Background: Large for gestational age (LGA; birth weight >90th centile) may affect 12% of newborns of healthy women and up to 45% of those with gestational diabetes (GDM). However, the correlation between maternal glucose levels and fetal birth weight (BW) is not always found. We aimed to investigate whether changes in maternal lipid species can predict the outcome of LGA independent of GDM.
Methods: 175 pregnant women (mean age 29.6 ± 4.7 years) were assessed by oral glucose tolerance test at 26-28 weeks of gestation, of which 17 women developed GDM, diagnosed by the ADIPS1998 criteria. 305 circulating lipid species were assessed in maternal fasting plasma samples collected at 26-28 weeks gestation (during OGTT) using liquid chromatography electrospray ionisation-tandem mass spectrometry and MultiQuant 2.1.1. Data analysis used linear regression modelling to assess association of change in BW centiles with an IQR increase in lipid concentration.
After adjustment for maternal age, dihydroceramides were the most significant predictors of increased birth weight. For each IQR increase in dihydroceramides BW centiles increased by 11.9 (p<0.001). The greatest associations were seen with Cer(d18:0/16:0), Cer(d18:0/22:0) and Cer(d18:0/24:0). Increase in cholesterol esters also showed strong association with BW (IQR=8.8 BW centiles; p<0.01). Total ceramides, cholesterol, triglycerides, and alkylphosphatidylethanolamine were also significant predictors of BW centiles (p<0.05). These effects were independent of presence or absence of GDM. When corrected for GDM, dihydroceramides and cholesterol esters predicted increased birth weight to a similar extent (IQR=11.8 BW centiles; p<0.001 and IQR=8.7 BW centiles; p<0.01, respectively).
Independent of GDM status, dihydroceramides followed by cholesterol esters are the strongest predictors for LGA. Total ceramides, triglycerides, cholesterol and alkylphosphatidylethanolamines are also predictive of increased fetal size. We conclude that increase in certain maternal circulating lipid species may predict development of LGA independent of GDM.