Ted S. Rosenkrantz

Prognostic value of the electroencephalogram in term and preterm infants following neonatal seizures

There is controversy in the literature regarding the prognostic value of the EEG following neonatal seizures. This report reviews the results of a prospective study comparing EEG findings and outcome in 74 term and preterm infants following neonatal seizures. EEGs were evaluated for both background rhythms and epileptiform activity. Outcome was evaluated at an average age of 33 months. Background rhythms were highly correlated with outcome. Low voltage, electrocerebral inactivity and burst suppression EEGs were associated with poor outcomes while normal EEGs were associated with favorable outcomes. Slow, maturationally delayed and asymmetrical EEGs were associated with variable outcomes. The presence of epileptiform activity on the EEG was correlated with adverse outcomes but was not as highly significant as background rhythms. Electroencephalographic seizures, whether associated with clinical manifestations or not, were highly correlated with poor outcomes. The significance of these EEG findings was similar in both term and preterm infants. The study demonstrates that the EEG is predictive of outcome following neonatal seizures.

Cerebral blood flow velocity in infants with polycythemia and hyperviscosity: Effects of partial exchange transfusion with Plasmanate

To determine if there are significant changes in cerebral blood flow velocity and vascular resistance in neonates with polycythemia and hyperviscosity, 11 such infants were studied before and after partial exchange transfusion with Plasmanate. Seven matched control infants were also studied. Blood flow velocity of the anterior cerebral artery was measured with a bidirectional continuous waveform Doppler velocimeter. Blood flow and vascular resistance were calculated from the velocity tracings, using the area under the velocity curve and the Pulsatility Index. Reduction in hematocrit and viscosity produced significant increases in blood flow velocity and a reduction in vascular resistance. The postexchange values were similar to those of the control group. These results indicate that infants with polycythemia and hyperviscosity have decreased cerebral blood flow velocity and increased vascular resistance which normalize after partial Plasmanate exchange transfusion.

Effects of chronic fetal hyperglycemia upon oxygen consumption in the ovine uterus and conceptus.

Hyperglycemia has been shown to induce arterial hypoxemia in the chronically catheterized fetal sheep. To investigate the mechanism behind this glucose-induced hypoxemia, eight pregnant ewes and their fetuses were studied. Fetal glucose infusion (11.9 +/- 0.6 mg glucose/kg per min) was associated with a doubling of the fetal plasma glucose concentration with concomitant elevation of the umbilical vein-distal arterial O2 content difference by 24 h of infusion (P less than 0.01). Calculated fetal O2 consumption increased from 8.1 +/- 0.4 ml/kg per min in the control period to a maximum value of 10.6 +/- 0.3 ml/kg per min by third infusion day (P less than 0.01), which is an increase of approximately 30%. The degree of stimulation of fetal O2 consumption was related to the degree of fetal hyperglycemia but not to the degree of fetal hyperinsulinemia. The increase in fetal O2 consumption was accompanied by a significant increase in fetal O2 extraction with no change in either fetal O2 delivery or fetal blood O2 affinity. In addition, fetal hypercapnea with a mild fetal respiratory acidosis was induced by fetal hyperglycemia. The increase in fetal arterial PCO2 was linearly related (P less than 0.001) to the magnitude of increase in fetal O2 consumption. These studies suggest that chronic fetal hyperglycemia induces a state of accelerated fetal oxidative metabolism and may be important in explaining the etiology behind certain unusual findings in human infants of diabetic mothers.

Comparisons of mortality and pre-discharge respiratory outcomes in small-for-gestational-age and appropriate-for-gestational-age premature infants

BackgroundThere are differences in the literature regarding outcomes of premature small-for-gestational-age (SGA) and appropriate-for gestational-age (AGA) infants, possibly due to failure to take into account gestational age at birth.ObjectiveTo compare mortality and respiratory morbidity of SGA and AGA premature newborn infants.Design/MethodsA retrospective study was done of the 2,487 infants born without congenital anomalies at ≤36 weeks of gestation and admitted to the neonatal intensive care unit (NICU) at John Dempsey Hospital, between Jan. 1992 and Dec. 1999. Recent (1994–96) U.S. birth weight percentiles for gestational age (GA), race and gender were used to classify neonates as SGA (<10th percentile for GA) or AGA (10th–90th percentile for GA). Using multivariate logistic regression and survival analyses to control for GA, SGA and AGA infants were compared for mortality and respiratory morbidity.ResultsControlling for GA, premature SGA infants were at a higher risk for mortality (Odds ratio 3.1, P = 0.001) and at lower risk of respiratory distress syndrome (OR = 0.71, p = 0.02) than AGA infants. However multivariate logistic regression modeling found that the odds of having respiratory distress syndrome (RDS) varied between SGA and AGA infants by GA. There was no change in RDS risk in SGA infants at GA ≤ 32 wk (OR = 1.27, 95% CI 0.32 – 1.98) but significantly decreased risk for RDS at GA > 32 wk (OR = 0.41, 95% CI 0.27 – 0.63; p < 0.01). After controlling for GA, SGA infants were observed to be at a significantly higher risk for developing chronic lung disease as compared to AGA infants (OR = 2.2, 95% CI = 1.2 – 3.9, P = 0.01). There was no significant difference between SGA and AGA infants in total days on ventilator. Among infants who survived, mean length of hospital stay was significantly higher in SGA infants born between 26–36 wks GA than AGA infants.ConclusionsPremature SGA infants have significantly higher mortality, significantly higher risk of developing chronic lung disease and longer hospital stay as compared to premature AGA infants. Even the reduced risk of RDS in infants born at ≥32 wk GA, (conferred possibly by intra-uterine stress leading to accelerated lung maturation) appears to be of transient effect and is counterbalanced by adverse effects of poor intrauterine growth on long term pulmonary outcomes such as chronic lung disease.

Neonatal polycythemia and hyperviscosity

Neonatal polycythemia and hyperviscosity are defined as a hematocrit > or =65% and a viscosity value >2 standard deviations greater than the norm. Although polycythemia can reflect normal fetal adaptation, it has been thought to be responsible for abnormalities in the neonate. Polycythemia and hyperviscosity are associated with blood-flow changes in some organs, which alter their function. Partial exchange transfusion (PET) has been used to treat both symptomatic and asymptomatic patients. At present, no data support the use of PET in asymptomatic infants; the potential benefit in symptomatic infants depends on the symptoms. Studies of long-term neurodevelopmental status do not show any clear long-term benefits for PET. Crystalloids are as effective as colloids in PET and have the advantage of being cheaper and more readily available; also, they do not confer any risk of infection or anaphylaxis.

Infantile Hemangiomas and Retinopathy of Prematurity: Possible Association

OBJECTIVE. The goal was to study the clinical association between infantile hemangiomas and retinopathy of prematurity in preterm infants. METHODS. A retrospective study of preterm neonates weighing ≤1250 g at birth who were born during a 5-year period (November 1, 2000, to October 31, 2005) at John Dempsey Hospital was performed by using a prospectively collected, neonatal database. Data were collected on demographic features (gestational age, birth weight, and gender) and prenatal/postnatal steroid use. In the physical examination at discharge, all infants were checked for infantile hemangiomas, and the size and number of lesions were noted. The highest stage of retinopathy of prematurity diagnosed at any time before discharge also was noted. Analyses were performed to identify associated risk factors. RESULTS. Of 406 neonates admitted with birth weights of ≤1250 g, 351 (86.4%) survived. Of the survivors, 49 (13.9%) had infantile hemangiomas at discharge. Infantile hemangiomas were present for 16.8% of neonates with retinopathy of prematurity, compared with 6.7% of those without retinopathy of prematurity. Multiple infantile hemangiomas were present in 14 (28.5%) of 49 neonates, whereas 18 (42.8%) of 42 neonates had infantile hemangiomas that were ≥1 cm in size. Univariate analyses showed lower gestational age, lower birth weight, and postnatal steroid use to be predictors of retinopathy of prematurity, whereas prenatal steroid use, race, and gender were not significantly related. In multivariate logistic regression analyses controlling for gestational age and postnatal steroid use, infantile hemangiomas were found to be independently associated with any stage of retinopathy of prematurity. Neither the number nor the size of infantile hemangiomas showed any association with the severity of retinopathy of prematurity. CONCLUSIONS. Infantile hemangiomas are associated with the development of retinopathy of prematurity in infants weighing ≤1250 g. The biological significance of this association may yield clues to the management of retinopathy of prematurity.

Inguinal hernia in preterm infants (≤32-Week Gestation)

Abstract The current incidence of inguinal hernia (IH) in premature infants is not well-established. It is also unclear whether common co-morbidities in this population, i.e., chronic lung disease (CLD) or nutritional status or both contribute to the development of IH. The purpose of this study was to establish the epidemiologic profile of preterm infants of 32 weeks gestational age (GA) or less at birth with IH and determine whether the severity of CLD or poor nutritional status predisposes to the development of IH. Perioperative profiles of infants undergoing surgery were also reviewed. A retrospective study of 1,057 infants born at 23–32 weeks GA from January 1990 to December 1995 was done. Specific risk and demographic factors were identified. Factors used to determine severity of CLD were: days on intermittent mandatory ventilation (IMV); days on positive pressure (IMV + continuous positive airway pressure); and total number of days on supplemental oxygen. Overall nutritional status was determined by weight gain in g/kg per day. The incidence of IH in preterm infants of 32 weeks GA or less who were admitted for 28 days or more was 9.34% (65/696) prior to discharge. The incidence in infants weighing 1,500 g or less was 11.11% (63/567) and in infants 1,000 g or less 17.39% (48/276). All parameters that determined the severity of CLD were statistically significant in infants with IH by univariate analysis. In a multivariate regression model, male gender was the most important variable that was significantly associated with IH (odds ratio OR=9.6; 95% confidence interval CI=3.90–23.59), followed by total days on supplemental oxygen (adjusted OR=1.00; 95% CI= 1.01–1.02). Weight gain (g/kg per day) was not significantly different between the two groups. Surgical correction before discharge was well tolerated. We conclude that the incidence of IH is GA-dependent. Factors related to severity of CLD play a more important role than weight gain in predisposing to IH.

Cerebral blood flow in the newborn lamb with polycythemia and hyperviscosity

We measured hematocrit, whole blood viscosity, arterial oxygen content, and cerebral blood flow in seven newborn lambs in which polycythemia and hyperviscosity were induced by partial exchange transfusion with packed red blood cells from a donor lamb. After the exchange transfusion, the hematocrit, whole blood viscosity, and arterial oxygen content were significantly elevated, whereas cerebral blood flow was reduced from baseline measurements. Sodium nitrite was then infused to reduce the arterial oxygen content to baseline values while the hematocrit and viscosity remained elevated. Under this condition, cerebral blood flow returned to baseline values. Oxygen delivery to the brain remained constant throughout the study. These results indicate that the reduction of cerebral blood flow in neonatal polycythemia and hyperviscosity is a physiologic response to increased arterial oxygen content and not a result of hyperviscosity.

Behavioral and histological outcomes following neonatal HI injury in a preterm (P3) and term (P7) rodent model.

Hypoxia-ischemia (HI) occurs when blood and/or oxygen delivery to the brain is compromised. HI injuries can occur in infants born prematurely (<37 weeks gestational age) or at very low birth weight (<1500 g), as well as in term infants with birth complications. In both preterm and term HI populations, brain injury is associated with subsequent behavioral deficits. Neonatal HI injury can be modeled in rodents (e.g., the Rice-Vannucci method, via cautery of right carotid followed by hypoxia). When this injury is induced early in life (between postnatal day (P)1-5), neuropathologies typical of human preterm HI are modeled. When injury is induced later (P7-12), neuropathologies typical of those seen in HI term infants are modeled. The current study sought to characterize the similarities/differences between outcomes following early (P3) and late (P7) HI injury in rats. Male rats with HI injury on P3 or P7, as well as sham controls, were tested on a variety of behavioral tasks in both juvenile and adult periods. Results showed that P7 HI rats displayed deficits on motor learning, rapid auditory processing (RAP), and other learning/memory tasks, as well as a reduction in volume in various neuroanatomical structures. P3 HI animals showed only transient deficits on RAP tasks in the juvenile period (but not in adulthood), yet robust deficits on a visual attention task in adulthood. P3 HI animals did not show any significant reductions in brain volume that we could detect. These data suggest that: (1) behavioral deficits following neonatal HI are task-specific depending on timing of injury; (2) P3 HI rats showed transient deficits on RAP tasks; (3) the more pervasive behavioral deficits seen following P7 HI injury were associated with substantial global tissue loss; and (4) persistent deficits in attention in P3 HI subjects might be linked to neural connectivity disturbances rather than a global loss of brain volume, given that no such pathology was found. These combined findings can be applied to our understanding of differing long-term outcomes following neonatal HI injury in premature versus term infants.

Effects of Fetal Insulin Deficiency on Growth in Fetal Lambs

Insulin may be an important regulator of growth in late fetal life. To assess the importance of endogenous insulin release in regulation of normal fetal growth, eight fetal lamb pairs were given either an intravenous injection of streptozocin (STZ), a nitrosourea that selectively damages pancreatic β-cells, or buffer infusion (controls). In six preparations, twins were used, and in two cases, triplets, thus allowing for comparison between treated and control fetuses residing in the same intrauterine environment. Fetal STZ injection was associated with relative fetal hyperglycemia, hypoinsulinemia, and a decrease in the fetal plasma insulin-glucose ratio. Fetal lambs exposed to STZ also developed a mild nonprogressive metabolic acidosis compared with controls. Fetal body weight was depressed by 21% overall, the magnitude of reduction related to length of time in utero after STZ injection. Similar reductions in organ weights (liver, heart, and kidney) were also observed in STZ-administered fetuses compared with controls. Protein accretion in carcass, liver, and kidney after STZ was also depressed, but no significant changes in fetal lipid accretion were observed. Skeletal growth, as measured by tail and tibial lengths, was also depressed after STZ but to a lesser extent than body weight or protein accretion. Thus, in a stable maternal environment, isolated fetal insulin deficiency is associated with significant retardation of somatic and skeletal growth and protein deposition.