Developmental follow-up of breastfed term and near-term infants with marked hyperbilirubinemia.

OBJECTIVE: In recent years, the increased prevalence of breastfeeding in conjunction with early discharge practices has increased the risk for marked hyperbilirubinemia in neonates. This has resulted in the potential for bilirubin brain injury in affected infants. The purpose of this study was to identify all infants >/=36 weeks' gestational age with bilirubin levels >25 mg/dL and evaluate them for early and late evidence of bilirubin brain injury. METHODS: We reviewed the charts of all infants (from 1993-1996) >/=36 weeks' gestational age who were readmitted to the hospital during the first week of life with bilirubin levels >25 mg/dL. Readmission records were reviewed for early signs of bilirubin encephalopathy. Magnetic resonance imaging (MRIs) and Brainstem auditory-evoked responses (BAERs) were reviewed for evidence of bilirubin toxicity. At follow-up, study infants had a complete neurodevelopmental examination, repeat MRIs, and behavioral hearing evaluations. RESULTS: From 1993 to 1996, we identified 6 term and near-term infants readmitted to the hospital within the first week of life with peak bilirubin values ranging from 26.4 mg/dL (451 micromol/L) to 36.9 mg/dL (631 micromol/L). Five of 6 infants had bilirubin values >30 mg/dL (513 micromol/L). All were exclusively breastfed or fed a combination of breast and bottle feedings. Five of 6 infants presented with abnormal neurologic signs. Four infants had initial MRIs, 3 of whom had increased signal intensity in the basal ganglia consistent with kernicterus. Two infants had abnormal BAERs; both also had abnormal MRIs. Five of 6 infants received exchange transfusions and all were treated with phototherapy and intravenous fluids. Follow-up examinations between 3 months and 2 years showed resolution of clinical signs in all but 1 infant. Four infants had a subsequent normal MRI and 1 had residual hearing impairment. One infant demonstrated severely abnormal developmental evaluations, as well as both an abnormal initial MRI and BAERs. Follow-up MRI showed evidence of encephalomalacia with changes not characteristic of kernicterus. CONCLUSIONS: We observed transient neurologic abnormalities in 5 of 6 infants readmitted to the hospital during the first week of life with marked hyperbilirubinemia. The abnormalities resolved following aggressive management using hydration, phototherapy, and exchange transfusion and may not correlate with long-term prognosis. Less aggressive therapy may be associated with residual neurologic abnormalities. We speculate that inadequate establishment of breastfeeding coupled with early discharge practices may play a role in the development of marked hyperbilirubinemia in these infants.

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.

Results at age 8 years of early intervention for low-birth-weight premature infants. The Infant Health and Development Program.

OBJECTIVE: To reevaluate at age 8 years children who had participated during the first 3 years of life in a randomized clinical trial of special services for low-birthweight (LBW) premature infants. DESIGN: Follow-up of a randomized controlled trial of premature infants (< or = 37 weeks' gestation), stratified by 2 LBW groups (lighter [< or = 2000 g] and heavier [2001-2500 g]) and divided into intervention (n=377) and follow-up only (n=608) groups. SETTING: Eight sites serving diverse populations. PARTICIPANTS: At age 8 years, 874 children were assessed: 336 in the intervention group and 538 in the follow-up only group. INTERVENTION: The 3-year intervention consisted of home visits (birth to 3 years), child development center services (ages 1 to 3 years), and parent group meetings (ages 1 to 3 years). PRIMARY OUTCOME MEASURES: Cognitive functioning (Weschler Intelligence Scale for Children-III; Peabody Picture Vocabulary Test-Revised); academic achievement (Woodcock-Johnson Tests of Achievement-Revised); and parental reports of school performance, behavior (Child Behavior Checklist), and health (Child General Health Survey). RESULTS: At age 8 years, in the entire cohort and in the lighter LBW stratum, the intervention and follow-up only groups were similar on all primary outcome measures. Differences favoring the intervention group were found within the heavier LBW group: full-scale IQ score (4.4 points higher, P=.007), verbal IQ score (4.2 points higher, P=.01), performance IQ score (3.9 points higher, P=.02), mathematics achievement score (4.8 points higher, P=.04), and receptive vocabulary score (6.7 points higher, P=.001). On a physical functioning subscale, the whole intervention group received less favorable ratings, while the lighter LBW intervention group had lower maternal ratings assessing social limitations caused by behavior. CONCLUSION: Although at age 8 years there were modest intervention-related differences in the cognitive and academic skills of heavier LBW premature children, attenuation of the large favorable effects seen at 3 years was observed in both the heavier and lighter LBW groups. This indicates a need to develop additional intervention strategies for LBW premature children that can provide sustained benefits.

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)

Early intervention in low-birth-weight premature infants. Results through age 5 years from the Infant Health and Development Program.

OBJECTIVE: To evaluate the persistence of effects on health and development at age 5 years of the Infant Health and Development Program, an early childhood intervention that was provided to low-birth-weight (LBW) premature infants from neonatal discharge through age 3 years. DESIGN: Randomized, controlled, multicenter trial, stratified by two LBW groups: lighter (< or = 2000 g) and heavier (2001 to 2500 g). SETTING: Eight socioeconomically heterogeneous clinical sites. PARTICIPANTS: Of 985 eligible infants weighing 2500 g or less and at 37 weeks' or less gestational age, 377 infants were randomly assigned to the intervention group and 608 to the follow-up only group. About two thirds of the infants in each group were in the lighter LBW stratum, and one third were in the heavier LBW stratum. INTERVENTION: The intervention group received home visits (from neonatal discharge through age 3 years) as well as center-based schooling (from 1 to 3 years of age). Children in both groups received pediatric surveillance. MAIN OUTCOME MEASURES: Cognitive development, behavioral competence, and health status. RESULTS: At age 5 years, the intervention group had full-scale IQ scores similar to children in the follow-up only group. However, in the heavier LBW stratum, children in the intervention group had higher full-scale IQ scores (3.7 points higher; P = .03) and higher verbal IQ scores (4.2 points higher; P = .02). No significant differences between intervention and follow-up only groups in cognitive measures at age 5 years were noted in the lighter LBW infants. The intervention and follow-up groups were similar in behavior and health measures regardless of LBW stratum. CONCLUSION: The early childhood intervention provided in the first 3 years of life had effects on heavier LBW premature infants' IQ and verbal performance at age 5 years that were not observed for lighter LBW premature infants. The intervention did not affect health or behavior at age 5 years in either LBW stratum.

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.

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.

Growth and metabolic response of premature infants fed whey- or casein-dominant formulas after hospital discharge.

We conducted a double-blind, randomized study to test the hypothesis that a whey-dominant formula permits a growth and metabolic advantage over a casein-dominant formula in preterm infants after hospital discharge. Nineteen low birth weight infants were studied for 6 months from the time of discharge. Ten received a casein-dominant formula, and nine received a whey-dominant formula. Growth (weight, length, head circumference, mid-arm circumference, and skin-fold thickness), biochemical measurements (alkaline phosphatase activity, acid-base status, and hemoglobin, serum total protein, albumin, and urea nitrogen levels), and quantity of formula intake did not differ significantly between the groups over a 6-month study period. Serum transthyretin and urea nitrogen concentrations differed significantly between the two feeding groups at the day of entry into the study only. The results indicate that, after hospital discharge, premature infants fed a whey-dominant formula do not differ in growth or biochemical measurements from those fed a casein-dominant formula.

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.

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.

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.

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.

Response of preterm infants to diphtheria-tetanus-pertussis immunizations.

To establish guidelines for the routine use of diphtheria, tetanus, and pertussis (DTP) vaccine in preterm infants, we quantitated antibody responses of preterm infants to DTP and determined the nature and extent of side effects. Twenty-five preterm infants were immunized with 0.5 ml DTP vaccine at routine intervals. Term infants served as controls. Immediately before each immunization and 2 months after the third, DTP-specific antibodies were quantitated. Clinical side effects were determined by parental report. After the second immunization, 100% of preterm infants had evidence of specific antibody production against diphtheria, tetanus, and pertussis. The incidence of side effects was low, but irritability was significantly more common in preterm infants after the second immunization. These observations suggest that the initiation of primary immunization with DTP in preterm infants need not be delayed beyond 2 months of age.

Long-term follow-up of newborns with persistent pulmonary hypertension.

Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome associated with high morbidity and mortality. Mechanical ventilation attempts to maintain a PaCO2 less than 30 torr and a pH greater than 7.5 until pulmonary hypertension resolves. To assess whether the disease or its therapy adversely affects neurodevelopmental or cardiorespiratory outcome, 11 infants diagnosed and treated for PPHN were evaluated at a mean age of 31 months. Nine had normal developmental quotients (DQs) and 2 had mildly delayed DQs. Eight children were entirely normal neurologically, 2 had slightly increased lower-extremity tone, and 1 had unilateral hypertonia. All cardiac exams, echocardiograms, and ECGs were normal. Four children had chronic lung disease requiring either daily or intermittent bronchodilator therapy; however, their activity levels were unaffected. These results suggest that subsequent normal development with little significant medical compromise may be expected in this group of critically ill infants.

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.