William P. Kanto

Prevention of respiratory syncytial virus infections: Indications for the use of palivizumab and update on the use of RSV-IGIV

The Food and Drug Administration recently approved the use of palivizumab (palē-vizhū-mäb), an intramuscularly administered monoclonal antibody preparation. Recommendations for its use are based on a large, randomized study demonstrating a 55% reduction in the risk of hospitalization attributable to respiratory syncytial virus (RSV) infections in high-risk pediatric patients. Infants and children with chronic lung disease (CLD), formerly designated bronchopulmonary dysplasia, as well as prematurely born infants without CLD experienced a reduced number of hospitalizations while receiving palivizumab compared with a placebo. Both palivizumab and respiratory syncytial virus immune globulin intravenous (RSV-IGIV) are available for protecting high-risk children against serious complications from RSV infections. Palivizumab is preferred for most high-risk children because of ease of administration (intramuscular), lack of interference with measles–mumps–rubella vaccine and varicella vaccine, and lack of complications associated with intravenous administration of human immune globulin products. RSV-IGIV, however, provides additional protection against other respiratory viral illnesses and may be preferred for selected high-risk children including those receiving replacement intravenous immune globulin because of underlying immune deficiency or human immuno-deficiency virus infection. For premature infants about to be discharged from hospitals during the RSV season, physicians could consider administering RSV-IGIV for the first month of prophylaxis. Most of the guidelines from the American Academy of Pediatrics for the selection of infants and children to receive RSV-prophylaxis remain unchanged. Palivizumab has been shown to provide benefit for infants who were 32 to 35 weeks of gestation at birth. RSV-IGIV is contraindicated and palivizumab is not recommended for children with cyanotic congenital heart disease. The number of patients with adverse events judged to be related to palivizumab was similar to that of the placebo group (11% vs 10%, respectively); discontinuation of injections for adverse events related to palivizumab was rare.

Epidemiology of necrotizing enterocolitis: A case control study

All neonates with necrotizing enterocoltis cared for at Grady Memorial Hospital from July, 1977, through February, 1979, were compared with controls matched for birth weight and time of admission to the nursery, to examine risk factors which have been implicated in the etiology of the disease. Data on maternal history, birth history, and hospital course were uniformly collected and contrasted for 35 cases and 98 controls. Low birth weight was associated with an increased incidence of NEC and an increased case fatality rate. All babies 36 weeks or more at birth were diagnosed by seven days. More immature infants developed the disease later in their hospital course. In addition, preterm babies who developed NEC after 2 weeks of age appear to be smaller and sicker. Factors previously thought to predispose an infant to the development of the disease, such as prolonged rupture of membranes, infectious complications of pregnancy, low Apgar scores, patent ductus arteriosus, and use of umbilical catheters, were found with equal frequency in cases and controls and may simply represent the descriptive characteristics of a population of sick premature infants. Feeding history and antibiotic use were examined in depth and were not correlated with the development of NEC.

Use of telemedicine for children with special health care needs

Objective. In 1995, the Childrens Medical Services (CMS) of the State of Georgia contracted with the Department of Pediatrics of the Medical College of Georgia (MCG) and the MCG Telemedicine Center to develop telemedicine programs to provide subspecialty care for children with special health care needs. This article presents project statistics and results of client evaluation of services, as well as physician faculty attitudes toward telemedicine. Design. A demonstration project using telemedicine between a tertiary center and a rural clinic serving children with special health care needs was established. Data were collected and analyzed for December 12, 1995 to May 31, 1997, during which 333 CMS telemedicine consultations were performed. Results. Most CMS telemedicine consultations (35%) involved pediatric allergy/immunology. Other subspecialties included pulmonology (29%), neurology (19%), and genetics (16%). Overall, patients were satisfied with the services received. Initially, physician faculty members were generally positive but conservative in their attitudes toward using telemedicine for delivering clinical consultation. After a years exposure and/or experience with telemedicine, 28% were more positive, 66% were the same, and only 4% were more negative about telemedicine. The more physicians used telemedicine, the more positive they were about it (r = .30). Conclusions. In terms of family attitudes and individual care, telemedicine is an acceptable means of delivering specific pediatric subspecialty consultation services to children with special health care needs, living in rural areas distant to tertiary centers. Telemedicine is more likely to be successful as part of an integrated health services delivery than when it is the sole mode used for delivery of care.

Greater Fructose Consumption Is Associated with Cardiometabolic Risk Markers and Visceral Adiposity in Adolescents

Though adolescents consume more fructose than any other age group, the relationship between fructose consumption and markers of cardiometabolic risk has not been established in this population. We determined associations of total fructose intake (free fructose plus one-half the intake of free sucrose) with cardiometabolic risk factors and type of adiposity in 559 adolescents aged 14-18 y. Fasting blood samples were measured for glucose, insulin, lipids, adiponectin, and C-reactive protein. Diet was assessed with 4-7 24-h recalls and physical activity (PA) was determined by accelerometry. Fat-free soft tissue (FFST) mass and fat mass were measured by DXA. The s.c. abdominal adipose tissue (SAAT) and visceral adipose tissue (VAT) were assessed using MRI. Multiple linear regression, adjusting for age, sex, race, Tanner stage, FFST mass, fat mass, PA, energy intake, fiber intake, and socioeconomic status, revealed that fructose intake was associated with VAT (β = 0.13; P = 0.03) but not SAAT (P = 0.15). Significant linear upward trends across tertiles of fructose intake were observed for systolic blood pressure, fasting glucose, HOMA-IR, and C-reactive protein after adjusting for the same covariates (all P-trend < 0.04). Conversely, significant linear downward trends across tertiles of fructose intake were observed for plasma HDL-cholesterol and adiponectin (both P-trend < 0.03). When SAAT was added as a covariate, these trends persisted (all P-trend < 0.05). However, when VAT was included as a covariate, it attenuated these trends (all P-trend > 0.05). In adolescents, higher fructose consumption is associated with multiple markers of cardiometabolic risk, but it appears that these relationships are mediated by visceral obesity.

Right common carotid artery ligation in extracorporeal membrane oxygenation

The effect of right common carotid artery ligation required for arteriovenous extracorporeal membrane oxygenation (ECMO) was investigated in 35 infants. Their neonatal course was reviewed for evidence of right-sided ischemia of the brain, as suggested by the presence of focal seizures, hemiparesis, focal abnormalities on electroencephalography, or infarct or hemorrhage demonstrable on neuroimaging studies. A significant incidence of left focal seizures (9/35) versus right focal seizures (2/35) was noted, suggesting an effect of the carotid ligation on right hemisphere function. Computed tomographic scans (20/35 infants), electroencephalograms (18/35), ultrasound scans (31/35), and neurologic examinations did not reveal an increased incidence of right hemisphere abnormalities. These data suggest that systematic evaluation of the effects of right common carotid ligation should proceed as discussion continues on expanding the use of ECMO.

Hidden mortality rate associated with extracorporeal membrane oxygenation

We reviewed the outcome of all infants referred to, and accepted in, our extracorporeal membrane oxygenation (ECMO) program during a 52-month period. One hundred sixty-seven referrals, representing 158 infants and nine mothers who had not yet delivered their infants, were accepted. Eighteen infants (11.3% of all neonates transported) died before leaving the referring hospital, during transport, or shortly after admission to our unit. Contraindications to ECMO excluded 17 (10.1%) of the 167 referrals. Sixty-two infants (37.1%) initially did not meet ECMO criteria. Two died before ECMO could be started. Sixty-eight infants (40.7%) were given ECMO therapy, and 11 died (16.1%). Nine mothers were referred because of fetal conditions that might require ECMO; of these infants, two died during delivery and three had contraindications to the use of ECMO. The four remaining infants were given ECMO therapy; three survived. The overall mortality rate was 27.5% (46/167); 18 (39.1%) of the 46 deaths were associated with transfer. The mortality rate associated with congenital diaphragmatic hernia was 63.6%. We recommend early transport of infants with this type of hernia during the postoperative honeymoon or during in utero transport with delivery at an ECMO center. We also recommend that infants with meconium aspiration syndrome be transported to an ECMO center when an oxygenation index of 25 is reached. The mortality rate associated with transport needs to be considered in evaluating ECMO programs. Earlier, expedited transfers may increase the survival rate.

Significance of seizures associated with extracorporeal membrane oxygenation

We previously reported a predominance of left focal motor seizures in infants receiving extracorporeal membrane oxygenation (ECMO), raising concerns about possible ischemia resulting from the right common carotid artery ligation. We therefore evaluated the neurologic and psychologic outcome at 2 years of age of all infants with ECMO-related seizures. Although 8 of 12 infants had left focal seizures in infancy, there was no lateralization of motor findings at 2 years of age; left hemiparesis was present in three of the infants and right hemiparesis in three. The developmental quotient was normal in 6 of 12 infants, low-average in three, borderline in two, and in the mentally handicapped range in one. We conclude that any ischemia resulting from carotid ligation is not great enough to produce long-term lateralizing findings but that seizures during ECMO are a risk factor for later cerebral palsy or developmental delay.

Relationships of mesenteric thromboembolism, oral feeding, and necrotizing enterocolitis

Mesenteric blood vessels were examined in postmortem specimens of 30 selected infants. The infants had had necrotizing enterocolitis (16 cases) or other lesions (14 cases). Mesenteric thromboemboli were observed in 12 of the infants with necrotizing enterocolitis (P less than 0.001). Umbilical vessel catheters were apparently responsible for the emboli. Multiple instances of thrombosis and thromboembolism were detected in other organs. Ninety-four percent of infants with necrotizing enterocolitis were orally fed (P less than 0.001). Mesenteric thromboemboli were more frequent in infants who were fed via the digestive route while an umbilical arterial catheter was in place. Mesenteric thromboembolism in these infants was postulated to have been attributable to increased postprandial blood flow in the mesenteric vessels.

Bypass circuits as the source of thromboemboli during extracorporeal membrane oxygenation

To determine the presence and extent of thrombus formation in the apparatus used for extracorporeal membrane oxygenation we studied various portions of the polyvinylchloride circuit from five infants who received extracorporeal membrane oxygenation for 70 to 330 hours. All infants had right-sided cannulation. Sections were cut from the circuit at the time of decannulation and subjected to light and scanning electron microscopy. The site that contained the most thrombus formation was the membrane oxygenator bypass circuit, which is subjected to repeated periods of unclamping and clamping to direct blood flow through the membrane oxygenator. Autopsy results from nonsurvivors showed evidence of pulmonary and renal infarcts, a left frontal lobe infarct, a thromboembolus of the left external and internal carotid arteries, and thrombi in the lungs, kidney, brain, and coronary arteries. One survivor had computed tomographic evidence of infarction of the left middle cerebral artery distribution. We suggest that the areas of the extracorporeal membrane oxygenation circuit subjected to repeated changes in flow dynamics may be the source of microemboli.

Incidence of hypertension in infants on extracorporeal membrane oxygenation

Systemic hypertension has been associated with extracorporeal membrane oxygenation (ECMO) applied in neonatal respiratory failure. To determine the incidence of ECMO-related hypertension, we reviewed blood pressure measurements from indwelling aortic catheters in 31 infants consecutively placed on ECMO. Systemic hypertension (systolic blood pressures greater than 100 mm Hg for 4 or more consecutive hours) developed in 18 of the 31. Causes investigated included the roles of renin secretion, sodium, and colloid loads. There was no evidence of increased plasma renin activities in hypertensive infants (H), when compared with their own pre-ECMO controls or with the nonhypertensive infants (NH). Sodium and colloid loads and their rates of delivery were not different between H and NH. No consistent duration of ECMO was clearly associated with development of hypertension (mean time on ECMO at onset of hypertension, 43.8 +/- 38.5 hours; range, 1 to 142 hours). Demographic information was not statistically significant. Contrary to previous reports, H did not seem predisposed to an increased incidence of intracranial hemorrhage. Development of hypertension during ECMO is not related to increased plasma renin activity, sodium or colloid loads, or their rates of infusion.