Human herpesvirus 6 as a potential copathogen.

The molecular, biological and immunological studies of the recently identified human herpesvirus 6 (HHV-6) suggest that the virus is involved in the etiology of at least three lymphoproliferative diseases. Furthermore, HHV-6 may be an important cofactor in the pathogenesis of several other diseases, including HIV-associated disease and some cancers, but further investigation is needed to establish a causal relationship.

Abnormal shoulder girdle muscle tone in premature infants during their first 18 months of life.

To document the incidence of and neonatal factors associated with abnormal shoulder girdle muscle tone in premature infants at follow-up, we studied 125 consecutively admitted infants weighing less than 1,750 g treated in The Children's Hospital of Philadelphia intensive care nursery and subsequently seen in the Neonatal Follow-up Program up to 18 months of age. Fifty-seven infants (46%) displayed abnormal shoulder girdle muscle tone which presented clinically as scapular retractions. These infants had significantly lower birth weights (P less than .001) and gestational age (P less than .001) as well as a higher incidence of acute and chronic pulmonary disease (P less than 0.01) and CNS insults (P less than .05) when compared with infants without scapular retractions. The 57 infants with scapular retractions were further divided into two groups: 42 infants (74%) in whom scapular retractions were associated with generalized mild hypertonicity and 15 infants (26%) in whom scapular retractions compensated for trunk and neck hypotonicity. The infants with scapular retractions and hypotonicity had a significantly higher incidence of neonatal neurologic morbidity including seizures, major resuscitations, and birth asphyxia (P less than .01) when compared with the infants with scapular retractions and hypertonicity. Shoulder girdle tone abnormalities in the first year of life inhibit crawling, sitting, and object manipulation and, therefore, may manifest as delays in motor development. Identification of infants with significant neonatal risk factors for tone abnormalities is important to allow for earlier therapeutic intervention.

Half-dose immunization for diphtheria, tetanus, pertussis: response of preterm infants.

The American Academy of Pediatrics currently recommends administering full-dose diphtheria, tetanus, pertussis, (DTP) vaccine to preterm infants, beginning at 2 months' chronologic age. Many physicians, however, continue to administer DTP vaccine at a reduced dosage in an attempt to lessen side effects. This study was designed to quantitate the immune response of 20 preterm infants immunized with half-dose DTP vaccine and to determine the nature and extent of side effects. Control subjects were 25 preterm infants immunized with full-dose vaccine. Although 96% of infants who received a full dose were able to mount a serologic response to pertussis after a second dose of DTP, 45% of infants who received a half dose were unable to mount a similar immune response to pertussis even after a third dose of DTP and required a full-dose (fourth dose of DTP) vaccine to better ensure protection. Serologic responses to diphtheria and tetanus were similar in the two groups. The incidence of side effects in preterm infants receiving both full-dose and half-dose DTP was less than that seen in a full-term population. Thus, the physician caring for the preterm infant should adhere to the American Academy of Pediatrics' recommendation for the immunization of preterm infants and offer full-dose DTP vaccine at the routine time intervals of 2, 4, 6, and 15 or 18 months' chronologic age to ensure adequate protection.

Abnormal truncal muscle tone as a useful early marker for developmental delay in low birth weight infants.

Thirty-four outborn premature infants of appropriate gestational ages with birth weights less than 1,750 g were seen in follow-up at 3, 6, 12, and 18 months, corrected age to assess the incidence of abnormalities of muscle tone and the relationship of the site of early abnormalities to 18-month developmental status. The incidence of abnormal tone was most common at 3 months and declined with increasing age. The percentages of infants with abnormal tone at 3, 6, 12, and 18 months, respectively, were: increased lower extremity tone--62%, 71%, 38%, 9%; decreased lower extremity tone--3%, 3%, 6%, 9%; increased truncal tone--41%, 15%, 6%, 0%; decreased truncal tone--21%, 18%, 15%, 6%. Infants with truncal hypertonicity at 3 months had significantly lower Bayley motor and mental scores at 18 months when compared with infants with normal truncal tone (P less than .05). However, infants with lower extremity hypertonicity at 3 months were no different developmentally at 18 months from infants with normal tone. Infants with truncal or lower extremity hypotonicity fared the worst developmentally (P less than .05). We conclude that there is a high incidence of abnormal muscle tone in premature infants up to 18 months of age and that early truncal tone abnormalities are associated with a worse developmental outcome.

Nonnutritive sucking during gavage feeding enhances growth and maturation in premature infants.

The effects of nonnutritive sucking (NNS) by means of a pacifier during gavage feeding were studied in 30 premature infants whose birth weight was less than 1,500 g. The addition of NNS accelerated the maturation of the sucking reflex, facilitating a more rapid transition from gavage to oral feedings. Additionally, NNS decreased intestinal transit time and caused a more rapid weight gain despite comparable caloric intake resulting in a shortened hospital stay. Although the physiologic mechanisms resulting from this form of oral stimulation remain to be investigated, our data suggest that NNS may be an important factor to consider in the feeding of premature infants.

Costs incurred by parents of very low birth weight infants after the initial neonatal hospitalization.

To assess the economic impact of the posthospitalization care of very low birth weight (VLBW) infants, the costs incurred in the first year of life by 32 VLBW infants were compared with those incurred by 34 term, comparison infants. Diaries and quarterly interviews revealed that VLBW infants averaged $10,139 in direct medical charges compared with $1179 for the term infants; the differential in charges was greatest in the first two quarters and virtually disappeared by the fourth quarter. In addition, expenditures associated with transportation and child care presented an added substantial burden, although only the former were significantly higher for the VLBW infants. Clinicians may need to inquire specifically about the burden on family resources because, despite the economic burden and evidence of less social support, the parents of VLBW infants were less likely to perceive their child's care as having an impact on the family than were the parents of term children.

Survivors of extracorporeal membrane oxygenation at 1 year of age: the relationship of primary diagnosis with health and neurodevelopmental sequelae.

OBJECTIVE: Although extracorporeal membrane oxygenation (ECMO) has been responsible for the improved survival of infants with cardiorespiratory failure, its use over the last decade has raised concern as to the health of the survivors and the severity of neurodevelopmental sequelae. Though infants meeting ECMO criteria have a variety of reasons prompting the use of this therapy, most studies to date have simply reported outcome on the entire population that has survived without regard to the original nature of the child's illness. The purpose of this study was to determine the type and extent of health-related problems and neurodevelopmental sequelae in infants requiring ECMO therapy and the association of these findings with the infants' primary diagnosis. METHODS: Eighty-two neonates required ECMO therapy between May 1990 and December 1993. The most common diagnosis prompting ECMO therapy included 26% with meconium aspiration syndrome, 34% with congenital diaphragmatic hernia (CDH), 16% with persistence of the fetal circulation, and 9% with sepsis. Information concerning the hospital course was obtained through chart review, and the infants were seen at 6 and 12 months of age for medical and neurodevelopmental follow-up. Data were analyzed using descriptive statistics and Fisher's exact test, t-tests, and analysis of variance where appropriate. Assessment of hospital course and discharge data focused on the four main diagnostic groups, whereas follow-up data were further limited to the two most frequently encountered groups (meconium aspiration syndrome and CDH). RESULTS: Overall survival was 79%. Significant differences in survival were noted based on primary diagnostic category. Those with CDH fared the worst, with an overall survival rate of 68% and a more complicated hospital course with a longer duration of ECMO. At discharge, the CDH group demonstrated a greater incidence of bronchopulmonary dysplasia, gastroesophageal reflux, feeding dysfunction, and hypotonia. No significant differences were noted in the incidence of intraventricular hemorrhage, cerebral infarction, extra-axial fluid collection, or seizures. Hearing loss was uncommon. During the first year of life, although no differences were noted in growth rate, infants in the CDH group continued to experience a higher incidence of gastroesophageal reflux (43%) and feeding dysfunction, with 36% of this group requiring tube feedings for nourishment. Although 40% of the entire ECMO population was diagnosed with bronchopulmonary dysplasia before initial discharge, by 1 year of age, 50% of those with CDH versus 17% of those with meconium aspiration syndrome continued to be clinically symptomatic. Although the ECMO population as a whole scored in the normal range developmentally, CDH infants had significantly lower motor and slightly lower cognitive scores at 1 year of age. Despite finding abnormal muscle tone in a high percentage of the entire ECMO population at discharge, most demonstrated resolution by 1 year of age. Of the CDH infants, however, 75% continued to evidence some degree of hypotonicity, which affected acquisition and quality of gross motor skills. CONCLUSION: Despite the impact that ECMO has had on the survival of infants with severe respiratory failure, the efficacy of ECMO cannot be assessed accurately without an analysis of the extent and morbidity in the surviving population. Most centers are reporting relatively low morbidity for the entire ECMO population. However, upon separating this population into primary diagnostic categories, we found that the CDH population encountered a greater number of neurodevelopmental, respiratory, and feeding abnormalities during the first year of life. The reasons for these differences are unclear but may be related to the severity of the primary illness itself or the variables associated with prolonged ECMO therapy. Stratifying outcome by primary diagnosis gives the health care provider more information to improve

Preliminary observations on maternal rating of health of children: data from three subspecialty clinics.

Although routinely used in health surveys, the factors affecting maternal perceptions of health in children, especially those with health problems, have received little examination. This question has been addressed using a telephone interview of families of 483 children followed in one of three clinics at Children's Hospital of Philadelphia: the Neonatal Follow-up Program, the Pediatric Rheumatology Center and the Spina Bifida Program. Limitations in activities of daily living due to the health of the child, medical care use and variables indicative of socio-economic disadvantage were associated with a maternal rating of child health as fair/poor in all groups. The relationship was strongest in the rheumatologic group and less strong in the other two, suggesting that mothers may distinguish between a chronic active disease in a previously healthy child and the disability following a neonatal event in conceptualizing health. The results add to our information about maternal perceptions in assessing child health and suggest ways in which such ratings may prove useful in assessing health and health services for children with health problems.

Propagation and characterization of human herpesvirus-7 (HHV-7) isolates in a continuous T-lymphoblastoid cell line (SupT1).

After initial culture of HHV-7 in PHA-stimulated human cord blood mononuclear cells (HCBMC), six HHV-7 isolates were propagated successfully in an immature continuous T-lymphoblastoid cell line SupT1. All six isolates infected efficiently the SupT1 cells, and the infected cells became grossly enlarged and multinucleated 7-21 days post-infection. Various stages of HHV-7 morphogenesis were detected. Cell-free supernatants from HHV-7-infected SupT1 cells were infectious to HCBMC as well as to SupT1 cells. The HHV-7-infected SupT1 and HCBMC cell lysates contained more infectious virus than the centrifuged cell culture fluid supernates from the same culture. The HHV-7 isolates H7-2, H7-3, JHC, and JB, concentrated 500 times, had average infectivity titers of 10(3.0) TCID50/ml while strains H7-4 and KHR titered approximately 1-2 logs higher. When all six HHV-7 isolates were propagated in SupT1 and culture fluid supernatants were examined 14-21 days post-infection by negative stain electron microscopy they contained an average of 1.9 x 10(9) virus particles/liter. IFA and ELISA, using HHV-7/SupT1 cell lysate as an antigen, seem to correlate well in detecting high and low HHV-7 antibody in sera from chronic fatigue patients and healthy donors as controls. HHV-7 from SupT1 cell culture was free of HHV-6 and other human herpesviruses as tested by PCR, and the HHV-7 PCR signal was still strong when the viral preparation was diluted to 4.82 x 10(2) genome copies. Since HCBMC are expensive to obtain and available in only small amounts, it is difficult to obtain large quantities of HHV-7 antigen. On the other hand, the SupT1 cell is an excellent source to produce consistently sufficient quantities of HHV-7 for purification studies, development of immunodiagnostics, in vivo infectivity studies, evaluation of antiviral drugs, and molecular biological studies.

MRI, MRA, and neurodevelopmental outcome following neonatal ECMO.

Cranial magnetic resonance imaging (MRI) of 31 newborn infants treated with venoarterial cardiopulmonary bypass for severe but reversible respiratory failure, revealed major focal parenchymal lesions in 7 of 31 infants (23%) and demonstrated abnormal enlargement of extra-axial and ventricular cerebrospinal fluid spaces in 16 of 31 (51%). No preferential left versus right lateralization of focal injury was observed in conjunction with right common carotid artery and jugular vein ligation. No statistically significant relationships were found between major brain lesions on MRI scans and the clinical characteristics of the pre-extracorporeal membrane oxygenation (ECMO), ECMO, and post-ECMO course. Major focal brain lesions were significantly associated with an asymmetric cerebrovascular response to carotid ligation of the right versus left middle cerebral arteries as detected by magnetic resonance angiography (P < .05). Enlarged cerebrospinal fluid spaces were not significantly related to the presence of parenchymal MRI lesions, but were associated with lower Bayley neurodevelopmental scores for mental (MDI) and psychomotor evaluations (PDI) at 6 and 12 months (P < .05). It is concluded that asymmetries of cerebral vascular adaptation detected by magnetic resonance angiography after ECMO may be associated with major brain lesions revealed by MRI. Thereafter, the presence of enlarged cerebrospinal fluid spaces on MRI is associated with a poor shortterm developmental outcome.

Pulmonary hypertension in children following extracorporeal membrane oxygenation therapy and repair of congenital diaphragmatic hernia.

OBJECTIVE: Pulmonary hypertension (PHT) is present in all children at birth, but its degree and rate of resolution in infants diagnosed with congenital diaphragmatic hernia (CDH) requiring extracorporeal membrane oxygenation (ECMO) need to be established. STUDY DESIGN: Twenty-one ECMO/CDH survivors (aged 3.2 +/- 1.4 years) were prospectively evaluated by Doppler echocardiography (ECHO) to determine the presence of PHT. Twenty children without structural heart disease were used as controls. Study patients received a physical examination and an electrocardiograph examination, and their charts were reviewed for neonatal course data. Patients found to have PHT by ECHO received a complete history and exercise treadmill/oxygen desaturation study. RESULTS: Eight of the 21 patients (38%) met echocardiographic criteria for PHT. No neonatal course data were found to be predictive of eventual PHT status. There was no correlation between physical examination or electrocardiographic findings and PHT. Complete histories showed five of the eight patients with PHT had some degree of exercise intolerance and seven had wheezing. Two of the seven patients studied on the treadmill desaturated 5% or greater from baseline. CONCLUSION: There is evidence that PHT either persists or recurs in a significant portion of the ECMO/CDH population and may remain symptomatic well beyond the neonatal period.

Pulmonary hypertension and persistent fetal circulation in the newborn.

Despite these infants' very significant medical instabilities, which require vigorous therapeutic intervention, we have seen a population of infants with little in the way of persistent residual problems. Although many of their pulmonary complications persist after hospital discharge, most resolve within the first year of life. In addition, there are few neurodevelopmental disabilities encountered in such a high-risk population of children.

The very low birth weight transport goes home: impact on the family.

Very low birth weight (VLBW) infants are known to experience more health problems after discharge from the hospital, but the effects of such problems in terms of the demand for medical care and of the effect of this on the family are only just beginning to be described. A survey of the families of 132 children who were born weighing less than 1750 g at mostly suburban hospitals and transported to a Children's Hospital, who were 1-4 years old at the time of the survey, has revealed that these children continue to experience health problems to the extent that 35% are limited in one or more activities of daily living. They also incur greater use of health care services (17% hospitalized in the prior year; 54% with a doctor's visit in the prior month). The most important predictors of high perceived impact of these problems on the family is related to the number of activities limited by health, the age of the child, and the financial resources the family could bring to coping with the child's care. These findings provide further characterization of the families which may be most vulnerable to the ongoing health problems of the VLBW infant.

Outcome for infants with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation: the first year.

Congenital diaphragmatic hernia (CDH) has been associated with a high mortality rate. The purposes of this study were to determine the impact of extracorporeal membrane oxygenation (ECMO) on the survival of infants with CDH and to document the sequelae and 1-year neurodevelopmental outcome for CDH infants who required ECMO. Thirty neonates with CDH were admitted between May 7, 1990 and October 1, 1992. Twenty required ECMO and were enrolled in our neonatal follow-up program. Information about the infants' neonatal course was obtained from chart review, and the infants were seen at 3, 6, and 12 months of age for medical and neurodevelopmental follow-up. Primary diaphragmatic repair was performed in 13 infants. Five required Goretex graft reconstruction (GGR), and two did not have repair. Sixteen (80%) of the 20 infants who required ECMO survived. The overall survival rate increased from 31% (10 of 32) in the 5 years previous to the start of the ECMO program to 63% (19 of 30) since then (P = .01). The most common sequelae noted by the time of discharge included gastroesophageal reflux (GER; 81%), the need for tube feeding (69%), and chronic lung disease (CLD; 62%). At 1 year of age, mean cognitive skills were average (87 +/- 23) and motor skills were borderline (75 +/- 24) according to the Bayley Scales of Infant Development. Hypotonia was present in 10 of 13 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of sweet taste stimulation on growth and sucking in preterm infants.

OBJECTIVE: To evaluate the effect of sweet taste stimulation in augmenting the reported growth-enhancing effects of nonnutritive sucking in preterm infants who are gavage-fed. DESIGN: Random assignment of preterm infants to receive stimulation by one of three methods during each feeding until totally orally fed. SETTING: Hospital intensive-care and infant transitional units. PATIENTS: Eligibility criteria included body weight greater than or equal to 1,250 g, gestational age younger than 34 weeks, growth parameters appropriate for gestational age, tolerating at least 100 kcals/kg/day by gavage feeding with evidence of weight gain, and no clinical evidence of health complications. Data are presented for 42 infants who completed 14 days of treatment. INTERVENTIONS: Exposure to a sweet pacifier, a latex pacifier, or maternal heartbeat sounds during gavage feedings. MAIN OUTCOME MEASURES: Growth, time to total oral feeding, and sucking responses. RESULTS: No significant differences in sucking measures were noted among treatment groups. Differences in progression time to total oral feedings and weight gain favored the sweet-pacifier group but were not statistically significant. CONCLUSIONS: Oral stimulation of gavage-fed, preterm infants during a 2-week hospitalization was not sufficient to elicit a significant improvement in growth efficiency, progression to total oral feedings, or sucking maturation. Additional studies may show a beneficial effect of chemosensory stimulation in preterm infants.

Follow-up care of the low birth weight infant.

Care of the preterm infant after discharge is a challenge for the pediatric follow-up team. All premature infants should be followed through infancy and into preschool and school years because of the common ongoing medical concerns and the high risk of developmental disabilities. Although impossible to predict with great accuracy in the neonatal period, it is appropriate to select those preterm infants who have the highest risk for disabilities and provide to them a closer degree of surveillance.

Longitudinal neurodevelopmental and neuromotor outcome in congenital diaphragmatic hernia patients in the first 3 years of life.

OBJECTIVE: The objective of this study was to longitudinally evaluate the neurodevelopmental (ND) outcome in congenital diaphragmatic hernia (CDH) survivors during the first 3 years of life. STUDY DESIGN: The study cohort consists of 47 CDH survivors that were enrolled in our prospective, follow-up program between July 2004 and September 2010, and underwent serial ND evaluations during the first 3 years of life. ND outcomes were evaluated using the Bayley Scales of Infant Development (BSID)-II or BSID-III. Persistent ND impairment was defined as a score that remained 79 for the cognitive, language and psychomotor domains at the most recent follow-up visit compared with the first assessment. RESULT: The median age at first and last evaluation was 8 (range, 5 to 15) and 29 (range, 23 to 36) months, respectively. During the follow-up, ND scores improved to average in 17%, remained average in 60%, remained delayed in 10%, improved from severely delayed to mildly delayed in 2% and deteriorated from average to delayed in 15%. Motor scores improved to average in 26%, remained average in 55%, remained delayed in 8% and improved from severely delayed to mildly delayed in 11%. Intrathoracic liver position (P=0.004), preterm delivery (P=0.03), supplemental O2 requirement at day of life 30 (P=0.007), age at discharge (P=0.03), periventricular leukomalacia (PVL; P=0.004) and initial neuromuscular hypotonicity (P=0.01) were associated with persistent motor delays. No relationship was found between patient's characteristics and the risk of persistent cognitive and language delays. CONCLUSION: (1) The majority of children with CDH are functioning in the average range by early preschool age, (2) most children who had early delays showed improvement in their ND outcome, (3) children showing delays in all the three domains were the least likely to show improvement and (4) CDH severity appears to be predictive of persistent psychomotor delays.

Growth status and growth rates of a varied sample of low birth weight, preterm infants: a longitudinal cohort from birth to three years of age.

To obtain follow-up growth data on a large sample of low birth weight, preterm infants, 985 infants were monitored longitudinally in an eight-site collaborative program until 3 years of age, corrected for prematurity. The growth of 608 of these infants was described previously through 1 year of age. In the full sample, 149 infants weighed less than or equal to 1250 gm at birth, 474 between 1250 and 2000 gm, and 362 between 2000 and 2500 gm. Thirty-three percent were white, 53% were black, and 11% were Hispanic. Weight, length, and head circumference were measured at birth and at 40 weeks and 4, 8, 12, 18, 24, 30, and 36 months gestation-corrected age in at least 862 infants each time. Descriptive statistics and estimated growth rates for all growth variables and a body mass index (height in kilograms per square meter), plotted by sex and birth weight group, demonstrated growth patterns lower than published standards for term infants of the same age and sex. These patterns of growth differed by birth weight group. Little catch-up was noted by the 36-month examination for gestation-corrected age for any birth weight group. We conclude that low birth weight, preterm infants have different patterns of growth than term infants during the first 3 years of life, even with plotting corrected for gestational age.

A new method for delivering a taste without fluids to preterm and term infants.

A new method for administering a taste to preterm and term infants has been developed that does not necessitate the delivery of rapid solutions. Sucrose, a sugar that in solution was shown to potentiate sucking behavior, was embedded in gelatin-based nipples that continuously release sweet taste when mouthed or sucked. The gelatin nipples and comparable latex nipples were adapted to measure sucking behavior and were tested in a within-subject design. The gelatin nipples potentiated sucking in preterm and term infants by increasing the frequency and strength of the responses. Few sucking measures varied significantly for preterm and term infants. Those that did vary might be attributable to differences in physical stamina, rather than to orosensory or hedonic factors. It was concluded that the flavored gelatin nipple provides an effective method for studying taste in infants and offers the possibility of routine chemosensory stimulation for research and clinical applications.