The reticulocyte level, and the erythrocyte production judged from reticulocyte studies, in newborn infants during the first week of life.

Summary The main purpose of this study has been to investigate the reticulocyte content and reticulocyte maturation time in the peripheral blood during the first week after birth, in order, thereby, to elucidate the formation of red cells and hemoglobin in this period of life. The considerable discrepancies found in the literature on this subject are to a large extent due to the fact that unsatisfactory methods have often been used. The author's methods are described. The reticulocytes have been classified in various stages of maturity according to Heilmeyer's classification (Fig. 1). Much attention has been paid to the problem of reducing, as far as possible, the technical errors involved in the counts. On the first day of life 51.9 reticulocytes per 1,000 red cells was found as an average in healthy, full-term newborn infants, with variations ranging from 41.6 to 63.0. In blood of normal adults examined by the same method, the average was 15.7 %o (9.6–23.8). The average reticulocyte formula for the first day of life was as follows, with the corresponding adult figures in parentheses: Gr. I: 4.6 %o (0.02), Gr. II: 18.3 %o (1.1), Gr. III: 16.0 %o (5.0), Gr. IV: 13.0 %o (9.5). The percentage of reticulocytes in the circulation is lower in full-term than in premature infants, and lower still in post-mature babies (Fig. 2). The red cells leave the blood forming organs in an earlier stage in newborn infants than in adults. The normal day-to-day changes in the reticulocyte content in the peripheral blood during the first week of life appear in Figs. 3 and 4. The reticulocyte level is high and remains approximately constant for three days after birth, whereafter a rapid drop occurs in the following 2–3 days, so that normal adult levels are finally reached. In some cases, especially if the cord is clamped early, a transitory rise in the reticulocyte level can be observed after birth. This is not caused by an increase in erythrocyte production, but is due to the fact, that the infant by the clamping of the cord is deprived of the blood present in the placental circuit, whereby the reticulocytes formed are distributed in a smaller amount of blood than immediately before birth. The formation of erythrocytes and hemoglobin at birth is 3–5 times as rapid as in healthy adults, depending on the basis on which the comparison is made (Fig. 5). In terms of hemoglobin synthesized per kg body weight/day the relationship is probably almost 5: 1. The erythrocyte production continues to be very rapid and not markedly changed for about 3 days after birth. Then it diminishes rapidly to normal adult levels within 2 or 3 days. A slightly declining tendency in erythrocyte formation, however, is found as early as 6 hours after birth. By studying newborn infants with prolonged asphyxia from various causes it could be demonstrated convincingly, that the dramatic changes in reticulocyte level and rate of erythrocyte formation in the first week of life are related to the alterations in oxygen supply after birth (Fig. 6). A discussion is also offered as to why a significant decrease in the reticulocyte level and erythrocyte formation does not take place until about 3 days after birth, whereas the oxygen saturation of the blood rises to normal, high levels in a very short time. One reason may be the presence of a humoral, reticulocytosis-producing and erythropoiesis-stimulating substance in relatively high concentrations in the organism at birth. This substance (or substances) supposedly requires a certain time to be consumed by the organism. The author has been able to demonstrate the presence of reticulocytosis-producing substances in plasma from newborn infants suffering from erythroblastosis, and in normal cord blood at birth. Le taux des reticulocytes et la formation d'hematies estimees par l'ende des reticulocytes chez le nouveau-ne au cours de la premiere semaine de la vie. Le taux moyen des reticulocytes observe le premier jour chez des nouveaux-nes sains, a terme, etait de 51,9 pour 1000 hematies, avec des variations entre 41,6 et 63,0. Chez l'adulte normal, la moyenne etait de 15,7 pour 1000. Le pourcentage des reticulocytes circulants est plus faible chez le nouveau-ne que chez le premature; il est encore plus bas chez le post-mature. Les hematies quittent donc les organes erythropoietiques plus tot chez le nouveau-ne que chez l'adulte. La reticulocytose est elevee, et le demeure durant les 3 jours qui suivent la naissance: apres quoi, s'amorce une chute brutale les 2 ou 3 jours suivants; on observe alors un taux analogue a celui de l'adulte. La formation d'hematies et d'hemoglobine a la naissance est 3 a 5 fois plus rapide, que chez l'adulte normal. Au bout de 3 jours, la formation d'hematies diminue rapidement, et atteint des valeurs egales a celles de l'adulte en 2 a 3 jours. Il n'a pu etre prouve que ces modifications dans la reticulocytose et l'erythropoiese etaient sous la dependance de variations de l'oxygenation apres la naissance. Retikulocytenspiegel und Erythrocytenproduktion beim Neugeborenen in der ersten Lebenswoche beurteilt nach den Retikulocyten. Beim ausgetragenen Neugeborenen wurden am I. Lebenstag 51,9 Retikulocyten auf 1000 Erythrocyten als Durchschnittswert mit Variationen zwischen 41,6 und 63.0 gefunden. Bei normalen Erwachsenen betrug der Durchschnittswert 15.7 auf 1000. Der Prozentsatz zirkulierender Retikulocyten ist beim ausgetragenen Kind niedriger als bei fruhgeborenen Sauglingen, noch niedriger jedoch bei ubertragenen Kindern. Die roten Blutkorperchen verlassen die Blutbildungsorgane beim Neugeborenen fruher als beim Erwachsenen. Der Retikulocytenspiegel ist hoch und bleibt etwa 3 Tage nach der Geburt konstant, wonach in den folgenden 2–3 Tagen eine rapide Abnahme bis zu den normalen Erwachsenenwerten einsetzt. Die Erythrocyten- und Hamoglobinbildung bei der Geburt geht 3–-5mal rascher vor sich als beim gesunden Erwachsenen, abhangend von der Basis, auf welcher der Vergleich gezogen wurde. Nach dem 3. Lebenstag sinkt die Erythrocytenproduktion rapid innerhalb von 2–3 Tagen auf den normalen Spiegel bei Erwachsenen ab. Es konnte gezeigt werden, dass die dramatischen Anderungen des Retikulocytenspiegels und der Erythrocytenbildungsrate in der ersten Lebenswoche mit den Anderungen der Sauerstoffversorgung nach der Geburt in Beziehung stehen. El nivel de reticulocitos y la produccion de eritrocitos juzgados a traves de la funcion reticulocitica en recien nacidos durante la primer semana de la vida. Recien nacidos sanos y de termino presentan en el primer dia de la vida, una cifra media de 51,9 reticulocitos por 1000 globulos rojos, con variaciones entre 41,6 y 63,0. En adultos normales, la cifra media es de 15,7 por 1000 g. r. El porcentaje de reticulocitos circulantes es mas bajo en recien nacidos a termino que en prematuros, siendo aun mas bajo en los postmaduros. Los globulos rojos migran fuera de los organos hematopoyeticos mas temprano en los recien nacidos que en los adultos. El nivel de reticulocitos es alto y permanece casi constante los tres primeros dias de la vida, en los 2–3 dias subsiguientes ocurre una rapida caida hasta llegar a cifras que son normales en adultos. La formacion de eritrocitos y hemoglobina al nacer es 3 a 5 veces mas rapida que en los adultos sanos, variando segum las bases tomadas como comparacion. Despues del tercer dia de la vida, la produccion de eritrocitos disminuye rapidamente hasta alcanzar niveles normales en la edad madura. No pudo ser demostrado que los bruscos cambios de nivel reticulocitario y formacion de eritrocitos en la primer semana de la vida tengan alguna relacion con la administracion de oxigeno al nacer.