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We evaluated the relationship between maternal cholesterol levels and its biologically active precursors and metabolites in the first trimester and subsequent risk for small-for-gestational-age birthweight (SGA). This is a secondary analysis of a prospective cohort study which enrolled healthy singleton pregnancies (n = 1337). Maternal fasting blood was taken in the first trimester and followed up till delivery. The lipid parameters were compared between women who delivered SGA neonates (SGA-group, birthweight < 10th percentile, n = 107) and women who did not (non-SGA-group, n = 1230). In addition, metabolic signatures of cholesterol were evaluated in a subset consisting of propensity-score matched SGA (n = 56) and control group (n = 56). Among lipid parameters, maternal high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in SGA-group than in non-SGA-group ( p  = 0.022). The risk for SGA was negatively correlated with maternal serum HDL-C quartiles ( p  = 0.003), and this association remained significant after adjustment for confounding variables. In metabolic signatures of cholesterol, the cholesterol/lathosterol ratio in SGA-group was significantly higher than non-SGA-group [(2.7 (1.6–3.7) vs. 2.1 (1.5–2.9), respectively;  p  = 0.034)], suggesting increased endogenous cholesterol biosynthesis. We demonstrated that dyslipidemia and increased cholesterol biosynthesis led to delivery of SGA neonates even in early pregnancy.

Maternal dyslipidemia and altered cholesterol metabolism in early pregnancy as a risk factor for small for gestational age neonates