A prospective, longitudinal diffusion tensor imaging study of brain injury in newborns.

OBJECTIVE: To establish the magnitude and time course of the changes in water diffusion coefficient (D(av)) following newborn infant brain injury. METHODS: Ten newborn infants at high risk for perinatal brain injury were recruited from the neonatal intensive care unit. Conventional and diffusion tensor MRI was performed on three occasions during the first week of life. Regions of injury were determined by evaluating conventional MR images (T1, T2, fluid-attenuated inversion recovery) at 1 week after injury. D(av) values were determined for these regions for all three scans. RESULTS: D(av) values were decreased in most infants 1 day after injury, but injury was not evident or underestimated in 4 of 10 infants despite the presence of injury on conventional imaging at 1 week. By the third day, D(av) values were decreased in injured areas in all infants, reaching a nadir of approximately 35% less than normal values. By the seventh day after injury, D(av) values were returning to normal (pseudonormalization). CONCLUSIONS: MR diffusion images (for which contrast is determined by changes in D(av)) obtained on the first day after injury do not necessarily show the full extent of ultimate injury in newborn infants. Images obtained between the second and fourth days of life reliably indicate the extent of injury. By the seventh day, diffusion MR is less sensitive to perinatal brain injury than conventional MR because of transient pseudonormalization of D(av). Overall, diffusion MR may not be suitable as a gold standard for detection of brain injury during the first day after injury in newborn infants.

Normal brain in human newborns: apparent diffusion coefficient and diffusion anisotropy measured by using diffusion tensor MR imaging.

PURPOSE: To establish quantitative standards for the directionally averaged water apparent diffusion coefficient (D) and quantitative diffusion anisotropy (A sigma) of normal brains in newborns by using diffusion tensor magnetic resonance (MR) imaging. MATERIALS AND METHODS: Diffusion tensor MR imaging was performed during the first 36 hours of life in 22 newborns (gestational age range, 31-41 weeks). Values of D and A sigma were measured in regions of interest chosen in the cortical gray matter, centrum semiovale, caudate nuclei, lentiform nuclei, thalami, internal capsules, and cerebellar hemispheres. RESULTS: The D values in the gray and white matter in newborns are considerably higher than those in adults. There is a striking correlation between gestational age and D, with D decreasing as gestational age increases. The A sigma values in the white matter in newborns are lower than those in adults. Values of A sigma show statistically significant correlations with gestational age only in the white matter of the centrum semiovale, in which A sigma values increase sharply near term. CONCLUSION: The D values primarily reflect overall brain water content. The A sigma values are more sensitive to tissue microstructure (e.g., white matter packing and myelination). The D and A sigma images reveal information and not apparent on T1- and T2-weighted images.

Antenatal steroids and intraventricular hemorrhage after premature rupture of membranes at 24-28 weeks' gestation.

To determine whether antenatal corticosteroid administration after midtrimester premature rupture of membranes (PROM) reduces the incidence or severity of neonatal intraventricular hemorrhage, we identified a cohort of infants delivered between 24 to 28 weeks gestation (n = 75) by mothers with PROM. Information was obtained from a computerized database (n = 3716) of all newborns admitted to the neonatal intensive care unit at a single medical center from 1991 to 1996. We reviewed records of each mother-infant pair to determine antenatal corticosteroid administration, presence, and severity of neonatal intraventricular hemorrhage, and frequency of infectious complications. Using a logistic regression model, antenatal corticosteroid administration was associated with a significantly reduced risk of severe (grade 3-4) intraventricular hemorrhage (0.1 odds ratio, 0.006-0.57, 95% confidence interval), but not a reduced incidence of intraventricular hemorrhage (grade 1-4, 0.4 odds ratio, 0.12-1.05, 95% confidence interval).

Influence of upper airway negative pressure reflex on response to airway occlusion in sleeping infants.

Artificially produced upper airway suction inhibits the diaphragm in animals and infants; however, the effects of spontaneously generated suction in humans are unknown. We studied nine tracheostomized infants because separation of the upper from the lower airway allowed us to channel suction created by an occluded inspiratory effort to both upper and lower airways (upper + lower airway occlusions) or to the lower airway only (lower airway occlusion). The tracheostomy airway was briefly occluded at end expiration during quiet sleep. In upper + lower airway occlusions, peak airway pressure of the first occluded breath was less negative and rate of pressure decrease slower than that of lower airway occlusions, indicating that upper airway suction inhibits thoracic inspiratory muscles. The threshold for this response was less than or equal to 4 cmH2O suction pressure. The effect on inspiratory time was variable. A decrease in slope of the inspiratory pressure waveform occurring at approximately 0.12 s after inspiration onset was more marked in upper + lower airway occlusions. We conclude that infants have an upper airway reflex response to inspiratory pressure that alters not only the peak and slope but also the shape of the inspiratory pressure waveform.

Effects of negative upper airway pressure on pattern of breathing in sleeping infants.

Negative upper airway (UAW) pressure inhibits diaphragm inspiratory activity in animals, but there is no direct evidence of this reflex in humans. Also, little is known regarding reflex latency or effects of varying time of stimulation during the breathing cycle. We studied effects of UAW negative pressure on inspiratory airflow and respiratory timing in seven tracheostomized infants during quiet sleep with a face mask and syringe used to produce UAW suction without changing lower airway pressure. Suction trials lasted 2-3 s. During UAW suction, mean and peak inspiratory airflow as well as tidal volume was markedly reduced (16-68%) regardless of whether stimulation occurred in inspiration or expiration. Reflex latency was 42 +/- 3 ms. When suction was applied during inspiration or late expiration, the inspiration and the following expiration were shortened. In contrast, suction applied during midexpiration prolonged expiration and tended to prolong inspiration. The changes in flow, tidal volume, and timing indicate a marked inhibitory effect of UAW suction on thoracic inspiratory muscles. Such a reflex mechanism may function in preventing pharyngeal collapse by inspiratory suction pressure.

Pharyngeal fluid clearance and aspiration preventive mechanisms in sleeping infants.

We sought to characterize ventilatory and airway protective responses to pharyngeal stimulation in young infants during sleep. We studied the various responses with respect to frequency of occurrence, effect of increased stimulus intensity, and relation of stimulus fluid to laryngeal structures. Two groups of infants were studied: healthy full-term infants (n = 5) and preterm infants with a history of prolonged apnea (n = 9). We used a nasopharyngeal catheter to deliver small boluses of warm saline (0.02-0.35 ml) to the oropharynx. Responses repeatedly observed in both infant groups included swallows, obstructed respiratory efforts, brief apnea, prolonged apnea, and cough. In both infant groups, swallows and obstructed breaths occurred frequently and cough and prolonged apnea infrequently. The functional significance of some response patterns was clear, whereas that of others was obscure. Larger stimulus volumes yielded more frequent responses (P less than 0.01), and preterm infants responded much more frequently than full-term infants (P less than 0.01). Prolonged apnea was a composite of the other responses and was much more common in preterm than full-term infants (P less than 0.01). The stimulus technique was performed under direct visualization of the airway in two deceased infants. The findings suggested that the relation of the piriform fossae to the interarytenoid notch is important in determining response frequency. Implications for regulation of the removal of upper airway secretions during sleep are discussed.

Characterization of prolonged apneic episodes associated with respiratory syncytial virus infection.

We used high-speed polygraphic recordings to document in detail the sequence of events during prolonged apneic spells in two infants with respiratory syncytial viral (RSV) infection. Also, we elicited upper airway reflexes by stimulating the airway with saline during sleep. Spontaneous prolonged apneic spells were recorded in both infants, and these consisted of two distinctly different apnea types. A number of similarities between apnea of prematurity, upper airway reflex apnea and the apneas in these two infants with RSV infection suggests the possibility that these various kinds of apnea may have related causal mechanisms.

Airway protective and abdominal expulsive mechanisms in infantile regurgitation.

To define the expulsive and airway protective mechanisms involved in infantile regurgitation, we studied 15 infants (9 premature and 6 mature infants) with histories of frequent postfeeding regurgitation. In 13 infants we recorded pharyngeal pressure, pH, nasal and oral airflow, and abdominal respiratory movements. In two additional infants we recorded gastric pressure. In eight infants observations were made without intrapharyngeal recording devices. Distinctive abdominal regurgitation movements (RMs) immediately preceded 84% of regurgitation episodes. These RMs were characterized by one or more large brief increases in abdominal girth. In the two infants with gastric pressure recordings, large increases in gastric pressure, with duration and frequency characteristics similar to the RMs, immediately preceded regurgitation episodes. Thus, in contrast to the generally accepted concept that flow of gastric contents out of the stomach is passive during infantile regurgitation, we documented an active expulsive mechanism similar to that of vomiting in the adult. In all regurgitation episodes, upper airway closure occurred at the onset of the regurgitation movement. One or more swallows occurred immediately following RMs and prior to airway reopening in 97% of regurgitation episodes. Brief respiratory pauses occurred during regurgitation in all premature infants and occasionally in mature infants. Nasal regurgitation, coughing, and sneezing occasionally accompanied regurgitation episodes. Thus upper airway closure and swallowing prior to airway reopening were the most frequently observed airway protective mechanisms during regurgitation. Brief respiratory pauses, sneezing, and coughing may be secondary airway protective mechanisms. Nasal regurgitation likely represents immaturity of airway protective mechanisms.

Apnea associated with regurgitation in infants.

To determine whether regurgitation might be a factor in the pathogenesis of apnea in certain infants, we compared the frequency of short and prolonged apnea immediately following regurgitation to that during control periods. Ten infants (nine preterm and one term) with histories of frequent regurgitation and also apneic spells were studied for 2 to 3 hours by monitoring nasal airflow, abdominal respiratory movements, electrocardiogram, pharyngeal pH, and pharyngeal pressure. In six of these infants additional observations were made without the intrapharyngeal recording devices. Fourty-four episodes of regurgitation were observed. Both prolonged apnea (P less than 0.05) and short apnea (P less than 0.01) occurred much more frequently during regurgitation than during the control period; however, the majority of prolonged apneic spells observed were unassociated with regurgitation. The increased frequency of apnea during regurgitation was not related to the presence of intrapharyngeal recording devices. Although nasal regurgitation was frequently associated with short apnea, no prolonged apnea was observed during the seven episodes of nasal regurgitation observed. The 14-fold increase in prolonged apnea frequency immediately following regurgitation supports the hypothesis for a causal relationship between apnea and regurgitation.

Frequency and significance of swallowing during prolonged apnea in infants.

To better document and describe the phenomenon of swallowing during apneic spells, we compared the frequency of swallowing during epidsodes of prolonged apnea with nonapnea control periods in 9 preterm and 1 term infant. Infants with a history of idiopathic prolonged apnea were studied for 2 to 3 h by monitoring, electrocardiogram, nasal air flow, oral CO2, abdominal respiratory movements, chin electromyogram, pharyngeal pressure, and pH. In 7 of the infants, additional observations were performed without the intrapharyngeal recording devices. One or more swallows occurred during 75% of the 100 spells observed. Swallows were far more common during apneic spells than during nonapnea control periods, and were more frequent during mixed and obstructive apnea than during central apnea (p less than .01). Asphyxia, regurgitation, and the intrapharyngeal recording devices did not appear to cause the increased frequency of swallows during apneic spells. Swallowing was temporally related to spontaneous recovery from apnea, with a swallow usually preceding recovery by 5 to 6 s. During apneic spells, we observed that swallows were often associated with a brief obstructed inspiratory effort ("swallow-breath"), a normal component of nonfeeding swallows in infants. These swallow-breaths were interspersed with higher amplitude "ordinary" obstructed breaths during apneic episodes. Thus, 2 distinctly different types of obstructed inspiratory efforts were identified during mixed and obstructive apnea episodes in infants. The sequence of events during apneic spells in the term and preterm infants was similar.