Enzyme assays in the management of pregnancy.

Abstract

The occurrence of increased serum enzyme activity in patients with diseases involving tissue damage such as myocardial infarcation suggested that placental damage may also give rise to characteristic changes in maternal serum enzymes, which might be useful diagnostically. One of the problems in obstetrics is the recognition of placental 'dysfunction' or 'insufficiency', terms which are used by obstetricians to indicate a process of impaired transmission of nutrients resulting in retarded fetal growth, and progressing eventually to impaired oxygen transfer resulting in fetal hypoxia and possibly death from anoxia. The diagnosis depends on the demonstration of fetal distress during labour, or on the delivery of a baby with a low Apgar' score, or a birth weight below the 10th centile for that duration ofpregnancy. These criteria have only recently been applied to the evaluation of tests of placental function. It has been established that a number of enzymes in maternal serum remain unchanged in normal pregnancy, but that others increase either during normal or abnormal pregnancy or in both (Table I). Serum enzymes which do not change during normal pregnancy are cholinesterase (EC 3.1.1.8) (Meade and Rosalki, 1963; Rimbach and Figge, 1966), 2-hydroxybutyrate dehydrogenase (EC 1.1. 1.27) (Meade and Rosalki, 1963), and alanine and aspartate aminotransferases (EC 2.6.1.2.4.2.6.1.1) (Meade and Rosalki, 1963; Szekely and Fritzsh, 1969). Studies of lactate dehydrogenase (EC 1.1.1.27) and isocitrate dehydrogenase (EC 1.1.1.42) have given less uniform results. Whereas most authors have found them to remain unchanged, an increase in lactate dehydrogenase at term was found by Pulkkinen and Willman (1968) and a marked increase in isocitrate dehydrogenase was found at 39-40 weeks by Kraussold (1969). Serum 3-glucuronidase (EC 3.2.1.31), hyaluronidase (EC 3.2.1.35) and 3-acetylglucosaminidase (EC 3.2.1.30) have all been described as increasing late in normal pregnancy (Platt and Platt, 1968). 'The Apgar score is based on assessment of the baby's colour, heart rate, respirations, muscle tone, and the response to a catheter in the nostril. The best prognosis is indicated by a score of 10 and the worst by a score of 0. In abnormal pregnancy, many of the above enzymes have been found to increase. Thus increased levels of both aminotransferases were found in two out of 14 patients with mild pre-eclampsia, and 11 out of 12 with eclampsia (Dass and Bhagwani, 1964). These results were taken to mean that toxaemia is associated with liver damage, and it was suggested that estimations of serum aminotransferases might be of prognostic value in toxaemia. Similarly isocitrate dehydrogenase may show transient increases in pre-eclampsia or accidental haemorrhage (Jeacock, Morris, and Plester, 1962; Meade and Rosalki, 1963; Pulkkinen and Willman, 1968), possibly due to placental infarction (Dawkins and Wigglesworth, 1961). Pulkkinen and Willman (1968) also found increased levels of lactate dehydrogenase in four patients with hypertension. Plasma renin (EC 3.4.4.15) levels were found to be increased during the third trimester in nine normal women (Geehoed and Vander, 1968), but the mean value at 13-27 weeks in 10 women who subsequently developed toxaemia was greater than that in 48 in whom pregnancy remained uneventful. None of the above enzymes has been used to assist in the management of pregnancy. However, diamine oxidase (EC 1.4.3.6.), 'oxytocinase', and the heatstable isoenzyme ofalkaline phosphatase (EC 3.1.3.1), all of which increase during normal pregnancy, have been found useful in the management of pregnancy and will be discussed in greater detail.