Production and excretion of nitrate by human newborn infants: neonates are not little adults.

Endothelium-derived relaxing factor, identified as nitric oxide or its adducts, is metabolized to nitrate and excreted in the urine. Since blood pressures are lower in newborn infants compared to adults, we hypothesized that newborn infants would have increased excretion of nitrate on the day of birth. Neonatal urine was collected before 24 h of age when exogenous intake of nitrate was low. Two different analytical methods showed that nitrate accounted for >99% of nitrogen oxides in urine of healthy neonates and adults. The absolute micromolar concentration of nitrate in urine from infants was significantly below that of adults. When nitrate content was standardized for the reduced renal function in the newborn infant (creatinine content) and body mass (kilogram weight), the concentration of nitrate in neonatal urine was significantly higher than that of adults. Nitrate concentrations in the urine of prematurely born infants were twice that of nitrate measured in urine from term infants. These findings suggested that nitric oxide is produced in larger intravascular quantities in newborn infants versus adults. Thus, we postulated that nitric oxide released from a nitrosothiol would be metabolized to nitrate more readily by neonatal erythrocytes compared to red blood cells obtained from adults. Neonatal erythrocytes, suspended at concentrations of 8, 12, or 16 g per deciliter of hemoglobin, produced 1.7- to 2.1-fold more nitrate than equivalent hemoglobin concentrations of adult erythrocytes that were each incubated with S-nitroso-N-acetylpenicillamine (100 microM) over a 2-h period. Taken together, the studies of urinary nitrate in newborn infants and the ability of neonatal erythrocytes to generate nitrate are consistent with a robust production of nitric oxide immediately after birth.     

Quantitative study of ABH antigens in the saliva of newborns and adults

The results of comparative quantitative investigations of the inhibiting strength of salivas from adults and newborn infants are presented. It is found that A and B salivary antigens of newborn infants have a significantly weaker inhibiting strength than those of adults. Opposite proportions are established in relation to salivary H antigens. Two types of quantitative changes of the inhibiting strength of the salivas from AB groups are registered and they are supposed to be a result of the competition of A and B gene products.     

Separate isolation of Clostridium difficile spores and vegetative cells from the feces of newborn infants.

A modified taurocholate-cefoxitin-cycloserine-fructose agar medium, pH 5.5, on which vegetative cells alone could grow, was newly devised for separate isolation of Clostridium difficile vegetative cells and spores from feces. The ratio of C. difficile-positive feces from healthy newborn infants younger than 10 days of the age was 30.8%, and 93.3% of feces from healthy infants older than 20 days were positive for C. difficile. C. difficile spores alone were detected in twenty-one samples (75%) of C. difficile-positive Twenty-eight specimens. Only 10.7% (3/28) C. difficile vegetative cells alone were detected. C. difficile spores alone were detected in one of nine healthy adults. These collective results offer potential explanations for high frequent isolations of C. difficile from newborn infants without occurrence of pseudomembranous colitis.     

Lymphotoxin production and blast cell transformation by cord blood lymphocytes: dissociated lymphocyte function in newborn infants

The correlation between phytohemagglutinin-induced blast cell transformation and production of lymphotoxin was studied in the cord blood lymphocytes of 17 normal newborn infants. Twelve normal adults served as controls. Blast cell transformation by newborn lymphocytes was somewhat greater than that of adults. By contrast, lymphotoxin production by the newborns was only 40% of the value for the adult controls. When a lymphotoxin index (ratio of lymphotoxin production to transformation) was calculated, it was found that, for any degree of transformation, newborn lymphocytes produced only about one-fourth as much lymphotoxin as did adult lymphocytes. The combination of normal blastogenesis with diminished lymphokine production represents a dissociation of in vitro lymphocyte function. This phenomenon, which appears to be a stage in the maturation of cellular immune competence, may in part explain the undue susceptibility of newborn infants to certain mycobacterial, fungal, and viral infections.     

Multicenter study on the immunogenicity and safety of two recombinant vaccines against hepatitis B

The immunogenicity and safety of a new recombinant hepatitis B vaccine from the Instituto Butantan (Butang) were evaluated in a multicenter, double-blind, prospective equivalence study in three centers in Brazil. Engerix B was the standard vaccine. A total of 3937 subjects were recruited and 2754 (70%) met all protocol criteria at the end of the study. All the subjects were considered healthy and denied having received hepatitis B vaccine before the study. Study subjects who adhered to the protocol were newborn infants (566), children 1 to 10 years old (484), adolescents from 11 to 19 years (740), adults from 20 to 30 years (568), and adults from 31 to 40 years (396). Vaccine was administered in three doses on the schedule 0, 1, and 6 months (newborn infants, adolescents, and adults) or 0, 1, and 7 months (children). Vaccine dose was intramuscular 10 microg (infants, children, and adolescents) or 20 microg (adults). Percent seroprotection (assumed when anti-HBs titers were > 10 mIU/ml) and geometric mean titer (mIU/ml) were: newborn infants, 93.7% and 351.1 (Butang) and 97.5% and 1530.6 (Engerix B); children, 100% and 3600.0 (Butang) and 97.7% and 2753.1 (Engerix B); adolescents, 95.1% and 746.3 (Butang) and 96% and 1284.3 (Engerix B); adults 20-30 years old, 91.8% and 453.5 (Butang) and 95.5% and 1369.0 (Engerix B); and adults 31-40 years old, 79.8% and 122.7 (Butang) and 92.4% and 686.2 (Engerix B). There were no severe adverse events following either vaccine. The study concluded that Butang was equivalent to Engerix B in children, and less immunogenic but acceptable for use in newborn infants, adolescents, and young adults.     

The effect of feeding on plasma immunoreactive ACTH and beta-endorphin levels in newborn infant.

In order to clarify whether an interaction between endogenous opioids and feeding occurs at birth, we studied Beta-endorphin (beta-EP) and ACTH plasma levels in response to a feed of 10% glucose, or formula, in 120 healthy full-term infants. Neither postprandial beta-EP nor ACTH increases were found at the 24th hour or on the fourth day of life. beta-EP physiology in newborn infants seems to be different from adults.     

Developmental changes in sequential activation of laryngeal abductor muscle and diaphragm in infants.

In animals and human adults, upper airway muscle activity usually precedes inspiratory diaphragm activity. We examined the interaction of the posterior cricoarytenoid muscle (PCA), which abducts the larynx, and the diaphragm (DIA) in the control of airflow in newborn infants to assess the effect of maturation on respiratory muscle sequence. We recorded tidal volume, airflow, and DIA and PCA electromyograms (EMG) in 12 full-term, 14 premature, and 10 premature infants with apnea treated with aminophylline. In most breaths, onset of PCA EMG activity preceded onset of DIA EMG activity (lead breaths). In all subjects, we also observed breaths (range 6-61%) in which PCA EMG onset followed DIA EMG onset (lag breaths). DIA neural inspiratory duration and the neuromechanical delay between DIA EMG onset and inspiratory flow were longer in lag than in lead breaths (P < 0.05 and P < 0.01, respectively). The frequency of lag breaths was greater in the premature infants [33 +/- 4% (SE)] than in either the full-term infants (21 +/- 3%, P < 0.03) or the premature infants with apnea treated with aminophylline (16 +/- 2%, P < 0.01). We conclude that the expected sequence of onset of PCA and DIA EMG activity is frequently disrupted in newborn infants. Both maturation and respiratory stimulation with aminophylline improve the coordination of the PCA and DIA.     

A spectral analysis of the periodic components in the heart rhythm structure of newborn infants

Spectral analysis of spontaneous heart rate fluctuations were assessed in 12 healthy newborn infants and in 14 low birth weight newborns. The orthostatic test was performed by the change of newborns posture. High-frequency fluctuations at the respiratory rate were detected in healthy infants and orthostatic reactions of heart rate resembled the same reactions in healthy adults. High-frequency (respiratory) fluctuations were diminished in low-birth weight infants. It is supposed that respiratory fluctuations can be used as a sign of newborn infants well-being and maturation.     

Passive smoking in utero: its effects on neonatal appearance.

Smoking causes changes in the appearance of adults and has profound effects on the fetus, but little is known about its effects on the appearance of newborn infants. Two colour photographs (face and whole body) of 15 newborn infants (seven born to mothers who had smoked during pregnancy and eight born to mothers who had not) were shown to 100 medical and nursing staff, who in a double blind trial were asked to identify which babies had been born to smokers. The mean number correctly identified was 9.1, which was significant compared with the number expected by random selection (7.5). No specific features were identified that distinguished the two groups of infants; selection was intuitive. Nevertheless, the fact that differences can be detected in some way may be useful for antismoking health education.     

Volume history and effect on airway reactivity in infants and adults.

Volume history is an important determinant of airway responsiveness. In healthy adults undergoing airway challenge, deep inspiration (DI) provides bronchodilating and bronchoprotective effects; however, the effectiveness of DI is limited in asthmatic adults. We hypothesized that, when assessed under similar conditions, healthy infants have heightened airway reactivity compared with healthy adults and that the effectiveness of DI is limited in infants. We compared the effect of DI on reactivity by using full (DI) vs. partial (no DI) forced-expiratory maneuvers on 2 days in supine, healthy nonasthmatic infants (21) and adults (10). Reactivity was assessed by methacholine doses that decreased forced expiratory flow after exhalation of 75% forced vital capacity during a full maneuver and maximal expiratory flow at functional residual capacity during a partial maneuver by 30% from baseline. Reactivity in adults increased when DI was absent, whereas infants' reactivity was unchanged. Infants were more reactive than adults in the presence of DI; however, adult and infant reactivity was similar in its absence. Our findings indicate that healthy infants are more reactive than adults and, like asthmatic adults, do not benefit from DI; this difference may be an important characteristic of airway hyperreactivity.     

A chronobiological study on the relation between heart rate and QT interval duration in newborn infants

The relation between heart rate and QT interval is the result of the autonomic nervous system control on cardiac function in healthy adults; accordingly, chronobiological studies have shown that adult subjects have circadian rhythms of heart rate (expressed as R-R interval) and QT interval in phase. We have employed chronobiological methods to study heart rate and QT interval relation in 10 newborn infants, who are known to have an immature cardiac control. Findings from this study indicate that not all the newborns show circadian rhythms of heart rate and QT interval and that when both rhythms are present they do not correlate like in the adults. Likely, this lack of relationship between heart rate and QT interval in newborns is due to different maturational stages of the newborns studied. As a practical implication, in newborn infants, mathematical correction of QT interval by heart rate is not a reliable method.     

ACP1 and human adaptability 2. Association with season of conception

We have studied the pattern of association between the season of conception and cytosolic low molecular weight phosphotyrosine phosphatase (ACP1) genetic polymorphism in 329 consecutively newborn infants from the population of Penne and 361 consecutively newborn infants from the population of Rome. In addition, 329 mothers were studied in the population of Penne. A concordant, highly significant association was observed in the two populations between ACP1 parameters and the season of conception of newborn infants. The total activity of ACP1 shows a minimum in infants conceived in January–February and a maximum in those conceived at the end of the solar year. Analysis of the joint mother-newborn ACP1 distribution in relation to the season of fertilisation has shown that among mothers carrying ACP1*A (the allele showing the lowest activity), the proportion of newborns carrying this allele is higher in those conceived in the first months of the year than in those conceived subsequently. Since ACP1 probably functions as a phosphotyrosine phosphatase and as a flavin mononucleotide phosphatase, low activity could enhance the metabolic rate and would be advantageous in a cold environment. The cycle of variation of ACP1 in infants follows the cycle of solar illumination. It is possible that individuals who have a genetic background allowing them to adapt easily and readily to seasonal demand are more successful in reproducing themselves. The population of zygotes conceived in a given season would therefore reproduce the pattern of gene combination more fit for that season. Received: 15 June 1997 / Accepted: 31 July 1997     

Interferon production by human leukaemic leucocytes.

The Sendai virus-induced interferon (IF) production by partially purified human leucocyte suspensions of normal donors and of leukaemic patients have been investigated in vitro. (i) An increased production was observed with leucocytes taken from patients suffering from chronic myelogenous leukaemia (CML) during exacerbation, but the production was approximately normal with cells taken during remission. (ii) IF production was not influenced by large doses of cytostatics (DBM, 5-FU, FUDR, 5-HU, 6-MP, cyclophosphamide) irrespective of whether normal or CML leucocytes were used. (iii) In contrast, production was inhibited in both systems by inhibitors of RNA or protein synthesis (actinomycin D, puromycin, cycloheximide). (iv) CML leucocytes produced IF for a prolonged period of time as compared to normal leucocytes. (v) Leucocytes from children with acute blastic leukaemia and those from adults with chronic lymphoid or acute paramyeloblastic leukaemia produce, in contrast to normal leukocytes, approximately as much IF in the absence as in the presence of serum. It is concluded that the Sendai virus-induced IF synthesis in CML leucocytes requires de novo protein synthesis.     

Ultrastructural and biochemical characteristics of leydig cells from newborn androgen-insensitive rats

Summary Leydig cells of the testis of newborn pseudohermaphrodite (tfm) rats have an ultrastructure similar to that of the normal, containing well developed organelles and inclusions. The cytoplasm is filled with smooth endoplasmic reticulum forming a network of interconnected tubules. Lipid droplets are surrounded by cisternae of smooth endoplasmic reticulum and are in close association with pleomorphic mitochondria. Many of the latter are cup-shaped and have tubular cristae and intramitochondrial dense bodies.Essentially, these are characteristics of normal Leydig cells. Accordingly, the production of testosterone by testes from newborn tfm rats is the same as that by testes from normal newborns and adults. However, it is significantly higher than that by testes of tfm adults. Also, the plasma testosterone levels of newborn tfm rats are the same as in the normal newborn, but lower than in normal adults and much lower than in adult tfm animals.Thus, since in the tfm rat the morphology of Leydig cells, androgen production, and maintenance of plasma levels of testosterone are normal in the newborn, but become abnormal with advancing age, it appears that defective androgen action rather than insufficient androgen production is the cause of male pseudohermaphroditism.     

Bilirubin and oxidative stress in term and preterm infants

Hyperbilirubinemia is the most frequent clinical problem neonatologists must deal with during the newborn period. It has been suggested that bilirubin is involved in the balance between antioxidant and pro-oxidant agents due to its antioxidant properties. However, the relevance of these effects in vivo in term and preterm infants is still debated. We performed a literature review of studies that investigated the association between total serum bilirubin (TSB) and oxidative stress in newborn infants. We found that studies in term infants give contradictory results, while studies in preterm infants suggest that the TSB increase is associated with an oxidative stress increase due to concurrent factors other than bilirubin level, such as heme oxygenase (HO) activity. Moreover, it could be speculated that low physiologic TSB values are associated with antioxidant effects, while high pathologic TSB values are associated with pro-oxidant effects. Literature data do not allow the establishment of whether if the antioxidant properties of bilirubin are important from a clinical point of view and can affect the outcome in ill infants.     

Virologic and serologic studies on an outbreak of echovirus type 11 infection in a hospital maternity unit.

An outbreak of echovirus type 11 (E-11) infection occurred among newborn babies in a hospital maternity unit in the summer of 1971. The results of studies are as follows: 1) Forty-one of 188 infants developed febrile illness with stomatitis during one and a half months from July to September. E-11 was isolated from stool specimens of 14 infants and two throat swabs. Antibody response to the virus was shown in all the 19 cases examined. Some of their mothers were suffering from subclinical infection. 2) The isolates were identified as a variant of E-11 which is not neutralized with antiserum against prototype E-11. Antiserum against the current virus neutralized both current and prototype viruses. 3) Sucrose gradient centrifugation of sera from infants revealed that the neutralizing antibody activity resided more predominantly in 19S than in 7S fractions. These antibodies reacted more specifically with the current strain than with the prototype Gregory strain.     

Haemorrhagic disease of the newborn in the British Isles: two year prospective study.

OBJECTIVE--To determine the incidence of haemorrhagic disease of the newborn in the British Isles, study risk factors, and examine the effect of vitamin K prophylaxis. DESIGN--Prospective survey of all possible cases of haemorrhagic disease of the newborn as reported by consultant paediatricians using the monthly notification cards of the British Paediatric Surveillance Unit and a follow up questionnaire for each case to validate the diagnosis and accrue further data. SETTING--Britain (England, Scotland, and Wales) and Ireland (Northern Ireland and the Irish Republic) during December 1987 to March 1990. PATIENTS--27 infants classified as having confirmed (n = 25) or probable (n = 2) haemorrhagic disease of the newborn. RESULTS--24 of the 27 infants were solely breast fed. 10 suffered intracranial haemorrhage; two of these died and there was clinical concern about the remainder. 20 infants had received no vitamin K prophylaxis, and seven had received oral prophylaxis. Relative risk ratios for these groups compared with babies who had received intramuscular vitamin K were 81:1 and 13:1 respectively. Six infants had hepatitis (alpha 1 antitrypsin deficiency in four), unsuspected until presentation with haemorrhagic disease of the newborn, of whom four had received oral prophylaxis. One other baby had prolonged jaundice. One mother had taken phenytoin during pregnancy. CONCLUSIONS--All newborn infants should receive vitamin K prophylaxis. Intramuscular vitamin K is more effective than oral prophylactic regimens currently used in the British Isles.     

Determination of total insulin (TIRI) in plasma of insulin-treated diabetics and newborn infants of insulin-treated diabetic mothers.

Plasma of insulin-treated diabetics and of newborn infants of insulin-treated diabetic mothers contains insulin antibodies which invalidates the radioimmunoassay of insulin. Therefore, the endogenous insulin antibody complex must be splitted at a pH lower than 5 and the total IRI (TIRI) is separated by ethanol extraction. It was investigated the recovery rate in dependence upon plasma volume used for extraction. By reduction of used plasma volume from 500 to 200 mul per extraction the recovery rate was increased from 65.1 +/- 8.4 to 88.3 +/- 4.2% (mean +/- SEM). The low plasma volume of 200 mul for TIRI extraction made it possible to determine TIRI during glucose loads of newborn infants. To eliminate different conditions of incubation for standard and unknown plasma samples the TIRI levels were computed by means of so-called "extracted" standard curve, obtained with extracted insulin from standard insulin dilution in insulin-free pooled human plasma. Using the described method a temporary regeneration of insulin secretion of a newly diagnosed juvenile diabetic after insulin treatment could be shown. In contrast to newborn infants of healthy mothers a biphasic/insulin release was found during the intravenous glucose loads in newborn infants of insulin-treated diabetic mothers.     

Developmental changes in upper airway dynamics.

Normal children have a less collapsible upper airway in response to subatmospheric pressure administration (P(NEG)) during sleep than normal adults do, and this upper airway response appears to be modulated by the central ventilatory drive. Children have a greater ventilatory drive than adults. We, therefore, hypothesized that children have increased neuromotor activation of their pharyngeal airway during sleep compared with adults. As infants have few obstructive apneas during sleep, we hypothesized that infants would have an upper airway that was resistant to collapse. We, therefore, compared the upper airway pressure-flow (V) relationship during sleep between normal infants, prepubertal children, and adults. We evaluated the upper airway response to 1). intermittent, acute P(NEG) (infants, children, and adults), and 2). hypercapnia (children and adults). We found that adults had a more collapsible upper airway during sleep than either infants or children. The children exhibited a vigorous response to both P(NEG) and hypercapnia during sleep (P < 0.01), whereas adults had no significant change. Infants had an airway that was resistant to collapse and showed a very rapid response to P(NEG). We conclude that the upper airway is resistant to collapse during sleep in infants and children. Normal children have preservation of upper airway responses to P(NEG) and hypercapnia during sleep, whereas responses are diminished in adults. Infants appear to have a different pattern of upper airway activation than older children. We speculate that the pharyngeal airway responses present in normal children are a compensatory response for a relatively narrow upper airway.     

Lymphocyte reactivity in pregnant women and newborn infants.

The mitotic response to phytohaemagglutinin (PHA) was determined in lymphocytes of mothers and their newborn infants obtained at delivery and seven days later by measuring the rate of 125 I-idoxuridine uptake into DNA in lymphocytes cultured in their own plasma and after washing and resuspension in fetal bovine serum. There was no difference in the unstimulated counts of maternal lymphocytes taken at delivery, whether unwashed or washed, compared with those from nonpregnant controls. With PHA stimulation the mitotic response of the maternal lymphocytes cultured in their own plasma was reduced compared with that of the control lymphocytes but washed maternal cells showed a similar response to the controls. These findings suggest that the reduced lymphocyte mitotic response to PHA in pregnancy is due to a plasma inhibitory factor This inhibition was not evident in maternal blood taken seven days after delivery. DNA synthesis in unstimulated cultures from newborn infants at birth and seven days after birth was greater than that in adult control cultures. With PHA stimulation the mitotic response of cord-blood lymphocytes cultured in their own plasma paralleled that of control lymphocytes but washed newborn cells showed a greater response. Thus plasma suppression similar to that observed in the mother seems also to affect infants at birth. This inhibition was not demonstrable in blood taken from infants of 7 days.