positions using each infant as his/her own control.More awakenings (ie, arousals >/=60 seconds) were seen during all sleep states in the supine sleeping position but overall the total sleep and percent sleep state were not affected by sleeping position. After each feeding, the first quiet sleep was significantly shorter, with more heart rate variability and awakenings in the supine position. There were no significant differences in the occurrence of arousals (<60 seconds) or the incidence or severity of apnea and periodic breathing. No clinically significant apnea (>/=15 seconds), bradycardia, or oxygen desaturations were seen.In 36-week-postconceptional age preterm infants, the supine sleeping position had less quiet sleep and was associated with greater heart rate variability during the first sleep cycle after the feeding. More awakenings were seen during all sleep states in the supine position. These data support the American Academy of Pediatrics recommendation for "Back to Sleep" for asymptomatic preterm infants because more awakenings and lower threshold for arousal may provide some benefit for the infant responding to a life-threatening event. However, further studies are needed to address positional effect on the physiologic measures in preterm infants at older ages (later stages of development). Precisely what constitutes the most healthy or advantageous sleep for newborn infants remains an important question.

    View details for Web of Science ID 000078960100012

    View details for PubMedID 10049964

  • Survey of sleeping position after hospital discharge in healthy preterm infants. Journal of perinatology Adams, M. M., Kugener, B., Mirmiran, M., Ariagno, R. L. 1998; 18 (3): 168-172

    Abstract

    To evaluate the prevalence of nonprone (supine or side) versus prone sleeping position in healthy preterm infants.A questionnaire on sleeping position was mailed to mothers of 167 preterm infants discharged from the intermediate nursery at Packard Children's Hospital at Stanford. The prevalence of nonprone sleeping at 1 month (term corrected age) and 3 months (2 months corrected age) after nursery discharge was analyzed by an unpaired t test.Nonprone position sleeping occurred in 64% initially and dropped to 35% at 2 months corrected age.Overall, nonprone sleeping was widespread in our healthy preterm infants after hospital discharge but may not persist. A majority of these infants were sleeping prone during a high-risk period for sudden infant death syndrome.

    View details for PubMedID 9659642

  • Developmental care does not alter sleep and development of premature infants PEDIATRICS Ariagno, R. L., Thoman, E. B., Boeddiker, M. A., Kugener, B., Constantinou, J. C., Mirmiran, M., Baldwin, R. B. 1997; 100 (6)

    Abstract

    The Neonatal Individualized Developmental Care Program (NIDCAP) for very low birth weight (VLBW) preterm infants has been suggested by Als et al to improve several medical outcome variables such as time on ventilator, time to nipple feed, the duration of hospital stay, better behavioral performance on Assessment of Preterm Infants' Behavior (APIB), and improved neurodevelopmental outcomes. We have tested the hypothesis of whether the infants who had received NIDCAP would show advanced sleep-wake pattern, behavioral, and neurodevelopmental outcome.Thirty-five VLBW infants were randomly assigned to receive NIDCAP or routine infant care. The goals for NIDCAP intervention were to enhance comfort and stability and to reduce stress and agitation for the preterm infants by: a) altering the environment by decreasing excess light and noise in the neonatal intensive care unit (NICU) and by using covers over the incubators and cribs; b) use of positioning aids such as boundary supports, nests, and buntings to promote a balance of flexion and extension postures; c) modification of direct hands-on caregiving to maximize preparation of infants for, tolerance of, and facilitation of recovery from interventions; d) promotion of self-regulatory behaviors such as holding on, grasping, and sucking; e) attention to the readiness for and the ability to take oral feedings; and f) involving parents in the care of their infants as much as possible. The infants' sleep was recorded at 36 weeks postconceptional age (PCA) and at 3 months corrected age (CA) using the Motility Monitoring System (MMS), an automated, nonintrusive procedure for determining sleep state from movement and respiration patterns. Behavioral and developmental outcome was assessed by the Neurobehavioral Assessment of the Preterm Infant (NAPI) at 36 weeks PCA, the APIB at 42 weeks PCA, and by the Bayley Scales of Infant Development (BSID) at 4, 12, and 24 months CA.Sleep developmental measures at 3 months CA showed a clear developmental change compared with 36 weeks PCA. These include: increased amount of quiet sleep, reduced active sleep and indeterminate sleep, decreased arousal, and transitions during sleep. Longest sleep period at night showed a clear developmental effect (increased) when comparing nighttime sleep pattern of infants at 3 months with those at 36 weeks of age. Day-night rhythm of sleep-wake increased significantly from 36 weeks PCA to 3 months CA. However, neither of these sleep developmental changes showed any significant effects of NIDCAP intervention. Although all APIB measures showed better organized behavior in NIDCAP patients, neither NAPI nor Bayley showed any developmental advantages for the intervention group. The neurodevelopmental outcome measured by the Bayley at 4, 12, and 24 months CA showed 64% of the NIDCAP intervention group at the lowest possible score compared with 33% of the control group. These findings could not be explained by the occurrence of intraventricular hemorrhage or the socioeconomic status of the parents, which showed no significant group effect.The results of this study, including measures of sleep maturation and neurodevelopmental outcome up to 2 years of age did not demonstrate that the NIDCAP intervention results in increased maturity or development. Buehler et al (Pediatrics. 1995;96:923-932) have reported that premature infants (N = 12; mean gestational age 32 weeks, mean birth weight 1700 g) who received developmental care compared with a similar group of infants who received routine care showed better organized behavioral performance on an APIB assessment at 42 weeks PCA. None of the medical outcome measures were significantly different in this study. Although our APIB results are in agreement, the results of the NAPI, the Bayley and sleep measures do not show an increase in neurodevelopmental maturation. In the earlier report by Als et al (Journal of the American Medical Associatio

    View details for Web of Science ID A1997YJ31400029

    View details for PubMedID 9382910

  • Dew-point hygrometry system for measurement of evaporative water loss in infants JOURNAL OF APPLIED PHYSIOLOGY Ariagno, R. L., GLOTZBACH, S. F., Baldwin, R. B., Rector, D. M., Bowley, S. M., Moffat, R. J. 1997; 82 (3): 1008-1017

    Abstract

    Evaporation of water from the skin is an important mechanism in thermal homeostasis. Resistance hygrometry, in which the water vapor pressure gradient above the skin surface is calculated, has been the measurement method of choice in the majority of pediatric investigations. However, resistance hygrometry is influenced by changes in ambient conditions such as relative humidity, surface temperature, and convection currents. We have developed a ventilated capsule method that minimized these potential sources of measurement error and that allowed second-by-second, long-term, continuous measurements of evaporative water loss in sleeping infants. Air with a controlled reference humidity (dew-point temperature = 0 degree C) is delivered to a small, lightweight skin capsule and mixed with the vapor on the surface of the skin. The dew point of the resulting mixture is measured by using a chilled mirror dew-point hygrometer. The system indicates leaks, is mobile, and is accurate within 2%, as determined by gravimetric calibration. Examples from a recording of a 13-wk-old full-term infant obtained by using the system give evaporative water loss rates of approximately 0.02 mgH2O.cm-2.min-1 for normothermic baseline conditions and values up to 0.4 mgH2O.cm-2. min-1 when the subject was being warmed. The system is effective for clinical investigations that require dynamic measurements of water loss.

    View details for Web of Science ID A1997WM77500042

    View details for PubMedID 9074995

  • BIOLOGICAL RHYTHMICITY IN PRETERM INFANTS PRIOR TO DISCHARGE FROM NEONATAL INTENSIVE-CARE PEDIATRICS GLOTZBACH, S. F., Edgar, D. M., Ariagno, R. L. 1995; 95 (2): 231-237

    Abstract

    The study of biological rhythms and the influence of environmental factors in the timing and synchronization of different rhythmic events have important implications for neonatal health. Preterm infants in the neonatal intensive care unit (NICU) are deprived of the patterned influences of maternal sleep, temperature, heart rate, and hormonal cycles. The impact of the NICU and nursing interventions on the development of the circadian system was studied in 17 stable preterm infants in the Intermediate Intensive Care Nursery at Stanford University for three consecutive days at about 35 weeks postconceptional age.Rectal temperature, abdominal skin temperature, heart rate, and activity were simultaneously recorded at 2-minute intervals during each 3-day study by a small microcomputer (Vitalog).Very low amplitude circadian rhythms were found for rectal and skin temperatures (maximum range 36.8 to 37.0 degrees C); population mean values for heart rate (158 bpm) and activity (3.5 counts per 2-min bin) did not differ significantly as a function of time of day. Rectal temperature, averaged in 6-hour bins over the 24-hour day as a function of both postconceptional age and postnatal age, was significantly higher during the first part of the circadian cycle. In all infants, rhythmicity in each variable was dominated by ultradian periodicities that were coincident with feedings and related interventions; moreover, several physiological variables charted during feeding differed significantly from values obtained during periods in which caregiving interventions did not occur.Quantitative data on the preterm infant circadian system may facilitate evaluation of factors that improve therapeutic responses, recovery, and outcome of neonatal intensive care patients.

    View details for Web of Science ID A1995QE31300014

    View details for PubMedID 7838641

  • BIOLOGICAL RHYTHMICITY IN NORMAL INFANTS DURING THE FIRST 3 MONTHS OF LIFE PEDIATRICS GLOTZBACH, S. F., Edgar, D. M., Boeddiker, M., Ariagno, R. L. 1994; 94 (4): 482-488

    Abstract

    The mammalian "biological clock," which resides in the hypothalamic suprachiasmatic nucleus, has an important role in both the timing and organization of sleep and in the coordination of sleep with other physiological rhythms such as temperature regulation and respiratory control. We wished to describe the development of the circadian system in normal infants during the first 3 months of life.Ten healthy full term infants were studied in the infant's home for three consecutive days at 1 month and 3 months postnatal age. Rectal temperature, abdominal skin temperature, heart rate, and activity were recorded at 2-minute intervals during each study using a small microcomputer.Circadian periodicity for most variables was seen at 1 month of age and significantly increased at 3 months. Differences in the pattern of rhythmicity during these two developmental periods were highlighted by an increase in activity during the subjective day and a decrease in Trec during the subjective night at 3 months compared to 1 month. Correlational analysis revealed that all pairs of variables, exclusive of Tsk, showed a significantly higher association at 3 months relative to 1 month. The lengthening of the interfeeding interval at 3 months of age corresponded with an increased consolidation of sleep during the night and a relatively lower nocturnal body temperature minima compared to 1 month of age.The results of this study underscore the subtle changes in the nature and interaction of several infant variables during this critical developmental period, which may reflect maturation of the circadian system and its coupling with homeostatic effector systems that are developing in parallel.

    View details for Web of Science ID A1994PK84000013

    View details for PubMedID 7936856

  • LIGHT VARIABILITY IN THE MODERN NEONATAL NURSERY - CHRONOBIOLOGIC ISSUES MEDICAL HYPOTHESES GLOTZBACH, S. F., ROWLETT, E. A., Edgar, D. M., Moffat, R. J., Ariagno, R. L. 1993; 41 (3): 217-224

    Abstract

    The role that nursery light variability may play in modulating infant biological rhythms is being studied in Stanford Medical Center's Neonatal Intensive Care (NICU) and Intermediate Care (IN) Nurseries. In this investigation, spatial and temporal variability in illuminance was determined at 20 sites within each nursery over a 5-day period. The analysis of 240 measurements at 30 min intervals from each site revealed marked variability in illumination with respect to both time and position in the nursery. These aperiodic lighting patterns differed greatly from the published characterization of NICUs as having 'constant' illumination. Light pulses of variable frequency, intensity, and duration were common at each of the 40 bedsites studied. Given the powerful impact of light on circadian rhythmicity and sleep in adults, the results from this study suggest that modern NICU lighting, while implemented to facilitate intensive care, may have adverse effects on infant development. Future studies on the influence of light on biological rhythmicity and sleep are essential to provide a framework for clinical and environmental interventions, which may play a significant role in improving developmental outcome in hospitalized preterm or term infants.

    View details for Web of Science ID A1993LX72000006

    View details for PubMedID 8259078

  • DELAYED COMPLIANCE INCREASE IN INFANTS WITH RESPIRATORY-DISTRESS SYNDROME FOLLOWING SYNTHETIC SURFACTANT PEDIATRIC PULMONOLOGY ARMSBY, D. H., Bellon, G., Carlisle, K., Rector, D., Baldwin, R., Long, W., Stevenson, D. K., Ariagno, R. L. 1992; 14 (4): 206-213

    Abstract

    Recent research has demonstrated that Exosurf (EXSF), a newly synthesized artificial surfactant, increases survival when administered endotracheally to premature infants with RDS. This study examines the effects of EXSF on static respiratory system compliance (Crs). Thirty-four patients received two doses of EXSF in this rescue protocol. Crs (mL/cmH2O/kg) did not significantly change within the first 4 hours after either dose. However, Crs values did increase significantly (paired Student's t-test, P = 0.005) when data collected after the second dose (0.36 +/- 0.13 mL/cmH2O/kg) were compared to first week follow-up data (0.51 +/- 0.21 mL/cmH2O/kg). Crs data collected between 2 and 4 weeks after treatments were again not significantly different from non-concurrent control data collected at 3-4 weeks of life. The measurement of Crs in infants receiving EXSF may have been affected by an increase in lung inflation, which could mask an increase in Crs. We speculate that improved lung inflation may occur with less barotrauma in the first week of life due to surfactant replacement treatment and may in part explain the improved Crs seen at 1 week of age. Many investigators using different surfactants, dosing schedules, and pulmonary function methodologies to evaluate lung mechanics have reported that the improvement in compliance after surfactant treatment usually follows the clinical improvement in gas exchange. Additional studies are needed to explain the mechanism of early improvement following surfactant replacement in infants with RDS.

    View details for Web of Science ID A1992KD24300002

    View details for PubMedID 1484754

  • NONINVASIVE METHODS FOR ESTIMATING INVIVO OXYGENATION CLINICAL PEDIATRICS Benaron, D. A., Benitz, W. E., Ariagno, R. L., Stevenson, D. K. 1992; 31 (5): 258-273

    Abstract

    Clinical signs of hypoxia and hyperoxia are nonspecific and unreliable, yet both are potentially injurious. Noninvasive methods of oxygen assessment fill the gap between clinical observation and invasive tests, helping physicians deliver sufficient oxygen with minimum toxicity. Potential sites for oxygen measurement vary between the blood and the mitochondria; each method measures at a different site and detects different types of hypoxia and hyperoxia. Thus, values obtained by two different methods are not equivalent, giving each method unique strengths and weaknesses. We review two clinical methods (pulse oximetry and transcutaneous oximetry), as well as four experimental methods (near-infrared spectrophotometry, magnetic resonance spectroscopy, magnetic resonance saturation imaging, and time-of-flight absorbance spectrophotometry). The principles of each method and the clinical situations in which each succeeds or fails are discussed. A fundamental understanding of each method can help in deciding which methods, if any, are appropriate for a given patient and how best to correct observed oxygenation problems once they are discovered.

    View details for Web of Science ID A1992HU95600001

    View details for PubMedID 1582091

  • A CONTROLLED TRIAL OF AEROSOLIZED RIBAVIRIN IN INFANTS RECEIVING MECHANICAL VENTILATION FOR SEVERE RESPIRATORY SYNCYTIAL VIRUS-INFECTION NEW ENGLAND JOURNAL OF MEDICINE Smith, D. W., Frankel, L. R., Mathers, L. H., TANG, A. T., Ariagno, R. L., Prober, C. G. 1991; 325 (1): 24-29

    Abstract

    Although the antiviral agent ribavirin improves the course of lower respiratory tract disease in spontaneously breathing infants with respiratory syncytial virus infection, it is not known whether ribavirin can benefit infants with severe respiratory syncytial virus disease who require mechanical ventilation.We conducted a randomized, double-blind, placebo-controlled evaluation of ribavirin (20 mg per milliliter) administered continuously in aerosolized form to infants receiving mechanical ventilation for respiratory failure that was caused by documented respiratory syncytial virus infection.Of the 28 infants (mean [+/- SD] age, 1.4 +/- 1.7 months) enrolled, 7 had underlying diseases predisposing them to severe infection (mean age, 3.0 +/- 2.6 months), and 21 were previously normal (mean age, 0.8 +/- 0.9 month). Among the 14 infants who received ribavirin, the mean duration of mechanical ventilation was 4.9 days (as compared with 9.9 days among the 14 who received placebo; P = 0.01), and the mean length of supplemental oxygen use was 8.7 days (as compared with 13.5 days; P = 0.01). The mean length of the hospital stay was 13.3 days after treatment with ribavirin and 15.0 with placebo (P = 0.04). When only the 21 previously normal infants were considered, the mean length of the hospital stay was 9.0 days for the ribavirin recipients and 15.3 days for those who received placebo (P = 0.005).In infants who require mechanical ventilation because of severe respiratory syncytial virus infection, treatment with aerosolized ribavirin decreases the duration of mechanical ventilation, oxygen treatment, and the hospital stay.

    View details for Web of Science ID A1991FU34200005

    View details for PubMedID 1904551

  • PULMONARY-FUNCTION TESTING IN INFANTS WITH RESPIRATORY SYNCYTIAL VIRUS BRONCHIOLITIS REQUIRING MECHANICAL VENTILATION PEDIATRIC INFECTIOUS DISEASE JOURNAL Smith, D. W., Rector, D. M., Derish, M. T., Frankel, L. R., Ariagno, R. L. 1990; 9 (9): S108-S111

    View details for Web of Science ID A1990DY65700016

    View details for PubMedID 2235204

  • Neonatal tuberous sclerosis: magnetic resonance appearance of subependymal tubers. Australasian radiology Dawson, K. L., Moore, S. G., Ariagno, R. L. 1990; 34 (3): 247-248

    Abstract

    A case of tuberous sclerosis in a neonate, with cerebral and cardiac hamartomas evaluated by MR imaging, is presented. Intracranial subependymal tubers in this neonate exhibit increased signal intensity on short TR images. This differs from the signal characteristics of subependymal tubers in older patients.

    View details for PubMedID 2275684

  • Fatal postoperative Legionella pneumonia in a newborn. Journal of perinatology Greene, K. A., Rhine, W. D., Starnes, V. A., Ariagno, R. L. 1990; 10 (2): 183-184

    Abstract

    This is a case of postoperative Legionella pneumonia in a full-term infant with hypoplastic left heart syndrome. The infant had an uncomplicated prenatal history, normal vaginal delivery, Apgars of 8 at 1 and 5 minutes, but was cyanotic at birth. At 3 days of age she had a stage 1 Norwood surgical procedure to palliate her congenital heart disease. A synthetic patch was placed over the thoracic midline because of difficulty in reapposing the sternum. Peritoneal dialysis was used to manage renal failure. At 20 days of age she had disseminated intravascular coagulopathy and pneumonia associated with sepsis. Four days later she died. Legionella pneumophila serogroup 1 was isolated from a lung culture taken at autopsy.

    View details for PubMedID 2358903

  • PERIODIC BREATHING IN PRETERM INFANTS - INCIDENCE AND CHARACTERISTICS PEDIATRICS GLOTZBACH, S. F., Baldwin, R. B., LEDERER, N. E., Tansey, P. A., Ariagno, R. L. 1989; 84 (5): 785-792

    Abstract

    The prevalence and characteristics of periodic breathing in preterm infants were measured by 24-hour impedance pneumograms in 66 preterm infants before discharge from the nursery. Four periodic breathing parameters (percentage of periodic breathing per quiet time, number of episodes of periodic breathing per 100 minutes of quiet time, mean duration of periodic breathing, and longest episode of periodic breathing) were compared to data available from healthy term infants and from term infants who subsequently died of sudden infant death syndrome (SIDS). Periodic breathing was found in all preterm infants studied and mean periodic breathing parameter values (12.0%, 8.6 episodes, 1.2 minutes, and 7.3 minutes, respectively) in our preterm population were substantially higher than values from healthy term infants and SIDS victims. Most periodic breathing parameters decreased significantly in infants studied at 39 to 41 weeks' postconceptional age compared with earlier postconceptional age groups. No relationship was found between central apneas of greater than or equal to 15 seconds' duration and postconceptional age or any periodic breathing parameter. Periodic breathing is a common respiratory pattern in preterm infants that is usually not of pathologic significance. Associations between elevated levels of periodic breathing and respiratory dysfunction or SIDS should be made with caution.

    View details for Web of Science ID A1989AX61000008

    View details for PubMedID 2797974

  • THE EFFECT OF DEXAMETHASONE ON CHRONIC PULMONARY OXYGEN-TOXICITY IN INFANT MICE PEDIATRIC RESEARCH Ohtsu, N., Ariagno, R. L., Sweeney, T. E., Davis, L., Moses, L., PETRICEKS, R., DAEHNE, I., Bensch, K., Northway, W. H. 1989; 25 (4): 353-359

    Abstract

    The effect of dexamethasone (0.1, 1, and 5 mg/kg/d given subcutaneously from d 14-18) was tested in infant mice continuously exposed from birth to either humidified air or 80% oxygen. Dexamethasone significantly decreased lung wet wt (p less than 0.01), lung water (p less than 0.021), lung dry wt, protein, and DNA (p less than 0.001) in both air- and oxygen-exposed animals. Dexamethasone, however, had no effect on lung compliance measured after animals were killed on d 18. It also had no effect on the increase in the blood-air barrier thickness or decrease in the blood-air exchange surface area seen in the 80% oxygen-exposed mice. Dexamethasone decreased thymus gland wt (p less than 0.001), body wt gain (p less than 0.001), brain wt (p less than 0.001), and lung lymphocytes (p less than 0.05) in both air- and oxygen-exposed animals. The effect of 1 mg/kg and 5 mg/kg of the drug could not be differentiated. During the 4 d of drug administration, one air- and one oxygen-exposed animal died; both received 5 mg/kg/d of dexamethasone; microscopic and culture evidence of infection was not found. If dexamethasone causes similar effects in human infants with bronchopulmonary dysplasia, it should be used with great caution even for short-term clinical management.

    View details for Web of Science ID A1989T947000008

    View details for PubMedID 2726308

  • PERIODIC BREATHING CYCLE DURATION IN PRETERM INFANTS PEDIATRIC RESEARCH GLOTZBACH, S. F., Tansey, P. A., Baldwin, R. B., Ariagno, R. L. 1989; 25 (3): 258-261

    Abstract

    Periodic breathing cycle duration (PCD), the time interval from the beginning of one respiratory pause to the beginning of the next pause within an episode of periodic breathing (PB), was measured by examination of 24-h impedance pneumograms in 51 preterm infants. Calculations of the SD of PCD within a given PB episode (approximately 3 s) and comparison of PCD values between two PB episodes in each infant (r = 0.68) revealed considerable variability in PCD. This variability was not related to the number of cycles in the PB episode or to the amount of PB in the recording. Contrary to the decrease in PCD from 15.0 s at 1 wk to 12.4 s at 12 wk in term infants reported previously, PCD did not vary as a function of postconceptional, gestational, or postnatal age in our preterm population. PCD has limited value as an indicator of chemoreceptor maturation in the preterm infant, and most likely reflects transient adjustments in respiratory system control.

    View details for Web of Science ID A1989T593200007

    View details for PubMedID 2704592

  • A RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF EFFECTS OF DEXAMETHASONE ON HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN PRETERM INFANTS JOURNAL OF PEDIATRICS Wilson, D. M., Baldwin, R. B., Ariagno, R. L. 1988; 113 (4): 764-768

    Abstract

    As part of a blinded, randomized, placebo-controlled study of dexamethasone therapy in 27 preterm infants with bronchopulmonary dysplasia, we investigated the effect of 7 days of high-dose glucocorticoid therapy on the hypothalamic-pituitary-adrenal axis. Before therapy the median basal cortisol concentration in all infants was 8.2 micrograms/dl (226 nmol/L). After stimulation with 1-24 ACTH, the serum cortisol concentration rose in all infants to a median concentration of 23.5 micrograms/dl (649 nmol/L), resulting in a median rise of 13.4 micrograms/dl (37 nmol/L). Immediately after 7 days of glucocorticoid therapy basal and peak cortisol concentrations were significantly decreased in the dexamethasone group. The rise in serum cortisol following 1-24 ACTH, however, remained equivalent in both groups. Ten days after the end of therapy basal and peak cortisol concentrations in the dexamethasone group had returned to levels equivalent to those seen in the placebo group. Weight gain was markedly diminished while the infants were receiving dexamethasone. Weight gains were, however, equivalent 10 days after the end of treatment. These data indicate that 7 days of dexamethasone therapy has significant but short-term effects on cortisol secretion and possibly on weight gain.

    View details for Web of Science ID A1988Q533800028

    View details for PubMedID 3050006

  • INTERFERENCE OF FETAL HEMOGLOBIN WITH THE SPECTROPHOTOMETRIC MEASUREMENT OF CARBOXYHEMOGLOBIN CLINICAL CHEMISTRY Vreman, H. J., RONQUILLO, R. B., Ariagno, R. L., Schwartz, H. C., Stevenson, D. K. 1988; 34 (5): 975-977

    Abstract

    We measured the concentration of carboxyhemoglobin (HbCO) in blood samples from 32 neonates by spectrophotometry (IL282 CO-Oximeter) and gas chromatography, finding a strong positive correlation (r = 0.89) between the concentration of fetal hemoglobin (Hb F) and HbCO as measured by spectrophotometry, but not by gas chromatography. Thus, Hb F interferes with the determination of HbCO by spectrophotometric techniques by falsely increasing apparent HbCO in direct proportion to Hb F. We conclude that, when Hb F is known or suspected to be present, blood HbCO cannot be reliably determined by methods based on spectrophotometry.

    View details for Web of Science ID A1988N563700035

    View details for PubMedID 2453310

  • DISSOCIATION OF MEAN AIRWAY PRESSURE AND LUNG-VOLUME DURING HIGH-FREQUENCY OSCILLATORY VENTILATION CRITICAL CARE MEDICINE Smith, D. W., Frankel, L. R., Ariagno, R. L. 1988; 16 (5): 531-535

    Abstract

    Eight kittens were studied during high-frequency oscillatory ventilation (HFOV) using an airway vibrator. HFOV was performed at 1000 and 1800 cycle/min at three present oscillatory amplitude settings and with lungs normal and injured by saline lavage. Change in lung volume (LV) during HFOV was compared to change in LV obtained during static inflation at matched mean airway pressure (Paw) of 5, 10, 15 and 20 cm H2O. LV during HFOV was significantly higher than during static inflation, and increased as oscillatory amplitude increased. LV was significantly lower after lung injury for matched HFOV settings, and was not affected by rate. Dissociation of Paw and LV during HFOV is observed implying that mean alveolar pressure (Palv) exceeds Paw during HFOV in this experimental model. The safe clinical application of HFOV may involve measurement of Palv or LV.

    View details for Web of Science ID A1988N250700012

    View details for PubMedID 3359791

  • RAPID ASSESSMENT OF VENTILATION BY MEASUREMENT OF CARBON-DIOXIDE ELIMINATION DURING HIGH-FREQUENCY VENTILATION OF KITTENS PEDIATRIC PULMONOLOGY Smith, D. W., Frankel, L. R., Walker, J. G., Cheng, E. Y., MEREDITH, K. S., Mihm, F. G., Ariagno, R. L. 1987; 3 (6): 406-412

    Abstract

    Monitoring of the effectiveness of ventilation is a significant problem during high-frequency ventilation (HFV). The time necessary to achieve equilibrium of the arterial tension of carbon dioxide (Paco2) following step changes in ventilation is appreciable, because of large body stores of CO2. Waiting for Paco2 to reach equilibrium is not only time-consuming but a potentially dangerous means of monitoring ventilator adjustments during HFV. Five kittens of mean +/- SD 1,082 +/- 383 gm weight were studied during HFV, both with normal lungs and lungs injured by saline lavage-induced surfactant depletion. The transcutaneous tension of carbon dioxide (Ptcco2) was monitored continuously to determine the time required to achieve equilibrium of Paco2 following a step change in ventilation. The rate of pulmonary CO2 elimination (VECO2) was measured immediately before and immediately after (less than 12 sec) step changes in ventilation and was used to predict the change in Paco2 achieved once equilibrium was reestablished. With normal lungs, equilibration time following step changes in ventilation was found to be approximately 20 minutes. After step decreases in ventilation of the injured lung, achieving equilibrium state took significantly longer, approximately 30 minutes. The Paco2 predicted was significantly related to the change in Paco2 achieved at equilibrium for both normal and injured lung studies. We concluded that direct monitoring of VECO2 during HFV may be a useful clinical monitoring technique, allowing rapid and accurate assessment of the efficiency of ventilation following step changes in ventilation and potentially assisting in optimizing ventilator settings.

    View details for Web of Science ID A1987L110400004

    View details for PubMedID 3122154

  • HOME MONITORING OF HIGH-RISK INFANTS CHEST Ariagno, R. L., GLOTZBACH, S. F. 1987; 91 (6): 898-900

    View details for Web of Science ID A1987H591600024

    View details for PubMedID 3581938

  • USE OF SODIUM-NITROPRUSSIDE IN NEONATES - EFFICACY AND SAFETY JOURNAL OF PEDIATRICS Benitz, W. E., MALACHOWSKI, N., Cohen, R. S., Stevenson, D. K., Ariagno, R. L., Sunshine, P. 1985; 106 (1): 102-110

    Abstract

    Sodium nitroprusside was administered to 58 neonates, including 11 with severe respiratory distress syndrome, 15 with persistent pulmonary hypertension of the newborn, 28 with clinical shock, three with systemic hypertension, and two with pulmonary hypoplasia, all refractory to conventional intensive therapy. Nitroprusside was infused at 0.2 to 6.0 micrograms/kg/min for periods of 10 minutes to 126 hours. Infants with severe respiratory distress syndrome had increased PaO2 and decreased PaCO2 or peak inspiratory pressure, and nearly all (82%) survived. Infants with persistent pulmonary hypertension of the newborn had variable responses; improvement did not correlate with survival, but survival (47%) was identical to that in an earlier series of infants given tolazoline. Infants in shock had improved perfusion, urine output, and serum bicarbonate levels, and these responses were significantly related to survival. Hypertension was controlled in all three hypertensive infants. Adverse effects were very uncommon. Toxic effects were not observed. Sodium nitroprusside is effective and can be used safely in circulatory disorders in the neonate.

    View details for Web of Science ID A1985AAH1500023

    View details for PubMedID 3917495

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