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Objective: To increase preoperative identification of at-risk infants for severe Retinopathy of prematurity (ROP) to >95% by August 2016, with a secondary aim of reducing the number of infants with 100% intraoperative peripheral oxygen saturation (SpO 2 ) during the same time., Study Design: Prospective quality improvement project centered on preterm surgical infants admitted to Primary Children's Hospital (n = 41). Preoperative ROP risk identification rates were analyzed using an annotated run chart, intraoperative SpO 2 and laser intervention were compared using un-paired t test., Results: Preoperative identification of ROP risk increased from 60 to 100% and no infant was exposed to 100% SpO 2 intraoperatively during the study period. The incidence of laser intervention in this population decreased by 45% from 22 to 12% (p = 0.21)., Conclusion: Simplifying our preoperative handoff increased our rates of correct identification and communication ROP risk in preterm infants while decreasing exposure to 100% SpO 2 .

Procalcitonin (PCT) and C-reactive protein (CRP) are commonly used biomarkers, but their diagnostic advantage for neonatal early-onset (EOS) or late-onset (LOS) sepsis is controversial. In a comprehensive literature review we found significant heterogeneity between studies in sample timing, cut-off values, consideration of blood culture results for sepsis classification, and definition of EOS versus LOS. We identified 39 studies directly comparing PCT with CRP, but only four in very low birth weight (VLBW) neonates. The mean sensitivity for EOS, LOS, and EOS + LOS was 73.6%, 88.9%, and 76.5% for PCT, compared to 65.6%, 77.4%, and 66.4% for CRP, respectively. Mean specificity of PCT and CRP was 82.8% versus 82.7% for EOS, 75.6% versus 81.7% for LOS, and 80.4% versus 91.3% for EOS + LOS. More studies directly comparing both biomarkers for EOS and LOS, especially in extremely and very-low-birth-weight infants, are needed to determine their clinical value for guidance of antibiotic therapy in neonatal sepsis.

Objective: The purpose of this study was to determine the normal hematological values in cord blood during gestation, the impact of the type of delivery and differences in gender., Study Design: The database included 10 287 live births of 30-44 weeks gestation from cesarean or vaginal deliveries. Cord blood was collected into bags containing lyophilized heparin. Specimens were stored for 24 h or less and analyzed using the SysmexXE-2100. Data from cesarean births were used to evaluate developmental hematopoietic changes., Result: Increases during maturation occurred in hemoglobin, hematocrit, red blood cell count, and decreases in mean corpuscular volume and mean corpuscular hemoglobin. The number of nucleated red blood cells per 100 white blood cells decreased but absolute counts remained constant. Quantitative counts of white blood cells, neutrophils, monocytes (MON), eosinophils and lymphocytes (LYMP) increased, but percentages of lymphocytes and monocytes decreased. Platelets increased from 30-35 weeks., Conclusion: Reference ranges were established for cord blood. Erythroid and myeloid cells show developmental changes. Mode of delivery has a significant effect on hematologic values. Only a rare parameter showed differences based on gender. The cord blood complete blood cell count has the potential for providing relevant clinical information for managing neonatal patients.

Objective: Little is known about the effect of obesity on inflammatory status in pregnant women. The objective of this study was to determine the effect of obesity on markers of inflammation, oxidative stress and micronutrient status in obese pregnant women and their infants compared with lean controls (Lc)., Study Design: This was a prospective case-control study. A total of 15 obese (Ob; body mass index (BMI) >30 kg m(-2)) and 15 lean (BMI 18-25 kg m(-2)) women were recruited based on prepregnancy BMI. Vitamins A, B6, C, E and 25-hydroxyvitamin D (25(OH)D), zinc, red blood cell (RBC) folate, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α and oxidized and reduced glutathione were measured from maternal blood between 24 and 28 weeks of gestation. Vitamins A, B6, C and E, 25(OH)D, zinc, red blood cell folate, CRP and IL-6 were measured from cord blood at delivery., Result: Ob pregnant women have statistically significantly lower levels of vitamin B6, vitamin C, vitamin E, RBC folate, higher CRP and IL-6 levels and higher ratio of oxidized to reduced glutathione compared with Lc pregnant women. Infants born to Ob mothers did not have statistically significantly higher measures of inflammation or oxidative stress. There were no differences in micronutrient concentrations between Lc and Ob infants, but folate, vitamin B6 and zinc levels correlated strongly between mother and infant. There was no statistically significant difference in any parameter between Ob and Lc cord blood., Conclusion: Ob pregnant women have increased inflammation and oxidative stress, and lower levels of nutritional antioxidant defenses compared with Lc pregnant women. We speculate that lower antioxidant defenses combined with increased oxidative stress and inflammation may contribute to the adverse outcomes associated with pregnancy in Ob women.

Objective: The American College of Obstetrics and Gynecology Committee on Obstetric Practice recently endorsed delayed cord clamping at preterm delivery. However, the committee report expressed the concern by some practitioners that delayed clamping or cord milking might induce hyperviscosity in preterm neonates. To address this issue we: (1) established reference ranges for whole-blood viscosity among preterm neonates (viscosity reference ranges had previously been reported only in term neonates) and (2) determined the effect of umbilical cord milking at deliveries <32 weeks gestation on subsequent blood viscosity measurements., Study Design: This was a prospective study in two Neonatal Intensive Care Units. Blood viscosity was measured using a cone and plate viscometer. Associations were sought with gestation, hematocrit/hemoglobin and mean corpuscular volume. Reference ranges were determined for preterm infants <32 weeks gestation. Then, after umbilical cord milking at deliveries <32 weeks, viscosity was measured at birth and again during the 12 h after birth. In neonates with viscosities >95th % range, we sought signs of hyperviscosity (plethora, hypotonia, hypoglycemia, hyperbilirubinemia, thrombocytopenia)., Result: Viscosity at higher and lower sheer rates were linearly related (n=32, r=0.971). Within the range of hematocrits measured (29-63%) viscosity correlated with hematocrit (r=0.877) and hemoglobin (r=0.853) but not with erythrocyte size (r=0.179). Viscosity was related to gestational age (n=58), primarily due to the lower hematocrits at lower gestational ages. In the 12 h after cord milking viscosity ranged from 3.1 to 9.5 centipoise. Three of twenty preterm, neonates had viscosities >95th % reference range. However, all values were well below those where hyperviscosity is defined in term neonates and all lacked features of hyperviscosity., Conclusion: Cord blood viscosity is directly proportional to hematocrit/hemoglobin, lower at early gestation and not associated with erythrocyte size. Cord milking at preterm delivery is associated with a low risk of clinical hyperviscosity. Practioners should not refrain from cord milking at preterm delivery because of a concern that it will commonly cause neonatal hyperviscosity.

Objective: To compare serum N-terminal pro-brain natriuretic peptide levels at birth between monochorionic diamniotic twins with and without selective intrauterine growth restriction., Study Design: Blood samples were collected from 73 monochorionic diamniotic twins without twin-to-twin transfusion syndrome. Two groups were studied on the basis of fetal ultrasonographic findings: 16 twins with and 57 twins without selective intrauterine growth restriction. Selective intrauterine growth restriction was defined as an estimated fetal weight below the 10th percentile in one twin at 18 to 26 weeks of gestation. Serum N-terminal pro-brain natriuretic peptide levels were measured., Result: Serum N-terminal pro-brain natriuretic peptide levels in monochorionic diamniotic twins with selective intrauterine growth restriction were significantly higher than in those without selective intrauterine growth restriction. Selective intrauterine growth restriction was independently associated with increased N-terminal pro-brain natriuretic peptide levels., Conclusion: N-terminal pro-brain natriuretic peptide levels at birth are elevated in monochorionic diamniotic twins with selective intrauterine growth restriction.

Objective: To measure the adrenocorticotropic hormone (ACTH) and cortisol (F) cord plasma levels in preterm and term infants in relation to their mode of delivery., Study Design: We studied 180 newborns appropriate for gestational age (GA) with birth weights between 365 and 4380 g and GAs between 21 and 41 weeks divided into three groups: born by vaginal delivery (VD), elective cesarean section (ECS) and emergency cesarean section (EMCS). ACTH and F levels were valued with enzyme-linked immunosorbent assay testing. Median concentrations were compared between groups by Student's T-test for independent and paired data. Multiple regression analysis was used to investigate the effect of GA on F and ACTH concentrations., Result: A significant positive correlation between GA and plasma concentrations of ACTH (P<0.05) was found in the whole population, but not between GA and F (P=NS). A significant positive correlation was found between GA and plasma concentrations of both ACTH (P=0.01) and F (P=0.03) in VD. In those born by ECS, we demonstrated a positive correlation not only between plasma concentrations of ACTH (P=0.0000) and F (P=0.00002), respectively, with GA, but also a correlation between ACTH and F (P=0.0004). No significant correlations were found in the EMCS group (P=NS)., Conclusion: Our results suggest simultaneous pituitary-adrenal maturation, which is complete only at term. The responsiveness of preterm babies to different stressful stimulations is similar to the terms' but quantitatively lower, and the secretion of ACTH and F may not suffice in severe pathological circumstances.

Objective: To determine the effect of neonatal and maternal blood group on the mortality risk from necrotizing enterocolitis (NEC)., Study Design: Retrospective chart review of all neonates admitted to the neonatal intensive care unit over 24 years. Data on birth date, gestational age, maternal/neonatal blood group, number of transfusions, and survival time (defined as date of birth to date of death/discharge) were collected on those with NEC., Result: 276 neonates with Bell stage II-III NEC were analyzed. AB neonates had a significantly higher risk of mortality from NEC compared with other blood groups (HR 2.87; 95% CI 1.40 to 5.89; P=0.003). Multivariate analysis showed AB blood group to be an independent risk factor for mortality from NEC., Conclusion: Neonatal and maternal blood groups are significantly associated with a neonate's survival from NEC. The increased mortality of AB neonates may be related to factors such as neonatal blood group antigens and/or transplacental transfer of isoagglutinins.

Objective: The pathological picture in ischemic tissue injury shares features with the inflammatory response. Hypoxia-mediated induction of interleukin-6 (IL-6) could set in motion the mechanisms limiting inflammation in ischemia. Intrauterine growth restriction (IUGR) represents a human model of chronic fetal hypoxia. The purpose of this study was a first-time exploration to determine whether cord blood obtained at the delivery of small-for-gestational-age (SGA) infants has increased concentrations of inflammatory markers., Study Design: Cord blood was collected from 20 SGA (term and near-term) infants and 20 appropriate-for-gestational-age (AGA) controls. Infants exposed to maternal smoking, diabetes, maternal chronic diseases, or alcohol or drug use were excluded. Both groups had Apgar score ≥7 at 1 min with a normal cord pH (>7.25). Cord-serum cytokines and thrombopoietin (TPO) levels were measured by enzyme linked immunosorbent assay. C-reactive protein (CRP) was measured using a turbidometric immunoassay., Result: SGA infants had a significantly smaller birth weight than AGA controls, with a smaller gestation age by 1 week. There were significant elevations in IL-6, tumor necrosis factor (TNF-α), CRP and TPO in the SGA compared with the AGA group, which persisted in multiple regression analysis even after gestational age was taken into account., Conclusion: As hypothesized, significant increases in the cord blood concentrations of known inflammatory markers were found in SGA infants compared with the controls.

Objective: To examine the effect of mode of birth on plasma purine and malondialdehyde levels in normal term infants., Study Design: Umbilical arterial cord blood was obtained immediately after birth from a convenience sample of 119 normal term newborns born by vaginal delivery, with or without oxytocin augmentation or by elective cesarean delivery. Plasma was analyzed for purine and/or malondialdehyde levels. Numeric data were analyzed utilizing independent samples t-test and ordinal data were analyzed using Mann-Whitney test. Correlation coefficients were obtained using Spearman's rho., Result: Uric acid levels were significantly elevated (P<0.001) in neonates undergoing vaginal birth, compared to neonates born by elective cesarean delivery. When the effect of oxytocin and length of labor was analyzed, neonates born to mothers on oxytocin had lower hypoxanthine, significantly lower xanthine (P=0.05) and higher uric acid levels. In addition, malondialdehyde levels were significantly higher (P<0.006) in neonates born to mothers who received oxytocin compared to neonates born to mothers without oxytocin augmentation. We also found significant correlations between malondialdehyde (MDA) and hypoxanthine (r=-0.465, P<0.039) and between MDA and xanthine (r=-0.753, P=0.003) in neonates born via oxytocin-augmented birth. Mode of birth had no statistically significant effect on clinical outcomes, although infants born by elective cesarean had higher incidence of acute respiratory distress and transient tachypnea of the newborn compared to those born vaginally., Conclusion: Neonates born by elective cesarean had the lowest purine levels in cord blood compared to neonates born vaginally. Oxytocin augmentation is associated with some degree of uterine hyperstimulation which may enhance the ATP degradation pathway resulting in the rapid conversion of hypoxanthine to xanthine and xanthine to uric acid. Significantly higher MDA levels in neonates whose mothers received oxytocin as well as significant correlation between MDA and the purines hypoxanthine and xanthine, suggest free-radical production, most likely due to xanthine oxidase activation. However, despite differences in plasma purine and malondialdehyde levels, no significant differences were seen in neonatal outcome. Further studies are required to fully characterize the effect of mode of birth on purine metabolism and free-radical production.

Objective: To investigate natural change of low-density lipoprotein (LDL) profile during the neonatal period and the impact of gestational age and birth weight on those changes., Study Design: We measured lipid composition in LDL fraction, LDL particle size and apolipoprotein B (apoB) concentration at birth, 5 days of age and 1 month of age in 63 healthy neonates that had 37 to 41-week gestational age., Result: Low-density lipoprotein cholesterol and apoB concentrations increased from birth to 5 days of age, and the concentration persisted at 1 month in breast-fed and mixed-fed infants. However, in formula-fed infants, the concentration decreased at 1 month. At 5 days of age, neonates had larger and more triglyceride (TG)-rich LDL particles than at birth. At 1 month of age, LDL particles were smaller and more cholesterol rich than at 5 days of age. Single regression analyses showed that gestational age had influenced the LDL profile at birth and 5 days of age, while at 1 month milk determined the profile., Conclusion: The number of LDL particles increased rapidly during the first 5 days of life, and the composition of LDL particles is modulated by TG content throughout the neonatal period. Gestational age and milk, rather than birth weight, determine postnatal changes in LDL profile.

Background: Upper and lower reference limits for blood neutrophil concentrations of neonates were reported by Manroe, Rosenfeld and co-workers in 1979 and by Mouzinho, Rosenfeld and co-workers in 1994. Studies by Carballo and co-workers and Maynard and co-workers suggested that at high altitude a much higher upper limit of values occurs, and that neutrophilia is often diagnosed inappropriately, at high altitude, if the Manroe and Mouzinho charts are used., Study Design: We revisited the Manroe and Mouzinho charts using modern cell counting instrumentation and very large sample sizes. This was accomplished with data from an 18-hospital health-care system, at hospitals averaging 4,800 feet above sea level. Data were obtained from neonates in the first 10 days following birth, using tests performed on a single type of automated blood cell counter (Beckman Coulter LH 750, Fullerton, CA, USA). To obtain a description of 'expected values,' patients with the following diagnoses, known to have a high proportion of abnormal neutrophil counts, were excluded from the analysis; (1) maternal pregnancy-induced hypertension, (2) early-onset bacterial sepsis, (3) a discharge diagnosis of congenital neutropenia and (4) trisomy 21, 18 or 13., Result: Blood neutrophil concentrations were tabulated from 30 354 tests performed on neonates of 23 to 42 weeks gestation, with dates of birth between 1 January 2004 and 31 May 2007. The reference range charts generated from these data have much higher upper value limits than do the Manroe and Mouzinho charts, and are similar to the high-altitude reports of Carballo and co-workers and Maynard and co-workers. Neonates whose mothers labored before delivery had significantly higher neutrophil counts (averaging 3,500 neutrophils per mul higher, P<0.0001; comparing cesarean section deliveries with vs without labor). Females had significantly higher counts (averaging 2,000 neutrophils per mul higher) than males (P<0.0001). Counts did not differ on the basis of racial/ethnic group., Conclusion: The figures of this report describe the expected ranges for blood neutrophil concentrations over the first 10 days of life among neonates of 23 to 42 weeks gestation at high altitude.

Objective: Darbepoetin can be administered either intravenously (i.v.) or subcutaneously (s.c.). However, no information is available regarding pharmacokinetics and pharmacodynamics following its i.v. administration to neonates., Study Design: We administered a single i.v. dose (4 microg/kg) of darbepoetin to 10 neonates who had a hemoglobin < or =10.5 g/dl. Blood was obtained for immature reticulocyte fraction (IRF) and absolute reticulocyte count (ARC), before and 48 h following the dose. Blood was also drawn for pharmacokinetic analysis once before and at four pre-set intervals after dosing., Results: The study subjects ranged from 704 to 3025 g (median, 1128 g) birth weight, and were 26.0-40.0 weeks (median, 29.2 weeks) gestation at delivery. When the darbepoetin dose was given, ages ranged from 3 to 28 days (median, 8.5 days) with a hemoglobin of 9.8 +/- 0.7 g/dl (mean +/- s.d.). Doses were administered by i.v. infusion over 4 h. No adverse effects of the infusions were detected. The half-life of darbepoetin (t (1/2)) was 10.1 h (range 9.0-22.7 h), the volume of distribution was 0.77 l/kg (range 0.18-3.05 l/kg) and the clearance was 52.8 ml/h/kg (range 22.4-158.0 ml/h/kg). In the preterm neonates, there was no significant correlation between gestational age, or age at darbepoetin administration, and pharmacokinetic parameters. However, in the term and near-term neonates, volume of distribution correlated significantly with both gestational and age at darbepoetin administration (P < 0.05). Forty-eight hours after dosing, the IRFs and ARCs were elevated in six subjects and not in four. Those with predosing reticulocyte counts >200,000/microl did not have an increase in reticulocytes by 48 h (P < 0.05)., Conclusions: Darbepoetin administered i.v. to neonates had a shorter t (1/2), a larger volume of distribution and more rapid clearance than reported in children. We observed a significantly shorter t (1/2) and a less consistent rise in IRF and ARC after i.v. dosing than we previously reported following 4 microg/kg administered SC.

Objective: We tested the hypothesis that, the red blood cell (RBC) mass, estimated by hematocrit (HCT) or hemoglobin (Hb) level, influences the carbon monoxide (CO) production rate., Study Design: The relationship between end tidal CO corrected for ambient carbon monoxide level (ETCOc) and the RBC mass have been studied in 58 full-term infants at the mean age 4.9 hours., Results: Mean ETCOc was 1.88 ppm (1.3 to 3.4 ppm). ETCOc correlated significantly with HCT (R 2=10.1%, p=0.015) and with Hb (R 2=11%, p=0.011). Infants with a capillary HCT >65% had significantly higher ETCOc (mean 1.99+/-0.49 ppm) than infants with a capillary HCT <65% (1.74+/-0.39 ppm), p=0.035. When CO production was corrected for HCT (ETCOc/HCT), this difference did not longer exist., Conclusions: In newborn infants ETCOc significantly correlates with RBC mass. Comparing different infant's CO generation rate one should take into consideration their initial RBC level. In order to adjust for the existing differences in RBC, we suggest the use of the ETCOc/HCT index.

Background: Optimising home oxygen delivery in infants has important logistical and safety implications. This can be aided by having a suitable reference range of normal values for arterial oxygen saturation using pulse oximetry (SpO(2))., Objectives: To describe oxygenation profiles in healthy preterm and term infants in relation to gestational and postnatal age, to extend reference values to guide home oxygen therapy., Study Design: Prospective monitoring of SpO(2) for 4 hours at 3 monthly intervals of 34 term, and 53 preterm healthy infants, took place over a 12-month period using an Ohmeda Biox 3700e pulse oximeter and data logger., Results: Group mean and 5th percentiles were used to construct cumulative frequency curves at each time interval, representing the normal reference range of SpO(2) profiles for term and preterm infants over time., Conclusions: These data may be used to test the benefits in the home or hospital of having a reference range of normal values for cumulative SpO(2).

Objectives: The aim of this study is to measure baseline serum cortisol levels and clinical response to glucocorticoid therapy in a group of term infants with refractory hypotension., Study Design: Seven term newborns with refractory hypotension were included. Serum cortisol levels were drawn before initiation of glucocorticoid therapy and measured by either fluorescence polarization immunoassay or radioimmunoassay. Baseline blood pressures, heart rate, and inotropes doses were recorded at baseline, then 4, 8, 12, 24, 48, 72, and 96 hours after glucocorticoid therapy. Urine output and volume expanders the infants received were recorded 24 hours before and after glucocorticoid therapy. Dexamethasone was used at a starting dose of 0.2 mg/kg per day divided every 12 hours. The statistical analysis was done using analysis of variance with repeated measures and paired t-test., Results: Serum cortisol levels of the infants ranged from 2.0 to 15.4 micrograms/dl. After initiation of glucocorticoid therapy, there was significant improvement of blood pressure. Vasopressors were rapidly weaned and discontinued within 72 hours. In three of seven infants, no volume expanders were required after initiation of steroids, and none needed volume expanders after 2 days. Urine output increased significantly within 24 hours. All infants survived., Conclusions: Glucocorticoids improved pressure and stabilized clinical conditions of a group of term newborns with refractory hypotension. Serum cortisol levels of these infants were relatively low. We speculate that a subset of critically ill term infants has relative adrenal insufficiency and glucocorticoid therapy may be essential.

Objective: We report recurrent seizures in a neonate after intravenous lidocaine administration at the recommended dose for intubation and supplementation of general anesthesia., Study Design: Further evaluation of this case included determination of serum lidocaine level, serum electrolyte levels, and arterial blood gas values; cerebral spinal fluid analysis; an electroencephalogram; head ultrasonography; brain stem auditory evoked response testing; and a complete developmental evaluation. Previously published literature discussing lidocaine toxicity and pharmacokinetics is reviewed., Results: The lidocaine level in the patient was 0.3 mg/L 2 hours after the last dose was administered. Results of the remaining studies were within normal limits, and the patient had no additional seizures several months after birth., Conclusion: We caution that lidocaine administration to newborn infants at previously accepted doses may result in life-threatening side effects, including prolonged seizures.

Objective: To determine the efficacy of transcutaneous carbon dioxide tension measurement during high-risk neonatal transport., Study Design: This was a prospective, randomized comparative study. Infants transported from hospitals more than 30 miles away from our center and who required respiratory intervention were enrolled. Alternating transports used a transcutaneous CO2/O2 monitor. Ventilation parameters and end transport blood gas values served as primary endpoints for the study., Results: Infants with transcutaneous carbon dioxide tension monitoring were more likely to have decreased ventilator peak pressures during transport than neonates not monitored (-1.5 cm H2O vs + 0.6 cm H2O; p = 0.04). Monitored neonates were more likely to arrive at the tertiary center with a more normal pH and a CO2 tension between 35 and 45 mm Hg (4.7 to 6.0 kPa) than nonmonitored infants (p = 0.03 and p = 0.01, respectively). The stabilization times before transport were not significantly prolonged by the use of the transcutaneous monitor., Conclusions: Transcutaneous monitoring of CO2 tension improves short-term respiratory outcome in neonates receiving mechanical ventilation during transport.

Objective: The purpose of this study was to determine whether blood chemistry measurements obtained by a bedside blood analyzer through an umbilical artery catheter agreed with those obtained with use of conventional laboratory analyzers., Study Design: Forty-two neonates (1910 +/- 1000 gm) being treated in a level III neonatal intensive care unit had 88 blood samples drawn through an umbilical artery catheter. Serum sodium, potassium, glucose, and hematocrit concentrations were measured (n = 352) with use of a laboratory analyzer (0.7 ml of blood) and a bedside blood analyzer (0.06 ml of blood)., Results: Only 5.7% of all measurement differences (20/352) were outside the predetermined clinically acceptable difference range, and just 1.4% (5/352) might have affected clinical decision making. Correlations between laboratory analyzer measurements and bedside blood analyzer measurements were excellent: serum potassium, r = 0.97, p = 0.0001; serum glucose, r = 0.93, p = 0.0001; and blood hematocrit, r = 0.93, p = 0.0001. Serum sodium measurement correlation was significant (p = 0.0001) but weaker (r = 0.86)., Conclusion: The bedside blood analyzer evaluated in this report is clinically useful for neonatal patients and could limit phlebotomy loss if used routinely.

Citrullinemia, a rare inborn error of metabolism, is characterized by a deficiency of argininosuccinic acid synthetase that results in large increases in plasma ammonia, citrulline, and glutamine, with normal acid-base balance. The neurologic symptoms vary from poor feeding, vomiting, and irritability to hypotonia, apnea, and death. The most common pathologic findings at autopsy are cerebral edema and focal neuronal necrosis. We describe a case of fulminant citrullinemia in an infant in whom the major pathologic findings included diffuse cerebral edema and a lack of overt metabolic derangement characteristic of neonates with a urea cycle defect. Our case differs from the classic presentation of citrullinemia in that subarachnoid hemorrhage was identified early in the clinical course. We report the first observation of subarachnoid hemorrhage in an infant with a urea cycle defect.

We reviewed retrospectively the incidence of complications encountered with two different umbilical artery catheters (UACs): a silicone-rubber end-hole catheter and an electrode-tipped, side-hole catheter for continuous, invasive monitoring of arterial oxygen tension (PaO2). During calendar year 1989, there were 457 admissions to the neonatal intensive care unit: 168 patients had placement of a UAC. Two of these were admitted only briefly for cardiac catheterization and were eliminated from analysis. One patient had both types of catheters placed sequentially. Thus the data on 166 patients with 51 PaO2 monitors and 116 silicone-rubber UACs were evaluated. The patients who had a PaO2 monitor UAC had a lower mean birth weight than those in the other group (1621 +/- 1043 gm vs 1972 +/- 1048 gm; p = 0.0473). The catheter life span was not different between the groups, with a range of 1 to 16 days for PaO2 monitors and 1 to 27 days for silicone-rubber UACs. Inability to withdraw blood, poor blood pressure tracing, or both conditions resulted in catheter removal for 5 of 51 PaO2 monitor UACs and 4 of 116 end-hole UACs. The incidence of these problems did not differ significantly between the two groups. There were no cases of thromboembolic complications in the patients who had a PaO2 monitor UAC, whereas two of the silicone-rubber UACs were removed because of perfusion problems in the lower limbs, which resolved with decannulation. We conclude that the use of the PaO2 monitor UAC allows for continuous, invasive monitoring of PaO2 without any significant increase in risk compared with that for the silicone-rubber end-hole UAC.

The birth of an infant with ambiguous genitalia constitutes a medical emergency. Ill infants with ambiguous genitalia often require blood transfusions. We studied steroid levels in packed red blood cells from 10 healthy adult donors to determine whether packed red blood cells contain significant amounts of donor steroids that might interfere with hormonal testing. Levels of cortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, aldosterone, and dihydrotestosterone were well below normal newborn values. Hemolyzed packed red blood cells were used to provide the maximum possible donor steroid contribution. The concentration of testosterone was substantial in hemolyzed packed red blood cells but was effectively reduced to below normal female newborn levels by washing packed red blood cells by a standard blood bank procedure. Corticotropin testing for evaluation of adrenal function can be done accurately, even in infants receiving frequent transfusions of packed red blood cells. To avoid any misinterpretation of testosterone levels, it might be prudent to use washed packed red blood cells during human chorionic gonadotropin testing to evaluate Leydig cell function.

The butterfly, or scalp vein infusion set, is a widely used and convenient way to collect arterial blood gas samples in neonates. Analyzing arterial blood gas values by using this technique in a clinical situation, we obtained elevated values of PO2 in blood samples collected and measured from butterfly tubing in comparison with tuberculin syringe controls. Diffusion of gas through the polyvinylchloride tubing was suggested and proved by a study of pairs of butterfly and tuberculin syringes filled with venous blood from the blood bank. In conclusion, the butterfly gives falsely elevated PO2 values as a result of gas diffusion and is not a reliable technique for arterial blood gas sampling in neonates.

The effects of conventional dosage of gentamicin of 2.5 mg/kg given every 12 hours was retrospectively investigated in a small community hospital. Consistent with previous results in large hospitals, the conventional dosage of gentamicin commonly resulted in serum concentrations associated with toxicosis. Results were compared with those obtained prospectively according to a gentamicin dosing protocol that used a formula based on gestational age. The gestational age regimen provided similar peak and significantly lower trough serum concentrations; statistical analysis indicated no demographic differences in the compared groups. Very few neonates who received gentamicin according the gestational age formula were exposed to gentamicin serum concentrations associated with an increased risk of toxicosis. An absence of any significant differences in mean peak and trough serum concentrations in subgroups of neonates treated according to the gestational age formula suggested that use of the gentamicin dosing protocol was appropriate for all neonates. The dose of 3.5 mg/kg used in the gestational age formula was predicted to have resulted in initial gentamicin peak serum concentrations > 5 micrograms/ml in nearly 90% of neonates. The experience obtained with the gestational age formula allowed revision of the gentamicin dosing protocol to provide for more cost-responsible serum concentration monitoring.

Baseline arterial red cell indices were determined at birth in 105 infants of various gestational ages. These arterial samples were obtained through an umbilical artery catheter or radial artery puncture from a selected group of patients who were evaluated for respiratory distress or possible infection. The red cell distribution width, a quantitative measure of heterogeneity of red cells in the peripheral blood, was consistently elevated, revealing a physiologic state of anisocytosis in the newborn. This new information has provided a useful baseline reference for normal red cell indices from arterial blood in neonates in the first 24 hours of life.

Anthropometric measurements and total bilirubin formation (TBF) estimates were performed on infants born to normal and diabetic mothers. Although we do not exclude the theoretical possibility of a low-frequency occurrence of increased TBF in macrosomic infants of normal mothers, we can conclude that infants of mothers whose diabetes is well managed may have normal TBF.

Neutropenia is common in neonates with sepsis and in those born to women with pregnancy-induced hypertension. Neutropenia has not previously been described, however, as a result of the twin-twin transfusion syndrome. We observed neutropenia of 4 to 8 days' duration in each of five "donor" (anemic) twins affected with the twin-twin transfusion syndrome. No evidence of infection was observed. Like neutropenia of pregnancy-induced hypertension, no left shift was seen. Neutrophil kinetic studies were performed on one of the neutropenic patients. Assessment of the marginal, storage, proliferative, and progenitor cell pools indicated that neutropenia resulted from diminished neutrophil production.

The C-reactive protein (CRP) level was evaluated in 142 infants requiring investigation for suspected infection. After excluding two neonates because of incomplete data, there remained 140 neonates, of whom 16 had septicemia. Fifteen of 16 had increased CRP levels. The CRP value was not elevated in any baby (n = 5) who had positive blood cultures for Staphylococcus epidermidis, all of whom had an uneventful clinical course. The CRP level was elevated in all six babies with meconium-aspiration syndrome, but was normal in five infants whose viral cultures were positive. Ninety-nine percent of uninfected babies had normal CRP values. Overall, CRP was a valuable test for diagnostic confirmation of bacterial infection. Elevated CRP level was always accompanied by at least one abnormality in the other tests performed. Although the study was not intended to predict clinical onset of bacterial disease, our results suggest that the CRP level, because of a high negative predictive value, may be useful in ruling out bacterial infection.

Standard estimates of gestational age are dependent on such subjective data as maternal recollection of last menstrual period, ultrasound examination of the fetus, and the postnatal physical and neurological examination (Ballard score). We hypothesized that a quantitative, objective laboratory test using flow cytometric analysis of erythroid differentiation antigens could be useful to predict gestational age. For this study erythrocyte samples were obtained within 24 hours of birth from 25 infants (gestational ages 20 to 41 weeks) who met the criteria that traditional estimates of gestational age, such as the Ballard score, fetal ultrasound, and maternal estimate of last menstrual period all agreed within 1 week for the assessed infant's gestational age. Study measurements included reticulocyte count and determination of the percentage of erythrocytes that expressed the 5F1 and 20.3 erythropoietic differentiation antigens. Linear regression analysis indicated that the best correlations with gestational age were reticulocyte count (R2 = .354) and the reciprocal of the percentage of erythrocytes expressing the 5F1 antigen (R2 = .470). When both variables were incorporated into a linear regression model, the predictability of gestational age achieved an R2 = .608. Through this study we have established the feasibility and methodology of using fetal and newborn erythrocytes to provide an objective assessment of gestational age by flow cytometric analysis of erythroid differentiation antigen expression. This methodology will allow for an independent assessment of gestational age when fetal blood sampling is performed for other prenatal diagnostic studies. Further investigation is needed to identify other erythroid differentiation markers that would improve the accuracy of our model to predict gestational age.

Thyroxine and triiodothyronine levels are lower in preterm infants than in term infants. Until a distinction is made among hypothyroidism, prematurity, and illness as the cause, the necessity of treatment is unclear. Thyroxine, triiodothyronine, free thyroxine, and thyroid-stimulating hormone were measured weekly in 75 patients of 25 to 42 weeks gestational age. The range of thyroxine values among hospitalized term and preterm infants was lower than has been previously reported for healthy term newborns or infants. Thyroxine and triiodothyronine levels were consistently lower in preterm infants, but there were only minor differences between term and preterm infants' free thyroxine levels, which were both stable over time. Mean (SD) free thyroxine levels by week were 0.0259 (0.0079), 0.0259 (0.0057), 0.0201 (0.0066), 0.0274 (0.0079), 0.0241 (0.0023) nmol/L for term infants, and 0.0215 (0.0072), 0.0223 (0.0056), 0.0212 (0.0066), 0.0186 (0.0064), and 0.0201 (0.0021) nmol/L for preterm infants at weeks 1, 2, 3, 4, and greater than 4, respectively. Maturity was the best predictor of thyroxine or triiodothyronine levels, but illness was the clinical variable most highly correlated with free thyroxine. All 71 surviving infants were euthyroid at discharge. The free thyroxine measurement results suggest that hypothyroxinemia is not hypothyroidism but is a result of a combination of reduced protein-bound thyroxine as well as nonthyroidal illness.

Plasma ammonia concentration in neonates has routinely been determined using arterial or venous blood. Expected plasma ammonia values in capillary blood obtained by heelstick have not been determined. We compared ammonia levels in 20 sets of plasma from simultaneously drawn arterial, venous, and capillary blood in a group of neonates receiving total parenteral nutrition. Mean ammonia concentrations in venous (107 +/- 44) and capillary blood (112 +/- 33) were 45% and 51% higher, respectively, than corresponding arterial (74 +/- 22) values (P less than .001). Ammonia levels in blood obtained by venipuncture (Ven), however, did not correlate consistently with arterial (Art) values (r = .43; Art = 51 + 0.21 Ven; P greater than .05). In contrast, ammonia levels in capillary blood (Cap) correlated well with arterial values (r = .86; Art = 10.3 + 0.6Cap; P less than .001). Ammonia levels in neonates may be reliably interpreted using the latter regression equation when blood for analysis is obtained by a properly performed heelstick, allowing the preservation of arteries and veins, and sparing the infant from repetitive needle punctures. Ammonia levels in blood obtained by venipuncture do not adequately correlate with arterial values and therefore may be therapeutically misleading.

The leukocyte count and differential white blood cell count during the first hour of life was determined in 164 neonates born of mothers receiving antenatal steroids and compared to 171 neonates of mothers randomly assigned to a placebo group. A leukemoid reaction (greater than 40,000 WBC/mm3) was seen only once each in the neonates born of placebo or steroid treated mothers. In addition, maternal steroid treatment had no general effect, except in a small subgroup of neonates born 3 to 7 days after the mother had been treated with 20 mg dexamethasone, where the total leukocyte and the absolute neutrophil counts were higher than the placebo group and other subgroups.

Maternal and cord blood 25-hydroxy vitamin D concentrations are positively and significantly correlated. If an easily obtainable maternal dietary history could be used to predict maternal and secondarily cord blood vitamin D status, it would be a useful means of assessing the vitamin D adequacy of the newborn. Therefore, a single assessment of maternal dietary vitamin D intake during the last trimester of pregnancy was correlated with maternal and newborn serum vitamin D concentration. Neither the correlation between maternal dietary history of vitamin D intake and maternal serum 25-hydroxy vitamin D level nor between maternal dietary history and cord blood 25-hydroxy vitamin D level was significant. These data indicate that a single maternal dietary history is an inadequate method of predicting neonatal vitamin status at delivery.

A series of 20 normal newborn term infants and 12 infants born to mothers who had abused opiates during pregnancy were studied. Auditory brainstem-evoked potentials were used to describe neurophysiologic dysfunction in a group of drug-addicted term infants. Significant differences in the auditory brainstem-evoked potentials were found between the two groups. Specifically, a decrease in the central conduction times was noted for the I-III interpeak interval, suggesting neurophysiologic dysfunction in the area of the pons and cerebellum.

Transcutaneous bilirubin index measurements (TcBI) were determined in ABO-incompatible term white newborn infants who had an indirect Coombs' test for detection of ABO incompatibility (ABO test) performed on cord blood. Serial transcutaneous measurements in the first 72 hours of life in 63 ABO test positive (group I) and 31 ABO test negative (group II) infants were compared with a control group of 109 term ABO compatible infants (group III). During the first phase of this study, the accuracy of TcBI was confirmed in 33 infants who had serum bilirubin determinations demonstrating a correlation coefficient of r = 0.93 between the jaundice meter index reading and total serum bilirubin. Determination of total serum bilirubin using TcBI did not show any statistically significant differences when groups I, II, and III were compared for maximum serum bilirubin values. These results reveal that a positive ABO test does not increase the predictive value of hyperbilirubinemia in ABO-incompatible white newborn infants.

Differences in serum glucose values obtained from different extremities in newborns with umbilical artery catheters (UAC) through which a dextrose solution was administered were studied. Control infants (n = 20) had no difference in simultaneous capillary glucose values obtained from both lower extremities. Infants with a low UAC had a significant difference between two (both lower extremities) or three (both lower and one upper extremity) simultaneous capillary glucose values. Infants with a high UAC did not. In the low UAC group, the serum glucose value was highest in the lower extremity through which the UAC entered the aorta and lowest in the upper extremity. The elevation in glucose value was related to the glucose infusion rate corrected for infant size (mg/kg/min). Clinicians caring for infants with low UACs should be aware of this potential error in order to prevent erroneous decision-making.

It was postulated that identification of term (LGA) large for gestational age newborns by the Portland Intrauterine Growth Curve rather than the Colorado Curve would classify a lesser number of neonates as LGA, but would identify the LGA neonates at risk for hypoglycemia. One hundred inborn neonates who plotted LGA on the Colorado Chart were reviewed. Sixty-one infants were LGA on the Portland Chart. Of the 100 infants, 17 were found to have dextrostix less than 45 mg% in the first two hours of life, 15 of these had quantitative blood glucose (BG) test performed. Eleven of the 15 neonates had a BG less than 40 mg%; all 11 hypoglycemic neonates were identified LGA on the Colorado Graph whereas only seven were identified LGA by the Portland Graph. The authors conclude that the Colorado Graph is a better tool in their population than the Portland in identifying term LGA neonates at risk for hypoglycemia.

Total nutrient admixture (TNA) combines amino acids, lipids, and glucose in a single bottle for continuous parenteral use. This cost-effective and easily administered solution is now available for use in neonates. The present study was performed to assess the metabolism of fat administered as TNA in sick neonates as reflected by serum free fatty acid (FFA) and triglyceride (TG) levels. During a 6-month period, TG and FFA levels were monitored in all infants receiving TNA. Levels were measured within 24 hours of a change in lipid dose and then weekly when maximum intake (about 2 g/kg/day) was achieved. Sixty-nine TG and 58 FFA levels were obtained from 42 neonates who at the time of sampling were receiving 2 g/kg/day or more of parenteral lipid. Ninety-one percent of TG levels were less than or equal to 200 mg/dL. Ninety-six percent of FFA levels were less than or equal to 2000 mumol/L. A weak but statistically significant correlation was noted between TG and FFA levels with a correlation coefficient of 0.54. In conclusion, although the range of FFA and TG levels obtained from sick neonates on TNA therapy is relatively wide, these levels are comparable to those reported in the literature for infants receiving standard intravenous lipid infusions.

Transcutaneous arterial oxygen saturation (TcSaO2) and directly measured oxygen saturation values from 25 neonates with a variety of respiratory problems were compared. At arterial oxygen saturations above 60 per cent, TcSaO2 measurements were accurate and reliable. However, SaO2 values less than 60 per cent were significantly overestimated by TcSaO2, so careful laboratory confirmation of low SaO2 values is necessary. The use, accuracy, and limitations of this noninvasive transcutaneous technique for measuring arterial hemoglobin-oxygen saturation are discussed.