Jane E. Brazy

Nursery neurobiologic risk score : important factors in predicting outcome in very low birth weight infants

We developed a nursery Neurobiologic Risk Score (NBRS) based on potential mechanisms of brain cell injury in preterm infants and correlated it with developmental outcome at the corrected ages of 6, 15, and 24 months. The NBRS was determined at 2 weeks of age and at the time of discharge from intensive care in 58 preterm infants with birth weights less than or equal to 1500 gm. The NBRS correlated significantly with the Bayley Scales of Infant Development, Mental Development Index (MDI) (r = -0.61 to -0.40) and Psychomotor Development Index (PDI) (r = -0.59 to -0.46), and with abnormal neurologic examination findings (r = 0.59 to 0.73) at the three testing periods. Although 12 of the 13 items composing the NBRS individually correlated with one or more outcome variables, seven items (infection, blood pH, seizures, intraventricular hemorrhage, assisted ventilation, periventricular leukomalacia, and hypoglycemia) accounted for almost all of the explained variance. Logistic regression of individual items demonstrated intraventricular hemorrhage to be the most important item for predicting the MDI at 24 months; pH was the most influential item for predicting the PDI at every testing period. A shorter, revised NBRS that included only the seven significant items demonstrated as strong a correlation with developmental outcome as the original NBRS. A revised 2-week score of greater than or equal to 5 or a discharge score of greater than or equal to 6 demonstrated 100% specificity and had a 100% positive predictive value for an abnormal outcome at 24 months of age in this group of infants. We conclude that the NBRS identifies during the intensive care nursery stay those infants at highest risk for an abnormal outcome related to nursery events. In addition, analysis of NBRS items provides insight into the relative importance of individual factors for influencing mental, motor, and neurologic outcome.

Neonatal manifestations of severe maternal hypertension occurring before the thirty-sixth week of pregnancy

The effects on the neonate of severe maternal hypertension originating before the thirty-sixth week of gestation were determined by comparing data obtained on 28 preterm infants born of hypertensive mothers with data from 28 gestational age-matched controls. All hypertensive mothers had diastolic blood pressures ≥110 mm Hg, proteinuria, and systemic symptoms of their disease; over half had thrombocytopenia and significant elevations of LDH and SGOT. All hypertensive mothers had been treated intravenously with magnesium sulfate, and 79% received other antihypertensive agents. When compared to control infants, the infants of hypertensive mothers had a significantly higher incidence of somatic growth retardation, microcephaly, thrombocytopenia, leukopenia, neutropenia, low Apgar scores, delayed adaptation, patent ductus arteriosus, hypotonia, and gastrointestinal hypomotility. Apgar scores, platelet count, WBC count, neutrophil count, and weight percentile correlated with the severity of maternal platelet and enzyme abnormalities. The occurrence of gastrointestinal hypomotility, hypotonia, and patent ductus arteriosus may be related to transplacental passage of maternally administered drugs.

Nursery neurobiologic risk score: levels of risk and relationships with nonmedical factors.

ABSTRACT. This study compares the Neurobiologic Risk Score (NBRS) with developmental outcome in 199 infants ≤1500 g birth weight to determine levels of risk and to investigate the relative contributions of the NBRS and nonmedical factors to developmental outcome. The NBRS correlated significantly (p < .0001) with the Bayley Mental (MDI) and Psychomotor (PDI) Indexes, and neurologic examination score (NS) at 6, 15, and 24 months. Three risk groups were identified: low, NBRS ≤4; intermediate, NBRS 5 to 7; and high, NBRS ≥8 with an incidence of major handicaps at 24 months of 7%, 32%, and 50%, respectively. Of eight factors considered, the NBRS accounted for the greatest variance: MDI, 14 to 27%; PDI, 25 to 29%; NS, 34 to 42%. Additional increments of variance were contributed by gender (MDI, PDI, NS), maternal intelligence and race (MDI), and maternal education (PDI). The NBRS is a useful tool for identifying risk for developmental abnormalities due to neonatal medical events. J Dev Behav Pediatr 14:375–380, 1993. Index terms: very low birth weight infants, developmental outcome, developmental follow-up, biologic risk, prematurity.

Changes in cerebral blood volume and cytochrome aa3 during hypertensive peaks in preterm infants

Relative changes in cerebral blood volume and in the oxidation/reduction state of cytochrome aa3, the terminal member of the electron transport chain in oxidative metabolism, can be simultaneously observed with near infrared spectroscopy. Using this technique, we studied movement-associated blood pressure elevations in three nonparalyzed very low birth weight infants receiving mechanical ventilation. We defined hypertensive peaks as increases in systolic and diastolic blood pressures greater than or equal to 30% over baseline and lasting at least 2 seconds. Ninety percent of monitored time, an increase in tissue blood volume (tBV) immediately followed each blood pressure elevation, with deoxygenated hemoglobin providing the sole or predominant increase in tBV. A simultaneous shift of cytochrome aa3 to a more reduced state usually accompanied the rise in tBV, probably indicating a transient imbalance between oxygen delivery and cellular oxygen utilization and a failure of mechanisms that normally regulate cerebral oxygenation. The consistent association of hypertensive peaks with body movement, coughing, and breath holding, and the predominant increase in deoxygenated hemoglobin suggest that increased intrathoracic pressure transiently impedes cerebral venous return. The repeated fluctuations in intracerebral blood volume and associated shifts to greater cytochrome aa3 reduction with hypertensive peaks provide a possible explanation for the association of fluctuating blood pressure patterns and increased risk for intraventricular hemorrhage.

Developmental outcome of very low birth weight infants as a function of biological risk and psychosocial risk.

The relative contribution of biological and psychosocial risk factors to developmental outcome of 102 very low birth weight infants (<1500 g) was delineated through 24 months corrected age. Biological risk, assessed by the Neurobiologic Risk Score (NBRS), accounted for significant amounts of variance in Bayley Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) at the 6-, 15-, and 24-month assessment points. Psychosocial risk, reflected in maternal appraisals of daily stress, accounted for a significant increment in cognitive outcome (MDI), over and above that accounted for by the NBRS, at each assessment point. Cognitive functioning at each assessment point differed as a function of biological risk and psychosocial risk status. The findings are discussed in terms of maternal stress as a marker of, and salient intervention target for, caregiving environments that can maximize or minimize the effects of biological vulnerability. J Dev Behav Pediatr 15:232–238, 1994. Index terms: very low birth weight infants, developmental outcome, biological risk, psychosocial risk.

Developmental Outcome of Very Low Birth Weight Infants at Four Years of Age as a Function of Biological Risk and Psychosocial Risk

The continuing contribution of early biological and psychosocial risk factors to developmental outcome of 55 very low birth weight infants (≤ 1500 g) was assessed at 4 years of age. Biological risk, assessed by the Neurobiologic Risk Score, accounted for significant portions of the variance in the perceptual-performance (17%) and motor (35%) dimensions of the McCarthy Scales of Childrens Abilities. Psychosocial risk, reflected in maternal appraisals of daily stress during the newborn period, did not account for a significant portion of variance in any of the McCarthy Scales. Maternal education level, however, another measure of psychosocial risk, accounted for significant portions of variance (from 6% to 34%) on each of the McCarthy Scales. Movement from low neurobiologic risk status to poor outcome status at 4 years of age was associated with a number of psychosocial variables, including maternal education and early levels of maternal daily stress. The findings are discussed in terms of early markers for very low birth weight infants who require careful follow-up and of potential intervention targets to promote developmental outcome.

Effects of crying on cerebral blood volume and cytochrome aa3

To determine if crying alters cerebral hemodynamics and oxidative metabolism in the brain, near infrared spectrophotometry was used to assess relative changes in cerebral blood volume and the oxidation-reduction state of cytochrome aa3. Thirty-six crying episodes were observed, 20 in healthy infants and 16 in infants with respiratory problems. Throughout all crying episodes cerebral blood volume and oxidized cytochrome aa3 demonstrated oscillatory fluctuations every 10 to 20 seconds, with maximum changes during prolonged exhalations. In 86% of episodes baseline blood volume rose and remained elevated during the cry. The relative content of deoxyhemoglobin in cerebral blood also rose, indicating that venous blood is the major contributor to the increase in blood volume. Changes in baseline cytochrome aa3 oxidation varied with the presence of lung disease and with the chronologic age of the infant. Cytochrome reduction with crying occurred significantly more often in infants with respiratory problems than in healthy infants. Cytochrome aa3 became more oxidized in 82% of crying episodes in healthy infants older than 3 days of age, but no change in cytochrome oxidation was usually noted in those younger than 3 days. Thus crying alters cerebral blood volume in all neonates in a pattern consistent with cyclic obstruction to cerebral venous return; it decreases cerebral oxygenation in infants with respiratory problems.

Cerebral oxygen monitoring with near infrared spectroscopy: Clinical application to neonates

Near infrared spectroscopy is a new noninvasive optical method for bedside monitoring of cerebral oxygenation. It uses differential absorbance of near infrared light to assess relative changes in the oxidation-reduction state of cytochrome aa3, as well as changes in the amounts of oxyhemoglobin, deoxyhemoglobin, and blood volume in the monitored field. Although this technique is applicable to all ages and sizes of patients and to multiple clinical settings, the majority of clinical studies to date have focused on the neonate. These studies have demonstrated its potential for advancing neonatal care and in understanding how diseases and therapies affect cerebral oxygenation. This paper reviews the near infrared spectroscopy technique and summarizes its potential applications in the field of neonatal intensive care.

Motor organization in very low birth weight infants during caregiving: effects of a developmental intervention.

The purpose of this study was to determine whether an individualized approach to handling very low birth weight (VLBW) infants designed to support development would result in less motor disorganization than the task-oriented approach in traditional use. Using a quasi-experimental crossover design, motor responses were investigated in 38 infants (< or = 1700 g, 53% male, 89% white) observed at 28, 32, and 36 weeks post-conceptional age. Subjects served as their own controls. Motor responses were coded from direct observation and videotapes. Results demonstrated that during developmental handling, (1) the overall amount of movement was less, the number of organized movements was greater, and the number of disorganized movements was less than during traditional handling; and (2) the amount of movement increased over time, but in the traditional condition, it peaked at 32 weeks. Results support positive effects of developmental handling and suggest the potential for reducing the prevalence of minor motor impairments in VLBW infants.

Isoxsuprine in the perinatal period. II. Relationships between neonatal symptoms, drug exposure, and drug concentration at the time of birth.

Forty preterm infants with maternal isoxsuprine exposure less than 24 hours delivery and 40 matched control infants were studied prospectively to determine the acute neonatal effects of maternal ISX exposure. The cord ISX concentration correlated inversely with the drug-free interval before delivery (P < 0.001). Cord ISX concentrations > 10 mg/ml were seen only with intravenous maternal therapy and a drug-discontinuance to delivery interval of two hours or less. The plasma half-life of ISX in neonates ranged from 1.7 to 8 hours; gestationally younger infants required a longer time for drug clearance. Ileus was 13 times more common in the ISX group and was not directly related to the cord ISX concentration. The incidence of hypotension and hypocalcemia rose directly with the cord ISX concentration, reaching 89% and 100%, respectively, when the cord ISX level exceeded 10 ng/ml. The incidence of respiratory distress syndrome was low in the ISX infants with low cord drug values, but increased to that of the control group when the cord ISX concentration reached > 10 ng/ml.