Changes in plasma and urinary nitrite after birth in premature infants at risk for necrotizing enterocolitis.

BACKGROUND: Plasma nitrite serves as a reservoir of nitric oxide (NO) bioactivity. Because nitrite ingestion is markedly lower in newborns than adults, we hypothesized plasma nitrite levels would be lower in newborns than in adults, and that infants diagnosed with necrotizing enterocolitis (NEC), a disease characterized by ischemia and bacterial invasion of intestinal walls, would have lower levels of circulating nitrite in the days prior to diagnosis. METHODS: Single blood and urine samples were collected from 9 term infants and 12 adults, 72 preterm infants every 5 d for 3 wk, and from 13 lambs before and after cord occlusion. RESULTS: Nitrite fell 50% relative to cord levels in the first day after birth; and within 15 min after cord occlusion in lambs. Urinary nitrite was higher in infants than adults. Plasma and urinary nitrite levels in infants who developed NEC were similar to those of preterm control infants on days 1 and 5, but significantly elevated at 15 and 20 d after birth. CONCLUSION: Plasma nitrite falls dramatically at birth while newborn urinary nitrite levels are significantly greater than adults. Acute NEC is associated with elevated plasma and urinary nitrite levels.

Oral, jaw, and neck injury in infants and children: from abusive trauma or intubation?

OBJECTIVES: The objective of this study was to identify the incidence of oral, jaw, and neck injury secondary to endotracheal intubation in young children. METHODS: This prospective observational study was conducted in the pediatric intensive care unit at a level 1 trauma center. From October 1998 to January 1999 and November 2007 to April 2008, all intubated patients younger than 3 years with no prior oral procedures were examined within 24 hours of intubation. A standardized form was used to record injuries. Separately, medical records were reviewed for prior injuries. Chi-square/Fisher exact test was used for statistical analysis. RESULTS: Of 105 patients included in the study, 12 had oral, jaw, or neck injury. One patient had a hard palate injury from a pen cap in his mouth during a seizure. Another broke a tooth biting the laryngoscope blade (the only injury directly attributable to intubation). The remaining 10 patients were determined to be those who experienced abusive trauma. The overall incidence of injury directly from intubation was 0.9%. Oral, jaw, and neck injuries were all significantly associated with abusive trauma (P < 0.001). Eleven patients had difficult intubations: 9 had no injuries, 1 experienced abusive trauma and the second was the patient who broke his tooth during intubation. CONCLUSIONS: Oral, jaw, or neck injury in young children is rarely caused by endotracheal intubation, regardless of difficulty during the procedure.

Oral sucrose for heel lance increases adenosine triphosphate use and oxidative stress in preterm neonates.

OBJECTIVE: To examine the effects of sucrose on pain and biochemical markers of adenosine triphosphate (ATP) degradation and oxidative stress in preterm neonates experiencing a clinically required heel lance. STUDY DESIGN: Preterm neonates that met study criteria (n = 131) were randomized into 3 groups: (1) control; (2) heel lance treated with placebo and non-nutritive sucking; and (3) heel lance treated with sucrose and non-nutritive sucking. Plasma markers of ATP degradation (hypoxanthine, xanthine, and uric acid) and oxidative stress (allantoin) were measured before and after the heel lance. Pain was measured with the Premature Infant Pain Profile. Data were analyzed by the use of repeated-measures ANOVA and Spearman rho. RESULTS: We found significant increases in plasma hypoxanthine and uric acid over time in neonates who received sucrose. We also found a significant negative correlation between pain scores and plasma allantoin concentration in a subgroup of neonates who received sucrose. CONCLUSION: A single dose of oral sucrose, given before heel lance, significantly increased ATP use and oxidative stress in premature neonates. Because neonates are given multiple doses of sucrose per day, randomized trials are needed to examine the effects of repeated sucrose administration on ATP degradation, oxidative stress, and cell injury.

Inhaled nitric oxide therapy increases blood nitrite, nitrate, and s-nitrosohemoglobin concentrations in infants with pulmonary hypertension.

OBJECTIVE: To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity after inhaled NO (iNO) therapy in infants with pulmonary hypertension. STUDY DESIGN: In this single center study, 5 sequential blood samples were collected from infants with pulmonary hypertension before, during, and after therapy with iNO (n = 17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n = 16) and from healthy adults for comparison (n = 12). RESULTS: After beginning iNO (20 ppm) whole blood nitrite levels increased approximately two-fold within 2 hours (P<.01). Whole blood nitrate levels increased to 4-fold higher than baseline during treatment with 20 ppm iNO (P<.01). S-nitrosohemoglobin increased measurably after beginning iNO (P<.01), whereas iron nitrosyl hemoglobin and total hemoglobin-bound NO-species compounds did not change. CONCLUSION: Treatment of pulmonary hypertensive infants with iNO results in increases in levels of nitrite, nitrate, and S-nitrosohemoglobin in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart, and other organs.

Comparison of Local and Systemic Inflammation During Invasive Versus Noninvasive Ventilation in Rats.

The impact of noninvasive ventilation (NIV) on local and systemic inflammation is poorly characterized, particularly when compared with invasive mechanical ventilation (IMV). We sought to quantify the local and systemic inflammatory response of these 2 respiratory treatments in rats with lipopolysaccharide (LPS)-induced lung injury (LPS-injured) and healthy rats. Animals were subjected to 4 h of NIV or IMV treatments at noninjurious settings, or 4 h of control treatment in which healthy or LPS-injured animals remained spontaneously breathing under isoflurane anesthesia with no respiratory support. Cytokines were then quantified in the serum and lung tissue by multiplex enzyme-linked immunosorbent assay. Contrary to our hypothesis, there were no significant differences in cytokine levels in serum or lung when comparing the NIV- and IMV-treated groups; this was true in both LPS-injured and healthy rats. However, within the LPS-injured group, pulmonary levels of interleukin (IL)-1α, IL-6, and tumor necrosis factor α were significantly lower in the NIV-treated group than in control but not in the IMV-treated group compared with control. We conclude that NIV, unlike IMV, could attenuate local inflammation.

Calcineurin inhibitor minimization using sirolimus leads to improved renal function in pediatric heart transplant recipients.

The introduction of cyclosporine revolutionized the practice of immunosuppression for solid organ transplant recipients, and has resulted in a significant increase in survival. While CNI use has been the mainstay of immunosuppressive therapy in pediatric heart transplantation, CNIs have been associated with an increased risk of nephropathy leading to significant morbidity and mortality. We evaluated the effect on renal function of a CNI minimization protocol using SRL in pediatric heart transplant patients with CNI induced renal insufficiency. An IRB approved retrospective chart review and case control study was performed. There were 20 patients identified with renal insufficiency who had been converted to SRL (target 5-8 ng/mL) and cyclosporine (target 50-75 vs. 125-150 ng/mL). Renal insufficiency was defined as isotopic (Indium 111 DTPA) GFR <60 mL/min per 1.73 m(2) or sCr >1 mg/dL. Outcome variables evaluated were GFR and sCr at time of conversion and at two yr post conversion. Comparison was made with case control subjects matched for age at Tx, time from Tx to conversion, and initial GFR. The median age at Tx = 81 days (S.D. ±26), median time of conversion after Tx = 10 yrs (s.d. ±0.65). Self-limited/treatable side effects included hypercholesterolemia (10), neutropenia (6), aphthous ulcer (3), edema (2), anemia (2), and tremor (1). One patient rejected in the two yr prior to conversion, and one patient had two rejection episodes following conversion. GFR at conversion for study group was 51 ± 14 vs. 60 ± 2 at two yr, p = 0.018. GFR at inclusion for control group was 56 ± 20 vs. 53 ± 21, p = 0.253. This report demonstrates that minimizing CNI exposure by addition of SRL to the immunosuppressant regimen in pediatric heart transplant recipients result in improved renal function in comparison to historically managed patients. Furthermore, immunotherapy with SRL and lower-dose CNI can effectively prevent rejection with an acceptable side-effect profile.

A pilot study on the biochemical effects of repeated administration of 24% oral sucrose vs. 30% oral dextrose on urinary markers of adenosine triphosphate degradation.

OBJECTIVES: Premature neonates often receive oral sucrose or dextrose before tissue-damaging procedures (TDPs). Previous work showed that a single dose of sucrose, but not dextrose, increased cellular energy utilization and ATP degradation. This pilot study probes the effects of repeated administration of sucrose or dextrose on energy metabolism. METHODS: Urinary markers of ATP metabolism (hypoxanthine, xanthine, uric acid) are measured in premature neonates randomized to receive: (a) standard of care, (b) 0.2 ml 24% oral sucrose, or (c) 0.2 ml 30% oral dextrose, before every painful procedure on days-of-life 3-7. RESULTS: Standard of care is associated with highest xanthine/creatinine and uric acid/creatinine, likely because of fewer pain treatments. Benefits of repeated oral sucrose are unclear. Neonates receiving oral dextrose had lower xanthine/creatinine and uric acid/creatinine. CONCLUSIONS: Repeated treatments of neonatal procedural pain with 30% oral dextrose are less energetically demanding. Larger clinical studies are needed for comparison with sucrose treatments.

Etiologies of apnea of infancy.

BACKGROUND: To date there are limited data in the literature to guide the initial evaluation for etiologies of apnea in full-term infants born at greater than or equal to 37 weeks conceptional age (apnea of infancy [AOI]). Pediatricians and pediatric pulmonologists are left to pursue a broad, rather than targeted and a stepwise approach to begin diagnostic evaluation. METHODS: We performed a retrospective chart review of 101 symptomatic full-term infants (age under 12 months) diagnosed with apnea with an inpatient multichannel pneumogram (six channels) or a fully attended overnight pediatric polysomnogram in our outpatient sleep center accredited by American Academy of Sleep Medicine (AASM), scored using the standards set forth by the AASM. The infant was diagnosed as having AOI if the apnea hypopnea index (AHI) was greater than 1 (AHI is defined as the number of apnea and hypopnea events per hour of sleep). The final diagnosis/etiology was determined based on physician clinical assessment and work up. We then determined the frequency for each diagnosis. RESULTS: We found that the three most common etiologies were gastroesophageal reflux disease (GERD) (48/101), upper airway abnormalities/obstruction (37/101), and neurological diseases (19/101). There were significant numbers of infants with multiple etiologies for AOI. CONCLUSION: Based on the frequencies obtained, pediatric practitioners caring for full-term infants with apnea of unknown etiology are advised to begin with evaluation of more likely causes such as GERD and upper airway abnormalities/obstruction before evaluating for less common causes.

Oxidative Stress Biomarker Decreased in Preterm Neonates Treated With Kangaroo Mother Care.

OBJECTIVE: Due to physiological and metabolic immaturity, prematurely born infants are at increased risk because of maternal separation in many neonatal intensive care units (NICUs). The stress induced from maternal-infant separation can lead to well-documented short-term physiologic instability and potentially lifelong neurological, sociological, or psychological sequelae. Based on previous studies of kangaroo mother care (KMC) that demonstrated improvement in physiologic parameters, we examined the impact of KMC on physiologic measures of stress (abdominal temperature, heart rate, oxygen saturation, perfusion index, near-infrared spectrometry), oxidative stress, and energy utilization/conservation in preterm infants. METHODS: In this randomized, stratified study of premature neonates, we compared the effects on urinary concentrations of biomarkers of energy utilization and oxidative stress of 1 hr of KMC versus incubator care on Day 3 of life in intervention-group babies (n = 26) and control-group babies (n = 25), respectively. On Day 4, both groups received 1 hr of KMC. Urinary samples were collected 3 hr before and 3 hr after intervention/incubator care on both days. Energy utilization was assessed by measures of adenosine triphosphate (ATP) degradation (i.e., hypoxanthine, xanthine, and uric acid). Oxidative stress was assessed using urinary allantoin. Mixed-models analysis was used to assess differences in purine/allantoin. RESULTS: Mean allantoin levels over Days 3 and 4 were significantly lower in the KMC group than in the control group (p = .026). CONCLUSIONS: Results provide preliminary evidence that KMC reduces neonatal oxidative stress processes and that urinary allantoin could serve as an effective noninvasive marker for future studies.

Oral dextrose reduced procedural pain without altering cellular ATP metabolism in preterm neonates: a prospective randomized trial.

OBJECTIVE: To examine the effects of 30% oral dextrose on biochemical markers of pain, adenosine triphosphate (ATP) degradation, and oxidative stress in preterm neonates experiencing a clinically required heel lance. STUDY DESIGN: Utilizing a prospective study design, preterm neonates that met study criteria (n = 169) were randomized to receive either (1) 30% oral dextrose, (2) facilitated tucking, or (3) 30% oral dextrose and facilitated tucking 2 min before heel lance. Plasma markers of ATP degradation (hypoxanthine, uric acid) and oxidative stress (allantoin) were measured before and after the heel lance. Pain was measured using the premature infant pain profile-revised (PIPP-R). RESULTS: Oral dextrose, administered alone or with facilitated tucking, did not alter plasma markers of ATP utilization and oxidative stress. CONCLUSION: A single dose of 30% oral dextrose, given before a clinically required heel lance, decreased signs of pain without increasing ATP utilization and oxidative stress in premature neonates.

Referral for Ophthalmology Evaluation and Visual Sequelae in Children With Primary Brain Tumors.

Importance: Visual impairment in children with brain tumors has received limited attention, as most pediatric neuro-oncology clinical trials neither require ophthalmologic evaluation on enrollment nor monitor effects of treatment on visual function during and after treatment. Objective: To investigate ophthalmology referral patterns for children with primary brain tumors, the prevalence of visual sequelae, and the association between tumor characteristics and vision-related diagnoses. Design, Setting, and Participants: This retrospective cohort study included 141 children with primary brain tumors treated at Loma Linda University Children's Hospital and Eye Institute, a university-based tertiary referral center, between January 2013 and September 2017. Data analysis was completed in March 2019. Intervention: Comprehensive ophthalmologic evaluation for children with primary brain tumors. Main Outcomes and Measures: Percentage of patients with ophthalmology evaluation, prevalence of abnormal ophthalmic findings, and their association with tumor characteristics. Results: A total of 141 children (73 [52%] male; median [range] age, 7 [0-18] years) with primary brain tumors were enrolled in this study. Seventy-three patients (41 [52%] male; median [range] age, 8 [0-17] years) never had formal ophthalmologic evaluation. Sixty-eight patients (32 [48%] male; median [range] age, 7 [0-18] years) were evaluated by 1 of 4 board-certified, fellowship-trained pediatric and/or neuro-ophthalmologists for any visual impairment over a total of 222 visits. Five-year overall survival for patients who had eye examination was not significantly different from those who did not (mean [SD] survival, 78.3% [6.2%] vs 84.9% [4.7%]). Median (range) time from tumor diagnosis to initial ophthalmologic evaluation was 9 (0-94) months. Only 10 of 68 children (15%) presented with visual symptoms at tumor diagnosis, while 61 of 68 (90%) had abnormal findings on examination, including strabismus (41 [60%]), visual acuity impairment (37 [54%]), amblyopia (26 [38%]), papilledema (24 [35%]), visual field defects (13 [19%]), optic atrophy (12 [18%]), and keratopathy (10 [15%]). Strabismus occurred more frequently in patients with posterior fossa tumors (26 of 68 in posterior fossa vs 15 of 68 in other locations; P = .02). The presence of visual field defects in patients with no visual symptoms was 15% (9 of 58). Radiation was significantly associated with amblyopia (odds ratio, 4.5; 95% CI, 1.2-15.7; P = .02). Conclusions and Relevance: In this study, more than 50% of children with primary brain tumors were not referred for ophthalmologic evaluation. Although visual symptoms were uncommon, visual impairments occurred more frequently than previously reported. Ophthalmologic evaluation is recommended to identify and manage visual impairment and prevent permanent vision loss in children with brain tumors.

Direct equilibrium dialysis compared with two non-dialysis free T4 methods in premature infants.

OBJECTIVE: To compare the incidence of low free T4 values reported by a direct equilibrium dialysis method to their incidence reported by 2 non-dialysis methods. STUDY DESIGN: Ninety-five infants, < or = 33 weeks gestational age at birth, admitted to Loma Linda University Children's Hospital before day 3 of life were studied. Infants were grouped by gestational age ranges: < or = 27, 28-30, and 31-33 weeks. Free T4 determinations were measured at 3, 7, and 14 days of life with 3 different free T4 methods. Gestational age-specific newborn reference ranges were available for the direct equilibrium dialysis method only. The only reference ranges available for the non-dialysis free T4 methods were not gestational age specific. Using available reference ranges we classified free T4 values as either low or not low. The incidence of low free T4 values was compared at 3, 7, and 14 days of life. RESULTS: Low direct equilibrium dialysis free T4 values were substantially less frequent than non-dialysis free T4 values. CONCLUSION: Substantial free T4 inconsistencies occur between dialysis and non-dialysis free T4 methods in preterm infants. It is unclear how much of this inconsistency is method dependent and how much is reference range dependent.

High Prevalence of Pulmonary Hypertension Complicates the Care of Infants with Omphalocele.

BACKGROUND: Omphalocele is one of the most common abdominal wall defects. Many newborn infants born with omphalocele present with significant respiratory distress at birth, requiring mechanical ventilatory support, and have clinical evidence of pulmonary hypertension. Little information exists on the prevalence of and risk factors associated with pulmonary hypertension in this cohort of infants. OBJECTIVES: To describe the prevalence of and risk factors associated with pulmonary hypertension among infants with omphalocele. METHODS: This is a multicenter retrospective chart review of demographic data and clinical characteristics of infants with omphalocele admitted to the neonatal intensive care units of Loma Linda University Children's Hospital and Children's Mercy Hospital between 1994 and 2011. Echocardiogram images were reviewed for pulmonary hypertension, and statistical analyses were performed to identify risk factors associated with the presence of pulmonary hypertension. RESULTS: Pulmonary hypertension was diagnosed in 32/56 (57%) infants with omphalocele. Compared to infants without pulmonary hypertension, infants with pulmonary hypertension were more likely to have a liver-containing defect (16/32 [50%] vs. 5/24 [21%], p = 0.03), require intubation at birth (18/32 [56%] vs. 6/24 [17%], p = 0.03), and die during initial hospitalization (12/32 [38%] vs. 2/24 [8%], p = 0.01). CONCLUSION: The majority of infants with omphalocele have evidence of pulmonary hypertension which is associated with increased mortality. Echocardiograms to screen for pulmonary hypertension should be obtained at ≥2 days of life in infants with omphalocele, especially in those with liver within the omphalocele sac and/or in those infants who require intubation at birth to screen for pulmonary hypertension.

Moderate acute rejection detected during annual catheterization in pediatric heart transplant recipients.

BACKGROUND: Acute rejection commonly occurs within the first year after heart transplantation, and then decreases in frequency with time. Recently, the long-term utility of endomyocardial biopsy during routine annual catheterization has been questioned. The purpose of this study was to retrospectively review the prevalence of biopsy-proven rejection during routine annual catheterization in our patient population, determine whether biopsies late after transplant are useful, and identify factors that correlate with late unsuspected rejection. METHODS: Biopsy results from the annual catheterization were evaluated from 1986 to August 2000. The prevalence of moderate rejection was evaluated and compared with the patient's immunosuppressive regimen; the prevalence of late rejection; and how late rejection correlated with recipient age, number of first-year rejections and presence of sub-therapeutic cyclosporine. RESULTS: A total of 1108 biopsies were performed in 269 children with a mean follow-up of 5 +/- 3 years (median 5 years, range 1 to 11 years). Three-drug immunosuppressive therapy, including steroids, was used in 93 patients. There was a persistent 8% to 10% prevalence of moderate rejection at up to 10 years post-transplantation. Moderate rejection was more likely in patients: (1). on 3-drug immunosuppressive therapy; (2). with a recipient age >1 year; and (3). with a relatively lower cyclosporine level. CONCLUSIONS: These data suggest that continued surveillance of pediatric transplant patients for acute rejection is indicated for long-term follow-up.

Comparison of 2 iron doses in infants receiving recombinant human erythropoietin therapy.

OBJECTIVE: To compare iron sufficiency in premature infants receiving high-dose recombinant human erythropoietin (r-HuEPO), 1200 IU/kg per week, supplemented with 6 or 12 mg/kg per day of enteral iron. DESIGN: We conducted a prospective, double-blind, controlled study of premature infants receiving r-HuEPO therapy, randomly assigned to receive 2 different doses of iron. Measurements of ferritin, iron, total iron-binding capacity, reticulocyte count, hemoglobin level, and hematocrit were obtained at baseline, 4, and 6 weeks. Transferrin saturation was calculated; the number of blood transfusions and the incidences of sepsis were recorded. SETTING: This study was performed in the neonatal intensive care unit at Loma Linda University Children's Hospital, Loma Linda, Calif. SUBJECTS: Infants with a gestational age of 32 weeks or younger, older than 7 days, and receiving r-HuEPO therapy from March 1, 1997, to June 30, 1998, were eligible for the study. Infants were randomly assigned to receive 6 mg/kg per day or 12 mg/kg per day of enteral iron during a course of r-HuEPO therapy for 4 to 6 weeks. RESULTS: Sixty-four infants were enrolled in the study. Twelve infants did not complete the study; 52 completed 4 weeks and 41 completed 6 weeks of the study. While ferritin levels and transferrin saturation decreased in both groups over the study period, there were no differences between the 2 study groups. CONCLUSIONS: Infants receiving high-dose r-HuEPO therapy (1200 IU/kg per week) decrease their ferritin levels (measure of iron stores) even when receiving high enteral iron supplementation. Given that the ferritin levels were similar between the 2 groups, we speculate that the additional iron either was not absorbed or was not stored.

QTc interval in infants receiving cisapride.

OBJECTIVE: To examine the effect of cisapride on the corrected QT (QTc) interval in infants over a 14-day period. STUDY DESIGN: A prospective cohort study of infants receiving cisapride (0.8 mg/kg per day). Twelve-lead electrocardiograms were obtained before and 3, 5, 7, and 14 days after cisapride initiation. RESULTS: Fifty infants completed the study; none had arrhythmias. Fifteen of 50 infants (30%) developed QTc interval > or =450 msec; QTc interval normalized in 13 of 15 infants. Infants with QTc interval on day 3 > or =2 standard deviations above the mean baseline QTc interval (401+40 msec) were more likely to develop prolonged QTc interval (p<0.0001). CONCLUSION: QTc interval prolongation was noted in 30% of infants. Subsequently, the majority of those infants had QTc interval normalization by day 14 of cisapride therapy. QTc interval 3 days following cisapride initiation may identify infants at risk for transient QTc interval prolongation. With appropriate monitoring, hospitalized infants receiving cisapride may have improved gastrointestinal motility without cardiac morbidity.

Proton magnetic resonance spectroscopy improves outcome prediction in perinatal CNS insults.

OBJECTIVE: Prediction of neurologic outcome is difficult in neonates with acute nervous system injury. Previous studies using proton magnetic resonance spectroscopy ((1)H-MRS) have been used to predict short-term neurologic outcome in neonates with a variety of neurologic insults. We were interested in determining the effectiveness of combining clinical evaluation and spectroscopy obtained at the time of injury in predicting neurologic outcome at 24 months. STUDY DESIGN: We studied 33 neonates with acute central nervous system injury, 5.8+/-3.7 days of injury, owing to hypoxic-ischemic encephalopathy. Neonates were assessed using clinical variables (initial arterial pH, initial blood glucose, Sarnat score, electroencephalography) and spectroscopy (NAA/Cho, NAA/Cre, Cho/Cre, and lactate). Neonates were divided into two outcome groups: good/moderate and poor. Differences between the groups were assessed using chi(2) and t-test analyses. We analyzed the best predictors of outcome using discriminant analysis and calculated sensitivity, specificity, positive, and negative predictive values for each variable independently and in combination. RESULTS: There were significant differences between the good/moderate and poor outcome for the Sarnat score, EEG, lactate, and NAA/Cho. Spectroscopy combined with clinical variables improved sensitivity, but not specificity for predicting outcome. The presence of lactate had the best individual predictive value. Combination of the clinical with the MRS variables had the highest predictive value. CONCLUSION: Proton magnetic resonance spectroscopy done early after injury improves the ability to predict neurologic outcome at 24 months of age.

Incidence of low free T4 values in premature infants as determined by direct equilibrium dialysis.

BACKGROUND: The incidence of transient reductions in serum free T(4) (FT(4)) in premature infants may be overestimated because certain FT(4) analytical methods underestimate FT(4) concentrations. Transient reductions of FT(4) measurements have been reported in the majority of premature newborn infants. Direct equilibrium dialysis (DED) does not underestimate FT(4) concentrations and is the best available technique to measure serum FT(4) in the premature infant. OBJECTIVE: To evaluate the incidence of low FT(4) concentrations in premature infants using DED to measure FT(4). DESIGN/METHOD: We measured FT(4) by DED in infants with birth weight <1500 g. Infants were excluded if the following conditions were present: congenital anomalies or maternal thyroid disorders. Free T(4) was measured at 14 days of life. Low FT(4) was defined using a statistical definition of FT(4) measurements <10.3 pmol/l (0.8 ng/dl). RESULTS: Free T(4) was measured by DED in 114 infants. Low FT(4) levels were seen in nine infants (7.9%). CONCLUSION: The incidence of low FT(4) was much lower than previously reported when FT(4) was measured using DED indicating that methodological issues are involved in the variability among estimates of the frequency of transient reduction in FT(4).

Pediatric recipient survival beyond 15 post-heart transplant years: a single-center experience.

BACKGROUND: We evaluated late survival among pediatric heart transplant patients who have lived more than 15 years. METHODS: This is a retrospective chart review of the pediatric patients who underwent heart transplantation (HTx) between 1985 and 1998. Multivariate and univariate analyses were examined. RESULTS: There were 183 recipients, of whom 151 are currently alive. Age at HTx ranged from 0 days to 17.48 years (median 56 days). Pretransplant diagnoses included congenital heart disease 142 (77.6%), cardiomyopathy 38 (20.8%), and tumor 3 (1.6%). Pretransplant renal dysfunction was present in 58 patients (31.7%). Perioperative peritoneal dialysis was instituted in 15 patients, all recovered. During the follow-up period (median 20.2 years), 17 (9.3%) have had renal transplants, and 2 require hemodialysis. There were 32 deaths from the following: cardiac allograft vasculopathy (CAV); 11 (34.3%); posttransplant lymphoproliferative disease 6 (18.8%); acute rejection 4 (12.5%); sepsis 2 (6.3%); multiorgan failure 1 (3.1%); and unknown 8 (25%). Immunosuppressive therapy for the living patients consists of monotherapy 25 (17.7%), dual therapy 87 (61.7%), triple therapy 24 (17%), quadruple therapy 5 (3.5%), and 10 unknown. Cardiac re-Tx was required for CAV in 30 patients and for graft failure in 6 patients. Four patients required a third transplant for CAV. For those who survived more than 15 years after HTx, actuarial survival to 20 years and 25 years is 82% and 78%, respectively. CONCLUSIONS: Pediatric HTx provides acceptable long-term survival. Cardiac re-Tx and renal transplantation offer reasonable palliation for recipients who develop CAV and renal dysfunction.