Fetal dependency on maternal fatty acids: A pilot study in human pregnancies using the natural abundance variation of 13C

The extent of de-novo biosynthesis of non-essential fatty acids (FAs) and the endogenous biosynthesis of long chain polyunsaturated FAs in human fetuses remains largely unknown. We used natural variations in the 13C:12C (δ13C) of plasma phospholipids of the woman at delivery and of cord blood to infer fetal biosynthesis of FAs. We studied 39 mother-fetus pairs with uncomplicated pregnancies and term delivery. Eighteen women were supplemented with docosahexaenoic acid (DHA), from pregnancy week 20 until delivery, sourced from an algae (n=13) or fish oil (n=5), each with slightly different 13C content. Twenty-one women did not receive DHA supplementation. We measured the δ13C value of selected phospholipid FAs (C16:0, C18:0, C18:1n-9, C18:2n-6, C20:4n-6, and C22:6n-3), in maternal and cord plasma samples at delivery using isotope ratio mass spectrometry. We found significant linear correlations for δ13C values of FAs between mothers and their fetuses (C16:0, r=0.8535; C18:0, r=0.9099; C18:1n-9, r=0.8079; C18:2n-6, r=0.9466; C20:4n-6, r=0.9257; and C22:6n-3, r=0.9706). Women supplemented with algal DHA had significantly lower DHA δ13C values in their plasma phospholipids than those supplemented with fish DHA or those who did not receive DHA supplementation (p<0.001). There was no significant difference in δ13C values of FAs between women at delivery and their fetuses. These findings strongly suggest that the human fetus is highly dependent on the placental transport of maternal plasma FAs, particularly DHA. The limited fetal biosynthesis of major FAs emphasizes the crucial role of maternal nutrition and placental well-being in fetal development.