Dynamics of the establishment of intestinal microflora in healthy full-term newborns]

A study was made of the dynamics of establishment of the intestinal microflora in 79 healthy mature neonates born of healthy mothers. A total of 223 bacteriological examinations were conducted. A stable prevalence of bifidobacteria over the aerobic portion of the intestinal biocenosis occurred in all the children from the 8th day after birth. Along with this the following bacteria were continuously present in the intestine: lactic bacilli and streptococci E. coli, enterococci and staphylococci; however, their portion in the biocenosis was not great. Bacteroids, microbes of the Proteus genus, and yeast-like fungi were found in the cultures only before the establishment of a high bifidobacteria level. Conditionally pathogenic microorganisms and their associations were continuously revealed in 19.8% of healthy mature neonates. Apparently the qualitative prevalence of bifidobacteria prevented the clinical expression of dysbacteriosis in these children.     

Postnatal maturation of vagal respiratory reflexes in preterm and full-term lambs.

The postnatal development of ventilatory reflexes originating from bronchopulmonary receptors was assessed in preterm vs. full-term lambs. Ventilation and arterial pressure were repeatedly measured in 10 preterm (gestational age, 132 days) and 7 full-term lambs without sedation from day 1 to day 42. The Hering-Breuer inhibitory reflex (slowly adapting stretch receptors) was assessed by the increase in expiratory time during end-inspiratory occlusion. The pulmonary chemoreflex (C-fiber endings) was assessed by the initial apnea + bradycardia + systemic hypotension and the secondary tachypnea after capsaicin intravenous injection. Results show the following. 1) Premature birth did not modify the maturation of the Hering-Breuer reflex. 2) Whereas a classic pulmonary chemoreflex was observed in the very first hours of life in preterm lambs, the tachypneic component of this reflex was weaker than in full-term lambs on day 1. 3) Premature birth led to a reversed postnatal maturation of this tachypneic response (tendency to increase with postnatal age). Our findings suggest that premature birth in lambs modifies postnatal maturation of the pulmonary chemoreflex.     

Effect of artificial surfactant on pulmonary function in preterm and full-term lambs

We hypothesized that agents very different from surfactant may still support lung function. To test this hypothesis, we instilled FC-100, a fluorocarbon, and Tween 20, a detergent, which have higher minimum surface tensions and less hysteresis than surfactant, into 15 full-term and 14 preterm lambs. FC-100 and Tween 20 were as efficient as natural surfactant in improving gas exchange and compliance in preterm lambs with respiratory failure. Dynamic compliance correlated with the equilibrium surface tension of the alveolar wash in both full-term (P less than 0.02) and preterm (P less than 0.008) lambs. Functional residual capacity in full-term and preterm lambs was lower after treatment with the two test agents than with surfactant, findings consistent with qualitative histology. Oxygenation in full-term lambs correlated with mean lung volumes (P less than 0.003), suggesting that the hysteresis and/or low minimum surface tension of surfactant may improve mean lung volume, and hence oxygenation, by maintaining functional residual capacity. The effects of the test agents suggest that agents with biophysical properties different from surfactant may still aid lung expansion.     

Urinary excretion rates of 8-oxoGua and 8-oxodG and antioxidant vitamins level as a measure of oxidative status in healthy,full-term newborns

The aim of the present study was to evaluate the oxidative status in healthy full-term children and piglets. Urinary excretion of 8-oxoGua (8-oxoguanine) and 8-oxodG (8-oxo-2′-deoxyguanosine) were determined using HPLC/GS/MS methodology and concentrations of vitamins A, C and E with HPLC technique. The levels of 8-oxoGua in urine samples were about 7–8 times higher in newborn children and piglets when compared with the level of adult subjects, while in the case of 8-oxodG the difference was about 2.5 times. The levels of vitamin C and E in umbilical cord blood of newborn children significantly depend on the concentration of these compounds in their mother's blood. However, the values of vitamin C in human's cord blood were about 2-times higher than in respective mother blood, while the level of vitamin E showed an opposite trend. The results suggest that: (i) healthy, full-term newborns are under potential oxidative stress; (ii) urinary excretion of 8-oxoGua and 8-oxodG may be a good marker of oxidative stress in newborns; and (iii) antioxidant vitamins, especially vitamin C, play an important role in protecting newborns against oxidative stress.     

Urinary excretion rates of 8-oxoGua and 8-oxodG and antioxidant vitamins level as a measure of oxidative status in healthy, full-term newborns

The aim of the present study was to evaluate the oxidative status in healthy full-term children and piglets. Urinary excretion of 8-oxoGua (8-oxoguanine) and 8-oxodG (8-oxo-2'-deoxyguanosine) were determined using HPLC/GS/MS methodology and concentrations of vitamins A, C and E with HPLC technique. The levels of 8-oxoGua in urine samples were about 7-8 times higher in newborn children and piglets when compared with the level of adult subjects, while in the case of 8-oxodG the difference was about 2.5 times. The levels of vitamin C and E in umbilical cord blood of newborn children significantly depend on the concentration of these compounds in their mother's blood. However, the values of vitamin C in human's cord blood were about 2-times higher than in respective mother blood, while the level of vitamin E showed an opposite trend. The results suggest that: (i) healthy, full-term newborns are under potential oxidative stress; (ii) urinary excretion of 8-oxoGua and 8-oxodG may be a good marker of oxidative stress in newborns; and (iii) antioxidant vitamins, especially vitamin C, play an important role in protecting newborns against oxidative stress.     

Chemokines plasma levels in preterm newborns of preeclamptic mothers

Information on leukocyte activation in newborn infants of preeclamptic mothers is scarce. IL-8 and GRO-α are the main pro-inflammatory cytokines involved in leukocyte activation. The objective was to evaluate IL-8 and GRO-α plasma levels in preterm newborns infants of preeclamptic mothers. Newborns with gestational age <36 weeks and birth weight <2000 g were included and divided: non-preeclamptic (n = 64) and preeclamptic groups (n = 55). Exclusion criteria were major congenital malformations, inborn errors of metabolism or chromosomal anomalies, congenital infections, death in delivery room, and maternal chronic hypertension without preeclampsia. IL-8 and GRO-α were measured by enzyme immunoassay in the first 48 h. Groups were similar in birth weight, gestational age, Apgar scores at 5 min, sepsis, RDS, mechanical ventilation, TPN, NEC, intraventricular hemorrhage and death. The preeclamptic group had more neutropenia, SGA, cesarean section, and less rupture of membranes >18 h. IL-8 was higher in the non-preeclamptic [157.1 pg/mL (86.4–261.3) and 26.54 pg/mL (3.6–87.2) p < 0.001]. GRO-α levels were similar in both groups [229.5 pg/mL (116.6–321.3) and 185.5 pg/mL (63.9–306.7) p = 0.236]. After multiple regression analysis only absence of preeclampsia was associated with high IL-8 levels. Our data suggest that leukocyte activation may be impaired in infants of preeclamptic mothers.     

Features of cyclic sleep organization and melatonin production in full-term newborns with intrauterine growth retardation

Data on the formation of cyclic sleep organization and melatonin production in full-term newborn infants with intrauterine growth retardation (IUGR) are presented. It has been shown that disordered cyclic sleep organization in IUGR newborns indicates the degree of intrauterine brain damage as a result of chronic hypoxia. The absence of cyclic sleep organization, the disordered formation of the paradoxical phase combined with delayed development of tonic, congenital reflex reactions, and low melatonin production give evidence of severe brain damage, which warrants combined therapy in the early neonatal period of life.     

Relationship between respiratory pauses and heart rate during sleep in normal premature and full-term newborns

To investigate the relationship between central respiratory pauses and heart rate, we performed polygraphic recordings in 23 normal newborns (35 to 41 weeks conceptional age). We monitored the electroencephalogram, rapid eye movements, movements of the upper and lower limbs, chin and diaphragmatic electromyogram, electrocardiogram, thoracic and abdominal respiratory movements, air flow and transcutaneous PO2. Heart rate changes were analysed by computer measurement of R-R intervals and by cardiotachography. Respiratory pauses occurring after body movements and those not preceded by movements were studied separately. We analysed 1128 respiratory pauses greater than 3 s duration. No respiratory pause lasted more than 12 s. Independently of age, sleep state and respiratory pause duration, heart rate was significantly lower at the onset of respiratory pause, compared to control periods (selected away from the pause: 10 s before its onset and 20 s after its end). Heart rate slowed still further through the respiratory pause and reverted toward the baseline level after its end. When no movements preceded the respiratory pause, heart rate just before the pause was lower compared to control periods. These findings suggest the existence of simultaneous central commands responsible for both respiratory pause and heart rate deceleration.     

Central blood oxygen saturation vs crying in preterm newborns

Infant cry characteristics reflect the development and possibly the integrity of the central nervous system. This study evaluates the distress occurring during cry in preterm newborn infants, as related to decrease of central blood oxygenation. A recording system was developed, that allows synchronised, non-invasive monitoring of blood oxygenation and audio recordings of newborn infant's cry. Cry episodes were identified by an automatic system allowing further analysis of the changes induced by the cry episodes on the oxygen saturation level in the central nervous system. Specifically, decrease in the oxygenation level appears during a cry episode, followed by recovery of the oxygenation after the cry episode is over. In the present work we compare a group of preterm infants with a control group of full term newborns in order to detect possible differences between the two sets of patients.Results indicate that a similar decrease in oxygenation level occurs in both groups of patients, but the recovery time after the crying episode is more stable and rapid in full term newborns than in preterm ones. This could prove useful for clinicians and nurses in the prevention of developmental diseases for this class of patients.     

Comprehensive brain MRI segmentation in high risk preterm newborns

Most extremely preterm newborns exhibit cerebral atrophy/growth disturbances and white matter signal abnormalities on MRI at term-equivalent age. MRI brain volumes could serve as biomarkers for evaluating the effects of neonatal intensive care and predicting neurodevelopmental outcomes. This requires detailed, accurate, and reliable brain MRI segmentation methods. We describe our efforts to develop such methods in high risk newborns using a combination of manual and automated segmentation tools. After intensive efforts to accurately define structural boundaries, two trained raters independently performed manual segmentation of nine subcortical structures using axial T2-weighted MRI scans from 20 randomly selected extremely preterm infants. All scans were re-segmented by both raters to assess reliability. High intra-rater reliability was achieved, as assessed by repeatability and intra-class correlation coefficients (ICC range: 0.97 to 0.99) for all manually segmented regions. Inter-rater reliability was slightly lower (ICC range: 0.93 to 0.99). A semi-automated segmentation approach was developed that combined the parametric strengths of the Hidden Markov Random Field Expectation Maximization algorithm with non-parametric Parzen window classifier resulting in accurate white matter, gray matter, and CSF segmentation. Final manual correction of misclassification errors improved accuracy (similarity index range: 0.87 to 0.89) and facilitated objective quantification of white matter signal abnormalities. The semi-automated and manual methods were seamlessly integrated to generate full brain segmentation within two hours. This comprehensive approach can facilitate the evaluation of large cohorts to rigorously evaluate the utility of regional brain volumes as biomarkers of neonatal care and surrogate endpoints for neurodevelopmental outcomes.     

Ultradian and circadian activity-rest rhythms of preterm neonates compared to full-term neonates using actigraphic monitoring

During the first weeks of life, preterm neonates show fewer circadian rhythms in their physiological parameters than full-term neonates. To determine whether preterm neonates differ in their temporal adaptation to the daynight cycle from full-term neonates at the early age of 1 week, we compared activity-rest behavior of both groups. Activity-rest behavior of 10 neurologically healthy preterm neonates (born in 34th to 36th week of gestation) and 10 neurologically healthy full-term neonates (born in 37th to 42nd week of gestation) was monitored longitudinally for 8 successive days in the first 2 weeks of life. Actigraphy was used to register and display time patterns of activity and rest in neonates by using small actometers, which resemble a wristwatch. Nursing/feeding was recorded using the actometer's integrated event marker button. Recordings for preterm neonates were conducted in the hospital; recordings for full-term neonates were carried out in the hospital and in their homes. In addition to the actigraphic recordings, a standardized diary was kept regularly. To assess periodic characteristics, frequency components of activity-rest behavior were analyzed using fast Fourier transformation (FFT). Amounts of daily sleep time, nightly sleep time, and sleep time during 24h were compared. Nursing/feeding epochs were also analyzed for 5 preterm and 5 full-term neonates to compare their food intake behavior. The majority of preterm neonates showed a multitude of ultradian frequencies in their spectra. In contrast, several full-term neonates showed a distinct circadian frequency. In preterm neonates, average nightly sleep and average daily sleep of all recorded days were very similar, but after the fourth day of life, only average nightly sleep increased. In full-term neonates, average nightly and daily sleep time of all recorded days differed by about 1h. Average sleep time during 24h for preterm and full-term neonates was similar. Preterm neonates showed longer intervals between events of food intake than full-term neonates. The circadian peaks in the frequency spectra of full-term neonates may indicate the initial adaptation in the first week of life to a 24h day. This is in agreement with our results concerning the different durations of nightly and daily sleep. The increase in nightly sleep time of preterm neonates may be attributed to the progressing adaptation to a circadian activity- rest pattern. (Chronobiology International, 18(4), 697-708, 2001)     

Trace element content in human milk during lactation of preterm newborns

The present study has been finalized to perform the content of Zn, Cu, Cr, Se, Mn, F, Mo, Ni, and B in the preterm human milk over 21 d of lactation. Trace element (TE) contents were analyzed by inductively coupled plasma atomic emission spectroscopy (ICP-MS), and median concentrations of Zn, Cu, Cr, Se, Mn, and F observed in preterm milk did not demonstrate significant differences in comparison to levels shown in term milk. A statistical significant difference (p<0.05) has been found among Mo, Ni, and B content in preterm milk for every stage of lactation. TE content of infant blood founded concentrations of Mo in preterm babies significantly (p<0.01) lower than in term offsprings. Similar values of other TE content were obtained in blood of preterm, and term newborns. These findings point to the need for a considerable reassessment of the existing dietary recommendation for Mo content in infant feeding.     

Actigraphic monitoring of the activity-rest behavior of preterm and full-term infants at 20 months of age

Differences in the activity-rest behavior of preterm and full-term infants provide an important contribution to the analysis of the ontogeny of circadian rhythms. In this study, we recorded the activity-rest behavior of 17 preterm and 8 full-term infants at the approximate age of 20 months over an average of 10 days by means of actigraphic monitoring (Actiwatch, Cambridge Neurotechnology Ltd.). At the same time, the parents of the infants kept a daily diary. The activity-rest rhythm, the nighttime sleep duration, the daytime rest duration, as well as the sleep quality of the infants were analyzed. Preterm and full-term infants at the age of 20 months show a circadian rhythm with a period length between 23 h 32 min (23:32 h) and 24 h 23 min (24:23 h). It can be concluded that the preterm and full-term infants all reached a vital developmental step by showing the dominant circadian rhythm in the spectrum. The daytime rest duration of preterm infants is significantly shorter than that of full-term infants. The sleep quality of preterm infants is significantly lower than that of full-term infants, which means that the preterm infants have a larger percentage of less restful nighttime sleep. In other studies preterm infants show an over-proportional frequency of attention deficit hyperactivity disorder (ADHD). For this reason, future analyses should reveal whether or not actigraphic monitoring is a suitable means for an early identification of activity-rest behavior in children who may develop ADHD.     

Proteomic analysis of salivary acidic proline-rich proteins in human preterm and at-term newborns

A 1 year follow-up investigation of salivary acidic proline-rich proteins (aPRPs) in preterm and at-term newborns using HPLC-ESI-IT-MS showed that (i) this class of proteins is constitutive rather than inducible, as it is still found in the oral cavity of preterm newborns from 180 days of postconception age (PCA); (ii) the expression of PRH-2 locus anticipates that of PRH-1, since Db isoforms are expressed some months after the PRP-1 and PRP-2 isoforms. The evaluation of the relative abundances of the different aPRPs isoforms and derivatives (differently phosphorylated and cleaved) as a function of PCA showed that (iii) the proteolytic enzymes generating truncated isoforms are also constitutive because they are fully active since 180 days of PCA; (iv) the kinase involved in aPRP phosphorylation is not fully mature in preterm newborns, but its activity increases with PCA, synchronizing with that of at-term newborns and reaching the adult levels at about 500-600 days of PCA, in concomitance with the beginning of deciduous dentition.