Metabolic profiling of pregnancies complicated by preeclampsia: A longitudinal study

Abstract

Introduction Preeclampsia is associated with maternal metabolic disturbances, but longitudinal studies with comprehensive metabolic profiling are lacking. We aimed to determine metabolic profiles across gestation in women who developed preeclampsia compared with women with healthy pregnancies. We also explored the respective effects of body mass index (BMI) and preeclampsia on various metabolic measures. Material and methods We measured 91 metabolites by high‐throughput nuclear magnetic resonance spectroscopy at four time points (visits) during pregnancy (weeks 14–16, 22–24, 30–32 and 36–38). Samples were taken from a Norwegian pregnancy cohort. We fitted a linear regression model for each metabolic measure to compare women who developed preeclampsia (n = 38) and healthy controls (n = 70). Results Among women who developed preeclampsia, 92% gave birth after 34 weeks of gestation. Compared to women with healthy pregnancies, women who developed preeclampsia had higher levels of several lipid‐related metabolites at visit 1, whereas fewer differences were observed at visit 2. At visit 3, the pattern from visit 1 reappeared. At visit 4 the differences were larger in most subgroups of very‐low‐density lipoprotein particles, the smallest high‐density lipoprotein, total lipids and triglycerides. Total fatty acids were also increased, of which monounsaturated fatty acids and saturated fatty acids showed more pronounced differences. Concentration of glycine tended to be lower in pregnancies with preeclampsia until visit 3, although this was not significant after correction for multiple testing. After adjustment for age, BMI, parity and gestational weight gain, all significant differences were attenuated at visits 1 and 2. The estimates were less affected by adjustment at visits 3 and 4. Conclusions In early pregnancy, the metabolic differences between preeclamptic and healthy pregnancies were primarily driven by maternal BMI, probably representing the women's pre‐pregnancy metabolic status. In early third trimester, several weeks before clinical manifestation, the differences were less influenced by BMI, indicating preeclampsia‐specific changes. Near term, women with preeclampsia developed an atherogenic metabolic profile, including elevated total lipids, very‐low‐density lipoprotein, triglycerides, and total fatty acids.

Maternal metabolic profiling across body mass index groups: An exploratory longitudinal study

“…In relation to our previous study on metabolic differences in pre-eclamptic pregnancies, 7 we observed a resemblance between the metabolic profiles of women with overweight/obesity in early pregnancy and those found in late pregnancy of late-onset preeclampsia, especially regarding particle concentration of the largest VLDL and triglycerides. Kivelä et al found that GDM, pre-eclampsia, and chronic hypertension were associated with metabolic alterations similar to obesity.…”

“…The metabolism of women with overweight and obesity was characterized by less accentuated increase in lipids but exaggerated increase in glucose and insulin compared to normal‐weight women. By detailed metabolic characterization of healthy pregnant women compared to women with late‐onset pre‐eclampsia, we showed differences in metabolites between these two groups already in early pregnancy 7 . Near term, women with pre‐eclampsia developed a metabolic profile that resembled the metabolic alterations observed in atherosclerotic disease, including elevated levels of total lipids, very‐low‐density lipoprotein (VLDL), triglycerides, and total fatty acids.…”

“…Each pregnant woman had four study‐related antenatal visits scheduled at weeks 14–16, 22–24, 30–32, and 36–38 and all participants gave birth at Oslo University Hospital between 2002 and 2008 12 . The study sample was previously used in a study investigating metabolic profiles in pre‐eclamptic pregnancies vs healthy pregnancies, where maternal BMI was identified as a strong confounder 7 . The independent metabolic effect of increased BMI was therefore relevant for further investigation.…”

“…12 The study sample was previously used in a study investigating metabolic profiles in pre-eclamptic pregnancies vs healthy pregnancies, where maternal BMI was identified as a strong confounder. 7 The independent metabolic effect of increased BMI was therefore relevant for further investigation. higher triglyceride and VLDL particle concentration in overweight/obese women.…”

The association between pregnancy levels of blood lipids and the risk of preterm birth

“…Recent epidemiological evidence suggests that there are common risk factors between PTB and cardiovascular disease 11 . Women who experience PTB have a twofold higher risk of developing cardiovascular disease later in life compared to those who have full-term deliveries 12 .…”