AAP-Section on Perinatal Pediatrics

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1. INTRACELLULAR ADHESION MOLECULE ONE (ICAM-1) IS expression of the inflammatory adhesion molecule, ICAM-1. This INCREASED IN THE CLARA CELL SECONDARY TO EXPOSURE TO supports the premise that the Clara cell may function to modulate LPS, TNF , AND HYPEROXIA pulmonary inflammation by either the secretion of the anti- W.D. Clark1, S.E. Welty2 and P.L. Ramsay3; 1Pediatrics, inflammatory protein, CCSP, or by the expression of the pro- Baylor College of Medicine, Houston, TX, 2Pediatrics, inflammatory protein, ICAM-1. These data further suggest that Children’s Research Institute, Columbus, OH, potential therapeutic interventions that modulate the gene expression 3Pediatrics and Molecular and Cell Biology, Baylor within the Clara cell may provide a method to regulate pulmonary College of Medicine, Houston, TX inflammation.

Purpose. Early lung inflammation in prematurely born newborns 2. GENETIC ENHANCEMENT OF GLUTATHIONE REDUCTASE results from a variety of exposures, including cytokines and hyperoxia. Previously, we have shown that serum levels of the PROTECTS CHINESE HAMSTER OVARY CELLS FROM HYPOXANTHINE/ inflammatory adhesion molecule, ICAM-1, are higher in infants XANTHINE OXIDASE–MEDIATED OXIDANT STRESS that develop BPD than in infants that do not. In addition, the D.J. O’Donovan, R.C. Husser, T. Tamura and C.J. content of an anti-inflammatory tracheal fluid protein secreted by Fernandes; Pediatrics, Baylor College of Medicine, the Clara cell, the Clara cell secretory protein (CCSP), is decreased Houston, TX in infants that develop BPD, whereas others have shown that the level of tracheal fluid ICAM-1 is increased. Therefore, this study was Purpose. Reactive oxygen species (ROS) have been implicated in designed to test the hypothesis that the Clara cell in response to the causation of diseases related to prematurity, such as known pro-inflammatory mediators will increase the expression of bronchopulmonary dysplasia and necrotizing enterocolitis. Inad- ICAM-1. equate and immature antioxidant defense function predisposes the premature infant to injury from ROS. The glutathione (GSH)- Methods. We utilized a mouse transformed Clara cell (mtCC) line to dependent antioxidant system protects against the damaging test whether the pro-inflammatory mediators lipopolysaccharide effects of ROS in the cytoplasm and mitochondria, and (LPS), TNF- , and hyperoxia would increase ICAM-1 mRNA. regeneration of GSH from glutathione disulfide by GR is vital for Following 0 to 24 hours of exposure to either LPS, TNF- ,or the optimal function of this system. Previously, we reported hyperoxia, the cells were harvested, ICAM-1 mRNA was assayed by resistance to t-BuOOH–induced cell injury in H441 cells Northern blot, and ICAM-1 protein was assayed immunohisto- following augmentation of mitochondrial GR activities by chemistry. Further analyses with variable length of the 50 upstream adenoviral-mediated transfer of GR cDNA with a mitochondrial region of the ICAM-1 promoter ligated to a luciferase reporter gene targeting sequence (MTS). The purpose of these studies was to were analyzed to identify the regions of the ICAM-1 promoter that determine whether CHO cells with stably enhanced cytoplasmic or were responsive to these pro-inflammatory stimuli. mitochondrial GR activities are resistant to injury from ROS enzymatically generated by HX/XO, and whether greater protection Results. We observed an increase in ICAM-1 mRNA by both LPS and against oxidant stress is conferred on cells with enhanced TNF- by 2 hours, which peaked at 4 hours and returned to baseline mitochondrial GR activities. by 8 to 12 hours. The immunohistochemistry demonstrated an increase in ICAM-1 protein secondary to LPS and TNF- at 4 hours. Methods. Transformed CHO cells with increased cytoplasmic (CHO- Hyperoxia increased ICAM-1 mRNA at 12 hours and increased GR) (17.0±2.0 vs 6.1±2.9 mU/mg Pr in native CHO cells) or ICAM-1 protein at 24 hours. The transient transfection studies mitochondrial (CHO-LGR) (77.5±3.9 vs 7.9±0.4 mU/mg Pr) GR demonstrated a several-fold greater induction of reporter gene activities were generated by liposomal transfer of GR cDNA±MTS activities with the 1520 and 1462 bp ICAM-1 promoter segments and growth in selection media. Native and transformed CHO cells than in the longer 2513 bp region. were grown for 24 hours, and exposed to media with 1 mM HX and XO (0, 5, 7.5, and 10 mU/ml). Percentage cellular lactate Conclusion. These results suggest that the Clara cell is capable of dehydrogenase (LDH) release (12 hours) and LDH activities in the responding to pro-inflammatory stimuli with an increase in media (0, 4, 8, 10, 12 hours) were determined as indices of

cytotoxicity. Data were analyzed by ANOVA with appropriate post-hoc radioimmunoassay. We observed a time-dependent decrease in tests (n=3, mean±SD). serum levels of hGH as a function of hyperoxia exposure. Further, our observed decrease in hGH occurred prior to the measurable onset of Results. Dose- and time-dependent increases in media LDH were lung injury. Next, we collected the cord blood of intubated premature observed in all cells exposed to XO of 7.5 and 10 mU/ml ( p<0.05). infants 29 weeks’ gestation and measured cord blood levels of Cells with increased CHO-GR and CHO-LGR activities exposed to 7.5 CCSP by Western blot and quantified by densitometry. and 10 mU/ml of XO released less LDH than did native CHO cells (CHO-GR: 16.1±2.9 and 39.2±3.1, CHO-LGR: 15.3±1.4 and Results. We detected soluble CCSP in 100% of the infants that 58.1±6.7, CHO: 22.8±1.6 and 66.7±3.8, respectively). Cells with developed CLD, whereas we detected soluble cord CCSP in only 66% of enhanced CHO-GR activities exposed to the 10 mU/ml XO released infants that did not develop CLD. The level of cord CCSP measured in less LDH than did cells with enhanced CHO-LGR activities similarly the infants that developed CLD was 80% greater that the level of cord exposed. CCSP that was detectable in infants that did not develop CLD. ( p<0.05). Conclusion. Stable enhancement of cytoplasmic or mitochondrial GR activities in CHO cells provides measurable protection against low Conclusion. These results suggest that soluble secreted lung levels of HX/XO-induced oxidant stress; however, at higher levels of proteins may serve as markers of intrapulmonary injury. Moreover, HX/XO-induced oxidant stress, enhancement of cytoplasmic GR that CCSP in the cord blood of extremely premature infants may activities provided greater cellular protection. reflect a degree of pulmonary immaturity that predisposes a subset of infants at greatest risk of developing CLD. Further investigations are underway to determine whether serum CCSP levels postnatally are 3. SOLUBLE CLARA CELL SECRETORY PROTEIN IS DECREASED IN associated with ongoing intrapulmonary inflammation in CLD. HYPEROXIA EXPOSURE AND CORD BLOOD LEVELS ARE PREDICTIVE OF THE DEVELOPMENT OF CHRONIC LUNG DISEASE A.C. Kanu1, P.L. Ramsay3,4, S.E. Hegemier3, S.E. Welty2 4. COMPARISON OF CYTOKINE RESPONSE BETWEEN PRETERM AND and F.J. DeMayo3,4; 1Pulmonary Medicine, Baylor TERM INFANTS IN NEONATAL SEPSIS College of Medicine, Houston, TX, 2Pediatrics, G. Laborada1, F. Cruz1, M. Rego1, J. DePaz1, Children’s Research Institute, Columbus, OH, M. Giulano2, J. Stavola1,A.Jain1, A. Krauss1 and 3Pediatrics, Baylor College of Medicine, Houston, TX, M. Nesin1; 1Pediatrics, New York Presbyterian Hospital- 4Molecular and Cellular Biology, Baylor College of Weill Medical College of Cornell University, New York, Medicine, Houston, TX NY, 2Pediatrics, Lenox Hill Hospital, New York, NY

Purpose. Advancements in neonatal care have improved survival for Purpose. Neonatal sepsis ranges from 5 to 10 per 1000 live births infants born prematurely. However, there is a growing population of and remains a major cause of mortality and morbidity. Recent extremely premature infants that develop chronic lung disease studies showed increased production of various cytokines such as (CLD). The underlying mechanisms that are responsible for the interleukin-8 (IL8), interleukin-6 (IL6), and tumor necrosis development of CLD remain ill defined. Early pulmonary factor-alpha (TNA) during sepsis. These cytokines have high inflammation in association with exposure to supplemental oxygen sensitivity and specificity, and are potentially useful diagnostic tests to and mechanical ventilation is recognized to play a critical role in the differentiate infected from non-infected neonates. However, there is development of CLD. We have previously shown that there are specific little data comparing the cytokine levels in preterm and term infants. oxidative changes and alterations in expression of the Clara cell This is particularly important if these cytokines become standard secretory protein (CCSP) in the airways of premature infants that inflammatory markers in neonatal sepsis. The objectives of the study subsequently develop CLD. This study was designed to test the were: (1) to determine if preterm infants could mount similar hypothesis that serum levels of proteins secreted by the Clara cell will cytokine response (IL8, IL6, TNA) when compared to term infants reflect lung injury secondary to hyperoxia exposure and be predictive during neonatal sepsis; and (2) to determine if these cytokines are of the development of CLD in prematurely born infants. significantly elevated in infected compared to non-infected infants.

Methods. To test these hypotheses, we utilized transgenic mice Methods. One hundred and nine neonates (59 preterm and 50 previously generated by ligating the CCSP promoter to hGH reporter term) suspected for sepsis were enrolled. Blood was drawn during the gene. These transgenic mice model have been shown to express hGH first 6 hours of sepsis evaluation. Cytokine values were expressed as in the Clara cell at levels comparable to the endogenous CCSP gene. mean±SEM. There were no significant differences in the clinical These mice were exposed to 0, 24, 48, or 72 hours of hyperoxia, and characteristics of the study population. Forty-eight patients (28 serum samples were obtained for measurement of hGH by preterm and 20 term) showed at least three of five clinical signs: (1)

Journal of Perinatology 2001; 21:482 – 509 483 AAP-Section on Perinatal Pediatrics Abstracts

apnea and bradycardia; (2) change in the level of consciousness; growth in livers and spleens were determined. RNase protection assays (3) increased ventilatory support; (4) signs of shock; (5) (RPA) for IRF-1 and the ‘‘housekeeping’’ gene mL32 were temperature instability, and were classified as septic; 32 neonates (21 performed on RNA harvested from livers and spleens of adults preterm and 11 term) had positive blood culture. Among the 48 injected with 8Â104 and neonates injected with 300 bacteria per septic neonates, 22 were early-onset sepsis and 26 were late-onset. gram body weight. The former is the LD50 dose for the adult mouse. The remaining 61 patients (31 preterm and 30 term) were non- The mRNA was quantified using phosphorimaging/densitometry. septic. Data are presented as IRF-1/mL32 mRNA ratios.

Results. There were no significant differences in the cytokine levels Results. Survival rates at 5 days post-infection with L. between non-septic preterm and term infants. There were also no monocytogenes were 0% (0/11) for 3- to 4-day-old mice, 57% significant differences in the septic preterm (IL8=318±78, (17/30) for 9- to 11-day-old mice, 100% (8/8) for 21-day-old IL6=346±97, TNA=73±45) and term infants (IL8=341±80, mice, and 100% (6/6) for adult animals. The change in the IRF-1/ IL6=371±108, TNA=61±34). All three cytokines were significantly mL32 mRNA ratio before and at 2, 4, 20, and 24 hours post-infection elevated in infected infants (IL8=329±55, IL6=357±71, is presented in the table below. Although adult mice had a greater TNA=68±29) compared to the non-infected infants (IL8=83±16, than 10-fold rise in the IRF-1/mL32 ration at 20 and 24 hours IL6=26±8, TNA=16±5). The p values for IL8, IL6 and TNA were post-infection with L. monocytogenes, ratios in neonatal mice were <0.001, <0.001, and 0.003, respectively, using the Mann-Whitney unchanged. test. Controls 2 hours 4 hours 20 hours 24 hours Adults 0.144 0.245 0.173 1.573 1.105 Conclusion. Preterm infants can mount a similar cytokine response ( ±0.031) ( ±0.034) ( ±0.029) ( ±0.247) ( ±0.318) compared to term infants during sepsis; thus, the same cut-off values Three- to 0.087 0.149 0.207 0.036 0.076 4-day-old ( ±0.017) ( ±0.081) ( ±0.009) ( ±0.014) ( ±0.017) may apply for both groups. IL8, IL6, and TNA were significantly Means (SD). elevated in infected compared to non-infected infants. These cytokines maybe useful diagnostic markers of neonatal sepsis for both Conclusion. (1) Three- to 4-day-old neonatal mice are more preterm and term infants. susceptible to L. monocytogenes than adults and have a mortality of 100% at doses of bacteria that do not kill adult animals. This susceptibility decreases by 9 to 11 days of age and corresponds with the 5. MURINE NEONATAL SUSCEPTIBILITY TO LISTERIA MONOCYTO- decrease in serum concentration of docosahexanoic acid that occurs GENES MAY BE CAUSED BY DEFICITS IN THE TRANSCRIPTION at weaning (10 days after birth). (2) In contrast to adults, 3- to 4- FACTOR INTERFERON REGULATORY FACTOR-1 (IRF-1) day-old neonates do not increase their abundance of IRF-1 mRNA K.M. Stewart1, M.A. Kielar2, D.R. Jeyarajah3, Y. Zhang2, after infection with L. monocytogenes. This may be an important J.S. Dunn2, V.K. Woodward2, A.C. Sorrells2 and C.Y. Lu2; factor in the increased susceptibility of neonates to infection. 1Pediatrics, UTSWMC, Dallas, TX, 2Internal Medicine, UTSWMC, Dallas, TX, 3Surgery, UTSWMC, Dallas, TX 6. CLINICAL CHORIOAMNIONITIS, ELEVATED CYTOKINES, AND BRAIN INJURY IN TERM INFANTS Purpose. Listeriosis is associated with significant morbidity/ L. Shalak, A. Laptook, H. Jafri, O. Ramilo and J. Perlman; mortality in human neonates but not in immunocompetent adults. Pediatrics, University of Texas Southwestern Medical Understanding the increased susceptibility of neonates to this Center at Dallas, Dallas, TX infection may improve clinical outcome. Previous studies show that docosahexanoic acid, a fatty acid found in high serum Purpose. Recent evidence suggests a role for inflammatory cytokines concentrations in the fetus and newborn, inhibits IRF-1 gene in the genesis of brain damage in term infants. Both infection and activation in interferon-gamma stimulated macrophages in vitro. ischemia are associated with elevated cytokines production. Deficits in this transcription factor will impair host defenses because IRF-1 initiates the interferon-gamma–mediated activation of genes Objective. To determine the initial inflammatory cytokine response important for immunity. We now report a murine model of listeriosis in term infants born to mothers with clinical chorioamnionitis (CA) used to test the hypothesis that enhanced neonatal mortality is due to and the relationship of this response to birth depression, abnormal deficient amounts of IRF-1 in the neonate. neurologic examination, and hypoxic ischemic encephalopathy (HIE). Methods. Adult and neonatal Balb/c mice received intraperitoneal injections of 5 (low dose) or 50 (high dose) bacteria (Listeria Design/Methods. CA infants admitted to NICU (n=61) were monocytogenes) per gram body weight. The mortality and bacterial studied prospectively. Cytokine concentrations were measured from

484 Journal of Perinatology 2001; 21:482 – 509 Abstracts AAP-Section on Perinatal Pediatrics

umbilical cord, at 6 hours, and at 30 hours. Control values (CTRL; Methods. A retrospective cohort study was conducted of ENTB n=50) were measured from cord blood samples from asymptomatic bacteremia and CVC in infants in a NICU over a 7-year period term infants born by repeat C-section. ELISA immunoassays were (1994–2000). Cases of ENTB bacteremia were identified from a performed for IL-1, IL-6, IL-8, RANTES, MIP1 , and TNF. Serial microbiology database and limited to late-onset cases occurring after blinded neurological examinations using Modified Dubowitz Scores 3 days of age. Clinical data were obtained from CVC and neonatal (MDS) were performed simultaneously with cytokines sampling at 6 databases. and 30 hours. Abnormal outcomes included Birth Depression defined as a need for positive pressure ventilation or Apgar score <6 at 5 Results. One hundred and nine cases of ENTB bacteremia occurred minutes; an abnormal MDS defined as >19; and HIE and/or in 97 infants, of which 33 were excluded: 12 died within 2 days of Seizures defined by AAP criteria. the first positive blood culture for ENTB and 21 did not have CVC. Blood cultures were positive for ENTB within a median of 11 hours Results. IL-6, IL-8, and RANTES only were elevated in CA (range: 5–44). Only 4 of 76 (5%) cases took >24 hours for blood infants. Only postnatal changes for the elevated cytokines are cultures to become positive. Timing of CVC removal was at the shown below. discretion of attending neonatologists. Twenty-nine cases had Cytokines A (Cord) B (6 hours) C (30 hours) early-removal CVC (ER-CVC) within 2 days and 47 cases had (pg/ml) Mean±SE Mean±SE Mean±SE late-removal CVC (LR-CVC) greater than 2 days after the first IL-6 1072±226 1451±214* 280±76** positive blood culture for ENTB. There were no significant IL-8 5243±3898 2324±1355* 1192±1106** differences between infants in ER-CVC and LR-CVC groups for birth 3 3 3 RANTES 95,917±26 50,355±4 * 41,920±3 weight, gestational age, case fatality rate, or recurrence of ENTB A versus B*; for B versus C**. bacteremia. ER-CVC cases had significantly shorter duration of ENTB bacteremia with a median of 1 day (range: 1–7) compared There was no relationship between cytokines and Birth to LR-CVC cases with a median of 3 days (range: 1–18), p=0.01. Depression. MDS correlated positively with IL-6 at 6 hours (r=0.5, Although 22 of 47 (47%; 95% CI: 32–62%) LR-CVC cases required p=0.01). The subgroup of infants that developed HIE and/or CVC removal to resolve ENTB bacteremia, 19 of 47 (40%; 95% CI: Seizures (n=5) was associated with significantly higher cytokines at 26–56%) LR-CVC cases resolved without removal of CVC. The 6 hours, i.e., IL-6 (3130 vs 1219), IL-8 (5433 vs 780), and RANTES remaining six cases had their CVC removed at times that precluded (92,177 vs 46,000) in (pg/ml) for HIE versus no HIE, respectively accurate evaluation of response to treatment. Thirteen of 17 (76%; ( p<0.05). 95% CI: 50–93%) LR-CVC cases with ENTB bacteremia lasting only 1 day resolved without CVC removal, but only 6 of 30 (20%; Conclusion. IL-6, IL-8, and RANTES are elevated in cord blood 95% CI: 8–39%) LR-CVC cases with >1 day of bacteremia of infants with CA. IL6 is the only cytokine with increased resolved without CVC removal. concentration at 6 hours after birth. IL6 is correlated with transient neurologic abnormalities, whereas the highest levels of Conclusion. (1) Failure to remove central venous catheters as all three cytokines are present in infants with HIE and/or seizures soon as Enterobacteriaceae bacteremia was detected in neonates was at 6 hours. These are the first observations linking chorioam- associated with significantly prolonged bacteremia. (2) Because nionitis and elevated blood cytokines to an abnormal neurological Enterobacteriaceae bacteremia is not necessarily due to CVC exam and HIE. infection in all patients, it may not be necessary to remove CVC in all cases.

7. SHOULD CENTRAL VENOUS CATHETERS BE REMOVED AS SOON AS ENTEROBACTERIACEAE BACTEREMIA IS DETECTED IN NEONATES? 8. ORAL–MOTOR SKILLS RESPONSIBLE FOR THE IMPROVED ORAL K.J. Nazemi1, M.G. Karlowicz1, R.E. Kelly, Jr.2 and FEEDING PERFORMANCE IN PRETERM INFANTS E.S. Buescher1; 1Pediatrics, Eastern Virginia Medical C. Lau, E.O. Smith and R.J. Schanler; Pediatrics, Baylor School, Norfolk, VA, 2Surgery, Eastern Virginia Medical College of Medicine, Houston, TX School, Norfolk, VA Purpose. Although the most frequent cause for delayed hospital Purpose. Controversy exists regarding the most appropriate acute discharge of preterm infants is their inability to feed orally, there is a management of central venous catheters (CVC) in neonates with paucity of data regarding the oral–motor skills needed to feed safely bacteremia, with several recent case series suggesting that removal of and successfully. An earlier study demonstrated that sucking CVC is often not necessary. Our objective was to determine whether efficiency, defined as the rate of milk transfer, improves over time. It CVC should be removed as soon as Enterobacteriaceae (ENTB) was hypothesized that such advancement was a result of increased bacteremia is detected in neonates. bolus size and/or swallowing rate.

Journal of Perinatology 2001; 21:482 – 509 485 AAP-Section on Perinatal Pediatrics Abstracts

Methods. Healthy preterm (n=12, 26–29 weeks’ gestation) and hundred and forty-three (5943–2506 in 1999 and 3437 in 2000) fullterm (n=8) infants were assessed at one to two and six to eight VLBW (0.5–1.5 kg) infants were provided care by Pediatrix Medical oral feedings per day and at 1 week and 2 to 4 weeks of life, Group. Eighty-seven centers reported data; 53 centers, which reported respectively. Outcomes were: rate of milk transfer (ml/min), sucking more than 15 VLBW infants in the database during the study periods, pattern (% time using suction/expression or expression only), bolus were used to establish the performance curves. We used these data to size (ml/sw), suction amplitude (mm Hg), swallowing and sucking compare overall improvements in the growth and outcome of (number/min) rate. These parameters were computed from the neonates cared for in 1999 and 2000 for each specific center and for average of two sucking bursts occurring within the first and last 2 our national group as a whole. minutes of the monitored sessions. Suction, expression, and swallows were monitored by means of a special device previously described. Results. (See table.) There were no significant differences in Milk transfer was measured from a graduated reservoir. gestational age (29±3 vs 29±3 weeks), birth weight (1.07±0.3 vs 1.07±0.3 g), reported antenatal steroid use (82% vs 84%), male Results. As rate of milk transfer increased with maturity, preterm gender (50% vs 52%), or small for dates (10% vs 10%) between the infants showed only a significant increase in the use of suction/ two study periods (1999 and 2000). Compared to 1999, averaged expression and suction amplitude ( p0.02). There was a daily weight gain increased in 2000 for both the first 28 days and significant difference in all variables between preterm and fullterm from birth to discharge. Despite no increase in length of stay, weight infants ( p<0.001). Bolus size and swallowing rate were not and head circumference at discharge increased. In addition, there correlated. However, when assessed simultaneously, both were was no evidence of adverse impact — in all inborn infants, the rates correlated with rate of milk transfer at both time periods ( p0.001, of severe IVH, NEC, mortality, and need for IMV at 28 days were not r0.8). There were also a significant relationship between bolus size different between 1999 and 2000. and suction amplitude ( p0.03, r0.55) and between swallowing and sucking rate ( p<0.001, r=0.77) at both times. Conclusion. Identification of a clinical outcome as an improvement target, and application of this method of rigorous observation, Conclusion. It is postulated that the increased bolus size was isolation, and implementation of meaningful differences were indicative of the infants’ ability to swallow larger volumes and/or successful. Weight gain for VLBW infants in our network of hospitals their improved sucking skills that allowed for greater volume/suck. increased during the year 2000 without adverse consequences. The latter is supported by the positive correlation between bolus size Continued semi-annual monitoring will be performed to establish and suction amplitude. The increase in swallowing rate may result the longevity and ability to sustain this improvement. from the maturation of the swallowing reflex, i.e., swallowing 1999 2000 p value occurred faster due to improved coordination of the swallowing n 2506 3437 musculature and/or the direct entrainment of sucking. The latter is Weight gain (first 28 days) 10.4±6 11.5±6 <0.01 supported by the positive correlation between swallowing and sucking Daily weight gain (to D/C) 18±5 19±5 <0.01 rate. In conclusion, the increase in milk transfer over time resulted HC at dismissal 31.8±2 32.1±2 <0.01 from increased bolus size and swallowing rate. In turn, the increase Mortality 9.6% 10.5% NS in suction amplitude and sucking rate are the respective factors that On vent day 28 16.7% 16.8% NS affected the improvement of these two components. IVH, grades 3–4 6.9% 6.8% NS NEC 5.2% 5.3% NS DC weight 2.15±0.5 2.25±0.5 <0.01 EGA at DC 38±3 38±3 NS 9. IMPROVING GROWTH OF VERY-LOW-BIRTH-WEIGHT INFANTS Mean±SD. DURING THE FIRST 28 DAYS IN THE NICU B.T. Bloom, R.H. Clark, J. Peabody, P. Thomas and The Weight Gain BDP Team; The Pediatrix–Obstetrix Center for Research and Education, Pediatrix Medical Group, 10. GLOBAL UNDERNUTRITION AND GROWTH FAILURE IN Sunrise, FL HOSPITALIZED VERY-VERY-LOW-BIRTH-WEIGHT INFANTS P.G. Radmacher1, S.T. Rafail2 and D.H. Adamkin1; Purpose. To track weight gain during the first 28 days of VLBW 1Pediatrics, University of Louisville, Louisville, KY, infants cared for by Pediatrix Medical Group after observing, isolating, 2Nutrition, Kosair Children’s Hospital, Louisville, KY and implementing meaningful differences in care processes. Purpose. Recently published studies have provided contemporary Methods. We previously reported the meaningful differences between neonatal growth grids for the very-very-low-birth-weight (VVLBW) sites with high and low average weight gain [Bloom, et al. Abstr infant. Comprehensive nutrient intake data were not included, nor Pediatr Res 2001.]. This is our impact report. Five thousand nine was intake compared with growth. The purpose of this study was to

486 Journal of Perinatology 2001; 21:482 – 509 Abstracts AAP-Section on Perinatal Pediatrics

substantiate growth patterns in (VVLBW) infants with nutrient intake pulmonary hypertension in critically ill newborns. When INO is data. instituted, infants are uniformly on 100% oxygen and vigorous mechanical ventilation. Neurodevelopmental outcomes of infants Methods. A retrospective chart review of infants admitted to Kosair enrolled in the NINOS study showed that newborns treated with INO Children’s Hospital NICU during 1998 and 1999 was conducted. had similar outcomes to that of infants treated with extracorporeal Eligible infants weighed 1000 g at birth, were 29 weeks’ membrane oxygenation, which has associated detrimental neuro- gestation, and free of major congenital anomalies. Admission within logic sequela. Therefore, neurodevelopmental toxicities associated 24 hours and survival greater than 7 days were required. Infants with with the exposure to INO in conjunction to hyperoxia need to be morbidities were included. Infants were stratified into three birth studied further. We hypothesize that developing newborn mouse pups weight cohorts: 600 g, 601 to 800 g, and 801 to 1000 g. Nutrient exposed to INO and hyperoxia will have lower percent brain per body intakes and weights were collected from birth to discharge or 100 days. weights than those exposed to hyperoxia alone.

Results. At no time during hospitalization did the mean weekly Methods. Two-week-old ICR mice (n=11 in each group) were intake for energy or protein (120 kcal/kg per day and 3.5 to 4.0 g/ exposed for 5 days to 95% oxygen (O2), 20 ppm NO (NO), 20 ppm kg per day, respectively) in any cohort reach current NO, and 95% oxygen (NO+O2) or room air (RA). The pups were recommendations. Despite these lower intakes, growth rates from weighed and the dams were rotated to room air every 24 hours. After return-to-birth-weight (RTBW) to discharge were comparable to 5 days of exposure, the pups were weighed, and the brains and lungs intrauterine rates of 14–16 g/kg per day. However, catch-up were harvested and weighed. The data were expressed as means growth, which exceeds intrauterine accretion rates, was not (SEM). Mouse growth was analyzed by repeated-measures ANOVA consistently achieved by any cohort. While 91% of infants was AGA and the organ weights were analyzed by two-way ANOVA. at birth (Lubchenco grids), only 47% was 10th percentile at hospital discharge ( p<0.001). Results. After 5 days of exposure, the mouse pups exposed to RA and Weight Change and Intake by 3-Week Intervals from RTBW to 12 Weeks NO, had an increase in weight gain, 1.07 (0.37) and 1.34 (0.32) g, Week of life 4–6 7–9 10–12 respectively, while the pups exposed to O2 and NO+O2 had a weight 600 g BW Cal/kg per day 92±27 102± 104±26 loss of 0.40 (0.11) and 0.69 (0.07) g, respectively, ( p<0.001). The n=11 Pro. g/kg per day 2.7±0.8 2.1±1.3 2.9±0.7 percent brain per body weight of the pups exposed to NO and Wt. g/kg per day 11±16 15±13 13±9 NO+O , 4.27 (0.29)% and 4.30 (0.17)%, respectively, were smaller 601–800 g BW Cal/kg per day 102±18 107±25 111±25 2 than that of the pups not exposed to INO, 5.14 (0.29)% in the RA n=35 Pro. g/kg per day 2.9±0.5 3.0±0.8 3.0±0.8 Wt. g/kg per day 15±10 14±9 12±6 group and 5.37 (0.19)% in the O2 group ( p<0.001). The percent 801–1000 g BW Cal/kg per day 106±24 117±17 114±17 lung per body weight in the oxygen-treated groups, 1.81 (0.10)% in n=27 Pro. g/kg per day 2.9±0.6 3.2±0.6 3.1±0.7 the O2 group and 2.03 (0.13)% in the NO+O2 group, was heavier Wt. g/kg per day 15±8 13±7 12±5 than that of the pups not exposed to oxygen, 1.27 (0.06)% in the RA group and 1.28 (0.05)% in the NO group,( p<0.001).

Conclusion. Growth failure may be partially due to early Conclusion. Exposure to 20 ppm INO exacerbated the effects of nutritional deficits, which often continue through convalescence, hyperoxia in the retardation of body growth in developing mouse without adjusting intake to provide for catch-up growth. To support pups. INO also retarded mouse pup brain growth independently of greater rates of growth, higher intakes of protein and energy may be hyperoxia and lung injury. Further investigation into neurologic required. Prospective trials of aggressive nutrition support throughout injury in the developing brain of mouse pups exposed to INO is hospitalization are needed. therefore warranted.

11. INHALED NITRIC OXIDE ADVERSELY AFFECTS BRAIN GROWTH IN 12. COMPARISON OF THREE TECHNIQUES OF PROGNOSTICATION IN THE DEVELOPING MOUSE PUP TERM INFANTS WITH HYPOXIC ISCHEMIC ENCEPHALOPATHY AND S.K. Whitbourne1, P.L. Ramsay1, S.E. Welty2, C.V. Smith2 CROSS-VALIDATION OF ARTIFICIAL NEURAL NETWORK–BASED and F.J. DeMayo3; 1Pediatrics, Baylor College of MODEL Medicine, Houston, TX, 2Pediatrics, Children’s Research P.S. Shah1, J. Beyene2 and M. Perlman1; 1Neonatology, Institute, Columbus, OH, 3Molecular and Cellular Hospital for Sick Children, Toronto, ON, Canada, Biology, Baylor College of Medicine, Houston, TX 2Pediatrics, Mount Sinai Hospital, Toronto, ON, Canada

Purpose. Inhaled nitric oxide (INO) is an important mode of Purpose. Different statistical approaches for prediction of long- therapy in the treatment of hypoxic respiratory failure secondary to term outcome in term infants with post-asphyxial hypoxic

Journal of Perinatology 2001; 21:482 – 509 487 AAP-Section on Perinatal Pediatrics Abstracts

ischemic encephalopathy (HIE) have yielded variable results. 13. PROSPECTIVE PRE-DISCHARGE (30±6 HOURS) DIAGNOSTIC Artificial neural network (ANN) has been found to make quite EVALUATION STRATEGIES FOR SEVERE NEONATAL accurate predictions in a variety of medical conditions. The HYPERBILIRUBINEMIA objectives of this study were: (1) to predict the individual adverse V.K. Bhutani1, L.H. Johnson1 and D.K. Stevenson2 outcome risk of term infants with HIE using three different (on behalf of the Jaundice Multinational Study Group); statistical techniques; (2) to compare ANN model, multiple 1Newborn Pediatrics, University of Pennsylvania School logistic regression analysis (MLRA), and classification and of Medicine, Philadelphia, PA, 2Pediatrics, Stanford regression tree (CART)–based models created at 240 minutes of University School of Medicine, Stanford, CA age; and (3) cross-validation of ANN model. Purpose. This report assesses whether end-tidal carbon monoxide Methods. Retrospective cohort study of 245 term infants with HIE (CO), corrected for ambient CO (ETCOc), in combination with attributed to intrapartum fetal asphyxia diagnosed by modified pre-discharge hour-specific total serum bilirubin (TSB) meas- American College of Obstetricians and Gynecologists criteria. urements, can differentiate between bilirubin load attributed to Severe adverse outcome was defined as death or major bilirubin production and/or delayed bilirubin elimination in sensorineural impairment detectable by age of 12 months. All infants who may unpredictably increase their TSB values during the three models were created using predictors found significant in first 7 days of life. univariate analyses as input parameters (Apgar score at 5 minutes, first base deficit value, age at onset of breathing, Methods. Using the database from nine multinational sites, 742 duration of chest compression, and onset of seizures within 4 neonates comprised this cohort study, which required measure- hours) and outcome as output parameter. ANN model perform- ments of both ETCOc and TSB at 30±6 hours of life, TSB at ance was cross-validated by leaving one variable out, leaving one 96±12 hours, and subsequent TSB following a hour-specific patient out, and three training and testing splits (75/25, 60/40, bilirubin nomogram (in Pediatrics 2001, in press). Hour-specific 50/50). Each split was randomly created 100 times to assess TSB >95th percentile at any time defined ‘‘severe’’ hyper- robustness of the model. bilirubinemia.

Results. Two hundred and eleven (86%) subjects had outcome data; Results. The table lists the distribution of infants according to 30±6 118 (56%) had severe adverse outcome. Comparison of the three hours TSB values (ranked by risk zones) with increasing ETCOc models is shown in the table. values (*p<0.001). In 36 of 742 (4.85%) infants, TSB values Model Sensitivity Specificity increased to an upward percentile track (or risk zone) by ‘‘jumping ANN 89 57 tracks’’ at 96±12 hours. Babies with TSB levels >75th percentile MLRA 79 57 track who ‘‘jumped’’ had mean ETCOc values of 1.7 ppm ( >75th CART 72 65 percentile). Mean ETCOc values were not elevated for babies that ‘‘jumped’’ up from TSB values in 40th to 75th percentile tracks Cross-validation of the ANN model revealed that sensitivity except those who ‘‘jumped’’ double tracks to severe hyper- varied from 77% to 85% and specificity varied from 56% to 61% bilirubinemia (n=2; ETCOc=2.3 and 1.7 ppm, >75th percentile of after elimination of one predictor each time. The mean sensitivity hour-specific ETCOc; p<0.01). Babies with TSB values <40th was 87% and the mean specificity was 56% with random percentile, unlikely to develop severe hyperbilirubinemia, had lower omission of one patient from model (performed 179 times). mean ETCOc values (all <1.7 ppm). Training and testing sets of different split revealed mean sensitivity of 73% to 76% and mean specificity of 48% to 50% for At 30±6 hours age At 96±12 hours Number of babies by ETCOc: Babies with Mean (range) prediction in testing sets. hour-specific mean±SD increased TSB ETCOc TSB percentiles (%) (range) values (30±6 hours) (‘‘jump tracks’’) in those who Conclusion. Overall, the sensitivity was higher with the ANN ‘‘jumped tracks’’ model than with MLRA- and CART-based models. This gain was >95th percentile, 2.1*±1.0 –– not offset by loss of specificity. Because prediction of adverse n=32 (4.3%) (1.0–5.8) 76–95th percentile, 1.6±0.5 11 1.7* outcome is important than prediction of good outcome in the n=126 (17.7%) (0.4–2.7) (0.8–2.1) context of emerging neuroprotective therapy trials, ANN may be 40–75th percentile, 1.5±0.5 14 1.5 the preferred method of predicting prognosis prior to decisions n=243 (34.2%) (0.2–2.7) (0.8–2.3) for enrolment in the trials. Cross-validation confirmed that this <40th percentile, 1.4±0.5 11 1.2 n=310 (43.6%) (0.2–2.9) (0.9–1.7) model is very robust; however, it needs validation in other Total n=742 1.6±0.5 36 1.5 cohort. (100%) (0.2–5.8) (0.8–2.3)

488 Journal of Perinatology 2001; 21:482 – 509 Abstracts AAP-Section on Perinatal Pediatrics

Conclusion. Measuring pre-discharge ETCOc to individually Conclusion. Our study suggests that little time is available for a identify increased bilirubin production (in babies with TSB values NICU nurse to add even a few minutes to pre-existing time demands >75th percentile) can differentiate increased bilirubin production to cope with slow computers (or anything else). If comprehensive from delayed bilirubin elimination as a basis for subsequent computerization of a NICU is to be helpful, the computers must ‘‘jumping of tracks’’ in babies with pre-discharge TSB values >75th decrease time spent in something like Charting or Communication. percentile tracks (22% of the babies). Further, 1% of babies (TSB Hardware and applications software will need redesign to support values 40–75th percentile) may ‘‘jump double tracks’’ to >95th users in intensive NICU environments. percentile track because of increased bilirubin production.

P1. MUSCLE-DERIVED MULTIPOTENT PRECURSORS ARE 14. WORKFLOW PROCESS OBSERVATIONS IN A NEONATAL DIFFERENTIALLY INDUCED TO FORM MUSCLE OR BLOOD CELLS INTENSIVE CARE UNIT IN VITRO W.H. Drummond1, J.L. Sowers2 and C.B. Thompson2; C.L. Royer and M.C. Yoder; Department of Pediatrics, 1Pediatrics, University of Florida College of Medicine, Wells Center for Pediatric Research, Indiana University Gainesville, FL, 2Clinical Informatics, University of Utah Medical Center, Indianapolis, IN College of Nursing, Salt Lake City, UT Purpose. To identify multipotent precursors found in skeletal Purpose. Existing PC computer systems and software were designed muscle and to induce differentiation of these precursors into for business work types, not ICU environments. Neonatal intensive skeletal muscle cells, cardiomyocytes, or blood cells, as evidenced care unit (NICU) work offers no place to sit, no desk space, low staff by morphologic characteristics in tissue culture, cell behavior typing skills, and limited person–time available, creating burst-like (spontaneous contraction), and mRNA expression of lineage- utilization patterns. All these important details differ markedly from specific transcripts. usual business-based situations. Specific references relating to NICU staff workflow or human factors concerns (light, noise, ergonomics) Methods. Lower extremity skeletal muscle was isolated from mouse were not found.The study was part of a project to develop a user- pups less than 1 month old. This tissue was digested using centered NICU database for bedside capture of patient data elements collagenase I, dispase II, and trypsin. The subsequent cellular slurry needed for a comprehensive daily note. was either preplated in accordance with previously published protocols, or was purified by flow cytometry using monoclonal Methods. We observed, documented to seconds, and analyzed in antibodies. We sorted two different populations of cells using a categorical groupings NICU nurse and respiratory therapist workflow combination of antigenic markers. The first population was negative processes in 240-minute observation blocks (60 patient hours) over for CD45 and c-kit, and positive for Sca-1. This population was day, night, and weekend shifts, after explaining the study in staff subdivided into CD34 positive and negative cells. The second meetings. Observers sat in corners with digital watches and log sheets. population was negative for markers of blood lineage and CD45. The Care processes out of the room (fetching feeds, meds, using hall resultant cell cultures were incubated in the presence of agents phones/computers, finding people) were not tabulated. known to induce muscle or blood cell differentiation, including FGF- 2 and BMP-4, DMSO, and 5-azacytidine. Cellular morphology and Results. The nurse work categories and percent of total time were: contractile behavior were compared to cultures incubated without direct patient care (22–34%), indirect patient care (11–21%), these agents. After a period of growth in culture, these cells were charting (8–14%), communicating (11–24%), computer use analysed by RT-PCR for mRNA transcripts specific for blood cells, (3–11%), cleanup (2–3%) and miscellaneous (3–14%). More cardiomyocytes, and skeletal muscle. than 100% of theoretically available nurse/respiratory therapist hours were counted from observed jobs within the pod because Results. We observed that preplated or sorted cells cultured categories overlapped into ‘‘doing more than one thing at once’’ without the specified agents undergo a predictable sequence of (8–23%). Important patient care processes can take just 3 skeletal myogenesis. When cells were incubated in the presence seconds (checking, resetting, and charting an alarming syringe of FGF-2 and BMP-4, cellular morphology was altered and pump). Communication included phone calls from parents, skeletal muscle differentiation was impaired. However, both answering and sending pages, discussing processes and plans DMSO and 5-azacytidine supported and enhanced skeletal between different caregivers, and bedside interactions with often myogenesis when compared to controls. DMSO-treated cultures upset, crying, or confused family members who visit often. were capable of spontaneous contraction, as were control Importantly, expected communication chores were not considered preplated cultures. We are currently assaying the cultured cells in the acuity matrix that nursing administration used to adjust for evidence of mRNA transcripts specific to blood, cardiomyo- staffing ratios. cytes, or skeletal muscle.

Journal of Perinatology 2001; 21:482 – 509 489 AAP-Section on Perinatal Pediatrics Abstracts

Conclusion. FGF-2, BMP-4, DMSO, and 5-azacytidine differ- at discharge. There were no significant temporal trends for the entially induce the formation of muscle or blood cells from muscle- incidence of RDS, BPD, or CLD from 1992 to 1999 despite a derived multipotent precursors. significant increase in the use of antenatal steroids (10–61%, p<0.001) and of high-frequency ventilation (0–20%; p<0.001) during these 8 years. There were no significant effects P2. RESPIRATORY MORBIDITY IN PREMATURE INFANTS 32 of multiple births, or race on the incidence of BPD or CLD; but WEEKS’ GESTATIONAL AGE IN THE ERA OF SURFACTANT USE RDS was significantly higher in whites ( p=0.03). As in (1992–1999) previous reports, males and out-born infants had significantly N. Hussain and T.S. Rosenkrantz; Pediatrics, University higher incidences of BPD ( p=0.002 and 0.0003) and CLD of Connecticut Health Center, Farmington, CT ( p=0.003 and 0.04). Purpose. The widespread use of surfactant and prenatal steroids Conclusion. This study presents the incidence of respiratory since 1991 had significant impact on survival and morbidity in morbidity in the era of surfactant use. Despite advances in care, the premature infants, especially those at 32 weeks’ gestational age incidence of respiratory morbidity has not changed significantly in (GA). However, it is unknown whether there has been a continual recent years. Findings from this single center study, however, need to improvement in respiratory morbidity of these infants with other be confirmed with other centers. advances since. The aim of this study was to describe the GA-related incidence of survival and respiratory morbidity in infants 32 weeks during 1992 to 1999. P3. DEVIATION OF THE ENDOTRACHEAL TUBE FROM MIDLINE Methods. A retrospective review of 3526 admissions from January DIMINISHES THE EFFICACY OF HIGH-FREQUENCY VENTILATION 1992 to December 1999 from a single tertiary NICU was done. Of the M.R. Goldstein, G.I. Furman, C.G. Ochikubo, 1381 infants 32 weeks’ GA, 133 (10%) died and 1248 were M.L. Pernia, L.L. Yang, B.D. Sindel, P. Lawas-Alejo and discharged. Respiratory morbidity in survivors was categorized as: G.I. Martin; Department of Neonatal Medicine, Pediatrix RDS, median ventilator days, BPD (O2 requirement at 28 days of Medical Group, Citrus Valley Medical Center, West age), CLD (O2 requirement at 36 weeks post-menstrual age), and Covina, CA discharge from the NICU on O2 therapy. Purpose. The proper positioning of the endotracheal tube in the Results. From 1992 to 1999, the patient demographics in this NICU neonatal trachea is never completely certain. Rotation of the baby were uniform. GA-dependent survival and respiratory morbidity are relative to the midline may cause considerable tension and shown in the table. resultant torsion. The addition of the ‘‘Murphy Eye’’ prevents absolute occlusion of the endotracheal tube lumen should the GA Patient RDS Survived Median BPD n CLD n Discharged number n n (%) ventilator (% survivors) (% survivors) on main outlet become ‘‘embedded’’ in the endotracheal wall. (%) days O2 n (%) Torsion of the trachea from a misplaced endotracheal tube may 23 44 43 16(36) 76 13(81) 12(75) 12(75) diminish the effectiveness of HFOV through absorption and (98) 24 93 84 54(58) 71 36(67) 26(48) 17(32) deviation of the bulk waveform. However, the diminished (90) endotracheal tube surface area for propagation of HFOV may 25 95 90 74(78) 60 63(85) 43(58) 15(20) cause significant change in the waveform output and result in (95) flow diminution. 26 90 80 84(93) 45 69(82) 45(54) 24(29) (89) 27 88 77 80(91) 35 56(70) 35(44) 16(20) Methods. For this study, the ventilator arm of a Sensormedics (88) 3100A high-frequency oscillator was connected in-line to the flow 28 156 126 146(94) 24 87(60) 58(40) 21(14) anemometer of Bicore CP-100 pulmonary function monitor and (81) 29 159 104 150(94) 13 59(39) 43(29) 19(13) then to an endotracheal adapter. This was in turn attached to an (65) endotracheal tube inserted in a test lung of known compliance. 30 178 103 175(98) 7 36(21) 28(16) 8(5) Using ventilator settings of PAW 10.5, f 10 Hz, and I time 0.33, (58) amplitude was varied from 10 to 40 cm. The as-previously- 31 189 72 184(97) 3 14(8) 12(7) 6(3) (38) described flow equation: Flow= –57.62+exp 32 289 80 285(99) 3 9(3) 9(3) 4(1) (3.588+0.01546*Amplitude+0.03034*Tube Size) (Snowbird, (28) 1995) was applied to the measured surface area of the Murphy Eye of a Tyco Sheridan Endotracheal tube and compared to the The overall incidence of RDS was 62%. Among survivors, surface area of the outlet of a non-occluded tube (i.e., the BPD was 35%, CLD was 25%, and 12% needed supplemental O2 internal diameter).

490 Journal of Perinatology 2001; 21:482 – 509 Abstracts AAP-Section on Perinatal Pediatrics

Results. Results are as presented in the table below. MO=91±18), paCO2 (ECMO=46±20 mm Hg, non-EC- ETT size Murphy Eye/ Amplitude 15 20 30 40 MO=39±13 mm Hg) within 6 hours of transfer. ECMO patients ETT SA had a lower paO2 at 6 hours after transfer compared to non- 2.5 2.4 mm2 / Flow Murphy 19.9/ 26.2/ 40.2/ 56.5/ ECMO patients (62±48 vs 95±49, p=0.02) and a higher 4.9 mm2 Eye/Midline 39.8 47.6 65.2 85.7 oxygenation index (52±41 vs 31±13, p=0.02). 3.0 4.7 mm2 / 36.8/ 46.0/ 63.3/ 83.5/ 7.1 mm2 55.7 64.8 85.3 109 3.5 7.8 mm2 / 62.8/ 70.5/ 92.0/ 117/ Conclusion. (1) Fifty-five percent of patients with MAS 2 9.6 mm 74.3 84.9 109 136 transferred due to PPHN failed to response to iNO and required 4.0 9.4 mm2 / 74.3/ 83.1/ 107/ 134/ 12.5 mm2 95.9 108 136 168 ECMO. (2) Persistent hypoxemia despite iNO predicts the need for ECMO. (3) Mean airway pressure, paCO2, and FiO2 does not predict ECMO needs. (4) Patients with MAS and severe PPHN Conclusion. From the results, there is a clear attenuation of flow should be transferred to an ECMO center without delay, especially incurred with occlusion of the main lumen of the endotracheal if no immediate improvement in oxygenation is demonstrated tube. This effect is more pronounced in the smaller tubes at lower with initiation of iNO. amplitudes (where up to 50% of entrained flow may be lost) than in larger tubes at higher amplitudes. Intubated neonates ventilated through the Murphy Eye are at significant risk for oscillation P5. USE OF FIBRIN GLUE FOR PERSISTENT PNEUMOTHORAX IN failure. NEONATES S. Sarkar1, N. Hussain1 and V. Herson2; 1Neonatology, University of Connecticut Health Center, Farmington, CT, P4. INHALED NITRIC OXIDE THERAPY SHOULD NOT DELAY 2Neonatology, Connecticut Children’s Medical Center, TRANSFER TO AN EXTRACORPOREAL MEMBRANE OXYGENATION Hartford, CT CENTER FOR NEONATES WITH MECONIUM ASPIRATION SYNDROME V. Chan, G. Tibaldi, N. Subramanian and P.S. Friedlich; Purpose. Fibrin glue is a biologic tissue adhesive found to be an Division of Neonatology, Department of Pediatrics, effective sealant and topical haemostatic agent consisting of Children’s Hospital Los Angeles, Keck School of concentrated fibrinogen and factor XIII combined with thrombin and Medicine, University of Southern California, Los calcium to form a coagulum. The intrapleural injection of fibrin Angeles, CA glue for intractable pneumothorax (PTX) has been reported to effective in two previous case reports of premature infants. Because Purpose. Inhaled nitric oxide (iNO) improves oxygenation in term the published data are limited, we reviewed our experience with fibrin and near-term infants with persistent pulmonary hypertension glue for persistent PTX to determine its efficacy and safety in this (PPHN) and reduces the need for extracorporeal membrane high-risk population. oxygenation (ECMO). The iNO response for patients with meconium aspiration syndrome (MAS) is often unpredictable. The purpose of Methods. Computerized databases (1990–present) from two this study was to determine: (1) the proportion of neonates with MAS tertiary care NICUs were used to identify patients who received unresponsive to iNO who required ECMO; and (2) clinical factors fibrin glue for PTX. Detailed chart reviews were performed on predicting the response to iNO. identified patients.

Methods. Retrospective review of all term neonates with MAS, Results. Eight infants with intractable PTX despite conventional referred to Children’s Hospital Los Angeles (CHLA) for iNO/ECMO management (chest tube drainage/high-frequency oscillation) between 1/1/1998 and 12/31/2000. Demographics, respiratory received a total of 10 fibrin glue treatments. Patients received support, arterial blood gases, and iNO/ECMO needs were reviewed. fibrin glue according to standard protocol. Separate injections of a Results expressed as mean±SD. thrombin/calcium chloride mixture and cryoprecipitate were introduced into the intrapleural air pocket through an Results. Forty-nine term neonates with MAS were transferred to angiocatheter, while the chest tube was briefly clamped. Mean CHLA due to PPHN. Twenty-seven (55%) required ECMO at a gestational age: 25 weeks (range 24–29), mean birth weight: mean age of 58±55 hours. No difference between ECMO and 1080 g (range 440–3455). Male to female ratio was 5:3. Seven of non-ECMO patients were noted in terms of birth weight eight infants were extremely premature [24 weeks (n=4), 25 (ECMO=3283±579 g, non-ECMO=3372±519 g), age of weeks (n=1), 26 weeks (n=1), 29 weeks (n=1)]. The eighth transfer (ECMO=30±32 hours, non-ECMO=37±32 hours), infant was a 39-week neonate with pneumonia and a persistent ventilatory mean airway pressures (ECMO=20±2 cm H2O, non- right-sided pneumothorax. The fibrin glue was used when the ECMO 19±6 cm H2O), FiO2 (ECMO=94±19, non-EC- PTX had persisted for an average of 9.8 days (range: 8–16). Six

Journal of Perinatology 2001; 21:482 – 509 491 AAP-Section on Perinatal Pediatrics Abstracts

of eight infants had reduction or resolution of air leak within 24 cations such as sepsis, lower extremity vascular events, focal hours of therapy with discontinuance of the chest tube(s) at a gastrointestinal perforation, and necrotizing enterocolitis were mean of 6 days (range 3–12) later. Re-occurrence of air leak documented. We identified 31 infants (study n=11; control n=20). occurred in two of these infants 1 week later and responded to a second course of therapy. Two infants who were critically unstable Results. We compared 50 ABG samples from each group. received fibrin glue but died hours later. Their response to therapy Regression analysis was used to compare pH, pCO2, and pO2 could not be adequately determined. Of the six responding infants, values obtained from the sensor and from laboratory analysis. The one died from respiratory failure 3 weeks later, four survived with pH, pCO2,pO2 correlated highly with a coefficient gradient of severe broncho-pulmonary dysplasia, and one is doing well at 2 0.972, 0.915, and 0.927, respectively. The average number of gases months of age. The complications encountered were bradycardia obtained by both methods was not significantly different requiring manual ventilation (n=2), significant hypercalcemia in ( p<0.225). However, the amount of blood removed for gas (n=2) (total calcium 17–18 mg/dl), diaphragmatic paralysis analyses was significant higher in the control group ( p<0.0001). (n=2), PTX on the contralateral side (n=1), and significant The total blood volume removed in the first 6 days was 12 ml for localized tissue necrosis (n=1). the study group compared to 16 ml for the control group ( p<0.021). The number of transfusions in the first 2 weeks was Conclusion. This series confirms the efficacy (75%) of the also lower for the study group ( p<0.019). Catheter-related intrapleural injection of fibrin glue for treatment of intractable PTX. complications were not significantly different. This therapy has significant risks, however, and therefore should be reserved for patients not responding to an adequate trial of Conclusion. We demonstrated an excellent ABG correlation between conventional treatments. the intra-arterial sensor and the laboratory measurement without increased complications. Our data also indicate that an intra-arterial blood gas monitor can reduce the amount of iatrogenic blood loss P6. IN-LINE ARTERIAL BLOOD GAS MONITORING IN THE NEONATAL resulting in a decreased number of blood transfusions within the first INTENSIVE CARE UNIT 2 weeks of life. Z. Ghorishi, G. Cummings and J.T. Adams; Neonatology, St. John Hospital and Medical Center, Detroit, MI P7. EXTRACORPOREAL MEMBRANE OXYGENATION NEED MAY BE Purpose. The neonatal intensive care unit has seen increased PREDICTED BY 6 HOURS OF INHALED NITRIC OXIDE THERAPY IN survival of very-low-birth-weight infants. Monitoring of respira- NEONATES WITH CONGENITAL DIAPHRAGMATIC HERNIA tory status by frequent arterial blood gases is critical in the T. Brady, M. Ramirez, M. Kriscunas, N. Subramanian management of these very sick neonates. To optimize clinical and P.S. Friedlich; Division of Neonatology, Department outcome, prompt ventilator adjustments need to be made in of Pediatrics, Childrens Hospital Los Angeles, Keck response to the rapid changes associated with their dynamic lung School of Medicine, University of Southern California, disease. However, arterial blood gas measurements may have Los Angeles, CA associated negative consequences. A primary concern is that because of the infant’s smaller circulating blood volumes, frequent Purpose. Inhaled nitric oxide (iNO) improves oxygenation in term blood transfusions are needed to replace on-going iatrogenic and near-term infants with persistent pulmonary hypertension blood loss. Intra-arterial blood gas monitors are now available. (PPHN) and reduces the need for extracorporeal membrane The reliability and efficacy of these monitors have not been well oxygenation (ECMO). The iNO response for patients with congenital studied in the neonatal intensive care unit. We evaluated this diaphragmatic hernia (CDH) is often unpredictable. The purpose of technology in a level III neonatal intensive care unit. Specifically, this study was to determine (1) the proportion of neonates with CDH we correlated the accuracy of the blood gas obtained by the intra- unresponsive to iNO who required ECMO, and (2) the clinical factors arterial device with standard laboratory analyses and assessed the predicting the need for ECMO. impact of this type of monitoring on the frequency of blood transfusions. Methods. Retrospective review of all term neonates with CDH, referred to Children’s Hospital Los Angeles (CHLA) for iNO/ECMO Methods. Selection criteria included infant’s birth weight 1250 g, between 1/1/1998 and 12/31/2000. Demographics, respiratory gestational age 30 weeks, diagnosed with respiratory distress support, arterial blood gases, and iNO/ECMO needs were reviewed. syndrome, and having an umbilical artery catheter in place for at Results were expressed as mean±SD. least six postnatal days. Charts were reviewed for all infants born between July 1998 and December 2000. Demographics, cardio- Results. Twenty-seven term neonates with CDH were transferred respiratory status, laboratory results, and catheter-related compli- to CHLA with PPHN. Fifteen (55%) required ECMO at a mean

492 Journal of Perinatology 2001; 21:482 – 509 Abstracts AAP-Section on Perinatal Pediatrics

age of 57±105 hours. No differences between ECMO and non- be affected by posture ( p<0.01). Paradoxically, QT and QTc were ECMO patients were noted in terms of birth weight longer in the supine than in the prone position. (ECMO=3402±356 g, non-ECMO=3147±562 g), Apgar scores, Supine Prone age at transfer (ECMO=19±41 hours, non-ECMO=12±20 QT QTc QTd QT QTc QTd (msec) (msec) (msec) (msec) (msec) (msec) hours), mean airway pressure (ECMO=16±4 cm H20, non- Machine 262±13 415±13 259±12 412±10 ECMO=16±7 cm H20), FiO2 (ECMO=93±14, non-EC- MO=79±27) by 6 hours of transfer. At 6 hours of transfer, Cardiologist 1 259±16 409±18 10±11 257±16 409±19 12±11 Cardiologist 2 255±17* 403±21* 10±9 250±18# 398±20# 13±11 ECMO patients had lower paO2 than non-ECMO patients (59±44 *p<0.001 cardiologist 2 versus machine; #p<0.001 cardiologist 2 versus machine and vs 99±68 mm Hg, p<0.001) and higher paCO2 (47±20 vs cardiologist 1. 38±13 mm Hg, p<0.01). Mean oxygenation index at the time of ECMO was 45±19. Conclusion. QT indices of preterm infants are similar to those previously reported for healthy term newborn infants. The prone Conclusion. (1) Fifty-five percent of patients with CDH failed to sleep position does not prolong QT indices. It is unlikely that improve with iNO and required ECMO. (2) At 6 hours of iNO therapy, arrhythmia secondary to prolongation of the QT interval is a persistent low paO2 and high paCO2 predict the need for ECMO. major cause of SIDS in this population. Therefore, obtaining QT indices in preterm infants prior to NICU discharge is not P8. EFFECT OF PREMATURITY AND SLEEPING POSITION ON QT warranted. INDICES

H.S. Tawakol, S.B. Fishberger, A.A. Romano and A.M. P9. LEFT VENTRICULAR CARDIAC FUNCTION OF TRANSIENT Steele; Neonatal, Schneider Children’s Hospital, New TACHYPNEA OF NEWBORN WITH LOW CARDIAC OUTPUT — LEFT Hyde Park, NY CARDIAC DIASTOLIC DYSFUNCTION INFLUENCED RESPIRATORY Purpose. A prolonged QTc ( >440 msec) has been purported as a DISTRESS risk marker for sudden infant death syndrome (SIDS) in term T.L. Yokoyama and M. Iwasa; Pediatrics, Nagoya Daini infants [Schwartz, et al. NEJM 1998;338:1709–1714.]. Prematurity Red Cross Hospital, Nagoya, Aichi Prefecture, Japan and prone sleeping position significantly increase the risk of SIDS. Thus, if prolonged QTc is a major cause of SIDS, QT indices should Purpose. We found TTNB with low CO. Therefore, we studied their be affected by prematurity and/or posture. Therefore, we determined left ventricular cardiac function. the effect of sleeping position on QT indices in preterm infants nearing discharge from the NICU. Methods. Cardiac function was assessed in 28 infants admitted to the neonatal intensive care unit. Group 1 consisted of three infants Methods. Twelve-lead EKGs were done in both supine and prone who had TTNB with low CO. Their COs were less than –1.9 SD positions in sleeping preterm infants <34 weeks’ gestation prior for group 2. Case 1: 3255 g, 37w4d. Case 2: 3212 g, 39w5d, to discharge from NICU. QT and QTc intervals were determined Down’s syndrome. Case 3: 1858 g, 35w4d. Group 2 consisted of by EKG machine (Marquette, recording at 25 mm/sec paper control infants who were 25 very-low-birth-weight infants speed) and by two cardiologists blinded to sleep position and without inotropic agents. Cardiac function of both group was patient information. Manual QT interval measurements were assessed by echocardiographies; two dimension, M-mode, Doppler obtained by a caliper as an average of five non-consecutive mode, tissue Doppler imaging (TDI). We calculated the end- cardiac cycles in lead 2. QTc was determined by dividing the QT systolic wall stress, rate-corrected mean velocity of circumferential interval on the square root of the RR interval (Bazett’s formula). fiber shortening, CO, left ventricular inflow velocity, and velocity of QT dispersion (QTd) was also determined by the two the mitral annular motion. Group 1 was studied once a day from cardiologists. Data were compared between sleeping positions and their admissions to the improvements of their CO within ±1.0 SD among machine and the two cardiologists by ANOVA, Tukey- for Group 2. Group 2 was studied 12, 24, 48, and 96 hours after Kramer, and paired t-test. birth.

Results. Forty-seven infants with birth weight 1398±600 g and Results. The blood pressure of group 1 was no hypotension. Their 29.2±3.1 weeks’ gestational age were studied at discharge weights of chest X-ray showed cardiomegaly and pulmonary venous congestion. 2245±43 and at 35.5±2.1 weeks postmenstrual age. In eight The contractilities between both groups were no different according to subjects, unrelated to sleep position, at least one EKG was found to the force–velocity relationship. The shunt flows of group 1 were left have a QTc >440 msec by machine and/or a cardiologist. However, to right shunts at their patent ductus arteriosus and interatrium. in no case was there unanimity that the QTc was >440 msec. Sleep Their COs were showed lower than –1.0 SD CO for A wave velocity of position did not affect QTd. Only cardiologist 2 found QT and QTc to mitral valve on TDI at admission. And the improvements of their

Journal of Perinatology 2001; 21:482 – 509 493 AAP-Section on Perinatal Pediatrics Abstracts

respiratory conditions were accompanied by the improvements of Cord hemoglobin did not correlate with MAP at 2, 3, and 4 hours. their relationship between A wave and CO. Furthermore, MAP did not change following packed red cell Tx. Forty-four percent of 54 concordant and 26% of 54 discordant twins Conclusion. We concluded that their left ventricular diastolic were treated for hypotension. Neonatal mortality was 48% for dysfunction without contractility dysfunction caused their low CO, concordant, 56% for 27 small, and 44% for 27 large discordant twins. and their diastolic dysfunction influenced their respiratory distresses. Conclusion. BP increased in all twins from birth to 24 hours. In concordant twins, males were less stable and had lower BP than P10. BLOOD PRESSURE VALUES DURING THE FIRST 24 HOURS FOR females. BP was higher among larger discordant twins. Whether 800 G BIRTH WEIGHT CONCORDANT AND DISCORDANT TWINS concordant or discordant, a significant number of twins required L. Cordero, H.H. Waters and J.R. Johnson; Pediatrics and treatment for hypotension. Obstetrics and Gynecology, The Ohio State University Medical Center and Public Health, Columbus, OH P11. CURRENT PRACTICE REGARDING THE ENTERAL FEEDING OF Purpose. To retrospectively determine mean arterial blood pressures HIGH-RISK NEWBORNS WITH UMBILICAL CATHETERS IN SITU for concordant and discordant extremely low birth weight (ELBW) K.F. Tiffany, B. Burke, C. Collins-Odom and D.G. twins during the first 24 hours of life. This will aid in the diagnosis of Oelberg; Pediatrics and Center for Pediatric Research, hypotension in this unique patient population as clinical signs may Eastern Virginia Medical School, Norfolk, VA be subtle and blood pressure reference values are not available. Purpose. Textbooks either fail to address or discourage the practice Methods. On admission to the NICU, blood pressures (BP) were of concomitant enteral nutrition (EN) in high-risk newborns with taken by oscillometry, all others by transducer via umbilical artery umbilical venous catheter (UVC) and umbilical arterial catheter (MAP). We studied 27 sets of concordant and 27 sets of discordant (UAC) usage. The only clinical trial addressing these practices is a (birth weight difference 20%), consecutively born twins (1989– recent small, but randomized, controlled trial of enterally fed 2001). Gestational age (GA) was determined by first trimester US newborns with UACs in situ [Davey, et al. J Pediatr 1994.] that did (2/3) and OB/Ped hx (1/3). Stable patients were defined as having not demonstrate any adverse consequences. We speculate that umbilical cord Hgb >14 g/dl, non-acidotic blood gases (albeit concomitant EN with UVC and UAC usage is more common than ventilated), never treated for hypotension, and survived at least 7 textbooks suggest — practiced by at least 20% of all US neonatal days. intensive care units (NICUs). The purpose of this study was to determine the prevalence of NICUs where high-risk newborns with Results. Concordant and discordant twins were similar in UVC or UAC placements receive concomitant EN. demographics, history of antenatal steroids (50% and 48%), incidence of preterm labor (78% and 56%), chorioamnionitis (17% Methods. Medical Directors listed in the AAP US Neonatologists and and 4%), preeclampsia (15% and 11%), Cesarean delivery (74% and Perinatologists Directory were surveyed by mail. Upon return of 87%), and neonatal mortality (48% and 50%), but were different in surveys, responses to multiple choice questions were recorded by mean birth weight (699 and 801 g) and GA (25 and 27 weeks). electronic scanning validated by manually conducted quality control Stable were 14 (26%) concordant and 22 (41%) discordant twins. checks. NICU identities were recorded by code to maintain Regardless of birth weight (range 550–910 g), concordant twins anonymity. had similar BP on admission and through 24 hours. At 3 hours, MAP was 25 Torr for 24 weeks’ and 31 for 25 weeks’ GA (r=0.53). Results. Following two requests for survey participation, 70% (549/ Although their mean birth weights were similar (703 and 696 g), 23 785) of surveys was returned. Respectively, 82% and 62% of NICUs concordant males had significantly lower MAP throughout than 31 with and without training programs were represented. On average, concordant females. Among them, 91% males and 60% females were surveyed medical directors had practiced neonatal medicine considered not stable. Discordancy in birth weight (range 20–71%) 18.1±0.3 years. Of surveyed NICUs, 99% reported placement of UVCs increased in proportion to GA. Of 27 discordant sets, 80% was and UACs. Of the 92% believing that it is safe to provide trophic EN to identical and, of them, 80% related to twin–twin Tx. Discordant newborns with UVCs in place, 51% practiced this some of the time, ELBW twins were divided by birth weight into 27 small (617 g) and and 37% practiced it most of the time. By comparison, it was reported 27 large (984 g); their BPs were different ( p<0.05): 27 and 37 that newborns with UACs in place receive trophic EN most of the time (admission), 26 and 36 (1 hour), 29 and 36 (6 hours), 30 and 34 (30%), some of the time (49%), or none of the time (22%). Of the (12 hours), 31 and 36 (18 hours), and 32 and 38 (24 hours). 80% believing that it is safe to provide more complete EN to newborns Although of different mean GA, small discordant (27 weeks) and all with UVCs in place, 44% practiced this some of the time, and 24% concordant twins (25 weeks) had similar birth weight and MAP. practiced it most of the time. For newborns with UACs in place, more

494 Journal of Perinatology 2001; 21:482 – 509 Abstracts AAP-Section on Perinatal Pediatrics

complete EN was provided most of the time (15%), some of the time recent onset of abnormal signs and symptoms ( p<0.001); and the (36%), or none of the time (49%). participating study center ( p<0.019). Enterally administered caffeine is not a significant variable ( p=1.0). Stepwise multiple Conclusion. Concurrent UVC and UAC usage with EN is more linear regression (MLR) excluding study center identified the commonly practiced than suggested by textbooks or published following significant variables: recent enteral theophylline, newly articles. The relative risk–benefit profiles of these practices remain diagnosed r/o sepsis, drug administration (midazolam, catechol- uncertain secondary to the limited number of controlled clinical amines, or cisapride), the 5-minute Apgar score, maternal observations and to the infrequent occurrence of adverse events. A preeclampsia, and maternal steroid therapy <24 hours prior to prospective, multicenter, controlled trial would address the continued delivery. When these variables are controlled, study center remains a advisability of these unexpectedly common practices. statistically significant variable. However, study center is highly correlated with midazolam use ( p<0.001). P12. GASTRIC ASPIRATES IN ENTERALLY FED, EXTREMELY LOW Conclusion. In conclusion, this study describes the nature and BIRTH INFANTS characteristics of the GAs of enterally fed ELBW infants. Enterally 1 2 R.E. McClead, Jr. , W.A. Engle and 1999 Nachri Nicu administered theophylline, but not caffeine, is associated with an 3 1 Focus Group ; Pediatrics, Children’s Hospital, increased number of GAs ( >2 ml). Columbus, OH, 2Pediatrics, Indiana University, Indianapolis, IN, 3Management Information Services, National Association of Children’s Hospitals and Related P13. ARE LOW-BIRTH-WEIGHT INFANTS AT RISK OF DEVELOPING Institutions (NACHRI), Alexandria, VA SEVERE CARNITINE DEFICIENCY? N.V. Esteban-Cruciani1, V.V. Gopalareddy 2 and Purpose. Gastric aspirates (GAs) are common during enteral D. Singh1; 1Albert Einstein College of Medicine, CHAM, feeding of extremely-low-birth-weight (ELBW) infants. Their Bronx, NY, 2Department of Pediatrics, UMDNJ, significance is often uncertain. The purpose of this study was to Morristown, NJ determine the significant factors associated with GAs. Purpose. Despite improved neonatal care and survival of low-birth- Methods. We collected data on 64 ELBW infants admitted to six weight (LBW) infants, rates of neurosensory abnormalities have not participating centers of the 1999 NACHRI NICU FOCUS group. Data changed. Several biological factors contribute to sensorineural included patient demographics, feeding and GA characteristics, and morbidity. A growing body of evidence suggests that micronutrients, associated factors. Data were recorded for every GA obtained from in particular L -carnitine, may be vital to neuronal mitochondrial initiation of enteral feeds until the patient had received >100 kcal/ metabolism, cell protection, and survival. LBW neonates have kg per day for 5 days. For statistical analysis, data from each infant decreased tissue stores of carnitine and limited ability to synthesize it. were aggregated. The fraction of each subject’s GA >2 ml was In the 1980s, several investigators demonstrated that, in contrast to compared to other variables by univariate and multivariate analysis breast-fed or formula-fed infants, LBW neonates receiving standard using SPSS 10.0 for Windows. total parenteral nutrition (TPN), which lacks carnitine, readily develop severe carnitine deficiency. We hypothesized that most LBW At birth, subjects were 25±1.5 weeks’ EGA, and weighed Results. infants in the US do not receive L -carnitine–supplemented TPN, and 749±115.4 g. Thirty-six infants (56.3%) had RDS treated with are therefore at risk of developing severe carnitine depletion and its surfactant, 52 (81.3%) were mechanically ventilated, and 46 associated neurosensory morbidity. (71.9%) received Indocin prophylaxis within 72 hours of birth. None had NEC. A total of 10,255 GAs were obtained from infants fed gastric Objective. To determine current practices regarding carnitine bolus (52.8%) or continuous drip feeds (32.3%). Infants were fed deficiency screening and L -carnitine TPN supplementation in LBW breast milk (51.7%) or commercial formulae (48%). Only 2747 GA infants ( <36 weeks and <2500 g). of fed-infants contained a measurable volume; the median GA volume was 1 ml (1.5 ml, 75 percentile). GAs were digested milk Methods. A 20-item written survey was mailed to a randomized (54.8%), undigested milk (21.8%), clear/yellow (6.1%), or bilious sample of 506 physicians drawn from a list of all board-certified (2.1%). In response to GAs, feedings were unchanged (82.6%), held neonatologists in the US (n=3037). Response rate=55% after two (3.1%), volume decreased (2%), or volume increased (12%). mailings. The survey assessed physicians’, institutions’, and patients’ Enteral medications were associated with 6.6% of all GA characteristics, as well as physicians’ practices regarding carnitine [methylxanthines (55%), iron (20%), and vitamins (16%)]. deficiency screening and TPN supplementation in LBW neonates. Univariate analysis identified three variables associated with a Questionnaire design, data entry and processing, and analysis were subject’s fraction of GA >2 ml. These were enteral administration of performed using an integrated software package (SphinxSurvey, theophylline prior to the feed that resulted in the GA ( p<0.006); the Scolari Sage Publications).

Journal of Perinatology 2001; 21:482 – 509 495 AAP-Section on Perinatal Pediatrics Abstracts

Results. Physicians’ characteristics: the majority of physicians Conclusion. Continuous IV glucagon for treatment of hypoglycemia surveyed were attending neonatologists (95%); 65% had >10 years in sick preterm infants is effective. Thrombocytopenia is not of experience in their field. Neonatologists reported spending a mean associated with this therapy. Severe hyponatremia occurs in very few of 31 weeks/year in direct patient care or supervision of care. patients (approximately 4%) and is easily corrected. Institutions’ characteristics: physicians reported an average of 560 Belik J, Musey J, Trussel RA. Continuous infusion of glucagon NICU admissions/year at their primary institution. Patients’ induces severe hyponatremia and thrombocytopenia in a premature characteristics: 63% of NICU infants was LBW; of those neonates, neonate. Pediatrics. 2001;107(3):595–597. 46% received TPN exclusively for >72 hours. Screening practices: ( p value: pre versus post and/or pre versus infusion. Values are only 2% of LBW neonates was screened for carnitine deficiency. TPN mean±SD.) supplementation practices: only 28% of LBW neonates was Pre Infusion Post p value supplemented with L -carnitine. Rationale regarding carnitine: 34% Blood glucose (mg%) 24±8 100±75 97±48 <0.001 of neonatologists believed that carnitine deficiency could have serious Number of boluses D10% 3±1 0.5±1 0 <0.01 consequences in LBW infants; 52% of physicians properly identified GIR (mg/kg per minute) 7.8±2.3 – 8.3±3.5 NS carnitine as ‘‘present in breast milk,’’ and 12% recognized that it is Number of Na + <130 mEq/l 2 10 1 <0.01 ‘‘normally secreted by the placenta.’’ Neither screening nor Number of Na + <120 mEq/l 0 1 0 NS supplementation practices were affected by physicians’ beliefs or Number of platelets <50,000/ml 3 2 0 NS knowledge.

Conclusion. In our sample, LVW neonates receiving TPN were not P15. CURRENT FACTORS ASSOCIATED WITH USE OF BREAST MILK routinely screened for carnitine deficiency (2%), and the majority FEEDINGS IN NEONATES DISCHARGED FROM NEWBORN INTENSIVE (72%) did not receive carnitine-supplemented TPN. Thus, LBW neonates continue to be at risk for unrecognized carnitine depletion. CARE UNITS The potential role of L -carnitine in preventing neurosensory R.H. Clark, N. Powers, B.T. Bloom, P. Thomas and abnormalities requires further investigation. J. Peabody; Center for Research and Education, Pediatrix Medical Group, Sunrise, FL

Purpose. To identify current factors associated with milk use at P14. GLUCAGON INFUSION FOR TREATMENT OF HYPOGLYCEMIA: discharge in neonates that were admitted to a neonatal intensive care EFFICACY AND SAFETY IN SICK PRETERM INFANTS unit. D.S. Charsha, P.S. McKinley and J.M. Whitfield; Pediatrics, Baylor University Medical Center, Dallas, TX Methods. We evaluated all neonates who admitted for neonatal intensive care from 124 different neonatal units between 1/1/99 and Purpose. Treatment of sick preterm infants with persistent 12/31/2000. Using a database formed from a computer-assisted tool hypoglycemia is challenging due to fluid limitations and need for that generates hospital notes, we reviewed the epidemiology of breast multiple infusions. Glucagon IV infusion (G) can be an effective milk use at discharge. Breast milk use was defined as receipt of any treatment for hypoglycemia. However, recently, the safety of G for breast milk feedings as reported in the discharge feeding notes. We treatment of hypoglycemia in preterm infants has been questioned. evaluated the differences between neonates sent on some breast milk Particularly, an association with hyponatremia and thrombocyto- and those who were not using stepwise logistic regression analysis to penia was observed. identify which factors were independently associated with a neonate being discharged on some breast milk. Methods. We undertook a retrospective chart review of all preterm infants with hypoglycemia treated with IV glucagon infusions (20– Results. We studied 42,891 neonates; 21,327 (49.7%) were sent 40 g/hr) between 1997 and 2000 inclusive. The charts were home receiving some breast milk and 21,564 (50.3%) were not. The reviewed for BW, GA, Apgar scores, length of glucagon infusion, as range of unit-specific success in receiving breast milk at discharge is well as pre-infusion (PRE), during infusion (infusion), and post- 71% for the upper third to 35% for the lower third of our centers. The infusion (post) glucose levels, glucose infusion rates (GIR), sodium most important variables associated with being discharged on breast concentration, and platelet counts. milk were white race, being married, and site of care (see table). Site variation remained significant when adjusted for gestational age, Results. A total of 2045 preterm infants <37 weeks were admitted to race, and martial status. NICU and 28 had continuous IV glucagon for hypoglycemia: BW 1814±780 g, GA 32±3 weeks, Apgar 5±3 at 1 minute, G began at Conclusion. The data suggest that neonates admitted to neonatal 42 (3–310) hours and was continued for 77 (9–344) hours, and intensive care units are often discharged on feedings that do not glucose increased to >60 mg% in 2.2±1.6 hours. include breast milk and that site of care influences this occurrence.

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Identification and implementation of meaningful process differences of asymptomatic term newborns. Treatment and testing are also should provide an opportunity to improve the site-specific success increased in infants when mother’s GBS status in unknown and risk rates. factors are present, compared to infants born to known GBS-positive Variable No breast milk Some breast milk p value mothers. Increased antibiotic usage may influence bacterial Number 21,564 21,327 n/a resistance patterns and should be investigated. Further work is also Birth weight (g) 2.4±0.9 2.6±0.9 NS needed to determine the impact of these approaches on other Gestational age (weeks) 35±4 36±4 NS neonatal outcomes, as well as optimal laboratory utilization and Race (% white) 46 63 0.001 appropriate length of stay. Married parent (%) 44 63 0.001

P17. MICROBIOLOGY OF EARLY-ONSET NEONATAL SEPSIS AFTER P16. IMPACT OF INTRAPARTUM TREATMENT FOR GROUP B IMPLEMENTATION OF NEONATAL SEPSIS PREVENTION PROGRAM STREPTOCOCCUS ON NEWBORN CARE M.M. Aouthmany1 and A.M. Aouthmany2; 1Pediatrics, R. Millar and S.F. Townsend; Pediatrics, UCHSC, Denver, Division of Neonatology, Mercy Children’s Hospital, CO Toledo, OH, 2Medical School, Northeastern Ohio Universities College of Medicine, Rootstown, OH Purpose. To assess the influence of adequate versus inadequate intrapartum chemoprophylaxis (ICP) of mothers for GBS on the Purpose. To study the microbiology of the early-onset nursery care of asymptomatic full-term infants. Length of stay, neonatal sepsis after implementation of the American Academy antibiotic use, and diagnostic testing were examined. We also of Pediatrics (AAP) and/or American College of Obstetrics and compared the care of asymptomatic, full-term infants born to Gynecology (ACOG) recommendation regarding GBS prophy- mothers treated because of risk factor(s) for GBS (GBS status laxis. unknown) to care of mothers treated because they were known to be GBS-positive. The approach of neonatologists was compared to Background. Reports from Yale-New Haven from 1928 to 1978, pediatricians. then from 1979 to 1988 showed a change in the microbiology of neonatal sepsis after the introduction of the antibiotics. In that Methods. A cross-sectional survey study was conducted by mail to a report, 55% of neonatal sepsis was caused by group B Streptococcus random sample of 700 pediatricians and 300 neonatologists across the (GBS); Escherichia coli (E. coli) was second with 14% of the cases. United States. Surveys included four case-based scenarios, along with After the recommendation of the AAP and the ACOG regarding several initial descriptive questions. Returned surveys were evaluated prevention of GBS neonatal sepsis, we suspect that the spectrum of using t-test, -squared analysis, and ANOVA analysis as appropriate. the causative bacteria in the early-onset neonatal sepsis may be changed. Results. Four hundred and eight surveys were returned, of which 283 (69%) indicated regular provision of care to term infants. Infants Methods. Retrospective chart review study design. Cultures from delivered to mothers who were NOT treated adequately had a blood, cerebrospinal fluid (CSF), and urine were reviewed in all significant increase in length of hospital stay compared to infants born admissions to the neonatal intensive care unit at Mercy Children’s to mothers who received adequate ICP ( p<0.0001, 2). Antibiotic Hospital from January 1996 through November 2000. Neonatal sepsis use was significantly increased in newborns of mothers treated was defined as a positive culture of any of the above sites. Early-onset inadequately for prevention of early-onset GBS disease (EOGBSD). An neonatal sepsis was defined as a positive in either blood, CSF, or urine increased proportion of infants underwent laboratory testing if born to culture during the first 7 days of life. The decision of whether the an inadequately treated mother ( p<0.01), and an increased number culture is a contaminant was based on repeat culture and/or on of diagnostic tests were used in newborns whose mothers had not been clinical judgment. adequately treated for prevention of EOGBSD ( p<0.01). Interest- ingly, a statistically significant increase in use of empiric antibiotics Results. Admissions during the study period were 1466 infants; 21 of and number of diagnostic tests ordered was found for newborns of these infants were diagnosed as having early neonatal sepsis mothers treated because of risk factors for GBS, regardless of adequacy (1.43%), 15 males and 6 females. Two of these infants were outborn. of ICP, compared to newborns of known GBS-positive mothers. There The (mean±SD) gestational age was (30.6±5.6 weeks) and the were no significant differences between Neonatologists and mean birth weight was (1704±918 g). Infection sites were 17 blood, Pediatricians in the management of newborns in our survey. 2 blood with CSF, and 2 CSF only. Eighteen infants survived, and three died (mortality rate 14.3%). Microbial agents were GBS 33.3%, Conclusion. Inadequate intrapartum chemoprophylaxis results in staphyloccocci 33.3%, E. coli 19%, then Enterobacter cloacae, yeast, increased lengths of stay, diagnostic testing, and antibiotic treatment Streptococcus pneumoniae 4.8% each.

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Conclusion. GBS is still a major microbial agent in the neonatal frequent. A combined approach of vigilance, appropriate sepsis in the first 7 days of life, but sepsis with other microbial agents, management at onset of symptoms, and adequate follow up may like Stapylococcus epidermidis, is increasing. This could be due to help reduce unnecessary testing and treatment of infants. Since increased maternal and neonatal antibiotic use. proven S is rare, confirmation of these results is necessary in a larger group of infants.

P18. FREQUENCY AND TIMING OF SYMPTOMS IN TERM AND NEAR- TERM INFANTS WITH SUSPECTED SEPSIS P19. EARLY DRUG MONITORING OF TOBRAMYCIN IN NEONATES A. Madan and A.G. Philip; Pediatrics, Stanford University J.N. van den Anker and M. de Hoog; Pediatrics, School of Medicine, Palo Alto, CA, Pediatrics, El Camino Columbus Children’s Hospital, Columbus, OH, Hospital, Mountain View, CA Pediatrics, Sophia Children’s Hospital, Rotterdam, the Netherlands Purpose. To determine the frequency and timing of symptoms in all term and near-term infants admitted for suspected sepsis (SS) to the Purpose. Optimization of aminoglycoside use in neonates warrants NICU at a community hospital which uses a sepsis (S) pathway for therapeutic drug monitoring (TDM) for both efficacy and toxicity screening infants with risk factors for sepsis (RF). reasons. Traditionally, TDM for aminoglycosides is performed at steady state around the administration of the fourth dose. However, Methods. Data were obtained prospectively from consecutive NICU large interindividual differences remain and predictive performance admissions for presumed (PS) or SS for 5 months (2000–2001). of current dosing regimens might be improved by using early Infants with RF, which included maternal fever >388C, therapeutic drug monitoring. intrapartum antibiotics (IA), fetal tachycardia, prolonged rupture of membranes, positive cervical culture for group B streptococci, or Methods. A prospective study in neonatal patients with suspected gestational age <37 weeks, were screened for S with a complete septicemia in the first week of life. All patients received 4 mg/kg blood count (CBC) and C-reactive protein (CRP) level at birth tobramycin with a gestational age (GA)-related dosing interval of and at 12 hours of age. Infants were admitted for symptoms of S, 48 hours (GA <32 weeks), 36 hours (GA 32–37 weeks), and 24 which included tachypnea, apnea, O2 requirement, CPAP or hours (GA >37 weeks). The target serum trough concentration positive pressure ventilation (PPV), fever ( >37.58C), temperature was 0.5 mg/l. Serum trough samples as well as 1- and 6-hour instability, hypoglycemia, poor perfusion, feeding difficulty, or a samples were taken after the first dose. Tobramycin concentrations CRP >1 mg/dl. were used to obtain GA-dependent population models with NPEM software. A second group of patients, with serum sampling times Results. Two hundred and twenty-four of 1011 live births were of 3 and 8 hours after the first dose and just before the second screened. Sixty-nine infants were admitted for SS. Twenty-seven of dose, was added to investigate the effect of sample timing. Serum these did not have any RF. Fifty-nine infants were symptomatic. BC trough concentrations were predicted using linear pharmacoki- was positive (staph epidermidis) in one term, symptomatic infant netics in both groups and by using the population models with with no RF. PS was diagnosed (dx) in 16/59 infants with an I/ Bayesian feedback of one or two serum concentrations in the T>0.2 and a CRP >1. SS was dx in 17/56 infants with either a CRP second group. These predicted concentrations were compared to >1 or I/T >0.2. S was ruled out in 26 infants. Six of 10 actual serum trough concentrations. The predictive performance of asymptomatic infants were between 35 and 37 weeks’ gestation. Four the 1- to 6-hour and 3- to 8-hour models was compared to a term infants were admitted secondary to a CRP >1. IA were GA-related model without TDM. administered in 31 cases. The most common symptom was tachypnea (46) and 15 needed CPAP or PPV. Other symptoms were Results. Two hundred and forty-seven patients were studied; 206 O2 requirement (22), poor perfusion (20), hypoglycemia (12), with 1- to 6-hour sampling and 41 with 3- to 8-hour sampling. temperature instability (7), fever (7), and feeding difficulties (7). Peak serum concentrations were above 5 mg/l in 90.8% and trough Symptoms presented within 6 hours of birth in 47 (80%), by 24 concentrations above 1 mg/l in 25.5%. The 3- to 8-hour linear hours in 53 (91%), and in 100% of infants by 48 hours. No infants model had a bias of –0.31 mg/l and a precision of 0.48 mg/l and were re-admitted to the NICU. performed significantly better than the 1- to 6-hour model. The best NPEM model had a bias of –0.11 mg/l and a precision of 0.45 mg/ Conclusion. The results indicate that screening for S prevents l. None of the models yielded a significant improvement of predictive unnecessary treatment with antibiotics. However, with the current performance over the model without TDM. frequent use of IA, it is unclear if screening is necessary. In our experience, all infants with SS or PS presented with symptoms by Conclusion. Our results indicate that routine early TDM is not 48 hours of age, with respiratory symptoms being the most useful in neonates in the first week of life. Prediction of individual

498 Journal of Perinatology 2001; 21:482 – 509 Abstracts AAP-Section on Perinatal Pediatrics

tobramycin dosing intervals cannot be improved by use of 1- to 6- P21. RESPIRATORY SYNCYTIAL VIRUS CODED US hour or 3- to 8-hour serum concentrations after the first dose. TDM HOSPITALIZATIONS, 1997 TO 1999 should probably only be performed routinely in neonates receiving S. Leader and K. Kohlhase; Medical Affairs, tobramycin for longer than 5 days for reasons of toxicity. MedImmune, Gaithersburg, MD

Purpose. To characterize severe RSV trends in US children based on P20. VANCOMYCIN CONCENTRATIONS IN NEONATES: DO WE NEED discharges from US non-federal short stay hospitals between 1997 TO MEASURE THEM? and 1999 and hospital charges. W.-H. Tan1, N.M. Brown2, A.W. Kelsall1 and R.J. McClure1; 1Neonatal Intensive Care Unit, The Rosie Methods. The 1997 to 1999 National Hospital Discharge Surveys Hospital, Addenbrooke’s NHS Trust, Cambridge, (NHDS) were analyzed for the annual number of discharges with Cambridgeshire, UK, 2Clinical Microbiology and Public a primary agnosis of either RSV bronchiolitis (ICD-9-CM Health Laboratory, Addenbrooke’s NHS Trust, 466.11), RSV pneumonia (ICD-9-CM 480.1), or RSV (ICD-9- Cambridge, Cambridgeshire, UK CM 079.6). We also extracted data on length of stay, patient demographics, and expected payment source. NHDS formulas were Purpose. To determine the appropriateness of a standard used to calculate 95% CI. Mean charges from the 1997 Healthcare vancomycin dosage regimen in neonates and the need to measure Cost and Utilization Project (HCUP) database were inflated for serum vancomycin concentrations in that population. 1998 and 1999 using the Medical Care component of the Consumer Price Index. Methods. The serum vancomycin concentrations of all neonates in a neonatal intensive care unit who received vancomycin (15 mg/kg 12 Results. For the years 1997 through 1999, an estimated cumulative or 18 hourly depending on post-natal age) between January 1, 1998 total of 319,156 discharges with a RSV-specific primary diagnosis and March 31, 2000 were reviewed retrospectively. and 1,199,614 inpatient days occurred among children under age 5. The proportion of infants whose serum vancomycin concen- Eighty-one percent was under 1 year of age; 66% was 6 months or trations fell within a conservative therapeutic range of trough: 5 to 10 younger. Among infants under age 1 year, there were a total of mg/l and peak: 20 to 40 mg/l, and a less conservative range of 259,832 discharges with a RSV-coded primary diagnosis. Eighty-one trough: 5 to 12 mg/l and peak: 15 to 60 mg/l was measured. percent was coded as RSV bronchiolitis [95% CI, 78–83%] and 17% as RSV pneumonia [95% CI, 17–18%]. Total RSV-coded discharges Results. One hundred and one neonates were included in the study. varied annually: peak numbers (126,933) were reported in 1999 The post-conceptual age (PCA) of 32 patients was less than 28 while the lowest total (82,528) was reported in 1998. Total hospital weeks; 48 patients were between 28 and 34 weeks PCA, and 21 charges for stays by children under age 5 with a primary diagnosis of patients had PCA greater than 34 weeks. RSV during the 3 years exceeded US$2.3 billion. Among those under Of all patients, 41.6% achieved both trough and peak age 1 year, 64% was white, 14% was black, and 22% was other/ concentrations within the conservative therapeutic range, and 55.4% unknown. Overall average length of stay (ALOS) for infants <1 year achieved the same within the less conservative therapeutic range. increased from 3.7 days in 1997 [95% CI 3.3–4.0] to 3.9 days in Of all infants, 83.2% had peak concentrations between 20 and 40 1998 [95% CI 3.4–4.3], and 4.0 days in 1999 [95% CI 3.6–4.4]. mg/l; 99.0% had peak concentrations between 15 and 60 mg/l. The ALOS over the 3 years was 6.4 days for RSV pneumonia [95% CI, Of the infants with trough concentrations between 5 and 10 mg/l, 5.3–7.4], 3.5 days for RSV bronchiolitis [95% CI, 3.2–3.8], and 3.0 89.4% had peak concentrations between 20 and 40 mg/l. All infants days for RSV [95% CI, 1.9–4.1]. Medicaid was the expected payment with trough concentrations between 5 and 12 mg/l had peak source for 47% of total discharges and private insurance accounted concentrations between 15 and 60 mg/l. for 24%.

Conclusion. The vancomycin dosage regimen used in this study Conclusion. Hospital stays with a primary diagnosis of RSV and produces acceptable therapeutic serum vancomycin concentrations. associated hospital charges are substantial. The estimated total Using this dosage regimen, peak serum vancomycin concentrations hospital charge of US$2.3 billion may underestimate the total burden do not need to be measured in neonates because almost 90% of due to possible miscoding, exclusion of secondary diagnoses, and neonates with acceptable conservative trough concentrations achieved unavailability of reliable national data on physician charges and lost therapeutic peak concentrations by the conservative range, and all productivity associated with an episode of severe RSV. Although the neonates achieved acceptable peak concentrations based on the less total number of RSV-coded discharges varied annually, the conservative range. dominance of RSV bronchiolitis-coded discharges, length of stay, It also suggests that vancomycin dosages may be adjusted based and population demographics remained relatively stable over this 3- on trough concentrations alone. year period.

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P22. RECENT TRENDS IN RESPIRATORY SYNCYTIAL Conclusion. Using more current data, the estimated number of VIRUS–ASSOCIATED US HOSPITALIZATIONS, 1997 TO 1999 RSV-associated hospital discharges among infants is higher S. Leader and K. Kohlhase; Medical Affairs, than previous estimates of 73,400 to 126,300 annually. RSV MedImmune, Gaithersburg, MD continues to cause significant numbers of infant hospitalizations in the US. Purpose. To update previously published estimates on the annual average number of RSV-associated hospitalizations among children under the age of 1 year. P23. SYNAGIS (PALIVIZUMAB) PROPHYLAXIS OF RESPIRATORY SYNCYTIAL VIRUS INFECTION — PATIENT DEMOGRAPHICS AND Methods. National Hospital Discharge Survey (NHDS) data for PRELIMINARY RESULTS FROM THE 2000 TO 2001 SYNAGIS 1997 to 1999 were searched for RSV-related discharges. The OUTCOMES REGISTRY database lists up to seven ICD-9-CM diagnostic codes per 1 2 discharge. Two methods were used to estimate RSV-associated M. Hudak , S. Chartrand and The Synagis Outcomes Registry3; 1Department of Pediatrics, University of hospitalizations among children less than 1 year of age. First, 2 we identified all discharges with one of three RSV-specific Florida, Jacksonville, FL, Department of Pediatrics, diagnostic codes: RSV bronchiolitis (ICD-9-CM 466.11), RSV Creighton University Medical Center, Omaha, NE pneumonia (ICD-9-CM 480.1), and RSV (ICD-9-CM 079.6). 1 Purpose. The Synagis Outcomes Registry is a prospective Next, we identified discharges occurring between November and multicenter effort designed to follow a population of infants April (the RSV season) and assumed 50% to 80% of cases 1 receiving Synagis for prophylaxis of serious lower respiratory tract diagnosed as other acute bronchiolitis (ICD-9-CM 466.19) and infection caused by RSV. The primary objective of the Registry is 30% to 60% of cases diagnosed as other pneumonia (ICD-9-CM to determine RSV hospitalization rates in a representative cross- 480.0, 480.2 486) were due to RSV. Cases were counted only 1 section of US infants receiving Synagis ; secondary objectives are once using the first applicable diagnosis code. Rates were to describe the number of injections, compliance and seasonality calculated using annual mid-year US census data for children 1 of Synagis dosing. under age 1 year. Methods. Infants from 61 sites across the US were eligible for Results. Between 1997 and 1999, a total of 286,072 infants 1 were discharged with a RSV-code specific diagnosis. In inclusion if they received their first Synagis dose between addition, we estimate that between 118,855 (lower estimate) September 1, 2000 and March 1, 2001. Patient demographics, and 205,802 (upper estimate) discharges coded as bronchiolitis risk factors, number of doses, compliance, and RSV hospital- or pneumonia may have been due to RSV. The more ization (if any) were recorded. Not all data were available for all conservative estimate yields an annual rate of 34/1000 infants enrollees. under age 1 year. The upper estimate is 42/1000 infants under age 1 year. Results. A total of 2044 infants were enrolled. The number of enrollees per site ranged from 1 to 209 (mean=34).Preliminary Total RSV-Associated Hospitalizations Among Infants Less Than Age 1, 1997 analysis suggests the overall RSV hospitalization rate in this cohort is to 1999 comparable with rates previously reported during 1998 to 1999 and Lower estimate Upper estimate 1999 to 2000 RSV seasons (2.3% and 2.4%, respectively). Other bronchiolitis 79,770 127,632 (466.19) Conclusion. These data confirm the consistent effectiveness of [50–80% of cases] Synagis prophylaxis for severe RSV infections in a large cohort Pneumonia 39,085 78,170 of high-risk infants. The Synagis Outcomes Registry also (480–486, except 480.1) 1 [30–60% of cases] provides a unique opportunity to monitor Synagis utilization RSV bronchiolitis 234,373 in the US. (466.11) [100% of cases] Subject demographics, RSV pneumonia (480.1) 37,616 n (%) [100% of cases] Gestational age Female 943 (46.1) RSV (079.6) 14,083 <28 weeks 472 (23.1) Race [100% of cases] 28–31 weeks 489 (23.9) Caucasian 1197 (58.6) Average annual 134,976 OR 163,958 32–35 weeks 918 (44.9) Black 392 (19.2) number of cases >35 weeks 163 (8.0) Hispanic 287 (14.0) Total 404,927 OR 491,874 [Lower estimate [Upper estimate Chronological age at enrollment Other Risk factors 164 (8.0) +RSV codes] +RSV codes] 0–3 months 810 (39.6)

500 Journal of Perinatology 2001; 21:482 – 509 Abstracts AAP-Section on Perinatal Pediatrics

3–6 months 536 (26.2) Multiple birth 654 (32.0) producers with ETCOc values >75th percentile corrected to age in 6–11 months 440 (21.5) Chronic lung disease 484 (23.7) hours: >1.6 ppm at 30 hours of age; low producers with values 12 months 242 (11.8) Child care center 458 (22.4) <25th percentile). In combination with clinical history, physical Birth weight (g) Smoke exposure 327 (16.0) examination, and presence of bilirubinemia, hour-specific ETCOc <1000 350 (17.1) Congestive heart disease 98 (4.8) 1000–1999 1065 (52.1) Cystic fibrosis 12 (0.6) values >75th percentile can help differentiate the basis for increased 2000–2999 513 (25.1) At least one risk factor 1459 (71.4) bilirubin levels. 3000 103 (5.0)

P24. END-TIDAL CARBON MONOXIDE HOUR-SPECIFIC NOMOGRAM: FOR EARLY AND PRE-DISCHARGE IDENTIFICATION OF BABIES WITH INCREASED BILIRUBIN PRODUCTION V.K. Bhutani1, M. Herschel2 and D.K. Stevenson3 (on behalf of the Jaundice Multinational Study Group); 1Newborn Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, 2Pediatrics, University of Chicago, Chicago, IL, 3Pediatrics, Stanford University School of Medicine, Stanford, CA P25. COMPARISON OF THE DIRECT COOMBS’ ANTIGLOBULIN TEST FOR IDENTIFICATION OF NEWBORNS AT RISK OR NOT AT RISK Purpose. To define normative data for end-tidal carbon monoxide (ETCOc) and develop an hour-specific nomogram in term and FOR HEMOLYSIS WITH A KNOWN INDICATOR OF THE RATE OF near-term healthy newborns (between 6 and 36 hours age) such HEMOLYSIS, THE END-TIDAL CARBON MONOXIDE that infants with high or low carbon monoxide elimination are more CONCENTRATION IN PARTS PER MILLION CORRECTED FOR clearly identified. INHALED CO (ETCOc) M. Herschel1, T. Karrison2, M. Wen2, L. Caldarelli1 and Methods. From 10 multinational clinical sites, we identified 1479 B. Baron3; 1Pediatrics, University of Chicago, Chicago, neonates (born to self-declared non-smoking mothers) and 207 IL, 2Health Studies, University of Chicago, Chicago, IL, neonates born to mothers who were smokers (later excluded from 3Pathology, University of Chicago, Chicago, IL the nomogram). All were healthy and cared for in the well-baby nurseries. Each was sampled for an ETCOc measurement Purpose. Blood group, Rh type, and DAT are performed on cord performed between 6 and 36 hours of age. In 551 babies, two blood for the recognition of hemolysis in the newborn. However, a measurements were made 12 hours apart soon after birth. Data positive DAT is not always associated with evidence of hemolysis, nor (2074 ETCOc samples) were tabulated for age (in hours), is increased bilirubin production due to causes other than gender, race, maternal smoking history, bruising, feeding, and isoimmunization identified by DAT. Our purpose was to define the known hemolysis (subsequently attributed to ABO or Rh sensitivity and specificity of the DAT for the identification of neonates incompatibility). with significant hemolysis.

Results. The mean, 25th, and 75th percentile values represented as Methods. During a 15-week period, 660 consecutive newborns in hour-specific tracks for ‘‘healthy’’ term and near-term babies the Regular Nursery of a university inner-city hospital were (born to non-smoking mothers) are shown in the figure. Mean enrolled. Cord blood group, type, and DAT were performed on all ETCOc values decreased from 2.6 ppm at 6 hours of age to 1.4 neonates. ETCOc was obtained at 12±6 hours and at 24±6 hours ppm at 36 hours age. There were no significant differences using the Natus CO-Stat End Tidal Breath Analyzer (Natus observed in babies born by C-section versus vaginal deliveries, Medical, San Carlos, CA) for the passive, non-invasive measure- breast-feeding versus formula-feeding, gender: male versus female, ment of ETCOc at the bedside, with immediate data printout. bruising versus no bruising, negative versus positive Coombs’ test. Infants of non-smoking mothers whose 12-hour ETCOc level was There was a significant difference in babies with history of 95th percentile were defined as having significant hemolysis. maternal smoking in babies sampled soon after birth that was Since the effect of in utero smoke exposure is no longer seen at absent by 12 hours of age. 24 hours, the infants of all mothers were included in the analysis of the ETCOc level 95th percentile at 24 hours. Statistical Conclusion. These data provide a useful framework for clinicians to analyses were performed using contingency tables and two sample define normal and potentially abnormal ETCOc values (high t-tests.

Journal of Perinatology 2001; 21:482 – 509 501 AAP-Section on Perinatal Pediatrics Abstracts

Results. At 12 hours, the mean ETCOc level in the newborns of and ETCO values above 2 ppm with an r value of 0.754. An ETCO of smoking mothers (n=114) was significantly different (mean±SD) 2.5 ppm had a 0.67% sensitivity and 0.89% specificity in identifying by 3.0±1.7 ppm from the mean ETCOc level in neonates of non- patients with significant hemolysis with a positive predictive value of smoking mothers (n=500), 2.1±0.7 ppm; p=0.0001. At 24 hours, 0.2 and negative predictive value of 0.8. Of the 12 patients who the means were no different: p=0.62. developed hyperbilirubinemia requiring phototherapy, nine had DAT was positive in 23/660 (3.5%), the majority being due to ETCO values >3 ppm. ABO incompatibility. Using the 12-hour ETCOc 95th percentile (3.2 ppm) in the neonates of non-smoking mothers as reference, the Conclusion. ETCO is comparable to reticulocyte count as an index DAT has a sensitivity of 38% (10/26) and a specificity of 99% (466/ of hemolysis. ETCO is a simple and sensitive test that identifies babies 473) for the identification of significant hemolysis. The positive at increase risk of hemolysis. It could potentially replace Coombs’ predictive value of the DAT in identifying significant hemolysis at 12 test. We propose an ETCO value of 2.5 ppm as the level for which hours is 59% (10/17). significant hemolysis would occur. With the 24-hour ETCOc 95th percentile (2.5 ppm) in the neonates of all mothers as reference, the DAT has a sensitivity of 8.5% (4/47) and a specificity of 97.7% (504/516). The positive predictive value of the DAT for identifying significant hemolysis at 24 hours is 25% (4/16).

Conclusion. The DAT is not as useful as the ETCOc test for the identification of hemolysis in newborns. Supported by a grant from Natus Medical.

P26. END TIDAL CARBON MONOXIDE AS AN INDICATOR FOR THE DEGREE OF HEMOLYSIS IN COOMBS’ POSITIVE BABIES M.-C. Javier, M. Nesin and A.N. Krauss; Perinatology, New York Presbyterian Hospital-Cornell, New York, NY P27. CORRELATION OF RETICULOCYTE COUNT AND END-TIDAL CARBON MONOXIDE PRODUCTION WITH THE HEMATOCRIT LEVELS Purpose. Coombs’ test done in cord blood alerts clinicians of IN PRETERM INFANTS possible hemolysis that could lead to hyperbilirubinemia. However, M.M. Aouthmany; Pediatrics, Division of Neonatalogy, not all of these babies hemolyze. There is therefore a need to Mercy Children’s Hospital, Toledo, OH identify which babies undergo significant hemolysis. Reticulocyte count approximates degree of hemolysis. Carbon monoxide, a Purpose. To evaluate the relationship between hematocrit level in byproduct of RBC degradation, can be used as an indirect measure stable preterm infants with reticulocyte count and ETCOc (end-tidal of hemolysis. Our objectives: (1) to determine if ETCO is carbon monoxide, corrected for inhaled CO). comparable to reticulocyte count as an index of hemolysis and (2) to determine at what level of ETCO would significant Background. Reticulocyte count reflects the newly produced red hemolysis occur. blood cells (RBC). Hemoglobin from RBC destruction is catabolized into globin and heme, which is degraded by Methods. Using the COstat Breath analyzer (Natus), ETCO was microsomal heme oxygenase into equimolar carbon monoxide performed in 45 healthy term and near-term Coombs-positive (CO) and bilivirdin. Bilivirdin is then reduced into bilirubin. CO infants at 24 to 48 hours of life. CBC and reticulocyte count were also is excreted exclusively by the lungs; therefore, end-tidal carbon performed. monoxide, corrected for inhaled CO (ETCOc), reflects hemoglobin degradation. Results. Subjects were classified as follows: no hemolysis (reticulocyte counts <5%: 28 patients), mild hemolysis (reticulocyte Methods. Prospective study design. Included were stable preterm counts 5–8%: 7 patients), and significant hemolysis (8% and above: infants, with insignificant or no blood draws. Infants with hemolytic 10 patients). Patients with reticulocyte counts <5% had ETCO values diseases, sepsis, recent blood transfusion, and infants on mechanical between 1.3 and 2.7 ppm. Those with reticulocytes 5% to 8% had ventilation were excluded. The endpoint was either a need for blood ETCO values between 1.6 and 4.2 ppm and 9 of 10 patients with transfusion for a symptomatic anemia of prematurity, or discharge reticulocyte counts above 8% had ETCO values between 2.5 and 6.1. home. Hematocrit, reticulocyte count, and ETCOc measurements There is a linear relationship between reticulocyte counts above 5% were performed weekly.

502 Journal of Perinatology 2001; 21:482 – 509 Abstracts AAP-Section on Perinatal Pediatrics

Results. Thirty-two preterm infants were included in the study; 16 (n=1), and unknown (n=5). Duration of PT prior to first ExTx males and 16 females. The (mean±SD) birth weight was was 77.8 hours (range: 4–521). All babies had significant (1075±383 g), gestational age (28.1±2.5 weeks), hematocrit concurrent co-morbidities before undergoing ExTx: 83% (n=39) (32.7±7.0 vol%), ETCOc (1.0±0.48 ppm), infant weight at the was on mechanical ventilation at time of ExTx. Serious adverse time of measurement (1595±441 g), date of life (46±29). The events, noted in 7/47 ExTx, included infection (n=2), NEC Pearson correlation between hematocrit levels and reticulocyte count (n=1), thrombocytopenia requiring platelet transfusion (n=3), was r= –0.341 ( p<0.005), also between hematocrit and ETCOc and recurrent bradycardia (n=1). These appeared more was r=0.444 ( p<0.001). frequently in babies 28 weeks’ GA. One additional baby (5-day- old, 29 weeks’ GA) with hydrops due to congenital syphilis died 24 Conclusion. Serial measurements of reticulocyte count and ETCOc hours after ExTx (TSB 17.9 mg/dl). (which is a simple non-invasive breath measurement) are GA 28 weeks 29–32 weeks 33–34 weeks important for evaluating the hemogoblin status in stable pretrem (n=19) (n=11) (n=17) infants. Mean age at 165 hours 62 hours 52 hours A decreasing trend of ETCOc measurements in a preterm first ExTx (4–533) (28–85) (8–140) Mean TSB at 11.7 mg/dl 16.7 mg/dl 17.5 mg/dl infant may indicate that the hematocrit mass is decreasing. first ExTx (8.5–15.6) (10.2–20.3) (13.1–26.2) ETCOc and reticulocyte values outside the ‘‘normal range’’ Adverse event Serious Minor Serious Minor Serious Minor may indicate low production or increased degradation of 24 hours 1405 0 6 hemoglobin. 24–72 hours 3000 0 0 This project was supported, in part, by F.M. Douglass Foundation 72 hours–7 days 1000 2 0 grant 134, and by a grant from St. Vincent Mercy Medical Center Total 5 4 0 5 2 6 Foundation. (26%) (21%) (0%) (45%) (11.8%) (35%)

P28. ADVERSE EVENTS ASSOCIATED WITH EXCHANGE TRANSFUSION Conclusion. ExTx in sick preterm babies may be associated with IN SICK PRETERM BABIES serious adverse events. Hence, risk of bilirubin-induced brain R.S. Chima, V.K. Bhutani and L.H. Johnson; Section on damage should be weighed against potential risks of ExTx as Newborn Pediatrics, Pennsylvania Hospital, University of influenced by the expertise and facilities available. Pennsylvania, Philadelphia, PA

Purpose. Preterm sick babies with hyperbilirubinemia who fail P29. A SUCCESSFUL MULTIPRONGED APPROACH TO REDUCTION OF intensive phototherapy (PT) require exchange transfusion (ExTx) to TRANSFUSIONS AND DONOR EXPOSURES IN THE promptly reduce bilirubin load and prevent bilirubin-related brain EXTREMELY-LOW-BIRTH-WEIGHT INFANT damage. We assessed the safety of ExTx in unstable patients managed W.M. Southgate1, L.A. Maes2, P. Wagstaff1, D.J. Eicher1, in a level III nursery. M. Murphy2 and D.J. Annibale1; 1Pediatrics, Medical University of South Carolina, Charleston, SC, 2Pathology, Methods. Adverse events that could have occurred during or Medical University of South Carolina, Charleston, SC following an ExTx in preterm neonates (34 weeks) were stratified according to gestational age (28 weeks, 29–32 weeks, and 33–34 Purpose. The purpose of this report is to present the results of a weeks) and severity (serious versus minor). Serious events required multidisciplinary, multipronged approach designed to reduce the therapeutic intervention (e.g., cardiorespiratory arrest, sepsis/ number of transfusions and donor exposures in our population of infection). Minor events were asymptomatic but prompted correction extremely-low-birth-weight (ELBW) neonates. (e.g., electrolyte abnormalities, transient desaturation). Temporal profile of adverse events following ExTx was noted (24 hours, 24– Methods. In an effort to reduce the frequency of small volume 72 hours, and 72 hours–7 days). packed red blood cell (PRBC) transfusions and donor exposures in our ELBW (less than 1000 g) population, a multipronged approach Results. From January 1990 to December 1998, 2088 preterm has been undertaken in our institution. This has included the phased babies were managed at Pennsylvania Hospital, of which 23 adoption of transfusion guidelines, followed by the use of extended (1.1%) required 47 ExTx. The mean GA and BW were 30 weeks storage media with specific units assigned to specific patients, and (range: 23–34) and 1613 g (range: 555–2907), respectively. most recently, the use of microsample point-of-care testing (POCT). Etiology of hyperbilirubinemia besides prematurity was Rh Data have been collected on 250 ELBW neonates who survived to isoimmunization (n=6), ABO isoimmunization (n=1), G6PD discharge. Data collected included (1) number of transfusions, (2) deficiency (n=1), bruising/cephalhematoma (n=5), sepsis number of donor exposures, (3) hematocrit prior to transfusion in (n=2), intrauterine infection (n=2), pulmonary hemorrhage the first 2 weeks of life, (4) hematocrit prior to transfusion in the

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second 2 weeks of life, (5) hematocrit prior to transfusion beyond the variance evaluating TAT and F1.2 over time in association with first month of life, and (6) last hematocrit prior to discharge. Data ultrasound evidence of thrombi and platelet count. have been analyzed for two birth weight groups (500–749 and 750– 999 g) covering five phases. Phase I was prior to the use of Results. Sixteen patients with 33 measurements of TAT, F1.2, and guidelines, extended storage media or POCT (baseline data). Phase platelet count were included. Thirty-one ultrasounds were performed. II reflects the use of transfusion guidelines only. Phase III reflects the Mean±SD birth weight, 919±635 g; gestational age, 26.3±3.1 use of transfusion guidelines and CPDA-preserved, patient-assigned weeks; SNAP score 16±7. Mean TAT (g/l) on day 1=5.56±4.7, PRBC units used for up to 21 days. Phase IV reflects the use of day 3=6.61±3.35, day 5=6.33±5.9. Mean F1.2 (nmol/l) on day extended storage media-preserved PRBCs assigned for up to 42 days. 1=5.20±2.0, day 3=4.13±1.7, day 5=3.36±1.19. Mean platelet Phase V encompasses the additional use of POCT. Erythropoietin was count on day 1=204,000±71,400, day 3=168,000±96,700, day not used. 5=144,000±74,300. Only 1 of 31 ultrasounds was positive for clot formation. Mean values of TAT did not change significantly over the Results. Results presented include data from phases I through IV. first week of life. Mean values of F1.2 and platelet count fell during Phase V has recently been implemented and data are currently being the first week of life, although the differences did not reach statistical collected. For infants with birth weights less than 750 g, the average significance (repeated-measures ANOVA). number of PRBC transfusions per infant decreased from 8.5 to 7.8 (9%), while donor exposures were reduced from an average of 7.8 to Conclusion. Preliminary data did not demonstrate significant 3 (62% reduction). For infants with birth weights from 750 to 999 g, changes in TAT, F1.2, platelet count, and thrombus formation during the average number of transfusions was reduced from 5 to 4.2 the study period. Although we describe trends in TAT, F1.2, and (16%), while donor exposures were reduced from an average of 4.2 platelet counts during the first week of life, statistical significance is to 1.8 (57% reduction). Average hematocrit values prior to limited to small sample size. Further study is ongoing to determine if transfusions and prior to discharge were not significantly altered a correlation exists between TAT, F1.2, platelet count, and the during these phases. development of UAC thrombosis.

Conclusion. The use of a multipronged, interdisciplinary approach to transfusion of the ELBW infant reduces transfusions as well as P31. RETINOPATHY OF PREMATURITY — INCIDENCE AND donor exposures. ASSOCIATED FACTORS IN INFANTS WITH BIRTH WEIGHT 1500 G OR GESTATIONAL AGE 32 WEEKS S. Rush, R. Rush, M. Naqvi and J.A. Rush; Department of P30. UMBILICAL ARTERY CATHETER THROMBOSIS: DETECTION BY Pediatrics, Texas Tech University Health Sciences Center, ULTRASOUND AND ASSOCIATION WITH TAT, F1.2, AND PLATELET Amarillo, TX COUNT M.M. Coleman1, M.L. Spear1, S.A. Pearlman1, Purpose. Etiology of retinopathy of prematurity (ROP) is M. Finkelstein2, K.H. Leef1, S.M. Taylor3 and multifactorial, of which gestational age 32 weeks is one of the S.E. McKenzie3; 1Neonatology, Christiana Care Health predictive factors. The aim of this study was to investigate maternal Services, Newark, DE, 2Radiology, Christiana Care and neonatal risk factors associated with ROP in our regional Health Services, Newark, DE, 3Cardeza Foundation for perinatal center. Hematologic Research, Thomas Jefferson University, Philadelphia, PA Methods. Retrospective data were collected from medical records of infants with birth weight 1500 g or gestational age 32 weeks Purpose. Thrombin anti-thrombin (TAT) and prothrombin admitted to the regional neonatal intensive care unit located in the fragment (F1.2) are sensitive markers of coagulation cascade Texas Panhandle from January 1995 to May 2000. A total of 300 activation and thrombin formation. Our purpose is to describe levels subjects were included in the study, of which 16% expired and was of TAT and F1.2 longitudinally and compare levels with ultrasound not included in the final analysis. The incidence of ROP was evidence of umbilical artery catheter thrombi and blood platelet compared with the incidence of other related factors. counts in neonates during the first week of life. Results. Overall incidence of ROP was 32%. The incidence increased Methods. Infants with an umbilical artery catheter (UAC) placed in with decreased birth weight and gestational age. The factors which the first 24 hours of life were studied. All received equal amounts of had significant correlation with a p value <0.05 were birth weight, heparin in the UAC. TAT and F1.2 levels along with abdominal aorta gestational age, need for oxygen >28 days, intraventricular ultrasounds were examined on days 1, 3, and 5 of life. ELISA for TAT hemorrhage, prolonged use of total parenteral nutrition, a therapy- and F1.2 was performed using a commercially available kit from based severity of illness index, the Neonatal Therapeutic Intervention Enzymgost. Data were analyzed with repeated-measures analysis of Scoring System (TISS) score >20, occurrence of one or more

504 Journal of Perinatology 2001; 21:482 – 509 Abstracts AAP-Section on Perinatal Pediatrics

surgeries, use of postnatal steroids, sepsis, and need for multiple associated with an increased risk of death and/or severe IVH (odds blood transfusions. The factors which had no significant correlation ratio for every 1 mg/dl decrease in T4 1.4, 95% confidence interval were maternal age, route of delivery, pregnancy-induced hyper- 1.1–1.7). tension, gender, and race. Conclusion. Low total T4 and TSH, measured soon after birth, Conclusion. The associated medical factors are important to are associated with death and severe IVH in VLBW infants. Our recognize in relation to ROP. Neonatologists and ophthalmologists data suggest that, despite the normal surge in thyroid hormones should be aware of these factors because they are statistically following birth, it may be feasible to design a study of very early indicative of neonates that are most likely to acquire ROP, thus thyroxine supplementation in infants with the lowest T4 rather spotlighting the infants that need to be most closely followed. than treating based on gestational age alone. The low TSH following birth also suggests a secondary or tertiary cause of hypothyroxinemia and may have implications for designing P32. DEATH AND SEVERE IVH ARE ASSOCIATED WITH LOW T 4 treatment strategies. IMMEDIATELY FOLLOWING BIRTH IN VERY-LOW-BIRTH-WEIGHT INFANTS M.J. Kantor1,2, K.H. Leef3, L. Bartoshesky4, J. Getchell5 P33. SIGNIFICANCE OF PLATELET-DERIVED GROWTH FACTOR-AB and D.A. Paul1; 1Neonatology, Christiana Care Health AND NITRIC OXIDE IN NEWBORN INFANTS SUFFERING FROM System, Newark, DE, 2Pediatrics, Thomas Jefferson PERINATAL ASPHYXIA University, Philadelphia, PA, 3Pediatrics, Christiana Care S.A. EL Meneza, N.A. Khodeir and S.S. Khattab; Pediatric Health System, Newark, DE, 4Pediatrics, DuPont Hospital Faculty of Medicine for Girls, AL Azhar University, Cairo, for Children, Wilmington, DE, 5Newborn Screening, Heliopolis, Egypt, Clinical Pathology, Al Azhar State of Delaware, Dover, DE University, Cairo, Egypt, Clinical Pathology, AL Azhar University, Cairo, Egypt Purpose. To determine if total T4 and TSH, measured soon after birth, would be associated with death and/or severe intraventricular Purpose. Perinatal asphyxia (PA) is a major cause of neonatal hemorrhage (IVH) in very-low-birth-weight (VLBW) infants. Low morbidity and mortality among the newborn infants. The impact of T4 measured at 1 week of life has been associated with IVH and death. cardiac involvement on the course of the asphyxiated neonates is still Because T4 and TSH surge after birth, it is unclear how earlier post- not fully studied; the aim of this work is to investigate the role of natal thyroid hormone levels are associated with outcome. We platelet-derived growth factor (PDGF) and nitric oxide (NO) in the hypothesized that early measurements of T4 and TSH would also be diagnosis and prognosis of the neonates with PA with and without associated with mortality and IVH. cardiac involvement.

Methods. Prospective observational study of consecutive liveborn Methods. A total of 64 newborn infants suffering from PA as well 12 infants with birth weights <1500 g born after 8/1/00. Informed cases were included in this study. PA was defined as Apgar score <3 written consent was obtained. Blood for total T4 and TSH was drawn at 1 minute and <7 at 5 minutes of life, presence of hypoxic immediately following birth and measured by radioimmunoassay. ischemic encephalopathy (HIE), multiple organ failure, and Routine thyroid screening was obtained on the fifth day of life to metabolic or mixed acidosis. The asphyxiated group was further screen for congenital hypothyroidism. All infants had cranial divided into two groups according to the presence of cardiac sonogram performed on day 4. IVH was diagnosed by a pediatric involvement. All cases were subjected to immediate resuscitation, full radiologist unaware of thyroid status. Severe IVH was considered clinical examination, gestational age estimation, morbidity score, grades III to IV. Statistical analysis included one-way ANOVA, Apgar score, thorough history taking, management according to case, Pearson correlation, and logistic regression. Data are expressed as monitoring for vital sign, ECG, TcO2, blood gases, electrolytes, CBC, mean±SD. blood sugar, CPK isoenzymes, PDGF, NO and echocardiography, EEG, and cranial ultrasound. All cases with congenital anomalies Results. The mean gestational age (EGA) of the study population were excluded from this study. PDGF-Ab and NO were measured (n=64) was 27±2.8 weeks and birth weight 975±291 g. Twelve of using Quantikine R&D systems. sixty-four (18%) infants died and 12/64 (18%) were diagnosed with severe IVH. Both T4 (R=0.30, p=0.013) and TSH (R=0.53, Results. There was significant increase in the mean values of serum p<0.01) at the time of birth correlated with EGA. Infants who died levels of PDGF-AB and NO among the newborn infants with and/or had severe IVH (n=21) had lower T4 (5.0±2.1 vs 8.4±4.1 perinatal asphyxia than the control group. p<0.001, comparing the g/dl, p<0.01) and TSH (5.5±6.0 vs 18.1±18.1 mIU/ml, mean values between the neonates with cardiac involvement and p=0.03) at the time of birth when compared to infants who survived those with HIE showed no statistical significant difference. A positive without severe IVH. After controlling for EGA, low T4 remained significant correlation between PDGF-AB and NO (r=0.79) was

Journal of Perinatology 2001; 21:482 – 509 505 AAP-Section on Perinatal Pediatrics Abstracts

detected. A negative significant correlation was detected between the were repaired before 25 weeks’ gestation (group 2). Surgery was done cardiac output/stroke volume and PDGF-AB (r=0.82, 0.66.) at median gestational age of 23.6 (range 22.4–24.5) weeks. The median gestational age at delivery was 34 (range 31.6–35.3) weeks Conclusion. Platelet-derived growth factor-AB is increased during ( p=0.88). the course of perinatal asphyxia; it may have a beneficial mechanism Group 1, n=51 Group 2, n=44 p value to prevent neuronal damage due to the increase of nitric oxide. Gestational age at 34.4 (32.6–35.3) 34 (31.6–35.3) 0.88 Transient myocardial ischemia during the course of perinatal delivery (weeks) asphyxia has impact on the immediate morbidity and mortality. Gestational age at 26.3 (25.6–27.6) 23.6 (22.4–24.5) <0.0001 surgery (weeks) Control Group II PA with Group III PA HIE Days from surgery 52 (37–62) 70 (55–84) <0.0001 cardiac involvement to delivery Number 12 26 26 Gestational 39+1.2 39+3.5 40+2.1 age (weeks) Birth weight (g) 3.1+0.32 3.19+0.98 3.5+0.35 Conclusion. Early IUMR before 25 weeks’ gestation does not Postnatal age (days) 1.9+1.1 1.2+0.5 1.3+0.27 decrease the gestational age at delivery when compared with repair Apgar score at 8.5+1 2.5+1 2.2+0.5 after 25 weeks. 1 minute Apgar score at 9.4+0.5 3+0.6 3.1+1.1 5 minutes pH 7.29+0.8 7.12+0.3 7.02+0.5 P35. SURVIVAL OF EXTREMELY-LOW-BIRTH-WEIGHT INFANTS AND pO2 65+12 35+5.5 38+8.5 CAUSE OF DEATH IN A LEVEL III NICU SERVING A HIGH-RISK URBAN pCO2 38+6.5 73+8.3 69+6.5 POPULATION Z. Panjvani1, B.K. Rajegowda1, S. Mahmoud1 and K. Schulze2; 1Department of Pediatrics, Lincoln Medical Center, Bronx, NY, 2Department of Pediatrics, New York P34. GESTATIONAL AGE AT INTRAUTERINE MYELOMENINGOCELE Presbyterian Hospital-Columbia University Medical REPAIR DOES NOT INFLUENCE THE RISK OF PREMATURITY Center, NY A.H. Hamdan1, W. Walsh1, A.A. Heddings2, J.P. Brunner2 and N. Tulipan3; 1Division of Neonatology, Vanderbilt Purpose. Improving survival rates are being reported for extremely- University Medical Center, Nashville, TN, 2Division of low-birth-weight (ELBW) infants from tertiary perinatal centers Perinatology, Vanderbilt University Medical Center, across the country. Our hospital, located in The Bronx, NY, serves a Nashville, TN, 3Division of Pediatric Neurosurgery, high-risk urban population: 70% Hispanic, 20% Black, and 10% Vanderbilt University Medical Center, Nashville, TN others. Of the 3000 deliveries/year, 50% to 60% are high-risk. The outcomes of all live births, 21 to 28 weeks’ gestational age (GA) and Purpose. Early gestational age of intrauterine myelomeningocele <1250 g birth weight (BW) over a 4-year period (January 97– repair (IUMR), as compared with late repair, would lower December 00) were reviewed (1) to compare our survival rates with gestational age at delivery. The aim of this study was to determine the other outcome data, and (2) to determine whether the causes of effect of gestational age at the time of IUMR on the duration of death suggested any changes in clinical practice. pregnancy and the gestational age at delivery. Methods. NICU admission logbooks and monthly morbidity– Methods. This study is a retrospective chart review of the maternal mortality reports were used to tabulate outcome by BW and by GA. GA and neonatal medical records of all infants undergoing IUMR at our was based on the expected date of delivery (EDC). When the EDC was institute. Birth weight, gestational age at the time of surgery, and not available, a clinical estimate of GA was used (25% cases). gestational age at delivery were recorded. Infants were divided into two groups depending on gestational age at the time of surgery, Results. The results are summarized in Table 1 below. From January either 25 weeks’ gestation (group 1) or <25 weeks (group 2). 1, 1997 to December 31, 2000, there were 12,264 total live births. One Results were expressed as medians and interquartile ranges. hundred and seventy-nine (1.4%) of these were 21 to 28 weeks’ GA. Statistical analysis was done using unpaired (two-sample) t-test. p During the same interval, 36 fetuses of the same GA were stillborn. values 0.05 were considered significant. Forty-eight infants died: 13 died with in 1 to 2 hours (11 in the delivery room, 2 in NICU, 6 considered too immature to resuscitate, 1 Results. Ninety-five infants were studied. Fifty-one infants were with contracture deformities); 19 infants died within 48 to 72 hours repaired after 25 weeks’ gestation (group 1) at a median gestational (13 due to RDS, 2 pulmonary hemorrhage, 2 bronchopneumonia, 1 age of 26.3 (range 25.6–27.6) weeks. Their median gestational age Escherichia coli sepsis and 1 tracheal agenesis). The remaining 16 at delivery was 34.4 (range 32.6–35.3) weeks. Forty-four infants infants who died between 4 and 60 days of age included three deaths

506 Journal of Perinatology 2001; 21:482 – 509 Abstracts AAP-Section on Perinatal Pediatrics

from NEC, four from BPD, four from sepsis, one from pulmonary Results. During a 2-year period, a total of 188 cases were identified hemorrhage, one from cardiac tamponade related to a percutaneous and analyzed. Complete data from 70 cases were available. All infants catheter in the heart, two unexplained sudden deaths, and one from had audiologic screening with a 94% passing rate. A mean unknown cause. chronological age of 8.5 months and a mean corrected age of 6 months were found upon speech pathologist evaluation. Mean Conclusion. Despite inconsistent prenatal care, survival rates in this Receptive and Expressive Quotients (REQ) were 94 and 90, high-risk urban population compare well with other published respectively. Receptive and Expressive Quotients were similar among reports (Vermont Oxford, Maryland). Sixty-percent of all deaths was different birth weight groups. The mean corrected ages for those related directly or indirectly to lung and gut immaturity. Although infants with low REQ (78) and those with higher scores ( >78) specific recommendations for changes in clinical practice cannot be were also similar. Advanced maternal age adversely affected REQ made from these data, prevention of lung injury and early detection ( p<0.05). Newborns requiring mechanical ventilation at birth had of intestinal inflammation appear to be important management lower REQ ( p<0.008). objectives. Table 1 EGA (weeks) Conclusion. Birth weight is not a determinant of poor language Birth weight 21–2223242526272829 Total Number outcome in high-risk newborns. Low Receptive and Expressive (g) % Quotients were not secondary to hearing deficit. Factors such as 350–500 0 33 0 – 0 – – – 6 1/16 maternal age and neonatal complications (mechanical ventilation) 501–750 67 27 44 57 100 100 – – 52 23/44 were associated with low Receptive and Expressive Quotients in this 751–1000 – 100 67 60 88 87 75 100 83 49/59 group. A prospective study will be conducted to have a larger and 1001–1250 – – – – 100 100 90 100 96 58/60 more representative population. Total % 15 33 75 58 87 92 84 100 73 131/179 Number 2/ 5/ 9/ 7/ 20/ 24/ 27/ 37/ 131/ 13 15 21 12 23 26 32 37 179

P38. RELATIONSHIP BETWEEN LANGUAGE DELAY AND ADOLESCENT MOTHERHOOD STATUS IN 9 MONTHS, HIGH-RISK INFANTS P37. LANGUAGE OUTCOME IN HIGH-RISK NEWBORNS M. Rivera, J. Gonzalez, I.E. Garcia, L. Garcia, S. Deynes E. Bezares, I.E. Garcı´a, L. Garcı´a, C. Santiago and and M. Valcarcel; Pediatrics/Neonatology Section, UPR M. Valcarcel; Pediatrics, University of Puerto Rico, School of Medicine, San Juan, Puerto Rico San Juan, Puerto Rico, Puerto Rico Purpose. It has been reported that adolescent mothers are more Purpose. Language is a strong predictor of neurological problems likely to experience poor pregnancy outcomes, especially low birth that could affect the emotional, social, and academic development of weight (LBW) and preterm delivery. There is a debate about a child. Delays in language development are more common than whether negative consequences on adolescent pregnancies are due delays in other developmental domains. Language includes to maternal age (biological factors) or caused by the adverse expressive and receptive skills. Expressive skills reflect the ability to economic and social factors, and circumstances of teenagers who express ideas, desires, and thoughts to others. Receptive skills reflect become mothers. Various studies suggest that LBW, short the ability to understand language. Language evaluation during the gestational age, and socio-demographic factors have an impact first year of life in high-risk newborns allows for early intervention on the language outcome. The purpose of this study is to assess and identification of deviations in language development. possible associations between adolescents and language outcome of their infants. Methods. This is a retrospective review of medical records from the University Pediatric Hospital to assess language outcome in high-risk Methods. Maternal age and socioeconomic status were assessed newborns. Neurodevelopment evaluations were obtained up to 18 during the newborn hospitalization in the neonatal intensive care months corrected age. Neonatal medical data and maternal unit. Neurodevelopment evaluations of infants were obtained from socioeconomic data were obtained during hospitalization at the the high-risk clinics. Hearing, speech, and language development at neonatal intensive care unit from an ongoing educational program. 9 months were compared among groups of adolescent and non- Receptive Expressive Emergent Language Scale (REEL-2) scores adolescent mothers. Statistical analysis was done using Pearson’s - were assessed, taking into consideration other variables such as squared analysis and frequency distribution. A p value less than 0.05 audiology evaluations and history of otitis media. Exclusion criteria was considered statistically significant. The Institutional Review included severe congenital anomalies and syndromes associated with Board approved the study. neurodevelopmental delays. The Institutional Review Board approved the study protocol. Statistical analysis was performed using Pearson’s Results. A total of 87 medical records were evaluated. Twenty-three -squared analysis, ANOVA, and frequency distribution. percent of infants evaluated at 9 months of age was from adolescent

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mothers. Eighty-seven percent of these mothers was in social classes month of age (17% vs 3%, p=0.04). At 9 months old, infants of IV and V by the Hollingshead Social Strata Scale. Sixty-one percent of non-adolescent mothers showed a higher incidence of fine motor them was not high-school graduate as compared to 20% of non- delays (43% vs 17%, p=0.04). Upon analysis of gross motor delays at adolescent mothers. Seventeen percent of the infants born to 9 and 15 months of age, no significant difference was found between adolescent mothers was identified to have speech delay at 9 months adolescent and non-adolescent mothers. Twenty-five percent of of age and 28%, some degree of hearing loss. Speech delay was not infants of adolescent mothers was on physical therapy and 8% on associated with maternal adolescent status ( p=0.26); however, occupational therapy. hearing loss was ( p=0.05). A higher percent of infants from adolescents was on speech therapy. This was marginally significant Conclusion. Being an adolescent mother in this high-risk setting ( p=0.09). does not correlate in a significant way with having an infant with fine or gross motor deficiencies at 9 and 15 months old. Even Conclusion. Language impairment presented by infants at 9 though a strong relationship between adolescent mothers and months is not associated with maternal adolescent status in this motor developmental delays in their infants was not identified, high-risk population. Our results suggest that independent of close follow-up is required to assure an early identification of the maternal age, presence of social, environmental, and infant deficiencies. Early identification will lead to an early intervention biological risk factors may be responsible for the developmental delay in order to develop the best potential and quality of life of NICU in language, hearing loss, and need for speech therapy. Study survivors. The fact that infants of adolescent mothers required supported, in part, by PR State Council for Developmental frequent hospitalizations emphasizes the importance of directed Deficiencies. educational programs to improve patient care once discharged home. This study is supported, in part, by PR State Council for P39. MOTOR DEVELOPMENTAL DEFICIENCIES IN INFANTS BORN TO Developmental Deficiencies. ADOLESCENT MOTHERS IN A HIGH-RISK CENTER N. Ortiz, L. Garcia, I. Garcia, M. Rivera, J. Gonzalez and M. Valcarcel; Pediatrics/Neonatology, UPR School of P40. GESTATIONAL SMOKING AND THE RISK OF CONGENITAL Medicine, San Juan, Puerto Rico DEFECTS S.E. Woods; Family Medicine, Bethesda Hospital, Purpose. Recent developments in the treatment and survival of Cincinnati, OH premature and high-risk neonates have reduced infant mortality. Trends in the short- and long-term morbidity of high-risk infants Purpose. The literature linking gestational smoking to congenital have not paralleled the reduction in mortality. Developmental defects has been very inconsistent. The purpose of this study is to follow-up studies have shown that low-birth-weight infants are at reinvestigate the relationship of gestational smoking and congenital high risk for physical and mental disabilities. The most frequent malformations. neurodevelopmental abnormalities encountered among preterm infants are motor problems, emerging as gross and fine motor, and Methods. This study is a gestational cohort study. Inclusion criteria visual–motor difficulties. Since young maternal age is associated required a live birth born in the TriHealth Hospital system from with an increased risk of perinatal and neonatal complications, January 1, 1998 to December 31, 1999. Exclusion criteria included adolescent pregnancy has been a concern for many years. The women who had a history of drug abuse, epilepsy, psychiatric objective of this study is to assess how adolescent pregnancies are disorders, alcohol abuse, DES exposure, or rubella. Data were associated with motor developmental deficits in their infants at 9 and collected concurrently during admission on maternal smoking 15 months of age. status, 1-minute apgar, 5-minute apgar, gestational age, birth weight, maternal age, race, and diabetes. Congenital defects were Methods. Infants outcome at 9 and 15 months in terms of grouped in 22 different categories. Logistic regression was used to find neurodevelopment was described using high-risk clinics’ medical any association between exposure and the 22 outcomes while records. Fine and gross motor problems were identified. controlling for age, race, and diabetes. Demographic data were also assessed. Statistical analysis was done using Pearson’s -squared analysis and frequency Results. The cohort included 18,016 patients (1943 smokers). distribution. A p value less than 0.05 was considered statistically Smokers were significantly younger, with lower birth weight babies, significant. and shorter gestational age ( p<0.05). Of the 22 categories of congenital defects, only the cardiovascular system abnormalities Results. A total of 87 records were reviewed. In the sample analyzed, demonstrated a significantly difference ( p<0.01) between the two 26% of the mothers was adolescent. Babies of adolescent mothers groups. The remaining 21 categories of congenital defects showed no were more likely to have frequent hospitalizations before the ninth statistical difference.

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Conclusion. Women who smoke during pregnancy have and sex, gestational age, and birth weight of the newborn babies were significantly smaller and shorter gestational age infants recorded. Aflatoxins B1 (AFB1), M1 (AFM1), and M2 (AFM2) were compared to mothers who do not smoke. Based on these data measured using high-performance liquid chromatography. Samples and the majority of the available literature, however, gestational were extracted by a method based on hexane partition and smoking is unlikely to cause a large increase in congenital chloroform extraction. Recovery, limit of detection, and sensitivity of birth defects. the method of extraction were calculated. Simple means and standard deviations were calculated for each toxin type. Mann- Whitney U test was used to show significance of differences between P41. FETAL EXPOSURE TO AFLATOXINS two means. Y.M. Abdulrazzaq1, N. Osman2 and A.I. Al-Bloushi1; 1Pediatrics, UAE University, Al Ain, United Arab Results. Ninety-one samples had undetectable amounts of Emirates, 2Obstetrics and Gynaecology, UAE University, aflatoxins. Of the 201 samples that were positive for aflatoxins Al Ain, United Arab Emirates (54.7%), 27 had B1, 106 had M1, and 31 had M2 types. Reproducibility of the measurements by HPLC ranged from 5.7% in Purpose. Aflatoxins may be present in peanuts, rice, barley, oats, and AFM1 to 10.9% for AFM2 and mean recovery ranged from 67.4% for wheat. After reports of high aflatoxin levels in some food grains AFM2 to 88.4% for AFB1. There was a significant negative correlation consumed, this study was undertaken to assess the exposure of between birth weight and aflatoxin levels. newborn babies to aflatoxins. Conclusion. The high positivity rate for aflatoxins confirms that a Methods. Serum aflatoxin levels were measured in blood samples significant proportion of newborn infants is exposed to aflatoxins from the umbilical cords of neonates of 201 women consecutively through maternal ingestion of aflatoxin-containing foods. Higher delivering in two regional hospitals. Information like age of mothers aflatoxin levels resulted in lower birth weights.

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