Clinical and microbiological profile of persistent coagulase-negative staphylococcal bacteraemia in neonates.

An atypical pattern of coagulase-negative staphylococcal (CoNS) sepsis, characterized by persistence despite aggressive antibiotic therapy, has been described in neonates cared for in neonatal intensive-care units. Our aim was to analyse the clinical, microbiological and molecular determinants of this persistent CoNS bacteraemia. Neonates with late-onset CoNS bacteraemia were studied for a 2-year period. Demographic, clinical, laboratory, microbiological and molecular data were compared between neonates with persistent (≥3 consecutive positive blood cultures) and non-persistent CoNS bacteraemia. Twenty-nine infants with persistent and 43 with non-persistent bacteraemia were identified, with no significant differences regarding demographic and clinical characteristics between the two groups. Of a total of 170 CoNS isolates, 80 showed biofilm production (54 persistent and 26 non-persistent; p 0.013), whereas 127 were positive for the icaA and icaD genes (74 persistent and 53 non-persistent; p 0.598). Sixty ica-positive isolates did not produce slime, whereas 13 ica-negative isolates showed biofilm production. Endotracheal intubation and the presence of central vascular catheters were significant risk factors for persistent bacteraemia, but, in a logistic regression model, only biofilm production was significantly related to the persistent form of the disease (p 0.005). In this study, persistent CoNS sepsis in neonates requiring intensive care was not related to most of the known clinical risk factors, and it was associated with severe thrombocytopenia. Isolates associated with persistent bacteraemia were more likely to produce biofilm, independently of the presence of the ica operon.

Dose and image quality optimization in neonatal radiography.

In a special care baby unit, neonates, mainly premature, encounter serious to life-threatening diseases, the timely diagnosis and treatment of which may require a large number of radiographs. Increased neonatal radiosensitivity and longer life expectancy increase the risk of radiation-induced cancer, which emphasizes the importance of minimizing dose while maintaining clinically satisfactory image quality. An optimization study on radiation dose and image quality in neonatal radiography is presented. Neonates were categorized into four groups depending on birthweight. For a total of 378 chest and chest-abdomen radiographs, exposure parameters were recorded. Entrance surface dose (ESD) was estimated and dose-area product (DAP) was measured. Image quality evaluation was performed by two observers and was based on the visibility of certain anatomical features and catheters placed during treatment using a five-grade scale. ESD values increased with neonatal weight and demonstrated wide variation (16.4-76.9 microGy, mean 38.2 microGy). A wide variation was also observed in DAP values (1.2-15.0 mGycm2, mean 7.2 mGycm2). Image quality evaluation revealed the feasibility of achieving a diagnostically satisfactory image (score >70%) using both low and high tube voltage techniques, with the latter resulting in reduced ESDs. The majority of estimated ESDs are in accordance with the reference level of 50 microGy recommended by the National Radiological Protection Board for neonatal radiography. The results suggest that the use of high tube voltage techniques could result in further reductions in neonatal dose, without image quality degradation, underlying the requirement for establishing standard examination protocols for neonatal radiography with respect to neonatal weight.

Qualitative and quantitative alterations of cell surface carbohydrate residues during epidermal morphogenesis.

The purpose of this study was to investigate the carbohydrate residue composition of cell surface in the developing epidermis and to define the chronological sequence of its alterations in human fetuses from the 10th to the 20th weeks of gestation and at the 23rd week of gestation, using a panel of six biotinylated lectins: Concanavalin A, Ulex europaeus agglutinin-I, Ricinus communis agglutinin-I, Peanut agglutinin, Wheat germ agglutinin, and Dolichos biflorus agglutinin. Distinct qualitative and quantitative alterations in the expression of cell surface carbohydrate residues were found during epidermal morphogenesis prior to keratinization (10th to 20th weeks). At the 23rd week of gestation, the already keratinized fetal human epidermis revealed a pattern of cell surface glycosylation very similar to that of the adult human epidermis. Further studies are now warranted to answer the question regarding whether the glycosylation pattern in the developing human epidermis is disturbed in fetuses with genodermatoses and whether these disturbances might be important for prenatally diagnosing the latter.

Determination of malondialdehyde by capillary electrophoresis, application to human plasma and relation of its levels with prematurity.

Malondialdehyde (MDA) is considered as the most important marker for monitoring lipid peroxidation, which is strongly associated with the development of serious diseases in adults and premature neonates. In this paper we report a method for determination of free MDA in human plasma using capillary zone electrophoresis. MDA was separated and determined as conjugate with tetrabutylammonium hydrogen sulphate (TBAS). Analysis was performed using 20 mM borare, pH = 9.3, as operating buffer and detection of the MDA-TBAS adduct at 267 nm. The method has a linear range up to 80 microM with a detection limit of 0.2 microM. The method was applied to the analysis of MDA in plasma of healthy adults, normal-gestation infants and of preterm neonates. Plasma proteins were successfully removed following centrifugation through a centricon-3 membrane. Results showed that the method can be easily and accurate applied for the determination of MDA in human plasma and that the level of MDA in pretern neonates is significantly higher (p

Elective use of nasal continuous positive airways pressure following extubation of preterm infants.

UNLABELLED: The aim of this study was to determine whether elective use of nasal continuous positive airways pressure (CPAP) following extubation of preterm infants was well tolerated and improved short- and long-term outcomes. A randomized comparison of nasal CPAP to headbox oxygen was undertaken and a meta-analysis performed including similar randomized trials involving premature infants less than 28 days of age. A total of 150 infants (median gestational age 30 weeks, range 24-34 weeks) were randomized in two centres. Fifteen nasal CPAP infants and 25 headbox infants required increased respiratory support post-extubation and 15 nasal CPAP infants and nine headbox infants required reintubation (non significant). Eight infants became intolerant of CPAP and were changed to headbox oxygen within 48 h of extubation; 19 headbox infants developed apnoeas and respiratory acidosis requiring rescue nasal CPAP, 3 ultimately were re-intubated. Seven other trials were identified, giving a total number of 569 infants. Overall, nasal CPAP significantly reduced the need for increased respiratory support (relative risk, 0.57, 95% CI 0.43-0.73), but not for re-intubation (relative risk 0.89, 95% CI 0.68-1.17). Nasal CPAP neither influenced significantly the intraventricular haemorrhage rate reported in four studies (relative risk 1.0, 95% CI 0.55, 1.82) nor that of oxygen dependency at 28 days reported in six studies (relative risk 1.0, 95% CI 0.8, 1.25). In two studies nasal CPAP had to be discontinued in 10% of infants either because of intolerance or hyperoxia. CONCLUSION: Elective use of nasal continuous positive airways pressure post-extubation is not universally tolerated, but does reduce the need for additional support.

Blood pressure rhythms during the perinatal period in very immature, extremely low birthweight neonates.

The aim of this study was to investigate if blood pressure (BP) rhythms were present in the perinatal period in very immature infants. Twenty-two infants, median gestational age 24-28 weeks, who had indwelling arterial lines with undamped arterial BP waveforms, were studied. The infants were all receiving intensive care under constant conditions. The hourly mean, systolic and diastolic BPs on days 2 and 7 were examined. A cosinor analysis of the mean BP was performed examining period lengths of 4, 8, 12, 16, 20, and 24 h to determine whether ultradian and/or circadian rhythms existed. On day 2, but not day 7, the mean and systolic BPs showed significant variation and circadian and ultradian rhythms were demonstrated. We suggest that maternal influences may be responsible for the BP rhythms noted in very immature infants on day 2.

Diurnal variation of plasma cortisol levels in infancy.

Normal children and adults show diurnal variation of plasma cortisol levels reaching peak values around 08.00 h and lower values around 24.00 h. Despite numerous studies on diurnal variation of plasma cortisol levels in children, the age of appearance of a circadian rhythm has not been definitely established. The purpose of this study was to investigate the development of cortisol circadian rhythm in infancy. In seventy healthy, full-term infants, less than six months old, plasma cortisol was measured at 10.30 h and 22.30 h. The mean +/- SEM values of daytime plasma cortisol at one to four weeks of life were 159 +/- 41, 116 +/- 43, 240 +/- 54 and 456 +/- 95 nmol/l and the night-time values were 129 +/- 40, 99 +/- 44, 131 +/- 78 and 430 +/- 105 nmol/l, respectively. No statistically significant differences were found between daytime and night-time cortisol values during the first four weeks of life. In contrast, the daytime values of plasma cortisol were 295 +/- 62 at the age of 2-3 months, 211 +/- 43 at 4-5 months and 291 +/- 31 nmol/l at 6 months of life, and night-time values were 166 +/- 52, 119 +/- 35 and 109 +/- 21 nmol/l, respectively, which were statistically significant (p < 0.05). These data clearly indicate that cortisol circadian rhythm starts between the second and third month of life.

Biotin plasma levels of the human fetus.

Biotin is an important vitamin for cellular function and growth and, therefore, essential for fetal development. The fetus is exclusively dependent on maternal biotin supply. Since biotin is not produced within the body, maternal biotin levels depend on dietary intake. In order to investigate the biotin status of the human fetus, we measured the plasma biotin levels in 15 pregnant women and their fetuses who underwent amniocentesis and fetal blood sampling at 18-24 weeks of gestation for prenatal diagnosis of thalassemia. Maternal biotin was found to be 131 +/- (SD) 102 ng/l and fetal biotin 784 +/- 327 ng/l (p < 0.0001). Our findings are indicative of an active transport mechanism of biotin through the placenta in favor of the fetus.

Outcome prediction in Greek neonatal intensive care units using a score for neonatal acute physiology (SNAP)

OBJECTIVES: This study was undertaken to evaluate the performance of the score for neonatal acute physiology (SNAP) in Greece, to examine the predictive power of SNAP calculated during the 12 hours after admission in comparison with customarily calculated SNAP during the first 24 hours, and to assess SNAP during the second 12 hours from admission as a measure of response to treatment. METHODOLOGY: A total of 579 newborns admitted to three neonatal intensive care units (NICUs) from two cities in Greece were enrolled in the study; SNAP was determined during the first 12 hours, the second 12 hours, and the first 24 hours from admission to the NICU and calculated using an algorithm based on deviations from normal values of 26 physiologic parameters. RESULTS: All three variants of SNAP were powerful predictors of vital status at discharge, as well as of duration of stay among survivors. A five-point increase in SNAP in the first 12 hours corresponds to a more than twofold ratio in the odds for death, whereas a five-unit difference in SNAP from the second 12 hours corresponds to a more than threefold ratio. The combined 24-hour score was similar to that for the first 12 hours. A considerable advantage of SNAP was its independence from more traditional predictors of neonatal death, notably gestational age, birth weight, and Apgar score. The combination of all of these predictors improved further the overall predictive potential. CONCLUSIONS: SNAP is a useful tool in medical research and can be applied in different population groups. Its independence from birth weight underlines its added value to predict fatality ratios. Moreover, the results of the present study indicate that SNAP can be estimated without loss of predictive efficiency during the first 12 hours from admission to the NICU, whereas SNAP during the second 12 hours adequately reflects the effectiveness of early medical interventions.

Neonatal-perinatal care in Greece.

Greece, a country of 10.25 million people and about 100,000 births per year, has changed its health care system significantly in the last 10 years and has made substantial improvements in neonatal-perinatal care. Infant mortality decreased from 18/1000 in 1983 to 9/1000 in 1991; neonatal mortality decreased from 15/1000 in 1983 to 6.1% in 1991; perinatal mortality decreased from 23.8% in 1983 to 11.06/1000 in 1991. There are currently 15 neonatal intensive care units in the Greece, with approximately 180 intensive care beds, which are adequately equipped for respiratory support and relatively well staffed with doctors. However, there is a great shortage of nursing personnel, and most neonatal units have an unacceptable ratio of nurses to infants. The goal of health policies for the upcoming years is to promote the regionalization of perinatal care, to increase the number of and personnel for neonatal intensive care units, and to develop several intermediate care units, which will minimize unnecessary admissions to the tertiary neonatal centers.

Mechanical behaviour of scalp hair in premature and full-term neonates.

Using a new computerized methodological procedure a separate analysis and a quantitative determination of the viscous and elastic parameters of the scalp hair shaft were performed in 37 neonates of both sexes with a gestational age of 28-29 weeks (n = 16) and 39-40 weeks (n = 21), respectively. A statistically significant (p < 0.001) decrease in the values of modulus of elasticity (E alpha) was found in the hair shaft of premature neonates, as compared to the full-term ones, whereas the values of post yield slope (E beta) and of SDIS/SSTOR (viscous parameter) did not significantly differ in the two groups. The decrease in modulus of elasticity in the hair shaft of premature neonates may be interpreted in terms of an insufficient number of disulphide bonds between the alpha-helical keratin units of the hair cortex or of a disordered arrangement of microfibrils within the matrix. Further studies are now warranted to determine the pattern of mechanical parameters of the scalp hair shaft in large numbers of newborn infants of different gestational ages and to answer the question as to whether this pattern might be useful in the accurate postnatal assessment of fetal maturation.

The effect of light on plasma melatonin levels in premature infants.

Recent studies have shown that full term neonates actively secrete melatonin and that light deprivation during the first 72 h of life significantly increases plasma melatonin levels. In order to evaluate pineal gland activity and responsiveness to light in premature infants, we measured plasma melatonin levels in 23 healthy infants, 33-36 weeks of gestation, during their first week of life. Nine infants (Group A) remained under constant illumination conditions for 48 hour prior to melatonin measurements. Fourteen infants (Group B) were exposed for the same time period to an artificial alternation of day and night cycles by covering the eyes of the infants with eye pads during the night (20.00-08.00 h). Mean +/- SEM plasma melatonin at 20.00 h, 04.00 h, 12.00 h and 20.00 h was 14.8 +/- 1.6, 16.2 +/- 2.8, 18.7 +/- 3.1, 20.9 +/- 3.1 pg/ml in Group A and 20.5 +/- 3.2, 22.3 +/- 2.9, 20.2 +/- 2.2, 18.5 +/- 2.2 pg/ml in Group B respectively. The differences observed between the two groups were not statistically significant. Our results indicate that at this gestational age the pineal gland is actively secreting melatonin but does not respond to the light alternations attempted. Further studies are needed in order to evaluate the developmental maturation of the pineal gland in humans.

Development of thyrotropin circadian rhythm in infancy.

Normal children and adults show a similar pattern of diurnal variation of TSH secretion with lower values at 1100 h and higher around 2300 h. The purpose of this study was to investigate the age of appearance of TSH circadian rhythm. In 57 fullterm infants 0-6 months old and in 37 premature infants 1-4 weeks old TSH was measured at 1030, 1100, 1130 h and 2230, 2300, and 2330 h. No diurnal rhythm was detected in both premature and fullterm infants less than 4 weeks of life. After the first month of life a significant difference between AM and PM values was observed in fullterm infants. In infants 1-2 months old mean +/- SEM AM and PM values were 2.8 +/- 0.2 and 3.5 +/- 0.4 mU/L, respectively (P less than 0.025), in infants 3-4 months old 3.0 +/- 0.6 and 4.1 +/- 0.8 (P less than 0.01) and in infants 5-6 months old 1.8 +/- 0.2 and 2.6 +/- 0.3 (P less than 0.0005). These data clearly indicate that the development of TSH circadian rhythm starts after the first month of life.

A simple stress test for the evaluation of hypothalamic-pituitary-adrenal axis during the first 6 months of life.

In 33 normal infants, divided into 3 age groups (less than 1 month, 1-3 months, and 3-6 months) plasma cortisol was measured at 2230, 2300, and 2330 h. Baseline plasma cortisol at 2230 h. was, as expected, low in all infants, with mean +/- SEM values of 41 +/- 5, 72 +/- 14, and 97 +/- 17 nmol/L in each group, respectively. Thirty and 60 min after the painful stimulus of the venipuncture, plasma cortisol increased significantly (P less than 0.0005), reaching a maximum increase up to 458 +/- 50, 392 +/- 66, and 455 +/- 97 nmol/L in each age group, respectively. We conclude that in these infants the hypothalamic-pituitary-adrenal axis was functionally intact and responded to the painful stimulus of the venipuncture by a significant increase in plasma cortisol. This test may be used as a simple procedure for the evaluation of the integrity of the hypothalamic-pituitary-adrenal axis without the administration of pharmacological agents. Its usefulness, however, should be validated with patients having a disorder of the system.

Plasma biotin levels in neonates.

Plasma biotin levels were measured by a new, very sensitive radioligand assay, in 47 normal full-term infants, receiving breast milk and/or different formulas, during the first 3 weeks of life. Exclusively breast fed infants and infants fed with a formula containing 11 micrograms/l biotin had plasma biotin levels of 538 +/- 78 and 502 +/- 117 ng/l, respectively, during the 1st week of life, and 321 +/- 48 and 503 +/- 153 ng/l, respectively, during the 3rd week of life. Infants fed with a formula very high in biotin (300 micrograms/l) had extremely high plasma biotin levels during the 1st week of life (13,741 +/- 659 ng/l) while during the 2nd week of life they showed a tendency towards decreasing plasma biotin levels. These changes of plasma biotin levels during the first weeks of life indicate that the in vivo kinetics of biotin is changing during this period.

Cardiac involvement in postnatal rubella.

Two cases of rubella myocarditis are reported: a 6-year-old boy who developed a complete, distal to His, atrioventricular block, during the third day of illness; and a 12-year-old boy who developed myocarditis with congestive heart failure 20 days following rubella infection. Although permanent pacing was required in the first patient, six years later he showed a normal growth and maintained normal activity. The second patient has deteriorated markedly and 6 months after the initial illness he had severe heart failure. It should be noted that myocarditis with abnormalities of the conduction system or congestive heart failure may be a complication to postnatal rubella.

Effect of light on diurnal variation of blood amino acids in neonates.

Normal newborns show a diurnal variation of blood amino acid concentration, with lower values at 04.00 h and higher at 12.00 h. Three groups of infants, each consisting of 10 normal, full-term neonates, remained under different lighting conditions for 24 h and blood amino acids were determined at 04.00 and 12.00 h. Group A remained under continuous light, group B had the eyes covered, and group C was exposed to intermittent light, with the lights dimmed between 22.00 and 04.00 h. Group A showed a reversal of blood amino acid periodicity with a mean decrease of total amino acid concentration by 17.7% at 12.00 h (p less than 0.025). In group B there was no statistically significant difference between 04.00 and 12.00 h values. Group C showed the usual amino acid periodicity with a mean increase of total amino acid concentration by 36.1% at 12.00 h (p less than 0.005). The differences observed between groups A and C were statistically highly significant (p less than 0.0005). These data indicate that lighting conditions may affect the diurnal variation of blood amino acids and this should be considered for infants who remain under continuous light for prolonged periods in neonatal units.

Transformation of lymphocytes from immunized Rh(D)-negative subjects by Rh(D) isoantigen.

Since immune memory in Rh(D)-negative isoimmunized subjects remains through life, even in the absence of measurable anti-Rh(D), we investigated the transformation of lymphocytes from such donors by Rh(D) antigen. The time lapse from the last stimulus was up to 13 years. Mononuclear cells from immunized women were stimulated by Rh(D)-positive erythrocyte stroma. Maximum transformation was observed on the sixth day of culture, with a stroma protein concentration of 8 micrograms/mL of culture medium. The stimulation index (SI) in cells from 11 immunized women was 6.8 +/- 3.1 (mean +/- SD), with a range from 3.1 to 15.0. In five different sets of control cultures, the SI ranged from 0.9 +/- 0.2 to 1.3 +/- 0.4. There was no overlap between stimulated and control cultures. No anti-D could be demonstrated in the serum of four of the 11 immunized cases studied. Also, transformation was observed in mononuclear cells from Rh(D)-negative immunized women with Rh(D)-positive erythrocytes. The findings demonstrate that lymphocytes from isoimmunized Rh(D)-negative subjects maintain the immune memory and are transformed in vitro by the Rh(D) isoantigen.

Gaucher disease: treatment of hypersplenism with splenic embolization.

Hypersplenism is a frequent complication of Gaucher disease requiring splenectomy. A patient with Gaucher disease and severe hypersplenism was treated with partial splenic embolization to avoid the increased risk of serious infectious complications and deterioration of the disease associated with splenectomy. A first embolization (25% ablation) was performed at 4 years. Because of persisting abdominal discomfort, failure to thrive and signs of hypersplenism a second embolization (40-50% ablation) was performed 18 months later. Subsequently, the patient's health improved remarkably and 4 years later he achieved normal growth, maintains normal haematologic parameters, is free of symptoms and has no skeletal abnormalities. No serious infections have occurred. The size of the liver and the spleen has not changed appreciably. It appears that partial splenic embolization may be preferable to splenectomy in patients with Gaucher disease, especially in those of young age.

Complete trisomy 9 in two liveborn infants.

Two unrelated newborn infants with multiple malformations were found to have complete trisomy 9 in all cells examined. In both, the phenotype was similar, consisting of characteristic facial appearance (microphthalmia, bulbous nose, micrognathia, cleft palate, low set ears), skeletal abnormalities (dislocated joints, flexion contractures of the fingers), cardiovascular malformations (persistent left superior vena cava, ventricular septal defect), hypoplastic genitalia, renal anomalies, and central nervous system malformations. Both died during the first few hours of life. Comparison of these two infants with the previously reported cases reveals a consistent pattern of malformations and very short survival associated with trisomy 9. These cases illustrate the importance of doing chromosome studies on infants with congenital malformations dying in the newborn period and the usefulness of such studies in counselling parents regarding the risk of recurrence.