[Cerebral ultrasonic examination of newborn infants. Normal case material].
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Biomedical subjects
Publications and source records attributed to A Meberg.
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The lactoferrin content of human plasma has been measured by an enzyme-linked immunosorbent assay. In cord blood the level was 0.02-0.3 mg/l, corresponding to 3-44 X 10-(10) mol/l lactoferrin; in plasma 5 d post partum the level had not changed. In adults the level was 0.02-0.2 in 29 out of 30 plasma samples and above 1 mg/l in 1 sample. Similar results were obtained with EDTA, citrate or heparin as anti-coagulant.
Plasma erythropoietin concentrations were studied in 11 preterm appropriate for gestational age infants at the age of 3-14 weeks. Their birth weights ranged from 860-1 690 g. Erythropoietin was measured by a cell culture technique. Significant concentrations of erythropoietin was detected in 18 out of 29 samples, at all stages of the early anemia. The highest levels were found at 3-9 weeks. Individual erythropoietin values did not correlate with hemoglobin concentrations, hematocrit levels or 'corrected' reticulocyte counts, nor did the 'corrected' reticulocyte count correlate with hemoglobin or hematocrit. The lack of correlation with hemoglobin concentration most likely reflects the importance of other factors as well as the hemoglobin in determining the oxygenation status of the infant. A significant positive correlation (r = 0.60, p less than 0.01) was found between erythropoietin concentration and weight gain in the preceding week. The study shows that small preterm infants are capable of erythropoietin production during their early anemia, and indicates that the hormone plays a role in the regulation of erythropoiesis also at this time of life.
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Fourteen infants with birth weight appropriate for gestational age (AGA) and 16 small for gestational age (SGA) infants were investigated for haemoglobin concentration, haematocrit level and thrombocyte count on the first day of life. Cord serum was tested for erythropoietin (ESF) and thrombopoietin (TSF) activity. The same investigations were performed on venous blood and serum from 18 healthy adult individuals. SGA infants had higher haemoglobin concentration and haematocrit level (p less than 0.05), and lower platelet count (p less than 0.001) than AGA infants. Significant ESF activity was present in cord serum, but was not detectable in serum from adults. Significant TSF activity was present in cord serum as well as in serum from adults, with higher levels in the newborn infants (p less than 0.05). An inverse relationship was found between serum TSF activity and the number of platelets in adults, which was not demonstrable in newborn infants. Long-term intrauterine hypoxia because of placental dysfunction may be the reason for polycythemia and thrombocytopenia in SGA infants. Thrombocytopenia may be caused by competitive mechanisms on common stem cells for erythropoiesis and thrombopoiesis, shunting stem cells in direction of erythropoiesis during hypoxic exposure. Normal serum TSF activity in SGA infants indicates that lack of the humoral factor for platelet production is not the reason for the thrombocytopenia in these infants. A negative feed-back mechanism may exist between platelet number and TSF production.
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Groups of female mice were starved or exposed to hypobaric hypoxia during pregnancy. A significantly lower weight gain during pregnancy occurred in the mothers starved or exposed to hypoxia compared to controls. Hypoxia also decreased maternal food intake. Therefore, the hypoxic groups included a combination of hypoxia and starvation. Body weight, brain weight, brain DNA (deoxyribonucleic aid) and total protein were investigated in the offspring at birth and at 20 and 70 days of age. Starvation and hypoxia impaired fetal growth, with reduction in body weight, brain weight, brain cell number (DNA content) and brain total protein content in a dose-related manner. In the most severely starved fetuses brain cell size (brain weight/DNA and total protein/DNA) was also reduced. Long-term effects were observed with lower body weight, brain weight and brain DNA content at adult age in the most severely malnourished and hypoxic offspring. Catch-up growth took place after a more moderate starvation and hypoxic exposure. It is concluded that intrauterine malnutrition interferes with fetal cellular mitotic rate. This may give rise to growth-retarded fetuses because of a decreased cell number. Depending o the degree of malnutrition a cell deficit may persist at adult age. Intrauterine hypoxia may aggravate these effects of fetal starvation.
Mice from newborn until adult age were exposed to hypobaric hypoxia of 0.5 atm for 6 h. In all age groups the animals responded with increased plasma erythropoietin (Ep) levels. A greater response was elicited from adult mice compared to newborn animals. No sex difference in response occurred. Twelve hours after the hypoxic exposure no plasma Ep activity was detectable. Though high plasma Ep levels were present in non-hypoxic mice 9 and 20 days old, hypoxia further increased the Ep activity. It is concluded that hypoxia stimulates Ep production during hepatic as well as during erythropoiesis. Though erythroid target cells may be maximally stimulated by Ep in the young mouse (9-20 days old) a reverse capacity for Ep production exists. Increased capacity for Ep production may develop towards adult age.
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Plasma erythropoietin (erythropoiesis stimulating factor(s), ESF), PCV and body weight were measured in normal mice from birth until the age of 70 d. Low but detectable ESF activity was present at birth, following by undetectable levels 12-48 h after birth. Thereafter the ESF level rapidly increased. Peak levels were obtained 15-20 d after birth. During the same phase an increased growth velocity occurred, coincident with decreased PCV levels. A fall to undetectable levels in plasma ESF activity coincided with decelleration of growth 40-50 d after birth. In small litters (four pups per litter) growth velocity and PCV levels were significantly higher than in large litters (16 pups per litter) 8 and 15 d after birth. The plasma ESF activity, however, did not differ between the two groups. Prohibiting suckling for a period of 16 h did not change the plasma ESF level. The hypothesis is put forward that growth directly or indirectly stimulates ESF production.
Capillary Hb concentration on the first day of life was registered in 201 infants with weight appropriate for gestational age (AGA) and in 99 infants small for gestational age (SGA). In both groups Hb increased towards term (P less than 0.01), while the SGA infants reached higher Hb concentration at term (21.5 +/- 1.9 g/dl; mean +/- SD) than the AGA infants (17.9 +/- 1.5 g/dl) (P less than 0.001). The cord serum erythropoietin (EP) level increased towards term equally in both groups. Delivery did not seem to influence the EP level as same values were obtained in cord serum from infants delivered by elective cesarean section as after uncomplicated vaginal delivery. No correlation was found between cord serum EP and first day capillary PCV. Postnatally a rapid fall in the EP level occurred. In healthy adults no serum EP activity was detected. It is suggested that increasing hypoxia, rapid growth, and shift from hepatic to myeloid erythropoiesis may be related to the increasing Hb concentration and serum EP level towards term. Improvement of oxygenation during air breathing may cause the decreasing serum EP level after birth.
Pregnant mice were exposed to hypobaric hypoxia (0.7 atmospheres) continuously during days 13 to 20 of pregnancy. In the newborn offspring, the body weights were decreased, and liver weight/body weight ratios were increased compared to nonhypoxic control animals (P < 0.001). After intrauterine hypoxia, the newborn animals were polycythemic, and a postnatal transitory thrombocytopenia lasting 7 days occurred. A rebound thrombocytosis appeared on days 13 to 15 after birth. Bone marrow megacaryocyte concentrations were increased in the hypoxic animals on days 5 to 15 after birth compared to the nonhypoxic controls. These findings may be explained by a competitive mechanism on common stem cells. Increased demand for erythropoiesis during hypoxia may shunt hematopoietic cells in direction of erythropoiesis at expense of thrombopoiesis.
Plasma erythropoietin (Ep) activity was detectable in fetal rats near term and in rats less than 2 old. Ep activity was not found 12--48 h after birth. A hypoxic period (0.5 atmospheres for 6 h) increased the plasma Ep level in fetal and newborn rats, and in pregnant animals. After long-term hypoxia (0.5 atmospheres for 8 days) the plasma Ep level was neither increased in fetal rats nor in their mothers, while a compensatory increase in the hematocrit level occurred. It is concluded that hypoxia stimulates Ep production during hepatic erythropoiesis. During long-term hypoxia compensatory mechanisms for tissue oxygenation occur.
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Twenty-eight mothers smoking 10--20 cigarettes daily during pregnancy had significantly higher serum thiocyanate concentrations at delivery compared in 25 non-smoking controls. The thiocyanate levels were positively correlated to cigarette consumption and inversely correlated to the birth weights of the infants. A highly significant correlation existed between serum thiocyanate levels of the mother and umbilical cord serum thiocyanate levels, reflecting a nearly complete equilibration. The thiocyanate concentrations in human milk on the 4th day after delivery were considerably lower than the serum concentrations, and no correlation existed between serum and milk concentrations. The infants of smoking mothers had significantly decreased weight and length at birth compared in infants of non-smokers. Birth weights were 3 344 +/- 434 g and 3 620 +/- 504 g respectively (p less than 0.05), and lengths 49.8 +/- 1.7 cm and 51 +/- 1.6 cm respectively (p less than 0.05). No differences were found between smokers and non-smokers in placental and umbilical cord histology, and umbilical cord artery medial area. It is concluded that serum thiocyanate concentration in smokers may be used as an objective measure for smoke exposure, and that maternal cigarette smoking acts as an exogenous factor which interferes with intrauterine development of the fetus in a dose related way.
Hematological values were measured in 28 newborn infants of mothers smoking 10-20 cigarettes daily during pregnancy, and in 25 infants of non-smokers. Higher hematocrit levels were found on the 1st day of life in infants of smoking mothers (60.8 +/- 5.0%, mean +/- S.D.) compared to controls (57.5 +/- 4.8%) (p less than 0.05). The hematocrit levels correlated positively with the maternal smoking level (r = 0.318, p less than 0.05) and the maternal serum thiocyanate concentrations at delivery (r = 0.389, p less than 0.01). Cord serum values for erythropoietin, serum-iron, transferrin and ferritin showed no statistically significant difference between the two groups. A significant inverse correlation was found between the hematocrit value on the 1st day of life and the cord serum ferritin concentration (r = -0.495, p less than 0.005). The present results suggest that maternal smoking stimulates fetal erythropoiesis, probably through a hypoxic effect on the fetus, dose related to the maternal smoking level. Increased erythropoiesis may cause increased iron incorporation into erythrocytes at expense of iron storage in the bone marrow and reticuloendothelial system.