Early identification of women at a high risk of preeclampsia might enable potential prophylactic treatment to reduce or avoid the onset of symptoms (9, 10). Preeclampsia is more common and has a lower detection rate (11). Predictive models for preeclampsia have employed a combination of maternal characteristics as well as biochemical and biophysical markers before 14 weeks of gestation to predict the syndrome at 30–60% sensitivity (10–14).
Our findings are consistent with the results of the few available prospective cohort studies on maternal non-fasting plasma lipid and lipoprotein concentrations in preeclamptic and normotensive pregnancies (15, 16). We observed an association between maternal dyslipidemia in the second trimester, particularly 4-h postprandial hypertriglyceridemia, and the subsequent risk of preeclampsia. We evaluated both the FTG and 4-h postprandial TG concentrations at the time of OLTT measurement to show that 4-h postprandial TG concentrations might be an independent predictive biomarker for preeclampsia, which might be more meaningful compared to the FTG concentrations (Table 5). This is in line with the results of a comprehensive study (15) showing the associations between non-fasting plasma TG at 18 weeks of gestation and the risk of preeclampsia. In another prospective cohort study (16), a linear increase in preeclampsia risk was observed with increasing non-fasting plasma TG concentrations before 16 weeks’ gestation. However, fasting TG concentrations in the second trimester were not associated with the development of preeclampsia, which was inconsistent with Oya’s cohort study findings (OR: 1.1 (1.1–1.2), p = 0.004) (17).
Although, the temporality, wherein 4-h postprandial hypertriglyceridemia clearly precedes the onset of preeclampsia, leads us to generate the hypothesis that we may be able to change the natural history of the disease if we intervene early by lowering the postprandial TG concentrations. Maternal lipids offer a potential therapeutic target, and it is worth noting that the current treatments for diabetes in pregnancy, including dietary and lifestyle changes as well as pharmacotherapy, all alter not only maternal glucose but also maternal lipids (3, 18, 19). Before such an intervention, it would be important to define the normal postprandial triglyceride concentrations in pregnancy and correctly identify women with lipid metabolic disturbances who could benefit most from this therapy.
High postprandial TG concentration is positively correlated with insulin resistance, and insulin resistance exists in preeclampsia patients (Tables 2 and 3). Changes in TG metabolism and clearance are mediated by insulin resistance. Women with elevated lipid concentrations are more likely to have preexisting endothelial dysfunction that worsens as a result of the physiological burden of pregnancy; this condition may be further exacerbated by increased maternal vascular inflammation (20). This was supported with evidence from a murine model, which suggested that, in pregnancy, excessive hyperlipidemia may lead to an accentuated inflammatory response, oxidative stress, and subsequent dysfunction of cerebral arteries, compromising cerebral percussion and contributing to preeclampsia-related neurological complications (21).
The sensitivity of the prediction of preeclampsia using 4-h postprandial TG concentration at the time of OLTT measurement in this study (72.7%) was markedly higher than that of previously published prediction of preeclampsia based on clinical markers such as mean arterial pressure, maternal age, and uterine artery pulsatility index in a cohort of women at 11 + 0 to 13 + 6 gestational weeks (38.5%) (22) and in another nulliparous cohort (37%) (23). However, the sensitivity at 10% false positive rate of prediction of preeclampsia is low (18.2%).
The major strength of our study was its prospective design with complete follow-up of 438 women with OLTT measurement. This study design more accurately reflects the predictive power of 4-h postprandial TG compared to a case-control design. Our high participation (86.6%) and follow-up (99.5%) rates minimized the likelihood of selection bias, which may affect the reported results. Second, the fasting and 4-h postprandial blood lipid concentrations obtained after a unified fat meal in the second trimester suggested that the disordered plasma lipid concentrations precede preeclampsia. The unified standard fat meal and blood sampling collection time can avoid lipid data deviation. Third, the exclusion of pregnant women with high risk factors for metabolic syndrome made the results more convincing. Fourth, compared to the fetus in the first trimester, the fetus in the second trimester grows rapidly and needs more energy. The mother gradually switches to a catabolic condition resulting in an increased breakdown of lipid. Therefore, detecting postprandial lipid concentration changes (the ability of lipid metabolism) in the second trimester is more sensitive. Finally, we used the logistic regression to adjust for a number of confounders to obtain a conclusion.
Several important limitations must be considered when interpreting the results of our study. First, our study included a limited number of cases, which is difficult to overcome given the low incidence of these disorders. Our relatively small number of patients with preeclampsia hindered us from making inferences from some of our analyses. Further studies involving multiple centers and a larger number of patients are necessary in order to validate our findings. In addition, although we compared many potential confounders, we cannot exclude the possibility of the other confounding factors from unmeasured covariates.