Effect of Maternal Intrahepatic Cholestasis

Thus, the changes in maternal steroid metabolism caused by cholestasis are reflected in the steroid profile of the fetoplacental circulation. Furthermore, maternal intrahepatic cholestasis may result in the production of some substance which crosses the placenta and affects fetal steroid metabolism. Received for publication 7 November 1973 and in revised form 13 February 1974. INTRODUCTION Intrahepatic cholestasis is a well-documented biochemical feature of the disease known as recurrent jaundice, or hepatosis, of pregnancy. In the maternal plasma, the direct fraction of bilirubin is elevated (1), and the concentration of total bile acids rises from 10to 100fold above the levels found in normal pregnancy (2). The excretion of administered bromsulphalein into the bile is reduced and so is the capacity of the liver to take up this substance (3). Recently, Sj6vall and Sjdvall (4) have shown that, as a result of cholestasis, the levels of several neutral steroid sulfates, mostly metabolites of progesterone,1 are high in maternal plasma in this condition. It is not known whether these biochemical changes are reflected in the fetoplacental compartment. Information on this point would be of interest, because the rate of premature deliveries and risks to fetal well-being are reported to be increased in pregnancies complicated by maternal intrahepatic cholestasis (5, 6). To obtain more detailed information on the metabolism and conjugation of steroids in the fetoplacental unit, we developed a method for determination of progesterone, estriol, estriol sulfate, and 13 neutral steroid monosulfates and 10 neutral steroid disulfates in the cord plasma (7). To study the fetoplacental steroid metabolism in pregnancies complicated by maternal intrahepatic cholestasis, we have analyzed 27 cord plasma samples collected after such pregnancies and compared the steroid levels with those obtained in the cord plasma after uncomplicated pregnancies. 1 Trivial and systematic names of steroids: dehydroepiandrosterone, 3fi-hydroxy-5-androsten-17-one; 16a-hydroxydehydroepiandrosterone, 3,8,16a-dihydroxy-5-androsten17-one; progesterone, A'4pregnene-3,20-dione; pregnenolone, 3,i-hydroxy-5'regnen-20-one; 16a-hydroxypregnenolone, 3,8,16a-dihydroxy-5-pregnen-20-one; 17a-hydroxypregnenolone, 3j9,17a-dihydroxy-5-pregnen-20-one; 21-hydroxypregnenolone; 3,8,21-dihydroxy-5-pregnen-20-one. The Journal of Clinical Investigation Volume 53 June 1974.1709-1715 1709 Downloaded from http://www.jci.org on October 29, 2017. https://doi.org/10.1172/JCI107722