Week Of Extrauterine Life Research Articles

Early changes in plasma brain and atrial natriuretic peptides in premature infants: correlation with pulmonary arterial pressure.

To define the change in plasma natriuretic peptides in newborns, we prospectively studied 10 premature infants. They were followed sequentially during the first week of extrauterine life by two-dimensional and pulsed Doppler echocardiography, and studied for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). We estimated mean pulmonary arterial pressure (MPAP) and measured blood pressure on days 1, 2, 3, 5, 7, respectively. Plasma ANP levels were 81.7 +/- 11.4 pg/ml on day 1 and 67.9 +/- 6.0 pg/ml on day 7, respectively. Between day 2 and day 7, there was a fall in MPAP, i.e. from 37 +/- 4 mmHg to 22 +/- 2 mmHg (P < 0.01), which was associated with a significant decrease in plasma BNP (41.8 +/- 10.1 pg/ml on day 2 vs. 10.4 +/- 0.9 pg/ml on day 7, P < 0.01). There was a positive correlation between MPAP and plasma BNP level (r = 0.643, P < 0.0001), but there was no correlation between MPAP and plasma ANP level. These data suggest that the pattern of secretion of BNP is different from that of ANP and that BNP levels reflect the changes of pulmonary arterial pressure in the neonatal period in premature infants.

In vivo and in vitro flow cytometry comparative analysis of somatostatin-positive cells in the pineal gland of the neonatal rat.

Flow cytometry was used for comparative in vivo and in vitro analysis of cell populations staining positively for somatostatin. Experiments were carried out with pineals obtained from neonatal, 8- and 15-day-old rats. Pineal cells were obtained by dispersion with collagenase and then processed in a flow cytometer or maintained in culture for 1 or 2 weeks. Identification of somatostatin-immunopositive cell populations was performed using a polyclonal somatostatin antibody and confirmed by indirect immunostaining of cytospun smears with the avidin-biotin-peroxidase method. In vivo, the percentage of somatostatin-positive cells was 60.6 +/- 4% in neonatal pineals and declined to 22.2 +/- 11% in 15-day-old animals (p < 0.04). The density of peptide immunostaining decreased in 8-day-old animals but recovered to the neonate levels in 15 day-old animals; homogeneity in the immunopositive population increased with age. Maintenance in culture for 1 week resulted in an increase in positive somatostatin staining in animals of 8 and 15 days with no changes in neonates; however, after 2 weeks of culture, the percent of immunopositive cells decreased from 53.3 +/- 6 to 12.2 +/- 4% in the older animals and remained unchanged in neonates. We conclude that somatostatin is found in pinealocytes and shows a declining pattern during the perinatal period; this probably implies that the peptide plays a paracrine role important for cell differentiation in these young animals, since maximal cellularity and a high mitotic index occur within the first 3 days of life, and pineal cell differentiation is completed before the end of the third week of extrauterine life.

147 TRANSIENT FORAMEN OVALE INCOMPETENCE IN NORMAL NEWBORNS

In contrast with the generally accepted mechanism of functional closure of the foramen ovale at birth, echocardiography studies in sick newborns revealed the presence of transient interatrial left to right shunts (IALRS) in several patients without structural heart disease. The aim of this study was to assess incidence and natural history of IALRS in healthy newborns. 20 healthy term newborns underwent an echocardiography and Doppler study daily during the first week after birth. Left atrial and aortic root dimensions were measured, as well as duration and direction of ductal and interatrial shunting. In 11 of these infants a predominant IALRS was detected on the first day of extrauterine life. In one infant IALRS persisted for as long as 6 weeks. Median persistance of IALRS in the remaining 10 infants was 3 days. Ductal left to right shunts were present in 3 infants with and in 2 without IALRS. There was no significant difference between infants with or without IARLS in respect to ductal patency, birthweight or sex. There was a statistically significant relation between lower gestational age and presence and duration of IALRS. We conclude that transient IALRS is common in normal newborns during the first week of extrauterine life. We suggest that this transient foramen ovale incompetence results from a relatively short foramen ovale flap in combination with the relative large extracellular volume as is present in the first days of life.

Selection criteria and follow-up of children presenting with retinopathy of prematurity

The recommendations of the American Academy of Pediatrics for eye examinations of premature infants are based on the following criteria: an age of gestation less than 35 weeks for infants having received oxygen or a birthweight under 1300 g with or without supplemental oxygen. The first examination should take place between the 5th and the 7th week of extra-uterine life, or prior to discharge of the hospital and repeated according to the first observations. It is specified that the examination must be done by a person experienced in neonatal ophthalmology and indirect ophthalmoscopy. In Zurich, following these recommendations, the criteria of the CRYO-ROP study, and our experience, we examine the infants with following features: (1) all premature infants with birthweight less than 1500 g independently of oxygen exposure, (2) neonates who have less than 35 gestational weeks and who were exposed in a FIO2 > 0.4 during more than 24 h. And (3) the first eye examination is done between the 5th and the 6th weeks of extra-uterine life. The follow-up of these children will depend on the primary state. The infants with ROP will be followed by the neonatal ophthalmologist as long as retinal complications can persist. Afterwards these infants will be controlled by the general ophthalmologist for the amblyopie prophylaxis (by anisomyopia or strabismus). Two controls during the first year, then one per year are advised in these cases. For children who had a cryocoagulation or an retinal detachment operation, the follow-up will be assured by the general ophthalmologist for the prevention of the amblyopia and by the neonatal ophthalmologist for the retina.

Evidence that circadian variations of circulating melatonin levels in fetal and suckling rats are dependent on maternal melatonin transfer.

Although the circadian variation of melatonin content in the pineal gland appears during the 3rd week of extrauterine life, recent studies suggest that the fetus perceives the day length through maternal melatonin transfer. Accordingly, we determined serum melatonin concentrations in pregnant and lactating rats and in their offsprings during the day (D) and at night (N). As compared with nonpregnant adult female rats (D: 6.0 +/- 0.5 and N: 112.0 +/- 5.0 pg/ml), significant increases of serum melatonin concentrations, both during the day and at night, were observed in 21-day pregnant (D: 21.0 +/- 2.6 and N: 222.0 +/- 7.2 pg/ml) and in 10-day (D: 20.0 +/- 2.6 and N: 145.0 +/- 12.3 pg/ml) and 20-day (D: 19.0 +/- 1.2 and N: 140.0 +/- 8.0 pg/ml) lactating animals, while a profound decrease was found in 5-day (D: 13.0 +/- 1.0 and N: 50.0 +/- 5.6 pg/ml) lactating rats. In addition, melatonin levels were significantly higher during the night than during the day in all the experimental groups. High levels and circadian variation of serum melatonin were detected also in 21-day-old fetuses (D: 13.0 +/- 0.8 and N: 108.0 +/- 4.8 pg/ml) and in 5- and 10-day-old suckling (in 5-day-old, D: 13.0 +/- 0.6 and N: 71.0 +/- 3.1 pg/ml; in 10-day-old, D: 17.0 +/- 1.4 and N: 63.0 +/- 3.8 pg/ml) rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of antihypertensive drugs in the neonatal period.

A consistent body of evidence indicates that in the preterm and full-term newborn drug disposition is reduced when compared to that of infants, grown-up children, and adults. Newborns are rarely treated directly with antihypertensive agents; however they can be exposed to the action of various antihypertensive drugs in utero and during their first week of extrauterine life in the case of hypertensive mothers treated through pregnancy. In such cases, the persistence of the antihypertensive agent during the first days of life may have important consequences on neonatal haemodynamics and on the function and the maturation of vital organs such as lungs and kidneys. The available information on the placental transfer and neonatal pharmacokinetics of alpha-methyldopa, clonidine, acebutolol, atenolol, betaxolol, metoprolol, propanolol, oxprenolol, and latetalol, are reviewed. Each product has its own pharmacokinetic characteristics which should influence, depending on the clinical situation, the therapeutic choice. In the presence of comparable efficacy, preference should be given to compounds with high bioavailability, eliminated mainly via metabolic degradation, with no active metabolites. In all cases, treatment should be discontinued 8-12 h before delivery.

Milk feeding and changes in intestinal permeability and morphology in the newborn.

The contrasting effects of natural versus cow's milk formula (CMF) on upper gastrointestinal development in the newborn were studied. The passive intestinal permeability of neonatal human infants and guinea pigs was measured using the nonmetabolisable markers lactulose and mannitol. Mucosal morphology was examined in guinea pigs by light microscopy. Nineteen full-term human infants and 63 guinea pigs were studied during the 1st week of extrauterine life. The naturally fed infants showed a decline in intestinal permeability to lactulose following the onset of feeding. This was not shared by those fed CMF. The CMF-fed guinea pigs showed a persistently higher intestinal permeability than the naturally fed animals throughout the 1st week of life. No differences were observed in the villous heights or crypt depths between feeding groups, but both showed an increase in intraepithelial lymphocyte number during the 1st week. Cow's milk formula may cause a persistently higher intestinal permeability, or natural feeding may promote a decline in permeability in the enterally fed newborn.

Milk Feeding and Changes in Intestinal Permeability and Morphology in the Newborn

SummaryThe contrasting effects of natural versus cow's milk formula (CMF) on upper gastrointestinal development in the newborn were studied. The passive intestinal permeability of neonatal human infants and guinea pigs was measured using the nonmetabolisable markers lactulose and mannitol. Mucosal morphology was examined in guinea pigs by light microscopy. Nineteen full‐term human infants and 63 guinea pigs were studied during the 1st week of extrauterine life. The naturally fed infants showed a decline in intestinal permeability to lactulose following the onset of feeding. This was not shared by those fed CMF. The CMF‐fed guinea pigs showed a persistently higher intestinal permeability than the naturally fed animals throughout the 1st week of life. No differences were observed in the villous heights or crypt depths between feeding groups, but both showed an increase in intraepithelial lymphocyte number during the 1st week. Cow's milk formula may cause a persistently higher intestinal permeability, or natural feeding may promote a decline in permeability in the enterally fed newborn.

Chromatographic characterization of endogenous digoxin-like immunoreactive substances present in serum and urine of infants using gel filtration with Sephadex G 25.

We assayed digoxin-like immunoreactivity in the serum of 19 healthy neonates (blood sample from umbilical cord), not receiving digoxin therapy, using a solid-phase radioimmunological method. In addition, urinary concentrations of a digoxin-like immunoreactive substance (DLIS) were assayed throughout the first 10 weeks of extrauterine life in 50 healthy infants. The mean (+/- SD) serum DLIS concentration obtained was 211 +/- 60 ng/l digoxin equivalents (d.e.) while, in the urinary samples of the first day of life, the mean concentration was 818 +/- 560 ng/l d.e. (n = 20). These DLIS values in infants were higher (about 5- to 10-fold) than those previously observed in adults. In addition, urinary DLIS values were very high in the first week of life and fell quite rapidly in the next weeks of life. We used serum and urine pools from neonates for gel filtration experiments using a Sephadex G 25 column. In the urine sample we found some immunoreactive peaks eluted at the end and after the region of salts, while the chromatographic profiles of the serum pool showed only a major peak eluted with the peak of proteins. After boiling, the same serum pool showed an elution pattern characterized by a smaller immunoreactive peak eluted with that of proteins and by other peaks similar to those observed for the urine sample. Our study demonstrated that a substance or more substances which cross-react with digoxin-specific antibodies are present in blood and urine of healthy infants. In addition, our chromatographic studies indicate that DLIS is probably a low molecular weight substance(s) which circulate(s) in blood bound to a higher molecular weight molecule.

Evolution of the granular cells of the juxtaglomerular apparatus during postnatal development in the albino rat. Effect of age, body weight, renal weight and sex.

The postnatal development of the juxtaglomerular apparatus was studied by fluorescent microscopy in a series of 275 albino Wistar rats aged from 2 to 90 days. After treatment of kidney sections with thioflavine T, the appearance and evolution of secretory function in the terminal segment of the afferent glomerular arteriole were assessed in terms of the granular cell index (GCI) and the juxtaglomerular cell granulation index (JGI). Variations in these indices were analyzed in function of age, body weight, renal weight and sex of the animals. It emerges quite clearly from these studies that granular cell differentiation and maturation takes place in four successive stages: (a) a growth and differentiation phase lasting from the 2nd day to the beginning of the 5th week of extra-uterine life; (b) a critical phase around day 30; (c) a declining phase from day 30 to day 45, and (d) a stabilization phase from day 45 onwards. Until day 30 this evolutionary pattern is paralleled by rising body weight in animals of both sexes; afterwards it becomes independent of the parameters studied, in the males as well as in the females. The pattern of kidney weight parallels that of growth in body size and weight and does not constitute a more specific variable than body weight in the study of the developing granules in the juxtaglomerular apparatus.

Characterization of a developmentally regulated perinatal myosin heavy-chain gene expressed in skeletal muscle.

A cDNA clone, labeled pFOD5, isolated from a fetal-rat skeletal-muscle cDNA library, has been characterized and found to contain sequences corresponding to a perinatal-specific skeletal myosin heavy-chain (MHC) mRNA. This MHC cDNA demonstrates a high degree of nucleotide- and amino acid-sequence conservation with other MHC genes, but its carboxyl-terminal peptide and 3'-untranslated region are highly divergent and specific for this gene. S1 nuclease mapping experiments have shown that the perinatal MHC gene represented by this cDNA clone is only transiently expressed during skeletal-muscle development. Perinatal MHC mRNA is first detected late in fetal life, reaches maximal levels of expression at the end of the first postnatal week, and is de-induced thereafter. Its levels are almost undetectable at 28 days of postnatal life. During fetal and early postnatal life, the expression of this perinatal gene in skeletal muscle overlaps with the expression of the embryonic MHC gene. After the first week of extrauterine life, this gene is coexpressed with two adult MHC genes. The transient expression of this perinatal MHC gene raises interesting questions about the physiological significance of the MHC transitions and offers an interesting model for the study of MHC gene regulation.

Sodium homeostasis in term and preterm neonates. I. Renal aspects.

Eighty five 24 hour sodium balance studies and creatinine clearance measurements were performed in 70 infants of gestational age 27-40 weeks and postnatal age 3-68 days. The kidney's capacity to regulate sodium excretion was a function of conceptional age (the sum of gestational age and postnatal age) and an independent effect of postnatal age was also observed--extrauterine existence increased the maturation of this function. The sodium balance was negative in 100% of infants of less than 30 weeks' gestation, in 70% at 30-32 weeks, in 46% at 33-35 weeks, and in 0% of greater than 36 weeks, and the incidence of hyponatraemia closely paralleled that of negative sodium balance. Despite a low glomerular filtration rate (GFR) urinary sodium losses were highest in the most immature babies but fractional sodium excretion (FENa) was exponentially related to gestational age. An independent effect of postnatal age could be identified on FENa but not in GFR. These findings indicate that in infants of greater than 33 weeks' gestation sodium conservation is possible because of a favourable balance between the GFR and tubular sodium reabsorption, but that below this age GFR exceeds the limited tubular sodium reabsorption capacity. The rapid increase in sodium reabsorption in the first few postnatal days seems to be due to maturation of distal tubular function, probably mediated by aldosterone. We suggest that the glomerulotubular imbalance for sodium is a consequence of the immaturity of the tubuloglomerular feedback mechanism, and we estimate that the minimum sodium requirement during the first 2 weeks of extrauterine life is 5 mmol (mEq)/kg/day for infants of less than 30 weeks' gestation and 4 mmol (mEq)/kg/day for those born between 30 and 35 weeks.

Plasma 17-OH-progesterone in fullterm and preterm infants at birth and during the early neonatal period.

The 17 alpha-hydroxyprogesterone (17-HP) levels of cord and peripheral blood plasma were determined in fullterm and in preterm neonates, in order to investigate the normal concentration range during the first week of extrauterine life. In both fullterm and preterm neonates, the 17-HP level of the peripheral blood is substantially lower than that of the cord blood. In fullterm neonates (aged 1-7 days) the mean 17-HP concentration of the peripheral blood is higher in boys than in girls; the difference is significant (p less than 0.05). In preterm neonates, however, the 17-HP level of the cord blood is higher for girls than for boys, the difference again being significant (p less than 0.05).

457 THE EFFECT OF POSTNATAL AGE ON THE METABOLISM OF INTRAVENOUS FAT EMULSION

To determine the effect of postnatal age on serum clearing of intravenous fat, 17 preterm, AGA infants with gestation age of 29 ± 0.4 SEM wks. and birthweight of 1.2 ± 0.07 SEM kg. and less than 3 wks. of age received 1 gm/kg of Intralipid over a 4 hour infusion. Plasma levels of triglyceride (TG), free fatty acids (FFA) and beta-hydroxibutyrate (BOB) were determined at 0, 4, and 8 hours after the infusion was started. Basal levels of TG, FFA, and BOB were similar in the 2 groups. Infants of less than 1 wk. old had higher peak TG levels at the end of the infusion (4 hr.), than infants 2-3 wks. old (p<0.01). 8 hours after the beginning of the infusion TG levels remained significantly higher in the younger group (p<0.05).The rise in TG levels seen in our older group was lower than that (reported in infants of less than 33 wks. of gestation and comparable with levels obtained from infants of more than 33 wks. of gestation studied within the first 48 hours from birth. This suggests an acceleration in the capacity to tolerate intravenous fats after the first week of extra-uterine life.

Synthesis of alpha-fetoprotein, albumin and total serum protein in neonatal pigs.

Studies on the incorporation of 3H-leucine established that synthesis of alpha-fetoprotein (AFP) does occur in the neonatal pig. This synthesis probably accounts for the increase in AFP concentration from 0.46 mg/ml on the day after birth to the maximum value of 1.02 mg/ml found 5 days after birth. After the 5th day, the concentration decreases successively and AFP cannot be detected by electroimmunoassay in the sera of 8-week-old pigs. During the first 3 weeks of extrauterine life, the albumin concentration in serum increases from 3 mg/ml to approximately 30 mg/ml due mainly to increased synthesis of albumin. The concentration of AFP in the fetal pig serum decreases from 3 mg/ml at 6.5 cm crown-to-rump (CR) length to 0.8 mg/ml at 28 cm CR length, whereas the albumin concentration increases from 0.2 mg/ml at 6.5 cm CR length to 1.0 mg/ml at 28 cm CR length. The total serum protein content in the fetus is approximately 20 mg/ml irrespective of gestational age. During the first day after birth there is a marked increase in both the synthesis and the concentration of total serum proteins. The concentration rises to 70 mg/ml during the first day and then slowly declines to 65 mg/ml during the 3 weeks following birth.

Maturation postnatale des noyaux vestibulaires chez le chat: Etude histologique par la methode de Golgi-Cox

Postnatal maturation of vestibular nuclei in the cat was studied from both the qualitative and quantitative points of view, following impregnation of the sections by the Golgi-Cox method. Three principal data arise from our results. (1) The different vestibular neurones undergo significant growth during the first two weeks of extra-uterine life: during this time, the progressive disappearance of dendritic growth cones and filopodia, an increase in area and volume of the perikarya as well as that of dendritic fields are remarkable; the smallest neurones completing their maturation before the largest. (2) Average sized neurones of the superior vestibular nucleus show a significant increase in the number of dendritic spines between birth and the age of 3 days. (3) On the 12th day, a decrease in the number of dendritic spines is noted. This decrease is accompagnied by a modification in spine density along the dendrites.

METABOLIC RATE AND TEMPERATURE CONTROL IN LOW BIRTH-WEIGHT INFANTS: LONGITUDINAL STUDY

In order the study metabolic rate and temperature control under controlled thermal conditions, we constructed a closed-circuit respirometer for newborn infants which permits the simultaneous measurement of oxygen consumption rate /Vo2/, and body and environmental temperatures. A total of 178 exams have been performed on 62 newborn infants. Over the first five weeks of extrauterine life, minimal Vo2 expressed per unit surface area or per unit body weight rises substantially. The neutral pperative temperature falls progressively. Both rectal-environmental and mean skin-environmental temperature gradients rise. Ambient thermal insulation is slightly low in comparison with the adult, and tissue insulation is substantially lower. Studies in babies under 1000 grams birthweight show the importance of gestational age differences even in this weight group in determining metabolic rate total specific thermal insulation, and neutral operative temperature. These observations allow the first estimate of the caloric requirement for extra-uterine growth in prematurely born infants, based on concurrently measured differences in their metabolic rates.

The renin-angiotensin system in newborn dogs.

A detailed evaluation of the rennin–angiotensin system by concurrent determinations of plasma renin activity, renal renin activity, and juxtaglomerular index in newborn dogs during the first 15 days of extrauterine life is described. Findings show that the plasma renin activity is significantly higher for the first 2 weeks of extrauterine life when compared with the values found in adult dogs, and that the renal renin activity is slightly greater despite a very low juxtaglomerular index with a few granular cells, mostly located in the juxtamedullary cortex. Stimulation (peritoneal dialysis) of renin release resulted in a marked increase in plasma renin activity. The juxtaglomerular index was not modified by the stimulation whereas the renal renin activity decreased slightly. From these results, it is suggested that the formation and secretion of renin is well developed in kidneys of newborn dogs despite the absence of demonstrable juxtaglomerular cell granules.

Normal neonatal behavior patterns: the first week of extrauterine life.

Normal neonatal behavior patterns: the first week of extrauterine life.

The development of hepatic glucokinase in the neonatal rat.

1. Glucokinase and hexokinase activities have been determined in the livers of newborn rats and attempts made to influence in vivo the development of the glucokinase. 2. Glucokinase first appears in rat liver about 16 days after birth and adult activities are reached 10-12 days later. Evidence is presented which indicates that this represents synthesis of new protein. Hexokinase activities remain constant throughout the period of glucokinase development. 3. Both exogenous glucose and insulin are necessary for the natural development of glucokinase, for this is retarded in starved and alloxan-diabetic neonatal rats. 4. The absence of glucokinase during the first 2 weeks of extrauterine life in the rat is not due to lack of insulin. 5. Attempts to advance the time at which glucokinase first appears by infusions of glucose, insulin and chlorpropamide alone and in various combinations have resulted in marginal effects only. 6. When rats are starved for 3 days during the period of glucokinase development and then re-fed, glucokinase is more rapidly synthesized, indicating that the potential ability to synthesize glucokinase continues to develop throughout the period of starvation. 7. Some possible reasons for the comparatively late development of glucokinase are discussed.