To evaluate the associations between maternal serum concentrations of high-density lipoprotein cholesterol (HDL-c) throughout pregnancy and neonatal birth weight (BW) and small for gestational age (SGA) births. A prospective cohort of 2241 pregnant women was followed from recruitment to delivery in three hospitals in Beijing, China between January 2014 and December 2017. Maternal fasting serum lipids concentrations were measured at gestational week 6-12, 16, 24 and 36. Major outcome was

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... BW. The associations between maternal HDL-c and BW were estimated by linear regression and linear mixed-effects models. Odds ratios (ORs) and 95% confidence intervals of SGA births in relation to HDL-c were evaluated via logistic regression analysis. There was a tendency that mothers with higher HDL-c concentrations throughout gestation gave birth to infants with lower BW. A negative association was found between maternal HDL-c concentrations and BW at 24th and 36th gestational weeks (B = - 34.044, P = 0.034; B = - 53.528, P = 0.000). The HDL-c trend of change was inversely associated with BW (B = - 442.736, P = 0.000). Mothers with SGA neonates had higher serum HDL-c concentration at the 36th gestational week (P < 0.01). The incidences of SGA in the three groups (HDL-c: 1.84-2.23 mmol/L, 2.24-2.59 mmol/L and ≥ 2.60 mmol/L) were higher than the group with the lowest concentration of HDL-c (< 1.83 mmol/L) (P < 0.01, P < 0.01, P < 0.001) at 36th week. Higher maternal HDL-c concentrations at 36th week (HDL-c: 1.84-2.23 mmol/L, 2.24-2.59 mmol/L and ≥ 2.60 mmol/L) were positively associated with the incidence of SGA (OR = 1.900, P = 0.008; OR = 1.893, P = 0.008; OR = 1.975, P = 0.004). The HDL-c trend of change was positively associated with SGA births (OR = 9.772, P = 0.000). Maternal serum HDL-c concentrations were inversely associated with BW at 24th and 36th gestational weeks. The high concentrations of HDL-c at the 36th gestational week increased the risk of SGA. The maternal HDL-c trend of change across pregnancy was associated with smaller neonatal size.