Comparable Postconceptional Age Research Articles

19. Early brain connectivity differences in premature infants

Brain maturation at early stages may be assessed by changes in electroencephalographic connectivity (Grieve et al., 2008). We determined the differences in brain maturation between infants born at different gestational age (GA) by comparing connectivity measures obtained at comparable post-conceptional age. Electroencephalogram was recorded on twenty-six infants (23–35 weeks GA) at 35 post-conceptional weeks. Infants were divided in groups according to GA: 23–27 (ELGA), 28–32 (VLGA) and 34–35 (LGA) weeks. Data were recorded on Fp1, Fp2, Fz, C3, Cz, C4, T3, T4, O1 and O2 channels referred to linked mastoids and transformed into the frequency domain using a Fast Fourier Transformation algorithm. A single- subject-connectivity-matrix approach was used to obtain measures of global/local connectivity (clustering coefficients, strength and modularity) in delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz) and beta (13–30 Hz) bands. Functional connectivity measures were compared between subgroups. A greater mean coherence strength of the theta band of the right hemisphere in LGA compared with ELGA (p = .006) were found. The comparison at the same post- conceptional age of infants born at different gestational weeks allowed to emerge early differences in brain electrical activity suggesting altered developmental trajectories for premature infants born at lower gestational ages.

60. Spectral analysis of the neurophysiological activity in the human developing brain

Brain maturation at early stages may be assessed by changes in spectral power frequencies of electroencephalogram, especially those in lower frequency range (Scher, 1997). Our aim was to determine differences in brain maturation between premature infants born at different gestational age by comparing the spectral power values obtained at comparable post-conceptional age. Electroencephalogram was recorded on forty infants (23–34 weeks) at 35 post-conceptional weeks. Infants were divided in groups according to gestational age: 23–27 (ELGA), 28–32 (VLGA) and 33–34 (LGA) weeks. In order to minimize handling in this very fragile population, one bipolar channel (C3–C4) was recorded. Electroencephalogram data were transformed into the frequency domain using a fast Fourier transform algorithm and divided in delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz) and beta (13–30 Hz) bands. Absolute and relative power values were compared between groups. Relative power values of ELGA differed significantly from those of LGA, showing an higher amount in delta and a lower amount in alpha and beta frequency bands. The comparison at the same post-conceptional age of infants born at different gestational weeks allowed to emerge early differences in brain electrical activity suggesting altered developmental trajectories for premature infants born at lower gestational ages.

COMPARISON OF REFLEX MODIFICATION PROCEDURES AND AUDITORY BRAINSTEM RESPONSE IN HIGH-RISK NEONATES

This study compared the results of reflex modification (RM)--an objective technique for assessing brainstem sensorineural processing--with those of auditory brainstem response (ABR) for a group of high-risk infants at comparable postconceptional ages. For the RM procedure, an eyeblink-eliciting tap to the glabella was presented either alone or accompanied by a brief 90dB SPL tone. 37 high-risk infants were tested with both RM and ABR at a mean postconceptional age of 37.3 weeks. Seven had an increased brainstem conduction time ('failed ABR') and eight did not exhibit significant reflex augmentation ('failed RM'), seven of whom also failed the ABR. These data provide evidence that sensory stimuli which affect the neural mechanisms responsible for the organization of the startle response and auditory processing share essential neural components.

Abstract

During periods of regular breathing, heart rate is slower and more variable in healthy (no history of respiratory distress syndrome) prematurely born infants with persistent apnea, relative to full-term control infants of comparable post-conceptional ages. We tested the hypothesis that the cardiovascular differences may be linked to the persistent apnea, rather than premature birth, by assessing heart rate and variability in full-term infants with persistent apnea. Thus, resting heart rate and variability were compared in full-term infants with apnea of infancy, prematurely born infants with persistent apnea, and full-term control infants. Full-term infants with persisting apnea showed slower heart rates than control infants, beginning at 4 months after birth, and enhanced heart rate variability beginning at 6 months. Healthy prematurely born infants with persistent apnea showed cardiovascular alterations similar to those of full-term infants with apnea; these alterations differed from those observed in very premature infants with histories of respiratory distress. The postnatal development of cardiovascular aberrations in infants with persistent apnea suggests that mechanisms accompanying apneic events may contribute to long-term alterations in autonomic control.

Developmental patterns of heart rate and variability in infants with persistent apnea of infancy.

During periods of regular breathing, heart rate is slower and more variable in healthy (no history of respiratory distress syndrome) prematurely born infants with persistent apnea, relative to full-term control infants of comparable post-conceptional ages. We tested the hypothesis that the cardiovascular differences may be linked to the persistent apnea, rather than premature birth, by assessing heart rate and variability in full-term infants with persistent apnea. Thus, resting heart rate and variability were compared in full-term infants with apnea of infancy, prematurely born infants with persistent apnea, and full-term control infants. Full-term infants with persisting apnea showed slower heart rates than control infants, beginning at 4 months after birth, and enhanced heart rate variability beginning at 6 months. Healthy prematurely born infants with persistent apnea showed cardiovascular alterations similar to those of full-term infants with apnea; these alterations differed from those observed in very premature infants with histories of respiratory distress. The postnatal development of cardiovascular aberrations in infants with persistent apnea suggests that mechanisms accompanying apneic events may contribute to long-term alterations in autonomic control.

Developmental patterns of heart rate and variability in prematurely-born infants with apnea of prematurity.

At equivalent post-conceptional ages, prematurely-born infants have higher heart rates and reduced heart rate variability, relative to full-term neonates. Premature birth might exert long-lasting effects on central and peripheral mechanisms that control cardiovascular activity. We assessed development of heart rate and heart rate variability in symptomatic preterm infants up to 6 months of age. Fifty 6.5-h evening recordings of EKG and breathing were obtained from prematurely-born infants (gestational ages: 24-35 weeks). Cardiac R-R intervals were captured with a resolution of +/- 0.5 msec. One-min epochs were selected from three periods of regular respiration in recordings from premature infants and 72 recordings of full-term infants at comparable post-conceptional ages. Mean heart rate and heart rate variability were determined for each recording. At 40 weeks post-conception, prematurely-born infants with apnea of prematurity showed higher heart rates and reduced heart rate variability than did full-term neonates. These differences between premature and full-term infants persisted throughout the next 6 months in those infants born prior to 30 weeks gestation, and in those infants born at 30-35 weeks who experienced respiratory distress syndrome (RDS) during the neonatal period. The findings suggest that premature delivery, or complications thereof, exerts long-lasting effects on cardiac control.

Normal electrographic-polysomnographic patterns in preterm and fullterm infants

Maturational changes occur in electroencephalogram (EEG)-sleep patterns for the neonate from preterm to fullterm postconceptional age. Electrical maturity of the neonatal brain is correlated within 1 to 2 weeks of other criteria for gestational maturity. Proper recording techniques of EEG-sleep studies in neonates will ensure accurate documentation of both cerebral and noncerebral parameters. Before 36 weeks postconceptional age (PCA), recognition of specific electrographic patterns are used to identify neonates of different PCAs. Following 36 weeks PCA, concordance between cerebral and noncerebral physiological behaviors are more predictable of neonatal EEG-sleep segments; this phenomena is independent of intrauterine or extrauterine development. Computer-assisted analyses of EEG sleep complement visual inspection by better characterizing relationships among EEG-sleep behaviors. Such analyses have documented group differences between preterm and fullterm infants of comparable postconceptional ages, suggesting adaptation of brain function to conditions of prematurity. Recognition of neonatal EEG-sleep patterns facilitate both an understanding of functional brain ontogeny and a recognition of pattern disturbances that underlie pathological or stressful conditions.

Bradycardia and gastroesophageal reflux in term and preterm infants: is there any relation?

Conflicting data are published regarding the influence of acid gastroesophageal reflux on the heart rate. In this study, heart rate was monitored simultaneously with esophageal pH in 50 infants with symptoms suggestive of gastroesophageal reflux disease (frequent vomiting and regurgitations). The data of 25 preterm infants (born at 28-36 6/7 weeks) were compared to those of 25 term infants (born after 37 weeks of gestation). However, both groups were investigated at identical postconceptional age of 47-49 weeks. Not one significant bradycardia (heart rate < or = 80/min during > or = 10 s) was recorded, although 71 "relative bradycardia episodes" (heart rate < or = 80/min during > or = 5 beats) were detected, none lasting for > 5 s. Although the number of infants with relative bradycardia episodes did not differ between groups, the relative bradycardia episodes occurred more frequently in some preterm infants (53 episodes in preterm infants vs. 18 in term babies). Acid gastroesophageal reflux episodes were observed in 46 infants (92%). Neither the number of reflux episodes nor their duration was different in both groups. Simultaneous relative bradycardia episodes and acid reflux episodes were observed in three of 23 preterm and two of 23 term infants (NS). It is concluded that in a population of preterm and term infants with symptoms suggestive of a moderate gastroesophageal reflux pathology, investigated at comparable postconceptional age, most reflux episodes are not time-related to changes in heart rate.

Bradycardia and Gastroesophageal Reflux in Term and Preterm Infants

SummaryConflicting data are published regarding the influence of acid gastroesophageal reflux on the heart rate. In this study, heart rate was monitored simultaneously with esophageal pH in 50 infants with symptoms suggestive of gastroesophageal reflux disease (frequent vomiting and regurgitations). The data of 25 preterm infants (born at 28–366/7 weeks) were compared to those of 25 term infants (born after 37 weeks of gestation). However, both groups were investigated at identical postconceptional age of 47–49 weeks. Not one significant bradycardia (heart rate %80/min during 3%10 s) was recorded, although 71 “relative bradycardia episodes” (heart rate %s80/min during s%5 beats) were detected, none lasting for &gt;5 s. Although the number of infants with relative bradycardia episodes did not differ between groups, the relative bradycardia episodes occurred more frequently in some preterm infants (53 episodes in preterm infants vs. 18 in term babies). Acid gastroesophageal reflux episodes were observed in 46 infants (92%). Neither the number of reflux episodes nor their duration was different in both groups. Simultaneous relative bradycardia episodes and acid reflux episodes were observed in three of 23 preterm and two of 23 term infants (NS). It is concluded that in a population of preterm and term infants with symptoms suggestive of a moderate gastroesophageal reflux pathology, investigated at comparable postconceptional age, most reflux episodes are not time‐related to changes in heart rate.

Altered brainstem sensory processing as assessed by reflex modification procedures in infants at risk for apnea.

Reflex modification procedures were used to test sensory processing in premature infants to examine the relationship between respiratory abnormalities and brainstem neuronal function. A total of 73 premature infants at risk for apnea and/or infants receiving methylxanthine therapy was given a 12-h pneumocardiogram and reflex modification test at a comparable postconceptional age, before discharge. Reflex modification was tested using a controlled eyeblink-eliciting tap to the glabella presented either alone or with a 1 kHz 90-dB SPL tone. The amplitude of the glabellar tap eyeblink and acoustically modified blink were lower in infants discharged on cardiac/apnea monitors (n = 36) than in the unmonitored group (1.44 and 1.59 volts versus 2.15 and 2.39 V, p less than 0.005, respectively). At follow-up, 12 monitored infants had clinically significant apnea after discharge. The records of this subgroup of infants revealed a significantly lower augmentation of the glabellar eyeblink response when compared to all infants screened for respiratory abnormalities and to the other monitored babies (p less than 0.01). The data suggest that abnormalities of the ventilatory pattern and occurrence of clinical apnea in preterm infants may in some measure be related to acoustic sensory processing, implying an alteration of brainstem neuronal function and organization.

THE EFFECT OF DIET COMPOSITION ON ENERGY METABOLISM, SUBSTRATE UTILISATION AND GROWTH IN THE VLBW INFANT

Medium-chain-triglycerides (MCT) induce a decrease in fat storage in adult animals. To study the effect of MCT on quality of growth in the VLBW infant, oxidation (ox) and accretion (accr) of energy, protein, fat and carbohydrate have been measured in 20 growing VLBW infants, fed either an MCT enriched formula (gp 1; n=8) or an LCT formula (gp 2; n=12). 16 studies were performed in each group, combining indirect calorimetry, macronutrient balance and anthropometry. Weight and length gain simulated intra-uterine growth rate in both groups. Subscapular skinfolds and calculated body fat were similar in both groups, but higher than in the fetus of comparable postconceptional age. CONCLUSIONS: 1) The similar energy expenditure and fat oxidation indicate that MCT are not preferentially oxidised. 2) Consequently, MCT have to be chain elongated before storage. 3) The improvement of protein accretion to a level exceeding the intra-uterine accretion rate and improved absorption for MCT vs LCT indicate that body composition can be manipulated by isocalorically altering diet composition.

1175 SUBSTRATE UTILIZATION IN THE GROWING VERY LOW BIRTHWEIGHT(VLBW) FORMULA FED INFANT

Nutritional needs of the growing VLBW infant are usually assessed in relation to fetal accretion rates1. However, we show in VLBW infants differences in accretion rates from those inferred from previous studies on cadaver composition. 20 studies were performed in 13 formula fed(SMA20/24) appropriate for gestational age infants(mean±SE B.Wt:1155±39g; study wt:1280±70g; study age: 22±2d) to determine the rate of deposition of fat(F), carbohydrate(CHO) and protein(P). 3 day balance, indirect calorimetric and urinary N2 studies permitted measurement of intake, losses, oxidation and deposition rates of F, CHO and P(mean±SE:g/kg.d):We conclude that in the growing VLBW infant: 1) CHO is the main energy source (85%); 2)80% of absorbed F is stored; 3) compared to the reference fetus gaining weight comparably, F and CHO deposition is higher and P accretion is similar. This implies that the daily weight gain of the VLBW infant contains more solids(54%) (excluding minerals) than the fetus of comparable post conceptional age(23%)1. Ref.1 Widdowson, E.M.: In: Scientific Foundations of Paeds. pp153-163(W.B. Saunders, 1974).