Adiponectin/leptin ratio - a marker of insulin sensitivity in pre-eclampsia and fetal growth

The serum adiponectin-leptin ratio (A/L ratio) is a surrogate marker of insulin sensitivity. Pre-eclampsia (PE) is associated with maternal metabolic syndrome and occasionally impaired fetal growth. We assessed whether the A/L ratio in first-trimester maternal serum was associated with PE and/or birth weight. Adiponectin and leptin were quantitated in first-trimester blood samples (gestational week 10+3-13+6) from 126 women who later developed PE with proteinuria, (98 mild PE; 21 severe PE; 7 HELLP syndrome), and 297 controls, recruited from the Copenhagen First-Trimester Screening Study. The A/L ratio was reduced in PE pregnancies, median 0.17 (IQR: 0.12-0.27) compared to controls, median 0.32 (IQR: 0.19-0.62), (p<0.001). A multiple logistic regression showed that PE was negatively associated with A/L ratio independent of maternal BMI (odds ratio = 0.08, 95% CI = 0.0322 to 0.214). Adiponectin (AUC = 0.632) and PAPP-A (AUC = 0.605) were negatively, and leptin (AUC = 0.712) was positively associated with PE. However, the A/L ratio was a better predictor of PE (AUC = 0.737). No significant association was found between A/L ratio and clinical severity of pre-eclampsia or preterm birth. PE was associated with significantly lower relative birth weight, (p<0.001). A significant negative correlation was found between relative birth weight and A/L ratio in controls but not in PE pregnancies, ({beta} = -0.144, 95% CI = -9.944 to -0.093), independent of maternal BMI. After correction for maternal BMI, leptin was significantly associated with relative birth weight, ({beta} = 0.197, 95 % CI = 2.361 to 14.353), while adiponectin was not significantly associated. Our findings suggest that an impairment of the A/L ratio (as seen in metabolic syndrome) in first-trimester is characteristic of PE, while aberrant fetal growth in PE is not dependent on insulin sensitivity but rather on leptin associated pathways.