One-year outcome of auditory-tactile-visual-vestibular intervention in the neonatal intensive care unit: effects of severe prematurity and central nervous system injury.

Thirty-seven infants with severe central nervous system injury or extreme prematurity were randomly assigned to a multisensory (auditory-tactile-visual-vestibular) intervention or control group. Intervention began in the hospital at 33 weeks' postconceptional age and continued twice daily in the home until 2 months' corrected age. Mother-infant interactions during feedings were videotaped, and the Bayley Scales of Infant Development were administered. Control mothers stimulated their infants more during feeding, but these significant differences dissipated by 4 months. The presence of periventricular leukomalacia was associated with significantly poorer mental development, regardless of group assignment. Experimental infants tended to exhibit better motor and mental performance and had 23% fewer cerebral palsy diagnoses at 1 year, but these trends were not statistically significant. The type of brain injury was more important in determining 1-year developmental outcome than type of postnatal experience, suggesting that periventricular leukomalacia presents a major challenge for infant development.

Heart rate variability in preterm brain-injured and very-low-birth-weight infants.

Heart rate variability (HRV) reflects the complex interplay of the sympathetic and parasympathetic innervation of the heart. Developmental maturation of the fetus and newborn results in predictable alterations in the neural cardiac control of heart rate. Furthermore, patterns of HRV are closely correlated to clinical outcome in several pathologic situations. The first aim of this study was to characterize the maturational patterns of HRV in a group of developmentally at-risk newborns (those with severe hemorrhagic or ischemic brain injury and extremely immature, low-birth-weight infants). Secondly, we sought to determine whether a correlation exists between HRV and length of hospital stay, diagnosis of cerebral palsy, and neurodevelopmental test scores at 1-year corrected age. Time domain indices of HRV were computed longitudinally from 32 to 37 weeks of corrected gestational age in 19 very low birth weight, preterm infants. Among the 19 infants studied, 7 infants had no evidence of brain injury, 7 infants had periventricular leukomalacia (PVL), 3 infants had grade III/IV intraventricular hemorrhage (IVH), and 2 infants had both IVH and PVL. Neurologic injuries were documented using ultrasound and neurodevelopmental progress was followed through 1 year of corrected gestational age. A multivariate repeated measures analysis was performed to determine the relationship between the type of perinatal brain injury and neurodevelopmental status at 1 year of corrected gestational age. The type of perinatal brain injury was highly correlated to specific patterns of HRV with multivariate regression models producing adjusted r(2) values ranging from 0.63 to 0.99. The type of perinatal brain injury was highly correlated to the developmental outcome measures (p < 0.0000) with PVL patients having the lowest neurodevelopmental scores, IVH patients having the highest scores, and noninjured infants having midrange, grossly normal values. Using ANOVA, HRV was correlated to outcome, but individual comparisons revealed statistical significance only for the noninjured group (p < 0.04). However, multivariate models, which characterized outcome within each brain injury group, were highly significant (adjusted r (2) ranged from 0.23 to 0.89). In summary, the type of perinatal brain injury determined the pattern of HRV and HRV was highly correlated to length of hospital stay and neurodevelopmental function assessed at 1 year of corrected gestational age.

Developmental intervention for preterm infants diagnosed with periventricular leukomalacia.

Preterm infants with periventricular leukomalacia (PVL) were evaluated to determine whether multi-sensory stimulation is safe and to assess whether it improved neurobehavior and neurodevelopment. Thirty preterm infants with documented PVL were randomly assigned to control (n= 15) or experimental (Group E) (n= 15) groups at 33 weeks post-conceptional age. Group E infants received 15 minutes of auditory, tactile, visual, and vestibular (ATVV) intervention twice a day, five days a week, for four weeks during hospitalization. Repeated measures ANOVA demonstrated that Group E infants experienced significant increases in heart and respiratory rate and a 0.72% drop in hemoglobin saturation, coinciding with a significant behavioral state shift from sleep to alertness during intervention. No differences were identified in neurobehavioral function and neurodevelopment, indicating that Group E suffered no injury. Group E had an average hospital stay nine days shorter than that of controls, with the associated cost savings of $213,840. The earlier hospital discharge indicates that ATVV intervention promotes alertness without compromising physiologic status in vulnerable infants.

Prevention of neonatal necrotizing enterocolitis.

There are a number of promising strategies to prevent necrotizing enterocolitis (NEC). These included induction of intestinal maturation with prenatal or postnatal steroids, passive immunization with oral immunoglobulin, modification of enteral feedings, administration of oral antibiotics to decrease bacterial overgrowth while avoiding the development of resistant strains, and acidification of oral fluids to prevent bacterial overgrowth. The initial results need to be confirmed, but it is likely that one or more of these prevention measures will lower the incidence of NEC in the future.

Intravenous immune globulin for the prevention of nosocomial infection in low-birth-weight neonates. The Multicenter Group for the Study of Immune Globulin in Neonates.

BACKGROUND: Nosocomial infection is a major risk for premature infants with very low birth weights. One reason for their susceptibility to infection may be antibody deficiency, since there is little transfer of maternal IgG to the fetus before 32 weeks' gestation. METHODS: We conducted a multicenter, double-blind study of neonates weighing 500 to 1750 g at birth. A total of 588 neonates were randomly assigned, with stratification for birth weight, to receive periodic intravenous infusions of either immune globulin (500 mg per kilogram of body weight per day) or a placebo. Mortality, morbidity, and nosocomial infection during the next 56 days were assessed. RESULTS: The infusions were well tolerated; mild, reversible adverse reactions occurred in five infants in each group. There was a significant reduction in the risk of a first nosocomial infection in the recipients of immune globulin as compared with the placebo recipients (relative risk, 0.7; 95 percent confidence interval, 0.5 to 0.9). About 85 percent of the nosocomial infections were bacterial; the majority of these were caused by coagulase-negative staphylococci or Staphylococcus aureus. The neonates who received immune globulin had fewer mean days of hospitalization than the controls (62 vs. 68, P = 0.15); among the infants with infections, the difference in the mean length of the hospital stay was even greater (80 days vs. 101 days, P = 0.02). CONCLUSIONS: For premature infants weighing between 500 and 1750 g at birth, treatment with intravenous infusions of immune globulin is safe and reduces the risk of nosocomial infection.

Bronchopulmonary dysplasia and postnatal growth in extremely premature black infants.

Bronchopulmonary dysplasia (BPD) may adversely affect the postnatal growth of the extremely premature infant; however, most studies have not controlled for birth weight. We studied 90 Black premature infants (mean birth weight 989 +/- 148 g). Weight was recorded biweekly until discharge and at 4, 8, and 12 months of age corrected for prematurity. Infants with BPD (N = 23) were contrasted with infants without BPD (N = 67). Data were modeled using the Count model: Stage I birth to term and Stage II term to 12 months. Birth weight was considered part of growth beginning in utero and multivariate analyses were used to control for BPD, gestational age, duration of hospitalization and socioeconomic status. After adjustment for birth weight, BPD did not explain the growth pattern. A lower gestational age was associated with a slower establishment of steady growth (P less than 0.01), while an increased duration of hospitalization was associated with a lower growth rate (P less than 0.05). Growth in stage II was not explained by study variables. 'Catch-up' growth was seen in both infants with and without BPD. We conclude that differences in growth among infants with BPD are mainly attributable to birth weight. We speculate that poorer growth may be seen in a sub-group of infants with severe BPD.

Cranial ultrasonography and the prediction of cerebral palsy in infants weighing less than or equal to 1200 grams at birth.

The rôle of serial cranial ultrasonography in the prediction of cerebral palsy was examined in 116 surviving infants with birthweights less than or equal to 1200 g. All underwent serial real-time sonographic examinations of the brain on days one, five and 21, then monthly, until term corrected age. Intraventricular hemorrhage (IVH) was diagnosed in 48 infants, and three had periventricular leukomalacia. Of the 116 infants, 31 had ultrasound abnormalities at term. At 12 to 18 months corrected age 12 infants had cerebral palsy and 38 were classified as suspect; the other 66 were normal. There was a clear association between risk group, based on sonographic findings at term, and outcome. Infants with IVH whose cranial ultrasounds failed to become normal by term corrected age were at higher risk for cerebral palsy than those with normal examinations at term, regardless of the severity of IVH. Thus an abnormal ultrasound at term corrected age was highly predictive of cerebral palsy, especially among survivors of IVH. It remained the best predictor of cerebral palsy, even when other perinatal and neonatal variables were considered. In contrast, duration of mechanical ventilation, rather than sonographic findings, was the best predictor of suspect neuromotor status.

Prolonged mechanical ventilation and intracranial hemorrhage: impact on developmental progress through 18 months in infants weighing 1,200 grams or less at birth.

In this prospective, longitudinal study, the relative impact of intracranial hemorrhage and prolonged mechanical ventilation on developmental progress during the first 18 months of life of infants weighing 1,200 g or less at birth was examined. A total of 159 surviving infants were divided into two groups: infants with and those without intracranial hemorrhage. These groups were then subdivided into groups of infants receiving prolonged mechanical ventilation (greater than 21 days) and those mechanically ventilated for 21 days or less, thus creating four subgroups. Group 1 (intracranial hemorrhage and prolonged mechanical ventilation) and group 3 (intracranial hemorrhage and no prolonged mechanical ventilation) showed no statistically significant differences for severity of intracranial hemorrhage, persistence of ventriculomegaly, or presence of periventricular leukomalacia. A repeated-measures analysis of variance demonstrated a main effect for prolonged mechanical ventilation on outcome as measured by the Bayley Mental Development Index and Bayley Psychomotor Development Index at 4, 8, 12, and 18 months of age (corrected for prematurity). Forward stepwise regression revealed prolonged mechanical ventilation to the best predictor of Bayley indexes at all ages except 4 months of age, for which the Psychomotor Development Index was best predicted by length of hospitalization. No main effect for intracranial hemorrhage was demonstrated, but the motor performance of infants with intracranial hemorrhage declined significantly with age. By contrast prolonged mechanical ventilation was associated with uniformly poor performance at every age and serves as a powerful marker for poor developmental progress during the first 18 months of life in infants weighing 1,200 g or less at birth.

Intravenous indomethacin and changes of renal function in premature infants with patent ductus arteriosus.

Selected parameters of renal function were studied in premature infants with a significant patent ductus arteriosus who were treated with intravenous indomethacin according to a specific protocol. Urine volume, glomerular filtration rate, urine sodium, and the fractional excretion of sodium were analyzed in 17; osmolar, sodium, and free water clearances in 8; and indomethacin pharmacokinetics in 7 premature infants. All renal function parameters analyzed decreased during indomethacin therapy: urine volume and glomerular filtration rate returned to normal, while urine sodium, fractional excretion of sodium, and the osmolar, sodium, and free water clearances remained low 24 hours after cessation of therapy. The water retention, shown by the reduced free water clearance, had no apparent deleterious effects, probably because of the infants' low fluid intake. Indomethacin pharmacokinetic parameters (clearance, area under the curve) may account in part for the variability of the fractional excretion of sodium, glomerular filtration, and urine flow rate.

Teratoma of the tonsil in a premature infant. Case report and review of the literature.

Among the causes of respiratory distress in the neonatal period, a tumor involving the oropharyngeal area is rare. The present case report describes a premature infant with a teratoma of the tonsil and reviews the clinical presentation and management of this tumor in the neonatal period.

Nemaline (rod) myopathy: a possible cause of rapidly fatal infantile hypotonia.

Two infant siblings (male and female) manifested extreme hypotonia and flaccidity at birth and had a rapidly fatal course. In each, rod-like structures were demonstrated within a variety of skeletal muscles, and accumulations of thin filaments were seen in numerous muscle fibers. The possibility exists that this represents a severe and rapidly fatal form of nemaline myopathy that should be included in the differential diagnosis of infantile hypotonias.

Sodium balance in very low-birth-weight infants.

Sodium balance was studied in 17 consecutively admitted neonates weighing less than 1,200 gm at birth. Infants whose gestation was less than or equal to 30 weeks were sicker and were in markedly negative sodium balance on day 3 (-9.25 mEq/kg day), despite a high sodium intake (7.22 mEq/kg/day). This negative balance was the result of a high fractional sodium excretion and resulted in hyponatremia in six (50%) of the patients. By day 8 these immature infants were in positive sodium balance, although fractional sodium excretion and daily sodium requirements remained high. More mature infants (greater than 30 weeks gestational age) were in positive sodium balance on both days 3 and 8. Creatinine clearance did not differ significantly between groups on either day 3 or 8 but increased within each group during the study period. These data suggest that the daily sodium requirement of immature sick infants may be much higher than was previously suggested.