Neurodevelopmental outcomes among extremely premature infants with linear growth restriction.

OBJECTIVE: To compare neurodevelopmental outcomes in linear growth-restricted (LGR) infants born <29 weeks with and without weight gain out of proportion to linear growth. STUDY DESIGN: We compared 2-year neurodevelopmental outcomes between infants with and without LGR and between LGR infants with and without weight gain out of proportion to linear growth. The outcomes were Bayley-III cognitive, motor, and language scores, cerebral palsy, Gross Motor Function Classification System (GMFCS) level ≥ 2, and neurodevelopmental impairment. RESULT: In total, 1227 infants were analyzed. LGR infants were smaller and less mature at birth, had higher BMI, and had lower Bayley-III language scores (82.3 vs. 85.0, p < 0.05). Among infants with LGR, infants with high BMI had lower language scores compared with those with low-to-normal BMI (80.8 vs. 83.3, p < 0.05), and were more likely to have GMFCS level ≥2 and neurodevelopmental impairment. CONCLUSION: Among infants with LGR, weight gain out of proportion to linear growth was associated with poorer neurodevelopmental outcomes.

Neonatal Acute Kidney Injury: A Survey of Neonatologists' and Nephrologists' Perceptions and Practice Management.

BACKGROUND: Neonatal acute kidney injury (AKI) occurs in 40 to 70% of critically ill neonatal intensive care admissions. This study explored the differences in perceptions and practice variations among neonatologists and pediatric nephrologists in diagnostic criteria, management, and follow-up of neonatal AKI. METHODS: A survey weblink was emailed to nephrologists and neonatologists in Australia, Canada, New Zealand, India, and the United States. Questions consisted of demographic and unit practices, three clinical scenarios assessing awareness of definitions of neonatal AKI, knowledge, management, and follow-up practices. RESULTS: Many knowledge gaps among neonatologists, and to a lesser extent, pediatric nephrologists were identified. Neonatologists were less likely to use categorical definitions of neonatal AKI (p < 0.00001) or diagnose stage 1 AKI (p < 0.00001) than pediatric nephrologists. Guidelines for creatinine monitoring for nephrotoxic medications were reported by 34% (aminoglycosides) and 62% (indomethacin) of respondents. Nephrologists were more likely to consider follow-up after AKI than neonatologists (p < 0.00001). Also, 92 and 86% of neonatologists and nephrologists, respectively, reported no standardization or infrastructure for long-term renal follow-up. CONCLUSION: Neonatal AKI is underappreciated, particularly among neonatologists. A lack of evidence on neonatal AKI contributes to this variation in response. Therefore, dissemination of current knowledge and areas for research should be the priority.

Neurodevelopmental outcomes in postnatal growth-restricted preterm infants with postnatal head-sparing.

OBJECTIVE: To compare neurodevelopmental outcomes in postnatal growth-restricted infants born <29 weeks with and without postnatal head-sparing (PHS). STUDY DESIGN: We analyzed developmental outcomes at 2 years of age among postnatally growth-restricted infants with and without head-sparing. The primary outcome was Bayley III cognitive composite score; secondary outcomes included Bayley III motor composite score, moderate/severe cerebral palsy, gross motor functional classification scale level⩾2, and presence or absence of neurodevelopmental impairment (NDI). RESULTS: Of 1098 infants evaluated at 18 to 22 months, 658 were postnatally growth restricted, of whom 301 had head-sparing. In the multivariate model including independent risk factors for poor growth and poor developmental outcome, infants with head-sparing had higher adjusted motor composite scores (mean difference 4.65, P<0.01), but no differences in other neurodevelopmental outcomes. CONCLUSION: PHS is associated with improved neurodevelopmental outcome in extremely preterm infants, specifically Bayley III motor scores, but whether beneficial effects of PHS persist later in life is unknown.

Impact of maternal and neonatal iron status on placental transferrin receptor expression in pregnant adolescents.

OBJECTIVE: To elucidate the role of maternal and neonatal iron status on placental transferrin receptor (TfR) expression. STUDY DESIGN AND OUTCOMES: Ninety-two healthy pregnant adolescents (ages 14-18 years) were followed across pregnancy. Maternal iron status (hemoglobin, hematocrit, serum ferritin, TfR, and total body iron) was assessed in mid-gestation (21-25 wks) and at delivery in the mother and neonate. Placental TfR protein expression was assessed by western blot in placental tissue collected at delivery. RESULTS: Placental TfR expression was inversely associated with maternal iron status at mid-gestation (hemoglobin p = 0.046, R(2) = 0.1 and hematocrit p = 0.005, R(2) = 0.24) and at delivery (serum ferritin p = 0.02, R(2) = 0.08 and total body iron p = 0.02, R(2) = 0.07). Mothers with depleted body iron stores had significantly greater placental expression of TfR than mothers with body iron stores greater than zero (p = 0.003). Neonatal iron stores were also inversely associated with the expression of placental TfR (p = 0.04, R(2) = 0.06). Neonates with serum ferritin values ≤ 34 µg/L had significantly greater protein expression of placental TfR compared to neonates with cord serum ferritin values >34 µg/L (p = 0.01). CONCLUSIONS: Expression of placental TfR is associated with both maternal and neonatal iron demands. Increased expression of placental TfR may be an important compensatory mechanism in response to iron deficiency in otherwise healthy pregnant women.

Sensitivity of the ultrasonic interferometry method (Echo-Cell) to changes of red cell aggregation: application to diabetes.

The sensitivity of the ultrasonic interferometry method (Echo-Cell) to changes in red blood cell (RBC) aggregation was investigated in comparison to the Regulest erythroaggregometry known as a reference method. In experiments where different concentrations of dextrans of 40 or 70 kD molecular weights were added to normal RBCs, the Echo-Cell was proved as sensitive as erythroaggregometry. A comparative study using RBC samples from normal and diabetic subjects showed that the Echo-Cell was much more sensitive when aggregation was measured in diluted than undiluted plasma. The sensitivity of Echo-Cell measurements in diluted plasma was similar to that of erythroaggregometry. Further analysis revealed that RBC aggregation was underestimated by Echo-Cell when measurements were made in undiluted plasma containing high fibrinogen levels, implying that in that case an elevated plasma viscosity might indirectly affect the sensitivity of the Echo-Cell. The low sensitivity of the Echo-Cell to detect an abnormal RBC aggregation when suspensions were prepared in undiluted plasma, is likely related to a relatively high shear stress exerted on RBC aggregates by the suspending medium. In conclusion, the sensitivity of the Echo-Cell to detect abnormal changes in RBC aggregation can be optimized by diluting the plasma.

Bilirubin and serial auditory brainstem responses in premature infants.

OBJECTIVES: To determine the usefulness of the bilirubin-albumin (B:A) molar ratio (MR) and unbound bilirubin (UB) as compared with serum total bilirubin (TB) in predicting bilirubin encephalopathy as assessed by auditory brainstem responses (ABR) in infants of 28 to 32 weeks' gestational age. STUDY DESIGN: During a 2-year period, serial ABRs were obtained on 143 infants of 28 to 32 weeks' gestational age during the first postnatal week. Waveforms were categorized on the basis of response replicability and the presence of waves III and V. Wave V latencies were also serially analyzed when measurable for individual infants. Maturation of the ABR was defined as abnormal when the waveform category worsened and/or latency increased during the study interval. Serum albumin was analyzed at 48 to 72 hours of age in all patients. Serum TB was analyzed as clinically indicated. Aliquots of the same samples were also analyzed for UB in a subset of infants. RESULTS: The mean peak TB concentration (10.1 +/- 1.7 mg/dL) for the 71 infants with normal ABR maturation was not significantly different from the mean peak TB (10.2 +/- 2.1 mg/dL) in the 24-hour period preceding the ABR's first showing abnormal maturation in the other 55 infants. However, in infants with UB analyzed, the mean peak UB (0.62 +/- 0.20 vs 0.40 +/- 0.15 microg/dL) was significantly higher in the infants with abnormal maturation (n = 25) than in infants with normal maturation (n = 20). The B:A MR results were equivocal. In the entire study population, there was no difference in B:A MR between infants with normal versus abnormal ABR maturation. However, in the subset of infants in whom UB was measured, although TB was not different, there was a significant difference in B:A MR. Based on receiver-operating characteristic curves, a UB level of 0.5 microg/dL was the best discriminator with a sensitivity of 70% and a specificity of 75%. The proportion of infants who had UB >0.5 microg/dL and UB 0.5 microg/dL compared with UB

Brainstem maturation in premature infants as a function of enteral feeding type.

OBJECTIVE: To determine whether brainstem maturation as measured by brainstem auditory-evoked responses (BAERs) in preterm infants is a function of dietary intake. STUDY DESIGN: We obtained serial BAERs on infants 28 to 32 weeks' gestation at birth, cared for in the neonatal intensive care unit of a regional referral center in Upstate New York. Waveforms were analyzed for replicability and for the presence of waves III and V. Absolute and interwave latencies were measured. Baseline and follow-up BAER measurements were compared, and the rates of change were calculated. Patient charts were reviewed for type of enteral feeding during the interval between BAERs. Student's t test was used to analyze continuous variables and chi(2) analysis was used to analyze categorical variables. RESULTS: Data from 37 study infants (17 fed breast milk and 20 fed commercial premature formula) revealed that there was no difference in absolute latencies of waves III and V at baseline; however, the rates of decrease of absolute latencies over the study interval were significantly greater in infants receiving human milk. CONCLUSIONS: Infants fed breast milk have faster brainstem maturation, compared with infants fed formula, based on the rate of maturation of BAERs. This effect may be attributable to the constituent composition of breast milk, compared with synthetic formulas.

Electrographic seizures in neonates correlate with poor neurodevelopmental outcome.

OBJECTIVE: To quantify the number, duration, and intensity of electrographic seizures (ESz) in neonates and to compare the outcome of neonates with ESz with those who were at risk but did not have ESz recorded. METHODS: The EEG and outcome data were reviewed from 68 infants who met at-risk criteria for neonatal seizures and underwent prolonged continuous EEG monitoring. Forty infants had ESz. The control group contained 28 infants monitored for at least 18 hours and found not to have ESz. Outcomes for both groups were evaluated using hospital and follow-up clinic records and a standardized telephone interview. RESULTS: The etiology of ESz included asphyxia (n = 23), stroke (n = 7), and other (n = 10, intraparenchymal, subdural, and subarachnoid bleeding; meningitis; sepsis; hyponatremia; and unknown). The cumulative recorded ESz duration was 8 minutes to 30 hours. Forty-three percent of infants with ESz spent 38 minutes to 32 hours in electrographic status. Despite doses of 40 mg/kg of phenobarbital and 20 mg/kg of phenytoin, 30% of infants continued to have ESz. Ten infants with ESz and one without died from causes related to neurologic instability. The occurrence of ESz was correlated with microcephaly (p = 0.04), severe cerebral palsy (CP) (p = 0.03), and failure to thrive (p = 0. 03). In the subgroup of infants with asphyxia, those with ESz were more likely to die of neurologic causes (p = 0.02) and have microcephaly (p = 0.05) or severe CP (p = 0.04). Additionally, those with the greatest number of ESz were more likely to have these severe outcomes. CONCLUSION: The authors' data indicate an association between the amount of electrographic seizure activity and subsequent mortality and morbidity in at-risk infants in general and in infants with perinatal asphyxia. Only with more effective treatment of neonatal electrographic seizures can their potential contribution to poor neurodevelopmental outcome, independent of degree of insult, be ascertained.

Early dexamethasone-attempting to prevent chronic lung disease.

BACKGROUND: We previously demonstrated improved survival and early outcomes in a pilot trial of 2 doses of intravenous dexamethasone for infants with surfactant-treated respiratory distress syndrome. (1) A multicenter, randomized, double-blind trial was undertaken to confirm these results. METHODS: Infants <30 weeks' gestation were eligible if they had respiratory distress syndrome, required mechanical ventilation at 12 to 18 hours of age, and had received at least 1 dose of exogenous surfactant. Infants were excluded if sepsis or pneumonia was suspected or if congenital heart disease or chromosomal abnormalities were present. A total of 384 infants were enrolled-189 randomized to dexamethasone (.5mg/kg birth weight at 12-18 hours of age and a second dose 12 hours later) and 195 to an equal volume of saline placebo. RESULTS: No differences were found in the dexamethasone versus placebo groups, respectively, regarding the primary outcomes of survival (79% vs 83%), survival without oxygen at 36 weeks' corrected gestational age (CGA; both 59%), and survival without oxygen at 36 weeks' CGA and without late glucocorticoid therapy (46% vs 44%). No significant differences between the groups in estimates from Kaplan-Meier survival analyses were found for median days on oxygen (50 vs 56 days), ventilation (20 vs 27 days), days to regain birth weight (15.5 vs 14 days), or length of stay (LOS; 88 vs 89 days). Infants given early dexamethasone were less likely to receive later glucocorticoid therapy for bronchopulmonary dysplasia during their hospitalization (27% vs 35%). No clinically significant side effects were noted in the dexamethasone group, although there were transient elevations in blood glucose and blood pressure followed by a return to baseline by study day 10. Among infants who died (40 vs 33), there were no differences in the median days on oxygen, ventilation, nor LOS. However, in survivors (149 vs 162), the following were observed: median days on oxygen 37 versus 45 days, ventilation 14 versus 19 days, and LOS 79 versus 81 days, for the dexamethasone versus placebo groups, respectively. CONCLUSIONS: This dose of early intravenous dexamethasone did not reduce the requirement for oxygen at 36 weeks' CGA and survival was not improved. However, early dexamethasone reduced the use of later prolonged dexamethasone therapy, and among survivors, reduced the median days on oxygen and ventilation. We conclude that this course of early dexamethasone probably represents a near minimum dose for instituting a prophylactic regimen against bronchopulmonary dysplasia.

Covalent binding of polyethylene glycol to the surface of red blood cells as detected and followed up by cell electrophoresis and rheological methods.

Cyanuric chloride activated polyethylene glycol (PEG)-5000 was covalently coupled to murine and human red blood cells (pegylated RBC). Our purpose was to camouflage RBC receptors, which is necessary for parasite invasion, a process essential to sustain parasitemia. Cell electrophoretic mobility analysis (CEM) of pegylated RBC distinguished a new population of cells bearing characteristic CEM. Pegylation of RBC also modified their rheological properties, which were documented by evaluation of cell deformability (based on cell transit time through calibrated micropores) and cell aggregation (as measured by ultrasonic interferometry). Homologous transfusion of pegylated RBC into murine malaria-infected mice had no significant effect on the cerebral malaria death rate in Plasmodium berghei-infected mice, but it reduced the peripheral blood parasitemia by a factor 2 while in Plasmodium yoelii infected mice, the parasitemia was dramatically reduced by a factor of 4. These experiments demonstrate that transfusion of pegylated RBC may inhibit peripheral parasitemia. Cell electrophoresis appears to be a useful tool to allow in vivo detection and to investigate the fate of transfused pegylated RBC.

Morphological changes in serial auditory brain stem responses in 24 to 32 weeks' gestational age infants during the first week of life.

OBJECTIVE: The purpose of this investigation was to describe and quantify the sequential morphological changes in the auditory brain stem response (ABR) during the first postnatal week of life in very premature infants < or = 32 wk gestational age. These normative data could be useful in predicting neurological outcome in infants with perinatal risk factors. DESIGN: Sequential ABRs were recorded on a total of 135 infants on 5 out of the first 7 days of life. For analysis, data were grouped by gestational age in 2 wk intervals. In addition, a unique system was devised to categorize waveform response types in premature infants: type 1, a response with normal morphology and replicable waves III and V; type 2, a replicable response with either a wave III or wave V; type 3, a replicable response with neither a wave III or wave V; type 4, a response with no replicable waveform. RESULTS: The frequency of detection of waves improves over the first week of life with the detectability of waves III and V being more frequent than wave I at all gestational ages. There was a gradual improvement in response types in infants > 26 wk with the greatest improvement occurring during the 28 to 29 wk gestation. ABRs were predominantly types 3 and 4 at 24 to 25 wk, type 3 at 26 to 27 wk, type 2 at 28 to 29 wk, and types 1 and 2 at 30 to 31 wk. Absolute wave latencies and interwave latencies also progressively decreased during the first postnatal week. In some infants there was a transient increase in latencies or worsening of response type on the second to third test day. CONCLUSIONS: There is progressive improvement in frequency of detection of waves I, III, and V with increasing gestational age. Response types gradually mature over the first postnatal week, particularly in premature infants 28 to 32 wk gestational age.

Gender, menstrual cycle, oral contraceptives and red blood cell deformability in healthy adult subjects.

Gender, menstrual cycle and oral contraceptives may have influence on mechanical properties of Red Blood Cell (RBC) and particularly on RBC deformability. So cell transit parameters have been assessed by filtration with the Cell Transit Analyser (CTA) for a large healthy adult population (seventy-nine males and one-hundred-fifteen females). The CTA provides the distribution of cell transit times of 5000 red blood cells, the mean transit time of the population and different percentiles such as p50, p75, p90 and p95. No effect of oral contraceptives was found. Nevertheless, influence of sex and menstrual cycle were demonstrated. A significant increase of the filtration parameters measured in the female population with respect to the male population and during menstruation, preovulation and post-ovulation periods was observed. During ovulation, the CTA parameters are comparable to the same parameters found in males.

Comparison of two strategies for surfactant prophylaxis in very premature infants: a multicenter randomized trial.

INTRODUCTION: Previous trials of surfactant therapy in premature infants have demonstrated a survival advantage associated with prophylactic therapy as an immediate bolus, compared with the rescue treatment of established respiratory distress syndrome. The optimal strategy for prophylactic therapy, however, remains controversial. When administered as an endotracheal bolus immediately after delivery, surfactant mixes with the absorbing fetal lung fluid and may reach the alveoli before the onset of lung injury. This approach, however, causes a brief delay in the initiation of standard neonatal resuscitation, including positive pressure ventilation, and is associated with a risk for surfactant delivery into the right main stem bronchus or esophagus. As an alternative approach, surfactant prophylaxis may be administered in small aliquots soon after resuscitation and confirmation of endotracheal tube position. Although this strategy has substantial logistical advantages in clinical practice, its efficacy has not been established. OBJECTIVE: The purpose of this study was to determine whether the established benefits of the immediate bolus strategy for surfactant prophylaxis could still be achieved using a postventilatory aliquot strategy after initial standard resuscitation and stabilization. DESIGN: Multicenter randomized clinical trial with patients randomized before delivery to immediate bolus or postventilatory aliquot therapy. PARTICIPANTS: Inborn premature infants delivered to mothers at an estimated gestational age of 24[0/7] to 28[6/7] weeks. INTERVENTIONS: Those infants who were randomized to the immediate bolus strategy were intubated as rapidly as possible after birth, and a 3-mL intratracheal bolus of calf lung surfactant extract (Infasurf) was administered before the initiation of positive pressure ventilation. Those infants who were randomized to the postventilatory aliquot strategy received standard resuscitation measures with intubation by 5 minutes of age, if not required earlier. At 10 minutes after birth, 3 mL of surfactant was administered in 4 divided aliquots of 0.75 mL each. Patients in both groups were eligible to receive up to three additional doses of surfactant as rescue therapy in the neonatal intensive care unit, if needed. OUTCOME MEASURES: The primary outcome variable was survival to discharge to home. Secondary variables included neonatal complications and requirement for oxygen therapy at 36 weeks' postmenstrual age. RESULTS: Among three centers, 651 infants were enrolled and randomized before delivery. Survival to discharge to home was similar for the two strategies for surfactant therapy as prophylaxis: 76% for the immediate bolus group and 80% for the postventilatory aliquot group. In a secondary analysis, the rate of supplemental oxygen administration at 36 weeks' postmenstrual age was 18% for the immediate bolus group and 13% for the postventilatory aliquot group. CONCLUSIONS: Survival to discharge to home was similar with immediate bolus and postventilatory aliquot strategies for surfactant prophylaxis. Because of its logistical advantages in the delivery room and its beneficial effects on prolonged oxygen requirements, we recommend the postventilatory aliquot strategy for surfactant prophylaxis of premature infants delivered before 29 weeks' gestation.

EEG background as predictor of electrographic seizures in high-risk neonates.

PURPOSE: Experience with continuous EEG monitoring in 29 consecutive infants at risk of neonatal seizures demonstrated that background abnormalities on the initial EEG were strongly associated with electrographic seizures in the subsequent 18-24 h. To test this association prospectively, we examined the relationship between EEG background and the presence of electrographic seizures in the next 22 at-risk infants monitored for seizures. METHODS: A standard EEG was recorded for each infant at risk for seizures. Based on specific criteria, the background was graded as normal; immature for age; or mildly, moderately, or severely abnormal. The EEG was then monitored continuously until no electrographic seizures were recorded for 18-24 h. RESULTS: Findings in the retrospective group of 29 infants and the prospective group of 22 infants did not differ. For the combined 51 infants, a normal or immature initial EEG background predicted the absence of seizures in the subsequent 18-24 h with a sensitivity of 96% [confidence interval (CI) 0.88, 1.0] and specificity of 81% (CI 0.67, 0.96). Administration of antiepileptic drugs (AEDs) before the start of the EEG recording did not affect this association. CONCLUSIONS: In 51 consecutively monitored infants at risk for neonatal seizures, a normal or immature EEG background strongly predicted the absence of electrographic seizures in the subsequent 18-24 h; background abnormalities strongly predicted the occurrence of electrographic seizures concomitantly or in the subsequent 18-24 h of recording. Screening infants at risk for neonatal seizures with a routine EEG allows identification of infants at highest risk for seizures, thus conserving resources required for continuous EEG monitoring and facilitating early intervention for seizures.

Casein peptide release and passage to the blood in humans during digestion of milk or yogurt.

In adult humans, after milk or yogurt ingestion, many peptides derived from alpha s1-, beta- or kappa-caseins were detected in stomach, including the kappa-caseinoglycopeptide, an inhibitor of platelet aggregation. Smaller peptides derived from casein and lactoferrin were recovered from duodenum. Two long peptides, the kappa-caseinoglycopeptide and the N-terminal peptide of alpha s1-casein, were absorbed and detected in plasma. These results support the concept that food-born peptides could have physiological activities in man.

Analgesia for neonatal circumcision: a randomized controlled trial of EMLA cream versus dorsal penile nerve block.

OBJECTIVE: To compare the efficacy of the dorsal penile nerve block (DPNB) with a less invasive form of local anesthesia, eutectic mixture of local anesthetic (EMLA) cream, for reduction of pain during neonatal circumcision. DESIGN: Prospective, blinded, randomized, controlled trial. SETTING: Tertiary referral, neonatal intensive care nursery in a university teaching hospital. PATIENTS: Fifty infants >/=341/2 weeks postmenstrual age and stable for discharge at time of circumcision; gestational age at birth 25 to 41 weeks; birth weight 600 to 4390 g; age at study 3 to 105 days. An additional cohort of term newborns (n = 20), who were not randomized, were circumcised without anesthesia. INTERVENTIONS: Administration of either EMLA cream (0.5 g topically 1 hour before circumcision) or 1% lidocaine (0.7-1.0 mL subcutaneously 3 minutes before circumcision). OUTCOME MEASURES: Primary: Neonatal Infant Pain Scale (NIPS) score; secondary: heart rate, respiratory rate. All outcome measures were assessed by an individual who was blinded to the group assignment and did not perform the circumcision. RESULTS: NIPS scores were significantly lower in the DPNB infants (2.3 +/- 1.8) compared with the EMLA infants (4.8 +/- 0.7). NIPS scores in patients circumcised without anesthesia indicated severe pain. There was a significantly greater increase in heart rate over the duration of the circumcision in the EMLA group than in the DPNB group (49 vs 9 beats per minute). Adverse effects included small hematomas at the site of injection in DPNB infants (10/23), mild erythema at 1 and/or 24 hours after circumcision in the EMLA infants (3/21), and penile edema noted 5 days after circumcision requiring removal of the circumcision bell in 1 DPNB infant. CONCLUSIONS: DPNB provides better pain reduction during neonatal circumcision than EMLA cream. EMLA cream may provide pain reduction compared with no anesthesia during neonatal circumcision.

Measurement of platelet aggregation peptide inhibitors by ultrasonic interferometry.

Several peptide inhibitors of thrombin- or collagen-induced platelet aggregation and of the interaction between glycoprotein Ib and von Willebrand factor were studied by a new method--ultrasonic interferometry (Echo Cell). Inhibition of aggregate formation in a concentration-dependent manner was observed. The sensitivity of the method was 3 to 40 times higher than that of classical turbidimetry.

Dextromethorphan ameliorates effects of neonatal hypoxia on brain morphology and seizure threshold in rats.

Hypoxic injury to the brain is mediated in part by NMDA receptors. Therefore, NMDA receptor blockade with dextromethorphan (DM), a non-competitive channel blocker, was hypothesized to ameliorate injury even when given after the hypoxic insult. Rats were exposed to 8% oxygen for 3 h on postnatal day 7. Within 20 min of exposure, animals received 30 mg/kg i.p. DM or normal saline. Littermates maintained in room air for 3 h also received DM or saline. At 14 days of age, 7 days after exposure, cortical thickness and hippocampal area were measured. At 70-90 days of age, approximately two months after exposure, in a separate group of rats, seizure threshold using pentylenetetrazol (PTZ) and passive avoidance learning and retention were determined. There were no gross changes in cellular morphology and no evidence for cellular necrosis in any of the exposure groups. However, cortical thickness was decreased in animals exposed to hypoxia. DM administration prevented this decrease. Hippocampal area was unaffected. Seizure susceptibility in adulthood was increased in animals exposed to hypoxia in the neonatal period. DM prevented the decrease in seizure threshold. There was no difference in passive avoidance learning or retention as a function of neonatal exposure condition. Mild to moderate hypoxia, previously thought not to produce any histologic changes, causes significant short-term loss of cortical thickness and long-term decrease in seizure threshold. DM appears to ameliorate these effects even when given after the hypoxic insult. These results implicate the glutamate receptor system in the pathophysiology of hypoxia damage and suggest that treatment with a glutamate receptor blocker when neonatal asphyxia is suspected would help ameliorate the consequences of such an insult.

Screening head ultrasound to detect intraventricular hemorrhage in premature infants.

OBJECTIVE: The objective of this case-control study was to develop a screening protocol using head ultrasound (HUS) to detect high-grade intraventricular hemorrhage (IVH) in very-low-birthweight infants with greater specificity than current practice, while maintaining a high degree of sensitivity. MATERIALS AND METHODS: All infants /= 10, or cardiopulmonary resuscitation in the neonatal intensive care unit. CONCLUSION: Infants born at 28-32 weeks with a high-grade IVH can be identified with a high degree of sensitivity using refined screening criteria, eliminating 50 % of the HUS scans currently obtained for IVH screening.