Fetal and Maternal Lipoprotein Metabolism in Human Pregnancy

1. Lipid, apolipoprotein concentration and composition were determined in maternal venous and umbilical arterial and venous blood at delivery by elective Caesarean section in 13 full-term pregnancies and in 25 healthy non-pregnant females. The indications of Caesarean section were a previous Caesarean section or breech presentation. None of the women was in labour and there were no other complications of pregnancy or fetal distress. 2. The objectives of the study were to establish whether the placenta has a role in feto-maternal cholesterol metabolism through either synthesis or transplacental cholesterol flux. The potential for free cholesterol diffusion between mother and fetus and rates of cholesterol esterification and transfer between lipoproteins were determined and related to the differences in composition between fetal and maternal lipoproteins. 3. Pregnant women had raised levels of all lipid and lipoprotein fractions compared with control subjects. The greatest increases were in free cholesterol and triacylglycerol (P < 0.0001). Lipoprotein (a) levels were significantly greater in the pregnant women [112(12.2) mg/l] than in the control women [50 (10.0) mg/l]. 4. The only significant correlation between maternal and fetal lipoprotein concentrations was in lipoprotein (a) levels (r = 0.791, P = 0.002). In both umbilical venous and arterial blood, concentrations of very-low- and low-density lipoproteins, particularly apolipoprotein B, cholesteryl ester and triacylglycerol, were lower than in maternal blood (P < 0.0001), but high-density lipoprotein levels were similar. 5. There was no umbilical arteriovenous differences in lipoprotein concentration or composition. This suggests that cholesterol synthesis or free cholesterol diffusion does not occur in the placenta. The relative concentrations of free cholesterol to phospholipid in maternal and fetal lipoproteins do not indicate the existence of a concentration gradient favouring free cholesterol diffusion across the placenta. 6. The esterification of free cholesterol was significantly reduced in maternal [17.7 (2.4) μmol h−1 l−1, P < 0.001] and fetal [6.7 (3.5) μmol h−1 l−1, P < 0.0001] compared with control [40.9 (13.2) μmol h−1 l−1] blood. 7. In fetal compared with maternal high-density lipoproteins the ratios cholesteryl ester/apoliproprotein A-I [0.84 (0.35) versus 0.40 (0.05), P < 0.01] and phospholipid/apolipoprotein A-I [1.66 (0.14) versus 0.58 (0.10), P < 0.0001] indicated lipid enrichment of these particles in the fetus. 8. Lipid enrichment of high-density lipoprotein is due in part to a marked reduction in transfer of cholesteryl ester in the fetus [1.0 (0.6) μmol h−1 l−1] compared with maternal [6.15 (1.3) μmol h−1 l−1, P = 0.004] and control [17.3 (7.2) μmol h−1 l−1, P < 0.0001] blood. 9. In conclusion, there was no evidence for involvement of the placenta in cholesterol metabolism during pregnancy. In fetal life high-density lipoproteins are lipid rich, partly because of a reduction in transfer of esterified cholesterol to other particles. Maternal and fetal lipoprotein levels are not correlated, although the results suggested that lipoprotein (a) levels may be related.