Leukocyte alkaline phosphatase in the newborn infant

Abstract

AMONG THE VARIOUS maternal enigmas which occur during pregnancy is a progressive increase in the leukocyte alkaline phosphatase (LAP) ; a fact which has been used in the early diagnosis of pregnancy.r Whatever the stimulus for this rise, it is important to know if a similar elevation occurs in the fetus.z Blood, anticoagulated with ammonium and potassium oxalate, was obtained from the fetal circulation of the placenta at the time of delivery of 25 consecutive Caucasian infants. Smears were made of this blood, air dried, fixed for 30 seconds in a solution of formaldehyde (10 ml.) and absolute methanol (90 ml.) at 4’ C., and frozen until staining, one to 6 days later. The smears were thawed and immediately incubated at room temperature for 10 minutes with a substrate containing sodium alpha naphthy1 phosphate and the diazonium salt Fast Blue RR, buffered to a pH of 9.6 with 0.05M propanediol buffer.3 The alkaline phosphatase present within the cytoplasm, presumably in the granules, of the granular leukocytes splits the phosphate from the sodium alpha naphthyl phosphate allowing coupling of the residue with the Fast Blue RR and the formation of a granular black precipitate. The smears were then counterstained with Mayer’s hematoxylin for 3 minutes and mounted in Permount. The cytoplasm of the granular leukocytes may fail to stain or may develop variable degrees of color from a diffuse pale brown to a heavy granular black precipitate. On the basis of this reaction, the cells were scored from zero through four, and 100 consecutive cells were counted. The sum of the scores of the 100 cells is considered the score for the slide. The scores ranged from 163 to 303 with a mean of 236 and a standard deviation of + or 37, whereas in our our institution 60 + or 20 is considered the normal range. Alkaline phosphatase is a seemingly ubiquitous phosphomonoesterase with optimal activity in the granular leukocyte in the pH range of 9.5 to 10.0.4 Polycythemia Vera, leukemoid reactions, and “stress” are associated with elevated LAP activity and chronic myelogenous leukemia with a profound depression of this activity.4 During pregnancy the maternal LAP increases until during labor very high levels are present.5 Similarly, at the time of birth the LAP of the newborn is quite high. It thus appears that the mechanism stimulating the increased LAP activity is active in both the mother and infant. During pregnancy there is a progressive increase in the amount of progesterone produced,6 an event which seemingly parallels the rising maternal LAP. Progesterone freely passes the placenta during pregnancy7 thus being capable of exerting an influence on both mother and infant. Interesting enough, the synthetic progestational agents are associated with similar elevations of the LAP8 to scores in the range of 120 to 150, and on the basis of 18 cases the scores seem to fall below 60 by the fourth day after withdrawal.9 By way of conclusion, LAP is detectable in large quantities in the fetus at birth, an event strikingly similar to that occurring in the mother. This elevation of the LAP is present in women being treated with synthetic progestational agents as well, strongly suggesting an etiologic relationship between elevated levels of progesterone and elevated LAP activity.